production and restraining glucose disposal after 4 h onset of hypoglycemia. It has only 20% of counter-regulatory response compared to the action of epinephrine. If counter-regulatory mechanism fails to maintain the glucose homeostasis and blood glucose value of 3.0–3.5 mmol/l, may trigger the autonomic nervous system mediated warning symptoms such as sweating, palpitation and hunger to warn subjective awareness of hypoglycemia and provoke feeling of eating to improve blood glucose level. If not consume adequate glucose during this stage, central nervous deprives for glucose, neuroglycopenia develops and cognitive function declines. Counter-regulatory responses to hypoglycemia also referred to as glycemic thresholds and may be altered to higher plasma glucose levels following chronic hyperglycemia [26] or to lower plasma glucose levels following repeated hypoglycemia [27–29]. On the whole, the magnitude of counter-regulatory function is decrease

The glycemic threshold has a dynamic and significant role in the activation of counter-regulatory physiological response against the low plasma glucose level [20]. Though the individuals have increased level of glycated hemoglobin (HbA1C) may perceive the symptoms of hypoglycemia at higher blood individuals who undergo intensive glucose level with diabetes [31]. It means sudden and rapid declines of blood glucose from higher level to a lower but not too low and at this level brain started reacting to change and release of counter-regulatory hormones. This phenomenon is called "**relative hypoglycemia**" and it is self-limiting. Brain will usually takes 2–4 weeks to readjust and to improve that relatively reduced circulat-

In contrast, among diabetic patients who are on the intensive treatment of control of plasma glucose level may not perceive hypoglycemia until their plasma glucose is considerably lower than the normal physiological glycemic thresholds [33, 35]. The changes in this glycemic control are highly influenced chronically by persistent hyperglycemia and acutely by antecedent hypoglycemia [12, 35–38]. **Antecedent hypoglycemia** is a condition caused by hypoglycemia itself which impairs and reduces the reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia. An experimental study found that there is a significant reduction in glucagon, epinephrine, cortisol, pancreatic polypeptide responses to next-day of hypoglycemia among antecedent hypoglycemic patients who experienced two episodes with the blood glucose level of 50 mg/dl. It was also demonstrated that antecedent hypoglycemia reduced the neurogenic and neuroglycopenic symptom responses [28]. In later another study investigated the responses of metabolic and neuroendocrine on the effect of morning hypoglycemia to subsequent afternoon hypoglycemia. The findings revealed that only one prolonged, moderate hypoglycemic episode can also blunt the substantial changes of physiological counter-regulatory defense and the neurogenic and neuroglycopenic

This impaired counter-regulatory responses otherwise called as "**hypoglycemiaassociated autonomic failure**" causes reduced neuroendocrine counter-regulatory responses to hypoglycemia and lowered glycemic thresholds for activation of physiological defenses against hypoglycemia, which together lead to a condition called **hypoglycemic unawareness**. During this stage, because of failure to trigger the epinephrine secretion against severe drop in blood sugar, the individuals unaware of hypoglycemic symptoms of sweating, palpitation, anxiety generated by epinephrine. These symptoms are very significantly important to warn the individuals of the

with age 18 and is more obvious in male than in female [30].

**6. Hypoglycemia and glycemic threshold**

symptom response to subsequent hypoglycemia [39].

ing glucose levels [27, 31–34].

#### *Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

*Blood Glucose Levels*

• Transcription errors

hyperkalemia and glucose and

• insulin infusion to blood glucose control

**5. Physiology of glucose counter-regulation**

further deterioration of effects of hypoglycemia.

are glucagon and epinephrine.

• Confusing the insulin strength with the dose

• Inappropriately withdrawing insulin using a standard insulin syringe

• Confusion between the prescription of a glucose and insulin infusion for

The most metabolically active organ is brain and it is the first organ affected by lower blood glucose level. The brain requires continuous supply of oxygen and glucose to meet the needs of energy requirement as it does not store excess energy and derives almost all of its energy from aerobic oxidation of glucose. Hence brain cells are vulnerable to glucose deprivation and also cannot survive more than 5–6 min without glucose. The sequence of counter-regulatory response will play significant role when the blood glucose levels fall below 70 mg/dl to protect the brain from

Decline in Blood glucose levels below the physiological range may trigger hierarchically organized sequence of responses in the non-diabetic individual [21, 22]. It includes release of neuroendocrine hormones or counter-regulatory or anti-insulin hormones, stimulation of the autonomic nervous system (ANS), and manifestation of neurogenic and neuroglycopenic symptoms. Pancreatic beta cells suppressed the insulin secretion when blood glucose levels declines within the physiological range results in reduction of peripheral glucose uptake and increase in hepatic glucose production to prevent true hypoglycemia. In further, declining intra-islet insulin plays an important role for the glucagon response to hypoglycemia by increase the release of glucagon by pancreatic alpha cells [23–25] and pancreatic polypeptide from the pancreas. Similarly catecholamines such as epinephrine secreted from the adrenal medullae and norepinephrine from sympathetic postganglionic nerve terminals and adrenal medulla. Cortisol from the adrenal cortex and growth hormone from the anterior pituitary gland also triggered when blood glucose level falls. The primary physiological fast acting hormones in response to hypoglycemia

Glucagon hormones enhance endogenous glucose production by the process of glycogenolysis and gluconeogenesis and generating glucose substrates such as lactate, pyruvate, alanine, and glycerol. In addition, epinephrine also has similar effects like glucagon in increase of endogenous glucose production and inhibition of utilization of glucose in the peripheral tissue and converts the gluconeogenic pathway. It can also stimulate net renal glucose production. However inhibition of insulin secretion is the primary physiological defense against decrease blood glucose and occurs at a plasma glucose concentration of less than 80 mg/dl. The response of sympathetic nervous system against hypoglycemia is activated by both circulating catecholamines and direct innervation results in increased fat metabolism of lipolysis in adipocytes which release free fatty acid. It is estimated that 25% of the total defense against hypoglycemia by the contribution of free fatty acid. Cortisol and growth hormone are metabolic defense which are released in response to prolonged hypoglycemia; but they have modest significant effect on glucose counterregulation during acute stage. The actions of these hormones are increasing glucose

**94**

production and restraining glucose disposal after 4 h onset of hypoglycemia. It has only 20% of counter-regulatory response compared to the action of epinephrine.

If counter-regulatory mechanism fails to maintain the glucose homeostasis and blood glucose value of 3.0–3.5 mmol/l, may trigger the autonomic nervous system mediated warning symptoms such as sweating, palpitation and hunger to warn subjective awareness of hypoglycemia and provoke feeling of eating to improve blood glucose level. If not consume adequate glucose during this stage, central nervous deprives for glucose, neuroglycopenia develops and cognitive function declines. Counter-regulatory responses to hypoglycemia also referred to as glycemic thresholds and may be altered to higher plasma glucose levels following chronic hyperglycemia [26] or to lower plasma glucose levels following repeated hypoglycemia [27–29]. On the whole, the magnitude of counter-regulatory function is decrease with age 18 and is more obvious in male than in female [30].

#### **6. Hypoglycemia and glycemic threshold**

The glycemic threshold has a dynamic and significant role in the activation of counter-regulatory physiological response against the low plasma glucose level [20]. Though the individuals have increased level of glycated hemoglobin (HbA1C) may perceive the symptoms of hypoglycemia at higher blood individuals who undergo intensive glucose level with diabetes [31]. It means sudden and rapid declines of blood glucose from higher level to a lower but not too low and at this level brain started reacting to change and release of counter-regulatory hormones. This phenomenon is called "**relative hypoglycemia**" and it is self-limiting. Brain will usually takes 2–4 weeks to readjust and to improve that relatively reduced circulating glucose levels [27, 31–34].

In contrast, among diabetic patients who are on the intensive treatment of control of plasma glucose level may not perceive hypoglycemia until their plasma glucose is considerably lower than the normal physiological glycemic thresholds [33, 35]. The changes in this glycemic control are highly influenced chronically by persistent hyperglycemia and acutely by antecedent hypoglycemia [12, 35–38]. **Antecedent hypoglycemia** is a condition caused by hypoglycemia itself which impairs and reduces the reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia. An experimental study found that there is a significant reduction in glucagon, epinephrine, cortisol, pancreatic polypeptide responses to next-day of hypoglycemia among antecedent hypoglycemic patients who experienced two episodes with the blood glucose level of 50 mg/dl. It was also demonstrated that antecedent hypoglycemia reduced the neurogenic and neuroglycopenic symptom responses [28]. In later another study investigated the responses of metabolic and neuroendocrine on the effect of morning hypoglycemia to subsequent afternoon hypoglycemia. The findings revealed that only one prolonged, moderate hypoglycemic episode can also blunt the substantial changes of physiological counter-regulatory defense and the neurogenic and neuroglycopenic symptom response to subsequent hypoglycemia [39].

This impaired counter-regulatory responses otherwise called as "**hypoglycemiaassociated autonomic failure**" causes reduced neuroendocrine counter-regulatory responses to hypoglycemia and lowered glycemic thresholds for activation of physiological defenses against hypoglycemia, which together lead to a condition called **hypoglycemic unawareness**. During this stage, because of failure to trigger the epinephrine secretion against severe drop in blood sugar, the individuals unaware of hypoglycemic symptoms of sweating, palpitation, anxiety generated by epinephrine. These symptoms are very significantly important to warn the individuals of the

lowering blood glucose level. Same scenario happened in intensively treated type 1 and type 2 diabetic individuals due to shifting of glycemic threshold to lower plasma glucose level [33, 39–42] which further limits the efforts to attain euglycemia [37, 38].

#### **7. Clinical manifestations of hypoglycemia**

Hypoglycemic signs and symptoms (**Table 3**) may occur unexpectedly and suddenly depends on the blood glucose level and may also vary from one person to another. The hyperglycemic individuals who have blood glucose level with 200 mg/dl or greater may feel adrenergic hypoglycemic symptoms when blood glucose suddenly falls to 120 mg/dl or less. Whereas a person with usual blood glucose levels in the low range may not experience symptoms when blood glucose slowly drops under 50 mg/dl and also patients who have had diabetes for many years have decreased hormonal (adrenergic) response to hypoglycemia.

Hypoglycemic symptoms may manifest as neurogenic (autonomic) symptoms and cholinergic-mediated symptoms. Low blood glucose level triggered the neurogenic symptoms by activating the autonomic nervous system which releases the catecholamines (norepinephrine and epinephrine) from the adrenal medullae and acetylcholine from postsynaptic sympathetic nerve endings. Elevated epinephrine levels leads the symptoms and signs of shakiness, palpitations, sweating, nervousness, anxiety, pupil dilation, dry mouth, pallor. The cholinergic-mediated symptoms are hunger, diaphoresis and paresthesia. However, only 20% of the total neurogenic symptom was found during hypoglycemia among epinephrine infusion in intensively and conventionally treated euglycemic type 1 diabetic individuals which indicates that the symptoms of hypoglycemic is multifocal and is mainly araised from efferent pathways of central nervous system [43].

Neuroglycopenic symptoms occur as a result of deprivation of glucose in the brain cells during hypoglycemia. Neuroglycopenic symptoms are very difficult to perceive by an individual rather it is most often recognized by family members, friends and bystanders. These symptoms include irritability, confusion, aphasia, paresthesias, ataxia, headache and the most severe symptoms are seizures stupor, coma, and even death. It can also include transient focal neurological deficits such as diplopia, hemiparesis.

**97**

**1 diabetes**

*Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

are reproduced in **Table 4**.

*Edinburgh hypoglycemia scale.*

Sweating Palpitations Shaking Hunger

**Table 4.**

**8. Levels of hypoglycemia**

**8.1 Level I (mild) hypoglycemia**

nervous system is stimulation.

**8.2 Level II (moderate) hypoglycemia**

**8.3 Level III (severe hypoglycemia)**

to impaired function of central nervous system.

Neurogenic and neuroglycopenic symptoms are manifested by the activation of the sympatho-adrenal system and brain's glucose deprivation. The brain is continuously depends on a circulating glucose for energy and for cognitive function. If blood glucose levels fall causes cognitive dysfunction [44]. The 11 most commonly reported symptoms were used to form the Edinburgh Hypoglycemia Scale [45] and

Headache Nausea

**Autonomic Neuroglycopenic General malaise**

Confusion Drowsiness Odd behavior Speech difficulty Incoordination

According to the blood glucose level and manifestation of signs and symptoms in response to low blood glucose level, hypoglycemia can be categorized into Level I,

The range of blood glucose level is 54–70 mg/dl. Symptoms include tremor, palpitations, tachycardia, nervousness, sweating and hunger due to sympathetic

The range of blood glucose level is 40–54 mg/dl. It may produce confusion, irritation, inability to concentrate, headache, lightheadedness, memory loss, numbness of the lips and tongue, slurred speech, lack of coordination, emotional changes, drowsiness, and double vision, or any combination of these symptoms due

In severe hypoglycemia, the blood glucose level is less than 40 mg/dl. Central nervous system function is impaired further. Symptoms may include disoriented behavior, seizures, stupor, or loss of consciousness. During this stage they need help from another as they unable to function because of physical and mental changes.

