Baseline Type 2 Diabetes Mellitus Research Articles

#437 A multicenter, single-arm study of roxadustat in Chinese patients with chronic kidney disease-associated anemia receiving peritoneal dialysis

Abstract Background and Aims Anemia increases morbidity and mortality in patients with chronic kidney disease (CKD). Phase 3 studies have demonstrated the efficacy of roxadustat for anemia treatment in patients with CKD undergoing dialysis; however, data from Chinese patients undergoing peritoneal dialysis (PD) are limited. We evaluated the efficacy and safety of roxadustat in Chinese patients with CKD-anemia undergoing PD. Method In this phase 4, single-arm, multicenter study, we planned to enroll at least 150 Chinese patients with CKD-anemia undergoing PD (either erythropoiesis-stimulating agent [ESA]-treated or ESA-naïve at enrollment), including at least 50 patients with type 2 diabetes mellitus (T2DM) and 50 patients without diabetes mellitus (DM). Study visits occurred every 2 weeks until Week 8 and then every 4 weeks. All patients received oral roxadustat treatment three times per week for 24 weeks according to the approved product package insert. The primary efficacy endpoint was the proportion of patients with a mean hemoglobin (Hb) ≥100 g/L at Weeks 20–24. The secondary efficacy endpoints were subgroup analyses (T2DM vs. non-DM). The exploratory endpoints were the dose required to maintain Hb at ≥100 g/L over Weeks 20–24, the proportion of time when Hb was 100–130 g/L, changes in residual renal function (RRF), urea clearance index (Kt/V), and creatinine clearance (Ccr), amongst others. For the safety analyses, adverse events (AEs) were assessed during treatment and at 4 weeks after completion. Results Overall, 195 patients (116 male [59.5%]) with a mean (standard deviation [SD]) age of 46.3 (12.3) years were enrolled from 22 centers, and 172 (88.2%) completed the study (main reasons for discontinuation: withdrawal, 7 [3.6%]; AE, 5 [2.6%]; switched from PD to hemodialysis, 5 [2.6%]). Overall, 189 patients (96.9%) were ESA-treated and 43 (22.1%) had T2DM. The median (interquartile range) dialysis duration was 16.1 (5.2–43.2) months. The mean (SD) baseline Hb was 98.1 (10.7) g/L, and the ferritin level and transferrin saturation were 320.9 (287.5) μg/L and 35.5% (17.0%), respectively. The mean (SD) treatment duration was 154.3 (35.6) days, and the mean (SD) weekly dose was 244.9 (88.7) mg. The intention-to-treat (ITT) set and safety analysis set (SAF) included all 195 patients. In the ITT set, 85.1% (95% confidence interval [CI] 79.8%–90.5%) of patients had Hb ≥100 g/L over Weeks 20–24. According to the subgroup analysis, 89.2% (95% CI 78.5%–99.9%) of T2DM patients and 84.0% (95% CI 77.8%–90.1%) of non-DM patients had Hb ≥100 g/L over Weeks 20–24 (Fig. 1). The mean (SD) weekly dose required to maintain Hb at ≥100 g/L at Weeks 20–24 was 215.9 (100.0) mg, and the proportion of time that Hb was 100–130 g/L was 76.4% (23.2%). There was a slight decrease in RRF and Ccr. Table 1 shows the RRF, Kt/V, and Ccr results. Of the 195 SAF patients, 158 (81.0%) had ≥1 treatment-emergent AE (TEAE), 20 (10.3%) had drug-related TEAEs, 40 (20.5%) had treatment-emergent serious AEs, and 1 (0.5%) had a TEAE that led to death. The top three TEAEs were upper respiratory tract infection (25 [12.8%]), hypokalemia (17 [8.7%]), and hypoalbuminemia (15 [7.7%]). Conclusion Treatment with roxadustat for 24 weeks effectively corrected anemia in Chinese CKD patients undergoing PD and maintained Hb at ≥100 g/L in the majority of patients, irrespective of baseline T2DM. The AEs were consistent with the characteristics of patients with CKD undergoing PD and with the known safety profile of roxadustat.

