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Home , Blood lipids, Blood sugar regulation

Consequences of Alcohol Use in Diabetics

Nicholas V. Emanuele, M.D., Terrence F. Swade, M.D., and Mary Ann Emanuele, M.D.

The , which is produced in the , is an important regulator of sugar levels. In people with , the pancreas does not produce sufficient insulin (type 1 diabetes) or the body does not respond appropriately to the insulin (). 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 , nerve damage, and eye disease. KEY WORDS: AODE (alcohol and other drug effects); diabetes; ; insulin; pancreas; heavy AOD use; adverse drug effect; disease complication; nutrient intake; ethanol metabolism; ; ketoacidosis; metabolism; ; ; 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., ), fat (i.e., lipid), effect on the progression and compli- and the Molecular Biology Program and and metabolism. The disease is cations of diabetes. This article first director of the Division of 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 . 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 , 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 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 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 and absorption in the .

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., ) 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 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 , 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 , 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 , serves two functions. The first function, which involves most of the pancreatic cells, is the production Effects of Alcohol Consumption of digestive enzymes. Those enzymes are secreted directly into the gut to in the Fed State ensure effective food digestion. The second function is the production of In people with either type 1 or type 2 several hormones. Two of the hormones (i.e., insulin and glucagon) are diabetes, single episodes of alcohol potent regulators of blood sugar levels. Both hormones are produced in areas consumption (i.e., acute alcohol con- of the pancreas called the Islets of Langerhans, which, quite literally, are sumption) generally do not lead to “islands” of hormone-producing cells in a “sea” of digestive enzyme-producing clinically significant changes in blood cells. Among other types, the Islets of Langerhans include an inner core sugar levels. In fact, some studies have of insulin-producing beta cells surrounded by a layer of glucagon-producing indicated that isolated episodes of alpha cells. drinking with a meal may have a ben- Insulin primarily serves to lower blood sugar levels by promoting the eficial effect by slightly lowering uptake of sugar (i.e., glucose) in the muscles and fat (i.e., adipose) tissue blood sugar levels that tend to rise too as well as the conversion of glucose into its storage form, glycogen. high in diabetics (Swade and Emanuele In addition, insulin inhibits the production of more sugar molecules (i.e., ) in the liver. Conversely, glucagon primarily serves to increase blood sugar levels. Accordingly, it promotes gluconeogenesis and 1The prefix “hyper-” always indicates higher than normal levels of a substance, whereas the prefix the breakdown of glycogen into glucose. The actions of insulin and “hypo-” indicates lower than normal levels. The glucagon must be finely balanced, because both lower than normal blood suffix “-emia” refers to the levels of a substance in sugar levels (i.e., hypoglycemia) and higher than normal blood sugar lev- the blood. Thus, hyperinsulinemia refers to els (i.e., ) can have deleterious effects on the body. higher than normal insulin levels in the blood, whereas hypoglycemia refers to lower than normal glucose levels in the blood.

Vol. 22, No. 3, 1998 213 1997). This potentially beneficial blood and is frequently measured as a effects on one or both of those variables. effect was observed in both men and reflection of the average insulin To date, no studies have specifically women, regardless of age. The alcohol secretion). evaluated the effect of chronic alcohol amounts administered in those studies ingestion on insulin secretion or insulin were usually between 0.5 g/kg (gram Based on those biochemical mark- resistance, although the study described per kilogram body weight) and 1 g/kg, ers, the researchers found the follow- previously by Ben and colleagues (1991) leading to blood alcohol levels (BALs) ing results: suggests that chronic alcohol exposure between approximately 0.03 and 0.1 does not diminish insulin secretion. percent2 (McDonald 1980). Those doses • On the day of admission to the hos- Consequently, studies of the effects of are equivalent to approximately 2.5 to pital and on the following day, the acute alcohol ingestion currently provide 5 standard drinks.3 Interestingly, studies fasting blood sugar levels of the drink- the best means of assessing alcohol’s of acute alcohol exposure in nondia- ing type 2 diabetics were significantly impact on insulin secretion and insulin betic people have yielded quite variable higher than those of the nondrinking resistance. Such experiments, which results, noting decreases, increases, or type 2 diabetics. On