Antidiabetic Drugs

Archive for the ‘Question – Answer’ Category

1. Is lipohypertrophy a painful condition?

According to our study, it’s only really painful in a minority of patients — about 20% to 30%. For about the same number, the injection is actually less painful. So it can go either way.

2. How serious can the swelling become in extreme cases of lipohypertrophy?

We’ve observed some extreme cases of lipohypertrophy. In one of those cases, we asked a surgeon to perform liposuction on a female patient. She had lipohypertrophy in the region of the umbilicus, in the thigh, and in the upper arm, because she had tried to rotate sites in order to avoid the condition, but wherever she injected she suffered lipohypertrophy. The surgeon, in this case, had to remove more than two litres of fat tissue to obtain a cosmetically satisfying result.

3. If some patients do everything right and still suffer lipohypertrophy, have patients been unfairly blamed for causing and aggravating the condition by trying to avoid painful injections?

This is a common belief, and while we found it to be true in some cases that patients would repeatedly use the same site because they found it to be less painful, they were certainly a minority. In those cases, according to our experience, it was often a lack of information or wrong advice. We had some patients who told us that they’d been informed to use only a very small area of the abdomen around the umbilicus. Under those circumstances, it’s hardly surprising that lipohypertrophy occurred.

4. Why is the abdomen particularly prone to this condition?

To my knowledge, that is not fully clear. But it is known that abdominal fat tissue responds more extensively to hormones or nutritional factors, for example. We did a study a few years ago that appeared in the Journal of Obesity in which we looked at preadipocytes (incipient fat cells) in different fat deposits and their capacity to form new fat cells. We found that the greatest capacity to create new fat tissue is in the abdomen, compared with femoral adipose tissue, for instance.

5. Apart from the appearance and inconvenience, are there any other negative effects of this disorder?

The kinetics of insulin absorption can be affected. We have observed patients in whom metabolic instability was traced to unpredictable absorption of insulin at sites of lipohypertrophy. But in my experience, this is only the case if there is some fibrotic conversion (ie. the formation of fibrous tissue). If there is only a soft swelling, there is less problem with varying absorption.

1. What would constitute a typical high-carbohydrate diet in terms of real food? What would constitute a diet of 40% monounsaturated fatty acids (MUFAs)?

In this study, we did not want any interference on the experiment by dietary fibre (which exerts a beneficial effect on blood glucose and plasma lipid metabolism) since this might have obscured the effects of dietary carbohydrate per se. Therefore, we selected for the high-carbohydrate diet food items which did not contain large amounts of vegetable fibre (white bread, spaghetti and other types of pasta dishes, rice and potatoes). These starchy foods were consumed every day in generous servings. The diet containing 40% monounsaturated fatty acids was based on a high consumption of virgin olive oil (five to six tablespoons per day), a typical source of monounsaturated fats in Mediterranean cuisine. This was utilized for salad dressing, on toasted bread together with garlic and tomatoes (bruschetta), and for cooking meat and fish.

2. What are the best natural sources of carbohydrate and of MUFAs?

The best natural sources of carbohydrate are foods rich both in carbohydrate and in fibre, since the latter counteracts most of the undesired metabolic effects of a high-carbohydrate diet. In particular, we advise our diabetic patients to consume often legumes (beans, lentils and peas), cereals (whole-grain bread, porridge and barley), and all types of vegetables and fresh fruit (apples, oranges, grapefruit, peaches, pears and plums). Other sources of carbohydrate, but not particularly rich in fibre, are the starchy foods employed in our experiment (white bread, spaghetti, rice, potatoes), which should be utilized often but in limited amounts, since they can increase the post prandial blood glucose concentration in some diabetic patients. The best source of monounsaturated fatty acids is represented by virgin olive oil which contains significant amounts of antioxidants (polyphenols) useful for prevention of cardiovascular diseases. Other suitable sources of MUFAs are peanut and rapeseed oil and margarine.

