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18.09.2017 | Original Research | Ausgabe 5/2017 Open Access

Diabetes Therapy 5/2017

Relation Between Different Measures of Glycemic Exposure and Microvascular and Macrovascular Complications in Patients with Type 2 Diabetes Mellitus: An Observational Cohort Study

Zeitschrift:
Diabetes Therapy > Ausgabe 5/2017
Autoren:
Rients P. T. van Wijngaarden, Jetty A. Overbeek, Edith M. Heintjes, Agata Schubert, Joris Diels, Huub Straatman, Ewout W. Steyerberg, Ron M. C. Herings
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s13300-017-0301-4) contains supplementary material, which is available to authorized users.

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Abstract

Introduction

This retrospective cohort study investigated the relation between different measures of glycemic exposure and micro- and macrovascular complications among patients with type 2 diabetes.

Methods

The analysis included patients receiving oral antihyperglycemic agents between 1 January 2006 and 31 December 2014 from the General Practitioner Database from the PHARMO Database Network. All recorded HbA1c levels during follow-up were used to express glycemic exposure in four ways: index HbA1c, time-dependent HbA1c, exponential moving average (EMA) and glycemic burden. Association between glycemic exposure and micro-/macrovascular complications was analyzed by estimating hazard ratios and 95% confidence intervals using an adjusted (time-dependent) Cox proportional hazards model.

Results

The analysis included 32,725 patients (median age, 65 years; 47% female). Median follow-up was 5.4 years; median number of HbA1c measurements per patient was 18.0. From all measures, HbA1c at index showed the weakest relation between all micro-/macrovascular complications, with coronary artery disease (CAD) having the highest HR (95% CI): 1.18 (1.04–1.34) for HbA1c ≥64 mmol/mol (8%). The time-dependent HbA1c model showed a significant association only for microvascular complications, with retinopathy having the highest HR (95% CI): 1.55 (1.40–1.73) for HbA1c ≥64 mmol/mol (8%). EMA-defined exposure showed similar findings, although the effect of retinopathy was more pronounced [HR (95% CI): 1.81 (1.63–2.02) for HbA1c ≥64 mmol/mol (8%)] and was also predictive for CAD [HR (95% CI): 1.29 (1.10–1.50) for HbA1c ≥64 mmol/mol (8%)]. A statistically significant relation with glycemic burden was found for all selected micro-/macrovascular complications, with retinopathy having the highest HR (95%): 2.60 (2.19–3.07) for glycemic burden years >3.

Conclusion

This study shows that greater and more prolonged exposure to hyperglycemia increases the risk of micro- and macrovascular complications.

Funding

Janssen Pharmaceutica NV.
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