The presence of polycystic ovary syndrome increases the risk of maternal but not neonatal complications in women with type 2 diabetes in pregnancy.

AIMS: Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. MATERIALS AND METHODS: We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. RESULTS: Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain (unadjusted 12.0 vs. 11.4 kg, adjusted mean difference 2.1 kg [0.3, 3.9], p = 0.021) and higher total insulin dose at 34-36 weeks (unadjusted 172 vs. 124 units per day, adjusted mean difference 44 units [15, 73], p = 0.004), but no difference was seen in neonatal outcomes. Unlike the non-PCOS subgroup, metformin treatment versus placebo in the PCOS subgroup was associated with an increase in extremely large-for-gestational-age infants (28.6 vs. 14.0%, p = 0.008 for interaction) and an increase in worsened pre-existing maternal hypertension (16.7 vs. 4.5%, p = 0.046 for interaction). CONCLUSIONS: Clinicians should be alerted to the potential for high insulin requirements and excess weight gain in pregnant patients with T2DM and comorbid PCOS. Moreover, metformin may not be as beneficial in this population as previously understood.

Latent tuberculosis infection and diagnostic performance of the tuberculin skin test among type 2 diabetics in Sana'a city, Yemen.

BACKGROUND: Tuberculosis (TB) is one of the most widespread infectious diseases worldwide, typically persisting in the body as a latent TB infection (LTBI). Patients with type 2 diabetes have an increased risk of LTBI progressing to active TB. Therefore, this study determined the prevalence and predictors of LTBI and assessed the agreement between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in diagnosing LTBI among type 2 diabetics in Sana'a city, Yemen. METHODS: A cross-sectional study was conducted among 150 type 2 diabetics in private health facilities in Sana'a in 2023. Data about demographics, diabetes-related characteristics, and potential risk factors for LTBI were collected using a structured questionnaire. Patients were then screened for LTBI using TST and IGRA. Univariate analysis was used to identify LTBI-associated risk factors, and multivariable binary logistic regression was used to identify independent predictors of LTBI. The agreement between TST and IGRA for diagnosing LTBI was assessed using Cohen's kappa coefficient (κ). RESULTS: LTBI was prevalent among 29.3% of type 2 diabetics using both types of tests (25.3% with IGRA and 21.3% with TST). Male gender was an independent predictor of LTBI (AOR = 4.4, 95% confidence interval: 1.30-15.08; P = 0.018). However, being employed (AOR = 0.3, 95% CI: 0.09-0.75; P = 0.013) and longer duration since diabetes diagnosis (AOR = 0.3, 95% CI: 0.12-0.98; P = 0.046) were identified as predictors of lower LTBI risk. The agreement between TST and IGRA for the diagnosis of LTBI was 88%, with a good and statistically significant agreement between the two test types (κ = 0.670; P < 0.001). CONCLUSIONS: LTBI is common among type 2 diabetics seeking medical care in Sana'a city, with about one-third of them possibly being latently infected. A higher LTBI risk can be predicted among males, while a lower risk can be predicted among those employed or being diagnosed with diabetes for at least five years. The TST shows good agreement with IGRA in diagnosing LTBI among type 2 diabetics, supporting its continued use as a cost-effective and easily accessible test for diagnosing LTBI in the country.

Adaptive measures to deal with the next pandemic caused by climate change in at-risk groups.

BACKGROUND: The intensity of the perceived stress during the pandemic is a very basic variable for the risk analysis and proper disaster response. The present study was conducted with the aim of determining the relationship between perceived stress and social support during covid-19 in diabetic patients in order to design a suitable plan for a possible pandemic. METHODS: This cross-sectional study was conducted in 2021 on 212 diabetics in Hormozgan province / southern Iran. Data were collected online using Whatsapp using social support and perceived stress questionnaires specific to COVID-19. Data were analyzed by SPSS 22 software using Pearson correlation coefficient tests. RESULTS: The mean and standard deviation (SD) of the stress score was 18.46 ± 4.41. Mean ± SD of social support dimensions were emotional support 30.76 ± 5.96, information support 21.63 ± 4.56, instrumental support 32.48 ± 6.68, and evaluative support 23.53 ± 4.83. There was a significant correlation between emotional support (r =-0.377, P < 0.001) and instrumental support (r =-0.280, P < 0.001) with perceived stress. CONCLUSION: The inverse relationship between emotional and instrumental support and perceived stress in diabetic patients during the Covid-19 pandemic suggests that health promotion interventions focus on increasing these two forms of social support in order to reduce stress during disasters. Especially when there are warnings about the release of microbial agents from melting polar ice and the possibility of the next epidemic.

Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review.

Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic.

The best internal structure of the Diabetes Quality of Life Measure (DQOL) in Brazilian patients.

BACKGROUND: Diabetes Mellitus (DM) is considered a chronic disease with numerous secondary complications that negatively affect the quality of life of patients. However, the specific, known and validated instruments for Brazilian Portuguese are too extensive, which often makes their use infeasible. OBJECTIVE: To validate the internal structure of the Brazilian version of the Diabetes Quality of Life (DQOL) measure. METHODOLOGY: Patients with DM type 1 or 2, between the ages of 18 and 76, were evaluated between April 2022 and May 2022. The survey was conducted online using the Google Forms platform. The original DQOL contains 46 multiple-choice questions organized into four domains. For structural validity, confirmatory factor analysis (CFA) was performed using RStudio software (Boston, MA, USA) with the packages lavaan and semPlot. RESULTS: A total of 354 subjects were evaluated. The 3-domain, 24-item version of the DQOL was the most adequate, with acceptable values for all fit indices (chi-square/GL < 3, TLI and CFI > 0.90, and RMSEA and SRMR < 0.08). CONCLUSION: The structure with three domains and 24 items is the most appropriate based on factor analysis. The Brazilian version of the DQOL with a structure of 3 domains and 24 items has adequate measurement properties that support its use in the clinical and scientific context in patients with DM.

ACE Gene I/D Polymorphism and Cardiometabolic Risk Factors: A Cross Sectional Study of Rural Population.

The D allele has been identified as being linked to cardiovascular disease since the discovery of an insertion/deletion (I/D) polymorphism in the ACE gene, this polymorphism has been found to have significant associations with a variety of cardiovascular risk factors. Recent findings indicate a rising prevalence of metabolic disorders among rural populations in developing nations. Research on health matters has been predominantly focused on urban populations, with relatively less attention given to their rural counterparts Hence, the present study attempts to estimate the prevalence of ACE gene I/D polymorphism and explore its association with various cardiovascular risk factors among Rural Yadav population from India. In the present study, 207 (Male 47, Female 160) members of the Yadav community participated in the cross-sectional study. All the socio-demographic factors, somatometric (anthropometric) variables, and the intravenous blood was collected and Physiological (blood pressure), and biochemical (fasting glucose and lipid profile) parameters were measured as recommended by the American Heart Association, allele-specific PCR of the ACE gene I/D polymorphism was carried out, the PCR products were genotyped on 2% agarose gel Electrophoresis and ACE gene polymorphism was analysed for its association with various cardiovascular risk factors. Among the analysed individuals, 34 (16.4%) were found to have the II genotype, 58 (28.0%) had the ID genotype, and 115 (55.6%) had the DD genotype. The allele frequency of the I allele was found to be 0.31, and the frequency of the D allele was 0.69. The frequency of the DD genotype was found to be significantly higher among individuals with high TC, high TG, and low non-HDL levels (p value < 0.05). When considered collectively, the findings of this study are consistent with the hypothesis that the DD genotype of ACE polymorphism represents a correlation with cardiovascular disease risk factors in this population.

Dietary Intake and Nutritional Status in Diabetic and Nondiabetic Patients With Chronic Kidney Disease Stage 4-5 (NutriDiab Study).

