Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design and Study Population
2.2. Data Collection
2.3. Laboratory Measurements
2.4. Outcome Ascertainment
2.5. Statistical Analyses
3. Results
3.1. Baseline Characteristics
3.2. Cross-Sectional Associations
3.3. Association of Proinsulin with Risk of Developing T2D
3.4. Model Performance Compared with the FOS Risk Score
3.5. Secondary Analyses of Proinsulin with Incident T2D in Various Groups
3.6. Sensitivity Analyses on Proinsulin and T2D
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Quintiles | 1,2,3 | 4 | 5 | p-Value for Trend * | |
---|---|---|---|---|---|
Proinsulin (pmol/L) | <7.78 | 7.78–10.37 | >10.37 | ||
Participants, N | 3001 | 1000 | 1000 | ||
Female (%) | 58.0 | 43.6 | 35.5 | <0.001 | |
Age | 49.9 ± 10.8 | 54.4 ± 11.5 | 57.6 ± 11.3 | <0.001 | |
Race, white (%) | 99.2 | 99.0 | 99.6 | 0.329 | |
Family history of diabetes (%) | 15.5 | 18.3 | 22.1 | <0.001 | |
Smoking status, | 0.004 | ||||
Never (%) | 31.0 | 29.5 | 26.2 | ||
Current (%) | 29.4 | 25.0 | 23.6 | ||
Former (%) | 39.0 | 45.5 | 50.0 | ||
Alcohol consumption, | <0.001 | ||||
None (%) | 21.7 | 23.8 | 28.4 | ||
1–4 units per month (%) | 16.5 | 17.9 | 17.5 | ||
2–7 units per week (%) | 34.6 | 30.9 | 28.9 | ||
1–3 units per day (%) | 23.3 | 22.7 | 21.2 | ||
>3 units per day (%) | 4.0 | 4.6 | 3.9 | ||
Gestational diabetes (%) | 1.0 | 2.3 | 2.8 | 0.002 | |
Length (cm) | 172 ± 8 | 173 ± 9 | 173 ± 8 | 0.002 | |
Weight (kg) | 75.4 ± 12.4 | 81.4 ± 13.0 | 88.9 ± 15.3 | <0.001 | |
BMI (kg/m2) | 25.2 ± 3.6 | 27.1 ± 3.8 | 29.4 ± 4.5 | <0.001 | |
Systolic blood pressure (mmHg) | 121.0 ± 16.5 | 128.1 ± 17.7 | 133.5 ± 19.0 | <0.001 | |
Diastolic blood pressure (mmHg) | 71.4 ± 8.7 | 74.7 ± 8.8 | 76.5 ± 8.5 | <0.001 | |
Use of antihypertension medication (%) | 9.6 | 18.3 | 28.2 | <0.001 | |
Hypertension (%) | 18.9 | 33.1 | 46.4 | <0.001 | |
Cholesterol (mmol/L) | 5.3 ± 1.0 | 5.6 ± 0.9 | 5.5 ± 1 | <0.001 | |
HDL (mmol/L) | 1.3 ± 0.3 | 1.2 ± 0.3 | 1.1 ± 10.3 | <0.001 | |
Triglycerides (mmol/L) | 0.9 (0.7–1.3) | 1.2 (0.8–1.7) | 1.5 (1.1–2.1) | <0.001 | |
Use of lipid-lowering medication (%) | 4.9 | 9.2 | 15.3 | <0.001 | |
Glucose (mmol/L) | 4.7 ± 0.5 | 4.9 ± 0.6 | 5.2 ± 0.7 | <0.001 | |
Insulin (mU/L) | 6.7 (5.0–9.1) | 9.1 (6.7–12.2) | 13.2 (9.2–19.3) | <0.001 | |
C-peptide (pmol/L) | 624 (514–771) | 789 (654–984) | 1078 (861–1353) | <0.001 | |
HOMA-IR ((mU mmol/L)/22.5) | 1.4 (1.0–1.9) | 1.9 (1.4–2.7) | 3.0 (2.0–4.5) | <0.001 | |
Serum creatinine (μmol/L) | 70.2 ± 12.8 | 73.6 ± 14.0 | 78.5 ± 30.7 | <0.001 | |
