Normally what you need before you can start up aerobic respiration in the mitochondria is a multienzyme complex known as pyruvate dehydrogenase complex—of which the main enzyme is pyruvate decarboxylase. The complex acts on pyruvate, produced from glycolysis, in an oxidative decarboxylation reaction to produce acetyl-coA, which then enters the citric acid cycle (1).
What happens when pyruvate dehydrogenase is deficient? An actual genetic deficiency is rare, but it is the most common mitochondria-associated neurodegenerative disorder (2). When it does occur it significantly effects energy metabolism, poor use of glucose and build-up of lactic acid (2). Along with probable neurological impairments, too much glucose can exacerbate the problem leading to hyperglycemia and diabetes (2).
Diabetics , in essence, can also be described as a condition where pyruvate dehydrogenase complex activity is reduced(3-5). The lack of insulin to bring glucose into cells may be a factor, leading to little activity, or a nutritional deficiency of a vitamin such as thiamine (vitamin B-1) due to poor diet or starvation may lead to decreased production of the complex (3-5). In these cases, just as genetic deficiency, inefficient use of glucose results in hyperglycemia.
A ketogenic diet is used to manage the disease of pyruvate dehydrogenase deficiency (2). And it’s important to understand why this higher-fat, adequate protein, low-carb diet works for possible use with diabetes. It is because production of acetyl-coA can come from lipid metabolism via beta-oxidation as well as from amino acids isoleucine, lysine, phenylalanine, tyrosine and leucine (other amino acids are formed into pyruvate) (1p252).
There is plenty of research available showing that a ketogenic diet can help to control blood sugar (6-10). As a short-term therapy, the diet has had success even with children with Type II diabetes (11). But what of the side effects? As we know from critiques of the Atkin’s diet, a ketogenic diet produces fast weight loss through polyuria, but comes back with water retention from refeeding of carbohydrates (12) . The diet increases plasma cholesterol, uric acid, and may even cause hypokalemia (12). Further, you suffer nausea, fatigue, and hypotension (12). One must weigh the goods and bads of a ketogenic diet and make modifications as necessary.
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10. Henwood MJ, Thornton PS, Preis CM, Chee C, Grimberg A. Reconciling diabetes management and the ketogenic diet in a child with pyruvate dehydrogenase deficiency. J Child Neurol 2006;21:436-9.
11. Willi SM, Martin K, Datko FM, Brant BP. Treatment of type 2 diabetes in childhood using a very-low-calorie diet. Diabetes Care 2004;27:348-53.
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