Search

Context: Prolactin (PRL) is a crucial mediator of glucoinsulinemic metabolism., Objective: This work aims to dissect glucose metabolism during and after pregnancy in patients with prolactinomas., Methods: A total of 52 patients treated with cabergoline (CAB) were evaluated before conception, during pregnancy, and up to 10 years after delivery. During pregnancy, CAB was discontinued, while it was restarted in 57.7% of patients after delivery, due to recurrent hyperprolactinemia (RH). Hormonal (serum PRL) and metabolic (glycated hemoglobin A1c [HbA1c], fasting glucose [FG], glucose tolerance) parameters were assessed., Results: During pregnancy, PRL gradually increased, while FG remained stable. An inverse correlation between PRL and FG was found in the first (P = .032) and third (P = .048) trimester. PRL percentage increase across pregnancy was inversely correlated with third-trimester FG. Serum PRL before conception emerged as a predictive biomarker of third-trimester FG (t = 2.603; P = .048). Older patients with lower HbA1c in the first trimester and lower FG at 3 years post partum delivered infants with reduced birth weight. Breastfeeding up to 6 months correlated with lower FG at 4 and 10 years post partum. A positive correlation between BMI and FG at 10 years after delivery (P = .03) was observed, particularly in overweight/obese patients requiring higher CAB doses. Patients with RH who had to restart CAB showed shorter breastfeeding duration and higher FG at 2 years post partum., Conclusion: Low PRL levels before pregnancy may be detrimental to FG during pregnancy. CAB duration and dose may influence long-term glucose tolerance, besides family history and BMI. Preconception metabolic management should be recommended to reduce the risk of gestational and type 2 diabetes mellitus., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown., Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the rate of incident viremia based on the diagnosis of DM among PWH. DM was defined as two consecutive fasting glucose measurements ≥126 mg/dl, use of antidiabetic medications, preexisting DM diagnosis, or a confirmed HbA1c >6.5%., Results: 1061 women (112 with DM, 949 without DM) and 633 men (41 with DM, and 592 without DM) were included in the analysis. The relative rate (RR) of incident HIV viremia for women with HIV and DM was lower when compared to women without DM (0.85 [95% CI: 0.72-0.99]; P  = 0.04). The RR of incident viremia for women with uncontrolled DM (HbA1c > 7.5%) was higher when compared to women with controlled DM (HbA1c < 7.5%) (1.46 [95% CI: 1.03-2.07]; P  = 0.03). In contrast, the RR of incident viremia for men with HIV and DM was not statistically different compared to men without DM (1.2 [95% CI: 0.96-1.50]; P  = 0.12). The results were stratified by adherence levels (100%, 95-99%, and <95% based on self-report)., Conclusions: Women with DM who are highly adherent to ART (100% self-reported adherence) have a lower risk of viremia compared to women with HIV without DM. However, women with poorly controlled DM were at higher risk of HIV viremia than women with controlled DM. Further research is necessary to understand the impact of sex, DM, and ART adherence on HIV viremia., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Suboptimal medication adherence among individuals with diabetes presents a significant challenge in low-income nations. Growing evidence demonstrates the effectiveness of text messaging interventions to enhance medication adherence. This study assesses the intention to use Short Messaging Service (SMS) based reminder services in promoting drug adherence among diabetic patients and associated factors in Addis Ababa, Ethiopia., Methods: An institution-based cross-sectional study was conducted from February 06, 2023, to March 27, 2023, in Addis Ababa, Ethiopia. A sample of 351 patients was selected using systematic random sampling. Structured questionnaires were used for data collection. Binary and multivariable logistic regression models were used to analyze the association between intention to use SMS reminders to promote drug adherence among individuals with diabetes and related factors., Results: A total of 333 respondents, with a 94.87% response rate, were interviewed for this study. The majority of respondents, 66.4 % (95% CI [61.9-71.2]), expressed an intention to use SMS-based reminder services to promote their drug adherence. Age < 45 years (AOR = 5.73, 95% CI [2.07-15.73]), higher educational level (AOR = 3.03, 95% CI [1.16-7.90]), type of diabetes (AOR = 3.71, 95% CI [1.16-7.90]), oral medication users (AOR = 2.99, 95% CI [1.42-6.32]), SMS as a preferred medium for communication (AOR = 2.86, 95% CI [1.17-7.00]) were deemed to be important variables linked to intention to use SMS reminders to promote drug adherence among individuals with diabetes., Conclusion: The findings suggest the majority of individuals with diabetes have intention to use SMS reminders to enhance adherence. This result indicates the potential for utilization of SMS reminders to enhance adherence to diabetic medications. Furthermore, the findings highlight the importance of tailored interventions that take into account patient characteristics and preferences as factors that influence intention when designing such an intervention., Competing Interests: The authors declare that they have no competing interests, (© 2024 Alem and Gulema.)

Purpose: To study epidemiology, complications, risk factors, clinical course and treatment patterns of diabetes, the Nanjing Diabetes Cohort (NDC) was established using anonymised electronic health records from 650 hospitals and primary care since 2020. This cohort provides valuable data for researchers and policy-makers focused on diabetes management and public health strategies., Participants: Diabetes was defined as having inpatient or outpatient encounters with a diagnosis of diabetes International Classification of Diseases-9/10 codes, any use of insulin or oral hypoglycaemic drugs, or one encounter with haemoglobin A1C >4.8 mmol/mol or 6.5%. Patients with diabetes have been continuously enrolled on hospitals and primary care in Nanjing since 2020. Demographic, medications and comorbidities data were extracted from clinical notes, diagnostic codes, labs, prescriptions and vital signs among different types of diabetes., Findings to Date: The NDC consisted of 1 033 904 patients from 1 January 2020 to 31 December 2022, the majority were male (50.62%) and from the Gulou district (30.79%). The clinical characteristics and medication usage of patients with type 1 diabetes, type 2 diabetes, gestational diabetes and other diabetes were assessed. The prevalences of hypertension, ischemic heart disease, and cerebrovascular disease were 49.72%, 17.85% and 24.90%, respectively., Future Plans: NDC will annually enrol eligible patients and include socioeconomic data in future updates. The data of NDC are maintained by the Department of Medical Informatics at Nanjing Medical University., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immune checkpoint inhibitor-related diabetes mellitus (ICI-DM) is a rare complication that medical oncologists seldom encounter in routine practice. The sporadic nature and intrinsic complexity of ICI-DM make it challenging to analyze comprehensively in experimental settings. In this review, we examine phase 3 clinical trials on ICIs and published case reports of ICI-DM, aiming to summarize its incidence, clinical features, management, and prognosis. Phase 3 clinical trials reveal that the incidence of ICI-DM is higher with combination therapies, such as anti-PD-1 and anti-CTLA-4 or anti-PD-L1, compared to anti-PD-1 monotherapy. ICI-DM typically presents as severe hyperglycemia with a fulminant onset and is often associated with diabetic ketoacidosis, accompanied by unexpectedly low HbA1c and C-peptide levels. ICI-DM shares similarities with classic type 1 diabetes, particularly in terms of autoimmunity and genetic predisposition. This includes a high prevalence of islet autoantibodies and susceptibility to certain HLA haplotypes, often with concurrent endocrine gland dysfunction. This suggests that genetic susceptibility and exposure to ICIs may both be necessary for triggering islet autoimmunity and inducing ICI-DM. Notably, patients with positive islet autoantibodies, such as glutamic acid decarboxylase antibody and islet-associated antigen 2 antibody, tend to experience rapid onset of ICI-DM after ICI exposure. Although patients with ICI-DM generally show a high objective response rate to immunotherapy, a significant proportion also face the need to permanently discontinued treatment. Further research is urgently needed to determine whether permanent discontinuation of immunotherapy is necessary and whether this discontinuation negatively impacts overall survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Yang, Li, Xue and Wan.)

