Editor’s Choice Articles

Background: Peripheral arterial disease (PAD) is known to be strongly linked to major adverse limb events, ultimately leading to an increased risk of limb-threatening conditions. We developed a predictive model using five identified biomarkers to predict major adverse limb events, limb loss, diabetic (DM) foot ulcers, and vascular intervention in patients with underlying PAD and DM over 2 years. Methods: A single-center prospective case control study with was conducted with 2 years’ follow up. In the discovery phase the cohort was randomly split into a 70:30 ratio, and proteins with a higher mean level of expression in the DM PAD group compared to the DM non-PAD group were identified. Next, a random forest model was trained using (1) clinical characteristics, (2) a five-protein panel, and (3) clinical characteristics combined with the five-protein panel. Demographic data were analyzed by independent t-test and chi-square test. The importance of predictive features was calculated using the variable importance (gain) score. The model was used and assessed for its ability to diagnose PAD, predict limb loss, predict major adverse limb events (MALEs), predict diabetic foot ulcers, and predict the need for vascular surgery. The model was evaluated using area under the receiver operating characteristic curve and net reclassification index. Results: The cohort of 392 patients was matched for age, sex, and comorbidities. Five proteins were identified (TNFa: tumor necrosis factor alpha, BMP-10: bone morphogenic protein 10, CCL15/MIP1 delta: chemokine (c-c motif) ligand 15/macrophage inflammatory protein 1 delta, MMP-10: matrix metalloprotease 10, and HTRA2/Omi: HTRA2, also known as Omi) as having a significantly higher level of expression in the DM PAD group. HTRA/Omi had the highest contribution to the model’s ability to diagnose PAD in diabetic patients. Model performance was best when combined with clinical characteristics to predict limb loss (AUROC 0.86, 0.76, 0.80), foot ulcer (AUROC 0.87, 0.82, 0.67), MALE (AUROC 0.81, 0.78, 0.67), and the need for vascular surgery (AUROC 0.82, 0.81, 0.61). Conclusions: In this study, we describe a biomarker panel that can be used in combination with clinical characteristics to create an accurate prediction model for diagnosis and prognostication of PAD in the setting of DM. Full article

Objectives: This study aims to explore perspectives and opinions from healthcare professionals and people at risk of type 2 diabetes mellitus (T2DM) to inform the design of PREDIABETEXT, a new digital multifaceted intervention to prevent T2DM. Methods: in this qualitative study, we purposefully recruited 15 healthcare professionals (doctors and nurses) working in primary healthcare centers in Mallorca (Spain), and 15 of their patients at risk of T2DM (HbA1c 6–6.4%, and/or fasting plasma glucose 110–125 mg/dL). We collected the data through semi-structured phone interviews, using an interview guide aimed at gathering participants’ views about the two PREDIABETEXT proposed co-interventions (educational intervention targeted at professionals and delivered as an online training course, and behavioral intervention targeted at individuals at risk of T2DM and delivered using SMS short text messages). The interviews were audio-recorded, verbatim transcribed, and analyzed using a thematic analysis approach. Results: Primary healthcare professionals valued a prediabetes training course for standardizing care and supporting diabetes prevention. They preferred a blended format with content on early detection, intervention, and monitoring. They perceived SMS reminders to their patients as potentially useful for reinforcing guidelines and improving care. Individuals at risk of T2DM, who faced challenges maintaining a healthy diet and exercise routine, viewed SMS as potentially motivational and informative, offering suggestions on content, format, and frequency to enhance its intended benefits. Conclusions: This qualitative study provided valuable insights from primary care professionals and people at risk of T2DM that will inform the user-centered design of the PREDIABETEXT intervention. Full article

Introduction: The most frequent local complication of insulin injection is the occurrence of subcutaneous nodules due to incorrect injection technique. Injection into nodules negatively impacts metabolic compensation and the requirement for greater insulin doses due to its partial and erratic absorption. Despite these concepts being accepted by the scientific community, it is not yet clear whether injection into nodules is causally related to worsening chronic diabetes (DM) complications and the morphological nature of such nodules. Aim: This multicenter study aimed to evaluate the associations between structural characteristics of skin nodules and chronic DM complications. A secondary endpoint was to evaluate the histological structure of those nodules, looking for differences between lipohypertrophies (LH) and amyloid nodules (LIDA). Methods: For this purpose, 816 DM patients with LH and 1033 without LH underwent a clinical and ultrasound study comparing metabolic data, injection habits, and frequency of complications. Excisional biopsies of the skin nodules were performed in a small series of eight subjects. Results: Data observed confirm a strong relationship between LH and diabetes chronic complications other than poor glycemic control. Histology of biopsies from the skin nodules showed mild foreign-body-like inflammation, prevailing mega-adipocytes (65%), apoptosis, and fibrosis but could not detect any amyloid fibrils. In four cases, intra-nodular fluid was present with an insulin concentration several times higher than in blood. Conclusions: We confirmed LHs to be significantly associated with insulin administration errors, duration of insulin therapy, greater daily doses and duration of insulin administration, and the presence of micro- and macro-vascular DM complications. LH nodules displayed no typical morphological features and were indistinguishable from LIDA nodules with which they shared several histologic similarities, albeit within the frame of a general picture of LIDA inhomogeneity. Further targeted studies are warranted to clarify the remaining doubts. Full article

Obesity and type 2 diabetes represent global public health challenges that are continuously growing at an alarming rate. The etiology of obesity is complex and multifactorial, with a substantial interplay between behavioral, biological, and environmental factors. Dysregulation of immunometabolism through chronic low-intensity inflammation in obesity has long been recognized as the main driver of insulin resistance and the development of type 2 diabetes. However, the intricate mechanisms underlying these alterations have yet to be fully elucidated. Exosomes are extracellular vesicles that carry biomolecules including various types of RNA molecules. Of particular importance are microRNAs (miRNAs), known as modulators of gene expression whose altered expression is observed in various pathophysiological conditions. Recent research suggests that exosome-derived miRNAs, such as miR-155, miR-27a, and miR-29, play an essential role in the regulation of inflammatory processes, while miR-122 and miR-192 are associated with metabolic dysfunction. These and many other miRNAs influence signaling pathways that are critical for maintaining insulin sensitivity, thereby contributing to the development of insulin resistance in individuals with obesity. Hence, there is a growing interest in the potential of exosomes and miRNAs as biomarkers for the early detection of insulin resistance and other obesity-related complications, as well as promising therapeutic targets or next-generation drug delivery carriers. This review provides a comprehensive overview of the interplay between exosome-derived miRNA, obesity, and type 2 diabetes and summarizes the latest findings in exosome biology. Full article

Background/Objectives: The National Diabetes Prevention Program (National DPP) assists individuals with lifestyle change for type 2 diabetes risk reduction through education, skills, and support. To further understand program effectiveness, implementation research needs to consider influences on retention, effectiveness, and sustainability of the program in rural settings. The purpose of this study was to understand National DPP implementation in two rural workplace settings as well as the factors that influence program participation and outcomes. Methods: Individuals who met criteria for being at risk for developing type 2 diabetes participated in two National DPPs. The first program (Technology-Augmented DPP) occurred in 2016 with the goal of understanding the role of psychosocial factors in relation to National DPP outcomes, and quantitative data were obtained from 47 participants. Variables of interest included the Lifestyle-Health-Related Self-Concept questionnaire (HRSC), weight, and physical activity. The second program (Hybrid-Format DPP) occurred in 2022 with the goal of understanding individual participant experiences within the program by conducting a reflexive thematic analysis on data obtained during a semi-structured group interview with 3 participants. Results: In the Technology-Augmented DPP, Lifestyle-HRSC dimensions of nutrition, social support, avoiding diabetes, and problem solving were associated with weight, steps per day, and activity minutes. In the Hybrid-Format DPP, the generated themes included Frequency Matters, Rules of Engagement, Promoting Self-Efficacy, and Bridging the Intention-Behavior Gap. Conclusions: Based on this study, a focus on understanding and responding to context-specific and participant-focused National DPP implementation is the essential next step in National DPP research. Prevention programs and policies individualized to people and communities will improve participation and outcomes. The National DPP should consider how to evolve to the changing needs of at-risk individuals in rural and underserved areas. Full article

