Metformin Use Correlates with Reduced Risk of Gallstones in Diabetic Patients: A 12-Year Follow-up Study

Liao, Kuan‐Fu; Chuang, Hsun‐Yang; Lai, Shih‐Wei

doi:10.3389/fphar.2017.00765

Cited by 10 publications

(6 citation statements)

References 36 publications

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“…A retrospective cohort study showed a significant reduction in the incidence of gallstones in diabetic patients on long-term metformin. 39 Our study similarly found that diabetics had a 27% increased risk of gallstones compared to non-diabetics (in Model 4). However, the precise mechanism by which AIP enhances the susceptibility to gallstones, as well as the significance of diabetes about this correlation, remains uncertain.…”

Section: Discussionsupporting

confidence: 71%

Diabetes Mellitus Mediates the Relationship Between Atherogenic Index of Plasma and Gallstones: A Population-Based Cross-Sectional Study

Du,

Wang,

Song

et al. 2024

DMSO

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Purpose Previous studies have shown a correlation between diabetes mellitus and gallstone formation. The atherogenic index of plasma (AIP) is associated with many metabolic diseases. However, insufficient evidence still exists to elucidate the association between AIP and gallstones. The primary objective of this study was to investigate the correlation between AIP and gallstones in US adults, and the secondary objective was to analyze whether diabetes plays a mediating role in the association. Patients and Methods Using data from the National Health and Nutrition Survey (NHANES) conducted between 2017 and March 2020, this study investigated the association between AIP and gallstone incidence in US adults. A variety of statistical methods were used to analyze the data in this study, including multivariate logistic regression, subgroup analyses, restricted cubic spline curves (RCS), and mediation effects analysis. In addition, two-stage linear regression was used to detect possible threshold and saturation effects. Results A total of 6952 subjects were enrolled in the trial, of which 748 patients were diagnosed with gallstones. A significant positive association between AIP and gallstones was observed by fully adjusted multivariate logistic regression analysis, with an odds ratio (OR) of 1.45 and a 95% confidence interval (CI) of (1.09, 1.93). In addition, a non-linear positive association and saturation effect between AIP and gallstones were found, with an inflection point of 0.2246. Mediation analysis showed that diabetes had a mediating effect of 16.9% in the association between AIP and gallstones. Conclusion This study suggests that elevated levels of AIP are linked to an augmented vulnerability to gallstone development, with diabetes serving as a mediating factor. These findings present a novel perspective on clinical approaches to prevent and manage gallstones.

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Section: Discussionsupporting

confidence: 71%

Diabetes Mellitus Mediates the Relationship Between Atherogenic Index of Plasma and Gallstones: A Population-Based Cross-Sectional Study

Du,

Wang,

Song

et al. 2024

DMSO

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“…In a population-based study involving 36 patients with polycystic ovary syndrome and 20 healthy controls, metformin treatment was associated with an improved metabolic and hormonal imbalance associated with polycystic ovary syndrome and increased gallbladder motility ( Isik et al, 2012 ) that is associated with a lower risk of cholesterol gallstones ( Pauletzki et al, 1996 ). A cohort study in diabetes also observed a reduced risk of gallstones in individuals with >180 cumulative defined daily dose of metformin compared to those with <29 cumulative defined daily dose of metformin ( Liao et al, 2017 ). Even though these findings nominally are conflicting with our findings, several issues in previous studies deserve consideration, including lack of direct GDF-15 measurement, unadjusted important confounders (e.g., smoking status), no examination of the nonlinearity of the association, and certain special features of the diabetic population and patients with polycystic ovary syndrome.…”

Section: Discussionmentioning

confidence: 99%

GDF-15 as a Therapeutic Target of Diabetic Complications Increases the Risk of Gallstone Disease: Mendelian Randomization and Polygenic Risk Score Analysis

Zhou

Wang

et al. 2022

Front. Genet.

