Glycaemic control and incidence of heart failure in 20 985 patients with type 1 diabetes: an observational study

Summary

Background

Poor glycaemic control is associated with microvascular and macrovascular complications in type 1 diabetes, but whether glycaemic control is associated with heart failure in such patients is not known. We aimed to assess this association in a large cohort of patients with type 1 diabetes identified from the Swedish national diabetes registry.

Methods

We identified all patients (aged ≥18 years) with type 1 diabetes and no known heart failure who were registered in the national diabetes registry between January, 1998, and December, 2003. These patients were followed up until hospital admission for heart failure, death, or end of follow-up on Dec 31, 2009. We calculated incidence categorised by glycated haemoglobin A_1c (HbA_1c) values, and we assessed the association between patients' characteristics, including HbA_1c, and heart failure.

Findings

In a cohort of 20 985 patients with mean age of 38·6 years (SD 13·3) at baseline, 635 patients (3%) were admitted to hospital with a primary or secondary diagnosis of heart failure during a median follow-up of 9·0 years (IQR 7·3–11·0), with an incidence of 3·38 events per 1000 patient-years (95% CI 3·12–3·65). Incidence increased monotonically with HbA_1c, with a range of 1·42–5·20 per 1000 patient-years between patients in the lowest (<6·5%) and highest (≥10·5%) categories of HbA_1c. In a Cox regression analysis, with adjustment for age, sex, duration of diabetes, cardiovascular risk factors, and baseline or intervening acute myocardial infarction and other comorbidities, the hazard ratio for development of heart failure was 3·98 (95% CI 2·23–7·14) in patients with HbA_1c of 10·5% or higher compared with a reference group of patients with HbA_1c of less than 6·5%. Risk of heart failure increased with age and duration of diabetes. Other modifiable factors associated with increased risk of heart failure were smoking, high systolic blood pressure, and raised body-mass index. In a subgroup of 18 281 patients (87%) with data for blood lipids, higher HDL cholesterol was associated with lower risk of heart failure, but there was no association with LDL cholesterol.

Interpretation

The positive association between HbA_1c and risk of heart failure in fairly young patients with type 1 diabetes indicates a potential for prevention of heart failure with improved glycaemic control.

Funding

AstraZeneca, Novo Nordisk Scandinavia, Swedish Heart and Lung Foundation, and Swedish Research Council.

Introduction

Cardiovascular disease, which includes heart failure, is the most common cause of death in diabetes,1, 2 with most cardiovascular disease occurring in patients with type 2 diabetes, which is a far more common disease than is type 1 diabetes.³ However, considering that patients with type 1 diabetes are younger at onset of their disease, they stand to lose many more life-years from cardiovascular disease than do those with type 2 diabetes. The excess mortality due to cardiovascular disease in young adults with type 1 diabetes is between eight and 40 times that of the general population and is higher in women than in men.⁴ In follow-up of patients in the Diabetes Control and Complications Trial (DCCT),⁵ intensive glycaemic control in type 1 diabetes reduced the risk of cardiovascular disease, and poor glycaemic control has been associated with cardiovascular disease in observational studies of type 1 diabetes.6, 7

In a meta-analysis of randomised trials of intensive glycaemic control in patients with type 2 diabetes, intensive glycaemic therapy had no preventive effect on heart failure.⁸ Results of observational studies in heart failure and type 2 diabetes have been contradictory.2, 9, 10 In type 1 diabetes, studies of the effect of intensive glycaemic control for prevention of heart failure are absent, as are, to our knowledge, large observational studies relating glycaemic control to heart failure. Bearing in mind the high relative risk of death from cardiovascular disease in type 1 diabetes and the major health burden associated with heart failure in people with diabetes, it is important to investigate potentially modifiable factors in the development of heart failure in type 1 diabetes. However, studies of this kind are hampered by the shortage of well characterised populations with type 1 diabetes, particularly with respect to development of heart failure.

In our study, we aimed to overcome these limitations by assessing the potential association between glycaemic control, measured with glycated haemoglobin A_1c (HbA_1c) concentration, and the risk of hospital admission for heart failure in a large cohort of patients with type 1 diabetes.