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Summary: Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown. Methods: Overall, 107 liver biopsies from PWH with MASLD (MASLD‐PWH) were matched to 107 biopsies from individuals with MASLD and without HIV (MASLD controls) on age at biopsy, race/ethnicity, sex, type 2 diabetes, body mass index (BMI) and alanine aminotransferase (ALT) level. Biopsies were scored using NAS. Results: Compared to MASLD‐controls, MASLD‐PWH had lower steatosis grade (OR: 0.65, 95% CI: (0.47–0.90), p = 0.01), lower lobular inflammation grade (OR: 0.55, 95% CI: (0.34–0.89), p = 0.02), less portal inflammation (OR: 0.42, 95% CI: (0.25–0.72), p = 0.002) and less ballooned hepatocytes (OR: 0.60, 95% CI: (0.41–0.88), p = 0.01). Thus, NAS was lower in MASLD‐PWH (OR: 0.69, 95% CI: (0.56–0.85), p < 0.001) than in MASLD controls. There was a trend towards lower prevalence of steatohepatitis in MASLD‐PWH (OR: 0.84, 95% CI: (0.68–1.03), p = 0.09). A multivariate analysis demonstrated that MASLD‐PWH cases had significantly less steatosis (OR: 0.66, p = 0.03), portal inflammation (OR: 0.34, p = 0.001) and ballooned hepatocytes (OR: 0.55, p = 0.01), yet higher stage fibrosis (OR: 1.42, p = 0.03) compared to MASLD controls. Conclusion: The NAS and histological drivers of fibrosis (e.g. inflammation and hepatocyte ballooning) are less pronounced in MASLD‐PWH, and yet fibrosis stage was generally higher when compared to matched controls with MASLD without HIV. This suggests HIV‐specific factors beyond hepatic necroinflammation may contribute to fibrosis progression in MASLD‐PWH. [ABSTRACT FROM AUTHOR]

Background and Purpose: Endothelin‐1 (ET‐1) receptor A (ETA) antagonists reduce proteinuria and prevent renal outcomes in chronic kidney disease (CKD) patients, but their utility has been limited because of associated fluid retention, resulting in increased heart failure risk. Understanding the mechanisms responsible for fluid retention could result in solutions that preserve renoprotective effects while mitigating fluid retention, but the complexity of the endothelin system has made identification of the underlying mechanisms challenging. Approach: We utilized a previously developed mathematical model of ET‐1 kinetics, ETA receptor antagonism, kidney function, haemodynamics, and sodium and water homeostasis to evaluate hypotheses for mechanisms of fluid retention with ETA antagonism. To do this, we simulated the RADAR clinical trial of atrasentan in patients with type 2 diabetes and CKD and evaluated the ability of the model to predict the observed decreases in haematocrit, urine albumin creatinine ratio (UACR), mean arterial pressure (MAP), and estimated glomerular filtration rate (eGFR). Background and Key Results: An effect of ETA antagonism on venodilation and increased venous capacitance was found to be the critical mechanism necessary to reproduce the simultaneous decrease in both MAP and haematocrit observed in RADAR. Conclusions and Impact: These findings indicate that fluid retention with ETA antagonism may not be caused by a direct antidiuretic effect within the kidney but is instead be an adaptive response to venodilation and increased venous capacity, which acutely tends to reduce cardiac filling pressure and cardiac output, and that fluid retention occurs in an attempt to maintain cardiac filling and cardiac output. [ABSTRACT FROM AUTHOR]

The global prevalence of chronic kidney disease (CKD) is approximately 9%. CKD is predicted to become the fifth largest global cause of death by 2040. Moreover, CKD causes disability, diminished quality of life and poses a high cost to healthcare systems. Delaying the development and progression of CKD is therefore of the utmost importance. Several kidney‐specific outcome trials on sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2s) have recently provided a paradigm shift in the treatment of people with CKD, with or without diabetes, as these agents have been shown to reduce the progression of CKD on top of maximally tolerated renin‐angiotensin‐aldosterone system (RAAS) blockade. The relative benefit and safety of SGLT‐2is seems to be consistent across ethnicities, ages and frailty categories; however, this needs to be tested in dedicated clinical trials. Guidelines make clear recommendations for the prescription of SGLT‐2is and RAAS inhibitors as standard of care for people with CKD. Their combination with other newer antidiabetic agents may provide further benefits by targeting different components of CKD mechanisms. Dedicated randomized controlled trials are needed to test whether combination with other agents could extend the use of SGLT2is and identify people in whom a combination of drugs may be most effective. Increased efforts to implement the guidelines on treatment with SGLT‐2is for people with CKD are needed, particularly in those at the highest risk of adverse outcomes and without type 2 diabetes. Moreover, strategies to target the equitable use of SGLT‐2is are needed. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major healthcare challenge, affecting >800 million people worldwide. Implications for population health result from the strong associations of CKD with increased rates of cardiovascular disease, heart failure, progressive CKD leading to kidney failure, acute kidney injury (AKI), and mortality. In addition to a single disease perspective, CKD commonly coexists alongside other long‐term conditions, in particular type 2 diabetes and cardiovascular disease. CKD is therefore an important component of multimorbidity that influences individual management and impacts prognosis. CKD is defined by abnormalities of kidney structure or function of any cause with implications for health that are present for longer than 3 months. The diagnosis is usually made on the basis of an abnormal glomerular filtration rate (GFR < 60 mL/min/1.73 m2) and/or the presence of proteinuria (urine albumin to creatinine ratio > 30 mg/g or >3 mg/mmol). GFR is usually estimated from serum creatinine concentration using a variety of validated equations. However, serum creatinine is closely related to muscle mass and may therefore not be an accurate marker of GFR in people with high or low muscle mass (sarcopaenia). Cystatin C is an alternative endogenous marker of GFR that is increasingly being used but also has limitations. An estimate of GFR based on both creatinine and cystatin C is the most accurate. Diagnosis should be followed by classification and risk stratification to guide the development of a risk‐based, personalized care plan. Improved detection and widespread implementation of optimal CKD management has the potential to bring major benefits to population health. [ABSTRACT FROM AUTHOR]

