Antidiabetic Drugs

Archive for the ‘Views & Reviews’ Category

The loss of bone mineral density and the subsequent risk for osteoporosis are higher for those with Type I diabetes than those with Type II, according to researchers from the University of Turku in Finland. The increased risk seems to be due to rapid bone loss that occurs at or soon after the onset of Type I diabetes, though why this bone loss occurs in unknown.

Most studies agree that Type I diabetes contributes to the loss of bone mineral density (BMD). But when it comes to people with Type II, the studies disagreed: Some found no change in bone mineral density, some found an increase, and others a decrease.

This study was the first to include both groups in the same study. There were 56 Type I participants, 62 with Type II diabetes, and 498 people serving as the control group. The participants ranged in age from 52 to 72, and all had developed diabetes after age 30, which means they’d had a chance to reach their highest level of bone mass.

Lower bone density was found in both men and women with Type I diabetes. However, when the researchers adjusted for age and body mass, the difference between males and females decreased somewhat.

The rate of bone fractures was higher in women with Type I diabetes than in women with Type II, which also indicates that bone mineral loss is more pronounced for women with Type I.

Researchers stated that the difference in bone density couldn’t be due to insulin therapy, since all participants were taking insulin. Previous studies suggest that insulin therapy may increase bone loss in Type I diabetics.

While the exact reason for the increased loss of bone density is not yet known, researchers urge people with Type I diabetes to make sure their health-care providers test them for low bone density and osteoporosis. Diabetes practitioners should test these patients for low-bone density and treat it immediately to prevent onset of osteoporosis and fractures.

Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors.

Lipodystrophy is a well-known local complication of insulin injection that has two very different outcomes, causing either the swelling or the wasting of subcutaneous fat. These two reactions appear to have two different causes and mechanisms, lipohypertrophy (swelling) being caused by a cellular reaction to the local accumulation of insulin, and lipatrophy stemming from an immune reaction to impurities in the insulin. Lipohypertrophy is common in all diabetic populations, but tends to occur with particular frequency among children and young women. A group of German physicians assembled 223 type I (insulin-dependent) and 56 type II (non-insulin-dependent) diabetes patients in order to assess what caused the complication and suggest methods whereby it might be better prevented.

Researchers found that lipohypertrophy was far more common in the type I diabetics (28.7%) than in the type II diabetics (3.6%). Lipatrophy was far rarer; only 4.5% of all patients reported having suffered the condition. In the great majority of patients only one site was affected by lipohypertrophy, but the swelling was more commonly considered distinct (over 3 cm wide and 0.5 cm high) rather than discrete (smaller). Lipohypertrophy had first appeared in some patients when they were as young as five, in others as old as 48, but in the majority of subjects it had appeared between 15 and 30 years of age, and within five years of first using an insulin syringe or pen. The type of insulin used (human, porcine or bovine) did not affect the risk of lipohypertrophy.

Use of insulin pens appeared to increase the risk of lipohypertrophy compared with those patients who used only syringes; 35.7% of those who used only pens and 35.8% of those who used both pens and syringes developed the condition, while only 23.4% of those who never used pens showed signs of it. However, neither a higher number of daily injections nor larger daily doses of insulin meant a significantly increased risk of lipohypertrophy.

A myth surrounding this disorder is that patients cause and then aggravate lipohypertrophy by continually injecting into the same site because it is less painful. Under 22% of patients said that injection into the lipohypertrophic site was actually less painful, while over 23% found it more painful. For the remainder, there was no difference in sensitivity. However, the link between the condition and patients’ failure to rotate injection sites is real: 60% of those patients who always used the same injection site were afflicted, as opposed to only 22.1% of those who rotated regularly. Women were also almost twice as likely to suffer, and patients who used the abdomen as an injection site were also at greater risk. The upper arm, followed by the thigh, were found to be the safest places. More obese people, who naturally tend to have more subcutaneous fat, were at less risk than leaner people.

Previous studies have shown that children may be at particular risk. One 1993 survey at a summer camp for diabetic kids found that 45% had the condition. Lipohypertrophy is also quite common among young women with diabetes, and is frequently a cosmetic problem. Once it occurs, it is unusual for it to regress in the short term even if the injection site is no longer used. Fortunately, liposuction can be used to remove it. While improvements in insulin purity have greatly reduced the problem of lipatrophy in recent years, lipohypertrophy rates have barely changed. Patient education might achieve what science has not. Far simpler than surgery, and far better than waiting months or years for the swelling to disappear, is to avoid lipohypertrophy in the first place. The best way to do that is by rotating injection sites, particularly in the abdomen.

