Acta Diabetologica最新文献

Aim: Semaglutide exerts metabolic effects and cardiovascular protection in type 2 diabetes (T2D), also acting on hepatic steatosis and inflammation. No data are, so far, available on the effect of semaglutide on oxidative stress, neither a comparison of injective (InjS) and oral (OrS) formulations has been performed in subjects with T2D and liver steatosis.

Methods: In a real-life, open label, prospective study we compared standard doses of InjS and OrS in targeting liver inflammation and fibrosis and systemic markers of inflammation and oxidative stress by consecutively prescribing InjS or OrS formulation in a 2:1 ratio to sixty T2D + MASLD subjects (T0), observing them for 6 months (T1). Anthropometry, biochemistry and transient elastography (TE) data were collected; hormones, inflammatory cytokines and peroxidation products were measured.

Results: At baseline, InjS and OrS subjects were similar, except for waist circumference, liver enzymes and Controlled Attenuation Parameter (CAP), a measure of liver steatosis (InjS > OrS, all p < 0.05). Differences emerged in T0-T1 variation between the formulations in HbA1c, lipid profile, blood pressure. CAP significantly decreased only in InjS. GLP-1 quite similarly increased; insulin, glucagon and GIP did not vary. InjS and OrS did not modify TNFα, IL-10 (an anti-inflammatory cytokine) and MCP-1, while IL-18 was reduced only by InjS. When exploring oxidative stress, AGEs were unaffected, Thiobarbituric acid reactive substances decreased in InjS, 4-Hydroxynonenal was reduced in OrS.

Conclusion: In T2D + MASLD subjects, InjS, better than OrS, improves metabolic control; a significant reduction of IL-18 by InjS, and a mild anti-oxidative effect of both formulations are reported for the first time.

Aims: The effectiveness of Hybrid Closed-Loop (HCL) therapy is rarely studied in type 1 diabetes (T1D) pregnancies.

Methods: T1D pregnancies (n = 15) managed off-label during gestation using a commercially available HCL system, Tandem Control IQ, were retrospectively reviewed for baseline characteristics, continuous glucose monitoring (CGM), insulin pump use, insulin doses, and gestational health outcomes. Analyses for unadjusted descriptive statistics of baseline characteristics, glycemic parameters, and gestational health outcomes were performed (mean ± standard deviation (SD) or median with interquartile range (IQR) for continuous variables). Control IQ was used prior to pregnancy by 12 of the 15 cases, with 3 initiating use during gestation.

Results: On average, targets were met for pregnancy-specific Time-In-Range (psTIR, 63-140 mg/dL for > 70%) during most of gestation, pregnancy-specific Time-Below-Range (psTBR, < 63 mg/dL for < 4%) throughout gestation, and pregnancy-specific Time-Above-Range (psTAR, > 140 mg/dL for < 25%) from 10- to 17-week gestation. Targets for non-pregnancy TIR (70-180 mg/dL), TAR (> 140 mg/dL), and TBR (< 70 mg/dL) were met preconception and post-partum. Glycemic metrics improved after the first pregnancy visit wherein assistive techniques were applied for off-label use of this HCL system. Gestational health outcomes were as anticipated for T1D pregnancies.

Conclusions: Tandem Control IQ HCL therapy used with assistive techniques in 15 T1D pregnancies was associated with improved glycemic levels from the first clinic visit onward.

Aims: One of the primary pathological features in the early stages of diabetic nephropathy is mesangial cell (MC) hypertrophy in the glomerulus. Considering the role of E3 ubiquitin ligases in regulating MC hypertrophy, the aim of this study was to identify the functional ubiquitin protein ligase E3 component N-recognin 5 (UBR5) during MC hypertrophy under high glucose conditions.

Methods: Human MCs (HMCs) transduced with UBR5 silencing or overexpression vector were treated with high glucose, AKT inhibitor, or glycolysis inhibitor. Cell proliferation, cell cycle, hypertrophy and glycolysis were evaluated in the HMCs after indicated treatment. m6A methylated RNA immunoprecipitation, luciferase reporter assay, and RNA immunoprecipitation were performed to determine the regulation of UBR5 by Wilms tumor 1-associating protein (WTAP)/insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) induced m6A modification. Western blot was performed to determine the protein expression levels.

Results: UBR5 expression was upregulated in db/db mice and in high glucose-induced HMCs. UBR5 silencing inhibited high glucose-induced HMC cell cycle arrest, cell hypertrophy, and glycolysis. UBR5 facilitated HMC hypertrophy and glycolysis by promoting the phosphorylation levels of AKT. Additionally, the promoting effect of glycolysis on cell hypertrophy were also elucidated. Further investigation into upstream regulators revealed that WTAP promoted m6A modification of UBR5 through the m6A reader IGF2BP1.

Conclusions: Our study unveils a novel mechanism involved in high glucose-induced cell hypertrophy, offering new insights into the understanding and treatment of early pathological mechanisms in diabetic nephropathy.

