Can the onset of type 2 diabetes be delayed by a group-based lifestyle intervention? A randomised control trial The epidemic of obesity and diabetes: trends and treatments. Lifestyle intervention is associated with lower prevalence of urinary incontinence: the Diabetes Prevention Program. The prevention or delay of type 2 diabetes. The Cost-Effectiveness of Lifestyle Modification or Metformin in Preventing Type 2 Diabetes in Adults with Impaired Glucose Tolerance HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial Regression From Pre-Diabetes to Normal Glucose Regulation in the Diabetes Prevention Program Within-trial cost-effectiveness of lifestyle intervention or metformin for the primary prevention of type 2 diabetes. The comparative efficacy of lifestyle intervention and metformin by educational attainment in the Diabetes Prevention Program. Relationship of body size and shape to the development of diabetes in the diabetes prevention program. Screening for Type 2 Diabetes Mellitus: A Cost-Effectiveness Analysis The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up. Costs associated with the primary prevention of type 2 diabetes mellitus in the diabetes prevention program. Lifestyle and Metformin Interventions Have a Durable Effect to Lower CRP and tPA Levels in the Diabetes Prevention Program Except in Those Who Develop Diabetes Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. Effects of Genetic Variants Previously Associated with Fasting Glucose and Insulin in the Diabetes Prevention Program A clinical trial to maintain glycemic control in youth with type 2 diabetes. Effect of Intervention in Subjects with High Risk of Diabetes Mellitus in Pakistan Long-term Effects of Lifestyle Intervention or Metformin on Diabetes Development and Microvascular Complications: the DPP Outcomes Study The diabetes prevention program and its global implications. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. The 10-Year Cost-Effectiveness of Lifestyle Intervention or Metformin for Diabetes Prevention Prevention of type 2 diabetes - where is the evidence?
This study was a r and omised control trial with a waiting control group . It was design ed to evaluate the effectiveness of a 6-month , group-based diabetes prevention programme , The Healthy Living Course and assess whether participation in the programme led to changes in modifiable risk factors for type 2 diabetes among an already at-risk pre-diabetic population . Individuals design ated at risk for diabetes by their general practitioners ( GPs ) were screened using an Oral Glucose Tolerance Test . Volunteers ( N = 307 ) with pre-diabetes were assigned to an intervention or wait-control group in the ratio of approximately 2 : 1 . The sample was pre-tested on biochemical , anthropometric and self-report behavioural , cognitive and mood variables and post-tested either at the end of the educational/support-based lifestyle programme or the end of the wait period . The intervention group significantly improved their diabetes knowledge , motivation to change , positive affect , healthy eating and activity levels and showed significantly greater reductions in weight , body mass index , waist circumference , diastolic blood pressure and fasting plasma glucose in comparison with controls . The intervention group also changed their diagnostic status from pre-diabetes to non-diabetes at a greater rate than the wait group ( 43 % vs. 26 % ) who received st and ard care from their GPs Cardiovascular disease remains the leading cause of death in women . Both obesity and diabetes mellitus are important independent risk factors for the development of cardiovascular disease . Obesity is the leading risk factor for type 2 diabetes . The Centers for Disease Control and Prevention report that 32 % of white and 53 % of black women are obese . Women with a body mass index ( BMI ) of 30 kg/m2 have a 28 times greater risk of developing diabetes than do women of normal weight . The risk of diabetes is 93 times greater if the BMI is 35 kg/m2.1 The presence of diabetes can increase a woman 's risk of heart disease 2-fold . In addition , the presence of diabetes overshadows the protective effects of the premenopausal state . In 2007 , 11.5 million of all women over the age of 20 ( 10.2 % ) had diabetes , and rates were slightly higher in ethnic minority groups : 10.4 % in Hispanic women and 11.8 % in non-Hispanic black women.2 The national prevalence rates of diabetes have increased in parallel with the rates of obesity ( Fig. 1 ) . Fig. 1 Age-adjusted percentage of U.S. adults who were obese or who had a diagnosis of diabetes mellitus . Screening Screening for obesity and diabetes is the 1st step to treatment and often reveals individuals who are at risk for but do not yet have overt disease . The United States Preventive Services Task Force ( USPSTF ) recommends that all adults be screened for obesity . Obesity signifies excess adipose tissue . The most widely used method for screening is determination of the BMI . The BMI is weight in kilograms divided by height in meters squared ( BMI = kg/m2 ) ( Table I ) . Most electronic medical records automatically calculate BMI if height and weight are entered . There are also many smart-phone applications and online calculators that can calculate BMI ( for example , http://www.nhlbisupport.com/ bmi ) . Other screening tools include  waist circumference and the waist-to-hip ratio . In women , a waist circumference > 35 in ( 88 cm ) or a waist-to-hip ratio > 0.7 indicates excess visceral fat and increased risk for disease . TABLE I. Body Mass Index ( BMI ) Classification Recommendations for screening for diabetes vary by guideline author . The USPSTF recommends screening asymptomatic patients who have  blood pressures > 135/80 mmHg  . The American Diabetes Association ( ADA ) recommends that individuals who are ≥18 years of age and have a BMI ≥25 kg/m2 and 1 additional risk factor for diabetes should be screened annually ( Table II).3 Individuals over the age of 45 without risk factors should be screened every 3 years . In January 2010 , the ADA released new recommendations for the use of hemoglobin A1C as a screening tool . An A1C greater than 6.5 % indicates diabetes . In addition , the results of screening tests for diabetes can identify individuals with “ prediabetes ” who have a markedly increased risk of developing overt disease.3 TABLE II . American Diabetes Association Recommendations on Screening for Type 2 Diabetes3 Non-Pharmaceutical Treatment Lifestyle-treatment options for diabetes mellitus and excess weight are similar , and 2 recent studies 4,5 have demonstrated the critical components for treating pre-diabetes and diabetes through weight loss , using caloric restriction and physical activity . The 1st study was the Diabetes Prevention Program.4 The purpose of the study was to identify individuals who were at risk for developing diabetes because of elevated fasting plasma glucose or impaired glucose tolerance levels that were not yet in the diagnostic range , in order to determine if metformin or an intensive lifestyle intervention could delay or prevent the onset of diabetes . More than 3,000 individuals with prediabetes were r and omized to receive placebo , metformin , or a 16-session lifestyle-modification program . The intensive lifestyle program set a goal of 7 % weight loss and 150 min/wk of moderate physical activity . Fifty percent of the lifestyle-intervention group lost 7 % of their body weight . The 3-year incidence of diabetes in the metformin group was 31 % lower than that in the placebo group . The incidence was 58 % lower in the lifestyle group than in the placebo group.4 The clinical implication s of this study are that we should 1 ) identify individuals with pre-diabetes and 2 ) recommend lifestyle modifications that result in a 7 % weight loss and include 150 min/wk of moderate physical activity . The 2nd study that examined lifestyle treatment of diabetes and obesity is the Look AHEAD Trial . The purpose of the study was to determine the effect of intentional weight loss on cardiovascular risk factors in individuals with diabetes . Approximately 5,100 individuals with type 2 diabetes and an elevated BMI were r and omized . Study conditions specified a 36-session intensive lifestyle intervention with the option of using partial meal replacements for caloric restriction or 4 sessions of st and ard diabetes support and education ( DSE ) . At 1 year , 55 % of the