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Aim: To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis., Methods: This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes., Results: Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05)., Conclusion: We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Diabetes mellitus (DM) is a common metabolic disease associated with severe macrovascular and microvascular complications that influence nearly every tissue in the body, including the anterior and posterior segments of the eye. In the cornea, DM is associated with recurrent epithelial erosion and reduced wound-healing capacity, which increases the risk of corneal scarring. We previously developed a co-culture model of the cornea consisting of immortalized human corneal epithelial cells (hCE-TJ) overlaying a self-assembled stromal layer generated by human corneal fibroblasts (hCFs) over a 4-week period. In this study, we investigated epithelial-stromal constructs generated from hCFs derived from subjects with Type 1 (T1DM) or 2 diabetes (T2DM) compared to controls. We found that T2DM constructs exhibited a disrupted epithelium and a thicker, stratified stromal layer compared to controls or T1DM. Both T1DM and T2DM stromal constructs expressed lower expression of thrombospondin-1 in isolated extracellular vesicles (EVs) compared to controls with no significant difference observed in the presence of epithelial cells, suggesting that reduced provisional matrix secretion in the corneal stroma may be a factor that promotes delayed corneal wound healing in diabetes. The tetraspanins are established extracellular vesicle (EV) markers and include CD63, CD81, and CD9, and were highly expressed by EVs in all three cell types. Control corneal stromal fibroblasts produced more and larger EVs when compared to T1DM and T2DM hCF-derived EVs, supporting a role for altered cell-cell communication in the context of DM. Further characterization of EVs and their cargo is expected to aid in the development of targeted treatments to improve corneal wound healing., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This is a summary of the original article 'Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan'. The slowing down of kidney function decline is important for managing chronic kidney disease (CKD) and preventing its complications. Clinical trials of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), have shown reductions in disease progression and death in patients with CKD and elevated levels of albuminuria. This summary of research provides an overview of a previously published article that aimed to find out whether dapagliflozin is also effective in patients with lower levels of albuminuria [urinary albumin-to-creatinine ratio (UACR) below 200 mg/g]. Starting dapagliflozin was associated with slower kidney function decline in patients with CKD and UACR below 200 mg/g compared with not starting. This effect was also observed in a subgroup analysis of patients without type 2 diabetes. These results suggest that the established benefits of SGLT-2is may extend to patients with lower levels of albuminuria., (© 2024. The Author(s).)

Aim: To analyse patterns of glucose-lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023., Materials and Methods: We examined time trends in the clinical profiles of people with T2D who initiated different glucose-lowering therapy classes for the first time. We furthermore investigated individual-level treatment trajectories following first-ever glucose-lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first-ever prescription for metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) or insulin, excluding those without HbA1c-confirmed T2D or probable type 1 diabetes., Results: We included 260 393 individuals initiating a new glucose-lowering therapy class from 2016 to 2023, during which there were 6- and 3-fold increases in initiators of GLP-1RAs and SGLT-2is, respectively. The median HbA1c level at treatment initiation with GLP-1RAs or SGLT-2is decreased, from 67-68 mmol/mol in 2016-2017 to 57-58 mmol/mol in 2022-2023. Among individuals who initiated metformin as first-line therapy, the proportion who started additional glucose-lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first-ever glucose-lowering therapy in 2020, 22% used SGLT-2is and 18% GLP-1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively., Conclusions: Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP-1RAs and SGLT-2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD., Objective: To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD., Design, Setting, and Participants: This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health Administration hospitals and associated ambulatory clinics and who initiated either a GLP-1 RA or dipeptidyl peptidase 4 inhibitor (DPP-4i) between January 1, 2006, and June 30, 2022, were included. Patients were followed up from baseline until one of the study outcomes or the end of the study period (December 31, 2022), whichever came first., Exposures: Each GLP-1 RA new user was propensity score matched in 1:1 ratio to a patient who initiated a DPP-4i during the same month. Separate analyses were conducted among patients without and with cirrhosis at baseline., Main Outcomes and Measures: For patients without cirrhosis, the primary outcome was progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, and secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant, and all-cause mortality. For patients with cirrhosis, the primary outcome was a composite outcome of cirrhosis complications, and secondary outcomes were decompensation, HCC, and all-cause mortality., Results: Of 16 058 patients who initiated GLP-1 RAs, 14 606 did not have cirrhosis (mean [SD] age, 60.56 [10.31] years; 13 015 [89.1%] male), and 1452 had cirrhosis (mean [SD] age, 66.99 [7.09] years; 1360 [93.7%] male) at baseline. These patients were matched to an equal number of patients who initiated a DPP-4i. In patients without cirrhosis, GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of cirrhosis (9.98 vs 11.10 events per 1000 person-years; hazard ratio [HR], 0.86; 95% CI, 0.75-0.98). Similar results were seen for the secondary outcomes. GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of the composite outcome of cirrhosis complications (1.89 vs 2.55 events per 1000 person-years; HR, 0.78; 95% CI, 0.59-1.04) and mortality (21.77 vs 24.43 events per 1000 person-years; HR, 0.89; 95% CI, 0.81-0.98). There were no associations between GLP-1 RA use and outcomes in patients with cirrhosis., Conclusions and Relevance: In this cohort study, GLP-1 RA use was associated with a lower risk of progression to cirrhosis and mortality among patients with MASLD and diabetes. The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the disease course.

Aim: Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are used to maintain glycaemic control as well as for their beneficial cardiovascular and renal effects in diabetes patients. However, increased risk of amputation and peripheral artery disease (PAD) have been observed with the use of some SGLT-2is. A meta-analysis was conducted to understand the effect of SGLT-2is on amputation and PAD events using data from randomized controlled trials (RCT)., Materials and Methods: A systematic literature review was conducted using Medline and Central databases for RCTs that involved the administration of SGLT-2is versus placebo/active comparators to diabetic patients. The primary outcome was amputation events and PAD. A random-effects model was used to calculate the pooled odds ratio, and subgroup analyses was performed., Results: A total of 51 RCTs were included in the meta-analysis with data from 97 589 patients. Meta-analysis of the data showed that there was a significant increase in PAD risk (p = 0.04) but no significant increase in amputation risk with SGLT-2i use versus placebo/active comparators (p = 0.43). Subgroup analyses demonstrated no significant difference between SGLT-2i type, duration of treatment or patient risk factors on amputation or PAD incidence. However, length of drug treatment (> 100 weeks) was associated with a significant increase in both PAD and amputation risks in the SGLT-2i treatment groups., Conclusions: The results of the meta-analysis showed no significant association between SGLT-2i use and PAD and amputation risks in diabetic patients when used for shorter treatment durations., (© 2024 John Wiley & Sons Ltd.)

Hypertension and diabetes are currently the most common, treatable, and controllable cardiovascular and metabolic risk factors for stroke, heart, and renal diseases in Cameroon. Hypertension affects 30% of adults aged ≥ 20 years with 90% as uncontrolled cases, while type 2 diabetes affects 6% of the same population, with 70% remaining underdiagnosed. Despite publication of the first Roadmap on raised blood pressure by the World Heart Federation in 2015, the Pan African Society of Cardiology Roadmap in 2017, and the technical package for cardiovascular disease management in primary health care (WHO-HEARTS) in 2020, very little progress has been made in improving the diagnosis, treatment, and control of cardiovascular risk factors and diseases in Cameroon. The Cameroon Cardiac Society and a dozen Cameroon non-communicable diseases societies, national organizations from the community and the civil society, along with researchers and members of academia and the health sector, came together under the patronage of representatives of the government to propose new strategies to improve hypertension and diabetes control and save lives in Cameroon. Two simple and practical algorithms for the management of hypertension and diabetes were developed. The ten recommendations tailored to be efficiently implemented in our country were summarized under the acronym 'A SMART VIEW' (Awareness, Screening, Manufacture, Activity, Research, Task-shifting, HIV/AIDS, Insurance, Education, and WHO-HEARTS). It is our hope that all stakeholders will further collaborate to remove barriers and enhance facilitators to deploy the proposed actions and reduce the burden of uncontrolled hypertension and untreated diabetes in Cameroon., (© 2024. The Author(s).)

