Acta Diabetologica最新文献

Aims: This study aimed to assess the proportions of type 2 diabetes (T2D) subjects meeting cardiovascular outcome trials (CVOTs) criteria for sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and estimate SGLT2i utilization, along with associated demographic and clinical characteristics, in a primary care setting.

Methods: T2D patients in Italy were selected between January 1, 2021, and December 31, 2022, from The Health Improvement Network (THIN^®) database. Representativeness was determined by dividing patients meeting key inclusion criteria for four CVOTs (CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, VERTIS-CV) to the total T2D population. Demographic and clinical characteristics of eligible T2D subjects and SGLT2i users were compared, and logistic regression models assessed the likelihood of receiving SGLT2i.

Results: Out of 17,102 T2D patients, 8,828 met eligibility criteria for at least one CVOT. DECLARE-TIMI 58 exhibited the highest representativeness (51.1%), compared to CANVAS (21.1%), EMPA-REG OUTCOME (5.5%), and VERTIS-CV (4.9%) trials. Eligible CVOTs patients were older (74.6 vs. 68.3 years), with a longer disease duration (10.2 vs. 9.7 years), and higher established cardiovascular disease (CVD) prevalence (36.0 vs. 27.3%) compared to SGLT2i users. Less than 10% of eligible T2D patients received SGLT2i. Males (OR: 1.43; 95%CI: 1.24-1.66) were more likely to be prescribed SGLT2i than other antidiabetic drugs, while the elderly (80 + vs. 40-64 years, OR: 0.17; 95% CI: 0.14-0.22) were less likely. Eligible T2D patients with CVD reported an increased likelihood of receiving SGLT2is compared to other antidiabetics.

Conclusion: This study highlights significant variability in the proportion of T2D subjects meeting SGLT2i CVOT inclusion criteria, with DECLARE-TIMI-58 being the most represented. Low SGLT2i prescription rates in the Italian primary care setting, along with substantial demographic and clinical differences between SGLT-2i users and T2D eligible patients, emphasize the need for targeted interventions to optimize the use of these medications in primary care settings.

Aim: To investigate the effects of hypertension (HTN) on inner retinal thickness and macular microvasculature in patients with diabetic retinopathy (DR).

Methods: Subjects were classified into three groups: patients with type 2 diabetes mellitus (T2DM) (T2DM group), patients with DR (DR-HTN group), and patients with DR and HTN (DR + HTN group). The ganglion cell complex (GCC) thicknesses and the macular vessel density (VD) were compared. Linear regression analyses were performed to identify factors associated with the VD in the DR + HTN group.

Results: The mean GCC thicknesses were 112.2 ± 12.3, 109.2 ± 13.7, and 106.2 ± 11.2 μm in the T2DM, DR-HTN, and DR + HTN groups, respectively (P = 0.045). The mean VDs were 25.4 ± 5.0, 24.3 ± 8.9, and 21.2 ± 7.1% (P = 0.014) for the superficial capillary plexus (SCP) and 25.9 ± 4.3, 22.9 ± 8.5, and 20.2 ± 6.6% (P < 0.001) for the deep capillary plexus (DCP) in the T2DM, DR-HTN, and DR + HTN groups, respectively. In multivariate analyses, the duration of HTN was a significant factor associated with the VD of both SCP (B = -0.24, P = 0.010) and DCP (B = -0.21, P = 0.016).

Conclusions: Patients with both DR and HTN had a thinner GCC and lower VDs of SCP and DCP than those with DR alone. These outcomes could be associated with the synergistic ischemic effects in DR patients with HTN. Moreover, the duration of HTN in DR patients was significantly associated with macular VD in both SCP and DCP.

Aims: Monogenic diabetes is one of the few examples in metabolic diseases in which a real precision medicine approach can be implemented in daily clinical work. Unfortunately, most of what is known today comes from studies in Whites, thus leaving much uncertainty about the genetics and the clinical presentation of monogenic diabetes in non-Europeans. To fill this gap, we report here two pedigrees from Bangladesh with CEL- and RFX6- diabetes, two rare types of monogenic diabetes which have never been described so far in individuals of the Indian subcontinent.

