Search

Neonatal diabetes mellitus (NDM), defined as diabetes with an onset during the first 6 months of life, is a rare form of monogenic diabetes. The initial publications on this condition began appearing in the second half of the 1990s and quite surprisingly, the search for new NDM genes is still ongoing with great vigor. Between 2018 and early 2024, six brand new NDM-genes have been discovered (CNOT1, FICD, ONECUT1, PDIA6, YIPF5, ZNF808) and three genes known to cause different diseases were identified as NDM-genes (EIF2B1, NARS2, KCNMA1). In addition, NDM cases carrying mutations in three other genes known to give rise to diabetes during childhood have been also identified (AGPAT2, BSCL2, PIK3R1). As a consequence, the list of NDM genes now exceeds 40. This genetic heterogeneity translates into many different mechanism(s) of disease that are being investigated with state-of-the-art methodologies, such as induced pluripotent stem cells (iPSC) and human embryonic stem cells (hESC) manipulated with the CRISPR technique of genome editing. This diversity in genetic causes and the pathophysiology of diabetes dictate the need for a variety of therapeutic approaches. The aim of this paper is to provide an overview on recent achievements in all aspects of this area of research., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Diabetes is a widespread disease that needs to be controlled. Therapeutic monitoring of drugs is very helpful in maintaining desirable doses. To study a correlation between the blood level of metformin (to a lesser extent, glimepiride) and genotyping (mainly the SULT1A1 genotype). Determine drug levels using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) tool. A validated LC-MS/MS method was developed to determine metformin and glimepiride levels in human plasma. DNA extraction was performed using Jena Bioscience's Blood DNA preparation, in which a column kit was used to extract DNA for genetic polymorphism. The investigation was carried out using both medications in type 2 diabetes patients alongside the genetic polymorphism. One hundred and six patients were assessed. The prevalence of homozygosity for SULT1A1 and wild-type CYP2D6 * 4 were 72.6% and 73.6%, respectively. After adjustment for daily intake of metformin, three patients out of five with the highest levels of metformin had no homozygosity (SULT1A1 genotype). Statistically, variables that demonstrated an insignificant correlation with the level of metformin were body mass index (rs (87) = 0.32, P = 0.011) and age (rs (87) =0.26, P = 0.017). The homozygous (SULT1A1 genotype) correlation was moderate (rs (87) =0.21, P = 0.052). According to the findings, patients with the wt/wt CYP2D6 genotype had considerably greater levels of endoxifen than those with the v/v CYP2D6 genotype. The study's results reported a probable correlation between the blood level of metformin (to a lesser extent, glimepiride) and genotyping (mainly the SULT1A1 genotype). Genotype-guided drug therapy may provide a novel contribution to maximize drug efficacy and/or minimize toxicity., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Advanced Pharmaceutical Technology & Research.)

Atorvastatin, a widely prescribed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (HMG-CoA reductase inhibitor), is associated with various adverse effects, including many dermatologic manifestations. We present the case of a 73-year-old man who developed eosinophilic spongiosis shortly after initiating atorvastatin therapy, an adverse effect which to our knowledge has not yet been reported in association with atorvastatin. Our investigation explores the clinical and histopathologic characteristics of eosinophilic spongiosis induced by atorvastatin, delving into potential mechanisms behind statin-induced eosinophilia. A literature review, focusing on atorvastatin's dermatological side effects, revealed a limited number of relevant studies, emphasizing the scarcity of documented cases. Our aim is to raise awareness of eosinophilic spongiosis as a potential side effect of atorvastatin, emphasizing its impact on patients' quality of life. This case prompts further research into the mechanisms underlying such dermatologic reactions, contributing to a better understanding of atorvastatin's diverse adverse effects., Competing Interests: This work was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. This material is the result of work supported with resources and the use of facilities at the Orlando VA Healthcare System (Orlando, Florida). The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government., (Copyright © 2024, Al-Moussally et al.)

In patients with diabetes, diabetic ketoacidosis (DKA) is a well-documented potential complication, usually presenting with hyperglycemia, anion gap acidosis, and positive ketones. Metformin toxicity in the setting of acute renal failure is also a well-known cause of lactic acidosis. However, metformin-induced euglycemic ketoacidosis is less well-known or studied. We report a case of metformin toxicity in the setting of acute renal failure with both lactic acidosis and ketosis and an initial confounded clinical presentation of sulphonylurea-induced hypoglycemia. A high index of suspicion for metformin-associated lactic acidosis (MALA) and metformin-associated lactic acidosis with euglycemic ketoacidosis (MALKA) should be in place in patients who are taking metformin and presenting with acute renal failure and euglycemia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Al-Moussally et al.)

