Diabetes Treatments

or the body does not respond appropriately to the insulin (type 2 diabetes) can worsen diabetes-related medical complications, such as disturbances in fat …

Consequences of Alcohol Use in Diabetics
Nicholas V Emanuele, MD, Terrence F Swade, MD, and Mary Ann Emanuele, MD
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 alcohol 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; pathologic process; cardiovascular disorder; neuropathy; psychosexual dysfunction; visual system disorder; literature review

D

iabetes mellitus, which affects an estimated 16 million people in the United States, is a complex disorder interfering with the bodys sugar ie, carbohydrate, fat ie, lipid, and protein metabolism The disease is caused in most cases by a deficiency or complete lack of the hormone insulin, which is produced in the pancreas, or by an inability of the body to respond appropriately to insulin ie, insulin resistance The results of both conditions can include chronically elevated blood sugar levels, excessive excretion of sugar in the urine, and the accumulation of certain acidic substances in the blood If not prevented or treated properly, these changes can lead to coma and even death Other adverse events associated with diabetes affect the eyes, kidneys, nervous system, skin, and circulatory system
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Because alcohol use, at least on a social level, is widespread among diabetics as well as nondiabetics, clinicians and researchers must understand alcohols effect on the progression and
complications of diabetes This article first reviews the pathophysiology of the two major forms of diabetes, type 1 and type 2 It then summarizes the current state of knowledge regarding alcohols effects on blood sugar regulation and other aspects of metabolism as well as on the cardiovascular, neurological, and eye complications associated with the disease

NICHOLAS V EMANUELE, MD, is a professor in the Department of Medicine, the Division of Research on Drugs of Abuse, and the Molecular Biology Program and director of the Division of Endocrinology and Metabolism at Loyola University Stritch School of Medicine, Maywood, Illinois, and a staff physician at the Veterans Affairs Hospital, Hines, Illinois TERRENCE F SWADE, MD, is in the private practice of endocrinology in the Chicago, Illinois, area MARY ANN EMANUELE, MD, is a professor in the Department of Medicine, the Department of Molecular and Cellular Biochemistry, and the Division of Research on Drugs of Abuse, Loyola University Stritch School of Medicine, Maywood, Illinois
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Pathophysiology of Diabetes Mellitus
The two most common forms of diabetes are type 1 and type 2 diabetes, with type 2 diabetes accounting for
at

least 90 percent of all cases Type 1 diabetes is an autoimmune disease– that is, a disease in which the bodys immune system attacks and destroys not only foreign molecules or organisms but also some of the bodys own cells In most patients, the disease develops before age 40, primarily during childhood or adolescence In those patients, the immune system attacks certain cells of the pancreas, called beta cells For more information on the structure and function of the pancreas, see textbox, p 213 Beta cells produce insulin, one of the two major hormones involved in regulating the bodys blood sugar levels and other metabolic functions Most

importantly, insulin leads to the uptake of the sugar glucose into muscle and fat tissue and prevents glucose release from the liver, thereby lowering blood sugar levels eg, after a meal see figure As a result of the immune systems attack, the beta cells can no longer produce insulin Consequently, the patient essentially experiences total insulin lack Because insulin is a key metabolic hormone, insulin deficiency leads to major impairment of the bodys regulation of carbohydrate, lipid, and protein metabolism Type 2 diabetes, which in most cases
develops in people over age 40, has a somewhat different pathophysiology than type 1 People with type

2 continue to produce insulin in early disease stages; however, their bodies do not respond adequately to the hormone ie, the patients are resistant to insulins effects Thus, insulin does not lower blood sugar levels to the extent that it does in people without diabetes The insulin resistance is partly inherited and partly acquired For example, obesity, inactivity, and cigarette smoking may worsen genetically determined insulin resistance Insulin resistance does not immediately lead to overt diabetes, because the patients pancreatic beta cells initially can increase their insulin production 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 production No or very little insulin production Normal or even elevated insulin production

Blood glucose is taken up into muscle and fat tissue and used in metabolic processes No additional glucose is generated in the liver, and existing glucose is converted into a
storage form ie, glycogen as a reserve in case blood glucose levels drop too low Blood glucose levels return to their normal range

Blood glucose levels remain high, eventually leading to serious complications Both protein and fat metabolism are impaired, eventually leading to serious complications

The body resists insulins effects Initially, resistance can be overcome by increasing insulin production Eventually, the body can no longer produce enough insulin; the same complications occur as with type 1 diabetes