Insulin resistance, defined as an impaired biological response to insulin stimulation in target tissues, arises most frequently in the presence of central obesity. Although obesity is generally associated with increased bone mass, recent data challenge this view and, if complicated by T2DM, obese patients are at high risk for fragility fractures. IR may play a key role in this increased fracture risk through effects on bone quality rather than bone quantity. Further understanding of the mechanisms and approaches to prevent osteoporotic fractures in IR-related diseases is needed., Clinical Relevance: The dramatic increase in obesity and metabolic syndrome (MetS) over the last half-century has led to a worldwide epidemic of type 2 diabetes mellitus (T2DM) as well as in the incidence of insulin resistance (IR). IR is defined as an impaired biological response to insulin stimulation in target tissues and is primarily related to the liver, muscle, and adipose tissue. The most frequent underlying cause is central obesity, and it is known that excess abdominal adipose tissue secretes increased amounts of free fatty acids, which directly affects insulin signalling, reduces glucose uptake in muscle, and triggers excessive triglyceride synthesis and gluconeogenesis in the liver. When pancreatic β cells are unable to secrete the higher levels of insulin needed, T2DM, the main complication of IR, occurs., Observations: Although obesity is generally associated with increased bone mass, recent data challenge this view and highlight the multifaceted nature of the obesity-bone relationship. Patients with T2DM are at significant risk for well-known complications of diabetes, including retinopathy, nephropathy, macrovascular disease, and neuropathy, but it is clear that they are also at high risk for fragility fractures. Moreover, recent data provide strong evidence that IR may key role in the increased fracture risk observed in both obesity and T2DM., Conclusions: In this concise review article, the role of IR in increased risk of osteoporotic fractures in MetS, obesity, and T2DM is discussed and summarised, including consideration of the need for fracture risk assessment as a 'preventive measure', especially in patients with T2DM and chronic MetS with abdominal obesity. Personalised and targeted diagnostic and therapeutic approaches to prevent osteoporotic fractures in IR-related diseases are needed and could make significant contributions to health outcomes., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Optimal glycaemic control has well-established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver-related outcomes., Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver-related mortality., Methods: In a population-based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3-year lead-in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver-related mortality., Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow-up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver-related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61-0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29-1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54-0.80), sex (SHR 0.68-0.69), BMI <25 or ≥25 kg/m 2 (SHR 0.63-0.75), smoking (SHR 0.61-0.72), hepatic steatosis (SHR 0.67-0.68) and aspirin/statin/metformin use (SHR 0.67-0.75). A lower risk of liver-related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61-0.80)., Conclusions: Glycaemic control is an independent risk factor for HCC and liver-related mortality, and should be incorporated into oncoprotective strategies in the general DM population., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Aims/introduction: To assess whether the sodium-glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes., Materials and Methods: We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis., Results: Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19-23) versus 22 (IQR 20-25; P < 0.0001) in all patients, 21 (IQR 19-23) versus 24 (IQR 22-26; P < 0.0001) in the henagliflozin group and 21 (IQR 19-22) versus 21 (IQR 19-23; P > 0.05) in the non-sodium-glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224-6.056, P < 0.0001). Additionally, plasma phosphorylated tau181 levels significantly decreased at 6-month follow up in all patients (OR 11.5, 95% CI 9.9-13.7 vs OR 10.1, 95% CI 7.8-12.9, P < 0.0001) and in the henagliflozin group (OR 11.5, 95% CI 10.3-13.0 vs OR 9.2, 95% CI 7.1-10.7, P < 0.0001), but not in the non-sodium-glucose cotransporter 2 inhibitor group. Henagliflozin treatment was independently associated with decreased phosphorylated tau181 levels (OR 3.670, 95% CI 1.598-4.213, P < 0.0001)., Conclusions: Henagliflozin treatment was independently associated with improvements in Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels, indicating significant beneficial effects on cognitive impairment in patients with type 2 diabetes., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Non-alcoholic (now: metabolic) steatohepatitis (MASH) is the progressive inflammatory form of metabolic dysfunction-associated steatotic liver disease (MASLD), which often coexists and mutually interacts with type 2 diabetes (T2D), resulting in worse hepatic and cardiovascular outcomes. Understanding the intricate mechanisms of diabetes-related MASH progression is crucial for effective therapeutic strategies. This review delineates the multifaceted pathways involved in this interplay and explores potential therapeutic implications. The synergy between adipose tissue, gut microbiota, and hepatic alterations plays a pivotal role in disease progression. Adipose tissue dysfunction, particularly in the visceral depot, coupled with dysbiosis in the gut microbiota, exacerbates hepatic injury and insulin resistance. Hepatic lipid accumulation, oxidative stress, and endoplasmic reticulum stress further potentiate inflammation and fibrosis, contributing to disease severity. Dietary modification with weight reduction and exercise prove crucial in managing T2D-related MASH. Additionally, various well-known but also novel anti-hyperglycemic medications exhibit potential in reducing liver lipid content and, in some cases, improving MASH histology. Therapies targeting incretin receptors show promise in managing T2D-related MASH, while thyroid hormone receptor-β agonism has proven effective as a treatment of MASH and fibrosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SG declares no competing interests. MR reports consulting fees and/or speaker’s fees from Astra Zeneca, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk and Boehringer Ingelheim and is supported for investigator-initiated trials by Boehringer Ingelheim and Novo Nordisk. LC reports consulting fees from Boston pharmaceutical, Echosens, Gilead, GSK, Madrigal, MSD, Novo Nordisk, Pfizer, Sagimet and Siemens Healthineers and speaker fees from Echosens, Gilead, Inventiva, Madrigal and Novo Nordisk., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: To examine the likelihood of mortality or rehospitalization following acute coronary syndrome with glyburide versus gliclazide use in adults with type 2 diabetes undergoing cardiac catheterization., Research Design and Methods: This retrospective cohort study used clinical data linked with administrative health data from Alberta, Canada between April 2008 and March 2021. Three methods were used to define exposure to glyburide and gliclazide in the year before catheterization. Multivariable logistic regression was used to compare the likelihood of a composite outcome of 1-year mortality or rehospitalization with use of glyburide versus use of gliclazide., Results: A total of 11 140 individuals with type 2 diabetes had a cardiac catheterization for acute coronary syndrome. Their mean age was 66 years and 31% were female. In the year before catheterization, 5% used glyburide and 19% used gliclazide. Any glyburide or gliclazide exposure in the year before catheterization was associated with a similar likelihood of all-cause mortality or rehospitalization (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 0.93-1.41; p = 0.20). However, current glyburide exposure (aOR 1.37, 95% CI 1.06-1.79; p = 0.018) and long exposure to glyburide (aOR 1.37, 95% CI 1.03-1.83; p = 0.030) were associated with a higher likelihood of the composite outcome compared to current and long exposure to gliclazide, respectively., Conclusions: Current and long exposure to glyburide was associated with a greater likelihood of mortality or rehospitalization following cardiac catheterization for acute coronary syndrome, when compared to similar gliclazide exposure definitions. This study adds further evidence of the need to avoid using glyburide if a sulphonylurea is required for type 2 diabetes management., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA)., Methods: In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted., Results: Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality)., Conclusions: The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA., (© 2024 John Wiley & Sons Ltd.)

