Efficacy and Safety of Vildagliptin and Remogliflozin as Add-on Therapy to Metformin in Patients of Type 2 Diabetes Mellitus: An open-label comparative study.

Objectives: This study aimed to evaluate the safety and efficacy of remogliflozin compared to vildagliptin as an add-on drug to metformin in type 2 diabetes mellitus (T2DM) treatment. Metformin is considered a first-line drug in T2DM. However, as the disease progresses with heightened insulin resistance and declining ß-cell function, the use of metformin alone is often inadequate to achieve optimum glucose levels. Methods: This prospective, randomised study was conducted at Maulana Azad Medical College and Associated Hospital in New Delhi, India, between February 2020 to January 2021. This study recruited 60 T2DM patients aged 35-70 years with glycated haemoglobin (HbA1c) >6.5% taking metformin at a daily dosage of 1,500-3,000 mg for ≥3 months. Patients were randomly assigned in a 1:1 ratio to receive either vildagliptin (50 mg) or remogliflozin (100 mg) twice daily for 90 days. The primary endpoint was a change in HbA1c levels from baseline to the end of 90 days whereas secondary endpoints were changes in lipid profile and weight. Results: The decrement in mean HbA1c levels was significantly higher in the remogliflozin group than in the vildagliptin group (-8.1% versus -2.4%; P <0.001). In addition, more significant weight loss was found in remogliflozin-treated patients (-5.2% versus -0.6%; P <0.01). Both treatments were well tolerated throughout the study. Conclusion: Compared to vildagliptin, remoglilflozin was significantly more effective in glycaemic control and weight loss in patients with T2DM and can therefore be considered as an add-on drug in T2DM not adequately controlled by metformin monotherapy.

Alterations of Gut Microbiota in Pyogenic Liver Abscess Patients with and without Type 2 Diabetes Mellitus.

Purpose: The clinical manifestations of pyogenic liver abscess (PLA) vary between patients with and without diabetes mellitus (DM). However, the relationship between PLA and the gut microbiome remains unknown. This study analyzed the composition of gut microbiota in PLA patients with and without DM and healthy controls (HCs) with the goal of identifying potential reasons for the observed variations in clinical manifestations. Patients and Methods: Using 16S ribosomal RNA(16S rRNA) gene sequencing, we analyzed the compositions of gut microbiota in 32 PLA patients with DM, 32 PLA patients without DM, and 29 matched HCs. Results: In PLA patients with DM, the D-dimer level, fibrinogen degradation products, and thrombin time were significantly higher compared to the PLA patients without DM (P < 0.05). The abundance and diversity of intestinal flora were reduced in both groups of PLA patients compared with the HCs (P < 0.05). Specifically, the PLA patients with DM showed significant decreases in the relative abundances of Bacteroides, Blautia, Prevotella9, and Faecalibacterium, whereas Enterococcus and Escherichia-Shigella were relatively more abundant (P < 0.05). Compared to PLA patients without DM, those with DM had lower relative abundances of Lactobacillus and Klebsiella (P < 0.05) and showed different bacterial flora, including Anaerosporobacter and Megamonas. Conclusion: PLA patients with DM exhibited more severe clinical manifestations of PLA compared to patients without DM. It is important to monitor blood coagulation in PLA patients with DM to prevent the development of thrombotic diseases. Additionally, PLA patients with DM exhibit distinct differences in the composition and diversity of their intestinal flora compared to both PLA patients without DM and HCs.

Integrated biomarker profiling for predicting the response of type 2 diabetes to metformin.

AIM: To explore biomarkers that can predict the response of type 2 diabetes (T2D) patients to metformin at an early stage to provide better treatment for T2D. METHODS: T2D patients with (responders) or without response (non-responders) to metformin were recruited, and their serum samples were used for metabolomic analysis to identify candidate biomarkers. Moreover, the efficacy of metformin was verified by insulin-resistant mice, and the candidate biomarkers were verified to determine the biomarkers. Five different machine learning methods were used to construct the integrated biomarker profiling (IBP) with the biomarkers to predict the response of T2D patients to metformin. RESULTS: A total of 73 responders and 63 non-responders were recruited, and 88 differential metabolites were identified in the serum samples. After being verified in mice, 19 of the 88 were considered as candidate biomarkers. Next, after metformin regulation, nine candidate biomarkers were confirmed as the biomarkers. After comparing five machine learning models, the nine biomarkers were constructed into the IBP for predicting the response of T2D patients to metformin based on the Naïve Bayes classifier, which was verified with an accuracy of 89.70%. CONCLUSIONS: The IBP composed of nine biomarkers can be used to predict the response of T2D patients to metformin, enabling clinicians to start a combined medication strategy as soon as possible if T2D patients do not respond to metformin.

Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled Trials.

Objective: This meta-analysis aimed to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in overweight/obese and/or type 2 diabetes mellitus (T2DM) adolescents aged <18 years. Methods: Herein, we searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data up to August 2023 for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, P<0.001) than the control group. However, there was no difference in fasting blood glucose (FPG; RD=-2.07mg/dL, P=0.065) between the two groups. Nonetheless, the experimental group that administered exenatide showed a no significant reduction in HbA1c (P=0.253) and FPG (P=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28kg, P=0.002) and BMI (RD=-1.63kg/m2, P=0.002) compared to the control group. The experimental group was adopted with liraglutide (RD=-2.31kg, P=0.038) or exenatide (RD=-2.70kg, P<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. But for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81kg/m2, P=0.260). For the experimental group that was adopted with exenatide, BMI revealed a more significant decline in the intervention group than in the control group (RD=-1.14kg/m2, P<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide is better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide is better than liraglutide.

The impact of surgery and oncological treatment on risk of type 2 diabetes onset in patients with colorectal cancer: nationwide cohort study in Denmark.

Background: Comorbidity with type 2 diabetes (T2D) results in worsening of cancer-specific and overall prognosis in colorectal cancer (CRC) patients. The treatment of CRC per se may be diabetogenic. We assessed the impact of different types of surgical cancer resections and oncological treatment on risk of T2D development in CRC patients. Methods: We developed a population-based cohort study including all Danish CRC patients, who had undergone CRC surgery between 2001 and 2018. Using nationwide register data, we identified and followed patients from date of surgery and until new onset of T2D, death, or end of follow-up. Results: In total, 46,373 CRC patients were included and divided into six groups according to type of surgical resection: 10,566 Right-No-Chemo (23%), 4645 Right-Chemo (10%), 10,151 Left-No-Chemo (22%), 5257 Left-Chemo (11%), 9618 Rectal-No-Chemo (21%), and 6136 Rectal-Chemo (13%). During 245,466 person-years of follow-up, 2556 patients developed T2D. The incidence rate (IR) of T2D was highest in the Left-Chemo group 11.3 (95% CI: 10.4-12.2) per 1000 person-years and lowest in the Rectal-No-Chemo group 9.6 (95% CI: 8.8-10.4). Between-group unadjusted hazard ratio (HR) of developing T2D was similar and non-significant. In the adjusted analysis, Rectal-No-Chemo was associated with lower T2D risk (HR 0.86 [95% CI 0.75-0.98]) compared to Right-No-Chemo.For all six groups, an increased level of body mass index (BMI) resulted in a nearly twofold increased risk of developing T2D. Conclusions: This study suggests that postoperative T2D screening should be prioritised in CRC survivors with overweight/obesity regardless of type of CRC treatment applied. Funding: The Novo Nordisk Foundation (NNF17SA0031406); TrygFonden (101390; 20045; 125132).

Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Preventing Type 2 Diabetes after Gestational Diabetes: A Systematic Review Mapping Physical Activity Components using the Socio-Ecological Model.

OBJECTIVES: Gestational diabetes commonly occurs during pregnancy and increases lifetime risk of type 2 diabetes following pregnancy. Engaging in physical activity postnatally can reduce this subsequent risk. Interventions aiming to increase physical activity after gestational diabetes may not address the wide range of post-pregnancy barriers. A socio-ecological approach highlights the need to include multi-level factors such as social, community and organisational factors. The aim of the review was to map intervention components to prevent type 2 diabetes after gestational diabetes using the socio-ecological model as a framework and investigate how physical activity changes align with different intervention components utilised. METHODS: Eligible studies included any study type within 5 years of a gestational diabetes diagnosis and targeted physical activity. A systematic search of MEDLINE, Cochrane Library, Web of Science, CINAHL Complete, and Scopus was conducted in October 2022. Results were categorised based on whether findings demonstrated no increases, non-statistically significant increases or statistically significant increases in physical activity. RESULTS: Forty-eight studies were included (37 different interventions). Thirty-eight studies were assessed as "adequate" quality, only two studies were "good" quality, and the remaining were limited quality. Mixed physical activity outcomes were observed across components used at the intrapersonal level, with components across other levels of the socio-ecological model showing more increases in physical activity. Intervention components within the social and organisational levels, for example childcare provision, providing group-based sessions and offering remote delivery, were more often present in interventions with physical activity increases. CONCLUSIONS FOR PRACTICE: Future interventions targeting physical activity after gestational diabetes should aim to include social and organisational-level components in their intervention design. This systematic review was registered in PROSPERO (ID: CRD42021272044).

