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Magnesium intake in relation to insulin sensitivity and risk of type 2 diabetes

國立台灣大學微生物與生化學研究所營養科學組專題討論. Magnesium intake in relation to insulin sensitivity and risk of type 2 diabetes. 鎂攝取與胰島素敏感度及第二型糖尿病危險性之相關. 1. Magnesium intake and risk of type 2 diabetes in men and women 2. Oral magnesium supplementation improves insulin sensitivity and

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Magnesium intake in relation to insulin sensitivity and risk of type 2 diabetes

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  1. 國立台灣大學微生物與生化學研究所營養科學組專題討論國立台灣大學微生物與生化學研究所營養科學組專題討論 Magnesium intake in relation to insulin sensitivity and risk of type 2 diabetes 鎂攝取與胰島素敏感度及第二型糖尿病危險性之相關 1.Magnesium intake and risk of type 2 diabetes in men and women 2. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetes subjects. 【講者】李妮臻 Ni-Jen Lee 【日期】 October 25, 2004

  2. Introduction

  3. Global prevalence of diabetes • People with diabetes is increasing • Population growth • Aging • Urbanization • Increasing prevalence of obesity and physical inactivity • Global prevalence (20+ years)(Sarah Wild et al. 2004) • Developed--- Japan: 6.7%, USA: 8.8% • Developing--- China: 2.4%, • Prevalence in Taiwan (NAHSIT I) • 19+ years • Male: 3.2% • Female: 5.5%

  4. Western diets • High intake • Saturated and trans fats • Refined grains • Low intake • Whole grains • Vegetables • Fibers • Magnesium • Whole grains, nuts, green leafy vegetables • Largely lost during processing • Industrialized countries: magnesium intake↓

  5. Hypomagnesemia and type 2 diabetes • Patients with diabetes • 25%-38% prevalence of hypomagnesemia • Is magnesium deficiency a cause of diabetes? • Epidemiological studies • ARIC study (Atherosclerosis Risk in Communities Study) White Americans: Lower serum Mg, DM risk↑ (Kao WH et al. 1999) • WHS (Women’s Health Study) Women (especially in overweight) : Higher Mg intake, DM risk↓ (Yiqing Song et al. 2004)

  6. Possible mechanism • ↓Mgi • Excess Cai • Stimulates insulin secretion • Inhibits insulin action on glucose transport • Hyperinsulinemia & insulin resistance • Mg as an essential cofactor for many enzymes • Phosphorylation reactions • Glucose metabolism • Tyrosine kinase activity of insulin receptor • Insulin signal transduction

  7. Signal transduction in insulin action

  8. Hypothesis Dietary Mg↓ ↓ Serum Mg↓ ↓ Mgi ↓ ↙ ↘ Cai ↑ Tyrosine kinase activity ↓ ↘ ↙ Insulin resistance ↑ ↓ Type 2 Diabetes Mellitus

  9. ARTICLE 1 Magnesium Intake and Risk of Type 2 Diabetes in Men and Women 男性及女性鎂攝取量與第二型糖尿病之危險性 【作者】Ruy Lopez-Ridaura, Walter C. Willett, Eric B. Rimm, Simin Liu, Meir J. Stampfer, Joann E. Manson, Frank B. Hu 【出處】Diabetes Care 27:134-140, 2004

  10. Research Design and Methods

  11. Study population • Nurses’ Health Study (NHS) • Initiated in 1976 • 121,700 female registered nurses • Aged 30-55 years • Mailed questionnaires every 2 years • Health Professionals’ Follow-up Study (HPFS) • Began in 1986 • 51,529 male health professionals • Aged 40-75 years • Questionnaires every 2 years

  12. Exclusion criteria • Baseline reported disease • Diabetes • Cardiovascular disease • Cancer • Baseline dietary questionnaire • > 10 blank in food item • Did not satisfy criteria of plausible daily caloric intake • Women: 85,060 subjects (Follow-up: 1980-1998) • Men: 42,872 subjects (Follow-up: 1986-1998)

  13. Assessment of magnesium intake • Semiquantitative food frequency questionnaire (sFFQ) • Walter C. Willett • Cumulative average intake • Reduce within-person variation • Example: Diabetes incidence in the 1990-1992 period • Average of 1986 and 1990 intakes NHS 1980 1984 1986 1990 1994 1998 HPHS

  14. Measurement of nondietary factors • Body weight: self-reported • Physical activity • NHS Hours spent in moderate to vigorous activity/week • HPFS Total weekly energy expenditure (METs) • Smoking status • Number of cigarettes/day • Family history of diabetes • First-degree relatives • Hypertension • High cholesterol

  15. Ascertainment of diabetes • Biennial questionnaire • Supplementary questionnaire • Symtoms, diagnostic tests, and therpy • Diagnostic criteria • National Diabetes Data Group (NDDG) • At least one classic symptom of type 2 diabetes and elevated plasma glucose. Fasting: ≧140 mg/dl Random: ≧200 mg/dl • Elevated plasma glucose on two different occasions • Treatment with hypoglycemic therapy

