Diabetes & metabolism最新文献

Pancreatic diabetes is associated with glycemic variability, poor metabolic control, and reduced quality of life. Though hybrid closed-loop (HCL) insulin delivery systems were not originally developed for these types of diabetes, they could address the therapeutic challenge. We aimed to evaluate long-term metabolic control in ten adult patients (mean ± SD age: 59 ± 12) treated with HCL insulin delivery systems for pancreatitis or pancreatectomy-induced diabetes. After a median of 346 days (range 64 - 631) with HCL insulin delivery, continuous glucose monitoring showed 59±19 % time-in-range [70–180 mg/dl] (versus 49±24 % before HCL insulin delivery, P = 0. 049) and 0.8 ± 1.0 % time-below-range [< 70 mg/dl] (versus 2.2 ± 2.6 %, P = 0.142), with the coefficient of glucose variability at 35.4 ± 7.6 (versus 37.8 ± 7.1, P = 0.047). Hb_A1c decreased from 8.5 ± 1.7 % to 7.7 ± 1.3 % [69±18 to 60±14 mmol/mol] (P = 0.076). No patient experienced an acute adverse metabolic event.

Aim

Preclinical studies have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have a neuroprotective effect. This study compared the risks of carpal tunnel syndrome and carpal tunnel release surgery between new users of SGLT2is and new users of glucagon-like peptide-1 receptor agonists (GLP-1RAs).

Methods

A retrospective new-user active comparator cohort study with a target trial design was conducted by using the TriNetX platform. Patients with type 2 diabetes mellitus prescribed SGLT2is or GLP-1RAs were identified. Covariates were balanced using propensity score matching to form 2 homogenous treatment groups. Outcomes were the risk of carpal tunnel syndrome and the risk of carpal tunnel release surgery. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using the TriNetX platform.

Results

The crude cohort included 86,188 and 100,244 patients in the SGLT2is group and GLP-1RAs group, respectively. After matching, each group included 65,464 patients. The SGLT2is group had an average age of 59.6 years, and 46 % were women. The GLP-1RAs group had an average age of 59.5 years, and 45.9 % were women. The incidences of carpal tunnel syndrome (HR: 0.928; 95 % CI: 0.869 to 0.991) and carpal tunnel release surgery (HR: 0.840; 95 % CI: 0.726 to 0.971) were significantly lower in the SGLT2is group than in the GLP-1RAs group.

Conclusion

In patients with type 2 diabetes mellitus, SGLT2is seem to decrease the risk of carpal tunnel syndrome and the need for carpal tunnel release surgery. Prospective studies are required to confirm our results.

Autism spectrum disorders (ASD) encompass a collection of neurodevelopmental disorders that exhibit impaired social interactions and repetitive stereotypic behaviors. Although the exact cause of these disorders remains unknown, it is widely accepted that both genetic and environmental factors contribute to their onset and progression. Recent studies have highlighted the potential negative impact of maternal diabetes on embryonic neurodevelopment, suggesting that intrauterine hyperglycemia could pose an additional risk to early brain development and contribute to the development of ASD. This paper presents a comprehensive analysis of the current research on the relationship between various forms of maternal diabetes, such as type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus, and the likelihood of ASD in offspring. The study elucidates the potential mechanisms through which maternal hyperglycemia affects fetal development, involving metabolic hormones, immune dysregulation, heightened oxidative stress, and epigenetic alterations. The findings of this review offer valuable insights for potential preventive measures and evidence-based interventions targeting ASD.

Aim

New tools are required to better assess cardiovascular risk in individuals with type 2 diabetes mellitus (T2DM). Plasma ceramides emerge as promising candidates, given their substantial influence on the pathogenesis of both T2DM and atherosclerosis. The current study aimed to investigate whether plasma ceramides in patients with T2DM are a predictive factor for carotid intima-media thickness (CIMT), a well-established noninvasive marker for atherosclerosis that predicts adverse cardiovascular outcomes.

Methods

A lipidomic analysis was carried out on the circulating ceramides of a large cohort consisting of 246 patients with T2DM who underwent a high-resolution real-time B ultrasonography to measure CIMT.

