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Diabetes mellitus is a group of metabolic disorder where a person has high blood sugar because of 2 reasons. Body does not produce enough insulin. Cells do not respond to the insulin. There are three main types of diabetes. Symptoms include increased thirst, frequent urination, constant hunger, weight loss, blurred vision etc. Complications include hypo / hyperglycaemias, hypertension, diabetic ketoacidosis, nephropathy, neuropathy etc. For the treatment of diabetes by administration of exogenous insulin, Insulin therapy is used. Islet cell transplantation is a procedure which effectively controls blood glucose level for diabetic patients. A number of plants have been described as a traditional medicine for the treatment of diabetes. Vitamin D supplementation has been found to lower the incidence of type I diabetes. Several classes of oral hypoglycemic agents like sulfonylureas, biguanides and alpha-glucosidase inhibitors are available for the treatment of type II diabetes. Targeted drug delivery for the treatment of Diabetes using nanotechnology is one of the recent advances in nanomedicine. An oral of insulin has been the elusive goal for many investigators since the discovery of proteins. A lot investigation using different technologies is being carried for the oral delivery of insulin. Insulin chewing gums have also been developed which provide a very easy means for the delivery of insulin.
Keywords: Diabetes mellitus, oral agents, insulin resistance,
Glucose homeostasis, a balance between glucose production and glucose utilization is primarily regulated by the pancreatic islet Î²-cells, which secrete insulin and Î±-cells, which secrete glucagon. Glucose production occurs firstly in liver whereas glucose utilization occurs in muscles & adipose, brain, kidney, red blood cells etc. Diabetes mellitus affect most of the people of both developed and developing countries. This can usually be controlled with dietary management, exercise, oral hypoglycaemic drugs and insulin therapy. The diet most often recommended is low in fat, but high in dietary fibre, especially soluble fibre.
It is estimated that more than 100 million people worldwide are affected by the diabetes mellitus and in recent years prevalence of type II diabetes has significantly increased. In 1995 the estimated prevalence of disease in worldwide adults was 4% and projected to 5.4 % by year2025 which amounts to 300 million. There are three main types of diabetes. They are Type I diabetes mellitus also called insulin dependent diabetes mellitus (IDDM), Type II diabetes mellitus also called Non Insulin Dependent Diabetes Mellitus (NIDDM) and Gestational diabetes.
TYPE I DIABETES MELLITUS:
Type I diabetes mellitus is caused by immunological destruction of pancreatic Î² cells leading to insulin deficiency. It is associated with ketoacidosis. Immune-mediated nature is the majority of type I diabetes, where the beta cell is destroyed due to T-cell mediated autoimmune attack. Type I diabetes can affect children or adults but it was traditionally termed as "juvenile diabetes" as it represents a majority of the diabetes cases in children. Type I diabetes can develop in people with a family history of type I diabetes. Environmental factors may also trigger autoimmune response. Symptoms of type I diabetes include increased thirst, frequent urination, constant hunger, weight loss, blurred vision and extreme tiredness. Due to the binding of diminished insulin to its receptor in the cell membrane, glucose uptake into the cells is decreased. Due to this, glucose builds up in the bloodstream causing hunger, thirst, fatigue and increased urination. In 5 to 10 years insulin producing cells are all destroyed causing type I diabetes. Autoimmune destruction of Î²-cells has multiple genetic predispositions.CD4 T cells are major immune players in the initiation and pathogenesis of type I diabetes. Nearly 20 different proteins have been identified as targets for T cells in the NOD mouse and 12 of these are auto antigens in humans. Diabetic patients are prone to other autoimmune disorders such as Graves' disease, Hashimoto's thyroiditis, Addison's disease, autoimmune hepatitis, myasthenia gravis and pernicious anaemia.
