2021 Chrystyne Olivieri, DNP, FNP-BC, CDCES

2021 Chrystyne Olivieri, DNP, FNP-BC, CDCES

You cannot fool Mother Nature for very longby attempting to alter the way your body works with pills and drugs

Hopefully you will come to realize thatthe answer liesin how you live your life

Chrystyne Olivieri, DNP, FNP-BC, CDCES


OBESITY & INSULIN RESISTANCE

What does it have to do with Type 2 Diabetes and Cardiovascular Disease?

Chrystyne Olivieri, DNP, FNP-BC, CDCESAssistant Graduate Nursing Professor, Long Island University

[email protected]

mailto:[email protected]


Learner Goals

After this presentation, the learner will be able to: 1. Accurately identify patients with Obesity and Insulin Resistance

risk factors 2. Feel confident to provide early intervention education to at risk

patients 3. Discover the use of diagnostic tools and pharmacological

interventions to help discourage the progression to Type 2 Diabetes and Cardiovascular Disease

4. Understand the importance of close follow up with at-risk populations


Statistics• Obesity:

• Prevalence in US increased from 30.5% to 42.4% (2000-2018)* 1

• Morbid Obesity rose from 4.7% to 9.2%

• Diabetes:• 34.2 m Americans (1:10) have Diabetes 2

• 88 m Americans (1:3) have Prediabetes• Most don’t know

• 2030 there will be over 19.6 million more people living with diabetes (to almost 55 million people) 3

• This is believed to reach a staggering 1 in 3 Americans by 2050


Statistics

• Cardiovascular Disease: 3

• #1 cause of death among Americans*• 1:4 American deaths attributed to CVD• Annual American MI’s

• >600,000 are primary• 200,000 are subsequent

• According to AHA, having diabetes is considered a “cardiovascular risk equivalent”** 4


Recent Scientific Data on Human Health• Early 20th century anthropological studies of Indigenous Cultures• Astonishing lack of chronic disease

• Health deterioration with Standard American Diet

• Studies 1906-1990’s:• Vilhjhalmur Stefansson 5: Alaskan & Canadian natives• George V. Mann 6: Masai tribesmen, Kenya• Pedro Carrera-Bastos 7: Kitava, Trobriand Islands• Magdelena Hurtado 8: Ache, Paraguay• Herman Pontzer 9: Hazda, Savannah, Northern Tanzania• Leslie Schulz10: Pima Indians, Arizona and Mexico


Dual Burden of Disease*

• Overfed, Undernourished 12

• WHO declared obesity a worldwide epidemic 13

• Overweight/obese in U.S. 68% of population• Obesity in U.S. 35% men and >40% women 14

• AHA, ADA and USDA guidelines• Data collection flawed, Observational Data• Ancel Keys 7 Countries Study 15

• SAD**• Food distribution, food deserts


Is Obesity the Main Problem*?

• Obesity is a disease of leptin & insulin resistance• Hormonally driven**• Occurs over decades due to overexposure to insulin

• Causes of Modern Obesity:• Low fat, high carb diet• More overall daily eating• More eating out including fast-food• Increased portion sizes• More time spent sedentary• More dietary sweets and sugars (HFCS)**

• Not everyone has the genetics for Obesity


The Thin-Unhealthy 16,17

TOFI – Thin on the outside, Fat on the inside

• Health is not about overall body weight

• Exposure to sugar and carbs tells the story

• Chronic state of “hyperinsulinemia”

• Eventually “insulin resistance” develops


Types of Body Fat

• White vs Brown Fat – Each very different

• White Adipose Tissue• Subcutaneous fat is peripheral• Visceral fat is inflammatory, deep around organs• Result of excessive carbohydrates stored as potential energy

• Brown Adipose Tissue• Produces energy as warmth, increases energy expenditure• Increases with regular exercise and exposure to cold


Calories in = Calories out?Why conventional diets fail*

• Energy input and output are dependent upon each other• If input decreases, so does output• If input increases, fat storage occurs

• Dysmetabolic Syndrome (IR) is the driver• Fats may be calorically dense, but do not spark insulin release• Carbohydrates spark the most insulin release• Insulin is the driver of weight gain and weight loss**

• Diets fail because insulin is ignored• Insulin levels rise YEARS before blood glucose levels rise


Insulin Resistance in the Modern World

• 88% of American adults are metabolically unfit* 11• Based on WC, B/P, blood glucose, TG and HDL

