Treatment of postprandial hyperglycemia in type 2 diabetes yahoo,treating diabetes with sugar,type 2 diabetes nice cks - Test Out


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IntroductionMadhu meha (diabetes mellitus) has been known since ages, mentioned in Ayurveda by Sushruta, as sweetness of urine in a diabetic patient. It is an insulin oligomer conjugate formed by covalent bonding of an ampiphilic polymer (alkyl polyethylene glycol) to the lysine moiety on position 29 of the insulin beta chain112,113,8 it is easily absorbed from the intestine because its ampiphilic side chain confers on it resistance to the enzymatic degradation and enhances absorption from the bowel wall.
Even though many scientists tried to extract insulin from islets in pancreas (Paul Langerhans in1869 and Zeulzer in early 1900’s)1 banting and best tested the active extract of insulin on a diabetic patient with success, and were awarded the Nobel Prize in 1923. Postprandial plasma glucose concentrations on day 1 of treatment in patients with type 2 diabetestreated with a sulfonylurea, or both (N=54). Short acting bolus deliveries using regular human insulin, Lispro, aspart, glulisine are available but few options are available for basal insulin delivery (Glargine - only peak less locally acting insulin available). Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Islet amyloid polypeptide tonally inhibits beta-, alpha-, and delta-cell secretion in isolated rat pancreatic islets.
Oralin, a buccal spray insulin developed has unreliable pharmacokinetics and questionable outcomes. This review fo-cuses on pramlintide, an amylin analog, GLP-1 agonists and exenatide, an exendin 4 analog re-cently approved for use in type 2 diabetes by US FDA. It improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.
The fatty acyl group binds the insulin to albumin, slowing its absorption and prolonging circulation time.83,84 Other fatty acids (palmitic acids) are similarly being investigated. HIM2 insulin is in early phase 1 and 2 studies in subjects with type 1 diabetes and type 2 diabetes. The half-life after single injection is 11-15 hours causing a decrease in glucagon and an increase in insulin levels.
It restores the first phase insulin response to iv glucose administration along with the second phase response. Only the monomeric form is active and can affect its biological response when the 14-C fattyacyl moiety on B29 position is dissociated from plasma albumin.89 Time to peak concentration appears to be ~ 4-6 hours with 12 hours duration of action.
Poor palatability, unpredictable pharmacokinetics (especially poor bio-availability (1%-4%) if overcome could make oral HIM2 insulin a mainstay in type 2 DM as a whole, either as monotherapy or in combination with oral agents.


All carboxyl groups in pramlintide are amidated rendering the molecule cationic at acidic pH. Detemir has a neutral pH and is soluble (Glargine, has an acidic pH) making miscibility with other insulins a much better prospect. Results of an ongoing head – to head study93 comparing add-on insulin glargine Vs Insulin detemir with oral agents in insulin-naive type 2 DM patients, are eagerly awaited. Pancreatic islets develop predominantly from differentiation from progenitor cells derived from the ductal epithelium.
Nausea is common during the first few weeks of therapy and tends to resolve after continuous use.24-30 All side effects are dose dependent and tolerance occurs after continued use. Subsequent b-cell growth is a result of differentiation of existing b-cells (~12% of islets regenerative capacity) and differentiation of progenitor stem cells. These will have a utility as oral agents, adjuncts or monotherapy in subjects with early onset type 2 diabetes, especially obese people.
Pancreatic islet neogenesis was initially serendipitously observed and then isolated from regenerating pancreata, shown to stimulate pancreatic neogenesis and reverse streptozocin – induced diabetes in animal models.
Oral metformin also inhibits DPPIV in type 2 diabetes suggesting its potential role in combination therapy. The open sinusoids of liver allow free access to the hepatocytes for large insulin linked molecules that are excluded from peripheral tissues by normal endothelial barrier. They may be associated with mild weight loss and demonstrated efficacy in controlling fasting and postprandial hyperglycemia in twice daily and thrice daily dosing schedules so far tested. Insulin linked to thyroxine is highly protein bound giving a long plasma half-life and its limited transport across the endothelium reduces action in peripheral tissue i.e. Its core biologic activity resides in a 15 – amino acid stretch, which has been synthesized as the INGAP peptide. This incretin effect is responsible for 50-70% of insulin response to oral glucose in healthy individuals. Thus glitazars might lower both glucose and lipids, being dual agonists (PPAR-g & PPAR-a). The degree of b-cell growth induced correlated directly with dose of peptide administered and duration of use. Techno sphere is a diketopiperazine derivative, able to reversibly bind insulin and other peptides. It may have a role in diabetes prevention in high-risk groups, thus becoming a cure for diabetes especially in type I DM with no insulin resistance.


Major pulmonary insulin products have consistently shown a rapid onset of action, generally faster than SC regular insulin and Lispro in clinical trials.101-103 They are now of acceptable size with acceptable clinical efficacy.
Various adverse effects seen are local site reactions to injections (local pain, lipoatrophy, lipohypertrophy, pruritis).
Biologically active GLP-1 is of two major types, GLP-1 (7-37) and GLP-1 (7-36) amide differing by a single amino acid.
Glitazars up regulate human macrophage lipoprotein lipase activity,72 which could be beneficial in atherosclerotic vascular disease.81 In spite of promising results, many candidate drugs have been abandoned because of unexpected clinically significant adverse events like excessive peripheral edema, volume overload, heart failure, cardiomyopathy, bone marrow haemopoeitic changes and soft tissue neoplasm in rodent models. Because of its viscid nature, INGAP administration requires large bore needles making it more painful, leading to poor patient compliance. It is caused by entry of nutrients into proximal GIT and subsequent contact of open type L cells with nutrients that have been digested. Techno sphere insulin shows pharmacokinetics similar to IV insulin with more rapid onset of action. Stage of development is the early phase 1 and 2 human trials.ConclusionsVarious molecules are being tried to find a cure for type 2 diabetes. Amylin and its analog pramlintide, an incretin mimetic and GLP1 agonists and exenatide, an analog of Exendin 4 are the currently approved drugs for type 2 diabetes. GLP-1 is an insulinotropic hormone that also inhibits secretion of glucagon in a glucose dependent manner requiring at least euglycemia or hyperglycemia. Newer insulins delivery methods are also being tried to replace animal insulins with oral insulins taking the early lead.
This makes the molecule soluble and stable in the acid solution of the formulation when injected, the relatively alkaline environment of interstitial fluid causes the insulin molecules to associate into hexamers.
Aerodose inhaler uses liquid aerosol insulin with a biopotency of ~ 10% to that of SC insulin, faster clinical effects than SC regular insulin with short time to peak concentration and a shorter time to peak metabolic effect. Therefore there is hope that we will soon be able to fight the disease in a more effective way and prevent the co morbidities. It can be an adjunct to oral hypoglycemic agents.Potential effects on pulmonary function and mitogenic activity include lung irritation and inflammation, allergic reactions, development of insulin antibodies.



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