  16. Statistical analysis • Quintiles of total magnesium intake • Reference group: lowest intake of quintile • Relative risks (RRs) • Cox proportional hazards models • Multivariate analysis • Estimate adjusted RRs • Stratified analyses • BMI • Physical activity • Family history of diabetes • SAS version 8.2

  17. Results

  18. Table 1

  19. Table 2

  20. Table 3

  21. Discussion and Conclusion

  22. Consistent inverse association • Men • Women • Independent of other risk factors for type 2 DM (including several dietary factors) • Stratified analyses • BMI • Physical activity Main predictors of type 2 diabetes • Family history of diabetes • Consistent across different subgroup

  23. Strength • Prospective design • Reduce possibility of recall and selection bias • High rate of follow-up • Reduce bias due to loss to follow-up • Multiple times of diet assessment • Reduce measurement error • Changes in eating behaviors

  24. Limination • Screening for blood glucose • Information from self-report, undiagnosed cases? Validation study • Health professionals • Undiagnosed diabetes was rare! • New diagnostic criteria for type 2 diabetes • 1997 • American Diabetes Association (ADA) • Fasting plasma glucose ≧ 126 mg/dl • Bias toward the null!

  25. Conclusion • An inverse association between magnesium intake and diabetes risk. • Dietary recommendation • Increase consumption of major food sources of magnesium • Whole grains, nuts, and green leafy vegetables • The effect of magnesium supplementation • Randomized clinical trials

  26. ARTICLE 2 Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects 口服鎂補充劑改善第二型糖尿病受試者的胰島素敏感度及代謝控制 【作者】Martha Rodríguez-Morán, Fernando Guerrero-Romero 【出處】Diabetes Care 26:1147-1152, 2003

  27. Research Design and Methods

  28. Study design • Randomized double-blind placebo-controlled trial Study subjects • Type 2 diabetic subjects • Durango, Northern Mexico • Eligibility • Decrease serum magnesium (≦ 0.74 mmol/l) • Exclusion criteria • Chronic diarrhea • Alcohol intake (≧ 30 g/day) • Use of diuretic or calcium antagonist drugs • Reduced renal function • Receiving magnesium supplementation

  29. Lifestyle intervention • 3 months before the trial • Withdrew pharmacological treatment • Advised dietary consumption (calories sources) • Carbohydrate: > 50% • Saturated fat: < 10% • Mono- and polyunsaturated fat: 20% • Protein: ~ 1 g /kg ideal body wt • Physical activity (30 min/time) at least 3 times per week • Exclusion • Serum glucose ≧ 16.7 mmol/l during this period

  30. Group assignment • Randomly allocation • Magnesium supplementation group • Fasting condition • 50 ml, 5% MgCl2 solution (2.5 g MgCl2 daily) • Placebo group • Placebo • 16 weeks of treatment

  31. Study participant flow diagram

  32. Measurements • Height, weight, BMI, waist circumference • HbA1c • Lipid profile • Serum glucose • Glucose-oxidase method • Serum insulin • Radioimmunoassay • Serum magnesium • Colorimetric method • HOMA-IR index

  33. Statistical analysis • Differences between groups • Normally distributed variables: Student’s t test • Skewed data: Mann Whitney U test • Categoric variables: X2 test • Before and after treatment comparisons • Paired t test • SPSS version 10.0

  34. Results

  35. Table 1

  36. Figure 2

  37. Discussion and Conclusion

  38. Necessity of oral magnesium supplementation • Type 2 diabetic subjects (decreased serum Mg level) • ↑Serum magnesium conc. • ↓ Fasting glucose • ↓ HbA1c • ↓ HOMA-IR index • Increase in serum magnesium conc. • Improve insulin sensitivity

  39. Early change in serum magnesium • Shift of Mg into intracellular stores • Magnesium compartment redistribution • Did not measure: • Duration of hypomagnesemic status • Magnesium pool distribution • Cannot be sure

  40. Limitation-1 • Mg: predominantly intracellular ion • Erythrocyte or lymphocyte content? • Serum Mg • Mg status • Intracellular pool • Normal serum conc. • In fact, intracellular Mg depletion? • Diabetes subjects with decreased serum Mg • Did not influence

  41. Limitation-2 • Daily Mg intake sources? • Food • Water • No variations in the source of water in Durango • Subjects received similar foods • Randomly allocated • Minimally influencing the results

  42. Conclusion • Type 2 diabetic patients with decreased serum Mg • Oral magnesium supplementation • 2.5g MgCl2 • Restores serum magnesium • Improves insulin sensitivity & metabolic control

  43. My Comments

  44. NAHSIT II (1999-2000) • 65+ years • Mg intake ~ 69-70% DRIs • Increasing risk of diabetes • Different Mg preparations in Taiwan • Effect of magnesium supplementation in health or high risk populations? • Further research

  45. Thanks for your attention!

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