New-onset Diabetes Mellitus Research Articles

HPB SO15 - Developing protocol for managing diabetes after Distal pancreatectomy

Abstract Background The incidence of new-onset diabetes mellitus (NODM) has been reported to be 18% to 39% after pancreaticoduodenectomy and 5% to 42% after distal pancreatectomy. Postoperative NODM is historically referred to as type 3c diabetes mellitus (DM). Postoperative HbA1c levels over 7% or 52 mmol have been identified as one of the independent risk factors for tumor recurrence and overall poor survival after cancer-related resections. This study aimed to evaluate the current practice in glycemic monitoring of patients who had distal pancreatectomy and to develop a departmental protocol for Glycemic monitoring in the perioperative period. Method Electronic medical records of 74 patients were reviewed, of these, 61 patients who underwent distal pancreatectomy from Jan 2019 to Dec 2023 was included in the study. All patients with distal pancreatectomy were included irrespective of their pathological diagnosis. age or gender. Patients who died in the perioperative period or the ones who did not have distal pancreatectomy were excluded. (necrosectomy, drainage procedures, GIST, central pancreatectomy. Data analysis performed using Microsoft Excel Results The Age ranged from 24-86. 61 patients were included in the study where whereas male-to-female ratio is shown in the Pie Chart. 80% of the patients had investigations for glycemic status, Only 59% (36/61) had HBA1C done, additional 21% others had only glucose levels measured. 19.7% had no investigations to date. This graph shows the current diabetic status of patient The graph shows the variability in practice with no consistency. Overall 36% of our patients have become diabetic or Pre-diabetic post distal pancreatectomy. Conclusion There is a lack of consistency in the follow-up of our patients regarding glycemic control. This calls for the development of a defined departmental protocol for the follow-up of our patients. Every patient with pancreatectomy should have a glucose tolerance test/HBA1C pre-op in close liaison with the diabetic team. We made the following suggestions. HBA1C at 1 month post surgery in 1st clinic follow up. HBA1C every 6 months thereafter or advice GP if they were to be discharged after benign disease surgery. Information charts are to be made available to the ward base and added to the induction pack.

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.

Abstract 4137922: Cardiovascular Prognosis of Statin Users Developing Diabetes in Secondary Prevention: A Prospective Multicenter Study

Background: In primary prevention, statin use with new-onset diabetes mellitus (DM) was associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. In high-risk and secondary prevention settings, the cardiovascular prognosis of statin users progressing to new-onset DM remains unclear. Methods: We collected data from inpatients with or without baseline ASCVD from four medical centers affiliated to Qingdao University. Patients were categorized into 4 phenotypes: (1) statin non-users without diabetes; (2) statin users with incident diabetes; (3) statin users with pre-existing diabetes; and (4) statin users without diabetes. The primary outcome was ASCVD events. The stratified Cox proportional hazard model was used to investigate the association between the four distinct phenotypes and the risk of ASCVD. Results: Among 12,800 high-risk patients, over a median follow-up of 118 days (interquartile range, 48-379 days), 1447 ASCVD events were documented. Compared with statin non-users without diabetes, statin users without diabetes (hazard ratio [95% confidence interval], 0.77 [0.65, 0.91], P=0.001) and statin users with pre-existing diabetes (0.80 [0.66, 0.99], P=0.035) were associated with lower risk of ASCVD, whereas statin users with new-onset diabetes were not (0.91 [0.70, 1.19], P=0.50), overall P for trend =0.013.( Figure 1 ) In patients with baseline ASCVD (i.e., secondary prevention settings), we observed similar findings ( Figure 2 ) Conclusions: In high-risk patients with pre-existing ASCVD, new-onset diabetes after statin use was likely associated with compromised cardiovascular benefits of statins.

Efficacy and diabetes risk of moderate-intensity statin plus ezetimibe versus high-intensity statin after percutaneous coronary intervention

BackgroundsHigh-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI.MethodData was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM).ResultsA total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89–1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73–0.97, P = 0.02).ConclusionIn patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI.Graphical abstractCumulative incidence according to the first-line lipid-lowering strategy in patients undergoing percutaneous coronary intervention. Abbreviation: MACCE, major adverse cardiac cerebrovascular events; PCI, percutaneous coronary intervention.

Association of relative handgrip strength on the development of diabetes mellitus in elderly Koreans.

