Table 1

Cohort studies investigating incident type 2 diabetes in metabolic health and BMI categories

First author, year; PubMed identification no.Country/years of recruitmentDefinition of metabolic healthaDefinition of BMI categories (kg/m2)Study populationSample size and incident cases (Ntotal/NT2D)Incident T2D ascertainmentLength of follow-up (years)AdjustmentQuality scoreb
Meigs, 2006; 16735483Framingham Offspring Study, U.S./1991–19951) MetS: 3 of 5 ATPIII criteria (FG <5.6, WC ≤88 102 M or 88 W, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85); 2) IR: HOMA-IR ≤75th percentile of distribution in subjects without T2DLean <25, OW 25–29.9, obese ≥30Offspring of community-based study; European ancestry, free from CVD and T2D at baseline, mean age 54 years, women 55%1) 2,902/141; 2) 2,803/135FG ≥7.0 or new use of hypoglycemic therapyMean 6.8Age, sex, family history of diabetes, impaired glucose tolerance6
Arnlöv, 2011; 20852030Uppsala Longitudinal Study of Adult Men, Sweden/1970–19731) MetS: 3 of 5 ATPIII criteria (FG <6.1,c BMI ≥29.4,d TG <1.7, HDL ≥1.04, BP <130/85); 2) IR: HOMA-IR ≤75th percentile of distribution in subjects without T2D, i.e., 3.43Lean <25, OW 25–30, obese >30Community-based study of men born in 1920–1924 free from T2D at baseline, mean age 50 years, women 0%1) 1,675/160; 2) 1,385/117FG ≥7.0 at follow-up or data from national hospital-discharge registryUp to 20Age, smoking status, level of physical activity6
Hadaegh, 2011; 21609497Tehran Lipid and Glucose Study, Iran/1999–2001MetS: 3 of 5 harmonized criteria (FG <5.5, WC <94.5, TG <1.7, HDL ≥1.04 M or 1.3 W, BP <130/85)Lean <25, OW 25–29.9, obese ≥30Population-based cohort study in Tehran; mean age 42 years, women 58%5,250/369Self-reported or OGTT based at 2 follow-up visitsMedian 6.5Age, family history of T2D, history of CVD, education, smoking status6
Kim, 2012; 22621338South Korea/2005MetS: 3 of 5 2009 harmonized criteria (FG <5.6, WC <90 M or 80 W, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85)Lean <23, OW 23–27.4, obese ≥27.5Subjects attending baseline and follow-up visits at Health Promotion Centre; mean age 48 years, women 35%8,748/308FG ≥7.0 or HbA1c ≥6.5% or treatment5Age, sex, smoking, alcohol consumption, physical activity6
Bo, 2012; 23034958Italy/2001–2003MetS plus IR: 3 of 5 harmonized criteria (FG <5.6, WC <94 M or 80 W, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85,and HOMA-IR <2.5)Lean <25, OW 25–30, obese >30Caucasian volunteers from local health units; mean age 54 years, women 53%1,658/72Self-reported, FG, demographic registries9Nonee6
Appleton, 2013; 23491523North West Adelaide Health Study, Australia/1999–2003MetS: 3 of 4 IDF criteria (FG <5.6, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85)Lean 18.5–24.9, OW 25–29.9, obese ≥30Community-based study; adults of European ancestry, free from T2D and CVD at baseline; mean age 42 yearsf, women 57%f2,315/112Self-reported doctor diagnosis or FG ≥7.0Median 8.2Age, sex, household income, family history of diabetes6
Soriguer, 2013; 23559087Prospective Pizarra Study, Spain/1997–1998MetS plus IR: 3 of 3 criteria (FG <6.1, TG <1.7, HOMA-IR <90th percentileg)Lean <25, OW 25–29.9, obese ≥30Population-based cohort study; mean age 40 years, women, 62%h387/38eSelf-reported or FG at follow-up11Age, sexe5
Aung, 2014; 24257907San Antonio Heart Study, U.S./1979–1988MetS plus IR: 4 of 5 criteria (FG <5.6, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85, HOMA-IR ≤5.13)Lean <25, OW 25–29.9, obese ≥30Population-based cohort study of Mexican and Caucasian Americans; mean age 42 years, women 57%2,814/262OGTT or medication at follow-upMedian 7.4Age, sex, ethnicity, family history of diabetes, FG6
Sung, 2012; 22338098South Korea/2003IR: HOMA-IR <2, i.e., 75th percentileLean <23, OW 23–27.49, obese ≥27.5eParticipants of health examination at hospital; mean age 41 years, women 29%12,853/223Self-reported, medical history, or FG at follow-up5Age, sex, alcohol, smoking status, exercise, educational status, baseline glucosee5
Bell, 2014; 24661566English Longitudinal Study of Ageing, U.K./2004–2005Definition 1, MetS plus CRP: 3 of 5 customized criteria (HbA1c <6%, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85, CRP <0.3 mg/dL); definition 2, MetS plus CRP: 4 of 5 of the criteria used in definition 1Lean <25, OW 25–29.9, obese ≥30Population-based cohort study; mean age 65 years; women 57%3,060/138Self-reported physician diagnosisMean 5.9Age, sex, smoking, alcohol intake, physical activity, wealth, depressive symptoms5
Jung, 2014; 24706434South Korea/2005–2006MetS: 4 of 4 IDF criteria (FG <5.6, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85)Lean <23, OW 23–27.4, Obese ≥27.5eCohort study of employees of large Korean company and their spouses; mean age 37 years; women, 44%34,994/889eFG ≥7, HbA1c ≥6.5%, or medication5Age, sex, smoking, alcohol intake, physical activitye6
Heianza, 2014; 24823457Toranomon Hospital Health Management Centre Study, Japan/1997–2002MetS: 3 of 4 IDF criteria (FG <5.6, TG <1.7, HDL ≥1.03 M or 1.29 W, BP <130/85)Lean <23, OW 23–27.4, obese ≥27.5eCohort study of Japanese government employees; mean age 48 years, women 27%8,090/274eFG ≥7, HbA1c ≥6.5%, or self-reported5Age, sex, smoking, physical activity, alcohol intake, family history of diabetese6
Rhee, 2014; 24870949South Korea/2005MetS plus IR: 3 of 4 criteria (FG <5.6, TG <1.7, HDL ≥1 M or 1.3 W, BP <130/85 and HOMA-IR <90th percentile)Lean <23, OW 23–27.4, obese ≥27.5eParticipants of medical check-up program; mean age 43 years, women 27%6,748/277FG, HbA1c, or self-reported history or medication4Age, sex, ALT, creatinine, total cholesterol, hs-CRPe6
Heianza, 2014; 25131796Japan/1999–2004MetS: 3 of 4 IDF criteria (FG <5.6, TG <1.7, HDL ≥1.03 M or 1.29 W, BP <130/85)Lean <23, OW 23–27.4, obese ≥27.5eCohort study of individuals occupational health examinations; mean age 47 years; women 36%27,891/1,668eFG ≥7, HbA1c ≥6.5%, or self-reported8Age, sex, smoking, physical activitye6
Twig, 2014; 25139886Metabolic, Lifestyle and Nutrition Assessment in Young Adults, Israel/1995–2011MetS: 3 of 4 ATPIII criteria (FG <5.6, TG <1.7, HDL ≥1, BP <130/85e,i)Lean <25, OW 25–29.9, obese ≥30Cohort study of men from the Israel Defense Forces; mean age 31 years; women 0%33,939/734FG or physician diagnosisMedian 6.1Age, family history of diabetes, country of origin, WBCe6
Hinnouho, 2015; 24670711Whitehall II Study, U.K./1991–1993MetS: 3 of 4 ATPIII criteria (FG <5.6, TG <1.7, HDL ≥1.04 M or 1.29 W, BP <130/85)Lean 18.5–24.9, OW 25–29.9, obese ≥30Cohort study of office workers in central London; mean age 49 years; women 30%7,122/798OGTT, physician diagnosis, or use of medication at follow-upMedian 17.5Sex, socioeconomic status, marital status, ethnicity, physical activity, smoking, alcohol, fruit and vegetable consumption, CVD medications and procedures6
  • ALT, alanine aminotransferase; ATPIII, Adult Treatment Panel III; BP, blood pressure; CRP, C-reactive protein; CVD, cardiovascular disease; FG, fasting glucose; HOMA-IR, HOMA of insulin resistance; IDF, International Diabetes Federation; IR, insulin resistance; MetS, metabolic syndrome; M, men; OGTT, oral glucose tolerance test; OW, overweight; T2D, type 2 diabetes; TG, triglycerides; W, women; WBC, white blood cells; WC, waist circumference.

