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Disclosures. No conflict of interest to report Supported by National Institutes of Health (NIDDK/ODS) R01DK76092, R01DK79003, R21DK78867 - directly related to present presentation. Acknowledgments. Frank Hu MD, PhD Harvard School of Public Health (Boston, MA) Bess Dawson-Hughes, MD
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Disclosures No conflict of interest to report Supported by • National Institutes of Health (NIDDK/ODS) • R01DK76092, R01DK79003, R21DK78867 - directly related to present presentation Acknowledgments • Frank Hu MD, PhD • Harvard School of Public Health (Boston, MA) • Bess Dawson-Hughes, MD • Human Nutrition Research Center on Aging at Tufts U. (Boston, MA)
Vitamin D and type 2 Diabetes Type 2 Diabetes Prevalent Current Vitamin D Status Hypovitaminosis D is prevalent Vitamin D & Type 2 Diabetes - Evidence Mechanisms Observational Studies Randomized Trials
Vitamin D and Type 2 DiabetesCross-Sectional / Case-Control Studies • Low 25(OH)D levels in type 2 diabetes vs. controlsHeath et al, 1979 • 25(OH)D inversely associated w Diabetes, Odds Ratio 0.25 • NHANES (6,228 adults) Scragg et al, 2004 • 25(OH)D inversely associated w Met Syndrome, Odds Ratio 0.38 • NHANES (8,421 adults) Ford et al, 2005 Problem: Causality cannot be determined in cross-sectional studies Studies reviewed in Pittas et al JCEM 2007
Risk of Incident Type 2 Diabetes by Joint Categories of Vitamin D and Calcium Intake Risk by 33% RR adjusted for age, BMI, hypertension, family history of diabetes, smoking physical activity, caffeine, alcohol, state of residence, type of fat (saturated, polyunsaturated, trans) cereal fiber, glycemic load, magnesium and, retinol. Pittas et al Diabetes Care 2006 29:3:650
Risk of Incident Type 2 Diabetes by Joint Categories of Vitamin D and Calcium Intake Risk by 33% Risk by 33% RR adjusted for age, BMI, hypertension, family history of diabetes, smoking physical activity, caffeine, alcohol, state of residence, type of fat (saturated, polyunsaturated, trans) cereal fiber, glycemic load, magnesium and, retinol. Pittas et al Diabetes Care 2006 29:3:650
Nurses Health Study, 1976, n=121,700 25OHD and Incident type 2 DiabetesNested Case Control – Study Design Cohort with blood specimen, 1989 n=32,826 No blood specimen available Free of Diabetes Matched Controls 1989-2004; n=1275 Incident t2DM 1989-2004; n=1275 Case-Control pairs (n=600)
Association of 25OHD with Incident t2DM Cohort: Nurses Health Study, Nested Case-Control Supported by NIH R21-78867 Risk by 48% P for trend 0.008 33 ng/ml OR adjusted for age, BMI, hypertension, family history of diabetes, smoking physical activity, caffeine, alcohol, state of residence, type of fat (saturated, polyunsaturated, trans) cereal fiber, glycemic load, magnesium and fish intake. Pittas et al, Diabetes Care (in press)
Association of 25OHD with Incident t2DM Cohort: Nurses Health Study, Nested Case-Control Supported by NIH R21-78867 OR adjusted for age, BMI, hypertension, family history of diabetes, smoking physical activity, caffeine, alcohol, state of residence, type of fat (saturated, polyunsaturated, trans) cereal fiber, glycemic load, magnesium and fish intake.
Association of 25OHD with Incident t2DMMeta-analysis - Observational Longitudinal Studies Risk by 40% Knekt et al, 2008; Liu et al 2010; Pittas et al 2010 (in press)
Pitfalls of Observational Studies with Vitamin D Confounding Is vitamin D simply a marker of increased risk for disease? Need Randomized Clinical Trials
Limitations of studies on vitamin D supplementation and type 2 diabetes • Small, underpowered studies • Large dropout rates (20-40%) • Post-hoc analyses • Large infrequent vitamin D doses • Populations studied, not likely to benefit • Normal glucose tolerance • Established type 2 diabetes
Vitamin D and type 2 Diabetes - Conclusions Type 2 Diabetes Prevalent Current Vitamin D Status Hypovitaminosis D is prevalent Vitamin D & Type 2 Diabetes - Evidence Mechanisms Observational Studies Due to Confounding? Randomized Trials X Need Randomized Controlled Trials in appropriate populations to assess the issue of causality