Development Of New-onset Diabetes Mellitus Research Articles

Assessing blood sugar measures for predicting new-onset diabetes and cardiovascular disease in community-dwelling adults.

Diabetes mellitus (DM) is a global health concern linked to various complications, including cardiovascular disease (CVD). However, long-term follow-up studies on the risk of DM and CVD using different blood glucose assessment methods in the general Korean population are lacking. This study aimed to assess the predictive abilities of fasting plasma glucose (FPG), 2-h oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) for new-onset DM and high CVD risk in a middle-aged and older Korean population. This study used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort. Blood sugar measures (FPG, OGTT, and HbA1c) were examined. The primary endpoint was the development of new-onset DM, and CVD risk was evaluated using the Framingham risk score. The predictive abilities for new-onset DM based on glycemic values were evaluated using Harrell's Concordance index and 95% confidence intervals. Among the 10,030 participants, data of 6813 participants without DM at baseline were analyzed. The study revealed that OGTT outperformed FPG and HbA1c in predicting new-onset DM. The combination of FPG and HbA1c did not significantly enhance predictions for DM compared with OGTT alone. OGTT also outperformed FPG and HbA1c in predicting high CVD risk, and this difference remained significant even after adjusting for additional confounders. OGTT has superior predictive capabilities in identifying new-onset DM and high CVD risk in the Korean population. This suggests that relying solely on individual blood sugar measures may be insufficient for assessing DM and CVD risks.

New onset diabetes mellitus and cardiovascular outcomes according to statin intensity in patients after drug-eluting stent implantation in Asian patients

We investigated the effect of statin intensity on the development of new onset diabetes mellitus (NODM) in Korean patients after percutaneous coronary intervention (PCI). A total of 1013 consecutive patients without diabetes mellitus were retrospectively analyzed. All study patients received high- or moderate-intensity statin (high-intensity statin; 321 [31.7%], moderate-intensity statin; 692 [68.3%]). The primary endpoint was development of NODM, and the secondary one was the composite of cardiac death, non-fatal myocardial infarction, and any revascularization. In 264 pairs (528 patients) of propensity score-matched patient, NODM developed in 34 patients (6.4%) and composite cardiac events occurred in 73 patients (13.8%) during a median follow-up of 36.7 months. The incidence rate of NODM was significantly higher in patients with high-intensity statin than with moderate-intensity statin (8.3% vs. 4.5%, log-rank P = 0.026). The incidence rate of composite events was not significantly different between the two groups (12.5% vs.15.2%, log-rank P = 0.495). The use of high-intensity statins was associated with NODM after adjustment for multiple risk factors (adjusted hazard ratio, 2.18, 95% confidence interval 1.10‒4.51, P = 0.025). High-intensity statin therapy is associated with a higher incidence of NODM, but not with better cardiovascular outcomes, in Korean patients undergoing PCI. A new cholesterol lowering intensity-based approach rather than stain intensity-based approach to the high-risk patients without diabetes mellitus may be helpful in maximal treatment effect without safety concern of NODM in Asian patients.

The effects of colchicine in patients with diabetes mellitus and chronic coronary artery disease: a post-hoc analysis of the LoDoCo2-trial