**9. Mechanisms of counter-regulatory responses to hypoglycemia in type**

Type 1 diabetes mellitus is otherwise called insulin dependent diabetes mellitus which occur due to little production of insulin or no insulin from pancreatic betacells characterized by hyperglycemia and its associated symptoms. The treatment include for the management of diabetes mellitus is insulin, diet and exercise and

Level II and Level III or mild, moderate and severe hypoglycemia.

**Table 3.** *Signs and symptoms of hypoglycemia.*

#### **Table 4.**

*Blood Glucose Levels*

lowering blood glucose level. Same scenario happened in intensively treated type 1 and type 2 diabetic individuals due to shifting of glycemic threshold to lower plasma glucose level [33, 39–42] which further limits the efforts to attain euglycemia [37, 38].

Hypoglycemic signs and symptoms (**Table 3**) may occur unexpectedly and suddenly depends on the blood glucose level and may also vary from one person to another. The hyperglycemic individuals who have blood glucose level with 200 mg/dl or greater may feel adrenergic hypoglycemic symptoms when blood glucose suddenly falls to 120 mg/dl or less. Whereas a person with usual blood glucose levels in the low range may not experience symptoms when blood glucose slowly drops under 50 mg/dl and also patients who have had diabetes for many years have decreased

Hypoglycemic symptoms may manifest as neurogenic (autonomic) symptoms and cholinergic-mediated symptoms. Low blood glucose level triggered the neurogenic symptoms by activating the autonomic nervous system which releases the catecholamines (norepinephrine and epinephrine) from the adrenal medullae and acetylcholine from postsynaptic sympathetic nerve endings. Elevated epinephrine levels leads the symptoms and signs of shakiness, palpitations, sweating, nervousness, anxiety, pupil dilation, dry mouth, pallor. The cholinergic-mediated symptoms are hunger, diaphoresis and paresthesia. However, only 20% of the total neurogenic symptom was found during hypoglycemia among epinephrine infusion in intensively and conventionally treated euglycemic type 1 diabetic individuals which indicates that the symptoms of hypoglycemic is multifocal and is mainly

Neuroglycopenic symptoms occur as a result of deprivation of glucose in the brain cells during hypoglycemia. Neuroglycopenic symptoms are very difficult to perceive by an individual rather it is most often recognized by family members, friends and bystanders. These symptoms include irritability, confusion, aphasia, paresthesias, ataxia, headache and the most severe symptoms are seizures stupor, coma, and even death. It can also include transient focal neuro-

> Blurred vision Difficulty speaking Feeling faint Difficulty thinking Confusion Dizziness Feeling drowsy Irritability

Transient Focal Neurological Deficit occasionally

**7. Clinical manifestations of hypoglycemia**

hormonal (adrenergic) response to hypoglycemia.

araised from efferent pathways of central nervous system [43].

**Autonomic symptoms Neuroglycopenic symptoms**

**Autonomic signs Neuroglycopenic signs**

logical deficits such as diplopia, hemiparesis.

**96**

**Table 3.**

Sweating Tingling Trembling Feeling shaky Feeling hungry Palpitations Anxiety

Tachycardia

Pallor Diaphoresis Mydriasis

Increased systolic blood pressure

*Signs and symptoms of hypoglycemia.*

*Edinburgh hypoglycemia scale.*

Neurogenic and neuroglycopenic symptoms are manifested by the activation of the sympatho-adrenal system and brain's glucose deprivation. The brain is continuously depends on a circulating glucose for energy and for cognitive function. If blood glucose levels fall causes cognitive dysfunction [44]. The 11 most commonly reported symptoms were used to form the Edinburgh Hypoglycemia Scale [45] and are reproduced in **Table 4**.

#### **8. Levels of hypoglycemia**

According to the blood glucose level and manifestation of signs and symptoms in response to low blood glucose level, hypoglycemia can be categorized into Level I, Level II and Level III or mild, moderate and severe hypoglycemia.

#### **8.1 Level I (mild) hypoglycemia**

The range of blood glucose level is 54–70 mg/dl. Symptoms include tremor, palpitations, tachycardia, nervousness, sweating and hunger due to sympathetic nervous system is stimulation.

#### **8.2 Level II (moderate) hypoglycemia**

The range of blood glucose level is 40–54 mg/dl. It may produce confusion, irritation, inability to concentrate, headache, lightheadedness, memory loss, numbness of the lips and tongue, slurred speech, lack of coordination, emotional changes, drowsiness, and double vision, or any combination of these symptoms due to impaired function of central nervous system.

#### **8.3 Level III (severe hypoglycemia)**

In severe hypoglycemia, the blood glucose level is less than 40 mg/dl. Central nervous system function is impaired further. Symptoms may include disoriented behavior, seizures, stupor, or loss of consciousness. During this stage they need help from another as they unable to function because of physical and mental changes.

#### **9. Mechanisms of counter-regulatory responses to hypoglycemia in type 1 diabetes**

Type 1 diabetes mellitus is otherwise called insulin dependent diabetes mellitus which occur due to little production of insulin or no insulin from pancreatic betacells characterized by hyperglycemia and its associated symptoms. The treatment include for the management of diabetes mellitus is insulin, diet and exercise and

lifestyle modification. Insulin helps to convert the glucose into glycogen and store in the liver and muscles. If there is an imbalance between the insulin administration and food intake leads to hypoglycemia. Physiologically glucagon will be secreted by the pancreatic alpha-cells to convert the stored glycogen into glucose or from non-carbohydrate substances. However in patients with type 1 diabetes for more than years epinephrine is main physiological defense in response to hypoglycemia because glucagon secretory response to hypoglycemia is irreversibly lost. In later, epinephrine response to hypoglycemia also impaired unfortunately among patients with type 1 diabetes undergoing intensive treatment of insulin and at greater risk for recurrent hypoglycemia [46, 47]. There is more than 50% reduction in counterregulatory responses toward the future hypoglycemia due to repeated attack of hypoglycemia which results in vicious cycle of iatrogenic hypoglycemia-associated autonomic failure and also subsequent hypoglycemia may also leads to antecedent hypoglycemia. Even short durations 20 minutes of antecedent hypoglycemia can produce significant impairment in counter-regulatory responses and also two episodes of hypoglycemia of 70 mg/dl can also blunt subsequent counter-regulatory responses by ∼30% in men [48]. Patient may experience severe and significant clinical consequences due to reduced adrenergic sensitivity of poor tissue responsive to circulating epinephrine and deficient responses of glucagon with reduction in ANS counter-regulatory responses. These patients also had reduced β-adrenergic sensitivity compared to patients with normal counter-regulatory responses to hypoglycemia and healthy control subjects [49] and had reduced whole-body tissue sensitivity to epinephrine, which was exacerbated by intensive glycemic control. This reduced tissue responsiveness to epinephrine is an additional contributor to the syndrome of hypoglycemia-associated autonomic failure and reduced tissue sensitivity to epinephrine resulted in decrease endogenous glucose production and less inhibition of insulin-stimulated glucose uptake. Despite with persistent blunted epinephrine response to hypoglycemia, hypoglycemic symptom and β-adrenergic sensitivity responses increase [50] to restore the endocrine and autonomic function. Although controversial, other studies have also stated that with strict avoidance of antecedent hypoglycemia some or all of the features of hypoglycemia-associated autonomic failure can be reversed [51–53].

#### **9.1 Mechanisms of counter-regulatory responses to hypoglycemia in type 2 diabetes**

Type 2 diabetes mellitus is a heterogeneous group of disease caused by inadequate secretion of insulin or improper utilization of secreted insulin or both. It may the affect all groups of people from children to older adults. Children are more commonly affected nowadays due to rise in childhood obesity. Treatment regime includes diet, exercise, oral hypoglycemic agents, glucagon like peptide-1 analogs, insulin, or combination of these and varies depending on the response to treatment and progressive β-cell failure [54]. The symptoms of hypoglycemia associated autonomic failure among type 2 diabetes depends on age, treatment modality (diet versus oral hypoglycemic agents versus insulin), comorbidity, body fat composition, metabolic control, and the presence of diabetic neuropathies [54, 55]. However, neuroendocrine contributes in glycemic responses to hypoglycemia in advanced type 2 diabetes. The glucagon response to low blood glucose level was also absent in advanced insulin-treated type 2 diabetes. Autonomic and symptomatic responses by glycemic threshold to hypoglycemia were also altered to lower plasma glucose concentrations by recent antecedent hypoglycemia. Hence, the risk for hypoglycemia-associated autonomic failure was high in advanced type 2 diabetes as like those with type 1 diabetes and leads to harmful cycle of recurrent iatrogenic hypoglycemia [46, 55].

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*Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

**10.1 Fasting (postabsorptive) hypoglycemia**

**10.3 Postprandial (reactive) hypoglycemia**

**10.4 Exercise-induced hypoglycemia**

Fanconi-Bickel syndrome.

**10.2 Patients with GSD**

intolerance.

β cells.

**10. Inborn errors of metabolism causing hypoglycemia**

postprandial hypoglycemia, and exercise-induced hypoglycemia.

Non-diabetic hypoglycemia also results from inborn errors of metabolism. Such hypoglycemia most commonly occurs in infancy but can also occur in adulthood. Cases in adults can be classified into those resulting in fasting hypoglycemia,

It is rare; disorders of glycogenolysis can result in fasting hypoglycemia. These

Type 1 and 3 characteristically have high blood lactate levels before and after meals, respectively. Both groups have hypertriglyceridemia, but ketones are high in GSD type 3. Defects in fatty acid oxidation also result in fasting hypoglycemia. These defects can include (1) defects in the carnitine cycle; (2) fatty-acid β-oxidation disorders; (3) electron transfer disturbances; and (4) ketogenesis disorders. Finally, defects in gluconeogenesis (fructose-1, 6-biphosphatase) have

Inborn errors of metabolism resulting in postprandial hypoglycemia are also rare. These errors include (1) glucokinase, SUR1, and Kir6.2 potassium channel mutations; (2) congenital disorders of glycosylation; and (3) inherited fructose

Exercise-induced hypoglycemia, by definition, follows exercise. It results in hyperinsulinemia caused by increased activity of monocarboxylate transporter 1 in

Hypoglycemia caused by endogenous hyperinsulinism due to functional β-cell disorders, insulinoma, or the insulin autoimmune syndrome is called as accidental, surreptitious, or malicious hypoglycemia. It may also occur by accidental administration of insulin, or accidental ingestion of an insulin secretagogue such as sulfonylurea because ingestion of an insulin secretagogue causes hypoglycemia with increased C-peptide levels and hypoglycemia caused by exogenous insulin with

disorders include glycogen storage disease (GSD) of types 0, 1, 3, and 4 and

been reported to result in recurrent hypoglycemia and lactic acidosis.

**11. Accidental, surreptitious, or malicious hypoglycemia**

decrease C-peptide levels reflecting suppression of insulin secretion.

**12. Assessment and diagnostic methods**

• History collection

• Physical examination

*Blood Glucose Levels*

autonomic failure can be reversed [51–53].

**diabetes**

**9.1 Mechanisms of counter-regulatory responses to hypoglycemia in type 2**

secretion of insulin or improper utilization of secreted insulin or both. It may the affect all groups of people from children to older adults. Children are more commonly affected nowadays due to rise in childhood obesity. Treatment regime includes diet, exercise, oral hypoglycemic agents, glucagon like peptide-1 analogs, insulin, or combination of these and varies depending on the response to treatment and progressive β-cell failure [54]. The symptoms of hypoglycemia associated autonomic failure among type 2 diabetes depends on age, treatment modality (diet versus oral hypoglycemic agents versus insulin), comorbidity, body fat composition, metabolic control, and the presence of diabetic neuropathies [54, 55]. However, neuroendocrine contributes in glycemic responses to hypoglycemia in advanced type 2 diabetes.

The glucagon response to low blood glucose level was also absent in advanced insulin-treated type 2 diabetes. Autonomic and symptomatic responses by glycemic threshold to hypoglycemia were also altered to lower plasma glucose concentrations by recent antecedent hypoglycemia. Hence, the risk for hypoglycemia-associated autonomic failure was high in advanced type 2 diabetes as like those with type 1 diabetes and leads to harmful cycle of recurrent iatrogenic hypoglycemia [46, 55].

