Diabetes, Obesity & Metabolism最新文献

Aims: To explore the associations between cuprotosis-related genes (CRGs) across different stages of liver disease in metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatocellular carcinoma (HCC).

Materials and methods: We analysed several bulk RNA sequencing datasets from patients with MAFLD (n = 331) and MAFLD-related HCC (n = 271) and two MAFLD single-cell RNA sequencing datasets. To investigate the associations between CRGs and MAFLD, we performed differential correlation, logistic regression and functional enrichment analyses. We also validated the findings in an independent Wenzhou PERSONS cohort of MAFLD patients (n = 656) used for a genome-wide association study (GWAS).

Results: GLS, GCSH and ATP7B genes showed significant differences across the MAFLD spectrum and were significantly associated with liver fibrosis stages. GLS was closely associated with fibrosis stages in patients with MAFLD and those with MAFLD-related HCC. GLS is predominantly expressed in monocytes and T cells in MAFLD. During the progression of metabolic dysfunction-associated fatty liver to metabolic-associated steatohepatitis, GLS expression in T cells decreased. GWAS revealed that multiple single nucleotide polymorphisms in GLS were associated with clinical indicators of MAFLD.

Conclusions: GLS may contribute to liver inflammation and fibrosis in MAFLD mainly through cuprotosis and T-cell activation, promoting the progression of MAFLD to HCC. These findings suggest that cuprotosis may play a role in MAFLD progression, potentially providing new insights into MAFLD pathogenesis.

Aims: The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo.

Materials and methods: This was a double-blind study (NCT05804162) in which healthy participants were randomized to cagrilintide, administered as a once-weekly subcutaneous injection dose escalated to 4.5 mg, or a placebo. The primary end point was the time-matched change from baseline in Fridericia heart rate-corrected QT interval (QTcF) at 12-, 24-, 48- and 72 h after the last cagrilintide 4.5-mg dose. To conclude that cagrilintide does not induce a clinically relevant prolongation, the upper limit of the two-sided 90% confidence interval (CI) for the treatment difference at each of the four time points must fall below 10 ms. To establish QT assay sensitivity, participants in the placebo arms received a single 400-mg oral moxifloxacin dose as a positive control and moxifloxacin placebo in a nested cross-over fashion.

Results: A total of 105 participants received cagrilintide (n = 53) or placebo (n = 52). No clinically relevant QTcF prolongation occurred after the last cagrilintide 4.5-mg dose; the upper limits of the two-sided 90% CIs of the placebo-adjusted QTcF changes from baseline were below 10 ms at all time points. QT assay sensitivity was demonstrated with moxifloxacin as a positive control.

Conclusions: Cagrilintide did not result in clinically relevant QTcF prolongation, indicating no increased risk of ventricular tachyarrhythmias.

Aims: To conduct a systematic review in order to better understand the association of glycaemic risk factors and diabetes duration with risk of heart failure (HF) in individuals with type 2 diabetes (T2D).

Methods: We identified longitudinal studies investigating the association of glycaemic factors (glycated haemoglobin [HbA1c], HbA1c variability, and hypoglycaemia) and diabetes duration with HF in individuals with T2D. Hazard ratios and odds ratios were extracted and meta-analysed using a random-effects model where appropriate. Risk of bias assessment was carried out using a modified Newcastle-Ottawa Scale. Egger's test along with the trim-and-fill method were used to assess and account for publication bias.

Results: Forty studies representing 4 102 589 people met the inclusion criteria. The risk of developing HF significantly increased by 15% for each percentage point increase in HbA1c, by 2% for each additional year of diabetes duration, and by 43% for having a history of severe hypoglycaemia. Additionally, variability in HbA1c levels was associated with a 20%-26% increased risk of HF for each unit increase in the metrics of variability (HbA1c standard deviation, coefficient of variation, and average successive variability). All included studies scored high in the risk of bias assessment. Egger's test suggested publication bias, with trim-and-fill analyses revealing a significant 14% increased risk of HF per percentage point increase in HbA1c.

Conclusions: Glycaemic risk factors and diabetes duration significantly contribute to the heightened risk of HF among individuals with T2D. A reduction in risk of HF is anticipated with better management of glycaemic risk factors.

