Dietary carbohydrates and metabolic outcomes: assessing the totality, consistency and quality of epidemiologic observations and clinical interventions

Transcription

1 Dietary carbohydrates and metabolic outcomes: assessing the totality, consistency and quality of epidemiologic observations and clinical interventions Simin Liu Department of Epidemiology Brown University Division of Endocrinology, Department of Medicine Rhode Island Hospital

2 Overview A diet that affects glucose homeostasis may be fundamental to vascular health outcomes Glycemic response, glycemic index, and glycemic load Supports from evolutionary theory, epidemiologic observations, and experimental evidence Functional measures to study diet and disease in human populations Biological intermediaries for diabetes and cardiovascular disease Sex, body weight, and age as important modifiers Conclusions Integrative framework for research Preventive recommendation

3 Pathogenesis of DM/CHD Related to Insulin Resistance Genes Obesity Gluco-recognition Beta-cell mass; Amyloid deposit Relative insulin deficiency Glycation of LDL Sorbitol NO/vasodilatory response Diets (high GL/insulin demand) Insulin resistance Hyperglycemia Hyperinsulinemia Dyslipidemia +TG - HDL Hypertension: Na+ retention; SNS+ Contractility+ Coronary Heart Disease Hemodynamic changes: inflammation, Impaired fibinolysis and tthrombosis Liu, 1998; Liu and Manson, 2001

4 Traditional Epidemiology: Common Risk Factors for Three Major Metabolic Diseases Risk factors Type 2 DM CHD Colon Ca. Age Tobacco Physical inactivity Obesity Sex?? Excess energy intake??? Saturated fat??? Red meat?? Refined carbohydrates??? Dietary fibers?? Fruits & vegetables?? Whole grains? Nuts/legumes?? Moderate Alcohol? Modified from Giovannucci 1995 and Liu 1998

5 Sex differences related to vascular outcomes in prospective studies BMI and risk of type 2 diabetes stronger in women Diabetes and risk of CVD mortality stronger in women Willett NEJM 1999; Huxley BMJ 2005

6 Dose-response relation between blood glucose and CHD risk (Levitan et al. Arch Int Med, 2004) Postchallenge Log relative risk Fasting Fasting Postchallenge Plasma glucose (mg/dl)

7 The effect of decreasing PPG with acarbose, an -glucosidase inhibitor, on DM development in a multicenter double-blind, placebo-controlled, randomized trial Chiasson et al. Lancet 2002

8 The effect of decreasing PPG with acarbose, an -glucosidase inhibitor, on CVD development in a multicenter double-blind, placebo-controlled, randomized trial Chiasson et al. JAMA 2004

9 GI & Voluntary Food Intake Ludwig et al. Pediatrics 1999, 103:e261 Kilocalories Consumed! 1500! 1000! 500! 0! 1! 2! 3! 4! 5! Time (hr) High GI! Med GI! Low GI! Cumulative Voluntary Food Intake

10 Low GI diets improve triglycerides Low GI diet compared with high GI diet Frost et al 1994 Fontvieille et al 1992 Wolever et al 1992 Fontvieille et al 1988 Jenkins et al 1985 Jenkins et al 1987 Jarvi et al 1999 Brand et al type 2, 12 wks 18 type 1 & 2, 5 wks 6 type 2, 6 wks 8 type 1, 3 wks 12 CHD, 4 wks 30 CHD, 4 wks 20 type 2, 24 days Average change in 8 studies = -12%! *Include extensive data from Prof.Y.X. Yang Chinese CDC

11 Average difference in HbA 1c in 9 studies = -11%! Adapted from Brand-Miller et al. 2001! Changes in HbA 1c or fructosamine Low GI diets compared with high GI diets Frost et al type 2, 12 wks! Fontvieille et al type 1 & 2, 5 wks! Brand et al type 2, 12 wks! Wolever et al type 2, 6 wks! Wolever et al type 2, 2 wks! Jenkins et al type 2, 4 weeks! Fontvielle type 1, 3 weeks! Collier et al type 1 children, 6 wks! Gilbertson et al type 1 children, 12 mo! !

12 Change in Glycemic Control Low vs high GI diets Glycemic control - 10% improvement for a 10 unit decrease in GI Comparison with other interventions DCCT - 20% UKPDS % Acarbose - 6.5% Insulin analogues - 2.5% Adapted from Stephen Colagiuri Aust Nutr Soc 2001

13 Fasting plasma TG concentrations by GL, GI and carbohydrate intake Fasting Triglycerides (mg/dl) Nurses Health Study Glycemic Index (p=0.03) Carbohydrate (p=0.005) Glycemic Load (p<0.001) Quintile of Intake b Liu et al. AJCN 2001

14 Fasting Plasma TG Levels by Dietary Glycemic Load Postmenopausal Women with Different BMI s 200 Fasting TG (mg/dl) BMI > 25 BMI < Q1 Q2 Q3 Q4 Q5 Quintile of Energy-adjusted Glycemic Load Liu et al. AJCN, 2001

15 Adjusted geometric mean plasma concentrations of high-sensitivity C-reactive protein (hs-crp) by quintiles (Q1 Q5) of energy-adjusted dietary glycemic load in 244 women in 2 BMI categories Liu S et al. Am J Clin Nutr 2002;75: ubsequently confirmed by Rhodes et al in a randomized trial of overweight pregnant women AJCN 2010