Methods: Next generation, Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) were performed. Variants' interpretation was according to the American College of Medical Genetics and Genomics guidelines.

Results: In the pedigree with CEL-diabetes, a large and never described deletion of exon 2-11 of CEL (confirmed by MLPA) affecting the entire catalytic domain and being likely pathogenic (LP) was observed in both the proband (who had diabetes at 16) and his mother (diabetes at 31), but not in relatives with normoglycemia. In the pedigree with RFX6-diabetes, a LP protein truncation variant (PTV, p.Tyr192*) in RFX6 was found in both the proband (diabetes at 9) and his mother (diabetes at 30), thus suggesting high heterogeneity in disease onset. Normoglycemic relatives were not available for genetic testing.

Conclusions: We report genetic features and clinical presentation of the first two cases of CEL- and RFX6-diabetes from the Indian subcontinent, thus contributing to fill the gap of knowledge on monogenic diabetes in non-Europeans.

Aims: To address the scarcity of continued education for insulin pump users, we developed and evaluated a new program (NP) for individuals transitioning to a different insulin pump.

Methods: In a randomized, controlled 3-month study, adults with type 1 diabetes and suboptimal HbA1c received either NP or usual care program (UC). The NP was designed in collaboration with representatives of the target group and incorporated technical training, case-based learning, and peer experience sharing - encompassing two group sessions, and two follow-up telephone calls. The UC included a single training session led by the pump company with hotline assistance (clinic) but no structured follow-up. The primary endpoint was the difference in time in range (TIR) (70-180 mg/dL (3.9-10.0 mmol/L)), measured by continuous glucose monitoring from baseline to 3 months post-course. Psychosocial self-efficacy was measured by the Diabetes Empowerment Scale (DES-SF).

Results: Thirty-nine participants (median age 43, 74% female) were included. Mean TIR increased significantly in the NP group and remained unchanged in the UC group (between-group difference in change was 13.5% [95% CI: 4.0 to 22.9], p = 0.0064). Psychosocial self-efficacy improved and HbA1c decreased only significantly in the NP group.

Conclusions: Applying a novel education program at pump transition significantly improved glycemic outcomes and self-efficacy.

Purpose: To compare diabetic retinopathy screening among patients with type 1 or type 2 diabetes under care in two distinct setups: hospital-based multidisciplinary and general practice-based.

Materials and methods: In this retrospective observational case series, we collected data from a total of 133 diabetic patients: subjects from the hospital-based multidisciplinary setting were referred by the diabetologist and screened by an ophthalmologist using the Optomed Aurora IQ fundus camera. These patients were compared with those who underwent DR screening arranged through a general practice-based setting.

Results: The proportion of patients treated with insulin was higher in the hospital-based multidisciplinary group, both considering the totality patients and those affected by type 2 diabetes (71.6% vs. 32.2%; p < 0.001, and 58.8% vs. 31.0%; p = 0.004 respectively). Patients from the hospital-based multidisciplinary group had a longer mean diabetes duration (19.6 vs 14.9 years, p < 0.001), underwent DR screening more frequently in the previous three years (2.9 vs 1.4, p < 0.001), the mean time between two DR screenings was shorter (14.6 vs 77.9 weeks, p < 0.001), and DR was detected more frequently (32,4% vs 13.5%; p = 0.011).

Conclusion: We were able to demonstrate that patients screened in the multidisciplinary center, which had characteristics predisposing to a higher risk of DR, were more likely to be diagnosed with DR on time, with a higher mean number of DR screenings and a shorted interval between diabetic and ophthalmological assessments.

Objective: Previous studies have investigated the association between diabetes medications and thyroid cancer, but the results have not been conclusive. This study used a Mendelian randomization approach to investigate the causal relationship between diabetes medications and thyroid cancer (TC).

Methods: Exposures were six major diabetes medications target, while outcomes were TC and its differentiated forms, including papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Mendelian randomization was conducted using IVW, MR-Egger, and weighted median methods. Tests for heterogeneity, horizontal pleiotropy, and leave-one-out were also performed.