Diabetes mellitus poses a substantial global health challenge, necessitating innovative approaches to improve patient outcomes. Conventional one-size-fits-all treatment strategies have shown limitations in addressing the diverse nature of the disease. In recent years, personalized medicine has emerged as a transformative solution, tailoring treatment plans based on individual genetic makeup, lifestyle factors, and health characteristics. This review highlights the role of genetic screening in predicting diabetes susceptibility and response to treatment, as well as the potential of pharmacogenomics in optimizing medication choices. Moreover, it discusses the incorporation of lifestyle modifications and behavioral interventions to empower patients in their health journey. Telemedicine and remote patient monitoring are also examined for their role in enhancing accessibility and adherence. Ethical considerations and challenges in implementing personalized medicine are addressed. The review envisions a future where personalized medicine becomes a cornerstone in diabetes management, ensuring improved patient outcomes and fostering more effective and patient-centric care on a global scale., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sugandh et al.)

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with maternal and infant health. Although the pathogenesis of PE and GDM remains controversial, oxidative stress is involved in the underlying pathology of GDM and PE. Protein lysine acetylation (Kac) plays an important regulatory role in biological processes. There is little data regarding the association of the maternal acetylome with GDM and PE. This study aimed to assess the potential value of the proteome and acetylome for GDM and PE. In our study, we included placental tissues from healthy individuals (n = 6), GDM patients (n = 6), and PE patients (n = 6) to perform 4D-label free quantification proteomics analysis and PRM analysis. We identified 22 significantly regulated proteins and 192 significantly regulated acetylated proteins between the GDM and PE groups. Furthermore, 192 significantly regulated acetylated proteins were mainly enriched in endoplasmic reticulum stress (ERS) and ferroptosis pathways. Seventeen acetylated sites in these two pathways were verified by PRM analysis. Our comprehensive analysis revealed key features of GDM/PE-significantly regulated acetylated proteins in the placentas from GDM and PE. The results of signaling pathway analysis focused on ERS and ferroptosis. These findings may help explore the underlying pathology, new biomarkers, and therapeutic targets of GDM and PE., (© 2022 Wiley-VCH GmbH.)

Aims and Objectives: The aim of the present paper is to provide a narrative review of the markers and pathways of periodontitis-associated insulin resistance (IR)., Materials and Methods: Research papers published in peer-reviewed scientific journals from 2000 to 2021 were searched systematically in Online Cochrane Library, Google Scholar, and MedLine/PubMed database. The medical subject headings (MeSH) terms used for literature search were "diabetes AND periodontal disease," "diabetes AND periodontitis," "inflammation AND insulin resistance," "Insulin resistance AND periodontal disease," and "insulin resistance AND periodontitis." Manual search for applicable work in review article peer-reviewed print journals, and latest editions of standard textbooks of pharmacology and pathology were searched for updated additional information. Relevant papers in English language on the topic and abstracts of pertinent articles after excluding the duplicates, animal studies, and in-vitro studies were also scrutinized thoroughly and finally included as required in this narrative review., Results: Literature search in MedLine/PubMed with MeSH words mentioned above revealed 4,621, 4,993, 19,349, 414, and 434 papers, respectively. Seven out of 13 systematic reviews and a total of 18 randomized clinical trials to evaluate periodontitis-induced IR were short-listed to update current evidences. The current literature in the past two decades has evaluated the effect of periodontal therapy on various type-2 diabetes (T2D) biomarkers following periodontal therapy. These indicators of periodontal disease activity and surrogate biomarkers of T2D in periodontitis may be an important diagnostic tool for the early prediction of complications due to IR. This increased systemic burden of proinflammatory cytokines by periodontitis can be reduced by periodontal therapy, thus improving the patient's overall systemic condition., Conclusion: The inflammatory response in periodontitis is characterized by dysregulated secretion of host-derived mediators of inflammation and tissue breakdown that may lead to IR. It can be comprehended that periodontal disease is a recognized amendable risk factor for T2D., Competing Interests: None to declare., (Copyright: © 2022 Journal of International Society of Preventive and Community Dentistry.)