later days, no have been conducted mainly on non- no changes in glucose levels. significant differences in fasting diabetics, have demonstrated that acute Conversely, research has indicated blood sugar levels existed between alcohol administration leads to increased that long-term (i.e., chronic) alcohol the two groups of diabetics. insulin resistance (Avogaro et al. 1983; consumption in well-nourished diabet- Yki-Jarvinen and Nikkila 1985; Shelmet ics results in increased blood sugar levels • HbA1c levels (and, by extension, et al. 1988; Boden et al. 1993). In (i.e., hyperglycemia). For example, average blood sugar levels) were sig- diabetic people, elevated insulin secre- Ben and colleagues (1991) compared nificantly higher in drinking type 2 tion cannot compensate for increased the blood sugar levels of 46 type 2 diabetics than in nondrinking type insulin resistance. The same mecha- diabetics who were “habitual drinkers”; 2 diabetics who, in turn, had signifi- nism might occur in chronically 35 nondrinking type 2 diabetics; and cantly higher HbA1c levels than did drinking diabetics and thus account 40 nondiabetic, nondrinking control the nondiabetic control subjects. for the deterioration of blood sugar subjects. The habitual drinkers con- Whether the elevated blood sugar control observed in those patients. sumed an average of 45 grams of pure levels in diabetics were caused directly Alternatively, chronically drinking alcohol, corresponding to approxi- by alcohol’s impact on blood sugar diabetics may show worse compliance mately 3 to 4 standard drinks, per day. regulation or by the patients’ alcohol- with their dietary and pharmacological For the study, the participants were related failure to comply with their treatment regimens, which also may hospitalized for 7 days and received a diabetes treatment is unknown. result in uncontrolled blood sugar standard hospital diet. The researchers levels. Clearly, more studies in this area evaluated the following biochemical • C-peptide levels, and thus insulin are needed. markers, which can serve as indicators production, were significantly lower in of blood sugar control: both groups of diabetics than in non- Effects of Alcohol Consumption diabetics. No difference in C-peptide in the Fasting State • Blood sugar levels in the fasting state levels existed, however, between drink- ing and nondrinking diabetics, indi- In contrast to chronic alcohol consump- • Hemoglobin A1c (HbA1c), a cating that chronic alcohol consump- tion in the fed state—which raises blood blood component that reflects tion did not alter the diabetics’ insulin sugar levels, resulting in hyperglycemia— blood sugar control over the past production. Consequently, the elevated alcohol consumption in the fasting 2 to 3 months (the higher the glucose levels observed in the drink- state can induce a profound reduction in HbA1c levels, the higher were ing diabetics likely were not caused blood glucose levels (i.e., hypoglycemia). the average blood sugar levels) by alcohol’s effects on insulin levels, That effect has been observed in both but may have resulted from an type 1 and type 2 diabetics as well as in • C-peptide, a molecule that is pro- alcohol-induced increase in insulin nondiabetics (Arky and Freinkel 1964). duced together with insulin (because resistance in those diabetics. Hypoglycemia can have serious, even C-peptide is more stable than insulin, life-threatening, consequences, because it can be detected longer in the The mechanism(s) underlying the adequate blood sugar levels are needed increasing hyperglycemia in chronically to ensure brain functioning. drinking diabetics are still unknown. Alcohol-induced hypoglycemia 2In most States, BALs of 0.08 to 0.1 percent are the legal limits for intoxication. Because the most common form of typically occurs in people (both diabet- diabetes, type 2 diabetes, is associated ics and nondiabetics) who, sometimes 3 A standard drink contains 12 grams (approxi- with both insufficient insulin secretion for days, have been drinking alcohol mately 0.5 ounce) of pure alcohol. This amount is equal to one 12-ounce bottle of beer or wine and insulin resistance, it appears likely but not eating. In such a fasting state, cooler, one 5-ounce glass of wine, or 1.5 ounces that the alcohol-induced increase in the body has two major mechanisms of distilled spirits. blood sugar levels results from adverse for maintaining the blood sugar levels

214 Alcohol Health & Research World Consequences of Alcohol Use in Diabetics

