A Cohort Study of Gallstones and Incidence of Diabetes in a Korean Population

Byung Seong Suh

doi:10.15384/kjhp.2015.15.4.217

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Suh: A Cohort Study of Gallstones and Incidence of Diabetes in a Korean Population

Original Article

Korean J Health Promot 2015;15(4):217-224.

Published online: 19 December 2015

DOI: https://doi.org/10.15384/kjhp.2015.15.4.217

A Cohort Study of Gallstones and Incidence of Diabetes in a Korean Population

Byung Seong Suh

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

Received 27 October 2015 Accepted 13 November 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.

Abstract

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.

Keywords: Gallstones, Diabetes mellitus, Insulin resistance, Cohort study, Incidence

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Figure 1.

Flow diagram for the selection of study subjects.

Table 1.

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

Characteristics	Men		P value	Women		P value^d
Characteristics	No GSD	GSD	P value	No GSD	GSD	P value^d
Number	26,057	498		14,587	376
Age, y^a	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, mmHg^a	115.9 (12.4)	116.4 (12.0)	0.446	105.9 (11.2)	108.9 (11.9)	＜0.001
Diastolic BP, mmHg^a	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-IR^b	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

^a Mean (standard deviation),

^b Median (interquartile range), or percentage.

^c ≥ once time per week.

^d χ

² -test and student t-test were used.

Table 2.

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 HR^a (95% CI)		HR (95% CI)^b in the model using time-dependent variables
	Number	Person-years	Incident case	Incidence density (1000 person-year)	Age-adjusted HR (95% CI)	Model 1	Model 2	HR (95% CI)^b in the model using time-dependent variables
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.

^a Estimated from Parametric Cox models

^a 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.

^b 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).

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