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Diet and Metabolic Syndrome: Practical Approaches to Lowering Risks of Heart Disease and Diabetes

Diet and Metabolic Syndrome: Practical Approaches to Lowering Risks of Heart Disease and Diabetes . Kevin C. Maki, PhD, FNLA, FTOS Midwest Center for Metabolic & Cardiovascular Research and DePaul University Chicago, Illinois. The Metabolic Syndrome.

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Diet and Metabolic Syndrome: Practical Approaches to Lowering Risks of Heart Disease and Diabetes

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  1. Diet and Metabolic Syndrome: Practical Approaches to Lowering Risks of Heart Disease and Diabetes Kevin C. Maki, PhD, FNLA, FTOS Midwest Center for Metabolic & Cardiovascular Research and DePaul University Chicago, Illinois

  2. The Metabolic Syndrome • A cluster of risk factors for heart disease and type 2 diabetes that occur together more than would be predicted by chance • Has been known by several names: • Syndrome X • Insulin Resistance Syndrome • The Deadly Quartet

  3. Metabolic Syndrome: Prevalence in U.S. by Age – 2001 ATP III Defn. Ford, et al. JAMA. 2002;287:356-9.

  4. Metabolic Syndrome Definition (AHA/NHLBI Revised) • Any three of the following: • Abdominal obesity: waist circumference • >102 cm (40 inches) for men • > 88 cm (35 inches) for women • Triglycerides: ≥150 mg/dL (or meds) • HDL cholesterol (or meds) • < 40 mg/dL (men) • < 50 mg/L (women) • Blood pressure: ≥130/85 mmHg (or meds) • Fasting glucose: ≥100 mg/dL (or meds)

  5. Additional Features of the Metabolic Syndrome (Under the Surface) • Insulin resistance and hyperinsulinemia • Small, dense LDL particles (Pattern B) • Pro-thrombotic and inflammatory states • ↑ fibrinogen • ↑ plasminogen activator inhibitor-1 • ↑ C-reactive protein • Elevated uric acid • Hypertrophy or hyperplasia • Heart, blood vessels, prostate, tumors

  6. Diabetes Mellitus: a US Pandemic • Diabetes mellitus affects 25.8 million people or 8.3% of the US population (1/3 undiagnosed) • It is estimated that 79 million US adults have pre-diabetes • Type 2 diabetes mellitus (T2DM) is a major cause of heart disease and stroke, and is the leading cause of kidney failure, lower-limb amputations, and blindness • Annual economic impact (direct and indirect): $174 billion http://www.ndep.nih.gov/diabetes-facts/#howmany

  7. Pathogenesis of Type 2 Diabetes: the Traditional Triumvirate HGP = hepatic glucose production DeFronzo RA. Diabetes. 2009;58:773-795.

  8. Glucose and Insulin Responses During 100 g Oral Glucose Tolerance Test (OGTT) Maki KC. Unpublished data.

  9. Beta-Cell Function in NFG, IFG, and Diabetes Oral disposition index All comparisons p < 0.001 Maki KC, et al. Nutr J. 2009;8:22.

  10. Glucose and Insulin Responses During a Liquid Meal Tolerance Test NFG = normal fasting glucose, IFG = impaired fasting glucose Maki KC, et al. Nutr J. 2009;8:22.

  11. Pathogenesis of Type 2 Diabetes: Quartet of Essential Defects DPP-IV = dipeptidyl peptidase-4 TZDs = thiazolidinediones DeFronzo RA. Diabetes. 2009;58:773-795.

  12. Role of Nocturnal Free Fatty Acids (FFAs) in Diet-Induced Obesity/Insulin Resistance in Dogs Dashed lines indicate 9:00 am feeding Open bars are pre- and filled bars are post- diet-induced obesity Kim SP, et al. Am J Physiol Endocr Metab. 2007;292:E1590-E1598.

  13. Raising FFA Induces Insulin Resistance in Healthy Subjects FFA level (µmol/L) • Saline n = 422 • Intralipid n = 588 LBM = lean body mass Mathew M, et al. Cardiovascular Diabetology. 2010:9:9.