Molecular Mechanism of Pasteurized Akkermansia muciniphila in Alleviating Type 2 Diabetes Symptoms.

Type 2 diabetes (T2DM) significantly diminishes people's quality of life and imposes a substantial economic burden. This pathological progression is intimately linked with specific gut microbiota, such as Akkermansia muciniphila. Pasteurized A. muciniphila (P-AKK) has been defined as a novel food by the European Food Safety Authority and exhibited significant hypoglycemic activity. However, current research on the hypoglycemic activity of P-AKK is limited to the metabolic level, neglecting systematic exploration at the pathological level. Consequently, its material basis and mechanism of action for hypoglycemia remain unclear. Drawing upon this foundation, we utilized high-temperature killed A. muciniphila (H-K-AKK) with insignificant hypoglycemic activity as the control research object. Assessments were conducted at pathological levels to evaluate the hypoglycemic functions of both P-AKK and H-K-AKK separately. Our study unveiled for the first time that P-AKK ameliorated symptoms of T2DM by enhancing the generation of glucagon-Like Peptide 1 (GLP-1), with pasteurized A. muciniphila total proteins (PP) being a pivotal component responsible for this activity. Utilizing SDS-PAGE, proteomics, and molecular docking techniques, we deeply analyzed the material foundation of PP. We scientifically screened and identified a protein weighing 77.85 kDa, designated as P5. P5 enhanced GLP-1 synthesis and secretion by activating the G protein-coupled receptor (GPCR) signaling pathway, with free fatty acid receptor 2 (FFAR-2) being identified as the pivotal target protein for P5's physiological activity. These findings further promote the widespread application of P-AKK in the food industry, laying a solid theoretical foundation for its utilization as a beneficial food ingredient or functional component.

Determinants of Course of Type 2 Diabetes in Indian Adolescents.

OBJECTIVES: To identify determinants of the course of Type 2 diabetes in Indian adolescents. METHODS: Records of 37 adolescents (24 boys; 29 post pubertal and eight pubertal) with Type 2 diabetes (initial HbA1C 10.1 ± 1.9% and BMI SDS 2.0 ± 0.8; family history of diabetes in 33, 89.2%) diagnosed at 15.2 ± 2.5 y and followed up for 3.8 ± 2.2 y till 19.1 ± 3.3 y of age, were reviewed. RESULTS: Initial treatment included insulin in 11 (29.7%), metformin alone in 22 (59.5%), and a combination of anti-diabetic medication in four (10.8%). Eleven subjects (29.7%) achieved remission at a median period of 5.3 mo (IQR- 17.13) after diagnosis; six of these relapsed within 0.9 ± 0.3 (range 0.4-1.3) y. The proportion of subjects requiring multiple anti-diabetic agents increased over follow-up (19% at six months, 32.5% at one year, 50% at two years, 59.1% at three, and 64.8% at four years), with the need for combination therapy after 0.9 ± 1.4 y. At the last follow-up, five were off treatment (13.5%), 10 (27%) were on metformin alone, and 22 (59.5%) were on multiple medications. The need for combination therapy at the last follow-up was lower in subjects with remission (27% against 73.1%, p = 0.02). CONCLUSIONS: The findings of this study suggest delayed presentation and rapid progression of Type 2 diabetes in Indian adolescents. Diagnosis on screening and achievement of remission were predictors of good outcome.

Transferability of the NHS low-calorie diet programme: A qualitative exploration of factors influencing the programme's transfer ahead of wide-scale adoption.

INTRODUCTION: Although behavioural interventions have been found to help control type 2 diabetes (T2D), it is important to understand how the delivery context can influence implementation and outcomes. The NHS committed to testing a low-calorie diet (LCD) programme designed to support people living with excess weight and T2D to lose weight and improve diabetes outcomes. Understanding what influenced implementation during the programme pilot is important in optimising rollout. This study explored the transferability of the NHS LCD Programme prior to wider adoption. METHODS: Twenty-five interviews were undertaken with stakeholders involved in implementing the LCD programme in pilot sites (health service leads, referring health professionals and programme deliverers). Interviews with programme participants (people living with T2D) were undertaken within a larger programme of work, exploring what worked, for whom and why, which is reported separately. The conceptual Population-Intervention-Environment-Transfer Model of Transferability (PIET-T) guided study design and data collection. Constructs of the model were also used as a deductive coding frame during data analysis. Key themes were identified which informed recommendations to optimise programme transfer. RESULTS: Population: Referral strategies in some areas lacked consideration of population characteristics. Many believed that offering a choice of delivery model would promote acceptability and accessibility of the eligible population. INTERVENTION: Overall, stakeholders had confidence in the LCD programme due to the robust evidence base along with anecdotal evidence, but some felt the complex referral process hindered engagement from GP practices. ENVIRONMENT: Stakeholders described barriers to accessing the programme, including language and learning difficulties. Transferability: Multidisciplinary working and effective communication supported successful implementation. CONCLUSION: Referral strategies to reach underrepresented groups should be considered during programme transfer, along with timely data from service providers on access and programme benefits. A choice of delivery models may optimise uptake. Knowledge sharing between sites on good working practices is encouraged, including increasing engagement with key stakeholders.