3. Up to what limit of glucose intolerance would you recommend a high-carbohydrate diet?

A high-carbohydrate and high-fibre diet is recommended for any type of glucose intolerance, even for insulin-dependent diabetes. The only limitation is represented by the presence of hypertriglyceridemia, which is usually exacerbated by a high-carbohydrate intake. Conversely, a high-carbohydrate diet constituted in large part by starchy foods should not be recommended to diabetic patients treated with hypoglycemic drugs and insulin, and in general to patients with unsatisfactory blood glucose control and/or hypertriglyceridemia.

4. Is one type of diet best for obese NIDDM patients, and another for lean ones?

High-fat diets are more energy-dense, and therefore they are not suitable for overweight patients. Conversely, these patients will certainly benefit from a high-carbohydrate, high-fibre diet which has a low-energy density, a low energy-sparing ability, and moreover has a very good satiating effect. Therefore it might facilitate weight reduction in patients who can benefit from this therapeutic manoeuver.

Question: I am a type II diabetic. I monitor my blood sugar 4 times a day. Since reading the results of the DCCT, I have chosen to take 4 insulin shots a day for tighter control. My control has been good until about 3 weeks ago. Now it seems that nothing I do will bring down my blood sugar levels ( over 300). What should I be doing?

Answer: The most important thing you should do is get in touch with your physician to let him know that your sugars are that high. As you know the DCCT study demonstrated that bringing the sugar average close to normal was very important in trying to prevent long term complications in type 1 diabetics. They also concluded this is probably true for type II diabetics.

If blood sugars remain elevated, patients should always check to be certain that the insulin has not expired or rendered ineffective by heat exposure. Sometimes it helps to administer insulin injections in the abdomen, which has been demonstrated to be the most reliable site of insulin absorption.

Another common cause of persistently elevated blood sugars are any types of infections. Most of these are obvious, such as upper respiratory infections or urinary tract infections. Some need to be checked out by your physician.

Also other medications (such as cortisone or certain diuretics) can cause elevated blood sugars. Other less common causes are other diseases such as thyroid or adrenal gland conditions, or a decrease in your own pancreatic insulin production. As you can see there are many reasons for persistently elevated blood sugars and it is impossible to list them all, which is why contacting and consulting your own physician is probably the most important thing you can do.

Question: I am 70 years old with type II diabetes. What is an acceptable am glucose level? Is 130mg/dl acceptable?

Answer: Optimal normalization of glucose levels in diabetes patients has been shown to lower the long term risks of diabetic complications (such as diabetic eye, kidney, blood vessel and nerve diseases). Normal fasting morning blood glucose level is 70-120 mg/dl. Therefore, am fasting blood glucose level of 130mg/dl is acceptable. However, having satisfactory am blood glucose level is not enough. Ideally, blood glucose levels before lunch, before dinner, and at bedtime should also be well controlled. Oftentimes, doctor will order a blood test for HgA1C test. Normal HgA1C level indicates good glucose control, while abnormally high level indicates inadequate glucose control.

The risk of medication treatment of high blood glucose is overshooting, causing hypoglycemia (low blood glucose). Symptoms of hypoglycemia include sweating, palpitations, tremor, and weakness. Severe, prolonged hypoglycemia is dangerous and can lead to syncope and other problems. In patients who do not experience early warning symptoms of hypoglycemia, and in patients with coronary heart disease or who have seizures with hypoglycemia, doctors will settle for less ideal control of blood glucose to avoid problems of hypoglycemia.

Question: Is the term “borderline diabetes” a misnomer? Does it really mean adult onset diabetes (type II diabetes)?

Answer: There are two types of diabetes ( type I and type II). Patients with Type I diabetes lack insulin, and need insulin injections for survival. Patients with type II diabetes have insufficient insulin or resistance of body cells to insulin action. Exercise, diet, weight loss, and oral medications can be effective in controlling high blood glucose in many patients with type II diabetes. Insulin injections are used when these measures fail to adequately control blood glucose levels.

