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BACKGROUND: A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes. OBJECTIVE: To investigate the association between GLP-1 RAs, compared with sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is), and risk for suicidal ideation and behaviors in older adults with type 2 diabetes (T2D). DESIGN: Two target trial emulation studies comparing propensity score (PS)-matched cohorts for GLP-1 RAs versus SGLT2is and GLP-1 RAs versus DPP4is. SETTING: U.S. national Medicare administrative data from January 2017 to December 2020. PATIENTS: Older adults (≥66 years) with T2D; no record of suicidal ideation or behaviors; and a first prescription for a GLP-1 RA, SGLT2i, or DPP4i. MEASUREMENTS: The primary end point was a composite of suicidal ideation and behaviors. New GLP-1 RA users were matched 1:1 on PS to new users of an SGLT2i or DPP4i in each pairwise comparison. A Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CIs within matched groups. RESULTS: This study included 21 807 pairs of patients treated with a GLP-1 RA versus an SGLT2i and 21 402 pairs of patients treated with a GLP-1 RA versus a DPP4i. The HR of suicidal ideation and behaviors associated with GLP-1 RAs relative to SGLT2is was 1.07 (95% CI, 0.80 to 1.45; rate difference, 0.16 [CI, -0.53 to 0.86] per 1000 person-years); the HR relative to DPP4is was 0.94 (CI, 0.71 to 1.24; rate difference, -0.18 [CI, -0.92 to 0.57] per 1000 person-years). LIMITATIONS: Low event rate; imprecise estimates; unmeasured confounders, such as body mass index; and potential misclassification of outcomes. CONCLUSION: Among Medicare beneficiaries with T2D, this study found no clear increased risk for suicidal ideation and behaviors with GLP-1 RAs, although estimates were imprecise and a modest adverse risk could not be ruled out. PRIMARY FUNDING SOURCE: American Foundation for Pharmaceutical Education, Pharmaceutical Research and Manufacturers of America Foundation, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.
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BACKGROUND: Diabetes patients are at higher risk for mortality than the general population; however, little is known about whether the excess mortality risk associated with diabetes could be mitigated or nullified via controlling for risk factors. METHODS: We included 18,535 diabetes patients and 91,745 matched individuals without diabetes without baseline cancer or cardiovascular disease (CVD), followed up from 2006 to 2021. The main exposure was the number of optimized risk factors including glycated hemoglobin < 53 mmol/mole, systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, no albuminuria, non-current smoking and low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L. We used Cox proportional hazards models to explore the association of the degree of risk factor control with all-cause mortality, cancer mortality, CVD mortality and other mortality. RESULTS: Each additional risk factor control was associated with a 16, 10, 21 and 15% lower risk of all-cause mortality, cancer mortality, CVD mortality and other mortality, respectively. Optimal risk factors control (controlling 5 risk factors) was associated with a 50% (HR 0.50, 95% CI 0.41-0.62), 74% (HR 0.26, 95% CI 0.16-0.43) and 38% (HR 0.62, 95% CI 0.44-0.87) lower risk of all-cause mortality, CVD mortality and other mortality, respectively. Diabetes patients with 4, 3 and 5 or more controlled risk factors, respectively, showed no excess risk of all-cause mortality, cancer mortality and CVD mortality compared to matched non-diabetes patients. CONCLUSIONS: The results from this study indicate that optimal risk factor control may eliminate diabetes-related excess risk of all-cause mortality, CVD mortality and other mortality.