Background: Given sparse relevant data, the aim of this study was to determine whether Helicobacter pylori infection, including cytotoxin-associated gene-A (CagA) producing strains, is associated with dementia in type 2 diabetes (T2DM)., Methods: Longitudinal data from 1115 participants in the community-based Fremantle Diabetes Study Phase I (mean age 64.0 years, 48.0 % males; 38.0 % H. pylori seronegative, 24.3 % H. pylori seropositive/CagA seronegative, and 37.7 % H. pylori/CagA seropositive at baseline) were analyzed., Results: During up to 19 years of follow-up, 50.3 % and 83.5 % of participants without and with incident dementia, respectively, died. In Cox proportional hazards models, H. pylori/CagA seropositivity (hazard ratio (95 % CI) 1.68 (1.15, 2.46), P = 0.008), but not H. pylori seropositivity/CagA seronegativity (P = 0.541) was an independent predictor of incident dementia, but neither H. pylori seropositivity/CagA seronegativity nor H. pylori/CagA seropositivity were significant predictors in competing risks models (P ≥ 0.280)., Conclusions: Although CagA seropositivity in T2DM may have a contributory etiologic role in the risk of dementia, this may be through its association with reduced cardiovascular/all-cause mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: This study aimed to investigate the factors associated with the exacerbation of the severity of atherothrombotic brain infarction at discharge in patients with type 2 diabetes using a large-scale claims database., Materials and Methods: This retrospective cross-sectional study utilized the Medical Data Vision administrative claims database, a nationwide database in Japan using acute care hospital data, and the Diagnosis Procedure Combination system. Diagnosis Procedure Combination data collected between April 1, 2008, and December 31, 2022, were extracted. Patients with type 2 diabetes were included. Severe atherothrombotic brain infarction was defined as a modified Rankin scale score of ≥3., Results: Severe atherothrombotic brain infarction occurred in 43,916/99,864 (44.0%) patients with type 2 diabetes. The odds ratio for severe atherothrombotic brain infarction increased significantly per 10 year increments in age (odds ratio: 1.69, 95% confidence interval: 1.66-1.71). A body mass index of <25 kg/m 2 , with a body mass index of ≥25 kg/m 2 as reference, also increased the risk for severe atherothrombotic brain infarction (odds ratio: 1.11, 95% confidence interval: 1.08-1.15). The odds ratios in insulin and dipeptidyl peptidase 4 inhibitor use were significantly higher than 1. In particular, statin use (odds ratio: 0.85, 95% confidence interval: 0.83-0.88), fibrate use (odds ratio: 0.68, 95% confidence interval: 0.59-0.78), aspirin use (odds ratio: 0.78, 95% confidence interval: 0.75-0.80), and P2Y12 inhibitor use (odds ratio: 0.88, 95% confidence interval: 0.85-0.91) were associated with a lower odds ratio for severe atherothrombotic brain infarction., Conclusions: The active management of lipid levels using statins and fibrates may be beneficial in preventing the exacerbation of atherothrombotic brain infarction in type 2 diabetes patients., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To assess the association between glycated haemoglobin (HbA1c) variability and risk of renal function decline in type 2 diabetes mellitus (T2DM)., Research Design and Methods: A comprehensive search was carried out in PubMed, Embase, Web of Science and the Cochrane Library (until 12 March 2024). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines were followed for this meta-analysis. HbA1c variability was presented as indices of the standard deviation (SD), coefficient of variation (CV), HbA1c variability score (HVS) and haemoglobin glycation index (HGI). This meta-analysis was performed using random-effect models., Results: Eighteen studies met the objectives of this meta-analysis. The analyses showed positive associations between HbA1c variability and kidney function decline, with hazard ratio (HR) 1.26 (95% confidence interval [CI] 1.15-1.38) for high versus low SD groups, HR 1.47 (95% CI 1.30-1.65) for CV groups, HR 1.32 (95% CI 1.10-1.57) for HVS groups and HR 1.53 (95% CI 1.05-2.23) for HGI groups. In addition, each 1% increase in SD and CV was linked to kidney function decline, with HR 1.26 (95% CI 1.17-1.35), and 1.13 (95% CI 1.03-1.23), respectively. Also, each 1-SD increase in SD of HbA1c was associated with deterioration in renal function, with HR 1.17 (95% CI 1.07-1.29)., Conclusions: The four HbA1c variability indicators were all positively associated with renal function decline progression; therefore, HbA1c variability might play an important and promising role in guiding glycaemic control targets and predicting kidney function decline progression in T2DM., (© 2024 John Wiley & Sons Ltd.)

Purpose of Review: Body fat distribution plays a significant role in the cardiometabolic consequences of obesity. We review the impact of visceral and hepatic fat and highlight important interventions., Recent Findings: Several epidemiologic studies have established a clear association between visceral fat and cardiovascular disease. The association between hepatic fat and cardiovascular disease is less clear with discordant results. Novel evidence demonstrates sodium glucose co-transporter-2 (SGLT2) inhibitors facilitate modest weight loss and reductions in ectopic fat depots in patient with type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with decreased visceral/hepatic fat and reductions in MACE in populations with type 2 diabetes and with overweight/obesity. Clear associations between visceral fat and cardiometabolic outcomes have been established, whereas the impact of hepatic fat remains less clear. Lifestyle modification and pharmacologic interventions remain the initial therapies, while surgical intervention is associated with improved long-term outcomes. Emerging therapies have demonstrated a profound impact on body fat distribution and cardiometabolic risk., (© 2024. The Author(s).)

Purpose of Review: Cardiovascular disease (CVD) is the leading cause of death globally and is closely associated with obesity and type 2 diabetes mellitus (T2DM). This review examines the interplay between obesity, T2DM, and CVD, highlighting the increasing prevalence and economic burden of these conditions., Recent Findings: Pharmacologic therapies, particularly glucagon-like peptide-1 receptor agonists, show promise in substantial weight loss and subsequent reduction of adverse cardiovascular events in obese individuals with and without diabetes. Obesity significantly contributes to the development of insulin resistance and T2DM, further escalating CVD risk. The common co-occurrence of these three conditions may involve several other pathophysiological mechanisms, such as chronic inflammation, increased visceral adiposity, and endothelial dysfunction. Until recently, lifestyle modifications and bariatric surgery had been the primary methods for weight loss and mitigating obesity-associated cardiovascular risk. Newer pharmacological options have led to a paradigm shift in our approach to obesity management as they provide substantial benefits in weight loss, glycemic control, and cardiovascular risk reduction., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To study the association between femoral neck (FN) bone mineral density (BMD) T-score and fracture risk in individuals with and without type 2 diabetes (T2D)., Materials and Methods: We performed a single-centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual-energy X-ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T-score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10-year absolute fracture risk., Results: In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T-score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24-2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01-2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64-1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73-2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10-year fracture risk., Conclusions: The FN BMD T-score was significantly associated with hip, non-spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T-score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T-score to predict fracture risk., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Materials and Methods: This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as scheduled and were included in an efficacy analysis. Dose adjustments of oral semaglutide were determined by each physician while monitoring efficacy and adverse events., Results: Significant improvements in body weight, liver enzymes, lipid profile, and glycaemic control were found at 48 weeks compared with baseline values (all p < 0.01). Controlled attenuation parameter values significantly decreased from baseline to 48 weeks (p < 0.01). Changes in alanine aminotransferase concentrations (r = 0.37, p < 0.01) and controlled attenuation parameter values (r = 0.44, p < 0.01) were significantly correlated with changes in body weight. Liver fibrosis markers, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2-binding protein, fibrosis-4 index, and liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.01). The most common adverse events were Grades 1-2 transient gastrointestinal symptoms, such as nausea (23 patients, 28.8%), dyspepsia (12, 15.0%) and appetite loss (4, 5.0%)., Conclusions: Oral semaglutide treatment for T2DM in patients with MASLD leads to an improvement in liver steatosis and injury, surrogate markers of fibrosis, diabetic status, and lipid profile, and reduces body weight., (© 2024 John Wiley & Sons Ltd.)