Background: Surrogate indexes of insulin resistance (IR) are less expensive than the euglycemic glucose clamp. The simultaneous impact of sex and gender, smoking, and combined oral contraceptives (COC) on IR surrogate indexes was studied in a cohort of healthy young men and women (stratified in COC-free women and COC users). Methods: Glycemia, insulin, C-peptide, TG, and HDL were measured in serum samples and used to calculate IGR, HOMA-IR-IR, QUICKI, FIRI, METS-IR, TG, and MCAi. Results: Men had higher BMI, glycemia, TG, METS-IR, TyG, and lower HDL than COC-free women and they had lower IGR and higher METS-IR and MCAi than COC users. TG, HDL, and TyG were lower and MCAi is higher in COC-free women than in COC users. In non-smokers, men had higher BMI and METS-IR and lower HDL than both cohorts of women. COC-free women showed a lower TyG index than men and COC women and lower TG, HDL, and IGR. MCAi was higher in COC-free women than in COC users. Smoking reduced sex and gender differences: HDL was lower in men than COC users and IGR was lower in men than COC-free women. Intra-sex differences were reported only in COC-free women: smokers had higher insulin, C-peptide, TG, and IGR and lower MCAi than non-smokers. Cluster analysis evidenced a significant separation between the sexes and smokers and non-smokers. Conclusions: Smoking leads to changes in the phenotype of both men and women, as well as COC in women; they should be considered independent variables in clinical studies given, representing a fundamental cornerstone in the personalization of prevention and care. Full article

Background: The Beat It program is a clinician-led, community-based group exercise intervention for adults with Type 2 Diabetes Mellitus (T2DM). While previous studies have demonstrated its effectiveness in improving physical and mental health outcomes, this study explores the perspectives of Beat It Trainers to identify key factors contributing to the program’s success and areas for improvement. Methods: Semi-structured interviews were conducted with 11 Accredited Exercise Physiologists who had delivered both in-person and online versions of the program. Interviews were thematically analyzed using inductive approaches. Results: Eight main themes emerged: customization to individual needs, capability building, outcome improvement, affordability, accessibility, sustainability, and a holistic approach delivered in a group setting. Challenges identified included managing group dynamics, maintaining participant commitment in a fully subsidized program, and providing nutrition advice within the trainers’ scope of practice. The program’s adaptability to both in-person and online delivery modes was highlighted as enhancing its accessibility and resilience. Conclusions: This study provides valuable insights into the factors contributing to the success of the Beat It program from the implementers’ perspective. The findings suggest that investing in comprehensive training for facilitators, particularly in group dynamics management, could benefit similar programs. While the program’s fully subsidized structure reduces financial barriers to entry, innovative strategies to enhance participant engagement and perceived value should be explored. The success of the online delivery mode indicates that hybrid models offering both in-person and virtual options could increase accessibility in future supervised, community-based exercise programs for T2DM management. Full article

Background: In the emergency department (ED), hyperglycemia may be overlooked due to non-diabetes mellitus (DM) primary diagnoses. We compared the risk of all-cause hospital revisits within 30 days after ED discharge in DM patients with normal blood glucose (BG), moderate hyperglycemia, and severe hyperglycemia. Methods: This was a retrospective cohort study of patients 18 years and older discharged from a tertiary care ED between 1 January and 31 March 2018. The severe hyperglycemia group had BG levels of 300 mg/dL (16.7 mmol/L) or greater. The moderate hyperglycemia group had a history of DM, all BG levels less than 300 mg/dL (16.7 mmol/L), and at least one BG level of 180 mg/dL (10 mmol/L) or greater. The normal BG group had a history of DM and BG less than 180 mg/dL (10 mmol/L). Results: Of 302 patients who met criteria, 118 had severe hyperglycemia, 67 had moderate hyperglycemia, and 117 had normal BG. No significant difference between the severe hyperglycemia, moderate hyperglycemia, and normal BG groups was found in 30-day all-cause hospital revisits (19.5% vs. 10.4% vs. 15.4%, respectively, p = 0.25). Patients with a past medical history (PMH) of atherosclerotic cardiovascular disease (ASCVD) or any ED visit in the year preceding the index visit each had an increased risk of a hospital revisit within 30 days (p = 0.025) after covariate adjustment; the adjusted risk of a 30-day hospital revisit among those with a PMH of ASCVD was 2.68 times greater than the risk among those without a history of ASCVD (95% CI: 1.59 to 4.53), and the adjusted RR of a 30-day revisit among those who had an ED visit in the prior year was 1.92 times greater than those without an ED visit in the prior year (95% CI: 1.10 to 3.35). Conclusions: The results suggest no significant association between hyperglycemia in the ED and 30-day hospital revisits. In any patient with DM with a history of ASCVD or any ED visit in the previous year, there may be an increased risk of revisits. Full article

Background: Effective self-management is crucial in diabetes care. This study investigates the impact of Personal Health Records (PHR) on diabetes management and person self-management behaviors. Methods: Retrospective cohort study was conducted involving individuals with diabetes using insulin and prescribed FreeStyle Libre^®. Participants were categorized into PHR users and non-users. Key metrics such as HbA1c, Time in Range (TIR), Time above Range (TAR), and body weight were analyzed. Results: Among 212 intermittently scanned continuous glucose monitoring (isCGM) users, 25 individuals used PHR. Comparing 21 individuals using a PHR with 42 matched controls, the TIR significantly increased (ΔTIR 17.2% vs. 1.90%, p = 0.020), and HbA1c levels showed a greater decrease (ΔHbA1c −0.83% vs. −0.22%, p = 0.023). A significant reduction was also observed in TAR among PHR users (ΔTAR −17.6% vs. −1.63%, p = 0.017). There were no significant changes in body weight (ΔBW −0.51 kg vs. −1.60 kg, p = 0.578). Conclusions: PHR systems demonstrate potential in improving diabetes management by enhancing self-management practices and glycemic control. Although the sample size of PHR users was relatively low, PHR should be more widely used. The study underscores the need for further research on PHR’s long-term impact and its applicability in diverse diabetic populations. Full article

Background: Handheld cameras may increase access to teleretinal diabetic retinopathy screenings (TDRS), as they are more economical and nimbler than traditional desktop cameras. However, their use in safety net clinical settings is less understood. Methods: The Los Angeles County Department of Public Health collaborated with the Los Angeles County Department of Health Services (DHS) to pilot the use of handheld cameras in DHS’s TDRS program. This study assessed screening metrics and interviewed TDRS coordinators and photographers about their experiences using these cameras. Results: Handheld cameras were harder to operate and performed less optimally on key screening metrics (e.g., image quality) compared to desktop cameras. However, this challenge appeared to be linked to the selected model rather than to all handheld cameras. The adoption of handheld cameras in DHS was aided by their integration into an existing agency infrastructure that already supported the use of desktop cameras; these operational supports included an established workflow, a data platform, and experienced photographers. Conclusions: The use of handheld cameras for TDRS is a promising practice for assuring equitable access to screenings. Handheld cameras are portable, smaller in size, and lower in cost than desktop cameras. Future projects should invest in and assess the performance of higher-quality models of these cameras, especially their use in safety net clinical settings. Full article

Background: Studies of pharmacists’ clinical programs have demonstrated improvements in controlling chronic diseases. However, significantly less data are available regarding pharmacist impact in a value-based Patient-Centered Medical Home (PCMH). The present study assessed a population health initiative to incorporate pharmacists for the management of type 2 diabetes (T2D), hypertension, and hyperlipidemia in a PCMH. Methods: This was a single-center retrospective cohort study of patients with T2D and baseline glycated hemoglobin (HbA1c) greater than 9%. Patients were excluded if they received care from an endocrinology provider or were lost to follow-up during the observation window of 1 January 2023 through 31 July 2023. Patients were analyzed in two cohorts: (1) patients who received any outpatient care from a clinical pharmacist (pharmacist cohort) and (2) patients who did not receive any outpatient care from a clinical pharmacist (usual care cohort). The primary outcome was the proportion of patients achieving an HbA1c of less than 8%. Secondary outcomes included blood pressure control and receipt of guideline-directed statin therapy. Results: Ninety-one patients were identified, twenty-nine in the pharmacist cohort and sixty-two in the usual care cohort. The overall population was older (mean age ~66 years), 59% female, and racially diverse (<50% Caucasian). HbA1c less than 8% was achieved in 34% of patients in the pharmacist cohort and 29% of patients in the usual care cohort (p = 0.001). A blood pressure goal of less than 140/90 mmHg was achieved more frequently in the pharmacist cohort (90% vs. 61%, p = 0.006), but guideline-directed statin therapy was similar between groups (90% vs. 79%, p = 0.215). Conclusions: Pharmacists can play an integral role within a PCMH to improve value-based measures for HbA1c and blood pressure control. Further research is needed to assess the impact of pharmacist care on statin use and economic outcomes. Full article