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Doenças Cardiovasculares , Diabetes Mellitus , Neoplasias , Humanos , Estudos de Coortes , Biobanco do Reino Unido , Bancos de Espécimes Biológicos , Fatores de RiscoRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) results in heavy economic and disease burdens in Louisiana. The Centers for Medicare and Medicaid Services has reimbursed non-face-to-face chronic care management (NFFCCM) for patients with two or more chronic conditions since 2015. OBJECTIVE: To assess the impacts of NFFCCM on healthcare utilization and health outcomes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included Medicare fee-for-service beneficiaries with T2DM and at least one additional chronic disease between 2014 and 2018. EXPOSURES: At least one record of NFFCCM Current Procedural Terminology codes. MAIN MEASURES: The health outcomes in the study included major adverse cardiovascular events (MACE), all-cause mortality, and heart failure. The monthly service utilization and continuity of care index for primary care were also included. The propensity score method was used to balance the baseline differences between the two groups. Weighted multivariate regression models were developed using propensity score weights to assess the impacts of NFFCCM on outcomes. KEY RESULTS: During the 5 years of study period, 8415 patients among the 118,643 Medicare beneficiaries received at least one NFFCCM. Patients receiving any NFFCCM had reduced healthcare utilization compared with patients not receiving NFFCCM, including 0.012 (95% CI - 0.014 to - 0.011; p < 0.001) fewer monthly hospital admissions, 0.017 (95% CI - 0.019 to - 0.016; p < 0.001) fewer monthly ED visits, and 0.399 (95% CI 0.375 to 0.423; p < 0.001) more monthly outpatient encounters. Patients receiving NFFCCM services had lower MACE event rates of 7.4% (95% CI 7.1 to 7.8%; p < 0.001), all-cause mortality rate of 7.8% (95% CI 7.4 to 8.1%; p < 0.001), and heart failure rate of 0.3% (95% CI 0.2 to 0.5%; p < 0.001), respectively. CONCLUSIONS AND RELEVANCE: These findings suggest that reimbursement for NFFCCM was associated with the shifting high-cost utilization to lower-cost primary health care settings among patients with diabetes in Louisiana.
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Diabetes Mellitus Tipo 2 , Medicare , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Estados Unidos/epidemiologia , Feminino , Masculino , Idoso , Medicare/estatística & dados numéricos , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso de 80 Anos ou mais , Planos de Pagamento por Serviço Prestado , Doença CrônicaRESUMO
BACKGROUND: This analysis assessed the cost-effectiveness of insulin glargine 300 units/mL (Gla-300) versus insulin glargine 100 units/mL (Gla-100) in insulin-naïve adults with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs (OADs). METHODS: Costs and outcomes for Gla-300 versus Gla-100 from a US healthcare payer perspective were assessed using the BRAVO diabetes model. Baseline clinical data were derived from EDITION-3, a 12-month randomized controlled trial comparing Gla-300 with Gla-100 in insulin-naïve adults with inadequately controlled T2D on OADs. Treatment costs were calculated based on doses observed in EDITION-3 and 2020 US net prices, while costs for complications were based on published literature. Lifetime costs ($US) and quality-adjusted life-years (QALYs) were predicted and used to calculate incremental cost-effectiveness ratio (ICER) estimates; extensive scenario and sensitivity analyses were conducted. RESULTS: Lifetime medical costs were estimated to be $353,441 and $352,858 for individuals receiving Gla-300 and Gla-100 respectively; insulin costs were $52,613 and $50,818. Gla-300 was associated with a gain of 8.97 QALYs and 21.12 life-years, while Gla-100 was associated with a gain of 8.89 QALYs and 21.07 life-years. This resulted in an ICER of $7522/QALY gained for Gla-300 versus Gla-100. Thus, Gla-300 was cost-effective versus Gla-100 based on a willingness-to-pay threshold of $50,000/QALY. Compared with Gla-100, Gla-300 provided a net monetary benefit of $3290. Scenario and sensitivity analyses confirmed the robustness of the base case. CONCLUSION: Gla-300 may be a cost-effective treatment option versus Gla-100 over a lifetime horizon for insulin-naïve people in the United States with T2D inadequately controlled on OADs.
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Diabetes Mellitus Tipo 2 , Insulina Glargina , Adulto , Humanos , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Estados UnidosRESUMO
AIM: Women with diabetes are at higher risk of cardiovascular diseases (CVD) than men with diabetes; however, the sex difference in the association between the degree of risk factor control and the risk of CVD in patients with diabetes is unclear. METHODS: In total, 17 260 participants diagnosed with diabetes from the UK Biobank were included and matched with 86 300 non-diabetes controls based on age, sex and assessment centre. The main exposure was the number of risk factors within the target range, including glycated haemoglobin level <53 mol/mol (7%), blood pressure <140/90 mm/Hg, low-density lipoprotein cholesterol <100 mg/dl, non-current smoking and absence of microalbuminuria. RESULTS: During a median follow-up of 13.3 years, a total of 3338 incident CVD cases, including 2807 ischaemic heart disease and 793 strokes, were documented. A more stringent control of risk factors was significantly associated with a lower risk of incident CVD, and such an association was significantly stronger in women than men. Compared with non-diabetes participants, the diabetes-related risk of CVD appeared to be eliminated if more than three risk factors were well controlled among women and men with diabetes. Moreover, clinical biomarkers (e.g. glycated haemoglobin and blood pressure) showed greater relative importance than other factors in women, whereas socio-economic and psychological factors (e.g. education and depression) exhibited similar relative importance to clinical biomarkers in men with diabetes. CONCLUSION: Our findings highlighted the importance of raising awareness of sex differences in the management of CVD risk factors among patients with diabetes.
