Onset Of Diabetes Mellitus Research Articles

HPB SO33 - Transcriptomic characterisation of the diabetogenic pancreatic ductal adenocarcinoma phenotype

Abstract Background New-onset diabetes mellitus (NOD) can manifest as a consequence of pancreatic ductal adenocarcinoma (PDAC), although not all PDAC patients develop NOD. For many patients, hyperglycaemia begins 3 years prior to PDAC diagnosis, with 30% of PDAC patients experiencing NOD by the time their cancer is diagnosed. The mechanisms underlying the onset of diabetes mellitus (DM) in PDAC and its consequences for disease development, detection and treatment are not well understood. The aim of this study was to characterise the transcriptomic differences between PDAC tumours that present with NOD compared to those that do not. Method Eight tumour samples from patients undergoing surgery for PDAC (4 without DM (HbA1c <35), 4 with NOD (HbA1c >65, within 3 years of cancer diagnosis) underwent single cell-RNA sequencing (scRNAseq) after taking intra-operative biopsies using Chromium 10X Genomics technology. Unique cell clusters were identified using CellRanger and cell types annotated using scATOMIC and singleR datasets. Manual annotation was undertaken when results were not agreeable after consulting the literature. Differential expression between groups was performed using DESeq2. Significant genes were identified as having a log2 fold-change >1.5 and p<0.05. Gene set enrichment was performed using Reactome. Analysis was conducted in RStudio. Results Single cell suspensions were created with a mean cell count of 1.2 million cells and a mean viability of 90%. PDAC cells and the full complement of tumour microenvironmental cells were recovered. Significant differential expression was seen in the PDAC cells themselves, CD4+ cells, macrophages, mast cells and fibroblasts. Cancer associated fibroblasts (CAFs) seemed not to differ. PDAC cells with NOD seemed to be enriched in MYC oncogenes whereas those without DM seemed to be enriched in KRAS mutations. There was a mixture of “basal” and “classical” transcriptional subtypes between the two groups. Conclusion Differences between diabetogenic PDAC and non-diabetogenic PDAC have been observed at the transcriptional level. Diabetogenic tumours seem to be promoted by MYC oncogenes and be more inflammatory than non-diabetogenic tumours. These findings require validation which will be done on independent samples using spatial transcriptomics to allow endocrine-exocrine crosstalk to be determined. Understanding the molecular pathways in diabetogenic pancreatic tumours could enhance future strategies to detect PDAC earlier and to target diabetes-associated vulnerabilities for therapeutic purposes.

Association of time in range with cognitive impairment in middle-aged type 2 diabetic patients

ObjectiveThis study investigated the association of Time In Range (TIR) obtained from Blood Glucose Monitoring (BGM) with Cognitive Impairment (CI) inpatients with middle-aged Type 2 Diabetes Mellitus (T2DM) and further explored whether a TIR goal for T2DM in adults with > 70% possess a protective effect on cognitive function.Research design and methodsA total of 274 inpatients with T2DM aged 40–64 years, who underwent seven-point BGM ( pre meals and 120 min post meals and at bedtime) were recruited in this cross-sectional study. TIR was defined as the percentage of blood glucose within the target range of 3.9-10.0mmol/L. Subjects were divided into Normal Cognitive Function (NCF) (n = 160) and CI (n = 114) groups according to the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The association of TIR and other glycemic metrics, calculated from seven-point BGM data, with cognitive dysfunction was analyzed.ResultsThe prevalence of CI was 41.6% in patients with middle-aged T2DM (median age 58 years). TIR was lower in CI group than in NCF group (28.6% vs. 42.9%, P = 0.004). The prevalence of CI decreased with ascending tertiles of TIR (p for trend < 0.05). Binary logistic regression analysis showed a significant association between TIR and CI (odds ratio [OR] = 0.84, p < 0.001) after adjusting for confounders (age, education, marital status, age at Diabetes Mellitus (DM) onset, cerebrovascular disease). Further adjustment of Standard Deviation (SD)(OR = 0.84, p = 0.001) or Coefficient of Variation (CV)(OR = 0.83, p < 0.001), TIR was still associated with CI. While a TIR goal of > 70% probably possessed independent protective effect on cognitive function (OR = 0.25, p = 0.001) after controlling for confounders above.ConclusionsTIR obtained from BGM was related to CI in middle-aged T2DM individuals and a TIR goal of > 70% probably possessed a protective effect on cognitive function for middle-aged T2DM .

