

Diabetes is perhaps the most common problem encountered in the outpatient departments, medical clinics and in the wards. It comes in all varieties of severity and complications and involves many systems. When a patient with type 2 diabetes comes to a doctor they have probably already had the disease for many years without being aware of it. Younger more educated people and people with access to good health care are often aware that they have borderline diabetes and are usually taking measures to keep their blood sugar under the radar but does this really prevent or completely stop the development of systemic damage? What else should we be looking for? Can this information lead to better medical management?

Why do we use HbA1c to evaluate the state of blood sugar control? Historical information, such as polyuria, nocturia, or home urine testing for glucose, and laboratory information, such as fasting or random blood glucose levels, are weak predictors of the actual mean concentration of blood glucose. (N Engl J Med 1984; 310:341–6.) So we have known since 1984 that we needed something else to measure the control of blood sugar. The glycosylated hemoglobin assay was developed as a powerful research tool that is unique as a retrospective index of glucose control over time in patients with diabetes. A properly performed assay has been demonstrated to correlate with mean plasma glucose levels, 24-hour urinary glucose concentrations, and other indexes of metabolic control, determined over the preceding two to three months. The serial measurement of HbA1c is a valuable tool in the clinical armamentarium as its variability or average stability may have predictive value for further progression of the disease.

A study published in Diabetes Care on November 14th 2019 looks at the predictability of of serial measurement of HbA1c measurements during visits to the doctor for the likelihood of development of various complications. What constitutes variability?

Based on HbA1c variability score (HVS) (calculated as the percentage of the number of changes in HbA1c >0.5% [5.5 mmol/mol] among all HbA1c measurements within an individual) patients were categorised into:

  • ≥0 to ≤20% group (reference),
  • >20 to ≤40% group,
  • >40 to ≤60% group,
  • >60 to ≤80% group and
  • >80% group.

The association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications were assessed. The data used was from retrospective study of 21,352 newly diagnosed diabetes patients (>40 years), who had ≥5 HbA1c measurements, using data from the electronic health record of Scottish Care Information-Diabetes Collaboration.
Funding: Sichuan University and the Department of Science and Technology of Sichuan Province.

 Key results

  • Overall, 62% of the patients had HVS (HbA1c Variability Score) 40%, and 12.5% had >60%.
  • Patients with HVS >80-100% vs those with HAV ≥0 to ≤20% had significantly increased risks for:
    • major adverse cardiovascular events (MACEs; HR, 2.38; 95% CI, 1.61-3.53; P<.001),
    • all-cause mortality (HR, 2.40; 95% CI, 1.72-3.33; P<.001),
    • atherosclerotic CV death (HR, 2.40; 95% CI, 1.13-5.11; P=.023),
    • coronary artery disease (HR, 2.63; 95% CI, 1.81-3.84; P<.001),
    • ischaemic stroke (HR, 2.04; 95% CI, 1.12-3.73; P=.020),
    • heart failure (HR, 3.23; 95% CI, 1.76-5.93; P<.001),
    • diabetic retinopathy (HR, 7.40; 95% CI, 3.84-14.27; P<.001),
    • diabetic peripheral neuropathy (HR, 3.07; 95% CI, 2.23-4.22; P<.001),
    • diabetic foot ulcer (HR, 5.24; 95% CI, 2.61-10.49; P<.001) and
    • chronic kidney disease (HR, 3.49; 95% CI, 2.47-4.95; P<.001).

So be on the lookout for variability of the HbA1c which means very good record keeping preferably electronic. Why do we need to be careful? Type 2 diabetes is the leading cause of blindness, nontraumatic lower-limb amputation, and chronic kidney disease world wide. It is a major cause of cardiovascular disease, leading to early death. As the Centers for Disease Control and Prevention do not tire of reminding us, the number of persons with type 2 diabetes in the United States will more than triple by 2050 from the current estimate of 26 million and probably will be worse in the Third world. The increasing incidence of type 2 diabetes is largely attributable to changes in lifestyle (diet and activity levels) and obesity, though the awareness created by this constant reminder is slowing down the progression to diabetes.