Impact of Empagliflozin on Insulin Use in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF) and Type 2 Diabetes: Sub-Analysis from EMPEROR-Preserved Trial

AimWe assessed the impact of empagliflozin on insulin requirement, and outcomes according to insulin use in patients with heart failure with preserved ejection fraction (HFpEF). MethodsOf 5988 patients randomised to empagliflozin or placebo, 2938 (49%) had type 2 diabetes mellitus (T2DM) and 1980 (33%) preDM at baseline. We analysed the effects of empagliflozin vs. placebo on time-to-first sustained insulin initiation in patients with T2DM or preDM not using insulin at baseline. ResultsAt baseline, 861 patients were using insulin. Patients on insulin were younger, had longer DM duration, lower eGFR, and more co-morbidities such as coronary artery disease and macroalbuminuria. During a median observation time of 26 months, among patients with T2DM or preDM not using insulin at baseline, empagliflozin reduced the risk of sustained initiation of insulin by 31% (HR 0.69 [95% CI 0.49, 0.98], p=0.038). Among patients with T2DM, those using insulin at baseline had higher incidence rates of the primary endpoint (first hospitalisation for HF [HHF] or cardiovascular [CV] death), total HHFs and first HHF that were reduced by empagliflozin but still remained higher than in the placebo arm of those not using insulin. Beneficial effects of empagliflozin on CV outcomes did not differ by baseline insulin use. ConclusionsEmpagliflozin reduced the rate of insulin initiation by 31% in patients with HFpEF and T2DM or preDM. Insulin-users at baseline were at higher risk of adverse CV outcomes; still, the effects of empagliflozin on CV outcomes were consistent in patients with T2DM irrespective of insulin treatment.Figure: The effect of empagliflozin vs placebo on clinical outcomes and mortality in patients with HFpEF and baseline T2DM with or without insulin.

Serum 25-hydroxyvitamin D, type 2 diabetes, and liver-related outcomes: Secondary data analysis of a prospective recruited cohort.

The association of vitamin D deficiency, which is prevalent in type 2 diabetes mellitus (T2DM), with liver disease and related mortality has not been quantified. Our study aimed to (1) investigate whether there is a synergistic association of vitamin D deficiency and T2DM with liver-related outcomes and (2) explore whether high 25-hydroxyvitamin D [25(OH)D] concentrations are associated with a lower risk of liver-related outcomes in T2DM. Leveraging the data from UK Biobank, we conducted 2 studies: study I assessed the joint associations of vitamin D deficiency [25(OH)D <50nmol/L] and T2DM with liver-related outcomes among 439,276 participants, and study II explored the associations of vitamin D status with liver-related outcomes among 21,519 individuals with T2DM. Baseline T2DM was identified through medication, laboratory test, and electronic health-related records. Serum 25(OH)D was measured by direct competitive chemiluminescent immunoassay. Liver-related outcomes included 6 liver disease end points and mortality by overall liver disease, chronic liver disease, and severe liver disease. During an average follow-up duration of 11.6 years, we observed a significant positive additive interaction effect (all synergy index>1.0) of T2DM and vitamin D deficiency on the risk of liver-related outcomes. Compared with participants without either T2DM or vitamin D deficiency, the multivariable-adjusted HRs of overall liver diseases were 1.29 for participants without T2DM but with vitamin D deficiency, 1.73 for participants with T2DM but without vitamin D deficiency, and 2.19 for participants with both T2DM and vitamin D deficiency. In individuals with T2DM, we observed that participants without vitamin D deficiency were inversely associated with incident liver disease and related mortality (multivariable-adjusted HRs 0.41-0.81) when compared with individuals with vitamin D deficiency. There are positive synergistic associations of vitamin D deficiency and T2DM with liver-related outcomes. Inverse associations between serum 25(OH)D concentrations and liver-related outcomes were observed in individuals with T2DM.

