Acta Diabetologica最新文献

Aims: To evaluate the efficacy of oral semaglutide, either as an add-on or replacement therapy, in improving glycemic control, body weight, and cardiovascular parameters in patients with type 2 diabetes mellitus (T2DM).

Methods: This real-world study evaluated changes in glycated hemoglobin (HbA1c), body weight, and parameters of cardiovascular risk from baseline to a 12-month follow-up visit. The primary endpoint was the change in HbA1c between baseline and follow-up. Secondary endpoints included changes in body weight, the proportion of patients achieving HbA1c ≤ 7%, and combined reductions in HbA1c (≥ 1%) and body weight (≥ 5%). Exploratory endpoints were evaluated as well.

Results: Data from 950 patients, predominantly female (63.7%) and with a mean age of 68.3 ± 10.1 years, were included in the study. Prior to starting semaglutide, most patients were on sulfonylureas, either as monotherapy or in combination with metformin or basal insulin. At baseline, mean HbA1c was 8.0 ± 1.3% (64.0 ± 14.2 mmol/mol), and body weight was 82.5 kg. Following 12 months of oral semaglutide treatment, HbA1c decreased significantly of -0.84% (p < 0.001) and 53% of patients achieved HbA1c ≤ 7%. HbA1c reductions were influenced by baseline levels and patient's age. Body weight decreased by 2.28 kg (p < 0.001) and 18.4% of patients achieved both ≥ 1% reduction in HbA1c and ≥ 5% in body weight. Diastolic blood pressure and LDL levels decreased significantly (p < 0.001), while systolic blood pressure and eGFR remained stable.

Conclusions: When used as an add-on or replacement therapy, oral semaglutide significantly improves glycemic control, body weight, renal and cardiovascular risk factors in T2DM patients.

Aims: Recent studies indicate that cell-derived exosomes are effective in treating diabetic renal injury, though their precise mechanisms remain unclear. This meta-analysis evaluates the therapeutic efficacy of exosomes in diabetic nephropathy.

Methods: In addition to reviewing references and consulting experts, we systematically searched PubMed, Cochrane Library, EMBASE, and Web of Science for studies on exosome therapy for diabetic nephropathy. Seven outcome measures were selected to evaluate efficacy: blood glucose [(fasting blood glucose (FBG) and random blood glucose (RBG)], renal function parameters [serum creatinine (SCR), blood urea nitrogen (BUN), 24-hour urinary protein (24 h UP) and albumin-to-creatinine ratio (UACR)], and inflammatory factors. Study quality was assessed using the SYRCLE risk of bias tool, and data were analyzed using RevMan (version 5.3) software.

Results: We included 17 studies involving 288 animals, with follow-up durations ranging from 2 to 14 weeks. Pooled analysis demonstrated that exosome treatment significantly improved GLU (FBG: SMD - 1.39, 95% CI -2.70 to -0.08, P = 0.04; RBG: SMD - 1.29, 95% CI -2.25 to -0.34, P < 0.008), SCR (SMD - 1.45, 95% CI -2.14 to -0.76, P < 0.0001), BUN (SMD - 2.06, 95% CI -3.01 to -1.11, P < 0.0001), 24 UP (SMD - 2.88, 95% CI -3.97 to -1.78, P < 0.00001), and UACR (SMD - 2.00, 95% CI -3.15 to -0.85, P = 0.0007) compared to the diabetic model group. Qualitative analysis revealed that exosomes increased anti-inflammatory factors while reducing pro-inflammatory factors (P < 0.05). No adverse effects of exosomes were reported in any of the included studies.

Conclusions: Current evidence indicates that exosomes attenuate diabetic nephropathy progression through anti-inflammatory, anti-fibrotic, anti-apoptotic, and autophagy-inducing mechanisms. To demonstrate the most efficient exosomes and therapeutic parameters for the treatment of diabetic nephropathy, future studies should conduct sizable, randomized, double-blind trials with high-quality, long-term follow-ups.

Objectives: The mean amplitude of glycemic excursion (MAGE) is widely recognized for representing glucose fluctuation extent, its implications in cerebral small vessel disease remain unclear. This study aims to investigate the correlation between MAGE and white matter hyperintensity (WMH).

Materials and methods: This cross-sectional study, spanning from March 2021 to October 2022, included 212 type 2 diabetic patients aged between 50 and 80. Participants underwent MRI scans and continuous glucose monitoring. Clinical and laboratory data were compiled for analysis. WMH volumes were evaluated using both the Fazekas visual rating scale and a quantitative approach. Based on Fazekas scores, patients were categorized into low level of WMH (L-WMH, n = 88) and high level of WMH (H-WMH, n = 124) groups.

Results: MAGE levels were significantly higher in the H-WMH group compared to the L-WMH group. Time below range [TBR^< 3.9] emerged as an independent risk factor for elevated MAGE. Both MAGE and TBR^< 3.9 independently correlated with an increased WMH burden. Additionally, MAGE was identified as a partial mediator in the relationship between TBR^< 3.9 and WMH volumes.

Conclusion: MAGE and hypoglycemia exhibit independent associations with WMH in diabetic patients. Moreover, hypoglycemia may indirectly influence WMH progression through the augmentation of glucose fluctuations.

Aim: To systematically assess randomized controlled trials that evaluated the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on fracture incidence, bone mineral density, and bone metabolism markers in individuals with type 2 diabetes.

