1. Effects of Alcohol Use on the Incidence and Management of Diabetes Deborah Patrick Wubben, MD, MPH University of Wisconsin School of Medicine and Public Health

2. Objectives  Prevalence of co-occurring diabetes and alcohol abuse  Association of alcohol and diabetes incidence  Association of alcohol and heart disease incidence  Effects of alcohol on long-term and short-term glycemic control  Interactions of alcohol and antiglycemic medications

3. Prevalence of Diabetes and Alcohol Abuse  How likely am I to encounter a patient with diabetes and alcohol abuse in my primary care practice? How many adults with diabetes abuse alcohol? How many adults with diabetes abuse alcohol? How many adults who abuse alcohol have diabetes? How many adults who abuse alcohol have diabetes?

4. Prevalence of Alcohol Abuse in Patients with Diabetes  Among patients attending primary care clinics with DM type 1 or 2, prevalence of problem drinking was 8.1%.  Lower than other clinic averages, but similar to community samples. Variable Odds Ratio Black2.7 Male3.8 Black Men 13.4 Spangler et al. J Fam Pract, 1993. 37(4): p. 370-5.

5. Prevalence of Diabetes among Patients who Abuse Alcohol  ? DM prevalence in Wisconsin DM prevalence in Wisconsin All ages, 5.7% diagnosed, 2.3% undiagnosed, 8% totalAll ages, 5.7% diagnosed, 2.3% undiagnosed, 8% total Ages 45-64, 8% diagnosed, 3.2% undiagnosed, 11.2% totalAges 45-64, 8% diagnosed, 3.2% undiagnosed, 11.2% total Higher rates among Blacks/Hispanics/clinic populationsHigher rates among Blacks/Hispanics/clinic populations  Among patients with co-occuring psychotic and substance use disorders, 21% had diabetes. Over 12 years, 41% died, compared to 10% of those without diabetes Over 12 years, 41% died, compared to 10% of those without diabetes Wisconsin Diabetes Surveillance Report, 2005 Jackson et al. Psychiatr Serv, 2007. 58(2): p. 270-2

6. Association of Alcohol and Diabetes Incidence  Your patient’s question: Doc, doesn’t alcohol prevent diabetes? Doc, doesn’t alcohol prevent diabetes?  Your question: In adults, is the amount of alcohol use associated with diabetes incidence? In adults, is the amount of alcohol use associated with diabetes incidence?

7. Association of Alcohol and Diabetes Incidence  Definition of Alcohol Consumption Best studies used nondichotomous categorical measures Best studies used nondichotomous categorical measures However, most studies only measured use at baseline However, most studies only measured use at baseline  Definition of Diabetes Best studies used objective, standard screening test Best studies used objective, standard screening test  Study Design: Prospective Cohorts Many confounders that had to be controlled Many confounders that had to be controlled BMI, family history of diabetes, race, SES, smoking, prevalent CAD and cancer, diet and physical activityBMI, family history of diabetes, race, SES, smoking, prevalent CAD and cancer, diet and physical activity

8. Incidence of Type 2 DM in Men by Alcohol Drinks/Day Wei et al. Diabetes Care, 2000. 23(1): p. 18-22

9. Association of Alcohol and Heart Disease Incidence  Your patient’s question: Doc, doesn’t alcohol prevent heart disease? Doc, doesn’t alcohol prevent heart disease?  Your question: In adults with diabetes, is the amount of alcohol use associated with the incidence of heart disease? In adults with diabetes, is the amount of alcohol use associated with the incidence of heart disease?

10. Adjusted Relative Risks of CHD among Patients with Diabetes Solomon et al. Circulation, 2000. 102(5): 494-99 Tanasescu et al. J Am Col Card, 2001. 38(7): 1836-42.

11. Mechanisms for the Association between Alcohol and CHD: the difference between a little and a lot Blood Pressure ↓ ↑ Alcohol Use Moderate Heavy Insulin Sensitivity ↑ ↓ HDL ↑↑ Triglycerides ↑ Platelet Aggregation ↓ ↑ Fibrinolytic Activity  

12. Adjusted Mean Insulin Sensitivity by Alcohol Drinks/Day Model 1: adjusted for demographic (clinic, sex, ethnicity, age) and lifestyle (smoking, diet, physical activity) variables Model 2: also adjusted for BMI and waist circumference * * Bell et al. Diabetes Care 2000. 23: 1630-36.