Does a high-carbohydrate diet have different effects in NIDDM patients treated with diet alone or hypoglycemic drugs?

Monounsaturated fatty acids (MUFAs) have become the latest dietary revelation in the management of diabetes. Dietary diabetes control has progressed a good deal over time, and a lot is now known about the effect of various drug regimens on the different indicators of metabolic well-being. MUFAs, when consumed as part of a diet that provides a caloric deficit (in other words, less calories in food than calories burned in activity), have been found to offer benefits in improving lipid and cholesterol profiles beyond those offered by low-calorie/high-carbohydrate diets.

Suspecting that different diets might have different effects on people with less serious glucose intolerance, a group of Italian specialists decided to compare a group of NIDDM (non-insulin-dependent diabetes mellitus) patients with reasonably mild hyperglycemia who were controlled by diet alone and a group of more hyperglycemic NIDDM patients who needed oral hypoglycemic drugs (in this case, glibenclamide) in addition to dietary control. The patients were isolated in the metabolic ward and fed rigourously controlled diets in which calories came either mostly from carbohydrate (carbohydrate 60%, fat 20%, protein 20%) or equally from fat and carbohydrate (carbohydrate 40%, fat 40%, protein 20%). The fat portion of the diet consisted mostly of MUFAs, and this being a Neapolitan study, was supplied by olive oil. The carbohydrate portion of the diet was based heavily on bread which is rich in starch, a complex carbohydrate that is better for metabolic control than simple monodisaccharides. After 15 days the two groups switched diets and continued for another 15 days; glucose and insulin monitoring continued throughout.

No difference was found between the two regimens in fasting glucose concentrations or body weight, which remained unchanged. However, glucose levels after meals were higher in the high carbohydrate regime, but only in the drug-treated patients. The patients treated with diet alone showed higher insulin levels after meals on the high-carbohydrate diet. Both glibenclamide-treated patients and diet-managed patients showed a tendency to higher triglyceride levels following meals on the high-carbohydrate diet.

The reason appears to be that in patients with less severe glucose intolerance (including all borderline non-insulin-dependent diabetes mellitus cases, but probably none of those that require hypoglycemic drugs) there is a natural insulin secretory response to the intake of carbohydrates that keeps glucose following meals at controlled levels. A high-fat, low-carbohydrate diet does not seem to present any problem for people with milder cases of diabetes either, provided most of the fats are unsaturated and total caloric intake does not increase. In conclusion, dieticians should be flexible to the particular profile of each patient, looking at body weight, cholesterol levels, triglyceride levels and glucose intolerance before prescribing any particular regimen.

This study looked at the link between the progress of diabetes and peroxidative damage of body tissues in a population of almost 500 patients with NIDDM attending a diabetes centre in Madras, India. It had previously been noted that diabetes mellitus patients displayed an imbalance in their antioxidant protective mechanism, placing cells under oxygen stress. When that happens, dangerous oxygen-derived products such as free radicals are created that can damage DNA, deactivate enzymes, oxidize hormones, and harm membranes. All aerobic cells create the dangerous oxygen-derived products, most notably (and in ascending order of cell lethality) superoxide radical, hydrogen peroxide and hydroxyl radical. But the healthy body also contains “scavengers” known as antioxidants that hunt down these menacing free radicals and detoxify them.

This is the role of vitamins A, B-carotene, C and E, and a group of less well-known scavengers such as glutathione. Each of these scavengers has the ability to exist in oxidized and reduced form, which means they can take on oxygen atoms or shed them without becoming toxic. When they encounter a free radical such as hydroxyl radical (OH-), their ability to take on the extra oxygen detoxifies the hydroxyl radical and prevents it from dumping its oxygen elsewhere. If no scavenger finds the free radical, it will oxidize cellular lipids, proteins, or nucleic acids, causing cell tissue damage. People with diabetes are especially prone to the creation of such reactive oxygen products in the blood because of the auto-oxidation of glucose and glycosylated (glucose-bound) proteins.

Evidence of increased peroxidation was found in the 467 cases of NIDDM examined. The body contains certain substances that protect against peroxidation: Vitamin C (a potent antioxidant), glutathione (which protects red blood cells from oxidative stress and destruction), superoxide dismutase (an enzyme that regulates the transfer of oxygen atoms) and catalase (a blood protein that breaks peroxides up into harmless water and oxygen). Deficiencies in all of these vital protective substances were noted in the first two years after onset of NIDDM. Moreover, lipid peroxidation appeared to increase with the duration of NIDDM.

