Age Obesity And Glucose Counterregulation

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In children with type 1 diabetes, the glucagon response to hypoglycaemia is markedly attenuated compared to non-diabetic individuals but compensated for by vigorous secretion of other counterregulatory hormones, particularly epinephrine, with the peak epinephrine responses being almost two-fold higher than in adults (Amiel et al., 1987). The total sympathoadrenal responses to hypoglycaemia are also influenced by pubertal stage (Ross et al., 2005).

Furthermore, it appears that the glycaemic thresholds for the secretion of epinephrine and growth hormone are set at a higher blood glucose level in non-diabetic children compared to adults (Jones et al., 1991). In children with type 1 diabetes, the secretion of epinephrine in response to hypoglycaemia commences at an even higher level. In children who have markedly elevated HbA1c values, there is a further shift of the blood glucose threshold to a higher level for the release of counterregulatory hormones.

Advanced age, in otherwise healthy people, does not appear to diminish or delay coun-terregulatory responses to hypoglycaemia (Brierley et al., 1995), although the magnitude of responses of epinephrine and glucagon is lower at milder hypoglycaemic levels (around 3.4mmol/l ) compared to younger non-diabetic subjects, but is much more comparable with a more profound hypoglycaemic stimulus (2.8 mmol/l) (Ortiz-Alonso et al., 1994) (See Chapter 11). The magnitude of counterregulatory responses to low blood glucose levels following preceding hypoglycaemia also appears to depend on the gender of experimental subjects, with men having blunted responses compared to women (Davis et al., 2000b).

Both the autonomic nervous system and the hypothalamic-pituitary-adrenal axis are activated in excess in the morbidly obese. Before and after bariatric surgery (average weight loss 40 kg over 12 months), severely obese non-diabetic subjects, underwent a hyperinsulinaemic hypoglycaemic clamp (blood glucose 3.4 mmol/l). Before weight reduction, patients demonstrated brisk peak responses in glucagon, epinephrine, pancreatic polypeptide, and norepinephrine. After surgery and during hypoglycaemia, all these responses were attenuated and most markedly so for glucagon, which was totally abolished in association with a marked improvement in insulin sensitivity. In contrast, the growth hormone response was increased after weight reduction (Guldstrand et al., 2003).

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