Abstract Background Atherosclerosis is an inflammatory disease and is accelerated by diabetes mellitus (DM). Patients with chronic coronary artery disease (CAD) who also have DM are at high risk of recurrent cardiovascular events. The role of inflammation in atherosclerosis is well established, whereas the role of inflammation on incident and progression of DM has been hypothesized. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in particular, may play an important role in the onset and progression of T2DM. The anti-inflammatory drug colchicine attenuates the NLRP3-inflammasome. The Low-Dose Colchicine 2 (LoDoCo2) trial showed that colchicine reduces cardiovascular risk in patients with chronic CAD. Purpose The purpose of this study was to assess the effects of colchicine in patients with chronic CAD and DM on cardiovascular events as well as the effect of colchicine on the development of new-onset DM. Methods The LoDoCo2 trial randomized 5522 to placebo or colchicine, with a median follow-up of 28.6 months (interquartile range 20.5–44.4). The primary endpoint was a composite of cardiovascular death, spontaneous myocardial infarction, ischaemic stroke, or ischaemia-driven revascularization. Secondary outcomes consisted of the aforementioned events, separately. Cox proportional hazards models were used to investigate univariable associations between DM status for all endpoints in the placebo group. The interactions between treatment group and DM status were evaluated with the addition of treatment and the treatment-by-DM variable interaction. Results In total, 1007 participants (18.2%) had DM at baseline. The hazard ratio for the primary endpoint was 0.87 (95% CI, 0.61–1.25) in those with DM and 0.64 (95% CI, 0.51–0.80) in those without DM (p for interaction>0.05). Treatment effects of colchicine were consistent over all secondary endpoints (p for interaction>0.05). The incidence of new-onset DM was 1.5% (34/2270) in the colchicine group and 2.2% (49/2245) in the placebo group (p=0.10). Participants with DM were at higher risk for all endpoints. The primary composite end point in the placebo group occurred in 13.0% (67/515) patients with DM and in 8.8% (197/2245) of the patients without DM (unadjusted hazard ratio 1.54 [95% CI 1.16–2.03, p<0.01]) compared to the group without DM. DM was also strongly associated with the occurrence of all secondary end points. Conclusion This study shows that the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The data indicate that larger trials are needed to assess whether colchicine reduces the incidence of new-onset DM. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): National Health Medical Research Council of Australia and the Netherlands Organization for Health Research and Development

Assessing the Incidence of New-onset Diabetes Mellitus with Statin Use: A Systematic Review of the Systematic Reviews and Meta-analyses.

Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.

Organophosphate pesticides and new-onset diabetes mellitus: From molecular mechanisms to a possible therapeutic perspective.

Organophosphate is a commonly used pesticide in the agricultural sector. The main action of organophosphate focuses on acetylcholinesterase inhibition, and it therefore contributes to acute cholinergic crisis, intermediate syndrome and delayed neurotoxicity. From sporadic case series to epidemiologic studies, organophosphate has been linked to hyperglycemia and the occurrence of new-onset diabetes mellitus. Organophosphate-mediated direct damage to pancreatic beta cells, insulin resistance related to systemic inflammation and excessive hepatic gluconeogenesis and polymorphisms of the enzyme governing organophosphate elimination are all possible contributors to the development of new-onset diabetes mellitus. To date, a preventive strategy for organophosphate-mediated new-onset diabetes mellitus is still lacking. However, lowering reactive oxygen species levels may be a practical method to reduce the risk of developing hyperglycemia.

Development of a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy: A retrospective cohort study.

Pancreatectomy is an invasive surgery that is sometimes associated with complications. New-onset diabetes mellitus sometimes develops after partial pancreatectomy and severely affects the patient's quality of life. This study aimed to develop a preoperative prediction model of new-onset diabetes mellitus after partial pancreatectomy, which will help patients and surgeons to achieve more easily better common decisions on regarding whether to perform partial pancreatectomy. This retrospective cohort study analyzed medical records of patients who underwent partial pancreatectomy (total pancreatectomy excluded) from April 1, 2008, to February 28, 2016, which were available in the database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). The predictors were preoperative age, body mass index, hemoglobin A1c level, blood glucose level, and indication for partial pancreatectomy. The outcome was the development of new-onset diabetes mellitus at 1 to 12 months after partial pancreatectomy. We used a logistic regression model and calculated the scores of each predictor. To determine test performance, we assessed discrimination ability using the receiver operating characteristic curve and calibration with a calibration plot and the Hosmer-Lemeshow test. We also performed internal validation using the bootstrap method. Of 681 patients, 125 (18.4%) had new-onset diabetes mellitus after partial pancreatectomy. The developed prediction model had a possible range of 0 to 46 points. The median score was 13, and the interquartile range was 9 to 22. The C-statistics of the receiver operating characteristic curve on the score to predict the outcome was .70 (95% confidence interval [CI], .65–.75). Regarding the test performance, the Hosmer-Lemeshow test was not significant (P = .17), and calibration was good. In the bootstrapped cohorts, the C-statistics was .69 (95% CI, .62–.76). We developed a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy. This would provide important information for surgeons and patients when deciding whether to perform partial pancreatectomy.

