Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study

OBJECTIVE Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included direct measures of adiposity. Furthermore, the degree to which vitamin D is associated with metabolic traits after adjusting for adiposity measures is unclear. RESEARCH DESIGN AND METHODS We investigated the relations of serum 25-hydroxyvitamin D (25[OH]D) concentrations with indexes of cardiometabolic risk in 3,890 nondiabetic individuals; 1,882 had subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes measured by multidetector computed tomography (CT). RESULTS In multivariable-adjusted regression models, 25(OH)D was inversely associated with winter season, waist circumference, and serum insulin (P < 0.005 for all). In models further adjusted for CT measures, 25(OH)D was inversely related to SAT (−1.1 ng/ml per SD increment in SAT, P = 0.016) and VAT (−2.3 ng/ml per SD, P < 0.0001). The association of 25(OH)D with insulin resistance measures became nonsignificant after adjustment for VAT. Higher adiposity volumes were correlated with lower 25(OH)D across different categories of BMI, including in lean individuals (BMI <25 kg/m2). The prevalence of vitamin D deficiency (25[OH]D <20 ng/ml) was threefold higher in those with high SAT and high VAT than in those with low SAT and low VAT (P < 0.0001). CONCLUSIONS Vitamin D status is strongly associated with variation in subcutaneous and especially visceral adiposity. The mechanisms by which adiposity promotes vitamin D deficiency warrant further study.

[1]  J. Norris,et al.  Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. , 2009, The Journal of clinical endocrinology and metabolism.

[2]  Darrell M. Wilson,et al.  Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. , 2009, The American journal of clinical nutrition.

[3]  R. Vasan,et al.  Abdominal Subcutaneous Adipose Tissue: A Protective Fat Depot? , 2009, Diabetes Care.

[4]  M. Holick,et al.  Vitamin D status: measurement, interpretation, and clinical application. , 2009, Annals of epidemiology.

[5]  R. Vasan,et al.  Subcutaneous Abdominal Adipose Tissue: a Protective Fat Depot? , 2009 .

[6]  Stefan Pilz,et al.  Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. , 2008, Archives of internal medicine.

[7]  E. Rimm,et al.  25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. , 2008, Archives of internal medicine.

[8]  R. Jorde,et al.  Serum 1,25-dihydroxy vitamin D is inversely associated with body mass index , 2008, European journal of nutrition.

[9]  M. Horowitz,et al.  Vitamin D, glucose, insulin, and insulin sensitivity. , 2008, Nutrition.

[10]  D. Mauricio,et al.  Role of vitamin D in the pathogenesis of type 2 diabetes mellitus , 2008, Diabetes, obesity & metabolism.

[11]  J. Kichler,et al.  Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. , 2008, Metabolism: clinical and experimental.

[12]  Michael J. Pencina,et al.  Vitamin D Deficiency and Risk of Cardiovascular Disease , 2008, Circulation.

[13]  Caroline,et al.  Patterns of Abdominal Fat Distribution: The Framingham Heart Study , 2008 .

[14]  R. Wood.  Vitamin D and adipogenesis: new molecular insights. , 2008, Nutrition reviews.

[15]  P. Tseke,et al.  Vitamin D, the renin-angiotensin system, and insulin resistance , 2008, International Urology and Nephrology.

[16]  J. Murabito,et al.  Visceral and Subcutaneous Adipose Tissue Volumes Are Cross-Sectionally Related to Markers of Inflammation and Oxidative Stress: The Framingham Heart Study , 2007, Circulation.

[17]  Udo Hoffmann,et al.  Abdominal Visceral and Subcutaneous Adipose Tissue Compartments: Association With Metabolic Risk Factors in the Framingham Heart Study , 2007, Circulation.

[18]  A. Mitrakou,et al.  The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults , 2007, Diabetes Care.

[19]  Keith C. Norris,et al.  Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. , 2007, Archives of internal medicine.

