Steno 2 Study - Steno 2 Study

Description:

The goal of the trial was to evaluate the effect on cardiovascular disease of an intensive intervention regimen of behavior modification and polypharmacologic therapy compared with a conventional therapy regimen among patients with type 2 diabetes and microalbuminuria.

Study Design

Study Design:

Patients Enrolled: 160
Mean Follow Up: Mean follow-up 7.8 years
Mean Patient Age: Mean age 55.1 years
Female: 26

Patient Populations:

Presence of diabetes and urine albumin excretion rates of 30-300 mg in four of these six samples collected during a 24-hour period

Exclusions:

Age >65 or <40 years; a stimulated serum C-peptide concentration <600 pmol/l six minutes after intravenous injection of 1 mg glucagon; pancreatic insufficiency or diabetes secondary to pancreatitis; alcohol abuse; nondiabetic kidney disease; malignancy; or life-threatening disease with death probable within four years

Primary Endpoints:

Development of diabetic nephropathy after four years of intervention; and composite of cardiovascular disease, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation at eight years

Secondary Endpoints:

Nephropathy, retinopathy, and neuropathy

Drug/Procedures Used:

Patients were randomized to an intensive intervention regimen (n=80) compared with a conventional therapy regimen (n=80) in accordance with national guidelines. The intensive intervention regimen consisted of behavior modification (diet, exercise, and smoking cessation) and polypharmacologic therapy (angiotensin-converting enzyme inhibitor or angiotensin II–receptor antagonist, daily multivitamin, and aspirin) that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria.

Principal Findings:

Behavior modification did not differ between the treatment groups, with no significant difference in change in exercise (median 30 minutes per week for intensive group vs. 0 min/week for conventional group, p=0.38), smoking (-5% for intensive vs. -6% for conventional, p=0.73), or caloric intake (-57 kcal vs. -43 kcal, p=0.33). Reduction in percent of fat intake was greater in the intensive group (-10.4% vs. -6.8%, p<0.001). Reductions in both systolic and diastolic blood pressure were larger in the intensive group (-14/-12 mm Hg vs. -3/-8 mm Hg, p<0.001 for systolic blood pressure and p=0.006 for diastolic blood pressure).

The intensive therapy group had larger reductions in glucose (-52 mg/dl vs. -18 mg/dl, p<0.001), glycosylated hemoglobin (-0.5% vs. 0.2%, p<0.001), triglycerides (-41 mg/dl vs. 9 mg/dl, p=0.015), total cholesterol (-50 mg/dl vs. -3 mg/dl, p<0.001), and LDL cholesterol (-47 mg/dl vs. -13 mg/dl, p<0.001). Additionally, the reduction in urinary albumin excretion was greater in the intensive therapy group (-20 mg/24 hours vs. 30 mg/24 hours, p=0.007).

The intensive therapy group had a significantly lower risk of cardiovascular disease (hazard ratio [HR] 0.47, 24% vs. 44% for p=0.008), nephropathy (HR 0.39, 20% vs. 39%, p=0.003), retinopathy (HR 0.42, p=0.02), and autonomic neuropathy (HR 0.37, p=0.002). There was no significant difference between groups in the number of patients with a minor hypoglycemic episode (n=42 for intensive vs. n=39 for conventional, p=0.50) or major hypoglycemic episode (n=5 for intensive vs. n=12 for conventional, p=0.12).

Interpretation:

Among patients with type 2 diabetes and microalbuminuria, use of an intensive intervention regimen of behavior modification and polypharmacologic therapy was associated with a reduction in long-term cardiovascular disease compared with a conventional therapy regimen.

The benefits of the intervention strategy continued throughout the eight years of the study with ongoing divergence of the Kaplan-Meier curves, suggesting the continual reinforcement of risk factor reduction was effective. While the trial showed improvements with use of the intensive therapy intervention, it is not clear which component of the strategy drove the reduction or if it was multiple components together.

References:

Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348:383-93.

Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet 1999;353:617­-22.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Diet, Hypertension

Keywords: Hyperglycemia, Behavior Therapy, Cholesterol, LDL, Diabetes Mellitus, Type 2, Risk Factors, Glucose, Hemoglobin A, Glycosylated, Dyslipidemias, Blood Glucose, Energy Intake, Hypoglycemic Agents, Triglycerides, Hypertension, Smoking Cessation


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