TYPE II DIABETES MELLITUS:
Type II diabetes is characterized with insulin resistance and is the most common type of diabetes. Type II diabetic patient's foods are converted to glucose but the cells cannot utilize it and hence the glucose remains in the blood & don't enter into the cells where it should have been actually present. It is a common disorder with a prevalence that rises markedly with increasing degrees of obesity. Type II diabetes is common in individual whose age is over 40 years. Symptoms include frequent urination, feeling tired or ill, unusual thirst, weight loss, blurred vision, frequent infections and slow wound healing. Type II diabetes is associated with physical inactivity and obesity. Some of the risk factors are
1) Having food with high fat content
2) Not doing enough exercise
3) Fatty deposit in Pancreas
4) Set of genes inherited from parents makes islets cells of pancreas to wear out easily
5) Genes responsible for insulin resistance
Gestational diabetes occurs during pregnancy. Some pregnant women, who have never had a history of diabetes before, have a high blood glucose level during pregnancy. Such type of diabetes is called Gestational diabetes. It occurs in about 2%-5% of all pregnancies & may get cured after delivery. About 20%-50%of affected women develop type 2 diabetes later in life. Pre-diabetes is a condition which occurs when blood glucose levels of a person are higher than normal but not high enough for a diagnosis of type II diabetes. Many years are being spent by people in a state of pre-diabetes before getting type II diabetes which has been termed "America's largest healthcare epidemic". Latent Autoimmune Disease of Adult (LADA) is a kind of type I diabetes that occurs in adults. It is frequently misdiagnosed as having type II diabetes, based on age rather than etiology.
Studies have been done to find the possible association of type I diabetes with 10 validated type II diabetes loci i.e. WFS1, HNF1B, IDE/HHEX, PPARG, KCNJ11, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2and FTO/RPGRIP1L. This give a clear picture that the type II diabetes loci do not play any obvious role in type I diabetes genetic susceptibility. The distinct molecular mechanisms of the two diseases highlighted the importance of differentiation diagnosis and different treatment principles.
The disease is characterized by chronic hyperglycaemia which if not effectively controlled can cause blindness, kidney, heart failure or nerve damage. Both genetic & environmental factors such as lack of exercise, obesity are the loop hole for the occurrence of diabetes. The cause of diabetes is dependent on the type. Type I diabetes is partly inherited & then is triggered by few infections (by Coxsackie B4 virus). Type II diabetes is due primarily to lifestyle factors and genetics. Complications are of three types. They are Acute, Sub acute & chronic. Acute complications may include hypoglycaemia, diabetic ketoacidosis, hyperosmolar and hyper glycaemic non-ketosis syndrome. Sub-acute complications may include thirst, polyuria, lack of energy, visual blurriness and weight loss. Chronic complications include hypertension, neuropathy, nephropathy & diabetes foot ulcer. In a study of elderly nursing home patients who were initially free of heart failure, 39% of those with diabetes vs. 23% of those without diabetes had developed heart failure after 43 months of follow up. The risk of heart failure was 2-fold higher in men and 5-fold higher in women with diabetes. Patients with heart failure also have a higher risk of developing diabetes. Some of the complications of diabetes, including retinopathy and atherosclerotic vascular disease, have been compared to oxidative stress in diabetic patients. In diabetic patients, isoorientin decreases the circulating of radical scavengers and reduces symptoms of associated complications. The diabetic patients have a 25 fold increased risk of blindness, a 20 fold increased risk of renal failure, a 20 fold increased risk of amputation as a result of gangrene and a 2 to 6 fold increased risk of coronary heart disease and brain damage. Increases by 8-10 folds during moderate exercise and oxygen flux through the muscle may increase by 90-100 folds. The exercise may increase free radical production and overwhelm antioxidant defences, resulting in oxidative insult. Diabetes is found to affect many of the parts of the body especially the blood vessels and nerves. The best screening test for diabetes, the fasting plasma glucose (FPG), are also a component of diagnostic testing. The FPG test & the 75-g oral glucose tolerance test (OGTT) are both suitable tests for diabetes; however, the FPG test is preferred in clinical settings because it is easier & faster to perform, more convenient, less expensive and acceptable to patients.