The question to be examined next is whether antioxidant deficiency is a cause — and not just a consequence — of diabetes. This can be done by analyzing the antioxidant levels in people susceptible to NIDDM, such as people who are obese and glucose intolerant or who have a family history of the disease. As well, researchers can evaluate treatments capable of increasing the antioxidant level in patients with NIDDM, which may help to control lipid peroxidation. This type of treatment could reduce some of the secondary complications of diabetes mellitus, most of which flow from the vascular and capillary damage done by unchecked oxidation.

Questions – Answers

1. Are there any treatments now available to raise antioxidant levels?

It is always possible to take supplements such as the scavenger vitamins A, C, and E. In fact, it is normal for such antioxidant supplements to be given to antioxidant-deficient diabetics. But that does not necessarily mean that the patient’s levels of antioxidant enzymes such as glutathione will rise. There is no drug treatment that can ensure that. However, high levels of antioxidant vitamins will partly compensate for low levels of antioxidant enzymes.

2. What exactly is peroxidation, in simple terms?

Oxidation is what we call the process of combination between oxygen, created naturally in all aerobic cells, and a molecule, in which oxygen atoms are transferred to the new molecule to create an oxidized form. Peroxidation occurs when the molecule is loaded with the maximum number of oxygen atoms it can handle. This molecule then becomes a reactive and unstable free radical, and will shed its extra oxygen on cellular lipids, proteins and so on. Normally, the body prevents this by scavenging free radicals and stripping them of their toxic extra oxygen. People who are deficient in antioxidants, including many diabetics, are unable to scavenge all of the free radicals in circulation and suffer oxidative tissue damage.

3. Do people with NIDDM seem to be more at risk from oxidative stress because they have more oxygen free radicals, or because they have fewer antioxidants?

Studies suggest that people with both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes, on average, have cells that produce toxic oxygen by-products such as peroxides in larger quantities than other people. They also seem to suffer more tissue damage due to oxidation. So it may be that diabetics have more free radicals, fewer antioxidants, and the free radicals do more harm than in other people. This is certainly one of the main mechanisms linking diabetes to cardiovascular complications, though I would hesitate to say it is the most important.

NIDDM (non-insulin dependent diabetes mellitus) is by far the most common form of diabetes, accounting for about 90% of all sufferers. The proportion of people affected by this condition climbs in each age group, reaching 18% in 64- to 75-year-olds and as many as 40% in those over 80. Moreover, it has been estimated that for every known elderly diabetic another remains undiagnosed. All face a greatly increased risk of arterial problems leading to coronary heart disease, stroke and circulatory dysfunction, as well as the known eye, kidney and nervous system complications of the disease, which can cause impaired vision or blindness, foot ulcers or amputations.

What is non-insulin dependent diabetes mellitus?

Usually NIDDM is the combination of two problems: firstly, the failure of patients to secrete enough glucose, and secondly, insulin resistance, or the reduced efficiency of insulin owing to a failure by the body’s tissues to respond to it as they should. Although people with non-insulin dependent diabetes mellitus all have some degree of insulin deficiency in the pancreas, they often have quite high levels of insulin in the blood. Their problem is that becuase of insulin resistance, even those fairly large amounts of insulin are not enough to control their glucose levels.

Large injected doses of insulin can overcome insulin resistance and increase the uptake of glucose by skeletal muscle, but prolonged heavy use of insulin tends to increase body weight and may also increase the risk of cardiovascular disease. Perhaps most importantly, it greatly increases the risk of hypoglycemic episodes (glucose deficiency) – particularly serious in elderly patients who are weaker and may have underlying heart problems. Therefore, the goal in treating elderly patients with non-insulin dependent diabetes mellitus should be to control glycemic levels with the minimum possible amount of insulin.

Why target the liver?

Fortunately, while it takes a lot of insulin to increase glucose uptake, it takes a lot less to decrease glucose production by the liver. Because of this, a single bedtime injection can give similar results in terms of glycemic control to a daytime administration, but with smaller doses and therefore reduced side effects. In general, doctors should be more tolerant of glucose levels in older patients because their kidneys have a higher threshold of tolerance for glucose, and because trying too strictly to maintain glycemic levels at optimum produces fewer benefits and greater risks for older patients.

