Elsevier

The Lancet

Volume 353, Issue 9153, 20 February 1999, Pages 617-622
The Lancet

Articles
Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study

https://doi.org/10.1016/S0140-6736(98)07368-1Get rights and content

Summary

Background

In type 2 diabetes mellitus the aetiology of long-term complications is multifactorial. We carried out a randomised trial of stepwise intensive treatment or standard treatment of risk factors in patients with microalbuminuria.

Methods

In this open, parallel trial patients were allocated standard treatment (n=80) or intensive treatment (n=80). Standard treatment followed Danish guidelines. Intensive treatment was a stepwise implementation of behaviour modification, pharmacological therapy targeting hyper-glycaemia, hypertension, dyslipidaemia, and microalbuminuria. The primary endpoint was the development of nephropathy (median albumin excretion rate >300 mg per 24 h in at least one of the two-yearly examinations). Secondary endpoints were the incidence or progression of diabetic retinopathy and neuropathy.

Findings

The mean age was 55·1 years (SD 7·2) and patients were followed up for 3·8 years (0·3). Patients in the intensive group had significantly lower rates of progression to nephropathy (odds ratio 0·27 [95% CI 0·10–0·75]), progression of retinopathy (0·45 [0·21–0·95]), and progression of autonomic neuropathy (0·32 [0·12–0·78]) than those in the standard group.

Interpretation

Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria slows progression to nephropathy, and progression of retinopathy and autonomic neuropathy. However, further studies are needed to establish the effect of intensified multifactorial treatment on macrovascular complications and mortality.

Introduction

Although macrovasular events cause most deaths in patients with type 2 diabetes, there is a great demand on health resources to manage the microvascular complications. Many patients develop retinopathy and neuropathy and type 2 diabetes is a principal cause of end-stage renal disease.1 Some of the risk factors of microvascular complications are modifiable and a multifactorial approach has been suggested.

Our randomised trial was designed to find out whether intensive multifactorial intervention that includes changes in behaviour and pharmacological therapy, slows the initiation and progression of microvascular complications in microalbuminuric patients with type 2 diabetes compared with a standard multifactorial treatment. Patients with microalbuminuria were selected since this is a strong predictor for the development of both microvascular and macrovascular complications.2, 3 Each year, 4–8% of patients with microalbuminuria have progression of their retinopathy or progression to nephropathy.1, 4

Section snippets

Patients

All patients were recruited from the Steno Diabetes Center during 1992–93. 315 patients who had urine albumin excretion rates (AER) of 30–300 mg in a 24 h urine sample were eligible. Patients were then asked to collect six 24 h urine samples. We defined microalbuminuria for this study as an AER of 30–300 mg per 24 h in four of these six samples: these criteria were used to improve the specificity of the diagnosis. Diabetes was diagnosed by 1985 WHOcriteria. The exclusion criteria were: age

Results

The flow of patients in the study is shown in figure 1. No patients were at any time excluded because of unwillingness to adhere to the assigned treatments. Clinical and biochemical characteristics of the 160 patients assigned standard or intensive treatment are in table 3. The medications taken by the participants are shown in table 2.

The mean (SD) follow-up was 3·8 (0·3) years. The changes in lifestyle, biochemistry in the two groups at the end of the study and differences between groups are

Discussion

We found that nearly 4 years of intensive multifactorial treatment slowed the progression to nephropathy and progression of retinopathy and autonomic neuropathy in our patients with type 2 diabetes and microalbuminuria—most of whom were obese.

By comparison, the impact of intensive antihyperglycaemic treatment on the progression from microalbuminuria to overt nephropathy in type 1 diabetes mellitus is controversial.14, 15, 16, 17, 18 An analysis of all 218 patients with type 1 diabetes patients

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