New-onset Diabetes Research Articles

Prevención y detección precoz del cáncer de páncreas

In western countries, pancreatic ductal adenocarcinoma (PDAC) has shown a rising incidence and is currently one of the leading causes of cancer related mortality. Due to its aggressive biology, most patients diagnosed with PDAC present with advanced disease not suitable for curative treatment. An early detection strategy could potentially improve results by detecting more PDAC patients within the initial stages of the disease.Currently, diagnosis of PDAC is mostly based in cross sectional imaging, including computed tomography and magnetic resonance imaging (MRI) as well as biomarkers such as CA 19-9. Selected cases might be further studied using endoscopic ultrasound (EUS) with the option of EUS guided biopsy if histology is needed to confirm diagnosis.Due to its low incidence, screening general population for PDAC has been shown to be an ineffective and expensive approach. For this reason, efforts have shifted towards surveillance of specific groups of patients known to be at risk for development of PDAC. In these groups, screening has shown to have a higher yield for early cases and improved results in terms of resection rates and survival. These groups include carriers of certain oncogenic germline mutations, patients with strong family history for PDAC, and patients diagnosed with mucinous cystic neoplasms of the pancreas. Patients over 50 years old diagnosed with new-onset diabetes and patients living with chronic pancreatitis are also considered to be at risk for PDAC development. Patients selected for surveillance should be included in screening protocols including periodic imaging with MRI or EUS.Development of biomarkers is an area of active research in the field of pancreatic cancer. New genetic or molecular biomarkers, to be measured in an isolated or combined manner, are an interesting approach looking to improve current diagnostic capabilities and to provide new tools for effective screening in wider groups of patients.The aim of this article is to describe strategies currently available for early detection of PDAC, including promising research areas for the near future.

IDF23-0240 Association of COVID-19 with new-onset diabetes in a geographically and ethnically diverse cohort of US adults

IDF23-0240 Association of COVID-19 with new-onset diabetes in a geographically and ethnically diverse cohort of US adults

Prevalence and risk factors of new-onset diabetes after transplantation: A single-center experience

Prevalence and risk factors of new-onset diabetes after transplantation: A single-center experience

Characteristics of Early Pancreatic Cancer: Comparison between Stage 1A and Stage 1B Pancreatic Cancer in Multicenter Clinical Data Warehouse Study.

Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer. A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023. In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2-4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival. IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.

Late post-COVID syndrome: clinical complications beyong 12 weeks

The persistent and diverse manifestations of post-COVID syndrome present a significant challenge for global healthcare. Beyond the acute phase of infection, individuals continue to grapple with lingering symptoms affecting various organ systems, including the respiratory, cardiovascular, neurological, and endocrine systems. In the respiratory realm, symptoms such as cough, dyspnea, and fatigue endure, particularly in those with a history of severe COVID-19. The cardiovascular impact manifests as chest pain, arrhythmias, and heightened risks of thromboembolic events, emphasizing the intricate connection between COVID-19 and cardiovascular complications. Neurological complications, ranging from headaches to more severe disorders, further contribute to the complex sequelae of post-COVID syndrome. Additionally, disruptions in the endocrine system, including new-onset diabetes and thyroid abnormalities, pose long-term challenges for affected individuals. The review discusses the clinical management challenges posed by the multifaceted nature of post-COVID complications and the necessity for tailored multidisciplinary approaches. A holistic and compassionate response to the long-term effects of COVID-19 requires collaboration across healthcare professionals, researchers and the broader community. By navigating these challenges collectively, we can pave the way for a more comprehensive and effective approach to post-COVID care.

Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice.