  14. Lowering FFA with AcipimoxIncreasesInsulin Sensitivity Cusi K, et al. Am J Physiol Endocrinol Metab. 2007;292:E1775-E1781.

  15. Relation Between Weight Loss and Insulin Sensitivity According to Dietary CHO SSPG = steady-state plasma glucose McLaughlin T, et al. Am J Clin Nutr. 2006;84:813-821.

  16. Defects in Dysglycemia: Muscle, Liver, Pancreas, Adipose Tissue • Insulin resistance • Reduced ability of a given circulating level of insulin to enhance tissue uptake of glucose (particularly in skeletal muscle) • Reduced ability of a given circulating level of insulin to suppress hepatic glucose output and release of FFA from adipose depots • Excessive hepatic glucose output • Hepatic insulin resistance • Excess glucagon release + other factors (e.g., neural control) • Pancreatic beta-cell dysfunction • Reduced insulin response to a rise in plasma glucose • Reduced sensitivity to glucose signaling • Incretin resistance and deficiency • Lower insulin secretion capacity in advanced T2DM

  17. Risk Factors for Diabetes • Pre-diabetes (IGT, IFG, elevated HbA1C) • Overweight/obesity • Physical inactivity • Age ≥45 y • Family history of diabetes • Metabolic syndrome and its components • Certain racial and ethnic groups (e.g., Non-Hispanic Blacks, Hispanic/Latino Americans, Asian Americans, Pacific Islanders, American Indians and Alaska natives) • Women who have had gestational diabetes, or given birth to a baby weighing ≥9 lbs http://www.diabetes.org/diabetes-basics/prevention/risk-factors/

  18. Pre-Diabetes ADA. Diabetes Care. 2010;33(Suppl 1):S62-S69.

  19. Diabetes Prevention Studies Overview: Hypoglycemic Agents ACT NOW = Actos Now for the prevention of diabetes; TRIPOD = TRoglitazone in the Prevention Of Diabetes; XENDOS = XENical in the prevention of diabetes in obese subjects; DREAM = Diabetes REduction Assessment with rampiril and rosiglitazone Medication; CANOE = CANadian Normoglycemia Outcomes Evaluation

  20. Diabetes Prevention Studies Overview: Lifestyle Modification CHD = coronary heart disease DPP = Diabetes Prevention Program PREDIMED = Prevención con Dieta Mediterránea

  21. Diabetes Prevention ProgramLifestyle Targets: 7% Weight Loss, 150 min/wk Activity DPP N Engl J Med 2002; 346:393-403.

  22. Effect of Lifestyle Changes (Diet and Exercise) on Incidence of T2DM • A review of studies of 4864 high-risk individuals followed for 2.5-6 y reported • Lifestyle changes may lower incidence of T2DM by 28-59% • 6.4 individuals need to be treated to prevent or delay 1 case of diabetes through lifestyle changes (over 3-4 years) • Various weight loss diets (low fat, high protein, or Mediterranean) may be effective (weight loss more important than how achieved) • Maintenance of weight loss requires regular exercise with additional expenditure of ~2000 kcal/week (~15 miles of walking) Walker KZ, et al. J Hum Nutr Diet. 2010;23:344-352.

  23. Meta-Analysis: Estimates of Associations Between Macronutrient Intake and T2DM Risk CHO analysis: 10 cohort studies; fat analysis: 14 cohort studies; protein analysis: 4 cohort studies * A high vs. low intake of total CHO was associated with higher risk of T2DM (p = 0.035). † A high vs. low intake of vegetable fat was associated with lower risk of T2DM (p < 0.001). Alhazmi A, et al. J Am Coll Nutr. 2012;31:243-258.

  24. Risk of Developing T2DM Associated with Increased Glycemic Index and Load Results for glycemic load were similar to those for glycemic index. Glycemic load is affected by carbohydrate intake and glycemic index. Barclay AW, et al. Am J Clin Nutr.2008;87:627-637.

  25. Dietary Fibers and Diabetes Risk Schulze et al. Arch Intern Med 2007;167:956-965.

  26. Nurses Health Study: Relative Risk of T2DM by Different Levels of Cereal Fiber and Glycemic Load Salmeron J, et al. JAMA. 1997;227:472-477.