Diabetes mellitus (DM) is a significant public health concern, particularly in the elderly population. Absolute handgrip strength (HGS) serves to quantify muscle strength. It is recommended that the risk of low muscle strength and increased body mass index be concurrently evaluated using relative HGS. There are currently insufficient evidence regarding the relationship between relative HGS and DM in the elderly Korean population. Therefore, the association between relative HGS and the development of DM in Korean elderly was investigated. Data from the Korean Longitudinal Study of Ageing were used to determine the odds ratio (OR) between relative HGS and DM during the follow-up period from 2006-2020 among Korean men and women aged ≥65 years without DM when they first participated in this survey. Analysis was conducted using the Generalized Estimating Equation method. Trend analysis was performed for DM development based on relative HGS. Among elderly males, higher relative HGS groups had reduced odds of developing DM (Middle tertile: OR 0.87, 95% CI 0.61-1.23, p = 0.419.) (Upper tertile: OR 0.82, 95% CI 0.56-1.18, p = 0.281.) Among elderly females, the reductions were similar. (Middle tertile: OR 0.82, 95% CI 0.66-1.03, p = 0.087.) (Upper tertile: OR 0.79, 95% CI 0.50-1.25, p = 0.306.) However, these differences were not statistically significant. Significant predictors of new-onset DM included age, BMI (overweight/obese), household income, alcohol consumption, hypertension, and chronic liver disease. Trend tests indicated a substantial decrease in the OR as the relative HGS increased for male and total groups (p for trend < 0.05). Relative HGS did not achieve statistical significance. Our findings indicate that BMI, particularly overweight and obesity, significantly predicts new-onset DM. However, trend tests indicated a substantial decrease in the OR as the relative HGS increased for male and total groups (p for trend < 0.05), even after adjusting for BMI categories. Despite the lack of statistical significance in some cases, the trend suggests that promoting resistance exercises to enhance HGS could be beneficial in DM prevention. Comprehensive DM prevention strategies should include managing obesity and chronic conditions for elderly.

Impact of dapagliflozin on cardiometabolic outcomes after myocardial infarction according to baseline glycaemic status and body mass index: a DAPA-MI substudy

Abstract Background Dapagliflozin improved cardiometabolic outcomes compared with placebo following acute myocardial infarction (MI) in participants without prior diabetes mellitus (DM) or chronic heart failure (HF) in the DAPA-MI trial. Purpose To assess cardiometabolic outcomes in the DAPA-MI trial according to glycaemic status and body mass index (BMI) at randomisation (baseline). Methods Participants were categorised, according to their baseline HbA1c, as normoglycaemic (&amp;lt;5.7% [39 mmol/mol]) or having pre-DM (5.7-&amp;lt;6.5% [48 mmol/mol]). Those with HbA1c &amp;gt;6.5%, diagnosis of DM during hospitalisation, or missing HbA1c result were excluded. New-onset DM during follow-up was defined as either investigator-reported DM diagnosis or HbA1c &amp;gt;6.5%. Time to first occurrence of new-onset DM was assessed according to randomised treatment with dapagliflozin or placebo over median 11.6 months. Incidences of hospitalisation for HF (HHF), cardiovascular death/MI/stroke (MACE), first occurrence of NYHA class III or IV, and weight reduction &amp;gt;5% were assessed according to baseline HbA1c subgroup. Hazard ratios with 95% confidence intervals (CI) were determined using Cox proportional hazards models, stratified by country (UK and Sweden), including randomized treatment as covariate. Similar analyses were performed according to baseline BMI ranges &amp;lt;25, &amp;gt;25-&amp;lt;30, and &amp;gt;30 kg/m2. Results 3,425 out of 4,017 (85.3%) participants met the inclusion criteria, of whom 1,926 (56.2%) were normoglycemic and 1,499 (43.8%) had pre-DM at baseline. In those with normoglycaemia, new-onset DM during follow-up occurred in 6 (0.6%) and 15 (1.6%) participants assigned to dapagliflozin and placebo, respectively (HR 0.40, CI 0.15-1.03; P=0.06); in those with pre-DM, this outcome occurred in 77 (10.1%) and 97 (13.1%) participants, respectively (HR 0.74, CI 0.55-0.99; P&amp;lt;0.05), without significant interaction between the subgroups (P int=0.23)(Figure). A similar pattern was seen for new-onset DM during follow-up according to the BMI subgroup (P int=0.22), with greater absolute risk reduction seen in patients with obesity (5.0% vs. 9.8%, HR 0.52, 0.32-0.82; P&amp;lt;0.01)(Figure). There was no significant treatment effect or interaction according to baseline HbA1c for incidences of HHF or MACE, whereas first occurrence of NYHA class III or IV was reduced more with dapagliflozin versus placebo in the pre-DM subgroup (HR 0.38, CI 0.23-0.61; P&amp;lt;0.001) compared with the normoglycaemia subgroup (HR 0.87, CI 0.58-1.30; P=0.50; P int&amp;lt;0.01). Dapagliflozin increased the incidence of &amp;gt;5% weight loss in both HbA1c subgroups and all BMI subgroups with no significant interactions. Conclusions Dapagliflozin, compared with placebo, reduces the occurrence of new-onset DM following MI, regardless of baseline HbA1c or BMI and with greater absolute risk reduction in those with pre-DM or obesity. Dapagliflozin has a greater beneficial effect on HF symptom burden (NYHA class III-IV) in those with pre-DM versus normoglycaemia.