1266-P: Validation of a Predictive Model of Diabetes in People with Overweight and Obesity

Obesity is the most common chronic disease in the U.S. A substantial subset of people with obesity are at high risk for type 2 diabetes mellitus (T2DM) and many of their risk factors for T2DM are modifiable. It is important to identify this at-risk subset to appropriately direct treatment and resources for earlier intervention and the prevention of T2DM. The original model was developed using EMR data of 338,653 adults &amp;lt; 65 years old with BMI ≥ 25 kg/m2 and without baseline T2DM between 2000 and 2019. Variables were selected from a literature-based pool of risk factors for T2DM using LASSO penalized Cox regression. A Cox model (adjusted for the competing risk of death) was developed using an 80% training dataset with selected variables and internally validated on a held-out 20% dataset of EMR data. This model was then externally validated on a dataset of 103,419 participants of the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). Over a mean of 7.0 years of follow-up, 30,100 (8.9%) patients in the EMR dataset developed T2DM (1.3% annual incidence). The predictive model included BMI (HR 1.47 for 5 kg/m2; 95% CI 1.46 - 1.49), age, history of hypertension, systolic blood pressure and family history of diabetes. The model achieved a Harrell’s C-statistic of 0.76 on the held-out EMR dataset and the calibration slope for 10-year estimates was 1.09. In the NHS-HPFS external validation dataset, 12,402 (12.0%) individuals developed T2DM over a mean 14.2 years of follow-up (0.85% annual incidence). On this dataset, the model achieved Harrell’s C-statistic of 0.72 and the calibration slope for 10-year estimates of 0.78. It is feasible to use predictive modeling to identify people with overweight and obesity at high risk of T2DM. This approach could be utilized to guide population management and clinical treatment decisions. Disclosure A.Turchin: Consultant; Proteomics International, Covance, Research Support; AstraZeneca, Edwards Lifesciences Corporation, Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Brio Systems. M.Shubina: None. F.J.Morrison: None. N.Ahmad: Employee; Eli Lilly and Company. L.M.Neff: Employee; Eli Lilly and Company, Research Support; Aegerion Pharmaceuticals, Stock/Shareholder; Eli Lilly and Company. H.Kan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

Association of Type 2 Diabetes Mellitus with Cognitive Function in Adults: A Prospective Cohort Study.

The Cognitive role of untreated type 2 diabetes mellitus (T2DM) has been less well substantiated. We sought to explore the prospective association of T2DM and untreated T2DM with cognitive function among middle-aged and older Chinese adults. Data of 7,230 participants without baseline brain damage/mental retardation, or memory-related diseases in China Health and Retirement Longitudinal Study (CHARLS) from 2011- 2012 to 2015, were analyzed. Fasting plasma glucose and self-reported information on T2DM diagnosis and treatment were assessed. Participants were categorized into normoglycemia, impaired fasting glucose (IFG), and T2DM (including untreated and treated T2DM) groups. Episodic memory and executive function were assessed by modified Telephone Interview for Cognitive Status every two years. We used generalized estimating equation model to examine the association of baseline T2DM status with cognitive function in succeedingyears. Compared to those with normoglycemia, T2DM was associated with worse overall cognitive function after controlling for demographic variables, lifestyles, follow-up time, major clinical factors, and baseline cognitive function, although the associations were statistically non-significant (β= -0.19, 95% CI: -0.39, 0.00). However, a significant association was mainly observed for those with untreated T2DM (β= -0.26, 95% CI: -0.47, -0.04), especially in the domain of executive function (β= -0.19, 95% CI: -0.35, -0.03). In general, IFG and treated T2DM individuals had similar levels of cognitive function with normoglycemia participants. Our findings supported a detrimental role of untreated T2DM on cognitive function among middle-aged and older adults. Screening and early treatment for T2DM are warranted for maintaining better cognitive function in later life.

Impact of diabetes duration on left ventricular mass regression with empagliflozin.