• Insulin Resistance is strongly associated with:• Obesity• T2DM• CVD• Cancer• NAFLD• PCOS, Infertility and ED• Migraines, Arthritis, Stroke, Dementia…*


Insulin Resistance = Dysmetabolic Syndrome• Fasting glucose (FPG) 100-125• 2 hour post glucose 140-199• A1C 5.7% to 6.4%• Waist circumference > 40”(m), >35”(f)• Serum TG >150• HDL <40 (m), <50 (f)• B/P >130/85 or on anti-hypertensives• Left unaddressed can ABSOLUTELY progress to T2DM


Insulin ResistanceDysmetabolic Syndrome

• Insulin Resistance is the result of overexposure• Insulin drives abdominal fat accumulation• Adipose tissue develops insulin resistance• Muscle cells develop insulin resistance• Liver stimulates lipogenesis and glycogenesis (storage)

• Very delicate hormonal system gone awry• When blood glucose falls, glucagon releases stored liver glucose• Hypoglycemia and A1c below 5% can be early signs


Complications of Insulin ResistanceCommonly seen at time of T2DM diagnosis

Well known:• Retinopathy• Nephropathy• Neuropathy• CVD-MI-PVD

Not well known:• NAFLD*• ED• Vitamin D deficiency• Reflux• Cataracts• Anxiety/Depression*• Osteoporosis*• Gout

• Sleep Apnea• Alzheimer’s*• Chronic UTI’s• Chronic Candida• Asthma*• Eczema/Psoriasis• Macular Degeneration• Hypothyroidism*


NAFLD and IRNon-Alcoholic Fatty Liver Disease

• Fructose drives NAFLD 23

• HFCS* associated with elevated uric acid and MetSynd• Fructose must be first metabolized through the liver (glycolysis) 24

• Sucrose = 50% fructose/50% glucose• HFCS = 55% fructose/45% glucose

• Obese children (as young as 5) with NAFLD 25

• Present in 1/3 boys and ¼ girls

• Associated with dysbiosis, DysmetSynd, T2DM and obesity 26,27

• Affecting 50-75% in Prediabetes and T2DM**


NAFLD and IR

• NAFLD most rapidly growing liver disease worldwide* 28

• Estimates of 80 million Americans have NAFLD 29

• How does fat get into the liver?• Corn-fed beef vs Grass-fed beef• Sugar from Fructose (fruit, sucrose and HFCS)

• Liver fat is MORE dangerous than visceral fat• New! Non-Alcoholic Fatty Pancreas Disease 30


Cardiovascular Disease and IR

• Sugar and Insulin* 31,32

• Constant, long-term intake• Hyperlipidemia concurrent*

• Related to intake of sugar and carbohydrates• Reflection of elevated inflammation

• Micro and Macrovascular damage• Inflammatory response to tissue injury• Oxidative Stress*

• Reduced NO causes ROS dysfunction 37


Pathway to Diabetic CardiomyopathyHFrEF

EF% <45% Systolic Dysfunction

LV Hypertrophy Elevated BNP

Metabolic Syndrome w/o Hyperglycemia Oxidative Stress T2DM

HyperinsulinemiaDevelopment of AGEs (Glycation)

HFpEFDiastolic Diabetic Cardiomyopathy

Diastolic Dysfunction

Elevated CRP

Increased FFA, ROS, Cardiac Remodeling

ROSEndothelial Dysfunction

Hyper-coaguabilityand Fibrosis

Increased Risk of MI, Stroke, HF

Typical HF pathway is result of MI

Typical Pathway usually Systolic HFrEFDiabetic Cardiomyopathy usually Diastolic HFpEF


Cardiovascular Disease and IR• Prediabetes strongly associated with atherosclerotic CVD events 33

• Hyperinsulinemia• Link between Diabetes and Heart Failure is well documented*34

• Microvascular Dysfunction• Long-term overweight/obese are on a trajectory for CVD 35

• UK cohort of over 260,000 individuals• Artificial sweeteners contribute to higher CVD risk 31

• ACC cohort of over 100,000 individuals – risk increases 20-32%• Ultra-processed foods worsens CVD outcomes 36

• Framingham Heart Study*• High GI diets definitively linked to CVD** 32

• All carbohydrates are NOT the same


Sugar vs Fat Metabolism

• Sugar (glucose) is an easier molecule for the body to burn than fat• Fat is larger and more complex but preferred fuel source• Insulin is the main driver of weight loss/gain• Insulin levels drop with a diet low in sugar/carbohydrates• Must reduce/eliminate dietary sugar and simple carbohydrates to

encourage fat metabolism


Macronutrients

• Carbohydrates burn at 4 calories/gram

• Fats burn at 9 calories/gram

• These calories must be converted to the more basic fuel source:ATP (Adenosine Triphosphate)