Type 2 diabetes mellitus is a heterogeneous group of disease caused by inadequate

lifestyle modification. Insulin helps to convert the glucose into glycogen and store in the liver and muscles. If there is an imbalance between the insulin administration and food intake leads to hypoglycemia. Physiologically glucagon will be secreted by the pancreatic alpha-cells to convert the stored glycogen into glucose or from non-carbohydrate substances. However in patients with type 1 diabetes for more than years epinephrine is main physiological defense in response to hypoglycemia because glucagon secretory response to hypoglycemia is irreversibly lost. In later, epinephrine response to hypoglycemia also impaired unfortunately among patients with type 1 diabetes undergoing intensive treatment of insulin and at greater risk for recurrent hypoglycemia [46, 47]. There is more than 50% reduction in counterregulatory responses toward the future hypoglycemia due to repeated attack of hypoglycemia which results in vicious cycle of iatrogenic hypoglycemia-associated autonomic failure and also subsequent hypoglycemia may also leads to antecedent hypoglycemia. Even short durations 20 minutes of antecedent hypoglycemia can produce significant impairment in counter-regulatory responses and also two episodes of hypoglycemia of 70 mg/dl can also blunt subsequent counter-regulatory responses by ∼30% in men [48]. Patient may experience severe and significant clinical consequences due to reduced adrenergic sensitivity of poor tissue responsive to circulating epinephrine and deficient responses of glucagon with reduction in ANS counter-regulatory responses. These patients also had reduced β-adrenergic sensitivity compared to patients with normal counter-regulatory responses to hypoglycemia and healthy control subjects [49] and had reduced whole-body tissue sensitivity to epinephrine, which was exacerbated by intensive glycemic control. This reduced tissue responsiveness to epinephrine is an additional contributor to the syndrome of hypoglycemia-associated autonomic failure and reduced tissue sensitivity to epinephrine resulted in decrease endogenous glucose production and less inhibition of insulin-stimulated glucose uptake. Despite with persistent blunted epinephrine response to hypoglycemia, hypoglycemic symptom and β-adrenergic sensitivity responses increase [50] to restore the endocrine and autonomic function. Although controversial, other studies have also stated that with strict avoidance of antecedent hypoglycemia some or all of the features of hypoglycemia-associated

**98**

### **10. Inborn errors of metabolism causing hypoglycemia**

Non-diabetic hypoglycemia also results from inborn errors of metabolism. Such hypoglycemia most commonly occurs in infancy but can also occur in adulthood. Cases in adults can be classified into those resulting in fasting hypoglycemia, postprandial hypoglycemia, and exercise-induced hypoglycemia.

#### **10.1 Fasting (postabsorptive) hypoglycemia**

It is rare; disorders of glycogenolysis can result in fasting hypoglycemia. These disorders include glycogen storage disease (GSD) of types 0, 1, 3, and 4 and Fanconi-Bickel syndrome.

#### **10.2 Patients with GSD**

Type 1 and 3 characteristically have high blood lactate levels before and after meals, respectively. Both groups have hypertriglyceridemia, but ketones are high in GSD type 3. Defects in fatty acid oxidation also result in fasting hypoglycemia. These defects can include (1) defects in the carnitine cycle; (2) fatty-acid β-oxidation disorders; (3) electron transfer disturbances; and (4) ketogenesis disorders. Finally, defects in gluconeogenesis (fructose-1, 6-biphosphatase) have been reported to result in recurrent hypoglycemia and lactic acidosis.

#### **10.3 Postprandial (reactive) hypoglycemia**

Inborn errors of metabolism resulting in postprandial hypoglycemia are also rare. These errors include (1) glucokinase, SUR1, and Kir6.2 potassium channel mutations; (2) congenital disorders of glycosylation; and (3) inherited fructose intolerance.

#### **10.4 Exercise-induced hypoglycemia**

Exercise-induced hypoglycemia, by definition, follows exercise. It results in hyperinsulinemia caused by increased activity of monocarboxylate transporter 1 in β cells.

#### **11. Accidental, surreptitious, or malicious hypoglycemia**

Hypoglycemia caused by endogenous hyperinsulinism due to functional β-cell disorders, insulinoma, or the insulin autoimmune syndrome is called as accidental, surreptitious, or malicious hypoglycemia. It may also occur by accidental administration of insulin, or accidental ingestion of an insulin secretagogue such as sulfonylurea because ingestion of an insulin secretagogue causes hypoglycemia with increased C-peptide levels and hypoglycemia caused by exogenous insulin with decrease C-peptide levels reflecting suppression of insulin secretion.

### **12. Assessment and diagnostic methods**

**Whipple triad** is the clinical presentation of pancreatic insulinoma and consists of: fasting hypoglycemia (<50 mg/dl), symptoms of hypoglycemia, immediate relief of symptoms after the administration of IV glucose.

#### **13. Management of hypoglycemia**

The aim of the treatment includes correction of glucose deficiency, prevent the complication associated with hypoglycemia and treat the underlying the cause. Treat the patient in the emergency department as shown in the **Figure 1**.

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*Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

70 mg/dl

**Figure 1.**

repeated up to 1–3 times

glycemia in later hours.

especially in type 1 diabetes mellitus.

*Schematic representation of emergency management of hypoglycemia.*

sulfonylurea-induced hypoglycemia.

• Identify and treat the underlying cause

• Assessment of glasgow coma scale

• Monitor airway, breathing, circulation

• Constant monitoring of blood glucose level

**13.1 Management of hypoglycemia in the unconscious patient**

• Administer 1 g of glucagon subcutaneously or intravenously

• Administer 50% dextrose in 25–50 mL of water intravenously

• Instruct the patient to eat protein and carbohydrate containing snack to maintain their blood glucose after 60 min if the blood glucose is higher than

• Treatment is repeated with 15 g of carbohydrates if glucose level is remains less than 70 mg/dl after the initial intake of 15 g of glucose. It may be probably

• Instruct the patient to avoid adding more table sugar to juice, even "unsweetened" juice, which may cause a sudden increase in glucose, resulting in hyper-

• Administer parenteral therapy with 25% dextrose if unable to take oral foods

• The somatostatin analog octreotide can be used to suppress insulin secretion in

• Administer inj. glucagon 1.0 mg subcutaneous/intramuscular can be used

• Check for blood glucose 15 min later.

#### *Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

#### **Figure 1.**

*Blood Glucose Levels*

• Insulin

• C-peptide

• Proinsulin

• Diagnostic investigation: It includes

• Antibodies for insulin and its receptors

• cortisol and thyroid levels, growth hormone level

relief of symptoms after the administration of IV glucose.

• History collection and physical examination

• Assess the mental status of the client

• Check for blood glucose 15 min later.

• Access intravenous line if needed

• Monitor blood glucose level

• Check the blood glucose—capillary blood glucose

**Whipple triad** is the clinical presentation of pancreatic insulinoma and consists

The aim of the treatment includes correction of glucose deficiency, prevent the complication associated with hypoglycemia and treat the underlying the cause. Treat the patient in the emergency department as shown in the **Figure 1**.

• Administer 15 g of fast acting glucose in the form of glucose tablets or glucose containing fluids, candy or food. For, e.g., three or four commercially prepared glucose tablets; 4–6 oz. of fruit juice or regular soda, 6–10 hard candies, 2–3 tsp. of sugar or honey is appropriate if the patient is able to take orally

of: fasting hypoglycemia (<50 mg/dl), symptoms of hypoglycemia, immediate

• Sulfonylurea and meglitinide screen

• Complete blood count

• Beta-hydroxybutyrate

• Electrolytes, BUN/Cr, UA

• Other tests: CT and MRI

**13. Management of hypoglycemia**

• liver function tests,

• Glucose—fasting and postprandial blood glucose

**100**

*Schematic representation of emergency management of hypoglycemia.*

#### **13.1 Management of hypoglycemia in the unconscious patient**

#### **13.2 Management of non-diabetic hypoglycemia**

Depend on the underlying etiology

#### **13.3 Health education**

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*Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

etc.

identity card.

**Acknowledgements**

**Conflict of interest**

**Author details**

Thenmozhi Paluchamy

**14. Conclusion**

ticularly that caused by a sulfonylurea.

• Regular check-up and follow-up care.

expiry date and replacing the used content in the kit.

their hypoglycemia management plan while caring the clients.

Saveetha College of Nursing, SIMATS, Chennai, Tamil Nadu, India

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to<EMAIL_ADDRESS>
opportunity to write the chapter on Hypoglycemia.

The author declares no conflict of interest.

provided the original work is properly cited.

• Intravenous glucose is the preferable treatment of severe hypoglycemia, par-

• Keeping the hypo box hypoglycemic kit which contains glucose, glucagon, juice,

• Instructing the family members and care givers about usage this kit, check for

• Always carry the sweetener which contains easily absorbable simple sugar and

Hypoglycemia is a common, potentially avoidable consequence of diabetes treatment. This chapter emphasis on causes and risk factors of hypoglycemia, recognition of symptoms of hypoglycemia, glucose regulatory and counter regulatory mechanism, management and prevention of hypoglycemia thereby prevent the potential complications of hypoglycemia. Health care professionals have a major role in educating clients with diabetes mellitus about hypoglycemia and to follow

The author would like to thank the IntechOpen publishers for offering me an

#### **14. Conclusion**

*Blood Glucose Levels*

tumor.

**13.3 Health education**

agent.

for medication and/or insulin.

• Quit alcohol and smoking.

• Maintain the body weight.

• Follow medication dose regularly.

symptoms of hypoglycemia.

15 min during hypoglycemia state.

makes the blood glucose level drop.

may cause permanent brain damage.

conscious and restore normal brain function

• Discontinue the offending drugs or reduce their doses

• Replace the cortisol and growth hormone if levels are deficient.

possible and in patient with a non-tumor beta cell tumor

• Surgical, radiotherapeutic, or chemotherapeutic reduction of a non–islet cell

• Medical therapy with diazoxide or octreotide can be used if resection is not

• Consult with a dietitian to develop or adjust meal plan to maintain consistency in carbohydrates at meals by calculating grams of carbohydrates so that plan

• Self-monitoring of blood glucose to detect the episodes of hypoglycemia at the earliest. Self-monitoring of blood glucose level should give an idea of what

• Do not skip meal and balance the meal plan with insulin or oral hypoglycemic

• Avoidance of exercise while having the symptoms of hypoglycemia.

• Ingestion of carbohydrate especially rapidly absorbed glucose during the

• Remember and follow rule of 15 which means 15 g of glucose raise 50 mg/dl in

**13.2 Management of non-diabetic hypoglycemia**

Depend on the underlying etiology

• Treat the underlying critical illnesses

• Surgical resection of an insulinoma is curative

• Check the patient for regaining from the state of unconsciousness. If hypoglycemic state extends for more than 5 h results in profound hypoglycemia which

• Administer IV Mannitol and dexamethasone, IV glucose with constant glucose monitoring to necessary until regain from the state of unconsciousness to

**102**

Hypoglycemia is a common, potentially avoidable consequence of diabetes treatment. This chapter emphasis on causes and risk factors of hypoglycemia, recognition of symptoms of hypoglycemia, glucose regulatory and counter regulatory mechanism, management and prevention of hypoglycemia thereby prevent the potential complications of hypoglycemia. Health care professionals have a major role in educating clients with diabetes mellitus about hypoglycemia and to follow their hypoglycemia management plan while caring the clients.

#### **Acknowledgements**

The author would like to thank the IntechOpen publishers for offering me an opportunity to write the chapter on Hypoglycemia.

#### **Conflict of interest**

The author declares no conflict of interest.