Background/Objectives: Individuals with diabetes often experience discrimination and barriers at work and are confronted with the challenge of deciding whether to disclose their health status in their workplace. This study explores the disclosure of diabetes in the workplace. The research was based on a previously developed questionnaire. Methods: Two hundred and five persons with diabetes who were employed in Greece participated in the research. Results: The majority of the participants chose to disclose. Demographic characteristics influenced their disclosure decision, with the diabetes type and the employment sector showing a more significant impact. The majority of the participants showed a strong preference for early disclosure. Conclusions: The main reasons for disclosure were the belief that there was no reason to conceal it and the need to know in an emergency. In contrast, the main reasons for concealment were the fear of being fired or not being hired, the belief that disclosure was unnecessary, and concerns about being treated differently. The present research brings to light the reality of employed people with diabetes in Greece. Future research could focus on a deeper understanding of the disclosure issues of people with diabetes and other non-visible disabilities. Full article

Aims: The accurate prediction of blood glucose (BG) levels is critical for managing Type-1 Diabetes (T1D) in pediatric patients, where variability due to factors like physical activity and developmental changes presents significant challenges. Methods: This work explores the application of foundational models, particularly the encoder–decoder model TimeGPT, for BG forecasting in T1D pediatric patients. Methods: The performance of TimeGPT is compared against state-of-the-art models, including ARIMAX and LSTM, and multilayer perceptron (MLP) architectures such as TiDE and TSMixer. The models were evaluated using continuous glucose monitoring (CGM) data and exogenous variables, such as insulin intake. Results: TimeGPT outperforms or achieves comparable accuracy to the state of the art and MLP models in short-term predictions (15 and 30 min), with most predictions falling within the clinically safe zones of the Clarke Error Grid. Conclusions: The findings suggest that foundational models like TimeGPT offer promising generalization capabilities for medical applications and can serve as valuable tools to enhance diabetes management in pediatric T1D patients. Full article

Aims: This study aims to assess the perspective of doctors and nurses regarding the clinical settings and barriers to implementing opportunistic diabetic retinopathy screening with handheld fundus cameras. Design: This study was a cross-sectional, online questionnaire study. Methods: An online survey was distributed to doctors and nurses working in Portuguese primary care units and hospitals between October and November 2021. The survey assessed current fundus observation practices, potential contexts, and barriers to using handheld fundus cameras. Results: We received 299 eligible responses. About 87% of respondents (n = 255) believe in the clinical utility of handheld fundus cameras to increase patients’ access to diabetes-related retinopathy screening, and 74% (n = 218) attribute utility to identify other eye or systemic diseases. More than a third of participants (37%, n = 111) envisioned using such devices multiple times per week. The main potential barriers identified included limited time (n = 90), equipment cost (n = 48), or the lack of skills in retinal image acquisition (n = 47). Most respondents (94%, n = 275) expected a follow-up recommendation to accompany the telemedicine diagnosis. Conclusions: Doctors and nurses support the use of handheld fundus cameras. However, to optimize their implementation, some strategies should be considered, including training, telemedicine-based diagnosis, and support for follow-up through accessible, user-friendly, and efficient information systems. Full article

Introduction: Limited studies have explored the impact of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators on glucose tolerance and insulin secretion in patients with CF, yielding varied results. This study aims to assess alterations in glucose metabolism and insulin secretion over 24 and 52 weeks following CFTR modulator initiation in a cohort of pediatric and adult patients with CF. Materials and Methods: A prospective longitudinal study conducting oral glucose tolerance test (OGTT) with C-peptide and insulin levels. The insulin secretion rate at 60 min (ISR60) and the insulinogenic index (IGI) were calculated during the first 60 and 30 min of the OGTT, respectively. Glucose metabolism status was categorized as normal (NGT), indeterminate (INDET), impaired glucose tolerance (IGT), or cystic fibrosis-related diabetes (CFRD). Additionally, continuous glucose monitoring (CGM) was performed for 14 days at each visit. We employed a repeated-measures general linear model to assess changes in insulin secretion and CGM metrics, with glucose tolerance status as the between-subjects factor and visit (baseline, 24 and 52 weeks) as the within-subjects factor. Results: The study comprised 25 patients (11 adults and 14 pediatrics). At baseline, 2 patients (8%) had NGT, 8 (32%) had INDET, 10 (40%) had IGT, and 5 (20%) had CFRD. Overall, there were no significant changes in insulin and C-peptide area under the curve (AUC), IGI and DI after 52 weeks. However, we observed an increase in ISR60 among NGT patients (mean change: 1.766; 95% CI: 1.414; 2.118, p < 0.001). Consistently, average glucose exhibited a significant decrease in NGT patients between 24 and 52 weeks (mean change: −5.645; 95% CI: −4.233; −10.866, p = 0.028). Conclusions: Treatment with CFTR modulators potentially enhances insulin secretion in patients with CF NGT. Early initiation of treatment, as evaluated through long-term prospective trials, is essential to further investigate whether decreased glucose control is preventable or reversible. Full article

This study investigates glucose conditions preceding and following various hypoglycemia levels in individuals with type 1 diabetes using open-source automated insulin delivery (AID) systems. It also seeks to evaluate relationships between hypoglycemia and subsequent glycemic variability. Methods: Analysis of continuous glucose monitor (CGM) data from 122 adults with type 1 diabetes using open-source AID from the OpenAPS Data Commons was conducted. This study comprehensively analyzed the effects of hypoglycemia on glycemic variability, covering time periods before and after hypoglycemia. Results: Glucose variability normalization post-hypoglycemia can take up to 48 h, with severe hypoglycemia (41–50 mg/dL) linked to prolonged normalization. A cyclical pattern was observed where hypoglycemia predisposes individuals to further hypoglycemia, even with AID system use. A rise in glucose levels often precedes hypoglycemia, followed by an elevated mean time above range (TAR) post-hypoglycemia, indicating a ‘rebound’ effect. The experimental results are further validated on T1DEXI data (n = 222), originating from commercial AID systems. Different hypoglycemia categorization approaches did not show significant differences in glycemic variability outcomes. The level of hypoglycemia does influence the pattern of subsequent glucose fluctuations. Conclusion: Hypoglycemia, especially at lower levels, significantly impacts subsequent glycemic variability, even with the use of open-source AID systems. This should be studied further with a broader set of commercial AID systems to understand if these patterns are true of all types of AID systems. If these patterns occur in all types of AID systems, it underscores potential opportunities for enhancements in AID algorithms and highlights the importance of educating healthcare providers and people with diabetes about post-hypoglycemia glucose variability. Full article

Objectives: This uncontrolled open study aimed to measure the levels of self-care of patients before and after education, their initial knowledge, and their knowledge two months after interacting with healthcare providers using the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire. Methods: The data for this study were collected over 14 months from 396 patients with diabetes. This study was conducted in three phases: initial questionnaire testing, education, and retesting after two months. The education included specific diabetes-related topics: nutrition, exercise, self-monitoring of blood glucose, foot care, and smoking. Results: The results showed that all self-care activities between the first and second assessments were different. The initial assessment showed that the more successful the general diet, the specific diet, and physical activity were, the better the hemoglobin A1c value was. When considering the impact of gender on self-care effectiveness results, it was noted that women were more successful in foot care and specific diet in the initial testing, while men excelled in physical activity. The most successful age group in the scales of general diet, physical activity, and blood glucose testing was 31–45 years. Those with type 1 diabetes (36% of the study population) were more successful in self-care in the first and second measurements but without any differences in self-care in the retesting. Conclusions: our study observed a difference in self-care results between the two measurements of self-care activities in patients with diabetes, evaluated by the SDSCA questionnaire. Full article

