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Introduction: Individuals with type 2 diabetes and increased albuminuria, a well-established marker of microvascular complications, are at a higher risk for cardiovascular disease (CVD) and premature mortality. Therefore, a better understanding of the underlying pathophysiology is needed to improve risk stratification and tailor prevention and intervention., Methods: We conducted a cross-sectional study including 463 individuals with type 2 diabetes, various degrees of albuminuria and without CVD. We analysed the association between albuminuria and markers of endothelial function (thrombomodulin and syndecan-1), thrombin generation (thrombin-antithrombin complex, prothrombin fragment 1 + 2), fibrinogen, platelet function (activation using soluble plasma selectin and aggregation using Multiplate® Analyzer) using regression models., Results: In the study cohort 33 % were women, the mean ± SD age was 65 ± 9 years, and median [IQR] diabetes duration was 15 [9-20] years. In total, 344 (74 %) individuals had normal albuminuria, 87 (19 %) moderately- and 32 (7 %) severely increased albuminuria levels. Higher markers of endothelial function and fibrinogen were independently associated with higher albuminuria levels (p < 0.01). No association between albuminuria and markers of thrombin generation and platelet was demonstrated., Conclusion: We demonstrated an independent association between albuminuria and markers of endothelial function and fibrinogen in individuals with type 2 diabetes and no history of CVD., Competing Interests: Declaration of competing interest LFFD, CGP, VRC, OBP, MFM, TWH and AMH report no conflicts of interest. NT is a full-time employee of Novo Nordisk Inc. PR has received grants for research to Steno Diabetes Center Copenhagen from Astra Zeneca, Bayer and Novo Nordisk, and has received honoraria to Steno Diabetes Center Copenhagen from Abbott, AstraZeneca, Bayer, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Sanofi and Gilead., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: To evaluate the relationship between adherence to the Mediterranean diet (MD) and periphereal artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM)., Methods: An observational sectional study was conducted with 174 patients diagnosed with T2DM, of which 78 patients had PAD. A patient was considered to have PAD if they obtained an ankle-brachial index (ABI) < 0.9 and/or absence of both distal pulses in one of the two feet. Data on sociodemographic and anthropometric variables, physical activity, smoking habits, biochemical blood parameters, and comorbidities were recorded. Good adherence to the MD was considered with a score ≥ 9 in MEDAS-14. Vascular factors independently associated with adherence to the MD in patients with T2DM were identified through multivariate logistic regression analysis., Results: ABI, DFU, intermittent claudication and pedal pulse absence correlated with MD adherence. DFU, intermittent claudication and posterior tibial pulse absence were associated with the final score obtained in the MEDAS-14. Nut consumption, white meat preference and sautéed dish intake were associated with PAD presence. Multivariate analysis linked MD adherence to sex (OR = 0.044, 95 % CI 0.003-0619), age (OR = 0.139, 95 % CI 0.029-0.666), duration of T2DM (OR = 7.383, 95 % CI 1.523-35.779) and age at diagnosis of T2DM (OR = 6082, 95 % IC 1.415-26.136), as well as the presence of DFU (OR = 0.000, 95 % IC 0.000-0.370) and intermittent claudication (OR = 0.004, 95 % IC 0.000-0.534)., Conclusions: Adherence to the MD is associated with a reduction in vascular complications in T2DM, highlighting its potential as a dietary intervention strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: To assess the Type 2 Diabetes Mellitus (T2DM) patients in association with Chronic Microvascular Complications at Glucose Peak Time and the association among chronic microvascular complications in T2DM patients and the glucose peak period in the typical steamed bread meal test., Methods: Overall 1095 T2DM patients were classified as three groups: (1) Group G1: glucose peak time ≤ 1 h (n = 84), Group G2: 1 h < glucose peak time ≤ 2 h (n = 648) and Group G3: glucose peak time > 2 h (n = 363). The clinical characteristics, insulin characteristics and glucose peak time and chronic microvascular complications markers of patients in each group was analyzed and compared. Statistical analyses were performed using SPSS 23.0, employing chi-square tests, Kruskal-Wallis tests, one-way ANOVA, and binary logistic regression analysis, with significance set at P < 0.05., Results: Age, length of disease, glycated hemoglobin (HbA1c), urine albumin-creatinine ratio (UACR), and the number of patients with diabetic retinopathy (DR) increased (all P < 0.05) in those with postponed glucose peak time, while insulinogenic indexes, the AUC for C-p (AUCC-p), fasting, and 120-min C-peptide (C-p) decreased (all P < 0.05). Only age was connected to patients with diabetic kidney disease (DKD) independently in binary logistic regression analysis, although delayed glucose peak time was related to the presence of patients with DR. (all P < 0.05)., Conclusion: Delayed glucose peak time contributed to DR. Attention should be paid to condition of chronic microvascular complications in T2DM patients with a postponed peak glucose timing., Competing Interests: Declaration of competing interest There is no potential conflict of interest about this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Given sparse relevant data, the aim of this study was to determine whether Helicobacter pylori infection, including cytotoxin-associated gene-A (CagA) producing strains, is associated with dementia in type 2 diabetes (T2DM)., Methods: Longitudinal data from 1115 participants in the community-based Fremantle Diabetes Study Phase I (mean age 64.0 years, 48.0 % males; 38.0 % H. pylori seronegative, 24.3 % H. pylori seropositive/CagA seronegative, and 37.7 % H. pylori/CagA seropositive at baseline) were analyzed., Results: During up to 19 years of follow-up, 50.3 % and 83.5 % of participants without and with incident dementia, respectively, died. In Cox proportional hazards models, H. pylori/CagA seropositivity (hazard ratio (95 % CI) 1.68 (1.15, 2.46), P = 0.008), but not H. pylori seropositivity/CagA seronegativity (P = 0.541) was an independent predictor of incident dementia, but neither H. pylori seropositivity/CagA seronegativity nor H. pylori/CagA seropositivity were significant predictors in competing risks models (P ≥ 0.280)., Conclusions: Although CagA seropositivity in T2DM may have a contributory etiologic role in the risk of dementia, this may be through its association with reduced cardiovascular/all-cause mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Aim to this study is to investigate the association of Dietary Counseling, Meal Patterns, and Diet Quality (DietQ) in Patients with Type 2 Diabetes Mellitus (T2DM) with/without chronic kidney disease (CKD) in primary healthcare., Methods: Cross-sectional study acquired data on dietary counseling and meal patterns by direct interview with a food-frequency questionnaire and one 24-h food-recall. The Healthy Eating Index (HEI) was used to classify DietQ ["good" DietQ (GDietQ, score ≥ 80) and "poor" DietQ (PDietQ, score < 80)]., Participants/setting: This study included 705 patients with T2DM: 306 with normal kidney function; 236 with early nephropathy, and 163 with overt nephropathy (ON)., Statistical Analyses Performed: Multivariate linear-regression models for predicting HEI and χ 2 tests for qualitative variables and one-way ANOVA for quantitative variables were employed. Mann-Whitney U and independent Student t were performed for comparisons between GDietQ and PDietQ., Results: Only 18 % of the population was classified as GDietQ. Patients with ON and PDietQ vs. with GDietQ received significantly less dietary counseling from any health professional in general (45 % vs 72 %, respectively), or from any nutrition professional (36 % vs. 61 %, respectively). A better HEI was significantly predicted (F = 42.01; p = 0.0001) by lower HbA 1C (β -0.53, p = 0.0007) and better