As corticosteroids can cause diabetes, it is important to assess the benefit-risk balance for patients before introducing them, and to monitor the development of hyperglycemia in people treated with this therapeutic class. As soon as cortico-induced diabetes is discovered, multidisciplinary, cross-disciplinary management improves follow-up conditions., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: Erectile dysfunction (ED) is a neglected complication in patients with pre-diabetes or diabetes mellitus (DM)., Areas Covered: A summary and review of the role of standard ED treatment and the contribution of lifestyle modification and hypoglycemic drugs., Expert Opinion: Oral phosphodiesterase type 5 inhibitors (PDE5i) represent the first-line therapy even in patients with DM. Testosterone replacement therapy (TRT) is mandatory in all hypogonadal (total testosterone < 12 nmol/l) subjects. Alprostadil and/or combined approaches can be considered when PED5i with or without TRT fail. The glycometabolic optimization through lifestyle modification and the use of hypoglycemic drugs represents a crucial step, even for ED treatment. Considering the strong association between ED and forthcoming cardiovascular diseases, the selection of glucagon-like peptide type 1 analogues or sodium glucose cotransporter-2 inhibitors seems to represent the best option due to their long-term effect on chronic complication prevention. Metformin can be considered a possible alternative in less complicated subjects. Penile prostheses (PP) can be offered when all other options are not effective, but the patients should be informed that poor glycometabolic control can increase the risk of PP infection.

Background: Increasingly, pharmacists are asked to incorporate social determinants of health (SDoH) identification and referral into clinical practice. However, to date, no studies have evaluated clinical changes from embedding SDoH screening into the delivery of comprehensive medication management (CMM) in patients with chronic conditions., Objective: To examine the clinical effectiveness of implementing a clinical pharmacist-led SDoH screening and referral process as part of CMM encounters across a network of 7 Federally Qualified Health Centers (FQHCs)., Methods: We used a retrospective cohort design to evaluate the effectiveness of integrating SDoH screening into CMM across a network of 7 FQHCs. A difference-in-difference approach was used to compare the effectiveness of CMM between patients with and without SDoH needs on the probability of achieving clinical control for blood pressure (<140 systolic/90 diastolic mm Hg) and diabetes (<9% hemoglobin A1c)., Results: Among 807 patients receiving CMM in 2023, 595 (74%) were screened for SDoH. 55.1% of patients screened had 1 or more SDoH, most commonly facing barriers related to insurance (22.0%), language (11.3%), transportation (9.1%), health behaviors (7.1%), income/employment (5.9%), and food insecurity (5.6%). Comparing patients with SDoH needs with those without, the proportion of patients controlled at baseline was 66.3% vs 72.3% for hypertension and 39.0% vs 75.4% for diabetes, respectively. Following a CMM encounter, the proportion of patients who achieved blood pressure control increased 7.6% more ( P = 0.225) among patients with SDoH needs than in those without SDoH, whereas diabetes control rates increased 13.3% more ( P = 0.143)., Conclusions: Although not statistically significant, the results of this pilot evaluation suggest the potential for meaningful clinical improvements from screening and referral of SDoH needs as a part of CMM encounters. These results should be corroborated using a larger, more robust study design.

We have already published a review about the results of clinical trials evaluating the effects of selected nutraceuticals on glycemia in humans. In this second part, we describe the role of other nutraceuticals involved in dysglycemia. The available evidence showed promising hypoglycemic effects of the nutraceuticals reviewed both for their efficacy and safety profile. However, contradictory results as regard the efficacy of some supplements such as Allium sativum, Juglans regia, and Lycium barbarum on glucose homeostasis have emerged from some clinical studies. Other nutraceuticals including Aloe vera, Amorphophallus Konjac, Bauhinia forficata, Coccinia, Ganoderma lucidum, Ipomoea batatas, and Lupinus mutabilis require larger and long-term studies rigorously designed to confirm their hypoglycemic effects due to the scarce data available and the poor quality of clinical trials. Further studies are also required for Cinnamomum, Cynara scolymus, Momordica charantia, Olea europaea, and Opuntia streptacantha. Moreover, well-designed large and long-term clinical trials including the use of standardized nutraceutical preparations are necessary for Phaseolus vulgaris and Vaccinium myrtillus., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Introduction: Aldose reductase (AKR1B1, EC: 1.1.1.21) is a recognized target for the treatment of long-term diabetic complications since its activation in hyperglycemia and role in the polyol pathway. In particular, the tissue-specificity of AKR1B1 expression makes the design of the traditional Aldose Reductase Inhibitors (ARIs) and the more recent Aldose Reductase Differential Inhibitors (ARDIs) exploitable strategies to treat pathologies resulting from diabetic conditions., Areas Covered: A brief overview of the roles and functions of AKR1B1 along with known ARIs and ARDIs was provided. Then, the design of the latest inhibitors in the scientific scenario was discussed, aiming at introducing the research achievement in the field of intellectual properties. Patents dealing with AKR1B1 and diabetes filed in the 2019-2023 period were collected and analyzed. Reaxys, Espacenet, SciFinder n , and Google Patents were surveyed, using 'aldose reductase' and 'inhibitor' as the reference keywords. The search results were then filtered by PRISMA protocol, thus obtaining 16 records to review., Expert Opinion: Although fewer in number than in the early 2000s, patent applications are still being filed in the field of ARIs, with a large number of Chinese inventors reporting new synthetic ARIs in favor of the repositioning approach.

The field of peptide drug research has experienced notable progress, with stapled peptides featuring stabilized α-helical conformation, emerging as a promising field. These peptides offer enhanced stability, cellular permeability, and binding affinity and exhibit potential in the treatment of diabetes and metabolic disorders. Stapled peptides, through the disruption of protein-protein interactions, present varied functionalities encompassing agonism, antagonism, and dual-agonism. This comprehensive review offers insight into the technology of peptide stapling and targeting of crucial molecular pathways associated with glucose metabolism, insulin secretion, and food intake. Additionally, we address the challenges in developing stapled peptides, including concerns pertaining to structural stability, peptide helicity, isomer mixture, and potential side effects., 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 Masson SAS.. All rights reserved.)

Patients with hyperglycemia, thyroid dysfunction, and adrenal insufficiency face increased perioperative risk, which may be mitigated by appropriate management. This review addresses preoperative glycemic control, makes evidence-based recommendations for the increasingly complex perioperative management of noninsulin diabetes medications, and provides guideline-supported strategies for the perioperative management of insulin, including suggested indications for continuous intravenous insulin. The authors propose a strategy for determining when surgery should be delayed in patients with thyroid dysfunction and present a matrix for managing perioperative stress dose corticosteroids based on the limited evidence available., (Published by Elsevier Inc.)

Aim: To examine changes in the use of glucose-lowering medicine (GLM) 12 months before and 12 months after long-term care facility (LTCF) entry among people with diabetes., Materials and Methods: A national retrospective cohort study was conducted using linked health and aged care data from the Registry of Senior Australians National Historical Cohort. Residents of LTCFs with diabetes aged 65 years or older from 2015 to 2019 were included. Prevalence of GLM use and the number of defined daily doses (DDDs) dispensed per 1000 resident-days were estimated quarterly (91-day) using Poisson regression models, or negative binomial regression when overdispersion was present., Results: Among the 50 993 residents studied (median age 84 years), the prevalence of GLM use was 58.4% (95% confidence interval [CI] 58.0%-58.8%) in the 9-12 months pre-LTCF entry and 56.3% (95% CI 55.9%-56.8%) in the 9-12 months post-entry. The number of DDDs/1000 resident-days increased from 1015.2 (95% CI 1002.3-1028.1) to 1253.8 (95% CI 1168.4-1339.3) during the same period. GLM use in the 3 months pre-entry was 56.8% (95% CI 56.4%-57.2%) compared with 61.7% (95% CI 61.3%-62.1%) in the 3 months post-entry, with the increased use driven mainly by insulin. No marked changes in the number of GLMs dispensed or GLM type were observed at 9-12 months post-entry compared with 3 months pre-entry. Among 22 792 individuals dispensed a GLM in the 3 months prior to LTCF entry, 50.2% continued the same GLM at 9-12 months post-entry., Conclusions: GLM use peaked in the first 3 months following LTCF entry, driven mainly by insulin, hence, residents may benefit from close monitoring of diabetes treatment during this period., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Five active compounds, daidzein, luteolin, alpinumisoflavone (AI), 6,8-diprenylgenistein (DG), and warangalone (WA), were identified from the fruits of Maclura tricuspidata via LC-Q/TOF-MS. WA and DG were shown to reverse the high glucose (HG)-induced injury in human umbilical vein endothelial cells (HUVECs), indicating their potential protective effects in alleviating diabetic symptoms. Network pharmacology was conducted to reveal the potential mechanisms of action of the compounds, and Hsp90α (degree: 47), Src (degree: 49), Akt (degree: 69) and p53 (degree: 60) were shown as the core targets related to antidiabetic properties. Further experimental verification suggested that the compounds could enhance phosphorylation of Src and Akt, increase p53 expression act as Hsp90 inhibitors, and protect against HG induced endothelial dysfunction. Our findings will provide a comprehensive understanding of the active substances of M. tricuspidata , which will be helpful for their utilisation.