Objectives: This study aims to examine the association between state Medicaid coverage of podiatry services and the outcomes of beneficiaries with new diabetic foot ulcers (DFUs). Methods: Medicaid beneficiaries who developed a DFU between 2010 and 2015 were identified using the PearlDiver claims database. The states were categorized into covered states (CS) and non-covered states (NCS) based on podiatric coverage during the study period. The outcomes included major amputation, minor amputation, and hospitalization due to foot infection within 12 months of index diagnosis. Logistic regression was used to assess the association of state coverage type and outcomes, controlling for age, sex, and the Charlson Comorbidity Index (CCI). Results: Our study included 16,905 Medicaid beneficiaries who developed new DFUs: 14,748 in CS and 2157 in NCS. The overall major amputation rate was 2.6%. The risk of major amputation was 48% lower among Medicaid beneficiaries in CS (OR 0.52, 95% CI 0.31–0.90) than in NCS. The Medicaid beneficiaries in CS had a 24% lower risk of hospitalization for foot infection (OR 0.76, 95% CI 0.67–0.85) but had a 58% higher risk of minor amputation (OR 1.58, 95% CI 1.22–2.07) than in NCS. Conclusions: Medicaid coverage of podiatry services might be associated with lower rates of major amputation and reduced risk of hospitalization for foot infection. Full article

Diabetes mellitus (DM) is a common non-communicable and chronic metabolic disorder regarded as a global epidemic with high morbidity and mortality. Although, conventional medicines are available for the management of DM, Indigenous knowledge, including the use of botanicals, has contributed to the management of this life-threatening disease in Africa. This is due to the perceived effectiveness and minimal side effects associated with plants and plant-derived compounds as an affordable remedy against DM. This review focuses on the contribution of Indigenous African plants to the management of DM. Relevant literatures were reviewed from online scientific databases, such as PubMed, ScienceDirect, and Google Scholar, using keywords singly and in combination. The review revealed that Indigenous health practitioners use several medicinal plants in the management of DM, with a range of 14–255 botanicals recorded. Approximately 80 compounds with antidiabetic potency have been isolated from different parts of African medicinal plants, with the majority belonging to flavonoids and terpenoids. Particularly, compounds such as apigenin, combretin B, convallatoxin, kaempferol, and quercetin remain the most promising antidiabetic compounds isolated from African medicinal plants. Limited clinical trials have been conducted on these compounds despite these milestones. There is, therefore, the need for further investigations to explain their antidiabetic effects, particularly under clinical conditions. Plants from which these compounds were isolated were selected based on ethnopharmacological knowledge. With these developments, medicinal plants and Indigenous knowledge remain an integral part of the global strategy to combat DM. Full article

Postprandial hyperglycemia was shown to be an independent risk factor for microvascular and macrovascular complications in type 2 diabetes mellitus (T2D). We aimed to investigate the glucose, insulin, and subjective appetite at 0, 15, 30, 45, 60, 90, 120, 150, and 180 min of three treatments: diabetes-specific formula (DSF), noodle soup, and glutinous rice. This was a randomized, crossover study with a one-week interval between treatments. Sixty-four T2D adults with oral glucose-lowering medication and HbA1c between 7% and <10% were randomized. The glucose positive area under the curve from 0 to 180 min (pAUC) was significantly lower with DSF than with glutinous rice (LSM ± SE: DSF 354 ± 32 vs. glutinous rice 451 ± 32 mmol.min/L, p = 0.033). The insulin pAUC was significantly lower with DSF (median [IQR]: 2733 [1542, 4204]) compared to glutinous rice (3359 [2193, 4744] µIU.min/mL), p = 0.042). The insulinogenic index at 30 min was significantly higher in DSF (median [IQR], 8.1 [4.2, 19.7]) compared to glutinous rice (5.4 [2.7, 11.7], p < 0.001). No significant differences were found in subjective appetite between the three treatments (all, p ≥ 0.827). There were also no significant differences in hunger, fullness, desire to eat, and prospective consumption ratings between DSF and the other two breakfasts (all p ≥ 0.181). Noodle soup led to the shortest time for hunger to return to baseline (165 min), 21 min earlier than DSF (186 min) and 32 min earlier than glutinous rice (197 min). DSF significantly reduced postprandial glucose and insulin responses compared with glutinous rice and had a higher satiating value than noodle soup in T2D adults. Replacing common Asian breakfasts with DSF may improve glycemia and hunger control. Full article

Metabolic syndrome (MetS) presents a significant global health challenge, characterized by a cluster of metabolic alterations including obesity, hypertension, insulin resistance/dysglycemia, and atherogenic dyslipidemia. Advances in understanding and pharmacotherapy have added complexity to MetS management, particularly concerning drug interactions and pharmacogenetic variations. Limited literature exists on drug–drug–gene interactions (DDGIs) and drug–drug–transporter gene interactions (DDTGIs), which can significantly impact pharmacokinetics and pharmacodynamics, affecting treatment outcomes. This narrative review aims to address the following three key objectives: firstly, shedding a light on the PK metabolism, transport, and the pharmacogenetics (PGx) of medicines most commonly used in the MetS setting (relevant lipid-lowering drugs, antihypertensives and antihyperglycemics agents); secondly, exemplifying potential clinically relevant pharmacokinetic drug interactions, including drug–drug interactions, DDGIs, and DDTGIs; and, thirdly, describing and discussing their potential roles in clinical practice. This narrative review includes relevant information found with the use of interaction checkers, pharmacogenetic databases, clinical pharmacogenetic practice guidelines, and literature sources, guided by evidence-based medicine principles. Full article

Background: Lifestyle medicine (LM) is a contemporary scientific discipline with a multidisciplinary approach. Case Management offers a viable alternative for the care of patients with Type 2 Diabetes (T2D). This study aimed to identify the role and clinical applications of the lifestyle medicine case manager nurse (LMCMN) for T2D patients internationally and to analyze the role of specialist nurses in Italy through a narrative review. A secondary objective was to define a job description (JD) for a future Delphi method. Methods: A narrative review of the literature was conducted using PubMed/Medline, Scopus, and grey literature sources to analyze the international and Italian regulatory contexts. Subsequently, a JD for the LMCMN was developed for application in a future Delphi Study. Results: Nurses play a strategic role in managing T2D, and the LM approach has demonstrated strong evidence of effectiveness. This study developed a specific JD for the LMCMN suitable for both Italian and international contexts. Conclusions: The specific role of the LMCMN is still underdeveloped internationally. In the context of territorial assistance and chronic disease management, this professional is crucial for delivering quality care and shaping health policies that meet community needs. Full article

Mental health today includes much more than the treatment of psychiatric disorders. More and more interventions aim to bring mental health support closer to people and psychotherapeutic interventions to people with somatic conditions. Since the treatment of people with metabolic syndrome and diabetes mellitus type 2 also requires a change in lifestyle, mental health has a prominent role. This overview paper wants to offer a solution after recognizing the given patterns where psychotherapy certainly has a significant and irreplaceable role. Precisely because of this phenomenon, psychological eating patterns associated with diabetes mellitus and hence metabolic syndrome should be studied, and attempts should be made to uncover patterns in occurrence. The aim of this study is to review the literature and consider the connection among diabetes mellitus, metabolic syndrome, and psychological eating patterns such as emotional and compulsive eating, as well as through the lens of food addiction. Furthermore, we have attempted to uncover the role of psychiatry and psychotherapy in the treatment of diabetes mellitus and metabolic syndrome and delve into the complexity of recognizing these patterns and emphasize the importance of a multidisciplinary approach in the treatment of diabetes mellitus and metabolic syndrome. Full article

Objective: This study investigates the outcomes of Medicaid beneficiaries with diabetic foot ulcers (DFUs) who had transitioned to commercial insurance. Methods: We utilized the PearlDiver claims database to identify adult patients diagnosed with a new DFU between 2010 and 2019. The study cohort comprised 8856 Medicaid beneficiaries who had at least three years of continuous enrollment after DFU diagnosis. Medicaid beneficiaries who transitioned to Medicare during follow-up were excluded. Adjusted comparisons of outcomes were performed by propensity matching the two groups for age, gender, and Charlson Comorbidity Index (CCI) in a 1:1 ratio. We used logistic regression and Kaplan–Meier estimate to evaluate the association between insurance change (from Medicaid to commercial insurance) and major amputation. Results: Among the 8856 Medicaid beneficiaries with DFUs, 66% (n = 5809) had transitioned to commercial insurance coverage during follow-up. The overall major amputation rate was 2.8% (n = 247), with a lower rate observed in patients who transitioned to commercial insurance compared to those with continuous Medicaid coverage (2.6% vs. 3.2%, p < 0.05). In multivariable analysis, Medicaid beneficiaries who transitioned to commercial insurance had a 27% lower risk of major amputation (study cohort: odds ratios [OR] 0.75, 95% CI 0.56–0.97, p = 0.03; matched cohort: OR 0.65, 95% 0.22, 0.55, p = 0.01) compared to those with continuous Medicaid coverage. Conclusions: Transitioning from Medicaid to commercial insurance may be associated with a lower risk of major amputation among Medicaid beneficiaries with DFUs. Full article

