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Introduction Methods Results Conclusion The cumulative impact of metabolic syndrome (MetS) components on micro‐ and macrovascular disease in metabolic dysfunction‐associated steatotic liver disease (MASLD) is unclear. We aimed to determine whether the number of the MetS components increases the risk of micro‐ and macrovascular disease in patients with MASLD.We performed a retrospective cohort study of electronic medical records using the TriNetX network, a global federated database. The exposure arm was patients with hepatic steatosis (defined via International Classification of Diseases, 10th Revision coding, or modified hepatic steatosis index), and ≥1 MetS components (obesity/central adiposity, insulin resistance, hypertension, or dyslipidaemia), compared with a reference arm of adults without any MetS components or hepatic steatosis. Our propensity score matched (1:1) for confounders with 5 years of follow‐up. Primary outcomes included microvascular (peripheral neuropathy, retinopathy, and nephropathy) and macrovascular (cardiovascular events, cerebrovascular accidents, and peripheral vascular disease) disease. Secondary analyses assessed the impact of additional MetS components on these outcomes, as well as the impact of sex.MASLD, defined by hepatic steatosis and insulin resistance (n = 15 937), carried the highest risk of microvascular disease (HR 13.93 (95% CI 8.55–22.68)), whilst MASLD, defined by hepatic steatosis and hypertension (n = 53 028), carried the highest risk of macrovascular disease (7.23 (6.45–8.13)). MASLD with all MetS components carried greatest risk of both micro‐ (31.20 (28.88–33.70) (n = 462 789)) and macrovascular (8.04 (7.33–8.82) (n = 336 010)) disease.We demonstrate a differential effect of MetS components on micro‐ and macrovascular disease risk in patients with MASLD, with a cumulative impact of multiple MetS on overall risk. The impact of MetS components was most pronounced in women. Aggressive metabolic risk factor management is critical for prevention of micro‐ and macrovascular complications. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long‐term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all‐cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta‐analysis. Methods: A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long‐term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random‐effects meta‐analysis. Risk of bias and evidence quality were assessed using Cochrane‐endorsed tools. Results: Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78‐0.88]). Secondary analysis showed significant risk reduction in all‐cause mortality (0.79 [0.72‐0.87]) and foot ulceration (0.67 [0.53‐0.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta‐analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79‐0.87]) (I2 = 10.76%). Conclusions: This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all‐cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Sodium–glucose cotransporter 2 inhibitors (SGLT2is), used as a glucose‐lowering therapy in people with type 2 diabetes (T2D), have significant cardiorenal benefits, reducing hospitalization for heart failure (HF) and cardiovascular mortality in patients with and without T2D. Recent clinical trial evidence suggests their potential utility in preventing incident T2D among the high‐risk HF populations. Therefore, we aimed to assess whether this finding was reproducible in a real‐world setting.We performed a retrospective cohort analysis of 484 643 patients with HF, without baseline diabetes, prescribed either angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers with/without SGLT2is (treatment, n = 42 018; reference, n = 442 625) across 95 global health care organizations, using a large real‐world ecosystem. Propensity score matching balanced arms 1:1 for confounders (n = 39 168 each arm). Subgroup analysis further evaluated the impact on patients with prediabetes and the efficacy of dapagliflozin/empagliflozin, specifically, on incident T2D and secondary outcomes, including all‐cause mortality, acute pulmonary oedema and hospitalization.Treatment with SGLT2is significantly reduced incident T2D {hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.63, 0.75]} in patients with HF. The analysis of patients with prediabetes found that SGLT2is further reduced incident T2D [HR 0.62 (95% CI 0.45, 0.80)]. The magnitude of reduction in incident T2D was higher in patients prescribed dapagliflozin [HR 0.47 (95% CI 0.39, 0.56)] versus empagliflozin [HR 0.81 (95% CI 0.70, 0.93)].Treatment with SGLT2is in patients with HF was associated with a reduced risk of incident T2D, most strikingly in people with prediabetes. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusions We examined the impact of a co‐diagnosis of metabolic dysfunction‐associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.Using TriNetX, a global federated research network (n = 114 million), we undertook two retrospective cohort studies, using time‐to‐event analysis. Analysis 1 compared MASLD with T2D to MASLD alone; analysis 2 compared T2D with MASLD to T2D alone. Propensity score matching using greedy nearest neighbour (calliper .1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes‐related, and cancer events over 5 years.Analysis 1 (n = 95 275): a co‐diagnosis of T2D significantly increased the risk of ischaemic heart disease (IHD) (HR 1.39; CI: 1.34, 1.44), ischaemic stroke (HR 1.45; CI: 1.35, 1.56), heart failure (HR 1.42; CI: 1.36, 1.49), atrial fibrillation (HR 1.09; CI: 1.03, 1.16), hepatocellular carcinoma (HR 1.96; CI: 1.69, 2.27), pancreatic cancer (HR 1.25; CI: 1.06, 1.48) and liver‐related complications over 5 years from MASLD diagnosis. Analysis 2 (n = 15 208): a co‐diagnosis of MASLD significantly increased risk of all‐cause mortality (HR 1.11; CI: 1.02, 1.22), IHD (HR 1.181; CI: 1.08, 1.29), hepatocellular (HR 50.31; CI: 6.94, 364.72), pancreatic (HR 1.78; CI: 1.12, 2.84), breast (HR 1.43; CI: 1.09, 1.88) and renal cancer (HR 2.01; CI: 1.24, 3.26), and diabetic neuropathy (HR 1.17; CI: 1.09, 1.27) over 5 years from metformin initiation.T2D significantly potentiates the risk of cardiovascular, malignancy and liver‐related outcomes in people with MASLD. The effect of MASLD on people with T2D, although less dramatic, still potentiated risk of death, IHD, malignancy and peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Aim: To assess the relationship of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), glucagon‐like peptide‐1 receptor analogues (GLP‐1RA) and their combination (SGLT2i + GLP‐1RA) with 5‐year risk of all‐cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes. Materials and Methods: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP‐1RA and SGLT2i + GLP‐1RA) were compared against a control cohort (no SGLT2i/GLP‐1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP‐1RA, n = 186 841; SGLT‐2i + GLP‐1RA, n = 108 504). A sub‐analysis comparing combination and monotherapy cohorts was also performed. Results: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all‐cause mortality (SGLT2i 0.49, 0.48‐0.50; GLP‐1RA 0.47, 0.46‐0.48; combination 0.25, 0.24‐0.26), hospitalization (0.73, 0.72‐0.74; 0.69, 0.68‐0.69; 0.60, 0.59‐0.61) and acute myocardial infarct (0.75, 0.72‐0.78; 0.70, 0.68‐0.73; 0.63, 0.60‐0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub‐analysis showed a significant risk reduction in all‐cause mortality for combination therapy versus SGLT2i (0.53, 0.50‐0.55) and GLP‐1RA (0.56, 0.54‐0.59). Conclusions: SGLT2i, GLP‐1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all‐cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5‐year all‐cause mortality when compared directly against either monotherapy. [ABSTRACT FROM AUTHOR]

Based on the author's work with the American Indian Housing Initiative, this essay presents the reflections of a faculty member whose experiences with public scholarship have shaped his views on teaching global citizenship. [ABSTRACT FROM AUTHOR]