Indian Write-Ups

Management

Insulin use in Type 2 Diabetes Mellitus

V. K. Bhardwaj.

MD (Ped), DM (Endocrinology) Asstt. Prof., Dept. of Pediatrics, NSCB Medical College, Jabalpur (MP)

The pathogenesis of Type 2 diabetes mellitus (DM) involves 3 basic defects viz. 1) Defective first phase of insulin secretion, 2) Inadequate insulin secretion and 3) Peripheral and hepatic resistance to insulin. The varying combination of these three defects leads to hyperglycemia and other biochemical abnormalities, which are responsible for clinical symptoms and diabetes related complications. The treatment modality for the management of Type 2 diabetes mellitus has to rectify one or more of these 3 pathogenetic mechanisms.

The aim of treatment in Type 2 diabetes mellitus is to relieve the patient of his/her symptoms and to prevent/delay the development of diabetes related organ damage. Relief from symptoms can be achieved to a large extent by reducing plasma glucose to <200mg/dl. However, United Kingdom Prospective Diabetes Study (UKPDS) and Diabetes Control and Complications Trial (DCCT) have shown that a tighter metabolic control, as close to normal as possible, is required to delay the diabetic complications. Thus American Diabetes Association (ADA) and other medical bodies dealing with the care of diabetes have recommended that good metabolic control is to be attempted in all diabetics. UKPDS has also shown that it is the degree of control which matters, rather than the drug used to achieve the control and that sulphonylureas, metformin and insulin alone or in combination were safe and effective. It also showed that majority of patients require combination of drugs to achieve and maintain plasma glucose levels in the desired range.

Insulin is one of the pharmaceutical agents used for the management of Type 2 diabetes mellitus. There are certain situations in Type 2 DM in which use of insulin is well established, e.g. during acute metabolic decompensation like diabetic ketoacidosis & hyperosmolar non-ketotic coma, during stressful situations like sepsis, acute myocardial infarction, cerebal stroke etc., during perioperative period and during pregnancy (1). In these situations the gravity of the problem and the likelihood of short-term use is helpful to convince the patients and family members to use insulin. However the situation is different in a Type 2 diabetes who is sub-optimally controlled on oral anti-diabetic drugs and is free from symptoms. In this case, the misconceptions regarding insulin (once on insulin always on insulin, severe disease etc.) and perceived inconveniences due to insulin use (difficult and painful procedure, restriction of eating out and travelling etc.) are strong hindrance to timely initiation of insulin therapy.

One of the common misconception regarding insulin use is the permanence of insulin therapy once it is started. This can be removed by explaining the concept of glucose-toxicity, i.e. the adverse effect of elevated glucose level on beta cell function and insulin receptor sensitivity. Elevated Plasma Glucose for long time causes persistent beta cell stimulation, which may lead to beta cell exhaustion. Persistent hyperglycemia also causes glycosylation of insulin receptor leading to impaired insulin sensitivity. Good metabolic control for few months gives rest to beta cells and thereafter they may resume their secretory activity and at the same time hyperglycemia induced insulin receptor glycosylation and consequent insulin resistance also declines. Thus there is a possibility of decreasing and sometimes withdrawing insulin. Another point which needs to be emphasized is the fact that many patients delay insulin initiation for so long that they land up with target organ damage, e.g. nephropathy, which precludes use of some of the anti-diabetic drugs thereby necessitating long term insulin therapy. Additionally, diabetes mellitus in adults is a heterogenous entity. Some of the patients with adulthood onset diabetes may be having auto-immune mediated beta cell damage i.e. Latent Auto-immune Diabetes of Adults (LADA). These patients respond to oral hypoglycemic agents (OHA) initially but progressive beta cell damage would lead to a stage when OHA would no longer be able to control hyperglycemia and insulin alone or in combination with other anti – diabetic drugs, e.g. alpha glucosidase inhibitors may become necessary (2,3). There are reports suggesting that use of small doses of insulin started early, may prevent the slowly progressive failure of beta cells in patients with LADA (4). It is desirable to preserve the beta cell function as endogenous insulin secretion is helpful in achieving smooth metabolic control. Thus it is clear from the foregoing that not every patient who is put on insulin would invariably be on insulin for the rest o f the life. By timely institution of insulin therapy, the diabetes related organ damage is prevented/ delayed and the beta cell function is also preserved. The residual beta cell function helps in smooth metabolic control and also raises the possibility that after few months of good glycemic control, insulin may be withdrawn at least partially.

Another factor responsible for resistance to insulin therapy is the perceived inconvenience. The likelihood of pain during injection is often cited as a reason to avoid therapy. However the currently available silicon coated 30G / 31G needles are associated with very little pain and once a patient uses them, he / she is relieved of unnecessary apprehension. Teaching the correct technique of injection, i.e. injecting with needle at an angle of 45-900 from the skin surface, rotating the site of injection, observing proper asepsis and discarding the needle when it becomes blunt, would lead to minimally painful injection. The inconvenience of using a bottle and syringe, particularly during traveling and eating out is cited as another reason for not accepting insulin therapy. This problem can be solved by use of devices like disposable prefilled insulin pen or the conventional insulin pen with insulin cartridges. Problem of storage of insulin in summer months with high ambient temperature can be taken care of by keeping the insulin vial in use in water filled earthenware after putting the vial in a polythene pack. It is clear that many of the problems cited as reasons to resist insulin therapy are minor and based on pre-conceived ideas. These erroneous perceptions can be removed by devoting some time to discussion and demonstration of correct technique of insulin injection. Intersection with well controlled juvenile diabetics may also be helpful in removing the wrong perceptions.