[20]  Qiong Yang,et al.  The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: design, recruitment, and initial examination. , 2007, American journal of epidemiology.

[21]  Zhenqi Liu.  The renin-angiotensin system and insulin resistance , 2007, Current diabetes reports.

[22]  C. Fox,et al.  Comparison of anthropometric, area- and volume-based assessment of abdominal subcutaneous and visceral adipose tissue volumes using multi-detector computed tomography , 2007, International Journal of Obesity.

[23]  M. Chonchol,et al.  25-Hydroxyvitamin D, insulin resistance, and kidney function in the Third National Health and Nutrition Examination Survey. , 2007, Kidney international.

[24]  R. Wood,et al.  Vitamin D status and the metabolic syndrome. , 2006, Nutrition reviews.

[25]  R. Krauss,et al.  Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement , 2005, Current opinion in cardiology.

[26]  J. Manson,et al.  Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. , 2005, Diabetes care.

[27]  Fernando Costa,et al.  Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. , 2005, Circulation.

[28]  M. Visser,et al.  Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. , 2005, The Journal of clinical endocrinology and metabolism.

[29]  E. Ford,et al.  Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. , 2005, Diabetes care.

[30]  A. Looker.  Body fat and vitamin D status in black versus white women. , 2005, The Journal of clinical endocrinology and metabolism.

[31]  B. Boucher,et al.  Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. , 2004, The American journal of clinical nutrition.

[32]  M. Saad,et al.  Hypovitaminosis D is associated with insulin resistance and β cell dysfunction , 2004 .

[33]  J. Yanovski,et al.  The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. , 2004, The Journal of clinical endocrinology and metabolism.

[34]  C. Thomas,et al.  PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body weight. , 2003, Medical hypotheses.

[35]  T. Spector,et al.  Moderate alcohol consumption, estrogen replacement therapy, and physical activity are associated with increased insulin sensitivity: is abdominal adiposity the mediator? , 2003, Diabetes care.

[36]  E. Wolf,et al.  Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[37]  J. Aloia,et al.  Body fat content and 25-hydroxyvitamin D levels in healthy women. , 2003, The Journal of clinical endocrinology and metabolism.

[38]  M. Holick,et al.  Decreased bioavailability of vitamin D in obesity. , 2000, The American journal of clinical nutrition.

[39]  E. Bonora,et al.  Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. , 2000, Diabetes care.

[40]  M. Holick,et al.  Environmental factors that influence the cutaneous production of vitamin D 13 , 1995 .

[41]  M. Riddle,et al.  Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus. , 1994, The American journal of clinical nutrition.

[42]  G A Colditz,et al.  Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. , 1992, American journal of epidemiology.

[43]  L. Lind,et al.  Long-term treatment with active vitamin D (alphacalcidol) in middle-aged men with impaired glucose tolerance. Effects on insulin secretion and sensitivity, glucose tolerance and blood pressure. , 1989, Diabetes research.

[44]  A. Norman,et al.  Rapid normalization/stimulation by 1,25-dihydroxyvitamin D3 of insulin secretion and glucose tolerance in the vitamin D-deficient rat. , 1987, Endocrinology.

[45]  J N Morris,et al.  Assessment methods for physical activity and physical fitness in population studies: report of a NHLBI workshop. , 1986, American heart journal.

[46]  C. Paterson,et al.  Vitamin D nutrition in relation to season and occupation. , 1981, The American journal of clinical nutrition.

[47]  G. Grodsky,et al.  Vitamin D deficiency inhibits pancreatic secretion of insulin. , 1980, Science.

[48]  W. Kannel,et al.  An investigation of coronary heart disease in families. The Framingham offspring study. , 1979, American journal of epidemiology.

[49]  C. Rich,et al.  Deposition in and release of vitamin D3 from body fat: evidence for a storage site in the rat. , 1971, The Journal of clinical investigation.

[50]  T. Dawber,et al.  Epidemiological approaches to heart disease: the Framingham Study. , 1951, American journal of public health and the nation's health.