Effects of Alcohol Use Effects of Alcohol Use on the Incidence and on the Incidence and

Management of DiabetesManagement of Diabetes

Deborah Patrick Wubben, MD, MPHDeborah Patrick Wubben, MD, MPH

University of Wisconsin School of University of Wisconsin School of Medicine and Public HealthMedicine and Public Health

ObjectivesObjectives Prevalence of co-occurring diabetes and alcohol Prevalence of co-occurring diabetes and alcohol

abuseabuse Association of alcohol and diabetes incidenceAssociation of alcohol and diabetes incidence Association of alcohol and heart disease Association of alcohol and heart disease

incidenceincidence Effects of alcohol on long-term and short-term Effects of alcohol on long-term and short-term

glycemic controlglycemic control Interactions of alcohol and antiglycemic Interactions of alcohol and antiglycemic

medicationsmedications

Prevalence of Diabetes and Prevalence of Diabetes and Alcohol AbuseAlcohol Abuse

How likely am I to encounter a patient with How likely am I to encounter a patient with diabetes and alcohol abuse in my primary diabetes and alcohol abuse in my primary care practice?care practice? How many adults with diabetes abuse How many adults with diabetes abuse

alcohol?alcohol?

How many adults who abuse alcohol have How many adults who abuse alcohol have diabetes?diabetes?

Prevalence of Alcohol Abuse in Prevalence of Alcohol Abuse in Patients with DiabetesPatients with Diabetes

Among patients Among patients attending primary attending primary care clinics with DM care clinics with DM type 1 or 2, type 1 or 2, prevalence of prevalence of problem drinking was problem drinking was 8.1%.8.1%.

Lower than other Lower than other clinic averages, but clinic averages, but similar to community similar to community samples.samples.

VariableVariable Odds Odds RatioRatio

Black Black 2.72.7

MaleMale 3.83.8

Black Black MenMen

13.413.4

Spangler et al. J Fam Pract, 1993. 37(4): p. 370-5.

Prevalence of Diabetes among Prevalence of Diabetes among Patients who Abuse AlcoholPatients who Abuse Alcohol

?? DM prevalence in WisconsinDM 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% Ages 45-64, 8% diagnosed, 3.2% undiagnosed, 11.2%

totaltotal• Higher rates among Blacks/Hispanics/clinic populationsHigher rates among Blacks/Hispanics/clinic populations

Among patients with co-occuring psychotic and Among patients with co-occuring psychotic and substance use disorders, 21% had diabetes.substance use disorders, 21% had diabetes. Over 12 years, 41% died, compared to 10% of Over 12 years, 41% died, compared to 10% of

those without diabetes those without diabetes

Wisconsin Diabetes Surveillance Report, 2005

Jackson et al. Psychiatr Serv, 2007. 58(2): p. 270-2

Association of Alcohol and Association of Alcohol and Diabetes IncidenceDiabetes Incidence

Your patient’s question:Your patient’s question: Doc, doesn’t alcohol prevent diabetes? Doc, doesn’t alcohol prevent diabetes?

Your question:Your question: In adults, is the amount of alcohol use In adults, is the amount of alcohol use

associated with diabetes incidence?associated with diabetes incidence?

Association of Alcohol and Association of Alcohol and Diabetes IncidenceDiabetes Incidence

Definition of Alcohol ConsumptionDefinition of Alcohol Consumption Best studies used nondichotomous categorical Best studies used nondichotomous categorical

measuresmeasures However, most studies only measured use at However, most studies only measured use at

baselinebaseline Definition of DiabetesDefinition of Diabetes

Best studies used objective, standard screening Best studies used objective, standard screening testtest

Study Design: Prospective CohortsStudy Design: Prospective Cohorts Many confounders that had to be controlledMany confounders that had to be controlled

• BMI, family history of diabetes, race, SES, smoking, BMI, family history of diabetes, race, SES, smoking, prevalent CAD and cancer, diet and physical activityprevalent CAD and cancer, diet and physical activity