Hepatocyte nuclear factor 1 alpha variants as risk factor for hepatocellular carcinoma development with and without diabetes mellitus

BackgroundHNF1A gene variants have been reported to be involved in developing mature onset diabetes mellitus (DM). Many studies reported the role of DM as a risk factor for hepatocellular carcinoma (HCC) development. To date, it has not been reported whether HNF1A gene variants are associated with the risk of DM in cirrhotic patients and their subsequent HCC. ObjectiveTo evaluate the HNF1A (the hepatocyte nuclear factor 1 homeobox A) genetic variants as a cofactor with DM for HCC development in hepatitis C virus (HCV)-infected patients. Subjects and methodsThis study was conducted on 140 subjects; 30 had HCC without DM, 30 HCC with DM, and 40 patients had DM with no HCV infection or had HCC; in addition, 80 healthy volunteers with matched ages and genders were enrolled in the study as a control group. Liver function tests, hepatitis viral markers, alpha-fetoprotein (AFP), fasting sugar and HBA1c and HNF1A (rs2464196 and rs1169310) using real-time polymerase chain reaction (PCR) were done for all participants. ResultsThe frequency of HNF1A rs2464196 (AA) genotype in patient groups (DM, HCC, HCC + DM) was significantly higher compared to the control group (P = 0.006, P = 0.018, P < 0.001 respectively). The combined dominant model (AA + GA) of rs 2,464,196 was significantly higher than the (GG) genotype in patient groups (DM, HCC, HCC + DM) than the control group. In addition, the frequency of the AA genotype is more prevalent in HCC + DM (73 %) compared to the group of DM or HCC patients. In contrast, the HNF1A rs1169310 (TT, TC or CC genotypes) showed no significant difference among the four studied groups and their T or C allele distributions. ConclusionThis finding suggested that the HNF1A rs2464196 (AA) genotype could be associated with DM and may raise the possibility of HCC development among HCV-infected patients who harbour this genotype more than (GG). On the contrary, the HNF1A rs1169310 polymorphism was of no significance as a risk factor in the current study. However, as we limited our study to Egyptian participants, more research on other ethnic groups would be required. Also, large scale studies are recommended on other variants of HNF1A to clarify the role of this gene in HCC development.

The epidemiology of type 1 diabetes mellitus in older adults.

Although type 1 diabetes mellitus (T1DM) is traditionally viewed as a youth-onset disorder, the number of older adults being diagnosed with this disease is growing. Improvements in the average life expectancy of people with T1DM have also contributed to the growing number of older people living with this disease. We summarize the evidence regarding the epidemiology (incidence, prevalence and excess mortality) of T1DM in older adults (ages ≥60 years) as well as the genetics, immunology and diagnostic challenges. Several studies report an incidence peak of T1DM in older adults of a similar size to or exceeding that in children, and population prevalence generally increases with increasing age. Glutamic acid decarboxylase antibody positivity is frequently observed in adult-onset T1DM. Guidelines for differentiating T1DM from type 2 diabetes mellitus in older adults recommend measuring levels of C-peptide and autoantibodies, including glutamic acid decarboxylase antibodies. However, there is no gold standard for differentiating T1DM from type 2 diabetes mellitus in people aged 60 years and over. As such, the global variation observed in T1DM epidemiology might be in part explained by misclassification, which increases with increasing age of diabetes mellitus onset. With a growing global population of older adults with T1DM, improved genetic and immunological evidence is needed to differentiate diabetes mellitus type at older ages so that a clear epidemiological picture can emerge.

Association between dietary antioxidant levels and diabetes: a cross-sectional study.