The extensive use of smokeless tobacco and the worldwide occurrence of diabetes mellitus (DM) poses significant public health obstacles. A comprehensive review of the literature was undertaken to assess epidemiological research, clinical trials, and meta-analyses that examine the link between smokeless tobacco use and DM. The key results indicate that the biological constituents of smokeless tobacco may interfere with the process of glucose metabolism and lead to an increase in insulin resistance. An association between consumption levels and diabetes risk is evident, with higher levels of usage being positively correlated with an increased chance of developing diabetes. Smokeless tobacco usage is identified as a significant risk factor for DM. This highlights the need to implement focused public health initiatives and policies aimed at decreasing the usage of smokeless tobacco and its influence on the incidence of diabetes. Future research should prioritize elucidating the processes behind this correlation and developing efficacious preventative methods to mitigate the worldwide burden of diabetes.

The prevalence of gestational diabetes mellitus (GDM) is rising and poses important health risks for the mother, developing fetus and offspring, even when maternal glycemic control is well managed. This study aimed to identify the differently expressed metabolites (DEMs) in maternal plasma between GDM pregnancies with good glycemic control and healthy pregnancies, along with the DEMs-related metabolism in adipose tissue. Pregnant women with scheduled caesarean sections were recruited. Venous blood samples were collected on the day prior to delivery for targeted metabolomics analysis focusing on the 200 polar metabolites in central carbon metabolism. Subcutaneous and omental white adipose tissue (sWAT and oWAT) were harvested at delivery. A total of 162 metabolites were quantified, revealing 2 up-regulated (D-glucose 6-phosphate (G6P), succinate) and 8 down-regulated DEMs, which exhibited a fold change of ≥ 1.5 or ≤ 0.67, respectively. Among the down-regulated DEMs, 5 metabolites-pyridoxine, glycine, S-methyl-L-cysteine, methionine, and S-carboxymethyl-L-cysteine-are related to one-carbon metabolism (OCM). In response to perturbation in circulating OCM, boosted methionine cycle, NAD + metabolism, and adipogenesis were observed in sWAT of GDM subjects, with no changes detected in oWAT. None of the 10 DEMs correlates with either blood glucose or insulin, but showed significant correlations with TG, TC, LDL-C and HDL-C. The present study indicates that sWAT compensates for the perturbations in circulating OCM associated with GDM and targeting to the OCM may be an effective strategy to control the long-term metabolic risk of GDM offsprings.

Aims: The oral administration of linoleic acid immediately before glucose tolerance test (OGTT) ameliorated postprandial hyperglycemia via GPR120 pathway in normal and type 1 diabetes (T1DM) rats. Linoleic acid could promote inflammatory mediators, but 10-hydroxy-cis-12-octadecenoic acid (HYA) converted from linoleic acid by Lactobacillus plantarum has higher GPR120 agonistic activity without promoting inflammatory mediators. This study examined whether the oral-administration of HYA immediately before OGTT also ameliorated the postprandial hyperglycemia in normal rats and T1DM rats injected with bolus insulin.

Methods: Normal and T1DM male Sprague-Dawley rats received HYA immediately before OGTT. Other T1DM rats were given HYA and Humulin R immediately before OGTT. We measured the concentration of glucose, insulin, glucagon-like peptide 1 (GLP-1) and cholecystokinin in blood before and after OGTT. We also measured the amount of glucose in the gastric tract after OGTT, and the amount of uptake of methyl-α-D-glucopyranoside in CACO-2 cells.

Results: Postprandial hyperglycemia was ameliorated by HYA in normal rats, and the postprandial blood glucose levels were slowly elevated by HYA in the T1DM model rats. HYA partially inhibited the uptake of methyl-α-D-glucopyranoside in CACO-2 cells. HYA slowed gastric motility and increased the plasma GLP-1 and cholecystokinin levels in normal rats. HYA also ameliorated the postprandial hyperglycemia in T1DM rats given bolus insulin.

Conclusion: Oral administration of HYA immediately before OGTT ameliorated postprandial hyperglycemia through inhibition of glucose absorption and slowing of gastric motility in normal rats. Furthermore, this beneficial effect of HYA was also revealed in T1DM rats injected with bolus insulin.

Background: Sarcopenia is a common condition in the elderly, especially in diabetics (DM). Metformin (MTF), known to reduce glucose levels, can also be a therapeutic intervention in age-related diseases, although it may contribute to muscle loss.

Objectives: To compare the prevalence of sarcopenia among elderly people treated for DM, with or without MTF, and non-diabetic patients (NDM) and evaluate whether there is an association between the use of MTF and the development of sarcopenia.

Methods: 194 independent elderly people over 80 years old were analyzed. Sarcopenia was defined by handgrip (HG), calf circumference (CC), and gait speed (GS). Non-parametric statistical analysis and Kaplan-Meier survival curves were used.

Results: The prevalence of DM was 24.7%, of which 56.25% used MTF. The median fasting blood glucose in the NDM and DM groups was 95 and 104 mg/dL. The median glycated hemoglobin in the NDM and DM groups was 5.7% and 6.4%. There was no statistical difference between the DM and NDM groups when comparing clinical characteristics, functionality, weight, physical tests, and mortality. The prevalence of sarcopenia was similar between NDM and DM (16.55% and 14.63%), with few cases of severe sarcopenia in both groups, without statistical differences. We did not find differences in the same variables when we analyzed NDM and DM using or not MTF. Survival curves showed no significant differences between patients with and without sarcopenia/severe sarcopenia.

Conclusions: Long-lived people with well-controlled DM did not show significant differences concerning those without DM for the outcome of sarcopenia or death.