necessary to provide energy to the increased risk of severe hypoglycemia. etate, and β-hydroxybutyrate) in the brain: (1) breakdown of glycogen, or Alcohol-related hypoglycemic unaware- blood. Elevated levels of those com- , and (2) production of ness likely results from the cognitive pounds can cause nausea, vomiting, glucose, or gluconeogenesis. impairment that occurs when BALs impaired mental functioning, coma, Glycogen is a large molecule that reach 0.08 to 0.1 percent. and even death. Ketoacidosis is caused consists of numerous glucose molecules Second, diabetics who have con- by complete or near-complete lack of and serves as a storage form of glucose sumed alcohol, particularly those with insulin and by excessive glucagon levels. in the tissues, particularly the liver. In type 1 diabetes, experience a delayed Among their many functions, insulin the fasting state, as a first line of glucose recovery from hypoglycemia. and glucagon regulate the conversion defense against hypoglycemia, glyco- This means that after an episode of of fat molecules (i.e., fatty acids) into gen is broken down into its constituent hypoglycemia, glucose levels return to larger molecules (i.e., triglycerides), glucose molecules, which are secreted normal more slowly in drinking dia- which are stored in the fat tissue. In by the liver into the blood to main- betics than in nondrinking diabetics, the absence of insulin, the triglycerides tain normal or near-normal blood suggesting an alcohol-related impair- are broken down into free fatty acids, sugar levels. Generally, the glycogen ment in the counter-regulatory which are secreted into the blood- supply is depleted after 1 or 2 days of response to hypoglycemia (Avogaro et stream and delivered to the liver. The fasting. Thus, a person who has been al. 1993). Detailed analyses demon- liver normally re-incorporates free drinking alcohol and not eating for 1 strated that although the glucagon fatty acids into triglycerides, which or more days has exhausted his or her and epinephrine responses to hypo- are then packaged and secreted as part glycogen supply. glycemia were unaffected, the growth of a group of particles called very low- Gluconeogenesis, which also occurs hormone and cortisol responses were density (VLDL). In primarily in the liver, involves the for- reduced after alcohol consumption. patients with ketoacidosis, however, mation of new glucose molecules from The combination of alcohol-induced the liver metabolizes the incoming alanine and glycerol. Alanine is gener- hypoglycemia, hypoglycemic unaware- free fatty acids in an additional, unusual ated during the breakdown of ness, and delayed recovery from way. Under the influence of excess in the muscles, whereas glycerol is hypoglycemia can lead to deleterious glucagon, some of the free fatty acids formed during the metabolism of cer- health consequences. For example, are converted to ketone bodies and tain fat molecules (i.e., triglycerides). Arky and colleagues (1968) studied five secreted into the blood, causing severe Alcohol metabolism in the liver, how- diabetics who experienced severe hypo- health consequences. ever, actually shuts down the process glycemia after ingesting alcohol. In all Ketoacidosis typically occurs in of gluconeogenesis and thus the second five patients, the alcohol-induced patients with type 1 diabetes who line of defense against hypoglycemia. hypoglycemia induced neurological completely lack insulin. In rare cases, Consequently, both of the body’s changes, such as incontinence, inability however, the condition also may affect mechanisms to sustain blood sugar lev- to follow simple commands, persevera- people with type 2 diabetes. In a milder els are inactivated in people who con- tion,4 disorientation, and impairment form, ketoacidosis may even occur in sume alcohol but do not eat, resulting of recent memory. In three patients, people who are fasting. In those peo- in profound hypoglycemia. those changes did not reverse, even ple, insulin levels are diminished, Two additional factors may further after months or years. The two other because the fasting has considerably compound the risk of alcohol-related patients died as a result of complications lowered their blood sugar levels, thereby hypoglycemia and its associated con- indirectly related to their hypoglycemia- depriving the pancreas of its stimulus sequences in alcohol-drinking but induced neurological changes. Therefore, to produce and secrete insulin. otherwise fasting people, particularly to avoid alcohol-related hypoglycemia Heavy alcohol consumption (i.e., diabetics. First, alcohol consumption and its consequences, diabetics should 200 grams of pure alcohol, or approx- can lead to a situation called hypo- consume alcohol only with or shortly imately 16 standard drinks, per day) glycemic unawareness in both diabetics after meals. can cause ketoacidosis in both diabet- and nondiabetics (Kerr et al. 1990). A ics and nondiabetics (Wrenn et al. hypoglycemic person normally experi- 1991). People who consume those ences several warning symptoms, such Alcohol’s Effects on high amounts of alcohol typically have as sweating, weakness, shakiness, ner- Complications of Diabetes been drinking and not eating for days vousness, and pounding or racing of and/or have vomited or developed the heart. Diabetics in particular learn other illnesses from drinking. As a to recognize those symptoms and pre- Diabetic Ketoacidosis result, those patients frequently have vent a further decline in blood sugar very low blood sugar levels (although levels by eating some food. A person Ketoacidosis, which occurs primarily in some people with alcoholic ketoacido- in a state of hypoglycemic unawareness, diabetics, is a condition characterized however, may not notice or recognize by excessive levels of certain acids called 4Perseveration is the involuntary repetition of those warning signs and is therefore at ketone bodies (e.g., acetone, acetoac- words or actions.