The onset and progression of diabetes mellitus (DM) is strongly linked to oxidative stress. Previous studies have highlighted the protective effects of individual dietary antioxidants against diabetes. However, the relationship between a comprehensive combination of dietary antioxidants and diabetes has rarely been examined. Therefore, this study assessed the association between various dietary antioxidant intake levels and diabetes among US adults and further investigated potential associations using the Composite Dietary Antioxidant Index (CDAI). The study employed data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018 for cross-sectional analysis. Dietary information was obtained from two 24-h dietary recall interviews. The CDAI was calculated using intakes of six dietary antioxidants from the dietary information. Multifactorial logistic regression models were employed to investigate the association of different dietary antioxidants and CDAI with DM. The relationship between CDAI and DM was further explored using subgroup analyses and restricted cubic spline curves. A total of 7,982 subjects (mean age 47.32 ± 16.77 years; 48.50% male and 51.50% female) were included in this study. In the multivariate-adjusted single antioxidant model, vitamin C intake was significantly and negatively associated with diabetes prevalence (P for trend = 0.047), while zinc intake demonstrated a potential trend toward reduced diabetes risk (P for trend = 0.088). This association was similarly observed in the multivariate-adjusted model for the Composite Dietary Antioxidant Index (CDAI) in the female population (p = 0.046). Intake of vitamin C was negatively associated with DM prevalence. Additionally, CDAI was found to reduce the risk of DM in the female population.

8070 Atypical New Onset Diabetes Mellitus in a Young Male: Is this LADA vs Type 1 or Type 2?

Abstract Disclosure: S.K. Devineni: None. S. Shaik: None. J.L. Gilden: None. Background: Recent literature suggests that autoantibody seropositivity is common in new onset autoimmune Diabetes Mellitus (DM), especially in younger patients. Latent autoimmune diabetes of adults (LADA), a form of adult-onset autoimmune DM. is considered a mix of type 1 and type 2 DM, sharing similar immune cell characteristics to both subtypes. Unlike type 1, LADA patients do not require insulin for glycemic control for the first six months after diagnosis. Unlike type 2, LADA patients are positive for single islet autoantibody, glutamic acid decarboxylase (GAD), and anti-gliadin antibodies. Patients with LADA often present with symptoms (polyuria, polydipsia, nocturia, fatigue, and visual changes). We present a case of new onset Diabetes Mellitus in a young male, autoantibody seronegative, at the time of diagnosis. Case report: A 19-year-old Caucasian male was sent to the Emergency Department with a serum blood glucose (BG) level of 579 mg% after routine blood tests. He denied any clinical symptoms and serum levels showed no elevation in ketones, nor bicarbonate levels, ruling out ketoacidosis. His hemoglobin A1c at that time was 14.7%. He denied prior knowledge of personal or family history of DM. or other autoimmune disorders. However, it was discovered that routine labs done 1 ½ months earlier on a Health Screen revealed BG=295 mg% with urine positive for ketones (80 mg/dl) and glucose (&amp;gt;1000 mg/dL). Physical Exam: (HT=178 cm; WT=79 Kg) was unremarkable. Autoantibodies for GAD 65, islet-cell, Zinc transporter 8, and Islet Antigen 2 were all negative. He was hospitalized for 9 days. BG levels were difficult to control and required increasing doses of both long acting and short acting insulin. He was discharged with insulin therapy (30 units of glargine at nighttime and 12 units of premeal aspart). One week later, the patient ate several gummy bears as a nighttime snack and subsequently woke up in the middle of the night feeling shaky and having blurry vision. BG was greater than 300 mg%. In the emergency room, he. received intravenous fluids. No insulin was given as his BG normalized and he was discharged. Later, a continuous glucose monitor revealed multiple hypoglycemic episodes. The patient was living in a situation where he only had limited access to certain foods, and thus his insulin regimen was decreased (28 units glargine and 10 units aspart for meals) Conclusion: We present the case of new onset atypical DM in a young patient whose insulin sensitivity and risk factors seem to resemble a pattern of type 1 DM; despite seronegative autoantibodies We predict that he may eventually seroconvert to type 1 DM. It is also possible that he may have an unusual presentation of LADA or type 2 DM, although he had no hyperglycemic symptoms. Presentation: 6/3/2024