Background: Comorbidities are similarly associated with short‐term mortality for COVID‐19, acute respiratory distress syndrome (ARDS) and sepsis in intensive care unit (ICU) patients, but their adjusted frequencies at admission are unknown. Thus, we aimed to evaluate the adjusted distribution, reported as odds ratios, of known risk factors (i.e., age, sex and comorbidities) for ICU admission between COVID‐19, sepsis and ARDS patients in this nationwide registry‐based study. Methods: In this cohort study, we included adult patients admitted to Swedish ICUs with COVID‐19 (n = 7382) during the pandemic and compared them to patients admitted to ICU with sepsis (n = 22,354) or ARDS (n = 2776) during a pre‐COVID‐19 period. The main outcomes were the adjusted odds for comorbidities, sex, and age in multivariable logistic regression on diagnostic categories in patients admitted to ICU, COVID‐19 or sepsis and COVID‐19 or ARDS. Results: We found that most comorbidities, as well as age, had a stronger association with sepsis admission than COVID‐19 admission with the exception of male sex, type 2 diabetes mellitus, and asthma that were more strongly associated with COVID‐19 admission, while no difference was seen for chronic renal failure and obesity. For COVID‐19 and ARDS admission most risk factors were more strongly associated with ARDS admission except for male sex, type 2 diabetes mellitus, chronic renal failure, and obesity which were more strongly associated with COVID‐19 admission, whereas hypertension, chronic obstructive pulmonary disease and asthma were not different. Conclusions: Patients admitted to ICU with sepsis or ARDS carry a heavier burden of comorbidity and high age than patients admitted with COVID‐19. This is likely caused by a combination of: (1) respiratory failure in COVID‐19 being less dependent on comorbidities than in other forms of ARDS, and the cause of critical illness in other infections causing sepsis and (2) COVID‐19 patients being deferred admission in situations where patients with the other syndromes were admitted. [ABSTRACT FROM AUTHOR]

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

This scoping review synthesizes evidence on metformin's use during pregnancy, encompassing diverse conditions like gestational diabetes, type 1 and type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity. Metformin demonstrates comparable efficacy to insulin in gestational diabetes, positive outcomes in type 2 diabetes pregnancies, and potential benefits in reducing complications. The review highlights nuances in its effects across conditions, indicating advantages such as reduced risk of macrosomia and cesarean section in gestational diabetes. However, its prophylactic role in preventing gestational diabetes and associated complications remains inconclusive. In obese pregnant women, mixed results are observed, with potential benefits in reducing pre‐eclampsia risk. Metformin shows promise in preventing preterm birth and late miscarriage in PCOS pregnancies. Categorizing patient subgroups is crucial for identifying advantages, especially in gestational diabetes and type 2 diabetes. Challenges arise from study heterogeneity, necessitating standardized indications for dosage, timing, and postpartum follow ups. Efforts to identify patient characteristics influencing metformin efficacy are crucial for tailored therapy. Although metformin emerges as a viable option in complicated pregnancies, comprehensive research, standardized protocols, and subgroup identification efforts will enhance clinical utility, ensuring evidence‐based therapies and optimal maternal and fetal outcomes. Bridging existing knowledge gaps remains imperative for advancing metformin's role in pregnancy management. [ABSTRACT FROM AUTHOR]

Objective: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100–125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first‐trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first‐ trimester fasting plasma glucose levels, as compared with gestational diabetes, a well‐established risk factor for diabetes, in up to 5‐year follow‐up postpartum. Methods: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post‐delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic‐area under the curve (ROC‐AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. Results: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut‐off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. Conclusions: Increased first‐trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first‐trimester fasting plasma glucose has a more pronounced impact on progression to diabetes. Synopsis: First‐trimester fasting plasma glucose levels exceeding 86.5 mg/dL carry at least a comparable risk for type 2 diabetes progression as gestational diabetes, regardless of obesity status. [ABSTRACT FROM AUTHOR]

Objective: To compare ultrasound‐assessed fetal head circumference (HC), abdominal circumference (AC), HC/AC ratio, and estimated fetal weight (EFW) in prediction of large‐for‐gestational‐age (LGA) at birth in pregnancies affected by type 1 (T1DM) and type 2 (T2DM) diabetes. Methods: This retrospective cohort study included all women with T1DM and T2DM giving birth to singletons between 2010 and 2019 at Aalborg University Hospital, Denmark. Ultrasound scans were performed at 16, 20, 28 and 34 weeks of pregnancy. LGA was defined as birth weight deviation of 15% or greater from the expected for gestational age (≥90th centile). Prediction of LGA was assessed by logistic regression adjusted for maternal characteristics and glycated hemoglobin (HbA1c) and area under the receiver operating characteristics curve (AUC). Results: Among 180 T1DM pregnancies, 118 (66%) had an LGA neonate at birth. At 28 weeks of pregnancy, they were predicted with AUCHC/AC = 0.67, AUCAC = 0.85, and AUCEFW = 0.86. The multivariate analysis did not improve the predictive performance of the HC/AC ratio or AC. Among 87 T2DM pregnancies, 36 (41%) had an LGA neonate at birth. At 28 weeks, they were predicted with AUCHC/AC = 0.73, AUCAC = 0.83, and AUCEFW = 0.87. In T2DM, the multivariate analysis significantly improved the predictive performance for both HC/AC ratio and AC from 20 weeks of pregnancy. Conclusion: In T1DM and T2DM pregnancies, LGA is characterized by a general fetal overgrowth including both AC and HC. Therefore, AC and EFW perform better than the HC/AC ratio in the prediction of LGA. In T2DM, as opposed to T1DM, the predictive performance was improved by the inclusion of maternal characteristics and HbA1c in the analysis. Synopsis: In pregnancies involving type 1 and type 2 diabetes, estimated fetal weight and abdominal circumference are superior to head circumference/abdominal circumference ratio, in predicting large‐for‐gestational‐age. [ABSTRACT FROM AUTHOR]