Aim: To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D)., Materials and Methods: We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication., Results: A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications., Conclusion: In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims/hypothesis: Although the benefits of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) are well established, the effects of these therapeutic agents in patients with advanced CKD are less certain. We hypothesised that the continued use of these drugs, even when renal function deteriorates to stage 4 CKD or worse, is safe and associated with improved cardiorenal survival., Methods: This is a retrospective cohort study utilising data from medical records from two institutions. All patients with type 2 diabetes mellitus who were prescribed an SGLT2i between 1 January 2016 and 31 December 2021, who subsequently had eGFR <30 ml/min per 1.73 m 2 recorded on two occasions at least 90 days apart, were identified. The date on which the eGFR first reached any level less than 30 ml/min per 1.73 m 2 was defined as the index date. Individuals were then categorised into the SGLT2i continuation group or the discontinuation group according to the use of SGLT2i after the index date. Inverse probability of treatment weighting (IPTW) was performed to minimise confounding. Outcomes of interest included heart failure outcomes, cardiovascular outcomes, renal outcomes and safety outcomes., Results: According to the eligibility criteria, 337 patients in the continuation group and 358 in the discontinuation group were identified. After IPTW, continuation of SGLT2i use was associated with significantly lower risks of the composite of major adverse cardiovascular events compared with discontinuation of SGLT2i use (HR 0.65 [95% CI 0.43, 0.99]), largely driven by reduced risk of myocardial infarction during follow-up (subdistribution HR [SHR] 0.43 [95% CI 0.21, 0.89]). The incidences of an eGFR decline of 50% or more (SHR 0.58 [95% CI 0.42, 0.81]) and all-cause hospital admission (SHR 0.77 [95% CI 0.64, 0.94]) were also significantly lower in the continuation group. None of the studied safety outcomes were significantly different when comparing the two groups. Blood haemoglobin levels were significantly higher in the continuation group at the end of follow-up (114.6 g/l vs 110.4 g/l, with a difference of 4.12 g/l; p=0.047)., Conclusions/interpretation: In patients with CKD who were treated with an SGLT2i, continuation of SGLT2i use after eGFR declined to 30 ml/min per 1.73 m 2 or less was associated with lower risks of cardiovascular and renal events compared with discontinuation of SGLT2i use. Continued use of SGLT2i throughout the course of CKD should be considered to optimise patient outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To assess the likelihood of dementia in individuals with type 2 diabetes (T2D), distinguishing between those with and without microvascular diseases., Methods: Leveraging the National Health Insurance Research Database in Taiwan, we identified individuals newly diagnosed with T2D from 1 January 2009 through 31 December 2014. Multivariable Cox proportional hazard models were used to compare the risk of outcomes., Results: Individuals with microvascular disease had a significantly higher risk of all-cause dementia (adjusted hazard ratio [95% confidence interval] 1.13 [1.09, 1.17]) compared with matched individuals without microvascular disease. In addition, individuals with diabetic kidney disease and diabetic neuropathy were associated with a significantly increased risk of Alzheimer's disease (1.16 [1.02, 1.32] and 1.14 [1.03, 1.27]), vascular dementia (1.21 [1.06, 1.38] and 1.14 [1.02, 1.28]) and other dementia (1.11 [1.04, 1.19] and 1.10 [1.04, 1.16]), respectively, compared with those without microvascular disease., Conclusions: This nationwide cohort study showed that patients with T2D and microvascular disease, particularly diabetic kidney disease and diabetic neuropathy, were associated with a significantly higher risk of Alzheimer's disease, vascular dementia, other dementia and all-cause dementia than those without microvascular disease., (© 2024 John Wiley & Sons Ltd.)