Plasma albumin (g/L) | 43.9 ± 5.5 | 43.8 ± 2.6 | 43.9 ± 2.6 | 0.22 | |
eGFR (mL/min/1.73 m2) | 97.5 (86.9–106.9) | 94.1 (81.6–104.4) | 87.7 (75.6–98.9) | <0.001 | |
UAE (mg/24 h) | 7.7 (5.8–11.8) | 9.4 (6.3–17.3) | 11.7 (7.1–25.4) | <0.001 |
Quintiles of Plasma Proinsulin, pmol/L | Proinsulin Per 1 SD Increase | |||||
---|---|---|---|---|---|---|
p-Value | ||||||
1,2,3 | 4 | 5 | ||||
Cases | 66 | 49 | 156 | 271 | ||
Crude analysis | 1.00 (ref) | 2.24 (1.55–3.25) | 8.10 (6.07–10.81) | 2.66 (2.41–2.93) | <0.001 | |
Model 1 | 1.00 (ref) | 1.99 (1.37–2.90) | 6.69 (4.94–9.06) | 2.55 (2.29–2.84) | <0.001 | |
Model 2 | 1.00 (ref) | 1.99 (1.37–2.90) | 6.62 (4.89–8.97) | 2.53 (2.27–2.81) | <0.001 | |
Model 3 | 1.00 (ref) | 1.56 (1.07–2.27) | 3.84 (2.79–5.29) | 2.05 (1.81–2.32) | <0.001 | |
Model 4 | 1.00 (ref) | 1.44 (0.98–2.09) | 3.14 (2.27–4.35) | 1.88 (1.65–2.15) | <0.001 | |
Model 5 | 1.00 (ref) | 1.41 (0.96–2.08) | 3.18 (2.28–4.44) | 1.90 (1.66–2.18) | <0.001 | |
Model 6 | 1.00 (ref) | 1.08 (0.73–1.60) | 1.90 (1.34–2.68) | 1.37 (1.18–1.59) | <0.001 | |
Model 7 | 1.00 (ref) | 1.06 (0.71–1.57) | 1.84 (1.27–2.65) | 1.37 (1.16–1.61) | <0.001 | |
Model 8 | 1.00 (ref) | 1.05 (0.70–1.56) | 1.51 (1.02–2.23) | 1.28 (1.08–1.52) | 0.005 |
C-Statistics | p-Value for Change in C-Statistics | IDI | p-Value | |
---|---|---|---|---|
FOS risk model | 0.886 (0.867–0.906) | - | - | - |
+ Proinsulin | 0.888 (0.869–0.907) | 0.019 | 0.0069 | 0.004 |
+ C-peptide | 0.888 (0.870–0.908) | 0.018 | 0.0056 | 0.02 |
+ Insulin | 0.887 (0.867–0.906) | 0.241 | 0.0020 | 0.112 |
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Sokooti, S.; Dam, W.A.; Szili-Torok, T.; Gloerich, J.; van Gool, A.J.; Post, A.; de Borst, M.H.; Gansevoort, R.T.; Heerspink, H.J.L.; Dullaart, R.P.F.; et al. Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population. J. Pers. Med. 2022, 12, 1131. https://doi.org/10.3390/jpm12071131
Sokooti S, Dam WA, Szili-Torok T, Gloerich J, van Gool AJ, Post A, de Borst MH, Gansevoort RT, Heerspink HJL, Dullaart RPF, et al. Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population. Journal of Personalized Medicine. 2022; 12(7):1131. https://doi.org/10.3390/jpm12071131
Chicago/Turabian StyleSokooti, Sara, Wendy A. Dam, Tamas Szili-Torok, Jolein Gloerich, Alain J. van Gool, Adrian Post, Martin H. de Borst, Ron T. Gansevoort, Hiddo J. L. Heerspink, Robin P. F. Dullaart, and et al. 2022. "Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population" Journal of Personalized Medicine 12, no. 7: 1131. https://doi.org/10.3390/jpm12071131