Proteinuria and the risk of incident atrial fibrillation according to diabetes stage in patients with diabetes: a nationwide population-based cohort study

Abstract Background Proteinuria and diabetes mellitus (DM) are established cardiovascular risk factors, both independently associated with an increased risk of atrial fibrillation (AF). Despite previous findings correlating proteinuria amount with incident AF, regardless of DM diagnosis, the nuanced association at different stages of DM warrants further investigation. Purpose This study aimed to delve into and compare the relationship between proteinuria amount and the risk of incident AF in patients across various stages of DM. Methods A cohort of 3,866,428 individuals without prior AF and type 1 DM, who underwent the 2009 health checkup provided by the National Health Insurance Service in Korea, were categorized into five DM stages: normal, prediabetes, new-onset DM, early DM (diagnosed &amp;lt; 5 years), and late DM (diagnosed ≥ 5 years). Proteinuria was graded using the urine dipstick test, ranging from negative to 3+ or more. AF incidence was tracked until December 31, 2020. Results The cohort, with an average age of 47.0 ± 13.9 years and 45.4% females, demonstrated escalating annual AF incidence rates from 1.90 to 6.45 per 1000 person-years across DM stages (p&amp;lt;0.001) (Figure). Similarly, the rates increased from 2.28 to 7.28 per 1000 person-years by proteinuria levels (p&amp;lt;0.001) (Figure). Adjusted Cox regression models revealed a heightened risk of incident AF associated with higher proteinuria amounts in all DM stages (adjusted hazard ratios for urine dipstick 3+ or more: 1.57, 1.76, 1.44, 2.32, and 2.23, respectively). Notably, the association between proteinuria and incident AF was more pronounced in individuals with early and late DM compared to those with prediabetes and new-onset DM (Figure). Conclusions At each DM stage, from prediabetes to late DM, a higher level of proteinuria corresponds to an increased risk of AF development. Furthermore, a stronger association was observed in patients with longer DM duration compared to those with prediabetes or new-onset DM. These findings underscore the significance of monitoring proteinuria levels across DM stages to assess AF risk comprehensively.

Assessment of Glucose and HbA1c Monitoring in a Pancreatic Cancer Surveillance Program for High-Risk Individuals.

Several studies suggest that new-onset diabetes mellitus is an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the International Cancer of the Pancreas Screening Consortium recommends glucose and hemoglobin A1c (HbA1c) monitoring in high-risk individuals (HRIs) undergoing surveillance. However, evidence that such monitoring improves PDAC detection is lacking. Our aim was to investigate the association between serum glucose and HbA1c values and the development of PDAC in HRIs undergoing surveillance. Participants were recruited from the familial pancreatic cancer surveillance cohort, which follows hereditary predisposed HRIs yearly by magnetic resonance imaging and/or endoscopic ultrasound and blood sampling. Those who underwent fasting glucose and/or HbA1c monitoring at least once were eligible candidates. Four hundred four HRIs met the inclusion criteria. During a median follow-up of 41 months (range 14-120), 9 individuals developed PDAC and 4 (without PDAC) were diagnosed with new-onset diabetes mellitus. Glucose levels ranged from 3.4 to 10.7 mmol/L (mean 5.6 ± 0.7) and HbA1c levels from 25 to 68 mmol/mol (mean 37.7 ± 4.1). The mean values did not differ significantly between PDAC cases and controls. The percentage of individuals with at least one elevated value were comparable between PDAC cases and controls for glucose (33% and 27%, P = 0.707) and HbA1c (22% and 14%, P = 0.623). No consistent glucose or HbA1c trends over time suggested a correlation with PDAC development. In this HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer-term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance.