Results

Both plasma 16:0 ceramide and the 16:0/24:0 ceramide ratio were positively associated with CIMT, even after adjustment for traditional cardiovascular risk factors [standardized β ± standard error: 0.168 ± 0.072 (P = 0.020) and 0.180 ± 0.068 (P = 0.009), respectively]. Similar independent associations were found with respect to the prediction of CIMT ≥ 0.80 mm [β = 8.07 ± 3.90 (P = 0.038) and 16.5 ± 7.0 (P = 0.019), respectively]. The goodness-of-fit for multivariate models in predicting CIMT was 5.7 and 7.6 times higher when plasma 16:0 ceramide or the 16:0/24:0 ceramide ratio were included in combination with traditional cardiovascular risk factors (P = 0.020 and 0.015, respectively). This reached a 3.1 and 10.0-fold increase regarding the ability to predict CIMT ≥ 0.80 mm (P = 0.039 and 0.008, respectively).

Conclusions

Our findings suggest that 16:0 ceramide and the 16:0/24:0 ceramide ratio may serve as plasma biomarkers to improve cardiovascular risk assessment in individuals with T2DM.

Objective

Diabetic kidney disease favors diabetic foot ulcers, however we do not know whether the reverse relation exists. We investigated whether diabetic foot disease (DFD) related to an increased risk of developing renal events.

Research design and methods

We conducted a retrospective analysis of a cohort of patients hospitalized for type 2 diabetes mellitus (T2DM) between 2009 and 2017, stratified for the risk of diabetic foot ulcer grades 0 (no risk), 1 and 2 (at risk), and 3 (DFD) according to the International Work Group on Diabetic Foot (IWGDF) classification. We highlighted new renal events (end-stage renal disease or a doubling of serum creatinine) in their medical records until December 2020. The relationship between DFD and later renal events was analyzed by multivariable Cox regression model.

Results

Among 519 patients, 142 (27 %) had a DFD at baseline, and 159 (30 %) were classified as Grades 1 or 2. Thirty-six renal events occurred during the 54 ± 27 months of follow-up: 19 subjects started dialysis, 1 had a renal transplantation, and 16 had a doubling of serum creatinine: 15 each in subjects with DFD and subjects at risk, versus 6 in subjects with Grade 0 DFD (logrank: P = 0.001). Adjusted for i) age and sex; ii) hyperglycemic exposure; iii) conventional cardiovascular risk factors; iv) renal parameters: and v) new diabetic foot ulcers during follow-up, DFD (HR 2.7 to 5.9) and being at risk of DFD Grades 1–2 (HR 2.8 to 5.1) were significantly related to new renal events.

Conclusion

The risk of renal events was increased in people with T2DM and DFD.

Aim

The catabolism of high density lipoprotein (HDL) apolipoprotein AI (apoAI) is accelerated in patients with type 2 diabetes (T2D), related to hypertriglyceridemia, insulin resistance and low plasma adiponectin levels. Since liraglutide is likely to partly correct these abnormalities, we hypothesized that it might have a beneficial effect on HDL apoAI kinetics in patients with T2D.

Methods

An in vivo kinetic study of HDL apoAI was performed in 10 patients with T2D before and after 6 months of treatment with 1.2 mg/day of liraglutide, using a bolus of l-[1–¹³C]leucine followed by a 16-hour constant infusion.

Results

Liraglutide reduced BMI (34.9 ± 4.7 vs 36.6 ± 4.9 kg/m², P = 0.012), HbA1c (7.1 ± 1.1 vs 9.6 ± 2.6%, P = 0.003), HOMA-IR (5.5 ± 1.9 vs 11.6 ± 11.2, P = 0.003), fasting triglycerides (1.76 ± 0.37 vs 2.48 ± 0.69 mmol/l, P < 0.001) and triglycerides during kinetics (2.34 ± 0.81 vs 2.66 ± 0.65 mmol/l, P = 0.053). Plasma HDL cholesterol and adiponectin concentrations were unchanged (respectively 0.97 ± 0.26 vs 0.97 ± 0.19 mmol/l, P = 1; 3169 ± 1561 vs 2618 ± 1651 µg/l, P = 0.160), similar to triglyceride content in HDL (5.13 ± 1.73 vs 5.39 ± 1.07%, P = 0.386). Liraglutide modified neither HDL apoAI fractional catabolic rate (0.35 ± 0.11 vs 0.38 ± 0.11 pool/day, P = 0.375), nor its production rate (0.44 ± 0.13 vs 0.49 ± 0.15 g/l/day, P = 0.375), nor its plasma concentration (1.26 ± 0.19 vs 1.29 ± 0.14 g/l, P = 0.386).