13. Effects of Alcohol on Glycemic Control  Does alcohol use/abuse affect a patient’s long-term glycemic control?

14. A1C by daily Alcohol Use among Adults with DM Ahmed et al. Journal of General Internal Medicine, 2008. 23(3): p. 275-282

15. Effects of Alcohol on Glycemic Control  Does alcohol use/abuse affect a patient’s short-term glucose levels?

16. Hypoglycemia  Ethanol inhibits gluconeogenesis Oxidation of alcohol by dehydrogenases depletes NAD, a cofactor needed for entry of gluconeogenic precursors into the hepatocyte Oxidation of alcohol by dehydrogenases depletes NAD, a cofactor needed for entry of gluconeogenic precursors into the hepatocyte  lactate  gluconeogenesis  lactate  gluconeogenesis  After 48 g (4 glasses) of alcohol, gluconeogenesis decreases about 45%  If glycogen stores depleted, hypoglycemia occurs within 6 to 36 hours Wiel. Diabetes Metab Res Rev 2004. 20: 263-67.

17. Alcohol consumption with meals  Potential of reactive hypoglycemia After carbohydrate-rich meal plus alcohol, exaggerated insulin response can cause hypoglycemia after 2 to 3 hours After carbohydrate-rich meal plus alcohol, exaggerated insulin response can cause hypoglycemia after 2 to 3 hours Other studies have found only temporary post-meal hyperglycemia Other studies have found only temporary post-meal hyperglycemia  Most studies show no effect on glycemic profile Study of mineral water vs alcohol with a meal Study of mineral water vs alcohol with a meal Only difference was ↑ meal-induced insulin secretion with ↓ fasting glucose in patients with type 2 diabetes – not clinically significant Only difference was ↑ meal-induced insulin secretion with ↓ fasting glucose in patients with type 2 diabetes – not clinically significant Koivisto et al. Diabetes Care, 1993. 16(12): 1612-4.

18. Alcohol Consumption without Food  Type 1 DM ↓ glucose values throughout the night ↓ glucose values throughout the night ↑ hypoglycemic episodes the next morning, can be prolonged ↑ hypoglycemic episodes the next morning, can be prolonged Blunted nocturnal growth hormone response to hypoglycemia Blunted nocturnal growth hormone response to hypoglycemia  Type 2 DM Study varied % of alcohol content in non-alcoholic beer with same carbohydrate Study varied % of alcohol content in non-alcoholic beer with same carbohydrate Glucose levels similarGlucose levels similar  Alcohol =  Insulin levels  Alcohol =  Insulin levels Recovery from induced hypoglycemia was not affected by alcohol in diet-treated patients Recovery from induced hypoglycemia was not affected by alcohol in diet-treated patients Normal counter-regulatory hormone responses, but decreased peak glucagon responseNormal counter-regulatory hormone responses, but decreased peak glucagon response Rasmussen et al. Metabolism, 2001. 50(4): p. 451-7 Lange et al. Med Klin 1991. 86: 551-54. Turner et al. Diabetes Care 2001. 24: 1888-93. Christiansen et al. Eur J Clin Nutr 1993. 47:648-52.

19. Interactions of Alcohol and Antihyperglycemic Medications  Are there any diabetes medications that have negative side-effects when combined with alcohol?

20. Antihyperglycemic Meds and Alcohol  Sulfonylureas Possible increased risk of hypoglycemia if drinking alcohol while fasting Possible increased risk of hypoglycemia if drinking alcohol while fasting  Metformin Possible increased risk of lactic acidosis with heavy alcohol intake and/or liver disease Possible increased risk of lactic acidosis with heavy alcohol intake and/or liver disease

21. Summary of Possible Good Effects of Moderate Alcohol  ↑ insulin sensitivity  ↑ HDL  ↑ fibrinolytic activity  ↓ platelet aggregation  ↓ blood pressure  ↓ incidence of MI and death from CHD  ↓ incidence of diabetes

22. Summary of Possible Bad Effects of Heavy Alcohol in Patients with Diabetes  ↓ insulin sensitivity Also inhibits insulin secretion Also inhibits insulin secretion  ↑ triglycerides  ↑ free fatty acids, ketones, lactate ketoacidosis, and lactic acidosis  ↑ blood pressure  ↑ risk of hypoglycemia  All the other known risks – pancreatitis, cancers, liver disease, psychiatric problems, addiction, and shortened life-span