Diabetes Risk Factors in People With HIV Receiving Pitavastatin Versus Placebo for Cardiovascular Disease Prevention : A Randomized Trial.

REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) led to new guidelines for statin use among people with HIV (PWH) with low to moderate risk for atherosclerotic cardiovascular disease (ASCVD). Little is known about the natural history of diabetes mellitus (DM) or mechanisms contributing to statin effects on DM among this population. To determine the contribution of known DM risk factors to excess risk for DM with pitavastatin in REPRIEVE. Phase 3, primary ASCVD prevention trial over a median of 5.6 years of follow-up. (ClinicalTrials.gov: NCT02344290). Global, multicenter trial. 7731 PWH aged 40 to 75 years with low to moderate ASCVD risk (by the pooled cohort equations from the American College of Cardiology and American Heart Association) without DM at study entry. Random 1:1 assignment to pitavastatin, 4 mg daily, or placebo. New-onset DM was determined at each visit by clinical diagnosis requiring initiation of medication treatment for DM. The incidence of new-onset DM was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group. Treatment effects of pitavastatin on progression to new DM in key subgroups were determined. Participants with at least 3 DM risk factors (vs. no risk factors) had increased risk for DM in each treatment group (incidence rate, 3.24 per 100 person-years [PY] vs. 0.34 per 100 PY [pitavastatin] and 2.66 per 100 PY vs. 0.27 per 100 PY [placebo]). The incidence of DM was highest in South Asia. In adjusted analyses, high body mass index, prediabetes, and metabolic syndrome components were strongly associated with new-onset DM (all P < 0.005). Pitavastatin was the only statin assessed; DM was assessed clinically. Metabolic risk factors, including prediabetes and obesity, contributed to new-onset DM in statin- and placebo-treated participants. A clinically significant effect of pitavastatin on DM was seen primarily among those with multiple risk factors for DM at entry. Strategies targeting key metabolic risk factors, like obesity and prediabetes, may help protect against DM among PWH. National Heart, Lung, and Blood Institute of the National Institutes of Health.

7725 Could COVID-19 Be the Trigger for Type 1 Diabetes?

Abstract Disclosure: E. Ahsan: None. F.F. Foo: None. A. Ravin: None. M. Akula: None. K. Hu: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. Introduction: COVID-19 disrupts glucose homeostasis, which may result in hyperglycemia and new-onset diabetes mellitus. It has been hypothesized to be caused by an increased inflammatory response, increased insulin resistance, and a degree of acute viral pancreatic damage. A meta-analysis showed that the incidence of new-onset diabetes was found to be as high as 14.4% (95% CI: [5.9%-25.8%]). Here, we report a case of COVID-19-induced diabetes to spread awareness among healthcare providers and encourage early detection to prevent long-term complications. Clinical Case: A 54-year-old African American female with a past medical history of hyperlipidemia, obesity, and hypothyroidism presented to our endocrinology office for evaluation and management of diabetes mellitus (DM). She presented with symptoms of 66-pound weight loss, polydipsia, polyphagia, and polyuria. Her labs on diagnosis were significant for blood glucose of 550 mg/dl (70-100 mg/dl), hemoglobin A1c &amp;gt;15.5% (&amp;lt;5.7%), and bicarbonate 23 mmol/L (20-31 mmol/L). She started on insulin and then switched to semaglutide after six months. Her fasting glucose on the follow-up visit was 103 mg/dl, the anti-glutamic acid decarboxylase 65 (GAD-65) antibody was 8,558.9 units/ml (&amp;lt;5 units/ml), C peptide was 1.9 ng/ml (0.5-2ng/ml), and Islet Antigen-2 (IA-2) autoantibody was &amp;lt;7.5 U/ml (0-7.49 U/ml). Despite positive antibodies, her C-peptide suggested enough beta-cell function, and she was switched from insulin to semaglutide. The patient was diagnosed with autoimmune diabetes, which may be from the COVID-19 infection, and was educated about regular follow-up and new medications like teplizumab that may help prevent the progression to needing insulin. Clinical Lesson: The exact mechanism of new-onset COVID-19-induced diabetes is still unknown. However, multiple risk factors are theorized to play a role in COVID-induced DM. These include defects in insulin production and glucose clearance, obesity, stress hyperglycemia, insulin resistance, and steroid therapy. Our patient had a history of obesity but no history of diabetes, steroid use, or any personal or family history of autoimmune processes. Compared to COVID-19 patients with normoglycemia or hyperglycemia, patients with preexisting diabetes and newly diagnosed diabetes experienced more severe complications, such as shock, ARDS, acute kidney injury, hypoalbuminemia, and severe COVID-19 complications. Additional research is required to investigate the various pathophysiologies and treatment options, including new medications that may prevent the disease's further progression. Diabetes caused by COVID-19 should be treated cautiously, and prompt diagnosis and care are essential to preventing further complications. Presentation: 6/3/2024