Studies of the effect of intensive insulin therapy on elderly patients have shown that while a single evening dose of insulin brought glucose levels down appreciably, an additional two, three, or more injections during the day had little further effect. During follow-up, however, those patients who received intensive insulin treatment experienced a twofold increase in major cardiovascular events compared with patients who received a single dose.

Why use insulin at all?

While such data suggest that large doses of insulin may do more harm than good in elderly patients, it is important to remember that insulin, and insulin alone, can always lower blood glucose levels; it is simply a matter of finding the right dose. Recent studies have shown that poor control of blood glucose is, in the long run, a recipe for increased cardiovascular risk. Today, most doctors feel it is better to intervene to try to improve glycemic control. Innovations such as the insulin pen have made self-injection easier, and self-administration of an evening dose now presents no problem for most elderly patients if they are clearly and patiently taught how to do it.

It is reasonable to set the same goals for insulin therapy for elderly patients as for middle-aged diabetes sufferers. Hyperglycemic symptoms, such as thirst, blurred vision, frequent urination and even coma, can and should be prevented through insulin therapy. Exercise, within the limits of what’s possible for an elderly patient, can cut body mass and improve metabolic control. Finally, bacterial infections and diabetic complications can be reduced, delayed, or prevented. The non-interventionist philosophy of the past did not achieve any of these goals.

Who should receive insulin therapy?

Two considerations are important when evaluating a patient’s likely response to insulin therapy aimed at cutting glucose production. One is that not all non-insulin dependent diabetes mellitus patients have the same metabolism. As a general rule, obese patients are more likely to have higher insulin resistance, whereas leaner patients are more likely to have poor insulin secretion.

Secondly, NIDDM can transmute with time into insulin-dependent diabetes mellitus (IDDM), particularly in women who are not obese and who have a history of other auto-immune diseases. The transition to frank IDDM is often harder to detect in elderly patients, who will require insulin therapy as a matter of course – and the earlier it begins, the better.

In other cases, however, an apparent failure of diet and oral drug therapy, which would seem to indicate the need for insulin therapy, may be traced to an unrelated infection or heart problem which increases insulin resistance. Rather than simply bombarding the patient with insulin, the root of the problem should be addressed. Under certain circumstances, even psychological problems such as depression can cause this kind of fluctuation in glycemic control.

Conclusion

NIDDM remains notoriously difficult to treat in elderly patients. But there is no excuse for inaction, nor should older patients be lumped together in treatment programs more suited to younger patients. There is a way to offer them the benefits of improved glycemic control, without exposing them to the risks of intensive insulin therapy. A single nightly injection of insulin can allow an elderly patient to enjoy a normal day of meals and exercise without undue fear of a disastrous hypoglycemic episode.

It’s never easy to isolate the causes of any disease. An individual who smokes and then suffers a stroke did not necessarily suffer stroke because of smoking; it may have been because he or she ate too much fat or didn’t exercise or had too high blood pressure. Or it may have been a combination of all of those factors or none of them. Human diet, health and behaviour is sometimes too complicated to nail down any one risk factor as greater or lesser than others.

But two Finnish studies, involving 16,649 men and women between the ages of 30 and 59, set out to evaluate the causes of stroke by rigourously analyzing all known major risk factors, separately and jointly.

The Finns looked at smoking, cholesterol levels, individual blood pressure, rates of hypertension, exposure to drug therapy for hypertension, and body mass index, or obesity. They looked especially hard at glucose tolerance, monitoring both those men and women who were already diabetic when the study began, and those who developed diabetes as the studies progressed over 15 and 20 years.

What they found was more or less as expected. Smoking, hypertension, obesity and high cholesterol all increase the risk of stroke in men, and all but cholesterol were shown to have the same effect on women. Most factors had a markedly greater effect on women. For example, though far more men in the survey smoked than women, women who did smoke ran a risk of fatal stroke 1.8 times greater than women who did not. For men, the comparable figure was under 1.4 (though it was higher among non-diabetics).

An even clearer indicator was drug treatment for hypertension. Men who had taken antihypertensive drugs were twice as likely to die of stroke as men who had not. Among women, again, the disparity was even greater. These figures reflect the fact that patients who need antihypertensive drugs are obviously more likely to be hypertensive. It is the hypertension that contributes to stroke, not the drug that combats hypertension. And of course, when drug therapy succeeds in controlling hypertension, the risk of stroke is reduced.

Of all the indicators of stroke, by far the strongest proved to be diabetes. Other things being equal, men with diabetes were 3.8 times more likely and women six times more likely to die of stroke than non-diabetics of the same sex and age. Put another way, twice as many of the men who died from stroke were diabetics as of the men who remained alive at the end of the follow-up. Among women who died of stroke, the proportion of diabetics was three times as high as among women who died of other causes and eight times as high as among women who survived to the end of the survey.