Objective: Gain‐of‐function (GOF) variants of KCNJ11 cause neonate diabetes and maturity‐onset diabetes of the young (KCNJ11‐MODY), while loss‐of‐function (LOF) variants lead to hyperinsulinemia hypoglycemia and subsequent diabetes. Given the limited research of KCNJ11‐MODY, we aimed to analyse its phenotypic features and prevalence in Chinese patients with early‐onset type 2 diabetes (EOD). Design, Patients and Measurements: We performed next‐generation sequencing on 679 Chinese EOD patients to screen for KCNJ11 exons variants. Bioinformatics prediction and the American College of Medical Genetics and Genomics guidelines was used to determine the pathogenicity and diagnosed KCNJ11‐MODY. A literature review was conducted to investigate the phenotypic features of KCNJ11‐MODY. Results: We identified six predicted deleterious rare variants in six EOD patients (0.88%). They were classified as uncertain significance (variant of uncertain significance [VUS]), but more common in this EOD cohort than a general Chinese population database, however, without significant difference (53/10,588, 0.50%) (p =.268). Among 80 previously reported patients with KCNJ11‐MODY, 23.8% (19/80) carried 9 (32.1%) LOF variants, who had significantly older age at diagnosis, higher birthweight and higher fasting C‐peptide compared to patients with GOF variants. Many patients carrying VUS were not correctly diagnosed. Conclusions: Some rare variants of KCNJ11 might contribute to the development of Chinese EOD, although available evidence has not enough power to support them as cause of KCNJ11‐MODY. The clinical features of LOF variants were different from GOF variants in KCNJ11‐MODY patients. It is necessary to evaluate the pathogenicity of VUS through function experiments. [ABSTRACT FROM AUTHOR]

Aims: While randomized controlled trials data on the long‐term effect of glucose‐lowering drugs (GLDs) on liver‐related outcomes are lacking, population‐based studies have evaluated the associations of GLDs with liver‐related outcomes in individuals with type 2 diabetes (T2D). we aimed to conduct a systematic review of population‐based studies evaluating the effects of GLDs on liver‐related outcomes in people with T2D. Methods: PubMed, Web of Science, and Embase databases were systematically searched for population‐based studies testing the associations of GLDs with liver‐related outcomes in individuals with T2D and no liver disease other than non‐alcoholic fatty liver disease (NAFLD) from inception to 23 February 2024. GLDs included SGLT2is, TZDs, insulin, GLP‐1 RAs and dipeptidyl peptidase‐4 inhibitors (DPP4Is). Results: Ten cohort studies, comprising 1,274,641 participants, met the inclusion criteria. The median follow‐up period ranged from 8.9 to 76 months. Of all the GLDs under investigation, SGLT2is were associated with the strongest reduction in NAFLD incidence, cirrhosis, and composite liver‐related events compared to other medications. TZDs were associated with a reduced risk of developing NAFLD and cirrhosis but were not significantly associated with a lower incidence of hepatocellular carcinoma. GLP‐1 RAs demonstrated a significant association with reduced liver‐related mortality. Conclusions: Observational data from population‐based studies suggest that GLDs such as SGLT2is are associated with beneficial long‐term liver‐related outcomes in T2D patients with NAFLD. Additional studies, including randomized controlled trials with long‐term follow‐up, are needed to confirm these findings. Registration Number: PROSPERO CRD442024536872. [ABSTRACT FROM AUTHOR]

Aim: Adults with intellectual and developmental disabilities (IDD) have a significantly higher prevalence of Type 2 diabetes than the general population. Evidence that lifestyle and/or behavioural interventions, such as participation in Special Olympics, decreases the risk of developing diabetes in adults with IDD could help minimize health disparities and promote overall health in this population. Methods: This was a 20‐year retrospective cohort study of adults with IDD (30–39 years) in the province of Ontario, Canada, that compared hazard rates of diabetes among Special Olympics participants (n = 4145) to non‐participants (n = 31,009) using administrative health databases housed at ICES. Using cox proportional hazard models, crude and adjusted hazard ratios were calculated for the association between the primary independent variable (Special Olympics participation status) and the dependent variable (incident diabetes cases). Results: After controlling for other variables, the hazard ratio comparing rates for developing diabetes between Special Olympics participants and non‐participants was 0.85. This represents a 15% reduction in the hazard among Special Olympics participants when followed for up to 20 years. This result was statistically significant and represents a small effect size. Conclusions: Special Olympics could be considered a complex intervention that promotes physical activity engagement through sport participation, health screenings, and the promotion of healthy eating habits through educational initiatives. This study provides evidence that Special Olympics participation decreases the rate for developing diabetes. [ABSTRACT FROM AUTHOR]

Background and Aims: Gastrointestinal (GI) symptoms, common in type 2 diabetes (T2D), are typically bothersome, socially embarrassing, and impact negatively on quality of life. They may also contribute to diabetes distress (DD), but this has never been formally evaluated. We aimed to investigate the relationships between GI symptoms, DD and depressive symptoms in a large cohort of individuals with T2D in Bangladesh. Materials and Methods: 1406 unselected T2D individuals (female 58.8%; mean age 51.0 ± 12.5 years) from four diabetes clinics in Bangladesh completed validated questionnaires evaluating GI symptoms (PAGI‐SYM), DD (DDS‐17) and depressive symptoms (PHQ‐9). Results: 31.1% of participants reported GI symptoms (36.2% females, 23.7% males), while 51.1% had elevated DD and 37.8% depressive symptoms. GI symptoms exhibited independent relationships with both DD and depressive symptoms, and their likelihood was higher among those with DD (OR: 3.6 [2.2–5.6] and with depressive symptoms (OR: 5.9 [3.5–9.9]). Conclusions: GI symptoms are independently associated with both DD and depressive symptoms in people with T2D in Bangladesh. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL‐sRNA‐h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose‐6‐phosphatase. Oral administration of sphingosine (d18:1)‐JGL‐sRNA‐h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)‐JGL‐sRNA‐h7 bencaosomes‐treated beagle dogs. Our study indicates that JGL‐sRNA‐h7 could be a promising hypoglycemic oligonucleotide drug. [ABSTRACT FROM AUTHOR]