Blood glucose regulation by insulin in healthy people and in people with type 1 or type 2 diabetes

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resistance In fact, insulin-resistant people have higher than normal insulin levels ie, are hyperinsulinemic1 In time ie, probably after several years, however, the pancreas cannot keep up with the increased demand for insulin; although insulin production still may be higher than in nondiabetic people, it is no longer sufficient to overcome insulin resistance Ultimately, insulin secretion declines even further, to levels below those seen in nondiabetics although generally still higher than
those seen in type 1 diabetics At that point, when a deficit in insulin secretion is combined with a state of insulin resistance, the person develops type 2 diabetes Thus, whereas type 1 diabetes is characterized by a complete lack of insulin production, type 2 is characterized by reduced insulin production plus insulin resistance The reasons underlying defective insulin secretion and insulin resistance, which are still under investigation, are complex and beyond the scope of this article for a review, see DeFronzo 1997 People with either type 1 or type 2 diabetes generally are treated with insulin injections or–for people with

type 2–with medications that stimulate the bodys own insulin production eg, a class of medications called sulfonylureas or an agent called repaglinide Those medications, however, may lead to lower than normal blood sugar levels ie, hypoglycemia: As the medications enhance insulin production, the body responds to the increased insulin levels by increasing glucose uptake into the muscle and fat tissue and decreasing glucose secretion from the liver As a result, the bodys hormone system mounts a counter-regulatory response: It secretes an array of hormones
that through various mechanisms raise blood sugar levels back to normal The most important of those counter-regulatory hormones are glucagon, which is produced in pancreatic alpha cells, and epinephrine, which is secreted from the adrenal glands Other hormones involved in the counter-regulatory response include growth hormone, which is produced in the pituitary gland, and cortisol, which is produced in the adrenal glands For more information on those hormones and their functions, see the article by Hiller-

Sturmhöfel and Bartke, pp 153164 With increasing duration of diabetes, however, the counter-regulatory responses of first glucagon and then epinephrine wane, rendering the diabetic patient more vulnerable to severe hypoglycemia, whether it results from medications or other causes Two additional medications–metformin and troglitazone–are now being used to treat people with type 2 diabetes These agents act to lower the patients blood sugar levels by decreasing insulin resistance rather than by increasing insulin secretion Accordingly, these medications help control blood sugar levels without causing hypoglycemia

Alcohols Effects on Blood Sugar Levels of Diabetics
Numerous
studies have investigated alcohols effects on the control of blood sugar levels in diabetics Those effects differ substantially depending on whether alcohol consumption occurs when the person has just eaten and blood sugar levels are relatively high ie, in the fed state or when the person has not eaten for several hours and blood sugar levels are relatively low ie, in the fasting state

The Pancreas and Its Hormones
The pancreas, which is located behind the stomach, serves two functions The first function, which involves most of the pancreatic cells, is the production of digestive enzymes Those enzymes are secreted directly into the gut to ensure effective food digestion The second function is the production of several hormones Two of the hormones ie, insulin and glucagon are potent regulators of blood sugar levels Both hormones are produced in areas of the pancreas called the Islets of Langerhans, which, quite literally, are islands of hormone-producing cells in a sea of digestive enzyme-producing cells Among other cell types, the Islets of Langerhans include an inner core of insulin-producing beta cells surrounded by a layer of glucagon-producing alpha cells Insulin primarily
serves to lower blood sugar levels by promoting the uptake of sugar ie, glucose in the muscles and fat ie, adipose tissue as well as the conversion of glucose into its storage form, glycogen In addition, insulin inhibits the production of more sugar molecules ie, gluconeogenesis in the liver Conversely, glucagon primarily serves to increase blood sugar levels Accordingly, it promotes gluconeogenesis and the breakdown of glycogen into glucose The actions of insulin and glucagon must be finely balanced, because both lower than normal blood sugar levels ie, hypoglycemia and higher than normal blood sugar levels ie, hyperglycemia can have deleterious effects on the body

Effects of Alcohol Consumption in the Fed State In people with either type 1 or type 2 diabetes, single episodes of alcohol consumption ie, acute alcohol consumption generally do not lead to clinically significant changes in blood sugar levels In fact, some studies have indicated that isolated episodes of drinking with a meal may have a beneficial effect by slightly lowering blood sugar levels that tend to rise too high in diabetics Swade and Emanuele
1