#### **Author details**

Thenmozhi Paluchamy Saveetha College of Nursing, SIMATS, Chennai, Tamil Nadu, India

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on hypoglycemia. Diabetes Care. 2005;**28**:1245-1249

[2] Hinkle JL. Brunner and Siddarth's Textbook of Medical-Surgical Nursing. 13th ed. Philadelphia, PA: Wolters Kluwer Health Publication; 2014. pp. 862-865

[3] Metchich LN, Petit WA, Inzucchi SE. The most common type of hypoglycemia is insulin-induced hypoglycemia in diabetes. The American Journal of Medicine. 2002;**113**:317-323

[4] American Diabetes Association. Hospital admission guidelines for diabetes (position statement). Diabetes Care. 2004;**27**(Suppl. 1):S103

[5] Briscoe VJ, Davis SN. Hypoglycemia in type 1 and type 2 diabetes: Physiology, pathophysiology, and management. Clinical Diabetes. 2006;**24**(3):115-121

[6] Dajkovich G, Barkley TW Jr. Understanding insulin pump therapy. Journal of Community Health Nursing. 2015;**32**(3):131-140

[7] Cryer PE. Hypoglycemia: Pathophysiology, Diagnosis, and Treatment. New York, NY, USA: Oxford University Press; 1997

[8] The Writing Team for the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002;**287**(19):2563-2569

[9] Edridge CL, Dunkley AJ, Bodicoat DH, Rose TC, Gray LJ, Davies MJ,

et al. Prevalence and incidence of hypoglycaemia in 532,542 people with type 2 diabetes on oral therapies and insulin: A systematic review and metaanalysis of population based studies. PLoS One. 2015;**10**(6):e0126427. DOI: 10.1371/journal.pone.0126427

[10] Donnelly LA, Morris AD, Frier BM, et al. Frequency and predictors of hypoglycaemia in type 1 and insulintreated type 2 diabetes: A populationbased study. Diabetic Medicine. 2005;**22**(6):749-755

[11] Laing SP, Swerdlow AJ, Slater SD, Botha JL, Burden AC, Waugh NR, et al. The British Diabetic Association Cohort Study. II. Cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabetic Medicine. 1999;**16**:466-471

[12] The U.K. Prospective Diabetes Study Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes. Lancet. 1998;**352**:837-853

[13] Cryer PE. Glucose homeostasis and hypoglycemia. In: Larsen RP, Kronenberg HM, Melmed S, Polonsky KS, editors. Williams Textbook of Endocrinology. 10th ed. Vol. 88. St. Louis, MO: WB Saunders; 2003. pp. 1589-1590

[14] Adler E, Paauw D. Medical myths involving diabetes. Primary Care. 2003;**30**:607-618

[15] Malouf R, Brust JC. Hypoglycemia: Causes, neurological manifestations, and outcome. Annals of Neurology. 1985;**17**:421-430

[16] Stahl M, Berger W. Higher incidence of severe hypoglycaemia leading to hospital admission in type 2 diabetic patients treated with long-acting versus

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short-acting sulphonylureas. Diabetic

[25] Ter Braak E, Appelman A, Erkelens D, van Haeften T. Glibenclamide decreases glucagon release during mild hypoglycaemia. Diabetologia.

[26] Banarer S, McGregor VP, Cryer PE. Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response.

[27] Boyle PJ, Schwartz NS, Shah SD, Clutter WE, Cryer PE. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in non-diabetics. The New England Journal of Medicine.

[28] Heller SR, Cryer PE. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans. Diabetes.

1998;**41**(suppl 1):A68

Diabetes. 2002;**51**:958-965

1988;**318**:1487-1492

1991;**40**:223-226

1991;**73**:995-1001

2000;**49**:65-72

2001;**18**:690-705

[29] Davis MR, Shamoon H. Counterregulatory adaptation to recurrent hypoglycemia in normal humans. The Journal of Clinical Endocrinology and Metabolism.

[30] Davis SN, Fowler S, Costa F. Hypoglycemic counterregulatory responses differ between men and women with type 1 diabetes. Diabetes.

[31] Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes. Diabetes Care. 2005;**28**:2948-2961

[32] McAuley V, Deary IJ, Freier BM. Symptoms of hypoglycemia in people with diabetes. Diabetic Medicine.

[33] Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effect of intensive insulin therapy on glycemic thresholds

[18] Kalsi A, Singh S, Taneja N, Kukal S, Mani S. Current treatments for type 2 diabetes, their side effects and possible complementary treatments. International Journal of Pharmacy and Pharmaceutical Sciences. 2015;**7**:13-18

[19] Holstein A, Egberts EH. Risk of hypoglycaemia with oral

antidiabetic agents in patients with type 2 diabetes. Experimental and Clinical Endocrinology & Diabetes.

[20] Diedrich L, Sandoval D, Davis SN. Hypoglycemia associated autonomic failure. Clinical Autonomic Research.

Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The American Journal of Medicine.

[22] Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. The Journal of Clinical

[23] Mitrakou A, Ryan C, Veneman T, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. The American Journal of

[24] Unger RH. The Berson memorial lecture. Insulin-glucagon relationships in the defense against hypoglycemia.

Investigation. 1987;**79**:777-781

Physiology. 1991;**260**:E67-E74

Diabetes. 1983;**32**:575-583

[21] The DCCT Research Group.

Medicine. 1999;**16**:586-590

2016;**8**:337-341

2003;**111**:405-414

2002;**12**:358-365

1991;**90**:450-459

[17] Moradi M, Mousavi S. Drug use evaluation of diabetes mellitus in non-hospitalized patients. International Journal of Pharmacy and Pharmaceutical Sciences.

*Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

short-acting sulphonylureas. Diabetic Medicine. 1999;**16**:586-590

[17] Moradi M, Mousavi S. Drug use evaluation of diabetes mellitus in non-hospitalized patients. International Journal of Pharmacy and Pharmaceutical Sciences. 2016;**8**:337-341

[18] Kalsi A, Singh S, Taneja N, Kukal S, Mani S. Current treatments for type 2 diabetes, their side effects and possible complementary treatments. International Journal of Pharmacy and Pharmaceutical Sciences. 2015;**7**:13-18

[19] Holstein A, Egberts EH. Risk of hypoglycaemia with oral antidiabetic agents in patients with type 2 diabetes. Experimental and Clinical Endocrinology & Diabetes. 2003;**111**:405-414

[20] Diedrich L, Sandoval D, Davis SN. Hypoglycemia associated autonomic failure. Clinical Autonomic Research. 2002;**12**:358-365

[21] The DCCT Research Group. Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The American Journal of Medicine. 1991;**90**:450-459

[22] Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. The Journal of Clinical Investigation. 1987;**79**:777-781

[23] Mitrakou A, Ryan C, Veneman T, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. The American Journal of Physiology. 1991;**260**:E67-E74

[24] Unger RH. The Berson memorial lecture. Insulin-glucagon relationships in the defense against hypoglycemia. Diabetes. 1983;**32**:575-583

[25] Ter Braak E, Appelman A, Erkelens D, van Haeften T. Glibenclamide decreases glucagon release during mild hypoglycaemia. Diabetologia. 1998;**41**(suppl 1):A68

[26] Banarer S, McGregor VP, Cryer PE. Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response. Diabetes. 2002;**51**:958-965

[27] Boyle PJ, Schwartz NS, Shah SD, Clutter WE, Cryer PE. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in non-diabetics. The New England Journal of Medicine. 1988;**318**:1487-1492

[28] Heller SR, Cryer PE. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans. Diabetes. 1991;**40**:223-226

[29] Davis MR, Shamoon H. Counterregulatory adaptation to recurrent hypoglycemia in normal humans. The Journal of Clinical Endocrinology and Metabolism. 1991;**73**:995-1001

[30] Davis SN, Fowler S, Costa F. Hypoglycemic counterregulatory responses differ between men and women with type 1 diabetes. Diabetes. 2000;**49**:65-72

[31] Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes. Diabetes Care. 2005;**28**:2948-2961

[32] McAuley V, Deary IJ, Freier BM. Symptoms of hypoglycemia in people with diabetes. Diabetic Medicine. 2001;**18**:690-705

[33] Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effect of intensive insulin therapy on glycemic thresholds

**104**

*Blood Glucose Levels*

**References**

2005;**28**:1245-1249

[1] Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on hypoglycemia. Diabetes Care.

et al. Prevalence and incidence of hypoglycaemia in 532,542 people with type 2 diabetes on oral therapies and insulin: A systematic review and metaanalysis of population based studies. PLoS One. 2015;**10**(6):e0126427. DOI:

10.1371/journal.pone.0126427

2005;**22**(6):749-755

1999;**16**:466-471

pp. 1589-1590

2003;**30**:607-618

1985;**17**:421-430

[10] Donnelly LA, Morris AD, Frier BM, et al. Frequency and predictors of hypoglycaemia in type 1 and insulintreated type 2 diabetes: A populationbased study. Diabetic Medicine.

[11] Laing SP, Swerdlow AJ, Slater SD, Botha JL, Burden AC, Waugh NR, et al. The British Diabetic Association Cohort Study. II. Cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabetic Medicine.

[12] The U.K. Prospective Diabetes Study Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes. Lancet. 1998;**352**:837-853

[13] Cryer PE. Glucose homeostasis and hypoglycemia. In: Larsen RP, Kronenberg HM, Melmed S, Polonsky KS, editors. Williams Textbook of Endocrinology. 10th ed. Vol. 88. St. Louis, MO: WB Saunders; 2003.

[14] Adler E, Paauw D. Medical myths involving diabetes. Primary Care.

[15] Malouf R, Brust JC. Hypoglycemia: Causes, neurological manifestations, and outcome. Annals of Neurology.

[16] Stahl M, Berger W. Higher incidence of severe hypoglycaemia leading to hospital admission in type 2 diabetic patients treated with long-acting versus

[2] Hinkle JL. Brunner and Siddarth's Textbook of Medical-Surgical Nursing. 13th ed. Philadelphia, PA: Wolters Kluwer Health Publication; 2014. pp. 862-865

[3] Metchich LN, Petit WA, Inzucchi SE. The most common type of hypoglycemia is insulin-induced

[4] American Diabetes Association. Hospital admission guidelines for diabetes (position statement). Diabetes

[5] Briscoe VJ, Davis SN. Hypoglycemia

Care. 2004;**27**(Suppl. 1):S103

in type 1 and type 2 diabetes: Physiology, pathophysiology, and management. Clinical Diabetes.

[6] Dajkovich G, Barkley TW Jr. Understanding insulin pump therapy. Journal of Community Health Nursing.

[7] Cryer PE. Hypoglycemia: Pathophysiology, Diagnosis, and Treatment. New York, NY, USA: Oxford

[8] The Writing Team for the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA.

[9] Edridge CL, Dunkley AJ, Bodicoat DH, Rose TC, Gray LJ, Davies MJ,

2006;**24**(3):115-121

2015;**32**(3):131-140

University Press; 1997

2002;**287**(19):2563-2569

hypoglycemia in diabetes. The American Journal of Medicine. 2002;**113**:317-323

for counterregulatory hormone release. Diabetes. 1988;**37**:901-907

[34] Korzon-Burakowska A, Hopkins D, Matyka K, Lomas J, Pernet A, Macdonald I, et al. Effects of glycemic control on protective responses against hypoglycemia in type 2 diabetes. Diabetes Care. 1998;**21**:283-290

[35] Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003;**26**:1902-1912

[36] The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long term complication in insulindependent diabetes mellitus. The New England Journal of Medicine. 1993;**329**:977-986

[37] Cryer PE. Hypoglycemia risk reduction in type 1 diabetes. Experimental and Clinical Endocrinology & Diabetes. 2001;**109**:S412-S423

[38] Cryer PE. Current concepts: Diverse causes of hypoglycemia-associated autonomic failure in diabetes. The New England Journal of Medicine. 2004;**350**:2272-2279

[39] Davis SN, Tate D. Effects of morning hypoglycemia on neuroendocrine and metabolic responses to subsequent afternoon hypoglycemia in normal man. The Journal of Clinical Endocrinology and Metabolism. 2001;**86**:2043-2050

[40] Dagogo-Jack SE, Craft S, Cryer PE. Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. The Journal of Clinical Investigation. 1993;**91**:819-828

[41] Segel SA, Paramore DS, Cryer PE. Defective glucose counterregulation in type 2 diabetes (Abstract). Diabetes. 2000;**49**:A131

[42] Spyer G, Hattersley AT, MacDonald IA, Amiel S, MacLeod KM. Hypoglycaemic counterregulation at normal blood glucose concentrations in patients with well controlled type 2 diabetes. Lancet. 2000;**356**:1970-1974

[43] Aftab-Guy D, Sandoval D, Richardson MA, Tate D, Davis SN. Effects of glycemic control on target organ responses to epinephrine in type 1 diabetes. American Journal of Physiology. Endocrinology and Metabolism. 2005;**289**:E258-E265

[44] Inkster B, Frier BM. The effects of acute hypoglycaemia on cognitive function in type 1 diabetes. The British Journal of Diabetes and Vascular Disease. 2012;**12**:221-226

[45] Deary IJ, Hepburn DA, MacLeod KM, Frier BM. Partitioning the symptoms of hypoglycaemia using multi-sample confirmatory factor analysis. Diabetologia. 1993;**36**:771-777

[46] Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes. 2005;**54**:3592-3598

[47] White NH, Skor A, Cryer PE, Levandoski L, Dier DM, Santiago JV. Identification of type 1 diabetic patients at increased risk for hypoglycemia during intensive therapy. The New England Journal of Medicine. 1993;**308**:485-491

[48] Davis SN, Shavers C, Mosqueda-Garcia R, Costa F. Effects of differing antecedent hypoglycemia on subsequent counterregulation in normal humans. Diabetes. 1997;**46**:328-1335

[49] Korytkowski MT, Mokan M, Veneman TE, Mitrakou A, Cryer PE, Gerich JE. Reduced betaadrenergic sensitivity in patients with type 1 diabetes and hypoglycemia unawareness. Diabetes Care. 1998;**21**:1939-1943

**107**

*Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

[50] Fritsche A, Stefan N, Haring H, Gerich J, Stumvoll M. Avoidance of hypoglycemia restores hypoglycemia awareness by increasing betaadrenergic sensitivity in type 1 diabetes. Annals of Internal Medicine. 2001;**134**:729-736

[51] Cranston I, Lomas J, Maran A, Macdonald I, Amiel SA. Restoration of hypoglycemia awareness in patients with long-duration insulin-dependent diabetes. Lancet. 1994;**344**:283-287

[52] Fanelli C, Pampanelli S, Epifano L, Rambotti AM, Ciofetta M, Modarelli F, et al. Relative roles of insulin and hypoglycemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycemia in male and female humans. Diabetologia.