diet diversity (β 8.09, p = 0.0001)., Conclusions: Patients with more advanced stages of CKD had less nutritional counseling and worse dietary patterns, as well as more frequent PDietQ. Our findings reinforce the need for dietitians and nutritionists in primary healthcare to provide timely nutritional counseling., Competing Interests: Declaration of competing interest Authors declare that there are no financial relationships or other potential conflicts of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recently, a health-care database study showed that persons with type 2 diabetes taking GLP-1 receptor agonists (GLP-1 RA) had a significantly lower risk of 10 out of 13 obesity-related cancers than patients taking insulin (Wang L, et al. JAMA Netw Open. 2024 7: e2421305). For some cancers, hazard ratios <0.5 were reported. This is reminiscent of studies published >10 years ago showing that people with type 2 diabetes taking metformin had a lower risk of many types of cancer than those not taking metformin. In some studies, also risk reductions of >50 % were reported. The strong effects observed in the metformin studies were explained by time-related biases, in particular, immortal time bias. In the current GLP-1 RA study, it was striking that the curves for the cumulative incidence of several cancers in GLP-1 RA and insulin users diverged immediately after therapy onset. This indicates that there is most likely a time-related bias: insulin is given at much later stages of type 2 diabetes than GLP-1 RA. The current study suggests that one should be sceptical about database results when spectacular risk reductions are reported. Time-related bias should always be considered as an alternative explanation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To assess the difference in microvascular changes between males and females with diabetes mellitus (DM) without diabetic retinopathy (NoDR) and with mild-to-moderate non-proliferative diabetic retinopathy (NPDR) using Optical Coherence Tomography Angiography (OCT-A)., Design: Retrospective cross-sectional study., Methods: 267 DM patients, 133 females (49.81 %), 111 with NoDR (41.57 %) and 156 NPDR (58.43 %) were included. Foveal-centered 3 × 3 mm OCT-A images corresponding to the superficial (SCP), intermediate (ICP) and deep capillary plexus (DCP), and full retinal (RET) slab were used for analysis. For each slab, FAZ area, perimeter, and circularity index (CI) were determined, following manual delineation of the FAZ; perfusion (PD) and vessel density (VD), fractal dimension (FD), vessel length density (VLD), geometric perfusion deficits (GPD) were also computed. Flow voids (FV) were determined in the choriocapillaris plexus; and perfused capillary density (PCD) in the RET slab., Results: Females showed larger FAZ CI in SCP and greater FAZ area and perimeter than males in NPDR group. Males had higher central macular thickness than females in NPDR group. All density metrics at the level of ICP and DCP were affected in the NPDR group with no gender differences. Of note, the same significant findings were found in type 1 DM patients, and not in type 2 DM patients., Conclusions: Our OCT-A findings suggest significant microvascular changes in females with NPDR compared to males, but no such differences in patients without DR. Therefore, gender-related vascular alterations might be present in early stages of DR with potential role., Competing Interests: Declaration of competing interest Stela Vujosevic: Consultant to Abbvie, Apellis, Bayer, Novartis, Hoffman La Roche, Zeiss; Paolo Nucci: Thea, Hoya, Essilor Luxottica e Fondazione One-sight, Sifi, Bausch& Lomb, Alfa Intes, Alcon, Doc, Santen, Eyerising. Mariacristina Parravano reports personal fees from Abbvie, Novartis, Bayer, La-Roche, Zeiss outside the submitted work. Celeste Limoli, Gabriele Piccoli, Eliana Costanzo, Elisa Marenzi, Emanuele Torti, Daniela Giannini, Maria Sole Polito and Livio Luzi have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the relationship between age at diagnosis of type 2 diabetes and the risk of macrovascular disease, heart failure, and microvascular disease., Methods: In August 2022, PubMed/EMBASE were searched for articles reporting (i) coronary artery disease, cerebrovascular disease, peripheral vascular disease, amputation; (ii) heart failure; and (iii) retinopathy, neuropathy, nephropathy (albuminuria, chronic kidney disease [CKD], end-stage renal disease) by age at diagnosis of type 2 diabetes. Random effects, non-linear dose-response meta-analysis was undertaken for each outcome to assess the association with age at diagnosis (40 years = reference), using both crude and maximally adjusted odds ratios separately, with and without adjustment for current age (age at sampling)., Results: We identified 42 articles (230,003 to 3,465,590 participants; 1035 to 391,140 events). Age at diagnosis was positively associated with the risk of macrovascular diseases, heart failure, and CKD, independent of current age, and negatively associated with retinopathy. For other microvascular outcomes, when adjusting for current age, a "reverse U" relationship was observed (peak risk = 55-60 years)., Discussion: Retinopathy was negatively associated with age at diagnosis, highlighting the importance of retinopathy screening in early-onset type 2 diabetes. The implications of other associations were unclear due to the heterogeneity in methodologies and findings., Competing Interests: Declaration of competing interest KK has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim and Bayer. MJD has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk and Sanofi, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Pfizer, Medtronic and ShouTi Pharma Inc. and as a speaker for Napp Pharmaceuticals, Novartis and Takeda Pharmaceuticals International Inc. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen. JAS received a grant for an investigator-initiated study for AstraZeneca. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To compare the time in range (TIR) obtained from self-monitoring of blood glucose (SMBG) with that obtained from continuous glucose monitoring (CGM), and explore the relationship of TIR with microalbuminuria outcome, HOMA-IR and HOMA-β test., Methods: We recruited 400 patients with type 2 diabetes to carry out blood glucose monitoring by both SMBG and CGM for 3 consecutive days. TIR, TAR, TBR and other blood glucose variation indices were calculated respectively through the glucose data achieved from SMBG and CGM. The HOMA-IR and HOMA-β test was evaluated by an oral glucose tolerance test. Urinary microalbumin-to-creatinine ratio completed in the laboratory., Results: The median (25 %, 75 % quartile) of TIR CGM and TIR SMBG were 74.94(44.90, 88.04) and 70.83(46.88, 87.50) respectively, and there was no significant difference, p = 0.489; For every 1 % increase in TIR CGM , the risk of microalbuminuria decreased by 1.6 % (95%CI:0.973, 0.995, p = 0.006) and for every 1 % increase in TIR SMBG , the risk of microalbuminuria decreased by 1.3 % (95%CI:0.975, 0.999, p = 0.033). Stepwise multiple linear regression analysis showed an independent positive correlation between TIR (including TIR CGM and TIR SBMG ) and LnDI30 and LnDI120 levels (p = 0.000)., Conclusions: The TIR calculated by SMBG was highly consistent with that reported by CGM and was significantly associated with the risk of microalbuminuria and the HOMA-β. Higher TIR quartiles were associated with lower incidence of microalbuminuria as well as higher lever of HOMA-β. For patients with limited CGM application, SMBG-derived TIR may be an alternative to CGM-derived TIR, to assess blood glucose control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Atherogenic indices: Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, Atherogenic Index of Plasma (AIP), Atherogenic Coefficient (AC), Castelli's Risk Index I and II (CRI-I, CRI-II) are used in clinical studies as surrogates of major adverse cardiac and cerebrovascular events (MACCE). Risk prediction of MACCE in patients with acute myocardial infarction (AMI) has vital role in clinical practice. We aimed to assess prognostic value of these indices following AMI., Methods: We analyzed patients with AMI with and without T2DM and the prognostic values of atherogenic indices for in-hospital death and MACCE within 12 months after AMI., Results: Of 2461 patients, 152 in-hospital deaths (6.2 %) were reported (74 patients [7.4 %] with T2DM and 78 [5.3 %] without T2DM; p = 0.042). MACCE occurred in 22.7 % of patients (29.7 % with T2DM and 17.9 % without T2DM; p < 0.001). TG/HDL-C and AIP were higher in T2DM patients compared to those without T2DM (p < 0.001). Long-term MACCE was more prevalent in patients with T2DM (p < 0.001). The AUC-ROC for predicting in-hospital death based on TG/HDL-C and AIP was 0.57 (p = 0.002)., Conclusions: None of the atherogenic indices was an independent risk factor for in-hospital death or MACCE at 12-month follow-up in patients with AMI. AIP was an independent risk factor for death at 12-month follow-up., Competing Interests: Declaration of competing interest There is no conflict of interest in this project., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are increasingly being used among hospitalized patients. Our objective was to assess the risk of diabetic ketoacidosis (DKA) among hospitalized patients receiving an SGLT-2i., Research Design and Methods: We conducted a multicentre cohort study of patients hospitalized at 19 hospitals. We included patients over 18 years of age who received an SGLT-2i or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in hospital. The primary outcome was the risk of DKA during their hospitalization., Results: 61,517 patients received a DPP-4i and 11,061 received an SGLT-2i. The risk of inpatient DKA was 0.07 % (N = 41 events) among adults who received a DPP-4i and 0.18 % (N = 20 events) among adults who received an SGLT-2i; adjusted odds ratio of 3.30 (95 % CI: 1.85-5.72)., Conclusions: In hospitalized patients, the absolute risk of DKA was 0.2 %, which corresponded to a three-fold higher relative risk., Competing Interests: Declaration of competing interest MF was a consultant for ProofDx, a start-up company creating point of care diagnostic tests for COVID-19 using CRISPR. MF is an advisor for SIGNAL1, a start-up company deploying machine learned models to improve inpatient care. MF has been paid for medicolegal cases unrelated to the content of this study. FR is a provincial clinical lead for quality improvement at Ontario Health (as a part-time salaried employee). This research was undertaken, in part, with funding from the Canada Research Chairs Program. AV is a part-time employee of Ontario Health and is supported by the Temerty Professorship of AI Research and Education in Medicine at the University of Toronto., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM)., Methods: Clinically cognitively normal T2DM individuals were recruited (NCT04455867). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry., Results: The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F 1,101  = 6.094, p = 0.015 and F 1,101  = 5.598, p = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F 1,100  = 12.137, p < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F 1,100  = 6.481, p = 0.012) and 11(12)-EpETrE (F 1,100  = 4.409, p = 0.038), and 2) verbal memory, including 9(10)-EpOME (F 1,100  = 4.286, p = 0.041), 5(6)-EpETrE (F 1,100  = 6.845, p = 0.010), 11(12)-EpETrE (F 1,100  = 3.981, p = 0.049) and 14(15)-EpETrE (F 1,100  = 5.019, p = 0.027)., Conclusions: Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bariatric surgery leads to considerable weight loss and improved glycaemic control and seems to have a favourable impact on diabetes related foot complications (DFC)., Objectives: To assess the effect of bariatric surgery on diabetes related foot complications in patients with type 2 diabetes and determine whether DFC symptoms are improved after bariatric surgery., Methods: We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials. The primary outcome was the presence of DFC after bariatric surgery. The secondary outcome was the improvement of DFC after bariatric surgery among patients who already had DFC before surgery., Results: There were nine studies showing the presence of DFC post bariatric surgery and six detailing the changes in DFC post bariatric surgery. Bariatric surgery was not associated with a lower risk of developing or worsening DFC compared to conventional medical treatment based on 4 randomised control trials (IR 0.87, 95 % CI, 0.26, 2.98), while from observational studies was associated with 51 % lower risk of DFC (IR 0.49, 95 % CI, 0.31, 0.77). Bariatric surgery was associated with improvement in diabetic neuropathy assessment parameters including toe tuning fork score, self-reported neuropathy symptoms, neuropathy symptom score, and neuropathy symptom profile., Conclusion: Bariatric surgery led to a greater reduction in developing or worsening DFC among patients with type 2 diabetes compared to medical treatment in observational studies, but not among RCTs. Bariatric surgery was associated with improvements in diabetic neuropathy related assessment parameters and symptoms. Bariatric surgery could be a promising treatment for patients with type 2 diabetes who are at high risk of DFC., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Gastric emptying of a glucose drink was measured in people with type 2 diabetes given lixisenatide (20 μg/day or placebo) for 8 weeks. Intragastric retention at 240 min (2 (0-11)% vs 48 (3-97)%; P < 0.0001) was much greater with lixisenatide than placebo. Accordingly, lixisenatide may delay liquid gastric emptying markedly., Competing Interests: Declaration of competing interest This manuscript represents a secondary analysis of our published randomised clinical trial (RCT) evaluating the effect of chronic (8 week) treatment with the short-acting glucagon-like peptide-1 (GLP-1) receptor agonist, lixisenatide on gastric emptying, using the gold standard technique, scintigraphy, and glucose metabolism in people with type 2 diabetes (Rayner et al. Diabetes Care 2020;43:1813–1821). An erratum of the original paper was subsequently published (Rayner et al. Diabetes Care 2021;44:297) correcting some minor errors unrelated to this submission., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Diabetic foot ulcers (DFU) are a major sequela of uncontrolled diabetes with a high risk of adverse outcomes. Poor DFU outcomes disproportionately impact patients living in rural and economically distressed communities with lack of access to consistent, quality care. This study aimed to analyze the risk of geographic and economic disparities, including rural status and county economic distress, on the disease burden of DFU at presentation utilizing the SVS WIfI classification system., Methods: We conducted a retrospective review of 454 patients diagnosed with a DFU from 2011 to 2020 at a single institution's inpatient and outpatient wound care service. Patients >18 years old, with type II diabetes mellitus, and diabetic foot ulcer were included., Results: ANCOVA analyses showed rural patients had significantly higher WIfI composite scores (F(1,451) = 9.61, p = .002), grades of wound (F(1,439) = 11.03, p = .001), and ischemia (F(1,380) = 12.574, p = .001) compared to the urban patients. Patients that resided in at-risk economic counties had significantly higher overall WIfI composite scores (F(2,448) = 3.31, p = .037) than patients who lived in transitional economic counties, and higher foot infection grading (F(2,440) = 3.02, p = .05) compared to patients who lived in distressed economic counties. DFU patients who resided in distressed economic counties presented with higher individual grades of ischemia (F(2, 377) = 3.14, p = .04) than patients in transitional economic counties. Chi-Square analyses demonstrated patients who resided in urban counties were significantly more likely to present with grade 1 wounds (χ2(3) = 9.86, p = .02) and grade 0 ischemia (χ2(3) = 16.18, p = .001) compared to patients in rural areas. Economically distressed patients presented with significantly less grade 0 ischemia compared to patients in transitional economic counties (χ2(6) = 17.48, p = .008)., Conclusions: Our findings are the first to demonstrate the impact of geographic and economic disparities