The prefix hyper- always indicates higher than normal levels of a
substance, whereas the prefix hypo- indicates lower than normal levels The suffix -emia refers to the levels of a substance in the blood Thus, hyperinsulinemia refers to higher than normal insulin levels in the blood, whereas hypoglycemia refers to lower than normal glucose levels in the blood 213

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1997 This potentially beneficial effect was observed in both men and women, regardless of age The alcohol amounts administered in those studies were usually between 05 g/kg gram per kilogram body weight and 1 g/kg, leading to blood alcohol levels BALs between approximately 003 and 01 percent2 McDonald 1980 Those doses are equivalent to approximately 25 to 5 standard drinks3 Interestingly, studies of acute alcohol exposure in nondiabetic people have yielded quite variable results, noting decreases, increases, or no changes in glucose levels Conversely, research has indicated that long-term ie, chronic alcohol consumption in well-nourished diabetics results in increased blood sugar levels ie, hyperglycemia For example, Ben and colleagues 1991 compared the blood sugar levels of 46 type 2 diabetics who were habitual drinkers; 35 nondrinking type 2 diabetics; and 40
nondiabetic, nondrinking control subjects The habitual drinkers consumed an average of 45 grams of pure alcohol, corresponding to approximately 3 to 4 standard drinks, per day For the study, the participants were hospitalized for 7 days and received a standard hospital diet The researchers evaluated the following biochemical markers, which can serve as indicators of blood sugar control: Blood sugar levels in the fasting state Hemoglobin A1c HbA1c, a blood component that reflects blood sugar control over the past 2 to 3 months the higher the HbA1c levels, the higher were the average blood sugar levels C-peptide, a molecule that is produced together with insulin because C-peptide is more stable than insulin, it can be detected longer in the
2

blood and is frequently measured as a reflection of the average insulin secretion Based on those biochemical markers, the researchers found the following results: On the day of admission to the hospital and on the following day, the fasting blood sugar levels of the drinking type 2 diabetics were significantly higher than those of the nondrinking type 2 diabetics On later days, no significant differences in fasting blood sugar levels
existed between the two groups of diabetics HbA1c levels and, by extension, average blood sugar levels were significantly higher in drinking type 2 diabetics than in nondrinking type 2 diabetics who, in turn, had significantly higher HbA1c levels than did the nondiabetic control subjects Whether the elevated blood sugar levels in diabetics were caused directly by alcohols impact on blood sugar regulation or by the patients alcoholrelated failure to comply with their diabetes treatment is unknown C-peptide levels, and thus insulin production, were significantly lower in both groups of diabetics than in nondiabetics No difference in C-peptide levels existed, however, between drinking and nondrinking diabetics, indicating that chronic alcohol consumption did not alter the diabetics insulin production Consequently, the elevated glucose levels observed in the drinking diabetics likely were not caused by alcohols effects on insulin levels, but may have resulted from an alcohol-induced increase in insulin resistance in those diabetics The mechanisms underlying the increasing hyperglycemia in chronically drinking diabetics are still unknown Because the most common form of diabetes, type
2 diabetes, is associated with both insufficient insulin secretion and insulin resistance, it appears likely that the alcohol-induced increase in blood sugar levels results from adverse

effects on one or both of those variables To date, no studies have specifically evaluated the effect of chronic alcohol ingestion on insulin secretion or insulin resistance, although the study described previously by Ben and colleagues 1991 suggests that chronic alcohol exposure does not diminish insulin secretion Consequently, studies of the effects of acute alcohol ingestion currently provide the best means of assessing alcohols impact on insulin secretion and insulin resistance Such experiments, which have been conducted mainly on nondiabetics, have demonstrated that acute alcohol administration leads to increased insulin resistance Avogaro et al 1983; Yki-Jarvinen and Nikkila 1985; Shelmet et al 1988; Boden et al 1993 In diabetic people, elevated insulin secretion cannot compensate for increased insulin resistance The same mechanism might occur in chronically drinking diabetics and thus account for the deterioration of blood sugar control observed in those patients Alternatively, chronically
drinking diabetics may show worse compliance with their dietary and pharmacological treatment regimens, which also may result in uncontrolled blood sugar levels Clearly, more studies in this area are needed

Effects of Alcohol Consumption in the Fasting State
In contrast to chronic alcohol consumption in the fed state–which raises blood sugar levels, resulting in hyperglycemia– alcohol consumption in the fasting state can induce a profound reduction in blood glucose levels ie, hypoglycemia That effect has been observed in both type 1 and type 2 diabetics as well as in nondiabetics Arky and Freinkel 1964 Hypoglycemia can have serious, even life-threatening, consequences, because adequate blood sugar levels are needed to ensure brain functioning Alcohol-induced hypoglycemia typically occurs in people both diabetics and nondiabetics who, sometimes for days, have been drinking alcohol but not eating In such a fasting state, the body has two major mechanisms for maintaining the blood sugar levels
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In most States, BALs of 008 to 01 percent are the legal limits for intoxication
3