intensive-lifestyle-intervention group achieved 7 % weight loss . Hemoglobin A1C , systolic and diastolic blood pressure , and lipids improved significantly more in the intensive-lifestyle group than in the DSE group.5 The clinical implication of this study is that intentional weight loss of at least 7 % can improve the cardiovascular risk profile of patients with type 2 diabetes . Conclusions Excess weight affects two thirds of the U.S. adult population and increases risk for cardiovascular disease and diabetes . All patients should be screened for obesity and most should be screened for pre-diabetes and diabetes . The best treatment for diabetes is prevention . Prevention of diabetes can be accomplished through a 7 % weight loss through intensive lifestyle interventions that include caloric reduction and approximately 30 min of daily moderate physical activity . Practitioners will have access to these evidence -based programs soon . The Centers for Disease Control and Prevention are promoting community-based diabetes prevention programs throughout the country OBJECTIVE Diabetes is associated with increased urinary incontinence risk . Weight loss improves incontinence , but exercise may worsen this condition . We examined whether an intensive lifestyle intervention or metformin therapy among overweight pre-diabetic women was associated with a lower prevalence of incontinence . RESEARCH DESIGN AND METHODS We analyzed data from the Diabetes Prevention Program , a r and omized controlled trial in 27 U.S. centers . Of the 1,957 women included in this analysis , 660 ( 34 % ) were r and omized to intensive lifestyle therapy  , 636 ( 32 % ) to metformin  , and 661 ( 34 % ) to placebo with st and ard lifestyle advice . The main outcome measure was incontinence symptoms by frequency and type by a vali date d question naire completed at the end-of-trial visit ( mean 2.9 years ) . RESULTS The prevalence of total ( stress or urge ) weekly incontinence was lower among women in the intensive lifestyle group ( 38.3 % ) than those r and omized to metformin ( 48.1 % ) or placebo ( 45.7 % ) . This difference was most apparent among women with stress incontinence ( 31.3 % for intensive lifestyle group vs. 39.7 % for metformin vs. 36.7 % for placebo , P = 0.006 ) . Changes in weight accounted for most of the protective effect of the intensive lifestyle intervention on stress incontinence . CONCLUSIONS Less-frequent urinary incontinence may be a powerful motivator for women to choose lifestyle modification to prevent diabetes D iabetes is one of the most costly and burdensome chronic diseases of our time and is a condition that is increasing in epidemic proportions in the U.S. and throughout the world ( 1 ) . The complications result ing from the disease are a significant cause of morbidity and mortality and are associated with the damage or failure of various organs such as the eyes , kidneys , and nerves . Individuals with type 2 diabetes are also at a significantly higher risk for coronary heart disease , peripheral vascular disease , and stroke , and they have a greater likelihood of having hypertension , dyslipidemia , and obesity ( 2–6 ) . There is also growing evidence that at glucose levels above normal but below the diabetes threshold diagnostic now referred to as pre-diabetes , there is a substantially increased risk of cardiovascular disease ( CVD ) and death ( 5,7–10 ) . In these individuals , CVD risk factors are also more prevalent ( 5–7,9,11–14 ) , which further increases the risk but is not sufficient to totally explain it . In contrast to the clear benefit of glucose lowering to prevent or retard the progression of microvascular complications associated with diabetes ( 15– 18,21 ) , it is less clear whether the high rate of CVD in people with impaired glucose homeostasis , i.e. , those with impaired fasting glucose ( IFG ) , impaired glucose tolerance ( IGT ) , or diabetes , is caused by elevated blood glucose levels or will respond to treatments that lower blood glucose . Epidemiological studies have shown a clear relationship ( 19,20 ) , whereas intervention trials in people with diabetes suggest , but have not demonstrated , a clear benefit of glycemic control ( 15,16,21,22 ) . Additionally , there are no studies that have investigated a benefit of glucose lowering on macrovascular disease in subjects with only pre-diabetes ( IFG or IGT ) but not diabetes . Although the treatment of diabetes has become increasingly sophisticated , with over a dozen pharmacological agents available to lower blood glucose , a multitude of ancillary supplies and equipment available , and a clear recognition by health care professionals and patients that diabetes is a serious disease , the normalization of blood glucose for any appreciable period of time is seldom achieved ( 23 ) . In addition , in well-controlled socalled “ intensively ” treated patients , serious complications still occur ( 15–18,21 ) , and the economic and personal burden of diabetes remains . Furthermore , microvascular disease is already present in many individuals with undiagnosed or newly diagnosed type 2 diabetes ( 11,24– 28 ) . Given these facts , it is not surprising that studies have been initiated in the last decade to determine the feasibility and benefit of various strategies to prevent or delay the onset of  type 2 diabetes .  Two early reports ( 29,30 ) suggested that changes in lifestyle can prevent diabetes , but weaknesses in study design limited their general relevance . Recently , however , four well- design ed r and omized controlled trials have been reported ( 31–35 ) . In the Finnish study ( 31 ) , 522 middleaged ( mean age 55 years ) obese ( mean BMI 31 kg/m ) subjects with IGT were r and omized to receive either brief diet and exercise counseling ( control group ) or intensive individualized instruction on weight reduction , food intake , and guidance on increasing physical activity ( intervention group ) . After an average follow-up of 3.2 years , there was a 58 % relative reduction in the incidence of diabetes in the intervention group compared with the control subjects . A strong correlation was also seen between the ability to stop the progression to diabetes and the degree to which subjects were able to achieve one or more of the following : lose weight ( goal of 5.0 % weight reduction ) , reduce fat intake ( goal of 30 % of calories ) , reduce saturated fat intake ( goal of 10 % of calories ) , increase fiber intake ( goal of 15 g/1,000 kcal ) , and exercise ( goal of 150 min/week ) . No untoward effects of the lifestyle interventions were observed . In the Diabetes Prevention Program ( DPP ) ( 32–34 ) , the 3,234 enrolled subjects were slightly younger ( mean age 51 years ) and more obese ( mean BMI 34 kg/m ) but had nearly identical glucose intolerance compared with subjects in the Finnish study . About 45 % of the participants were from minority groups ( e.g , AfricanAmerican , Hispanic ) , and 20 % were 60 years of age . Subjects were r and omized to one of three intervention groups , which included the intensive nutrition and exercise counseling ( “ lifestyle ” ) group or either of two masked medication treatment groups : the biguanide metformin group or the placebo group . The latter interventions were combined with st and ard diet and exercise recommendations . After an average follow-up of 2.8 years ( range 1.8–4.6 years ) , a 58 % relative reduction in the progression to diabetes was observed in the lifestyle group ( absolute incidence 4.8 % ) , and a 31 % relative reduction in the progression of diabetes was observed in the metformin group ( absolute incidence 7.8 % ) compared with control subjects ( absolute incidence 11.0 % ) . ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● Context The Diabetes Prevention Program ( DPP ) showed that lifestyle changes or metformin effectively decreased the development of  type 2 diabetes in adults with impaired glucose tolerance . The economics of these interventions is important to policymakers . Contribution This cost-effectiveness model estimates that the DPP life-style intervention would cost society about $ 8800 and metformin would cost about $ 29900 per quality -adjusted life-year saved . While lifestyle intervention had a favorable cost-effectiveness profile at any adult age , metformin was not cost-effective after age 65 years . Implication s The cost-effectiveness of lifestyle intervention to prevent type 2 diabetes  in high-risk individuals is within the range that American society typically finds acceptable for health care interventions . The Editors During the past half century , the number of persons with diagnosed diabetes in the United States has increased 4- to 6-fold ( 1 ) . Recent large clinical trials from Asia , Europe , and North America have demonstrated that behavioral and medication interventions can delay or prevent the development of type 2 diabetes in persons with impaired glucose tolerance , which is defined by a plasma glucose level between 7.77 mmol/L ( 140 mg/dL ) and 11.04 mmol/L ( 199 mg/dL ) 2 hours after a 75-g oral glucose load ( 2 - 6 ) . The Diabetes Prevention Program ( DPP ) r and omly assigned 3234 nondiabetic persons 25 years of age or older with impaired glucose tolerance and fasting glucose levels between 5.27 mmol/L ( 95 mg/dL ) and 6.94 mmol/L ( 125 mg/dL ) to placebo ; a lifestyle-modification program with the goals of at least a 7 % weight loss and 150 minutes of physical activity per week ; or metformin , 850 mg twice daily ( 4 ) . The mean age of participants was 51 years , and the mean body mass index was 34.0 kg/m2 ; 68 % were women and 45 % were members of minority groups ( 4 ) . The average follow-up was 2.8 years . Compared with the placebo intervention , the lifestyle intervention reduced the incidence of type 2 diabetes by 58 % and the metformin intervention reduced the incidence of type 2 diabetes by 31 % ( 4 ) . We have previously described the costs of the DPP interventions and their cost-effectiveness within the 3-year trial period ( 7 , 8) . In this analysis , we project the costs , health outcomes , and cost-effectiveness of the DPP lifestyle and metformin interventions over a lifetime relative to the placebo intervention . Methods Clinical Trial The lifestyle intervention involved a healthy , low-calorie , low-fat diet and moderate physical activity , such as brisk walking . The lifestyle intervention was implemented with a 16-lesson core curriculum covering diet , exercise , and behavior modification that was taught by case managers on a one-on-one basis , followed by individual sessions ( usually monthly ) and group sessions with case managers ( 9 ) . At the end of the study , 38 % of participants in the lifestyle intervention group had lost at least 7 % of their initial body weight .  The metformin and placebo interventions were initiated at a dosage of 850 mg once a day . At 1 month , the dosage of metformin or placebo was increased to 850 mg twice daily . Case managers reinforced adherence during individual quarterly sessions ( 10 ) . At the end of the study , 72 % of participants in the metformin intervention group and 77 % of participants in the placebo intervention group took at least 80 % of the prescribed dose . All participants received st and ard lifestyle recommendations through written information and an annual 20- to 30-minute individual session that emphasized the importance of a healthy lifestyle ( 10 ) . Simulation Model We assessed the progression from impaired glucose tolerance to onset of diabetes to clinical ly diagnosed diabetes to diabetes with complications and death by using a lifetime simulation model originally developed by the Centers for Disease Control and Prevention and Research Triangle Institute International . The model has a Markov structure and includes annual transition probabilities between disease states ( 11 ) . In addition to disease progression , the model tracks costs and quality -adjusted life-years ( QALYs ) . The model has been described elsewhere ( 11 ) . For our analyses , we modified the model to include data from the DPP on progression , costs , and quality of life associated with impaired glucose tolerance , data from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) on diabetes progression and complications , and new data on cost and quality of life associated with diabetes . A technical report describing the model is available . Supplement . Technical Report Disease Progression , Complications , and Comorbid Conditions Impaired Glucose Tolerance to Onset of Type 2 Diabetes We analyzed data from the DPP to assess the annual hazard of diabetes onset in the lifestyle , metformin , and placebo intervention groups . For patients receiving the placebo intervention , the annual hazard of diabetes onset was 10.8 per 100 person-years . At 3 years of follow-up , the risk reductions for the lifestyle and metformin interventions were 55.8 % and 29.9 % , respectively . In the base-case analysis , we assumed that the lifestyle and metformin interventions would be applied until diabetes onset and that the health and quality -of-life benefits associated with the interventions persisted until diabetes onset . Complications and Comorbid Conditions Associated with Impaired Glucose Tolerance We analyzed data from the DPP and other published sources to assess the prevalence of complications and comorbid conditions in participants with impaired glucose tolerance . At baseline , 6.0 % of DPP participants had microalbuminuria and 0.4 % had nephropathy .  The DPP did not measure peripheral neuropathy , but previous studies found that the prevalence of neuropathy in persons with impaired glucose tolerance was 74 % of that in persons with newly diagnosed type 2 diabetes ( 12 ) and 12.3 % of persons with newly diagnosed type 2 diabetes have neuropathy ( 13 ) . Therefore , we assumed that at baseline , 8.5 % of DPP participants had clinical neuropathy . At baseline , 28 % of DPP participants had hypertension , 45 % had dyslipidemia , 7 % were smokers , 1.1 % had a history of cerebrovascular disease , and 2.0 % had a history of myocardial infa rct ion . No other complications were present . We assumed that during impaired glucose tolerance , microvascular or neuropathic complications would not progress . We assumed that hypertension and dyslipidemia developed at the rates observed in the DPP . On the basis of 2 large studies ( 14 , 15 ) , we assumed that the incidences of coronary heart disease and cerebrovascular disease in patients with impaired glucose tolerance were 58 % and 56 % , respectively , of those observed in patients with type 2 diabetes . We further assumed that nondiabetes-related mortality for persons with impaired glucose tolerance was the same as for persons with diabetes ( 16 ) . Onset of Type 2 Diabetes to Clinical Diagnosis of Type 2 Diabetes In the DPP , participants were tested for diabetes every 6 months ; diabetes was diagnosed at onset . In routine clinical practice , type 2 diabetes is estimated to develop 8 to 12 years before its clinical diagnosis ( 17 , 18 ) . In our base-case analysis , we therefore assumed that a 10-year delay occurred between the onset and clinical diagnosis of diabetes . Participants in the DPP  had a mean hemoglobin A1c level of 6.4 % at the onset of diabetes . Participants in the UKPDS had a mean hemoglobin A1c of 7.1 % after a dietary run-in period but before r and omization ( 13 ) . Both DPP placebo participants and UKPDS participants received st and ard lifestyle recommendations . Accordingly , we assumed that during the 10-year interval between onset and clinical diagnosis of diabetes , patients were treated for type 2 diabetes and that hemoglobin A1c level increased at 0.07 % per year from 6.4 % to 7.1 % . Complications and Comorbid Conditions Associated with Undiagnosed Diabetes We further assumed that between onset and clinical diagnosis of diabetes , microvascular and neuropathic complications progressed slowly , such that by clinical diagnosis of type 2 diabetes , their prevalence reached the level observed in the UKPDS cohort at r and omization ( 13 , 19 , 20 ) . We assumed that blood pressure and lipid levels progressed as they did in DPP participants and that cardiovascular complications occurred as they would in type 2 diabetes according to risk factors and hemglobin A1c level ( 21 , 22 ) . Clinical Diagnosis of Type 2 Diabetes to Diabetes with Complications and Death We assumed that after clinical diagnosis , all persons with type 2 diabetes received intensive glycemic management as described in the UKPDS ( 13 ) . We modeled changes in hemoglobin A1c and diabetes treatments to reflect those observed in the UKPDS intensive therapy group . We based risk for retinopathy progression on UKPDS 38 ( 23 ) , risk for nephropathy progression on UKPDS 64 ( 20 ) , and risk for neuropathy progression on UKPDS 33 ( 13 ) . We based risk for cerebrovascular disease on UKPDS 60 ( 22 ) and risk for