12394 "Sugar And Tumors: A Case Report On New-onset Diabetes In Metastatic Pheochromocytoma With Elevated Dopamine Levels"

Abstract Disclosure: B. Agrawal: None. V. mehta: None. R. naseem: None. M. Renzu: None. R. rashid: None. Introduction: Metastatic pheochromocytoma is a rare neuroendocrine tumor with potential complication of new-onset diabetes mellitus (DM). We present a case highlighting the challenges in managing a patient with metastatic pheochromocytoma and concurrent DM. Case presentation: A 66-year-old male with a history of hypertension and gout initially presented in 2010 with an adrenal mass, later identified as pheochromocytoma and resected. In 2018, he presented with bilateral leg pain, revealing metastatic disease-causing spinal cord compression along with metastatic lung nodules and metastasis in adrenalectomy bed. Despite interventions including T6,7,8 laminectomy in 2020 and radiation therapy, metastases persisted. In 2024, he presented with polyuria, polydipsia, and hyperglycemia (blood glucose &amp;gt;500 mg/dL). Laboratory findings showed elevated a1c of 15 in addition to elevated normetanephrines, metanephrines, and dopamine with levels of 3880, 48 and 488 respectively. He was diagnosed with new-onset DM and started on insulin therapy in addition to metformin and jardiance. Discussion: Secondary diabetes mellitus (DM) in secretory pheochromocytoma occurs in approximately 50% of cases, manifesting from mild insulin resistance to severe presentation like DKA. Epinephrine-secreting tumors contribute to glucose intolerance by activating beta receptors, thereby stimulating gluconeogenesis. Patients with higher levels of epinephrine and preoperative glucose intolerance were more prone to developing postoperative hypoglycemia, requiring close monitoring during the postoperative period. Additionally, research by DiSalvo et al. Epinephrine-secreting tumors have a more significant impact on hyperglycemia by impairing insulin secretion and stimulation GLP-1. Tumor resection has been found to be more effective effective in restoring normal glucose homeostasis in these patients. Dopamine-secreting pheochromocytomas are rare neoplasms characterized by the presence of immature catecholamine vesicles that inhibit dopamine conversio owing to localized dopamine beta hydroxylase. Typically presenting around the age of 48, these tumors often lack excess catecholamines, leading to atypical symptoms such as local discomfort or pain from tumor compression. These neoplasms are less detectable on metaiodobenzylguanidine (MIBG) scans, necessitating positron emission tomography (PET) for accurate diagnosis. Surgical resection is the treatment, with preoperative management involving metyrosine instead of alpha blockers. These tumors are frequently diagnosed late, often in a malignant stage, contributing to poor prognosis Conclusion: Overall, understanding the complex interplay between catecholamines and glucose metabolism is crucial for the comprehensive management of patients with pheochromocytoma and secondary DM. Presentation: 6/1/2024

6938 An Unusual Case of New-onset autoimmune insulin dependent Diabetes Mellitus Complicating Gestational Diabetes Mellitus in A Pregnant Female Diagnosed Early Postpartum - The Enigma of Autoimmunity and Diabetes During Pregnancy

