Pathophysiology

Coma diabeticum can appear not only in patients with type 1 diabetes but also in patients with type 2 diabetes. The high concentration of glucose in serum is always associated with an increased serum osmolality. In the untreated patient with type 1 diabetes, the absolute deficiency of insulin leads not only to hyperglycemia, but also to diabetic ketoacidosis. The extent of hyperglycemia in diabetic ketoacidosis is mainly determined by an increased hepatic glucose production; the peripheral insulin resistance plays only a minor role in this situation (5). The blood levels of the insulin antagonizing hormones, like catecholamines, glucagon, cortisol and growth hormone, are in most cases increased in diabetic coma. Because of the complete deficiency of insulin in type 1 diabetes, the missing antilipolytic effect of insulin causes a dramatic increase in free fatty acids from adipose tissue. Metabolic pathways of fatty acids in liver regulate the ratio of insulin and glucagon. A low ratio of insulin to glucagon, as seen in insulin-deficient type 1 diabetes, is associated with low intracellular levels of Malonyl-CoA, a major inhibitor of carnitin palmitoyl transferase and reduced citrate cyclus activity. Free fatty acids are taken up in the liver concentration dependently and are shuttled into mitochondria for P-oxidation and subsequent ketogenesis. Since the ratio of insulin to

TABLE 1 Triggering Situations for Hyperglycemia

Manifestation coma (25%) Feverish infection (especially gastrointestinal) Therapy with corticosteroids or catecholamines Myocardial infarction, critical ischemia in pAVK Thromboses, pulmonary embolism

Failure to increase insulin dose in situations with higher insulin needs Erroneous or iatrogenic discontinuation of insulin therapy Interruption of intravenous insulin supply, e.g., in insulin pump therapy Repeated vomiting, decreased ingestion, diarrhea Preexisting acidosis when beginning an intensive physical exercise Thyrotoxicosis glucagon in the liver is different in patients with type 2 diabetes, most of them do not develop ketoacidosis although high levels of glucose and decreased insulin action in the periphery are present.

In addition, catabolism of proteins can enhance ketogenesis in the liver via the Cori-cycle. The increase of p-hydoxbutyrate and acetate are the main causes for metabolic acidosis leading to compensatory hyperventilation, hyperkalemia, and hypotension.

Since patients with type 2 diabetes have only relative insulin deficiency, the small residual amount of insulin appears to be sufficient to prevent ketogenesis in the liver. However, mild ketosis may develop in some patients with type 2 diabetes, too.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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