Aim: To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout-related outcomes., Materials and Methods: Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.3 mg/dL [≤255.8 µmol/L], >4.3-5.1 mg/dL [>255.8-303.4 µmol/L], >5.1-5.8 mg/dL [>303.4-345.0 µmol/L], >5.8-6.9 mg/dL [>345.0-410.4 µmol/L] and >6.9 mg/dL [>410.4 µmol/L]), glycated haemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. The effect of ertugliflozin on a composite of gout onset or initiation of anti-gout medication was assessed., Results: The mean UA levels at baseline were 5.67 and 5.62 mg/dL in the placebo and ertugliflozin groups, respectively. Ertugliflozin reduced UA over Weeks 6-260 compared with placebo, with least squares mean (LSM) changes (95% confidence interval [CI]) from baseline at Week 260 of 0.07 mg/dL (-0.02, 0.15) and -0.19 mg/dL (-0.25, -0.13) in the placebo and pooled ertugliflozin groups, respectively. At Week 260, placebo-adjusted LSM change (95% CI) from baseline in UA was -0.26 mg/dL (-0.36, -0.16) with ertugliflozin. Ertugliflozin was associated with reductions in UA across baseline UA quintiles compared with placebo. The incidence of the composite of gout-related outcomes was 84/2539 (3.3%) for placebo and 133/5091 (2.6%) for ertugliflozin (hazard ratio for the composite 0.76 [95% CI 0.580, 1.002])., Conclusions: Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout-related outcome events., (© 2024 Merck Sharp & Dohme LLC. Pfizer Inc and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To investigate whether the physician-encounter interval for patients with type 2 diabetes (T2D) can be optimized from 2-3 to 4-6 months among those with a calculated 10-year cardiovascular disease (CVD) risk score of less than 20% without compromising their long-term outcomes., Materials and Methods: Using territory-wide public electronic medical records in Hong Kong, we emulated a target trial to compare the effectiveness of the physician-encounter intervals of 4-6 versus 2-3 months for T2D patients without prior CVDs and with a predicted risk for CVDs of less than 20% (i.e. those patients not in the high-risk category). Propensity score matching was used to emulate the randomization of participants at baseline, where 42 154 matched individuals were included for analysis. The marginal structural model was applied to estimate the hazard ratio (HR) for CVD incidence and all-cause mortality, the incidence rate ratio of secondary and tertiary care utilization, as well as the between-group differences in HbA1c, blood pressure and cholesterol levels., Results: During a follow-up period of up to 12 (average: 5.1) years, there was no significantly increased risk of CVD in patients with physician-encounter intervals of 4-6 months compared with those patients with physician-encounter intervals of 2-3 months (HR [95% confidence interval {CI}]: 1.01 [0.90, 1.14]; standardized 10-year risk difference [95% CI]: -0.1% [-0.7%, 0.6%]), nor for all-cause mortality (HR: 1.00 [0.84, 1.20]; standardized 10-year risk difference: -0.1% [-0.5%, 0.3%]). Additionally, there was no observable difference in the utilization of secondary and tertiary care or key clinical parameters between these two follow-up frequencies., Conclusions: For T2D patients with a calculated 10-year CVD risk of less than 20%, the interval of regular physician encounters can be optimized from 2-3 to 4-6 months without compromising patients' long-term outcomes and saving substantial service resources in primary care., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: The association between dental caries, salivary alterations, and type 2 diabetes (T2D) is inconclusive. This systematic review evaluated the caries status and salivary alterations in adults with T2D., Data: Observational studies (cross-sectional, case-control, or cohort studies) that evaluated the association between type 2 diabetes and dental caries and/or salivary changes were included., Sources: Systematic searches of PubMed/Medline, Web of Science, Embase, and the Cochrane Library for relevant literature published up to January 2024 were performed., Study Selection: Ninety-eight studies were selected from the 1981 records obtained after screening the databases. Thirty-nine studies that met the eligibility criteria were included in the qualitative synthesis, and twenty-eight of the included studies were suitable for the quantitative synthesis (meta-analysis)., Results: The meta-analysis showed that compared to non-diabetic individuals, type 2 diabetic individuals had higher DMFT (mean difference: 2.27; 95 % CI, 1.31 to 3.22; P < 0.00001). Moreover, type 2 diabetic individuals had lower salivary flow rate (standardized mean difference: -2.62; 95 % CI, -4.38 to -0.86; P = 0.003), salivary pH (standardized mean difference: -1.35; 95 % CI, -1.89 to -0.80; P < 0.00001) and salivary buffering capacity (standardized mean difference: -0.60; 95 % CI, -0.93 to -0.27; P = 0.0004). Whereas DMFT (mean difference: -2.15; 95 % CI, -6.47 to 2.17; P = 0.33) and salivary buffering capacity (standardized mean difference: -0.05; 95 % CI, -0.48 to 0.37; P = 0.80) were not significantly different between individuals with well-controlled diabetes and those with poorly-controlled diabetes., Conclusions: Type 2 diabetes may lead to an increased index of dental caries and a reduction in salivary flow rate, salivary pH, and salivary buffering capacity in adults., Clinical Significance: Individuals with type 2 diabetes exhibit an elevated risk of dental caries and salivary alterations that facilitate the progression of dental caries. It is recommended that dentists and endocrinologists focus their attention on the oral health of this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual's change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m 2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, -30.8% (95% confidence interval -42.6 to -16.8). The between-group difference (canagliflozin group - control group) of change in eGFR slope (chronic - pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m 2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Although the use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with obesity and heart failure with preserved ejection fraction (HFpEF) has demonstrated improvement in cardiovascular outcomes, the incremental benefits of GLP-1 RA for patients already on sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored., Objectives: This study aimed to assess the incremental benefits of GLP-1 RA in patients with type 2 diabetes mellitus, overweight/obesity, and HFpEF receiving SGLT2i therapy., Methods: The authors conducted a retrospective cohort study using the TriNetX research database including patients ≥18 years with type 2 diabetes mellitus, body mass index ≥27 kg/m 2 , and HFpEF on SGLT2i. Two cohorts were created based on GLP-1 RA prescription. The outcomes were heart failure exacerbation, all-cause emergency department visits/hospitalizations among others over a 12-month period., Results: A total of 7,044 patients remained in each cohort after propensity score matching. There was a significantly lower risk of heart failure exacerbations, all-cause emergency department visits/hospitalizations, new-onset atrial arrhythmias, new-onset acute kidney injury, and pulmonary hypertension in the GLP-1 RA plus SGLT2i cohort compared with the SGLT2i-only cohort. The associated benefits persisted across different body mass indexes and ejection fractions as well as in patients with elevated natriuretic peptide. The risk of diabetic retinopathy was higher in the combination therapy group than with SGLT2i-only use., Conclusions: GLP-1 RA, in addition to SGLT2i, was associated with a significantly lower risk of heart failure hospitalizations in this patient population, suggesting a potential incremental benefit. This highlights the need for prospective studies to confirm the clinical benefits., Competing Interests: Funding Support and Author Disclosures Dr Bhatt is on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; he is on the Board of Directors for American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); he is a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; he is on the Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, Rutgers University (for the National Institutes of Health–funded MINT Trial); he has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor, Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee), Clinical Cardiology (Deputy Editor); he is named on a patent for sotagliflozin (assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither he nor Brigham and Women's Hospital receive any income from this patent); he has received research funding for Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; he has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); he is Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; he is trustee for American College of Cardiology; and he has done unfunded research for FlowCo. Dr Butler has been a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Kosiborod has received research grants from AstraZeneca and Boehringer Ingelheim; and has served as a consultant for Alnylam, AstraZeneca, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, and Vifor. Dr Fonarow has done consulting for Abbot, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We studied the regulation dynamics of cerebral blood velocity (CBv) at middle cerebral arteries (MCA) in response to spontaneous changes of arterial blood pressure (ABP), termed dynamic cerebral autoregulation (dCA), and end-tidal CO 2 as proxy for blood CO 2 tension, termed dynamic vasomotor reactivity (DVR), by analyzing time-series data collected at supine rest from 36 patients with Type-2 Diabetes Mellitus (T2DM) and 22 age/sex-matched non-diabetic controls without arterial hypertension. Our analysis employed a robust dynamic modeling methodology that utilizes Principal Dynamic Modes (PDM) to estimate subject-specific dynamic transformations of spontaneous changes in ABP and end-tidal CO 2 (viewed as two "inputs") into changes of CBv at MCA measured via Transcranial Doppler ultrasound (viewed as the "output"). The quantitative results of PDM analysis indicate significant alterations in T2DM of both DVR and dCA in terms of two specific PDM contributions that rise to significance (p < 0.05). Our results further suggest that the observed DVR and dCA alterations may be due to reduction of cholinergic activity (based on previously published results from cholinergic blockade data) that may disturb the sympatho-vagal balance in T2DM. Combination of these two model-based "physio-markers" differentiated T2DM patients from controls (p = 0.0007), indicating diabetes-related alteration of cerebrovascular regulation, with possible diagnostic implications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To investigate the association between fish oil supplementation and subsequent risk of chronic kidney disease (CKD) among patients with diabetes, and further evaluate the mediation effect of typical glycolipid and inflammatory biomarkers., Methods: In total, 24 497 patients with diabetes from the UK Biobank were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD risk, and the rate advancement period was calculated to quantify and communicate the impact of fish oil upon that risk. In addition, we also used mediation analysis to assess the mediating role of plasma biomarkers., Results: Overall, 7122 patients reported taking fish oil supplements. During a mean of 11.3 years of follow-up, 3533 CKD cases occurred. In the fully adjusted model, fish oil use was inversely associated with the incidence of CKD (HR 0.90; 95% CI: 0.83, 0.97), which was mediated by serum levels of HbA1c (4.7%), C-reactive protein (CRP) (3.4%) and high-density lipoprotein cholesterol (HDL-C) (2.3%). Participants who took fish oil supplements displayed the same risk of CKD events, but that risk was delayed by approximately 2.79 years compared with non-users of fish oil., Conclusions: Our findings advocate the beneficial role of fish oil use in preventing CKD among patients with diabetes, which may be mediated by serum levels of HbA1c, CRP and HDL-C, and support public health policies aiming to promote fish oil supplementation for the prevention of diabetes complications., (© 2024 John Wiley & Sons Ltd.)

Aim: Efficient primary prevention of diabetic kidney disease (DKD) is currently lacking. The identification of people at high DKD risk and timely intervention are key to preventing DKD. Therefore, a model to classify people according to their risk for developing DKD was developed previously and used in the current analysis to assess the effect of semaglutide versus placebo on primary DKD prevention., Methods: Participants with type 2 diabetes from the randomized, double-blind, placebo-controlled SUSTAIN 6 trial without DKD at baseline who received 0.5/1.0 mg semaglutide or placebo were grouped by baseline DKD risk, calculated using a validated model. The main post hoc outcome was the effect of semaglutide versus placebo on the proportion of participants who developed DKD [urinary albumin/creatinine ratio (UACR) ≥30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m 2 ]. Additional post hoc outcomes included changes in DKD risk score, UACR and estimated glomerular filtration rate over time., Results: Of the total 1139 participants included in the analysis, 28.7% developed DKD; more participants with a high DKD risk (952/1139) developed DKD. Semaglutide significantly reduced the risk of developing DKD in both the total [odds ratio 0.56 (95% confidence interval: 0.42; 0.74; p < 0.0001)], and high DKD risk population [odds ratio 0.51 (95% confidence interval: 0.38; 0.69; p < 0.0001)] and significantly delayed DKD development versus placebo. The beneficial effects of semaglutide were largely driven by UACR changes. The number needed to treat for semaglutide in the high DKD risk population was 7., Conclusions: This post hoc study indicates that semaglutide may have beneficial effects on primary DKD prevention in people with T2D., (© 2024 John Wiley & Sons Ltd.)