Background: Overweight and obesity are well-known risk factors for type 2 diabetes mellitus (T2DM). The effect of the maximum body mass index (BMImax), which indicates the highest body weight before the diagnosis of T2DM, is not fully understood. This study aimed to explore the predictive value of BMImax in the progression of diabetes., Methods: This prospective study recruited 2018 subjects with normal glucose tolerance in Beijing, China. The subjects were followed up for eight years, and the association between BMImax and glucose outcomes was evaluated., Results: Ninety-seven of the 2,018 participants developed diabetes by the end of the study. Compared to individuals with normal glucose tolerance, those who developed diabetes were characterized by higher levels of fasting plasma glucose (FPG), 2 h postload glucose (PBG), glycosylated hemoglobin (HbA 1c ), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-c), a higher prevalence of a familial history of diabetes and a lower level of high-density lipoprotein cholesterol (HDL-c). Multivariate regression analysis of sex-stratified groups suggested that FPG, HbA 1c , SBP and familial history of diabetes were independent risk factors for diabetes, but that BMImax was a unique indicator for female patients., Conclusions: BMImax might be an independent predictor of T2DM in females, but it does not seem to be associated with the risk of diabetes in males. BMImax could be regarded as an indicator in the prevention and management of diabetes., 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 © 2022 Jia, Wang, Yang, Cheng, Wang, Ba, Dou, Mu, Zhao and Lyu.)

Glucagon-like peptide-1 (GLP-1) receptor agonists modified with albumin ligands which can specificity bind to the human serum albumin (HSA) was an efficient strategy to prolong the half-time of GLP-1. Herein, we investigated the effect of small-molecule albumin ligand modification on the hypoglycemic activities of GLP-1 derivatives. Two GLP-1 derivatives MPA-C12-GLP-1 and Rhein-C12-GLP-1 were achieved by modification of the side chain amino of lysine in position 26 of the Arg34-GLP-1(7-37)-OH with Rhein and 3-Maleimidopropionic acid respectively using 12-aminolauric acid as a linker, and its specific albumin-conjugating characteristics, pharmaceutical characterization, and the antidiabetic effects were investigated. In vitro level, two GLP-1 derivatives demonstrated a higher binding capacity to GLP-1 receptor than that of Arg34-GLP-1(7-37)-OH. Interestingly, although the binding ability of MPA-C12-GLP-1 was equal to liraglutide, the binding ability of Rhein-C12-GLP-1 was 10-fold higher than liraglutide. In vivo level, the two GLP-1 derivatives can significantly increase their glucose tolerance and prolong their half-life in ICR mice, and they were also superior to GLP-1 in controlling glucose homeostasis and suppression of food intake and water consumption in db/db mice. Importantly, the two GLP-1 derivatives showed comparable efficacy to liraglutide for the therapy of type 2 diabetes mellitus. The in vitro INS-1 cells toxicity and the in vivo hepatotoxicity indicated that the Rhein-C12-GLP-1 was a safe candidate for the therapy of type 2 diabetes, and the serum biomarkers determination results showed that the Rhein-modified GLP-1 could significantly improve the HbA 1c and blood lipids, and the H&E stain exhibited that the Rhein-C12-GLP-1 can effectively promote β-cell proliferation and differentiation. In conclusion, the 3-Maleimidopropionic acid or Rhein-modified GLP-1derivatives have great potential for development as a Type 2 diabetes mellitus therapeutic drug., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: In this study, the prevalence of diabetes and pre-diabetes (pre-DM) has been estimated; also, some factors related to diabetes and pre-diabetes in the city of Kharameh, southern Iran, were investigated., Methods: This cross-sectional study was conducted on a total of 10,474 subjects aged 40-70 years who participated in phase one of PERSIAN Kharameh cohort carried out between 2015 and 2016. Eligible individuals were included in the study by census method., Results: Prevalence of diabetes is 20.17% (95% CI: 19.95-20.39) and that of pre-diabetes is 15.74% (95% CI 15.54-15.93). Multivariate logistic regression results showed that the prevalence of diabetes had a direct relationship with increasing age (p < 0.001), being single (p = 0.005), family history of diabetes (p < 0.001), abdominal obesity (p < 0.001), hypertension (p: < 0.001), and high triglycerides (p: < 0.001); also, it had an inverse relationship with residence in rural areas (p < 0.001), education (p < 0.001), and employment (p < 0.001).Also, the prevalence of pre-diabetes showed a direct relationship with increasing age (60-70 years p = 0.010), being single (p = 0.004), living in rural areas (P < 0.001), having a family history of diabetes ( both P = 0.023), abdominal obesity (P < 0.001), hypertension (P < 0.001), high cholesterol (P < 0.001) and high triglycerides (P < 0.001), and an inverse relationship with female gender (P < 0.001), education (high school P = 0.022), employment (P = 0.010), and smoking habit (P = 0.019). These results were all statistically significant., Conclusion: The present study shows the high prevalence of diabetes and pre- diabetes in the city of Kharameh. Diabetes prevention policies should be developed and implemented for the public., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest to the publication of this article., (© Springer Nature Switzerland AG 2021.)