The duration of type 2 diabetes mellitus (T2DM) is an important determinant of diabetes severity. The EMPA-HEART CardioLink-6 trial reported significant left ventricular (LV) mass indexed to body surface area (LVMi) regression in patients treated with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin for 6months. This exploratory sub-analysis of the same trial investigated the association between T2DM duration and LVMi regression. A total of 97 individuals with T2DM and coronary artery disease (CAD) were randomly assigned to receive empagliflozin 10mg daily or placebo. LVMi was measured at the baseline and 6month visit using cardiac magnetic resonance imaging. The study population was divided into those with a baseline T2DM duration <10years (n=40) or ≥10years (n=57). A linear model adjusting for baseline values in each of the subgroups (ANCOVA) was used to assess the treatment effect of 6month change in LVMi, LV end systolic volume indexed to body surface area, LV end diastolic volume indexed to body surface area and LV ejection fraction. Patients in the T2DM duration <10years group (38 males [95.0%], median age 63 [IQR: 55years to 70years]) had a median T2DM duration of 4years (IQR: 2.0years to 7.0years). Those in the T2DM duration ≥10years group (52 males [91.2%], median age 65 [IQR: 57years to 71years]) had a median duration of 15years (IQR: 12years to 20years). There was no significant difference in baseline LVMi according to T2DM duration (median 62g/m2 [IQR: 53.1g/m2 to 70.0g/m2 ] for T2DM duration <10years; median 57.5g/m2 [IQR: 52.1g/m2 to 66.2g/m2 ] for T2DM duration ≥10years; P=0.11). Empagliflozin was associated with reductions in LVMi irrespective of duration of T2DM above and below 10years (T2DM duration <10years group, mean adjusted difference -2.90g/m2 [95% CI: -6.64g/m2 to 0.84g/m2 ]; T2DM duration ≥10years group, mean adjusted difference -3.69g/m2 [95% CI: -0.14g/m2 to -7.24g/m2 ]; Pinteraction =0.07). In the EMPA-HEART CardioLink-6 trial, empagliflozin treatment was associated with reductions in LVMi in people with T2DM and CAD irrespective of the duration of diabetes assessed categorically above and below 10years.

1005-P: Patients with Overweight and Obesity at High-Risk for Type 2 Diabetes: A Predictive Model

Obesity is the most common chronic disease in the U.S. Patients with obesity are at high risk for type 2 diabetes mellitus (T2DM); however, many of their risk factors for T2DM are modifiable. It is important to identify patients with obesity at high risk for T2DM to appropriately direct treatment and resources. We conducted an observational study of EMR data of 399,711 adults with BMI ≥ 25 kg/m2 and without baseline T2DM between 2000 and 2019. We first identified a literature-based pool of risk factors for T2DM onset and conducted variable selection by applying LASSO penalized Cox regression with ten-fold cross-validation on an 80% training dataset. We estimated a regular Cox model on the training dataset with selected variables and evaluated model performance on the remaining 20% dataset. Over a mean of 7.4 years of follow-up, 38,898 (9.8%) study patients developed T2DM. The predictive model achieved a Harrell’s C-statistic of 0.81. The greatest risk of T2DM was associated with gestational diabetes (HR 2.53; 95% CI 2.12-3.01), Asian and Hispanic race/ethnicity (HRs 2.38 and 1.94; 95% CIs 2.24-2.53 and 1.86-2.02, respectively), family history of DM (HR 2.00; 95% CI 1.95-2.04) and PCOS (HR 1.84; 95% CI 1.63-2.07). Female sex (HR 0.77; 95% CI 0.75-0.79), having a partner (HR 0.90; 95% CI 0.88-0.92) or commercial insurance (HR 0.86; 95% CI 0.84-0.88) were associated with a lower risk of T2DM. Characteristics found in &amp;gt;5% of patients that carried additional risk included proteinuria (5.0% of patients; HR 1.53; 95% CI 1.47-1.59), hypertension (23.9%; HR 1.21; 95% CI 1.18-1.25), high cholesterol (11.9%; HR 1.19; 95% CI 1.15-1.23), and history of smoking (40.5%; HR 1.18; 95% CI 1.15-1.21). Each standard deviation increase in BMI (5.2 kg/m2) was associated with a 1.51-fold (95% CI 1.49-1.52) increase in T2DM onset. It is feasible to use predictive modeling to identify patients with overweight and obesity at high risk of T2DM. This approach could be utilized to guide population management and clinical treatment decisions. Disclosure A. Turchin: Consultant; Self; Proteomics International, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Stock/Shareholder; Self; Brio Systems. F. J. Morrison: None. M. Shubina: None. S. Shinde: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company

The Risk of Type 2 Diabetes Mellitus in a Russian Population Cohort According to Data from the HAPIEE Project.