[53] Dagogo-Jack S, Rattarasarn C, Cryer PE. Reversal of hypoglycemia unawareness, but not defective glucose counterregulation, in IDDM. Diabetes.

[54] de Galan BE, Hoekstra JBL. Glucose counterregulation in type 2 diabetes

[55] Segel SA, Paramore DS, Cryer PE. Hypoglycemia-associated autonomic failure in advanced type 2 diabetes.

mellitus. Diabetic Medicine.

Diabetes. 2002;**51**:724-732

1994;**37**:797-807

1994;**43**:1426-1434

2001;**18**:519-527

*Hypoglycemia: Essential Clinical Guidelines DOI: http://dx.doi.org/10.5772/intechopen.86994*

*Blood Glucose Levels*

Diabetes. 1988;**37**:901-907

Care. 2003;**26**:1902-1912

1993;**329**:977-986

2001;**109**:S412-S423

2004;**350**:2272-2279

[39] Davis SN, Tate D. Effects of morning hypoglycemia on neuroendocrine and metabolic responses to subsequent afternoon hypoglycemia in normal man. The Journal of Clinical Endocrinology and Metabolism. 2001;**86**:2043-2050

[37] Cryer PE. Hypoglycemia risk reduction in type 1 diabetes. Experimental and Clinical Endocrinology & Diabetes.

[38] Cryer PE. Current concepts: Diverse causes of hypoglycemia-associated autonomic failure in diabetes. The New England Journal of Medicine.

[40] Dagogo-Jack SE, Craft S, Cryer PE. Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. The Journal of Clinical Investigation. 1993;**91**:819-828

[41] Segel SA, Paramore DS, Cryer PE. Defective glucose counterregulation in type 2 diabetes (Abstract). Diabetes.

for counterregulatory hormone release.

[42] Spyer G, Hattersley AT,

[43] Aftab-Guy D, Sandoval D, Richardson MA, Tate D, Davis SN. Effects of glycemic control on target organ responses to epinephrine in type 1 diabetes. American Journal of Physiology. Endocrinology and Metabolism. 2005;**289**:E258-E265

[44] Inkster B, Frier BM. The effects of acute hypoglycaemia on cognitive function in type 1 diabetes. The British Journal of Diabetes and Vascular

[45] Deary IJ, Hepburn DA, MacLeod KM, Frier BM. Partitioning the symptoms of hypoglycaemia using multi-sample confirmatory factor analysis. Diabetologia. 1993;**36**:771-777

[46] Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes. 2005;**54**:3592-3598

[47] White NH, Skor A, Cryer PE, Levandoski L, Dier DM, Santiago JV. Identification of type 1 diabetic patients at increased risk for hypoglycemia during intensive therapy. The New England Journal of Medicine.

[48] Davis SN, Shavers C, Mosqueda-Garcia R, Costa F. Effects of differing antecedent hypoglycemia on subsequent counterregulation in normal humans.

Diabetes. 1997;**46**:328-1335

[49] Korytkowski MT, Mokan M, Veneman TE, Mitrakou A, Cryer PE, Gerich JE. Reduced betaadrenergic sensitivity in patients with type 1

Diabetes Care. 1998;**21**:1939-1943

diabetes and hypoglycemia unawareness.

1993;**308**:485-491

Disease. 2012;**12**:221-226

MacDonald IA, Amiel S, MacLeod KM. Hypoglycaemic counterregulation at normal blood glucose concentrations in patients with well controlled type 2 diabetes. Lancet. 2000;**356**:1970-1974

[34] Korzon-Burakowska A, Hopkins D, Matyka K, Lomas J, Pernet A, Macdonald I, et al. Effects of glycemic control on protective responses against hypoglycemia in type 2 diabetes. Diabetes Care. 1998;**21**:283-290

[35] Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes

[36] The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long term complication in insulindependent diabetes mellitus. The New England Journal of Medicine.

**106**

2000;**49**:A131

[50] Fritsche A, Stefan N, Haring H, Gerich J, Stumvoll M. Avoidance of hypoglycemia restores hypoglycemia awareness by increasing betaadrenergic sensitivity in type 1 diabetes. Annals of Internal Medicine. 2001;**134**:729-736

[51] Cranston I, Lomas J, Maran A, Macdonald I, Amiel SA. Restoration of hypoglycemia awareness in patients with long-duration insulin-dependent diabetes. Lancet. 1994;**344**:283-287

[52] Fanelli C, Pampanelli S, Epifano L, Rambotti AM, Ciofetta M, Modarelli F, et al. Relative roles of insulin and hypoglycemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycemia in male and female humans. Diabetologia. 1994;**37**:797-807

[53] Dagogo-Jack S, Rattarasarn C, Cryer PE. Reversal of hypoglycemia unawareness, but not defective glucose counterregulation, in IDDM. Diabetes. 1994;**43**:1426-1434

[54] de Galan BE, Hoekstra JBL. Glucose counterregulation in type 2 diabetes mellitus. Diabetic Medicine. 2001;**18**:519-527

[55] Segel SA, Paramore DS, Cryer PE. Hypoglycemia-associated autonomic failure in advanced type 2 diabetes. Diabetes. 2002;**51**:724-732

**109**

Section 4

Lifestyle and Metabolic

Syndrome

Section 4

## Lifestyle and Metabolic Syndrome

**111**

**Chapter 8**

**Abstract**

**1. Introduction**

fasting plasma glucose and blood pressure.

**2. Lifestyle during the month of Ramadan**

*Khalid S. Aljaloud*

The Effect of Ramadan Fasting on

The effect of Ramadan fasting on most of the metabolic syndrome (MetS) markers is still controversial. However, most of the available evidences showed positive effect on most of the MetS markers. In general, Ramadan fasting may help to reduce the risk of MetS. Nevertheless, most of the positive results seem to be impermanent and reading many variables (MetS markers) return to the previous reading after few weeks (~3–4 weeks). Therefore, intermittent fasting such as Ramadan fasting could be one of the cure alternatives especially in people with MetS, cardiovascular or metabolic diseases with considering their physician supervision. Again, more evidences are recommended to clarify the controversial

**Keywords:** Ramadan fasting, cholesterol, glucose, metabolic syndrome (MetS)

Lifestyle plays significant role in metabolic syndrome. Habitual diet, physical activity status, type of sleep—including quantity and quality—and unhealthy behaviors such as smoking, consuming alcohol, etc. may affect metabolic syndrome markers [1]. This chapter will demonstrate overview of lifestyle during the month of Ramadan including diet, physical activity and sleep. Moreover, the effects of Ramadan fasting on each metabolic syndrome (MetS) markers will be revealed including central obesity, plasma triglyceride, high density lipoprotein-cholesterol,

The month of Ramadan is a holy month in the Islamic calendar (lunar calendar

vary between 29 or 30 days) once a year. About 1.5 billion Muslims worldwide are—religiously—abstained from having any kind of food, oral intake such as medicine (unless in necessary cases) or smoking during the daylight starting from dawn to sunset. The Holy month of Ramadan retreats 11 days each year. As a result, Ramadan month moves in all seasons over time including summer season. Usually fasting time extends between 13 and 18 hours per day depending on season (spring, summer, autumn or winter) and the geographical location of the country. During the month of Ramadan, lifestyle of most Muslim people changes. In most Muslim country, people become less active during the daytime (before the sunset) compared with the nighttime (after the sunset), especially when most

Metabolic Syndrome (MetS)

issues related to the role of Ramadan fasting on MetS markers.

#### **Chapter 8**

### The Effect of Ramadan Fasting on Metabolic Syndrome (MetS)

*Khalid S. Aljaloud*

#### **Abstract**

The effect of Ramadan fasting on most of the metabolic syndrome (MetS) markers is still controversial. However, most of the available evidences showed positive effect on most of the MetS markers. In general, Ramadan fasting may help to reduce the risk of MetS. Nevertheless, most of the positive results seem to be impermanent and reading many variables (MetS markers) return to the previous reading after few weeks (~3–4 weeks). Therefore, intermittent fasting such as Ramadan fasting could be one of the cure alternatives especially in people with MetS, cardiovascular or metabolic diseases with considering their physician supervision. Again, more evidences are recommended to clarify the controversial issues related to the role of Ramadan fasting on MetS markers.

**Keywords:** Ramadan fasting, cholesterol, glucose, metabolic syndrome (MetS)

#### **1. Introduction**

Lifestyle plays significant role in metabolic syndrome. Habitual diet, physical activity status, type of sleep—including quantity and quality—and unhealthy behaviors such as smoking, consuming alcohol, etc. may affect metabolic syndrome markers [1]. This chapter will demonstrate overview of lifestyle during the month of Ramadan including diet, physical activity and sleep. Moreover, the effects of Ramadan fasting on each metabolic syndrome (MetS) markers will be revealed including central obesity, plasma triglyceride, high density lipoprotein-cholesterol, fasting plasma glucose and blood pressure.

#### **2. Lifestyle during the month of Ramadan**

The month of Ramadan is a holy month in the Islamic calendar (lunar calendar vary between 29 or 30 days) once a year. About 1.5 billion Muslims worldwide are—religiously—abstained from having any kind of food, oral intake such as medicine (unless in necessary cases) or smoking during the daylight starting from dawn to sunset. The Holy month of Ramadan retreats 11 days each year. As a result, Ramadan month moves in all seasons over time including summer season. Usually fasting time extends between 13 and 18 hours per day depending on season (spring, summer, autumn or winter) and the geographical location of the country. During the month of Ramadan, lifestyle of most Muslim people changes. In most Muslim country, people become less active during the daytime (before the sunset) compared with the nighttime (after the sunset), especially when most

are Muslims population [2]. The reason is mainly due to their nature of life during the night as majority of them engaging in social activities with friends and family. Moreover, most of the markets and media become more vital. However, the lifestyle of some Muslims will not change greatly during Ramadan [3]. Hence, the change in habitual diet, physical activity and sleep may change the body composition and some blood markers such as cholesterol, triglyceride, glucose which may alert MetS markers.

#### **3. Diet during the month of Ramadan**

Muslims break their fasting just after sunset by having a main meal and then they may have two or three meals during the night until the dawn time. Current study found that diet did not change significantly during the month of Ramadan while comparing before or after Ramadan [2]. However, Al-barha's study recruited apparently healthy graduate and undergraduate students. Data from different studies reported that diet during the month of Ramadan varies due to the differences between Muslim population in different countries and their habitual lifestyle. Further, seasonal and weather differences may play role in the quality and quantity of the food intake as well as the diet behavior during the month of Ramadan. In a review study, 9 out of 13 publications reported either significant reduction or no significant difference in energy intake between during and pre-or-post the month of Ramadan [4–12]. Only four studies showed a significant increase in energy intake during Ramadan [13–16]. However, all of the studies in these publications use selfreport to assess the energy intake, which is known to be less accurate comparing to objective measures [17, 18]. Amount and type of food intake as well as timing are key factors in diet and its effect on body including metabolic syndrome. During the month of Ramadan, carbohydrate and fat are consumed just after sunset. Different Muslim population reported high intake of dietary fat during Ramadan which exceeded the dietary recommendations [6, 11, 19]. In contrast, some studies found no significant change in carbohydrate and protein. However, the type of carbohydrate switched from complex sugar such as bread, cereal and vegetable to more simple sugar such as sweets [20]. These changes could elevate blood parameters such as blood lipids level. Hence, it could affect the metabolic syndrome markers negatively.