Type 1 diabetes (T1D) is an autoimmune disease where pathogenic lymphocytes target autoantigens expressed in the pancreatic islets, leading to the destruction of insulin-producing β-cells. Zinc transporter 8 (ZnT8) is a major autoantigen abundantly present on the β-cell surface. This unique molecular target offers the potential to shield β-cells against autoimmune attacks in T1D. Our previous work showed that a monoclonal antibody (mAb43) against cell-surface ZnT8 can home in on the pancreatic islets and prevent autoantibodies from recognizing β-cells. This study demonstrates that mAb43 binds to exocytotic sites on the β-cell surface, masking the antigenic exposure of ZnT8 and insulin following glucosestimulated insulin secretion. In vivo administration of mAb43 to nonobese diabetic (NOD) mice selectively increased the proportion of regulatory T-cells (Tregs) in the islet, resulting in complete and sustained protection against T1D onset as well as reversal of new-onset diabetes. The mAb43-induced self-tolerance was reversible after treatment cessation and exhibited no adverse effects during long-term monitoring. Our findings suggest that mAb43 masking of the antigenic exposure of β-cells suppresses the immunological cascade from B-cell antigen presentation to T-cell mediated β-cell destruction, providing a novel islet-targeted and antigen-specific immunotherapy to prevent and reverse clinical T1D.

Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus.

People with new-onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new-onset diabetes. We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti-diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. Among 99687 women aged ≥50years with new-onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta-blockers, acid disorder drugs, and lipid-modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. Our model doubled the PPV of pancreatic cancer in women with new-onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.

Comparing New-onset Diabetes in Post Moderate-to-severe Coronavirus Disease 2019 Patients with Newly Diagnosed Diabetes Patients with Mild or without Prior Coronavirus Disease 2019 Infection

Background: Systemic inflammation and various drugs used for treating coronavirus disease 2019 (COVID-19) including high-dose corticosteroids play a role in the development of new-onset diabetes (NOD). Patients of all ages and genders recovering from COVID-19 reportedly have an increased incidence and relative risk of developing diabetes. The present study thus tried to compare NOD in post moderate-to-severe COVID-19 patients with newly diagnosed diabetes patients with mild or without prior COVID-19 infection. Methods: This cross-sectional study included 100 newly diagnosed diabetes patients with a previous history of moderate-to-severe COVID-19 and those with no or mild history of previous COVID-19 infection (50 each in both groups). A detailed history was taken, and a clinical examination was done. Data on symptomatology, family history of diabetes, behavioral habits, anthropometry, and glycemic parameters was captured. Stress levels were assessed using the 5-point Perceived Stress Scale-10. The data obtained were statistically analyzed. Results: Assessing for the glycemic indices – fasting blood glucose, postprandial blood glucose, and glycosylated hemoglobin – was significantly higher in the moderate/severe COVID-19 arm as in comparison to the no/mild COVID-19 arm (P &lt; 0.0001). C-peptide was significantly higher in the moderate/severe COVID-19 arm (P &lt; 0.0001). The stress score was as high as 23.54 for the moderate/severe COVID-19 arm in comparison to 15.00 for the no/mild COVID-19 arm. Conclusion: NOD following COVID-19 pneumonia differs to some extent from NOD without COVID-19 in terms of having increased insulin resistance and worsened glycemic parameters. Clinicians should be aware of this entity as more aggressive control of dysglycemia is warranted to avoid complications arising out of it.

Diabetes duration, cholesterol levels, and risk of cardiovascular diseases in individuals with type 2 diabetes.

To investigate the association of diabetes duration with cardiovascular disease (CVD) risk and to examine the relationship between lipid levels and CVD risk over the duration. Using the Korean National Health Insurance Service Cohort database, we identified 2,359,243 subjects with type 2 DM aged ≥20 years in 2015-2016. Baseline lipid levels and diabetes duration were evaluated, and followed up until December 2020 (mean follow-up, 3.9 years). Subjects were categorized according to diabetes duration (new-onset, <5 years, 5-9 years, or ≥10 years). We analyzed the new-onset diabetes group with low-density lipoprotein cholesterol (LDL-C), <70 mg/dL, as the reference group. The hazard ratios (HRs) and 95% confidence intervals (CIs) of myocardial infarction (MI), and ischemic stroke (IS) were estimated using a Cox proportional hazards model adjusted for potential confounders. During follow-up, 45,883 cases of MI and 53,538 cases of IS were identified. The risk of MI or IS began to increase at LDL-C ≥160 mg/dL in the new-onset diabetes group, and at LDL-C ≥130 mg/dL in the diabetes duration <5 years group. Among subjects with a diabetes duration of 5-9 years, LDL-C 100-129 mg/dL, LDL-C 130-159 mg/dL, and ≥160 mg/dL were significantly associated with the risk of MI, with HRs (95% CI) of 1.13 (1.04-1.22), 1.28 (1.17-1.39), and 1.58 (1.42-1.76), respectively. The risk of MI in the diabetes duration ≥10 years group was increased by 16%, even in the LDL-C 70-99 mg/dL population (HR [95% CI] 1.16 [1.08-1.25]). This population-based longitudinal study revealed that the LDL-C cutoff level for increasing the risk of cardiovascular disease varied with diabetes duration, and that the target LDL-C level should depend on the duration.