Aim: To analysis the change of electrogastrogram (EGG) in patients with type 2 diabetes mellitus (T2DM), and evaluate the prevalence of abnormal gastric electrical rhythm (AGER) and its relative influencing factors., Methods: A total of 65 patients with T2DM hospitalized at the Second Affiliated Hospital of Soochow University from Dec. 2020 to Dec. 2021 were included in the cross-sectional study. General information, clinical data, and medical history data of all study subjects, including name, gender, body mass index (BMI), duration of diabetes, anti-diabetic therapies, high blood pressure (HBP) history, smoking history, and medication history, were completely collected. The results of laboratory tests, including biochemical parameters, glycosylated hemoglobin (HbA1c), fasting C-peptide, 2 h postprandial C-peptide, 24 h urine total protein (24 hUTP), urine microalbumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were recorded. EGG, Gastroparesis Cardinal Symptom Index (GCSI), gastric emptying ultrasound, fundus examination, carotid artery ultrasonography, cardiac autonomic function test, heart rate variability (HRV) were all examined and recorded as well. According to the results of EGG, the subjects were divided into normal gastric electrical rhythm (NGER) group and abnormal gastric electrical rhythm (AGER) group., Results: (1) Fasting blood glucose (FBG), HbA1c, the presence of diabetic peripheral neuropathy (DPN) and diabetic cardiac autonomic neuropathy (DCAN) were significantly higher in the AGER group (p < 0.05). Low frequency (LF) and high frequency (HF), the indicators of HRV, were significantly lower in the AGER group (p < 0.05). In addition, the prevalence of feeling excessively full after meals, loss of appetite, and stomach or belly visibly larger after meals of gastrointestinal symptoms of gastroparesis were significantly higher in the AGER group (p < 0.05). Multiple logistic regression analysis showed that FBG and the prevalence of DCAN were the independent risk factors., Conclusion: AGER was associated with high FBG and the presence of DCAN. EGG examination is recommended for patients with gastrointestinal symptoms and clues of DCAN., (© 2024. The Author(s).)

Aims: To investigate the independent contributions of glycated haemoglobin (HbA1c) reduction and weight loss to clinical outcomes in patients with type 2 diabetes (T2D) treated with antidiabetic drugs, including glucagon-like peptide-1 receptor agonists (GLP-1RAs)., Materials and Methods: This observational, retrospective cohort study used deidentified electronic health record-derived data from patients evaluated at the Cleveland Clinic (1 January 2000-31 December 2020). Cohort A included 8876 patients with newly diagnosed T2D treated with any of six antidiabetic drug classes. Cohort B included 4161 patients with T2D initiating GLP-1RA treatment. The effects of body mass index (BMI) and HbA1c reduction, variability, and durability on clinical outcomes were investigated., Results: In Cohort A, each 1% BMI reduction was associated with 3%, 1%, and 4% reduced risk of heart failure (p = 0.017), hypertension (p = 0.006), and insulin initiation (p = 0.001), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 29% reduced risk of hypertension (p = 0.041) and insulin initiation (p = 0.001), respectively. In Cohort B, each 1% BMI reduction was associated with 4% and 3% reduced risk of cardiovascular disease (p = 0.008) and insulin initiation (p = 0.002), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 16% reduced risk of chronic kidney disease (p = 0.014) and insulin initiation (p = 1 × 10 -4 ), respectively. Lower BMI variability and greater BMI durability were associated with decreased risk of clinical outcomes in both cohorts., Conclusions: Antidiabetic medication-associated, and specifically GLP-1RA-associated, weight loss and HbA1c reductions independently reduce real-world clinical outcome risk., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: In nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers., Methods: In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistical approach., Results: In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2., Conclusion: MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling., Clinical Relevance Statement: Liver fibrosis may be considered a cardiovascular risk factor in patients without cirrhosis. Further research on the mechanisms that link liver fibrosis to left ventricular concentricity may reveal potential therapeutic targets in patients with non-alcoholic fatty liver disease (NAFLD)., Key Points: Previously, studies on liver fibrosis and cardiac remodeling have focused on advanced stages of liver fibrosis. Liver fibrosis is associated with left ventricular (LV) concentricity and may relate to interleukin-1 receptor type 2. Interleukin-1 signaling is a potential mechanistic interlink between early liver fibrosis and LV remodeling., (© 2024. The Author(s).)

Aims: Diastolic dysfunction represents the earliest and most common manifestation of diabetic cardiomyopathy. Nitric oxide (NO), a potent vasodilator and anti-inflammatory mediator released from the subendocardial and coronary endothelium, favors left ventricular distensibility and relaxation. In type 2 diabetes (T2D), the NO bioavailability is reduced due to the oxidative stress and inflammatory state of the endothelium, because of chronic hyperglycemia. The aim of the present research is to evaluate the relationship between endothelial function and diastolic function in subjects with T2D., Method: Subjects with T2D and age and sex-matched healthy controls were consecutively recruited. All participants underwent flow-mediated dilation (FMD) to assess endothelial function, and echocardiography to evaluate diastolic function., Results: Thirty-five patients (6 women, 29 men) and 35 healthy controls were included in the final analysis. FMD was significantly lower in T2D than controls (4.4 ± 3.4 vs. 8.5 ± 4.3%, p = 0.001). T2D presented different abnormalities in diastolic function compared to controls: lower E/A (early to late diastolic transmitral flow velocity), lower septal and lateral e' (early diastolic myocardial tissue velocity at septum and lateral wall), and higher E/e' (surrogate of filling pressure). In subjects with T2D, we observed a significant correlation between FMD and E/e' (r = -0.63, p = 0.001), lateral e' (r = 0.44, p = 0.03), and septal e' (r = 0.39, p = 0.05)., Conclusions: Our observational study demonstrated a link between FMD and diastolic dysfunction in subjects with type 2 diabetes., (© 2024. The Author(s).)