#### **4. Physical activity during the month of Ramadan**

The recent guidelines of physical activity and exercise encourage people to be physically active. The recommendation has been issued for each age group such as children and adult as well as people with special conditions such as elderly, diabetics and obese individuals [21]. The changes in people lifestyle may affect health and wellbeing [3]. During Ramadan, lifestyle may change including habitual physical activity. Although some studies found that there is no significant change in physical activity levels during Ramadan comparing to pre-Ramadan [2], numerous evidences reported significant changes in physical activity levels during the month of Ramadan. Ramadan fasting has been found to affect physical activity level in different ways. Some studies indicated that habitual physical activity may change during the month of Ramadan [22, 23]. Moreover, number of previous studies has investigated the association between Ramadan fasting and physical activity in Muslim population. These studies reported that physical activity levels were

**113**

*The Effect of Ramadan Fasting on Metabolic Syndrome (MetS)*

lowered in Muslim population during the month of Ramadan [24–28]. For instant, about one-third of Saudi families reported a decrease in physical activity levels [29]. Furthermore, recent study found that Ramadan fasting is associated with decrease in physical activity levels [30]; and may causes a decline in the physical work capacity in adolescent soccer players especially cardiorespiratory fitness capability [31]. However, these evidences showed no significant change in resting metabolic rate

The reduction in physical activity and exercise may alert the metabolic syndrome markers. Several studies have shown significant association between low physical activity level and negative changes in some of the metabolic syndrome markers. Individuals with low physical activity are more likely to have negative changes in metabolic syndrome [20, 32]. More about the impact of low physical activity in MetS will be discussed later in this chapter. These results may help to understand the influence of Ramadan fasting on body composition and the charac-

Body mass, BMI and waist circumference (WC) decreased gradually, especially in the end week of Ramadan compared with the reading before Ramadan. However, most of the recent studies concluded that the slightly decrease in some body composition parameters were not significant [4, 20, 33–36]. Although some the studies reported significant reduction in body weight at the end of Ramadan, the reduction was temporary. In a recent review study, the relationship between body composition parameters (i.e. body mass, body mass index, fat percentage and waist circumference) and Ramadan fasting is elucidated. Fernando and colleagues [29] concluded that there was a significant reduction in fat percentage at the end of Ramadan compared with pre-Ramadan in overweight or obese individuals, but not in those of normal weight. Moreover, even the change in body composition during the month of Ramadan was temporary as most of the investigated body composi-

In terms of sleep pattern, working hours during the month of Ramadan—at least in some countries—are shorter for those who fast. In such countries, workers are given more time to sleep after having the last meal just before the dawn time. For this reason, people start work later in the morning (between 09:00 and 10:00 am) instead of the early morning (i.e. 07:00–08:00 am). This change could affect sleep patterns. Hence, this may affect the times they go to bed and wake up [38]. Moreover, sleep habits may change more during the daytime. In turn, the change in sleep pattern may lead to some changes in some of the physiological parameters including metabolic syndrome as well as body composition [39, 40]. In a recent review study, they found that well-organized studies that controlled sleep/wake time, sleep duration and light exposure do not influence Ramadan fasting.

Furthermore, well-designed studies showed no effect of Ramadan fasting on circadian rhythms. However, in unstable society in which they do not control for lifestyle changes, evidences have demonstrated sudden and significant delays in bedtime and wake time [41]. Controllable and uncontrollable MetS risk factors may

lead to cardiovascular and metabolic diseases as illustrated in **Figure 1**.

*DOI: http://dx.doi.org/10.5772/intechopen.89333*

(RMR) or total energy expenditure (TEE) [30].

tion parameters return to the normal weight [37].

**6. Sleep during the month of Ramadan**

teristics of metabolic syndrome.

**5. Body composition**

#### *The Effect of Ramadan Fasting on Metabolic Syndrome (MetS) DOI: http://dx.doi.org/10.5772/intechopen.89333*

lowered in Muslim population during the month of Ramadan [24–28]. For instant, about one-third of Saudi families reported a decrease in physical activity levels [29]. Furthermore, recent study found that Ramadan fasting is associated with decrease in physical activity levels [30]; and may causes a decline in the physical work capacity in adolescent soccer players especially cardiorespiratory fitness capability [31]. However, these evidences showed no significant change in resting metabolic rate (RMR) or total energy expenditure (TEE) [30].

The reduction in physical activity and exercise may alert the metabolic syndrome markers. Several studies have shown significant association between low physical activity level and negative changes in some of the metabolic syndrome markers. Individuals with low physical activity are more likely to have negative changes in metabolic syndrome [20, 32]. More about the impact of low physical activity in MetS will be discussed later in this chapter. These results may help to understand the influence of Ramadan fasting on body composition and the characteristics of metabolic syndrome.

#### **5. Body composition**

*Blood Glucose Levels*

alert MetS markers.

**3. Diet during the month of Ramadan**

**4. Physical activity during the month of Ramadan**

The recent guidelines of physical activity and exercise encourage people to be physically active. The recommendation has been issued for each age group such as children and adult as well as people with special conditions such as elderly, diabetics and obese individuals [21]. The changes in people lifestyle may affect health and wellbeing [3]. During Ramadan, lifestyle may change including habitual physical activity. Although some studies found that there is no significant change in physical activity levels during Ramadan comparing to pre-Ramadan [2], numerous evidences reported significant changes in physical activity levels during the month of Ramadan. Ramadan fasting has been found to affect physical activity level in different ways. Some studies indicated that habitual physical activity may change during the month of Ramadan [22, 23]. Moreover, number of previous studies has investigated the association between Ramadan fasting and physical activity in Muslim population. These studies reported that physical activity levels were

are Muslims population [2]. The reason is mainly due to their nature of life during the night as majority of them engaging in social activities with friends and family. Moreover, most of the markets and media become more vital. However, the lifestyle of some Muslims will not change greatly during Ramadan [3]. Hence, the change in habitual diet, physical activity and sleep may change the body composition and some blood markers such as cholesterol, triglyceride, glucose which may

Muslims break their fasting just after sunset by having a main meal and then they may have two or three meals during the night until the dawn time. Current study found that diet did not change significantly during the month of Ramadan while comparing before or after Ramadan [2]. However, Al-barha's study recruited apparently healthy graduate and undergraduate students. Data from different studies reported that diet during the month of Ramadan varies due to the differences between Muslim population in different countries and their habitual lifestyle. Further, seasonal and weather differences may play role in the quality and quantity of the food intake as well as the diet behavior during the month of Ramadan. In a review study, 9 out of 13 publications reported either significant reduction or no significant difference in energy intake between during and pre-or-post the month of Ramadan [4–12]. Only four studies showed a significant increase in energy intake during Ramadan [13–16]. However, all of the studies in these publications use selfreport to assess the energy intake, which is known to be less accurate comparing to objective measures [17, 18]. Amount and type of food intake as well as timing are key factors in diet and its effect on body including metabolic syndrome. During the month of Ramadan, carbohydrate and fat are consumed just after sunset. Different Muslim population reported high intake of dietary fat during Ramadan which exceeded the dietary recommendations [6, 11, 19]. In contrast, some studies found no significant change in carbohydrate and protein. However, the type of carbohydrate switched from complex sugar such as bread, cereal and vegetable to more simple sugar such as sweets [20]. These changes could elevate blood parameters such as blood lipids level. Hence, it could affect the metabolic syndrome markers

**112**

negatively.

Body mass, BMI and waist circumference (WC) decreased gradually, especially in the end week of Ramadan compared with the reading before Ramadan. However, most of the recent studies concluded that the slightly decrease in some body composition parameters were not significant [4, 20, 33–36]. Although some the studies reported significant reduction in body weight at the end of Ramadan, the reduction was temporary. In a recent review study, the relationship between body composition parameters (i.e. body mass, body mass index, fat percentage and waist circumference) and Ramadan fasting is elucidated. Fernando and colleagues [29] concluded that there was a significant reduction in fat percentage at the end of Ramadan compared with pre-Ramadan in overweight or obese individuals, but not in those of normal weight. Moreover, even the change in body composition during the month of Ramadan was temporary as most of the investigated body composition parameters return to the normal weight [37].

#### **6. Sleep during the month of Ramadan**

In terms of sleep pattern, working hours during the month of Ramadan—at least in some countries—are shorter for those who fast. In such countries, workers are given more time to sleep after having the last meal just before the dawn time. For this reason, people start work later in the morning (between 09:00 and 10:00 am) instead of the early morning (i.e. 07:00–08:00 am). This change could affect sleep patterns. Hence, this may affect the times they go to bed and wake up [38]. Moreover, sleep habits may change more during the daytime. In turn, the change in sleep pattern may lead to some changes in some of the physiological parameters including metabolic syndrome as well as body composition [39, 40]. In a recent review study, they found that well-organized studies that controlled sleep/wake time, sleep duration and light exposure do not influence Ramadan fasting.

Furthermore, well-designed studies showed no effect of Ramadan fasting on circadian rhythms. However, in unstable society in which they do not control for lifestyle changes, evidences have demonstrated sudden and significant delays in bedtime and wake time [41]. Controllable and uncontrollable MetS risk factors may lead to cardiovascular and metabolic diseases as illustrated in **Figure 1**.

**Figure 1.**

*Risk factors of MetS including controllable and uncontrollable factors that might lead to cardiovascular and metabolic diseases.*

#### **7. Metabolic syndrome**

Historically, the first time metabolic syndrome (MetS) was defined by Kylin , a Swedish physician, in 1923 [42]. He described MetS as a cluster of cardiovascular risk factors comprising of hypertension, hyperglycemia and gout. Since then, the metabolic syndrome has gradually progressed over time with definition modification. However, the core turbulences, hypertension, consisting of glucose intolerance, obesity and dyslipidemia remain the cornerstone of all diagnostic criteria. In turn, these features may develop and increase the risk of cardiovascular morbidity and mortality [43, 44]. The term "Syndrome X" was commonly used in 1980s to describe the proposed interrelationships between resistance to insulin-stimulated glucose uptake, hypertension, type 2 diabetic and cardiovascular diseases. Now, the term MetS has the International Classification of Disease (ICD-9) code 277.7. In 1990s, visceral adiposity becomes important when obesity is considered as a main factor of the insulin resistance syndrome [45]. World Health Organization (WHO) launched the first formal definition of the MetS in 1998 [46]. In 2001, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP:ATPIII) issued a set of criteria based on common clinical investigations: WC, blood lipids, blood pressure and fasting glucose [47–49].

#### **8. Diagnostic criteria for MetS**

Over the years, there have been several societies attempted to issue the diagnostic criteria for metabolic syndrome [50]. In 1998, WHO is the first organization that launched the worldwide definition of MetS, which was modified by other organizations such as the European Group for the Study of Insulin Resistance (EGSIR). In 2003, the American Association of Clinical Endocrinologists (AACE) proposed

**115**

*The Effect of Ramadan Fasting on Metabolic Syndrome (MetS)*

**WHO, 1998 EGIR, 1999 NCEP:ATPIII,**

Top 25% of the fasting insulin values among nondiabetic individuals and two of the following:

WC: 94 cm for men, 80 cm for women

Triglycerides 2.0 mmol/liter and HDLC 1.0 mg/dl

BP 140/90 mm Hg or antihypertensive medication

Fasting glucose 6.1 mmol/liter

**2001**

Three or more of the following:

WC: 40 inches for men, 35 inches for women

Triglycerides 150 mg/dl

HDL-C: 40 mg/ dl for men, 50 mg/dl for women

BP 130/85 mm

FPG 110 mg/dla

Hg

*WHR, Waist-to-hip ratio; BP, blood pressure; FPG, fasting plasma glucose. In 2003, the ADA changed the criteria*

**AACE, 2003 IDF, 2006**

Central obesity as defined by ethnic/ racial, specific WC, and two of the following:

Triglycerides 150 mg/dl

HDL-C: 40 mg/dl for men, 50 mg/dl for women

BP 130/85 mm Hg

FPG 100 mg/dl

IGT and two or more of the following:

Triglycerides 150 mg/dl

HDL-C: 40 mg/ dl for men, 50 mg/dl for women

BP 130/85 mm

Hg

their definition. However, the definition of the cut-off for obesity was not agreed yet. **Table 1** illustrates the development stages of the MetS diagnostic criteria [52].

In this section, the role of Ramadan fasting positively affect the MetS markers including central obesity, waist circumference (WC), fasting plasma glucose (FPG) level, triglycerides (TG) level, high density lipoprotein (HDL) and blood pressure (BP), will be deliberated with recent evidences. In terms of metabolism and hormonal serum levels, Ramadan fasting may affect the metabolism of lipids, carbohydrates and proteins, as well as related hormones levels. Although there are beneficial changes in HDL and LDL levels, evidences showed that Ramadan fasting could lead to elevate the urea and uric acid which may be attributed to dehydration during the Holy month of Ramadan [23]. In the next sessions, the effect of Ramadan fasting on

Intermittent fasting during the month of Ramadan may enhance the cure from some of the MetS markers including body weight reduction. Although some evidence showed increase in some of the body composition parameters [53], Ramadan

**9. The effect of Ramadan fasting on metabolic syndrome**

metabolic syndrome markers will be elucidated with more details.