New onset diabetes mellitus and cardiovascular events in Korean patients with acute myocardial infarction receiving high-intensity statins

BackgroundHigh-intensity statin therapy is typically used in patients with acute myocardial infarction (AMI) for secondary prevention. However, there have been consistent concerns regarding its association with diabetes mellitus. We investigated the effect of high-intensity atorvastatin and rosuvastatin on new-onset diabetes mellitus (NODM) and cardiovascular outcomes over a 3-year follow-up period.MethodsData from the Korea Acute Myocardial Infarction Registry were collected from November 2011 to October 2015, and 13,104 patients with AMI were enrolled from major cardiovascular centers. Among them, 2221 patients without diabetes who had been administered with high-intensity atorvastatin (40–80 mg) and rosuvastatin (20 mg) were investigated. The atorvastatin and rosuvastatin groups were evaluated for the incidence of NODM and major adverse cardiac events (MACE) including death, myocardial infarction, and revascularization cases in the following 3 years.ResultsBaseline characteristics were comparable between the two groups. Event-free survival rate of NODM was not significantly different between the atorvastatin and rosuvastatin groups (92.5% vs. 90.8%, respectively; Log-rank P-value = 0.550). The event-free survival rate of MACE was also not significantly different between atorvastatin and rosuvastatin groups (89.0% vs. 89.6%, respectively; Log rank P-value = 0.662). Multivariate Cox analysis revealed that statin type was not a prognostic factor in the development of NODM and MACE.ConclusionsAdministering high-intensity atorvastatin and rosuvastatin in patients with AMI produced comparable effects on NODM and clinical outcomes, suggesting their clinical equivalence in secondary prevention.

Abstract 15098: New-Onset Diabetes Mellitus Risk in Statin Users Depends on Baseline HemoglobinA1c Value - Results of VA Database Analysis

Introduction: Statin use in non-diabetic patients is associated with an increased risk of development of new-onset diabetes mellitus (NODM). However, little is known if baseline hemoglobin A1c (HbA1c) can affect diabetogenic risks and mortality benefits of statin therapy. Methods: In a retrospective cohort study between 01/2011 and 12/2018 we collected the data of 152358 non-diabetic US veterans on statin and not on statin therapy who had available baseline HbA1c value and full demographic and clinical information prior to DM diagnosis. The risk of statin-induced DM and all-cause mortality rate were assessed in the whole cohort and based on baseline HbA1c categories: ≤5.6%, 5.7-5.9% and 6.0-6.4%. DM rate and mortality rate were calculated by Cox proportional hazards model adjusted for case-mix. Results: After mean follow up of 6.89 (SD 2.26) years in non-statin users and 3.85 (SD 2.29) years in statin users and adjustments for multiple covariates such as age, gender, ethnicity, obesity, hypertension (HTN), cardiovascular disease, and metformin use, we found that the rate of statin-induced DM depends on baseline HbA1c (Table 1). Analysis by HbA1c categories showed that NODM rate is inversely related to HbA1c level, while statin use in patients with HbA1c 6.0-6.4% was not associated with increased rate of NODM. We did not observe increase in all-cause mortality in statin users and statin users with HTN across HbA1c categories. Atorvastatin use was associated with decrease in all-cause mortality in HTN patients (Table 1). Conclusions: The results of this largest to date analysis of non-diabetic US veterans closely matched for baseline characteristics suggest that the rate of statin-induced DM depends on baseline HbA1c. The significant increase in NODM rate is only observed in patients with baseline HbA1c <6.0% regardless of statin type prescribed. The increased NODM risk is not associated with all-cause mortality in statin users in general including patients with HTN.

Statins and Higher Diabetes Mellitus Risk: Incidence, Proposed Mechanisms, and Clinical Implications.

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors are ubiquitously prescribed for cardiovascular disease (CVD) prevention and treatment. However, the use of statins has been linked to the development of new-onset diabetes mellitus (NODM), which could possibly increase future CVD risk. This phenomenon necessitates a clear discussion of the possible etiologies of this relationship and its broader clinical consequences. We discuss the reported incidence of NODM in statin users through a rigorous review of data from metaanalyses of randomized control trials examining this association. We also highlight the various possible mechanisms responsible for the development of statin-induced diabetes mellitus. Finally, we examine the clinical implications of this effect on future CVD risk and identify specific patient factors that can be used for risk-stratification strategies. Data from 14 randomized control trials metaanalyses suggest a 9-33% higher risk of NODM with statin use. Several cellular, molecular, and genetic mechanisms, as well as lifestyle habits, have been identified as potential underlying factors responsible for this elevated risk. The principle mode of the diabetogenic action of statins is still unclear, though it is likely the result of a complex interplay of pancreatic and extrapancreatic effects. It is understood that patient populations with a greater predisposition to diabetes mellitus, and those with thicker epicardial adiposity are more at risk for the development of statin-induced NODM. Despite these observations, robust data from a variety of investigations suggest that the CVD preventative benefits of statin treatment significantly outweigh the risks associated with the development of NODM. Nevertheless, further study must better identify the causative mechanisms involved in this process, its natural history, and the unique factors that will help clinicians risk stratify and appropriately monitor patients on statin therapy.

