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.