Vol. 22, No. 3, 1998 215 sis have very high blood sugar levels, tein (LDL) cholesterol, and elevated exhibits altered biological functions because the lack of insulin prevents levels of high-density and may more readily cause cardiovas- glucose uptake from the blood into (HDL) cholesterol. cular disease. The researchers found the tissues). that the levels of vitamin E, an agent The mechanisms underlying the Elevated Levels. Hyper- that in part is bound to LDL choles- development of alcoholic ketoacido- triglyceridemia is an important risk terol and which may decrease the risk sis are complex. However, some factor for cardiovascular diseases. of , also are typical contributing factors result Moreover, elevated triglyceride levels lower in alcoholics than in nonalco- in insulin lack and excess glucagon can cause severe inflammation of the holics. Those observations suggest levels, thereby promoting the devel- pancreas (i.e., pancreatitis). In addi- that the reduced levels of vitamin E in opment of ketoacidosis. As men- tion to being highly painful and alcoholics actually may have harmful tioned earlier in this article, poor potentially fatal, this inflammation long-term effects. food intake can lead to depleted may interfere with the production of glycogen levels. Furthermore, contin- insulin, thereby potentially worsening Elevated HDL Cholesterol Levels. ued alcohol metabolism results in control of blood sugar levels and mak- HDL cholesterol has a protective effect diminished gluconeogenesis. Both ing hypertriglyceridemia a particularly against cardiovascular disease and is the depletion of glycogen and serious complication in diabetics. called “good” cholesterol. This protec- diminished gluconeogenesis lead to Heavy drinking (i.e., more than 140 tive effect results at least partly from a lower blood sugar levels. As blood grams of pure alcohol, or approxi- process called reverse cholesterol sugar falls, insulin secretion is mately 12 standard drinks, per day) transport, in which HDL particles reduced as well. Because insulin can cause alcohol-induced hyper- carry cholesterol from blood vessel restrains glucagon secretion, lower triglyceridemia in both diabetics and walls and other sites back to the liver, insulin secretion allows increased nondiabetics (Chait et al. 1972). In where it is broken down and subse- glucagon secretion, setting the fact, from a practical standpoint, quently eliminated from the body. stage for the development of keto- heavy drinking should be considered Two subtypes of HDL—HDL2 and acidosis. This situation can be as a possible contributing factor in all HDL3—are particularly effective in amplified if the drinker vomits patients with hypertriglyceridemia. this reverse cholesterol transport. repeatedly. Vomiting can lead to Abstinence from alcohol generally Studies in alcoholics found that the dehydration and a reduced blood leads to normalization of the triglyc- levels of HDL, and particularly of volume, which, in turn, increases the eride levels, unless the person has an HDL2 and HDL3, were elevated after levels of certain stress hormones in underlying genetic predisposition for a period of chronic drinking and the blood called catecholamines. hypertriglyceridemia. returned to normal levels after several Catecholamines further decrease Several mechanisms may con- days of abstinence (Taskinen et al. insulin production and increase tribute to alcohol-induced increases in 1982). Moreover, epidemiological glucagon production. Accordingly, triglyceride levels. First, alcohol likely data have demonstrated that moder- physicians who treat diabetics known stimulates the generation of VLDL ate alcohol consumption of up to to consume large amounts of alcohol particles in the liver, which are rich in three standard drinks per day is asso- must be aware of the risk of alcoholic triglycerides. Second, alcohol may ciated with a reduced risk of heart ketoacidosis in those patients. inhibit VLDL particle breakdown. attacks and that this effect is partly Third, alcohol may enhance the mediated by alcohol-induced Alterations of Lipid Metabolism increase in triglyceride levels in the increases in HDL2 and HDL3 levels blood that usually occurs after a meal. (Gaziano et al. 1993). Abnormalities in the levels and metab- olism of are extremely common Reduced LDL Cholesterol