OBJECTIVES: The aim of the present study was to assess the dietary intake and nutritional status of patients with chronic kidney disease (CKD) stage 4-5 according to the presence of diabetes. METHODS: This observational and cross-sectional study included adult patients with CKD stage 4-5 referred to a nephrology unit, between October 2018 and March 2019. Daily dietary intake was evaluated by 24-hour dietary inquiry and urine excretion. Nutritional status was assessed by measuring body composition using bioimpedance analysis and muscle function using handgrip strength. Undernutrition was considered using the protein energy wasting score. RESULTS: A total of 75 CKD patients were included, 36 (48%) of whom had diabetes; median age (interquartile range) was 71 (60-80) years. The median weight-adjusted dietary energy intake (DEI) was 22.6 (19.1-28.2) kcal/kg/day and the mean weight-adjusted dietary protein intake (DPI) was 0.86 ± 0.19 g/kg/day. There was no significant difference in DEI and DPI between patients with diabetes and those without, except for weight-adjusted DPI which was significantly lower in diabetic patients (P = .022). In univariate analysis, diabetes was associated with weight-adjusted DPI (coefficient [95% confidence interval] -0.237 [-0.446; -0.004] kcal/kg/day; P = .040), but this association did not remain significant in multivariate analysis. Nutritional status did not differ significantly between diabetic and nondiabetic patients except for lean tissue mass, which was lower in diabetic patients (P = .046). The proportion of patients with protein energy wasting was not significantly different between diabetic and nondiabetic patients (13.9% vs. 10.2%, respectively). CONCLUSIONS: In the present cohort, DPI and DEI were not significantly different between diabetic and nondiabetic CKD patients. Diabetes was not found to be associated with dietary intakes in CKD stage 4-5 patients.

The Impact of Metabolic Memory on Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes.

Metabolic memory refers to the long-term effects of achieving early glycemic control and the adverse implications of high blood glucose levels, including the development and progression of diabetes complications. Our study aimed to investigate whether the phenomenon of metabolic memory plays a role in the immune profile of young patients with uncomplicated type 1 diabetes (T1D). The study group included 67 patients with uncomplicated type 1 diabetes with a mean age of 15.1 ± 2.3 years and a minimum disease duration of 1.2 years. The control group consisted of 27 healthy children and adolescents with a mean age of 15.1 ± 2.3 years. Patients were divided into three groups according to their HbA1c levels at the onset of T1D, and the average HbA1c levels after one and two years of disease duration. The subgroup A1 had the lowest initial HbA1c values, while the subgroup C had the highest initial HbA1c values. Cytokine levels (including TNF-α, IL-35, IL-4, IL-10, IL-18, and IL-12) were measured in all study participants. Our data analysis showed that subgroup A1 was characterized by significantly higher levels of IL-35 and IL-10 compared to all other groups, and significantly higher levels of IL-4 compared to group B. Additionally, a comparative analysis of cytokine levels between the groups of diabetic patients and healthy controls demonstrated that subgroup A1 had significantly higher levels of anti-inflammatory cytokines. The lipid profile was also significantly better in subgroup A1 compared to all other patient groups. Based on our findings, it appears that an inflammatory process, characterized by an imbalance between the pro- and anti-inflammatory cytokines, is associated with poor glycemic control at the onset of diabetes and during the first year of disease duration. These findings also suggest that both metabolic memory and inflammation contribute to the abnormal lipid profile in patients with type 1 diabetes.

Multiscale Modeling of Macromolecular Interactions between Tau-Amylin Oligomers and Asymmetric Lipid Nanodomains That Link Alzheimer's and Diabetic Diseases.

The molecular events of protein misfolding and self-aggregation of tau and amylin are associated with the progression of Alzheimer's and diabetes, respectively. Recent studies suggest that tau and amylin can form hetero-tau-amylin oligomers. Those hetero-oligomers are more neurotoxic than homo-tau oligomers. So far, the detailed interactions between the hetero-oligomers and the neuronal membrane are unknown. Using multiscale MD simulations, the lipid binding and protein folding behaviors of hetero-oligomers on asymmetric lipid nanodomains or raft membranes were examined. Our raft membranes contain phase-separated phosphatidylcholine (PC), cholesterol, and anionic phosphatidylserine (PS) or ganglioside (GM1) in one leaflet of the lipid bilayer. The hetero-oligomers bound more strongly to the PS and GM1 than other lipids via the hydrophobic and hydrophilic interactions, respectively, in the raft membranes. The hetero-tetramer disrupted the acyl chain orders of both PC and PS in the PS-containing raft membrane, but only the GM1 in the GM1-containing raft membrane as effectively as the homo-tau-tetramer. We discovered that the alpha-helical content in the heterodimer was greater than the sum of alpha-helical contents from isolated tau and amylin monomers on both raft membranes, indicative of a synergetic effect of tau-amylin interactions in surface-induced protein folding. Our results provide new molecular insights into understanding the cross-talk between Alzheimer's and diabetes.

