The question is really, was the claim made by the NIH that “lowering blood sugar actually increased the risk of death” a valid claim and if not, what was really going on? Well, what I maintain is that the problem was in the treatment, not in the fact that blood sugars were lowered. When this study was started, the ADA very clearly mandated 60% to 65% dietary carbohydrate for diabetics. This high carbohydrate diet forced the use of industrial doses of insulin, large doses of sulfonylurea drugs and very possibly at the very least a hazard for hypoglycemia; and a great likelihood of rollercoaster blood sugars as we usually see in diabetics who are put on a high carbohydrate diet. So it looks like the likely high carbohydrate diet was at the core of the problem. Now, aside from the impossibility of real blood sugar control and indeed, although the Gina Colata article in the New York Times claims that the blood sugars were very low. They weren’t. They did not get below 6% on the A1C.

Six percent corresponds to an average blood sugar of 140 mg/dL. So the blood sugars were still quite high. What hazards were introduced? Well, first of all, we know from a number of studies that high carbohydrate diets tend to increase rather than reduce cardiac risk factors. But in this case, probably much more significant was the likelihood of weight gain. We use low carbohydrate diets to reduce weight. So if you’re going to give them high carbohydrate diets and large doses of insulin to off set the resulting high blood sugars, you’re going to be building fat. And doing that to someone who’s already at high cardiac risk is just adding to their burden, probably adding tremendously. In addition, there’s been a lot written about the adverse effects of high serum insulin levels, principally, on the vasculature. For example, high serum insulin levels increase vascular leakage, cause pathologic proliferation of the vascular endothelium, arterial stiffening, and hypertension. In addition, the obesity also exacerbates hypertension. So if you’re making people fatter, you’re making their hypertension worse.

On the other hand, there have been articles pointing out that for insulin deficient individuals, if you put them on insulin, you facilitate vascular repair. So there’s a balance. Small physiologic blood levels of insulin help the vasculature whereas these industrial blood levels of insulin are harmful for the vasculature. So simultaneously, you’re increasing hypertension, you’re making them fat and you’re causing vascular damage in a number of different ways just from the high carbohydrate and the high insulin.

So the conclusion that the study should be terminated perhaps should have been replaced with a revamping of the study so that the treatment would be changed to mandate very low carbohydrate diets and physiologic instead of industrial doses of insulin. One other point to remember is that high doses of insulin combined with high carbohydrate cause the rollercoaster effect. If you take a type 2 diabetic who already has cardiac disease, and you put them on the rollercoaster blood sugars, up and down, and up and down, you’re not doing his heart any good.

A similar situation occurred in the DCCT trial in the intensive arm, more hypoglycemia. I wrote an article that was published in the American Journal of Medicine, after the DCCT. They were complaining that they had so much hypoglycemia, even at A1C’s of 6% and they didn’t get below 6%, but approaching 6% they got more and more severe hypos. I pointed out the laws of small numbers wherein high carbohydrate plus high insulin causes unpredictable blood sugars..

Items missing in the NIH press release included what sort of diet they were on and which oral medications they were using. I’d be very foolish if they were put on a low carbohydrate diet. I’m willing to bet that they were put on an ADA diet and it was probably very high in carbohydrate.
I am assuming that they used high doses of insulin and sulfonylureas because it’s very hard to offset carbohydrate with metformin, Actos® or Avandia®; whereas sulfonylureas, are almost as potent as insulin but they work by boosting your insulin levels. If you can make insulin and you get a sulfonylurea, you’ll have very high serum insulin levels.

Dr. Richard K. Bernstein is the Author of Diabetes Solution, http://www.diabetes911.net

Your link to UKPDS 35 refers to an association study of sugars and outcomes. It showed that higher A1Cs are associated with worse health outcomes. We know and accept that. A1C is a marker of disease. Those with higher A1Cs have worse disease, which translates to worse outcomes.

The real question then becomes, what happens if we randomize diabetics and see if those that are pushed down to a lower A1C with drugs/insulin do any better. UKPDS answered that, if you read the links provided in previous posts, and showed that it doesn’t improve clinically meaningful outcomes. And ACCORD is confirming that. So treating the marker (A1C) doesn’t treat the underlying disease and doesn’t improve outcomes.

Here’s another BMJ link with a published letter in response to UKPDS 35 saying the same thing.

http://www.bmj.com/cgi/eletters/321/7258/405#9168