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Dr. Aaron I. Vinik on Early Insulin Use in the Progression of Diabetes

VinikOne of the leading diabetes researchers in the world, Dr. Aaron I. Vinik, Director of Research and Neuroendocrine Unit, EVMS Strelitz Diabetes Research Center, shares his views on early insulin initiation.

The natural history of type 2 Diabetes (T2DM) is a progressive worsening of glycemic control as a consequence of progressive beta cell failure so that ultimately all patients with T2DM are equivalent to patients with type 1 DM and are insulin deficient. In addition the clock starts ticking for macrovascular complications such as heart attacks, strokes and peripheral vascular diseases before the advent of fasting or postprandial hyperglycemia indicating that there are, in addition to hyperglycemia, a host of risk factors conducive to macrovascular disease. In contrast, the glycemia milieu is the single most important determinant of microvascular complications such as retinopathy, nephropathy and neuropathy….

Major studies in T2DM have indubitably shown a reduction of microvascular complications by good glycemic control and the effect persists despite failure to maintain A1c’s near normal. This is in stark contrast with the recent attempts to show that intensive glycemic control in the ACCORD, ADVANCE and VADT studies reduce macrovascular events: somewhat disconcerting was the finding in the ACCORD study of an increase in sudden death by 22% in the intensively treated group. Thus, the window of opportunity to aggressively treat T2DM is early and patients can enjoy a ‘legacy effect’ or what has been reported as metabolic memory. Why then did we not see this benefit in the three studies above and what have we learned? The lessons were invaluable and suggest that there can be a bad metabolic memory or legacy effect in certain situations:

1. If the diabetes has been there for > 12-15 years;
2. Older people and African Americans;
3. Significant impairment of renal function;
4. The presence of coronary calcification;
5. The history of peripheral neuropathy and the findings of autonomic neuropathy.

So the window of opportunity has to be early in the absence of kidney, somatic and autonomic dysfunction, established cardiovascular disease and there are gender and ethnic group sensitivities. Perhaps the only protective factor appears to be obesity but that is almost contrary to everything we are trying to achieve in T2DM.

So armed with this information, why is it that we have developed a treat-for-failure approach trying several medications, diet and exercise and only when we have failed to reach goal do we make adjustments? The median delay of adjusting a sulfonylurea is 24 months and metformin is 36 months. Titration is a tardy task and treating for failure is doomed to failure. A fundamental change in physicians’ management of T2DM is required and the traditional treatment algorithm should emphasize treatment for success not failure.

Traditional oral hypoglycemic agents such as sulfonylurea, metformin, the glitazones and the Incretins and Gliptins are able to lower A1c’s about 0.5 to 2.0 %. Combinations of these agents can under optimum conditions achieve an A1c reduction of 3%. Thus in people close to goal of 6.5% (AACE) or 7.0% (ADA) then exercise, diet and a single agent are appropriate. If the A1c is between 7.5% and 9.0%, combinations of oral agents are an appropriate first choice. When A1c is > 9.0 we need the unlimited capacity of insulin to achieve goal. This can be accomplished in a number of ways which include addition to the oral regimen, use of a single long acting insulin analog, use of combinations of different forms of insulin and finally a basal long acting insulin together with a short acting bolus based upon the prevailing blood glucose and the anticipated carbohydrate intake. Data from the UKPDS indicate that after insulin is introduced either alone or in combination with oral therapy, the long term outcome is improved glycemic control. There is however a clinical inertia amongst generalists and even endocrinologists to make these change.

The barriers to initiation of insulin therapy are legion. Physicians have a fear of hypoglycemia and imagine there are adverse health consequences of the insulin itself. They have misconceptions of the regimens as being too complex and that it should be the therapy of last resort or limited efficacy. They are indeed major contributors to the fear patients have of the needle. This is a paradox when the needle per se is more benevolent than, for example, a finger stick. Patient-related behaviors are fear of hypoglycemia, adverse health outcomes, medication errors, needles and pain, weight gain and the complicated regimens and scheduling of injections. Unfortunately patients have been brainwashed into thinking that use of insulin is a personal failure, their disease is too advanced, it is the therapy of last resort and it greatly increases cost. Our own studies comparing insulin with oral agents have shown that insulin is associated with improved quality of life, less fatigue, increase in energy and enhanced state of emotion. Patient education along with the use of insulin formulations that reduce risk of hypoglycemia and weight gain, simplified treatment regimens and easy to use insulin delivery systems, should help to reduce the barriers to early aggressive insulin use when the window of opportunity presents itself and clinicians need to overcome inertia and not allow the window to close upon them. Every day here at the EVMS Strelitz Diabetes Center we see patients who are grateful for the restoration of their quality of life as well as the anticipated reduction of the burden of diabetes complications.

Dr. Aaron I. Vinik has written five books, published more than 250 papers in medical journals, and is recognized as a pioneer and scholar. Dr. Vinik has received research funding for his studies from the National Institutes of Health, the National Cancer Institute, the Kroc Foundation and the American Diabetes Association.  He is a leader in research on the diagnosis and treatment of diabetic neuropathy with a particular expertise in the area of autonomic diabetic neuropathy, a complex and challenging condition. Dr. Vinik has also been a leader in research on new approaches to generate islet cell tissue from pancreatic duct tissue which may one day lead to a true cure for diabetes.

For more information on Dr. Vinik and his groundbreaking work at the Strelitz Diabetes Center, just follow this link, Eastern Virginia Medical School Strelitz Diabetes Center.

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