Background
Methods
Literature search and data extraction
Statistical analysis
Results
Characteristics of studies included in the meta-analysis
Author, year [reference number] | Country | Study name | Sample sizea
| Age, years | Women, % | Follow-up, years | Exposure assessment | Ascertainment of T2DM |
---|---|---|---|---|---|---|---|---|
Iron intakes and T2DM (n = 5) | ||||||||
Jiang et al, 2004 [20] | USA | HPFS | 1168/38,394 | 40 to 75 | 0 | 12 | FFQ (validated) | Symptoms plus fasting glucose, OGTT, or use of anti-diabetic medication |
Lee et al, 2004 [24] | USA | IWHS | 1921/35,698 | 55 to 69 | 100 | 11 | FFQ (validated) | Self-report |
Song et al, 2004 [23] | USA | WHS | 1558/37,309 | ≥ 45 | 100 | 8.8 | FFQ (validated) | Self-report |
Rajpathak et al, 2006 [21] | USA | NHS | 4599/85,031 | 34 to 59 | 100 | 20 | FFQ (validated) | Symptoms plus fasting glucose, OGTT, or use of anti-diabetic medication |
Shi et al, 2010 [30] | China | JIN | 23/1,056 | ≥ 20 | 57.9 | 5 | 3-day weighed food records | Fasting glucose |
Body iron stores and T2DM (n = 6) | ||||||||
Salonen et al, 1998 [9] | Finland | KIHD | 41/82 | 42 to 60 | 0 | 4 | sTfR (EIA) ferritin (RIA) | Fasting glucose, OGTT, clinical diagnosis of diabetes or use of anti-diabetic treatment |
Jiang et al, 2004 [10] | USA | NHS | 698/716 | 56.5/56.4 | 100 | 10 | sTfR (ITA); ferritin (ITA) | Symptoms plus fasting glucose, or use of anti-diabetic medication |
Forouhi et al, 2007 [11] | UK | EPIC- Norfolk | 360/758 | 62.4/62.1 | 42.0 | 5.1 | Ferritin (FIA) | Self-report, HbA1c |
Jehn et al, 2007 [15] | USA | ARIC | 599/690 | 53.5/52.8 | 60.4 | 7.9 | Ferritin (ITA) | Fasting or non-fasting glucose, anti-diabetic medication use, self-report |
Le et al, 2009 [16] | USA | ACLS | 220/5,292 | NA | 32.0 | 4.3-4.7 | Ferritin (no details of test available) | Fasting glucose, hypoglycemic medication, or ever-diagnosed T2DM |
Rajpathak et al, 2009 [17] | USA | DPP | 280/280 | 50.4/50.2 | 63.6 | 2.8 | Ferritin (ITA) | OGTT, fasting glucose |
Iron intake and risk of type 2 diabetes
Source | Gender | Comparison | RRs (95% CI) | Matched or adjusted covariates |
---|---|---|---|---|
Jiang et al, 2004, USA [20] | Men | Dietary total iron intake: highest (median 34.2 mg/day) versus lowest (median 11.1 mg/day) quintile | 1.16 (0.92 to 1.47) | Age, BMI, FH, PA, cigarette smoking, alcohol consumption, TEI, intakes of trans fat, cereal fiber, magnesium, whole grains, vegetables, fruit, ratio of polyunsaturated fat to saturated fat intake, glycemic load, and multivitamin use |
Dietary heme iron intake: highest (median 1.9 mg/day) versus lowest (median 0.8 mg/day) quintile | 1.28 (1.02 to 1.61) | |||
Lee et al, 2004, USA [24] | Women | Dietary non-heme iron intake: highest (median 20.8 mg/day) versus lowest (median 6.5 mg/day) quintile | 0.80 (0.64 to 1.01) | Age, BMI, WHR, PA, cigarette smoking status, alcohol consumption, education, marital status, residential area, hormone replacement therapy, TEI, intakes of animal fat, vegetable fat, cereal fiber, dietary magnesium, dietary non-heme iron, dietary heme iron, and supplemental iron |