8494 A Case of Diabetic Ketoacidosis in Setting of COVID-19 Infection and SGLT-2 Inhibitor Use

Abstract Disclosure: N. Abrahimi: None. S. Bajpay: None. A. Abrahimi: None. Background: COVID-19 infection can cause endocrine system disruptions leading to the development of diabetic ketoacidosis (DKA) in patients with type 1, 2 or new onset diabetes mellitus. (1) DKA is a side effect of SGLT-2 inhibitor use and its development on the medication can lead to discontinuation of SGLT-2 inhibitor. (2) SGLT-2 inhibitors are part of guideline directed medical therapy for management of heart failure with reduced ejection fraction (HFrEF). (3) Case: 67-year-old female history of non-insulin dependent diabetes mellitus type 2 on Empagliflozin presented with shortness of breath and hypoxia. Initial BMP: Glucose 141 mg/dL, bicarb 24 mmol/L, anion gap of 10 mmol/L. Patient test positive for COVID-19 and was admitted for acute hypoxic respiratory failure in setting of COVID-19 infection. Six hours after patient received first dose of dexamethasone, labs showed BMP: Glucose 582 mg/dL, bicarb 14 mmol/L, anion gap of 20 mmol/L. ABG: pH 7.09, bicarb 13.2 mmol/L, glucose 509 mg/dL, lactate 9.6, beta-hydroxybutyrate 1.15 mmol/L. Patient was diagnosed and treated for DKA. Patient had an echocardiogram which showed new HFrEF. There was initial hesitation to restart patient on home Empagliflozin due to recent development of DKA. Literature review showed cases of DKA associated with COVID-19 infection. Etiology of DKA remained unclear. Ultimately, it was decided to restart patient on home Empagliflozin for management of diabetes and HFrEF. Conclusion: An abundance of evidence support the benefits of SGLT-2 inhibitors for patients with and without type 2 diabetes mellitus. (4) It is important to consider other causes of DKA for patients who develop DKA on SGLT-2 Inhibitors. Furthermore, additional research into endocrinopathies related to COVID-19 infections should be considered.

6779 The Diversity of Immune Checkpoint Inhibitor Associated Diabetes

Abstract Disclosure: V.A. Mendpara: None. M. Lansang: None. M. Caromori: None. L. Kennedy: None. K. Zhou: None. Immune checkpoint inhibitor (ICI) treatment has become a first-line therapy for a variety of cancers, including use of nivolumab (a programmed death 1 [PD-1] inhibitor) for metastatic melanoma. Though able to prolong survival, ICIs cause immune-related adverse events (irAE) through down-regulation of immune control pathways. One irAE is diabetes mellitus (DM), referred to as ICI-induced DM. Despite its low incidence (2%), ICI-induced DM carries with it high morbidity, with need for hospitalization in up to 25% of patients, and burden as patients are typically committed to multiple daily insulin injections (MDII). Here we report diverse presentations of four patients treated with ICI for metastatic melanoma who developed ICI-induced DM. The median age at DM presentation was 60.5 years (range 59-78 years). All patients received nivolumab and one patient was also treated with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 inhibitor). The median time from start of ICI to development of ICI-induced DM was 32.5 wks, ranging from 27-46 wks. Three of the 4 patients previously developed hypothyroidism at median of 15 wks from starting ICI. Two patients presented in DKA and the other 2 with severe hyperglycemia (glucose &amp;gt;300 mg/dL). Median HbA1c was 7.05% (range 6.4%-7.4%) at presentation. GAD Ab was negative in 3 of 4 patients, including one who had DKA. C-peptide was undetectable (&amp;lt;0.2 ng/mL) in the 2 patients with DKA, 0.4 ng/mL in one other patient, and not measured in the fourth. All patients were immediately started on MDII. However, the two patients without DKA on presentation were eventually initiated on non-insulin agents. One of them was started on a DPP-4 inhibitor and discontinued fast-acting insulin, and the other started a GLP-1 receptor agonist and reduced their fast-acting insulin requirement. The heterogeneity of DM presentation and its clinical course reported here highlights a few important points. The first is that the onset of ICI-induced DM is often much later than that of the most common endocrine irAE, hypothyroidism, which has an onset around 10 weeks in average. Second, DM often presents as severe hyperglycemia incidentally detected on blood work. GAD Ab positivity is relatively less common, suggesting a different underlying etiology than classic type 1 DM. Onset of severe hyperglycemia can occur over many weeks (as indicated by higher HbA1c), making it important to monitor for hyperglycemia in those with no previous history of prediabetes or DM. Finally, it may be possible to use a combination of non-insulin antihyperglycemic agents to provide better glycemic management. No widely validated strategies for the surveillance of irAEs are currently available, and a better understanding in the propensity of patients to develop irAEs is clearly required. Importantly, optimal management of irAEs relies on early recognition and frequently demands a multidisciplinary approach. Presentation: 6/2/2024