Methods: From database setup to March 21, 2024, a search was conducted across nine Chinese and English databases. The Cochrane Risk of Bias Tool was applied to assess potential bias. Data analysis was performed using RevMan 5.3 and Stata 14.0. Subgroup analysis and meta regression were employed to explore sources of heterogeneity, and publication bias was evaluated using funnel plots and Egger's test.

Results: Twenty-five studies were included. The results of the meta-analysis indicated that GLP-1 receptor agonist was not significantly associated with an increased risk of fracture (RR = 0.80; 95% CI 0.47 to 1.36; P = 0.41). Additionally, improvement in lumbar spine BMD (MD = 0.07 g/cm², 95% CI 0.06 to 0.09, P < 0.00001), hip neck BMD (MD = 0.05 g/cm², 95% CI 0.03 to 0.08, P = 0.0001) and total hip BMD (MD = 0.06 g/cm², 95% CI 0.04 to 0.07, P < 0.00001) was superior to the control group. Similarly, GLP-1 receptor agonists significantly improved P1NP (SMD = 0.33, 95% CI 0.07 to 0.59, P = 0.01), OC (MD = 1.46 ug/L, 95% CI 1.10 to 1.83, P < 0.00001), 25-OH-D (SMD = 0.45, 95% CI 0.06 to 0.83, P = 0.02), and b-ALP (MD = 0.91ug/L, 95% CI 0.19 to 1.63, P = 0.01) while reducing β-CTX (SMD = - 0.34, 95% CI - 0.54 to - 0.14, P = 0.001). There was no significant impact on other bone metabolism markers, including N-MID-OT (SMD = 0.43, 95% CI 0.01 to 0.86, P = 0.05), ALP (SMD = - 0.00, 95% CI: - 0.25 to 0.25, P = 0.98), Calcium (MD = 0.00 mmol/L, 95% CI - 0.04 to 0.04, P = 0.94) and Phosphate (MD = 0.02 mmol/L, 95% CI - 0.04 to 0.07, P = 0.57).

Conclusion: This meta-analysis demonstrated no significant effect of GLP-1 receptor agonists on elevated fracture risk. There was a statistically significant improvement in BMD and certain bone turnover markers (β-CTX, P1NP, OC, b-ALP, and 25-OH-D). However, due to some limitations, further high-quality clinical studies with sufficient follow-up time are needed to draw more definitive conclusions.

Background: Glucose-lowering medications with established reno-protective effects are still underused in Italy. We explored whether attending an integrated nephrology and diabetology (NPD) outpatient service can improve clinical outcomes and adherence to treatment guidelines for diabetic kidney disease (DKD).

Methods: We retrospectively included 110 DKD patients (aged 71.1 ± 10.1 years; 74.5% males) having attended the NPD outpatient service of CTO Hospital (Rome) between June and November 2023. Age- and gender-matched control group included DKD patients attending regular Diabetology outpatient service. Drugs prescriptions, clinical and biochemical parameters related to routine evaluation of DKD were collected at first and 6-months control visit.

Results: This DKD population was made of 28.2% of patients with urine albumin-creatinine ratio (UACR) > 30 mg/gr, 33.6% with glomerular filtration rate (GFR) < 60 ml/min, 38.2% with both abnormalities. Proportion of patients prescribed with most recent anti-diabetic medications significantly increased after attending the NPD service (for SGLT-2 inhibitors, 54.5 vs. 25.5%, p < 0.01; for GLP1-R agonists, 28.3 vs. 21.8%, p = 0.01), as well as for statins (p < 0.01) and calcium channel-blockers (p = 0.01). During the same observation period we registered significant reduction in LDL cholesterol (p = 0.01) and UACR levels (p = 0.007), with a trend toward improvement in HbA1c and eGFR. Conversely, no significant differences in drugs prescriptions were reported in the control group, except for SGLT-2 inhibitors.

Conclusions: Enhanced real-time interaction and collaborative decision-making in an outpatient setting that integrates both diabetology and nephrology expertise can lead to better clinical outcomes and greater adherence to DKD management guidelines, ultimately providing a more comprehensive strategy for cardio-renal risk reduction.

Aims: We aimed to analyse Sirtuin 1 (SIRT1) and Vitamin D receptor (VDR) expression levels in the peripheral blood of patients with type 2 diabetes (T2D), characterized for the presence of diabetic neuropathy (DN), and to evaluate possible genetic factors that could influence the VDR expression levels.

Methods: Fifty-one participants with T2D, who underwent neurological assessment for DN were recruited. We quantified the mRNA levels of SIRT1 and VDR in peripheral blood mononuclear cells. Moreover, we analysed the methylation status and the rs2228570 genetic variant of VDR promoter.

Results: Patients with DN (n = 32) showed lower expression of SIRT1 (p_corr=0.018) and VDR (p_corr=0.009), compared to those without DN. Furthermore, we observed a positive correlation between the mRNA levels of SIRT1 and VDR (p = 0.01). The expression levels of these genes negatively correlated with the score based on cardiovascular reflex tests (CARTs score). Moreover, the variant allele of rs2228570 in the VDR gene was associated with higher expression of this gene compared to the wild-type allele (p = 0.003).

Conclusion: In patients with DN, both SIRT1 and VDR expression levels are reduced and interrelated. Low VDR expression levels could negatively affect SIRT1 transcription, thus influencing all the most pathogenetic pathways of DN regulated by this protein.

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.