Trends in the representation of specialties caring for patients with diabetes in the Czech Republic.

The increasing prevalence of diabetes mellitus (DM) leads to the differentiation of the registration of diabetics in individual specialties. Objective of this paper was the evaluation of changes in the representation of expertise providing care for patients with DM (pDM) in the Czech Republic, based on data analysis from the National Register of Paid Health Services (NRHZS) 2010-2021. In the entire pDM group, the number of patients treated by a diabetologist (DIA) increased from 491,490 (57.0 %) to 537,430 (50.4 %), with a general practitioner (GP) from 27,719 (3.2 %) to 181,330 (17.0 %) and by internist (INT) from 172,918 (20.0 %) to 161,291 (15.1 %). In 2021, 57.9 % DIA, 17 % GP, 12.2 % INT were treated from the group treated with antidiabetics (813,873). In 2021, 84,345 were treated with insulin alone (87.2 % DIA), 129,127 were treated with a combination of insulin and non-insulin antidiabetics; 115,604 (91.6 %) in DIA, 322 (0.3 %) in GP and 7,983 (6.3 %) in INT. 603,331 treated only with non-insulin antidiabetic drugs, of which 281,929 (46.7 %) DIA, 137,744 (22.8 %) GP and 85,273 (14.1 %) INT. For other specialties, 98,385 (16.3 %) persons. 185,838 patients without reported DIA/GP/INT control, of which 80,144 without therapy. The increasing prevalence of DM and changes in reimbursement conditions are reflected in the dynamic development of the distribution of diabetes care by individual specialties.

Correlation of uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine.

Objective: To find the correlation of serum uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine. Methods: This cross-sectional study was conducted in the Department of Diabetes, Endocrinology and Metabolic diseases, Hayatabad Medical Complex, Peshawar, Pakistan from 1st April, 2022 to 30th September, 2022. Total 160 diabetic patients between the age of 30 and 65 years were enrolled in the study. Type-2 diabetic patients with microalbuminuria between 2.5 and 30 mg/mmol were included. The demographic details of patients were recorded in the questionnaire after taking consent. Fasting Uric acid, lipid profile and glucose along with creatinine and HbA1C were estimated from patient's venous blood samples. Ratio of albumin to creatinine (ACR) in the random spot urine sample was used to detect microalbuminuria. Results: Out of 160 participants enrolled in the study there were 86 (54%) males and 74 (46%) females with the mean age of 50.15 ± 11.1 years and BMI of 20.93 kg/m2. Ninety six (60%) of the patients had Type-2 DM for less than five years, while remaining 64 (40%) were more than five years diabetic. Mean serum uric acid calculated was 6.85±2.06(mg/dl), while microalbuminuria was calculated as 8.02±0.78 (mg/mmol). The Pearson correlation of serum uric acid and microalbuminuria based on sex and age was statistically significant(p<0.05). Conclusion: We found that uric acid level was significantly associated with microalbuminuria in people with Type-2 diabetes with normal serum creatinine. Uric acid level can be a potential screening tool for early detection of DKD.

Effect of sample fractionation and normalization when immunoblotting for human muscle Na+/K+-ATPase subunits and glycogen synthase.

