scholarly journals Gallstone disease, diabetes, calcium, triglycerides, smoking and alcohol consumption and pancreatitis risk: Mendelian randomization study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Yuan ◽  
Edward L. Giovannucci ◽  
Susanna C. Larsson
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Pancreatitis ◽  
Alcohol Consumption ◽  
Mendelian Randomization ◽  
Gallstone Disease ◽  
Smoking Initiation ◽  
Disease Type ◽  
Uk Biobank ◽  
Increased Risk

AbstractWe conducted a Mendelian randomization study to determine the potential causal associations of gallstone disease, diabetes, serum calcium, triglyceride levels, smoking and alcohol consumption with acute and chronic pancreatitis. Genetic variants associated with the exposures at p < 5 × 10−8 were selected from corresponding genome-wide association studies. Summary-level data for pancreatitis were obtained from the FinnGen consortium and UK Biobank. Univariable and multivariable Mendelian randomization analyses were performed and results from FinnGen and UK Biobank were combined using the fixed-effects meta-analysis method. Genetic predisposition to gallstone disease, type 2 diabetes and smoking initiation was associated with an increased risk of acute pancreatitis. The combined odds ratios (ORs) were 1.74 (95% confidence interval (CI), 1.57, 1.93) for gallstone disease, 1.14 (95% CI, 1.06, 1.21) for type 2 diabetes and 1.56 (95% CI, 1.32, 1.83) for smoking initiation. The association for type 2 diabetes attenuated after adjustment for gallstone disease. Genetic predisposition to gallstone disease and smoking initiation as well as higher genetically predicted serum calcium and triglyceride levels were associated with an increased risk of chronic pancreatitis. The combined ORs of chronic pancreatitis were 1.27 (95% CI, 1.08, 1.50) for gallstone disease, 1.86 (95% CI, 1.43, 2.43) for smoking initiation, 2.20 (95% CI, 1.30, 3.72) for calcium and 1.47 (95% CI, 1.23, 1.76) for triglycerides. This study provides evidence in support that gallstone disease, type 2 diabetes, smoking and elevated calcium and triglyceride levels are causally associated with the risk of acute or chronic pancreatitis.

scholarly journals Alcohol use and cardiometabolic risk in the UK Biobank: a Mendelian randomization study

2020 ◽  
Author(s):  
Joanna Lankester ◽  
Daniela Zanetti ◽  
Erik Ingelsson ◽  
Themistocles L. Assimes
Keyword(s):  
Type 2 Diabetes ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Mendelian Randomization ◽  
Lower Amount ◽  
Cardiometabolic Health ◽  
Uk Biobank ◽  
The Uk ◽  
Cardiometabolic Traits

AbstractObservational studies suggest alcohol use promotes the development of some adverse cardiometabolic traits but protects against others including outcomes related to coronary artery disease. We used Mendelian randomization to explore causal relationships between the degree of alcohol consumption and several cardiometabolic traits in the UK Biobank. We found carriers of the ADH1B Arg47His variant (rs1229984) reported a 26% lower amount of alcohol consumption compared to non-carriers. In our one-sample, two-stage least squares analyses of the UK Biobank using rs1229984 as an instrument, one additional drink/day was associated with statistically significant elevated level of systolic blood pressure (3.0 mmHg), body mass index (0.87 kg/m^2), waist circumference (1.3 cm), body fat percentage (1.7%), low-density lipoprotein levels in blood (0.16 mmol/L), and the risk of myocardial infarction (OR=1.50), stroke (OR=1.52), any cardiovascular disease (OR=1.43), and all-cause mortality (OR=1.41). Conversely, increasing use of alcohol was associated with reduced levels of triglycerides (−0.059 mmol/L) and HbA1C (−0.42 mmol/mol) in the blood, the latter possibly a consequence of a statistically elevated mean corpuscular volume among ADH1B Arg47His carriers. Stratifications by sex and smoking revealed a pattern of more harm of alcohol use among men compared to women, but no consistent difference by smoking status. Men had an increased risk of heart failure (OR = 1.76), atrial fibrillation (OR = 1.35), and type 2 diabetes (OR = 1.31) per additional drink/day. Using summary statistics from external datasets in 2-sample analyses for replication, we found causal associations between alcohol and obesity, stroke, ischemic stroke, and type 2 diabetes. Our results are consistent with an overall harmful effect of alcohol on cardiometabolic health at all levels of use and suggest that even moderate alcohol use should not be promoted as a part of a healthy diet and lifestyle.