Dietary heme iron intake: highest (median 2.2 mg/day) versus lowest (median 0.5 mg/day) quintile | 1.28 (1.04 to 1.58) | |||
Supplemental iron: highest (≥30 mg/day) versus lowest (0 mg/day) intake | 1.16 (0.92 to 1.46) | |||
Song et al, 2004, USA [23] | Women | Dietary total iron intake: highest (median 33.8 mg/day) versus lowest (median 10.0 mg/day) quintile | 1.13 (0.93 to 1.37) | Age, BMI, PA, FH, smoking status, alcohol consumption, TEI, dietary intakes of fiber, magnesium, and total fat, glycemic load |
Dietary heme iron intake: highest(median 1.55 mg/day) versus lowest (median 0.59 mg/day) quintile | 1.46 (1.20 to 1.78) | |||
Rajpathak et al, 2006, USA [21] | Women | Dietary total iron intake: highest (median 14.0 mg/day) versus lowest (median 8.0 mg/day) quintile | 1.02 (0.91 to 1.15) | Age, BMI, FH, PA, smoking status, alcohol consumption, postmenopausal hormone use, multivitamin use, TEI, intakes of cereal fiber and magnesium, caffeine, and trans fat (total iron, ratio of polyunsaturated to saturated fat, glycemic load, additional adjustment for intakes of whole grains, fruits and vegetables (heme iron), and additional adjustment for red meat intake (supplemental iron) |
Dietary heme iron intake: highest (median 1.9 mg/day) versus lowest (median 0.8 mg/day) quintile | 1.28 (1.14 to 1.45) | |||
Supplemental iron intake: highest (median 22.0 mg/day) versus lowest (median 0 mg/day) quintile | 0.96 (0.84 to 1.10) | |||
Shi et al, 2010, China [30] | Both | Dietary heme iron intake: highest (median 4.4 mg/day) versus lowest (median 0.1 mg/day) quartile | 9.84 (1.41 to 68.75) | Age, gender, BMI, central obesity, hypertension, FH, PA, sedentary behavior, cigarette smoking, alcohol consumption, TEI, intakes of fat, fiber and magnesium, education, income, and job |
Body iron stores and risk of type 2 diabetes
Source | Gender | Comparison | Models | RR (95% CI) | Matched or adjusted covariates |
---|---|---|---|---|---|
Ferritin as indicators of body iron stores (n = 5) | |||||
Jiang et al, 2004, USA [10] | Women | Highest (≥107.2 ng/ml) versus lowest (<21.1 ng/ml) quintile | Model 1a
| 2.68 (1.75 to 4.11) | Age, ethnicity, fasting status, BMI, FH, PA, smoking, alcohol consumption, menopausal status, glycemic load, intake of total energy, cereal fiber, magnesium, and trans fat, and ratio of polyunsaturated fat to saturated fat |
Model 2b
| 2.61 (1.68 to 4.07) | Additional adjustment for CRP | |||
Forouhi et al, 2007, UKc [11] | Men | Highest (≥135.7 ng/ml) versus lowest (<34.4 ng/ml) quintile | Model 1a
| 1.97 (1.12 to 3.45) | Age, sex, BMI, FH, PA, smoking, dietary factors (TEI, alcohol consumption, intake of dietary iron, magnesium, and red meat and processed meat, plasma vitamin C) |
Model 2b
| 1.78 (0.99 to 3.19) | Additional adjustment for CRP, fibrinogen, and IL-6 | |||
Model 3 | 1.13 (0.58, 2.19) | Additional adjustment for ALT, GGT, and adiponectin | |||
