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9/2/2016
1
A Dietary Approach to Insulin Resistance
and Associated Conditions
Developed in partnership with the National Board of Physician Nutrition Specialists
Faculty
Melina B. Jampolis, MD
Immediate Past President
National Board of Physician Nutrition Specialists
Author, The Doctor on Demand Diet
Los Angeles, California
Disclosures
Dr. Jampolis: Consultant – Prevention Pharmaceuticals; Board of Directors – TerraVia; Stock Shareholder—TerraVia
Learning Objectives
• Discuss the importance of dietary therapy in the prevention and treatment of insulin resistance (IR)
• Explain how specific macronutrients and foods affect IR
• Analyze the latest research on the role of phytonutrients, micronutrients, and the emerging importance of the microbiome in IR
• Discuss specific dietary approaches for diseases associated with IR
IR = insulin resistance.
Factors Associated with IR
PCOS = polycystic ovary syndrome.Adapted from Bays H. J Am Coll Cardiol. 2011;57(25):2461-2473.
Extrinsic factors
• Diet
• Sedentary
• Obesity
• Toxins
• Medications
• Immune
• Psych
• Statins
• Thiazides
• Beta-blockers
• Anti-retrovirals
Intrinsic factors
• Genetics
• Microbiome
• Sarcopenia
• Aging
• Diseases
• Pancreas
• Liver
• Endocrine
• Ovarian signaling
• Menarche
• Pregnancy
• Menopause
• PCOS
Does Diet Matter in IR?
VS
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Sodas
Cakes, pastries, donuts
Burgers/Cheeseburgers
Pizza
Chips/Popcorn
Rice
Rolls, buns, muffins, bagels
Cheese
Beer
French fries
7%
10%
13.8%
16.8%
19.7%
22.4%
25%
27.6%
30.2%
32.4%
Food Calories(cumulative)
Calorie Contribution of Foods in US Diet
Courtesy of Dr. Zhaoping Li.
Healthful Dietary Indexes
Harmon BE, et al. Am J Clin Nutr. 2015;01:587-597.
Healthy Eating Index: Waist circumference, HOMA-IR, CRP inversely related to adherence; adiponectin direct
association
Mediterranean Diet: Strongly reduced risk of cardio-metabolic disease
Alternative Healthy Eating Index: Greater adherence associated with MetS reversion mainly with central
obesity and high TG
DASH Diet: Reduced fasting insulin independent of weight loss (no benefit FBG or HOMA-IR)
Healthful Dietary Indexes and IR
HOMA-IR = homeostasis model assessment of insulin resistance; CRP = C-reactive protein; MetS = metabolic syndrome; TG = triglyceride; FBG = fasting blood glucose.Monfort-Pires, et al. Appl Physiol Nutr Metab. 2014;39(4):497-502. Akbaraly TN, et al. Diabetes Care. 2010;33(11):2339-2341. Shirani F, et al. Nutrition. 2013;29(7-8):939-947.
Macronutrients and IR
Dietary Fat: Composition of Oils
Personal Nutrition, 6th ed. Boyle & Anderson, Thomson/Wadsworth, 2007.
Common Sources of Saturated Fat
US Department of Agriculture. US Department of Health and Human Services. Dietary Guidelines for Americans 2010. www.dietaryguidelines.gov. Accessed September 2, 2016.
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Common Sources of Unsaturated Fat
PUFA = polyunsaturated fatty acid; MUFA = monounsaturated fatty acid.http://www.health.harvard.edu/staying-healthy/the-truth-about-fats-bad-and-good.
MUFAs
olive oil,
peanut oil
canola oil
avocados
most nuts
N3 PUFAs
fatty fish (salmon,
mackerel, and sardines)
flaxseeds
walnuts
canola oil
N6 PUFAs
vegetable oils:
safflower
soybean
sunflower
walnut
corn
• Many observational studies do not show an association between total fat intake and insulin sensitivity or risk of diabetes mellitus
• Excess saturated fat induces IR
• Trans fats strongly increase IR
• Unsaturated fats (PUFA, MUFA), especially when substituted for SFA or CHO, improve insulin sensitivity
Dietary Fat and IR
PUFA = polyunsaturated fat; MUFA = monounsaturated fat; SFA = saturated fat; CHO = carbohydrates.Sears B, et al. Lipids in Health and Disease. 2015;14:121.
MUFA and Diabetes Mellitus
Courtesy of Dr. Garcia-Fernandez, PREDIMED Study Group.
Avocados and Metabolic Syndrome
Fulgoni V, et al. Nutr J. 2013;12:1. Nutrition facts: http://www.ubuntufitness.com/ubuntofitblog/2015/8/8/lets-all-cool-it-on-the-healthy-fats.
Omega-3 Fatty Acids and IR
Kim YS, et al. Nutrients. March 2015;7(4):2085-2100.
Fat Modification and HOMA-IR Status
HSFA = high saturated fatty acid; HMUFA = high monounsaturated fatty acid; LFHCC = low-fat, high complex carbohydrate; LFHCC n-3 = low-fat, high complex carbohydrate with polyunsaturated fat. Modified from Yubero-Serrano EM, et al. Am J Clin Nutr. 2015;102(6):1509-1517.