Levels. Cardiovascular Disease in people with either type 1 or type 2 LDL cholesterol is strongly related to diabetes and may contribute to those cardiovascular disease and stroke and Cardiovascular disease continues to be patients’ risk of developing cardiovas- has been called “bad” cholesterol. one of the leading causes of death cular disease (Durrington 1995). Reduction of LDL cholesterol decreases among all Americans and is the lead- Alcohol consumption can exacerbate a person’s likelihood of suffering a ing cause of death in people with type the diabetes-related lipid abnormali- heart attack or stroke. LDL cholesterol 2 diabetes (Bierman 1992). The rela- ties, because numerous studies have levels tend to be lower in alcoholics tionship of alcohol consumption to shown that heavy drinking can alter than in nondrinkers (Castelli et al. cardiovascular disease in diabetic peo- lipid levels even in nondiabetics. Alcohol 1977), suggesting that chronic alcohol ple has not been well evaluated. can induce several types of lipid alterations, consumption may have a beneficial However, substantial information on including elevated triglyceride levels effect on cardiovascular risk. However, the association of alcohol and cardio- in the blood (i.e., hypertriglyceridemia), Lin and colleagues (1995) reported vascular disease exists from population reduced levels of low-density lipopro- that the LDL cholesterol in alcoholics studies that included an unknown

216 Alcohol Health & Research World Consequences of Alcohol Use in Diabetics

percentage of diabetics. For example, many patients do not experience that may reverse or protect against in one 10-year study of 1,422 men, symptoms of peripheral neuropathy, the neuropathy. overall death rates (and, by extension, other patients suffer from varied death rates from cardiovascular dis- and troublesome symptoms, such Impotence. Neuropathy, in addition ease) were lowest among those who as tingling, burning, pain, and numb- to other factors (e.g., vascular disease consumed 0.1 to 34 grams of alcohol ness. Those symptoms occur most in the penis or altered hormone levels), per day (i.e., between 1 standard commonly in the legs and feet and are also may contribute to impotence, drink every few months and approxi- frequently worse at night. Numbness which is a common and troublesome mately 3 standard drinks per day) in particular can be a serious problem: complication in diabetic men. The (Marmot et al. 1981). Both complete Patients may not sense lesions, such as nerves that control erection are part of abstainers and people drinking more cuts or ulcers, which may then become the autonomic nervous system, which than 34 grams of alcohol per day had seriously infected and result in ampu- controls numerous vital processes that higher death rates, with abstainers tation of the affected limb. occur without conscious efforts (e.g., exhibiting the highest death rates Diabetes and alcohol consumption breathing and the contractions of the from cardiovascular disease and heavy are the two most common underlying gut necessary for proper digestion). drinkers exhibiting the highest death causes of peripheral neuropathy. Among Despite the high prevalence of impo- rates from noncardiovascular disease. diabetics, the prevalence of neuropathy tence in male diabetics and the fact that Those findings suggest that alcohol with obvious symptoms (i.e., symp- many of these men consume alcohol, consumption, particularly moderate tomatic neuropathy) increases with few studies have evaluated the relation- consumption, may have a protective increasing disease duration. Moreover, ship between alcohol intake and impo- effect against cardiovascular disease. McCulloch and colleagues (1980) tence in diabetics. In one study of 275 Alcohol consumption also can reported that for any given duration originally potent diabetic men, heavy influence blood pressure. In popula- of diabetes, the prevalence of symp- drinkers were significantly more likely tion studies, moderate alcohol tomatic peripheral neuropathy was to develop impotence during the 5- consumption of less than two drinks greater in men who consumed at least year study period than were moderate per day was associated with slightly three to four alcohol-containing bev- drinkers (McCulloch et al. 1984). Based lower blood pressure than