Hypoglycaemia

An excess of insulin can cause hypoglycaemia and the hormones that respond to this condition to restore normal glucose levels are known as the counter-regulatory hormones. They are adrenaline, glucagon, growth hormone and cortisol. An increase in the blood levels of these hormones can sometimes be used to conhrm a diagnosis of hypoglycaemia. 

The concentration of glucose in the blood is maintained as a balance between rates of glucose utilisation and glucose supply and changes in one or both of these can lead to hypoglycaemia. Three situations are considered. 

Hypoglycaemia caused by stimulation of the rate of glucose utilisation and inhibition of the rate of release of glucose by the liver 

This situation arises mainly when the blood level of insulin is high - abnormally high for the given condition. Insulin not only stimulates peripheral utilisation but also inhibits glucose output by the liver so that hypoglycaemia can develop rapidly. Four examples are given. 

Hypoglycaemia that arises when an increased rate of utilisation exceeds that of glucose release by the liver 

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Sulphonylureas Severe liver or renal disease0 Hypoglycaemia b... 

Incretin mimetic Severe renal or gastrointestinal disease Nausea, hypoglycaemia if used with another antidiabetic agent b... 

Gliptins Severe renal disease Abdominal pain, hypoglycaemia when used with another antidiabetic agent Creatinine 3... 

Amylin analogue Gastro paresis Hypoglycaemia, nausea b... 

Hypoglycaemia A lower-than-normal blood glucose concentration. 

Pre-approval safety and efficacy clinical studies involved product administration to 2500 adults with either type-1 or -2 diabetes. The primary efficacy parameter measured was glycaemic control (as measured by the reduction from baseline in haemoglobin Ale). Hypoglycaemia was the most commonly reported adverse effect. Trials also showed a greater decline in pulmonary function in the Exubera group, and product should not be administered to patients with underlying lung disease, or to smokers. Exubera was developed by Nektar Inc. and is marketed under licence by Pfizer. 

Hypoglycaemia remains the most frequent complication of insulin administration to diabetics. It usually occurs due to (a) administration of an excessive amount of insulin (b) administration of insulin prior to a mealtime, but with subsequent omission of the meal or (c) due to increased physical activity. In severe cases this can lead to loss of consciousness, and even death. Although it may be treated by oral or i.v. administration of glucose, insulin-induced hypoglycaemia is sometimes treated by administration of glucagon. 

Butterworth, R. F. Metabolism of gluatamate and related amino acids in insulin hypoglycaemia. In L. Hertz, E. Kvamme, E. G. McGeer and A. Schousboe (eds), Glutamine, Glutamate and GABA in the Central Nervous System. New York Alan R. Liss, 1983, pp. 595 - 608. 

Nomura et al. (2000) showed that hypoglycaemia-induced apoptosis of basophile leukemia ceUs involves the generation of cardiolipin hydroperoxide and the subsequent release of cytochrome c from mitochondria. (Nomura et al., 2000). The gaieration of cardiolipin hydroperoxide occurred in mitochondria of basophile leukaemia cells which had been induced to undergo apoptosis by exposure to hypoglycaemia with... 

Nomura, K., Imai H., Koumura T., Kobayashi, T., andNakagawa, Y., 2000, Mitochondrial phosphohpid hydroperoxide glutathione peroxidase inhibits the release of cytochrome c from mitochondria by suppressing the peroxidation of cardiohpin in hypoglycaemia-induced apoptosis, Biochem. J. 351 183-193. 

He then recalls the feelings of one person suffering from hypoglycaemia ... 

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