Looking Ahead
This chapter gives a bare outline of research in diabetes. A diabetic may be reassured to know that a lot is being done by the National Associations of Diabetes, the International Diabetes Federation, National Research Councils, Universities and the pharmaceutical industry. A diabetic owes his/her well-being, nay very existence to research in diabetes. Therefore, it should be the duty of every diabetic to support research in diabetes.
ANIMAL STUDIES
Spontaneous or experimental diabetes is known in certain rodents, cows, pigs and subhuman primates. Rodent models have mainly been selected for study. Although no animal model has characteristics identical to those in humans, they are useful to understand the causative mechanisms as well as toxicity and efficacy of therapeutic measures in diabetes.
NEW ANTI-DIABETIC AGENTS
In the light of the biochemical abnormalities in type 2 diabetes, a variety of novel pharmacological approaches are undergoing evaluation. Some of these drugs directly stimulate insulin secretion while others mimic and/or promote the effect of insulin on target tissues. Though most of them are still in an experimental stage or are too toxic, they offer exciting prospects. Drugs for the treatment of diabetic complications involving the kidney, eyes and the blood vessels are being developed. Agents that inhibit the formation of glycation products that cause long-term complications of diabetes are also being studied. Glucagon-like peptide-1 (GLP-1) is a substance secreted from cells in the lower portion of the intestine. It promotes insulin secretion stimulated by oral glucose. Interestingly, a naturally occurring GLP-1 analogue was originally isolated in extracts of Gila monster lizard salivary glands. This naturally occurring analogue (exendin-4) is under clinical investigation. It lowers blood glucose, suppresses appetite and promotes beta cell growth and differentiation. Like insulin, this drug has to be injected subcutaneously. It is now known that insulin alone is not the sole regulator of circulating insulin levels. Amylin is a hormone secreted by pancreatic beta cells and is packaged with insulin into the same secretory granules. Amylin complements the action of insulin by suppressing post meal glucagon hormone levels and slowing the rate of emptying of the stomach. It thus regulates the entry of glucose into the blood. On the other hand, insulin regulates the uptake of glucose from the blood circulation after meals. Thus both hormones act as signals to orchestrate postprandial glucose levels. Subcutaneously injectable analogue of amylin (pramlintide) is under investigation.
INSULIN
Improved varieties of insulin for example, short-acting, long-acting, are undergoing evaluation. Specific insulin-like molecules are "designed" (designer insulins) with specific aims in mind. "Many such insulin analogues are available today and more are likely to be introduced." In the near future, widespread use of insulin analogues could become a reality and possibly the norm. The possibility of insulin analogues which correct hyperglycaemia without risk of hypoglycemia cannot be discounted in the future.
The search continues for improved insulin formulations that can reproduce as closely as possible the physiological profile resulting from insulin secretion in the body. Alternative routes of insulin delivery such as oral, inhaled, nasal, rectal, ocular (eye), intravaginal, transdermal (through skin) are being studied. Problems related to absorption of insulin and unpredictability of action arc major stumbling blocks. Of all these routes, pulmonary (lung) route has been most vigorously studied. Current delivery systems include a variety of pressurized metered dose inhalers, dry powder inhalers, nebulizers and aqueous mist inhalers. Transferring the gene responsible for insulin production, into diabetic individuals, remains a dream for the present.
Implantable Insulin Pump Systems
Current Implantable pump technologies require the patient to monitor capillary blood glucose and adjust the rate of insulin infusion. Instead of intermittent sampling of blood glucose, continuous blood glucose monitoring with an implanted glucose sensor is under evaluation. These sensors could be used with an external or an implantable insulin infusion pump.