Diabetes, Obesity & Metabolism最新文献

Diabetic ketoacidosis (DKA) is a life-threatening complication usually affecting people with type 1 diabetes (T1D) and, less commonly, people with type 2 diabetes. Early identification of ketosis is a cornerstone in DKA prevention and management. Current methods for ketone measurement by people with diabetes include capillary blood or urine testing. These approaches have limitations, including the need to carry testing strips that have a limited shelf life and a requirement for the user to initiate a test. Recent studies have shown the feasibility of continuous ketone monitoring (CKM) via interstitial fluid with a sensor inserted subcutaneously employing an enzymatic electrochemical reaction. Ketone readings can be updated every 5 minutes. In the future, one would expect that commercialized devices will incorporate alarms linked with standardized thresholds and trend arrows. Ideally, to minimize the burden on users, CKM functionality should be integrated with other devices used to implement glucose management, including continuous glucose monitors and insulin pumps. We suggest CKM provision to all at risk of DKA and recommend that the devices should be worn continuously. Those who may particularly benefit are individuals who have T1D, are pregnant, on medications such as sodium-glucose linked transporter (SGLT) inhibitors that increase DKA, people with recurrent DKA, those with T1D undertaking high intensity exercise, are socially or geographically isolated, or those on low carbohydrate diets. The provision of ketone profiles will provide important clinical insights that have previously been unavailable to people living with diabetes and their healthcare professionals.

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.

Aim: The distribution pattern of abdominal adiposity may help determine cardiovascular disease (CVD). Waist circumference (WC) is the most common but imprecise method for measuring abdominal adiposity, as it fails to differentiate between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT). This study aimed to determine whether elevated VAT or ASAT provides greater prognostic value for CVD events compared to elevated WC in the general population using data from the UK Biobank.

Materials and methods: In this secondary analysis of UK Biobank study, 24 265 participants with available abdominal magnetic resonance imaging data were included. The primary outcome of the study was coronary heart disease (CHD), and secondary outcomes included stroke, heart failure (HF) and atrial fibrillation (AF). Cox regressions for VAT, ASAT and WC were examined in relation to the predefined outcomes on continuous scales using standard deviation (SD) changes and by categories of concordant and discordant values defined by medians.

Results: During a mean follow-up period of 12.9 ± 1.8 years, 2641 participants developed CVD events (1296 CHD, 165 stroke, 286 HF and 894 AF) Each 1 SD increase in VAT yielded a hazard ratio (HR) of 1.15 (95% confidence interval [CI]: 1.09-1.22) for CHD risk, whereas ASAT had a HR of 1.10 (95% CI: 1.04-1.18). Further adjustment for WC eliminated the association between ASAT and CHD risk, in contrast to the association between VAT and CHD risk, which remained almost unaffected. Discordant VAT above the median with WC below presented a HR of 1.43 (95% CI: 1.15-1.78) for CHD, compared with concordant VAT and WC below the median. Similar results were found for discordant WC above the median with VAT below, with a HR of 1.46 (95% CI: 1.18-1.81). In contrast, discordant ASAT above the median with WC below was not associated with an increased risk of CHD. Similarly, discordant ASAT above the median with VAT below was not associated with an increased risk of CHD. Additionally, there was no observed association between VAT or ASAT and the risks of stroke, HF or AF after further adjustment for WC. Additionally, there was no observed association between VAT or ASAT and the risks of stroke, HF or AF after further adjustment for WC.

Conclusion: Incorporating VAT measurements alongside WC data improved the ability to identify individuals at high risk for CHD compared to using WC alone. Both VAT and WC proved to be more accurate indicators of CHD risk than ASAT. However, VAT alone did not fully account for the CHD risk associated with elevated WC levels. Neither VAT nor ASAT showed an association with the risk of stroke, HF and AF.

Aim: To assess the variation in patterns of use of insulin and other antidiabetic medicines across China, both geographically and over time.

Materials and methods: Nationally, we calculated the relative change in antidiabetic medicine purchases between the first and last quarters of 2020 through 2022 based on the number of defined daily doses procured per quarter. We used annual data to analyse differences in antidiabetic medicine use and patterns across seven regions of China. Considering large regional variations, we used multifactor linear regression to preliminarily explore the possible factors influencing this variation.

Results: Nationally, the procurement of antidiabetic medicines and insulin increased from 2020 to 2022, while the proportion of insulin among antidiabetic medicines remained stable at approximately 22%. Among all insulins, premixed insulin (human) was ranked first. Of the three subgroups of insulin, analogues were the most preferred and had the largest procurement, but different categories showed different trends in terms of purchases and proporation. Regionally, the growth rate of antidiabetic medicines, the proportion of insulin procurement and the preferred types of insulin across the seven regions were different. Regarding preliminary influencing factors, the level of education and owning a domestically funded producer had a positive effect on insulin procurement.

Conclusions: From 2020 to 2022, the procurement of insulin increased, which may be due to the increased attention for diabetes from the country and residents.However, the proportion of insulin among all antidiabetic medicines was essentially unchanged, while the use of some non-insulin hypoglycemic drugs increased significantly, especially the SGLT2i and GLP-1 RA. Given the economic and cultural diversity, Insulin procurement and utilization patterns varied greatly across the regions. Owning domestic enterprises potentially influences the procurement of insulin. Enhancing education to further improve the self-management of patients with diabetes is essential.