Impact of disconnected pancreatic duct on recurrence of fluid collections and new-onset diabetes: do we finally have an answer?

Disconnected pancreatic duct (DPD) is a frequent occurrence in cases with walled-off necrosis (WON). The impact of DPD on recurrence of collection after removal of metal stents is not clear....

1689-P: Perioperative Hyperglycemia around Renal Transplantation Surgery and the Development of New-Onset Diabetes Mellitus after Transplantation

Background: New onset of diabetes after transplantation (NODAT) is an important problem as it increases infectious and cardiovascular complications reducing patient and graft survival. Aim: To establish the impact of perioperative hyperglycemia on the development of NODAT and the other known risk factors for its development in patients who go to renal transplant surgery, in a renal transplant unit dependent on an academic center. Methods: Study of cases and controls of patients with renal transplantation who developed or not NODAT within the year of follow-up, with more than 18 years of age, with the same immunosuppressive scheme (prednisone, tacrolimus, mycophenolate mofetil). Results: Of 71 transplanted patients, 14 (19.7%) developed NODAT per year, with an average age of 37.57 ± 15.02 years vs. 36.08 ± 12.43 years for those who did not develop it (p: 0, 73) respectively; those who developed NODAT were male in 57.14% vs. 70.18% of those who did not develop it respectively. Patients whose preoperative laboratory evaluation showed blood glucose equal to or greater than 100 mg/dl and less than 126 mg/dl had a NODAT frequency of 21.3% vs. 5.26% (OR 4.9 p: 0.005) in those who they had values ​​lower than 100 mg/dl at the same time of the evaluation. In addition, if the blood glucose prior to hospital discharge was ≥140 mg/dl, the frequency of NODAT was 35.71% vs. 1.75% (OR 31.11 p: 0.0003) if the blood glucose was lower than 140 mg/dl at the same time of the evaluation. None of the other risk factors considered: age >40 years, female sex, overweight, obesity, hypertriglyceridemia, family history of diabetes had significant statistical differences between the two groups. Conclusion: In our experience, poor glycemic controls, especially before surgery and prior to hospital discharge, marked a higher frequency trend of NODAT one year after follow-up. The patients presenting with this phenomenon should be observed with special attention in the follow up. Disclosure M. Méndez Ferreira: None. E.D. Bueno: None. A. Benitez: None. C.M. Palacios: None. J.T. Jimenez: None. A. Amarilla: None. F. Da Ponte: None. I. Stanley: None.

Comparison between calcium channel blocker with angiotensin converting enzyme inhibitor or angiotensin II type 1 receptor blocker combination on the development of new-onset diabetes in hypertensive Korean patients.

Rare comparative studies investigated the relationship between combination therapy of antihypertensive drugs and the incidence of new-onset diabetes mellitus (NODM). The aim of this study was to evaluate which combination therapy, calcium channel blocker (CCB) with angiotensin converting enzyme inhibitor (ACEI) or CCB with angiotensin II type 1 receptor blocker (ARB), is best in reducing/preventing the development of NODM during 4-year follow-up periods in non-diabetic hypertensive Korean patients. Finally, a total of 1221 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled and divided into the two groups, an ACEI group (combination CCB with ACEI, n = 251) and an ARB group (combination CCB with ARB, n = 970). The primary endpoint was NODM, defined as a fasting blood glucose ≥126mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, non-fatal myocardial infarction (MI) and percutaneous coronary intervention (PCI). After propensity-score matched (PSM) analysis, two propensity-matched groups (243 pairs, n = 486, C-statistic = 0.696) were generated. During 4-year follow-up periods, there were similar incidence of NODM (Hazard ratio [HR]; 1.198, 95% confidence interval [CI]; 0.591-2.431, P = 0.616), MACE (HR; 1.324, 95% CI; 0.714-2.453, P = 0.373), total death, MI and PCI between the two groups after PSM analysis. CCB with ACE or CCB with ARB combination strategies are equally acceptable in hypertensive Korean patients regarding the occurrence of NODM.

