group significant relative risk reductions emerged for myocardial infarction (15%, p=0.014) and all-cause mortality (12%, p=0.007). autoimmune processes research from 2007 suggested that in type 1 diabetics, the continuing autoimmune disease which initially destroyed the beta cells of the pancreas may also cause neuropathy, and nephropathy. in 2008 it was even suggested to treat retinopathy with drugs to suppress the abnormal immune response rather than by blood sugar control. genetic factors the known familial clustering of the type and degree of diabetic complications indicates that genetics play a role in causing complications: the 2001 observation, that non-diabetic offspring of type 2 diabetics had increased arterial stiffness and neuropathy despite normal blood glucose levels, the 2008 observation, that non-diabetic first-degree relatives of diabetics had elevated enzyme levels associated with diabetic renal disease and nephropathy. the 2007 finding that non-diabetic family members of type 1 diabetics had increased risk for microvascular complications, such as diabetic retinopathy some genes appear to provide protection against diabetic complications, as seen in a subset of long-term diabetes type 1 survivors without complications. mechanisms chronic elevation of blood glucose level leads to damage of blood vessels called angiopathy. the endothelial cells lining the blood vessels take in more glucose than normal, since they do not depend on insulin. they then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker. the resulting problems are grouped under "microvascular disease" due to damage to small blood vessels and "macrovascular disease" due to damage to the arteries. studies show that dm1 and dm2 cause a change in balancing of metabolites such as carbohydrates, blood coagulation factors, and lipids, and subsequently bring about complications like microvascular and cardiovascular complications. the role of metalloproteases and inhibitors in diabetic renal disease is unclear. numerous researches have found inconsistent results about the role of vitamins in diabetic risk and complications. thiamine: thiamine acts as an essential cofactor in glucose metabolism, therefore, it may modulate diabetic complications by controlling glycemic status in diabetic patients. additionally, deficiency of thiamine was observed to be associated with dysfunction of β-cells and impaired glucose tolerance. different studies indicated possible role of thiamin supplementation on the prevention or reversal of early stage diabetic nephropathy, as well as significant improvement on lipid profile. vitamin b12: low serum b12 level is a common finding in diabetics especially those taking metformin or in advanced age. vitamin b12 deficiency has been linked to two diabetic complications; atherosclerosis and diabetic neuropathy. folic acid: low plasma concentrations of folic acid were found to be associated with high plasma homocysteine concentrations. in clinical trials, homocysteine concentrations were effectively reduced within 4 to 6 weeks of oral supplementation of folic acid. moreover, since the activity of endothelial no synthase enzyme might be potentially elevated by folate, folate supplementation might be capable of restoring the availability of no in endothelium, therefore, improving endothelial function and reducing the risk for atherosclerosis. van etten et al., found that a single dose of folic acid might help in reducing the risk of vascular complications and enhancing endothelial function in adults with type 2 diabetes by improving nitric oxide status. antioxidants: three vitamins, ascorbic acid; α-tocopherol; and β-carotene, are well recognized for their antioxidant activities in human. free radical-scavenging ability of antioxidants may reduce the oxidative stress and thus may protect against oxidative damage. based on observational studies among healthy individuals, antioxidant concentrations were found to be inversely correlated with several biomarkers of insulin resistance or glucose intolerance. management blood pressure control modulating and ameliorating diabetic complications may improve the overall quality of life for diabetic patients. for example; when elevated blood pressure was tightly controlled, diabetic related deaths were reduced by 32% compared to those with less controlled blood pressure. vitamins many observational and clinical studies have been conducted to investigate the role of vitamins on diabetic complications, in the first national health and nutrition examination survey (nhanes i) epidemiologic follow-up study, vitamin supplementations were associated with 24% reduction on the risk of diabetes, observed during 20 years of follow-up. many observational studies and clinical trials have linked several vitamins with the pathological process of diabetes; these vitamins include folate, thiamine, β-carotene, and vitamin e, c, b12, and d. vitamin d: vitamin d insufficiency is common in diabetics. observational studies show that serum vitamin d is inversely associated with biomarkers of diabetes; impaired insulin secretion, insulin resistance, and glucose intolerance. it has been suggested that vitamin d may induce beneficial effects on diabetic complications by modulating differentiation and growth of pancreatic β-cells and protecting these cells from apoptosis, thus improving β-cells functions and survival. vitamin d has also been suggested to act on immune system and modulate inflammatory responses by influencing proliferation and differentiation of different immune cells., moreover, deficiency of vitamin d may contribute to diabetic complications by inducing hyperparathyroidism, since elevated parathyroid hormone levels are associated with reduced β-cells function, impaired insulin sensitivity, and glucose intolerance. finally, vitamin d may reduce the risk of vascular complications by modulating lipid profile. antioxidants may have beneficial effects on diabetic complications by reducing blood pressure, attenuating oxidative stress and inflammatory biomarkers, improving lipid metabolism, insulin-mediated glucose disposal, and by enhancing endothelial function. vitamin c has been proposed to induce beneficial effects by two other mechanisms. it may replace glucose in many chemical reactions due to its similarity in structure, may prevent the non-enzymatic glycosylation of proteins, and might reduce glycated hemoglobin (hba1c) levels. secondly, vitamin c has also been suggested to play a role in lipid regulation as a controlling catabolism of cholesterol to bile acid.