Fast forward in diabetes therapy

Diabetes Mellitus, a condition where the body is unable to automatically regulate blood glucose levels is caused by the loss of the body8217;s ability to transport glucose to cells 8212; either because not enough insulin is produced or because the response to insulin is weak.

The disease derives its name from the Greek word 8220;diabetes8221; meaning siphon 8211; to pass through 8211; and 8216;mellitus,8217; the Latin word for sweet.

The disease has been recognized for over 3,500 years. The earliest known record exists in a 3rd Dynasty Egyptian papyrus 1552 BC, which mentions polyuria frequent urination as its symptom.

The first chemical tests to indicate and measure the presence of sugar in urine were developed in the early 19th Century and the two major types of diabetes 8211; Type 1 insulin-dependent, 8220;juvenile onset8221; diabetes and Type 2 non-insulin-dependent, 8220;adult-onset8221; diabetes 8211; were recognized only in 1959.

The treatment involves regulating blood glucose level with the help of insulin, a hormone made in the pancreas. Insulin injections are necessary for Type 1 diabetes. Type 2 diabetes can usually be controlled by regular exercise and diet. But oral medication and eventually insulin injection may be needed as the disease progresses.

WHY 038; HOW

The Treatment over 80 years

Insulin was discovered in 1921, the standard insulin syringe was developed in 1944 and it was only in 1955 that the oral hypoglycemic agents were discovered. The blood glucose meters and insulin pumps were developed in 1970 and the pen delivery system was introduced to deliver the exact quantity of insulin at the right time in 1986. In fact, the last two decades has seen many advances.

Oral Drugs

8226; Work in the 1940s and 1950s led to the discovery and development of hypoglycemic sulfonylureas Glibenclamide, Glimipiride, a therapeutic class unique for specificity and safety. These drugs stimulate insulin secretion by pancreas.

8226; A novel class of drugs, thiazolidinediones Pioglitazone, Rosiglitazone increases the glucose uptake by fat and muscle cells, and have multiple other beneficial effects on heart and blood vessels.

8226; Alpha-Glucosidase inhibitors acarbose, voglibose are another class of drugs which slows down absorption of sugars from the gut.

Insulin Therapy:

8226; The isolation of insulin from dog pancreas and demonstration of its biological effectiveness by Banting, Best, Collip, and Macleod in 1921 represents perhaps the greatest medical discovery of modern medicine, which got the 1923 Nobel Prize in physiology and medicine. The antidiabetic substance was initially called 8216;Isletin8217; and later 8216;Insulin8217;.

8226; For the first 60 years of the insulin era, preparations were purified crudely from pancreas tissue extracted from pigs or cattle.

8226; In 1980s, human insulin was introduced

8226; Today, insulin is made biosynthetically by DNA technology or 8220;genetic engineering8221;

Newer Insulins

The insulin molecule can be modified to create insulins with vastly altered pharmacokinetic characteristics: the insulin analogues lispro, insulin aspart and glargine. These have a better profile and causes fewer instances of 8220;low blood sugar8221; hypoglycemia. However, these insulins are also costlier.

Newer Insulin delivery systems:

8226; The traditional needle/syringe that was cumbersome to use and required cold storage gave way to insulin pens, making it easier for patients to self-administer the injections with little or no pain. Nowadays most insulin injections are delivered using pen injectors. These, along with new modes of delivery and monitoring, now hold promise of even more individualised and physiological treatment.

8226; With the help of insulin pump, insulin can also be delivered continuously in the body almost simulating the natural insulin secretion. A new insulin pump with facility of continuous glucose readings will allow more accurate insulin therapy according to blood sugar levels. But Insulin pumps are costly and have limited application in India.

The 6th W: What Next:

8226; Promising new drugs still under development include the synthetic analogs of Amylin Pramlintide, and Glucagon-like peptide GLP-1 derivatives. The GLP-1 has many benefits, including enhancement of insulin secretion. But ahead of the field is Exenatide, a molecule originally found in the saliva of the American lizard 8220;Gila Monster8221;.

8226; The most exciting is the development of an oral cannabinoid receptor-1 CB1 inhibitor8221; Rimonabant, which blocks action of a receptor which mediate action of cannabis in brain. It has recently been shown to be an antiobesity agent too, reducing appetite and fat deposition. It also improves blood sugar and lipid control in diabetics. Interestingly, this also helps quit smoking and keeps in check the acompanying weight gain.

8226; Scientists are also looking for alternative ways to administer insulin 8212; nasal and oral by inhalation or pills. Clinical trials of inhaled insulin has been permitted in India and oral insulin will hit the markets soon.

8226; Current molecular research indicates a future of pancreatic transplantation, incorporation of insulin gene and stem cell therapy to provide a long lasting endogenous source of insulin to the diabetic patient, making diabetes cure a reality.

The writer is Director and HoD of Diabetes and Metabolic diseases, Fortis Hospitals