Background: It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study., Methods: This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006-2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35 mg/kg/min) to T3 (≤ 4.14 mg/kg/min, highest IR)., Results: CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p < 0.0001, and hazard ratio [HR] adjusted for multiple confounders including DKD, 1.140 [95% confidence interval [CI], 1.049-1.238], p = 0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072-1.375], p = 0.002) and in those with nonalbuminuric DKD (1.276 [1.034-1.575], p = 0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and in younger individuals and was observed in those without but not with prior CVD, though interaction was significant only for age., Conclusions: The proxy of insulin sensitivity eGDR predicts all-cause mortality in type 2 diabetes, independent of confounders including DKD. However, the impact of IR in individuals with albuminuric DKD may be mediated by its relationship with albuminuria., Trial Registration: ClinicalTrials.gov , NCT00715481, retrospectively registered 15 July 2008.

Purpose : To investigate whether diabetes mellitus (DM) affects ocular surface of children with well-controlled type 1 DM. Methods : Sixty-five diabetic patients and 55 age-matched controls enrolled to study. Detailed ocular surface assessment including, ocular surface disease index (OSDI) questionnaire, tear film break-up time (TBUT) analysis, Schirmer test, and conjunctival impression cytologic analysis were performed. Results : Schirmer test and TBUT results were significantly lower in DM group than controls ( p = 0.001, for all). OSDI scores of all participants were within normal range. Impression cytology analysis showed grade 0 changes in all participants and there was no difference between groups for goblet cell density ( p > 0.05). The TBUT results were significantly associated with duration of DM ( r = -0.309, p = 0.036). Conclusion : Diabetic children without symptoms, signs, and definite diagnosis of dry eye still had lower TBUT and Schirmer test results than controls; however, impression cytology analysis was similar in both groups.

Approximately 60% of patients with type 2 diabetes mellitus (T2D) develop hypertension. Recent work also indicates greater blood pressure (BP) excursions throughout the day in T2D. Collectively, these findings suggest altered BP control in T2D. Although muscle sympathetic nerve activity (MSNA) recordings in T2D have provided equivocal results, quantification of MSNA alone does not account for ensuing vasoconstriction and BP responses elicited by MSNA. Thus, we tested the hypothesis that patients with T2D exhibit enhanced sympathetic transduction to BP. MSNA (microneurography) and beat-to-beat BP (Finometer) were measured at rest in 21 T2D and 13 age-matched and body mass index-matched control subjects and, signal-averaging was performed to quantify the mean arterial pressure and total vascular conductance responses to spontaneous bursts of MSNA. The peak mean arterial pressure and total vascular conductance responses to spontaneous MSNA were similar between T2D and control (both P>0.05). However, further analysis, separating T2D into those taking statins (n=13, T2D +statin) and not taking statins (n=8, T2D -statin), indicated that T2D -statin patients (4.2±0.6 mm Hg) exhibited greater peak mean arterial pressure responses compared with both T2D +statin patients (2.5±0.3 mm Hg, P=0.01) and control (control: 2.8±0.3 mm Hg, P=0.02). Likewise, nadir total vascular conductance responses to spontaneous MSNA bursts were greater in T2D -statin patients (T2D -statin: -3.3±0.6 mL/(min·mm Hg), T2D +statin: -1.6±0.3 mL/(min·mm Hg), P=0.03; control -2.2±0.3 mL/(min·mm Hg), P=0.08). Notably, T2D +statin patients exhibited similar peak mean arterial pressure and total vascular conductance responses to MSNA compared with control. Collectively, these findings demonstrate, for the first time, that patients with T2D exhibit augmented sympathetic transduction and this effect seems to be offset by statin therapy.