Introduction: The management of chronic diabetes mellitus and its complications demands customized glycaemia control strategies. Polypharmacy is prevalent among people with diabetes and comorbidities, which increases the risk of adverse drug reactions. Clinical decision support systems (CDSSs) may constitute an innovative solution to these problems. The aim of our study was to conduct a systematic review assessing the value of CDSSs for the management of antidiabetic drugs (AD)., Materials and Methods: We systematically searched the scientific literature published between January 2010 and October 2023. The retrieved studies were categorized as non-specific or AD-specific. The studies' quality was assessed using the Mixed Methods Appraisal Tool. The review's results were reported in accordance with the PRISMA guidelines., Results: Twenty studies met our inclusion criteria. The majority of AD-specific studies were conducted more recently (2020-2023) compared to non-specific studies (2010-2015). This trend hints at growing interest in more specialized CDSSs tailored for prescriptions of ADs. The nine AD-specific studies focused on metformin and insulin and demonstrated positive impacts of the CDSSs on different outcomes, including the reduction in the proportion of inappropriate prescriptions of ADs and in hypoglycaemia events. The 11 nonspecific studies showed similar trends for metformin and insulin prescriptions, although the CDSSs' impacts were not significant. There was a predominance of metformin and insulin in the studied CDSSs and a lack of studies on ADs such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists., Conclusion: The limited number of studies, especially randomized clinical trials, interested in evaluating the application of CDSS in the management of ADs underscores the need for further investigations. Our findings suggest the potential benefit of applying CDSSs to the prescription of ADs particularly in primary care settings and when targeting clinical pharmacists. Finally, establishing core outcome sets is crucial for ensuring consistent and standardized evaluation of these CDSSs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nour Elhouda TLILI reports financial support was provided by National Center for Precision Diabetic Medicine. 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 B.V. All rights reserved.)

Purpose: Methylprednisolone is widely used during the COVID-19 epidemic. We aimed to evaluate the glucose profile of COVID-19 patients with and without diabetes receiving methylprednisolone., Methods: 36 patients with COVID-19 admitted to hospital were included: 17 with and 19 without diabetes. Methylprednisolone 40 mg was administered at about 9:00 a.m. Glucose levels were assessed by blinded intermittently scanned continuous glucose monitoring (isCGM) for an average of 6.8 ± 2.4 days. Excess hyperglycemia was defined as time above range (TAR) > 10.0 mmol/L (TAR >10.0 ) ≥ 25%, or TAR > 13.9 mmol/L (TAR >13.9 ) ≥ 10%., Results: Glucose management indicator (GMI) was significantly higher than the admission glycated hemoglobin A 1c (HbA 1c ) level in patients without diabetes [6.7 (6.1-7.0) % vs. 5.9 (5.9-6.1) %, P < 0.001], while no significant difference was found in patients with diabetes [9.0 (7.5-9.5) % vs. 8.9 (7.5-10.2) %, P > 0.05]. The difference between GMI and HbA 1c (∆GMI-HbA 1c ) in patients without diabetes was significantly higher than in patients with diabetes [0.7 (0.2-1.0) % vs. -0.2 (-1.5-0.5) %, P = 0.005]. The circadian patterns of glucose were similar in the two groups. In patients without diabetes, excess hyperglycemia occurred in 31.6% (6/19) of participants, with 31.6% (6/19) having a TAR >10.0  ≥ 25%, while 21.1% (4/19) had a TAR >13.9  ≥ 10%., Conclusion: The impact of methylprednisolone on glycemia was more pronounced in COVID-19 patients without diabetes, compared to those with diabetes. A significant burden of methylprednisolone-induced hyperglycemia was observed in patients without diabetes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cystic fibrosis (CF)-related diabetes (CFRD), characterized by partial to complete impaired insulin secretion, is the most common extra-pulmonary complication of CF. Actually, insulin is the only approved therapy for its management. Advanced hybrid closed loop (AHCL) systems are the gold standard therapy for type 1 diabetes and have been proposed for other insulin-dependent forms of diabetes, including CFRD. With AHCL systems, people with CFRD can better manage several typical disease-related issues, such as minimal insulin requirements, its variability due to exacerbations or concomitant steroid therapies, nutritional behaviors, the co-existence of CF complications as intestinal malabsorption or liver disease. SmartGuard, the AHCL system for Medtronic Minimed 780G, requires a minimum of 8 units per day to operate. In this paper, we expose a case of two young women with CFRD with total daily insulin requirements < 8 UI, using off-label SmartGuard system over a 3 years of follow-up period, suggesting an evaluation of its use also in people with minimal insulin needs, considering its beneficial impact in glucose control and quality of life., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Paeoniflorin (Pae) can improve diabetes mellitus (DM), especially endothelial dysfunction induced by high glucose (HG). Molecularly, the mechanism pertinent to Pae and DM lacks further in-depth research. Hence, this study determined the molecular mechanism of Pae in treating DM through network pharmacology. The target of Pae was analyzed by TCMSP database, and DM-related genes were dissected by Genecards database and Omim database. PPI network was constructed for cross targets through Cytoscape 3.9.1 and STRING platform. GO and KEGG analyses were carried out on the cross targets. Protein molecular docking verification was completed by AutoDockTools and Pymol programs. Human umbilical vein endothelial cells (HUVECs) were separately treated with HG, Pae (5, 10, 20 μM) and/or HRAS overexpression plasmids (oe-HRAS). The cell viability, apoptosis and the protein expressions of HRAS and Ras-GTP were evaluated. There were 50 cross targets between Pae and DM, and VEGFA, EGFR, HRAS, SRC and HSP90AA1 were the key genes identified by PPI network analysis. GO and KEGG analyses revealed signal paths such as Rap1 and Ras. Molecular docking results confirmed that Pae had a good binding ability with key genes. In HG-treated HUVECs, Pae dose-dependently facilitated cell viability, attenuated cell apoptosis, and dwindled the expressions of HRAS and Ras-GTP, but these effects of Pae were reversed by oe-HRAS. In conclusion, Pae regulates the viability and apoptosis of HG-treated HUVECs by inhibiting the expression of HRAS.

