Dr. Ron’s Research Review – February 16, 2011

This week’s research review contains information on vitamin D and diabetes.

The high prevalence of vitamin D deficiency and plausible molecular mechanisms linking this to diabetes and cardiovascular risk suggest treatment of vitamin D deficiency to prevent and/or treat diabetes is a promising field to explore. (Baz-Hecht and Goldfine 2010)

Vitamin D may have a protective role in insulin secretion and an effect on insulin resistance. Low levels of vitamin D are indicated as a risk factor for both type 1 and type 2 diabetes. (Krans 2009)

A study of 808 non-diabetic participants of the Framingham Offspring Study found that among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. (Liu, Meigs et al. 2009)

        

Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D. The presence of vitamin D receptors (VDR) and vitamin D-binding proteins (DBP) in pancreatic tissue and the relationship between certain allelic variations in the VDR and DBP genes with glucose tolerance and insulin secretion have further supported this hypothesis. The mechanism of action of vitamin D in type 2 diabetes is thought to be mediated not only through regulation of plasma calcium levels, which regulate insulin synthesis and secretion, but also through a direct action on pancreatic beta-cell function. Therefore, owing to its increasing relevance, this review focuses on the role of vitamin D in the pathogenesis of type 2 diabetes mellitus. (Palomer, Gonzalez-Clemente et al. 2008)

Dr. Ron


Articles

Vitamin D, glucose tolerance and insulinaemia in elderly men

            (Baynes, Boucher et al. 1997) Download

Vitamin D status was assessed in 142 elderly Dutchmen participating in a prospective population-based study of environmental factors in the aetiology of non-insulin-dependent diabetes mellitus. Of the men aged 70-88 years examined between March and May 1990, 39% were vitamin D depleted. After adjustment for confounding by age, BMI, physical activity, month of sampling, cigarette smoking and alcohol intake the 1-h glucose and area under the glucose curve during a standard 75-g oral glucose tolerance test (OGTT) were inversely associated with the serum concentration of 25-OH vitamin D (r = -0.23, p < 0.01; r = -0.26, p < 0.01, respectively). After excluding newly diagnosed diabetic patients total insulin concentrations during OGTT were also inversely associated with the concentration of 25-OH vitamin D (r = -0.18 to -0.23, p < 0.05). Hypovitaminosis D may be a significant risk factor for glucose intolerance.

The impact of vitamin D deficiency on diabetes and cardiovascular risk

            (Baz-Hecht and Goldfine 2010) Download

PURPOSE OF REVIEW: To review the association between vitamin D deficiency and diabetes and cardiovascular risk. RECENT FINDINGS: Vitamin D deficiency is newly recognized as a common condition of increasing prevalence worldwide. Clinically, vitamin D has an established role in calcium and bone metabolism and has recently been shown to be associated with increased risk of developing type 1 and type 2 diabetes mellitus and cardiovascular disease (CVD), as well as with cardiovascular risk factors such as hypertension and obesity. The molecular mechanisms of these associations remain incompletely understood. The active metabolite of vitamin D regulates transcription of multiple gene products with antiproliferative, prodifferentiative, and immunomodulatory effects. Although vitamin D deficiency is frequently unrecognized clinically, laboratory measurement is easy to perform and treatment of vitamin D deficiency is relatively well tolerated and inexpensive. Limited, yet promising, results of proof-of-concept intervention studies of using vitamin D in diabetes will be presented. SUMMARY: The high prevalence of vitamin D deficiency and plausible molecular mechanisms linking this to diabetes and cardiovascular risk suggest treatment of vitamin D deficiency to prevent and/or treat diabetes is a promising field to explore.


Baseline serum 25-hydroxy vitamin D in predicting glycemic status and insulin levels

            (Krans 2009) Download

Vitamin D may have a protective role in insulin secretion and an effect on insulin resistance. Low levels of vitamin D are indicated as a risk factor for both type 1 and type 2 diabetes, however, clinical evidence that increased vitamin D levels benefit diabetic patients has not yet been established.

Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults

            (Liu, Meigs et al. 2009) Download

We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistant phenotype. Plasma 25(OH)D concentrations were measured in 808 nondiabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-h post 75-g oral glucose tolerance test (OGTT) glucose and insulin; these were used to calculate the homeostatic model assessment-insulin resistance (HOMA-IR) and insulin sensitivity index (ISI(0,120)). We also measured plasma adiponectin, triacylglycerol, and HDL cholesterol concentrations as markers of the insulin-resistant phenotype. After adjusting for age, sex, BMI, waist circumference, and current smoking status, plasma 25(OH)D concentration was inversely associated with fasting plasma glucose and insulin concentrations, and HOMA-IR. Compared with the participants in the lowest tertile category of plasma 25(OH)D, those in the highest tertile category had a 1.6% lower concentration of fasting plasma glucose (P-trend = 0.007), 9.8% lower concentration of fasting plasma insulin (P-trend = 0.001), and 12.7% lower HOMA-IR score (P-trend < 0.001). After adjusting for age and sex, plasma 25(OH)D was positively associated with ISI(0,120), plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

25-OH vitamin D: is it the universal panacea for metabolic syndrome and type 2 diabetes?

            (Osei 2010) Download


Role of vitamin D in the pathogenesis of type 2 diabetes mellitus

            (Palomer, Gonzalez-Clemente et al. 2008) Download

Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. It has been reported that vitamin D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes mellitus. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D, thereby suggesting a role for vitamin D in the pathogenesis of type 2 diabetes mellitus. The presence of vitamin D receptors (VDR) and vitamin D-binding proteins (DBP) in pancreatic tissue and the relationship between certain allelic variations in the VDR and DBP genes with glucose tolerance and insulin secretion have further supported this hypothesis. The mechanism of action of vitamin D in type 2 diabetes is thought to be mediated not only through regulation of plasma calcium levels, which regulate insulin synthesis and secretion, but also through a direct action on pancreatic beta-cell function. Therefore, owing to its increasing relevance, this review focuses on the role of vitamin D in the pathogenesis of type 2 diabetes mellitus.

The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis

            (Pittas, Lau et al. 2007) Download

CONTEXT: 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. EVIDENCE SYNTHESIS: 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. CONCLUSIONS: Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.

Vitamin D and diabetes

            (Takiishi, Gysemans et al. 2010) Download

Type 1 (T1D) and type 2 (T2D) diabetes are considered multifactorial diseases in which both genetic predisposition and environmental factors participate in their development. Many cellular, preclinical, and observational studies support a role for vitamin D in the pathogenesis of both types of diabetes including: (1) T1D and T2D patients have a higher incidence of hypovitaminosis D; (2) pancreatic tissue (more specifically the insulin-producing beta-cells) as well as numerous cell types of the immune system express the vitamin D receptor (VDR) and vitamin D-binding protein (DBP); and (3) some allelic variations in genes involved in vitamin D metabolism and VDR are associated with glucose (in)tolerance, insulin secretion, and sensitivity, as well as inflammation. Moreover, pharmacologic doses of 1,25-dihydroxyvitamin D (1,25(OH)(2)D), the active form of vitamin D, prevent insulitis and T1D in nonobese diabetic (NOD) mice and other models of T1D, possibly by immune modulation as well as by direct effects on beta-cell function. In T2D, vitamin D supplementation can increase insulin sensitivity and decrease inflammation. This article reviews the role of vitamin D in the pathogenesis of T1D and T2D, focusing on the therapeutic potential for vitamin D in the prevention/intervention of T1D and T2D as well as its complications.


References

Baynes, K. C., B. J. Boucher, et al. (1997). "Vitamin D, glucose tolerance and insulinaemia in elderly men." Diabetologia 40(3): 344-7.

Baz-Hecht, M. and A. B. Goldfine (2010). "The impact of vitamin D deficiency on diabetes and cardiovascular risk." Curr Opin Endocrinol Diabetes Obes 17(2): 113-9.

Krans, H. M. (2009). "Baseline serum 25-hydroxy vitamin D in predicting glycemic status and insulin levels." F1000 Med Rep 1.

Liu, E., J. B. Meigs, et al. (2009). "Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults." J Nutr 139(2): 329-34.

Osei, K. (2010). "25-OH vitamin D: is it the universal panacea for metabolic syndrome and type 2 diabetes?" J Clin Endocrinol Metab 95(9): 4220-2.

Palomer, X., J. M. Gonzalez-Clemente, et al. (2008). "Role of vitamin D in the pathogenesis of type 2 diabetes mellitus." Diabetes Obes Metab 10(3): 185-97.

Pittas, A. G., J. Lau, et al. (2007). "The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis." J Clin Endocrinol Metab 92(6): 2017-29.

Takiishi, T., C. Gysemans, et al. (2010). "Vitamin D and diabetes." Endocrinol Metab Clin North Am 39(2): 419-46, table of contents.