A standard drink contains 12 grams approximately 05 ounce of pure alcohol
This amount is equal to one 12-ounce bottle of beer or wine cooler, one 5-ounce glass of wine, or 15 ounces of distilled spirits 214

Consequences of Alcohol Use in Diabetics

necessary to provide energy to the brain: 1 breakdown of glycogen, or glycogenolysis, and 2 production of glucose, or gluconeogenesis Glycogen is a large molecule that consists of numerous glucose molecules and serves as a storage form of glucose in the tissues, particularly the liver In the fasting state, as a first line of defense against hypoglycemia, glycogen is broken down into its constituent glucose molecules, which are secreted by the liver into the blood to maintain normal or near-normal blood sugar levels Generally, the glycogen supply is depleted after 1 or 2 days of fasting Thus, a person who has been drinking alcohol and not eating for 1 or more days has exhausted his or her glycogen supply Gluconeogenesis, which also occurs primarily in the liver, involves the formation of new glucose molecules from alanine and glycerol Alanine is generated during the breakdown of proteins in the muscles, whereas glycerol is formed during the metabolism of certain fat molecules ie, triglycerides Alcohol
metabolism in the liver, however, actually shuts down the process of gluconeogenesis and thus the second line of defense against hypoglycemia Consequently, both of the bodys mechanisms to sustain blood sugar levels are inactivated in people who consume alcohol but do not eat, resulting in profound hypoglycemia Two additional factors may further compound the risk of alcohol-related hypoglycemia and its associated consequences in alcohol-drinking but otherwise fasting people, particularly diabetics First, alcohol consumption can lead to a situation called hypoglycemic unawareness in both diabetics and nondiabetics Kerr et al 1990 A hypoglycemic person normally experiences several warning symptoms, such as sweating, weakness, shakiness, nervousness, and pounding or racing of the heart Diabetics in particular learn to recognize those symptoms and prevent a further decline in blood sugar levels by eating some food A person in a state of hypoglycemic unawareness, however, may not notice or recognize those warning signs and is therefore at
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increased risk of severe hypoglycemia Alcohol-related hypoglycemic unawareness likely results from the cognitive impairment that
occurs when BALs reach 008 to 01 percent Second, diabetics who have consumed alcohol, particularly those with type 1 diabetes, experience a delayed glucose recovery from hypoglycemia This means that after an episode of hypoglycemia, glucose levels return to normal more slowly in drinking diabetics than in nondrinking diabetics, suggesting an alcohol-related impairment in the counter-regulatory response to hypoglycemia Avogaro et al 1993 Detailed analyses demonstrated that although the glucagon and epinephrine responses to hypoglycemia were unaffected, the growth hormone and cortisol responses were reduced after alcohol consumption The combination of alcohol-induced hypoglycemia, hypoglycemic unawareness, and delayed recovery from hypoglycemia can lead to deleterious health consequences For example, Arky and colleagues 1968 studied five diabetics who experienced severe hypoglycemia after ingesting alcohol In all five patients, the alcohol-induced hypoglycemia induced neurological changes, such as incontinence, inability to follow simple commands, perseveration,4 disorientation, and impairment of recent memory In three patients, those changes did not reverse, even after months or
years The two other patients died as a result of complications indirectly related to their hypoglycemiainduced neurological changes Therefore, to avoid alcohol-related hypoglycemia and its consequences, diabetics should consume alcohol only with or shortly after meals

Alcohols Effects on Complications of Diabetes
Diabetic Ketoacidosis Ketoacidosis, which occurs primarily in diabetics, is a condition characterized by excessive levels of certain acids called ketone bodies eg, acetone, acetoac-