  • aAll cutoff values expressed as cm for waist circumference; mmol/L for fasting glucose, HDL cholesterol, or triglycerides; kg/m2 for BMI; and mmHg for blood pressure. In some studies, treatment with medication (e.g., antihypertensive drugs) was used as a complementary factor to adjudicate metabolic risk criteria.

  • bWe used a quality score similar to the one reported by Bell, Kivimaki, and Hamer (6). Study quality was assessed according to the definition of exposure, outcome, and to the extent of adjustment. Points were assigned as follows: 2 points if the study considered metabolic risk factor clustering as in the metabolic syndrome; 1 point if the study considered insulin resistance only; 2 points if diabetes diagnosis was based on objective clinical measurements (e.g., fasting or 2-h glucose levels); 1 point if diabetes adjudication was based on self-report only; 2 points for extensive adjustment, i.e., age and sex plus at least two of the following: family history of diabetes, ethnicity, alcohol consumption, smoking status, physical activity, dietary habits and socioeconomic status, and impaired glucose tolerance status; 1 point for basic adjustment, i.e., age and sex; and 0 points for crude estimates. Studies were scored out of 6 possible points. Adjustment in the original report was used to adjudicate the extent of adjustment.

  • cOf fasting blood glucose, corresponding to fasting plasma glucose of 5.6 mmol/L.

  • dBMI used in lieu of waist circumference criterion.

  • eInformation as reported by the authors in a personal communication (G. Twig, A. Tirosh, C. Gutiérrez Repiso, G. Rojo Martínez, F. Soriguer, K.-C. Sung, S. Bo, Y. Heianza, H. Sone, Y. Arase, K. Kato, S.R.Y. Chang, E.-J. Rhee, and W.-Y. Lee).

  • fAverage of metabolically healthy lean, metabolically healthy obese, metabolically unhealthy obese groups.

  • gThe authors reported 4 different definitions of metabolic health. Here, we report the one we used in the meta-analysis, for which the authors provided detailed results of type 2 diabetes incidence in a personal communication (C. Gutiérrez Repiso, G. Rojo Martínez, and F. Soriguer).

  • hIn the full baseline study.

  • iIn the original report, metabolic health was the absence of any metabolic syndrome criteria and the risk of type 2 diabetes was evaluated for individuals with 1, 2, 3, or more criteria separately.