The aim of the study was to explore the clinical efficacy of bisphosphonates in patients with osteoporosis in diabetes patients by meta-analysis. Six databases were systematically searched from inception to January 30,2023. Studies evaluating the treatment of diabetic osteoporosis with bisphosphonates were included. Key outcome measures, such as bone mineral density (BMD), bone metabolism markers, pain improvement, and safety assessments, were extracted and analyzed. STATA MP V17.0 was used to calculate the combined effect size. After searching Chinese and English databases, 15 studies met the inclusion criteria of this study. The results of the meta-analysis showed that the BMD of patients with osteoporosis in diabetes increased significantly after bisphosphonate treatment, and the lumbar BMD increased by 0.08 g/cm² (95% CI: 0.05-0.11). Femoral neck BMD increased by 0.06 g/cm² (95% CI: 0.01-0.11); Ward's triangle BMD increased 0.07 g/cm² (95% CI: 0.04-0.09); and trochanter BMD increased by 0.06 g/cm² (95% CI: 0.04-0.08). In addition, bone alkaline phosphatase increased 1.95 μg/l (95% CI: 1.18-2.72), while serum tartrate-resistant acid phosphatase-5b decreased 1.28 U/l (95% CI: -1.81-0.75). Moreover, improvements in pain were statistically significant. The effects of bisphosphonates on osteocalcin (MD: -0.07; 95% CI: -1.12-1.25), serum calcium (MD: 0.01; 95% CI: -0.03-0.04), serum phosphorus (MD: 0.04; 95% CI: -0.03-0.10) and medication safety (OR: 1.75; 95% CI: 1.29-2.37) were not statistically significant. Bisphosphonates have a significant positive effect on bone mineral density and bone metabolism in patients with osteoporosis in diabetes and have good safety., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background and Aims: Guidelines now recommend inpatient continuous glucose monitor (CGM) use with confirmatory blood glucose measurements. However, the Food and Drug Administration has not yet officially approved CGM for inpatient use in large part because its accuracy has not been established in this setting. We tested the accuracy of the Dexcom G6 (G6) in 28 adults on an insulin infusion in a medical-surgical intensive care unit with 1064 matched CGM and arterial point-of-care pairs. Methods: The participants were on average 57.29 (SD 2.39) years, of whom 13 had a prior diagnosis of diabetes and 14 were admitted for a surgical diagnosis. The first 19 participants received the G6 without calibration and had a mean absolute relative difference (MARD) of 13.19% (IQR 5.11, 19.03) across 659 matched pairs, which just meets the critical care expert recommendation of MARD <14%. We then aimed to improve accuracy for the subsequent 9 participants using a calibration protocol. Results: The MARD for calibrated participants was 9.65% (3.03, 13.33), significantly lower than for uncalibrated participants ( P < 0.001). Calibration also demonstrated excellent safety with 100% of values within the Clarke Error Grid zones A and B compared with 99.07% without calibration. Our protocol achieved the lowest MARD and safest CEG profile in the critical care setting and well exceeds the critical care expert recommendations. Our large sample of heterogenous critically ill patients also reached comparable accuracy to the MARD of 9% for G6 in outpatients. We believe our calibration protocol will allow G6 to be used with sufficient accuracy in inpatients.

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro-inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid-lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro-inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre-β-HDL-the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study., (© 2024 The Author(s). Lipids published by Wiley Periodicals LLC on behalf of AOCS.)

Immune checkpoint inhibitors (ICIs) have become extensively utilized in the early-stage treatment of various cancers, offering additional therapeutic possibilities for patients with advanced cancer. However, certain patient populations are susceptible to experiencing toxic adverse effects from ICIs, such as thyrotoxicosis, rashes, among others. Specifically, ICIDM, induced by immune checkpoint inhibitors, exhibits characteristics similar to insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). ICIDM is characterized by a rapid onset and may coincide with severe ketoacidosis. Despite a favorable response to insulin therapy, patients typically require lifelong insulin dependence. After discussing the autoimmune adverse effects and the specifics of ICIs-induced diabetes mellitus (ICIDM), it is important to note that certain patient populations are particularly susceptible to experiencing toxic adverse effects from ICIs. Specifically, ICIDM, which is triggered by immune checkpoint inhibitors, mirrors the characteristics of insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). This article conducts an in-depth analysis of the literature to explore the pathogenesis, disease progression, and treatment strategies applicable to diabetes induced by immune checkpoint inhibitors (ICIDM)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The COVID-19 pandemic has added to the pre-existing challenges of diabetes management in many countries. It has accelerated the wider use of digital health solutions which have tremendous potential to improve health outcomes for people with diabetes. However, little is known about the attributes and the implementation of these solutions., Objective: To identify and describe digital health solutions for community-based diabetes management and to highlight their key implementation outcomes., Methods: We searched Ovid Medline, CINAHL, Embase, PsycINFO, and Web of Science for relevant articles. A purposive search was also used to identify grey literature. Articles that described digital health solutions that aimed to improve community-based diabetes management were included in this review. We applied a thematic synthesis of evidence to describe the characteristics of digital health solutions, and to summarize their key implementation outcomes., Results: We included 15 articles that reported digital health solutions that primarily focused on community-based diabetes management. Nine of the 15 innovations involved were mobile applications and/or web-based platforms, and five were based on social media platforms. The majority of the digital health solutions were used for diabetes education and support. High engagement, utilization, and satisfaction rates with digital health solutions were observed. The use of digital health solutions was also associated with improvement in self-management, taking medication, and reduction in glycated hemoglobin (HbA1c) levels., Conclusion: COVID-19 triggered digital health solutions have tremendous potential to improve health outcomes for people with diabetes. Further studies are needed to evaluate the sustainability and scale-up of these solutions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Diabetes currently affects approximately 500 million people worldwide and is one of the most common causes of mortality in the United States. To diagnose and monitor diabetes, finger-prick blood glucose testing has long been used as the clinical gold standard. For diabetes treatment, insulin is typically delivered subcutaneously through cannula-based syringes, pens, or pumps in almost all type 1 diabetic (T1D) patients and some type 2 diabetic (T2D) patients. These painful, invasive approaches can cause non-adherence to glucose testing and insulin therapy. To address these problems, researchers have developed miniaturized blood glucose testing devices as well as microfluidic platforms for non-invasive glucose testing through other body fluids. In addition, glycated hemoglobin (HbA1c), insulin levels, and cellular biomechanics-related metrics have also been considered for microfluidic-based diabetes diagnosis. For the treatment of diabetes, insulin has been delivered transdermally through microdevices, mostly through microneedle array-based, minimally invasive injections. Researchers have also developed microfluidic platforms for oral, intraperitoneal, and inhalation-based delivery of insulin. For T2D patients, metformin, glucagon-like peptide 1 (GLP-1), and GLP-1 receptor agonists have also been delivered using microfluidic technologies. Thus far, clinical studies have been widely performed on microfluidic-based diabetes monitoring, especially glucose sensing, yet technologies for the delivery of insulin and other drugs to diabetic patients with microfluidics are still mostly in the preclinical stage. This article provides a concise review of the role of microfluidic devices in the diagnosis and monitoring of diabetes, as well as the delivery of pharmaceuticals to treat diabetes using microfluidic technologies in the recent literature., (© 2024. The Author(s).)

Diabetes mellitus is a metabolic disease with an escalating global prevalence. Despite the abundance and relative efficacies of current therapeutic approaches, they primarily focus on attaining the intended glycaemic targets, but patients ultimately still suffer from various diabetes-associated complications such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis. There is a need to explore innovative and effective diabetic treatment strategies that not only address the condition itself but also combat its complications. One promising option is the reproductive hormone relaxin, an endogenous ligand of the RXFP1 receptor. Relaxin is known to exert beneficial actions on the cardiovascular system through its vasoprotective, anti-inflammatory and anti-fibrotic effects. Nevertheless, the native relaxin peptide exhibits a short biological half-life, limiting its therapeutic potential. Recently, several relaxin mimetics and innovative delivery technologies have been developed to extend its biological half-life and efficacy. The current review provides a comprehensive landscape of the cardiovascular effects of relaxin, focusing on its potential therapeutic applications in managing complications associated with diabetes. The latest advancements in the development of relaxin mimetics and delivery methods for the treatment of cardiometabolic disorders are also discussed., 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.)

Objectives: Diabetes mellitus is a metabolic condition with hyperglycemia. Literature has shown a correlation between poor sleep quality and duration with an increased incidence of insomnia in diabetic individuals. The goal of this study was to determine the magnesium and potassium supplementation effect among diabetic individuals with insomnia., Methods: A randomized controlled trial (single blind) was conducted on 320 patients with diabetes; after 2 months of follow-up, 290 patients completed the trial. The Insomnia Severity Index (ISI) was used to assess the severity and duration of insomnia, before and after the trial. Tablets containing supplements were prepared: placebo (T1), magnesium (Mg, T2), potassium (K, T3), and a combination of Mg and K (T4). Melatonin and cortisol (sleep hormones) were measured from blood (serum) using an enzyme-linked immunosorbent assay (ELISA), before and after the trial., Results: The study included 93 (32.1%) male and 197 (67.9%) female participants. According to the analysis, there was a significant association between the treatment groups and ISI after the trial (post-trial), p = 0.0001. Analysis showed that there was significant association between pre- and post-serum cortisol levels in treatment groups 2, 3, and 4 (T2, T3, and T4) as p -values are 0.001, 0.001, and 0.001 respectively. Similar findings were observed for serum melatonin., Conclusions: The study revealed that magnesium, potassium, and magnesium and potassium combined had a significant effect on serum cortisol and melatonin levels (sleep hormones). In addition, supplementation significantly decreased the severity of insomnia among patients with diabetes by improving sleep duration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khalid, Bashir, Mehboob, Anwar, Ali, Hashim, Waseem and Basharat.)