The aim of this study is to investigate the 14-year risk of type 2 diabetes mellitus (T2DM) and develop a risk score for T2DM in the Siberian cohort. A random population sample (males/females, 45–69 years old) was examined at baseline in 2003–2005 (Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE) project, n = 9360, Novosibirsk) and re-examined in 2006–2008 and 2015–2017. After excluding those with baseline T2DM, the final analysis included 7739 participants. The risk of incident T2DM during a 14-year follow-up was analysed using Cox regression. In age-adjusted models, male and female hazard ratios (HR) of incident T2DM were 5.02 (95% CI 3.62; 6.96) and 5.13 (95% CI 3.56; 7.37) for BMI ≥ 25 kg/m2; 4.38 (3.37; 5.69) and 4.70 (0.27; 6.75) for abdominal obesity (AO); 3.31 (2.65; 4.14) and 3.61 (3.06; 4.27) for fasting hyperglycaemia (FHG); 2.34 (1.58; 3.49) and 3.27 (2.50; 4.26) for high triglyceride (TG); 2.25 (1.74; 2.91) and 2.82 (2.27; 3.49) for hypertension (HT); and 1.57 (1.14; 2.16) and 1.69 (1.38; 2.07) for family history of diabetes mellitus (DM). In addition, secondary education, low physical activity (PA), and history of cardiovascular disease (CVD) were also significantly associated with T2DM in females. A simple T2DM risk calculator was generated based on non-laboratory parameters. A scale with the best quality included waist circumference >95 cm, HT history, and family history of T2DM (area under the curve (AUC) = 0.71). The proposed 10-year risk score of T2DM represents a simple, non-invasive, and reliable tool for identifying individuals at a high risk of future T2DM.

Hypertriglyceridemic Waist Phenotype and Lipid Accumulation Product: Two Comprehensive Obese Indicators of Waist Circumference and Triglyceride to Predict Type 2 Diabetes Mellitus in Chinese Population.

Purpose To determine whether hypertriglyceridemic waist (HTGW) and high lipid accumulation product (LAP) preceded the incidence of type 2 diabetes mellitus (T2DM), and to investigate the interactions of HTGW and LAP with other components of metabolic syndrome on the risk of T2DM. Methods A total of 15,717 eligible participants without baseline T2DM and aged 35 and over were included from a Chinese rural cohort. Cox proportional hazards regression models were used to estimate the association of HTGW and LAP with the incidence of T2DM, and the restricted cubic spline model was used to evaluate the dose-response association. Results Overall, 867 new T2DM cases were diagnosed after 7.77 years of follow-up. Participants with HTGW had a higher hazard ratio for T2DM (hazard ratio (HR): 6.249, 95% confidence interval (CI): 5.199-7.511) after adjustment for potential confounders. The risk of incident T2DM was increased with quartiles 3 and 4 versus quartile 1 of LAP, and the adjusted HRs (95% CIs) were 2.903 (2.226-3.784) and 6.298 (4.911-8.077), respectively. There were additive interactions of HTGW (synergy index (SI): 1.678, 95% CI: 1.358-2.072) and high LAP (SI: 1.701, 95% CI: 1.406-2.059) with increased fasting plasma glucose (FPG) on the risk of T2DM. Additionally, a nonlinear (P nonlinear < 0.001) dose-response association was found between LAP and T2DM. Conclusion The subjects with HTGW and high LAP were at high risk of developing T2DM, and the association between LAP and the risk of T2DM may be nonlinear. Our study further demonstrates additive interactions of HTGW and high LAP with increased FPG on the risk of T2DM.

Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH

Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients. We included 178 metabolically healthy-defined by the absence of baseline T2DM, AHT, dyslipidemia-patients with biopsy-proven NAFLD from the HEPAmet Registry (N= 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia. During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19-7.31; p= 0.019), glucose levels (p= 0.008), age (p= 0.007) and BMI (p= 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14-5.10; p= 0.028), age (p= 0.0001), BMI (p= 0.006), glucose (p= 0.021) and platelets (p= 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS <0.12 4.5% [4/88]; logRank 6.658, p= 0.010). Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM. Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.

Type 2 diabetes increases the long-term risk of heart failure and mortality in patients with atrial fibrillation.