Immunoblotting is widely used in muscle physiology to determine protein regulation and abundance. However, research groups use different protocols, which may result in differential outcomes. Herein, we investigated the effect of various homogenization procedures on determination of protein abundance in human m. vastus lateralis biopsies. Furthermore, we investigated differences in abundance between young healthy males (n = 12) and type-2 diabetics (n = 4), and the effect of data normalization. Fractionated lysates had the lowest variation in total protein determination as compared to non-fractionated homogenates. Abundance of NKAα2, NKAß1, FXYD1, and glycogen synthase was higher (P < 0.05) in young healthy than in type-2 diabetics determined in both fractionated and non-fractionated samples for which normalization to the stain-free signal and/or standard curve did not affect outcomes. Precision and reliability of protein abundance determination between sample types showed a moderate to good reliability for these proteins, whereas the commonly used house-keeping protein, actin, showed poor reliability. In conclusion, fractionated and non-fractionated immunoblotting samples yield similar data for several sarcolemmal and cytosolic proteins, except for actin, which, therefore appears inappropriate for data normalization in immunoblotting of human skeletal muscle. Thus, fractionation does not seem to be a major source of bias when immunoblotting for NKA subunits and GS.

Diabetes and seeds: New horizon to promote human nutrition and anti-diabetics compounds in grains by germination.

Type 2 diabetes (T2D) is a complex and heterogeneous chronic metabolic disorder disease that is associated with high blood sugar. Because of the side effects of synthetic drugs on T2D patients and their economic burden, interest in plant-derived functional foods like grains with biological activities has developed. Based on scientific reports, whole grains are rich sources of energy, nutrients, and bioactive compounds and are assumed to have beneficial health effects on glucose enzymes regulation or hyperglycemia. Nowadays, different methods have been applied to enhance whole seed healthful properties and anti-diabetic compounds, and germination is one of them. Germination (sprouting) is a cost-effective method for boosting the activity of endogenous seed enzymes and modifying the structure of macromolecules. Some of these macromolecules like bioactive peptides, polyphenols, dietary fiber, and vitamins are related to diabetes management. Determining the best germination condition can help to promote these anti-diabetics properties of compounds. This study presents relevant information about diabetes, the effect of seed germination on releasing bioactive compounds, and optimizing environmental germination conditions to improve the anti-diabetic compounds in seeds for reaching functional food.

Advancements of fish-derived peptides for mucormycosis: a novel strategy to treat diabetic compilation.

Mucormycosis, an extremely fatal fungal infection, is a major hurdle in the treatment of diabetes consequences. The increasing prevalence and restricted treatment choices urge the investigation of novel therapeutic techniques. Because of their effective antimicrobial characteristics and varied modes of action, fish-derived peptides have lately emerged as viable options in the fight against mucormycosis. This review examines the potential further application of fish-derived peptides in diagnosing and managing mucormycosis in relation to diabetic complications. First, we examine the pathophysiology of mucormycosis and the difficulties in treating it in diabetics. We emphasize the critical need for alternative therapeutic methods for tackling the limitations of currently available antifungal medicines. The possibility of fish-derived peptides as an innovative approach to combat mucormycosis is then investigated. These peptides, derived from several fish species, provide wide antimicrobial properties against a variety of diseases. They also have distinct modes of action, such as rupture of cell membranes, suppression of development, and modification of the host immunological response. Furthermore, we investigate the problems and prospects connected with the clinical application of fish-derived peptides. Ultimately, future advances in fish-derived peptides, offer interesting avenues for the management of mucormycosis in the context of diabetic comorbidities. More research and clinical trials are needed to properly investigate these peptide's therapeutic potential and pave the way for their adoption into future antifungal therapies.

Length and rigidity of the spacer impact on aldose reductase inhibition of the 5F-like ARIs in a dual-occupied mode.