The iron-sulfur domain (CISD) proteins of CDGSH are classified into three classes: CISD1, CISD2, and CISD3. During premature ageing, mutations that affect these proteins, namely their binding sites, could result in reduced protein production and an inability to preserve cellular integrity. Consequently, this leads to the development of conditions such as diabetes. Notably, CISD3 plays a crucial role in the management of age-related disorders such as Wolfram syndrome, which is often referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Computational analyses have predicted that CISD3 regulates the redox state, safeguards the endoplasmic reticulum and mitochondria, and maintains intracellular calcium levels. CISD3, a member of a recently discovered gene family associated with the CDGSH iron protein apoptotic compensatory response, fulfils a crucial function in mitigating the effects of accelerated ageing. The compound "(-)-(2S)-7,4'-Dihydroxyflavanone" has been discovered by computational drug design as a possible activator of CISD3. It shows potential therapeutic benefits in ameliorating metabolic dysfunction and enhancing glucose regulation. The ligand binds to the binding pocket of the CISD3 protein, increasing the stability of the protein and enhancing its functionality. The current research investigates the binding processes of the molecule in various structures and its anticipated effects on these tissues, therefore providing valuable insights into the mitigation of age-related diabetes and metabolic dysfunction. The projected tripling of the worldwide population of individuals aged 50 and above by 2050 necessitates the urgent development of immunoinformatics-based approaches, including pharmaceutical therapies that target CISD3, to prevent age-related pathologies. The stimulation of CISD3, namely by compounds such as "(-)-(2S)-7,4'-Dihydroxyflavanone", has the potential to counteract telomere shortening and improve metabolic pathways., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Diabetes is closely associated with risk of stroke and its adverse sequelae. Approximately 20%-33% of patients with stroke have diabetes. In China, however, it is unclear how stroke affects healthcare utilisation, medications and complications among people with diabetes. This study aimed to analyse the clinical characteristics, treatment options, medical expenses and complications of hospital outpatient healthcare associated with stroke in patients with diabetes in China., Design: A retrospective, multicentre, observational study., Setting: Beijing Municipal Medical Insurance Database, with data from 2016 to 2018., Participants: The study included patients with diabetes whose data included 2016-2018 outpatient medication records and who had Beijing medical insurance. Patients who did not have continuous prescription records for more than 2 months were excluded from the analysis. In total, 2 853 036 people with diabetes were included, and patients who had and did not have a stroke were compared., Results: In our study, 19.75%-22.30% of patients with diabetes suffered from stroke between 2016 and 2018. The average annual medical cost for a patient diagnosed with diabetes is ¥9606.65, and the cost increases to ¥13 428.39 when diabetes was combined with stroke; thus, stroke increases the medical cost for patients with diabetes by 39.78% (p<0.0001). Among patients with diabetes who had a stroke, 4.76 medications were used (1.8 hypoglycaemic drugs and 2.97 non-hypoglycaemic drugs); these numbers were significantly greater than for patients with diabetes who did not have a stroke receiving both hypoglycaemic drugs and non-hypoglycaemic drugs (p<0.0001). Among patients with diabetes who did not have a stroke, 3.58 medications were used (1.66 hypoglycaemic drugs and 1.92 non-hypoglycaemic drugs). Patients with diabetes who had a stroke also had significantly greater incidences of diabetic peripheral neuropathy, diabetic kidney disease, diabetic retinopathy and diabetic angiopathy than those who did not have a stroke (p<0.0001). These drugs and costs increased with the number of complications (p<0.0001). The increased medical costs for each specific complication are also listed. We also analysed the medical costs and medication regimens stratified by sex, age group and complications., Conclusions: Stroke is associated with a significant increase in complications and medications for patients with diabetes and greatly adds to the economic burden of these patients. Early identification of stroke risk factors in patients with diabetes, as well as targeted poststroke diabetes management, is crucial from a socioeconomic perspective for a comprehensive management and treatment of stroke in patients with diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Oral diabetes medications are important for glucose management in people with diabetes. Although there are many health-related videos on Douyin (the Chinese version of TikTok), the quality of information and the effects on user comment attitudes are unclear., Objective: The purpose of this study was to analyze the quality of information and user comment attitudes related to oral diabetes medication videos on Douyin., Methods: The key phrase "oral diabetes medications" was used to search Douyin on July 24, 2023, and the final samples included 138 videos. The basic information in the videos and the content of user comments were captured using Python. Each video was assigned a sentiment category based on the predominant positive, neutral, or negative attitude, as analyzed using the Weiciyun website. Two independent raters assessed the video content and information quality using the DISCERN (a tool for assessing health information quality) and PEMAT-A/V (Patient Education Materials Assessment Tool for Audiovisual Materials) instruments., Results: Doctors were the main source of the videos (136/138, 98.6%). The overall information quality of the videos was acceptable (median 3, IQR 1). Videos on Douyin showed relatively high understandability (median 75%, IQR 16.6%) but poor actionability (median 66.7%, IQR 48%). Most content on oral diabetes medications on Douyin related to the mechanism of action (75/138, 54.3%), precautions (70/138, 50.7%), and advantages (68/138, 49.3%), with limited content on indications (19/138, 13.8%) and contraindications (14/138, 10.1%). It was found that 10.1% (14/138) of the videos contained misinformation, of which 50% (7/14) were about the method of administration. Regarding user comment attitudes, the majority of videos garnered positive comments (81/138, 58.7%), followed by neutral comments (46/138, 33.3%) and negative comments (11/138, 8%). Multinomial logistic regression revealed 2 factors influencing a positive attitude: user comment count (adjusted odds ratio [OR] 1.00, 95% CI 1.00-1.00; P=.02) and information quality of treatment choices (adjusted OR 1.49, 95% CI 1.09-2.04; P=.01)., Conclusions: Despite most videos on Douyin being posted by doctors, with generally acceptable information quality and positive user comment attitudes, some content inaccuracies and poor actionability remain. Users show more positive attitudes toward videos with high-quality information about treatment choices. This study suggests that health care providers should ensure the accuracy and actionability of video content, enhance the information quality of treatment choices of oral diabetes medications to foster positive user attitudes, help users access accurate health information, and promote medication adherence., (©Baolu Zhang, Surintorn Kalampakorn, Arpaporn Powwattana, Jutatip Sillabutra, Gang Liu. Originally published in JMIR Formative Research (https://formative.jmir.org), 18.10.2024.)

Diabetic wounds pose a significant challenge in healthcare due to impaired healing and increased risk of complications. In recent years, various drug delivery systems with stimuli-responsive features have been developed to address these issues. These systems enable precise dosage control and tailored drug release, promoting comprehensive tissue repair and regeneration. This review explores targeted therapeutic agents, such as carboxymethyl chitosan-alginate hydrogel formulations, nanofiber mats, and core-shell nanostructures, for diabetic wound healing. Additionally, the integration of nanotechnology and multifunctional biomimetic scaffolds shows promise in enhancing wound healing outcomes. Future research should focus on optimizing the design, materials, and printing parameters of 3D-bio-printed wound dressings, as well as exploring combined strategies involving the simultaneous release of antibiotics and nitric oxide for improved wound healing.