Diabetes significantly impacts the immune system; however, its role in worsening sepsis prognosis remains poorly understood. This study investigated the effect of hyperferritinemia on immune modulation in septic diabetic patients. A cohort study at Kyungpook National University Hospital stratified sepsis patients by diabetes status and followed them for 28 days. Additionally, CD4⁺ T cells from mice were analyzed for proliferation, apoptosis, and metabolic changes under ferritin treatment. Results from the clinical study showed higher ferritin levels in diabetic patients, and those with lower lymphocyte counts had increased mortality. In the mice study, ferritin inhibited T cell activation and proliferation by shifting metabolism from glycolysis to oxidative phosphorylation without increasing cell death. These findings suggest that the suppression of T cell proliferation due to elevated ferritin levels contributes to an immunosuppressive environment, leading to worse outcomes. In conclusion, hyperferritinemia is a biomarker for sepsis severity, particularly in diabetic patients, highlighting potential therapeutic strategies targeting ferritin levels or glycolytic pathways. Full article

Introduction: Type 2 diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constraint in the management of this disease. We evaluated the use, the adherence, and the safety of antidiabetic drugs in patients with T2DM. Methods: We performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners in Catanzaro (Calabria, Italy). Drug adherence was measured considering the packages of antidiabetic drugs prescribed at the time of admission, after three months, and 1 year later. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study, we evaluated 12,170 medical records of seven general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (p = 0.023). During the study, we recorded 26 ADRs that were correlated with sex (women) and insulin treatment. Conclusions: this real-life study shows that patients with T2DM have a high adherence, probably related to their having a low number of ADRs. Full article

Metabolic syndrome (MS), a complex pathology with features like abnormal body fat distribution, insulin resistance, and dyslipidaemia, contributes to higher cardiovascular (CV) risk. A cross-sectional study including 87 individuals assessed CV risk score in elderly patients with type 2 diabetes and MS in Algarve, Portugal. The 10-year CV risk score was estimated using the ADVANCE risk score calculator. The reductions in CV risk score were estimated by adjusting the data inputted on the online tool to achieve systolic blood pressure (SBP) <130 or <120 mmHg, and LDL cholesterol <70 mg/dL Beyond waist circumference, the mean number of clinical features of MS was 3.14 ± 0.84, without significant sex differences. The mean CV risk score was 22.5% (CI: 20.3–24.7). Sex-specific analysis showed higher risk score in males (24.2%, CI: 21.3–27.0) vs. females (19.7%, CI: 16.2–23.3; p = 0.028). Hypothetical risk score reductions show that lowering SBP to <130 mmHg could significantly lower the risk score by an average of 9.2% (CI: 7.7–10.7), whereas 34.5% of the participants would be out of the diagnostic criteria for MS. When comparing each potential intervention with current risk score, all interventions significantly reduce the 10-year CV risk score. The study highlights the potential of blood pressure control in reducing CV risk score and the importance of multifaceted risk score reduction strategies. Full article

Metabolic syndrome prevalence is between 24 and 27% and poses a significant risk for the development of atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes (T2D), or other comorbidities. Currently, no drugs are approved for metabolic syndrome treatment itself, so the risk factors are treated with therapies approved for cardiac and metabolic conditions. These are approved drugs for dyslipidemia treatment such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, cornerstone antihypertensive drugs, or novel class glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RA) for T2D and overweight or obesity treatment. We have also evaluated new pharmacological interventions in clinical development that have reached Phase 2 and/or Phase 3 randomized clinical trials (RCTs) for the management of the risk factors of metabolic syndrome. In the pipeline are glucose-dependent insulinotropic polypeptide (GIP), GLP-1, glucagon receptor (GCGR), amylin agonists, and a combination of the latter for T2D and overweight or obesity treatment. Non-entero-pancreatic hormone-based therapies such as ketohexokinase (KHK) inhibitor, growth differentiation factor 15 (GDF15) agonists, monoclonal antibodies (mAbs) as activin type II receptors (ActRII) inhibitors, and a combination of anti-α-myostatin (GFD8) and anti-Activin-A (Act-A) mAbs have also reached Phase 2 or 3 RCTs in the same indications. Rilparencel (Renal Autologous Cell Therapy) is being evaluated in patients with T2D and chronic kidney disease (CKD) in a Phase 3 trial. For dyslipidemia treatment, novel PCSK9 inhibitors (oral and subcutaneous) and cholesteryl ester transfer protein (CETP) inhibitors are in the final stages of clinical development. There is also a surge of a new generation of an antisense oligonucleotide (ASO) and small interfering RNA (siRNA)-targeting lipoprotein(a) [Lp(a)] synthesis pathway that could possibly contribute to a further step forward in the treatment of dyslipidemia. For resistant and uncontrolled hypertension, aldosterone synthase inhibitors and siRNAs targeting angiotensinogen (AGT) messenger RNA (mRNA) are promising new therapeutic options. It would be interesting if a few drugs in clinical development for metabolic syndrome such as 6-bromotryptophan (6-BT), vericiguat, and INV-202 as a peripherally-acting CB1 receptor (CB1r) blocker would succeed in finally gaining the first drug approval for metabolic syndrome itself. Full article

Lifestyle behaviors and their potential effects on diabetes are being investigated for optimal diabetes management. In patients with type 2 diabetes mellitus (T2DM), the necessary dietary modifications extend to psychological components for consideration. This study aimed to determine the eating behavior of T2DM patients with different sociodemographic characteristics in an urban Turkish population. The Dutch Eating Behavior Questionnaire (DEBQ) was distributed via social media and a smartphone application to 108 T2DM patients, 58 males and 50 females, age 26–40 years (20 individuals, 18.6%) and over 40 years (88 individuals, 81.4 %). Basic component factor analysis varimax rotation was used for the item-total correlation coefficient. The 26–40 years age group exhibited high correlation for both restrained and emotional eating behavior (r > 0.8), while participants over 40 years displayed medium correlation for restrained eating and high correlation for emotional eating (r = 0.6–0.8). Compared to married and single participants, participants with “other” marital status showed significant correlation with all eating behavior categories (r > 0.8). Married participants were less correlated with all categories compared to single participants. Participants with lower education levels exhibited high correlation (r > 0.8) for all forms of eating, more so compared to those with higher levels of education attained. Overweight patients demonstrated moderately high (r = 0.4–0.6) restrictive eating correlation, while normal weight and obese patients exhibited higher correlation (r = 0.6–0.8) for emotional and restrained eating compared to overweight patients. Regardless of demographic factors, when all participants were combined, the strongest correlation was found to be with emotional eating compared to other types of eating. Full article

A correct injection technique is essential in order to ensure the effectiveness of insulin and to achieve good metabolic control, and the use of suitable needles is fundamental. Today, technological evolution has transformed insulin needles into innovative tools able to guarantee an effective and safe administration of insulin, to reduce local complications, such as lipodystrophies that are an obstacle to the effectiveness of the treatment itself, and to minimize the pain of the injection, a crucial factor in the acceptance of therapy and for compliance. The steering committee of the scientific society SIMDO has commissioned the scientific committee and some members of the board to draw up an official SIMDO point of view/consensus on the use of insulin needles. In this way, a group that has combined the experience gained in their field of expertise—diabetologists operating in the public and private sectors, nurses, psychologists, and patients—was set up. The aim is to give indications regarding insulin injection techniques, combining themes such as technology innovation, education in self-management, and psychological support for the patient into a unified approach based on the priority area of patient quality of life. The document will provide operational recommendations that integrate the directions regarding the standards of care for diabetes resulting from the most recent scientific acquisitions with the concept of quality at 360°, as it emerged from the point of view of all the operators involved, but with the patient’s interests as a central focal point. Full article