**10. The effect of Ramadan fasting on central obesity**

*DOI: http://dx.doi.org/10.5772/intechopen.89333*

High insulin levels, IFG or IGT, and two of the following:

Abdominal obesity: WHR 0.9, BMI 30 kg/m2

37 inches

BP 140/90 mm

*for IFG tolerance from 110 to 100 mg/dl.*

*Criteria for the definitions of the metabolic syndrome.*

Lipid panel with triglycerides 150 mg/dl, HDL-C 35 mg/dl

Hg

*Source: Ref. [51].*

**Table 1.**

, WC

*The Effect of Ramadan Fasting on Metabolic Syndrome (MetS) DOI: http://dx.doi.org/10.5772/intechopen.89333*

*WHR, Waist-to-hip ratio; BP, blood pressure; FPG, fasting plasma glucose. In 2003, the ADA changed the criteria for IFG tolerance from 110 to 100 mg/dl. Source: Ref. [51].*

#### **Table 1.**

*Blood Glucose Levels*

**7. Metabolic syndrome**

**Figure 1.**

*metabolic diseases.*

pressure and fasting glucose [47–49].

**8. Diagnostic criteria for MetS**

Historically, the first time metabolic syndrome (MetS) was defined by Kylin , a Swedish physician, in 1923 [42]. He described MetS as a cluster of cardiovascular risk factors comprising of hypertension, hyperglycemia and gout. Since then, the metabolic syndrome has gradually progressed over time with definition modification. However, the core turbulences, hypertension, consisting of glucose intolerance, obesity and dyslipidemia remain the cornerstone of all diagnostic criteria. In turn, these features may develop and increase the risk of cardiovascular morbidity and mortality [43, 44]. The term "Syndrome X" was commonly used in 1980s to describe the proposed interrelationships between resistance to insulin-stimulated glucose uptake, hypertension, type 2 diabetic and cardiovascular diseases. Now, the term MetS has the International Classification of Disease (ICD-9) code 277.7. In 1990s, visceral adiposity becomes important when obesity is considered as a main factor of the insulin resistance syndrome [45]. World Health Organization (WHO) launched the first formal definition of the MetS in 1998 [46]. In 2001, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP:ATPIII) issued a set of criteria based on common clinical investigations: WC, blood lipids, blood

*Risk factors of MetS including controllable and uncontrollable factors that might lead to cardiovascular and*

Over the years, there have been several societies attempted to issue the diagnostic criteria for metabolic syndrome [50]. In 1998, WHO is the first organization that launched the worldwide definition of MetS, which was modified by other organizations such as the European Group for the Study of Insulin Resistance (EGSIR). In 2003, the American Association of Clinical Endocrinologists (AACE) proposed

**114**

*Criteria for the definitions of the metabolic syndrome.*

their definition. However, the definition of the cut-off for obesity was not agreed yet. **Table 1** illustrates the development stages of the MetS diagnostic criteria [52].

#### **9. The effect of Ramadan fasting on metabolic syndrome**

In this section, the role of Ramadan fasting positively affect the MetS markers including central obesity, waist circumference (WC), fasting plasma glucose (FPG) level, triglycerides (TG) level, high density lipoprotein (HDL) and blood pressure (BP), will be deliberated with recent evidences. In terms of metabolism and hormonal serum levels, Ramadan fasting may affect the metabolism of lipids, carbohydrates and proteins, as well as related hormones levels. Although there are beneficial changes in HDL and LDL levels, evidences showed that Ramadan fasting could lead to elevate the urea and uric acid which may be attributed to dehydration during the Holy month of Ramadan [23]. In the next sessions, the effect of Ramadan fasting on metabolic syndrome markers will be elucidated with more details.

#### **10. The effect of Ramadan fasting on central obesity**

Intermittent fasting during the month of Ramadan may enhance the cure from some of the MetS markers including body weight reduction. Although some evidence showed increase in some of the body composition parameters [53], Ramadan fasting has been found to reduce waist circumference even in apparently healthy young adults [54]. In some studies, the reported weight reduction occurred without significant changes in energy and macronutrient intake and physical activity level [4]. The reduction was interpreted as loss of body water and body fat percentage.

There is a strong recent evidence that support the effect of Ramadan fasting on reducing body fat percentage and even fat-free mass especially with obese/ overweight people. In a recent review and meta-analysis study, data obtain from 70 publications found a significant reduction in fat percentage between pre-Ramadan and post-Ramadan in overweight and obesity individuals. (−1.46 [95% confidence interval: −2.57 to −0.35]%, *P* = 0.010). However, there was no changes reported in those of normal weight (−0.41 [−1.45 to 0.63]%, *P* = 0.436). The reduction also reported in fat-free mass between pre-Ramadan and post-Ramadan. Nevertheless, the changes in body composition measurements seem to be temporary. Evidences showed that body weight body composition parameters were returned toward the pre-Ramadan measurements just after 2–5 weeks from the month of Ramadan [37]. Furthermore, it has been suggested that this decrease in body weight could be attributed to a decrease in fluid intake [34, 55–57]. Sequentially, dehydration during the month of Ramadan may cause increase in urea and uric acid which is attributed to the reduction of the glomerular filtration rate [58]. The physiological aspects that may explain the association between Ramadan fasting and body composition parameters has been investigated. For instance, plasma leptin and insulin have been found to play a key role in body weight regulation homeostasis. Leptin level send signals to the brain about the amount of energy stores which in turn, stimulates the hypothalamic centers to regulate the energy intake and energy expenditure [59]. Although an evidence showed that there is a positive association between plasma leptin and insulin levels and body fat, the elevation in plasma leptin and insulin during the month of Ramadan is probably due to the energy intake and diet behavior [14]. In sum, Ramadan fasting may help to reduce body composition including central obesity such as waist circumference. However, the reduction may not be healthy as the weight loss attribute to loss of body water. One possible reason for this greater weight loss is that people with greater BMI are due to greater glycogen stores than people of normal weight, and hence would be expected to lose more fluid in response to fasting [60], and in some cases loss of lean tissue [34] carry more body. One of the most challenges is that body composition parameters are affected by different factors including calorie intake, physical activity level, age and gender. More investigations are needed to clarify the role of Ramadan fasting on central obesity.

#### **11. The effect of Ramadan fasting on triglycerides**

In general, the role of Ramadan fasting on triglyceride concentration tends to be more positive in many case studies. This may enhance health promotion for people who have no clinical conditions that may prevent them from fasting during the month of Ramadan. In a systematic review study, data revealed that 6 out of 15 studies reported reduction in triglyceride level at the end of Ramadan month. Nevertheless, other 9 studies showed no significant changes in triglycerides concentration [61]. Moreover, Ramadan fasting also has been found to be healthy by helping diabetic patients to reduce triglycerides level especially those who can fast the whole month of Ramadan. Recent evidence indicated clear effect of Ramadan fasting on triglycerides level in diabetic patients. Bener et al. [62] tried to investigate the effect of Ramadan fasting on some blood parameters including blood lipids (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, etc.)

**117**

*The Effect of Ramadan Fasting on Metabolic Syndrome (MetS)*

fasting on HDL in different cases and population.

**13. The effect of Ramadan fasting on fasting plasma glucose**

Unhealthy elevation in fasting plasma glucose (FPG) has been found to be one of the MetS markers. The holy month of Ramadan has different lifestyle in most Muslim populations including diet and physical activity pattern which may influence the FPG [20]. Nevertheless, Ramadan fasting may help to reduce FPG even in diabetic individuals in both male and female [62]. However, the beneficial reduction in FPG during or end of Ramadan month seems to be temporary [67, 68]. Hence, any change in blood glucose during Ramadan is minor and improbable to affect healthy people especially if there is no major changes in diet or physical inactivity levels [69]. Recently, the effect of Ramadan fasting on FPG has been investigated in health young adults. The study found that Ramadan fasting elevated FPG significantly during the end of Ramadan comparing the levels before Ramadan. Nevertheless, the elevated value of FPG was within the normal level in both occasions [2]. On the other hand, Ramadan fasting may reduce FPG of apparently healthy young adults (19–23 years old) during the end of Ramadan month [70]. Furthermore, intermittent fasting such as Ramadan fasting improve FPG in obese/ overweight adults. One of the main outcomes of Ramadan fasting is losing weight and FPG as well as related metabolic parameters such as insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [71]. Insulin promotes the storage of glucose in liver and muscles as glycogen. However, during Ramadan fasting, circulating glucose levels decrease which lead to decrease the secretion of insulin and increase the level of glucagon hormone and catecholamines to enhance the

in patients with type 2 diabetes mellitus (T2DM) in Turkey. They concluded that fasting during the month of Ramadan may help to reduce triglycerides level even in people with type 2 diabetes [62]. Interestingly, rare of the available evidences showed negative effect of Ramadan fasting on triglycerides concentration. Thus, Ramadan fasting could enhance health promotion and reduce the risk of cardiovascular and metabolic diseases via the positive control of different lipid profile including triglyc-

**12. The effect of Ramadan fasting on high-density-lipoprotein (HDL)**

Health organizations recommend lifestyle that help to elevate high-densitylipoprotein (HDL) [46]. In general, a desired improvement has been found in plasma HDL at the end of Ramadan month and even after few weeks afterward [63]. Although there are some few studies that found no favorable changes in HDL as a result of Ramadan fasting [2, 64], recent strong evidences approved the health effect of Ramadan fasting on plasma HDL [61, 62]. However, the contradictory may due to the limitations of some studies. Kul et al. [65] did a meta-analysis to investigate the impact of Ramadan fasting on some health-related parameters in healthy population including blood lipids. They analyzed the data obtained from 13 studies to explore the effect of Ramadan fasting on HDL concentration (661 healthy individuals: 462 men and 199 women). They concluded that Ramadan fasting may help to reduce HDL concentration in women but not in men [65]. Moreover, the negative effect of Ramadan fasting has been observed in special population such as older adults with hypertension disease [66]. In sum, most of the recent and soled evidences have proved the beneficial effect of Ramadan fasting on plasma HDL level. Furthermore, more studies are encouraged to clarify the role of Ramadan

*DOI: http://dx.doi.org/10.5772/intechopen.89333*

erides level.

*Blood Glucose Levels*

fasting has been found to reduce waist circumference even in apparently healthy young adults [54]. In some studies, the reported weight reduction occurred without significant changes in energy and macronutrient intake and physical activity level [4]. The reduction was interpreted as loss of body water and body fat percentage. There is a strong recent evidence that support the effect of Ramadan fasting on reducing body fat percentage and even fat-free mass especially with obese/ overweight people. In a recent review and meta-analysis study, data obtain from 70 publications found a significant reduction in fat percentage between pre-Ramadan and post-Ramadan in overweight and obesity individuals. (−1.46 [95% confidence interval: −2.57 to −0.35]%, *P* = 0.010). However, there was no changes reported in those of normal weight (−0.41 [−1.45 to 0.63]%, *P* = 0.436). The reduction also reported in fat-free mass between pre-Ramadan and post-Ramadan. Nevertheless, the changes in body composition measurements seem to be temporary. Evidences showed that body weight body composition parameters were returned toward the pre-Ramadan measurements just after 2–5 weeks from the month of Ramadan [37]. Furthermore, it has been suggested that this decrease in body weight could be attributed to a decrease in fluid intake [34, 55–57]. Sequentially, dehydration during the month of Ramadan may cause increase in urea and uric acid which is attributed to the reduction of the glomerular filtration rate [58]. The physiological aspects that may explain the association between Ramadan fasting and body composition parameters has been investigated. For instance, plasma leptin and insulin have been found to play a key role in body weight regulation homeostasis. Leptin level send signals to the brain about the amount of energy stores which in turn, stimulates the hypothalamic centers to regulate the energy intake and energy expenditure [59]. Although an evidence showed that there is a positive association between plasma leptin and insulin levels and body fat, the elevation in plasma leptin and insulin during the month of Ramadan is probably due to the energy intake and diet behavior [14]. In sum, Ramadan fasting may help to reduce body composition including central obesity such as waist circumference. However, the reduction may not be healthy as the weight loss attribute to loss of body water. One possible reason for this greater weight loss is that people with greater BMI are due to greater glycogen stores than people of normal weight, and hence would be expected to lose more fluid in response to fasting [60], and in some cases loss of lean tissue [34] carry more body. One of the most challenges is that body composition parameters are affected by different factors including calorie intake, physical activity level, age and gender. More investigations are needed to clarify the role of Ramadan fasting on

**116**

central obesity.

