High serum ACE activity predicts severe hypoglycaemia over time in patients with type 1 diabetes

Abstract

Aims/hypothesis. High serum angiotensin-converting enzyme (ACE) activity is associated with increased risk of severe hypoglycaemia (SH) within 1 year in type 1 diabetes. We wanted to find out whether ACE activity is stable over time and predicts SH beyond 1 year, and if gender differences exist in the association between ACE activity and risk of SH. Methods. A follow-up study of 128 adult patients with type 1 diabetes was conducted. At entry, ACE activity was measured. For 12 months, patients prospectively recorded events of severe hypoglycaemia (SH). At a median of 40 months, ACE activity was measured again and participants recalled the number of SH in the last year. Results. ACE activity is reproducible over 40 months (p < 0.00001). Patients with SH during the baseline study also had SH during follow-up (p < 0.00001). Serum ACE activity measured at baseline was positively associated with the rate of SH at follow-up (p = 0.0003) with a 3.2-fold increased rate of SH in subjects belonging to the upper ACE quartile compared to subjects in the three lowest quartiles (p < 0.00001). The association between high serum ACE activity and increased risk of SH did not differ significantly in women and men. Conclusion. In type 1 diabetes individual serum ACE activity is reproducible over time. High ACE activity predicts recurrent SH over at least 40 months with no differences between genders.

Key Words::

• C-peptide
• duration of diabetes
• HbA1c
• hypoglycaemia unawareness
• diabetes complications

Acknowledgements

This study was funded by grants from The EFSD/JDRF/Novo Nordisk Programme for Research in Type 1 Diabetes, The Foundation of Harald Jensen and wife, Region 3 Foundation, The Foundation of Tvergaard, The Foundation of Frederiksborg County, and a research grant from Hillerød Hospital. We thank research nurses P. Banck and T. Larsen, Hillerød Hospital, for the handling of patients and data, and Børge Nordestgaard, MD, DMSc, Herlev Hospital, Denmark, for analysing serum ACE activity.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.