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Growth differentiation factor 15 (GDF-15) levels have been revealed as a robust biomarker for metformin use. We conducted Mendelian randomization (MR) analysis to explore the association between GDF-15 and gallstone disease to inform potential therapeutic effects targeting GDF-15. Four genetic variants associated with GDF-15 levels at p < 5 × 10–8 were selected as instrumental variables from a genome-wide association meta-analysis including 21,758 individuals. Two-sample MR analysis was conducted using summary-level data from UK Biobank (10,520 gallstone cases and 350,674 controls) and FinnGen consortium (19,023 gallstone cases and 195,144 controls). Polygenic risk score analysis using individual-level data in UK biobank was performed to complement the MR findings by examining the non-linearity of the association. Diabetic complications were taken as positive controls to validate the therapeutic effect of targeting GDF-15. Linear and nonlinear associations between genetically predicted GDF-15 levels and gallstones were estimated with stratification by the diabetic status. In the two-sample MR analysis, the odds ratio (OR) of gallstones was 1.09 (95% confidence interval (CI), 1.03–1.15; p = 0.001) for one standard deviation increase in genetically predicted GDF-15 levels in the meta-analysis of two datasets. Polygenic risk score analysis found this association to be U-shaped (p = 0.037). The observed association was predominantly seen in nondiabetic population (OR = 1.11, 95% CI: 1.01–1.21; p = 0.003). An inverse association between genetically predicted GDF-15 levels and diabetic complications (OR = 0.77, 95% CI: 0.62–0.96; p = 0.023) was observed, validating the potential therapeutic effects of targeting GDF-15 levels. This MR study indicates that the increased risk of gallstone disease should be taken into account when considering GDF-15 as a therapeutic target for diabetic complications.

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“…This was supported by the fact that diabetes control can affect the incidence of cholelithiasis. A retrospective cohort study demonstrated a significant reduction in gallstone formation among diabetic patients with long-term use of metformin [ 32 ]. In addition, Liu et al .…”

Section: Discussionmentioning

confidence: 99%

The association between diabetes and gallstones: a nationwide population-based cohort study

Ratheesh,

Ulrich,

Ghozy

et al. 2023

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Introduction Evidence regarding the association between diabetes mellitus (DM) and cholelithiasis is still inconsistent. Aim To examine the association between diabetes and gallstones and the commonly associated factors in a nationwide population-based cohort investigation. Material and methods The demographic and outcome variable data were extracted from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017–2018. Results A total of 5376 individuals were included in the final analysis, with a mean age of 51.3 ±17.8 years. Females constituted 51.5% of the included individuals, and the overall mean body mass index (BMI) was 29.8 ±7.4 kg/m 2 . The prevalence of diabetes was 16.2% among the included individuals, with a mean age of 50.6 ±13.6 years at diagnosis of diabetes, and only 4.5% were taking insulin. The prevalence of cholelithiasis was 11.2%, with a mean age of 44.4 ±16.1 years at diagnosis, and 11.3% had previous cholecystectomy (gallbladder surgery.) There was a significant increase in gallstone rates among diabetic patients as compared to non-diabetics in the unadjusted (OR = 2.30; 95% CI: 1.89–2.79; p < 0.001) and adjusted (OR = 1.52; 95% CI: 1.20–1.92; p < 0.001) models. Moreover, this association was not time-dependent where the “age when first told you had diabetes” did not show a significant influence on the gallstone rate, whether in unadjusted (OR = 1.01; 95% CI: 1.00–1.02; p = 0.221) or adjusted (OR = 1.01; 95% CI: 0.99–1.03; p = 0.395) models. Furthermore, insulin usage was found to be a significant predictor of cholelithiasis, whether in unadjusted (OR = 2.39; 95% CI: 1.74–3.28; p < 0.001) or adjusted (OR = 1.52; 95% CI: 1.05–2.19; p = 0.026) models. Conclusions DM and insulin therapy are possible risk factors for developing cholelithiasis.

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Metformin Use Correlates with Reduced Risk of Gallstones in Diabetic Patients: A 12-Year Follow-up Study

Cited by 10 publications

References 36 publications

Diabetes Mellitus Mediates the Relationship Between Atherogenic Index of Plasma and Gallstones: A Population-Based Cross-Sectional Study

Diabetes Mellitus Mediates the Relationship Between Atherogenic Index of Plasma and Gallstones: A Population-Based Cross-Sectional Study

GDF-15 as a Therapeutic Target of Diabetic Complications Increases the Risk of Gallstone Disease: Mendelian Randomization and Polygenic Risk Score Analysis

The association between diabetes and gallstones: a nationwide population-based cohort study

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