on the disease burden of DFU at presentation utilizing the SVS WIfI classification system. This may indicate need for improved multidisciplinary primary care prevention strategies with vascular specialists in these communities to mitigate worsening DFU and promote early intervention., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: In-hospital dysglycemia is associated with adverse outcomes. Identifying patients at risk of in-hospital dysglycemia early on admission may improve patient outcomes., Methods: We analysed 117 inpatients admitted with pneumonia and type 2 diabetes monitored by continuous glucose monitoring. We assessed potential risk factors for in-hospital dysglycemia and adverse clinical outcomes., Results: Time in range (3.9-10.0 mmol/l) decreased by 2.9 %-points [95 % CI 0.7-5.0] per 5 mmol/mol [2.6 %] increase in admission haemoglobin A1c, 16.2 %-points if admission diabetes therapy included insulin therapy [95 % CI 2.9-29.5], and 2.4 %-points [95 % CI 0.3-4.6] per increase in the Charlson Comorbidity Index (CCI) (integer, as a measure of severity and amount of comorbidities). Thirty-day readmission rate increased with an IRR of 1.24 [95 % CI 1.06-1.45] per increase in CCI. In-hospital mortality risk increased with an OR of 1.41 [95 % CI 1.07-1.87] per increase in Early Warning Score (EWS) (integer, as a measure of acute illness) at admission., Conclusions: Dysglycemia among hospitalised patients with pneumonia and type 2 diabetes was associated with high haemoglobin A1c, insulin treatment before admission, and the amount and severity of comorbidities (i.e., CCI). Thirty-day readmission rate increased with high CCI. The risk of in-hospital mortality increased with the degree of acute illness (i.e., high EWS) at admission. Clinical outcomes were independent of chronic glycemic status, i.e. HbA1c, and in-hospital glycemic status., Competing Interests: Declaration of competing interest MTO, CKK, and KBH have nothing to disclose. UPB has served on advisory boards and received lecture fees from Novo Nordisk and Sanofi. PLK has received speaker fees from Sanofi, Boehringer Ingelheim, Novo Nordisk, and AstraZeneca., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To demonstrate cardiovascular safety of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) across age-groups., Methods: PubMed, Embase and Cochrane were searched for cardiovascular outcome trials (CVOTs) testing newer agents until August 31, 2022 (PROSPERO ID CRD42021260167). Studies with ≥1000 T2D participants enrolled for ≥12 months were included. Random effect models were used to report relative-risk (RR) for three-point major adverse cardiovascular events (3P-MACE) and its components by age subgroups (65 years; 75 years)., Results: For SGLT-2is, five CVOTs (46,969 patients, 45-50 % ≥65 years) were included. SGLT-2is reduced risk of MACE (RR; 0.91 [CI, 0.85-0.98]); cardiovascular death (CV-death) (RR; 0.84 [CI, 0.73-0.96]); and all-cause mortality (ACM) (RR; 0.86 [CI, 0.79-0.93]) with no difference in subgroups <65 or ≥65 years. For GLP-1RAs, nine CVOTs (n = 64,236, 34-75 % ≥65 years) were included. GLP-1RAs reduced risk of MACE (RR; 0.89 [CI, 0.83-0.95]), stroke (RR; 0.86 [CI, 0.76-0.97]) and ACM (RR; 0.90 [CI, 0.83-0.97]) with no significant difference in subgroups <65 or ≥65 years. Additionally, GLP-1RAs reduced risk of MACE (10 %), ACM (12 %) and CV-death (12 %) with no significant difference in subgroups <75 or ≥75 years. Four CVOTs (n = 33,063; 35-58 % ≥65 years) with DPP-4is were included. There were no significant differences in risk for CV outcomes with DPP-4is compared to placebo in any of the age subgroups., Conclusion: The overall cardiovascular safety profile of newer anti-hyperglycemic agents is consistent in older and younger individuals., Competing Interests: Declaration of competing interest REP reports speaker fees from Merck and Novo Nordisk; consulting fees from Bayer AG, Endogenex, Inc., Gasherbrum Bio, Inc., Hengrui (USA) Ltd., Intas Pharmaceuticals, Inc., Lilly, Novo Nordisk, Pfizer, Rivus Pharmaceuticals Inc., and Sun Pharmaceutical Industries; and grants from Dompe and Novo Nordisk. All funds are paid directly to Dr. Pratley's employer, AdventHealth, a nonprofit organization that supports education and research. TKT reports consulting fees from Novo Nordisk and Lilly, research support from Novo Nordisk and Bayer. She is on the speaker bureau for Bayer and Lilly. CTR received research grant through institution from Anthos, AstraZeneca, Daiichi Sankyo, Janssen and Novartis; Honoraria for scientific advisory boards and consulting fees from Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Pfizer. CTR and KI are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, The Medicines Company, Zora Biosciences. All other authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: There are limited studies on dipeptidyl-peptidase 4 inhibitor (DPP-4i), sodium glucose cotransporter 2 inhibitor (SGLT2-i), and glucagon-like peptide 1 (GLP-1) receptor agonist use and occurrence of diabetic macular edema (DME). The objective of this study was to determine the association between DPP-4i, SGLT2-i, and GLP-1 receptor agonist use and occurrence of DME., Methods: Proportional hazard models were used to evaluate the change in hazard of developing DME associated with DPP-4i, SGLT2-i, or GLP-1 receptor agonist use. Models accounted for age at DR diagnosis, DR severity (proliferative vs non-proliferative stage), time-weighted average of HbA1c level, sex, and self-reported race/ethnicity. A p-value ≤ 0.05 was considered statistically significant., Results: The hazard ratio of developing DME after diagnosis of DR was 1.2 (CI = 0.75 to 1.99; p = 0.43) for DPP-4i use, 0.93 (CI = 0.54 to 1.61; p = 0.81) for GLP-1 receptor agonist use, 0.82 (CI = 0.20 to 3.34; p = 0.78) for SGLT2-i use, 1.1 (CI = 0.75 to 1.59; p = 0.66) for any one medication use, 1.1 (CI = 0.62 to 2.09; p = 0.68) and for any two or more medications use., Conclusions: We did not find an association between DPP-4i, SGLT2-i, or GLP-1 receptor agonist use and increased hazard of development of DME among patients with DR., Competing Interests: Declaration of competing interest RMW reports receiving research support from Novo Nordisk outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To examine whether prior gestational diabetes mellitus (GDM) is associated with prevalent coronary heart disease (CHD), cerebrovascular disease (CeVD) and peripheral arterial disease (PAD), and all-cause mortality, in community-based women with type 2 diabetes., Methods: Baseline prevalences of CHD/CeVD/PAD/prior GDM were determined in 718 females (mean ± SD age 65.5 ± 11.9 years) from the Fremantle Diabetes Study Phase II. Deaths between baseline (2008-2011) and end-2016 were ascertained. Cox regression identified predictors of mortality with GDM as a candidate variable., Results: Compared to the 673 women without GDM, the 39 (5.4 %) with prior GDM were younger, more likely Aboriginal, smokers and obese, had longer diabetes duration and higher HbA 1c levels, and were more dyslipidemic (P ≤ 0.046). Prevalences of CHD (24.6 versus 23.1 %), CeVD (7.5 % versus 2.6 %) and PAD (27.5 % versus 23.7 %) were not significantly different in those without versus with prior GDM (P ≥ 0.35). There were 116 deaths (16.2 %) during 6.8 ± 1.6 years of follow-up. Age, Aboriginal ethnicity, marital status, current smoking, heart rate, estimated glomerular filtration rate, CHD and PAD were independently associated with all-cause mortality (P ≤ 0.023); GDM status did not add to the most parsimonious model (P = 0.62)., Conclusions: Prior GDM does not increase CVD risk or all-cause mortality in women with type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM)., Methods: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM., Results: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN., Conclusion: The review presents a possible relationship between DPN and CAN, such as in their severity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vinicius Saura Cardoso reports financial support was provided by Foundation for Research Support of Piauí State. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest None.

