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Diabetes mellitus is a metabolic disease that is mainly characterized by high blood sugar level this occurs because of the problems in the insulin secretion. Generally blood glucose levels in the body are controlled and maintained in normal levels by a hormone called insulin which is secreted by the pancreas . But in the diabetic patients due to the absence or insufficient production of insulin leads to hyperglycemia.
The diabetes is mainly caused by the insufficient production of insulin in the body. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. Essentially, if someone is resistant to insulin, the body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycemia develops. Insulin which is produced by the beta cells of pancreas helps glucose to enter the cells and insulin is also important in regulating the level of glucose in the blood. Â After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucoseÂ .
Diabetes is mainly classified on to two types:
1.Type 1 diabetes
2. Type 2 diabetes
Type 1 diabetes is called as insulin dependent diabetes and type 2 diabetes is called as non insulin dependent diabetes.
"Type 2 diabetes mainly occurs when beta cell function fails to compensate for insulin resistance. Beta cell function progressively deteriorates with an increasing duration of diabetes, partly because of beta cells demise through apoptosis".( Claus M. Larsen et.al.,2007).
The symptoms of the diabetes 2 is that the loss of excess glucose in the urine this leads to dehydration.
Some other symptoms include:
Body weight loss
Nausea , vomiting
Infections on skin, bladder etc
Blurred vision and lethargy.
Blood tests are generally used to diagnose the diabetic patients.
Fasting blood glucose +or- 100mg/dl and less than 126mg/dl.
Two hour after eating blood glucose level +or - 140 mg/dl and less than 200mg/dl.
Hg A1c 5.7-6.64%
Fasting blood glucose +or - 126mg/dl on two different test occasions.
Two hours after eating blood glucose level +or - 200mg/dl.
Random blood glucose over 200mg/dl and symptoms present.
Hg A1c greater than 6.5%.
New Diagnosis Test:
TheÂ American Diabetes AssociationÂ along with an internationalÂ Diabetes Federation Committee announced the glycated haemoglobin test, commonly callÂ haemoglobin A1CÂ can be used to diagnose diabetes. This test represents the last three months of blood glucose levels
If haemoglobin A1C is 6.5 or higher then they will be diagnosed with diabetes, unless there is a special condition, such as a blood disorder, haemodialysis, or pregnancy.
OGTT (Oral Glucose Tolerance Test): This is a screening test during pregnancy for gestational diabetes. This is usually done between 24 and 28 weeks of pregnancy.
AÂ C-peptideÂ test is done to determine if insulin is being produced by the beta cells of theÂ pancreas. People with type 1 diabetes have little or noÂ insulinÂ production and therefore their C-peptide levels are very low.
Â Different treatment methods for diabetes:
Dietary management and physical activity
Present treatments :
In present treatments metformin is mostly used in the treatment of diabetes type 2 . metformin is very effective in reducing the rate of conversion of IGT to diabetes. It also helps in reducing the body weight in the obese people and without change of body weight in non obese people .metformin is also helps in the improvement of pathophysiology components like impaired secretion and impaired action of insulin. but there are some limitations like gastrointestinal side effects.
The insulin sensitizing properties of thiazolidinedione have played important role in prevention of diabetes." Troglitazone reduced the development of diabetes by around
50% over 2.5 years in a group of women with prior gestational diabetes. Troglitazone administration in the DPP was discontinued prematurely owing to its hepatotoxic effects, but during the average 0.9 years of exposure, diabetes incidence was reduced by 75%. Administration of rosiglitazone over 3 years has since been studied in 5,269 patients with impaired fasting glucose, impaired glucose tolerance, or both. The incidence of diabetes was reduced by 62%, and 50% of rosiglitazone treated patients reverted to normoglycemia"( Jill P Crandall et al., 2008) .
Like metformin, rosiglitazone seems to be most effective in individuals with a high BMI.
Side effects like weight gain , edema etc were observed when treating with these drugs.The frequency of congestive heart failure was also increased in some of the cases. In some diabetic women osteoporotic fracture were observed when treated with this drug. These concerns indicate an unacceptable risk-to-benefit ratio for thiazolidinediones, particularly rosiglitazone, in diabetes prevention.
The Î±-glucosidase inhibitor acarbose which helps to prevent the Type 2 diabetes mellitus very effectively. But later in the studies it was found that there many limitation of this drug. The patients who were treated with this drug there reported many gastro intestinal side effects and it has limited value for prevention of diabetes in general practice.
Weight loss agents such as orlistat an intestinal lipase inhibitor had reduced the development of diabetes in large number of obese people with impaired glucose tolerance. But there are some limitation of the drug. This drug reduces the weight of the body in obese people but it was greater than that achieved with life style alone. So there is limited acceptability of the drug in the treatment.
"Following post hoc analyses that suggested angiotensin-converting-enzyme inhibitors might
reduce diabetes risk, ramipril was studied for diabetes prevention in the DREAM (Diabetes
Reduction Assessment with Ramipril and Rosiglitazone Medication) trial. The hazard ratio
for developing diabetes was 0.91 (95% CI 0.80-1.03). There was no additive effect of therapy in participants who were randomly allocated both ramipril and rosiglitazone.
A post hoc analysis of data from a study of coronary artery disease prevention suggested that
statins might have diabetes-prevention benefits, but this finding has not been replicated
and the hypothesis has not been tested in a randomized clinical trial.
Preliminary investigation of incretin-based therapies (e.g. exenatide and dipeptidyl peptidase
IV inhibitors) suggests these agents not only enhance insulin secretion, but also promote Î²-cell proliferation.These agents might, therefore, be suitable for diabetes prevention, but clinicaltrials will be needed to address this hypothesis ,"( Jill P Crandall et al., 2008) .
Because of the limitations and the side effects of the drugs which are giving in the treatment of the Type 2 diabetes there are some recent advances took place and noval drugs are being introduced with less side effects and limitations.
Some of the noval drugs are:
Exenide-4 that directly binds to gon like peptide 1 receptor (GLP-1). Exenatide it improves the glycemic control and also decreases the body weight of the obese diabetic patients.
"The studies also showed that ameriolation of surrogate measures of the beta cell function and also shows improvement in the first phase and second phase glucose stimulated insulin secretion and in meal derived indexes of beta cell function".( MATHIJS C. BUNCK, MD et.al.,2009).
Liraglitide is the noval drug it is GLP-1 analogue with high homology to native hormone. Liraglutide is very well tolerated and improved metabolic control, reduced body weight with low rates of hypoglycaemia and the common side effects of the drug is nausea. Other beneficial effects of the drug is that it helps in the improvement of beta cell function.
Bromocryptine mesylate is adopamine D2 receptor agonist . it can reverse many of the metabolic alterations associated with insulin resistance . It reduces ventromedial arcuate, paraventricular hypothalamic drive for increasing hepatic glucose production , lipid synthesis mobilization and insulin resistance.