Impact of type 2 diabetes mellitus (T2DM) on non-thromboembolic outcomes in atrial fibrillation (AF) is insufficiently explored. This prospective cohort study of AF patients aimed (i) to analyse the association between T2DM and heart failure (HF) events (including new-onset HF), and all-cause and cardiovascular mortality, (ii) to assess the impact of baseline T2DM treatment on outcomes, and (iii) to explore characteristics of new-onset HF phenotypes in relation to T2DM status. Of 1803 AF patients (515/1288, with/without prior HF), 389 (22%) had T2DM at baseline. After 5 years of median follow-up, T2DM patients had an 85% greater risk of HF events [adjusted hazard ratio (aHR) 1.85; 95% confidence interval (CI) 1.51-2.28; P< 0.001], including a 45% increased risk for new-onset HF (1.45; 1.17-2.28; P= 0.015). T2DM conferred a 56% higher all-cause (1.56, 1.22-2.01; P= 0.003) and a 48% higher cardiovascular mortality (1.48; 1.34-1.93; P= 0.007). Fine-Gray analysis, with mortality as a competing risk, confirmed greater HF risk among T2DM patients. All risks were highest among insulin-treated patients. The prevalence of new-onset HF phenotypes was as follows: 67% preserved ejection fraction (HFpEF), 20% mid-range ejection fraction (HFmrEF) and 13% reduced ejection fraction (HFrEF). On time-dependent Cox regression, adjusted for baseline characteristics and an interim acute coronary event, T2DM increased aHRs for new-onset HFpEF (2.38; 1.30-4.58; P<0.001) and the combined HFmrEF/HFrEF (1.77; 1.11-3.62; P= 0.017). Atrial fibrillation patients with T2DM have independently increased risk of new-onset/recurrent HF events, cardiovascular and all-cause mortality, particularly when insulin-treated. The prevailing phenotype of new-onset HF was HFpEF; T2DM conferred higher risk of both HFpEF and HFmrEF/HFrEF.

Bidirectional association between depressive symptoms and type 2 diabetes mellitus: The China Health and Retirement Longitudinal Study

ObjectiveTo prospectively examine the bidirectional relationship between depressive symptoms and type 2 diabetes mellitus (T2DM) among middle-aged and elderly Chinese. MethodsParticipants were enrolled in 2011–2012 (Wave 1) and followed up in 2013–2014 (Wave 2) and 2015–2016 (Wave 3) in the China Health and Retirement Longitudinal Study. Depressive symptoms were evaluated by the Chinese language version of 10-item Center for Epidemiological Studies Depression Scale (CESD-10) at three waves. T2DM was assessed by biochemical biomarkers at Wave 1 and reported physician-diagnosis at Wave 2 and 3. Cox proportional hazards regression was applied to calculate hazard ratio (HR) and 95% confidence intervals (CIs) for the bidirectional association. ResultsParticipants with baseline depressive symptoms were 1.33 times as likely to develop T2DM (HR, 1.33; 95% CI: 1.06, 1.66), compared to their counterparts after adjusting for demographic characteristics and T2DM risk factors. The risk of T2DM increased linearly with higher severity of depression as determined by a higher CESD-10 score (P for trend ≪ 0.001). In addition, baseline T2DM was associated with increased risk of incident depressive symptoms (1.15; 1.00, 1.31) and persistent depressive symptoms (1.35; 1.03, 1.77). ConclusionThere is a positive bidirectional association between depressive symptoms and T2DM in middle-aged and elderly Chinese.

Diabetes mellitus, genetic variants in the insulin-like growth factor pathway and colorectal cancer risk.

Genetic variation in the insulin‐like growth factor (IGF) pathway may further increase the risk of colorectal cancer (CRC) associated with type 2 diabetes mellitus (T2DM). Joint effects of T2DM and genetic variation in the IGF pathway on CRC risk can increase mechanistic insights. Participants from the Netherlands Cohort Study (n = 120, 852) completed a baseline questionnaire in 1986 when 55–69 years old (case–cohort, n subcohort = 5,000, n cases = 3,441 after 16.3 years follow‐up). Self‐reported DM at baseline with onset at ≥30 years was classified as T2DM. Eighteen single nucleotide polymorphisms (SNPs) from the IGF pathway were aggregated in a genetic risk score (GRS). Cox proportional hazard ratios (HRs) for CRC were estimated according to combinations of T2DM status with GRS tertiles and categories of an IGF1 19‐CA repeat polymorphism. Baseline T2DM prevalence was 3.1% in subcohort members and 3.8% in CRC cases. Comparison of combined categories with non‐T2DM individuals in the lowest GRS tertile as reference showed that those in the highest GRS tertiles with and without T2DM had significantly increased CRC risks, particularly those with T2DM (HR = 2.28, 95% CI: 1.11, 4.66). As compared to IGF1 19‐CA wild‐type carriers without T2DM, carrying two IGF1 19‐CA variant repeat alleles were associated with a significantly decreased CRC risk in those without T2DM (HR = 0.76, 95% CI: 0.63–0.91). This association was absent when T2DM was present. Our study of joint effects indicated that the presence of unfavorable alleles in the IGF pathway may further increase the risk of CRC associated with T2DM.