Aims: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance., Methods: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups., Results: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm., Conclusions: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile., Trial Registration: ClinicalTrials.gov, NCT05624853., Competing Interests: Declaration of competing interest The authors declare the following potential conflicts of interest with respect to the research, authorship, and publication of this paper: “ The authors declare no competing financial interest in the publication of our data.”, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven cardiovascular disease and some classic cardio-metabolic risk factors., Patients and Methods: The study included 461 obese patients with an average age of 53.2 ± 10.7 years, divided into three groups - group 1 without carbohydrate disturbances (n = 182), group 2 with prediabetes (n = 193) and group 3 with newly diagnosed diabetes mellitus (n = 86)., Results: The patients with new-onset diabetes had significantly higher mean CIMT values compared to those with prediabetes or without carbohydrate disturbances and a higher frequency of abnormal IMT values. CIMT correlated significantly with age, systolic BP, diastolic BP and fasting blood glucose and showed a high predictive value for the presence of diabetic neuropathy and sudomotor dysfunction. Patients with abnormal CIMT values had a higher incidence of arterial hypertension, dyslipidemia, metabolic syndrome, peripheral neuropathy, and sudomotor dysfunction. Patients who developed type 2 diabetes during follow-up had a significantly higher initial mean CIMT, which showed the highest predictive value for the risk of new-onset diabetes, with CIMT≥0.7 mm having 53 % sensitivity and 83 % specificity for the risk of progression to diabetes mellitus., Conclusion: Patients with new-onset diabetes mellitus had significantly greater intima media thickness of the common carotid artery and a greater frequency of abnormal CIMT values compared to those with normoglycemia and prediabetes. CIMT has a high predictive value for the presence of diabetic neuropathy, sudomotor dysfunction and the risk of new onset diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We evaluated the effect of sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) on arterial stiffness indices., Methods: We searched PubMed (up to January 2024) for RCTs assessing the effect of SGLT2i or GLP1-RA on arterial stiffness with reporting outcomes PWV and AIx. Effect sizes of the included studies were expressed as weighted mean difference (WMD) and 95 % confidence interval. Subgroup analyses were performed based on comparator (placebo vs. active comparator), design (RCT vs. crossover), population (diabetic vs. all) and blindness (yes vs. no)., Results: A total of 19 studies (SGLT2i, 12 studies; GLP1-RA, 5 studies; SGLT2i/GLP1-RA combination, 2 studies) assessing 1212 participants were included. We did not find any statistically significant association between GLP1-RA or SGLT2i and PWV or AIx. None of the subgroup analyses showed any statistically significant result., Conclusion: No evidence of a favorable change in arterial stiffness indices (PWV, AIx) was found following the administration of SGLT2i or GLP1-RA., Competing Interests: Declaration of competing interest ER has received speaker honoraria and consulting fees for clinical trials unelated to this work (Novartis, Sanofi, NovoNordisk, Pfizer, AstraZeneca/BMS, Eli Lilly, MSD/Vianex, Boehringer Ing, Amgen, GSK, Plus Pharmaceuticals, WinMedica, Servier). The rest of the authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Population-based prevalence estimates of distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathy (DAN) are scares. Here we present neuropathy estimates and describe their overlap in a large cohort of people with type 1 and type 2 diabetes., Methods: In a large population of outpatient participants, DPN was assessed using vibration perception threshold, sural nerve function, touch, pain and thermal sensation. Definite DPN was defined by the Toronto Consensus Criteria. Painful DPN was defined by Douleur Neuropathique 4 Questions. DAN measures were: cardiovascular reflex tests, electrochemical skin conductance, and gastroparesis cardinal symptom index., Results: We included 822 individuals with type 1 (mean age (±SD) 54 ± 16 years, median [IQR] diabetes duration 26 [15-40] years) and 899 with type 2 diabetes (mean age 67 ± 11 years, median diabetes duration 16 [11-22] years). Definite DPN was prevalent in 54 % and 68 %, and painful DPN was in 5 % and 15 % of type 1 and type 2 participants, respectively. The prevalence of DAN varied between 6 and 39 % for type 1 and 9-49 % for type 2 diabetes. DPN without other neuropathy was present in 45 % with T1D and 50 % with T2D., Conclusion: The prevalence of DPN and DAN was high. DPN and DAN co-existed in only 50 % of cases., Competing Interests: Declaration of competing interest PR has received honoraria to his institution for consultancy and/or speaking fees from Astellas, Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, and Sanofi Aventis and research grants from AstraZeneca and Novo Nordisk (to institution). The funders of the study had no role in study design, data collection, analysis, interpretation or writing of the report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Information on BMI and risk of developing hypertension in type 1 diabetes (T1D) is scarce, and it comes mostly from cross-sectional analyses. This study underscores a risk of developing hypertension in T1D individuals with high BMI, and this risk appears to be higher than in those with type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest relevant to this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This post-hoc study investigated whether biomarkers reflecting extracellular matrix (ECM) turnover predicted cardiovascular disease (CVD), mortality, and progression of diabetic kidney disease (DKD) in individuals with type 2 diabetes (T2D) and microalbuminuria., Methods: Serum levels of specific ECM turnover biomarkers were assessed in 192 participants with T2D and microalbuminuria from an observational study conducted at Steno Diabetes Center Copenhagen from 2007 to 2008. Endpoints included CVD events, mortality, and DKD progression, defined as decline in estimated glomerular filtration rate (eGFR) of >30 %., Results: Participants had a mean age of 59 years, with 75 % males. Over a median follow-up of 4.9 to 6.3 years, the study recorded 38 CVD events, 24 deaths, and 40 DKD events. Elevated levels of a degradation fragment of collagen type I (C1M) were associated with an increased risk of >30 % eGFR decline, although this association was not independent of other risk factors. No significant associations were found between other ECM turnover biomarkers and DKD progression, mortality, or CVD risk., Conclusion: Elevated C1M levels were linked to DKD progression in individuals with T2D and microalbuminuria, but not independently of other risk factors. None of the ECM turnover biomarkers were associated with CVD or mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ALM, DGKR, FG, and MAK are employees of Nordic Bioscience. Nordic Bioscience is a privately owned, small- to medium-sized enterprise, partly focused on the development of biomarkers. None of the authors received fees, bonuses, or other benefits for the work regarding this article. DGKR, FG, and MAK holds stocks in Nordic Bioscience. Outside this work, BJvS is employed by Novo Nordisk, and PR has received institutional grants from Bayer, Novo Nordisk and AstraZeneca and has acted as consultant for Novo Nordisk, Bayer, Astellas, Boehringer Ingelheim, AstraZeneca, Gilead, Merk, Mundipharma, and Sanofi (honoraria to institution). The results presented in this paper have not been published previously in whole or part, except in abstract format., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: We aimed to investigate the association between glycemic variability (GV) and the abnormal differentiation of T-cell subpopulations in patients with type 2 diabetes mellitus (T2DM)., Methods: In total, 108 hospitalized patients with T2DM were enrolled and divided into two subgroups (normal glycemic excursion (NGE) and high glycemic excursion (HGE)) according to their mean amplitude of glycemic excursion (MAGE) level. The MAGE was evaluated via continuous glucose monitoring for 72 h consecutively. Flow cytometry was used to determine the proportions of T cell subpopulations., Results: The T helper (Th) 1 cell/Th2 cell ratio was significantly higher, and the proportion of regulatory T cells (Tregs) was significantly lower in the NGE group than in the HGE group (all P < 0.05). After fully adjusting for confounders, the MAGE was positively associated with the Th1 cell/Th2 cell ratio (β = 0.370; P = 0.009) and negatively associated with the proportion of Tregs (β = -0.554; P = 0.001)., Conclusion: The MAGE was an independent risk factor for abnormally high Th1 cell/Th2 cell ratio and proportion of Tregs. Abnormal differentiation of T cell subpopulations induced by GV may impair β-cell function, aggravate insulin