Intensive therapy delayed microvascular complications in patients with type 2 diabetes mellitus and microalbuminuria
ACP J Club. 1999 July-Aug;131:1. doi:10.7326/ACPJC-1999-131-1-001
Gaede P, Vedel P, Parving H-H, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and micro-albuminuria: the Steno type 2 randomized study. Lancet. 1999 Feb 20;353:617-22.
Does intensive multifactorial therapy slow the initiation and progression of microvascular disease in patients with type 2 diabetes mellitus and microalbuminuria?
Randomized, unblinded trial with mean follow-up of 3.8 years.
Diabetes center in Denmark.
160 patients (mean age 55 y, 74% men) with diabetes and a urinary albumin excretion rate (UAER) between 30 and 300 mg/24 h. Exclusion criteria were age < 40 or > 65 years, stimulated serum C-peptide level < 600 pmol/L, pancreatic insufficiency or pancreatitis, alcohol abuse, nondiabetic kidney disease, cancer, or life-threatening disease. Follow-up was 93%.
Patients were allocated to either intensive multifactorial intervention in a specialized diabetes center (n = 80) or standard treatment by a general practitioner (n = 80). The intensive intervention included a low-fat diet and exercise; smoking cessation (if needed); angiotensin-converting enzyme inhibitors; vitamins C and E; aspirin for ischemic cardiovascular disease; and stepwise pharmacologic therapy to reduce glucoselevels, blood pressure, and lipid levels.
Main outcome measures
Nephropathy (UAER > 300 mg/24 h), retinopathy, neuropathy, death, and macrovascular events.
Compared with patients in the standard group, those in the intensive group had reduced risks for nephropathy (P = 0.01), progression of retinopathy (P = 0.04), blindness in 1 eye (P = 0.03), autonomic neuropathy (P = 0.01), and the combined outcome of death and macrovascular events or signs (P = 0.03) (Table). Groups did not differ for the development of new retinopathy, maculopathy or proliferative retinopathy, or peripheral neuropathy.
Multifactorial therapy reduced development of nephropathy and progression of retinal and neuropathic complications in patients with type 2 diabetes mellitus and microalbuminuria.
Source of funding: No external funding.
For correspondence: Professor Oluf Pedersen, Steno Diabetes Center, Niels Steensens Vej 2, DK 2820 Gentofte, Copenhagen, Denmark. FAX 45-33-91-09-60.
Table. Intensive vs standard treatment in patients with type 2 diabetes mellitus and microalbuminuria at 4 years*
|Outcomes||Intensive||Standard||RRR (95% CI)||NNT (CI)|
|Nephropathy||11%||25%||56% (9 to 79)||7 (4 to 59)|
|Progression of retinopathy||26%||43%||40% (6 to 63)||6 (3 to 49)|
|Blindness in 1 eye||1%||9%||85% (11 to 98)||3 (6 to 134)|
|Progression of autonomic neuropathy||11%||29%||62% (23 to 82)||6 (3 to 19)|
|Combined death and macrovascular events||34%||54%||37% (10 to 57)||5 (3 to 23)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
Metabolic abnormalities, including hyperglycemia, obesity, hypertension, and dyslipidemia, are frequently present inpatients with type 2 diabetes and are risk factors for both microvascular and macrovascular disease. The risk is further increased in patients with microalbuminuria. Clinical trial evidence has shown that reducing plasma glucose levels, blood pressure, or both slows the development or progression of microvascular complications. Individual trials have focused on 1 or, at most, 2 interventions. However, in routine clinical practice, multifactorial interventions are often needed to improve the many possible metabolic derangements.
Gaede and colleagues' study shows the benefits of intensively managing type 2 diabetes. A major strength of the study is its pragmatic design that compares multifactorial interventions (similar to those recommended by the American Diabetes Association) in a diabetes center with routine care by primary care providers. An impressive reduction in the development of microvascular complications was found; a cumulative end point assessing cardiovascular disease morbidity and mortality was also improved. The intensively treated group gained weight during the study.
Delivery of this type of care should become standard practice for patients with type 2 diabetes. However, optimal chronic disease management presents many challenges to health care delivery systems. Several recent reports have examined methods that may facilitate optimal delivery of this type of care. These include a case management approach in a U.S. health maintenance organization (1), shared care between hospital and general practice in the United Kingdom (2), and the use of electronic management tools in the physician's office (3).
Sean F. Dinneen, MD
Mayo ClinicRochester, Minnesota, USA
1. Aubert RE, Herman WH, Waters J, et al. Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization. A randomized, controlled trial. Ann Intern Med. 1998;129:605-12.