abstinence, erages almost every night compared on assumptions regarding the alcohol particularly among women (Harburg content of the beverages mentioned in with men who drank less. That increase et al. 1980; Klatsky et al. 1977). the study, “heavy” drinkers were defined in prevalence was most apparent in Consumption of more than three as those who ingested 29 grams of drinks, however, resulted in elevated patients with a disease duration of less alcohol, or approximately two to three blood pressure in both men and than 4 years. Other researchers observed standard drinks, per day. women compared with nondrinkers. that the prevalence of neuropathy in Many impotent diabetic men also Because high blood pressure is a risk type 1 diabetics increased in a linear have lower than normal levels of factor for cardiovascular disease, those fashion with the alcohol amount con- the sex hormone testosterone in their results also suggest that moderate sumed (Mitchell and Vinik 1987). blood. Alcohol reduces blood levels of alcohol consumption can have benefi- Those researchers also reported that testosterone and may thereby further cial effects for cardiovascular disease diabetics who consumed more than exacerbate the existing hormonal risk. It is unknown, however, whether eight standard drinks per week devel- deficit. Clinical experience indicates, that effect applies equally to diabetics oped peripheral neuropathy faster however, that a testosterone deficit and nondiabetics, because those stud- than did diabetics who consumed eight rarely is the sole reason for impotence ies did not specify the proportion of or fewer drinks per week. in diabetic men, because treatment with diabetic participants. The mecha- Alcohol use also is associated testosterone rarely restores potency in nisms underlying alcohol’s impact on with an inability to sense vibrations those men. Thus, both neuropathy and blood pressure have not been fully from a tuning fork (i.e., absent vibra- vascular disease likely play significant elucidated. tory perception), which serves as a roles in impotence in diabetic men. convenient semiquantitative measure of peripheral neuropathy (Sosenko Peripheral Neuropathy et al. 1986). All of these findings Retinopathy Peripheral neuropathy is a condition suggest that alcohol and diabetes can Diabetic eye disease (i.e., retinopathy) in which nerves are damaged that enhance each other’s effects in terms is another troublesome tissue compli- extend from the spinal cord to control of causing nerve damage. Because neu- cation of diabetes and one of the muscle function (i.e., motor nerves) ropathy is a major clinical problem leading causes of blindness in the or that transmit various sensations— in diabetics, more analyses are needed United States today. Good blood such as touch, pain, temperature, and of the precise quantitative relationship sugar and blood pressure control as vibration—back to the spinal cord between alcohol intake and neuropa- well as regular eye examinations are and brain (i.e., sensory nerves). Although thy in diabetics as well as on factors essential for the prevention of retinopa-

Vol. 22, No. 3, 1998 217 thy. Heavy alcohol consumption may • Metformin, a medication that References increase a person’s risk for developing decreases insulin resistance, can this disease. Thus, in one study of cause potentially lethal side effects ARKY, R.A., AND FREINKEL, N. Alcohol hypo- 296 male diabetics who had no eye glycemia. Archives of Internal Medicine 114:501– in patients whose liver is not func- 507, 1964. disease at the beginning of the study, tioning properly. Accordingly, those men who drank the equivalent patients who abuse alcohol and are ARKY, R.A.; VEVERBRANTS, E.; AND ABRAMSON, E.A. Irreversible hypoglycemia. Journal of the of more than 10 pints of beer per week therefore at risk for liver damage were more likely to develop retinopa- American Medical Association 206:575–578, 1968. must not take metformin. thy over 5 years than were those men AVOGARO, A.; DUNER, E.; MARESCOTTI, C.; FERRARA, who drank less or were abstainers • D.; DEL PRATO, S.; NOSADIN, R.; AND TIENGO, A. (Young et al. 1984). Interestingly, the Troglitazone, another medication Metabolic effects of moderate alcohol intake with that decreases insulin resistance, meals in insulin-dependent diabetics controlled by risk