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Chronic systemic inflammation

Vitamin D deficiency has been linked to altered immune status. Particular attention has been paid to the role of vitamin D in T-cell responses. While this is relevant to autoimmune cardiovascular disease (CVD) risk factors such as diabetes mellitus type 1 and the cellular responses in the chronic inflammatory process of atherosclerosis. The pro-inflammatory effect of vitamin D deficiency is thought to be of greatest relevance to CVD risk. The detrimental role of inflammation in many forms of CVD is well established. Amer et al. determined that the inverse relationship between vitamin D and the widely studied inflammatory marker, high sensitivity C-reactive protein (hs-CRP) was only present when vitamin D was below the median of the National Health and Nutrition Examination Survey (NHANES) population (1). Conversely, the inverse inter-correlation between vitamin D and the level of inflammatory mediators may infer a shared mechanism of action.

Diabetes mellitus and adipositas

Evidence continues to accumulate to suggest that vitamin D may support pancreatic beta cell function. Consequently, vitamin D deficiency might adversely affect metabolic risk factors for CVD including type 2 diabetes and other conditions that are associated with insulin resistance. The strengthening of the evidence in support of a relationship between vitamin D status and carbohydrate metabolism is one of the most recent developments in the role of vitamin D in CVD. Although studies have varied in design, most but not all studies have reported an inverse relationship between vitamin D status and type 2 diabetes (2). Overall, meta-analyses conclude that such a relationship is significant. Supporting evidence includes the observation that the expected lower prevalence of type 2 diabetes in subjects with adequate vitamin D levels is accompanied by a longer femoral bone length, consistent with preservation of bone mass (3). Central to the issue is the observation that vitamin D status is inversely associated with both subcutaneous, and more particularly, visceral obesity (4). Studies of the association between vitamin D and clinical features of insulin resistance resemble those described for type 2 diabetes. Low levels of vitamin D are associated with measures of insulin insensitivity and the risk of future development of manifestations of the metabolic syndrome in non-diabetic subjects (5). Meta-analyses suggest that the association is significant and that it is independent of the individual components of the metabolic syndrome. The dyslipidemic pattern that is frequently encountered in insulin resistance (elevated triglyceride with reduced high-density lipoprotein cholesterol and small, dense low-density lipoprotein particles) is associated with low vitamin D levels (6).


1.     Amer M, Qayyum R. Relation between serum 25-hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol 2012;109:226-30.
2.     Grimnes G, Emaus N, Joakimsen RM, Figenschau Y, Jenssen T, Njolstad I et al. Baseline serum 25-hydroxyvitamin D concentrations in the Tromso Study 1994-95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up. Diabet Med 2010;27:1107-15.
3.     Liu J, Tan H, Jeynes B. Serum 25OH vitamin D level, femur length, and risk of type 2 diabetes among adults. Appl Physiol Nutr Metab 2011;36:264-70.
4.     Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL et al. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes 2010;59:242-8.
5.     Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ et al. Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab). J Clin Endocrinol Metab 2012;97:1953-61.
6.     Karhapaa P, Pihlajamaki J, Porsti I, Kastarinen M, Mustonen J, Niemela O, Kuusisto J. Diverse associations of 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D with dyslipidaemias. J Intern Med 2010;268:604-10.