Importance of genetic polymorphisms in liver transplantation outcomes.

Although, liver transplantation serves as the only curative treatment for patients with end-stage liver diseases, it is burdened with complications, which affect survival rates. In addition to clinical risk factors, contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes. Determination of single nucleotide polymorphisms (SNPs) is one of the most important tools in development of personalized transplant approach. To provide a better insight in recent developments, we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation: Acute cellular rejection, development of new-onset diabetes mellitus and non-alcoholic fatty liver disease, hepatocellular carcinoma recurrence, and tacrolimus concentration variability. Reviewed studies confirmed previously established SNP prognostic factors, such as PNPLA3 rs738409 for non-alcoholic fatty liver disease development, or the role of CYP3A5 rs776746 in tacrolimus concentration variability. They also identified several novel SNPs, with a reasonably strong association, which have the potential to become useful predictors of post-transplant complications. However, as the studies were typically conducted in one center on relatively low-to-moderate number of patients, verification of the results in other centers is warranted to resolve these limitations. Furthermore, of 29 reviewed studies, 28 used gene candidate approach and only one implemented a genome wide association approach. Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.

Abstract P2-08-11: High prevalence and incidence of new onset diabetes in metastatic breast cancer

Abstract Background: The association between pre-existing diabetes mellitus (DM) and subsequent increased incidence of breast cancer (BC), as well as worse survival after BC diagnosis, is well described. However, the reverse relationship of BC or metastases to development of new onset DM is unknown. Preclinical evidence suggests that increased bone destruction due to bone metastases or endocrine therapy impairs insulin secretion via TGFβ-mediated oxidation of the ryanodine receptor in pancreatic β- cells, predisposing patients to development of new onset DM. This analysis describes the prevalence and new onset of DM in metastatic BC compared to matched, unaffected controls and non-metastatic BC. Methods: This retrospective study collected data on women from the Indiana Network for Patient Care (INPC, a multi-health system electronic health record data warehouse), and the Indiana State Department of Health Cancer Registry from 2015 to 2017. Diagnosis of BC and metastases were established using ICD codes from INPC and confirmed in the cancer registry. DM was defined using a combination of ICD codes, diabetic medication prescriptions, and hemoglobin A1c >6.5%. Controls without BC were matched to all BC cases by birth year and race. The prevalence of DM before, or < 30 days after, BC diagnosis is described for non- cancer controls, all patients with BC, and subgroups without metastases, any metastases, and with bone metastases. In patients without evidence of DM prior to or < 30 days after BC diagnosis, the incidence of new onset DM was compared to matched controls over the same time period. The occurrence of new DM was evaluated both including and excluding the first 6 months after BC diagnosis to account for potential DM diagnosis simply due to medical attention. Prevalence and subsequent incidence of DM was compared between cases and controls using Pearson’s chi-square tests. Variables including demographics, comorbidities, BC treatment, A1c values, and DM treatments were also collected. Results: Any DM diagnosis, pre-existing DM, and new onset DM were higher in breast cancer cases compared to controls (Table). While pre-existing DM was similar between those with metastatic and non-metastatic DM (35.0% vs. 32.2%, p=0.22), new onset DM was higher in metastatic disease compared to non-metastatic BC (14.4% vs. 7.0%, p<0.001). Hemoglobin A1c was higher in those with metastatic disease, particularly those with bone metastases (8.8 vs 7.5, p<0.001). Conclusions: Diabetes is highly prevalent in this Indiana BC cohort. Incidence of new onset DM after BC is higher in those with metastatic BC compared to both controls and BC cases without metastatic disease. Hemoglobin A1c was highest in those with bone metastases, further supporting the hypothesis that bone turnover may influence insulin secretion and glucose metabolism. Additional investigation will analyze the influence of medications (chemo-, endocrine, and bone protective therapy) on development of DM. As more patients live longer with metastatic BC, identification and management of DM will be imperative given its impact on BC survival, treatment delivery, healthcare costs, and quality of life. ControlsBreast cancer (BC) casesAllNon-metAll metBone metNon-bone metTotal n10212102129760452236216Any DM, n (%)2464 (24.1)4406 (43.1)3823 (39.2)223 (49.3)111 (47.0)112 (51.9)p-value2<0.001<0.001<0.001<0.001<0.001Pre-existing DM1, n (%)2111 (20.1)3301 (32.2)3143 (32.2)158 (35.0)81 (34.3)77 (35.6)p-value2<0.001<0.001<0.001<0.001<0.001New DM after BC1, n (%)353 (3.5)745 (7.3)680 (7.0)65 (14.4)30 (12.7)35 (16.2)p-value2<0.001<0.001<0.001<0.001<0.001New DM > 6 months after BC1, n (%)336 (3.3)621 (6.1)565 (5.8)56 (12.4)27 (11.4)29 (13.4)p-value2<0.001<0.001<0.001<0.001<0.001HgbA1c in those with DM, Mean (SD)7.6 (1.6)7.6 (1.6)7.5 (1.6)8.3 (2.1)7.5 (1.6)8.8 (2.3)p-value21.00.001<0.0010.40<0.0011- For controls, values in relation to index date. 2 - p-values versus controls. Citation Format: Tarah Ballinger, Sarah El-Azab, Ziyue Liu, Theresa Guise, Erik Imel. High prevalence and incidence of new onset diabetes in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-11.

