Evaluation of hypoglycemia resulting from hyperglycemic clamps

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Medicine and Health Sciences


Hyperglycemic clamps are used as a gold standard measurement of beta cell function, allowing for measurement of a biphasic insulin response. Under this technique, the plasma glucose concentration is raised to a target concentration of 200 mg/dL by exogenous infusion of dextrose. The target glucose concentration is sustained by regular titration of the dextrose infusion rate. An adverse event commonly associated with hyperinsulinemic clamps or arginine infusions is post-clamp hypoglycemia (blood glu-cose <60mg/dL). However, hyperglycemic clamp testing of nondiabetic individuals has not traditionally been associated with this outcome. In a recent study of beta cell function in nondiabetic individuals at genetic risk for type 1 diabetes and unrelated controls, we observed hypoglycemia in 11/67 clamps post discontinuation of dextrose infusion. We hypothesized that demographic or clamp related factors may be associated with hypoglycemia in the 60 minutes after discontinuation of dextrose infusion. Three non-diabetic populations were analyzed: islet Ab negative first-degree relatives of T1D pro-bands (n=19), Ab positive relatives of T1D probands (n=5), and healthy controls with no family history of T1D and undetectable Abs (n=15). Demographic factors (study group, age, BMI, sex, HbA1c, fasting glucose) and clamp factors (average glucose infusion rate during the clamp, maximum glucose infusion rate during the clamp, urine glucose, and urine volume) were compared among those who became hypoglycemic and those who did not. Intraindividual variability of post clamp hypoglycemia was also evaluated in those who had two clamp visits (n=27). Ten (25.64%) participants exhibit-ed hypoglycemia (average glucose of 50.97 mg/dL) in at least one clamp visit and 29 (74.36%) were normoglycemic (average glucose of 81.07 mg/dL) during the 60 minutes after discontinuation of dextrose. No differences were present in rates of hypoglycemia between participant groups. The mean HbA1c (5.009%) of participants who developed hypoglycemia post-clamp was lower than the mean HbA1c (5.195%) for participants who were normoglycemic after the clamp (p value=0.0403), however absolute differences were small and significant overlap existed between both groups. We did not detect significant differences between hypoglycemic and normoglycemic participants for any other demographic or clamp factors analyzed. With regards to patients with 2 available clamp visits, of the 8 subjects who developed hypoglycemia, only one experienced it during both visits. Hypoglycemia is not uncommon after hyperglycemic clamp testing. Hyperglycemic clamp testing should include universal post-clamp glucose monitoring, as no clear demographic factors could be used to identify risk of hypoglycemia.


Copyright 2019 all authors


Uroosa Amir1, Kelly Moors2, Anna Neyman MD2, Emily K. Sims MD2

1Marian University COM 2Indiana University School of Medicine, Department of Pediatrics.

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