Incidence of Type 2 DM in Men Incidence of Type 2 DM in Men by Alcohol Drinks/Dayby Alcohol Drinks/Day

00.5

11.5

22.5

33.5

4

incidence/1000 years

Wei et al. Diabetes Care, 2000. 23(1): p. 18-22

Association of Alcohol and Association of Alcohol and Heart Disease IncidenceHeart Disease Incidence

Your patient’s question:Your patient’s question: Doc, doesn’t alcohol prevent heart disease? Doc, doesn’t alcohol prevent heart disease?

Your question:Your question: In adults with diabetes, is the amount of In adults with diabetes, is the amount of

alcohol use associated with the incidence of alcohol use associated with the incidence of heart disease?heart disease?

Adjusted Relative Risks of CHD Adjusted Relative Risks of CHD among Patients with Diabetesamong Patients with Diabetes

00.20.40.60.8

1

None 0.1-4.9

>5

Grams/day

Risk of CHD among Women

0

0.2

0.4

0.6

0.8

1

None <0.5 0.5-2 >2

Drinks/day

Risk of CHD among Men

Solomon et al. Circulation, 2000. 102(5): 494-99 Tanasescu et al. J Am Col Card, 2001. 38(7): 1836-42.

Mechanisms for the Association between Mechanisms for the Association between Alcohol and CHD:Alcohol and CHD:

the difference between a little and a lotthe difference between a little and a lotBlood

Pressure↓↑

Alcohol UseModerate

Heavy

InsulinSensitivity

↑↓

HDL↑↑↑

Triglycerides

↑

Platelet Aggregation

↓↑ Fibrinolytic

Activity

Adjusted Mean Insulin Sensitivity Adjusted Mean Insulin Sensitivity by Alcohol Drinks/Dayby Alcohol Drinks/Day

00.20.40.60.8

11.21.41.61.8

Insulin Sensitivity

Never <0.5 0.5-0.99

1-2.99 >3

Drinks/Day

model 1model 2

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.

Effects of Alcohol on Effects of Alcohol on Glycemic ControlGlycemic Control

Does alcohol use/abuse affect a patient’s Does alcohol use/abuse affect a patient’s long-term glycemic control?long-term glycemic control?

A1C by daily Alcohol Use among A1C by daily Alcohol Use among Adults with DMAdults with DM

Ahmed et al. Journal of General Internal Medicine, 2008. 23(3): p. 275-282

Effects of Alcohol on Effects of Alcohol on Glycemic ControlGlycemic Control

Does alcohol use/abuse affect a patient’s Does alcohol use/abuse affect a patient’s short-term glucose levels?short-term glucose levels?

HypoglycemiaHypoglycemia Ethanol inhibits gluconeogenesisEthanol inhibits gluconeogenesis

Oxidation of alcohol by dehydrogenases depletes NAD, Oxidation of alcohol by dehydrogenases depletes NAD, a cofactor needed for entry of gluconeogenic precursors a cofactor needed for entry of gluconeogenic precursors into the hepatocyteinto the hepatocyte

lactate lactate gluconeogenesis gluconeogenesis

After 48 g (4 glasses) of alcohol, gluconeogenesis After 48 g (4 glasses) of alcohol, gluconeogenesis decreases about 45%decreases about 45%

If glycogen stores depleted, hypoglycemia occurs If glycogen stores depleted, hypoglycemia occurs within 6 to 36 hourswithin 6 to 36 hours

Wiel. Diabetes Metab Res Rev 2004. 20: 263-67.

