Diabetes Mellitus - Long term side effects of Sulfonylureas

The pancreas is a gland that produces hormones insulin, glucagon, somatostatin and digestive enzymes. These hormones play an important role in regulating the metabolic activities of the body and particularly regulation of blood glucose. Diabetes Mellitus is characterised by an elevation of blood glucose caused by a relative or absolute deficiency of insulin. Diabetes Mellitus can be divided into two main groups Insulin dependent Diabetes Mellitus (Type 1) and Non insulin dependent Diabetes Mellitus (Type 2). Other types of Diabetes have also been identified which are Maturity onset Diabetes of the young (Type 3) and Gestational Diabetes.

Insulin dependent Diabetes Mellitus (Type 1) commonly affects individuals around puberty but can occur at any age. Prevalence of Type 1 Diabetes is 5­10 %. It is associated with absolute deficiency of insulin caused by a loss in beta cell function. Loss of beta cell function is usually attributed to environmental factors and autoimmune mediated process against beta cell. It is often triggered by the invasion of virus or chemical toxins. Unlike Type 1 prevalence of non insulin dependent Diabetes Mellitus (Type 2) is 90­95 %. Type 2 Diabetes is influenced by genetic factors, aging, obesity and peripheral insulin resistance. In Type 2 Diabetes pancreas retains some beta cell function but variable insulin secretion is insufficient to maintain glucose homeostasis. Maturity onset Diabetes of the young (Type 3) is associated with dysregulation of glucose sensing or insulin secretion due to mutation in particular genes. Type 3 Diabetes is hereditary in nature occurs before the age of 25 years. It is estimated that prevalence of Type 3 Diabetes is around 5 %. Gestational Diabetes Mellitus classified as (Type 4) is defined as glucose intolerance associated with pregnancy. Hyperglycemia associated with it can lead to congenital abnormalities and hence tight glycemic control is mandated during pregnancy. Incidence of Diabetes Mellitus is growing rapidly worldwide. It is estimated that 135 million of the world's population is affected by Type 2 Diabetes Mellitus. Each year about 650,000 people learn they have the disease. Diabetes Mellitus is the seventh leading cause of all deaths and the sixth leading cause of all deaths caused by disease. 16 million people suffer from Diabetes mellitus in the US and only half of these individuals are diagnosed. Diabetes can develop gradually, often without symptoms over many years. In fact many learn that they have diabetes only on developing one of its common cardiovascular, renal or vision complications. In people with diabetes, glucose levels build up in the blood and urine causing excessive urination, thirst, hunger and weight loss associated with problems with fat and protein metabolism. Diabetes is detected by measuring the amount of glucose in the blood after the individual has fasted (abstained from food) for several hours, either overnight or several hours after breakfast. In some cases, physicians diagnose diabetes by administering an oral glucose tolerance test, the measurement of glucose levels before and after a specific amount of sugar is ingested. The goal in treating Type 2 Diabetes Mellitus is to maintain blood glucose concentration within normal limits and prevent long term complications associated with it. Emphasis has been laid on weight reduction, exercise and dietary modification. It has shown to decrease insulin resistance and correct hyperglycemia of Type 2 Diabetes without medical intervention. However failure in maintaining blood glucose levels with lifestyle measures often leads to therapeutic intervention. Use of therapeutics generally center on clinical presentation. Current pharmacologic intervention for management of Type 2 Diabetes Mellitus are oral hypoglycemic agents and insulin therapy. During early 1903s many people died from diabetes because insulin treatment was unavailable. Frederick Banting and Charles Best extracted insulin from the pancreases of pigs and cows and injected them into diabetic animals. Their experiments were a dramatic success. In 1955,oral hypoglycemic agents were introduced to help lower blood glucose levels and in 1960 the purity of insulin was improved. Over the years, the methods of insulin manufacturing have changed. Porcine and bovine insulin was common for diabetic use but

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some did not respond to it. Further research by drug companies produced human insulin with a structure identical to insulin in 1978. Over the past few years oral hypoglycemic agents are among the top 10 drugs that have been prescribed worldwide. Sulfonylureas and Biguanides are the first line oral hypoglycemic agents used based on severity. Sulfonylureas are insulin secretagogues and they promote insulin release from beta cells of the pancreas Therapy with Sulfonylureas can sometimes work "too well," producing more insulin than actually is needed. Excess insulin reacts with available sugar in the bloodstream which causes the blood sugar to dip abnormally low. Hypoglycemia is what is commonly referred as low blood sugar .Normal fasting blood glucose level is between 70 and 105 mg/dl. Hypoglycemia is diagnosed by monitoring of blood glucose levels. At levels below 50 mg/dl, the diagnosis is fasting hypoglycemia. Symptoms of hypoglycemia usually include headache, depression, anxiety, irritability, blurred vision,excessive sweating,mental confusion,incoherent speech,psychological disturbances and convulsions. Other side effects include weight gain, hyperinsulinemia, renal impairment, gastrointestinal upset and rash. Despite these adverse reactions many Type II diabetics benefit from the pills. Recent prospective cohort study done by Dr. Li and her colleagues from Harvard school of Public health revealed long­term use of sulfonylureas could increase coronary heart disease risk in diabetic women. Dr.Oz show recently commented on the concept of Natural medication better than prescription drugs. His show discussed a recent survey that revealed 70 % of Americans take one prescription drug every year. Adverse reactions to those medications are the fourth leading cause of death in the US. 70 % of chronic daily headaches are drug induced. Prescription drugs are now commonly referred to as a biochemical bandage that suppress the symptoms but don't get to the cause of the underlying disorder. This underlying rationality in prescribing medications has led to the cause of adverse drug reactions. Diet lifestyle and attitude is now gaining impetus knowing the impact of adverse side effects from prescription medication. Over the recent years a lot of attention has been laid on the use of natural medications to treat chronic diseases. There are number of clinical studies that have been carried out in recent years that show potential links between herbal therapies and blood glucose control. Many people with diabetes have resorted to the use of more 'natural' ingredients to help manage their condition. Mulberry extracts are known to have special soluble fiber blend which has shown to reduce the severity of hypoglycemia. Although it should be kept in mind that certain herbs, vitamins and supplements may interact with diabetes medications (including insulin) and accentuate the drugs hypoglycemic effects. Few experts also argue that the use of natural therapies could reduce blood sugars to dangerously low levels and raise the risk of other diabetes complications. There are not many natural remedies known for counteracting hypoglycemia. Hence advice should be taken from an expert before availing natural remedies for drug induced adverse effects.

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References

"Diabetes mellitus," Diabetes Timeline, http://www.diabetes.ca/atoz/diatime.htm, "Diabetes," Treatment, http://members.aol.com/m4ynk/treatment.html, Metabolic control and prevalent cardiovascular disease in non­insulin dependant diabetes mellitus (NIDDM); The American Journal of Medicine, January 1997 Lippincott's Illustrated Reviews:Pharmacology, Third edition.Richard D Howland and Mary J Mycek “Natural remedies” https://doctormurray.com/health­conditions/hypoglycemia/ http://www.diabetes.co.uk/Diabetes­herbal.html

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