coronary heart disease on UKPDS 56 ( 21 ) . Costs Costs of Impaired Glucose Tolerance To estimate the total direct medical costs of impaired glucose tolerance , we considered the costs of the DPP interventions ( the cost of identifying participants , implementing and maintaining the interventions , and monitoring and treating the side effects of the interventions ) and the costs of the medical care outside the DPP ( 7 ) . In analyses from the perspective of society , we included both direct medical costs and direct nonmedical costs . We did not include indirect costs because they are captured in the assessment of QALYs ( 24 ) . Table 1 shows the total direct medical costs by treatment group , sex , and year in the DPP ( 7 ) . Costs were higher in the lifestyle and metformin interventions than in the placebo intervention and higher in women than in men . Costs decreased over time in all 3 intervention groups but after year 1 tended to decrease more in the lifestyle than OBJECTIVE Glycated hemoglobin ( HbA1c ) , a st and ard measure of chronic glycemia for managing diabetes , has been proposed to diagnose diabetes and identify people at risk . The Diabetes Prevention Program ( DPP ) was a 3.2-year r and omized clinical trial of preventing type 2 diabetes with a 10-year follow-up study , the DPP Outcomes Study ( DPPOS ) . We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5 % ( 48 mmol/mol ) . RESEARCH DESIGN AND METHODS We r and omized 3,234 nondiabetic adults at high risk of diabetes to placebo , metformin , or intensive lifestyle intervention  and followed them for the development of diabetes as diagnosed by fasting plasma glucose ( FPG ) and 2-h postload glucose ( 2hPG ) concentrations ( 1997 American Diabetes Association [ ADA ] criteria ) . HbA1c was measured but not used for study eligibility or outcomes . We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG , 2hPG , or HbA1c ( 2010 ADA criteria ) .  RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups . Diabetes incidence defined by HbA1c ≥6.5 % was reduced by 44 % by metformin and 49 % by lifestyle during the DPP and by 38 % by metformin and 29 % by lifestyle throughout follow-up . Unlike the primary DPP and DPPOS findings based on glucose criteria , metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c . CONCLUSIONS HbA1c predicted incident diabetes . In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes , metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes . The long-term implication s for other health outcomes remain to be determined OBJECTIVE Participants in the Diabetes Prevention Program ( DPP ) r and omized to intensive lifestyle modification  ( ILS ) or metformin had a significantly reduced incidence of diabetes compared with those r and omized to placebo , yet most were still at risk because they had pre-diabetes . We explored the effect of baseline characteristics , weight change , ILS , and metformin on regression from pre-diabetes to the lowest-risk state of normal glucose regulation ( NGR ) defined by American Diabetes Association criteria . RESEARCH DESIGN AND METHODS The DPP was a prospect i ve r and omized trial . Cox proportional hazards modeling was used to identify predictors of regression from pre-diabetes to NGR over 3 years of follow-up . RESULTS Lower baseline fasting ( hazard ratio 1.52 , P < 0.01 ) and 2-h ( 1.24 , P < 0.01 ) glucose predicted regression to NGR , as did younger age ( 1.07 , P < 0.01 ) and greater insulin secretion ( 1.09 , P = 0.04 ) .  ILS  ( 2.05 , P < 0.01 ) and weight loss ( 1.34 , P < 0.01 ) had significant and independent effects on regression . A nonsignificant trend for regression was also observed for metformin ( 1.25 , P = 0.06 ) , male sex ( 1.17 , P = 0.08 ) , and insulin sensitivity ( 1.07 , P = 0.09 ) . In those entering the study with both impaired fasting glucose ( IFG ) and impaired glucose tolerance ( IGT ) , male sex and insulin sensitivity predicted regression to isolated IFG , whereas ILS , metformin , female sex , and greater insulin secretion predicted regression to isolated IGT . CONCLUSIONS Insulin secretion , and other biologic processes retained with younger age , are key in restoring NGR in people with pre-diabetes . However , NGR may also be attained through weight loss and additional aspects of ILS OBJECTIVE The Diabetes Prevention Program ( DPP ) demonstrated that intensive lifestyle and metformin interventions reduced the incidence of type 2 diabetes compared with a placebo intervention . The aim of this study was to assess the cost-effectiveness of the lifestyle and metformin interventions relative to the placebo intervention . RESEARCH DESIGN AND METHODS Analyses were performed from a health system perspective that considered direct medical costs only and a societal perspective that considered direct medical costs , direct nonmedical costs , and indirect costs . Analyses were performed with the interventions as implemented in the DPP and as they might be implemented in clinical practice . RESULTS The lifestyle and metformin interventions required more re sources than the placebo intervention from a health system perspective , and over 3 years they cost approximately US dollars 2250 more per participant . As implemented in the DPP and from a societal perspective , the lifestyle and metformin interventions cost US dollars 24400 and US dollars 34500 , respectively , per case of diabetes delayed or prevented and US dollars 51600 and US dollars 99200 per quality -adjusted life-year ( QALY ) gained . As the interventions might be implemented in routine clinical practice and from a societal perspective , the lifestyle and metformin interventions cost US dollars 13200 and US dollars 14300 , respectively , per case of diabetes delayed or prevented and US dollars 27100 and US dollars 35000 per QALY gained . From a health system perspective , costs per case of diabetes delayed or prevented and costs per QALY gained tended to be lower . CONCLUSIONS Over 3 years , the lifestyle and metformin interventions were effective and were cost-effective from the perspective of a health system and society . Both interventions are likely to be affordable in routine clinical practice , especially if implemented in a group format and with generic medication pricing OBJECTIVE Educational attainment is inversely associated with type 2 diabetes risk , but it is unknown whether education impacts individuals ' diabetes prevention efforts . We examined the comparative efficacy of intensive lifestyle intervention and metformin by educational attainment among participants in the Diabetes Prevention Program ( DPP ) , an ongoing U.S. multi-site trial beginning in 1996 . METHODS We studied 2,910 DPP participants r and omized to receive lifestyle intervention , metformin , or placebo .  Stratifying by educational attainment , diabetes incidence and relative risk reductions by treatment assignment were estimated using Cox proportional hazards regression . RESULTS 47 % of participants had completed college and 53 % had not . Compared to placebo , lifestyle participants who had completed college demonstrated a 68 % reduction in diabetes incidence ( 95 % CI=56 , 77 ) , whereas those with less education experienced a 47 % risk reduction ( 95 % CI=29 , 61 ) . For metformin participants , college graduates experienced a 49 % relative risk reduction ( 95 % CI=33 , 62 ) , compared to 23 % ( 95 % CI=1 , 41 ) among those with lower educational attainment . There was a statistically significant education-by-treatment interaction with incident diabetes ( p=0.03 ) . CONCLUSIONS Intensive lifestyle intervention and metformin have greater efficacy among highly educated individuals . Future efforts to deliver these treatments and study their dissemination may be more effective if tailored to individuals ' educational background OBJECTIVE We report the effects of several different measures of body size at baseline on the subsequent development of diabetes . High levels of body fat predict the onset of diabetes , but this association has not been previously reported in a large multiethnic population of overweight or obese people with impaired glucose tolerance . RESEARCH METHODS AND PROCEDURES Height , weight , waist circumference , hip circumference , and skinfolds were measured at baseline in 3234 participants enrolled in a r and omized clinical trial to treat individuals with impaired glucose tolerance with placebo , metformin , or a lifestyle modification program .  