etate, and -hydroxybutyrate in the blood Elevated levels of those compounds can cause nausea, vomiting, impaired mental functioning, coma, and even death Ketoacidosis is caused by complete or near-complete lack of insulin and by excessive glucagon levels Among their many functions, insulin and glucagon regulate the conversion of fat molecules ie, fatty acids into larger molecules ie, triglycerides, which are stored in the fat tissue In the absence of insulin, the triglycerides are broken down into free fatty acids, which are secreted into the bloodstream and delivered to the liver The liver normally re-incorporates free fatty acids into triglycerides, which are then packaged and secreted as
part of a group of particles called very lowdensity lipoproteins VLDL In patients with ketoacidosis, however, the liver metabolizes the incoming free fatty acids in an additional, unusual way Under the influence of excess glucagon, some of the free fatty acids are converted to ketone bodies and secreted into the blood, causing severe health consequences Ketoacidosis typically occurs in patients with type 1 diabetes who completely lack insulin In rare cases, however, the condition also may affect people with type 2 diabetes In a milder form, ketoacidosis may even occur in people who are fasting In those people, insulin levels are diminished, because the fasting has considerably lowered their blood sugar levels, thereby depriving the pancreas of its stimulus to produce and secrete insulin Heavy alcohol consumption ie, 200 grams of pure alcohol, or approximately 16 standard drinks, per day can cause ketoacidosis in both diabetics and nondiabetics Wrenn et al 1991 People who consume those high amounts of alcohol typically have been drinking and not eating for days and/or have vomited or developed other illnesses from drinking As a result, those patients frequently have very low blood
sugar levels although some people with alcoholic ketoacido4

Perseveration is the involuntary repetition of words or actions 215

sis have very high blood sugar levels, because the lack of insulin prevents glucose uptake from the blood into the tissues The mechanisms underlying the development of alcoholic ketoacidosis are complex However, some typical contributing factors result in insulin lack and excess glucagon levels, thereby promoting the development of ketoacidosis As mentioned earlier in this article, poor food intake can lead to depleted glycogen levels Furthermore, continued alcohol metabolism results in diminished gluconeogenesis Both the depletion of glycogen and diminished gluconeogenesis lead to lower blood sugar levels As blood sugar falls, insulin secretion is reduced as well Because insulin restrains glucagon secretion, lower insulin secretion allows increased glucagon secretion, setting the stage for the development of ketoacidosis This situation can be amplified if the drinker vomits repeatedly Vomiting can lead to dehydration and a reduced blood volume, which, in turn, increases the levels of certain stress hormones in the blood called catecholamines
Catecholamines further decrease insulin production and increase glucagon production Accordingly, physicians who treat diabetics known to consume large amounts of alcohol must be aware of the risk of alcoholic ketoacidosis in those patients

tein LDL cholesterol, and elevated levels of high-density lipoprotein HDL cholesterol Elevated Triglyceride Levels Hypertriglyceridemia is an important risk factor for cardiovascular diseases Moreover, elevated triglyceride levels can cause severe inflammation of the pancreas ie, pancreatitis In addition to being highly painful and potentially fatal, this inflammation may interfere with the production of insulin, thereby potentially worsening control of blood sugar levels and making hypertriglyceridemia a particularly serious complication in diabetics Heavy drinking ie, more than 140 grams of pure alcohol, or approximately 12 standard drinks, per day can cause alcohol-induced hypertriglyceridemia in both diabetics and nondiabetics Chait et al 1972 In fact, from a practical standpoint, heavy drinking should be considered as a possible contributing factor in all patients with hypertriglyceridemia Abstinence from alcohol generally leads to
normalization of the triglyceride levels, unless the person has an underlying genetic predisposition for hypertriglyceridemia Several mechanisms may contribute to alcohol-induced increases in triglyceride levels First, alcohol likely stimulates the generation of VLDL particles in the liver, which are rich in triglycerides Second, alcohol may inhibit VLDL particle breakdown Third, alcohol may enhance the increase in triglyceride levels in the blood that usually occurs after a meal Reduced LDL Cholesterol Levels LDL cholesterol is strongly related to cardiovascular disease and stroke and has been called bad cholesterol Reduction of LDL cholesterol decreases a persons likelihood of suffering a heart attack or stroke LDL cholesterol levels tend to be lower in alcoholics than in nondrinkers Castelli et al 1977, suggesting that chronic alcohol consumption may have a beneficial effect on cardiovascular risk However, Lin and colleagues 1995 reported that the LDL cholesterol in alcoholics