Background: The aim of this study was to investigate the efficacy and safety of tenecteplase versus alteplase in patients with acute ischemic stroke, considering their diabetes history and admission hyperglycemia status., Methods and Results: This was a post hoc analysis of the TRACE-2 (Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-2) randomized clinical trial that enrolled patients in China between June 2021 and May 2022. Eligible patients with acute ischemic stroke for standard intravenous thrombolysis, but ineligible for endovascular thrombectomy, were randomly assigned (1:1) to tenecteplase or alteplase within 4.5 hours of symptom onset. Admission hyperglycemia was defined as plasma glucose >7.8 mmol/L. The primary efficacy and safety outcome were excellent functional outcome at 90 days (modified Rankin Scale score of 0-1) and symptomatic intracranial hemorrhage within 36 hours, respectively. The Cochran-Mantel-Haenszel χ 2 test was used for the outcomes. Of the 1382 patients included, 369 (26.7%) had a history of diabetes, and 482 (34.9%) experienced admission hyperglycemia. The primary efficacy outcome, comparing tenecteplase to alteplase, was achieved in 93 (56.7%) versus 97 (48.3%) among patients with a history of diabetes ( P =0.11) and 335 (64.6%) versus 300 (62.2%) among those without diabetes ( P =0.45), respectively. The primary efficacy outcome for tenecteplase versus alteplase was comparable among patients with and without admission hyperglycemia (57.5% versus 53.9%, P  = 0.44; 65.4% versus 60.4%, P =0.12, respectively). No significant difference in the risk of symptomatic intracranial hemorrhage within 36 hours was observed between tenecteplase and alteplase, regardless of diabetes history or admission hyperglycemia., Conclusions: This study demonstrated that intravenous tenecteplase exhibits similar clinical outcomes compared with alteplase, irrespective of the patient's glucose metabolism status., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04797013.

Objective: To review and validate a questionnaire on knowledge of injectable insulin management (JH-SEFAC) by patients with diabetes for use in community pharmacies., Methods: Study design: cross-sectional observational in Spanish community pharmacies during the first half of 2023. Inclusion criteria: patients with diabetes, of legal age, on insulin treatment. Questionnaire design: a nominal group of community pharmacists reviewed and piloted the initial questionnaire to determine its feasibility. It was approved by the CEIC of Aragón (PI22/375). Content validation: by a multidisciplinary group of experts in diabetes, using an ad hoc evaluation questionnaire of 10 questions (Likert scale of 1-5). Reliability: by means of the internal consistency index (Cronbach's alpha) and the intraclass correlation coefficient (ICC). Reproducibility (test/retest): the results of the questionnaire administered twice 2-3 weeks apart to the group of patients were compared. Pharmacists members of the SEFAC Diabetes Working Group collaborated. Sample: calculated in 127 subjects (95% CI and precision of 10%)., Results: 20 community pharmacies from 13 autonomous communities included 131 patients. The expert assessment was 4.52 out of 5 (90.4%). The Keiser-Meyer-Olkin test was 0.626 and Bartlett's test was significant (p<0.001). The Cronbach's alpha of the global questionnaire was 0.804 and the ICC was 0.902. The mean score of the questionnaire was 15.98 out of 31 points., Conclusions: The JH-SEFAC questionnaire was validated to evaluate the management of insulin injectables, providing community pharmacists with a valuable tool for therapeutic education., (Copyright SEFAC. Sociedad Española de Farmacia Clínica, Familiar y Comunitaria. This article is available from url https://www.farmaceuticoscomunitarios.org/.)

Diabetes mellitus is associated with chronic wound-healing problems that significantly impact patients' quality of life and substantially increase expenditure on healthcare. Therefore, the identification of compounds that can aid healing is justified. Anredera cordifolia (Ten.) has been used in folk medicine for curative purposes; however, the causal mechanisms underlying its healing effects remain to be elucidated. In this study, the effect of the ethanolic extract of A. cordifolia was evaluated in an in vitro healing model using fibroblasts cultivated under normoglycemic and hyperglycemic environments. The extract was predominantly composed of phytol and exhibited genoprotective activity. Fibroblast migration attenuated the adverse effects of hyperglycemia, favoring cell proliferation. Collagen levels were significantly increased in ruptured fibroblasts under both standard and hyperglycemic environments. The phytogenomic effect of the extract on three genes related to extracellular matrix formation, maintenance, and degradation showed that A. cordifolia increased the expression of genes related to matrix synthesis and maintenance in both normoglycemic and hyperglycemic individuals. Furthermore, it reduced the expression of genes related to matrix degradation. Overall, this is the first study to demonstrate the effectiveness of A. cordifolia in wound healing, elucidating possible causal mechanisms that appear to be based on the genoprotective effect of this plant on the migratory and proliferative phases of the wound healing process; these effects are probably related to phytol, its main constituent., Competing Interests: The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2024 Elisa Vanessa Heisler et al.)

The integrated stress response (ISR) is a vital signaling pathway initiated by four kinases, PERK, GCN2, HRI and PKR, that ensure cellular resilience and protect cells from challenges. Here, we investigated whether increasing ISR signaling could rescue diabetes-like phenotypes in a mouse model of diet-induced obesity (DIO). We show that the orally available and clinically approved GCN2 activator halofuginone (HF) can activate the ISR in mouse tissues. We found that daily oral administration of HF increases glucose tolerance whilst reducing weight gain, insulin resistance, and serum insulin in DIO mice. Conversely, the ISR inhibitor GSK2656157, used at low doses to optimize its selectivity, aggravates glucose intolerance in DIO mice. Whilst loss of function mutations in mice and humans have revealed that PERK is the essential ISR kinase that protects from diabetes, our work demonstrates the therapeutic value of increasing ISR signaling by activating the related kinase GCN2 to reduce diabetes phenotypes in a DIO mouse model., (© 2024 MRC Laboratory of Molecular Biology.)

Hormone therapy, especially androgen deprivation therapy (ADT), is effective against prostate cancer (PC), whereas long-term ADT is a risk for metabolic/cardiovascular disorders including diabetes (DM), hypertension (HT) and dyslipidemia (DL), and might result in progression to castration-resistant prostate cancer (CRPC). We thus conducted a multicenter retrospective cohort study to ask whether CRPC progression would be associated positively with HT, DM or DL and negatively with statins prescribed for treatment of DL. In this study, 1,112 nonmetastatic PC patients undergoing ADT were enrolled. Univariate statistical analyses clearly showed significant association of HT or DM developing after ADT onset, though not preexisting HT or DM, with early CRPC progression. On the other hand, preexisting DL or statin use, but not newly developed DL or started statin prescriptions following ADT, was negatively associated with CRPC progression. Multivariate analysis revealed significant independent association of the newly developed DM or HT, or preexisting statin use with CRPC progression [adjusted hazard ratios (95% confidence intervals): 3.85 (1.65-8.98), p = 0.002; 2.75 (1.36-5.59), p = 0.005; 0.25 (0.09-0.72), p = 0.010, respectively]. Together, ADT-related development of HT or DM and preexisting statin use are considered to have positive and negative impact on CRPC progression, respectively., (© 2024. The Author(s).)

Introduction: The primary objective of this study is to report the results of an online questionnaire and the in-person discussion sessions of physicians specializing in diabetes care in which their opinions about current diabetes management was obtained., Methods: The Diabetes Innovation Summit 2023 drew attendance from a diverse group of specialized physicians from multiple countries. A comprehensive literature review was conducted to examine the technologies and medical needs associated with diabetes management. Using the results of the review, a questionnaire was developed by three experts from the steering committee to solicit feedback from specialized physicians. The online survey was made accessible between 10th December 2022 and 10th January 2023. Following the online survey, six structured in-person discussion sessions were conducted with specialized physicians from the Middle East, Central-Eastern Europe, and North Africa regions., Results: The study revealed that about 59% of survey requests were answered, with many participants being pediatric endocrinologists from North Africa. Around 60% of diabetes patients followed Multiple Daily Injections (MDI) according to specialized physicians. Among MDI users, 62% employed Blood Glucose Monitors (BGM), 31% used intermittent-scanning Continuous Glucose Monitors (isCGM), and 23% used CGM. In North Africa, nearly 90% of patients used MDI due to financial constraints. While physicians focused on both Time in Range (TIR) and HbA1c for MDI-treated patients, satisfaction with TIR achieved was expressed by 31%, while 74·1% believed Real-Time CGM (rtCGM) was effective. Concerns arose about potentially misleading HbA1c results and the relatively low patient achievement of target TIR despite CGM usage. The Smart MDI System was seen favorably compared to other applications. The system's affordability was a significant barrier, particularly in the Middle East and Africa., Conclusion: The present study highlights that physicians are generally supportive of utilizing new technology. The questionnaires and the open discussion revealed the expectation that the Smart MDI technology provides better control, primarily by identifying missed boluses, while expressing concerns on the use of the technology by teenagers and children, who might forget the device and be reluctant to use in public, and by the older population, who might be challenged by the technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Koçkaya, Battelino, Petrovski, Jendle, Sármán, Elbarbary, Gökşen, Alharbi, Tibet, Sharaf, Ökçün, Öztürk and Kurnaz.)