16 Geometric mean high density lipoprotein cholesterol and triglyceride levels* High density lipoprotein cholesterol level (mg/dl) High density lipoprotein cholesterol level (mg/dl) 40 P for interaction = 0.87 P for interaction = Normal weight Over weight Quintile of dietary glycemic index Quintile of dietary glycemic load Triglyceride level (mg/dl) P for interaction = 0.81 P for interaction = Triglyceride level (mg/dl) Quintile of dietary glycemic index Quintile of dietary glycemic load * Adjusted for age, smoking (current, past, never), exercise (4 category), hormone replacement therapy use (current, past, never), family history of MI, history of diabetes, body mass index (4 category), and intakes of total energy, alcohol intake (4 category), and quintile of total fat, protein, cholesterol, folate, and magnesium intake. Dietary glycemic load additionally adjusted for quintile of fiber intake

17 Relation between HDL-cholesterol concentration and glycemic index in men and women (Frost et al, 1999)

18 Adjusted for age, race or ethnicity, education, smoking status, body mass index, alcohol intake, physical activity, percent kilocalories from protein (quintiles), percent kilocalories from fat (quintiles), total energy intake (quintiles). Mean concentrations of HDL by glycemic index among men and women aged 20+ years, NHANES III, (Ford and Liu, Arch Int Med 2000) Women HDL cholesterol (mmol/l) Men P< <76% 76-79% 80-83% 84-87% >87% <76% 76-79% 80-83% 84-87% >87% Glycemic index quintiles

19 Results: Diet- by- sex interac3on % Total Adipose Growth (0 to 8 Weeks) 1200" 1000" 800" 600" 400" 200" 0" -200" Male Female BXD-20/TyJ" AXB-19/PgnJ" BXHA1" BXD-34/TyJ" C57BL/6J" BXA-16/PgnJ" BXD49" BXA-24/PgnJ" BXD-40/TyJ" NON/LtJ" BXA-14/PgnJ" BXD-13/TyJ" BXD79" CXB-6/ByJ" BXD-24/TyJ" CXBH" BXA-11/PgnJ" BXD51" C3H/HeJ" AXB-10/PgnJ" BXD66" BXH-6/TyJ" MA/MyJ" BUB/BnJ" CBA/J" BXH-19/TyJ" BXD56" CXB-12/HiAJ" BXD-6/TyJ" BXD-38/TyJ" AXB-15/PgnJ" RIIIS/J" AXB-18/PgnJ" BXA-2/PgnJ" DBA/2J" BXHB2" BXH-9/TyJ" BXD60" BXD-31/TyJ" BXD-12/TyJ" BXD-14/TyJ" FVB/NJ" BXD-19/TyJ" BTBRT<+>tf/J" AXB-6/PgnJ" A/J" BXA-7/PgnJ" C57BLKS/J" BXD43" BXD-32/TyJ" BXD55" BALB/cJ" BXD-1/TyJ" BXD-21/TyJ" CXB-11/HiAJ" BXA-4/PgnJ" BXA-1/PgnJ" SEA/GnJ" BXD-9/TyJ" CXB-13/HiAJ" PL/J" CXB-7/ByJ" SWR/J" CXB-3/ByJ" Slide courtesy of Drs Tom Drake & Jake Lusis

20 Mean conce among 1527 Crptox µ mol/l 0.5 lycopene Lutei beta-carote 0.25 α-carotene 0 Q1(Low) Q2Q3Q4Q5(Hig Quintile

21 Mean con by glycem 20 Q1(Low) Q2Q3Q4Q5(H Quintile O Vitam Vitam µmol

22 Potential biochemical mechanisms High GI/GL feeding causes: Postprandial hyperglycemia & hyperinsulinemia - (immediate responses) Counterregulatory hormonal responses which stimulate appetite, FFA production, and possibly protein breakdown (late responses) Shifts in substrate utilization away from fat towards carbohydrates Increased enzymatic capacities for carbohydrate oxidation and lipogenesis, and decreased enzymatic capacity of fat oxidation

23 Adjusted estimates of relative risk of type 2 diabetes according to GL by sex from a meta-analysis of all prospective cohorts with 7.5 million years of followup (up to August 2012) Livesay et al. Am J Clin Nutr 2013

24 Multivariate relative risk of CHD by body mass index and glycemic load Test for interaction, P < RR < >29 Tertile 3 Tertile 2 Tertile 1 GL BMI Liu et al 2000

25 Dairy foods Different constituents of a low GI/ GL diet Fruits and vegetables Whole grains Nuts Legumes (peas, beans, soybeans) Fish

26 Can we conclusively demonstrate the efficacy of glucose homeostasis diet on vascular health in randomized trials: Not feasible Not ethical Not necessary Conclusion Due to our genetic mal-adaptation to westernized lifestyle/ environment, we are increasingly becoming a metabolically efficient population Substantial evidence indicates significant biological importance and clinical utilities of the GI/GL concepts, in that 1) carbohydrate-containing foods differ in their abilities to raise plasma glucose and insulin (Level A), 2) diets characterized by high GL adversely affect metabolic intermediates (Level B), 3) may increase risk of vascular outcomes (diabetes and cardiovascular diseases) especially among those who are prone to insulin resistance (Level B and C)

27 Conclusion When thinking about diet, which is only one aspect of our westernized environment, we need to keep in mind what kind of people we have become metabolically. Consider sex, body weight, and age as important modifiers when assessing diet-disease relation and making dietary recommendation Reduce heterogeneity and improve biological understanding of the glucose homeostasis diet Regarding the clinical utility of the GI concept, It is better than the simple/complex in classifying carbohydrates Does go beyond individual food-based guidelines, even in the context of caloric density and nutrient composition GI is most useful for ranking high/dense-carbohydrate foods