The term “borderline diabetes” has been used to refer to type II (adult onset diabetes) patients whose blood glucose are well controlled with diet and/ or oral medications. These patients do have diabetes mellitus as diagnosed by abnormal fasting blood glucose and glucose tolerance tests. They are also at risk of future complications of diabetes. Close and continued monitoring is important to prevent worsening of blood glucose levels and to reduce future diabetes complications.

“Borderline diabetes” has also been used to describe patients who do not have diabetes mellitus. Their fasting blood glucose levels are normal, but their oral glucose tolerance test is minimally abnormal (not in levels seen in diabetic patients). These patients may have body cells that are resistant to the action of insulin, causing impaired glucose tolerance (but not overt diabetes). Some of these patients may develop diabetes later in life.

Question. I am a forensic psychiatrist with a special interest in psychopathology and psychiatric disorders associated with diabetes, such as aggression and violence. What is your experience in such cases ? What references can you suggest?

Answer. You are raising an interesting question, which is reviewed nicely in W.A. Lishman’s superb text, Organic Psychiatry, 3rd Edition (Blackwell, 1998). It is difficult to separate psychopathology attributable to diabetes mellitus (DM) from that due to poorly controlled blood sugar, hypoglycemic attacks and subsequent brain damage. For example, a study by Schwandt (1979) found that nine out of 45 unstable diabetics who had been overtreated with insulin showed mood swings, irritability, and chronic fatigue.

Apart from hypoglycemia-related disturbances, it is not clear that diabetes mellitus per se is associated with specific types of psychopathology, although fatigue, depression and irritability have been observed in some surveys. A few studies suggest a higher than expected prevalence of diabetes mellitus in psychiatric hospital populations, but this is usually the late onset, non-insulin-dependent type. Episodes of diabetic coma or hypoglycemia may contribute to brain damage and cognitive deficits, but a causal connection is not clear. There is, finally, some evidence for increased rates of depression (vs. non-diabetic populations) in patients with diabetes mellitus (see the American Psychiatric Press Textbook of Neuropsychiatry, edited by Yudofsky and Hales). Mania, on the other hand, is rare. Diabetics with major depression may benefit from use of SSRIs (Luvox, Paxil, Prozac, Zoloft), since these medications (unlike tricyclics) seem to improve glucose tolerance.

Question. I have a close friend whose husband is a brittle diabetic. In the last couple of years, he has lost interest in hobbies and activities that used to be enjoyable to him. He has violent outbursts without provocation. His father is bipolar. Are diabetics at higher risk for mood disorders and does this effect his blood sugar level? Are there certain chemical/neurotransmitters that are implicated in both mood disorders as well as diabetes? Are there medications that he can take that will not further destabilize his diabetes?

Answer. You may be interested in obtaining the article by Paul Goodnick et al in the Journal of Clinical Psychiatry, April 1995, on Treatment of Depression in Patients with Diabetes Mellitus. Goodnick et al discuss some data showing higher rates of depression in diabetic populations than in non-diabetic controls; evidence that depression may have a less favorable course in diabetic patients (e.g., higher relapse rate); and evidence that depression is associated with both hyperglycemia (high blood sugar) and increased complications of diabetes.

There does seem to be a neurochemical link between depression and diabetes, in that serotonin–a chemical in the brain that regulates mood–can affect blood sugar. Specifically, serotonin seems to reduce blood sugar, independent of insulin secretion. Antidepressants that boost serotonin (SSRIs such as Prozac and Zoloft) are therefore preferred to the older tricyclic antidepressants in depressed diabetics. The tricyclics can lead to elevated blood sugar. However, in the case of your friend’s husband, the issue of a bipolar disorder must be examined carefully, especially given the father’s history. This may be present independent of the diabetes, but could, in theory, be precipitated by fluctuations in blood sugar.

So as far as I know, the mood stabilizer valproate (Depakote) does not adversely affect diabetes. I would recommend referring this individual to a medical-school based mood disorders clinic, which could work closely with his general physician.