Attenuated Glucose Recovery from Hypoglycemia in the Elderly

Abstract

Advanced age is a risk factor for hypoglycemia caused by sulfonylureas (and insulin) used to treat diabetes mellitus. Therefore, we hypothesized that there is an age-associated impairment of glucose counterregulation and further that this is the result of a sedentary life-style. To test these hypotheses, glycemic and neuroendocrine responses to hypoglycemia, produced by 0.05 U/kg body wt insulin i.v. were measured in nondiabetic elderly subjects (age 65.1 +/- 0.9 yr n = 23)--and in a subset (n = 11) again after 1 yr of physical training (which increased VO2 max by 5.2 +/- 0.9 ml.kg-1.min-1, P less than 0.05)--and compared with these responses in nondiabetic young subjects (23.8 +/- 0.6 yr, n = 18). Recovery from hypoglycemia was attenuated (analysis of variance P less than 0.001) in the elderly (plasma glucose recovery rate 29.4 +/- 2.2 vs. 42.7 +/- 5.0 microM/min, P less than 0.02). This attenuation was the result of a smaller counterregulatory increment in glucose production (maximum increment 13.3 +/- 1.1 vs. 17.2 +/- 1.1 mumol.kg-1.min-1; P less than 0.05) rather than a greater increment in glucose utilization in the elderly. The attenuated glucose recovery was associated with higher plasma insulin concentrations (maximum increment 1385 +/- 122 vs. 940 +/- 72 pM, P less than 0.01) and reduced glucagon responses to hypoglycemia (maximum increment 43 +/- 6 vs. 66 +/- 12 ng/L). The epinephrine, norepinephrine, cortisol, and growth hormone responses were similar, although the epinephrine response was slightly delayed and the growth hormone response appeared smaller in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Association between hypoglycemia and the type of insulin in diabetic patients treated with multiple injections: an observational study

“…17 The stronger relationship between age and hypoglycemia in type 1 diabetes may be due to a larger age span of the affected patients, as compared with type 2 diabetic patients, and hence, more apparent manifestation of the association in the statistical analysis. Our observation is in line with some other studies, 18,19 but not all. 20 There is evidence that, in type 2 diabetic patients, hypoglycemia -induced counterregulatory hormonal release occurs at higher blood glucose levels than in nondiabetic subjects 21,22 or patients with type 1 diabetes.…”

A Clinical Trial of Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections in Older Adults With Type 2 Diabetes

“…Risk factors associated with insulin-induced hypoglycemia in the elderly include insulin administration errors, missed meals, renal insufficiency, liver disease, and defective counterregulation (17)(18)(19)(20). In our study, there was no significant difference in the numbers of subjects experiencing hypoglycemia or the number of hypoglycemic events in the CSII and MDI groups.…”

Effects on the glucagon response to hypoglycaemia during DPP‐4 inhibition in elderly subjects with type 2 diabetes: A randomized, placebo‐controlled study

“…This study showed that the glucagon response to hypoglycaemia inhibition is now commonly used in the elderly 8 and as glucagon counter-regulation to hypoglycaemia may be impaired in this population. 12,13 Hence, this study is the first to provide evidence for the rationale of using DPP-4 inhibition in older patients based on its ability to maintain glucagon response to hypoglycaemia. The results are in accordance with the low risk of hypoglycaemia during incretin therapy in the elderly.…”

“…Thus, in one study in elderly subjects without diabetes, it was shown that the increase in glucagon levels after hypoglycaemia at 2.7 mmol/L, induced by exogenous insulin injection, is impaired as compared to younger individuals. 12 In another study, also in elderly subjects without diabetes, the submaximal glucagon response at 3.3 mmol/L, but not the maximal glucagon response at 2.8 mmol/L, during exogenous insulin infusion was impaired as compared to younger individuals. 13 In contrast, however, one study has shown a non-suppressed glucagon response to hypoglycaemia at 3.3 mmol/L, induced by exogenous insulin infusion in the elderly.…”