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Doenças Cardiovasculares , Diabetes Mellitus , Humanos , Feminino , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Hemoglobinas Glicadas , Diabetes Mellitus/epidemiologia , Fatores de Risco , BiomarcadoresRESUMO
AIM: This study compared the 5-year incidence rate of macrovascular and microvascular complications for tirzepatide, semaglutide and insulin glargine in individuals with type 2 diabetes, using the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model. RESEARCH DESIGN AND METHODS: This study was a 5-year SURPASS-2 trial extrapolation, with an insulin glargine arm added as an additional comparator. The 1-year treatment effects of tirzepatide (5, 10 or 15 mg), semaglutide (1 mg) and insulin glargine on glycated haemoglobin, systolic blood pressure, low-density lipoprotein and body weights were obtained from the SUSTAIN-4 and SURPASS-2 trials. We used the BRAVO model to predict 5-year complications for each study arm under two scenarios: the 1-year treatment effects persisted (optimistic) or diminished to none in 5 years (conservative). RESULTS: When compared with insulin glargine, we projected a 5-year risk reduction in cardiovascular adverse events [rate ratio (RR) 0.64, 95% confidence interval (CI) 0.61-0.67] and microvascular composite (RR 0.67, 95% CI 0.64-0.70) with 15 mg tirzepatide, and 5-year risk reduction in cardiovascular adverse events (RR 0.75, 95% CI 0.72-0.79) and microvascular composite (RR 0.79, 95% CI 0.76-0.82) with semaglutide (1 mg) under an optimistic scenario. Lower doses of tirzepatide also had similar, albeit smaller benefits. Treatment effects for tirzepatide and semaglutide were smaller but still significantly higher than insulin glargine under a conservative scenario. The 5-year risk reduction in diabetes-related complication events and mortality for the 15 mg tirzepatide compared with insulin glargine ranged from 49% to 10% under an optimistic scenario, which was reduced by 17%-33% when a conservative scenario was assumed. CONCLUSION: With the use of the BRAVO diabetes model, tirzepatide and semaglutide exhibited potential to reduce the risk of macrovascular and microvascular complications among individuals with type 2 diabetes, compared with insulin glargine in a 5-year window. Based on the current modelling assumptions, tirzepatide (15 mg) may potentially outperform semaglutide (1 mg). While the BRAVO model offered insights, the long-term cardiovascular benefit of tirzepatide should be further validated in a prospective clinical trial.
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Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Humanos , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Estudos ProspectivosRESUMO
AIM: The action to control cardiovascular risk in diabetes (ACCORD) trial showed a neutral average treatment effect of intensive blood glucose and blood pressure (BP) controls in preventing major adverse cardiovascular events (MACE) in individuals with type 2 diabetes. Yet, treatment effects across patient subgroups have not been well understood. We aimed to identify patient subgroups that might benefit from intensive glucose or BP controls for preventing MACE. MATERIALS AND METHODS: As a post-hoc analysis of the ACCORD trial, we included 10 251 individuals with type 2 diabetes. We applied causal forest and causal tree models to identify participant characteristics that modify the efficacy of intensive glucose or BP controls from 68 candidate variables (demographics, comorbidities, medications and biomarkers) at the baseline. The exposure was (a) intensive versus standard glucose control [glycated haemoglobin (HbA1c) <6.0% vs. 7.0%-7.9%], and (b) intensive versus standard BP control (systolic BP <120 vs. <140 mmHg). The primary outcome was MACE. RESULTS: Compared with standard glucose control, intensive one reduced MACE in those with baseline HbA1c <8.5% [relative risk (RR): 0.79, 95% confidence interval (CI): 0.67-0.93] and those with estimated glomerular filtration rate ≥106 ml/min/1.73 m2 (RR: 0.74, 95% CI: 0.55-0.99). Intensive BP control reduced MACE in those with normal high-density lipoprotein levels (women >55 mg/dl, men >45 mg/dl; RR: 0.51, 95% CI: 0.34-0.74). Risk reductions were not significant in other patient subgroups. CONCLUSIONS: Our findings suggest heterogeneous treatment effects of intensive glucose and BP control and could provide biomarkers for future clinical trials to identify more precise HbA1c and BP treatment goals for individualized medicine.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Masculino , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pressão Sanguínea , Glicemia , Hemoglobinas Glicadas , Fatores de Risco de Doenças Cardíacas , Biomarcadores , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controleRESUMO
AIM: To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). METHODS: A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. RESULTS: One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (ß 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (ß 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (ß ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (ß ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. CONCLUSIONS: Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Remodelação Ventricular , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/fisiopatologia , Masculino , Feminino , Adulto , Adulto Jovem , Idade de Início , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/patologia , Adolescente , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Fatores de Risco , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Glicemia/metabolismo , Glicemia/análise , Índice de Massa Corporal , Triglicerídeos/sangueRESUMO
