scholarly journals Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus

2019 ◽  
Vol 51 (1) ◽  
pp. 74-82 ◽  
Author(s):  
David Z.I. Cherney ◽  
Enrico Repetto ◽  
David C. Wheeler ◽  
Suzanne V. Arnold ◽  
Sharon MacLachlan ◽  
...  

Background: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. Methods: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. Results: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. Conclusion: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies.

2019 ◽  
Vol 8 (11) ◽  
pp. 1813 ◽  
Author(s):  
Erwin Garcia ◽  
Maryse C. J. Osté ◽  
Dennis W. Bennett ◽  
Elias J. Jeyarajah ◽  
Irina Shalaurova ◽  
...  

Background: Gut microbiota-related metabolites, trimethylamine-N-oxide (TMAO), choline, and betaine, have been shown to be associated with cardiovascular disease (CVD) risk. Moreover, lower plasma betaine concentrations have been reported in subjects with type 2 diabetes mellitus (T2DM). However, few studies have explored the association of betaine with incident T2DM, especially in the general population. The goals of this study were to evaluate the performance of a newly developed betaine assay and to prospectively explore the potential clinical associations of betaine and future risk of T2DM in a large population-based cohort. Methods: We developed a high-throughput, nuclear magnetic resonance (NMR) spectroscopy procedure for acquiring spectra that allow for the accurate quantification of plasma/serum betaine and TMAO. Assay performance for betaine quantification was assessed and Cox proportional hazards regression was employed to evaluate the association of betaine with incident T2DM in 4336 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Results: Betaine assay results were linear (y = 1.02X − 3.75) over a wide range of concentrations (26.0–1135 µM). The limit of blank (LOB), limit of detection (LOD) and limit of quantitation (LOQ) were 6.4, 8.9, and 13.2 µM, respectively. Coefficients of variation for intra- and inter-assay precision ranged from 1.5–4.3% and 2.5–5.5%, respectively. Deming regression analysis of results produced by NMR and liquid chromatography coupled to tandem mass spectrometry(LC-MS/MS) revealed an R2 value of 0.94 (Y = 1.08x – 1.89) and a small bias for higher values by NMR. The reference interval, in a cohort of apparently healthy adult participants (n = 501), was determined to be 23.8 to 74.7 µM (mean of 42.9 ± 12.6 µM). In the PREVEND study (n = 4336, excluding subjects with T2DM at baseline), higher betaine was associated with older age and lower body mass index, total cholesterol, triglycerides, and hsCRP. During a median follow-up of 7.3 (interquartile range (IQR), 5.9–7.7) years, 224 new T2DM cases were ascertained. Cox proportional hazards regression models revealed that the highest tertile of betaine was associated with a lower incidence of T2DM. Hazard ratio (HR) for the crude model was 0.61 (95% CI: 0.44–0.85, p = 0.004). The association remained significant even after adjusting for multiple clinical covariates and T2DM risk factors, including fasting glucose. HR for the fully-adjusted model was 0.50 (95% CI: 0.32–0.80, p = 0.003). Conclusions: The newly developed NMR-based betaine assay exhibits performance characteristics that are consistent with usage in the clinical laboratory. Betaine levels may be useful for assessing the risk of future T2DM.


Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 31 ◽  
Author(s):  
Jimin Jeon ◽  
Jiyoung Jang ◽  
Kyong Park

The effect of calcium consumption in the prevention of type 2 diabetes mellitus (T2DM) remains controversial, and depends on food calcium sources. This prospective study aimed to evaluate the association between calcium-rich food consumption and T2DM incidence among Korean adults. We analyzed the data of 8574 adults aged 40–69 years, without a history of T2DM, cardiovascular disease, and cancer at the baseline from the Korean Genome and Epidemiology Study. The consumption of calcium-rich foods was assessed using a validated semi-quantitative food frequency questionnaire. T2DM-related data were collected using biennial questionnaires, health examinations, and clinical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. In the multivariate-adjusted model, yogurt intake was inversely associated with T2DM risk (HR: 0.73; 95% CI: 0.61–0.88 in the fourth quartile as compared to the first quartile). However, the intakes of other calcium-rich foods, including milk and anchovies, were not significantly associated with T2DM risk. Yogurt may provide protective effects against T2DM in Korean adults, owing to the beneficial effects of probiotics. Further prospective large-scale cohort studies should be conducted to validate these findings.


Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 441 ◽  
Author(s):  
Yueh Pan ◽  
Chia-Yi Lee ◽  
Liang-Ming Lee ◽  
Yu-Ching Wen ◽  
Jing-Yang Huang ◽  
...  