• Protein is rarely used as a fuel source


ATP

• Glucose produces 36 ATP per molecule• Medium-chain Fatty Acids (fats) produce 50 ATP • Long-chain Fatty Acids (also fats) produce 155 ATP

• Body fat is triglycerides (1 glycerol + 3 LCFA) = 465 ATP

This can only happen when glucose is less available

18 Olivieri, C. Combating Insulin Resistance with the Paleo Diet. The Nurse Practitioner Journal. 49-55 February 2019

Triglyceride lowering diet


Sugar Availability

• Fruit in season• Increases insulin levels• Abdominal adiposity• WINTER!!• Thrifty gene Theory* 19,20

• DNA unchanged in last 40,000 years 21,22


MetforminBrand names: Glucophage, Glumetza, Fortamet & Riomet

• First used in 1929 when it was found to “lower” blood glucose• Widely released in U.K, then Canada in 1958, as a drug for hyperglycemia 38

• Gained popularity in the U.S. in 1995, with it’s utilization as an anti-diabetic agent for those with T2DM

• Dosing should be slow: Start with 500mg tablets• Week #1 – Start with 1 pill at dinner time• Week #2 – If tolerated, increase to 1 pill at breakfast & 1 pill at dinner time.• Week #3 – If tolerated, increase to 1 pill at breakfast & 2 pills at dinner time.• Week #4 – If tolerated, increase to 2 pills at breakfast & 2 pills at dinner time.

• Adult patients are usually best served to use a full 2000mg daily


Metformin• Pharmacology:

• CYP450, no substrate• NOT metabolized in the liver• excreted in urine 100%• half-life 6 hours (plasma) and 18 hours (blood)

• NOT known to cause hypoglycemia• May be used with patients with mild renal insufficiency* 39

• Several observational studies have shown it may have “anti-cancer” properties 40

• Watch Vitamin B12 levels


Metformin

Diarrhea often resultof a “sick” Microbiome

Must fix the Microbiomefor metformin to be tolerated

Alcohol intake not recommended


GLP-1 Agonists

• Activates GLP-1 receptors, leptin & ghrelin, increases insulin secretion, decreases glucagon secretion, delays gastric emptying

• Always start with lowest dose and titrate up as tolerated• Victoza (liraglutide)

• Daily injections; no timing issues

• Bydureon (exenatide), Trulicity (dulaglutide), Ozempic (semaglutide)• Weekly injections

• Rybelsus (semaglutide)• First oral GLP-1 Agonist• No hepatic or renal dose adjustments needed


GLP-1 Agonists for Weight Loss

• Saxenda (liraglutide) 3mg• SC daily injection, slowly titrate up

• Wegovy* (semaglutide) 2.4mg• SC weekly injection, slowly titrate up

• Just FDA approved 6.4.2021

Tirzepatide* – excellent weight loss and A1creduction – not yet FDA approved


SGLT2 Inhibitors

Inhibit sodium-glucose cotransporter 2 (SGLT2), reducing glucose reabsorption and increasing urinary glucose excretion

• canagliflozin (Invokana) - 100mg/300mg once daily• empagliflozin (Jardiance) – 10mg/25mg once daily• dapagliflozin (Farxiga) – 5mg/10mg once daily• ertugliflozin (Steglatro) – 5mg/15mg once daily

All available in combination with metformin


Weight Loss Drugs - oral

• Contrave (naltrexone/bupropion) 8mg/90mg BID• Schedule IV: low dependency/abuse potential• Many side effects – monitor B/P closely, slowly titrate up/down*

• Dextroamphetamine 5mg, 10mg, 15mg QD• Schedule II: high dependency/abuse potential• Many cardiovascular side effects, slowly titrate up/down*

• Phentermine 15mg, 30mg, 37.5mg QD• Schedule IV: low/moderate abuse potential• Many cardiovascular side effects, taper to d/c

• Qsymia* (phentermine/topiramate) 3.75/23mg, 7.5/46mg, 11.25/69mg, 15/92mg QD

• Slowly titrate up/down


Resources for NPs and CDCESs

• American Diabetes Association Membership for Professionals - ADA• www.professional.diabetes.org