FASTING BLOOD SUGAR (FBS) IN THE FIRST TRIMESTER: PREDICTIVE VALUE FOR GESTATIONAL DIABETES MELLITUS AND IMPACT ON PREGNANCY-RELATED OUTCOMES

Gestational diabetes mellitus (GDM) is a significant health concern in pregnancy, affecting maternal and neonatal outcomes. Early detection of GDM through fasting blood glucose (FBS) screening may help in timely management to prevent complications. Objective: To determine the fasting blood glucose threshold that accurately predicts the onset of gestational diabetes mellitus (GDM) and its impact on pregnancy outcomes. Methods: A prospective cohort study was conducted at the Obstetrics and Gynecology Department of Jinnah Postgraduate Medical Centre (JPMC), Karachi, from August 2023 to May 2024, involving 405 pregnant women selected through systematic random sampling. Inclusion criteria included singleton pregnancies, excluding women with pregestational diabetes or baseline fasting glucose levels of 126 mg/dL or higher. Baseline data on age, BMI, gestational age, and family history of diabetes were collected, and FBS levels were measured at the initial visit. Oral Glucose Tolerance Tests (OGTT) were conducted between 24 to 28 weeks of gestation to diagnose GDM. Maternal and fetal outcomes were monitored until delivery. Statistical analyses, including logistic regression and ROC curve analysis, were performed using IBM SPSS version 20. Results: Among the 405 participants, with a mean age of 28 ±6.49 years, the mean fasting blood sugar (FBS) was 89.5 mg/dL (±12.3). Impaired FBS (≥92 mg/dL) was noted in 24.70% of participants, and 18.27% were diagnosed with GDM following OGTT. A fasting glucose level of 127.4 mg/dL (±22.1) was observed among women diagnosed with GDM. Logistic regression showed a significant association between FBS ≥92 mg/dL and GDM risk (OR 1.08, CI 1.02-1.14, p=0.011). ROC analysis revealed an FBS cutoff of 92 mg/dL with 73% sensitivity and 68% specificity for predicting GDM. Gestational hypertension was observed in 8.64% of participants, and preeclampsia in 6.67%. Vaginal deliveries occurred in 72.1% of cases, while 27.9% required cesarean sections. Neonatal outcomes showed an 11% macrosomia rate, with 12% requiring NICU admission. Conclusion: Fasting blood glucose levels ≥92 mg/dL in early pregnancy are strongly predictive of gestational diabetes mellitus (GDM). Early FBS screening allows for timely intervention, potentially improving maternal and neonatal outcomes. This study underscores the importance of incorporating FBS screening in routine antenatal care for better pregnancy management.

7316 A Unique Presentation of Diabetes Mellitus in an 8-Year-Old Male Positive For 3 Different Mutations Related to MODY

Abstract Disclosure: R. Senguttuvan: None. A. Pamfil: None. Background: Maturity-Onset Diabetes of the Young (MODY) is the most common form of inherited non-autoimmune diabetes mellitus, characterized by autosomal dominant inheritance, young age at onset and beta cell dysfunction. There are at least 14 MODY mutations and we present a pediatric case not meeting criteria for type 1[T1DM] or type 2 diabetes mellitus[T2DM], who tested positive for mutations in 3 different genes known to cause MODY. Case: An 8-year-old male, born full term, 2776 grams and 48.3 cm, without history of neonatal hypoglycemia or hyperglycemia, was referred for new onset diabetes mellitus management. While undergoing evaluation for abdominal pain and constipation, he was found to have a fasting glucose of 126 mg/dL (7 mmol/L) and hemoglobin A1C of 6.5%. He endorsed polyuria, but no polydipsia. He had no clinical signs of insulin resistance (e.g., acanthosis nigricans) and a BMI of 23.65 kg/m2, at the 97th percentile. Family history is positive for diabetes mellitus requiring insulin, in father (diagnosed at 11 years) and paternal grandmother and T2DM in paternal aunt. Laboratory evaluation was negative for all 5 antibodies (GAD, IA-2, Anti-islet cell antibody, Zinc Transporter 8 and Insulin antibodies) and revealed an insulin level of 15.9 uIU/mL (RR: &amp;lt;2.0-13.0) and C peptide: 2.3 ng/mL (RR: 1.1-4.4). Lacking diagnostic criteria for T1DM or T2DM, genetic testing was performed. Patient tested heterozygous for mutations in 3 genes known to cause MODY: GCK [(c.350 G&amp;gt;T p. (G117V)], ABCC8 [(c.2270 C&amp;gt;G p.(T757R)], and HNF1B [(c.68A&amp;gt;G p.(K23R)], all variant of uncertain significance. Over an 8-month period, patient's weight decreased from 98 lbs. (44.9 kg) to 90 lbs. (41.1 kg) after meeting with our dietician and implementing healthy dietary changes, and his beta cell function markers improved from diagnosis: Fasting insulin (4.5 uIU/mL), C peptide (1.3 ng/mL), and glucose 119 mg/dL; Hemoglobin A1C remained relatively stable at 6.1%. A kidney ultrasound was normal. No medical intervention were started yet, and patient is being monitored clinically and biochemically every 3-4 months. Discussion: Clinical monitoring over time, genetic testing in the parents, are critical in this patient’s long-term treatment plan and prognosis. To our knowledge, this may be the first case of diabetes mellitus in a pediatric patient, positive for mutations in 3 different genes known to cause MODY. South Texas has one of the highest incidences of T2DM in the USA. In addition to screening for genetic forms of diabetes, in patients with negative T1DM antibodies and atypical phenotype for T2DM, we should consider genetic screening in mildly obese pediatric and young adult patients without significant acanthosis nigricans, who were already diagnosed as T2DM. Presentation: 6/1/2024