Introduction: Studies have shown the relative cardiovascular safety of hormone replacement therapy (HRT) for women in the general population. Evidence on women with diabetes remains scarce. We aimed to investigate the risk of cardiovascular disease (CVD) in menopausal women with diabetes who use HRT compared to non-users., Methods: Search across Medline, Embase, Web of Sciences, and Cochrane databases up to November 2023 was conducted. We combined keywords of menopause, diabetes, HRT, and various CVD outcomes. Non-English studies, observational studies other than cohort and case-control, reviews, and conference abstracts were excluded. Bias was checked using validated risk-of-bias tools. Random-effects model was used to calculate pooled relative risks (RR) for similar outcomes., Results: Out of 7625 identified articles, 19 (6 clinical trials and 13 observational studies) were included, primarily from Europe and the U.S.A. Most studies had moderate risk of bias. Meta-analysis of myocardial infarction (MI) risk from nine observational studies ( n  =  ~34,626) showed a pooled RR of 0.83 (95% CI 0.62-1.12). Limited data precluded meta-analysis for the clinical trials and other outcomes from observational studies., Conclusions: Observational studies do not suggest an increased risk of MI in menopausal women with diabetes prescribed HRT. Further research with a more robust method is warranted to validate this finding., Prospero Registration Number: CRD42023479335.

Numerous studies have demonstrated that use of continuous glucose monitoring (CGM) significantly improves overall glycemic control and reduces the frequency and severity of hypoglycemic events in individuals treated with intensive insulin, nonintensive insulin, and noninsulin therapies, with reductions in both all-cause and diabetes-related health care resource utilization and lower costs. However, implementation of CGM including prescribing and assessment of the ambulatory glucose profile to make clinical decisions in primary care settings is low. A recent pilot program was initiated at MetroHealth System (Cleveland, Ohio) to implement a CGM integration program for primary care offices throughout the system. Based on the experience and successes from this health system as well as current literature, rationale will be discussed to support the expansion of CGM to individuals enrolled in all Medicaid programs.

Ongoing innovations in glucose monitoring, insulin delivery, and telehealth technologies have created a digital diabetes ecosystem populated by connected tools and technologies that have been shown to improve clinical outcomes, lower costs, and reduce the burden of diabetes. Advances in connected continuous glucose monitoring devices, insulin pumps, and insulin pens have led to the development of automated insulin delivery systems that modulate insulin infusion based on sensor glucose data. Similar integrations of continuous glucose monitoring and connected blood glucose meter data into "smart" pens have lessened the guesswork of intensive insulin management for individuals who prefer traditional injection therapy. A growing number of health apps that can be accessed through smartphones and wearable devices provide information and advice that support individuals in adopting healthier lifestyles. The differences in features and functionality give users the ability to select the devices that best meet their unique requirements and preferences. This article reviews the most current digital diabetes technologies and discusses how the connectivity of these tools can create an overarching architecture of feedback mechanisms that monitor an individual's health status, motivate and enhance adherence to self-management, and provide advice and decision-support tools to clinicians as well as other members of the health care team to make living with diabetes more manageable.

Background: The coexistence of diabetes and hypertension is prevalent due to shared risk factors. Pharmacological treatment has been reported to be effective in managing both conditions. However, treatment effectiveness depends on the extent to which a patient adheres to their treatment. Poor adherence to long-term treatment for chronic diseases is a growing global problem of significant magnitude. Several interventions have been developed to help improve medication adherence in patients with coexisting diabetes and hypertension. This review aimed to determine the characteristics of these interventions and their impact on medication adherence., Methods: A systematic review of the literature was conducted using the PRISMA guidelines and registered in the PROSPERO International Registry of Systematic Reviews. Studies were searched in the databases CINAHL, Embase and Medline to identify relevant articles published during 2012-2023. The search concepts included 'medication adherence', 'hypertension', 'diabetes' and 'intervention'. Studies were included if they were in English and evaluated the impact of an intervention aimed at promoting adherence to medications for both diabetes and hypertension., Results: Seven studies met the inclusion criteria, with five demonstrating a statistically significant improvement in medication adherence. Of the five studies that improved medication adherence, four were multifaceted and one was a single-component intervention. All successful interventions addressed at least two factors influencing non-adherence. Patient education was the foundation of most of the successful interventions, supported by other strategies, such as follow-ups and reminders., Conclusion: Multifaceted interventions that also included patient education had a positive impact on medication adherence in patients with coexisting diabetes and hypertension. Improving adherence in patients with coexisting diabetes and hypertension requires a multipronged approach that considers the range of factors impacting medication-taking., Patient or Public Contribution: This systematic review provides comprehensive insights into the benefits of patient-centred approaches in intervention development and strengthening. Such patient involvement ensures that medication adherence interventions are more relevant, acceptable and effective, ultimately leading to better health outcomes and more meaningful patient engagement in healthcare research., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Diabetes is one of the common endocrine disorders generally characterized by elevated levels of blood sugar. It can originate either from the inability of the pancreas to synthesize insulin, which is considered as an autoimmune disorder, or the reduced production of insulin, considered as insulin resistivity. A wound can be defined as a condition of damage to living tissues including skin, mucous membrane and other organs as well. Wounds get complicated with respect to time based on specific processes like diabetes mellitus, obesity and immunocompromised conditions. Proper growth and functionality of the epidermis gets sustained due to impaired diabetic wound healing which shows a sign of dysregulated wound healing process. In comparison with synthetic medications, phytochemicals like flavonoids, tannins, alkaloids and glycosides have gained enormous importance relying on their distinct potential to heal diabetic wounds. Flavonoids are one of the most promising and important groups of natural compounds which can be used to treat acute as well as chronic wounds. Flavonoids show excellent properties due to the presence of hydroxyl groups in their chemical structure, which makes this class of compounds different from others. Based on the novel principles of nanotechnology via utilizing suitable drug delivery systems, the delivery of bioactive constituents from plant source amplifies the wound-healing mechanism, minimizes complexities and enhances bioavailability. Hence, the encapsulation and applicability of flavonoids with an emphasis on mechanistic route and wound-healing therapeutics have been highlighted in the subsequent study with focus on multiple drug delivery systems., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study investigates the efficacy of four previously studied compounds (Swertiamarin, Apigenin, Mangiferin, and Tatanan A) in activating GCK using computational methods. Initial molecular docking revealed binding affinities ranging from -6.7 to -8.6 kcal/mol. The compounds were then evaluated for drug-likeness and pharmacokinetic properties. Re-docking studies were performed for validation. Based on their favorable binding affinities and compliance with Lipinski's rule and ADMET criteria, three compounds (Swertiamarin, Apigenin, and Tatanan A) were selected for molecular dynamics (MD) simulations. MD simulations demonstrated that Swertiamarin showed excellent stability, as indicated by analyses of RMSD, RMSF, radius of gyration (Rg), hydrogen bonding, and principal component analysis (PCA). These results suggest that Swertiamarin holds promise for further investigation in in vivo and clinical settings to evaluate its potential in enhancing GCK activity and treating diabetes. This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating 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 Elsevier Ltd. All rights reserved.)

