Consequences of Alcohol Use in Diabetics Nicholas V. Emanuele, M.D., Terrence F. Swade, M.D., and Mary Ann Emanuele, M.D. The hormone insulin, which is produced in the pancreas, is an important regulator of blood sugar levels. In people with diabetes, the pancreas does not produce sufficient insulin (type 1 diabetes) or the body does not respond appropriately to the insulin (type 2 diabetes). Alcohol consumption by diabetics can worsen blood sugar control in those patients. For example, long-term alcohol use in well-nourished diabetics can result in excessive blood sugar levels. Conversely, long-term alco- hol ingestion in diabetics who are not adequately nourished can lead to dangerously low blood sugar levels. Heavy drinking, particularly in diabetics, also can cause the accumulation of certain acids in the blood that may result in severe health consequences. Finally, alcohol consumption can worsen diabetes-related medical complications, such as disturbances in fat metabolism, nerve damage, and eye disease. KEY WORDS: AODE (alcohol and other drug effects); diabetes; glucose; insulin; pancreas; heavy AOD use; adverse drug effect; disease complication; nutrient intake; ethanol metabolism; hypoglycemia; ketoacidosis; lipid metabolism; triglycerides; cholesterol; patho- logic process; cardiovascular disorder; neuropathy; psychosexual dysfunction; visual system disorder; literature review iabetes mellitus, which affects Because alcohol use, at least on a an estimated 16 million people social level, is widespread among diabet- NICHOLAS V. E MANUELE, M.D., is a Din the United States, is a com- ics as well as nondiabetics, clinicians and professor in the Department of Medicine, plex disorder interfering with the body’s researchers must understand alcohol’s the Division of Research on Drugs of Abuse, sugar (i.e., carbohydrate), fat (i.e., lipid), effect on the progression and compli- and the Molecular Biology Program and and protein metabolism. The disease is cations of diabetes. This article first director of the Division of Endocrinology caused in most cases by a deficiency or reviews the pathophysiology of the two and Metabolism at Loyola University complete lack of the hormone insulin, major forms of diabetes, type 1 and type Stritch School of Medicine, Maywood, which is produced in the pancreas, or 2. It then summarizes the current state Illinois, and a staff physician at the Veterans by an inability of the body to respond of knowledge regarding alcohol’s effects Affairs Hospital, Hines, Illinois. appropriately to insulin (i.e., insulin on blood sugar regulation and other resistance). The results of both condi- aspects of metabolism as well as on the TERRENCE F. S WADE, M.D., is in the tions can include chronically elevated cardiovascular, neurological, and eye com- private practice of endocrinology in the blood sugar levels, excessive excretion plications associated with the disease. Chicago, Illinois, area. of sugar in the urine, and the accumu- lation of certain acidic substances in MARY ANN EMANUELE, M.D., is a the blood. If not prevented or treated Pathophysiology of professor in the Department of Medicine, properly, these changes can lead to Diabetes Mellitus the Department of Molecular and coma and even death. Other adverse Cellular Biochemistry, and the Division events associated with diabetes affect The two most common forms of dia- of Research on Drugs of Abuse, Loyola the eyes, kidneys, nervous system, skin, betes are type 1 and type 2 diabetes, University Stritch School of Medicine, and circulatory system. with type 2 diabetes accounting for at Maywood, Illinois. Vol. 22, No. 3, 1998 211 least 90 percent of all cases. Type 1 importantly, insulin leads to the uptake 2 continue to produce insulin in diabetes is an autoimmune disease— of the sugar glucose into muscle and early disease stages; however, their that is, a disease in which the body’s fat tissue and prevents glucose release bodies do not respond adequately to immune system attacks and destroys from the liver, thereby lowering blood the hormone (i.e., the patients are not only foreign molecules or organ- sugar levels (e.g., after a meal) (see fig- resistant to insulin’s effects). Thus, isms but also some of the body’s own ure). As a result of the immune system’s insulin does not lower blood sugar cells. In most patients, the disease attack, the beta cells can no longer pro- levels to the extent that it does in develops before age 40, primarily dur- duce insulin. Consequently, the patient people without diabetes. The insulin ing childhood or adolescence. In essentially experiences total insulin resistance is partly inherited and those patients, the immune system lack. Because insulin is a key metabolic partly acquired. For example, attacks certain cells of the pancreas, hormone, insulin deficiency leads to obesity, inactivity, and cigarette called beta cells. (For more informa- major impairment of the body’s regula- smoking may worsen genetically tion on the structure and function of tion of carbohydrate, lipid, and pro- determined insulin resistance. the pancreas, see