Finnish Diabetes Prevention Study

In Review

Tuomilehto J, et al. "Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with Impaired Glucose Tolerance". The New England Journal of Medicine. 2001. 344(18):1343-1350.
PubMed • Full text • PDF

Clinical Question

In overweight patients with impaired glucose tolerance, do intensive lifestyle interventions prevent or delay the onset of diabetes, as compared to usual care?

Bottom Line

In overweight patients with impaired glucose tolerance, intensive lifestyle interventions decrease the risk of progression to diabetes, as compared to usual care.

Major Points

Obesity, sedentary lifestyle and impaired glucose tolerance (IGT) are risk factors for type 2 diabetes (T2DM). In patients with IGT, The risk of progression to T2DM is estimated to be 1-10% annually. The Finnish Diabetes Prevention Study (DPS) evaluated the effect of intensive lifestyle intervention on the risk of diabetes as compared to usual care.

The trial randomized 522 middle-aged (40-64 years of age) patients with IGT and increased BMI to receive intensive lifestyle interventions or usual care. The trial was terminated prematurely at 3.2 years after a significant improvement on the end-point was observed. Intensive lifestyle intervention was associated with a 58% decrease in the risk of developing T2DM as compared to usual care (hazard ratio 0.4, 95% CI 0.3-0.7, P<0.001). The cumulative incidence of diabetes after 4 years was 11% (95% CI 6-15%) in the intervention group as compared to 23% (95% CI 17-29%) in the control group (P<0.001). In the intervention and control groups, the net weight loss by year 2 was 3.5±5.5 kg and 0.8±4.4 kg (P<0.001), respectively. Other benefits of intensive lifestyle intervention were decrease in daily caloric intake and intake of fat and cholesterol. Fiber density in diet was increased. Intensive lifestyle intervention also led to greater decrease in waist circumference and the proportion of sedentary individuals. Beneficial effects were also seen in glycemic control and cholesterol levels in the intervention group as compared to control group.

The Diabetes Prevention Program (DPP) randomized 3,234 patients at high risk of T2DM (increased BMI, elevated fasting plasma glucose (5.3-6.9 mmol/L) and IGT to receive standard lifestyle modification and placebo, standard lifestyle modification and metformin, or an intensive lifestyle intervention program. The 2.8-year follow-up results showed that intensive lifestyle intervention reduced the incidence of T2DM by 58% (95% CI 48-66%) as compared to placebo.

The DPP and DPS study were included in a 2008 meta-analysis of 8 studies to assess the effects of exercise and diet interventions for preventing T2DM. Among 5,956 patients, exercise and diet interventions reduced the risk of developing diabetes as compared to standard recommendations (RR 0.63, 95% CI 0.49-0.79) and showed favorable effects on weight reduction.

Guidelines

ADA Standards of Medical Care in Diabetes (2016, adapted)

• An intensive diet and physical activity behavioral counseling program targeting 7% body weight loss and increasing moderate-intensity physical activity (eg, brisk walking) to at least 150 min/week should be offered to patients with prediabetes (Level of Evidence: A)
• Follow-up counseling is important for maintaining long-term success (Level of Evidence: B)
• Based on the cost-effectiveness of diabetes prevention, such programs should be covered by third-party payers (Level of Evidence: B)
• Metformin therapy for prevention of type 2 diabetes may be considered in those with prediabetes, especially for those with BMI >35 kg/m², age <60 years, and women with prior gestational diabetes mellitus (Level of Evidence: A)
• At least annual monitoring for the development of diabetes in those with prediabetes is suggested (Level of Evidence: E)
• Screening for and treatment of modifiable risk factors for cardiovascular disease is suggested (Level of Evidence: B)
• Diabetes self-management education and support programs are suitable venues for people with prediabetes to receive education and support to develop and maintain behaviors that can prevent or delay the onset of diabetes (Level of Evidence: C)
• Internet-based social networks, distance learning, DVD-based content, and mobile applications can be helpful for effective lifestyle modification to prevent diabetes (Level of Evidence: B)

Design

• Multicenter, double-blind, parallel-group, randomized, controlled trial
• N=522
  • Intensive lifestyle intervention (n=265)
  • Usual care (n=257)
• Setting: 5 centers in Helsinki, Kuopio, Turku, Tampere, and Oulu
• Enrollment: 1993-1998
• Follow-up: 3.2 years (ended prematurely)
• Analysis: Intention-to-treat
• Primary outcome: Diabetes diagnosed according to the 1985 criteria of the World Health Organization

Population

Inclusion Criteria

• Age 40-65 years
• BMI ≥25 kg/m²
• IGT: 2-hour post OGTT plasma glucose of 140-199 mg/dL (7.8-11.0 mmol/L)

Exclusion Criteria

• previous diagnosis of diabetes mellitus except gestational diabetes
• significant comorbidity limiting survival to <6 years
• regular participation in a vigorous exercise program
• anticipated difficulty with participation due to psychological or physical disabilities
• medical conditions that could interfere with glucose metabolism (eg, thyroid and liver disease)