Pancreatic cancer is one of the tumors with the worst prognosis, with the 5-year survival rate reported to be 6%. The number of patients suffering from pancreatic cancer in recent years has continued to increase dramatically. Carbohydrate antigen 19-9 is an established biomarker of pancreatic cancer, but it does not have sufficient ability to detect pancreatic cancer at an early stage. We focused on angiopoietin-like protein 2 (ANGPTL2), which has been reported to be related to chronic inflammation and Type 2 diabetes mellitus. In this study, whether ANGPTL2 can detect early pancreatic cancer was evaluated. It was found that the concentration of serum ANGPTL2 was significantly higher in pancreatic cancer patients and tumor stage 0-I patients than in healthy individuals (5.84 ± 1.82 ng/mL vs 3.61 ± 0.64 ng/mL; P < 0.001) (5.68 ± 0.79 ng/mL vs 3.61 ± 0.64 ng/mL; P = 0.010). In addition, the diagnostic capability of serum ANGPTL2 levels for pancreatic cancer was evaluated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) for ANGPTL2 was 0.906 (95% confidence interval (CI): 0.815-0.997; P < 0.001). To identify the risk factors for pancreatic cancer, multivariate regression models were used. Ten factors were included, and increasing age (odds ratio (OR), 1.318, 95% CI, 1.058-1.642; P = 0.014) and high ANGPTL2 levels (OR, 22.219, 95% CI, 1.962-251.659, P = 0.012) were found to be independent risk factors for pancreatic cancer, with ANGPTL2 having the strongest relationship. In addition, serum ANGPTL2 levels were strongly correlated with inflammatory markers, with blood sugar levels showing the strongest correlation with serum ANGPTL2 levels. In conclusion, this study suggested that an elevated serum ANGPTL2 level has the potential to be a biomarker capable of early detection of pancreatic cancer, and it was correlated with inflammation of the pancreas and the risk of developing diabetes mellitus., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Diabetes Mellitus (DM) is one of the biggest healthcare and financial problems worldwide. The disease is strongly associated with microvascular and macrovascular complications, causing co-existing diseases like Diabetic Retinopathy, Diabetic Neuropathy and Diabetic Nephropathy. Annual healthcare expenditures for diabetes treatment and complications prevention cost 727 billion USD in year 2017. Diabetes Mellitus, Diabetic Retinopathy and Diabetic Retinal Neuropathy are closely related diseases - originating from incorrectly controlled glycemia, blood pressure and lipid levels in the course of increasing resistance of the body tissues to insulin. Irrespectively of thorough programs for Diabetes Mellitus prevention and treatment, Diabetic Retinopathy management requires targeted treatment strategies for both microvasculopathy and retinal neurodegeneration, to delay disease severity course and risk of blindness. The study and conclusions in this article are based on web-available data and officially published articles related to the diabetes mellitus and associated diseases - Diabetic Retinopathy and Diabetic Retinal Neuropathy. The articles have been reviewed and analyzed to assess mutual relations between the discussed diseases., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to declare.

Type 2 diabetes is an emerging global health epidemic. Foundations for new therapies are arising from understanding interactions between body systems. Bone-derived factors that reduce RANKL (receptor activator of NF-kappa B ligand) signaling in the liver may prevent insulin resistance and the onset of type 2 diabetes. Here we demonstrate that deletion of the epigenetic regulator, Hdac3, in Osx1-expressing osteoprogenitors prevents insulin resistance induced by high fat diet by increasing serum and skeletal gene expression levels of osteoprotegerin (Opg), a natural inhibitor of RANKL signaling. Removal of one Opg allele in mice lacking Hdac3 in Osx1+ osteoprogenitors increases the insulin resistance of the Hdac3-deficient mice on a high fat diet. Thus, Hdac3-depletion in osteoblasts increases expression of Opg, subsequently preserving insulin sensitivity. The Hdac inhibitor vorinostat also increased Opg transcription and histone acetylation of the Opg locus. These results define a new mechanism by which bone regulates systemic insulin sensitivity., (© 2017 Wiley Periodicals, Inc.)