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Gestation diabetes is the most common metabolic disorder in pregnancy affecting 25% of pregnancies. T1DM accounts for 0.2-0.5% of all pregnancies in the United States yearly. New-onset autoimmune insulin-dependent diabetes mellitus during pregnancy is very uncommon and it might be overlooked. Diabetes-related autoantibodies have been studied in women with GDM with prevalence of 0-10%. There is controversial data regarding the clinical significance of checking diabetes antibodies in pregnancy. Case Presentation: A 22-year-old G1P1 female with history of Hashimoto hypothyroidism presented during early second trimester for evaluation of GDM with serum glucose of 300s mg/dl in a random blood sample with multiple subsequent high values, hemoglobin A1C of 9.4% (prepartum value was 5.3%). Patient was started on insulin during pregnancy. Pregnancy was complicated with cesarian section and macrosomia. 1 week postpartum, A1c was 5.4%, Insulin was discontinued, and patient was continued on Metformin. 2 months Postpartum, patient presented with persistent high blood glucose values of 300-400 mg/dl with no signs of DKA. Glipizide and Glargine 15 units daily were added though patient continued to have hyperglycemia. Laboratory workup were remarkable for high blood glucose of 342 mg/dl, low C peptide of 0.6 ng/dl, and positive glutamic acid decarboxylase antibodies (GAD Ab) 38.8 U/ml. oral antidiabetics were discontinued and prandial insulin was added. Discussion: GDM is a risk factor for DMII after pregnancy given high insulin resistance postpartum, Data regarding new-onset DMI and diabetes autoimmunity during pregnancy is lacking. About 0-10% of women with gestational diabetes develop DM autoantibodies. GAD Ab exhibits the highest sensitivity of 63% for type 1 diabetes prediction compared to Islet cell antibodies (48%), and tyrosine phosphatase-related islet antigen 2 (34%). Pathophysiology of autoimmune DM during pregnancy is not quite understood; It is thought that when autoimmune tendency is present, GDM causes β-cells to deteriorate due to excessive insulin production in setting of insulin resistance, and the burden of third-trimester gestation may cause the insulin deficiency to be expressed sooner than non-pregnant female. So far, Literature about the predictive value or specific clinical features of checking diabetes autoantibodies is discordant and inconclusive. It is suggested to screen for autoantibodies only when array of clinical hallmarks suggestive of an autoimmune DM form of GDM present as young age, low BMI, need for insulin therapy early in pregnancy, presence of ketones, concurrent other autoimmune conditions (e.g., thyroiditis). This case is to shed light on autoimmunity in pregnancy. More data is needed with longer follow-up to better identify women at risk, their characteristics, indications for autoantibodies testing, follow and prognosis. Presentation: 6/2/2024

Diabetic ketoacidosis as first presentation of undiagnosed pancreatic cancer in an octogenarian.

Diabetic ketoacidosis (DKA) is a complication of diabetes mellitus (DM) that can theoretically occur in people of any age. While DKA can typically be the first presentation of type 1 DM in younger people, a first presentation is rare in older adults. Pancreatic cancer often manifests with new DM or hyperglycaemia, but very rarely as DKA. We report a case of an 89-year-old woman who was incidentally diagnosed with DKA during workup for an unwitnessed fall. Her DKA was promptly managed, and she was subsequently diagnosed with metastatic pancreatic cancer. Given the advanced stage of her malignancy, the multidisciplinary team consensus was for a palliative approach. She passed away on day 10 of the admission. To our knowledge, this is the first report of a first DKA presentation as a manifestation of pancreatic cancer in an adult aged over 70 years. To date, there is no effective screening test for pancreatic cancer in the general population. However, new-onset DM in the appropriate context might indicate the need for further evaluation. While it is possible that unresectable tumours are identified, earlier diagnosis of DM with pancreatic cancer may facilitate more timely management, including earlier advanced care planning. A higher clinical suspicion for pancreatic cancer is required for older adults presenting with diabetic ketoacidosis without a previously diagnosed diabetes mellitus. A bi-directional relationship exists between diabetes and pancreatic cancer. Pancreatic cancer generally has a very poor prognosis due to its advanced stage at diagnosis and the lack of an effective screening test. New-onset diabetes in the appropriate context (such as weight loss) can indicate the need for further evaluation for underlying pancreatic cancer.