The magnification of Western eating habits has contributed to a large increase in the development of several diseases and conditions, namely cardiovascular disease, obesity, dyslipidemia, and hyperglycemia. These are part of a cluster of metabolic factors involved in metabolic syndrome. However, there are new dietary patterns more focused on the consumption of plant-based foods. Thus, the aim of this review was to investigate the impact of plant-based diets on metabolic syndrome and to achieve the inflammatory mediators and the antioxidant effects involved in this potential health benefits effect. Advanced research was performed for articles published in the last 10 years, which were analyzed and selected according to the defined inclusion and exclusion criteria. Of the articles analyzed, the majority supported the positive impact of plant-based diets on metabolic syndrome. Furthermore, several studies also showed that these diets appear to have an anti-inflammatory and antioxidant role. Thus, plant-based diets appear to have health benefits, contributing to the prevention of metabolic syndrome, and improving the cardiovascular and metabolic markers’ profile, mainly when including healthy foods. The total exclusion of animal source foods (especially meat and fish) from the diet, as well as the consumption of processed and additive plant-based foods, may contribute to an increased prevalence of metabolic syndrome. Full article

The primary aim of this study was to assess the size and shape of the Foveal Avascular Zone (FAZ) in patients with type 2 diabetes mellitus compared to healthy subjects. The study used 80 OCTA images from the FAZID dataset. The FAZ size was measured by its area, perimeter, and maximum/minimum Feret diameters. The shape was assessed using the axial ratio, circularity, roundness, and solidity. These metrics were calculated automatically using Matlab^® R2020b. Statistical analysis was performed using SPSS statistical software version 28.0, with a p-value of less than 0.01 considered significant. The results showed that the FAZ area was significantly larger in diabetic eyes (mean = 0.50 mm²) compared to control eyes (mean = 0.37 mm²), with a p-value of less than 0.01. Both the maximum and minimum diameters of the FAZ were also significantly larger in diabetic groups compared to the control group. Parameters associated with FAZ’s shape were significantly smaller in the diabetic groups than in the control group, except for the axial ratio. The main finding of this study is that diabetic eyes without clinically detectable diabetic retinopathy exhibit morphological changes and irregularities at the FAZ border. Full article

The prevalence of obesity in adults with type 1 diabetes is increasing and reflects the rates of the general adult population. The coexistence of overweight or obesity and type 1 diabetes poses a major challenge to effective glycemic and weight management. In addition, individuals living with T1D and overweight or obesity are at greater cardiometabolic risk and are more prone to develop chronic complications in comparison to normal weight individuals with type 1 diabetes. Although obesity represents a growing challenge in the type 1 diabetes population, awareness of this issue is still low. This review provides a summary of current data on prevalence trends, causes, current strategies, and challenges in managing obesity in adults with type 1 diabetes. Full article

Background: We assessed the pertinence of updating the International Working Group on the Diabetic Foot (IWGDF) risk classification yearly in people with diabetes by quantifying the changes in the risk group and its accuracy in identifying those developing an ulcer (DFU) in a primary care setting. Methods: In our retrospective cohort study, we included all people with diabetes with a foot assessment registry between January 2016 and December 2018 in the Baixo Alentejo Local Health Unit. Foot-related data were collected at baseline after one and two years. DFU and/or death until December 2019 were registered. The proportion of people changing their risk status each year was calculated. Accuracy measures of the IWGDF classification to predict DFU occurrence at one, two, and three years were calculated. Results: A total of 2097 people were followed for three years, during which 0.1% died and 12.4% developed a DFU. After two years, 3.6% of the participants had progressed to a higher-risk group. The IWGDF classification presented specificity values superior to 90% and negative predictive values superior to 99%. Conclusion: Foot risk status can be safely updated every two years instead of yearly, mainly for those at very low risk. The IWGDF classification can accurately identify those not at risk of DFU. Full article

Diabetic foot complications constitute a large and rapidly growing global health problem, causing one million lower-extremity amputations annually. These amputations are typically preceded by preventable diabetic foot ulcers (DFUs). However, 80% of the world’s diabetics now reside in low- and middle-income countries, where many healthcare settings lack the resources required to implement recommended DFU risk assessment and prevention strategies. There is an unmet need for a more resource-efficient DFU risk assessment method. In this study, a low-cost, purely mechanical plantar pressure evaluation device was designed toward this end. The device consists of a grid of plastic bistable compliant mechanisms, which present a visual series of binary outputs in response to applied pressure. By having diabetic patients step on the device, non-specialist healthcare providers can easily assess patients’ plantar pressures, which are predictive of future DFUs. A prototype was fabricated and pilot-tested with 41 healthy subjects. It demonstrated a sensitivity of 25.6%, although sensitivity reached 60% for heavier subjects. Sensitivity could likely be significantly improved by lowering the device’s profile and increasing the sensing area. Strained health systems may then be able to use this device to allocate scarce healthcare resources more efficiently to prevent costly DFUs and amputations. Full article

Type 2 diabetes mellitus (T2DM) patients suffer premature development of cardiovascular disease and commonly require cardiac revascularization using the autologous saphenous vein (SV). Smooth muscle cells (SMCs) are the principal cell type within the vascular wall and are dysfunctional in T2DM SV-SMCs, yet the mechanisms underpinning this are incompletely understood. The purpose of this study was to interrogate differential microRNA (miRNA) expression in SV-SMCs to enhance our understanding of T2DM SV-SMC phenotypic change. miRNA expression in primary human SV-SMCs from T2DM and non-diabetic (ND) donors was determined using an array (n = 6 each of ND and T2DM SV-SMCs). Differentially expressed miRNAs were ranked, and functional annotation of the 30 most differentially expressed miRNAs using DAVID and KEGG analysis revealed pathways related to SMC phenotype, including proliferation, migration, cytokine production and cell signaling. After selecting miRNAs known to be involved in SMC phenotypic regulation, miR-17, miR-29b-2, miR-31, miR-130b and miR-491 were further validated using qRT-PCR (n = 5 each of ND and T2DM SV-SMC), with miR-29b-2 subsequently being removed from further investigation. Potential mRNA targets were identified using mirDIP. Predicted target analysis highlighted likely dysregulation in transcription, epigenetic regulation, cell survival, intracellular signaling and cytoskeletal regulation, all of which are known to be dysfunctional in T2DM SV-SMCs. In conclusion, this paper identified four miRNAs that are dysregulated in T2DM SV-SMCs and are implicated in functional changes in the behavior of these cells. This provides a step forward in our understanding of the molecular and epigenetic regulation of vascular dysfunction in T2DM. Full article

Protein O-GlcNAcylation, a dynamic and reversible glucose-dependent post-translational modification of serine and threonine residues on target proteins, has been proposed to promote vascular smooth muscle cell proliferation and migration events implicated in vein graft failure (VGF). Therefore, targeting the enzymes (glutamine fructose-6P amidotransferase (GFAT), O-GlcNAc transferase (OGT), and O-GlcNAcase (OGA)) that regulate cellular O-GlcNAcylation could offer therapeutic options to reduce neointimal hyperplasia and venous stenosis responsible for VGF. However, it is unclear how type 2 diabetes mellitus (T2DM) and hyperglycaemia affect the expression of these enzymes in human saphenous vein smooth muscle cells (HSVSMCs), a key cell type involved in the vascular dysfunction responsible for saphenous VGF. Therefore, our aim was to assess whether T2DM and hyperglycaemia affect GFAT, OGT, and OGA expression levels in HSVSMCs in vitro. Expression levels of GFAT, OGT, and OGA were determined in low-passage HSVSMCs from T2DM and non-T2DM patients, and in HSVSMCs treated for 48 h with hyperglycaemic (10 mM and 25 mM) glucose concentrations, by quantitative immunoblotting. Expression levels of OGT, OGA, and GFAT were not significantly different in HSVSMC lysates from T2DM patients versus non-T2DM controls. In addition, treatment with high glucose concentrations (10 mM and 25 mM) had no significant effect on the protein levels of these enzymes in HSVSMC lysates. From our findings, T2DM and hyperglycaemia do not significantly impact the expression levels of the O-GlcNAcylation-regulating enzymes OGT, OGA, and GFAT in HSVSMCs. This study provides a foundation for future studies to assess the role of O-GlcNAcylation on VGF in T2DM. Full article