HSFA Diet(n=39)
HMUFADiet(n=38)
LFHCC Control Diet (n=41)
LFHCC n-3 Diet(n=44)
Pre Post Pre Post Pre Post Pre Post P2
LowHOMA-IR status
Fastinginsulin mU/L
4.7
+/-1.7
6.8
+/- 4.2
5.3
+/- 0.8
5.5
+/- 1.9
5.4
+/- 1.1
6.2
+/- 1.9
5.4
+/- 2.1
5.4
+/- 2.3
.039
HOMA-IR 1.2
+/-0.4
1.9
+/- 1.2
1.3
+/- 0.4
1.4
+/- 1.0
1.3
+/- 0.3
1.6
+/- 0.9
1.3
+/- 0.4
1.8
+/- 0.8
.021
HighHOMA-IR status
Fastinginsulin mU/L
16
+/-2.7
14.9
+/- 3.2
15.4
+/- 3.3
13.1
+/- 2.9
15.7
+/- 4.3
14.8
+/- 5.9
15.7
+/- 4.0
13.0
+/- 4.9
.019
HOMA-IR 4.6
+/-0.3
4.3
+/- 1.9
4.2
+/- 0.2
3.5
+/- 0.8
4.4
+/- 1.2
3.9
+/- 1.8
4.5
+/- 1.2
3.6
+/- 1.3
.035
Effect of dietary fat modification on fasting glucose, insulin and markers of insulin sensitivity and secretion according to tertiles of low, medium, and high HOMA-IR status
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• Quantity and quality matter • Added sugar controversial but may
contribute to or exacerbate IR• Fiber improves insulin sensitivity • Poor diet induces changes in the
microbiome, which may increase inflammation, IR, and obesity
Dietary Carbohydrates
Simpson HL, et al. Aliment Pharmacol Ther. 2015;42(2):158-179. Stanhope KL. Crit Rev Clin Lab Sci. 2016;53(1)52-67.
Cereal Fiber, GI/GL,and Diabetes Mellitus
GI = glycemic index; GL = glycemic load. Bhupathiraju SN, et al. Am J Clin Nutr. 2014;100(1):218-232.
Resistant Starch and IR
Keenan, et al. Adv Nutr. 2015;6:198-205.
SSBs and IR
aP trend. Linear trend across the categories of SSB intake was tested by using the median SSB intake in each group as a continuous variable.bModels adjusted for: age (years), sex, BMI (kg/m2), cohort, smoking dosage (0, 1-15, 16-25, 26+ cigarettes/d), menopausal status (y/n), energy intake (kcal/d), and DGAI.SSB = sugar-sweetened beverage.Green et al. Obesity. 2014;22(5):E157-E163.
• Protein has weight loss benefits
– Satiety, blood sugar control(reduced HOMA-IR), preservesLBM during weight loss
• Diet x phenotype interaction• Protein source matters
Dietary Protein
Hill AM, et al. Am J Clin Nutr. 2015;102(4):757-770.
Dietary Protein x Phenotype
Noakes M, et al. Am J Clin Nutr. 2005;81:1298-1306.
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Red Meat and IR
Modified from Ley et al. Am J Clin Nutr. 2014;99(2): 352-360.
Fasting Insulin (μU/mL)
Unprocessed Red Meat
Medianintake (g/d)
16 (n=446)
38 (n=442)
62 (n=475)
103 (n=420)
Model 1 4.66 4.93 4.81 5.38 .0003
Processed Red Meat
Medianintake (g/d)
0 (n=429)
3 (n=475)
6 (n=437)
12 (n=442)
Model 1 4.58 4.68 5.25 5.26 <.0001
Red Meat Substitutions
Ley SH, et al. Am J Clin Nutr. 2014;99(2):352-360.
• Effect estimates for changes in biomarkers corresponding to substitution of 1 serving of red meat (total, unprocessed, or processed) with alternative protein foods
Yogurt and Metabolic Syndrome
Adapted from Wang H, et al. Nutr Res. 2013;33(1):18-26.
Associations between yogurt consumption and levels of metabolic factors
Non-consumers
Consumers –Low intake
Consumers –High intake
P trend P con vs. non-con
Median energy contribution from yogurt (kcal)
0 111 570
HDL 53 53 53.4 .29 .53TG 111.2 109.5 104.3 <.001 .01Glucose 98.7 97.9 96.5 <.001 <.001Insulin 83.8 83.2 70.4 <.001 .009SBP 121.7 120.5 119.8 <.001 <.001HOMA-IR 3.42 3.37 3.17 <.001 .001
Micronutrients and More
Polyphenols and IR
Courtesy of Bill Lagakos, PhD.
Green Tea and Glucose Control
Liu K, et al. Am J Clin Nutr. 2013;98(2);340-348.
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Resveratrol and IR
Liu K, et al. Am J Clin Nutr. 2014;99(6):1510-1519.
Spices and IR
Jungbauer A, et al. Maturitas. 2012;(71):227-239.
Magnesium and IR
Wang J, et al. Nutrients. 2013;(5):3910-3919.