A112 THE EDMONTON PANCREATICOBILIARY INFLAMMATION AND CANCER (EPIC) PROGRAM – A NEW MULTIDISCIPLINARY COORDINATION OF CARE INITIATIVE

Abstract Background Pancreaticobiliary (PB) cancer is associated with a poor prognosis. A timely diagnosis and a coordinated, multidisciplinary effort may improve outcomes as patients navigate the healthcare system for investigations and treatment. Aims To establish and pilot a multidisciplinary (gastroenterology [GI], hepatopancreatic biliary [HPB] surgery, radiology, oncology, palliative medicine, and nutrition) collaborative care pathway (CCP) to coordinate timely referral and access to management for patients with PB cancer. Methods With multidisciplinary expert input, a CCP for PB cancer patients was developed. A donation to our hospital foundation facilitated the hiring of a nurse navigator (NN) to coordinate this process. The EPIC program was initiated as a 6-month pilot project on 01/07/23 for all consecutive patients referred to the University of Alberta Hospital with suspected PB cancer. Referrals were triaged by GI and HPB surgery into resectable, borderline resectable, or unresectable arms of the CCP. EUS biopsy and/or ERCP for stent were performed as needed. A referral to medical oncology was made after a diagnosis was established. Descriptive statistics were completed. Results At 3 months, 64 patients (39 M, 25 F), mean age 67±12 years (range 19-95 years), were referred to EPIC. Presenting symptoms were abdominal pain (73%), weight loss (40%), jaundice (27%), nausea/vomiting (21%), itching (8%), and new-onset diabetes (5%). Site of cancer was pancreas (77%, 49/64), bile duct (20%, 13/64), and ampulla (3%, 2/64). Timelines to care access were compared with a similar pre-CCP patient cohort as shown in Table. Conclusions The role of the NN is to reduce variability and coordinate timely referral, scheduling, and follow-up based on the care pathway, and to serve as a point of contact for ongoing patient issues. The EPIC program pilot is on track to meet the timelines set forth in the care pathway. Primary care outreach to increase awareness of symptoms and for prompt investigation may further improve access to care in these patients. Note: negative numbers indicate days where the GI/HPB review occurred before the CT/MRI, or intervention before GI/HPB review EPIC COLLABORATIVE CARE PATHWAY Funding Agencies None

A313 DISCONNECTED PANCREATIC DUCT SYNDROME: A RETROSPECTIVE OBSERVATIONAL STUDY REVIEWING AN IMPORTANT BUT OVERLOOKED COMPLICATION OF NECROTIZING PANCREATITIS

Abstract Background Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis (ANP) characterized by a complete disruption of the main pancreatic duct, leading to the loss of continuity between the pancreatic duct and the gastrointestinal tract (figure 1). Due to unopposed leakage of residual pancreatic fluid, patients with DPDS often experience a prolonged disease course with significant morbidity, including complications such as pancreatic fistulas. However, information about the epidemiology, clinical characteristics, and outcomes of DPDS remains scarce. Aims To assess clinical outcomes, diagnostic delay, burden of endoscopic and surgical interventions, and complications related to DPDS. Methods A retrospective review was conducted for all patients diagnosed with DPDS who underwent either endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) at our tertiary center between January 2010 and December 2022. Results Fifteen patients with DPDS following ANP were identified. The median age of patients at DPDS diagnosis was 56 years (range 33-86 years), with 47% being female. The most common etiology of ANP was biliary (40%), followed by idiopathic (33%) and alcoholic (27%). The median time between ANP diagnosis and DPDS diagnosis was 265 days (range 86-2023 days). Patients underwent a median of 3 (1-9) endoscopic interventions and 1 (0-5) surgical intervention between the initial ANP episode and DPDS diagnosis. 40% of patients experienced intra-abdominal sepsis secondary to infected pancreatic fluid collections. 20% developed pancreatic fistulas (two small bowel fistulas and one cutaneous fistula). 20% developed new-onset diabetes, and 13% had significant worsening of pre-existing diabetes. No mortalities were reported. Conclusions There is a significant delay in diagnosing DPDS following ANP, and a substantial burden of endoscopic interventions is required. Frequent complications of DPDS were pancreatic fistulas, recurrent pancreatic fluid collections, and pancreatogenic diabetes. Developing a predictive model for assessing the risk of DPDS development following ANP could aid in earlier diagnosis and potentially reduce morbidity and complications associated with DPDS. Figure 1. Contrast enhanced CT demonstrating typical finding in DPDS in coronal (A) and axial (B) views. CT demonstrates 3cm area of necrosis involving pancreatic neck/body (asterisk) with viable upstream parenchyma in the remainder of the body and tail (white arrow). Pancreatic head/uncinate parenchyma and main duct appear intact (black arrow). B, the distal pancreatic duct is not dilated. DPDS, disconnected pancreatic duct syndrome. Funding Agencies None

