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. Lancet 1999; 353: 617–22 See Commentary page 606 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 Methods 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 WHO criteria. The exclusion criteria were: age older than 65 or younger than 40; a stimulated serum C- peptide concentration less than 600 pmol/L 6 min after intravenous injection of 1 mg glucagon; pancreatic insufficiency or diabetes secondary to pancreatitis; alcohol abuse; non-diabetic kidney disease; malignancy; or life-threatening disease with death probable within 4 years. Informed consent was obtained from all participants. The protocol was in accordance with the Helsinki declaration and was approved by the ethics committee of Copenhagen County. Study design The study was a randomised, open, parallel trial. Patients were randomly assigned standard treatment—ie, treatment by their general practitioner according to the 1988 recommendations of the Danish Medical Association 5 (table 1)—or intensive multifactorial intervention with behaviour modification and stepwise introduction of pharmacological therapy. The stepwise approach was chosen to maximise compliance to the protocol. Since the distribution of urinary AER is positively skewed, patients were stratified by this characteristic (30–100 mg per 24 h and 101–300 mg per 24 h) before randomisation. Before randomisation all participants received individualised diabetic dietary advice. Concealed randomisation was done in groups of four with two in each treatment arm and thus allowed a maximum difference of two patients per group per stratum. Patients in the intensive group were treated by a project team (doctor, nurse, and dietician) at Steno Diabetes Center. The Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study Peter Gæde, Pernille Vedel, Hans-Henrik Parving, Oluf Pedersen ARTICLES Steno Diabetes Centre, Niels Steensens Vej 2, DK 2820 Gentofte, Copenhagen, Denmark (P Gæde MD, P Vedel PhD, Prof H-H Parving DMSc, Prof O Pedersen DMSc) Correspondence to: Professor Oluf Pedersen THE LANCET • Vol 353 • February 20, 1999 617