scholarly journals Association of leukocyte telomere length with chronic kidney disease in East Asians with type 2 diabetes: A Mendelian randomization study

2021 ◽  
Author(s):  
Resham L Gurung ◽  
Rajkumar Dorajoo ◽  
Yiamunaa M ◽  
Ling Wang ◽  
Sylvia Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Telomere Length ◽  
Mendelian Randomization ◽  
Random Effect ◽  
Leukocyte Telomere Length ◽  
Increased Risk ◽  
Genetically Determined

Abstract Background Chronic kidney disease (CKD) is common among type 2 diabetes (T2D) and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length is associated with CKD in patients with T2D. We previously reported single nucleotide polymorphisms (SNPs) associated with leukocyte telomere length in Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using Mendelian randomization (MR) approach. Methods The cross-sectional association of 16 leukocyte telomere length SNPs with CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min/1.73m2 was assessed among 4,768 (1,628 cases, 3,140 controls) participants in the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes and Diabetic Nephropathy cohorts. MR analysis was performed using the random-effect inverse-variance weighted (IVW) method, the weighted median, MR-Egger and Radial MR adjusted for age and sex-stratified by cohorts and ethnicity (Chinese and Malays), then meta-analysed. Results Genetically determined shorter leukocyte telomere length was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio = 1.51 [95% confidence interval, 1.12 - 2.12; P = 0.007; Phet= 0.547]). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (β  =  0.010, P = 0.751). Conclusions Our findings suggest that genetically determined leukocyte telomere length is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.

scholarly journals Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease

2020 ◽  
Vol 29 (19) ◽  
pp. 3327-3337
Author(s):  
Christopher S Thom ◽  
Zhuoran Ding ◽  
Michael G Levin ◽  
Scott M Damrauer ◽  
Kyung Min Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Mendelian Randomization ◽  
Smoking Behavior ◽  
Diabetes Risk ◽  
Genetic Determinants ◽  
Increased Risk ◽  
Artery Disease ◽  
Cad Risk

Abstract Clinical observations have linked tobacco smoking with increased type 2 diabetes risk. Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes. However, this association could be mediated by additional risk factors correlated with smoking behavior, which have not been investigated. We hypothesized that body mass index (BMI) could help to explain the association between smoking and diabetes risk. First, we confirmed that genetic determinants of smoking initiation increased risk for type 2 diabetes (OR 1.21, 95% CI: 1.15–1.27, P = 1 × 10−12) and coronary artery disease (CAD; OR 1.21, 95% CI: 1.16–1.26, P = 2 × 10−20). Additionally, 2-fold increased smoking risk was positively associated with increased BMI (~0.8 kg/m2, 95% CI: 0.54–0.98 kg/m2, P = 1.8 × 10−11). Multivariable Mendelian randomization analyses showed that BMI accounted for nearly all the risk smoking exerted on type 2 diabetes (OR 1.06, 95% CI: 1.01–1.11, P = 0.03). In contrast, the independent effect of smoking on increased CAD risk persisted (OR 1.12, 95% CI: 1.08–1.17, P = 3 × 10−8). Causal mediation analyses agreed with these estimates. Furthermore, analysis using individual-level data from the Million Veteran Program independently replicated the association of smoking behavior with CAD (OR 1.24, 95% CI: 1.12–1.37, P = 2 × 10−5), but not type 2 diabetes (OR 0.98, 95% CI: 0.89–1.08, P = 0.69), after controlling for BMI. Our findings support a model whereby genetic determinants of smoking increase type 2 diabetes risk indirectly through their relationship with obesity. Smokers should be advised to stop smoking to limit type 2 diabetes and CAD risk. Therapeutic efforts should consider pathophysiology relating smoking and obesity.