Endothelial Extracellular Vesicles Enriched in microRNA-34a Predict New-Onset Diabetes in Coronavirus Disease 2019 (COVID-19) Patients: Novel Insights for Long COVID Metabolic Sequelae.

Emerging evidence indicates that the relationship between coronavirus disease 2019 (COVID-19) and diabetes is 2-fold: 1) it is known that the presence of diabetes and other metabolic alterations poses a considerably high risk to develop a severe COVID-19; 2) patients who survived a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have an increased risk of developing new-onset diabetes. However, the mechanisms underlying this association are mostly unknown, and there are no reliable biomarkers to predict the development of new-onset diabetes. In the present study, we demonstrate that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts the risk of developing new-onset diabetes in COVID-19. This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. SIGNIFICANCE STATEMENT: We demonstrate for the first time that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells is able to reliably predict the risk of developing diabetes after having contracted coronavirus disease 2019 (COVID-19). This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. Our findings are also relevant when considering the emerging importance of post-acute sequelae of COVID-19, with systemic manifestations observed even months after viral negativization (long COVID).

Advancing nutrition risk assessment in middle-aged and older individuals with diverse food cultures: A data-driven personalized approach to predict incident hypertension, diabetes and mortality.

Personalized nutrition risk assessment is crucial in addressing the association between healthy dietary habits across the life course and the development of disease, functional capacity, and healthy aging, as specific dietary pattern recommendations may not be suitable for diverse food cultures. To develop a data-driven, personalized nutrition risk assessment algorithm linked to incident hypertension, diabetes, and all-cause mortality utilizing the food frequency questionnaire among middle-aged and older individuals. A retrospective, population-based cohort study conducted between 1999 and 2015 utilized the nationally representative Taiwan Longitudinal Study on Aging (TLSA) survey to examine personalized dietary risk clusters and their associations with health outcomes. Latent class analysis was performed to derive the dietary diversity clusters among community-dwelling middle-aged and older individuals. Outcomes were defined as new-onset hypertension, diabetes mellitus and all-cause mortality at 4-, 8-, 12- and 16-year follow-ups. Data from 1,811 participants (58.14% males, 43.90% aged 50-64 years) showed that around one-third of participants reported being illiterate, 21.98% widowed, and 51.46% engaging in regular physical exercise. Four dietary diversity clusters were identified: "least diverse", "fish and meat", "dairy, fruit, and vegetable", and "most diverse". The "most diverse" cluster was characterized by a high consumption of protein-rich foods, while the "dairy, fruit, and vegetable" cluster had the highest consumption of dairy products and beans/legumes. The "least diverse" cluster had the lowest intake of protein-rich foods, and dark-colored vegetables and fruits. The "most diverse" cluster had a significantly lower risk of hypertension development at the 4-year (aOR 0.58; p < 0.02) and 8-year (aOR 0.57; p < 0.01) follow-up and diabetes at the 4-year (aOR 0.44; p < 0.03) follow-up. Participants in the "most diverse" clusters exhibited lower risks of 8-year, 12-year, and 16-year mortality than those in the "least diverse" cluster (aOR 0.67, p < 0.05; 0.67, p < 0.03; and 0.50, p < 0.01, respectively). The personalized nutrition risk assessment algorithm from the food frequency questionnaire can effectively stratify personal health risks among diverse middle-aged and older individuals, making it a valuable tool in lifestyle modification and intervention studies.