Association of mid-pregnancy ferritin levels with postpartum glucose metabolism in women with gestational diabetes

BackgroundFerritin, a key indicator of body iron levels, has been reported to associate with type 2 diabetes (T2DM) and the onset of Gestational diabetes mellitus (GDM). However, limited research explores the association between mid-pregnancy ferritin levels and the risk of postpartum abnormal glucose metabolism (AGM) in patients with GDM.MethodsA retrospective cohort study was conducted in 1514 women with GDM recruited from January 2016 to January 2021, and 916 women were included. Demographic characteristics, medical history and family history, pregnancy complications were recorded. Multiple logistic regression models were performed to assess the association between mid-pregnancy ferritin levels and the risk of postpartum AGM.ResultsFollowing the postpartum oral glucose tolerance test, 307 (33.5%) exhibited AGM. The AGM group had higher mid-pregnancy serum ferritin levels [AGM vs NGT: 23 (11.7, 69) µg/L vs 17.80 (9.85, 40.7) µg/L, P < 0.001] and had a larger proportion of women with ferritin levels ≥30 µg/L (AGM vs NGT: 43.6% vs 31.4%, P < 0.001). Logistic regression analysis demonstrated that women with ferritin levels≥ 30 µg/L had a 1.566 times higher risk of developing postpartum AGM.ConclusionsThese findings indicate that elevated mid-pregnancy ferritin levels are significantly and independently associated with increased postpartum AGM risk in women with previous GDM. Consequently, cautious consideration is necessary for prescribing iron supplements in prenatal care, particularly for non-anemic women with GDM at high risk of developing diabetes after delivery.

Risk Factors of Chronic Kidney Diseases: A Retrospective, Record based Study from a Tertiary Care Hospital in India

Abstract Background: There is a alarming rise of chronic kidney diseases (CKDs) prevalence globally, which is associated with significant morbidity and mortality. The burden of Chronic Kidney Diseases is rapidly rising in developing countries. The study aimed to assess the major risk factors of CKD in patients of a tertiary hospital. Materials and Methods: Hospital-based, retrospective study was conducted at a hospital, in Mumbai, among CKD patients. Medical records of 500 CKD patients were analysed. Results: The mean age of participants was 53.87 years. Majority of the patients had risk factors for CKD such as hypertension and diabetes. The mean serum creatinine was 4.04 mg/dL. Majority of the cases were in G4 and G5 stages of CKD and 201 patients had undergone kidney transplant. Association between age and transplant was significant. Furthermore, association between developing New Onset Diabetes Mellitus After Transplantation (NODAT) was statistically significant. Conclusion: Major risk factors for CKD were hypertension, diabetes and advancing age. Most of the cases of CKD were diagnosed late. There should be increased awareness about CKD among the population with special emphasis on cases of hypertension and diabetes.

The role of high mobility group box-1 on the development of diabetes complications: A plausible pharmacological target.

Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s. Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.

New-onset diabetes mellitus in patients with COVID19 infection admitted to a tertiary care hospital: A single-center experience.

To determine the frequency of new-onset diabetes mellitus (NODM) in patients with COVID-19 in a tertiary care hospital. It was a retrospective descriptive study carried out in Lady Reading Hospital Peshawar, Khyber Pakhtunkhwa province of Pakistan from November 2021 to April 2022. All patients having new onset Diabetes Mellitus (NODM) were identified among a total of 300 patients admitted to the hospital with COVID-19 infection. Patients' data including relevant investigations were accessed through the hospital management information system (HMIS). SPSS version-23 was used for data entry and statistical analysis. Out of 300 COVID-19 patients included in the study, 163 (54.3%) were female and 137(45.7%) were male. The mean age of the patients was 56.80±13.72 (IQR 15) years. Frequency of the new onset diabetes was 44(14.7%); 19 (6.33%) male and 25(8.33%) female. Among the 44 NODM patients, the majority (57%) were female (p=0.720). Most (64%) of the patients with new-onset DM were in the middle age (p=0.018). A significant number of patients with COVID-19 infection are prone to develop new-onset diabetes during their admission to the hospital.

Risk of fungal infection in patients with psoriasis receiving biologics: A retrospective single-center cohort study

BackgroundThe risk of fungal infection in patients with psoriasis receiving biologics is not fully understood in clinical practice. ObjectiveTo assess the incidence and the risk of fungal infection onset in patients with psoriasis receiving biologics. MethodsRetrospective cohort study of 592 psoriasis cases treated with biologics at a single center. ResultsSeventy-three (12.3%) of the 592 cases involved a fungal infection. Fungal infection occurrence was more frequently associated with the use of interleukin (IL)-17 inhibitors than of other biologics. The risk factors of fungal infection were the type of biologic agent (P = .004), age at the start of biologic therapy (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06), and diabetes mellitus (OR: 2.40; 95% CI: 1.20-4.79). LimitationsThe present, retrospective study did not include patients who did not receive biologic therapy. Moreover, the type of biologic agent used was changed in many cases. ConclusionPsoriasis patients treated with IL-17 inhibitors were more likely to cause fungal infections, especially candidiasis, than other biologics. Moreover, the age at the start biologic therapy and diabetes mellitus onset were also independent risk factors of fungal infection.

Cardiovascular Risk in Rheumatoid Arthritis: Considerations on Assessment and Management.

In the context of holistic therapeutic practices, the cardiovascular risk of patients with rheumatoid arthritis (RA) needs to be addressed as a major factor of compromised disease prognosis and increased mortality. The elevated prevalence of cardiovascular disease (CVD) by more than twofold in RA has been attributed, inter alia, to chronic inflammation exacerbating arterial stiffness, increased onset of hypertension, dyslipidaemia and diabetes mellitus, sedentary lifestyle, and antirheumatic drug complications. CVD risk in RA can be currently assessed by practitioners through accessible adapted calculators, but it remains problematic as their diagnostic accuracy is not superior to calculators designed for the general population. Implementation of guideline-oriented personalised interventions remains the cornerstone for cardiovascular risk management in RA. Remarkably, there is lack of a consortium that brings together different health care providers engaged in the care of patients with RA (e.g., rheumatologists, cardiologists, general practitioners, etc), to guide cardiovascular risk assessment and management. This narrative review aims at providing an overview of current CVD risk assessment and management options, highlighting their pivotal role in the comprehensive treatment of RA patients.

Acarbose might be associated with reduced risk of gastric cancer in patients with diabetes mellitus: A nationwide population-based cohort study.

Several epidemiologic studies have revealed a higher risk of cancer in patients with diabetes mellitus (DM) relative to the general population. To investigate whether the use of acarbose was associated with higher/lower risk of new-onset cancers. We conducted a retrospective cohort study, using a population-based National Health Insurance Research Database of Taiwan. Both inpatients and outpatients with newly onset DM diagnosed between 2000 and 2012 were collected. The Adapted Diabetes Complications Severity Index (aDCSI) was used to adjust the severity of DM. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease. A total of 22 502 patients with newly diagnosed DM were enrolled. The Cox proportional hazards regression model indicating acarbose was neutral for risk for gastroenterological malignancies, when compared to the acarbose non-acarbose users group. However, when gastric cancer was focused, acarbose-user group had significantly lowered HR than non-acarbose users group (p = 0.003). After adjusted for age, sex, cancer-related comorbidity, severity of DM, and co-administered drugs, the HR of gastric cancer risk was 0.43 (95% CI = 0.25-0.74) for acarbose-user patients. This long-term population-based study demonstrated that acarbose might be associated with lowered risk of new-onset gastric cancer in diabetic patients after adjusting the severity of DM.

