Table 1.
Characteristics of included cohort studies in the meta-analysis.
| Studies | Country | Target population | Sample size/cases | Gender, age range | Exposure assessment | Outcome | Comparison | HR (95% CI) | Adjustment for covariate | Follow-up (years) | NOS scores |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Marx et al. (21) | Germany | Undergoing angiography | 2,306/440 | M, F 61.5 ± 11.2 years |
Enzyme immunoassay | All-cause mortality | C-peptide (T3 vs. T1) |
HR = 1.46 (1.10–1.93) | Age, sex, BMI, hypertension, smoking, GFR, triglycerides, LDL cholesterol, and HDL cholesterol, fasting glucose, fasting insulin, glycated hemoglobin, newly diagnosed type 2 diabetes per American Diabetes Association 2,010 guidelines, proinsulin, free fatty acids, free glycerol, and CRP. | 7.6 years | 9/9 |
| Marx et al. (21) | Germany | Undergoing angiography | 2,306/252 | M, F 61.5 ± 11.2 years |
Enzyme immunoassay | CVD mortality | C-peptide (T3 vs. T1) |
HR = 1.55 (1.07–2.24) | Age, sex, BMI, hypertension, smoking, GFR, triglycerides, LDL cholesterol, and HDL cholesterol, fasting glucose, fasting insulin, glycated hemoglobin, newly diagnosed type 2 diabetes per American Diabetes Association 2,010 guidelines, proinsulin, free fatty acids, free glycerol, and CRP. | 7.6 years | 9/9 |
| Pikkemaat et al. (17) | Sweden | Diabetic | 398/104 | M, F 52.4 ± 8.7 years |
Laboratory analyses | All-cause mortality | C-peptide per 1 nmol/L |
HR = 2.20 (1.49–3.25) | Age, sex, smoking, SBP, HbA1c, antihypertensive treatment, BMI, CRP, eGFR, cholesterol, and previous myocardial infarction or ischemic stroke. | 17 years | 8/9 |
| Pikkemaat et al. (17) | Sweden | Diabetic | 398/35 | M, F 52.4 ± 8.7 years |
Laboratory analyses | CVD mortality | C-peptide per 1 nmol/L |
HR = 2.69 (1.49–4.85) | Age, sex, smoking, SBP, HbA1c, antihypertensive treatment, BMI, CRP, eGFR, cholesterol, and previous myocardial infarction or ischemic stroke. | 17 years | 8/9 |
| Hirai et al. (23) | USA | Diabetic | 1,007/824 | M, F 68.6 ± 11.0 years |
N/A | All-cause mortality | C-peptide per 1 nmol/L |
HR = 1.15 (1.04–1.29) | Age, sex, BMI, diabetes duration, SBP, history of cardiovascular disease, presence of diabetic retinopathy, cigarette smoking, time since last meal, exogenous insulin use, and glycosylated hemoglobin. | 16 years | 8/9 |
| Hirai et al. (23) | USA | Diabetic | 1,007/358 | M, F 68.6 ± 11.0 years |
N/A | Ischemic heart mortality | C-peptide per 1 nmol/L |
HR = 1.19 (1.02–1.39) | Age, sex, BMI, diabetes duration, SBP, history of cardiovascular disease, presence of diabetic retinopathy, cigarette smoking, time since last meal, exogenous insulin use, and glycosylated hemoglobin. | 16 years | 8/9 |
| Hirai et al. (23) | USA | Diabetic | 1,007/137 | M, F 68.6 ± 11.0 years |
N/A | Stroke mortality |
C-peptide per 1 nmol/L |
HR = 1.09 (0.85–1.40) | Age, sex, BMI, diabetes duration, SBP, history of cardiovascular disease, presence of diabetic retinopathy, cigarette smoking, time since last meal, exogenous insulin use, and glycosylated hemoglobin. | 16 years | 8/9 |
| Patel et al. (18) | USA | General | 5,152/932 | M, F 40–74 years |
N/A | All-cause mortality | C-peptide per 1 nmol/L |