Gallstone Disease and Type 2 Diabetes Risk: A Mendelian Randomization Study

Hepatology ◽  
2019 ◽  
Vol 70 (2) ◽  
pp. 610-620 ◽  
Author(s):  
Fei Wang ◽  
Jing Wang ◽  
Yaru Li ◽  
Jing Yuan ◽  
Ping Yao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mendelian Randomization ◽  
Gallstone Disease ◽  
Diabetes Risk

scholarly journals Cigarette smoking, alcohol intake and the risk of diabetes mellitus in Gombe State, northeast Nigeria

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Sule J. Bathna ◽  
Jacob A. Dunga ◽  
Nura H. Alkali ◽  
Jafiada J. Musa ◽  
Abubakar A. Gombe ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Alcohol Consumption ◽  
Cigarette Smoking ◽  
Cross Sectional Survey ◽  
Chronic Lung Diseases ◽  
Increased Risk ◽  
Northeast Nigeria

Alcohol is consumed in almost all countries worldwide. Heavy drinking can reduce the body’s sensitivity to insulin, which can trigger type 2 diabetes mellitus. Diabetes can complicate chronic pancreatitis, which is overwhelmingly caused by heavy alcohol drinking. Alcohol is also high in calories, with heavy drinkers liable to obesity and a higher risk of type 2 diabetes mellitus. Similarly, cigarette smoking is associated with increased risk of type 2 diabetes mellitus among both middle-aged and elderly men and women. Nigeria is one of the three largest tobacco markets in Africa with a population of almost 13 million smokers. Northeast Nigeria ranks 3rd among the six geopolitical zones, with a smoking rate of 6.1%. In this study, we evaluated the risks of diabetes mellitus associated with alcohol consumption and cigarette smoking in Gombe State, Northeast Nigeria. This cross-sectional survey was conducted in a two-stage cluster sampling scheme based on existing administrative divisions. Study subjects were males and females aged 16 years and older who resided in the Jekadafari Ward of Gombe Metropolis. Subjects were excluded from this study if they were less than 16 years of age, pregnant women or suffered chronic conditions such as chronic kidney disease, chronic liver disease or chronic lung diseases based on clinical history and laboratory results. The calculated sample size was 1600 based on a 3.1% prevalence rate of DM, with a power of 85% and precision of 5%. We obtained complete data on 1302 subjects, of whom 50 (3.8%) had DM. (5.1% in males and 2.86% in females). Alcohol use was prevalent among 365 (28.03%) subjects, and was higher in males (49.4%) compared to females (11.4%). The risk of DM was significantly higher among alcoholusers compared to non-users, with an odds ratio of 4.1 (95%CI: 2.3- 7.3; P=0.0001). Eighty-eight subjects were cigarette smokers, of whom 87 were males and only one was female. We found no significant association between cigarette smoking and DM (OR=0.34, 95%CI 0.05-2.48; P=0.29). The overall prevalence of DM was 3.9%. Alcohol consumption, but not cigarette smoking, was associated with a higher risk of DM in this study.

scholarly journals Obesity and the relation between joint exposure to ambient air pollutants and incident type 2 diabetes: A cohort study in UK Biobank

PLoS Medicine ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. e1003767
Author(s):  
Xiang Li ◽  
Mengying Wang ◽  
Yongze Song ◽  
Hao Ma ◽  
Tao Zhou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Air Pollution ◽  
Air Pollutants ◽  
Ambient Air ◽  
Uk Biobank ◽  
Ambient Air Pollutants ◽  
Obesity Status ◽  
Increased Risk ◽  
The Relationship

Background Air pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship. Methods and findings A total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m2. Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 μm (PM2.5), between 2.5 μm and 10 μm (PM2.5–10), nitrogen oxide (NO2), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D (p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants. Conclusions We found that various air pollutants PM2.5, PM2.5–10, NO2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity.

scholarly journals Homogeneity in the association of body mass index with type 2 diabetes across the UK Biobank: A Mendelian randomization study

PLoS Medicine ◽  
2019 ◽  
Vol 16 (12) ◽  
pp. e1002982 ◽  
Author(s):  
Michael Wainberg ◽  
Anubha Mahajan ◽  
Anshul Kundaje ◽  
Mark I. McCarthy ◽  
Erik Ingelsson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
The Uk

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Hypertension ◽  
2022 ◽  
Author(s):  
Maddalena Ardissino ◽  
Eric A.W. Slob ◽  
Ophelia Millar ◽  
Rohin K. Reddy ◽  
Laura Lazzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Increased Risk

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

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