Aim: Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are used to maintain glycaemic control as well as for their beneficial cardiovascular and renal effects in diabetes patients. However, increased risk of amputation and peripheral artery disease (PAD) have been observed with the use of some SGLT-2is. A meta-analysis was conducted to understand the effect of SGLT-2is on amputation and PAD events using data from randomized controlled trials (RCT).

Materials and methods: A systematic literature review was conducted using Medline and Central databases for RCTs that involved the administration of SGLT-2is versus placebo/active comparators to diabetic patients. The primary outcome was amputation events and PAD. A random-effects model was used to calculate the pooled odds ratio, and subgroup analyses was performed.

Results: A total of 51 RCTs were included in the meta-analysis with data from 97 589 patients. Meta-analysis of the data showed that there was a significant increase in PAD risk (p = 0.04) but no significant increase in amputation risk with SGLT-2i use versus placebo/active comparators (p = 0.43). Subgroup analyses demonstrated no significant difference between SGLT-2i type, duration of treatment or patient risk factors on amputation or PAD incidence. However, length of drug treatment (> 100 weeks) was associated with a significant increase in both PAD and amputation risks in the SGLT-2i treatment groups.

Conclusions: The results of the meta-analysis showed no significant association between SGLT-2i use and PAD and amputation risks in diabetic patients when used for shorter treatment durations.

Aim: To elucidate the effects of ultra-processed foods (UPFs) on body weight and ad libitum energy intake compared with non-UPFs.

Materials and methods: In this randomized, open-label crossover study conducted at the University of Tokyo Hospital, overweight/obese Japanese male participants were randomly assigned (1:1) to start the study with consumption of either UPFs or non-UPFs for 1 week, followed by a 2-week washout period, before crossing over to the alternate food diet for 1 week. Individuals with diabetes, hypertension or any other medical conditions who visited a hospital regularly were excluded. The meals were designed to be matched for the total energy and macronutrient levels. The primary outcome was the difference in the body weight change between the UPF and non-UPF periods. The differences in the average daily energy intake and chewing frequency were assessed as one of the prespecified secondary outcomes.

Results: Nine eligible participants were randomly assigned to start the study with either UPFs or non-UPFs. All participants completed the study. During the UPF period, participants gained 1.1 kg more weight (95% confidence interval 0.2 to 2.0; P = .021) and consumed 813.5 kcal more per day (342.4 to 1284.7; P = .0041) compared with during the non-UPF period. Regarding the chewing frequency, the number of chews per calorie was significantly lower during the UPF period (P = .016).

Conclusions: Consumption of UPFs causes significant weight gain. Medical nutritional therapy focused on reducing the consumption of UPFs could be an effective strategy for preventing obesity.

Aim: To map the glycaemic variabilities and insulin requirements across different phases of the menstrual cycle and assess the efficacy and performance of the MiniMed 780G system on mitigating glycaemic variabilities during phases of the menstrual cycle.

Materials and methods: A pilot study recruiting 15 adolescent and young adult females with type 1 diabetes was conducted. Only females with regular spontaneous menstruation were enrolled in the current study. Phases of each menstrual cycle were determined as either follicular phase or luteal phase. The study analysed continuous glucose monitoring metrics during two study periods: the open loop period (OLP) and the advanced hybrid closed-loop (AHCL) period; each period lasted 3 consecutive months.

Results: During the OLP, the mean time in range (TIR) significantly decreased during the luteal phase compared with the follicular phase (65.13% ± 3.07% vs. 70.73% ± 2.05%) (P < .01). The mean time above range significantly increased from 21.07% ± 2.58% during the follicular phase to 24.87% ± 2.97% during the luteal phase (P < .01). After initiating the AHCL period, TIR was comparable during both phases of the menstrual cycle (P = .72), without increasing the time spent below 70 mg/dL (P > .05). Regarding insulin delivery during the AHCL period, the percentage of Auto basal and Auto correction delivered by the algorithm increased by 13.55% and 30.6%, respectively (P < .01), during the luteal phase.

Conclusions: The fully automated adaptive algorithm of the MiniMed 780G system mitigated menstrual cycle-dependent glycaemic variability, successfully attaining the recommended glycaemic outcomes with a TIR greater than 70% throughout the entire menstrual cycle.