A Polygenic Lipodystrophy Genetic Risk Score Characterizes Risk Independent of BMI in the Diabetes Prevention Program.

Context: There is substantial heterogeneity in insulin sensitivity, and genetics may suggest possible mechanisms by which common variants influence this trait.

Objectives: We aimed to evaluate an 11-variant polygenic lipodystrophy genetic risk score (GRS) for association with anthropometric, glycemic and metabolic traits in the Diabetes Prevention Program (DPP). In secondary analyses, we tested the association of the GRS with cardiovascular risk factors in the DPP.

Eradication of Hepatitis C Virus Is Associated With Reduction in Hematologic Malignancies: Major Differences Between Interferon and Direct-Acting Antivirals.

It is unclear whether eradication of hepatitis C virus (HCV) leads to a reduction in the risk of hematologic malignancies. We aimed to determine the impact of sustained virologic response (SVR) induced by either direct-acting antivirals (DAAs) or interferon (IFN) on the risk of hematologic malignancies. We identified 69,581 patients who initiated antiviral treatment in the Veterans Affairs national health care system from January 1, 1999, to December 31, 2015, including 40,410 (58%) IFN-only regimens, 4,546 (6.

Conjugated Estrogens and Bazedoxifene Improve Cell Function in Obese Menopausal Women.

Context: Studies suggest that menopausal hormone therapy (MHT) prevents type 2 diabetes (T2D). The combination of conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is an MHT that improves obesity and T2D in preclinical models of menopausal metabolic syndrome. The effect of CE/BZA on adiposity and glucose homeostasis in obese postmenopausal women is unknown.

Perioperative Evaluation and Management of Patients With Cirrhosis: Risk Assessment, Surgical Outcomes, and Future Directions.

Background And Aims: Patients with cirrhosis are at increased risk of perioperative morbidity and mortality. We provide a narrative review of the available data regarding perioperative morbidity and mortality, risk assessment, and management of patients with cirrhosis undergoing non-hepatic surgical procedures.

Methods: We conducted a comprehensive review of the literature from 1998-2018 and identified 87 studies reporting perioperative outcomes in patients with cirrhosis.

Association of Habitual Daily Physical Activity With Glucose Tolerance and β-Cell Function in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes From the Restoring Insulin Secretion (RISE) Study.

Objective: We examined the relationship between habitual daily physical activity and measures of glucose tolerance, insulin sensitivity, and β-cell responses in adults with impaired glucose tolerance (IGT) or drug-naive, recently diagnosed type 2 diabetes.

Research Design And Methods: Participants included 230 adults (mean ± SD age 54.5 ± 8.

Association of Self-Reported Sleep and Circadian Measures With Glycemia in Adults With Prediabetes or Recently Diagnosed Untreated Type 2 Diabetes.

Objective: Sleep disturbances and circadian misalignment (social jet lag, late chronotype, or shift work) have been associated with worse glycemic control in type 2 diabetes (T2D). Whether these findings apply to adults with prediabetes is yet unexplored. We hypothesized that self-reported short sleep, poor sleep quality, and/or circadian misalignment are associated with higher glycemia, BMI, and blood pressure (BP) in adults with prediabetes or recently diagnosed, untreated T2D.

Characteristics at the time of oxygen initiation associated with its adherence: Findings from the COPD Long-term Oxygen Treatment Trial.

Rationale: Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear.

Objectives: To identify patient characteristics at the time of oxygen initiation associated with its adherence.

Methods: We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial.

Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial.

Background: Although depression is common among patients receiving maintenance hemodialysis, data on their acceptance of treatment and on the comparative efficacy of various therapies are limited.

Objective: To determine the effect of an engagement interview on treatment acceptance (phase 1) and to compare the efficacy of cognitive behavioral therapy (CBT) versus sertraline (phase 2) for treating depression in patients receiving hemodialysis.

Design: Multicenter, parallel-group, open-label, randomized controlled trial.

Levels of phthalate acid esters and sex hormones and their possible sources in traffic-patrol policemen in Chongqing.

To investigate the correlation between the air phthalate acid ester (PAE) exposure and serum PAE concentration and the effects of PAE exposure on reproductive health among Chongqing traffic-patrol policemen. In 2013, 32 traffic-patrol policemen working in an area with poor air quality in Chongqing and 28 traffic-patrol policemen working in an area with good air quality were selected. Their blood levels of 14 PAEs and six reproductive hormones were determined.

Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA.

Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease.

Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial.

Importance: Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease.

Objective: To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events.

Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling.

The underlining mechanisms of dietary cholesterol and nonalcoholic steatohepatitis (NASH) in contributing to hepatocellular carcinoma (HCC) remain undefined. Here we demonstrated that high-fat-non-cholesterol-fed mice developed simple steatosis, whilst high-fat-high-cholesterol-fed mice developed NASH. Moreover, dietary cholesterol induced larger and more numerous NASH-HCCs than non-cholesterol-induced steatosis-HCCs in diethylnitrosamine-treated mice.

Genetic Ancestry Markers and Difference in A1c Between African American and White in the Diabetes Prevention Program.

Purpose: HbA1c levels are higher in blacks than non-Hispanic whites (NHWs). We investigated whether genetics could explain this difference in Diabetes Prevention Program (DPP) participants.

Methods: We tested (i) genetic variants causing hemoglobinopathies, (ii) a genetic risk score (GRS) based on 60 variants associated with HbA1c from genome-wide association meta-analysis, and (iii) principal component (PC) factors that capture continental ancestry derived from genetic markers distributed across the genome.

Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPα-p300 Axis.

The aging liver is affected by several disorders, including steatosis, that can lead to a decline of liver functions. Here, we present evidence that the cdk4-C/EBPα-p300 axis is a critical regulator of age-associated disorders, including steatosis. We found that patients with non-alcoholic fatty liver disease (NAFLD) have increased levels of cdk4 and that cdk4-resistant C/EBPα-S193A mice do not develop hepatic steatosis with advancing age.

An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women: Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants.

Background: The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D.

Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD.

Genetic ablation of Cyp8b1 preserves host metabolic function by repressing steatohepatitis and altering gut microbiota composition.

Both type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH) are associated with reduced hepatic mitochondrial respiratory capacity. Cholic acid (CA) is the predominant 12α-hydroxylated bile acid that regulates hepatic lipid metabolism, and its circulating levels are negatively correlated with insulin resistance. Abolishing CA synthesis via the genetic disruption of the enzyme sterol 12α-hydroxylase ( Cyp8b1) leads in resistance to diabetes and hepatic steatosis.

Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation.

Objective: Both lifestyle and metformin interventions can delay or prevent progression to type 2 diabetes mellitus (DM) in people with impaired glucose regulation, but there is considerable interindividual variation in the likelihood of receiving benefit. Understanding an individual's 3-year risk of progressing to DM and regressing to normal glucose regulation (NGR) might facilitate benefit-based tailored treatment.

Research Design And Methods: We used the values of 19 clinical variables measured at the Diabetes Prevention Program (DPP) baseline evaluation and Cox proportional hazards models to assess the 3-year risk of progression to DM and regression to NGR separately for DPP lifestyle, metformin, and placebo participants who were adherent to the interventions.

Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design.

Rationale: Colorectal cancer (CRC) is preventable through screening, with colonoscopy and fecal occult blood testing comprising the two most commonly used screening tests. Given the differences in complexity, risk, and cost, it is important to understand these tests' comparative effectiveness.

Study Design: The CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group trial to compare screening with colonoscopy vs.