AIM: Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this post-hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%-7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow-up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini-mental state examination and Stroop test. We used Cohen's d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD. RESULTS: Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini-mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen's d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen's d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: -0.57 in the Rey auditory verbal learning test, 95% CI: -1.09, -0.05, Cohen's d: -0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen's d: 0.13). All p < .05. CONCLUSIONS: Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Controle Glicêmico , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Idoso , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico/métodos , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Taxa de Filtração Glomerular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/fisiopatologiaRESUMO
AIMS: To investigate the prospective associations of the loneliness and social isolation scales with cardiovascular disease (CVD) risk in diabetes patients and compare the relative importance of loneliness and social isolation with traditional risk factors. Also, the interactions of loneliness or isolation with the degree of risk factor control in relation to CVD risk were evaluated. METHODS AND RESULTS: A total of 18 509 participants diagnosed with diabetes from the UK Biobank were included. A two-item scale and a three-item scale were used to assess loneliness and isolation levels, respectively. The degree of risk factor control was defined as numbers of glycated hemoglobin (HbA1c), blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), smoking, and kidney condition controlled within the target range. During a mean follow-up of 10.7 years, 3247 total CVD incidents were documented, including 2771 coronary heart disease and 701 strokes. In the fully adjusted model, compared with participants with the lowest loneliness score (zero), hazard ratios (95% confidence interval) for CVD were 1.11 (1.02 and 1.20) and 1.26 (1.11 and 1.42) for participants with a loneliness scale of 1 and 2, respectively (P-trend < 0.001). No significant associations were observed for social isolation. Loneliness ranked higher in relative strength for predicting CVD than the lifestyle risk factors in diabetes patients. A significant additive interaction between loneliness and the degree of risk factor control on the risk of CVD was observed (P for additive interaction = 0.005). CONCLUSION: Among diabetes patients, loneliness, but not social isolation scale, is associated with a higher risk of CVD and shows an additive interaction with the degree of risk factor control.
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Doenças Cardiovasculares , Diabetes Mellitus , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Solidão , Fatores de Risco , Diabetes Mellitus/epidemiologia , Fumar/epidemiologiaRESUMO
Importance: In 2013, the Trial to Assess Chelation Therapy (TACT) reported that edetate disodium (EDTA)-based chelation significantly reduced cardiovascular disease (CVD) events by 18% in 1708 patients with a prior myocardial infarction (MI). Objective: To replicate the finding of TACT in individuals with diabetes and previous MI. Design, Setting, and Participants: A 2 × 2 factorial, double-masked, placebo-controlled, multicenter trial at 88 sites in the US and Canada, involving participants who were 50 years or older, had diabetes, and had experienced an MI at least 6 weeks before recruitment compared the effect of EDTA-based chelation vs placebo infusions on CVD events and compared the effect of high doses of oral multivitamins and minerals with oral placebo. This article reports on the chelation vs placebo infusion comparisons. Interventions: Eligible participants were randomly assigned to 40 weekly infusions of an EDTA-based chelation solution or matching placebo and to twice daily oral, high-dose multivitamin and mineral supplements or matching placebo for 60 months. This article addresses the chelation study. Main Outcomes and Measures: The primary end point was the composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. Median follow-up was 48 months. Primary comparisons were made from patients who received at least 1 assigned infusion. Results: Of the 959 participants (median age, 67 years [IQR, 60-72 years]; 27% females; 78% White, 10% Black, and 20% Hispanic), 483 received at least 1 chelation infusion and 476 at least 1 placebo infusion. A primary end point event occurred in 172 participants (35.6%) in the chelation group and in 170 (35.7%) in the placebo group (adjusted hazard ratio [HR], 0.93; 95% CI, 0.76-1.16; P = .53). The 5-year primary event cumulative incidence rates were 45.8% for the chelation group and 46.5% for the placebo group. CV death, MI, or stroke events occurred in 89 participants (18.4%) in the chelation group and in 94 (19.7%) in the placebo group (adjusted HR, 0.89; 95% CI, 0.66-1.19). Death from any cause occurred in 84 participants (17.4%) in the chelation group and in 84 (17.6%) in the placebo group (adjusted HR, 0.96; 95% CI, 0.71-1.30). Chelation reduced median blood lead levels from 9.03 µg/L at baseline to 3.46 µg/L at infusion 40 (P < .001). Corresponding levels in the placebo group were 9.3 µg/L and 8.7 µg/L, respectively. Conclusions and Relevance: Despite effectively reducing blood lead levels, EDTA chelation was not effective in reducing cardiovascular events in stable patients with coronary artery disease who have diabetes and a history of MI. Trial Registration: ClinicalTrials.gov Identifier: NCT02733185.