textbox, p. 213.) tein metabolism. Insulin resistance does not immed- Beta cells produce insulin, one of the Type 2 diabetes, which in most iately lead to overt diabetes, because the two major hormones involved in reg- cases develops in people over age 40, patient’s pancreatic beta cells initially ulating the body’s blood sugar levels has a somewhat different pathophys- can increase their insulin production and other metabolic functions. Most iology than type 1. People with type enough to compensate for the insulin Food intake Blood glucose levels increase following food digestion and absorption in the gastrointestinal tract. Normal pancreas Type 1 diabetes Type 2 diabetes Beta cells Normal insulin No or very little Normal or even production insulin production elevated insulin production • Blood glucose is taken up into • Blood glucose levels remain • The body resists insulin’s effects. muscle and fat tissue and used high, eventually leading to in metabolic processes. serious complications. • Initially, resistance can be overcome by increasing • No additional glucose is • Both protein and fat metabolism insulin production. generated in the liver, are impaired, eventually leading and existing glucose is to serious complications. • Eventually, the body can no converted into a storage longer produce enough form (i.e., glycogen) as a insulin; the same complications reserve in case blood occur as with type 1 diabetes. glucose levels drop too low. • Blood glucose levels return to their normal range. Blood glucose regulation by insulin in healthy people and in people with type 1 or type 2 diabetes. 212 Alcohol Health & Research World Consequences of Alcohol Use in Diabetics resistance. In fact, insulin-resistant type 2—with medications that stimu- Sturmhöfel and Bartke, pp. 153–164.) people have higher than normal insulin late the body’s own insulin production With increasing duration of diabetes, levels (i.e., are hyperinsulinemic1). In (e.g., a class of medications called however, the counter-regulatory time (i.e., probably after several years), sulfonylureas or an agent called responses of first glucagon and then however, the pancreas cannot keep up repaglinide). Those medications, how- epinephrine wane, rendering the dia- with the increased demand for insulin; ever, may lead to lower than normal betic patient more vulnerable to although insulin production still may blood sugar levels (i.e., hypoglycemia): severe hypoglycemia, whether it results be higher than in nondiabetic people, it As the medications enhance insulin from medications or other causes. is no longer sufficient to overcome production, the body responds to the Two additional medications—met- insulin resistance. Ultimately, insulin increased insulin levels by increasing formin and troglitazone—are now being secretion declines even further, to levels glucose uptake into the muscle and used to treat people with type 2 diabetes. below those seen in nondiabetics fat tissue and decreasing glucose secre- These agents act to lower the patient’s (although generally still higher than tion from the liver. As a result, the blood sugar levels by decreasing insulin those seen in type 1 diabetics). At that body’s hormone system mounts a resistance rather than by increasing point, when a deficit in insulin secretion counter-regulatory response: It secretes insulin secretion. Accordingly, these is combined with a state of insulin an array of hormones that through medications help control blood sugar resistance, the person develops type 2 various mechanisms raise blood sugar levels without causing hypoglycemia. diabetes. Thus, whereas type 1 diabetes levels back to normal. The most is characterized by a complete lack of important of those counter-regulatory insulin production, type 2 is charac- hormones are glucagon, which is pro- Alcohol’s Effects terized by reduced insulin production duced in pancreatic alpha cells, and on Blood Sugar Levels plus insulin resistance. The reasons epinephrine, which is secreted from of Diabetics underlying defective insulin secretion the adrenal glands. Other hormones and insulin resistance, which are still involved in the counter-regulatory Numerous studies have investigated under investigation, are complex and response include growth hormone, alcohol’s effects on the control of beyond the scope of this article (for a which is produced in the pituitary blood sugar levels in diabetics. Those review, see DeFronzo 1997). gland, and cortisol, which is produced effects differ substantially depending People with either type 1 or type 2 in the adrenal glands. (For more on whether alcohol consumption diabetes generally are treated with information on those hormones and occurs when the person has just eaten insulin injections or—for people with their functions, see the article by Hiller- and blood sugar levels are relatively high (i.e., in the fed state) or when the person has not eaten for several hours and blood sugar levels are rela- The Pancreas and Its Hormones tively low (i.e., in the fasting state). The pancreas, which is located behind the stomach, serves two functions.