Conclusion

Six months of treatment with 1.2 mg/day of liraglutide had no effect on the kinetics of HDL apoAI in patients with T2D. The lack of decrease in triglyceride content in HDL related to an only moderate decrease in triglyceridemia, probably greatly explains these results. Insufficient improvement of insulin sensitivity and adiponectinemia may also be implied.

Aim

Left ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting.

Methods

This retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used.

Results

During 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02–1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P < 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01–1.42) and 1.36 (0.90–2.06), respectively (P = 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results.

Conclusions

This study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD.

Aim

This study aimed to investigate the association of social isolation, loneliness, and their trajectory with the risk of developing type 2 diabetes mellitus (T2DM) across genetic risk.

Methods

We included 439,337 participants (mean age 56.3 ± 8.1 years) enrolled in the UK Biobank study who were followed up until May 31, 2021. Social isolation and loneliness were self-reported and were further categorized into never, transient, incident, and persistent patterns.

Results

During a median follow-up of 12.7 years, 15,258 incident T2DM cases were documented. Social isolation (versus no social isolation: hazard ratio (HR) 95 % confidence interval (CI) 1.04 [1.00;1.09]) and loneliness (versus no loneliness: 1.26 [1.19;1.34]) were associated with an increased T2DM risk, independent of the genetic risk for T2DM. The interactions existed between social isolation and loneliness (P _interaction < 0.05); the increased T2DM risk associated with social isolation was only significant among participants without loneliness. In the longitudinal analysis, only persistent social isolation (versus never social isolation: 1.22 [1.02;1.45]) was associated with an increased T2DM risk, whereas incident loneliness (versus never loneliness: 1.95 [1.40;2.71]) and persistent loneliness (2.00 [1.31;3.04]) were associated with higher T2DM risks.

Conclusion

Social isolation and loneliness, especially their persistent pattern, were independently associated with an increased incident T2DM risk, irrespective of an individual's genetic risk. Loneliness modified the association between social isolation and incident T2DM.

Aims

Although cellular and animal models have suggested a protective effect of ketone bodies (KBs), clinical data are still lacking to support these findings. This study aimed to investigate the association of KB levels with incident chronic kidney disease (CKD) and death.

Methods

This was a prospective cohort study of 87,899 UK Biobank participants without baseline CKD who had plasma levels of β-hydroxybutyrate, acetoacetate, and acetone levels measured at the time of enrollment. The main predictor was plasma total KB, which was the sum of the aforementioned three KBs. The primary outcome was a composite of incident CKD, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome.

Results

During a median follow-up of 11.9 years, a total of 8,145 primary outcome events occurred (incidence rate 8.0/1,000 person-years). In the multivariable Cox model, a 1-standard deviation increase in log total KB was associated with a 7 % [adjusted hazard ratio (aHR), 1.07; 95 % confidence interval (CI), 1.05–1.10] higher risk of the primary outcome. When stratified into quartiles, the aHR (95 % CI) for Q4 versus Q1 was 1.18 (1.11–1.27). This association was consistent for incident CKD (aHR, 1.04; 95 % CI, 1.01–1.07), and all-cause mortality (aHR, 1.10; 95 % CI, 1.07–1.13). Compared with Q1, Q4 was associated with a 12 % (aHR 1.12; 95 % CI 1.02–1.24) and 26 % (aHR 1.26; 95 % CI 1.15–1.37) higher risk of incident CKD and all-cause mortality, respectively.

Conclusions

Higher KB levels were independently associated with higher risk of incident CKD and death.