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Obesity is associated with hypertension. However, the mechanisms involved are not fully understood. Therefore, we investigated the relationship between obesity and vasoactive mediators. In this cross-sectional study, blood pressure (BP) and vasoactive mediators of hypertension are compared among 135 adults in the nonobese, obese, and morbidly obese body mass index (BMI) ranges (BMI ≤27, 30-40, and >40 kg/m2, respectively). Angiotensinogen, angiotensin II, renin, aldosterone, endothelin-1 (ET-1), neprilysin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP) levels were measured and their relationship to BP, BMI, race, and gender were investigated. Systolic and diastolic BP (SBP and DSP) were significantly higher in subjects with obesity and morbid obesity compared with nonobese. Angiotensin II, ET-1, and neprilysin were significantly higher in subjects with morbid obesity while BNP was lower. Levels of angiotensinogen, renin, aldosterone, ANP, cGMP, and cAMP did not differ between the groups. BMI was positively related to SBP, DBP, angiotensin II, ET-1, and neprilysin, and inversely related to cGMP and BNP. Age, male gender, and African-American race were associated with higher SBP. SBP was positively related to angiotensin II and ET-1 and inversely related to aldosterone, renin, and cGMP. On multivariate analyses, age, BMI, gender, and race were the main determinants of SBP, and excluding these variables, angiotensin II, aldosterone, renin, and ET-1 accounted for 21.1% ability to predict SBP. Obesity, especially morbid obesity, is associated with higher BP, higher angiotensin II and ET-1 (vasoconstrictors), and lower levels BNP and cGMP (vasodilators). SBP variability can be partly explained by angiotensin II, aldosterone, renin, and ET-1.NEW & NOTEWORTHY Our data show that obesity, especially morbid obesity, is associated with higher blood pressure levels and increases angiotensin II and endotherlin-1 (ET-1) (vasoconstrictors) and lower levels BNP and cGMP (vasodilators) and that systolic blood pressure variability can be partly explained by levels of angiotensin II, aldosterone, renin, and ET-1. The effect of these mediators on blood pressure is in addition to the effects of other known factors related to age, male gender, and AA race.
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Hipertensão , Obesidade Mórbida , Adulto , Humanos , Masculino , Renina , Angiotensinogênio/farmacologia , Sistema Renina-Angiotensina , Aldosterona/farmacologia , Angiotensina II/farmacologia , Estudos Transversais , Neprilisina , Hipertensão/complicações , Pressão Sanguínea , Vasodilatadores , VasoconstritoresRESUMO
BACKGROUND: Evidence of the effectiveness of treatment for obesity delivered in primary care settings in underserved populations is lacking. METHODS: We conducted a cluster-randomized trial to test the effectiveness of a high-intensity, lifestyle-based program for obesity treatment delivered in primary care clinics in which a high percentage of the patients were from low-income populations. We randomly assigned 18 clinics to provide patients with either an intensive lifestyle intervention, which focused on reduced caloric intake and increased physical activity, or usual care. Patients in the intensive-lifestyle group participated in a high-intensity program delivered by health coaches embedded in the clinics. The program consisted of weekly sessions for the first 6 months, followed by monthly sessions for the remaining 18 months. Patients in the usual-care group received standard care from their primary care team. The primary outcome was the percent change from baseline in body weight at 24 months. RESULTS: All 18 clinics (9 assigned to the intensive program and 9 assigned to usual care) completed 24 months of participation; a median of 40.5 patients were enrolled at each clinic. A total of 803 adults with obesity were enrolled: 452 were assigned to the intensive-lifestyle group, and 351 were assigned to the usual-care group; 67.2% of the patients were Black, and 65.5% had an annual household income of less than $40,000. Of the enrolled patients, 83.4% completed the 24-month trial. The percent weight loss at 24 months was significantly greater in the intensive-lifestyle group (change in body weight, -4.99%; 95% confidence interval [CI], -6.02 to -3.96) than in the usual-care group (-0.48%; 95% CI, -1.57 to 0.61), with a mean between-group difference of -4.51 percentage points (95% CI, -5.93 to -3.10) (P<0.001). There were no significant between-group differences in serious adverse events. CONCLUSIONS: A high-intensity, lifestyle-based treatment program for obesity delivered in an underserved primary care population resulted in clinically significant weight loss at 24 months. (Funded by the Patient-Centered Outcomes Research Institute and others; PROPEL ClinicalTrials.gov number, NCT02561221.).