Background and objectives: Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide and is associated with increased incidence of kidney cancer and bladder cancer (BC). However, studies have produced conflicting results. Therefore, we retrospectively evaluated the incidence of BC in T2DM patients using the Taiwan National Health Insurance Research Database (NHIRD). Materials and Methods: We included 31,932 patients with a diagnosis of T2DM in the study group and 63,864 age- and sex-matched patients without T2DM at a ratio of 1:2 in the control group. The primary outcome was the diagnosis of BC. Cox proportional hazards regression was used to evaluate the incidence and adjusted hazard ratio (aHR) of BC in the multivariate model. Results: After a 16-year follow-up, we found that 67 BC cases occurred in the study group and 152 BC events in the non-T2DM group without a significantly higher risk (aHR: 0.842, 95% confidence interval: 0.627–1.13). Conclusions: T2DM patients do not have a higher risk of BC.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ailsa J. McKay ◽  
Laura H. Gunn ◽  
Thirunavukkarasu Sathish ◽  
Eszter Vamos ◽  
Manjula Nugawela ◽  
...  

Abstract Background The associations between England’s incentivised primary care-based diabetes prevention activities and hard clinical endpoints remain unclear. We aimed to examine the associations between attainment of primary care indicators and incident diabetic retinopathy (DR) among people with type 2 diabetes. Methods A historical cohort (n = 60,094) of people aged ≥ 18 years with type 2 diabetes and no DR at baseline was obtained from the UK Clinical Practice Research Datalink (CPRD). Exposures included attainment of the Quality and Outcomes Framework (QOF) HbA1c (≤ 7.5% or 59 mmol/mol), blood pressure (≤ 140/80 mmHg), and cholesterol (≤ 5 mmol/L) indicators, and number of National Diabetes Audit (NDA) care processes completed (categorised as 0–3, 4–6, or 7–9), in 2010–2011. Outcomes were time to development of DR and sight-threatening diabetic retinopathy (STDR). Nearest neighbour propensity score matching was undertaken and Cox proportional hazards models then fitted using the matched samples. Concordance statistics were calculated for each model. Results 8263 DR and 832 STDR diagnoses were observed over mean follow-up periods of 3.5 (SD 2.1) and 3.8 (SD 2.0) years, respectively. HbA1c and blood pressure (BP) indicator attainment were associated with lower rates of DR (adjusted hazard ratios (aHRs) 0.94 (95% CI 0.89–0.99) and 0.87 (0.83–0.92), respectively), whereas cholesterol indicator attainment was not (aHR 1.03 (0.97–1.10)). All QOF indicators were associated with lower rates of STDR (aHRs 0.74 (0.62–0.87) for HbA1c, 0.78 (0.67–0.91) for BP, and 0.82 (0.67–0.99) for cholesterol). Completion of 7–9 vs. 0–3 NDA processes was associated with fewer STDR diagnoses (aHR 0.72 (0.55–0.94)). Conclusions Attainment of key primary care indicators is associated with lower incidence of DR and STDR among patients with type 2 diabetes in England.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shan Gao ◽  
Hongliang Zhang ◽  
Chen Long ◽  
Zhenhua Xing

This study aimed to evaluate the association between obesity, evaluated by fat mass index (FMI) with the risk of microvascular diseases in patients with type 2 diabetes mellitus (T2DM) and compare the magnitude of associations of FMI, body mass index (BMI), and waist circumference (WC) with the risk of microvascular diseases. We performed a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes study. The primary microvascular outcomes of the present study included chronic kidney disease (CKD) progression, retinopathy, and neuropathy. Cox proportional-hazards models were performed to evaluate the association of FMI with microvascular diseases. A discordant analysis was performed to compare the magnitude of associations of FMI, BMI, and WC with the risk of microvascular diseases. Our study included 10,251 T2DM participants with a median of 5 years (interquartile range, 4.2–5.7) of follow-up. A total of 6,184 participants developed CKD progression, 896 participants had retinopathy, and 3,213 participants developed neuropathy (Michigan Neuropathy Screening Instrument, >2.0). After the confounding factors were adjusted for, patients in the highest FMI quartile had a higher risk of CKD progression (HR: 1.26, 95%CI: 1.16–1.36) and neuropathy (HR: 1.93, 95% CI: 1.74–2.15), except for retinopathy (HR: 1.17, 95% CI: 0.96–1.43), than those in the lowest quartile. Discordant analyses found that FMI and WC are better in identifying individuals with obesity-related risk of neuropathy, compared with BMI; neither is better in identifying individuals with obesity-related risk of CKD progression and retinopathy. Obesity is associated with CKD progression and neuropathy in T2DM participants. Further randomized trials are needed to test whether obesity control can improve the outcomes of T2DM participants with CKD or neuropathy. FMI and WC are more useful in identifying obesity-related risk of neuropathy compared with BMI in T2DM patients.Clinical Trial Registrationhttp://www.clinicaltrials.gov, NCT00000620.


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