Efficacy and safety of pasireotide treatment in acromegaly: A systematic review and single arm meta-analysis.

Acromegaly is a rare chronic endocrine disorder associated with significant comorbidities. Many patients fail to achieve biochemical control with current medical therapies, including surgery and first-generation somatostatin ligands (fg-SRLs). We aimed to perform a systematic review and single-arm meta-analysis to evaluate the efficacy of the multi-receptor somatostatin ligand pasireotidein patients with active or uncontrolled acromegaly. We systematically searched PubMed, Embase, and Cochrane databases for studies that assessed the efficacy of pasireotide in patients withacromegaly and reported the outcomes of (1)biochemical control and its composite indicators; (2)normalized IGF-1 level and (3)low GH level.For the statistical analysis, we used R software. We included nine studies with a total of 590 patients: four clinical trials and five observational cohorts. 82.2% of the overall population consisted of inadequately controlled acromegaly patients. After a follow-up of 12months, the pooled biochemical control rate was 26.50% (95% CI 14.87-42.66). The prevalence of normalized IGF-1 and low GH levels was 36.27% (95% CI 29.15-43.39) and 34.76% (95% CI 24.58-44.95), respectively. Additionally, biochemical response rates were sustained throughout the extension phase of these studies. In a pooled analysis including four studies with extension phase results, the prevalence of biochemical control rate was 29.03% (95% CI 11.49-46.58) with 76 events out of 281 patients. The most commonly reported adverse events were gastrointestinal disturbances in 31.26% (95% CI 7.44-72.01) and hyperglycemia in 29.55% (95% CI 21.80-37.29) of patients. The incidence of new-onset diabetes mellitus significantly increased after pasireotide treatment, with a rate of 23.36% (95% CI 19.58-27.13). Pasireotide demonstrates biochemical control in patients with active or uncontrolled acromegaly. Although a high rate of hyperglycemic adverse events and diabetes mellitus related to the treatment were observed, most of them were manageable.

Prevalence and short-term clinical impacts of new-onset diabetes mellitus among patients with COVID-19 in jazan region, Saudi Arabia

BackgroundDiabetes Mellitus is a major predictor for severity and mortality that is increased by 50% in COVID-19 infection. The aim of this study is to estimate the prevalence of new-onset DM among patients with COVID-19 and examined the short clinical outcomes of the disease.MethodThis is a retrospective study of revising electronic medical records to assess the prevalence of new-onset DM in COVID-19 patients and its impact on the severity of the disease. Adult patients with confirmed COVID-19 during the period from June 2020 to December 2021 were enrolled.Results725 patients were included. 53.8% of them were males and 46.2 were females, the mean age was 43.35 ± 16.76. 13.2% were diabetics; 2.2% with preexisting DM and 11.0% had new-onset DM. 6.34% had coexisting medical conditions. DKA at presentation was observed in 6 patients (0.8%) of newly diagnosed DM. There is a significant correlation between age and family history (FH), and BMI and new-onset DM (P < 0.05). The overall mortality rate was 2.2%, and it was significantly higher in diabetics in comparison to non-diabetics (P < 0.001). 8.6% had persistent hyperglycemia after 4 months of follow-up.ConclusionThe prevalence of COVID-19 related new-onset DM was correlated significantly with disease severity and mortality rate. Age, FH, and BMI, were the major predictors. We recommend that frequent monitoring of blood glucose for patients with COVID-19 infections to detect DM, therefore, prompt treatment can be initiated.

New-onset diabetes mellitus type 2 treated with metformin - is it possible to slow the development of pancreatic cancer?- case report

In this article, we present the case of an 87-year-old patient whose initial symptom of developing pancreatic cancer was newly diagnosed type 2 diabetes mellitus. She was treated with metformin, which, on the one hand, could slow the development of pancreatic cancer and, on the other hand, delayed a key cancer diagnosis. However, before the definitive diagnosis, the patient's symptoms were considered merely as side effects of metformin treatment, delaying the proper diagnosis. We consider that early diagnosis of pancreatic cancer remains a significant challenge. Often, the first symptom is newly diagnosed diabetes mellitus type 2. In this article, we aim to demonstrate the importance of being vigilant when diagnosing and treating diabetes mellitus with metformin. We also present the impact of metformin on the course of pancreatic cancer. Additionally, we emphasize the need to be attentive when patients complain of side effects of this medication, as they may often mask the development of pancreatic cancer.

