Fig. Causes of Type 2 Diabetes |
The risk of
hypoglycaemia is the main limitation to achievement of good glycaemic control
in diabetes. In normal subjects the
first response to falling blood glucose is reduction in insulin secretion
occurring at blood glucose level below 80 mg/dl. This is lacking in subjects
with type 1 diabetes or type 2 diabetes. Glucagon forms the next layer of
defence, stimulating hepatic glycogenolysis and gluconeogenesis. However, most
patients with type 1 and 2 are chronically hyperglucagonaemica and cannot
respond to hypoglycaemia in this way. The last level of defence against acute
hypoglycaemia is activation of the sympathetico-adrenal system, which normally
occurs when blood glucose falls to below 55 mg/dl. This increases lipolysis and
circulating NEFA (Non-esterified fatty acid) production and utilization, and mobilization of substrates for
gluconeogenesis further inhibits insulin secretion and promotes glucagon
release. Activation of the sympatheticopadrenal system gives first-clear
symptoms of hypoglycaemia which is due to autonomic activation and
Neuroglycopenia.
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