Baseline Characteristics

From the intensive lifestyle intervention group

• Demographics: males 34.3%, age 55±7 years
• BMI 31.3±4.6 kg/m², waist circumference 102±11 cm, hip circumference 110.4±10.5 cm
• Fasting plasma glucose 109±14 mg/dL, two-hour post OGTT 159±27 mg/dL
• Blood pressure: systolic 140±18 mm Hg, diastolic 86±9 mm Hg;
  • 30% patients were taking antihypertensives
• Serum lipids: total cholesterol 215±37 mg/dL, HDL-C 46±12 mg/dL, triglyceride 154±72 mg/dL;
  • 5% patients were taking cholesterol-lowering drugs

Interventions

Patients were randomized to receive intensive lifestyle intervention or usual care

• Intensive lifestyle intervention:
  • Nutritionist gives tailored dietary advice in face-to-face individual and group sessions.
  • At the start of the trial, participants were educated on risk factors for diabetes. Previous weight loss attempts were also discussed.
  • Dietary advice was: >50% of daily calories from carbohydrates; <10% from saturated fat and 20% from mono- and polyunsaturated fat, or up to 25% if the surplus is from monounsaturated fat; cholesterol <300 mg/day; and approximately 1 g protein/kg ideal body weight per day. Fiber intake of 15 g/1000 kcal or more was encouraged.
  • The goal is BMI <25 kg/m² or 5-10 kg weight loss. If this was not achieved during the first 6-12 months, a very low-calorie diet was considered
  • Participants were also guided to join individually tailored exercise programs.

• Usual care:
  • Nutritionist gives dietary advice at the start of the trial and during their annual follow-up visits.
  • Dietary advice given was <30% of daily calories from fat.
  • Participants were advised to reduce BMI to <25 kg/m^2.
  • Participants were also advised to reduce alcohol intake and stop smoking.
  • Verbal information about health effects of exercise was given but the program was not tailored.

Outcomes

Comparisons are intensive lifestyle intervention vs. usual care

Primary Outcomes

Cumulative incidence of diabetes after 4 years

11% (95% CI 6-15%) vs. 23% (95% CI 17-29%)

The risk of diabetes was reduced in the intervention group by 58% (P<0.001)

Secondary Outcomes

Change in weight

-4.2±5.1 vs. -0.8±3.7 kg (end of year 1; P<0.001)

-3.5±5.5 vs. -0.8±4.4 kg (end of year 2; P<0.001)

Change in waist circumference

-4.4±5.2 vs. -1.3±4.8 cm (P<0.001)

Change in fasting plasma glucose

-4±12 vs. 1±12 mg/dL (P<0.001)

Change in plasma glucose 2-hours post OGTT

-15±34 vs. -5±40 mg/dL (P=0.003)

Change in total cholesterol

-5±28 vs. -4±28 mg/dL (P=0.62)

Change in HDL-C

2±7 vs. 1±6 mg/dL (P=0.06)

Change in triglyceride

-18±51 vs. -1±60 mg/dL (P=0.001)

Change in blood pressure

systolic: -5±14 vs. -1±15 mm Hg (P=0.007)

diastolic: -5±9 vs. -3±9 mm Hg(P=0.02)

Self-reported changes in dietary habits

Decreased fat consumption: 87% vs. 70% (P=0.001)

Changed in quality of fat: 70% vs. 39% (P=0.001)

Increased vegetable consumption: 72% vs. 62% (P=0.01)

Decreased sugar consumption: 55% vs. 40% (P=0.001)

Decreased salt consumption: 59% vs. 50% (P=0.03)

Decreased alcohol consumption: 26% vs. 23% (P=0.43)

Self-reported increase in exercise

36% vs. 16% (P=0.001)

Successful achievement of intervention goals by 1 year

Weight reduction of >5%: 43% vs. 13% (P=0.001)

Fat intake <30% of total caloric intake: 47% vs. 26% (P=0.001)

Saturated-fat <10% of total caloric intake: 26% vs. 11% (P=0.001)

Fiber intake of 15 g/1000 kcal or more: 25% vs. 12% (P=0.001)

Exercise >4 hours/week: 86% vs. 71% (P=0.001)

Withdrawal from study

23 vs. 17 patients

Among these participants, 27 withdrew for personal reasons, 3 withdrew due to severe illness and 1 died

Subgroup Analysis

Not available

Adverse Events

Not available

Criticisms

• It is unclear how long can patients maintain their lifestyle changes. In fact, most patients may not maintain their weight loss after successful participation in weight-control programs.
• The trial was done in Finland therefore there is uncertainty if the interventions can be implemented in other populations.

Funding

• Finnish Academy
• The Ministry of Education
• The Novo Nordisk Foundation
• The Yrjö Jahnsson Foundation
• Finnish Diabetes Research Foundation