Role of Micronutrients and Trace Elements in Diabetes Mellitus: A Review

The present review evaluates the relationship between type 2 diabetes mellitus and individual or combined vitamins. Antioxidant vitamins A, C and E are found decreased in diabetic subjects, possibly due an increased need to control the excessive oxidative stress produced by abnormalities in glucose metabolism. On the other hand, retinol binding protein exerts a modulating effect, as it has adipokine functions. With respect to the B group vitamins, thiamin, pyridoxine and biotin have been found decreased but the mechanisms are not clear, however supplementation has shown some improvement of the metabolic control in diabetic patients. The absorption of folic acid and vitamin B12 is importantly decreased by the prolongued use of metformin, which is the first choice drug in uncomplicated diabetes, thus these two nutrients have been found deficient in the disease and most probably need to be supplemented regularly. On the other hand, vitamin D is considered a risk factor for the development of diabetes as well as its complications, particularly cardiovascular ones. Although some studies have found an association of vitamin K intake with glucose metabolism further research is needed. Studies on the use of multivitamin supplements have shown unconclusive results. After reviewing the evidence, no real recommendation on the use of vitamin supplements in type 2 diabetes mellitus can be issued, however patients using metformin during prolongued periods may need folic acid and vitamin B12.

The present review tries to understand the relationship between minerals, trace elements, and blood glucose levels in diabetic patients in chronic hyperglycemic conditions, a state where there is impaired metabolism of carbohydrates, proteins, and fats, which is caused by abnormal insulin secretion or insulin action or both. Diabetes mellitus is a metabolic syndrome characterized by increased blood sugar levels and glucose intolerance due to insulin resistance and deficiency. Many research trials have shed light on the relationship between trace elements and diabetes mellitus. Certain trace elements like copper, chromium, magnesium, vanadium, zinc, iron, and selenium are known to potentiate the insulin action. The mechanism behind this includes the activation of receptor sites of insulin, by involving in glucose metabolism enzyme systems serving as components or cofactors in it. Many studies have convincingly shown a link between micronutrients and glucose homeostasis. There is also evidence that the deficiency and efficiency of these micronutrients might have precise role in the pathogenesis and development of this disease.

Enormous progress in investigation of vitamin D currently being made from basic science to clinical medicine. The classic view of vitamin D function limited to calcium metabolism and bone homeostasis has undergone extensive revision and it has been revealed that vitamin D receptors exist in most tissues of the body. Nowadays, one of the most popular aspect of vitamin D in research area is its role in glucose metabolism and insulin resistance. The functional mechanism of vitamin D in metabolism includes genomic and rapid non-genomic actions which is expanded in this review. Briefly, the modulatory action of vitamin D in gene expression of insulin signaling compartments and secretion of insulin hormone may point to its role in pathogenesis and development of Type II diabetes. Vitamin D induced activation of the PI3K/AKT pathway is through PTEN-mediated AKT down regulation. Also, allelic variations in VDR and DBP might affect insulin secretion and diabetes occurrence. Vitamin D influences on insulin secretion from β-cell through calcium dependent endopeptidases which promotes the conversion of pro-insulin to insulin hence it can be declared that calcium and vitamin D are essential for insulin exocytosis. Hypovitaminosis D in obese individuals is also associated with higher levels of serum parathormone which this secondary hyperparathyroidism probably contributes to insulin resistance associated with obesity. Moreover, vitamin D is an immune modulator which may affect inflammation as a contributor of diabetes.

Recent studies have shown that micronutrients are involved in the pathology of type 2 diabetes. Micronutrients with antioxidant effects; such as vitamins C and B2 may have protective effects. Moreover, homocysteine-lowering vitamins including B6, folate and B12 may have possible roles. However, a few reports have investigated the association between the dietary water-soluble vitamins intakes and risk of diabetes. In a prospective study encompassing 19,168 healthy Japanese men and women aged 40-79 years, we examined the associations between dietary intakes of water-soluble vitamins, determined by a validated self-administered food frequency questionnaire, with risk of 5-year cumulative incidence of physician-diagnosed type 2 diabetes by using the logistic regression model. Within 5-year period, there were 494 self-reported new cases of diabetes. Higher dietary intakes of vitamins C, B2 and folate were associated with lower risk of incident diabetes only in women; whereas, no associations of dietary intakes of vitamins B1, B3, B5, B6 and B12 were observed in either gender. The multivariable ORs (95% CIs) in the highest versus the lowest quartile of intakes among women were 0.61 (0.44-0.94; p-trend = 0.04) for vitamin C, 0.56 (0.34-0.93; p-trend = 0.03) for vitamin B2 and 0.70 (0.46-0.98; p-trend = 0.03) for folate. Other than that for sex (p < 0.05), the p-interactions with age, body mass index, smoking status or having a family history of diabetes were >0.10. In conclusions, higher dietary intakes of vitamins C, B2 and folate, but not other water-soluble vitamins were associated with reduced risk of type 2 diabetes in Japanese women.

Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.