Women | Highest (≥71.7 ng/ml) versus lowest (<17.8 ng/ml) quintile | Model 1a
| 2.55 (1.22 to 5.34) | Age, sex, BMI, FH, PA, smoking, dietary factors (TEI, alcohol consumption, intake of dietary iron, magnesium, red meat and processed meat and plasma vitamin C) | |
Model 2b
| 2.11 (0.98 to 4.56) | Additional adjustment for CRP, fibrinogen, and IL-6 | |||
Model 3 | 1.08 (0.44, 2.62) | Additional adjustment for ALT, GGT, and adiponectin | |||
Jehn et al, 2007, USA [15] | Both | Highest (≥235.4 ng/ml; median, 354.5 ng/ml) versus lowest (<40.0 ng/ml; median, 20.0 ng/ml)quintile | Model 1a
| 1.51 (0.98 to 2.31) | Age, study center, ethnicity, smoking, alcohol consumption, and BMI |
Model 2 | 0.81 (0.49 to 1.34) | Additional adjustment for metabolic syndrome components (HDL-C, WC, hypertension, FPG, and TG) | |||
Model 3b
| 0.79 (0.48 to 1.32) | Additional adjustment for FPI and inflammation score | |||
Le et al, 2009, USA [16] | Men | Highest (>188 ng/ml) versus lowest (<80 ng/ml) quartile | Model 1a
| 1.79 (1.13 to 2.82) | Age, ethnicity, and BMI |
Women | Highest (premenopausal, >60 ng/ml, postmenopausal, >90 ng/ml) versus lowest (premenopausal,<21 ng/ml, postmenopausal,<37 ng/ml) quartile | Model 1a
| 0.87 (0.37 to 2.03) | Age, ethnicity, and BMI | |
Rajpathak et al, 2009, USA [17] | Both | Highest (median, 203.7 ng/ml) versus lowest (median, 20.1 ng/ ml) quartile | Model 1a
| 1.02 (0.60 to 1.74) | Age, sex, ethnicity, and BMI |
Model 2 | 1.65 (0.90 to 3.02) | Additional adjustment for FH, PA, HbA1c, and sTfR | |||
Model 3b
| 1.53 (0.83 to 2.82) | Additional adjustment for CRP | |||
Model 4 | 1.61 (0.85 to 3.02) | Additional adjustment for HOMA-IR | |||
Ratio of sTfR to ferritin as indicators of body iron stores (n = 2) | |||||
Salonen et al, 1998, Finland [9] | Men | Highest (< 9.4) versus quartile (no data available) | Model 1 | 2.40 (1.03 to 5.50) | Age, time of examination, place of residence, cigarette smoking, exercise, maximal oxygen uptake, socioeconomic status, height, weight, hip and waist circumferences, glucose, insulin, vitamin E, and serum SFA to (PUFA + MUFA) ratio |
Jiang et al, 2004, USA [10] | Women | Highest (<26.7) versus lowest (≥149.4) quintile | Model 1 | 2.44 (1.61 to 3.71) | Age, ethnicity, fasting status, BMI, FH, PA, smoking, alcohol consumption, menopausal status, glycemic load, intake of total energy, cereal fiber, magnesium, and trans fat, ratio of polyunsaturated fat to saturated fat |
Model 2 | 2.40 (1.55 to 3.71) | Additional adjustment for CRP | |||
sTfR as indicators of body iron stores (n = 1) | |||||
Rajpathak et al, 2009, USA [17] | Both | Highest (median, 4.4 mg/l) versus lowest (median, 2.3 mg/l) quartile | Model 1 | 1.55 (0.93 to 2.57) | Age, sex, ethnicity, and BMI |
Model 2 | 2.26 (1.27 to 4.01) | Additional adjustment for FH, PA, HbA1c, and sTfR | |||
Model 3 | 2.39 (1.34 to 4.28) | Additional adjustment for CRP | |||
Model 4 | 2.23 (1.22 to 4.06) | Additional adjustment for HOMA-IR |