Association between clinical and laboratory factors and response to sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: a retrospective observational study.

BACKGROUND: This study aimed toinvestigate the association between clinical and laboratory parameters andresponse to therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i) inpatients with type 2 diabetes mellitus (T2D). RESEARCHDESIGN AND METHODS: Weretrospectively analyzed the medical records of people with T2D in whom SGLT2iwas started. Clinical and laboratory parameters were recorded before, 3 and 6 months after starting treatment. Specific criteria were applied to classifyparticipants into good and poor responders in terms of weight loss (primaryoutcome) and glycemic control (secondary outcome), separately. RESULTS: Fifty individuals (64%men) with a mean age of 65.8 ± 8.5 years were included in the analysis. 86% and64% of the participants were classified into good response categories forglycemic control and weight loss, respectively. Good responders in terms ofglycemic control had lower high-density lipoprotein cholesterol levels atbaseline compared to poor responders (43.3 vs 57.4 mg/dl, p = 0.044). In thelogistic regression analysis, a higher baseline weight was associated with abetter response to therapy in terms of weight loss (p = 0.04). CONCLUSIONS: Our findings suggestthat specific clinical andlaboratory parameters are associated with response to SGLT2i treatment and cancontribute to a more personalized approach to T2D care.

An improved linear systems model of hydrothermal isometric tension testing to aid in assessing bone collagen quality: Effects of ribation and type-2 diabetes.

This study sought to further develop and validate a previously proposed physics-based model that maps denaturation kinetics from differential scanning calorimetry (DSC) to the isometric tension generated during hydrothermal isometric tension (HIT) testing of collagenous tissues. The primary objectives of this study were to verify and validate two physics-based model parameters: α, which indicates the amount of instantaneous isometric tension developed per unit of collagen denaturation, and ß, which captures the proportionality between temperature and the generated isometric tension post denaturation initiation. These parameters were used as measures of bone collagen quality, employing data from HIT and DSC testing of human bone collagen from two previous studies. Additionally, given the physical basis of the model, the study aimed to further validate Max.Slope, the rate of change in isometric tensile stress with change in temperature, as an independent measure of collagen network connectivity. Max.Slope has previously been positively correlated with measures of cortical bone fracture resistance. Towards this verification and validation, the hypotheses were a) that α would correlate strongly with HIT denaturation temperature, Td, and the enthalpy of melting (ΔH) from DSC, and b) that ß would correlate positively and strongly with Max.Slope. The model was employed in the analysis of HIT-DSC data from the testing of demineralized bone collagen isolated from cadaveric human femurs in two prior studies. In one study, data were collected from HIT-DSC testing of cortical bone collagen from 74 donors. Among them, 38 had a history of type 2 diabetes +/- chronic kidney disease, while the remaining 36 had no history of T2D again with or without CKD. Cortical bone specimens were extracted from the lateral mid-shaft. The second study involved 15 donor femora, with four cortical bone specimens extracted from each. Of these four, two specimens underwent a 4-week incubation in 0.1 M ribose at 37 °C to induce non-enzymatic ribation and advanced glycation endproducts, while the other two served as non-ribated controls. The examination involved investigating correlations between the model parameters α and ß and various measures, such as Max.Slope, Td, ΔH, age, and duration of type 2 diabetes. The results revealed positive correlations between the model parameter ß and Max.Slope (r = 0.55-0.58). The parameter α was found to be associated with Td, but also sensitive to the shape of the HIT curve around Td resulting in difficulties with variability and interpretation. As a result, while both hypotheses are confirmed, Max.Slope and ß are better indicators of bone collagen quality because they are measures of the connectivity or, more generally, the integrity of the bone collagen network.

Oxidative balance score as a useful predictive marker for new-onset type 2 diabetes mellitus in Korean adults aged 60 years or older: The Korean Genome and Epidemiologic Study-Health Examination (KoGES-HEXA) cohort.