**11. The effect of Ramadan fasting on triglycerides**

In general, the role of Ramadan fasting on triglyceride concentration tends to be more positive in many case studies. This may enhance health promotion for people who have no clinical conditions that may prevent them from fasting during the month of Ramadan. In a systematic review study, data revealed that 6 out of 15 studies reported reduction in triglyceride level at the end of Ramadan month. Nevertheless, other 9 studies showed no significant changes in triglycerides concentration [61]. Moreover, Ramadan fasting also has been found to be healthy by helping diabetic patients to reduce triglycerides level especially those who can fast the whole month of Ramadan. Recent evidence indicated clear effect of Ramadan fasting on triglycerides level in diabetic patients. Bener et al. [62] tried to investigate the effect of Ramadan fasting on some blood parameters including blood lipids (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, etc.)

in patients with type 2 diabetes mellitus (T2DM) in Turkey. They concluded that fasting during the month of Ramadan may help to reduce triglycerides level even in people with type 2 diabetes [62]. Interestingly, rare of the available evidences showed negative effect of Ramadan fasting on triglycerides concentration. Thus, Ramadan fasting could enhance health promotion and reduce the risk of cardiovascular and metabolic diseases via the positive control of different lipid profile including triglycerides level.

### **12. The effect of Ramadan fasting on high-density-lipoprotein (HDL)**

Health organizations recommend lifestyle that help to elevate high-densitylipoprotein (HDL) [46]. In general, a desired improvement has been found in plasma HDL at the end of Ramadan month and even after few weeks afterward [63]. Although there are some few studies that found no favorable changes in HDL as a result of Ramadan fasting [2, 64], recent strong evidences approved the health effect of Ramadan fasting on plasma HDL [61, 62]. However, the contradictory may due to the limitations of some studies. Kul et al. [65] did a meta-analysis to investigate the impact of Ramadan fasting on some health-related parameters in healthy population including blood lipids. They analyzed the data obtained from 13 studies to explore the effect of Ramadan fasting on HDL concentration (661 healthy individuals: 462 men and 199 women). They concluded that Ramadan fasting may help to reduce HDL concentration in women but not in men [65]. Moreover, the negative effect of Ramadan fasting has been observed in special population such as older adults with hypertension disease [66]. In sum, most of the recent and soled evidences have proved the beneficial effect of Ramadan fasting on plasma HDL level. Furthermore, more studies are encouraged to clarify the role of Ramadan fasting on HDL in different cases and population.

#### **13. The effect of Ramadan fasting on fasting plasma glucose**

Unhealthy elevation in fasting plasma glucose (FPG) has been found to be one of the MetS markers. The holy month of Ramadan has different lifestyle in most Muslim populations including diet and physical activity pattern which may influence the FPG [20]. Nevertheless, Ramadan fasting may help to reduce FPG even in diabetic individuals in both male and female [62]. However, the beneficial reduction in FPG during or end of Ramadan month seems to be temporary [67, 68]. Hence, any change in blood glucose during Ramadan is minor and improbable to affect healthy people especially if there is no major changes in diet or physical inactivity levels [69]. Recently, the effect of Ramadan fasting on FPG has been investigated in health young adults. The study found that Ramadan fasting elevated FPG significantly during the end of Ramadan comparing the levels before Ramadan. Nevertheless, the elevated value of FPG was within the normal level in both occasions [2]. On the other hand, Ramadan fasting may reduce FPG of apparently healthy young adults (19–23 years old) during the end of Ramadan month [70]. Furthermore, intermittent fasting such as Ramadan fasting improve FPG in obese/ overweight adults. One of the main outcomes of Ramadan fasting is losing weight and FPG as well as related metabolic parameters such as insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [71]. Insulin promotes the storage of glucose in liver and muscles as glycogen. However, during Ramadan fasting, circulating glucose levels decrease which lead to decrease the secretion of insulin and increase the level of glucagon hormone and catecholamines to enhance the

breakdown of glycogen to provide body with energy [64]. Hence, one can conclude that Ramadan fasting may improve FPG especially after a couple of weeks. One of the explanation is that alterations in lifestyle during the month of Ramadan may lead to changes in the rhythmic pattern of different related hormonal including thyroid hormones, melatonin, pituitary hormones (prolactin, luteinizing hormone, follicular stimulating hormone, growth hormone and thyroid-stimulating hormone) and steroid hormones (cortisol and testosterone) [72]. These hormones are related to energy metabolism and regulation of energy intake [14, 72]. These hormonal changes could explain decreases in blood glucose levels.

However, FPG may return to previous level afterward. Thus, intermittent fasting is recommended to reduce the risk of having one or more of the MetS markers such as FPG.

#### **14. The effect of Ramadan fasting on blood pressure**

Blood pressure (BP) is one of the complicated factors liked to different cardiovascular diseases.

High blood pressure is one of the MetS that may develop cardiovascular and metabolic diseases [52]. Although some studies reported slight, but significant, elevation in blood pressure in apparently healthy young adults during the month of Ramadan [2], different evidences concluded that Ramadan fasting may lead to reduce blood pressure in apparently healthy people as well as patients with hypertension, stable cardiovascular, metabolic syndrome and dyslipidemia [73]. In a systematical review study, Mazidi and colleagues found that data from different studies reported reduction in blood pressure especially systolic blood pressure (SBP) but no significant changes has been observed in diastolic blood pressure (DBP) [61]. Data from several investigations revealed that Ramadan fasting could reduce blood pressure unless there are some conditions that may influence BP such as diet and stress [74–76]. However, Topacoglu et al. [77] observed an increase in the number of admissions for hypertension during the holy month of Ramadan [77]. The reduction in blood pressure parameters during the month of Ramadan can be explained as a result of dehydration due to the long fasting time. On the other hand, it can be attributed to lower daytime activity which may cause a noticeable reduction in sympathetic tone [78]. In some countries the holy month of Ramadan comes in hot season (June–August) which makes people fast longer (~15 hours). Therefore, hypertensive patient should be advised to avoid diuretics during fasting and they can fast with paying attention to type and amount of food that may raise BP [79]. Remarkably, very few available evidences observed unhealthy effects of Ramadan fasting on hypertensive patients. In fact, the role of Ramadan fasting on controlling blood pressure is controversial. Partly, it is due to the lack of the available evidences that investigated the comprehensive effect of Ramadan fasting on blood pressure in people with different health conditions. Thus, more investigations are recommended to clarify the role of Ramadan fasting on blood pressure parameters.

#### **15. Conclusion**

The effect of Ramadan fasting on most of the MetS markers is still controversial. However, most of the available evidences showed positive effect on most of the MetS markers. In general, Ramadan fasting may help to reduce the risk of MetS. Nevertheless, most of the positive results seem to be impermanent and

**119**

**Author details**

Khalid S. Aljaloud

King Saud University, Riyadh, Saudi Arabia

provided the original work is properly cited.

\*Address all correspondence to<EMAIL_ADDRESS>
*The Effect of Ramadan Fasting on Metabolic Syndrome (MetS)*

reading of many of the variables (MetS markers) return to the previous reading after few weeks (~3–4 weeks). Therefore, intermittent fasting such as Ramadan fasting could be one of the cure alternatives especially in people with MetS, cardiovascular or metabolic diseases with considering their physician supervision. In general, Ramadan fasting is associated with positive improvements in different related hormones such as insulin, leptin, adiponectin, adipocytokine, Gamma glutamyl transferase and others that may be directly or indirectly affect MetS markers. Hence, Ramadan as an intermittent fasting might be more beneficial for most population and cardiovascular and metabolic patients should consult their physicians when they decide to fast during the month of Ramadan. Again, more evidences are recommended to clarify the controversial issues related to the role of

Department of Exercise Physiology, College of Sport Sciences and Physical Activity,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*DOI: http://dx.doi.org/10.5772/intechopen.89333*

Ramadan fasting on MetS markers.

#### *The Effect of Ramadan Fasting on Metabolic Syndrome (MetS) DOI: http://dx.doi.org/10.5772/intechopen.89333*

*Blood Glucose Levels*

such as FPG.

vascular diseases.

breakdown of glycogen to provide body with energy [64]. Hence, one can conclude that Ramadan fasting may improve FPG especially after a couple of weeks. One of the explanation is that alterations in lifestyle during the month of Ramadan may lead to changes in the rhythmic pattern of different related hormonal including thyroid hormones, melatonin, pituitary hormones (prolactin, luteinizing hormone, follicular stimulating hormone, growth hormone and thyroid-stimulating hormone) and steroid hormones (cortisol and testosterone) [72]. These hormones are related to energy metabolism and regulation of energy intake [14, 72]. These

However, FPG may return to previous level afterward. Thus, intermittent fasting is recommended to reduce the risk of having one or more of the MetS markers

Blood pressure (BP) is one of the complicated factors liked to different cardio-

High blood pressure is one of the MetS that may develop cardiovascular and metabolic diseases [52]. Although some studies reported slight, but significant, elevation in blood pressure in apparently healthy young adults during the month of Ramadan [2], different evidences concluded that Ramadan fasting may lead to reduce blood pressure in apparently healthy people as well as patients with hypertension, stable cardiovascular, metabolic syndrome and dyslipidemia [73]. In a systematical review study, Mazidi and colleagues found that data from different studies reported reduction in blood pressure especially systolic blood pressure (SBP) but no significant changes has been observed in diastolic blood pressure (DBP) [61]. Data from several investigations revealed that Ramadan fasting could reduce blood pressure unless there are some conditions that may influence BP such as diet and stress [74–76]. However, Topacoglu et al. [77] observed an increase in the number of admissions for hypertension during the holy month of Ramadan [77]. The reduction in blood pressure parameters during the month of Ramadan can be explained as a result of dehydration due to the long fasting time. On the other hand, it can be attributed to lower daytime activity which may cause a noticeable reduction in sympathetic tone [78]. In some countries the holy month of Ramadan comes in hot season (June–August) which makes people fast longer (~15 hours). Therefore, hypertensive patient should be advised to avoid diuretics during fasting and they can fast with paying attention to type and amount of food that may raise BP [79]. Remarkably, very few available evidences observed unhealthy effects of Ramadan fasting on hypertensive patients. In fact, the role of Ramadan fasting on controlling blood pressure is controversial. Partly, it is due to the lack of the available evidences that investigated the comprehensive effect of Ramadan fasting on blood pressure in people with different health conditions. Thus, more investigations are recommended to clarify the role of Ramadan fasting on blood pressure

The effect of Ramadan fasting on most of the MetS markers is still controversial. However, most of the available evidences showed positive effect on most of the MetS markers. In general, Ramadan fasting may help to reduce the risk of MetS. Nevertheless, most of the positive results seem to be impermanent and

hormonal changes could explain decreases in blood glucose levels.

**14. The effect of Ramadan fasting on blood pressure**

**118**

parameters.

**15. Conclusion**

reading of many of the variables (MetS markers) return to the previous reading after few weeks (~3–4 weeks). Therefore, intermittent fasting such as Ramadan fasting could be one of the cure alternatives especially in people with MetS, cardiovascular or metabolic diseases with considering their physician supervision. In general, Ramadan fasting is associated with positive improvements in different related hormones such as insulin, leptin, adiponectin, adipocytokine, Gamma glutamyl transferase and others that may be directly or indirectly affect MetS markers. Hence, Ramadan as an intermittent fasting might be more beneficial for most population and cardiovascular and metabolic patients should consult their physicians when they decide to fast during the month of Ramadan. Again, more evidences are recommended to clarify the controversial issues related to the role of Ramadan fasting on MetS markers.

### **Author details**

Khalid S. Aljaloud

Department of Exercise Physiology, College of Sport Sciences and Physical Activity, King Saud University, Riyadh, Saudi Arabia

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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**References**

[1] Ranasinghe P, Mathangasinghe Y, Jayawardena R, Hills A, Misra A. Prevalence and trends of metabolic syndrome among adults in the asiapacific region: A systematic review. BMC Public Health. 2017;**17**(1):101

fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. Nutrition Research. 2012;**32**(12):947-955. DOI: 10.1016/j.nutres.2012.06.021

[9] Haouari-Oukerro F, Ben-Attia M, Kaâbachi N, Haouari M. Ramadan fasting influences on food intake consumption, sleep schedule, body weight and some plasma parameters in healthy fasting volunteers. African Journal of Biotechnology.

[10] Haouari M, Haouari-Oukerro F, Sfaxi A, Rayana MB, Kaabachi N, Mbazaa A. How Ramadan fasting affects caloric consumption, body weight, and circadian evolution of cortisol serum levels in young, healthy male volunteers. Hormone and Metabolic Research.

[11] Ibrahim WH, Habib HM, Jarrar AH, Al Baz SA. Effect of Ramadan fasting on markers of oxidative stress and serum biochemical markers of cellular damage in healthy subjects. Annals of Nutrition and Metabolism. 2008;**53**(3-4):175-181.

Trepanowski JF, Stannard SR, Ghlissi Z, Ghozzi H, et al. Effects of ramadan