Results: In European populations, SGLT2 inhibitors were significantly negatively associated with TC (OR 0.051, 95% CI 0.006-0.465, P = 0.0082) as well as PTC (OR 0.034, 95% CI 0.003-0.411, P = 0.0079), while no correlation was found with FTC. These findings remained consistent even after applying the Bonferroni correction.

Conclusions: The evidence suggests that SGLT2 inhibitors could be potential therapeutic targets for TC, especially for PTC, in European populations. However, further large-scale randomized controlled trials are necessary to verify their ability to reduce the risk of and treat these types of cancer.

Aims: To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes.

Methods: This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups.

Results: The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, p˂0.001).

Conclusions: FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed.

Aims: This study aimed to investigate branched-chain amino acid (BCAA) catabolism in diabetic retinopathy (DR).

Methods: Wild-type and db/db mice were fed BCAAs (5 or 10 mg/kg/day) for 12 weeks, and hyperglycemia-exposed Müller cells were treated with BCAAs (2 or 5 mmol/L) for 24 and 48 h. BCAA levels were measured using MS/MS. Western blotting was performed to detect proteins. Flow cytometry, oxygen consumption rate, and Cell Counting Kit-8 assays were used to evaluate Müller cell viability. Each experiment was conducted at least thrice.

Results: BCAAs and branched-chain α-keto acids (BCKAs) were increased in the retina and systemic tissues of diabetic mice, and these changes were further enhanced to approximately 2-fold by extra BCAAs compared to wild-type group. In vitro, BCAAs and BCKAs were induced in hyperglycemic Müller cells, and augmented by BCAA supplementation. The aberrant BCAA catabolism was accompanied by mTORC1 activation and subsequently induced TNF-ɑ, VEGFA, GS, and GFAP in retinas and Müller cells under diabetic conditions. The cell apoptosis rate increased by approximately 50%, and mitochondrial respiration was inhibited by hyperglycemia and BCAA in Müller cells. Additionally, mTORC1 signaling was activated by leucine in Müller cells. Knockdown of Sestrin2 or LeuRS significantly abolished the leucine-induced mTORC1 phosphorylation and protected Müller cell viability under diabetic conditions.

Conclusions: We found that BCAA catabolism is hindered in DR through mTORC1 activation. Leucine plays a key role in inducing mTORC1 by sensing Sestrin2 in Müller cells. Targeting Sestrin2 may ameliorate the toxic effects of BCAA accumulation on Müller cells in DR.

Aims: To investigate immunometabolic associations of CD4⁺ T cell phenotypes with gestational diabetes mellitus (GDM).

Methods: A nested case-control study was conducted comprising 53 pairs of GDM patients and matched controls within a prospective cohort. Metabolomic signatures related to both CD4⁺ T cell phenotypes and glycemic traits among pregnant women were investigated by weighted gene co-expression network analysis (WGCNA). Multivariable-adjusted generalized linear models were used to explore the associations of CD4⁺ T cell phenotypes and selected metabolites with GDM. Mediation analysis was conducted to evaluate the mediating effect of selected metabolites on the relationship between CD4⁺ T cell phenotypes and glycemic traits.

Results: Higher levels of Treg cells (OR per SD increment (95%CI): 0.57 (0.34, 0.95), p = 0.031) and increased expression of Foxp3 (OR per SD increment (95%CI): 0.59 (0.35, 0.97), p = 0.039) and GATA3 (OR per SD increment (95%CI): 0.42 (0.25, 0.72), p = 0.002) were correlated with a decreased risk of GDM. Plasma pyruvaldehyde, S-adenosylhomocysteine (SAH), bergapten, and 9-fluorenone mediated the association between Tregs and fasting plasma glucose (FPG), with mediation proportions of 46.9%, 39.6%, 52.4%, and 56.9%, respectively.

Conclusions: Treg cells and Foxp3 expressions were inversely associated with GDM risk, with potential metabolic mechanisms involving metabolites such as pyruvaldehyde and SAH.