Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with Impaired Glucose Tolerance

Tuomilehto, Jaakko; Lindström, Jaana; Eriksson, Johan G.; Valle, Timo T.; Hämäläinen, Helena; Ilanne‐Parikka, Pirjo; Keinänen‐Kiukaanniemi, Sirkka; Laakso, Mauri; Louheranta, Anne; Rastas, Merja; Salminen, Virpi; Aunola, Sirkka; Čepaitis, Žygimantas; Moltchanov, Vladislav; Hakumäki, M. O. K.; Mannelin, Marjo; Martikkala, V.; Sundvall, Jouko; Uusitupa, Matti

doi:10.1056/nejm200105033441801

Cited by 9,083 publications

(6,728 citation statements)

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“…Evidence on type 2 diabetes prevention strategies is extensive, 1,[14][15][16] and currently, clinicians in the United States seeking to help patients reduce their diabetes risk recommend lifestyle change and monitor weight, fasting glucose, and/or HbA1c levels periodically. Among persons undergoing lifestyle change, we show that greater weight loss at 6 months predicts decreased 3-year diabetes risk in a graded fashion and that achievement of fasting glucose <100 mg/dl at 6 months is beneficial regardless of weight loss.…”

Section: Discussionmentioning

confidence: 99%

Early Response to Preventive Strategies in the Diabetes Prevention Program

Maruthur

Delahanty

et al. 2013

J GEN INTERN MED

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BACKGROUND:Recommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown. OBJECTIVE: To quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions. DESIGN: Analysis of results from a randomized controlled trial in 27 academic medical centers in the United States. PARTICIPANTS/INTERVENTIONS: 3,041 adults with hyperglycemia randomized to lifestyle (n=1,018), metformin (n=1,036), or placebo (n=987) with complete follow-up in The Diabetes Prevention Program. MAIN MEASURES: Independent variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months; hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main outcome was time to diabetes diagnosis. KEY RESULTS: After 6 months, 604 participants developed diabetes in the lifestyle (n=140), metformin (n=206), and placebo (n=258) arms over 2.7 years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI) 0.65 (0.35-1.22), 0.62 (0.33-1.18), 0.46 (0.24-0.87), 0.34 (0.18-0.64), and 0.15 (0.07-0.30) for 0-<3 %, 3-<5 %, 5-<7 %, 7-<10 %, and ≥10 % weight loss, respectively (reference: weight gain). Attainment of optimal 6-month FG and HbA1c and 12-month post-load glucose predicted >60 % lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P=0.038). CONCLUSION: Weight and glucose at 6 and 12 months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes.

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Section: Discussionmentioning

confidence: 99%

Early Response to Preventive Strategies in the Diabetes Prevention Program

Maruthur

Delahanty

et al. 2013

J GEN INTERN MED

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“…The subjects were at increased risk for T2DM either because of being overweight (body mass index (BMI)427 kg/m 2 ) or being a first-degree relative of a type 2 diabetic patient or having an IGT or females after gestational diabetes. This program includes the goals of the diabetes prevention study program (Tuomilehto et al, 2001): reduction of body weight by more than 5%, reduction of dietary intake of fat to less than 30% of calories, reduction of intake of saturated fatty acids to less than 10% of calories, increase of the daily amount of ingested fiber to more than 15 g per 100 kcal and increase of the amount of weekly exercise to more than 3 h per week. To achieve those goals, subjects were looked after by a team of dieticians.…”

Section: Subjectsmentioning

confidence: 99%

Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects

et al. 2006

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Background: Hypophosphatemia is associated with impaired glucose tolerance and insulin resistance in primary hyperparathyroidism. However, little is known about the association between serum phosphate and glucose metabolism in healthy subjects. Methods: We measured fasting serum phosphate levels (SP, normal range 2.6-4.5 mg/dl) and serum calcium (S-Ca, normal range 2.1-2.6 mmol/l) in 881 non-diabetic subjects (341 male/540 female, age: 3871 years, body mass index 25.970.2 kg/m 2 (mean7standard error of the mean). An oral glucose tolerance test (OGTT) with determination of glucose and insulin every 30 min was performed in all subjects. Insulin secretion and insulin sensitivity (IS) were estimated from the OGTT using validated indices. Furthermore, we tested whether serum phosphate predicts glucose tolerance in 115 subjects during a lifestyle intervention program (LIP). Results: Serum phosphate was negatively correlated with 2-h blood glucose levels independent of age, gender and percent body fat (r ¼ À0.13, Po0.0001). This association remained significant after additional adjustment for S-Ca, creatinine and parathyroid hormone. Serum phosphate was positively correlated with IS (r ¼ 0.10, P ¼ 0.0006), but not with insulin secretion. This was independent of age, gender, percent body fat, S-Ca and serum creatinine. In the subjects taking part in the LIP low serum phosphate levels at baseline were associated with higher postprandial glucose levels. Conclusions: In non-diabetic subjects, low serum phosphate levels are associated with high 2-h blood glucose levels and reduced IS. Whether low serum phosphate levels are a cause or a consequence of low IS and impairment of glucose tolerance needs to be tested in further studies.

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“…Insulin resistance, the central defect underlying the MS, most probably results from increased accumulation of lipids in the peripheral tissues (lipotoxicity) as a result of enhanced release of fatty acids from hypertrophic fat cells (1,2) . In addition to other lifestyle interventions (3,4) , adjustment of the quality of dietary lipids is also important for the prevention and treatment of MS. In particular, long-chain (LC) PUFA of the n-3 series, DHA (22: 6n-3) and EPA (20: 5n-3), which are abundant in marine fish, lower TAG while increasing HDL-cholesterol levels in plasma, prevent the development of heart disease and exert anti-inflammatory properties in human Proceedings of the Nutrition Society subjects (5)(6)(7) .…”

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confidence: 99%

n-3 PUFA: bioavailability and modulation of adipose tissue function

et al. 2009

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Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. The n-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA.

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Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with Impaired Glucose Tolerance

Abstract: Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.

Cited by 9,083 publications

References 17 publications

Early Response to Preventive Strategies in the Diabetes Prevention Program

Early Response to Preventive Strategies in the Diabetes Prevention Program

Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects

n-3 PUFA: bioavailability and modulation of adipose tissue function

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