Patterns of incidence and characteristics of youth with new-onset diabetes mellitus during the COVID era

Objectives: The incidence of diabetes mellitus (DM) in children, adolescents, and young adults has been on the rise for many decades. The COVID-19 pandemic has been associated with a dramatic increase in new cases of pediatric DM and a shift in the seasonal pattern of incidence. We aimed to determine the incidence of DM and its subtypes during the COVID-19 pandemic (2020–2022) and pre-pandemic (2017–2019). We sought to assess for a difference in seasonality and temporal pattern of new-onset DM between the two periods and aimed to describe and compare the clinical characteristics of the patients diagnosed during this time. Material and Methods: In this retrospective chart review, data were collected from medical records for all patients aged 1–21 years diagnosed with DM at our center between January 1, 2017 and December 31, 2022. Results: The incidence of DM at our center increased 38% during the pandemic (incidence rate ratio [IRR] 1.38, 95% confidence interval; [CI] 1.20–1.58). The incidence of type 1 diabetes (T1D) increased 11% (IRR 1.11, 95% CI 1.01–1.23) and the median body mass index percentile increased for those diagnosed during the pandemic (P = 0.012). The incidence of type 2 diabetes (T2D) increased 238% (IRR 3.38, 95% CI 2.17–5.28) during the pandemic, with the highest rate of diagnosis in a younger age group (P = 0.015). The pattern of incidence of T1D shifted from lowest in the summer pre-pandemic to highest in the summer during the pandemic (IRR 1.82, 95% CI 1.22–2.72). The overall incidence trend for DM, T1D, and T2D, peaked in spring 2021 and then declined until it stabilized in summer 2022. Conclusion: Our study showed a persistent increase in the incidence of both T1D and T2D in the pediatric population during the pandemic. Those diagnosed with T2D during the pandemic were younger than those diagnosed in the pre-pandemic period. There was a shift in seasonal pattern of T1D incidence during the pandemic with the highest rates of incidence during the summer. Further studies are needed to evaluate the underlying mechanisms of the persistent increase in incidence.

Association of Renal Hyperfiltration with Incidence of New-Onset Diabetes Mellitus: A Nationwide Cohort Study.

Background and Objectives: While the connection between decreased kidney function and diabetes mellitus (DM) is commonly acknowledged, there is insufficient research examining the relationship between higher-than-normal estimated glomerular filtration rate (eGFR) and the incidence risk of new-onset DM. Our research aimed to explore the relationship between an eGFR and the incidence risk of new-onset DM in the Korean general population through a nationwide longitudinal study. Methods: This research employed the cohort records of the National Health Insurance Service in Korea, analyzing records from 2,294,358 individuals between the ages of 20 and 79 who underwent health check-ups between 2010 and 2011. The eGFR levels from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used to assess the renal function. New-onset DM was defined as two or more claims with the International Classification of Diseases-10 classification codes E10 to E14, being prescribed any medication for lowering blood glucose, or having a record of fasting plasma glucose levels of ≥126 mg/dL from a health examination after the index date. Results: The mean age of subjects was 47.34 ± 13.76 years. The 150,813 (6.57%) new-onset DM cases were identified over a median follow-up of 9.63 years. In the multivariable Cox regression analysis, in comparison with the 5th decile, the 10th (≥114.12 mL/min/1.73 m2) (hazard ratio (HR): 0.52, 95% confidence interval (CI) (0.50-0.54), p < 0.001) eGFR decile was significantly associated with a decreased incidence of new-onset DM. Moreover, eGFR >120 mL/min/1.73 m2 was associated with a reduced risk of new-onset DM (HR: 0.40, 95% CI (0.39-0.42), p < 0.001). These results were consistent regardless of the presence of impaired glucose tolerance, age, or obesity. Conclusion: Our study showed higher-than-normal eGFR levels were associated with a lower risk of incidence for new-onset DM regardless of the presence of impaired glucose tolerance, age, or obesity. In general population, higher-than-normal eGFR may be associated with a lower risk of incidence of new-onset DM.

Selection strategy for endoscopic necrosectomy approaches of infected walled-off pancreatic necrosis: Analysis of 101 patients from a single center with long-term follow-up.

Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.

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.