kjhp Korean Journal of Health Promotion Korean J Health Promot 2234-2141 2093-5676 The Korean Society of Health Promotion and Disease Prevention 10.15384/kjhp.2015.15.4.217 kjhp-15-217 Original Article A Cohort Study of Gallstones and Incidence of Diabetes in a Korean Population SuhByung Seong Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Korea Corresponding author：Byung Seong Suh, MD, PhD Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea Tel: +82-2-2001-1863, Fax: +82-2-2001-2748 E-mail: byungseong.suh@samsung.com 122015 19122015 154 217224 27102015 13112015 Copyright © 2015 The Korean Society of Health Promotion and Disease Prevention 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background

Gallstones are associated with insulin resistance but the relation between gallstone disease and the risk of developing diabetes mellitus (DM) is unclear. We examined if gallstones are associated with an increased incidence of DM compared to no gallstones.

 Methods

A cohort study was performed in 41,518 Koreans aged 30-59 without DM, who underwent a health checkup during 2005-2006 and then were followed annually or biennially until December 2011. Throughout the study period, gallstones were defined as ultrasound-documented gallstones by standard criteria and DM was defined as fasting serum glucose ≥7.0 mmol l-1, A1c ≥6.5%, or use of DM medications.

 Results

During 192999 person-years of follow-up, 2,232 participants developed DM (incidence rate 11.6 per 1,000 person-years). The incidence of DM was higher in subjects with gallstones or cholecystectomy than in those without gallstones for women but not for men. In multivariate-adjusted models, the hazard ratios (95% confidence intervals) for DM comparing gallstones and cholecystectomy vs. no gallstones were 0.95 (0.63-1.42) and 1.13 (0.53-2.38), respectively, in men and 1.64 (1.13-2.40) and 2.04 (1.01-4.11), respectively, in women. These associations did not differ significantly between relevant subgroups.

 Conclusions

In an apparently healthy population, gallstones were independently and modestly associated with increased incidence for DM in women but not in men. Women with gallstones should be provided with adequate measures for preventing DM.

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Flow diagram for the selection of study subjects.

Baseline characteristics of study population according to gallstone diseases (GSD)

Characteristics Men P value Women P valued
No GSD GSD No GSD GSD
Number 26,057 498 14,587 376
Age, ya 37.0 (4.6) 38.3 (4.9) ＜0.001 36.4 (4.2) 37.5 (4.4) ＜0.001
BMI, kg m-2a 24.3 (2.8) 24.9 (3.1) ＜0.001 21.7 (2.7) 22.8 (3.3) ＜0.001
Current smoke, % 48.1 45.0 0.171 2.2 2.7 0.505
Alcohol intake, %c 43.1 37.6 0.014 9.4 9.6 0.930
Regular exercise, %c 45.9 47.2 0.554 35.3 39.1 0.125
Obesity, % 38.9 45.8 0.002 11.0 23.9 ＜0.001
Hypertension, % 11.9 14.1 0.150 2.7 5.1 0.005
Metabolic syndrome, % 17.7 21.7 0.021 3.9 8.0 ＜0.001
Fatty liver on ultrasound,% 37.8 44.8 0.001 6.8 15.7 ＜0.001
Systolic BP, mmHga 115.9 (12.4) 116.4 (12.0) 0.446 105.9 (11.2) 108.9 (11.9) ＜0.001
Diastolic BP, mmHga 75.3 (8.7) 76.4 (8.7) 0.006 67.3 (7.9) 69.1 (8.3) ＜0.001
Glucose, mmol l-1a 5.2 (0.4) 5.3 (0.5) 0.028 5.0 (0.4) 5.1 (0.4) ＜0.001
HbA1c, % 5.3 (0.3) 5.4 (0.3) 0.880 5.4 (0.3) 5.4 (0.3) 0.283
Total cholesterol, mmol l-1a 5.0 (0.8) 4.9 (0.9) 0.159 4.6 (0.8) 4.6 (0.8) 0.733
LDL-C, mmol l-1a 2.9 (0.7) 2.9 (0.8) 0.415 2.5 (6.4) 2.6 (0.7) 0.283
HDL-C, mmol l-1a 1.3 (0.3) 1.3 (0.2) 0.001 1.5 (0.3) 1.5 (0.3) 0.004
Uric acid, μmol l-1a 370.0 (70.2) 371.2 (71.4) 0.758 245.7 (49.4) 249.8 (48.8) 0.137
Triglycerides, mmol l-1b 1.4 (1.0-2.0) 1.4 (1.0-1.9) 0.271 0.9 (0.7-1.2) 0.9 (0.7-1.3) 0.027
AST, U l-1b 24 (20-29) 25 (20-29) 0.310 20 (17-23) 20 (17-24) 0.808
ALT, U l-1b 26 (19-37) 27 (19-39) 0.011 16 (13-20) 16 (13-21) 0.622
GGT, U l-1b 27 (18-44) 29.5 (20-55) 0.049 11 (8-15) 12 (9-17) ＜0.001
hsCRP, mg l-1b 0.50 (0.30-1.10) 0.60 (0.30-1.40) 0.007 0.30 (0.20-0.70) 0.40 (0.20-1.00) 0.903
HOMA-IRb 1.98 (1.58-2.55) 2.15 (1.67-2.80) ＜0.001 1.79 (1.45-2.28) 1.95 (1.57-2.63) ＜0.001