The risk of stroke from diabetes was also shown to grow with time. Men who had diabetes when the survey began were four times more likely to die of a stroke than men who developed diabetes during the course of the survey. In fact, late-developing diabetics were only 1.7 times more at risk of stroke than the non-diabetics. That’s a lower risk factor than non-diabetic smokers faced.

Women who had diabetes at the start of the survey were at more than twice the risk of a fatal stroke than those whose diabetes was diagnosed later on. All of this seems to show that it takes time for diabetes to really raise the risk of stroke significantly.

Finally, although women are more susceptible to the effects of most stroke risk factors, they should not feel especially at risk. No women need fear one risk factor this survey only touched upon: the risk of being a man. More men than women died of stroke in the survey although women outnumbered men. Men, in fact, are twice as likely as women to suffer a fatal stroke.

One should remember when reading these results that women in the various risk categories were compared only with other women. Insofar as it looks at gender, what this survey really tells us is that smoking, obesity and, above all, diabetes have much more impact on women than men in terms of stroke risk. While fewer women die of stroke than men, more female fatal strokes (one-third of the total) can be attributed directly to diabetes, double the rate for men.

International Textbook on Diabetes Mellitus. Volumes 1 and 2

K G M M Alberti, R A Defronzo, H Keen and P Zimmert, eds

Chichester: John Wiley, 1992, 2750 pp

ISBN 0-471-91497-5

Enormous strides have been made in the understanding and management of diabetes mellitus over the last few years. The subject is now so large that no one specialist is likely to be able to master all aspects. Professor K G M M Alberti and his colleagues have assembled a most distinguished panel of experts to produce a comprehensive volume covering all aspects of modern diabetes. These include diagnosis, epidemiology and aetiology, biochemistry and patho-physiology. There are beautiful chapters on the biochemistry of insulin action and on the pathogenesis of type 2 diabetes and its relationship to insulin resistance. The modern management of diabetes is comprehensively covered with excellent chapters on diet, oral hypoglycaemic drugs and insulin therapy. Newer aspects of insulin therapy are well covered. There are chapters on pancreas transplantation and the modern delivery and organization of diabetes care. The clinical aspects of diabetes in childhood and adolescence, brittle diabetes, and diabetes in pregnancy are also well covered. There are comprehensive chapters on diabetic emergencies and on the aetiology and management of the complications of diabetes. Also, ihere is comprehensive coverage on diabetes and public health and of the problems of diabetes in developing countries. All in all, this is a splendid reference book in two volumes. The specialist in diabetes will find a chapter on any aspect of diabetes on which he wants to up date himself. There is good uniformity of style despite the number of authors involved. The chapters are extensively referenced. There are many beautiful and informative illustrations and diagrams. I am confident that every diabetologist will want to have one in his study for reference.

When a Child Has Diabetes

When a Child Has Diabetes

Denis Daneman, Marcia Frank, Kusiel Perlman
Key Porter Books Ltd, 70 The Esplanade, Toronto, ON M5E 1R2
1999/209 pp

Strengths

Comprehensive, well written, easy to read, informative

Weaknesses

Might make the whole process seem too simple

Audience

Anybody involved with a child with diabetes, including the child

This book is well written. A short overview is followed by individual chapters dealing with the specifics of diagnosis and continuing management of this challenging condition.

Each chapter begins with an anecdote from an individual or family as a way to explore specific situations and to provide the information necessary to make decisions. At the end of each chapter, a series of questions most commonly asked by patients and their families are followed by appropriate answers.

Overview. The first chapter covers progress from presentation to treatment through an explanation of the mechanics, types of diabetes, causes and risk of development, the way insulin works, the effect of too little insulin, confirming the diagnosis.

Striking a balance. The authors discuss the concept of blood glucose balance and factors that have to be faced daily that influence this balance.

All about insulin. Types of insulin, their actions, combinations, and administration are described in a very practical manner.

Making meals work. An outstandingly simple explanation of meal planning offers examples of how to make meals interesting. An excellent exploration of carbohydrate counting provides extreme flexibility in meal planning and is an almost essential component of intensive insulin therapy.

Balancing blood sugar. The authors provide information to help a child live with diabetes rather than be ruled by diabetes. Useful information explains target ranges for blood sugars, the meaning of hemoglobin AIC levels, and how to adjust dosage of insulin. One item discussed, which is rarely seen in other sources, is the phenomenon of delayed low blood sugar.