Diabetic foot is a common complication of diabetes that affects quality and prognosis of life for patients and often requires hospitalization. Infection, alone or in association with ischemia, is the main cause of hospital admission and impacts prognosis. The aim of this study is to analyze the costs of diabetic foot lesions and assess factors that influence the economic impact, focusing on infection. We included all people with diabetes with a first visit for diabetic foot during 2018 in our diabetic foot center. Database interrogation identified 422 patients. Diabetic foot treatment required hospitalization for 242 patients (58%), while 180 (42%) were treated in outpatient services. Healing time was different between the two groups: it was 136 ± 124 days (mean ± SD) for outpatients and 194 ± 190 days for patients that require hospitalization (p < 0.001). Costs: Treatment of 422 patients for diabetic foot globally costs 2063 million EUR and the mean cost for patients is 4888 EUR, with hospital stay having a high impact on this, accounting for 88% of the costs. Infection impacts hospitalization duration and ischemia impacts healing time. Ischemia and infection prolonged hospitalization duration and costs. Our work underlines that hospital treatment costs have a high impact on total costs. Full article

(1) Background: It has been previously shown that sourdough bread, compared to commercial yeast bread, elicits a lower postprandial glycemic and insulinemic response in patients with impaired glucose tolerance (IGT). Aims: Our aim was to evaluate the following aspects in persons with type 2 diabetes (T2DM): (1) glucose variations induced by three different doughs: X = bread prepared with functional alkaline biocrystal water, Y = sourdough-leavened bread, and W = bakery yeast bread; (2) the utility of flash glucose monitoring (FGM) to measure GL. (2) Methods: Twelve T2DM following diets (six males, diabetes duration 10.9 ± 1.3 years with no complications, Hba1c < 7.0%), after 12 h of fasting, consumed 180 g of the study breads leavened/matured for 48 (X), 8 (Y), and 4 h (W) at room temperature with 200 mL of water, in a random order, in single-blind conditions, on three different days. All patients had FGM running for the entire period of the experiments. Insulin was determined by capillary blood obtained for the basal and peak glucose concentrations. (3) Results: The peak glucose and peak insulin concentrations were significantly (p < 0.05) higher for W versus both X and Y, without significant differences between X and Y. The area under the curve of glucose variations for over 240 min was significantly higher in W than X (p < 0.01) and Y (p < 0.05), without significant differences between X and Y. (4) Conclusions: (1) Bread prepared with biocrystal water has the same lower GL of sourdough bread compared to bakery yeast bread, and it is easier to manage its leavening/maturation period; (2) FGM is a reliable method for determining rapid glucose changes in response to a carbohydrate meal in persons with type 2 diabetes. Full article

The number of food-insecure individuals with diabetes is on the rise. FOODRx is a supplemental healthy food intervention program that gave disease-appropriate food boxes to food-insecure patients with diabetes at their care clinic and included nutrition and recipe materials in the patient’s preferred language (English, Spanish, or Somali). Implemented over a twelve-month period, we analyze FOODRx participants’ pre and post clinical measures, health care usage, and program/clinic satisfaction, and found that participation was linked to post improvements in fasting glucose and HgbA1c levels, reductions in ER visits and healthcare costs, and a decline in patients choosing between medication and food. Glucose levels decreased from 214 to 187 mg/dL and HgbA1c levels decreased from 9.6% to 9.1%. Average ER visits dropped from 1.21 to 1 visit and the reductions in healthcare costs were reflected in a decrease of an average of USD 250,000 in insurance claims. Patients were less likely to experience food insecurity, as measured in number of meals skipped and levels of hunger. Finally, the program improved patient satisfaction with the cultural responsiveness of the information shared with them. Full article

Common dysglycemia measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-derived 2 h plasma glucose, and hemoglobin A1c (HbA1c) have limitations for children. Dynamic OGTT glucose and insulin responses may better reflect underlying physiology. This analysis assessed glucose and insulin curve shapes utilizing classifications—biphasic, monophasic, or monotonically increasing—and functional principal components (FPCs) to predict future dysglycemia. The prospective cohort included 671 participants with no previous diabetes diagnosis (BMI percentile ≥ 85th, 8–18 years old); 193 returned for follow-up (median 14.5 months). Blood was collected every 30 min during the 2 h OGTT. Functional data analysis was performed on curves summarizing glucose and insulin responses. FPCs described variation in curve height (FPC1), time of peak (FPC2), and oscillation (FPC3). At baseline, both glucose and insulin FPC1 were significantly correlated with BMI percentile (Spearman correlation r = 0.22 and 0.48), triglycerides (r = 0.30 and 0.39), and HbA1c (r = 0.25 and 0.17). In longitudinal logistic regression analyses, glucose and insulin FPCs predicted future dysglycemia (AUC = 0.80) better than shape classifications (AUC = 0.69), HbA1c (AUC = 0.72), or FPG (AUC = 0.50). Further research should evaluate the utility of FPCs to predict metabolic diseases. Full article

This study aimed to investigate the use of and willingness to adopt web-based technology for self-management of type 2 diabetes among Arabic-speaking immigrants in Saudi Arabia. Conducted in Taif in 2022, it involved participants with type 2 diabetes mellitus, utilizing a study-specific questionnaire to gather data on demographics, disease specifics, and attitudes towards using this technology for diabetes management. Out of the 109 individuals who responded, 91 completed the survey and reported accessing web-based technology and an average usage of two hours per day. The primary use was for social media (90.1%) and information searching (73.6%). The study found a high willingness to use web-based technology for dietary planning (85.7%), physical activity monitoring (94.5%), and communication with healthcare providers (93.41%). Notably, younger participants, those with higher education, and married individuals showed more inclination towards using such technology, as indicated by significant correlations (p < 0.001, CI = 0.03–0.38; p < 0.039, CI = 1.06–10.26; p = 0.024, CI = 1.23–19.74). Over half of the participants (56%) considered web-based technology beneficial for diabetes management, with many finding it time-saving (61.5%). In conclusion, a significant proportion of participants demonstrated a strong preference for integrating web-based technology into their diabetes self-management routines. This preference was particularly evident in key areas such as diet, physical activity, and glucose monitoring. These findings underscore the potential of web-based technologies in supporting effective diabetes management among Arabic-speaking immigrants, highlighting the need for targeted interventions that leverage these digital tools. Full article

Diabetes mellitus (type I and II) is an advancing global health problem, concerningly increasing in prevalence in most of the developed and developing world. Current therapies, such as the subcutaneous injection of insulin, are invasive and require a close monitoring of blood glucose levels to prevent hypo- or hyperglycaemia from occurring. Despite an inexorable search for a cure since Banting and Best discovered and purified insulin in 1921, insulin remains a solitary insula, still the gold standard for treatment of type I and late-stage type II diabetes mellitus. Apropos of complications, diabetes causes a myriad of secondary maladies, ranging from diabetic kidney disease, diabetic retinopathy and diabetic neuropathy to erectile dysfunction and peripheral vascular disease. While scientists continue to interminably tinker with perfecting mechanical insulin pumps or dampening the immune response to pancreatic beta cells, an important aspect of the aetiology of diabetes should not be neglected, that of the metabolism. At its heart, diabetes can arguably be considered a metabolic disease, and this review suggests a return to focusing on preventing and treating diabetes by focussing on its metabolic causes. This narrative review summarises the potential of a recent class of synthetic peptides, the melanocortins, to help prevent and treat the complications of diabetes mellitus. The review summarises recent work showing the potential benefits of the melanocortins in treating diabetic complications through various pathways. Full article

Background: The number of people with type 2 diabetes is increasing daily, and therefore, effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1c ≥ 7%) on different oral or basal insulin supported oral therapy were enrolled in the study, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA-naive and consequently prescribed 0.5 or 1.0 mg of once weekly injectable semaglutide (IS) or 7 mg or 14 mg of once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglobin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and secondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥5% and ≥10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At the 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS −1.1% vs. OS −1.4%, p = 0.126) and weight loss (IS −6.50 kg vs. OS −5.90 kg, p = 0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥5% (56.7%, n = 30). A weight loss ≥ 10% was observed in 20.7% (n = 11) of participants administered IS and 15.1% (n = 8) of participants administered OS, respectively (p = 0.454). Conclusion: In a real-world setting, oral semaglutide as an add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated a similar effectiveness as injectable semaglutide in terms of glycemic control and weight loss after 6 months of treatment. Full article