Summary: α‐Glycosidase, a critical therapeutic target in type 2 diabetes mellitus (T2DM), can be modulated by inhibitors to reduce postprandial blood glucose levels. This study investigated the inhibitory effects of vine tea (Ampelopsis grossedentata) and its key compounds on α‐glycosidase. The results demonstrated that fifteen varieties of vine tea extracts inhibited α‐glycosidase in a dose‐dependent manner, with IC50 values ranging from 5.25 to 35.8 μg mL−1. HPLC analysis revealed dihydromyricetin (DHM) as the main compound in vine tea, with an IC50 value of 262.50 μM. Notably, the synergistic combination of DHM and the antidiabetic drug acarbose (ABS) significantly enhanced inhibitory effectiveness, with the optimal ratio (1:125) yielding a potentiation index (CI) of 0.09. Fluorescence and molecular docking analyses supported the hypothesis that DHM enhanced ABS's inhibitory effect through complex formation and specific interactions, offering a promising option for safer and more effective diabetes therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rice is considered a high estimated glycemic index (eGI) food because of its higher starch digestibility, which leads to type II diabetes and obesity as a result of a sedentary life style. Furthermore, the incresaing diabetes cases in rice‐consuming populations worldwide need alternative methods to reduce the glycemic impact of rice, with dietary prescriptions based on the eGI value of food being an attractive and practical concept. Rice is often paired with vegetables, pulses, tubers and roots, a staple food group in Africa, Latin America and Asia, which are rich in fibre and health‐promoting compounds. RESULTS: Rice from four categories (high protein, scented, general and pigmented) was analyzed for eGI and resistant starch (RS) content. Among the genotypes, Improved Lalat had the lowest eGI (53.12) with a relatively higher RS content (2.17%), whereas Hue showed the lowest RS (0.19%) with the highest eGI (76.3) value. The addition of tuber crops to rice caused a significant lowering of eGI where the maximum beneficial effect was shown by elephant foot yam (49.37) followed by yam bean (53.07) and taro (54.43). CONCLUSION: The present study suggests that combining rice with suitable tuber crops can significantly reduce its eGI value, potentially reducing the burden of diet‐associated lifestyle diseases particularly diabetics. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Tadalafil, commonly prescribed for benign prostatic hyperplasia (BPH), may benefit patients with Type 2 diabetes mellitus (T2DM) for glycemic markers and complications. However, the association between the long‐term use of tadalafil and the incidence of T2DM has not been investigated. Methods: We emulated a target trial of tadalafil use (5 mg/day) and the risk of T2DM using a population‐based claims database in Japan. Patients who initiated tadalafil or alpha‐blockers for BPH and had no history of diabetes diagnosis, no dispensing of glucose‐lowering drugs, and no history of hemoglobin A1c levels of ≥6.5% (47–48 mmol/mol) were included. The primary outcome was the incidence of T2DM. Pooled logistic regression was used to estimate adjusted risk ratios (RRs) and 5‐year cumulative incidence differences (CIDs). Results: A total of 5180 participants initiated tadalafil treatment and were compared with 20,049 patients who initiated alpha‐blockers. The median follow‐up time for each arm was 27.2 months (interquartile range [IQR], 12.0–47.9) in tadalafil users and 31.3 months (IQR, 13.7–57.2) in alpha‐blocker users. The incidence rates of T2DM in tadalafil and alpha‐blocker users were 5.4 (95% confidence interval [CI], 4.0–7.2) and 8.8 (95% CI, 7.8–9.8) per 1000‐person years, respectively. Initiation of tadalafil was associated with a reduced risk of T2DM (RR, 0.47; 95% CI, 0.39–0.62; 5‐year CID, −0.031; 95% CI, −0.040 to −0.019). Conclusion: The incidence of T2DM was lower in men with BPH treated with tadalafil than in those treated with alpha‐blockers. Thus, tadalafil may be more beneficial than alpha‐blockers in preventing T2DM. [ABSTRACT FROM AUTHOR]

Background: Increased thermogenic activity has shown to be a promising target for treating and preventing obesity and type 2 diabetes (T2DM). Little is known about the muscular influence on nonshivering thermogenesis (NST), and it remains unclear whether physical training and potential metabolic improvements could be associated with changes in this type of thermogenic activity. Objective: The present study aimed to assess muscular NST activity in overweight and T2DM before and after a combined training period (strength training followed by aerobic exercise). Methods: Nonshivering cold‐induced 18‐fluoroxyglucose positron emission computed tomography (18F‐FDG PET/CT) was performed before and after 16 weeks of combined training in 12 individuals with overweight and T2DM. The standard uptake value (SUV) of 18F‐FDG was evaluated in skeletal muscles, the heart and the aorta. Results: Muscles in the neck region exhibit higher SUV pre‐ and posttraining. Furthermore, a decrease in glucose uptake by the muscles of the lower and upper extremities and in the aorta was observed after training when adjusted for brown adipose tissue (BAT). These pre–post effects are accompanied by increased cardiac SUV and occur concurrently with heightened energy expenditure and metabolic improvements. Conclusions: Muscles in the neck region have greater metabolic activity upon exposure to cold. In addition, combined training appears to induce greater NST, favoring the trunk and neck region compared to limbs based on joint work and adaptations between skeletal muscles and BAT. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to evaluate the efficacy and safety of duodenal–jejunal bypass liner (DJBL) for obesity and type 2 diabetes mellitus. A comprehensive search of electronic databases was conducted up to September 15, 2022. Thirty studies involving 1751 patients were included. At 12 months post‐implantation, the reduction in body mass index (BMI) was 4.8 kg/m2 (95% CI 4.1, 5.5), with an excess weight loss of 41.3% (95% CI 33.4%,49.2%) and a total weight loss of 13.1% (95% CI 10.1%, 16.0%). Significant decrease was observed in HbA1c and fasting glucose, with a standardized mean difference of − 0.72 (95% CI − 0.95, − 0.48) and − 0.62 (95% CI − 0.82, − 0.42), respectively. However, these improvements in weight loss and glycemic control were only partially sustained after explantation. In situ, DJBL significantly improves blood pressure and lipid levels. The pooled early removal rate was 19%, and the incidence of severe adverse events was 17%, including device migration (6%), gastrointestinal hemorrhage (4%), device obstruction (4%), and hepatic abscess (2%). DJBL offers significant improvement in weight loss and glycemic control, as well as cardiovascular parameters while in situ. Further studies are warranted to better understand the long‐term efficacy and safety of DJBL. The benefits of DJBL need to be carefully weighed against the risks in clinical decision‐making. [ABSTRACT FROM AUTHOR]