Vitamin D and IR
Seida JC, et al. J Clin Endocrinol Metab. 2014;99(10):3551-3560.
Probiotics and IR
Ruan Y, et al. PLoS One. 2015;10(7):e0132121.
Advanced Glycation End-Products
Nowotny K, et al. Biomolecules. 2015;5(1):194-222. Courten BD, et al. Am J Clin Nutr. 2016;103:1426-1433.
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Diseases Associated with IR
Nonalcoholic fatty liver disease
Polycystic ovarian syndrome
Atherogenic dyslipidemia
Type 2 diabetes mellitus
Hypoandrogenemia
Obstructive sleep apnea
Dementia
Cancer
• Diets rich in whole grains, fruits, vegetables (especially leafy grains), legumes, nuts, moderate amount of dairy, and lower in refined grains, red/processed meats, and SSB reduce risk of diabetes mellitus and improve glycemic control in patients with diabetes mellitus
• Moderate alcohol consumption
• Optimal macronutrient ratio has not been clearly established
– Wide range of diet patterns that includenutrient-dense foods suitable
Diet and Type 2 Diabetes Mellitus
Sabaté J, et al. Br J Nutr. 2015;113(suppl 2):S136-S143.
Paleo Diet and Type 2Diabetes Mellitus
Masharani U, et al. Eur J Clin Nutr. 2015;69(8):944-948.
• Foods high in sugar/refined flour (CHO) may induce or amplify
• Replacing those CHO with protein is beneficial
• High-fiber, low sugar/refined CHO
• PREDIMED study
Atherogenic Dyslipidemia
CHO = carbohydrates. PREDIMED = Prevención con Dieta Mediterránea.Courtesy of Dr. Garcia-Fernandez, Predimed Study Group; Sears B, et al. Lipids in Health and Disease. 2015;14:121.
Atherogenic Dyslipidemia LC/HsF vs LC/LsF
1Values are mean ± SD, = 40. Means without a common letter differ, P < 0.05. The following traits were log-transformed prior to statistical analysis: TG, HDL-C, large VLDL, medium VLDL, small VLDL, total LDL, large LDL, medium LDL, small LDL, and very small LDL. HDL-C = HDL cholesterol; LCHSF = lower carbohydrate, high-saturated fat; LCLSF = lower carbohydrate, low-saturated fat; LDL-C = LDL cholesterol; non-HDL-C = non-HDL cholesterol; TC = total cholesterol.Mangravite LM, et al. J Nut. 2011;2180-2185.
ADMF and Atherogenic Dyslipidemia
*Significantly different between groups, P<.05 (one-way ANOVA). ADMF = alternate-day modified fasting. Varady KA, et al. Lipids Health Dis. 2011;10:119.
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• No consensus what diet best but moderate carbohydrates (40%-45%) + with increased MUFA and omega-3 PUFA + reduced SFAs may be beneficial
• Reduce SSB and added sugar and refined carbohydrates
• Vitamin E: Benefit in non-diabetic patients with NASH
• Polyphenols: Reduce liver fat accumulation
Diet and NAFLD
NAFLD = non-alcoholic fatty liver disease; NASH = non-alcoholic steatohepatitis. Sato K, et al. Nutrition. 2015;31(7-8):923-930. Del et al. Br J Clin Pharm. 2016; Nutr Res. Feb 2014: Houghton et al. Int J Mol Sci. 2016;17(4). pii: E447.
NAFLD and Mediterranean Diet
Sofi F, et al. World J Gastroenterol. 2014;20(23):7339-7346.
NAFLD, Diet, and Microbiome
Houghton D, et al. Int J Mol Sci. 2016;17(4).pii:E447.
• Lifestyle management first-line therapy, but optimal diet composition uncertain
• Weight loss MOST important
– Greater weight loss with MUFA-enriched diet
– Improved menstrual cycle with low GI diet
– Increased free androgen index for high CHO diet
– Greater reductions in IR, fibrinogen, total and HDL cholesterol with low-CHO or low GI diet
– Improved QOL with low GI diet
– Improved depression and self-esteem with high-protein diet
Diet and PCOS
Moran LJ, et al. J Acad Nutr Diet. 2013;113(4):520-545.
• Sit less• Boost exercise intensity (HIIT, HIRT)• Sleep better• Avoid tobacco• Manage stress (meditation)• Medications
Other Lifestyle Considerations for IR
HIIT = high-intensity interval training; HIRT = high-intensity resistance training. Jelleyman C, et al. Obesity Rev. 2015;16(11):942-961. Yates T, et al. Am J Prev Med. 2012;42(1):1-7.
What’s the “Take Home”?
• Healthful dietary patterns play an important role in the prevention and treatment of IR and associated conditions
• The optimal macronutrient composition of a healthful diet for IR and associated diseases has not been established, allowing for some flexibility in dietary approaches, which is helpful for compliance
• A healthful dietary pattern is naturally rich in beneficial micronutrients and phytonutrients, although supplementation may be beneficial in some situations
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Questions?
Special thanks to Drs. Zhaoping Li (VP, NBPNS) and Mike Rothkopf (President, NBPNS) for their assistance with this presentation