Table 1. Cohort studies investigating incident type 2 diabetes in metabolic health and body mass index categories.
| First Author Year; Pubmed ID |
Country / years of recruitment |
Definition of metabolic healtha | Definition of BMI categories, in kg/m2 |
Study population | Sample size and incident cases (Ntotal/NT2D) |
Incident T2D ascertainment |
Length of follow-up |
Adjustment | Quality scoreb |
|---|---|---|---|---|---|---|---|---|---|
| Meigs 2006; 16735483 | Framingham Offspring Study, USA 1991-1995 | (1) MetS, 3 / 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 T2D |
Lean < 25 OW 25-29.9 Obese ≥ 30 | Offspring of community-based study; European ancestry; free from CVD and T2D at baseline; mean age, 54 years; women, 55% | (1) 2902 / 141 (2) 2803 / 135 |
FG ≥ 7.0 mmol/L or new use of hypoglycaemic therapy | Mean 6.8 years | Age, sex, family history of diabetes, and impaired glucose tolerance | 6 |
| Arnlöv 2011; 20852030 | Uppsala Longitudinal Study of Adult Men, Sweden 1970-1973 | (1) MetS: 3 / 5 ATPIII criteria: FG < 6.1c, BMI ≥ 29.4d,TG < 1.7, HDL ≥ 1.04, BP < 130/85 (2) IR: HOMA-IR ≤ 75th percentile of distribution in subjects without T2D, i.e. 3.43 |
Lean < 25 OW 25-30 Obese > 30 | Community-based study of men born in 1920-1924 free from T2D at baseline; mean age, 50 years, women, 0% | (1) 1675 / 160 (2) 1385 / 117 |
FG ≥ 7.0 mmol/L at follow-up or data from national hospitaldischarge registry | Up to 20 years | Age, smoking status, and level of physical activity | 6 |
| Hadaegh 2011; 21609497 | Tehran Lipid and Glucose Study, Iran 1999-2001 | MetS: 3 / 5 harmonised 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 ≥ 30 | Population based cohort study in Tehran; mean age, 42 years; women, 58% | 5,250 / 369 | Self-reported or OGTT-based at two follow-up visits | Median 6.5 years | Age, family history of T2D, history of CVD, education, smoking status | 6 |
| Kim 2012; 22621338 | South Korea 2005 | MetS: 3 / 5 2009 harmonised 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 ≥ 27.5 | Subjects attending baseline and follow-up visits at Health Promotion Centre; mean age, 48 years; women, 35% | 8,748 / 308 | FG ≥ 7.0 mmol/L or HbA1c ≥ 6.5% or treatment | 5 years | Age, sex, smoking, alcohol consumption, and physical activity | 6 |
| Bo 2012; 23034958 | Italy 2001-2003 | MetS plus IR: 3 / 5 harmonised 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 > 30 | Caucasian volunteers from Local Health Units; mean age, 54 years; women, 53% | 1,658 / 72 | Self-reported, FG, demographic registries | 9 years | Nonee | 6 |
| Appleton 2013; 23491523 | North West Adelaide Health Study, Australia 1999-2003 | MetS: 3 / 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 ≥ 30 | Community-based study; Adults of European ancestry; free from T2D and CVD at baseline; mean age, 42 yearsf; womenf, 57% | 2315 / 112 | Self-reported doctor diagnosis or FG ≥ 7.0 mmol/L | Median 8.2 years | Age, sex, household income, and family history of diabetes | 6 |
| Soriguer 2013; 23559087 | Prospective Pizarra Study, Spain 1997-1998 | MetS plus IR: 3 / 3 criteria: FG < 6.1, TG < 1.7, HOMA-IR < 90th percentileg | Lean < 25 OW 25-29.9 Obese ≥ 30 | Population-based cohort study; mean age, 40 years; women, 62%h | 387 / 38e | Self-reported or FG at follow-up | 11 years | Age, sexe | 5 |
| Aung 2014; 24257907 | San Antonio Heart Study, USA 1979-1988 | MetS plus IR: 4 / 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 ≥ 30 | Population based cohort study of Mexican and Caucasian Americans; mean age, 42 years; women, 57% | 2,814 / 262 | OGTT or medication at follow-up | Median 7.4 years | Age, sex, ethnicity, family history of diabetes, fasting glucose | 6 |
| Sung 2012; 24361070 | South Korea 2003 | IR: HOMA-IR < 2, i.e. 75th percentile | Lean < 23 OW 23-27.49 Obese ≥ 27.5e | Participants of health examination at hospital; mean age, 41 years; women, 29% | 12,853 / 223 | Self-reported, medical history or FG at follow-up | 5 years | Age, sex, alcohol, smoking status, exercise, educational status, baseline glucosee | 5 |
| Bell 2014; 24661566 | English Longitudinal Study of Ageing, UK 2004-2005 | (1) MetS plus CRP: 3 / 5 customised criteria: Hba1c < 6%, TG < 1.7, HDL ≥ 1 M or 1.3, BP < 130/85, CRP < 0.3 mg/dL (2) MetS plus CRP: 4 / 5 of the criteria used in definition (1) |