The aim of this study is to analyze the risk factors that lead to cognitive impairment, depression, and psychosocial problems in type 2 diabetes and discern what aspects they have in common. Type 2 diabetes is associated with a higher risk of cognitive impairment, including dementia, which in turn increases the risk of hospitalization, falls, and premature mortality. In this study, we conducted a systematic review to achieve this goal, including searches on electronic databases such as PubMed, Medline, Web of Science, EBSCO Discovery, EBSCO host, Scopus, and ScienceDirect, from 2016 onwards. Additionally, we carried out manual searches in leading journals in the field. After evaluating and analyzing the articles, 60 remained, focusing on the following four main themes: disorders due to biological, psychological, social, and pharmacological causes that lead to neuropsychological complications. Based on the results, consistently analogous risk factors contributing to the onset of cognitive impairments, depression, and psychosocial predicaments encompass comorbid ailments, dysglycemia, gender, heightened levels of apprehension and anxiety, educational attainment, socio-economic standing, and pharmaceutical interventions. Furthermore, in the realm of type 2 diabetes, factors such as disease duration, adiposity, specifically overweight and obesity, and advancing age were also identified as significant contributors to cognitive impairments and depression. Concomitantly, the absence of a robust support system and social network emerged as a shared risk factor, predisposing individuals to psychosocial challenges and depressive states. These findings emphasize that the risk factors for cognitive impairments, depression, and psychosocial issues for type 2 diabetes are similar, highlighting the importance of psychosocial support, education, and patient-centered treatment to optimize outcomes and quality of life. Full article

Background: Diabetes is the primary contributor to cardiovascular disease risk, and when combined with obesity, it further underscores the significance of cardiovascular risk assessment. Methods: A retrospective study of 64 patients with type 2 diabetes (T2D) and obesity on once-weekly subcutaneous semaglutide stratified by cardiovascular risk categories determined using the SCORE2/SCORE2-OP, SCORE2-Diabetes, and ASCVD score calculations. We compare the differences between groups (ASCVD: low + borderline + intermediate versus high-risk group; SCORE2/SCORE2-OP: low + moderate versus high + very high-risk group and SCORE2-Diabetes: low + moderate versus high + very high-risk group) in terms of change from baseline in body mass index (BMI) and HbA1c and weight loss outcomes. Results: Patients in the high-risk group, according to ASCVD risk score, had statistically better results in weight loss ≥ 3%, ≥5%, and ≥10% compared to ASCVD low + borderline + intermediate and without difference regarding HbA1c. According to SCORE2/SCORE2-OP, the high + very high-risk group had statistically better HbA1c and weight loss results but only for ≥5% versus the low + moderate risk group. Based on the score SCORE2-Diabetes, the high + very high-risk group had statistically significant better results in lowering HbA1c and weight loss but only for ≥5% versus the low + moderate risk group. Conclusions: To the best of our knowledge, this study represents the initial investigation linking glycemic control and weight reduction outcomes in individuals with T2D and obesity treated with once-weekly semaglutide stratified by cardiovascular risk categories determined using the SCORE2/SCORE2-OP, SCORE2-Diabetes and ASCVD score calculations. Full article

Diabetes mellitus is a metabolic disorder that has a high global health burden and causes high mortality and morbidity in humans. Medicinal herbs and plants offer a promising alternative to conventional therapies for the management of diabetes. Rosemary (Rosmarinus officinalis L.) is a traditional medicinal herb that has been used for the management of several diseases. Therefore, the present study investigates the antidiabetic properties of diets supplemented with R. officinalis leaf powder on streptozotocin-induced diabetic Wistar rats. First, the phytochemicals and 2,2-dephenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity of aqueous R. officinalis leaf extract were determined. Streptozotocin-induced diabetic male Wistar rats were fed a diet supplemented with R. officinalis leaf powder (ROP) at 3%, 6%, and 12%, respectively, for 6 weeks. Investigations of food intake, body weight, rat relative organ weights, blood glucose, lipid profiles, creatinine, bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were estimated according to standard procedures. The results show that ROP aqueous extract contains significant amounts of phenolics, flavonoids, and tannins, which exhibit in vitro DPPH free-radical scavenging activity. Based on an in vivo study, ROP reduced blood glucose levels in streptozotocin-induced diabetic animals (p < 0.05). Dietary supplementation with ROP in diabetic rats significantly (p < 0.05) lowered ALT, AST, bilirubin, creatinine, total triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels while increasing high-density lipoproteins (HDLs) when compared with the diabetic control group. Our findings demonstrate that a diet supplemented with R. officinalis leaf powder exhibits an antidiabetic potential with improved health outcomes, as demonstrated by the improved lipid and liver profile enzymes in our animal model. Full article

Introduction: Early detection of type 2 diabetes is essential for preventing long-term complications. However, screening the entire population for diabetes is not cost-effective, so identifying individuals at high risk for this disease is crucial. The aim of this study was to compare the performance of five diverse machine learning (ML) models in classifying undiagnosed diabetes using large heterogeneous datasets. Methods: We used machine learning data from several years of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 to identify people with undiagnosed diabetes. The dataset included 45,431 participants, and biochemical confirmation of glucose control (HbA1c) were used to identify undiagnosed diabetes. The predictors were based on simple and clinically obtainable variables, which could be feasible for prescreening for diabetes. We included five ML models for comparison: random forest, AdaBoost, RUSBoost, LogitBoost, and a neural network. Results: The prevalence of undiagnosed diabetes was 4%. For the classification of undiagnosed diabetes, the area under the ROC curve (AUC) values were between 0.776 and 0.806. The positive predictive values (PPVs) were between 0.083 and 0.091, the negative predictive values (NPVs) were between 0.984 and 0.99, and the sensitivities were between 0.742 and 0.871. Conclusion: We have demonstrated that several types of classification models can accurately classify undiagnosed diabetes from simple and clinically obtainable variables. These results suggest that the use of machine learning for prescreening for undiagnosed diabetes could be a useful tool in clinical practice. Full article

Hospitalizations for diabetes and dementia can impose a significant health and economic toll on older adults in the United States. This study sought to examine differences in hospitalization characteristics and outcomes associated with diabetes and dementia, separately and together, using 2019–2021 discharge record data from the California Department of Health Care Access and Information. The sampled group were residents of Los Angeles County who were aged 50+ at the time of the study. The multivariable linear regression analysis showed that compared to those with no diabetes or dementia, patients with diabetes alone exhibited the highest total charges, while those with comorbid diabetes and dementia exhibited lower charges (p < 0.05). The multinomial logistic regression found that patients with comorbid diabetes and dementia had the highest odds of having a length of stay of 7+ days (Adjusted Odds Ratio = 1.49; 95% Confidence Interval (CI) = 1.44–1.53). A matched case–control analysis revealed that comorbid diabetes and dementia were associated with significantly lower odds of hypertensive disease than diabetes alone (Matched Odds Ratio = 0.81; 95% CI = 0.67–0.97). Collectively, these results highlight the complex factors that may influence the variable hospitalization outcomes that are common occurrences in these three distinct disease profiles. Study findings suggest a need to consider these complexities when developing policies or strategies to improve hospitalization outcomes for these conditions. Full article

The Centers for Disease Control and Prevention (CDC) indicates that individuals with prediabetes are significantly less likely to develop type 2 diabetes if they participate in a lifestyle change program that results in at least 5% weight loss and 150 min of physical activity per week. The CDC recognizes distance learning as an effective delivery mode for lifestyle change programs to prevent type 2 diabetes. The purpose of this study was to assess enrollment, engagement, and effectiveness of a type 2 diabetes prevention program (DPP) using synchronous distance technology. Eat Smart, Move More, Prevent Diabetes (ESMMPD) is an intensive 12-month DPP delivered using synchronous distance technology. Throughout 26 lessons, participants focused on healthy eating, physical activity, and mindfulness behaviors. Study findings showed a significant decrease in A1C (−0.24 p < 0.0001). Weight loss averaged 5.66% for those who completed the program. Based on the Wilcoxon signed-rank test, participants demonstrated statistically significant changes in self-reported confidence in their ability to perform all 18 health-promoting behaviors assessed (p < 0.0001). Participation in the program also resulted in the adoption of health promoting behaviors. A DPP using synchronous distance technology is an effective delivery mode to help participants adopt healthy behaviors, increase physical activity, and achieve the weight loss necessary to prevent or delay the onset of type 2 diabetes. Full article