Background: Diabetic Kidney Disease (DKD) is a complex disease associated with circadian rhythm and biological clock regulation disorders. Melatonin (MT) is considered a hormone with renal protective effects, but its mechanism of action in DKD is unclear., Methods: We used the GSE151325 dataset from the GEO database for differential gene analysis and further explored related genes and pathways through GO and KEGG analysis and PPI network analysis. Additionally, this study used a type 2 diabetes db/db mouse model and investigated the role of melatonin in DKD and its relationship with clock genes through immunohistochemistry, Western blot, real-time PCR, ELISA, chromatin immunoprecipitation (ChIP), dual-luciferase reporter technology, and liposome transfection technology to study DEC1 siRNA., Results: Bioinformatics analysis revealed the central position of clock genes such as CLOCK, DEC1, Bhlhe41, CRY1, and RORB in DKD. Their interaction with key inflammatory regulators may reveal melatonin's potential mechanism in treating diabetic kidney disease. Further experimental results showed that melatonin significantly improved the renal pathological changes in db/db mice, reduced body weight and blood sugar, regulated clock genes in renal tissue, and downregulated the TLR2/MyD88/NF-κB signaling pathway. We found that the transcription factor DEC1 can bind to the TLR2 promoter and activate its transcription, while CLOCK's effect is unclear. Liposome transfection experiments further confirmed the effect of DEC1 on the TLR2/MyD88/NF-κB signaling pathway., Conclusion: Melatonin shows significant renal protective effects by regulating clock genes and downregulating the TLR2/MyD88/NF-κB signaling pathway. The transcription factor DEC1 may become a key regulatory factor for renal inflammation and fibrosis by activating TLR2 promoter transcription. These findings provide new perspectives and directions for the potential application of melatonin in DKD treatment., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Objective: To evaluate the effectiveness of integrated personalized diabetes management (iPDM) through telemedicine (tele-iPDM) with regard to glycaemic control., Methods: A 6-month single-centre, open-label, prospective randomized controlled trial enrolled insulin-treated patients with type 2 diabetes, aged 18-65 years with glycated haemoglobin (HbA1c) levels of 7.5%-10.5%. The tele-iPDM group received insulin adjustment by investigators through a cloud-based telemonitoring platform for 6 months (blood glucose monitoring reviewed weekly from Weeks 0 to 12 and then monthly from Weeks 13 to 24). The control group performed self-monitoring and insulin adjustment. The primary outcome was the difference in HbA1c change from baseline between the two groups at 24 weeks. Secondary outcomes included changes in HbA1c at 12 weeks, fasting plasma glucose, body weight, body mass index (BMI), the percentage of individuals achieving HbA1c <7% at 24 weeks, the percentage of individuals with an HbA1c reduction of >0.5% at 24 weeks, and incidences of hypoglycaemic events., Results: A total of 151 participants were enrolled, with a mean age of 53.36 ± 8.08 years and a mean diabetes duration of 12.38 ± 8.47 years. The baseline HbA1c was 8.47 ± 0.76%. The mean HbA1c decreased from baseline to 12 and 24 weeks in both groups. At 12 weeks, HbA1c reduction from baseline was -1.2% (95%CI -1.42 to -0.98) in the tele-iPDM group and -0.57% (95%CI -0.79 to -0.36) in the control group. The mean difference in HbA1c between the tele-iPDM and usual care groups at 12 weeks was -0.63% (95%CI -0.94 to -0.32; p < 0.001). At 24 weeks, HbA1c reduction from baseline was -1.14% (95%CI -1.38 to -0.89) in the tele-iPDM group and - 0.49% (95%CI -0.73 to -0.25) in the control group. The mean difference in HbA1c between the tele-iPDM and usual care groups was -0.65% (95%CI -0.99 to -0.30; p < 0.001). There were no significant differences in body weight, BMI, or hypoglycaemic events between the two groups., Conclusion: Telemonitoring can support the iPDM care model in individuals with insulin-treated type 2 diabetes. It improves the efficiency of diabetes care, enhances glycaemic control at 12 weeks, and sustains glycaemic control at 24 weeks., (© 2024 John Wiley & Sons Ltd.)

Aim: To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort., Methods: Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs)., Results: In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings., Conclusions: T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases., (© 2024 John Wiley & Sons Ltd.)

Objective: Multiregional trials are designed under the assumption that treatment effect applies to the entire target population, yet several factors may introduce geographic heterogeneity in treatment effect. We explored whether such variations exist in trials assessing the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in major cardiovascular events (MACE) in type 2 diabetes., Research Design and Methods: A systematic search of Medline and the Cochrane Library was conducted from inception until 30 June 2020. We included international randomized controlled trials comparing any GLP-1RA versus placebo, with MACE as a primary end point. Individual participant data were subsequently requested from the sponsor or through data sharing platforms. For each trial, we calculated hazard ratios (HRs) and their 95% CIs for MACE, subgrouped by region. We then performed a random-effects meta-analysis and conducted meta-regressions to assess the influence of predetermined variables of interest on treatment effect., Results: We included six trials including 45,426 patients. Baseline risk of MACE ranged from 2.9 per 100 patient-years in Southern Asia to 7.4 per 100 patient-years in Sub-Saharan Africa. HRs for MACE ranged between 0.25 (95% CI 0.05, 1.12) in Northern Africa to 0.98 (0.79, 1.22) in Western Europe. There was no significant subgroup difference across regions (P = 0.70). Baseline risk of MACE and indexes of development status (i.e., Human Development Index, gross domestic product) were independently associated with GLP-1RA efficacy., Conclusions: This study does not suggest any regional heterogeneity of GLP-1RA efficacy in MACE. However, a higher baseline risk and lower development status were associated with a greater benefit of these drugs., (© 2024 by the American Diabetes Association.)

Background: Obesity and type 2 diabetes mellitus (T2DM) are risk factors for severe COVID-19 infection. Bariatric surgery (BSG) is an effective treatment of obesity through weight loss and may reduce COVID-19 severity., Objectives: We examined the effect of BSG on COVID-19 outcomes in patients with or at risk of T2DM., Setting: Electronic health record data from the PaTH Clinical Data Research Network, a partnership of 5 health systems reviewed from March 1, 2020, to December 31, 2020., Methods: Ambulatory and in-hospital patient encounters with COVID-19 diagnosis and obesity were identified. We constructed 2 patient groups: BSG and non-BSG (NBSG). The BSG group included patients with at least 1 encounter for the BSG procedure code and/or 1 BSG diagnosis code; the NBSG group included patients with no procedure or diagnosis code for BSG with body mass index (BMI) ≥40 or BMI ≥35 and at least 2 obesity-related co-morbidities. We matched 1 patient in the BSG group to 2 patients in the NBSG group based on age, gender (sex defined at birth), race and ethnicity, group (T2DM and at risk of T2DM), and site. The primary outcome was 30-day outcomes of COVID-19 severity., Results: After matching, we found that patients with BSG had lower odds of respiratory failure (41%) and ventilation/intensive care unit (ICU) admission/death (52%). Patients in the BSG group had lower odds of hospitalization, pneumonia, respiratory failure, and the most severe COVID-19 outcomes combined (ventilation/ICU admission/death). T2DM was identified as a risk factor for COVID-19 severity in the BSG group., Conclusions: This retrospective, matched-cohort analysis found BSG to have a protective effect against severe COVID-19 outcomes., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA., Methods: We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations., Results: Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, -1.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n=485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n=285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations., Conclusion: The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods., Competing Interests: Financial Disclosure Timothy Wen serves as an associate Chief Medical Officer for Delfina Care, Inc. Alexander M. Friedman served on an advisory group for Sage and Biogen and received NIH funding. Cynthia Gyamfi-Bannerman reports receiving payment from Sera. Camile E. Powe's institution received payments from Dexcom, Inc, and Dr. Powe received payment from UpToDate and the American Diabetes Association. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To assess the association of intake of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with new-onset atrial fibrillation (AF) in people with prediabetes or diabetes., Methods: A total of 31 433 participants with prediabetes and diabetes from the UK Biobank were included. Information on the intake of SSBs, ASBs and NJs was accessed by 24-hour dietary recalls from 2009 to 2012. The study outcome was new-onset AF., Results: During a median follow-up of 12.0 years, 2470 (7.9%) AF cases were documented. Both the intake of SSBs (per 1 unit/day increment; adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.04-1.18) and ASBs (per 1 unit/day increment; adjusted HR = 1.08; 95% CI: 1.02-1.14) were linearly and positively associated with new-onset AF, while NJ intake was not significantly associated with new-onset AF (per 1 unit/day increment; adjusted HR = 1.00; 95% CI: 0.93-1.08). Accordingly, compared with non-consumers, participants who consumed more than one unit per day of SSBs (adjusted HR = 1.30; 95% CI: 1.11-1.53) or ASBs (adjusted HR = 1.21; 95% CI:1.05-1.40) had an increased risk of AF. Substituting 1 unit/day of NJs for SSBs was associated with a 9% (adjusted HR = 0.91; 95% CI: 0.83-0.99) lower risk of new-onset AF, while replacing SSBs with ASBs was not significantly associated with new-onset AF (adjusted HR = 0.97; 95% CI: 0.89-1.06)., Conclusions: Both the intake of SSBs and ASBs were linearly and positively associated with new-onset AF, while NJ intake did not show a significant association with AF in people with prediabetes or diabetes. Replacing an equivalent amount of SSB intake with NJs, but not ASBs, was associated with a lower risk of AF., (© 2024 John Wiley & Sons Ltd.)