resistance, and contribute to the development of diabetic complications., Competing Interests: Declaration of competing interest The authors declare, that is, no conflict of interest that could be perceived as prejudicing the impartiality of this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet β-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function., Research Design and Methods: IResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors., Results: Higher IResp was associated with poorer performance on the DSST (-0.69 points per 100 unit increase in IGI, 95 % CI: -1.37, -0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT., Conclusions: These results suggest that a greater β-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: This systematic review and meta-analysis aimed to comprehensively evaluate the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in individuals with diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) or obesity., Methods: A search of PubMed, Embase, and Web of Science until October 2023 identified 13 Randomized Controlled Trials (RCTs) meeting the inclusion criteria. Bias risk was assessed using the Cochrane risk-of-bias instrument. Statistical analysis utilized standard mean differences (SMD) in Review Manager 5.4. Heterogeneity and publication bias were assessed. This study used the protocol registered with the Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110020)., Results: GLP-1RA treatment significantly reduced VAT (SMD -0.55, 95 % CI [-0.90, -0.19]), SAT (SMD -0.59, 95 % CI [-0.99, -0.19]), body weight (SMD -1.07, 95 % CI [-1.67, -0.47]), and body mass index (BMI) (SMD -1.10, 95 % CI [-1.74, -0.47]) compared to controls. Heterogeneity was observed for VAT (I 2  = 79 %, P < 0.01), SAT (I 2  = 73 %, P < 0.01), body weight (I 2  = 82 %, P < 0.01), and BMI (I 2  = 82 %, P < 0.01). No publication bias was detected for VAT (P = 0.57) and SAT (P = 0.18). GLP-1RA treatment improved fasting blood glucose (FBG), postprandial glucose (PPG), hemoglobin A1c (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and fibrosis-4 (FIB-4)., Conclusions: This meta-analysis highlights GLP-1RAs' potential to reduce fat accumulation, body weight, and BMI and improve glycemic control in individuals with diabetes mellitus and NAFLD or obesity. These findings supported using GLP-1RAs as promising therapeutic agents to address abnormal adipose tissue distribution and metabolic dysfunction., Competing Interests: Declaration of competing interest This study declares no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Chronic kidney disease (CKD) is prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate risk factors for CKD progression across the kidney disease-Improving Global Outcomes (KDIGO)categories in a Middle Eastern population beyond hyperglycemia as emphasized by KDIGO guidelines which classifying CKD by cause and severity., Methods: This cross-sectional study targeted 1603 patients with T2DM. Risk factors for CKD progression were determined using odds ratios (ORs) and 95 % confidence intervals (CIs)., Results: Overall, 35.5 %, 31.7 %, and 32.8 % of patients were classified as low-risk, moderate-risk, and high-/very high-/highest-risk, respectively. Several factors were associated with high/very high/highest risk categorization, including being aged >45 years (OR: 1.85, 95 % CI: 1.36-2.49; P < 0.001), male gender (OR: 1.87, 95 % CI: 1.38-2.54; P < 0.001), hypertension (OR: 3.66, 95 % CI: 2.32-5.78; P < 0.001), and T2DM duration of ≥15 years (OR: 3.2, 95 % CI: 2.27-4.5; P < 0.001). Patients with more concurrent risk factors were notably represented in the high/very high/highest risk category., Conclusions: Male patients, older patients, and those with comorbid hypertension, longstanding T2DM, and additional concurrent risk factors have a significantly higher risk of advanced CKD. Such findings should be considered when planning management approaches for patients with CKD., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To assess the association of adipose-to-lean ratio (ALR) with incident type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia in middle adulthood., Method: Black and White Coronary Artery Risk Development in Young Adults participants without T2DM, hypertension, or dyslipidemia in 2005-06 (baseline) were included. Baseline adipose and lean mass were assessed via dual-energy X-ray absorptiometry. ALR was calculated as adipose divided by lean mass and then standardized within sex strata. Single time-point incident morbidity was assessed every five years from baseline through 2016. Cox proportional hazards regression was used to estimate hazard ratios (HR) for morbidity over 10 years per 1-SD increment in ALR adjusted for cardiovascular risk factors., Result: The cumulative incidence of T2DM was 7.9 % (129 events/N = 1643; 16,301 person-years), 26.7 % (485 events/N = 1819; 17,895 person-years) for hypertension, and 49.1 % (435 events/N = 855, 8089 person-years) for dyslipidemia. In the adjusted models, ALR was positively associated with a risk of T2DM (HR [95 % CI]; 1.69 [1.31, 2.19]) and hypertension (1.23 [1.08, 1.40]). There was no significant interaction between ALR and sex for any morbidity., Conclusion: ALR in middle adulthood is associated with incident T2DM and hypertension. The extent to which localized body composition measures might inform morbidity risk merits further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The prevalence of diabetes mellitus is increasing year by year globally, and diabetic cardiomyopathy (DCM), as the most common complication of type 2 diabetes mellitus, seriously affects the prognosis of patients. Trimetazidine (TMZ), as a drug affecting myocardial energy metabolism, mainly reduces the oxidation rate of β-oxidation by inhibiting 3-ketoacyl-CoA thiolase (3-KAT), a key enzyme in β-oxidation of free fatty acid (FFA), so that the energy metabolism substrate of cardiomyocytes preferentially selects glucose rather than fatty acids, increases the content of intracellular adenosine triphosphate (ATP), enhances the contractile function of cardiomyocytes, and improves the state of cellular ischemia and hypoxia. Previous studies have shown that TMZ is closely related to the activation and induction of apoptosis of the MAPK pathway and AMPK pathway, and plays a role in the treatment of diabetic cardiomyopathy, but the specific mechanism is still unclear., Objective: This study aims to investigate the impact of TMZ on myocardial damage in mice exhibiting diabetic cardiomyopathy (DCM), and to furnish a laboratory foundation for the clinical treatment of diabetic cardiomyopathy., Method: Male db/db mice (6 weeks old, n = 21) and male wild-type (wt) (6 weeks old, n = 20) mice were selected for the study. The wt mice were randomly assigned to the wt group (n = 10) and wt + TMZ group (n = 10), while the remaining db/db mice were randomly allocated to the db/db group (n = 11) and db/db + TMZ group (n = 10). Following 8 weeks of feeding, the wt + TMZ group and db/db + TMZ group received TMZ via gavage, whereas the remaining groups were administered physiological saline. Periodic measurements of blood glucose, blood lipids, and myocardial enzymes were conducted in mice, with samples obtained after the 12th week for subsequent biochemical analysis, myocardial pathology assessment, immunohistochemistry, western blot analysis, and TUNEL staining (TdT-mediated dUTP Nick-End Labeling)., Result: GLU, TC, TG, LDL-C, and CK-MB levels were significantly higher in db/db mice compared to wt mice (GLU: M ± SD wt 5.94 ± 0.37, db/db 17.63 ± 0.89, p < 0.05, ES = 0.991; TC: M ± SD wt 3.01 ± 0.32, db/db 6.97 ± 0.36, p < 0.05, ES = 0.972; TG: M ± SD wt 0.58 ± 0.2, db/db 1.75 ± 0.14, p < 0.05, ES = 0.920; LDL-C: M ± SD wt 1.59 ± 0.12, db/db 3.87 ± 0.14, p < 0.05, ES = 0.989; CK-MB: M ± SD wt 0.12 ± 0.01, db/db 0.31 ± 0.04, p < 0.05, ES = 0.928). HDL-C levels were significantly lower in db/db mice (M ± SD wt 1.89 ± 0.08, db/db 0.64 ± 0.09, p < 0.05, ES = 0.963). Histopathological analysis confirmed myocardial damage in db/db mice. Treatment with TMZ reduced GLU, TC, TG, LDL-C, and CK-MB levels (p < 0.05, ES > 0.9) and increased HDL-C levels compared to untreated db/db mice. Additionally, TMZ treatment significantly decreased myocardial cell apoptosis (p < 0.05, ES = 0.980). These results demonstrate the efficacy of TMZ in reversing myocardial injury in DCM mice., Conclusion: TMZ can mitigate myocardial damage in db/db mice by downregulating the expression of caspase-12, a protein associated with the endoplasmic reticulum stress (ERS) cell apoptosis pathway, consequently diminishing cell apoptosis. This underscores the protective efficacy of TMZ against myocardial damage in mice afflicted with DCM., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes., Research Design and Methods: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA 1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately., Results: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group., Conclusions: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types., Competing Interests: Declaration of competing interest No disclosures., (Copyright © 2024. Published by Elsevier Inc.)

