In an interesting paper the question is asked what if the history of the development of our understanding of diabetes has it wrong? The paper (J. Denis McGarry. What If Minkowski Had Been Ageusic? An Alternative Angle on Diabetes. Science, Vol. 258, No. 5083 (Oct. 30, 1992), pp. 766-770).
Despite decades of intensive investigation, the basic pathophysiological mechanisms responsible for the metabolic derangements associated with diabetes mellitus have remained elusive. Explored here is the possibility that traditional concepts in this area might have carried the wrong emphasis. It is suggested that the phenomena of insulin resistanceand hyperglycemia might be more readily understood if viewed in the context of underlying abnormalities of lipid metabolism.
Some powerful food for thought in the paper. Another paper (Arius, Energy Metabolism) summarizes the argument as:
The author considers the possibility that the hyperinsulinemia of early non-insulin—dependent diabetes is coincident with hyperamylinemia, since insulin and amylin are cosecreted. Amylin would cause an increase in plasma lactate (Cori cycle); and lactate, a better precursor than glucose for fatty acid synthesis, would indirectly promote the production of very-low-density lipoproteins (VLDL). There would follow an increased flux of triglycerides from liver to muscle (and adipose tissue) and, as proposed and elaborated on, an increase in insulin resistance and production of many of the metabolic disturbances occurring in diabetes.
The author of the paper draws heavily on the Randle Cycle.
The Randle cycle is a biochemical mechanism involving the competition between glucose and fatty acids for their oxidation and uptake in muscle and adipose tissue. The cycle controls fuel selection and adapts the substrate supply and demand in normal tissues. This cycle adds a nutrient-mediated fine tuning on top of the more coarse hormonal control on fuel metabolism. This adaptation to nutrient availability applies to the interaction between adipose tissue and muscle. Hormones that control adipose tissue lipolysis affect circulating concentrations of fatty acids, these in turn control the fuel selection in muscle. Mechanisms involved in the Randle Cycle include allosteric control, reversible phosphorylation and the expression of key enzymes.[5] The energy balance from meals composed of differing macronutrient composition is identical, but the glucose and fat balances that contribute to the overall energy balance change reciprocally with meal composition.
Interesting thoughts.
Fatty acids may act directly upon the pancreatic β-cell to regulate glucose-stimulated insulin secretion. This effect is biphasic. Initially fatty acids potentiate the effects of glucose. After prolonged exposure to high fatty acid concentrations this changes to an inhibition.[13] Randle suggested that the term fatty acid syndrome would be appropriate to apply to the biochemical syndrome resulting from the high concentration of fatty acids and the relationship to abnormalities of carbohydrate metabolism, including starvation, diabetes and Cushing’s syndrome.
My own weight had been in the 280 range for a long time. In the months before I was diagnosed as Type 2 Diabetic my weight dropped 50 lbs without any lifestyle changes. After I went on Metformin my weight was relatively lower for a while. When I eventually went on Insulin my weight went up 40+ lbs fairly quickly. It is well known that Insulin adds weight.
My own thought is that the Insulin is both the lock and the key. Increased levels of Insulin pushes glucose or fat into cells and decreased levels of Insulin allows fat to come out of cells. That’s why Intermittent Fasting is such a great bullet for Type 2 diabetics. It allows our fasting Insulin levels to drop. Add to that Low Carbohydrate diets and the perfect recipe for controlling Diabetes comes into play.
The problem never really was Insufficient Insulin. The problem was too much Insulin. And clearly it is a fat related problem.