exhibits altered biological functions and may more readily cause cardiovascular disease The researchers found that the levels of vitamin E, an agent that in part is bound to LDL cholesterol and which may
decrease the risk of cardiovascular disease, also are lower in alcoholics than in nonalcoholics Those observations suggest that the reduced levels of vitamin E in alcoholics actually may have harmful long-term effects Elevated HDL Cholesterol Levels HDL cholesterol has a protective effect against cardiovascular disease and is called good cholesterol This protective effect results at least partly from a process called reverse cholesterol transport, in which HDL particles carry cholesterol from blood vessel walls and other sites back to the liver, where it is broken down and subsequently eliminated from the body Two subtypes of HDL–HDL2 and HDL3–are particularly effective in this reverse cholesterol transport Studies in alcoholics found that the levels of HDL, and particularly of HDL2 and HDL3, were elevated after a period of chronic drinking and returned to normal levels after several days of abstinence Taskinen et al 1982 Moreover, epidemiological data have demonstrated that moderate alcohol consumption of up to three standard drinks per day is associated with a reduced risk of heart attacks and that this effect is partly mediated by alcohol-induced increases in HDL2 and HDL3
levels Gaziano et al 1993

Alterations of Lipid Metabolism Abnormalities in the levels and metabolism of lipids are extremely common in people with either type 1 or type 2 diabetes and may contribute to those patients risk of developing cardiovascular disease Durrington 1995 Alcohol consumption can exacerbate the diabetes-related lipid abnormalities, because numerous studies have shown that heavy drinking can alter lipid levels even in nondiabetics Alcohol can induce several types of lipid alterations, including elevated triglyceride levels in the blood ie, hypertriglyceridemia, reduced levels of low-density lipopro216

Cardiovascular Disease Cardiovascular disease continues to be one of the leading causes of death among all Americans and is the leading cause of death in people with type 2 diabetes Bierman 1992 The relationship of alcohol consumption to cardiovascular disease in diabetic people has not been well evaluated However, substantial information on the association of alcohol and cardiovascular disease exists from population studies that included an unknown
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percentage of diabetics For example, in one
10-year study of 1,422 men, overall death rates and, by extension, death rates from cardiovascular disease were lowest among those who consumed 01 to 34 grams of alcohol per day ie, between 1 standard drink every few months and approximately 3 standard drinks per day Marmot et al 1981 Both complete abstainers and people drinking more than 34 grams of alcohol per day had higher death rates, with abstainers exhibiting the highest death rates from cardiovascular disease and heavy drinkers exhibiting the highest death rates from noncardiovascular disease Those findings suggest that alcohol consumption, particularly moderate consumption, may have a protective effect against cardiovascular disease Alcohol consumption also can influence blood pressure In population studies, moderate alcohol consumption of less than two drinks per day was associated with slightly lower blood pressure than abstinence, particularly among women Harburg et al 1980; Klatsky et al 1977 Consumption of more than three drinks, however, resulted in elevated blood pressure in both men and women compared with nondrinkers Because high blood pressure is a risk factor for cardiovascular disease, those results also
suggest that moderate alcohol consumption can have beneficial effects for cardiovascular disease risk It is unknown, however, whether that effect applies equally to diabetics and nondiabetics, because those studies did not specify the proportion of diabetic participants The mechanisms underlying alcohols impact on blood pressure have not been fully elucidated

Peripheral Neuropathy Peripheral neuropathy is a condition in which nerves are damaged that extend from the spinal cord to control muscle function ie, motor nerves or that transmit various sensations– such as touch, pain, temperature, and vibration–back to the spinal cord and brain ie, sensory nerves Although
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many patients do not experience symptoms of peripheral neuropathy, other patients suffer from varied and troublesome symptoms, such as tingling, burning, pain, and numbness Those symptoms occur most commonly in the legs and feet and are frequently worse at night Numbness in particular can be a serious problem: Patients may not sense lesions, such as cuts or ulcers, which may then become seriously infected and result in amputation of the affected limb Diabetes and alcohol consumption are the two most
common underlying causes of peripheral neuropathy Among diabetics, the prevalence of neuropathy with obvious symptoms ie, symptomatic neuropathy increases with increasing disease duration Moreover, McCulloch and colleagues 1980 reported that for any given duration of diabetes, the prevalence of symptomatic peripheral neuropathy was greater in men who consumed at least three to four alcohol-containing beverages almost every night compared with men who drank less That increase in prevalence was most apparent in patients with a disease duration of less than 4 years Other researchers observed that the prevalence of neuropathy in type 1 diabetics increased in a linear fashion with the alcohol amount consumed Mitchell and Vinik 1987 Those researchers also reported that diabetics who consumed more than eight standard drinks per week developed peripheral neuropathy faster than did diabetics who consumed eight or fewer drinks per week Alcohol use also is associated with an inability to sense vibrations from a tuning fork ie, absent vibratory perception, which serves as a convenient semiquantitative measure of peripheral neuropathy Sosenko et al 1986 All of these findings suggest that
alcohol and diabetes can enhance each others effects in terms of causing nerve damage Because neuropathy is a major clinical problem in diabetics, more analyses are needed of the precise quantitative relationship between alcohol intake and neuropathy in diabetics as well as on factors

