Insulin: Always in the news

      Affecting sixteen million Americans, half of whom remain unaware of their condition and thus unable to have it treated before it causes serious complications, diabetes mellitus is diagnosed in 650,000 Americans each year and contributes to the deaths of about 200,000. It’s annual financial impact, including medical care, disability payments, lost work, and premature death is estimated at around a hundred billion dollars, and it contributes to nerve damage, blindness, heart disease, strokes, kidney failure, amputations, and birth defects.
     Insulin-dependent diabetes (IDDM) accounts for only five percent of all cases of diabetes and is an autoimmune disease in which the patient’s own immune system destroys the pancreatic beta cells, resulting in an inability to secrete insulin. Both viral and genetic factors are suspected as primary contributors to the pathogenesis, and it usually occurs in children and young adults.
     Non-insulin-dependent diabetes (NIDDM) accounts for the other ninety-five percent of diabetic cases, generally occurs in patients over the age of forty, and becomes evident more gradually. It is typically characterized by ineffective utilization of produced insulin.
     Primary risk factors for NIDDM include advanced age, obesity, and African, Hispanic, or Native American ancestry. IDDM, though, occurs far more frequently in whites than non-whites, occurring rarely in Asians, Africans, and Native Americans.
     Though insulin is often adjunctive therapy in NIDDM, which may be treated with oral medications, insulin is essential in IDDM; while careful attention to diet, exercise, and lifestyle are essential for all diabetics.

WHAT’S NEW IN DIABETIC RESEARCH?

Obesity
     The obese patient is at particular risk of developing diabetes, and long before signs and symptoms appear, damage due to insulin resistance, a primary defect in Type-II diabetes, has likely taken a toll on glucose control. A recent study of obese patients involved administration of 1,000mcg of chromium picolinate on a daily basis, resulting in an overall 40% decrease in insulin resistance in the test group along with a reduction in the rate of increase in abdominal body fat deposition.

Dopamine
     Ergo Science Corporation is conducting Phase-III trials on its new product, Ergoset, a low-dose, rapid-release oral dopamine D1/D2 agonist that not only reduces blood sugar levels in obese Type-II patients, but also post-meal levels of atherosclerotic free fatty acids and triglycerides, other factors notoriously elevated and problematic in that patient population. The new combination treatment methodology apparently normalizes the dysfunctional secretory function, opening a treatment doorway to actually prevent diabetes by transforming obese patients predisposed to diabetes by high blood glucose and lipid levels into lean patients with normal blood values.
     Ergoset resets the hypothalamic “clock” responsible for abnormal daily metabolic variations. The inability to transport blood glucose into the tissues (glucose intolerance) is usually associated with impaired ability to utilize and produce insulin, all functions with seem to be associated with serotonin and noradrenaline activity in the brain. Further, metabolic improvements seen with dopamine D1/D2 agonists in the obese diabetic can be expected to accompany improvements in hyperphagia, hyperglycemia, and hyperlipidemia.

Leptin
     Leptin is a hormone, known to act in the mid-brain to affect appetite, metabolic rate, and ultimately obesity; but recent research has shown that leptin receptors in both adipose and non-adipose tissues of the liver, pancreas, and skeletal muscle point to a greater role of the hormone in the diabetic process. One theory is that in obese Type-II diabetics capable of producing insulin, the islet beta cells are so overloaded with lipids that they are unable to function properly. Adequate amounts of circulating leptin would rid these cells of fats to facilitate their normal functioning. Other hypotheses include the fact that leptin’s effects are more universal, acting not on only on lipid cells to reduce fat content, but on widespread cells with leptin receptors, facilitating many more aspects of metabolic functioning. When lipids are metabolized normally, excess deposits are eliminated, and much less insulin is required to normalize blood sugar levels.

Growth Hormone
     Recent studies have also shown that low levels in children of a protein resembling growth hormone are closely correlated with the development of Type-II diabetes in those same patients as adults. Amur Pharmaceuticals, Inc. is studying the results to develop preventive hormone replacement therapy as an alternative to symptomatic treatment.

Depression
     The fact that tight control of blood glucose in diabetics can substantially delay or even prevent diabetic damage to other organs has been well documented. Motivation, though, seems to be a major factor in the ability of any given patient to maintain such tight control; and patients who are clinically depressed frequently seem incapable of that goal, presumably via poor compliance and/or neurochemical abnormalities.
     Thus, successfully treating the depression, which affects some 20% of the diabetic population (as opposed to only 5% of the general population), should ultimately improve compliance and glucose level control. Nortriptyline was studied in this application; and though it actually tends to raise blood glucose levels in subjects without depression, it was shown to improve glucose control in depressed diabetics in direct correlation with improvements in the depressed state.

Genetics
     A genetic cause for diabetes has long been suspected, and genetic predisposition is undeniably involved in the development of both types of diabetes. Progress in gene mapping has resulted in the identification of several genetic markers for IDDM, providing a basis for screening of potential victims of the disease before symptoms indicate irreversible damage.
     A gene responsible for producing Neogenesis Associated Protein (INGAP) may prove to be a stepping stone to ultimately introducing the gene into diabetics to either prevent or cure islet cell damage by regenerating islet cells.
Insulin
     Longstanding problems associated with patients’ inability to learn and maintain proper administration technique with metered-dose inhalers (MDI’s) used for asthma has precluded use of such devices for insulin delivery, where painstaking accuracy and consistency are so crucial for predicting response. Aradigm Corporation has developed an aerosol delivery device for insulin (AERx) currently in clinical trials that enables the effective and predictable administration of insulin to the lungs for absorption. The new technology provides instant feedback to the patient on the effectiveness of his technique with each administration to reinforce proper technique and help predict the results of each dose.