A Pragmatic Clinical Trial to Compare the Real-World Effectiveness of V-Go versus Standard Delivery of Insulin in Patients with Advanced Type 2 Diabetes.

BackgroundMany patients with type 2 diabetes mellitus (T2DM) do not have adequate glycemic control, leading to poor patient outcomes and high healthcare costs.ObjectiveThis prospective pragmatic clinical trial evaluated V-Go, a wearable insulin delivery device, compared with standard treatment optimization (STO) among insulin-treated patients with T2DM in a real-world, community-based practice setting.MethodsStudy sites, rather than individual patients, were randomized to V-Go or STO via cluster randomization. Patients were treated according to routine clinical practice and followed up to 4 months. T2DM medications and supplies were purchased utilizing usual insurance and co-pay systems. The primary analysis was an unadjusted treatment group comparison of glycosylated hemoglobinA1c (HbA1c) change from baseline to end of study (EOS). A cost of therapy analysis was completed on patients who had received comparable baseline T2DM treatment with multiple daily basal-bolus insulin injections (MDI).ResultsAnalysis included 415 patients (169 V-Go, 246 STO) enrolled from 52 US sites. Mean baseline HbA1c (9.6%) was higher in V-Go (9.9%, range 8.0% – 14.2%) than STO (9.3%, range 7.9% – 13.9%, p <.001). HbA1c decreased from baseline to EOS in both V-Go (−1.0%, p<.001) and STO (−0.5%, p<.001); V-Go had significantly larger decrease (p=.002). V-Go had a significant reduction (p<.001) in mean insulin total daily dose (TDD; 0.76 U/kg baseline, 0.57 U/kg EOS), not seen in STO (0.72 U/kg baseline and EOS). The MDI group included 95 (56.2%) V-Go and 113 STO (45.9%) patients. Mean baseline HbA1c was significantly higher in V-Go (9.9%) than STO (9.4%). V-Go also experienced larger decrease in HbA1c from baseline (−1.0%) than STO (−0.36%) (p=.006) with a decrease in TDD, while STO TDD remained unchanged. EOS mean per patient per day cost of diabetes treatment was lower for V-Go ($30.59) vs STO ($32.20) (p=.006). V-Go was more cost effective than STO ($24.02 per 1% drop in HbA1c vs $58.86, respectively).ConclusionsThis pragmatic clinical trial demonstrated improved HbA1c levels, lower cost, and decreased insulin dose in patients with T2DM initiating V-Go vs STO in a real-world community-based practice setting. Observed baseline HbAlc indicated use of V-Go in more difficult to manage diabetes patients.

The role of triglyceride glucose index in development of Type 2 diabetes mellitus

AimsTriglyceride-Glucose (TyG) is an emerging surrogate indicator of insulin resistance. We explored the role of TyG in development of Type 2 Diabetes Mellitus (T2DM) and elucidated the mechanism for the relationship. Methods4109 subjects without baseline T2DM participated in a community screening programme in 2013–2016. TyG was calculated as Ln[fasting triglyceride level (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]. Outcome was T2DM defined as FPG ≥ 7.0 mmol/l; current treatment with anti-diabetes medication; and/or self-reported diabetes on follow-up screening. We used Cox proportion-hazard model to assess risk of T2DM by TyG quartiles at baseline. Binary mediation analysis was performed to examine extent of mediation by TyG between Body Mass Index (BMI) and T2DM development. ResultsAfter 5734.23 person-years of follow-up, T2DM developed in 117 subjects with an incidence of 20.40/1000 person-years. Risk of T2DM incidence was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG (adjusted HR 1.79(95%CI 0.80–3.99), 2.54 (1.18–5.49) and 4.68(2.19–10.01), Ptrend < 0.001) across TyG quartiles. TyG accounted for 35.1% of association between BMI and T2DM development, having adjusted for potential cofounders (p < 0.001). ConclusionsTyG is potentially useful for predicting T2DM in clinical practice. It is a potential mediator of association between BMI and T2DM development.