  27. Resistant Starch Intake Increases Insulin Sensitivity in Overweight and Obese Men HAM-RS2 = high-amylose maize type 2 resistant starch SI = insulin sensitivity Maki KC, et al. J Nutr. 2012;142:717-723.

  28. Effect of Short-Term (24 hr) Resistant Starch Consumption on Breath H2 and FFA (NEFA) Closed symbols are control and open symbols are resistant starch Robertson MD, et al. Diabetologia. 2003;46:659-665.

  29. Fermentable Dietary Fiber and Insulin Sensitivity Sleeth et al. Nutrition Research Reviews 2010;23:135–145

  30. Food Sources of Fermentable Fibers • Oats and barley (beta-glucan) • Prunes, apples and pears (pectin) • Nuts and seeds • Legumes • Multi-grain breads (those with ≥3 g fiber per slice)

  31. Sugar Sweetened Product Consumption Reduce Insulin Sensitivity Dairy = 2 servings per day of 2% milk and 1 serving of yogurt SSP = 2 servings per day of sugar-sweetened cola and 1 serving of non-dairy pudding Maki et al. Experimental Biology 2014 Abbreviations: AUC, area under the curve; HOMA2-%B, homeostasis model assessment 2-β-cell function; HOMA2-%S, homeostasis model assessment 2-insulin sensitivity Matsuda insulin sensitivity index; SSP, sugar-sweetened products. *P-values were calculated from a repeated measures ANCOVA model between dairy and SSP conditions (N = 34).

  32. Differences in Lipids and 25-OH Vitamin D Between Dairy and Sugar-sweetened Product Conditions Abbreviations: -C, cholesterol; HDL, high-density lipoprotein, LDL, low-density lipoprotein; SSP, sugar-sweetened products; TC, total cholesterol. *P-values were calculated from a repeated measures ANCOVA model between dairy and SSP conditions (N = 34).

  33. Dietary Macronutrient Compositionand T2DM Risk • Macronutrient changes and T2DM risk • Reduce intakes of foods high in refined carbohydrates (CHO) • Sugars and refined starches • Potential options for substitution • CHO-rich foods with low glycemic index, particularly whole grains that contain cereal and fermentable fibers • Fats (particularly vegetable fats) • Proteins • Alcohol

  34. High Cereal Fiber or Moderate Cereal Fiber and Moderate Protein Diet Improves Insulin Sensitivity Values are % of baseline, 3 = sig diff from HP, 4 = sig diff from baseline N = 111 overweight adults; M value = insulin-mediated glucose uptake as a measurement of whole-body insulin sensitivity; EGP = endogenous glucose production Weickert MO, et al. Am J Clin Nutr. 2011;94:459-471.

  35. Meta-Analysis of 74 Trials of High Protein vs. Lower Protein Diets on Health Outcomes Santesso N, et al. Eur J Clin Nutr. 2012;66:780-788.

  36. Potential Mechanisms for Higher Protein Diets and Weight Loss Hu FB. Am J Clin Nutr. 2005;82 (suppl):242S-247S.

  37. Energy Expenditure Higher After Protein vs. CHO Intake Acheson et al., Am J Clin Nutr 2011;93:525-534

  38. Appetite Visual Analog Scale Ratings Following Low vs. High Protein Breakfasts N = 34 healthy women; randomized controlled crossover trial 30 and 39 g protein produced greater appetite control throughout the morning vs. NB and LP (p < 0.001) LP = low protein breakfast (3 g protein), NB = no breakfast (water only) Rains TM, et al. Poster presented at The Obesity Society. November, 2013.

  39. Energy Intakes at Lunch Following Low vs. High Protein Breakfasts N = 34 healthy women; randomized controlled crossover trial LP = low-protein breakfast (3 g protein), NB = no breakfast (water only) Different letters indicate significant difference (p < 0.05); energy intake at lunch for 30 g Pro vs. LP was p = 0.053 Rains TM, et al. Poster presented at The Obesity Society. November, 2013.