Incretin hormones potentiate the glucose-induced insulin secretion following enteral nutrient intake. The best characterised incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) which are produced in and secreted from the gut in response to nutrient ingestion. The property of incretins to enhance endogenous insulin secretion only at elevated blood glucose levels makes them interesting therapeutics for type 2 diabetes mellitus with a better safety profile than exogenous insulin. While incretin therapeutics (especially GLP-1 agonists, and more recently also GLP-1 / GIP dual agonists and other drugs that influence the incretin metabolism (e.g., dipeptidyl peptidase-4 (DPP-4) inhibitors)) are already widely used treatment options for human type 2 diabetes, these drugs are not yet approved for the therapy of feline diabetes mellitus. This review provides an introduction to incretins and feline diabetes mellitus in general and summarises the current study situation on incretins as therapeutics for feline diabetes mellitus to assess their possible future potential in feline medicine. Studies to date on the use of GLP-1 receptor agonists (GLP-1RA) in healthy cats largely confirm their insulinotropic effect known from other species. In diabetic cats, GLP-1RAs appear to significantly reduce glycaemic variability (GV, an indicator for the quality of glycaemic control), which is important for the management of the disease and prevention of long-term complications. However, for widespread use in feline diabetes mellitus, further studies are required that include larger numbers of diabetic cats, and that consider and test a possible need for dose adjustments to overweight and diabetic cats. Also evaluation of the outcome of GLP-1RA monotherapy will be neceessary., Competing Interests: Declaration of competing interest Thomas A. Lutz is a consultant for Novo Nordisk, Boehringer Ingelheim, Zealand Pharma, Prolynx, Eracal and Structure Therapeutics. Thomas A. Lutz has ongoing collaborations with Novo Nordisk., (Copyright © 2024. Published by Elsevier Inc.)

Objective: We aimed to assess the feasibility, clinical accuracy, and acceptance of a hospital-wide continuous glucose monitoring (CGM) policy with electronic health record (EHR)-integrated validation for insulin dosing., Research Design and Methods: A hospital policy was developed and implemented at Stanford Health Care for using personal CGMs in lieu of fingerstick blood glucose (FSBG) monitoring. It included requirements specific to each CGM, accuracy monitoring protocols, and EHR integration. User experience surveys were conducted among a subset of patients and nurses., Results: From November 2022 to August 2023, 135 patients used the CGM protocol in 185 inpatient encounters. This group included 27% with type 1 diabetes and 24% with automated insulin delivery systems. The most-used CGMs were Dexcom G6 (44%) and FreeStyle Libre 2 (43%). Of 1,506 CGM validation attempts, 87.8% met the 20% or 20 mg/dL (%20/20) criterion for CGM-based insulin dosing and 99.3% fell within Clarke zones A or B. User experience surveys were completed by 27 nurses and 46 patients. Most nurses found glucose management under the protocol effective (74%), easy to use (67%), and efficient (63%); 80% of nurses preferred inpatient CGM to FSBG. Most patients liked the CGM protocol (63%), reported positive CGM interactions with nursing staff (63%), and felt no significant interruptions to their diabetes management (63%)., Conclusions: Implementation of a hospital-wide inpatient CGM policy supporting multiple CGM types with real-time accuracy monitoring and integration into the EHR is feasible. Initial feedback from nurses and patients was favorable, and further investigation toward broader use and sustainability is needed., (© 2024 by the American Diabetes Association.)

Glucagon was discovered about a hundred years ago and its role in health and disease is under continuous investigation. Glucagon is a counter regulatory hormone secreted by alpha cells of the pancreas in response to multiple stimuli. Although some of glucagon's actions and its clinical application have been described, clinical experience with glucagon has been historically overshadowed by that of insulin. To date, the role of glucagon's actions in pharmacotherapy has been under explored. Glucagon plays a considerable role as a hormonal regulator via its known actions on the liver. The rise in obesity and diabetes mellitus prevalence is bringing focus to glucagon's known physiological roles and possible clinical applications. Six glucagon products and a glucagon analog are approved for use in the United States. Clinical pharmacology studies provide crucial support of glucagon's actions as evident from comprehensive pharmacokinetics and pharmacodynamics evaluations in humans. Here, we briefly describe the established physiological role of glucagon in humans and its known relationship with disease. We later summarize the clinical pharmacology of available glucagon products with different routes of administration., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Background & Aims: Diabetes mellitus is a metabolic disorder, in which chronic systemic inflammation and oxidative stress contribute to the progression of this condition and its complications. Melatonin, a hormone known for its potent antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic intervention in diabetes. This review aims to evaluate the effects of melatonin supplementation on markers of oxidative stress and inflammation in diabetic patients., Methods: A thorough literature search of databases, including PubMed, Embase, Web of Science, Cochrane Central, CNKI, and Scopus, was conducted through October 2023. We included randomized controlled trials investigating the effects of melatonin on markers of inflammation and oxidative stress, compared to placebo in patients with diabetes. The data was analyzed using the random-effects model and the summary effect size was determined using the standardized mean difference (SMD) with 95% confidence interval (CI)., Results: Fourteen studies with 823 participants were included. Our analysis indicates that melatonin can lead to significant reductions in levels of C-reactive protein (CRP) [SMD = -0.75; 95% CI: -1.37, -0.12; P = 0.018], tumor necrosis factor-alpha (TNF-α) [SMD = -0.40; 95% CI: -0.64, -0.15; P = 0.001], interleukin (IL)-1 [SMD = -0.75; 95% CI: -1.03, -0.47; P < 0.0001], IL-6 [SMD = -0.79; 95% CI: -1.07, -0.51; P < 0.0001], and malondialdehyde (MDA) [SMD = -0.61; 95% CI: -0.80, -0.43; P < 0.0001]. Furthermore, we found a significant increase in levels of total antioxidant capacity (TAC) [SMD = 0.81; 95% CI: 0.12, 1.51; P = 0.021], glutathione (GSH) [SMD = 0.66; 95% CI: 0.28, 1.03; P = 0.001], and superoxide dismutase (SOD) [SMD = 1.69; 95% CI: 0.80, 2.58; P < 0.0001] following melatonin consumption in patients with diabetes., Conclusion: Melatonin supplementation is a promising complementary strategy to attenuate oxidative stress and inflammation in diabetic patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Purpose: Telemedicine has been essential during the coronavirus disease 2019 (COVID-19) pandemic. In March 2020, pharmacist-led chronic disease state management services at our family care centers and primary care clinics were converted to telemedicine. This study aimed to determine the impact of expanding telemedicine services on appointment adherence, clinical outcomes, and financial reimbursement. Methods: This was a single-center, retrospective, quasi-experimental study of the impact of expanding telemedicine services on adult patients with diabetes, hypertension, and/or hyperlipidemia. The study included patients scheduled with a pharmacist at a hospital-based (HB) or physician-based (PB) clinic. The primary outcome was the difference in the mean no-show rate. The secondary outcomes were differences in mean change in HbA1c, LDL, blood pressure, and reimbursement. Mean differences between pre- and post-telemedicine groups of each clinic were measured for all outcomes. Results: The mean difference (SE) in the no-show rate in the HB clinic was -12.09% (4.862; P = .014), compared to 2.88% (3.656; P = .431) in the PB clinic. The mean difference (SE) in the change in HbA1c in the HB clinic was .00% (.338; P = .992), compared to .01% (.239; P = .945) in the PB clinic. The mean difference (SE) in reimbursement in the HB clinic was $1.93 (4.209; P = .647), compared to $20.46 (3.210; P < .0001) in the PB clinic. Conclusion: Expansion of pharmacy telemedicine services provided evidence for improved appointment adherence in the HB clinic and increased reimbursement in the PB clinic. No change in healthcare outcomes was observed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Suboptimal glycaemic management in hospitals has been associated with adverse clinical outcomes and increased financial costs to healthcare systems. Despite the availability of guidelines for inpatient glycaemic management, implementation remains challenging because of the increasing workload of clinical staff and rising prevalence of diabetes. The development of novel and innovative technologies that support the clinical workflow and address the unmet need for effective and safe inpatient diabetes care delivery is still needed. There is robust evidence that the use of diabetes technology such as continuous glucose monitoring and closed-loop insulin delivery can improve glycaemic management in outpatient settings; however, relatively little is known of its potential benefits and application in inpatient diabetes management. Emerging data from clinical studies show that diabetes technologies such as integrated clinical decision support systems can potentially mediate safer and more efficient inpatient diabetes care, while continuous glucose sensors and closed-loop systems show early promise in improving inpatient glycaemic management. This review aims to provide an overview of current evidence related to diabetes technology use in non-critical care adult inpatient settings. We highlight existing barriers that may hinder or delay implementation, as well as strategies and opportunities to facilitate the clinical readiness of inpatient diabetes technology in the future., (© 2024. The Author(s).)