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BP, blood pressure; GGT, 약어풀이; HDL-C, high-density lipoprotein-cholesterol; hsCRP, high sensitivity C-reactive protein; HOMA-IR, homeostasis model assessment of insulin resistance. LDL-C, low-density lipoprotein cholesterol. Data are

Mean (standard deviation),

Median (interquartile range), or percentage.

≥ once time per week.

χ

-test and student t-test were used.

Development of type 2 diabetes according to gallstone diseases (GSD)

Number Person-years Incident case Incidence density (1000 person-year) Age-adjusted HR (95% CI) Multivariate HRa (95% CI) HR (95% CI)b in the model using time-dependent variables
Model 1 Model 2
Men 26,555
No GSD 26,057 122,403.3 1,343 11.0 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference)
GSD 498 2,377.1 31 13.0 1.10 (0.77-1.58) 0.97 (0.68-1.38) 0.98 (0.69-1.40) 0.88 (0.63-1.23)
Gallstone 406 1,945.6 24 12.3 1.06 (0.71-1.59) 0.96 (0.64-1.44) 0.95 (0.63-1.42) 0.88 (0.60-1.29)
Cholecystectomy 92 431.5 7 16.2 1.26 (0.60-2.65) 0.98 (0.46-2.07) 1.13 (0.53-2.38) 0.87 (0.43-1.77)
P for trend 0.520 0.866 0.975 0.456
Women 14,963
No GSD 14,587 66,578.6 821 12.3 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference)
GSD 376 1,640.3 37 22.6 1.88 (1.35-2.62) 1.66 (1.14-2.42) 1.74 (1.24-2.43) 1.73 (1.24-2.42)
Gallstone 300 1,312.2 29 22.1 1.83 (1.26-2.64) 1.66 (1.14-2.42) 1.64 (1.13-2.40) 1.67 (1.14-2.44)
Cholecystectomy 76 328.1 8 24.4 2.14 (1.06-4.29) 2.08 (1.03-4.18) 2.04 (1.01-4.11) 2.00 (1.003-3.97)
P for trend ＜0.001 0.001 0.001 0.001
P for interaction by gender 0.124 0.202 0.236 0.202

Abbreviations: CI, confidence intervals; HR, hazard ratio.

Estimated from Parametric Cox models

Model 1: adjusted for age, smoking status, alcohol intake regular exercise, and BMI; model 2: model 1 plus adjusted for total cholesterol, triglyceride, HDL-cholesterol, and HOMA-IR.

Estimated from a pooled logistic regression models with GSD as a time-dependent categorical variable adjusted for other covariates (smoking status, alcohol intake, regular exercise, triglyceride, HDL-cholesterol, and HOMA-IR over time as time-dependent variables).