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Risk Assessment Group Seminar. Magnesium and the Risk for Type 2 Diabetes Mellitus. 李妮臻 2004/08/03. INTRODUCTION. Type 2 Diabetes Mellitus. Definition Hyperglycemia resulted from insulin resistance with an insulin secretory defect Excess risk for: Blindness Renal failure
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Risk Assessment Group Seminar Magnesium and the Risk for Type 2 Diabetes Mellitus 李妮臻 2004/08/03
Type 2 Diabetes Mellitus Definition • Hyperglycemia resulted from insulin resistance with an insulin secretory defect Excess risk for: • Blindness • Renal failure • Cardiovascular disease
Hypomagnesemia in diabetes Intracellular magnesium • Cofactor for enzymes in glucose metabolism • Maintain tyrosine kinase activity at insulin receptor Insulin as a regulatory hormone • Stimulate magnesium uptake by cell • Insulin receptor-mediated process
Magnesium status in pathogenesis of diabetes • Serum magnesium • Dietary intake of magnesium
Reference 1:Serum and Dietary Magnesium and the Risk for Type 2 Diabetes Mellitus The Atherosclerosis Risk in Communities Study Arch Intern Med. 1999;159:2151-2159
The Atherosclerosis Risk in Communities Study Study design • Prospective study • 6 years of follow-up (2 visits) • Etiology of atherosclerosis and its clinical sequelae Participants • Aged 45-64 years • Four US communities: --- Forsyth County, North Carolina --- Jackson, Mississippi --- Suburbs of Minneapolis, Minnesota --- Washington County, Maryland
Participants Exclude: • Ethnicity other than black or white • Had diabetes at baseline • Missing exposure or outcome information • Nonfasting (< 8 hours) • Unavailable for follow-up • Dead 10871 participants
Exposure assessment Blood collection • Fasting ≧ 12 hrs • Serum magnesium, glucose level, insulin level, calcium level, potassium level Dietary intake • 61-item food frequency questionnaire (FFQ) • Mg intake: milligrams/4.2 kJ daily energy intake • Lack of validity study for magnesium
Outcome assessment Diabetes mellitus definition: • Fasting glucose level ≧ 126 mg/dL • Non-fasting glucose level ≧ 200 mg/dL • Current use of diabetic medication • Doctor ever told that he/she had diabetes Met any of these conditions at visit 2 or visit 3 →incident cases of diabetes
Statistical analysis Stratified by race Serum Mg level • Categorized into 6 groups • Highest level: ≧0.95 mmol/L (Reference group) Dietary Mg intake • Categorize into quartiles • Highest quartile as reference group
Statistical analysis (cont.) Statistical significance • Analysis of variance • χ2analysis Association between Mg and diabetes • Logistic regression model • Odds ratio
Comparison of cross-sectional and prospective association Cross-sectional Prospective
Three main conclusions • Inverse relationship between serum Mg level and development of type 2 diabetes ---White middle-aged adults. • Cross-sectional relationship ---Effect of diabetes on serum Mg level • No association between dietary Mg intake and incident type 2 diabetes.
Reference 2: Dietary Magnesium Intake in Relation to Plasma Insulin Levels and Risk of Type 2 Diabetes in Women Diabetes Care 27:59-65,2004
Women’s Health Study (WHS) Study design • Randomized, double-blind, placebo controlled trial • Low-dose aspirin and vitamin E • Primary prevention of cardiovascular disease and cancer Participants • Aged ≧ 45 years • 39876 female health professionals • Free of coronary heart disease, stroke, and cancer.
Assessment of Mg intake • 131-item SFFQ • Commonly used unit or portion size • 9 possible responses: never ~ 6 or more times per day • Good validity for magnesium SFFQ vs. 2 weeks of diet records r = 0.76
Ascertainment of incident type 2 diabetes Ask annually about type 2 diabetes diagnosis ↓ Questionnaire: • Onset of disease • Symptoms • Diagnostic tests • Hypoglycemic treatment ↓ Confirm type 2 diabetes: • Guidelines of the American Diabetes Association
Assessment of fasting insulin levels • 349 randomly selected health women (Serve as control in WHS) • Double antibody systems --- < 0.2 % cross-reactivity between insulin and its precursors
Data analysis • Magnesium intake --- Categorized into quintiles --- Lowest quintile as reference • Cox proportional hazard model → rate ratio • Stratified analyses by BMI (< or ≧ 25 kg/m2)
Data analysis (cont.) Cross-sectional analysis • Natural logarithm of insulin level • Multiple linear regression models • Modifying effect of BMI --- Stratified by BMI
For middle-aged women risk of type 2 diabetes Magnesium intake plasma insulin level • Inverse association • Significant among overweight (≧ 25 kg/m2) --- Highest quintile had a 22% lower risk • Beneficial effects --- Greater among overweight people --- Who are prone to insulin resistance.