Summary: Bipolar disorder (BD) is a complex and severe mental illness that causes significant suffering to patients. In addition to the burden of depressive and manic symptoms, patients with BD are at an increased risk for metabolic syndrome (MetS). MetS includes factors associated with an increased risk of atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), which may increase the mortality rate of patients with BD. Several studies have suggested a link between BD and MetS, which may be explained at an epigenetic level. We have focused on epigenetic mechanisms to review the causes of metabolic risk in BD. [ABSTRACT FROM AUTHOR]

Objective: The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes. Methods: A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6–18 years who underwent dual‐energy X‐ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta‐Analysis of Glucose and Insulin‐Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). Results: In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA‐IR) and homeostasis model assessment of pancreatic beta cell function (HOMA‐β) through FGF23, whereas fat‐free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat‐free mass with fasting glucose, fasting insulin and HOMA‐IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat‐free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01–1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77–0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: −0.05 [95% CI: −0.07, −0.02]) and fat‐free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose. Conclusions: Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the efficacy and safety of cofrogliptin, a novel dipeptidyl peptidase‐4 inhibitor taken once every 2 weeks (Q2W), compared with linagliptin (taken daily) in patients with type 2 diabetes inadequately controlled on metformin in China. Materials and Methods: In this phase 3 randomized, double‐blind, active‐controlled, multicentre study, patients were randomly assigned 1:1:1 to receive cofrogliptin 10 mg Q2W, cofrogliptin 25 mg Q2W, or linagliptin 5 mg daily, all as an add‐on treatment to metformin, for 24 weeks. Eligible patients could enter an open‐label extension period and receive cofrogliptin 25 mg Q2W for an additional 28 weeks. The primary endpoint was change in glycated haemoglobin from baseline to 24 weeks, with a non‐inferiority margin of 0.4% for cofrogliptin versus linagliptin treatment. Results: Overall, 465 patients entered the 24‐week treatment period (median age: 57.0 years). The least‐squares mean (standard error) change in glycated haemoglobin from baseline to week 24 was −0.96 (0.063), −0.99 (0.064) and −1.07 (0.065) for the cofrogliptin 10 mg, cofrogliptin 25 mg and linagliptin 5 mg groups, respectively. The between‐group difference met the predefined margin for non‐inferiority of cofrogliptin (10 and 25 mg) versus linagliptin treatment. The incidence of common adverse events (≥5% patients) during the 24‐week treatment period was similar between treatment groups. There were no serious hypoglycaemic events. Conclusion: In Chinese patients with type 2 diabetes inadequately controlled on metformin, the glucose‐lowering effect of cofrogliptin (Q2W) was non‐inferior to linagliptin (daily), with a similar safety profile maintained over 52 weeks of treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To analyse data from the All of Us Research Program to evaluate the real‐world application and long‐term effectiveness of semaglutide in treating type 2 diabetes and obesity patients in a large population. Materials and Methods: We identified patients prescribed semaglutide and analysed differences in route of administration and the time on semaglutide. For individuals diagnosed with obesity, we measured changes in body mass index (BMI) and weight from baseline, while measured changes in HbA1c for those patients with type 2 diabetes. We also examined the occurrence of newly diagnosed common adverse events from taking semaglutide. Results: For 3739 semaglutide patients, those on injectable semaglutide (3364 patients) averaged 301.54 days on the medication, with 20.36% having no end date, while those on oral semaglutide (435 patients) averaged 172.48 days, with 24.60% having no end date. We found average decreases of 1.54 kg/m2 in BMI, 4.65 kg in weight and 0.75% in HbA1c for semaglutide users. The decreases were larger in participants taking injectable formulation, probably because of higher starting values. Over time, improvements in these outcomes diminished, but the values remained significantly lower than baseline levels. Approximately only 1.0% of patients reported newly diagnosed common adverse events. Conclusions: Consistent with clinical trial findings, this real‐world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c, albeit to smaller magnitudes than observed in clinical trials. These findings provide valuable insights into real‐world experience and the long‐term effectiveness of semaglutide. [ABSTRACT FROM AUTHOR]