• Association for Diabetes Care and Education Specialists - ADCES• www.diabeteseducator.org

• Certification Board of Diabetes Care and Education – CDCES certification• www.cbdce.org

http://www.professional.diabetes.org/

http://www.diabeteseducator.org/

http://www.cbdce.org/


References1. Centers for Disease Control and Prevention: Overweight & Obesity: Adult Obesity Facts https://www.cdc.gov/obesity/data/adult.html

2. Centers for Disease Control and Prevention: Diabetes: National Diabetes Statistics Report, 2020 https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html

3. Centers for Disease Control and Prevention: Heart Disease: Heart Disease Facts in the U.S. https://www.cdc.gov/heartdisease/facts.htm

4. Cardiovascular Disease & Diabetes. American Heart Association, Conditions. www.heart.org/HEARTORG/Conditions/More/Diabetes/WhyDiabetesMatters/Cardiovascular-Disease-Diabetes_UCM_313865_Articles.jsp/#.

5. Stefansson, V. (1921). The Canadian Arctic Expedition of 1913 to 1918. Geographical Journal, 283-305.

6. Mann, G. V., Shaffer, R., Anderson, R., Sandstead, H., Prendergast, H., Mann, J., . . . Monah, J. O. (1964). Cardiovascular disease in the Masai. Journal of atherosclerosis research, 4(4), 289-312.

7. Carrera-Bastos, P., Fontes-Villalba, M., O’Keefe, J. H., Lindeberg, S., & Cordain, L. (2011). The western diet and lifestyle and diseases of civilization. Res Rep Clin Cardiol, 2, 15-35.

8. Hill, K. R., & Hurtado, A. M. (1996). Ache life history: The ecology and demography of a foraging people: Transaction Publishers.

9. Pontzer, H., Raichlen, D. A., Wood, B. M., Mabulla, A. Z., Racette, S. B., & Marlowe, F. W. (2012). Hunter-gatherer energetics and human obesity. Plos one, 7(7), e40503.

10. Schulz, L. O., Bennett, P. H., Ravussin, E., Kidd, J. R., Kidd, K. K., Esparza, J., & Valencia, M. E. (2006). Effects of traditional and Western environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the U.S. Diabetes Care, 29(8), 1866-1871.

11. Araujo, J., Cai, J., Stevens, J. “Prevalence of optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey (NHANES) 2009-2016”. Metabolic Syndrome and Related Disorders (2019): 17(1)

12. Varela-Silva, M. I., Dickinson, F., Wilson, H., Azcorra, H., Griffiths, P. L., & Bogin, B. (2012). The nutritional dual-burden in developing countries--how is it assessed and what are the health implications? Collegium Antropologicum, 36(1), 39-45.

13 World Health Organization (WHO) (2014) Double Burden of Malnutrition. Retrieved from https://www.who.int/nutrition/double-burden-malnutrition/en/

14. State of Obesity (2019) Obesity Rates and Trends: Adult Obesity in the U.S. (1990-2017). https://www.stateofobesity.org/data/

15. Keys, A. (1980). Seven countries. A multivariate analysis of death and coronary heart disease: Harvard University Press.

https://www.cdc.gov/obesity/data/adult.html

https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html

https://www.cdc.gov/heartdisease/facts.htm

http://www.heart.org/HEARTORG/Conditions/More/Diabetes/WhyDiabetesMatters/Cardiovascular-Disease-Diabetes_UCM_313865_Articles.jsp/


References16. Golabi, P et al. “Patients with Lean Nonalcoholic Fatty Liver Disease are Metabolically Abnormal and have a Higher Risk for Mortlity” ADA Clinical Diabetes Journal 37,1 (2019): 65-72

17. Zhou, Z., Macpherson, J., Gray, S.R. et al. “Are People with Metabolically Healthy Obesity Really Healthy? A Prospective Cohort Study of 381,363 UK Biobank Participant” Diabetologia (2021).

18. Olivieri, C. Combating Insulin Resistance with the Paleo Diet. The Nurse Practitioner Journal. 49-55 February 2019

19. Eaton, S. B. (2006). The ancestral human diet: what was it and should it be a paradigm for contemporary nutrition? Proceedings of the Nutrition Society, 65(01), 1-6.

20. Neel, J. V., Weder, A. B., & Julius, S. (1998). Type II diabetes, essential hypertension, and obesity as" syndromes of impaired genetic homeostasis": the" thrifty genotype" hypothesis enters the 21st century. Perspectives in biology and medicine, 42(1), 44-74.