ENT-03, a spermine bile acid we recently discovered in the brain of newborn mice acts centrally to regulate energy and metabolism. Obese, diabetic (ob/ob) mice treated with five doses of ENT-03 over 2 weeks, demonstrated a rapid decrease in blood glucose levels into the range seen in non-obese animals, prior to any significant weight loss. Weight fell substantially thereafter as food intake decreased, and serum biochemical parameters normalized compared with both vehicle and pair-fed controls. To determine whether ENT-03 could be acting centrally, we injected a single dose of ENT-03 intracerebroventricularly to Sprague-Dawley rats. Weight fell significantly and remained below vehicle injected controls for an extended period. By autoradiography, ENT-03 localized to the arcuate nucleus of the hypothalamus, the choroid plexus and cerebrospinal fluid. Significant cFos activation occurred in multiple anatomical regions within the hypothalamus and brainstem involved in appetite suppression, food-entrained circadian rhythmicity, autonomic function, and growth. These data support a role for ENT-03 in the treatment of type 2 diabetes and obesity. Phase 1 studies in subjects with obesity and diabetes are currently in progress.

Aims: Atrial fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations have not been fully elucidated, particularly with concomitant insulin use. This study aimed to analyse the associations between adverse events and DM, as well as adverse events and sole insulin use.

Materials and methods: Our analysis included individuals with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-year follow-up. Outcomes included all-cause death, major bleeding, cardiovascular (CV) death, myocardial infarction (MI), stroke, thromboembolism and major adverse cardiovascular events (MACE).

Results: A total of 15 861 AF individuals were included (age 70.0 ± 10.2 years; 55% male, 20% Asian), of whom, 3666 had DM (age 70.0 ± 9.5 years ; 59% male, 21% Asian). After adjustment, those with DM had higher risks of all-cause death (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.28-1.66), CV death (HR: 1.53 95% CI: 1.27-1.86), major bleeding (HR: 1.23, 95% CI: 1.01-1.48), MI (HR: 1.50, 95% CI: 1.17-1.94) and MACE (HR: 1.42, 95% CI: 1.23-1.63). Compared to individuals with DM receiving oral hypoglycaemic agents, those receiving insulin alone were associated with increased risks of all-cause death (HR: 2.16, 95% CI: 1.61-2.91), CV death (HR: 2.24, 95% CI: 1.45-3.47), major bleeding (HR: 1.89, 95% CI: 1. 21-2.95), MI (HR: 2.24, 95% CI: 1.31-3.82) and MACE (HR: 2.11, 95% CI: 1.54-2.88).

Conclusions: DM was independently associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE in AF individuals. Individuals receiving insulin alone were associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE.

Aim: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psychosocial outcomes following use of the tubeless Omnipod® 5 AID System in caregivers of very young children.

Materials and methods: This 3-month single-arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.0-5.9 years with T1D to use the Omnipod 5 AID System. Caregivers completed questionnaires assessing psychosocial outcomes-diabetes distress (Problem Areas in Diabetes), hypoglycaemia confidence (Hypoglycemia Confidence Scale), well-being (World Health Organization 5 Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), insulin delivery satisfaction (Insulin Delivery Satisfaction Survey) and system usability (System Usability Scale) at baseline with standard therapy and after 3 months of AID use.

Results: Following 3 months of Omnipod 5 use, caregivers experienced significant improvements across all measures, including diabetes-related psychosocial outcomes (Problem Areas in Diabetes; p < 0.0001, Hypoglycemia Confidence Scale; p < 0.01), well-being (World Health Organization 5 Well-Being Index; p < 0.0001) and perceived system usability (System Usability Scale; p < 0.0001). Significant improvements were seen in the Pittsburgh Sleep Quality Index total score and the overall sleep quality, sleep duration and efficiency subscales (all p < 0.05). Insulin Delivery Satisfaction Survey scores improved on all subscales (greater satisfaction, reduced burden and reduced inconvenience; all p < 0.0001).

Conclusions: Caregivers face unique challenges when managing T1D in very young children. While glycaemic metrics have unquestioned importance, these results evaluating psychosocial outcomes reveal additional meaningful benefits and suggest that the Omnipod 5 AID System alleviates some of the burdens caregivers face with diabetes management.

Aim: Elevated C-reactive protein (CRP), a marker of inflammation, is common in many chronic conditions. We aimed to examine to what extent elevated CRP in chronic conditions could be explained by concurrent adiposity.

Materials and methods: This cross-sectional study analysed UK Biobank data on 10 chronic conditions reported at baseline. Linear regression models explored the extent to which CRP concentrations were elevated in each condition, unadjusted; adjusted for sociodemographic confounders and lifestyle and body mass index (BMI) in a series of models; or adjusted for BMI and waist circumference together or for adiposity alone.

Results: After exclusion of participants with a potential acute infection at baseline, we tested the association in 292 772 UK Biobank participants. Linear regression showed that elevated CRP concentration was associated with all included conditions. After adjustment for sociodemographic confounders, lifestyle and BMI, chronic kidney disease, heart failure, liver disease, psoriasis, rheumatoid arthritis and chronic obstructive pulmonary disease were still associated with elevated CRP. In contrast, the association between prevalent diabetes, prior myocardial infarction (MI), hypertension and sleep apnoea and CRP could be mostly explained by adiposity alone. For example, the 42% higher CRP concentrations in diabetes compared to those without diabetes in the unadjusted model (lnCRP β: 0.35; 95% confidence interval [CI]: 0.32-0.37, p < 0.001) were completely attenuated after adjustment for BMI (lnCRP β: -0.07; 95% CI: -0.09-0.05, p < 0.001).

Conclusions/interpretation: In diabetes, MI, hypertension and sleep apnoea and elevated CRP appears to be accounted for by the greater adiposity typically evident in these conditions. However, for the other conditions, systemic inflammation cannot be explained by excess adiposity alone.

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.