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy.

To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P<0.01), with 95 (92.23%) FVPMs located in the nasal quadrants, and 74 (71.84%) in the inferior. The eyes with a central FVPM required the longest operation time, with silicon oil used in most patients, generally combined with tractional retinal detachment (RD) and rhegmatogenous RD, the worst postoperative best-corrected visual acuity (BCVA) and the highest rates of recurrent RD (all P<0.05). FVPM type, age of onset diabetes mellitus, preoperative BCVA, and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement (all P<0.05). Compared with the central type group, the arcade type group had higher rates of BCVA improvement. FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels. Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

Incidence of Postoperative Diabetes Mellitus After Roux-en-Y Reconstruction for Gastric Cancer: Retrospective Single-Center Cohort Study.

Sleeve gastrectomy is an effective surgical option for morbid obesity, and it improves glucose homeostasis. In patients with gastric cancer and type 2 diabetes mellitus (DM), gastrectomy, including total gastrectomy, is beneficial for glycemic control. This study aims to clarify the effects of gastrectomy and different reconstructive techniques on the incidence of postoperative DM in patients with gastric cancer. This retrospective, single-center, cohort study included 715 patients without DM who underwent total gastrectomy at the Tokyo Metropolitan Bokutoh Hospital between August 2005 and March 2019. Patients underwent reconstruction by Roux-en-Y (RY) gastric bypass or other surgical techniques (OT), with DM onset determined by hemoglobin A1c levels or medical records. Analyses included 2-sample, 2-tailed t tests; χ2 tests; and the Kaplan-Meier method with log-rank tests to compare the onset curves between the RY and OT groups, along with additional curves stratified by sex. A Swimmer plot for censoring and new-onset DM was implemented. Stratified data analysis compared the RY and OT reconstruction methods. The hazard ratio was 1.52 (95% CI 1.06-2.18; P=.02), which indicated a statistically significant difference in the incidence of new-onset diabetes between the RY and OT groups in patients with gastric cancer. The hazard ratio after propensity score matching was 1.42 (95% CI 1.09-1.86; P=.009). This first-of-its-kind study provides insight into how different methods of gastric reconstruction affect postoperative diabetes. The results suggest significant differences in new-onset DM after surgery based on the reconstruction method. This research highlights the need for careful surgical planning to consider potential postoperative DM, particularly in patients with a family history of DM. Future studies should investigate the role of gut microbiota and other reconstructive techniques, such as laparoscopic jejunal interposition, in developing postoperative DM.

CONSUMPTION PATTERNS AND NUTRITIONAL STATUS OF ADOLESCENTS AND PARENTS WITH DIABETES MELLITUS (DM)

Teenagers more often consume foods that are high in fat and glucose than vegetable and fruit consumption. This can trigger the onset of diabetes mellitus, especially in adolescents who have Diabetes Mellitus (DM) parents. The purpose of this study was to determine the differences in consumption patterns and status between adolescents and parents of DM and not DM. This cross sectional study involved 42 adolescents as samples, consisting of 21 adolescents with DM parents and 21 adolescents who were not DM parents, randomly using simle rendom sampling technique, the differences between variables were analyzed using the Independent T-test and Mann Whitney test (α=0.05). The results showed that there were no differences in the consumption patterns of high Glycaemic Index (GI) foods (p = 0.229) and fruit and vegetables (p = 0.14) between adolescents with DM parents and non-DM parents, but adolescents with DM parents tended to consume more high GI foods than adolescents with non-DM parents. There were differences in nutritional status between adolescents with DM parents and non-DM parents (p = 0.036). The conclusion of this study is that most adolescents with DM parents are very overweight at the time of nutritional status. In adolescents, it is necessary to reduce the frequency of consumption of foods with high IG and to increase the consumption of fruit and vegetables and physical activity, especially in adolescents with DM parents.