The primary objective of this study was to investigate the structure-activity relationship of a new series of 5F-like Aldose Reductase Inhibitors (ARIs) using in silico docking method. In this perspective, 6 novel ARIs have been designed and synthesized. Evaluation of the inhibition of these compounds to ALR2 was carried on with epalrestat and 5F as the references. It was found that the spacer of 5F-like ARIs has a great influence on their inhibitory activity. Rigid spacer with length equal to 3 âˆ¼ 4 carbon alkyl chain brings about better inhibitory activity. Among them, compound 4b was verified as the most active ARIs, where its IC50 value was 16.8 ± 1.3 nM. Furthermore, in silico docking studies using AutoDock 4.2 as well as molecular simulation using GROMACS 2022.1 showed that 5F-like ARIs adopt a dual-occupation mode. The interaction energy (-25 to -74 kcal/mol), as well as MM-GBSA binding free energy (-37 to -65 kcal/mol) was positively correlated with their ALR2 inhibition constant (2000 to 16.8 nM). Docking interaction explained well the structure-activity relationship. A pharmacophore model has been set up for 5F-like ARIs thereafter. This model indicates that as an effective ARI, the entity should have four characteristics: an aromatic center, two hydrogen bond donors, and one hydrogen bond acceptor. By the way, all the 5F-like ARIs reported here are good to mild antioxidant with EC50 value between 13.6 ± 1.2 and 71.1 ± 3.2 µM. All our data direct the further development of more optimal ARIs for the treatment of diabetic complication in the future.

Understanding the self-management experiences and support needs during pregnancy among women with pre-existing diabetes: a qualitative descriptive study.

BACKGROUND: With the increasing prevalence of pre-existing type 1 and type 2 diabetes in pregnancy and their associated perinatal risks, there is a need to focus on interventions to achieve optimal maternal glycemia to improve pregnancy outcomes. One strategy focuses on improving diabetes self-management education and support for expectant mothers with diabetes. This study's objective is to describe the experience of managing diabetes during pregnancy and identify the diabetes self-management education and support needs during pregnancy among women with type 1 and type 2 diabetes. METHODS: Using a qualitative descriptive study design, we conducted semi-structured interviews with 12 women with pre-existing type 1 or 2 diabetes in pregnancy (type 1 diabetes, n = 6; type 2 diabetes, n = 6). We employed conventional content analyses to derive codes and categories directly from the data. RESULTS: Four themes were identified that related to the experiences of managing pre-existing diabetes in pregnancy; four others were related to the self-management support needs in this population. Women with diabetes described their experiences of pregnancy as terrifying, isolating, mentally exhausting and accompanied by a loss of control. Self-management support needs reported included healthcare that is individualized, inclusive of mental health support and support from peers and the healthcare team. CONCLUSIONS: Women with diabetes in pregnancy experience feelings of fear, isolation and a loss of control, which may be improved through personalized management protocols that avoid "painting everybody with the same brush" as well as peer support. Further examination of these simple interventions may yield important impacts on women's experience and sense of connection.

Development and validation of a risk prediction model for frailty in patients with diabetes.

BACKGROUND: Frailty is the third most common complication of diabetes after macrovascular and microvascular complications. The aim of this study was to develop a validated risk prediction model for frailty in patients with diabetes. METHODS: The research used data from the China Health and Retirement Longitudinal Study (CHARLS), a dataset representative of the Chinese population. Twenty-five indicators, including socio-demographic variables, behavioral factors, health status, and mental health parameters, were analyzed in this study. The study cohort was randomly divided into a training set and a validation set at a ratio of 70 to 30%. LASSO regression analysis was used to screen the variables for the best predictors of the model based on a 10-fold cross-validation. The logistic regression model was applied to explore the associated factors of frailty in patients with diabetes. A nomogram was constructed to develop the prediction model. Calibration curves were applied to evaluate the accuracy of the nomogram model. The area under the receiver operating characteristic curve and decision curve analysis were conducted to assess predictive performance. RESULTS: One thousand four hundred thirty-six patients with diabetes from the CHARLS database collected in 2013 (n = 793) and 2015 (n = 643) were included in the final analysis. A total of 145 (10.9%) had frailty symptoms. Multivariate logistic regression analysis showed that marital status, activities of daily living, waist circumference, cognitive function, grip strength, social activity, and depression as predictors of frailty in people with diabetes. These factors were used to construct the nomogram model, which showed good concordance and accuracy. The AUC values of the predictive model and the internal validation set were 0.912 (95%CI 0.887-0.937) and 0.881 (95% CI 0.829-0.934). Hosmer-Lemeshow test values were P = 0.824 and P = 0.608 (both > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. ROC and DCA indicated that the nomogram had a good predictive performance. CONCLUSIONS: Comprehensive nomogram constructed in this study was a promising and convenient tool to evaluate the risk of frailty in patients with diabetes, and contributed clinicians to screening the high-risk population.

Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials.

Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aß production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.

Mean quality of life of hypertensive and diabetic patients: A comparative study of patients in secondary and tertiary health facilities in Kaduna State, Nigeria.

Introduction: Hypertension and diabetes have become major non-communicable diseases of public health importance globally, considering the magnitude of the diseases, the propensity to worsen the patients' quality of life and the associated mortality. This study compared the health-related quality of life (HRQOL) of hypertensive and diabetic patients in both tertiary and secondary health facilities in Kaduna State, north-western Nigeria. Materials and Methods: This was a descriptive comparative cross-sectional study amongst 325 patients, of which 93 (28.6%) were from the tertiary and 232 (71.4%) were from the secondary facilities. All eligible respondents participated in this study. Data were analysed with SPSS version 25 and STATA SE 12, t-test for comparison of two means, Chi-square and multivariate analyses were performed with P < 0.05. Results: The mean age was 55.72 ± 13 years. Two-thirds, 197 (60.6%), were hypertensive only, 60 (18.5%) were diabetic only (18.5%) and 68 (20.9%) were hypertensive diabetic. For the hypertensive only at the tertiary facility, the mean scores for vitality (VT) (68.0 ± 5.97, P = 0.01), emotional well-being (EW) (77.33 ± 4.52, P = 0.0007) and bodily pain (BP), (74.17 ± 5.94, P = 0.05) were significantly higher for tertiary compared with those at secondary facilities. The mean HRQOL for the people with diabetes only at the tertiary facilities also showed statistically significant higher scores for VT (72.2 ± 61, P = 0.01), social functioning (72.2 ± 8.4, P = 0.02), EW (75.44 ± 4.9, P = 0.001) and BP (85.56 ± 7.7, P = 0.01) when compared with the secondary facilities. Conclusion: Patients managed by specialists at the tertiary health facility had better HRQOL than those managed at the secondary health facilities. Continued medical education and the use of standard operating procedures are recommended for improved HRQOL.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers.

Pregestational Diabetes Mellitus (PDM) during pregnancy constitutes an unfavorable embryonic and fetal development environment, with a high incidence of congenital malformations (CM). Neural tube defects are the second most common type of CM in children of diabetic mothers (CDM), who also have an elevated risk of developing neurodevelopmental disorders. The mechanisms that lead to these neuronal disorders in CDM are not yet fully understood. The present study aimed to know the effect of hyperglycemia on proliferation, neuronal differentiation percentage, and expression of neuronal differentiation mRNA markers in human umbilical cord Wharton's jelly mesenchymal stem cells (hUCWJMSC) of children from normoglycemic pregnancies (NGP) and PDM. We isolated and characterized hUCWJMSC by flow cytometry, immunofluorescence, RT-PCR and were induced to differentiate into adipocytes, osteocytes, and neurons. Proliferation assays were performed to determine the doubling time, and Nestin, TUBB3, FOXO1, KCNK2, LMO3, and MAP2 mRNA gene expression was assessed by semiquantitative RT-PCR. Hyperglycemia significantly decreased proliferation and neuronal differentiation percentage in NGP and PDM cells treated with 40 mM d-glucose. Nestin mRNA expression decreased under control glycemic conditions, while FOXO1, KCNK2, LMO3, and MAP2 mRNA expression increased during neuronal differentiation in both NGP and PDM cells. On the other hand, under hyperglycemic conditions, Nestin was significantly decreased in cells from NGP but not in cells from PDM, while mRNA expression of FOXO1 and LMO3 was significantly increased in cells from NGP, but not in cells from PDM. We found evidence that maternal PDM, with hyperglycemia in culture, affects the biological properties of fetal cells. All these results could be part of fetal programming.