United Kingdom Prospective Diabetes Study - UKPDS

Description:

To determine whether improved blood glucose control prevents the complications of diabetes.

Hypothesis:

Among patients with type II diabetes, improved blood-glucose control will reduce the incidence of diabetes-related endpoints.

Study Design

Study Design:

Patients Screened: 7616
Patients Enrolled: 5102
Mean Follow Up: up to 13 years
Female: 42

Patient Populations:

Fasting plasma glucose (FPG) greater than 6 mmol/L on two mornings, 1­3 weeks apart Age 25-65 years

Exclusions:

Ketonuria >3 mmol/L; serum creatinine >175 mmol/L; myocardial infarction in the previous year; current angina or heart failure; more than one major vascular event; retinopathy requiring laser treatment; malignant hypertension; uncorrected endocrine disorder; occupation that precluded insulin therapy; severe concurrent illness that would limit life or require extensive systemic treatment; inadequate understanding.

Primary Endpoints:

Time to the first occurrence of: any diabetes-related endpoint (sudden death, death from hyperglycemia or hypoglycemia, fatal or non-fatal MI, angina, heart failure, stroke, renal failure, amputation of at least one digit, vitreous hemorrhage, retinal photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from MI, stroke, peripheral vascular disease, renal disease, hyperglycemia or hypoglycemia, and sudden death); all-cause mortality.

Secondary Endpoints:

MI (fatal and non-fatal) and sudden death; stroke (fatal and non-fatal); amputation or death due to peripheral vascular disease; microvascular complications (retinopathy requiring photocoagulation, vitreous hemorrhage, and or fatal or non-fatal renal failure).

Drug/Procedures Used:

Patients were stratified by ideal bodyweight (overweight was >120% ideal bodyweight). Non-overweight patients were randomly assigned intensive treatment with insulin (30%), intensive treatment with sulphonylurea (40%), or conventional treatment with diet (30%). Overweight patients were randomly assigned treatment with the additional possibility of metformin. Overweight patients who were randomly allocated metformin therapy are reported separately.

Principal Findings:

Over 10 years, hemoglobin A1c was reduced 11% in the intensive group compared with the conventional group (7.0% vs 7.9%, p<0.0001). The risk of any diabetes-related endpoint was 12% lower in the intensive group compared with the conventional group (p=0.029). Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction in microvascular endpoints (p=0.0099), including the need for retinal photocoagulation. The risk of diabetes-related death, while not significant, was 10% lower in the intensive group compared with the conventional group (p=0.34); likewise, all-cause mortality was 6% lower, although not statistically significant (p=0.44). There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycemic episodes than those in the conventional group on both types of analysis (both p<0.0001). Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).

Interpretation:

Intensive blood-glucose control by either sulphonylureas or insulin substantially decreased the risk of microvascular complications but only tended to be associated with reduced mortality in patients with type 2 diabetes. The disadvantages of intensive treatment are weight gain and risk of hypoglycaemia. None of the individual drugs had an adverse effect on cardiovascular outcomes, an important finding since prior epidemiological studies hinted at an association between high plasma insulin concentrations and myocardial infarction.

References:

Lancet 1998; 352:837­853.

Clinical Topics: Prevention, Diet

Keywords: Myocardial Infarction, Insulin, Overweight, Risk Reduction Behavior, Light Coagulation, Diabetes Mellitus, Type 2, Hemoglobin A, Glycosylated, Sulfonylurea Compounds, Metformin, Epidemiologic Studies, Hypoglycemic Agents, Chlorpropamide, Fasting, Glyburide


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