The purpose of this study was to exam the impact of type 2 diabetes mellitus (T2DM) on CD4 cell count trends in adults with HIV. In a longitudinal retrospective study in an urban primary care HIV clinic in the southeastern United States from 2010 to 2012, patients with HIV medical charts were audited to obtain their CD4 cell count, diabetes status, weight, and demographic information. Rates of increase of CD4 T cell count (i.e. slopes) were obtained using a linear mixed-effects model. Most of the HIV-T2DM cohort (n = 262) and HIV-only cohort (n = 2399) were African American (76%) and male (77%). The CD4 T cell counts were consistently higher in the HIV-T2DM cohort ( p < .0001). The mean rate of CD4 T cell count increase (mean ± SE) was 63 ± 9 cells/µl/year in HIV-T2DM African American women and 28 ± 7 cells/µl/year in HIV-T2DM African American men ( p = 0.003). In the multivariable slope analysis, the CD4 T cell count increase was significantly faster for HIV-T2DM African American women than for all other patients (mean difference = 30/cells/µl/year, 95% CI: 13-47; p < 0.001). Gender, race/ethnicity, and the diagnosis of diabetes influenced the recovery of CD4 cell counts.

Nowadays, diabetes is prevalent, and it can leave severe psychotic effects and causes depression; thus, it is necessary to consider effective factors to fight against diabetic patients' mental conditions. It seems that the role of religion is significant, and by augmenting religious attitudes, diabetic patient's depression intensity can be decreased. The purpose of the present study is to examine the relationship between religious beliefs and depression of diabetic patients in diabetes clinic of Ali Asghar Hospital in Zahedan. This is a descriptive analytical and cross-sectional study. Out of total 350 diabetic patients, 70 were selected by easy sampling method. Data gathering tool was Bach's religious beliefs and depression standard questionnaires. K 2 statistical test and Pearson's correlation index have been used for data analysis. SPSS software version 16 was used to analyze the data. The results of the study showed that there was not any relationship among age, sex, education, illness duration and family member's history of depression and depression. Results of the study showed that stronger religious beliefs decrease the depression severity (P < 0.001). Therefore, it is necessary to strengthen patient's religious attitudes by proper plans to decrease depression, and some strategies are presented in the study for these plans.

While data are accumulating on the association between neuropsychological performance and real-world endpoints, less is known about the association with medical self-management skills. The self-management of type 1 diabetes (T1D) is often complex, and mismanagement can result in hypoglycaemia and hyperglycaemia and associated morbidity and mortality. The T1D Exchange conducted a case-control study evaluating factors associated with severe hypoglycaemia in older adults (≥ 60 years old) with longstanding T1D (≥ 20 years). A battery of neuropsychological and functional assessments was administered, including measures of diabetes-specific self-management skill (diabetes numeracy) and instrumental activities of daily living (IADL). After adjusting for confounding variables, diabetes numeracy was related to memory and complex speeded attention; while IADL were associated with simple processing speed, executive functioning, complex speeded attention and dominant hand dexterity. The severity of overall cognitive deficit was uniquely associated with both diabetes numeracy and IADL, when controlling for age, education, frailty and depression. This study demonstrates that the cognitive deficits in older adults with T1D have functional implications for both diabetes management and IADL. Further research is needed to determine specific interventions to maximise diabetes self-management in older adults with declining cognition.

Objectives: The Muller cell is the principal glial cell of the vertebrate retina. The expression of Glial fibrillary acidic protein (GFAP) in the Muller cells was used as a cellular marker for retinal damage. This study was done to evaluate the effect of gestational diabetes on retinal Muller cells in rat's offspring., Materials and Methods: In this experimental study, 12 Wistar rat dams were randomly allocated in control and diabetic groups. Gestational diabetes was induced by 40 mg/kg/body weight of streptozotocin at the first day of gestation, intraperitoneally. Dams in control group received an equivalent volume normal saline. Eye of six offspring of each group were removed at postnatal day 28 (P28). The histopathological changes in retina were examined through H&E staining and ultrastructure transmission electron microscopy (TEM). The expression of GFAP was examined using Immunohisto-chemical staining of GFAP in Muller cells. Photographs of retina were taken using Olympus BX51 microscope and a digital camera DP12 and EM LEO906; Zeiss, Germany., Results: In the control rat's offspring, GFAP expression was not significant in Muller cells. According to the optical microscope images, GFAP expression was observed in the processes of the Muller cell in the inner plexiform layer of retina in offspring of diabetic mothers. In TEM technique, nuclear fragmentation and apoptotic bodies were observed in Muller cell of diabetic offspring., Conclusion: This study showed that the uncontrolled gestational diabetes can increase GFAP expression in Muller cells and retinal thickness of retinal layer in rat offspring's, therefore uncontrolled gestational can damage the Muller cells.