Handling highs and lows. This subject poses a problem to all caregivers and is addressed in an outstandingly clear way, with an explanation of how to take prompt and appropriate action.

Adjusting to diabetes. An often neglected subject, the effect of the diagnosis on people and the effect of diabetes on lifestyle, is addressed.

Growth and development. From infants to young adults, diabetes affects development.

Putting complications in perspective. The authors take a nonthreaten-ing approach.

Setting the stage for a healthy future. The years of rebellion from the teen years to early adulthood often involve poor diabetes control. This chapter finishes with the challenge of transferring from a pediatric to an adult health care milieu.

Future of diabetes. The authors offer a wish list and a promise.

Results of the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study trial confirm that excellent control leads to improved outcomes. This applies both to those who already have complications and those who do not. With the tools that we have today (newer insulins, newer delivery methods, excellent monitoring systems available at minimal cost), we should be able to approach the results obtained in those trials in the community at large, and this book will certainly help us work toward this goal.

As family physicians, up to 15% of patients we see daily are likely to have diabetes. Seventy percent or more of people with diabetes would prefer to be looked after by their family physicians. Family physicians, working closely with diabetes centres, achieve results comparable to those of diabetologists working in or with diabetes centres. We must meet the challenge and help those with diabetes to achieve healthier lifestyles and longer and healthier futures. This book, written to address the needs of children with type 1 diabetes, will help us with them and adults with type 2 diabetes, whether they need insulin or not.

I highly recommend this book.

The Everyday Diabetes Cookbook

The Everyday Diabetes Cookbook

Stella Bowling

Key Porter Books Limited, 70 The Esplanade, Toronto, ON M5E 1R2
1997/176 pp

Strengths

Nutritional overview given for each section, good variety of recipes, references to the Good Health Eating Guide and the Canadian Diabetes Association Food Choice Values, symbols for all recipes

Weaknesses

Title is misleading—not an everyday cookbook, no cooking time or preparation time given, food names that might not be well known or might sound unappetizing to the average consumer (eg, Mediterranean Cougere, Lambrhogan, Seafood Paella)

Audience

Those with diabetes who like eating and who have a discerning palate

Yes, there is eating for the gourmet after the diagnosis of diabetes. Stella Bowling provides recipes to satisfy the discerning palate. This book contains recipes for cooks who wish to serve interesting meals for family and guests who are fond of eating but who have diabetes. Courses from starters to desserts are covered. There are recipes for meat, fish, fowl, vegetables, pasta, bread, and cakes. Stella Bowling included a variety of sauces so that the recipes might be used in conjunction with the Good Health Eating Guide. The book contains addresses of the provincial divisional offices of the Canadian Diabetes Association (Association Canadien du Diabète). The book is published in English only.

I was medical officer at a camp for children with diabetes. My family attended the camp, and they so enjoyed the food there they wanted to become diabetic. This book contains recipes that would please all of us. It would help us develop healthy eating habits, with nutritious and interesting food, without having to develop diabetes.

I recommend this book to diabetics who have mastered the basic meal plan.

Antihypertensive therapy with nisoldipine resulted in more Mis than therapy with enalapril in type 2 diabetes. Commentator, Malmberg, K., Ryden, L. and Wedel, H. Karolinska Hospital and Nordic School for Public Health, Stockholm, Sweden.
Evidence-based Medicine, 3(6); 191, Nov./Dec. 1998.

The following article is briefly reported.

The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. Estacio, R.O., Jeffers, B.W., Hiatt, W.R. et al
N Engl J Med, 338: 645-652, 5 Mar. 1998.

This was a subgroup analysis of a randomized, double-blind placebo-controlled trial (Appropriate Blood Pressure Control in Diabetes [ABCD] Trial). Nine hundred and fifty patients were randomized into the trial. Analysis occurred on 470 patients. The authors found that after 5 years of follow-up, more patients taking nisoldipine had Mis than those taking enalapril.

Commentary

Subgroup analysis and publication bias may affect these results. β-blockers were also used a lot in the enalapril group. However, FACET (Fosinopril versus Amlodipine Cardiovascular Events Trial) also found a better cardiovascular outcome with ACE inhibitors. It is unclear whether ACE inhibitors are beneficial or calcium channel blockers are detrimental. The commentators believe that the following should be used as first-line agents in hypertensive patients with diabetes β-blockers, diuretics or ACE inhibitors.