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Disparidades em Assistência à Saúde , Estilo de Vida Saudável , Obesidade/terapia , Populações Vulneráveis , Redução de Peso , Adulto , Idoso , Dieta Redutora , Exercício Físico , Feminino , Letramento em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Obesidade/fisiopatologia , Educação de Pacientes como Assunto , Atenção Primária à Saúde , Fatores Socioeconômicos , Adulto JovemRESUMO
AIMS: We evaluated the impact of reimbursement for non-face-to-face chronic care management (NFFCCM) on comprehensive metabolic risk factors among multimorbid Medicare beneficiaries with type 2 diabetes in Louisiana. MATERIALS AND METHODS: We implemented a propensity score method to obtain comparable treatment (n=1501 with NFFCCM) and control (n=17,524 without NFFCCM) groups. Patients with type 2 diabetes were extracted from the electronic health records stored in REACHnet. The study period was from 2013 to February 2020. The comprehensive metabolic risk factors included the primary outcome of glycated hemoglobin (HbA1c) (as the primary outcome) and the secondary outcomes of body mass index (BMI), systolic blood pressure (BP), and low-density lipoprotein cholesterol. RESULTS: Receiving any NFFCCM was associated with improvement in all outcomes measures: a reduction in HbA1c of 0.063% (95% CI: 0.031%-0.094%; P <0.001), a reduction in BMI of 0.155 kg/m 2 (95% CI: 0.029-0.282 kg/m 2 ; P =0.016), a reduction in systolic BP of 0.816 mm Hg (95% CI: 0.469-1.163 mm Hg; P <0.001), and a reduction in low-density lipoprotein cholesterol of 1.779 mg/dL (95% CI: 0.988 2.570 mg/dL; P <0.001). Compared with the control group, the treatment group had 1.6% more patients with HbA1c <7% (95% CI: 0.3%-2.9%; P =0.013). CONCLUSIONS: Patients with diabetes in Louisiana receiving NFFCCM experienced better control of HbA1c, BMI, BP, and low-density lipoprotein outcomes.
Assuntos
Diabetes Mellitus Tipo 2 , Reembolso de Seguro de Saúde , Idoso , Humanos , Biomarcadores , Colesterol , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas , Lipoproteínas LDL , Medicare , Estados Unidos , Multimorbidade , LouisianaRESUMO
AIMS: A cost-effectiveness analysis was conducted to compare insulin glargine 300 U/mL (Gla-300) versus insulin degludec 100 U/mL (IDeg-100) in insulin-naïve adults with type 2 diabetes (T2D) sub-optimally controlled with oral anti-diabetic drugs (OADs). METHODS: The BRAVO diabetes model was used to assess costs and outcomes for once-daily Gla-300 versus once-daily IDeg-100 from a US healthcare sector perspective. Baseline clinical data were based on BRIGHT, a 24-week, non-inferiority, randomised control trial comparing Gla-300 and IDeg-100 in adults with T2D sub-optimally controlled with OADs (with or without glucagon-like peptide-1 receptor agonists). Treatment costs were based on doses observed in BRIGHT as well as net prices. Costs associated with complications were based on published literature. Lifetime costs (US$) and quality-adjusted life-years (QALYs) were predicted and used to calculate incremental cost-effectiveness ratio estimates; extensive scenario and sensitivity analyses were conducted. RESULTS: Overall lifetime medical costs were estimated to be $327,904 and $330,154 for people receiving Gla-300 and IDeg-100, respectively; insulin costs were $43,477 and $44,367, respectively. People receiving Gla-300 gained 8.024 QALYs and 18.55 life-years, while people receiving IDeg-100 gained 7.997 QALYs and 18.52 life-years. Because Gla-300 was associated with a cost-saving of $2250 and 0.027 additional QALYs, it was considered to be dominant compared with IDeg-100. Results of the scenario and sensitivity analyses confirmed the robustness of the base case results. CONCLUSION: Gla-300 was the dominant treatment option compared with IDeg-100 based on the willingness-to-pay threshold of $50,000/QALY. Results remained robust against a wide range of alternative assumptions on key parameters.
Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Insulina Glargina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Análise de Custo-Efetividade , Análise Custo-Benefício , Insulina/uso terapêuticoRESUMO
AIM: Early identification of incident chronic kidney disease (CKD) in individuals with diabetes may help improve patients' clinical outcomes. This study aimed to develop a prediction equation for incident CKD among people with type 2 diabetes (T2D). MATERIALS AND METHODS: A time-varying Cox model was applied to data from the ACCORD trial to predict the risk of incident CKD. A list of candidate variables was chosen based on literature reviews and experts' consultations, including demographic characteristics, vitals, laboratory results, medical history, drug use and health care utilization. Model performance was evaluated. Decomposition analysis was conducted, and external validation was performed. RESULTS: In total, 6006 patients with diabetes free of CKD were included, with a median follow-up of 3 years and 2257 events. The risk model included age at T2D diagnosed, smoking status, body mass index, high-density lipoprotein, very-low-density lipoprotein, alanine aminotransferase, estimated glomerular filtration rate, urine albumin-creatinine ratio, hypoglycaemia, retinopathy, congestive heart failure, coronary heart disease history, antihyperlipidaemic drug use, antihypertensive drug use and hospitalization. The urine albumin-creatinine ratio, estimated glomerular filtration rate and congestive heart failure were the top three factors that contributed most to the incident CKD prediction. The model showed acceptable discrimination [C-statistic: 0.772 (95% CI 0.767-0.805)] and calibration [Brier Score: 0.0504 (95% CI 0.0477-0.0531)] in the Harmony Outcomes Trial. CONCLUSION: Incident CKD prediction among individuals with T2D was developed and validated for use in decision support of CKD prevention.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Estados Unidos/epidemiologia , Pré-Escolar , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Fatores de Risco , Creatinina/urina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Taxa de Filtração Glomerular , AlbuminasRESUMO
AIMS: To explore the modifying effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on outcomes with finerenone across a wide spectrum of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the pooled analysis of FIDELIO-DKD and FIGARO-DKD. MATERIALS AND METHODS: Patients with T2D and CKD treated with optimized renin-angiotensin system blockade were randomized to finerenone or placebo. Effects of finerenone on a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite outcome (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decline, or renal death), change in urine albumin-to-creatinine ratio (UACR), and safety were analysed by GLP-1RA use. RESULTS: Of 13 026 patients, 944 (7.2%) used GLP-1RAs at baseline. Finerenone reduced the risk of the cardiovascular composite outcome (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.52-1.11 with GLP-1RA; HR 0.87, 95% CI 0.79-0.96 without GLP-1RA; P-interaction = 0.63) and the kidney composite outcome (HR 0.82, 95% CI 0.45-1.48 with GLP-1RA; HR 0.77, 95% CI 0.67-0.89 without GLP-1RA; P-interaction = 0.79) irrespective of baseline GLP-1RA use. Reduction in UACR with finerenone at Month 4 was -38% in patients with baseline GLP-1RA use compared with -31% in those without GLP-1RA use (P-interaction = 0.03). Overall safety and incidence of hyperkalaemia were similar, irrespective of GLP-1RA use. CONCLUSIONS: The cardiorenal benefits of finerenone on composite cardiovascular and kidney outcomes and UACR reduction in patients with CKD and T2D appear to be maintained, regardless of GLP-1RA use. Subsequent studies are needed to investigate any potential benefit of this combination.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Naftiridinas/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológicoRESUMO
OBJECTIVES: We evaluated the impact of reimbursement for non-face-to-face chronic care management (NFFCCM) on healthcare utilization among Medicare beneficiaries with type 2 diabetes in Louisiana. METHODS: We implemented group-based trajectory balancing and propensity score matching to obtain comparable treatment (with NFFCCM) and control (without NFFCCM) groups at baseline. Patients with diabetes with Medicare as their primary payer at baseline were extracted using electronic health records of 3 health systems from Research Action for Health Network, a Clinical Research Network. The study period is from 2013 to early 2020. Our outcomes include general healthcare utilization (outpatient, emergency department, and inpatient encounters) and health utilization related to diabetic complications. We tested each of these outcomes according to multiple treatment definitions and different subgroups. RESULTS: Receiving any NFFCCM was associated with an increase in outpatient visits of 657 (95% confidence interval [CI] 626-687; P < .001) per 1000 patients per month, a decrease in inpatient admissions of 5 (95% CI 2-7; P < .001) per 1000 patients per month, and a decrease in emergency department visits of 4 (95% CI 1-7; P = .005) per 1000 patients per month after 24-month follow-up from initial NFFCCM encounter. Both complex and noncomplex NFFCCM significantly increased visits to outpatient services and inpatient admissions per month. Receiving NFFCCM has a dose-response association with increasing outpatient visits per month. CONCLUSIONS: Patients with diabetes in Louisiana who received NFFCCM had more low-cost primary healthcare and less high-cost healthcare utilization in general. The cost savings of NFFCCM in diabetes management could be further explored in the future.
Assuntos
Diabetes Mellitus Tipo 2 , Idoso , Humanos , Estados Unidos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicare , Louisiana , Atenção à Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Estudos RetrospectivosRESUMO
BACKGROUND: Currently there are limited data as to whether dietary intake can be improved during pragmatic weight loss interventions in primary care in underserved individuals. METHODS: Patients with obesity were recruited into the PROPEL trial, which randomized 18 clinics to either an intensive lifestyle intervention (ILI) or usual care (UC). At baseline and months 6, 12, and 24, fruit and vegetable (F/V) intake and fat intake was determined. Outcomes were analyzed by repeated-measures linear mixed-effects multilevel models and regression models, which included random cluster (clinic) effects. Secondary analyses examined the effects of race, sex, age, and food security status. RESULTS: A total of 803 patients were recruited. 84.4% were female, 67.2% African American, 26.1% received Medicaid, and 65.5% made less than $40,000. No differences in F/V intake were seen between the ILI and UC groups at months 6, 12, or 24. The ILI group reduced percent fat at months 6, 12, and 24 compared to UC. Change in F/V intake was negatively correlated with weight change at month 6 whereas change in fat intake was positively associated with weight change at months 6, 12, and 24 for the ILI group. CONCLUSIONS: The pragmatic weight loss intervention in primary care did not increase F/V intake but did reduce fat intake in an underserved population with obesity. F/V intake was negatively associated with weight loss at month 6 whereas percent fat was positively correlated with weight loss throughout the intervention. Future efforts better targeting both increasing F/V intake and reducing fat intake may promote greater weight loss in similar populations. TRIAL REGISTRATION: NCT Registration: NCT02561221.
Assuntos
Ingestão de Alimentos , Populações Vulneráveis , Humanos , Feminino , Masculino , Obesidade/terapia , Redução de Peso , Atenção Primária à SaúdeRESUMO
Paired box 4 (Pax4) is a key transcription factor involved in the embryonic development of the pancreatic islets of Langerhans. Consisting of a conserved paired box domain and a homeodomain, this transcription factor plays an essential role in early endocrine progenitor cells, where it is necessary for cell-fate commitment towards the insulin-secreting ß cell lineage. Knockout of Pax4 in animal models leads to the absence of ß cells, which is accompanied by a significant increase in glucagon-producing α cells, and typically results in lethality within days after birth. Mutations in Pax4 that cause an impaired Pax4 function are associated with diabetes pathogenesis in humans. In adulthood, Pax4 expression is limited to a distinct subset of ß cells that possess the ability to proliferate in response to heightened metabolic needs. Upregulation of Pax4 expression is known to promote ß cell survival and proliferation. Additionally, ectopic expression of Pax4 in pancreatic islet α cells or δ cells has been found to generate functional ß-like cells that can improve blood glucose regulation in experimental diabetes models. Therefore, Pax4 represents a promising therapeutic target for the protection and regeneration of ß cells in the treatment of diabetes. The purpose of this review is to provide a thorough and up-to-date overview of the role of Pax4 in pancreatic ß cells and its potential as a therapeutic target for diabetes.