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.
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Table 1.
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
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 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 |