HR = 1.72 (1.34–2.21) | Age, sex, race, waist-to-hip ratio, BMI, blood pressure (normal, prehypertension, hypertension), total cholesterol, triglycerides, HDL, presence or absence of past history of stroke, heart attack, peripheral arterial disease, presence or absence of family history of diabetes and heart attack, history of chest pain (suggestive of angina, not suggestive of angina and no chest pain), level of education, smoking status, level of physical activity, alcohol use, CRP level, urinary albumin/creatinine ratio, GFR, and glycated hemoglobin levels. | 14.4 years | 8/9 |
| Patel et al. (18) | USA | General | 5,140/370 | M, F 40–74 years |
N/A | CVD mortality | C-peptide per 1 nmol/L |
HR = 1.60 (1.07–2.39) | Age, sex, race, waist-to-hip ratio, BMI, blood pressure (normal, prehypertension, hypertension), total cholesterol, triglycerides, HDL, presence or absence of past history of stroke, heart attack, peripheral arterial disease, presence or absence of family history of diabetes and heart attack, history of chest pain, level of education, smoking status, level of physical activity, alcohol use, CRP level, urinary albumin/creatinine ratio, GFR, and glycated hemoglobin levels. | 14.4 years | 8/9 |
| Min et al. (19) | USA | General | 5,902/2,020 | M, F 40- 70 years |
Radioimmunoassay | All-cause mortality | C-peptide per 1 unit |
HR = 1.80 (1.33–2.43) | Age, sex, ethnic background, education, smoking status, alcohol consumption status, day on which the last meal or snack was consumed, history of hypertension, hypercholesterolemia, heart attack and BMI, CRP, total cholesterol, triglyceride, serum insulin, glycated hemoglobin and fasting serum glucose levels. | – | 8/9 |
| Min et al. (19) | USA | General | 5,902/895 | M, F 40- 70 years |
Radioimmunoassay | CVD mortality | C-peptide per 1 unit |
HR = 3.20 (2.07–4.93) | Age, sex, ethnic background, education, smoking status, alcohol consumption status, day on which the last meal or snack was consumed, history of hypertension, hypercholesterolemia, heart attack and BMI, CRP, total cholesterol, triglyceride, serum insulin, glycated hemoglobin and fasting serum glucose levels. | – | 8/9 |
| Cardellini et al. (29) | Italy | Atherosclerotic | 268/44 | M, F 31–91 years |
Immunochemiluminescence assay | All-cause mortality | C-peptide per SD |
HR (97/5%CI) = 1.09 (0.90–1.32) | Age, sex, diabetes treatment, GFR and known diabetes status. | 4.6 years | 8/9 |
| Cardellini et al. (29) | Italy | Atherosclerotic | 268/20 | M, F 31–91 years |
Immunochemiluminescence assay | CVD mortality | C-peptide per SD |
HR (97/5%CI) = 1.38 (1.05–1.80) | Age, sex, diabetes treatment, GFR and known diabetes status. | 4.6 years | 8/9 |
| Volkova et al. (28) | New Zealand | Cancer | 344/91 | M, F 31–91 years |
Immunoassay | Survival (mortality) | C-peptide | HR = 1.02 (0.96–1.07) | - | 10 years | 8/9 |
| Wolpin et al. (22) | USA | Cancer | 350/98 | M, F 30–75 years |
Enzyme-linked immunosorbent assay | Overall mortality | C-peptide (Q4 vs. Q1) |
HR = 2.11 (1.06–4.21) | Age at diagnosis, cohort (sex), stage of disease, histologic differentiation, tumor location, time period of diagnosis, time between last meal and plasma collection, receipt of chemotherapy, and patient characteristics from the most recent questionnaire before blood draw, including smoking status, aspirin use, alcohol consumption (g/d), total vitamin D intake (U/d), and postmenopausal hormone use. | 5.9 years | 9/9 |