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have revolutionized the treatment of type 2 diabetes, chronic kidney disease (CKD), and chronic heart failure. Clinical trials have shown significant benefits in reducing blood glucose levels and improving cardiovascular outcomes. However, despite the growing evidence supporting their effectiveness, there is still a lack of widespread use of these drugs in clinical practice. The article emphasizes the need for better communication between healthcare providers and patients, addressing patient non-adherence and clinical inertia, and further research and education to bridge the gap between scientific knowledge and real-world practice. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the relationship between the stress‐hyperglycaemia ratio (SHR) and the clinical prognosis of patients with moderate‐to‐severe coronary artery calcification (MSCAC). Methods: We consecutively enrolled 3841 patients with angiography‐detected MSCAC. The individuals were categorized into three groups based on SHR tertiles: T1 (SHR ≤ 0.77), T2 (0.77 < SHR ≤ 0.89) and T3 (SHR > 0.89). The SHR value was calculated using the formula SHR = [admission glucose (mmol/L)]/[1.59 × HbA1c (%) − 2.59]. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs), including all‐cause death, non‐fatal myocardial infarction and non‐fatal stroke. Results: During a median follow‐up of 3.11 years, 241 MACCEs were recorded. Kaplan–Meier survival analysis showed that the SHR T3 group had the highest incidence of MACCEs (P <.001). Moreover, findings from the restricted cubic spline analysis showed a significant and positive association between the SHR and MACCEs. This correlation remained consistent even after considering other variables that could potentially impact the results (Pnon‐linear =.794). When comparing SHR T1 with SHR T3, it was found that SHR T3 was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio = 1.50; 95% confidence interval: 1.10‐2.03). Conclusions: Patients with MSCAC showed a positive correlation between the SHR and MACCE rate over a 3‐year follow‐up period. The study showed that an SHR value of 0.83 is the key threshold, indicating a poor prognosis. Future large‐scale multicentre investigations should be conducted to determine the predictive value of the SHR in patients with MSCAC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the utilization and costs of non‐insulin glucose‐lowering drugs (GLDs) in Australia from 2013 to 2023. Materials and Methods: We conducted a retrospective analysis of the Australian Pharmaceutical Benefits Scheme (PBS) administrative dataset of 118 727 494 GLD prescriptions. The main outcome measures were the annual number of GLD prescriptions dispensed, accounting for type 2 diabetes mellitus (T2DM) prevalence and healthcare system costs, adjusted for inflation. Results: Utilization of GLDs doubled from 6.4 million prescriptions in 2013 to 15.6 million in 2023. The average annual percent increase in utilization was 8.1%, compared to the average annual increase in prevalence of T2DM of 1.8%. The biggest change was in sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, for which there was an average annual increase in utilization of 59.4% (95% confidence interval [CI] 51.7%, 68.2%; p < 0.05) from 2014 (first full year of PBS listing), followed by glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), which showed an increase of 31.4% (95% CI 28.5%, 33.8%; p < 0.05) annually (2013 to 2023). Dipeptidyl peptidase‐4 inhibitor utilization tripled, with an average annual increase of 10.9% (95% CI 8.1%, 13.8%; p < 0.05), but this plateaued from 2020. Metformin utilization increased by 4.7% (95% CI 2.0%, 6.9%; p < 0.05) annually. In contrast, sulphonylurea, glitazone and acarbose utilization declined. Total GLD costs increased threefold over the same period. Despite only accounting for 11.7% of utilization, GLP‐1RAs contributed to 35% of the costs. Conclusion: Utilization of GLDs doubled, and associated costs tripled over the past 11 years, with no sign of either utilization or costs plateauing, predominantly due to increased GLP‐1RA and SGLT2 inhibitor prescribing. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: To investigate the impact of baseline characteristics on the efficacy of once‐weekly subcutaneous semaglutide 0.5 and 1.0 mg in participants with type 2 diabetes (T2D) from the SUSTAIN China trial. Methods: In this post hoc analysis, data for semaglutide 0.5 and 1.0 mg versus sitagliptin 100 mg were analysed in the total (n = 868) and Chinese‐only (n = 605) populations. Changes from baseline to end of treatment (EOT) in glycated haemoglobin (HbA1c) and body weight were analysed by baseline age, sex, body mass index, HbA1c, diabetes duration, and homeostatic model assessment of β‐cell function (HOMA‐β) tertile. Proportions of participants achieving HbA1c <7.0% (53 mmol/mol) by baseline HbA1c, change from baseline to EOT in standard deviation of seven‐point self‐monitored plasma glucose (SMPG), derived time‐in‐range (dTIR) of seven‐point SMPG at Week 30, and HOMA‐β ratio to baseline at Week 30 were assessed for both populations. Results: In both populations the efficacy of once‐weekly subcutaneous semaglutide 0.5 and 1.0 mg versus sitagliptin was not significantly affected by most of the baseline characteristics studied. The proportion of participants achieving the target HbA1c <7% was not affected by baseline HbA1c (pinteraction > 0.05). SMPG fluctuation and dTIR indicated less glucose variability in participants treated with semaglutide 0.5 and 1.0 mg versus sitagliptin, and the HOMA‐β ratios to baseline at EOT were greater with semaglutide 0.5 and 1.0 mg versus sitagliptin (p < 0.05). Conclusions: These results support the effectiveness of once‐weekly subcutaneous semaglutide 0.5 and 1.0 mg across a broad range of baseline characteristics, in participants with T2D from SUSTAIN China. [ABSTRACT FROM AUTHOR]

Aim: Normoglycaemia was achieved in a significant proportion of Japanese participants with type 2 diabetes in two phase 3 studies of tirzepatide. This post hoc exploratory analysis aimed to identify predictive factors associated with normoglycaemia achievement. Materials and Methods: SURPASS J‐mono and SURPASS J‐combo study data were pooled for this analysis. Characteristics of participants in whom normoglycaemia [glycated haemoglobin (HbA1c) <5.7%] was achieved were summarized. Logistic regression analyses were performed with HbA1c <5.7% achievement as the target variable. Results: Of 912 participants, normoglycaemia was achieved in 553 (60.6%) following 52 weeks of tirzepatide treatment. Overall, the mean (SD) age was 56.7 (10.6) years and mean diabetes duration was 7.7 (6.0) years, and 76% of participants were men. Mean (SD) change from baseline in HbA1c and bodyweight was −2.87% (0.95) versus −2.47% (1.1) and −10.30 (5.8) kg versus −3.75 (4.3) kg for participants in whom normoglycaemia was and was not reached, respectively. Multivariate regression analyses showed that lower baseline body mass index, shorter disease duration and lower baseline HbA1c were significantly associated with higher rates of normoglycaemia achievement (p = 0.009, p = 0.008, p < 0.001, respectively) as was a tirzepatide dose of 10 or 15 mg compared with 5 mg (p < 0.001). The highest percentage of participants in whom normoglycaemia (94%) was achieved were those with lower baseline HbA1c (<8%) and the greatest weight reduction (≥15%). Conclusions: Baseline HbA1c and body mass index, disease duration and the tirzepatide treatment group were shown to be predictive factors for achieving normoglycaemia. A lower baseline HbA1c was most strongly associated with normoglycaemia achievement. [ABSTRACT FROM AUTHOR]

