Severe hypoglycemia and coronary artery calcification during the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study

•The role of hypoglycemia in atherosclerosis is complex.•When evaluating the role of hypoglycemia in CVD, overall glycemic levels should be considered.•Our results are not in conflict with those of the DCCT.•Besides achieving good glycemic control, severe hypoglycemia needs to be avoided.•Patients with severe hypoglycemia might need to be monitored closely for CVD.

AimRecently, major attention has been paid to the role of hypoglycemia as a cardiovascular risk factor. While EURODIAB-investigators concluded that severe hypoglycemia is not a cardiovascular risk factor in type 1 diabetes, other investigators found the opposite. The primary purpose of this study was to investigate the role of severe hypoglycemia in atherosclerosis during the DCCT- and EDIC-years with special attention to overall glycemic levels.Research design and methodsThe effect of severe hypoglycemic rates on coronary artery calcification (CAC) was evaluated for the entire cohort (n = 1205) and glycemic stratified cohorts (HbA1C < 7.5% [58 mmol/mol], HbA1C ≥ 7.5%).ResultsThe association between CAC and mean DCCT-hypoglycemia rate was stronger than the association between CAC and mean EDIC-hypoglycemia rate. Although the DCCT-severe hypoglycemia rate without HbA1C-stratification was not significantly associated with a CAC-score ≥ 100 Agatston units (p = 0.093), the interaction between above glycemic ranges and DCCT-hypoglycemic rate was significant (p < 0.05). A sub-analysis of patients belonging to the lower glycemic range (HbA1C < 7.5%), adjusted for baseline age, gender, baseline diabetes duration, baseline neuropathy, baseline albumin excretion rate, systolic blood pressure, LDL-cholesterol, smoking status, body mass index and DCCT-A1 C, indicated significant (p = 0.02) associations between DCCT-severe hypoglycemia rate and CAC-score ≥ 100. One unit increase in the natural logarithm transformed DCCT-severe hypoglycemia rate increased the risk of having a CAC ≥ 100 by 30%.ConclusionsOur results suggest a cumulative effect of hypoglycemic events on cardiovascular risk. They provide a possible link between above mentioned contradictory reports. Our findings support the relevance of personalizing glycemic goals in diabetes management beyond HbA1C.