I recently read an article which discussed subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels, associated with adiposity and insulinemia in Pima Indians and Caucasians. Another study from the same journal discussed low adiponectin levels in adolescents as a marker for intramyocellular lipid accumulation. Now that I spit that all out, would it be theoretically possible for this theory to substantiate a situation in which an adolescent with diabetes could be so drastically insulin resistant that there could be little reaction to higher than normal subcutaneous insulin doses but increased sensitivity to intravenous insulin administration?

I am not sure how completely I can answer your questions; but you have certainly touched on some themes that are of considerable topical interest in diabetes. To begin with, I am assuming that the subject of your enquiry was designated as type 1 diabetes on the basis of an acute insulin dependant onset that was confirmed by positive antibody tests and that the type 2 component was because of accompanying obesity. With the recent increases in both type 1 and type 2 diabetes, this combination has attracted some interest. It been supposed that the insulin resistance that accompanies obesity increases the rate of the beta cells destruction caused by the autoimmunity. It is certainly possible that adiponectin, a rather abundant adipocytokine is playing a role in this situation. Expectedly the serum levels would be low and accompanied by the increased insulin resistance which has been observed. This subject has recently been rather extensively reviewed, and of course the special interest is that adiponectin has been synthesized and shown to combat both obesity and diabetes in laboratory mice. Since it also has significant anti-inflammatory properties for vascular epithelium and as a moderator of lipid metabolism, it is likely to be a promising target for clinical studies in man.

The study on Pima Indians was, I thought, less relevant, but nonetheless an explanation of the weight gain that accompanies cortisone treatment. Again the danger of over-interpreting these kinds of studies is that the fundamental defect may still be a more distant one in one or other of the various transcription factors that may be involved in the synthesis of an active principle.

I can’t account for the apparent increased sensitivity to intravenous insulin and in any case would want to review the validity of that statement. One final thought is that what is important for the time being is not so much the specific molecular problem as the effective control of the blood sugar.

DOB