by Peter J. Nebergall, Ph.D.
Includes Photo: Caption: Peter J. Nebergall, Ph.D.
On Tuesday, June 11, 2002, the International Diabetes Center, at Park Nicollett,
in Minneapolis, Minnesota, held an "open forum" on the subject of
insulin resistance. I was privileged to participate, and would like to discuss
some of the findings presented by Drs. Burton Sobel and David Kendall, co-chairs
of the Partners Against Insulin Resistance (PAIR) Advisory Panel.
Insulin resistance, the inability of the body to fully and properly utilize endogenous insulin (the insulin your body naturally provides) is the principal "engine" driving type 2 diabetes. For years, the role of insulin resistance in driving up blood sugars, in "causing diabetes," has been understood, but the focus, in research and treatment, has been on the diabetes. What does insulin resistance do to your body before sugars climb up into the "diabetic" range - before the development/diagnosis of diabetes?
One of the major ramifications of type 2 diabetes is coronary artery disease. Type 2 frequently co-occurs with obesity, with high cholesterol, with high blood pressure--but is it the diabetes, and its hyperglycemia, that cause them, or are their seeds sown before the diabetes develops? The presenters suggest the latter is true.
Dr. Kendall reminded us that insulin resistance is antecedent to diabetes; that overt diabetes should be seen as an endpoint in the disease process. Dr. Sobel pointed out that data prove the risks of cardiac events increase before the development of overt type 2, and thus it cannot be clinical hyperglycemia that engenders those cardiac events--that insulin resistance itself, not the diabetes the insulin resistance causes in approximately 50 percent of cases (about half the folks with measurable insulin resistance or "IGT," impaired glucose tolerance, will go on to develop overt type 2) is the cause of these cardiac events.
The presenters distinguished between microvascular complications, damage to capillaries, to the glomeruli in the kidneys, and to the retina, all caused by diabetes, by hyperglycemia, and macrovascular complications, occlusions, blockages, changes to blood vessel walls, caused by insulin resistance--and well underway before diabetes appears. Insulin resistance has been traditionally seen as a metabolic issue--but, from its consequences, it is as much a cardiac one.
This last is a breakthrough. The thinking has been: "Here's diabetes; We'll treat it," without real consideration of those complications well underway before the blood sugars climb into the measurable range. If insulin resistance, rather than its product, diabetes, is doing the damage, what can we do about it? Recognizing surgery (PTCA, "balloon angioplasty," or CABG, "bypass surgery") does not end coronary disease, but merely repairs its consequences, how do we directly attack the cause, the insulin resistance?
Diabetologists have known for decades that lifestyle changes offer significant benefits in the treatment of type 2. Getting your diet under control, and increasing your regular exercise are always good ideas, and obese diabetics who lose weight generally find their insulin resistance decreasing and their condition easier to control. Drs. Sobel and Kendall say the patient should not wait until a diagnosis of overt diabetes to adopt these lifestyle changes.
Knowing that one class of oral diabetes medications, the thiazolidinediones, directly attacks the problem of insulin resistance, I asked the presenters if, in light of the seriousness of their findings, such medications should be considered for pre-diabetic individuals who exhibit significant insulin resistance?
"From a medical standpoint, yes," was their reply. If insulin resistance, rather than overt diabetic hyperglycemia, is the source of so many cardiac problems, then whatever clearly reduces insulin resistance reduces the risk of these serious cardiac events. Where IR is present, and lifestyle changes do not make a significant impact, use of IR-reducing medications should be considered.
From an administrative standpoint, today's insulin-reducing medications, those that have passed FDA-mandated clinicals and received "licenses," are for the treatment of overt, diagnosed diabetes, not pre-diabetic IR. There's a lot of paperwork to endure before we can use them for people who aren't yet diabetic -- and may never become diabetic -- but who show demonstrable insulin resistance. For some time we've been seeing insulin resistance solely as a precursor to diabetes -- and this seminar suggests we need to see it as aggressor itself -- and then take appropriate action.
Thomas Kuhn, in The Structure of Scientific Revolutions, would say we stand on the cusp of a "paradigm shift." It appears we are going to have to change our thinking; about type 2 diabetes, its cardiac complications, and the root causes of those complications. We'll be healthier, once we do.