Cox proportional hazards models were used to assess the effect of baseline body size variables on the development of diabetes . RESULTS Over an average of 3.2 years in both the placebo and lifestyle groups , baseline waist circumference had the highest or second highest R(2 ) value for predicting diabetes in both sexes . Cox hazard ratios per 1 st and ard deviation were 1.43 and 1.49 for men in the placebo or lifestyle groups , respectively , and 1.29 and 1.53 for women in the placebo and lifestyle groups , respectively , adjusted for age and self-reported race/ethnicity . The c-statistic from the receiver operating characteristic curves also favored the waist circumference in men and women in the lifestyle group and men in the placebo group . No components of body size were predictive in the metformin-treated group , and metformin compared with the placebo group was effective in preventing diabetes only in individuals with a BMI > or = 35 kg/m(2 ) or a waist circumference > or = 98.0 cm . DISCUSSION Large waist circumference was a better predictor of risk for developing diabetes than most other measures in the placebo and lifestyle groups . No baseline measure of body size or shape predicted risk of diabetes in the metformin-treated group Context In 2003 , the U.S. Preventive Services Task Force recommended screening for type 2 diabetes in adults with hypertension or hyperlipidemia . The economic implication s of this recommendation are unclear . Contribution Diabetes screening for 55-year-old hypertensive persons would cost the U.S. health care system $ 34 375 per quality -adjusted life-year gained . Exp and ing screening to all adults regardless of the presence of hypertension would cost an additional $ 360 966 per quality -adjusted life-year . Implication s The cost-effectiveness of targeting diabetes screening to hypertensive adults older than 55 years of age is similar to the cost-effectiveness of many accepted health care interventions . Universal diabetes screening is far more costly . The Editors Although many adults who meet criteria for type 2 diabetes ( hereafter , diabetes ) have not been identified ( 1 ) , screening for diabetes remains controversial ( 2 - 11 ) . Direct evidence indicates that various treatments to reduce complications are effective among people with clinical ly detected diabetes ( 12 - 14 ) , but no direct evidence tells us the magnitude of any further benefit from starting these treatments earlier , after detection by screening ( 15 ) . In the absence of direct evidence , research ers have applied mathematical models of diabetes progression to the issue of screening . One analysis found that the cost per quality -adjusted life-year ( QALY ) gained by universal diabetes screening was lower for younger than for older people : $ 13 376 at age 25 to 34 years , increasing to $ 116 908 at age 55 to 64 years ( 16 ) . This conclusion followed from the model 's focus on the provision of glycemic control after screening to prevent microvascular complications . The analysis did not consider treatments to reduce the risks for complications of cardiovascular disease ( CVD ) . More recent research suggests that the benefits of CVD risk reduction may be substantial for people with diabetes . The Hypertension Optimal Treatment ( HOT ) trial found that the optimal blood pressure target is lower for people with hypertension and diabetes than for people with hypertension without diabetes ( 14 ) . Other research supports the finding that intensive control of hypertension is beneficial among people with diabetes ( 15 , 17 - 19 ) . Because the benefit may be greater for older people ( at greater risk for CVD ) , the conclusion of the previous analysis , that diabetes screening is most cost-effective among younger people , needs to be reconsidered . We performed a new cost-effectiveness analysis to compare universal diabetes screening ( universal screening ) and diabetes screening targeted to  patients with hypertension ( targeted screening ) . When an up date d version of the model used in the previous analysis that includes benefits from intensive treatment of hypertension was applied , we estimated the incremental cost-effectiveness of these 2 strategies for people in different age groups . Our analysis considers a one-time opportunistic screening for men and women of all races and ethnicities . Methods The Model We used a Markov model of diabetes disease progression to simulate lifetime diabetes-related health care costs and QALYs for people with diabetes ( Appendix Figure 1 ) . Demographic characteristics of the simulated cohort are based on 1997 population estimates projected from the 1990 U.S. Census and data on the distribution of people with diabetes by hypertension , cholesterol level , and smoking status ( 20 ) . As people progress through the simulation model from the onset of diabetes to death , they can develop 5 types of complications : nephropathy , neuropathy , retinopathy , coronary heart disease ( CHD ) , and stroke . People can die of some of these complications or of other causes . The model includes transition probabilities between disease stages on each of the 5 complication paths . The basic model structure has been described previously ( 16 , 21 ) . Key model parameters are presented in the Appendix Tables 1 to 10 . To incorporate screening into the model , we first added a screening module in which some patients with diabetes are identified earlier than they would usually have been in the absence of screening . Second , we made assumptions about the transition probabilities between disease stages from the onset of diabetes to the time of usual clinical diagnosis of diabetes on the basis of the knowledge that progression is relatively slow during this period ( 15 ) . After clinical diagnosis , disease progression depends on the number of years after normal diagnosis . Screening allows for earlier diagnosis , which in turn allows for earlier treatment interventions , such as intensive glycemic control and intensive hypertension control . These interventions decrease the transition probabilities , thereby delaying or preventing progression to diabetes complications . Costs are incurred for screening and diagnostic testing ; st and ard glycemic control and , if the person is hypertensive , st and ard hypertension control ; interventions ( intensive glycemic control and , if the person is hypertensive , intensive hypertension control ) ; and complications over the remaining lifetime of each person with diabetes . The sum of these costs and the model 's estimate of the expected QALYs for each screening strategy are used to calculate the incremental cost-effectiveness ratio of screening relative to no screening . We discounted future costs and QALYs at a 3 % annual rate . Costs are measured in 1997 U.S. dollars . Interventions We assumed that , in the absence of screening , diabetes would be diagnosed 10 years after its onset ( 15 ) . With one-time opportunistic screening , diabetes would be diagnosed on average 5 years after onset and therefore patients would begin treatment 5 years earlier . After diabetes diagnosis , all patients are treated with intensive glycemic control and , if they have hypertension , with intensive hypertension control . With targeted screening , only people with hypertension are screened . Those who screen positive and receive a diagnosis of diabetes begin intensive glycemic control and intensive hypertensive control 5 years earlier than they would in the absence of screening . With universal screening , all people , regardless of hypertension status , are screened . Those who screen positive and receive a diagnosis of diabetes begin intensive glycemic control 5 years earlier than in the absence of screening and begin intensive hypertension control 5 years earlier if they have hypertension . We defined hypertension as a blood pressure of 140/90 mm Hg or higher . We assumed that 19 % of people age 25 to 44 years , 47 % of people age 45 to 64 years , and 60 % of people age 65 to 74 years had hypertension and therefore were included in targeted screening ( 20 ) . Treatment of hypertension is modeled as st and ard ( with a target diastolic blood pressure of 90 mm Hg ) or intensive ( with a target diastolic blood pressure of 80 mm Hg ) , as in the HOT trial ( 14 ) . All persons with hypertension receive st and ard hypertension treatment until they receive a diagnosis of diabetes , after which they receive intensive hypertension treatment . The