Aim: This study aimed to investigate the association between changes in body composition, glycated hemoglobin, and lipid ratio during the treatment of patients with type 2 diabetes mellitus (T2DM)., Methods: This retrospective analysis used data from outpatients with T2DM who had confirmed body composition and measured laboratories at administration and after treatment. The baseline characteristics and prescribed treatment were collected. The total cholesterol/high-density lipoprotein cholesterol (HDL) ratio, low-density lipoprotein cholesterol (LDL)/HDL ratio, and triglyceride-glucose (TyG) index were also calculated., Results: A total of 207 patients (mean patient age, 62.0 ± 13.7 years; 68.1 % males) were enrolled. Fat mass index (FMI) changes correlated with the changes in the lipid ratio, whereas skeletal muscle mass index (SMI) changes inversely correlated with glycated hemoglobin (HbA1c) changes. Multiple regression analysis showed that changes in LDL/HDL and TyG correlated with FMI changes (t = 2.388, p = 0.017, t = 2.022, p = 0.044). Conversely, HbA1c changes correlated with SMI changes (t = -2.552, p = 0.011)., Conclusion: In patients with T2DM, increased SMI was involved in glycemic efficacy, and FMI changes were associated with LDL/HDL and TyG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: We aimed to investigate the effect of denosumab on pedal bone health and clinical resolution in active Charcot foot (CN)., Methods: This multicentre open-label phase 2 randomised controlled trial recruited adults with diabetes mellitus and active CN within 3 months of onset. Participants were randomised to standard care alone, or with denosumab 60 mg subcutaneously. Denosumab was administered at baseline and again at 6 months, unless foot temperature had normalised (i.e. <2 °C compared to contralateral foot). Co-primary outcomes were change in calcaneal Stiffness Index and foot temperature normalisation over 18 months., Results: Twelve participants per group were analysed; mean age 58 ± 11 years, 83 % male and 92 % had type 2 diabetes. Active CN duration was median 8 (IQR 7-12) weeks. Ninety-two percent were Eichenholtz stage 1 and 96 % involved the midfoot. After 1-month, median decline in Stiffness Index was less in the denosumab verses standard care group (0.5 [IQR -1.0 to 3.9] vs -2.8 [-8.5 to -1.0], p = 0.008). At 18-months, 92 % of the denosumab group attained foot temperature normalisation versus 67 % of the standard care group (p = 0.13)., Conclusions: Denosumab ameliorated the early decline in calcaneal Stiffness Index associated with active CN. However, no difference in normalisation of foot temperature was observed., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The complications of type 2 diabetes are a major global public health problem with high incidence and mortality, affecting almost all individuals with diabetes worldwide. Diabetic kidney disease (DKD) is one such primary complication and has become a leading cause of end-stage renal disease in patients with diabetes. Progression from diabetes to DKD is a complex process typically involving multiple mechanisms. Recent remarkable clinical benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in diabetes and DKD highlight the critical impact of renal ion homeostasis on disease progression. This review comprehensively examines the impact of ion homeostasis on the transition from diabetes to DKD, outlining possible therapeutic interventions and addressing the ongoing challenges in this rapidly developing field., Competing Interests: Declaration of interests There are no interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To analyze the systemic and ocular outcomes in patients with young-onset type 2 diabetes (YO-DM2) based on grade of presenting diabetic retinopathy (DR)., Methods: Retrospective cohort study analysis of empaneled patients with type 2 diabetes <40 years old with retinopathy screening within the Los Angeles Department of Health Services between 01/01/2017-07/01/2021 were included. Patients were stratified based on presenting severity of DR determined on fundus photographs or clinical examination. Patient's systemic co-morbidities and ocular outcomes were then compared across each group. Procedural (e.g. intravitreal injections) and surgical interventions (e.g. pars plana vitrectomy) were documented as performed by the treating physician., Results: 2795 patients were screened from 12,456 patients diagnosed with diabetes younger than age 40 (22.4 %). Of these, 1496 patients were diagnosed with type 2 DM. 1084 (72.4 %) of patients presented without DR, 307 (20.5 %) presented with non-proliferative diabetic retinopathy (NPDR), and 105 (7.0 %) of patients presented with proliferative diabetic retinopathy (PDR). Increasing presenting diabetic retinopathy severity was associated with longer duration of diabetes, greater systemic comorbidities (e.g. diabetic foot disease, neuropathy, chronic kidney or end stage renal disease), worse baseline and final visual acuity, and required more procedural and surgical interventions., Conclusions: Worse presenting DR severity in patients young-onset type 2 diabetes was associated with greater comorbid systemic and ocular disease with worse visual acuity outcomes. <1 % of patients without diabetic retinopathy or with mild NPDR were likely to progress to PDR. Diabetic kidney disease was an independent risk factor for developing neovascular glaucoma and retinal detachments. Prompt evaluation and intervention in patients with YO-DM2 may help reduce the associated systemic and ocular morbidity., Competing Interests: Declaration of competing interest Pradeep Prasad has the following financial disclosures: Abbvie: C; Alimera Sciences, Inc.: C; DORC International, bv/Dutch Ophthalmic, USA: L; OD-OS GmbH: L; Regeneron Pharmaceuticals, Inc.: L. C=Consultant, L=Speaker/Lecturer. The other authors have no financial disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate the effect of treatment with semaglutide and empagliflozin on the cortico-medullary sodium gradient (MCR; medulla/cortex ratio), urine sodium/creatinine ratio (UNACR), and estimated plasma volume (ePV) and to compare the MCR between persons with and without type 2 diabetes., Methods: Using the 23 Na magnetic resonance imaging ( 23 Na-MRI) technique, we investigated the effects of 32 weeks of treatment with semaglutide, empagliflozin or their combination on MCR in 65 participants with type 2 diabetes and high risk of cardiovascular disease. The participants were recruited from a randomized, controlled interventional trial and further characterized by UNACR and ePV. In addition, in a cross-sectional design, we compared MCR by 23 Na-MRI in 12 persons with type 2 diabetes and 17 matched controls. Data from the interventional trial were analyzed using a single, multivariate linear mixed model strategy for repeated measurements. Data from the cross-sectional study were analyzed by fitting a linear regression model adjusted for age and sex., Results: Compared to placebo, semaglutide, but not empagliflozin, significantly decreased the MCR (-9 %, 95%CI (-18, -0.06)%, p = 0.035 and -0.05 %, 95%CI(-0.15, 0.05)%, p = 0.319, respectively). The UNACR decreased in the semaglutide group(-35 %, 95 % CI(-52, -14) %, p = 0.003) but not in the empagliflozin group (7 %, 95 % CI(-21, 44)%, p = 0.657), whereas the ePV decreased in the combination group. The MCR was not different between persons with and without type 2 diabetes., Conclusion: 23 Na magnetic resonance imaging can identify drug induced changes in the MCR in persons with type 2 diabetes, and 32 weeks of semaglutide decreases the MCR in such persons. There is no difference in the MCR between persons with and without type 2 diabetes., Trial Number and Registry: EUDRACT 2019-000781-38, clinicaltrialsregister.eu., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine burden and identify correlates of erectile dysfunction (ED) among men with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS)., Research Design and Methods: The 2017 DPPOS visit included administration of the International Index of Erectile Function. Of 648 male participants, 88 % (n = 568) completed the survey. Associations between sociodemographic, behavioral, clinical, and glycemic measures at time of ED assessment, and ED were examined using multivariable logistic regression models in men with PreD and T2D separately., Results: Overall, 218 (38 %) men met ED criteria. Prevalence was similar in men with PreD (41 %) and T2D (37 %) (p = 0.4). In all men, age (p < 0.001) increased odds of ED. Among men with PreD, those assigned to intensive lifestyle intervention (ILS), but not metformin, had decreased odds of ED compared with the placebo group (OR = 0.35, 95 % CI = 0.13, 0.94). Non-Hispanic White race was associated with increased odds of ED compared with other races (OR = 4.3; 95 % CI = 1.92, 9.65). Among men with T2D, ED risk did not differ by DPP treatment assignment; however, individuals with metabolic syndrome defined by National Cholesterol Education Program criteria, had increased odds of ED (OR = 1.85, 95 % CI = 1.14, 3.01), as did individuals with depression (OR = 2.05; 95 % CI = 1.10, 3.79)., Conclusions: ED is prevalent in men with PreD and T2D. Our finding of reduced odds of ED in men randomized to ILS and with PreD suggests a potential opportunity for risk mitigation in the prediabetes interval. In men who have progressed to T2D, metabolic factors appear to be associated with ED., Competing Interests: Declaration of competing interest No conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: To evaluate the long-term effects of behavioral treatments on glycemic and psychological outcomes for patients with major depressive disorder (MDD) and type 2 diabetes (T2D)., Methods: Program ACTIVE II was a multicenter randomized controlled comparative effectiveness trial of cognitive behavioral therapy (CBT), exercise (EXER), combination treatment (CBT + EXER) and usual care (UC) for adults with MDD and T2D., Results: Primary outcomes: change in A1c and depressive symptoms at 6- (N = 87) and 12-months (N = 75) from baseline. In those with a baseline A1c ≥7.0 %, CBT + EXER showed lasting A1c benefit at 6- (-1.2 %; SE: 0.6; p = 0.032) and 12-months (-1.4 %; SE: 0.6; p = 0.025) compared to UC. All groups had clinically significant improvements in depressive symptoms. At 6 months, CBT + EXER had significant improvements in diabetes-related distress regimen burden (p = 0.005); and social support (CIRS, p = 0.043) compared to UC., Conclusions: The Program ACTIVE II CBT + EXER intervention demonstrated a sustained improvement in A1c for a subgroup of study participants with a baseline A1c ≥7.0 %. However, this finding should be considered preliminary because of small sample size. All 3 behavioral intervention groups demonstrated improvements in psychosocial outcomes one-year post-intervention. These findings point to the enduring benefits of community-based interventions to extend the availability of depression treatment for T2D patients., Competing Interests: Declaration of competing interest Program ACTIVE II was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R18DK092765 & R34DK071545). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The following conflicts of interest apply to the co-authors: Dr. Mary de Groot is a faculty consultant to Mediflix, Inc. Dr. Kieren Mather is an employee of Eli Lilly, Inc. No artificial intelligence was used in the creation or revision of this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim of this study is to evaluate any differences in VWF antigen, VWF activity and ADAMTS-13 activity before and after successful and non-successful Percutaneous Transluminal Angioplasty (PTA) in subjects with type 2 diabetes (T2DM) complicated by Chronic limb-threatening ischemia (CLTI) in diabetic foot vasculopathy., Methods: In this prospective observational pilot study, we enrolled 35 T2DM subjects who underwent lower limb PTA. Transcutaneous oximetry was performed in all patients before and 6 weeks after PTA. The change in oxygen partial pressure (TcpO2) before and after PTA was expressed as TcpO2-delta (ΔTcpO2). VWF antigen, VWF activity and ADAMTS-13 activity were measured before and 6 weeks after PTA; changes were expressed as delta and ratio from baseline., Results: Subjects with ∆TcpO2 < 15 mmHg presented higher ΔVWF activity (p = 0.050) and lower ADAMTS-13 activity ratio (p = 0.080). Subjects with ∆TcpO2 < 30 mmHg showed lower ADAMTS-13 activity Δ and ratio (p = 0.028)., Conclusions: VWF antigen levels and VWF activity may potentially affect PTA outcome. Higher levels of VWF could derive from VWF release as consequence of PTA-induced mechanical endothelial damage and/or oxidative stress-induced modifications of VWF structure with impairment of VWF-ADAMTS13 interactions., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest None.