Real-world evidence study finds no new-onset diabetes or drug-related hyperglycemia in Pompe disease patients treated with avalglucosidase alfa

Real-world evidence study finds no new-onset diabetes or drug-related hyperglycemia in Pompe disease patients treated with avalglucosidase alfa

Visceral Fat Predicts New-Onset Diabetes After Necrotizing Pancreatitis.

We aimed to estimate the incidence of new-onset diabetes (NOD) and identify risk factors for NOD in patients with necrotizing pancreatitis (NP). Necrotizing pancreatitis patients were reviewed for NOD, diagnosed >90 days after acute pancreatitis. Baseline demographics, comorbidities, clinical outcomes, computed tomography (CT) characteristics of necrotic collections, and CT-derived abdominal fat measurements were analyzed to identify predictors for NOD. Among 390 eligible NP patients (66% men; median age, 51 years; interquartile range [IQR], 36-64) with a median follow-up of 400 days (IQR, 105-1074 days), NOD developed in 101 patients (26%) after a median of 216 days (IQR, 92-749 days) from NP. Of the NOD patients, 84% required insulin and 69% developed exocrine pancreatic insufficiency (EPI). Age (odds ratio [OR], 0.98), male sex (OR, 2.7), obesity (OR, 2.1), presence of EPI (OR, 2.7), and diffuse pancreatic necrosis (OR, 2.4) were independent predictors. In a separate multivariable model assessing abdominal fat on CT, visceral fat area (highest quartile) was an independent predictor for NOD (OR, 3.01). New-onset diabetes was observed in 1 of 4 patients with NP, most within the first year and requiring insulin. Male sex, obesity, diffuse pancreatic necrosis, development of EPI, and high visceral adiposity identified those at highest risk.

Distinct changes to pancreatic volume rather than pancreatic autoantibody positivity: insights into immune checkpoint inhibitors induced diabetes mellitus

BackgroundImmune checkpoint inhibitors (ICI) are promising treatment options for various cancers. However, their use is associated with immune-related adverse events (irAEs), including ICI-induced diabetes mellitus (ICI-DM). This study aimed to investigate the clinical features of ICI-DM, with a particular focus on alterations to pancreatic volume.MethodsWe conducted a retrospective review of 2829 patients who received ICI treatment at the Chang Gung Memorial Hospital, Linkou, between January 2014 and December 2021. New-onset diabetes or diabetic ketoacidosis (DKA) was identified in ten patients receiving ICI therapy. Pancreatic volumes were assessed by manual segmentation of computed tomography (CT) images before and after ICI-DM diagnosis.ResultsAmong these ten patients, nivolumab was the most commonly used ICI (50.0%), followed by pembrolizumab (30.0%) and atezolizumab (20.0%). One patient received combination therapy with nivolumab and ipilimumab. The median age was 63.01 years (range: 40.1 − 87.8). ICI-DM developed after a median of 13.5 cycles (range: 2 − 42) of ICI treatment or 9.85 months (range:1.5 − 21.3) since ICI initiation. The initial presentation was DKA in 60.0% of patients. All patients had low or undetectable C-peptide levels (range: <0.033 − 0.133 nmol/L) and were negative for most type 1 diabetes mellitus (T1DM)-related autoantibodies; only one patient tested positive for glutamic acid decarboxylase antibodies. CT imaging revealed significant pancreatic atrophy, with a median pancreatic volume decrease of 19.92% (P = 0.038) from baseline and sustained significant decline at last follow-up (median − 37.14%, P = 0.012).ConclusionsICI-DM is often accompanied by pancreatic atrophy and approximately two-thirds of patients initially present with DKA. Although the majority of ICI-DM patients lack T1DM-related autoantibodies, identifying diminished pancreatic volumes through CT imaging provides valuable clues into the subclinical aspects of ICI-DM development, aiding in the prevention of diabetic emergencies.Trial registrationNot applicable.