Aim: To assess the safety and efficacy of a local skin substitute product in the treatment of chronic diabetic foot ulcers (DFUs)., Materials and Methods: Five patients were evaluated over 6 months. Skin substitutes were applied twice at 2-week intervals. Patients were monitored for any possible adverse effects and wound improvement., Results: The results indicated the overall safety of the skin substitute, with only few adverse effects unrelated to this product. Significant reduction in wound size was observed in four patients during the initial 12-week treatment phase, with complete closure in two patients at 24 weeks., Conclusions: The application of a bi-layered allogeneic keratinocyte and fibroblast skin substitute in patients with chronic DFU was safe and associated with favourable wound healing results. Adherence to standard treatment protocols, including optimal offloading, is essential to maximize the likelihood of successful wound healing., (© 2024 John Wiley & Sons Ltd.)

Background: Sodium Glucose Transporter 2 inhibitor (SGLT-2i) medications reduce inflammation, improve glycemic control, and impart weight loss, all of which may play a role in chronic obstructive pulmonary disease (COPD) pathophysiology., Objectives: The primary objective of our study was to explore the incidence of COPD exacerbation in patients with diabetes and COPD on SGLT-2i medications. The secondary objective was to assess the impact of SGLT-2i medications on COPD exacerbations needing hospitalization, ICU admission, and mechanical ventilation., Methods: This was a retrospective cohort analysis of COPD patients with diabetes enrolled in the COPD registry at a Mid-west Tertiary care teaching hospital from January 1, 2022, to December 31, 2022. We used Slicer-Dicer, a self-service cohort exploration tool embedded in EPIC for data extraction., Results: We had 31,411 patients registered with the COPD registry during the study period. Of these, 18,713 had diabetes, and 1295 patients were on SGLT-2i medication. The incidence of COPD exacerbation, including severe COPD exacerbation needing hospitalization, was significantly lower in the SGLT-2i medication group (3.16% vs 18.3%, p < 0.05; 1.2% vs 5.04%, p < 0.05). Also, there was a non-significant trend suggesting that the incidence of COPD exacerbation needing intensive care unit admission and intubation was lower in the SGLT-2i medication group (0.07% vs 3.4%; 0 vs 0.04%). SGLT-2i medication use was associated with reduced incidence of COPD exacerbation irrespective of underlying control of diabetes., Conclusions: Our study suggests possible role of SGLT-2i in preventing COPD exacerbation. Randomized trials are needed in the future to confirm or refute these findings., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions globally, particularly affecting individuals with type 2 diabetes mellitus (T2DM)., Objective: Our study aims to elucidate the diagnostic value of fasting C-peptide in combination with insulin resistance for assessing hepatic fibrosis in patients with T2DM and comorbid NAFLD., Design: This was a retrospective study., Setting: The study was conducted at the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine., Participants: The research involved 76 type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, diagnosed at our hospital from April 2020 to October 2022. Patients were categorized into the non-progressive hepatic fibrosis group (n = 64) and progressive hepatic fibrosis group (n = 12) based on fibrosis-4 value., Interventions: General data, systolic/diastolic blood pressure, fasting plasma glucose, fasting C-peptide, fasting insulin, glycosylated hemoglobin, uric acid, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were collected. Insulin resistance was calculated using a designated formula., Primary Outcomes Measures: The predictive impact of fasting C-peptide in combination with insulin resistance was evaluated through receiver operating characteristic curves., Results: The age, body mass index, fasting C-peptide, fasting insulin, aspartate transaminase, and insulin resistance showed a significant increase in the progressive hepatic fibrosis group compared to the non-progressive group (P = .006, P = .014, P < .001, P < .001, P = .004, and P = .021). The combination's sensitivity demonstrated an elevation compared to fasting C-peptide or insulin resistance alone (P = .005)., Conclusions: Fasting C-peptide in combination with insulin resistance proves to have a substantial predictive impact on hepatic fibrosis in type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, holding valuable clinical diagnostic potential.

Aim: Diminished hepatic insulin clearance (HIC) is observed in obese adults and is presumed to be mediated by fatty liver. However, few reports have examined HIC in Chinese children with metabolic (dysfunction)-associated fatty liver disease (MAFLD). This study aimed to investigate the correlation between HIC, insulin sensitivity and β-cell function in obese Chinese children with MAFLD., Methods: In total, 204 obese children (74 MAFLD) aged 4-17 years were enrolled into this study. HIC, insulin sensitivity and β-cell function were calculated using the oral glucose tolerance test (1.75 g/kg body weight). Correlation analyses between the HIC and clinical variables were performed using Pearson's product-moment correlation coefficients. HIC and glucose homeostasis were assessed in a high-fat diet mouse model, and liver samples were collected for molecular analysis., Results: Obese children with MAFLD exhibited significantly lower HIC (AUC C-peptide/insulin ratio , p = 0.0019), higher insulin resistance (homeostatic model assessment of insulin resistance, p = 0.002), and increased compensatory β-cell function (homeostatic model assessment-β, p = 0.046) than obese children without liver involvement. Notably, HIC was negatively correlated with insulin sensitivity (r = -0.5035, p < 0.0001) and β-cell function (r = -0.4576, p < 0.0001). However, pancreatic β-cell dysfunction (p = 0.046) was accompanied by future reduced HIC (p = 0.034) in children with MAFLD in prediabetes. In a high-fat diet mouse model, MAFLD mice showed a 50% reduction in insulin-degrading enzyme expression, consistent with the observed decrease in HIC., Conclusions: A lower HIC may offload pancreatic β-cells at an early stage. However, obese children with MAFLD are at risk of developing diabetes, and preventive efforts should be prioritized., (© 2024 John Wiley & Sons Ltd.)

Aim: To compare the effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) with dipeptidyl peptidase-4 inhibitors (DPP4is) on major liver outcomes (MLO) in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)., Materials and Methods: We included adult patients with T2D and MASLD, using metformin without specific liver conditions or surgeries, from the Merative MarketScan database. Patients initiating SGLT2is or DPP4is from 1 January 2014 to 31 December 2022 were identified. The primary outcome was time to MLO diagnosis. Overlap weighting balanced covariates, integrated with a Cox proportional hazards model for survival analysis., Results: Among 44 651 patients, 22 100 initiated SGLT2is, and 22 551 began DPP4is. After weighting, the incidence rate of MLO in the SGLT2i group was 3.8 per 1000 person-years, and it was 3.9 per 1000 person-years in the DPP4i group, resulting in an adjusted hazard ratio (aHR) of 0.82 (95% CI, 0.60-1.10). SGLT2i initiation was not associated with cirrhosis (aHR: 0.77; 95% CI, 0.55-1.06) or hepatocellular carcinoma (aHR: 0.99; 95% CI, 0.47-1.83) separately. Subgroup and sensitivity analyses did not yield significant results., Conclusions: In patients with T2D and MASLD, SGLT2is did not show a lower risk of MLO compared with DPP4is. Clinicians should consider the overall patient conditions and the additional benefits of SGLT2is to support the decision to switch from DPP4is., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: This study aims to investigate the impact of patient-centered health education on individuals with type 2 diabetes coexisting with hyperlipidemia., Methods: A cohort of 80 patients with type 2 diabetes and hyperlipidemia attending our hospital from February 2022 to August 2022 were randomly assigned to either the health education group or the control group. While the control group received routine health education, the health education group received additional patient-centered health education. Subsequently, we compared blood glucose and lipid levels, negative emotions, quality of life, and the incidence of unhealthy eating or overweight between the two groups post-education., Results: Following the health education intervention, the health education group exhibited superior improvements in blood glucose and lipid levels compared to the control group. Moreover, there was a significant decrease in SAS and SDS scores and a notable increase in quality of life compared to the control group. The health education group also demonstrated a lower incidence of unhealthy eating or overweight., Conclusions: Patient-centered health education for individuals with type 2 diabetes and hyperlipidemia proves effective in enhancing glucose and lipid metabolism, mitigating negative emotions, improving quality of life, and reducing unhealthy habits.