Background: Research proved the importance of dosing apolipoprotein B (ApoB) over LDL cholesterol as a predictor of cardiovascular events. In this study, we aimed to observe the input apolipoprotein A1 (ApoA1) and ApoB, primarily if its ratio could provide in patients with type 2 diabetes mellitus (T2DM) without known atherosclerotic events regarding the coronary heart disease (CHD) risk., Methods: We enrolled 83 patients with T2DM who attended the National Institute of Diabetes (Bucharest) between March 2022 and December 2022. A blood sample was taken from all patients to measure the different lipid parameters, including ApoA1 and ApoB. Spearman's correlation test for correlation between variables was used, and a multivariate regression analysis was performed to determine whether there are associations between CHD and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Values of p < 0.05 were considered significant., Results: Correlation analyses revealed that LDL-C was moderately associated with CHD (r = 0.199, p = 0.067). The non-HDL-C/HDL-C ratio exhibited a stronger, significant correlation with CHD (r = 0.366, p = 0.001). Evaluating apolipoproteins, ApoA1 levels negatively correlated with CHD (r = -0.233, p = 0.035), whereas ApoB levels showed a positive association (r = 0.292, p = 0.008). Notably, the severity of CHD risk increased with the ApoB/ApoA1 ratio (r = 0.530, p < 0.001). Similar trends in correlation coefficients were observed for fatal CHD and ASCVD, albeit with varied significance levels., Conclusions: Among patients with T2DM, the ApoB/ApoA1 ratio exhibited the strongest correlation with CHD risk, surpassing traditional LDL-C and even the non-HDL-C/HDL-C ratio, suggesting its potential utility as a more reliable marker for cardiovascular risk assessment in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To evaluate associations between 24-h ambulatory blood pressure monitor (ABPM) data vs. single casual blood pressure (BP) and albuminuria in youth with type 2 diabetes., Methods: A cross-sectional analysis of youth with type 2 diabetes 10-<18 yrs. from the iCARE cohort., Main Exposures: daytime HTN (+/- nocturnal), isolated nocturnal HTN and single casual BP., Main Outcome: non-orthostatic urine albumin: creatinine ratio (ACR) ≥ 3 mg/mmol and log-transformed urine ACR. Regressions evaluated associations between 1. HTN status based on ABPM and log-transformed urine ACR (continuous) and 2. ABPM-derived BP z-scores and casual BPcentiles and albuminuria status (categorical)., Results: Of 281 youth included, 19.6 % had daytime HTN (+/- nocturnal), and 28.5 % isolated nocturnal HTN on 24-h ABPM. In multivariate linear regression, HTN (ABPM) (ß = 0.553; p = 0.001), duration of diabetes (ß = 0.857; p = 0.02), HbA1c (ß = 1.172; p ≤0.0001) and ACEI/ARB use (ß = 3.94; p < 0.0001) were positively associated with log-transformed ACR; (R 2  = 0.184). In logistic regression analysis, all ABPM LMS z-scores were positively associated with albuminuria; casual BPcentile was not significant., Conclusions: Youth with type 2 diabetes have high rates of HTN based on 24-ABPM data. ABPM-derived measures of BP are associated with albuminuria. These data support the routine use of ABPM devices to diagnose hypertension in youth with type 2 diabetes., Competing Interests: Declaration of competing interest All authors have no potential conflicts of interest to report., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Declaration of competing interest Thaer Idrees has no declaration of interest. Guillermo E Umpierrez is partly supported by research grants from National Institutes of Health (NIH/NATS UL 3UL1TR002378-05S2) from the Clinical and Translational Science Award program, and from National Institutes of Health and National Center for Research Resources (NIH/NIDDK 2P30DK111024-06). GEU has received research support (to Emory University) from Abbott, Bayer, Dexcom and Sanofi.

Aims: Several psychiatric disorders are linked with an increased risk of developing type 2 diabetes (T2D), but the mediating mechanisms are unclear. We aimed to investigate health behaviors, obesity, psychotropic medication use, and comorbidity as potential mediating mechanisms explaining these associations., Methods: We combined data from a large population-based survey with register-based data and followed a sample of 250,013 Danes (≥16 years) for up to 8.9 years. We conducted mediation analyses investigating 10 potential mediators of the associations between psychiatric disorders and incident T2D., Results: Individuals with a substance use disorder, schizophrenia, mood disorder, neurotic disorder, eating disorder, or a personality disorder had a significantly higher risk of developing T2D. Organic disorders, intellectual disabilities, developmental and behavioral disorders were not associated with T2D-risk. For all psychiatric disorders significantly associated with T2D, the use of antidepressant medication had the largest proportional mediating effect on the association (13-32 %)., Conclusions: Use of antidepressant medication had the largest contribution to the associations between psychiatric disorders and incident T2D. Future epidemiological studies and prevention studies should focus on optimizing the use of antidepressant medication with minimal side effects, and the promotion of health behaviors in individuals with a psychiatric disorder to prevent T2D., Competing Interests: Declaration of competing interest GSA own shares in Novo Nordisk A/S. All other authors declare that they have no conflict of interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to observe the correlation between the visceral fat/subcutaneous fat area ratio (VSR) and peripheral blood monocyte/high-density lipoprotein ratio (MHR) in patients with type 2 diabetes mellitus (T2DM) and albuminuria., Methods: Based on the urinary albumin/creatinine ratio (UACR), 89 T2DM patients were divided into normo-albuminuria group (n = 49, UACR <30 mg/g) and albuminuria group (n = 40, UACR ≥30 mg/g). Gender, age, body mass index (BMI), duration of T2DM, blood pressure, visceral fat area (VA), subcutaneous fat area (SA), biochemical indexes of blood serum and urinary were collected and compared between the two groups, and the relationship between VSR and MHR was analyzed in albuminuria group., Results: No significant differences existed in gender, age, BMI, duration of diabetes, blood pressure, serum lipids, and hemoglobin Alc between the two groups. The levels of VA, VSR, MHR, and UACR were higher in the albuminuria group (P < 0.05). VSR was positively correlated with MHR (r = 0.39, P < 0.01), whereas VA was not significantly correlated with MHR in the albuminuria group., Conclusion: Compared with VA, VSR was significantly correlated with MHR, suggesting that VSR is more closely related to the occurrence of chronic inflammation in type 2 diabetics with albuminuria., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)