that may reverse or protect against the neuropathy Impotence Neuropathy, in addition to other factors eg, vascular disease in the penis or altered hormone levels, also may contribute to impotence, which is a common and troublesome complication in diabetic men The nerves that control erection are part of the autonomic nervous system, which controls numerous vital processes that occur without conscious efforts eg, breathing and the contractions of the gut necessary for proper digestion Despite the high prevalence of impotence in male diabetics and the fact that many of these men consume alcohol, few studies have evaluated the relationship between alcohol intake and impotence in diabetics In one study of 275 originally potent diabetic men, heavy drinkers were significantly more likely to develop impotence during the 5year study period than were moderate drinkers McCulloch et al 1984 Based on assumptions
regarding the alcohol content of the beverages mentioned in the study, heavy drinkers were defined as those who ingested 29 grams of alcohol, or approximately two to three standard drinks, per day Many impotent diabetic men also have lower than normal levels of the sex hormone testosterone in their blood Alcohol reduces blood levels of testosterone and may thereby further exacerbate the existing hormonal deficit Clinical experience indicates, however, that a testosterone deficit rarely is the sole reason for impotence in diabetic men, because treatment with testosterone rarely restores potency in those men Thus, both neuropathy and vascular disease likely play significant roles in impotence in diabetic men

Retinopathy Diabetic eye disease ie, retinopathy is another troublesome tissue complication of diabetes and one of the leading causes of blindness in the United States today Good blood sugar and blood pressure control as well as regular eye examinations are essential for the prevention of retinopa217

thy Heavy alcohol consumption may increase a persons risk for developing this disease Thus, in one study of 296 male diabetics who had no eye disease at the beginning of the study,
those men who drank the equivalent of more than 10 pints of beer per week were more likely to develop retinopathy over 5 years than were those men who drank less or were abstainers Young et al 1984 Interestingly, the risk of retinopathy was independent of the mens ability to control their blood sugar, suggesting that alcohol may directly damage the eyes or related structures The much larger United Kingdom Prospective Diabetes Study confirmed that alcohol consumption in men but not in women was associated with more severe retinopathy Kohner et al 1998 The relationship between alcohol consumption and retinopathy in that study, however, was not independent ie, it may have resulted from other intermediary factors, such as greater alcohol-related blood sugar elevation in drinking diabetics than in nondrinking diabetics Consequently, the information regarding the relationship between alcohol ingestion and diabetic eye disease remains inconsistent, underlining the need for further studies

Metformin, a medication that decreases insulin resistance, can cause potentially lethal side effects in patients whose liver is not functioning properly Accordingly, patients who abuse alcohol and are
therefore at risk for liver damage must not take metformin Troglitazone, another medication that decreases insulin resistance, also must not be used by patients with liver disease and therefore should not be used by alcohol abusers Moreover, troglitazone itself may impair liver function, and alcohol might further exacerbate this harmful effect

References
ARKY, RA, AND FREINKEL, N Alcohol hypoglycemia Archives of Internal Medicine 114:501 507, 1964 ARKY, RA; VEVERBRANTS, E; AND ABRAMSON, EA Irreversible hypoglycemia Journal of the American Medical Association 206:575578, 1968 AVOGARO, A; DUNER, E; MARESCOTTI, C; FERRARA, D; DEL PRATO, S; NOSADIN, R; AND TIENGO, A Metabolic effects of moderate alcohol intake with meals in insulin-dependent diabetics controlled by artificial endocrine pancreas AEP and in normal subjects Metabolism 32:463470, 1983 AVOGARO, A; BELTRAMELLO, P; GNUDI, L Alcohol intake impairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients: Evidence for a critical role of free fatty acids Diabetes 42:16261634, 1993 BEN, G; GNUDI, L; MARAN, A; GIGANTE, A; DUNER, E; LORI, E; TIENGO, A; AND AVOGARO, A Effects of chronic alcohol intake
on carbohydrate and lipid metabolism in subjects with type II non-insulin-dependent diabetes American Journal of Medicine 90:7076, 1991 BIERMAN, EL Atherogenesis in diabetes Arteriosclerosis and Thrombosis 12:647656, 1992 BODEN, G; CHEN, X; DESANTIS, R; WHITE, J; MOZZOLI, M Effects of ethanol on carbohydrate metabolism in the elderly Diabetes 42:28 34, 1993
AND

