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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