Recent Exposure to Hypoglycemia Increases Glucose Variability Following a Hyper/Hypoglycemic Metabolic Challenge in T1D

Aims: In type 1 diabetes (T1D), repeated hypoglycemic episodes may reduce hormonal defenses and increase the risk for severe hypoglycemia. In this work, we investigate the effect of a structured hyper/hypoglycemic metabolic challenge on the postintervention glucose variability in T1D subjects studied at home.

Methods: Thirty T1D subjects using insulin pump were monitored with blood glucose meters (SMBG) during a 1-month observation period. After 2 weeks of monitoring, participants were admitted at the University of Virginia Clinical Research Unit to undergo an 8-hour metabolic challenge. The intervention was designed to create hyperglycemia shortly followed by hypoglycemia, mimicking a real-life scenario of underbolused meal followed by overcorrection. After the intervention, subjects were monitored for 2 more weeks. Glycemic variability was assessed before and after the challenge using the low blood glucose index (LBGI). Glucagon counterregulation (GCR) response to induced hypoglycemia was also measured. LBGI variation and GCR were linked to prior exposure to hypoglycemia.

Results: Subjects significantly exposed to hypoglycemia in the 2 weeks before the intervention had a significant increase of postchallenge LBGI ( P < .001) and lower GCR response ( P < .05). Recent occurrence of hypoglycemia and number of years not using an insulin pump were identified as significant predictors of postchallenge LBGI ( P < .001).

Conclusion: Glycemic swings, a common result of suboptimal insulin treatment, have a significant impact on future (days) glycemic control in T1D subjects with a recent history of hypoglycemia, as measured in the field. Choice of past insulin therapy may also mediate this effect.