Lean < 25 OW 25-29.9 Obese ≥ 30 | Population-based cohort study; mean age, 65 years; women, 57% | 3,060 / 138 | Self-reported physician diagnosis | Mean 5.9 years | Age, sex, smoking, alcohol intake, physical activity, wealth, depressive symptoms | 5 |
| Hinnouho 2014; 24670711 | Whitehall II Study, UK 1991-1993 | MetS: 3 / 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 ≥ 30 | Cohort study of office workers in central London; mean age, 49 years; women, 30% | 7,122 / 798 | OGTT, physician diagnosis or use of medication at follow-up | Median 17.5 years | Sex, socioeconomic status, marital status, ethnicity, physical activity, smoking, alcohol, fruits and vegetables consumption, CVD medications and procedures | 6 |
| Heianza 2014 J Clin Endocrinol Metab; 24823457 | Toranomon Hospital Health Management Centre Study, Japan 1997-2002 | MetS: 3 / 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 ≥ 27.5e | Cohort Study of Japanese government employees; mean age, 48 years; women, 27% | 8,090 / 274e | FG ≥ 7, Hba1c ≥ 6.5%, or self-reported | 5 years | Age, sex, smoking, physical activity, alcohol intake, family history of diabetese | 6 |
| Rhee 2014; 24870949 | South Korea 2005 | MetS plus IR: 3 / 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 ≥ 27.5e | Participants of medical check-up programme; mean age, 43 years; women, 27% | 6,748 / 277 | FG, Hba1c or selfreported history or medication | 4 years | Age, sex, ALT, creatinine, total cholesterol, hs-CRPe | 6 |
| Heianza 2014 Obesity; 25131796 | Japan 1999-2004 | MetS: 3 / 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 ≥ 27.5e | Cohort Study of individuals occupational health examinations; mean age, 47 years; women, 36% | 27,891 / 1,668e | FG ≥ 7, Hba1c ≥ 6.5%, or self-reported | 8 years | Age, sex, smoking, physical activitye | 6 |
| Twig 2014; 25139886 | Metabolic, Lifestyle and Nutrition Assessment in Young Adults, Israel 1995-2011 | MetS: 3 / 4 ATPIII criteria: FG < 5.6, TG < 1.7, HDL ≥ 1, BP < 130/85 e,i | Lean < 25 OW 25-29.9 Obese ≥ 30 | Cohort study of men from the Israel Defence Forces; mean age, 31 years; women, 0% | 33,939 / 734 | FG or physician diagnosis | Median 6.1 years | Age, family history of diabetes, country of origin, WBCe | 6 |
| Jung 2014; 25155902 | South Korea 2005-2006 | MetS: 4 / 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 ≥ 27.5e | Cohort study of employees of large Korean company and their spouses; mean age, 37 years; women, 44% | 34,994 / 889e | FG ≥ 7, Hba1c ≥ 6.5% or medication | 5 years | Age, sex, smoking, alcohol intake, physical activitye | 6 |
Abbreviations: BMI, body mass index; T2D, type 2 diabetes; MetS, metabolic syndrome; IR, insulin resistance; HOMA-IR, Homeostatic model assessment – insulin resistance; ATPIII, Adult Treatment Panel III; FG, fasting glucose; TG, triglycerides; HDL, high-density lipoprotein cholesterol; BP, blood pressure; WC, waist circumference; M, men; W, women; OW, overweight; OGTT, oral glucose tolerance test; WBC, white blood cells; IDF, International Diabetes Federation; CVD, cardiovascular disease; hs-CRP, high-sensitivity C-reactive protein.
Notes: All cut-off 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. anti-hypertensive drugs) was used as a complementary factor to adjudicate metabolic risk criteria.
We used a quality score similar to the one reported by Bell et al. 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 two hour glucose levels); 1 point if diabetes adjudication was based on self-report only; 2 points for extensive adjustment, i.e. age, sex plus at least two of the following, family history of diabetes, ethnicity, alcohol consumption, smoking status, physical activity, dietary habits and socioeconomic status, impaired glucose tolerance status; 1 point for basic adjustment, i.e. age and sex; 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.
Of fasting blood glucose, corresponding to fasting plasma glucose of 5.6 mmol/L.
BMI used in lieu of waist circumference criterion.
Information as reported by the authors in a personal communication.
Average of metabolically healthy lean, metabolically healthy obese, metabolically unhealthy obese groups.
The 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.
In the full baseline study.
In 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