21. Prentice, A.M., B.J. Hennig, and A.J. Fulford. “Evolutionary Origins of the Obesity Epidemic. Natural Selection of Thrifty Genes or Genetic Drift Following Predation Release?” International Journal of Obesity 32 (2008): 1607.

22. Krishnaswamy, K. (2012). Evolutionary aspects of diets in the context of current chronic diseases. Bulletin of the Nutrition Foundation of India, 33(1).

23. Jensen, Thomas, et al. "Fructose and sugar: A major mediator of non-alcoholic fatty liver disease." Journal of hepatology 68.5 (2018): 1063-1075.

24. Kyoko Nomura, Toshikazu Yamanouchi, “The Role of Fructose-Enriched Diets in Mechanisms of Nonalcoholic Fatty Liver Disease”, The Journal of Nutritional Biochemistry (2012) Volume 23, Issue 3, pages 203-208

25. Elizabeth, L. Yu, et al. "Prevalence of nonalcoholic fatty liver disease in children with obesity." The Journal of pediatrics 207 (2019): 64-70.

26. Lee, Yong Ho et al. “Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis.” Diabetes & Metabolism Journal vol. 43,1 (2019): 31-45. doi:10.4093/dmj.2019.0011

27. Sivabal Vanjiappan, et al., “Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus and its Association with Cardiovascular Disease,” Diabetes & Metabolic Syndrome: Clinical Research & Reviews, Volume 12, Issue 4, (2018): 479-482

28. Paik, J.M., Golabi, P., Younossi, Y., Mishra, A. and Younossi, Z.M. “Changes in the Global Burden of Chronic Liver Diseases From 2012 to 201: The Growing Impact of NAFLD”. Hepatology, 72 (2020): 1605-1616.

29. Ciardullo, S, Perseghin, G. “Prevalence of NAFLD, MAFLD and Associated Advanced Fibrosis in the Contemporary United States Population”. Liver Int. (2021): 41: 1290–1293


References30. Filippatos, T.D., Alexakis, K., Mavrikaki, V. et al. “Nonalcoholic Fatty Pancreas Disease: Role in Metabolic Syndrome, Prediabetes, Diabetes and Atherosclerosis”. Digestive Diseases & Sciences (2021).

31. Eloi Chazelas, et al. “Sugary Drinks, Artificially-Sweetened Beverages, and Cardiovascular Disease in the NutriNet-Santé Cohort”. Journal of the American College of Cardiology, 2020; 76 (18): 2175

32. Jenkins, D.J.A., et al. “Glycemic Index, Glycemic Load and Cardiovascular Disease and Mortality”. New England Journal of Medicine. (2021) April, 8. 384:1312-1322

33. Honigberg, M.C., et al. “Cardiovascular and Kidney Outcomes across the Glycemic Spectrum: Insights from the UK Biobank”. Journal of the American College of Cardiology., May 17, 2021

34. Mehta, Adi, et al. “Diabetes and Heart Failure: A Marriage of Inconvenience.” Clinics in Geriatric Medicine, vol. 36, no. 3, Aug. 2020, pp. 447–455.

35. Iyen, B., Weng, S., Vinogradova, Y. et al. “Long-term body mass index changes in overweight and obese adults and the risk of heart failure, cardiovascular disease and mortality: a cohort study of over 260,000 adults in the UK”. BMC Public Health (2021): 21, 576

36. Ostfeld, R., Allen, K.E. “Ultra-Processed Foods and CVD: Where do we go from here?” Journal of the American College of Cardiology. (2021) March, 77(21) 1532-1534

37. Forrester, S.J., et al. “Reactive Oxygen Species in Metabolic and Inflammatory Signaling.” Circulation Research. (2018) 122:877-902

38. Dronsfield, A., Ellis, P. Drug Discovery: Metformin and the Control of Diabetes. Education in Chemistry, November 2011. www.rsc.org/eic

39. Metformin gains FDA approval to be used in patients with mild renal insufficiency. www.fda.gov/Drugs/DrugSafety/ucm493244.htm

40. Leone, A., Di Gennaro, E., Bruzzese, F., Avallone., A., & Budillon, A. (2014). New perspective for an old antidiabetic drug: metformin as anticancer agent. Advances in Nutrition and Cancer (pp.355-376): Springer

http://www.rsc.org/eic


Together, we can overcome Diabesity!!

Documents

2021 Chrystyne Olivieri, DNP, FNP-BC, CDCES