A pilot study was conducted to investigate the use of real-time continuous glucose monitoring (RT-CGM) in non-critical care insulin-treated inpatients under non-diabetes specialty teams in hospitals. The study found no significant differences in glycemic control between the group using RT-CGM and the group using capillary blood glucose (CBG) monitoring. While RT-CGM has been effective in outpatient settings, its effectiveness in hospitals without direct guidance from diabetes specialists is still uncertain. Further research is needed to determine the best use of RT-CGM in hospital settings. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of a small‐molecule nicotinamide N‐methyltransferase (NNMT) inhibitor, 5A1MQ, on body composition, metabolic variables, fatty liver pathologies, and circulating biomarkers in diet‐induced obese (DIO) mice, and characterize its plasma pharmacokinetics (PK) and tissue distribution in vivo. Materials and Methods: DIO mice were administered vehicle or 5A1MQ once daily for 28 days. Longitudinal measures of body composition, blood glucose and plasma insulin levels, and terminal measures of liver histopathology and serum markers, were evaluated. Plasma and tissue PK were established in age‐ and strain‐matched mice after intravenous, oral, and subcutaneous dosing of 5A1MQ. Results: 5A1MQ treatment dose‐dependently limited body weight and fat mass gains, improved oral glucose tolerance and insulin sensitivity, and suppressed hyperinsulinaemia in DIO mice. Liver histology from 5A1MQ‐treated DIO mice showed attenuated hepatic steatosis and macrophage infiltration, and correspondingly reduced liver weight, size, and triglyceride levels. 5A1MQ treatment normalized circulating levels of alanine transaminase, aspartate transaminase, and ketone bodies, supporting an overall improvement in liver and metabolic functions. The pharmacodynamic effects of 5A1MQ were further corroborated by its high systemic exposure and effective distribution to metabolically active tissues, including adipose, muscle and liver, following subcutaneous dosing of mice. Conclusions: This work validates NNMT inhibition as a viable pharmacological approach to ameliorate metabolic imbalances and improve liver pathologies that develop with obesity. [ABSTRACT FROM AUTHOR]

Objectives: To present the Real‐World Progression In Diabetes (RAPIDS) 2.0 Risk Engine, the only simulation model to study the long‐term trajectories of outcomes arising from dynamic sequences of glucose‐lowering treatments in type 2 diabetes (T2DM). Research Design and Methods: The RAPIDS model's risk equations were re‐estimated using a Least Absolute Shrinkage and Selection Operator (LASSO)‐based regularization of features that spanned baseline data from the last two quarters of current time and interactions with age. These equations were supplemented with estimates for the impact of dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 receptor agonists, and sodium‐glucose cotransporter‐2 inhibitor classes of drugs as monotherapies and their combinations with metformin based on newer trial data and comprehensive meta‐analyses. The probabilistic RAPIDS 2.0 model was calibrated (N = 25 000) and validated (N = 263 816) using electronic medical records (EMR) data between 2008 and 2021 from a national network of US healthcare organizations. Results: The EMR‐based cohort had a mean age of 61 years at baseline, with 50% women, 70% non‐Hispanic White individuals and 20% non‐Hispanic Black individuals, and was followed for 17.5 quarters (range: 3–50). The final RAPIDS 2.0 risk engine accurately predicted the long‐term trajectories of all nine biomarkers and nine outcomes in the hold‐out validation sample. Similar accuracies in predictions were observed in each of the 14 subgroups studied. Conclusion: The RAPIDS 2.0 model demonstrated valid long‐term predictions of outcomes in individuals with T2DM in the United States as a function of dynamic sequences of treatment use patterns. This highlights its potential to project long‐term comparative effectiveness between alternative sequences of glucose‐lowering treatment uses in the United States. [ABSTRACT FROM AUTHOR]

This article examines the early adoption of semaglutide, a drug used to treat type 2 diabetes, in Scandinavia, with a focus on Denmark. The study analyzes nationwide prescription data from Denmark, Norway, and Sweden to compare the use of semaglutide with other glucose-lowering drugs and to compare the characteristics of semaglutide initiators with initiators of other drugs. The findings reveal that semaglutide is widely used in Scandinavia and that the characteristics of semaglutide initiators differ slightly from initiators of other drugs. The study also identifies differences between early and late initiators of semaglutide, suggesting potential off-label use for weight loss. However, the study acknowledges limitations, such as the lack of data on specific indications for use. [Extracted from the article]

This article discusses the cost-effectiveness of using natriuretic peptides (NPs) to screen for and treat stage B heart failure (HF) in individuals with type 2 diabetes. The study used a Markov state-transition model and conducted simulations over multiple annual cycles. The results showed that NP screening and treatment provided high value after at least 7 years, according to the incremental cost-effectiveness ratio (ICER). However, the study has limitations, such as not considering additive therapy with finerenone and using probabilities from different studies. Further research is needed to fill in data gaps and determine the most cost-effective screening strategy for individuals at high risk of incident HF. [Extracted from the article]