BACKGROUND: The oxidative balance score (OBS) is a comprehensive pro- and anti-oxidative marker for assessing the risk of various metabolic diseases and cancers. However, it is not well established whether OBS is related to type 2 diabetes mellitus (T2DM), particularly in elderly populations. Therefore, our objective was to investigate the longitudinal effect of OBS on T2DM in a large cohort of Korean adults aged 60 years and older. METHODS: We assessed the data for 3516 participants aged 60 years and older without diabetes mellitus from the Health Examinees cohort of the Korean Genome and Epidemiology Study. We classified the participants into three groups according to OBS tertiles. We prospectively assessed hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional-hazard regression models during the mean 3.5 years following the baseline survey. RESULTS: A total of 109 participants (3.1 %) developed T2DM during a mean follow-up of 3.5 years. The incidence rates per 1000 person-years were 11.73 for the lowest OBS tertile (T1), 8.19 for the second tertile (T2), and 6.23 for the highest tertile (T3). Adjusting for all confounding factors, compared with the referent T1, the HR (95 % CI) of new-onset T2DM was not significant in T2 (0.71 [0.47-1.07]) but was significant in T3 at (0.47 [0.30-0.75]) (p for trend = 0.002). CONCLUSIONS: The study suggests that a OBS could serve as a valuable predictive marker for new-onset T2DM in older adults. Our study suggests that maintaining an appropriate body weight through healthy lifestyle modification has the potential to lower T2DM incidence in elderly. This implies that the OBS may be a useful tool for assessing the incidence of T2DM even in older individuals.

Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice.

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

Vitamin D and major chronic diseases.

Numerous observational studies have demonstrated a significant inverse association between vitamin D status and the risk of major chronic disease, including type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. However, findings from Mendelian randomization (MR) studies and randomized controlled trials (RCTs) suggest minimal or no benefit of increased vitamin D levels. We provide an overview of recent literature linking vitamin D to major chronic diseases. Because emerging evidence indicates a potential threshold effect of vitamin D, future well-designed studies focused on diverse populations with vitamin D deficiency or insufficiency are warranted for a more comprehensive understanding of the effect of maintaining sufficient vitamin D status on the prevention of major chronic diseases.

Erythema nodosum leprosum necroticans: a case report of an atypical severe type 2 leprosy reaction and literature review.

Until now, leprosy remains a problem and challenge in the world because it can cause disability and morbidity in affected individuals, including problems due to the emergence of type 2 lepra reaction or erythema nodosum leprosum (ENL). The clinical picture of ENL can appear in an atypical and severe form, called ENL necroticans (ENN), which becomes a problem in diagnosis and therapy. We report a 17-year-old female with lepromatous leprosy and ENN who received therapy in the form of a combination of steroids and methotrexate. Four months after consuming this therapy, the ulcers on the patient's body improved, leaving atrophic and hypertrophic scars. ENN's unusual clinical presentation poses diagnostic difficulties in that its appearance does not follow the typical patterns, making it challenging to identify correctly. Furthermore, managing cases of ENN may necessitate supplementary treatment beyond steroids alone.

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.

Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables.

OBJECTIVE: Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. METHODS: In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. RESULTS: The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. CONCLUSION: The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

Improved HbA1c and body weight in GADA-positive individuals treated with tirzepatide: A post hoc analysis of SURPASS.

CONTEXT: People with clinically diagnosed type 2 diabetes (T2D) but positive anti-glutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits. OBJECTIVE: Assess glycated hemoglobin (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive versus GADA-negative participants with clinical T2D diagnosis. DESIGN: Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status. SETTING: N/A. PATIENTS: N = 3791. INTERVENTION: Tirzepatide (5, 10, 15 mg). MAIN OUTCOME MEASURE(S): Change from baseline in HbA1c at Weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4)by GADA status. RESULTS: In participants with confirmed GADA status, 3671 (96.8%) were GADA-negative and 120 (3.2%) were GADA-positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive versus GADA-negative participants (mean [SD] BMI 32.2 [6.1] versus 33.6 [6.3] kg/m2). At Week 40/42, both groups achieved robust reductions in HbA1c (-2.11% versus -2.32%) and BW (9.2 kg versus -9.6 kg) (p < 0.001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; p = 0.024) and BW reductions did not differ between groups (0.38 kg [-0.99, 1.75]; p = 0.588). CONCLUSIONS: In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.

Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes.

AIM: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. MATERIALS AND METHODS: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. RESULTS: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. CONCLUSIONS: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.