Risk for hypoglycemia requiring hospitalization may be increased in adults with type 2 diabetes who have a poor or near-normal proximal hemoglobin A1c (HbA1c) level, according to study results published in The Journal of Clinical Endocrinology & Metabolism.1

For this nested case-control study, researchers examined data from Clinical Practice Research Datalink and Hospital Episode Statistics in England from 1997 to 2014. Investigators assessed adults with type 2 diabetes who had experienced hospitalization for hypoglycemia (304 cases) and those who had not (304 matched controls) to determine the association of proximal HbA1c level with first hypoglycemia hospitalization. Proximal HbA1c was measured within 90 days prior to the first hospitalization for hypoglycemia.

For patients with proximal HbA1c levels between 4.0% and 6.5%, every 0.5% level increase reduced the first hypoglycemia hospitalization risk (odds ratio range, 0.37-0.86), but when the proximal HbA1c level ranged between 8.0% and 11.5%, risk for first hypoglycemia hospitalization became higher with each 0.5% increase in HbA1c (odds ratio range, 1.16-1.34). The investigators also found a U-shaped association between proximal HbA1c level and first hospitalization for hypoglycemia in current insulin users but not in current sulfonylurea users. Overall, 92% of hospitalizations occurred in patients taking insulin (often those with poor glycemic control) and in those taking sulfonylureas (often those with near-normal HbA1c levels).

These study results may not have been applicable to all participants with type 2 diabetes. The investigators acknowledged that the study outcome was a selective sample and cautioned interpreting statistical significance for results from subgroup analyses. In addition, variables such as diet, physical activity, and medication adherence were not available.

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Despite these limitations, no previous studies have “utilized HbA1c measurements close to the time of hypoglycemia diagnosis (ie, within 3 months), which may be more predictive of hypoglycemia as an acute complication of diabetes than HbA1c measured more than 3 months or even years before.”2-7 In addition, “severe hypoglycemia can be recurrent and is a strong predictor of future severe hypoglycemic events,” wrote the researchers. “Thus, preventing first severe hypoglycemic event has important clinical implications for hypoglycemia management.”

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References

1. Zhong VW, Juhaeri J, Cole SR, et al. Proximal HbA1C level and first hypoglycemia hospitalization in adults with incident type 2 diabetes [published online January 3, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01402

2. Yu S, Fu AZ, Engel SS, Shankar RR, Radican L. Association between hypoglycemia risk and hemoglobin A1C in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2016;32(8):1409-1416.

3. The Diabetes Control and Complications Trial Research Group. Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes. 1997;46(2):271-286.

4. Lipska KJ, Warton EM, Huang ES, et al. HbA1c and risk of severe hypoglycemia in type 2 diabetes: the Diabetes and Aging Study. Diabetes Care. 2013;36(11):3535-3542.

5. Weinstock RS, Xing D, Maahs DM, et al; T1D Exchange Clinic Network. Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J Clin Endocrinol Metab. 2013;98(8):3411-3419.

6. Miller ME, Bonds DE, Gerstein HC, et al; ACCORD Investigators. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ. 2010;340:b5444.

7. Williams ME, Garg R, Wang W, Lacson R, Maddux F, Lacson E Jr. High hemoglobin A1c levels and glycemic variability increase risk of severe hypoglycemia in diabetic hemodialysis patients. Hemodial Int. 2014;18(2):423-432.