Aims: To assess the level of adherence to glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment using real‐world data and to investigate the sociodemographic and clinical factors associated with discontinuation of GLP‐1RAs. Methods: First‐time users of GLP‐1RAs with type 2 diabetes mellitus (T2DM), aged ≥18 years, in the period 2007 to 2020, were identified using Danish registries, allowing all participants a minimum of 18 months' follow‐up. Adherence to GLP‐1RA therapy (medication possession ratio >0.80) and discontinuation of GLP‐1RA therapy was estimated at 6‐ and 12‐month follow‐ups. Multivariable cause‐specific Cox regression was used to identify sociodemographic and clinical factors associated with risk of discontinuation. Results: In total, 44 343 first‐time users of GLP‐1RAs with T2DM were identified (mean age 58.6 years, 42.7% female, median duration of T2DM 6.8 years, median glycated haemoglobin level 65 mmol/mol). The absolute risk of discontinuing GLP‐1RA treatment within 6 months was 14.2% (95% confidence interval [CI] 13.9–14.6) and 21.2% (95% CI 20.8–21.5) within 12 months. At 6 months, 50.4% were adherent to GLP‐1RA therapy and at 12 months, 48.6% remained adherent. In the multivariable model, younger (<40 years) and older age (>75 years), higher Charlson Comorbidity Index score, lower household income, high school and longer university degree as educational attainment level, and longer diabetes duration were associated with a higher risk of discontinuing GLP‐1RA treatment. Conclusion: Approximately one in five patients discontinued GLP‐1RA therapy within the first 12 months and only half were adherent. Overall, lower socioeconomic status and higher comorbidity burden were associated with higher risk of discontinuing GLP‐1RA treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the long‐term impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). Materials and Methods: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP‐1 RA treatment and those who did not receive glucose‐lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. Results: After propensity score matching, the study included 12,123 individuals in each group. GLP‐1 RA treatment was associated with a significantly lower risk of all‐cause mortality (hazard ratio 0.23; 95% confidence interval 0.15–0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP‐1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. Conclusions: In this large observational study, GLP‐1 RAs showed long‐term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP‐1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population. [ABSTRACT FROM AUTHOR]

Aim: To examine the hypothesis that there would be ethnic differences in the relationship between ectopic fat and tissue‐specific insulin resistance (IR) across a spectrum of glucose tolerance in Black African (BA) and White European (WE) men. Materials and Methods: Fifty‐three WE men (23/10/20 normal glucose tolerance [NGT]/impaired glucose tolerance [IGT]/type 2 diabetes [T2D]) and 48 BA men (20/10/18, respectively) underwent a two‐step hyperinsulinaemic‐euglycaemic clamp with infusion of D‐[6,6‐2H2]‐glucose and [2H5]‐glycerol to assess hepatic, peripheral and adipose tissue IR. Magnetic resonance imaging was used to measure subcutaneous adipose tissue, visceral adipose tissue (VAT) and intrahepatic lipid (IHL). Associations between ectopic fat and IR were assessed using linear regression models. Results: There were no differences in tissue‐specific IR between ethnic groups at any stage of glucose tolerance. VAT level was consistently lower in the BA population; NGT (p = 0.013), IGT (p = 0.006) and T2D (p = 0.015). IHL was also lower in the BA compared with the WE men (p = 0.013). VAT and IHL levels were significantly associated with hepatic IR in the BA population (p = 0.001) and with peripheral IR in the WE population (p = 0.027). Conclusions: The present study suggests that BA and WE men exhibit the same degree of IR across a glucose tolerance continuum, but with lower VAT and IHL levels in the BA population, suggesting that IR may be driven by a mechanism other than increased ectopic fat accumulation in BA men. [ABSTRACT FROM AUTHOR]

Aim: The real‐world benefits of continuous glucose monitoring (CGM) in the broad type 2 diabetes (T2D) population are not well studied. Our study evaluated the impact of CGM use on health care resource utilization over 12 months in adults with T2D. Materials and Methods: This retrospective cohort analysis used Optum's de‐identified Market Clarity data of >79 million people to evaluate CGM use in people with T2D who were treated with non‐insulin (NIT), basal insulin (BIT) and prandial insulin therapy (PIT). The primary outcomes were changes in all‐cause hospitalizations, acute diabetes‐related hospitalizations and acute diabetes‐related emergency room visits during the 6‐ and 12‐month post‐index period following transition from blood glucose monitoring to CGM. A pre‐specified subgroup analysis assessed glucose control and medication changes among people with T2D over 1 year. Results: The analysis included 74 679 adults with T2D (NIT; n = 25 269), (BIT; n = 16 264) and (PIT; n = 33 146). Significant reductions in all‐cause hospitalizations, acute diabetes‐related hospitalizations and acute diabetes‐related emergency room visits were observed in the 6‐month post‐index period that were sustained during the 6–12 month post‐index period (NIT, −10.1%, −31.0%, −30.7%; BIT, −13.9%, −47.6%, −28.2%; and PIT, −22.6%, −52.7%, −36.6%, respectively). A subgroup analysis of 6030 people showed mean glycated haemoglobin reductions at approximately 3 months, which were also sustained throughout the post‐index period: NIT, −1.1 (0.05)%; BIT, −1.1 (0.06)%; and PIT, −0.9 (0.04)%, p < 0.0001. Conclusions: CGM use in real‐life across different therapeutic regimens in adults with T2D was associated with reductions in health care resource utilization with improved glucose control over 1 year. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study conducted in China that examined the effects of ISIS 449884, a medication for type 2 diabetes, on HbA1c levels in Chinese patients. The study found that ISIS 449884 significantly reduced HbA1c levels compared to a placebo after 16 weeks of treatment. The medication also increased fasting glucagon and total GLP-1 levels, and reduced fasting serum glucose. Adverse events were experienced by a majority of participants in both the ISIS 449884 and placebo groups, but there were no serious hypoglycemic events. The study concluded that ISIS 449884 improved HbA1c levels with an acceptable safety profile. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]