Summary
Occasional episodes of alcohol consumption generally do not worsen blood sugar control in people with diabetes and may even have beneficial effects Regular consumption of even moderate amounts of alcohol ie, two to four drinks per day, however, clearly interferes with diabetic blood sugar control and increases the risk of impotence; peripheral neuropathy; and, possibly, retinopathy At the same time, similar levels of alcohol consumption are associated with a decreased risk of heart attacks and death from cardiovascular disease The latter findings, however, were obtained with populations that included diabetics as well as nondiabetics, thereby limiting researchers ability to apply those findings to diabetics Accordingly, more studies are needed to determine whether the beneficial effects of daily moderate alcohol
consumption outweigh the deleterious effects Diabetics clearly should avoid heavy drinking ie, more than 10 to 12 drinks per day, because it can cause ketoacidosis and hypertriglyceridemia Moreover, heavy drinking in a fasting state can cause hypoglycemia and ultimately increase diabetics risk of death from noncardiovascular causes s

CASTELLI, WP; GORDON, T; HJORTLAND, MC; KAGAN, A; DOYLE, JT; HAMES, CG; HULLEY, SB; AND ZUKEL, WJ Alcohol and blood lipids: The Cooperative Lipoprotein Phenotyping Study Lancet 2:153155, 1977 CHAIT, A; MANCINI, M; FEBRUARY, AW; AND LEWIS, B Clinical and metabolic study of alcoholic hyperlipidaemia Lancet July:62-64, 1972 DEFRONZO, RA Pathogenesis of type 2 diabetes: Metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 53:177 269, 1997 DURRINGTON, PN Hyperlipidaemia: Diagnosis and Management 2d ed Oxford, Great Britain: Butterworth-Heinemann, Ltd, 1995 GAZIANO, JM; BURING, JE; BRESLOW, JL; GOLDHABER, SZ; ROSNER, B; VAN DENBURGH, M; WILLET, W; AND HENNEKENS, CH Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction New England Journal of
Medicine 329:18291834, 1993 HARBURG, E; OZGOREN, F; HAWTHORNE, VM; SCHORK, MA Community norms of alcohol usage and blood pressure: Tecumseh, Michigan American Journal of Public Health 70:813820, 1980 KERR, D; MACDONALD, A; HELLER, SR; TATTERSALL, RB Alcohol causes hypoglycaemic unawareness in healthy volunteers and patients with Alcohol Health Research World

Medication Interactions
In addition to exacerbating various medical complications of diabetes, alcohol consumption and its associated health consequences may interact with or alter the effects of several medications used to treat diabetes, including the following: Chlorpropamide is a medication used to treat type 2 diabetes by increasing pancreatic insulin secretion Some people treated with chlorpropamide experience an unpleasant, disulfiram-like reaction5 after drinking alcohol
5

Disulfiram Antabuse is a medication used to treat alcoholics It acts by inducing an unpleasant physical response eg, nausea and vomiting after alcohol consumption 218

Consequences of Alcohol Use in Diabetics

Type 1 insulin-dependent diabetes Diabetologia 33:216221, 1990 KLATSKY, L; FRIEDMAN, GD; SIEGELAUB, AB; AND GERARD, MJ Alcohol consumption
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Visit NIAAA in 1999
The
National Institute on Alcohol Abuse and Alcoholism NIAAA invites you to visit its scientific exhibit at upcoming conferences around the country

1999 Conferences
s Medical Library Association May 1518 Chicago, IL s American Psychiatric Association May 1520 Washington, DC s Digestive Disease Week 1999 May 1521 Orlando, FL s National Association of Alcoholism and Drug Abuse Counselors May 2628 Philadelphia, PA s American Psychological Society June 36 Denver, CO s National Association of State Alcohol and Drug Abuse Directors June 37 St Pete Beach, FL s Research Society on Alcoholism June 27July 1 Santa Barbara, CA s American Sociological Association August 610 Chicago, IL s American Psychological Association 107th Annual Convention August 2024 Boston, MA s Mothers Against Drunk Driving September 1619 Albuquerque, NM

The Alcohol and Alcohol Problems Science Database ETOH, recent NIAAA publications, and research grant information will be on display
Vol 22, No 3, 1998 219

Source:nhchc.org