| Rovere et al. (30) | Italy | Diabetic | 113/22 | M, F 66.9 ± 9.9 years |
Specific immunoassay | Macrovascular mortality | C-peptide | HR = 0.25 (0.08–0.74) | - | 9 years | 9/9 |
| Schrauben et al. (25) | USA | General | 1,883/379 | M, F 56.5 years |
NA | All-cause mortality | C-peptide per 1 SD |
HR = 1.09 (0.94–1.27) | Age, sex, race, ethnicity, level of education, clinical center, BMI, waist circumference, smoking status, SBP, ACEi/ARB use, HDL, LDL, triglycerides, high sensitivity CRP, fat-free mass, eGFR, hemoglobin, physical activity, use of statins, use of other lipid-lowering medications, history of CVD, 24-h urine protein, FGF-23, uric acid, serum albumin. | 7.7 years | 9/9 |
| Guercio et al. (26) | USA | Cancer | 1,086/932 | M, F 59 yeras |
Enzyme-linked immunosorbent assays | Overall survival | C-peptide (Q5 vs. Q1) |
HR = 1.13 (0.91- 1.40) | Age, sex, performance status, planned chemotherapy, prior adjuvant chemotherapy, assigned treatment arm, KRAS status, tumor sidedness, plasma albumin, diabetes, BMI, and fasting status. | 6.2 years | 8/9 |
| Bo et al. (27) | Italy | Diabetic | 2,112/973 | M, F 66 years |
Enzyme immunoassay | All-cause mortality | C-peptide (T3 vs. T1) |
HR = 1.10 (0.93–1.30) | Age, sex, BMI, smoking, time since diagnosis, insulin treatment, values of HbA1c, SBP, HDL-cholesterol and triglycerides, presence of retinopathy, nephropathy, neuropathy and CVDs. | 14 years | 9/9 |
| Bo et al. (27) | Italy | Diabetic | 2,113/458 | M, F 66 years |
Enzyme immunoassay | CVD mortality | C-peptide (T3 vs. T1) |
HR = 0.92 (0.73–1.17) | Age, sex, BMI, smoking, time since diagnosis, insulin treatment, values of HbA1c, SBP, HDL-cholesterol and triglycerides, presence of retinopathy, nephropathy, neuropathy and CVDs. | 14 years | 9/9 |
| Zhu et al. (24) | China | Cancer | 2,682/55 | F, 55.3 ± 12.4 years |
Electrochemiluminescence immunoassay | All-cause mortality | C-peptide high vs. low |
HR = 1.14 (0.63–2.08) | Age, BMI, menopausal status, tumor size, lymph node status, chemotherapy, radiotherapy, endocrine therapy, and targeted therapy. | 3.1 years | 8/9 |
| Irwin et al. (20) | USA | Cancer | 604/64 | F, >18 years |
Radioimmunoassay method | All-cause mortality | C-peptide (ng/ml) |
HR = 1.31 (1.06–1.63) | Age, race/site, and initial treatment; BMI, disease stage, and estrogen receptor status, and women with type 2 diabetes. | 6 years | 8/9 |
| Griffith et al. (26) | USA | Diabetic | 84/27 | M-F > 18 years | – | Overall survival | C-peptide (ng/ml) |
HR = 1.05 (1.01–1.09) | Peak steroid dose, myeloablative conditioning. | 1.46 years | 8/9 |
BMI, body mass index; CI, confidence interval; CRP, C-reactive protein; CVDs, cardiovascular diseases; FGF-23, fibroblast growth factor 23; F, female; GFR, glomerular filtration rate; HDL, high-density lipoprotein; HR, hazard ratio; HbA1c, hemoglobin A1C; LDL, low-density lipoprotein; NOS, Newcastle–Ottawa scale; M, male; Q, quartile; SD, standard deviation; SBP, systolic blood pressure; T, tertile.