of retinopathy was independent artificial endocrine pancreas (AEP) and in normal of the men’s ability to control their also must not be used by patients subjects. Metabolism 32:463–470, 1983. blood sugar, suggesting that alcohol with liver disease and therefore should not be used by alcohol AVOGARO, A.; BELTRAMELLO, P.; GNUDI, L. Alcohol may directly damage the eyes or related intake impairs glucose counterregulation during structures. abusers. Moreover, troglitazone acute insulin-induced hypoglycemia in IDDM The much larger United Kingdom itself may impair liver function, patients: Evidence for a critical role of free fatty Prospective Diabetes Study confirmed and alcohol might further exacer- acids. Diabetes 42:1626–1634, 1993. that alcohol consumption in men bate this harmful effect. BEN, G.; GNUDI, L.; MARAN, A.; GIGANTE, A.; (but not in women) was associated DUNER, E.; LORI, E.; TIENGO, A.; AND AVOGARO, with more severe retinopathy (Kohner A. Effects of chronic alcohol intake on carbohy- et al. 1998). The relationship between Summary drate and lipid metabolism in subjects with type II (non-insulin-dependent) diabetes. 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Consequently, moderate amounts of alcohol (i.e., two 34, 1993. the information regarding the rela- to four drinks per day), however, CASTELLI, W.P.; GORDON, T.; HJORTLAND, M.C.; tionship between alcohol ingestion clearly interferes with diabetic blood and diabetic eye disease remains KAGAN, A.; DOYLE, J.T.; HAMES, C.G.; HULLEY, sugar control and increases the risk of S.B.; AND ZUKEL, W.J. Alcohol and blood lipids: inconsistent, underlining the need for impotence; peripheral neuropathy; The Cooperative Lipoprotein Phenotyping Study. further studies. Lancet 2:153–155, 1977. and, possibly, retinopathy. At the same time, similar levels of alcohol con- CHAIT, A.; MANCINI, M.; FEBRUARY, A.W.; AND Medication Interactions LEWIS, B. Clinical and metabolic study of alcoholic sumption are associated with a hyperlipidaemia. Lancet July:62-64, 1972. In addition to exacerbating various decreased risk of heart attacks and DEFRONZO, R.A. Pathogenesis of type 2 diabetes: medical complications of diabetes, death from cardiovascular disease. The Metabolic and molecular implications for identi- alcohol consumption and its associated latter findings, however, were obtained fying diabetes genes. Diabetes Reviews 5(3):177– health consequences may interact with with populations that included diabet- 269, 1997. or alter the effects of several medica- ics as well as nondiabetics, thereby DURRINGTON, P.N. Hyperlipidaemia: Diagnosis tions used to treat diabetes, including limiting researchers’ ability to apply and Management. 2d ed. Oxford, Great Britain: the following: those findings to diabetics. Butterworth-Heinemann, Ltd., 1995. Accordingly, more studies are GAZIANO, J.M.; BURING, J.E.; BRESLOW, J.L.; • Chlorpropamide is a medication needed to determine whether the bene- GOLDHABER, S.Z.; ROSNER, B.; VAN DENBURGH, used to treat type 2 diabetes by M.; WILLET, W.; AND HENNEKENS, C.H. Moderate ficial effects of daily moderate alcohol alcohol intake, increased levels of high-density increasing pancreatic insulin secre- consumption outweigh the deleterious tion. Some people treated with lipoprotein and its subfractions, and decreased risk effects. Diabetics clearly should avoid of myocardial infarction. New England Journal of chlorpropamide experience an Medicine 329:1829–1834, 1993. unpleasant, disulfiram-like heavy drinking (i.e., more than 10 to reaction5 after drinking alcohol. 12 drinks per day), because it can cause HARBURG, E.; OZGOREN, F.; HAWTHORNE, V.M.; ketoacidosis and hypertriglyceridemia. SCHORK, M.A. Community norms of alcohol usage and blood pressure: Tecumseh, Michigan. American Moreover, heavy drinking in a fasting Journal of Public Health 70:813–820, 1980. 5Disulfiram (Antabuse®) is a medication used to state can cause hypoglycemia and ulti- treat alcoholics. It acts by inducing an unpleasant KERR, D.; MACDONALD, A.; HELLER, S.R.; physical response (e.g., nausea and vomiting) after mately increase diabetics’ risk of death TATTERSALL, R.B. Alcohol causes hypoglycaemic alcohol consumption. from noncardiovascular causes. unawareness in healthy volunteers and patients with

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