Why does diabetes develop? Insulin resistance is typically present for some years before diagnosis. This show as diminished stimulation of glucose transport in muscle and adipose tissue and inadequate suppression of glucose production in the liver in response to insulin. However, euglycemia is maintained as long as beta cells secrete higher amounts of insulin. Over time, insulin levels decline because of the decreased number of beta cells and their diminished secretory capacity. We would do well to remember that diabetes is really progressive failure of the pancreatic islet cells to secrete insulin. Beta-cell failure is mediated by genetic factors and exposure to chronically elevated levels of blood glucose (glucotoxicity) and free fatty acids (lipotoxicity). Older age, amyloid fibrils in islets, and chronically high rates of insulin secretion also play mechanistic roles. The majority of genetic abnormalities that have been identified in patients with type 2 diabetes are related to beta-cell function.

What criteria should we use for the diagnosis of diabete? According to the American Diabetes Association, the diagnosis of type 2 diabetes is based on a glycated hemoglobin level of 6.5% or more, a fasting plasma glucose level of 126 mg per deciliter (7.0 mmol per liter) or more, or a 2-hour plasma glucose level of 200 mg per deciliter (11.1 mmol per liter) or more during an oral glucose-tolerance test. The diagnosis can also be established by classic symptoms of hyperglycemia and a random plasma glucose level of 200 mg per deciliter or more. Test results require confirmation with the use of the above criteria, unless the diagnosis is obvious on the basis of the symptoms. Your next task is glycemic control and to wrestle with decisions like tight glycemic control, fasting blood sugar control or postprandial control.


Li S, Nemeth I, Donnelly L, Hapca S, Zhou K, Pearson ER. Visit-to-Visit HbA1c Variability Is Associated With Cardiovascular Disease and Microvascular Complications in Patients With Newly Diagnosed Type 2 Diabetes. Diabetes Care. 2019 Nov 14 

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3 thoughts on “How should we be assessing the risk for someone who has just developed diabetes? What causes beta cell failure?”

  1. Madam Is the use of insulin glargine recommended in GDM(gestational DM)?.A few studies have shown there is better glycemic control with fewer episodes of hypoglycemia and no adverse fetal outcome.But RCOG ,NICE guidelines and ACOG guidelines all recommend the use of regular and intermediate acting insulin in GDM.. Some of the endocrinologists have started glargine in pregnancy.A patient of mine who has been undergoing her antenatal checkup from UAE is on glargine only ,prescribed by an endocrinologist about 2 month back .(on 28 IU) started from 14 and adjusted according to Bl glucose levels.Will you recommend it.?


    1. Gestational diabetes needs to be treated. The risk of eclampsia, babies over 4000 gm, shoulder dystocia and macrosomia all go down. It does not appear to affect the long term fetal output whether glycemic is started at 20 weeks or later but at 3o weeks it must be started. Checking for ultrasound evidence of fetal overgrowth can indicate fetal hyperinsulinemia. Most physicians prefer intermediate insulin and Short acting insulins provide for better glycemic control but patients are not happy with 4 to 6 injections a day for glycemic control especially as they are eating upto 30 cal/kg/body weight. Most clinicians prefer intermediate and short acting insulin plus a diet plan. Both glargine and detemir can be used in gestational diabetes. FDA has moved detemir to class B from class C recently so it seems to be preferred but glargine can be used too. The problem is that short acting insulins cannot be used with glargine as it changes their mode of action. If your patient is controlled on her dose of glargine just continue it. You may need to ask her to take a protein snack at night to prevent nocturnal ketosis. Does that answer your question>


  2. Madam thanks for answering my question. The regime of three inj of short acting insulin and one NPH insulin at night (HS) has always been my favourite and has given me good results in most of the GDM patients .Yes,not very convenient for the patients…I’ve continued Glargine in that patient as you said.Her blood glucose levels are well controlled and fetal weight is according to the gestational age ,amniotic fluid index is also fine.I plan to deliver her after 3 weeks.Can you please share the link or the site on which drugs upgraded from category C to B by FDA in pregnancy are given.Thankyou


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