  40. Effect of a Reduced Glycemic Load Diet (Lower CHO, Higher Protein and Fat) on Weight Loss ♦ Control diet (low-fat, portion control – 46/19/37% CHO/PRO/Fat) ■ Reduced glycemic load diet (32/26/42% CHO/PRO/Fat) Maki KC, et al. Am J Clin Nutr. 2007;85:724-734.

  41. POUNDS LOST: All Diets Resulted in Clinically Meaningful Weight Loss, But… Macronutrient intake targets at 6 and 12 months were not met N = 811 overweight adults Sacks FM, et al. N Engl J Med. 2009;360:859-873.

  42. POUNDS LOST: Targeted Differential PRO Intake Was Not Achieved Targets Sacks FM, et al. N Engl J Med. 2009;360:859-873.

  43. Protein and Glycemic Index in Weight Loss Maintenance • 548 participants completed the study • Results suggest that the high-protein, low glycemic index diet may help to reduce weight regain, although the effect was modest (3-4 lb) LP = low protein (13% en) HP = high protein (25% en) LGI = low glycemic index HGI = high glycemic index Larsen TM, et al. N Engl J Med. 2010;363:2102-2113.

  44. Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart) N = 164 individuals with prehypertension or stage 1 hypertension without diabetes Each feeding period lasted 6 wks, and body weight was kept stable CARB: carbohydrate-rich diet similar to Dietary Approaches to Stop Hypertension PROT: replacement of 10% of CHO calories with PRO (mixed source) UNSAT: replacement of 10% of CHO calories with unsaturated fats MUFA = monounsaturated fatty acids PUFA = polyunsaturated fatty acids SFA = saturated fatty acids Appel LJ, et al. JAMA. 2005;294:2455-2464.

  45. OmniHeart: Results for Measures of Insulin Sensitivity *p < 0.05 (for 1/HOMA-IR the increase compared to CARB was ~15%) QUICKI = quantitative insulin sensitivity check 1/HOMA = homeostasis model assessment of insulin resistance reported as the reciprocal Gadgil MD, et al. Diabetes Care. 2013;36:1132-1137.

  46. Other Dietary Factors Associated with Lower Risk of T2DM – Need More Research Before Specific Recommendations • Coffee • Especially in place of sugar-sweetened beverages • Polyphenols • Found in some foods and beverages • Berries, cherries, cranberries, coffee, tea, cocoa • Cinnamon • High doses of cinnamaldehyde • Magnesium • High levels in whole grain foods • Chromium • Dairy foods (esp. fermented dairy products) • Moderate alcohol consumption

  47. Dietary Supplements and Diabetes • Despite an increasing body of literature investigating the use of natural [dietary] supplements on the treatment of diabetes, the American Diabetes Association (ADA) does not recommend their use because: • Clinical evidence showing efficacy is insufficient • Standardized formulations are [often] lacking Allen RW. Ann Fam Med. 2013;11(5):452-459

  48. Theoretical Causal Model for Effects of Coffee on Risk of T2DM

  49. Coffee Intake and Reduced Risk of T2DM: Potential Mechanisms? • Anti-inflammatory (Frost Anderson, Jacobs, et al. AJCN 2006) • Coffee is a rich source of minerals and phytochemical compounds, including phenolics, that may confer protection from systemic inflammation • Systemic inflammation has been found to predict type 2 diabetes independent or traditional risk factors • Antioxidants (Svilaas et al., J Nutr 2004) • Coffee is a rich source of antioxidant compounds, may confer protection from oxidative stress • Oxidative stress is elevated in obesity and type 2 diabetes

  50. Polyphenols • Natural phytochemical compounds in plant-based foods (such as fruits, vegetables, whole grains, cereal, legumes, tea, coffee, wine and cocoa) • More than 8000 polyphenolic compounds have been identified • Several biological activities and benefits have been documented: • Examples include: • Antioxidant • Anti-allergic • Anti-inflammatory • Anti-viral / anti-microbial • May modulate important cell signaling ways: • Examples include: • Nuclear factor kappa-β (NF-κβ) • Activator protein-1 DNA binding (AP-1) • Extracellular signal-related protein kinase (ERK) Bahadoran Z. J Diab Met Disor. 2013;12:43-52

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