Alcohol consumption with mealsAlcohol consumption with meals Potential of reactive hypoglycemiaPotential of reactive hypoglycemia

After carbohydrate-rich meal plus alcohol, exaggerated After carbohydrate-rich meal plus alcohol, exaggerated insulin response can cause hypoglycemia after 2 to 3 insulin response can cause hypoglycemia after 2 to 3 hourshours

Other studies have found only temporary post-meal Other studies have found only temporary post-meal hyperglycemiahyperglycemia

Most studies show no effect on glycemic profileMost studies show no effect on glycemic profile Study of mineral water vs alcohol with a mealStudy of mineral water vs alcohol with a meal Only difference was Only difference was ↑ ↑ meal-induced insulin secretion meal-induced insulin secretion

with with ↓ ↓ fasting glucose in patients with type 2 diabetes – fasting glucose in patients with type 2 diabetes – not clinically significantnot clinically significant

Koivisto et al. Diabetes Care, 1993. 16(12): 1612-4.

Alcohol Consumption without FoodAlcohol Consumption without Food Type 1 DMType 1 DM

↓ ↓ glucose values throughout the nightglucose values throughout the night ↑ ↑ hypoglycemic episodes the next morning, can be prolongedhypoglycemic episodes the next morning, can be prolonged Blunted nocturnal growth hormone response to hypoglycemiaBlunted nocturnal growth hormone response to hypoglycemia

Type 2 DMType 2 DM Study varied % of alcohol content in non-alcoholic beer with Study varied % of alcohol content in non-alcoholic beer with

same carbohydratesame carbohydrate• Glucose levels similarGlucose levels similar Alcohol = Alcohol = Insulin levels Insulin levels

Recovery from induced hypoglycemia was not affected by Recovery from induced hypoglycemia was not affected by alcohol in diet-treated patientsalcohol in diet-treated patients

• Normal counter-regulatory hormone responses, but decreased peak Normal counter-regulatory hormone responses, but decreased peak glucagon responseglucagon response

Rasmussen et al. Metabolism, 2001. Rasmussen et al. Metabolism, 2001. 5050(4): p. 451-7(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.

Interactions of Alcohol and Interactions of Alcohol and Antihyperglycemic MedicationsAntihyperglycemic Medications

Are there any diabetes medications that Are there any diabetes medications that have negative side-effects when combined have negative side-effects when combined with alcohol?with alcohol?

Antihyperglycemic Meds and AlcoholAntihyperglycemic Meds and Alcohol

SulfonylureasSulfonylureas Possible increased risk of hypoglycemia if Possible increased risk of hypoglycemia if

drinking alcohol while fastingdrinking alcohol while fasting

MetforminMetformin Possible increased risk of lactic acidosis with Possible increased risk of lactic acidosis with

heavy alcohol intake and/or liver diseaseheavy alcohol intake and/or liver disease

Summary of Summary of PossiblePossible Good Effects of Good Effects of Moderate AlcoholModerate Alcohol

↑ ↑ insulin sensitivityinsulin sensitivity ↑ ↑ HDLHDL ↑ ↑ fibrinolytic activityfibrinolytic activity ↓ ↓ platelet aggregationplatelet aggregation ↓ ↓ blood pressureblood pressure ↓ ↓ incidence of MI and death from CHDincidence of MI and death from CHD ↓ ↓ incidence of diabetesincidence of diabetes

Summary of Summary of PossiblePossible Bad Effects of Heavy Bad Effects of Heavy Alcohol in Patients with DiabetesAlcohol in Patients with Diabetes

↓ ↓ insulin sensitivityinsulin sensitivity Also inhibits insulin secretionAlso inhibits insulin secretion

↑ ↑ triglyceridestriglycerides ↑ ↑ free fatty acids, ketones, lactate ketoacidosis, free fatty acids, ketones, lactate ketoacidosis,

and lactic acidosisand lactic acidosis ↑ ↑ blood pressureblood pressure ↑ ↑ risk of hypoglycemiarisk of hypoglycemia All the other known risks – pancreatitis, cancers, All the other known risks – pancreatitis, cancers,

liver disease, psychiatric problems, addiction, liver disease, psychiatric problems, addiction, and shortened life-spanand shortened life-span