The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events.

Our study is the first study to investigate the effect of SNPs in CYP3A5, CYP3A4, ABCB1 and POR genes on the incidence of tremors, nephrotoxicity, and diabetes mellitus. A total of 223 renal transplant patients receiving tacrolimus and mycophenolate mofetil (MMF) were recruited. Both adults and children patients participated in the study. Genotyping was performed using PROFLEX-PCR followed by RFLP. MPA and tacrolimus plasma concentrations were measured by immunoassay. The AUC0-12h of MMF was estimated by a Bayesian method. We found a statistically significant association between the CYP3A5*3 and CYP3A4*1B genotypes and the tacrolimus exposure. We found a lower occurrence of nephrotoxicity (p = 0.03), tremor (p = 0.01), and new-onset diabetes (p = 0.002) associated with CYP3A5*1 allele. The CYP3A4*1B allele was significantly associated with a lower occurrence of new-onset diabetes (p = 0.026). The CYP3A5*1 allele was significantly associated with an increased risk of acute and chronic rejection (p = 0.03 and p < 0.001, respectively). Our results support the usefulness of tacrolimus pharmacokinetics in pre-kidney transplant assessments.

Dysregulation of autophagy activation induced by atorvastatin contributes to new-onset diabetes mellitus in western diet-fed mice

Background and aimsThe incidence of statin-induced new-onset diabetes (NOD) is increasing but its underlying mechanisms remain unclear. We aimed to investigate the effects of various doses of atorvastatin (ATO)-induced autophagy on the development of NOD. Methods and resultsThe isolated rat islets and MIN6 cells-treated with ATO, exhibited impaired glucose-stimulated insulin secretion, reduced insulin content, and induced apoptosis. Additionally, autophagy was induced at all doses (in vitro: 5, 10, 20 μM; in vivo: 10, 15, 20 mg/kg) in ATO-treated MIN6 cells or western diet (WD)-fed mice. In contrast to normal glucose-tolerant mice administered a low-dose (10 mg/kg) ATO, those treated with high-doses (15 or 20 mg/kg) exhibited impaired glucose tolerance. Furthermore, high-dose ATO-treated mice showed decreased β-cell mass and increased apoptosis compared to that of vehicle-treated mice. We also observed that the number of vesicophagous cells in the pancreas of 20 mg/kg ATO-treated WD-fed mice was higher than in vehicle-treated WD-fed mice. Inhibiting autophagy using 3-methyladenine (3-MA) and siAtg5 improved glucose tolerance in vivo and in vitro by preventing apoptotic β-cell death and restoring insulin granules. ConclusionThese results indicate that high doses of ATO induced hyperactivated autophagy in pancreatic cells, leading to impaired insulin storage, decreased cell viability, and reduced functional cell mass, ultimately resulting in NOD development.

The prognostic significance of insulin resistance in COVID-19: a review.

Emerging publications indicate that diabetes predisposes patients with COVID-19 to more severe complications, which is partly attributed to inflammatory condition. In the current review, we reviewed recent published literature to provide evidence on the role of insulin resistance (IR) in diabetes, the association between diabetes and COVID-19 severity and mortality, the impact of COVID-19 infection on incident new-onset diabetes, mechanisms responsible for IR in COVID-19 patients, and the predictive value of different surrogates of IR in COVID-19. The literature search performs to find out studies that have assessed the association between IR surrogates and morbidity and mortality in patients with COVID-19. We showed that there is a bulk of evidence in support of the fact that diabetes is a potent risk factor for enhanced morbidity and mortality in COVID-19 patients. COVID-19 patients with diabetes are more prone to remarkable dysglycemia compared to those without diabetes, which is associated with an unfavourable prognosis. Furthermore, SARS-COV2 can make patients predispose to IR and diabetes via activating ISR, affecting RAAS signaling pathway, provoking inflammation, and changing the expression of PPARɣ and SREBP-1. Additionally, higher IR is associated with increased morbidity and mortality in COVID-19 patients and different surrogates of IR can be utilized as a prognostic biomarker for COVID-19 patients. Different surrogates of IR can be utilized as predictors of COVID-19 complications and death.

Clinical characteristics of new-onset diabetes after liver transplantation and outcomes.

We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.