incremental cost of intensive hypertension control relative to st and ard control is $ 149 per year . In the HOT trial , the relative risk reduction for CHD events ( fatal and nonfatal myocardial infa rct ion ) was 51 % , and the relative risk reduction for stroke was about 30 % . Although neither of these separate relative risk reductions was statistically significant , the relative risk reduction ( 51 % ) for the aggregate outcome of major CVD events was statistically significant ( P = 0.005 ) . We initially modeled the relative risk reduction for CHD events for intensive hypertension control to be 51 % , with no risk reduction for stroke . We conducted a sensitivity analysis that included a 30 % relative risk reduction for stroke on the basis of other studies showing that intensive hypertension control reduces risk among people with diabetes ( 17 , 19 ) . Model estimates of the effects of glycemic control are based on the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , a 10-year r and omized , controlled trial of intensive versus conventional glycemic control ( 12 ) . On the basis of the UKPDS , the reduction in hemoglobin A1c from intensive glycemic treatment is modeled as slowing the progression of microvascular complications ( 12 ) . The incremental cost of intensive glycemic control ( relative to st and ard control ) ranges from $ 900 to $ 1100 per year , depending on the number of years since diagnosis . Screening and Diagnostic Tests The Figure illustrates the screening and diagnostic testing process and shows where costs are incurred . Figure . Progression of persons screened for diabetes . Appendix Figure 1 . Markov model of diabetes disease progression . LEA CA MI Screening Tests We assume a one-time opportunistic screening during a regularly scheduled physician office visit . The model assumes screening by a fasting capillary blood glucose ( CBG ) test ( 22 ) and an extra 10 minutes over the usual 15 minutes for the physician visit , incurring a cost of $ 24.40 per person screened . Costs for the CBG test are derived from the Medicare Clinical Diagnostic Laboratory Fee Schedule ( 23 ) ; physician visit costs are derived from Relative Values for Physicians ( 24 ) . Table 1 shows prevalence ( from the National Health and Nutrition Examination Survey III data tape ) , CBG sensitivity and specificity values ( 22 ) with exact data points clarified via personal communication ( Rolka DB , 18 January 2002 ) , and the number needed to screen to detect one previously undiagnosed person with diabetes by sex , hypertension status , and age . Table 1 . Number of Screenings and Diagnostic Tests  Needed To Identify One Undiagnosed Diabetes Case Diagnostic Tests All people who screen ( true or false ) positive receive a diagnostic test , the fasting plasma glucose test , which is repeated if the result is positive . Because 2 consecutive elevated fasting plasma glucose test results define diabetes ( 11 ) , we assume CONTEXT Gestational diabetes ( GDM ) confers a high risk of  type 2 diabetes .  In the Diabetes Prevention Program ( DPP ) , intensive lifestyle ( ILS ) and metformin prevented or delayed diabetes in women with a history of GDM . OBJECTIVE The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study . DESIGN This was a r and omized controlled clinical trial with an observational follow-up . SETTING The study was conducted at 27 clinical centers . PARTICIPANTS Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study . The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry . INTERVENTIONS Interventions included placebo , ILS , or metformin . OUTCOMES MEASURE Outcomes measure was diabetes mellitus . RESULTS Over 10 years , women with a history of GDM assigned to placebo had a 48 % higher risk of developing diabetes compared with women without a history of GDM . In women with a history of GDM , ILS and metformin reduced progression to diabetes compared with placebo by 35 % and 40 % , respectively . Among women without a history of GDM , ILS reduced the progression to diabetes by 30 % , and metformin did not reduce the progression to diabetes . CONCLUSIONS Women with a history of GDM are at an increased risk of developing diabetes . In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study , both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period . Among women without a history of GDM , lifestyle but not metformin reduced progression to diabetes OBJECTIVE To describe the costs of the Diabetes Prevention Program ( DPP ) interventions to prevent or delay type 2 diabetes . RESEARCH DESIGN AND METHODS We describe the direct medical costs , direct nonmedical costs , and indirect costs of the placebo , metformin , and intensive lifestyle interventions over the 3-year study period of the DPP . Re source use and cost are summarized from the perspective of a large health system and society . Research costs are excluded . RESULTS The direct medical cost of laboratory tests to identify one subject with impaired glucose tolerance ( IGT ) was $ 139 . Over 3 years , the direct medical costs of the interventions were $ 79 per participant in the placebo group , $ 2,542 in the metformin group , and $ 2,780 in the lifestyle group . The direct medical costs of care outside the DPP were $ 272 less per participant in the metformin group and $ 432 less in the lifestyle group compared with the placebo group . Direct nonmedical costs were $ 9 less per participant in the metformin group and $ 1,445 greater in the lifestyle group compared with the placebo group . Indirect costs were $ 230 greater per participant in the metformin group and $ 174 less in the lifestyle group compared with the placebo group . From the perspective of a health system , the cost of the metformin intervention relative to the placebo intervention was $ 2,191 per participant and the cost of the lifestyle intervention was $ 2,269 per participant over 3 years . From the perspective of society , the cost of the metformin intervention relative to the placebo intervention was $ 2,412 per participant and the cost of the lifestyle intervention was $ 3,540 per participant over 3 years . CONCLUSIONS The metformin and lifestyle interventions are associated with modest incremental costs compared with the placebo intervention . The evaluation of costs relative to health benefits will determine the value of these interventions to health systems and society OBJECTIVE We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes . RESEARCH DESIGN AND METHODS The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were r and omized to lifestyle , metformin , or placebo interventions for 3.4 years . Diabetes was diagnosed semiannually by fasting glucose and annually by oral glucose tolerance testing . In addition to baseline testing , anthropometry was performed every 6 months ; fasting insulin yearly ; and hs-CRP , tissue plasminogen activator ( tPA ) , and fibrinogen at 1 year and end of study ( EOS ) . RESULTS CRP and tPA levels were unchanged in the placebo group but fell in the lifestyle and metformin groups at 1 year and remained lower at EOS . These reductions were not seen in those who developed diabetes over the course of the study despite intervention . Fibrinogen was lower at 1 year in the lifestyle group . Differences in weight and weight change explained most of the influence of diabetes on the CRP response in the lifestyle group , but only partly in the placebo and metformin groups . Weight , insulin sensitivity , and hyperglycemia differences each accounted for the influence of diabetes on the tPA response . CONCLUSIONS Lifestyle and metformin interventions have durable effects to lower hs-CRP and tPA . Incident diabetes prevented these improvements , and this was accounted for by differences in weight , insulin resistance , and glucose levels CONTEXT A past history of gestational diabetes mellitus ( GDM ) confers a very high risk of postpartum development of diabetes , particularly type 2 diabetes . OBJECTIVE The Diabetes Prevention Program ( DPP ) sought to identify individuals with impaired glucose tolerance ( IGT ) and intervene in an effort to prevent or delay their progression to diabetes . This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM . DESIGN The DPP was a r and omized , controlled clinical trial . SETTING The study was a multicenter , National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites . PATIENTS A total of 2190 women were r and omized into the DPP and provided information for past history of GDM . This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM . INTERVENTIONS Subjects were r and omized to either st and ard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention . MAIN OUTCOMES The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing . Assessment s of insulin secretion and insulin sensitivity were also performed . RESULTS Whereas entering the study with similar glucose levels , women with a history of GDM r and omized to placebo had a crude incidence rate of diabetes 71 % higher than that of women without such a history . Among women reporting a history of GDM , both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50 % compared with the placebo group , whereas this reduction was 49 and 14 % , respectively in parous women without GDM . These data suggest that metformin may be more effective in women with a GDM history as compared with those without . CONCLUSIONS Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline . Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM Common genetic variants have been recently associated with fasting glucose and insulin levels in white population s. Whether these associations replicate in pre-diabetes is not known . We extended these findings to the Diabetes Prevention Program , a clinical trial in which participants at high risk for diabetes were r and omized to placebo , lifestyle modification or metformin for diabetes prevention . We genotyped previously reported polymorphisms ( or their proxies ) in/near G6PC2 , MTNR1B , GCK , DGKB , GCKR , ADCY5 , MADD , CRY2 , ADRA2A , FADS1 , PROX1 , SLC2A2 , GLIS3 , C2CD4B , IGF1 , and IRS1 in 3,548 Diabetes Prevention Program participants . We analyzed variants for association with baseline glycemic traits , incident diabetes and their interaction with response to metformin or lifestyle intervention . We replicated associations with fasting glucose at MTNR1B ( P<0.001 ) , G6PC2 ( P = 0.002 ) and GCKR ( P = 0.001 ) . We noted impaired β-cell function in carriers of glucose-raising alleles at MTNR1B ( P<0.001 ) , and an increase in the insulinogenic index for the glucose-raising allele at G6PC2 ( P<0.001 ) . The association of MTNR1B with fasting glucose and impaired β-cell function persisted at 1 year despite adjustment for the baseline trait , indicating a sustained deleterious effect at this locus . We also replicated the association of MADD with fasting proinsulin levels ( P<0.001 ) . We detected no significant impact of these variants on diabetes incidence or interaction with preventive interventions . The association of several polymorphisms with quantitative glycemic traits is replicated in a cohort of high-risk persons . These variants do not have a detectable impact on diabetes incidence or response to metformin or lifestyle modification in the Diabetes Prevention Program BACKGROUND Despite the increasing prevalence of type 2 diabetes in youth , there are few data to guide treatment . We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes . METHODS Eligible patients 10 to 17 years of age were treated with metformin ( at a dose of 1000 mg twice daily ) to attain a glycated hemoglobin level of less than 8 % and were r and omly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone ( 4 mg twice a day ) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors . The primary outcome was loss of glycemic control , defined as a glycated hemoglobin level of at least 8 % for 6 months or sustained metabolic decompensation requiring insulin . RESULTS Of the 699 r and omly assigned participants ( mean duration of diagnosed type 2 diabetes , 7.8 months ) , 319 ( 45.6 % ) reached the primary outcome over an average follow-up of 3.86 years . Rates of failure were 51.7 % ( 120 of 232 participants ) , 38.6 % ( 90 of 233 ) , and 46.6 % ( 109 of 234 ) for metformin alone , metformin plus rosiglitazone , and metformin plus lifestyle intervention , respectively . Metformin plus rosiglitazone was superior to metformin alone ( P=0.006 ) ; metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone . Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness , with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls . Serious adverse events were reported in 19.2 % of participants . CONCLUSIONS Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes . The addition of rosiglitazone , but not an intensive lifestyle intervention , was superior to metformin alone . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; TODAY Clinical Trials.gov number , NCT00081328 . ) Aims . To observe the rate of conversion from impaired glucose tolerance ( IGT ) to diabetes following lifestyle modification ( LSM ) or a combination of lifestyle and metformin compared to a control population with 18-month followup . Methods . Forty screening camps were organized , which 5000 people attended . Around 2300 persons filled the question naire and 1825 subjects were identified as high risk . Of 1739 subjects who took the oral glucose tolerance test , 317 subjects were identified as IGT . The 317 IGT subjects were r and omized into three groups : control group was given st and ard medical advice , LSM group was given intensive lifestyle modification advice , while LSM + drug group was given intensive lifestyle advice and metformin 500 mg twice daily . Results . At the end , 273 subjects completed the study , giving a compliance rate of 86 % . Total of 47 incident cases of diabetes were diagnosed ( overall incidence was 4 cases per 1000 person-months with the incidence of 8.6 cases in control group , 2.5 cases in the LSM , and 2.3 cases in the LSM + drug groups ) . Conclusions . Study showed that lifestyle intervention had a major impact in preventing diabetes among IGT subjects in this region . Adding drug did not show any improved results . We recommend lifestyle advice and followup should be incorporated in primary health care Background The worldwide epidemic of type 2 diabetes requires effective prevention . We determined the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention , originally demonstrated during the 3-year Diabetes Prevention Program ( DPP ) , and whether diabetes-associated microvascular complications are reduced . Methods The DPP ( 1996–2001 ) was a r and omized trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk to develop diabetes . All participants were offered lifestyle training at DPP-end . 2776 ( 88 % ) of the surviving DPP cohort were followed in the DPP Outcome Study ( DPPOS 2002–2013 ) and analyzed by intention-to-treat based on original DPP assignment . During DPPOS , the lifestyle group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin . Findings During 15 years of average follow-up , lifestyle intervention and metformin  reduced diabetes incidence rates by 27 % ( p<0.0001 ) and 18 % ( p=0.001 ) , respectively , compared with the placebo group , with declining between group differences over time . At year 15 , the cumulative incidences of diabetes were 55 , 56 and 62 % , respectively . The prevalences at study -end of the aggregate microvascular outcome , composed of nephropathy , neuropathy , and retinopathy , were not significantly different among the treatment groups ( 11–13 % ) in the total cohort . However , in women ( n=1887 ) lifestyle intervention was associated with a lower prevalence ( 8.7 % ) than in the placebo ( 11 % ) and metformin ( 11.2 % ) groups , with 21 % ( p=0.03 ) and 22 % ( p=0.02 ) reductions with lifestyle compared with placebo and metformin , respectively . Compared with participants who progressed to diabetes , those who did n’t progress had a 28 % lower prevalence of microvascular complications ( p<0.0001 ) . Interpretation Lifestyle intervention or metformin significantly reduce diabetes development over 15 years . There were no overall differences in the aggregate microvascular outcome among treatment groups ; however , those who did not progress to diabetes had a lower prevalence of microvascular complications than those who progressed . Funding National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK Type 2 diabetes affects over 150 million adults worldwide and this figure is expected to double over the next 25 yr . This increase will be accompanied by a marked increase in the number of patients with ESRD due to diabetes . We hypothesized that a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes We r and omly assigned 3234 nondiabetic persons with elevated fasting and postload plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 % weight loss and at least 150 min of physical activity per week . The mean age of the participants was 51 yr , and the mean body mass index was 34.0 kg/m(2 ) ; 68 % were women , and 45 % were members of non-Caucasian racial/ethnic groups . The average follow-up was 2.8 yr . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence of diabetes by 58 % ( 95 % CI : 48 to 66 % ) and metformin by 31 % ( 95 % CI : 17 to 43 % ) , compared with placebo ; the lifestyle intervention was significantly more effective than metformin . In conclusion , lifestyle changes and treatment with  metformin  both reduced the incidence of diabetes in persons at high risk and the lifestyle intervention was more effective than metformin . Because the lifestyle changes worked equally in all racial/ethnic groups in the Diabetes Prevention Program , they should be applicable to high-risk population s worldwide and may be able to reduce the projected progressive rise in the incidence of diabetes and the expected increase in ESRD BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program  with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin OBJECTIVE The Diabetes Prevention Program ( DPP ) and its Outcomes Study ( DPPOS ) demonstrated that either intensive lifestyle intervention or metformin could prevent type 2 diabetes in high-risk adults for at least 10 years after r and omization . We report the 10-year within-trial cost-effectiveness of the interventions . RESEARCH DESIGN AND METHODS Data on re source utilization , cost , and quality of life were collected prospect ively . Economic analyses were performed from health system and societal perspectives . RESULTS Over 10 years , the cumulative , undiscounted per capita direct medical costs of the interventions , as implemented during the DPP , were greater for lifestyle ( $ 4,572 ) than metformin ( $ 2,281 ) or placebo ( $ 752 ) . The cumulative direct medical costs of care outside the DPP/DPPOS were least for lifestyle ( $ 26,810 lifestyle vs. $ 27,384 metformin vs. $ 29,007 placebo ) . The cumulative , combined total direct medical costs were greatest for lifestyle and least for metformin ( $ 31,382 lifestyle vs. $ 29,665 metformin vs. $ 29,759 placebo ) . The cumulative quality -adjusted life-years ( QALYs ) accrued over 10 years were greater for lifestyle ( 6.89 ) than metformin ( 6.79 ) or placebo ( 6.74 ) . When costs and outcomes were discounted at 3 % and adjusted for survival , lifestyle cost $ 12,878 per QALY , and metformin had slightly lower costs and nearly the same QALYs as placebo . CONCLUSIONS Over 10 years , from a payer perspective , lifestyle was cost-effective and metformin was marginally cost-saving compared with placebo . Investment in lifestyle and metformin interventions for diabetes prevention in high-risk adults provides good value for the money spent Diabetes is an “ old disease ” . The first description of diabetes written on papyrus about 3500 years ago is found in the Ebers papyrus  , which was discovered in Egypt in 1873 by the German archeologist Georg Ebers . Humans , like most mammals , may develop diabetes , if sufficient environmental exposure to physical inactivity , unhealthy diet and obesity are present . Genetic effects are important for the individual risk of type 2 diabetes ( T2D ) but twin studies have shown that the genetic effects combined explain less than 50 % of the risk of T2D ( 1 ) . Today we know almost 100 susceptibility genes associated with T2D but the relative importance of each of these genes is low ( 2 ) , and together they explain only a small part of the disease risk . Thus , genetic screening can not be used for the prediction of T2D for individuals . On the other h and , healthy lifestyle can also prevent T2D in people who are genetically at high risk , e.g. those with positive family history ( 3 ) . Thus , the importance of lifestyle factors for the development and prevention of T2D is overwhelming . The strongest evidence in medicine is considered to come from r and omized controlled trials ( RCTs ) . They are also important in providing the link to causal inference that in most observational studies can not be derived . At the same time , observational studies are necessary for the identification of factors associated with an increased or decreased risk of a disease , and for generation of hypotheses on potential means for prevention based on modifiable risk factors . Observational studies have by now identified a large number of factors that are associated with the development of T2D or with the protection against it . Most of them are related to physical activity , diet and obesity . It has also been shown unequivocally that exposures ( poor nutrition , infections , smoking , etc . ) during fetal life and early infancy result ing in insufficient development ( often shown as low birth weight ) also predict T2D later in life ( 4 ) . Traditionally , T2D has been considered to be a disease of the elderly . However , with increasing obesity and sedentary lifestyle in children , there are increasing numbers of cases of T2D already occurring at a young age in many population s ( 5 ) . In the past two decades several innovative RCTs have repeatedly shown that interventions on modifiable risk factors can reduce the incidence of diabetes in high-risk groups . The evidence has been summarized in several systematic review s and meta-analyses ( 6,7 ) . There is compelling scientific evidence from RCTs that T2D can be prevented or its onset delayed . The key for prevention is a multimodal package of lifestyle changes that is a sum outcome of dietary and physical activity behaviours . The power of lifestyle was dramatically illustrated by the Finnish Diabetes Prevention Study ( DPS ) that explicitly showed that when the study participants with impaired glucose tolerance reached all five modest lifestyle intervention targets , none of them progressed to T2D ( 8) . Importantly , lifestyle intervention lasting for 3–6 years has been shown to have a carry-over effect on T2D incidence that lasts for several years ; up to 15 in the Finnish Diabetes Prevention Study ( 9 ) and 20 years in the China Da Qing Diabetes Prevention Study ( 10 ) . The observed sustained risk reduction seems to be a result of sustained lifestyle changes , but the legacy effect of improved glycaemia during the early intervention may also have contributed to the long-term effect . The follow-up data from the Chinese study indicate moreover that vascular risks are also reduced by lifestyle management . Several prognostic question naires exist for detecting people at risk of T2D ( 11 ) . One of the screening tools with an adequately high sensitivity and specificity is the Finnish Diabetes Risk Score ( FINDRISC ) developed in Finl and ( 12 ) . The FINDRISC has been successfully implemented in the Finnish primary health care system and used also in many other countries . The FINDRISC was also tested in the Omani population and as a result a slightly modified Omani Diabetes Risk Score was developed ( 13 ) which may be a suitable screening tool for the Arab population s in the Middle East . Lifestyle interventions aim ing at translating evidence from efficacy RCTs on T2D prevention into “ real world ” intervention programmes have also been carried out in various population s. Such data were recently combined in a meta- analysis considering the relationship between intervention effectiveness and adherence to guidelines ( 14 ) . The primary meta- analysis included 22 studies with outcome data for weight loss at 12 months . The pooled result of the direct pairwise meta- analysis shows that
Conclusions HbA1c is neither sensitive nor specific for detecting pre‐diabetes ; fasting glucose is specific but not sensitive .
Interventions in people classified through screening as having pre‐diabetes have some efficacy in preventing or delaying onset of type 2 diabetes in trial population s. As screening is inaccurate , many people will receives an incorrect diagnosis and be referred on for interventions while others will be falsely reassured and not offered the intervention .
These findings suggest that “ screen and treat ” policies alone are unlikely to have substantial impact on the worsening epidemic of type 2 diabetes .
& NA ; Objectives To assess diagnostic accuracy of screening tests for  pre‐diabetes  and efficacy of interventions ( lifestyle or metformin ) in preventing onset of type 2 diabetes in people with pre‐diabetes .