Cumulative increased risk of incident type 2 diabetes mellitus with increasing triglyceride glucose index in normal-weight people: The Rural Chinese Cohort Study

BackgroundRisk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China.MethodsWe included data from 5706 people with normal body mass index (BMI) (18.5–23.9 kg/m2) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure–response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2].ResultsRisk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20–5.11], 3.77 [1.83–7.79], and 5.30 [2.21–12.71], Ptrend < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22–6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index.ConclusionsRisk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM.

Human Immunodeficiency Virus and Risk of Type 2 Diabetes in a Large Adult Cohort in Jos, Nigeria.

Human immunodeficiency virus (HIV) infection and the use of antiretroviral therapy (ART) may increase the risk of type 2 diabetes mellitus (T2DM). However, data from regions with a high burden of HIV/AIDS are limited. We determined the prevalence of T2DM at the time of presentation to a large HIV clinic in Nigeria, as well as the incidence of diabetes 12 months following ART initiation. Data from patients enrolled for ART from 2011 to 2013 was analyzed, including 2632 patients on enrollment and 2452 reevaluated after 12 months of ART commencement. The presence of diabetes, and demographic, clinical, and biochemical data were retrieved from standardized databases. CD4(+), HIV RNA load, and hepatitis C virus status were noted. Bivariate and logistic regressions were used to identify risk factors for T2DM. Baseline T2DM prevalence was 2.3% (95% confidence interval, 1.8%-2.9%); age, but not body mass index (BMI), was a risk factor for diabetes. After 12 months of ART, an additional 5.3% had developed T2DM. Newly developed diabetes was not associated with age, but was associated with BMI. There were no significant associations between prevalent or incident diabetes and CD4(+), viral load, or type of ART. Diabetes is not uncommon in HIV-infected individuals at the time of presentation to HIV services. Patients initiating ART have a high risk of developing diabetes in the first year of ART. Excessive weight gain should be avoided, as incident diabetes was associated with a BMI ≥25.0 kg/m(2).

The efficacy of bariatric surgery performed in the public sector for obese patients with comorbid conditions.

To determine the efficacy of bariatric surgery in the public sector for the treatment of complicated obesity. A longitudinal observational study of obese participants with comorbid conditions, aged 21-73 years, who underwent publicly funded bariatric surgery. Data were extracted from clinical databases (1 October 2009 to 1 September 2013) and recorded at seven time points. Participants are from an ongoing public obesity program. Postoperative weight loss and partial or full resolution of: type 2 diabetes mellitus (T2DM), hypertension (HTN), dyslipidaemia and obstructive sleep apnoea (OSA). The 65 participants in the cohort lost a mean weight of 22.6 kg (SD, 9.5 kg) by 3 months, 34.2.kg (SD, 20.1 kg) by 12 months and 39.9 kg (SD, 31.4 kg) by 24 months (P < 0.001). Body mass index (BMI) decreased from a preoperative mean of 48.2 kg/m(2) (SD, 9.5 kg/m(2)) to 35.7 kg/m(2) (SD, 7.7 kg/m(2)) by 24 months (P < 0.001). Full resolution of comorbid conditions by 18 months (P < 0.001) was achieved by almost half of those with baseline T2DM, nearly two-thirds with HTN and three-quarters of those with OSA, with continued improvements beyond 24 months. Bariatric surgery performed in the public sector is efficacious in the treatment of obese patients with comorbid conditions. Our findings parallel similar studies suggesting that there is equal benefit in publicly funded and privately performed procedures. This study highlights that obese patients reliant on public health care maintain sufficient intrinsic motivation in the absence of payment and supposed value-driven incentive. Improved access to bariatric surgery in the public sector can justifiably reduce the health inequities for those most in need.