Objective: Urocortin, a novel identified corticotropin-releasing factor-related endocrinal peptide, has been shown to play an essential role in cardioprotection. Until recently, whether urocortin can protect the heart against diabetic cardiomyopathy (DCM) remained unclear. Herein, we evaluated the cardioprotective effect of urocortin on cardiac dysfunction, inflammation, and fibrosis and demonstrated the potential mechanism in a diabetic rat model., Methods: Diabetic rats were randomly divided into 4 groups: diabetic control group, urocortin, urocortin + astressin (a selective CRF receptor 2 antagonist) and urocortin + triciribine (an Akt pathway blocker). Cardiac catheterization was performed to evaluate cardiac function. The levels of creatine phosphokinase isoenzyme (CK-MB), plasma brain natriuretic peptide (BNP), myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI) were measured. Inflammatory factors (transforming growth factor beta 1, TGF-β1; connective tissue growth factor, CTGF) and activation of signaling proteins (Akt, GSK-3β) were also detected using western blot., Results: DCM was successfully induced by the injection of streptozotocin (STZ) as evidenced by abnormal heart mass and cardiac function as well as the imbalance of extracellular matrix homeostasis. Rats in the DCM group showed increased mRNA and protein levels of LVWI, BNP, CK-MB, CVF, TGF-β1 and CTGF compared to the control group, which were accompanied with diminished phosphorylation of Akt and GSK-3β. Interestingly, myocardial dysfunction, cardiac fibrosis, and inflammation were suppressed by urocortin in the heart of diabetic rats. Moreover, inhibition of phosphorylation of Akt and GSK-3β was also reversed by urocortin. These effects of urocortin were suppressed by astressin. In addition, triciribine partially reduced the effects of urocortin on myocardial dysfunction, inflammation, and cardiac fibrosis., Conclusions: These results suggest that urocortin exhibits a therapeutic benefit in the treatment of DCM by attenuating fibrosis and inflammation. Furthermore, inhibition of the Akt/GSK-3β signaling pathway may be partially responsible for these effects.

Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses., Competing Interests: Disclosure LF has received honoraria for educational seminars convened by MSD Animal Health during the past 3 years, but has no other financial interest in companies that make insulin or insulin pens. LF has also received honoraria for educational seminars and advisory committees on behalf of companies in the general veterinary field. PL has received an unspecified grant from Merck Animal Health for diabetic cat research. AT has no financial interest in companies in the general veterinary field or in those that make insulin or insulin or pens.

Objectives: The study was conducted to assess knowledge, attitude, and practice regarding insulin use among diabetic patients in tertiary care hospitals., Materials and Methods: Type 1 and 2 diabetic patients, aged 18 years and above, attending the Medicine/Endocrinology out-patient department or admitted as in-patients in three hospitals in and around Kolkata were enrolled. A pretested structured questionnaire comprising of 51 items was administered through face-to-face interview. Responses from 385 subjects were analyzed., Results: Both higher educational and higher economic standards were associated with better understanding of insulin use. Longer duration of diabetes and its treatment (oral anti-diabetic drugs and insulin) were associated with better knowledge of some parameters. Female subjects were less aware of HbA1c as a monitoring tool. Among current insulin users, 70% had never used a glucometer; only 27.33% carried simple carbohydrates for use in hypoglycemic attacks; and 32% failed to rotate sites for insulin injection., Conclusion: Knowledge and attitude were satisfactory on the whole but deficiencies in practice were pronounced, which can potentially be removed through appropriate counseling.

The management of postprandial hyperglycemia is an important strategy in the control of diabetes mellitus and complications associated with the disease, especially in the diabetes type 2. Therefore, inhibitors of carbohydrate hydrolyzing enzymes can be useful in the treatment of diabetes and medicinal plants can offer an attractive strategy for the purpose. Vaccinium arctostaphylos leaves are considered useful for the treatment of diabetes mellitus in some countries. In our research for antidiabetic compounds from natural sources, we found that the methanol extract of the leaves of V. arctostaphylos displayed a potent inhibitory activity on pancreatic α-amylase activity (IC50 = 0.53 (0.53 - 0.54) mg/mL). The bioassay-guided fractionation of the extract resulted in the isolation of quercetin as an active α-amylase inhibitor. Quercetin showed a dose-dependent inhibitory effect with IC50 value 0.17 (0.16 - 0.17) mM.