Importance of Hypomagnesemia on New-Onset Diabetes Mellitus in Pediatric Renal Transplant Patients.

Hypomagnesemia is considered as an independent risk factor for new-onset diabetes mellitus after kidney transplant. New-onset diabetes mellitus is an important comorbidity associated with allograft failure. In this study, our aim was to investigate the correlation between hypomagnesemia and preva-lence of posttransplant diabetes mellitus. We retrospectively evaluated 189 pediatric renal transplant recipients who underwent their first renal transplant. A patient with type 1 diabetes mellitus before transplant was excluded from the analysis. Hypomagnesemia was defined as having serum magnesium levels lower than 1.7 mg/dL. Diabetes was defined according to American Diabetes Association criteria. Serum magnesium and glucose levels at month 1 after transplant were recorded. We evaluated the records of 188 patients. New-onset diabetes mellitus was diagnosed in 7 patients (3.7%). Hypomagnesemia was shown in 50% of patients (64/120). Mean glucose levels were higher in those with hypomagnesemia than in patients without hypomagnesemia (119.2 vs 91.56 mg/dL, respectively; P = .01) A significant negative correlation was observed between serum magnesium and glucose levels (r = -0.53; P < .05). Mean serum magnesium level in patients with new-onset diabetes mellitus was lower than in patients without diabetes (1.56 ± 0.21 vs 1.75 ± 0.26 mg/dL; P = .052). Hypomagnesemia is a common problem in pediatric renal transplant. The relationship between serum magnesium and glucose levels suggests that hypomagnesemia plays a role in the development of new-onset diabetes mellitus after transplant. Compre-hensive studies are needed to support this association.

Diabetes development after distal pancreatectomy: results of a 10 year series

BackgroundLimited literature is available on the postoperative development of impaired glucose tolerance (IGT) and new-onset diabetes mellitus (NODM) following Distal Pancreatectomy (DP). We aimed to study the post-surgical clinical evolution of IGT/DM and its association with preoperative glycemic profiles of patients undergoing DP. MethodsPre- and postoperative glycemic laboratories were measured in patients undergoing DP by the senior author from 2007–2017. Multivariate risk factor analysis was performed to determine risk factors for new-onset IGT/DM after DP. Kaplan–Meier curves were constructed for development of NODM postoperatively. ResultsOf 216 included patients, n = 63, n = 68 and n = 85 were preoperatively diagnosed with no-diabetes (No-DM), pre-diabetes (Pre-DM), and diabetes (DM), respectively. At 2-year follow-up, n = 37, n = 80 and n = 99 were classified as No-DM, Pre-DM or DM, respectively. Pre-diabetics had a higher risk of developing postoperative dysglycemia (RR 2.230, 95% CI 1.732–2.870, p = 0.001). Preoperative OGTT>130, HbA1c >6.0, and chronic pancreatitis were risk factors for postoperative DM. Conclusion40% of patients undergoing DP were unaware of their dysglycemic status (pre-DM or DM) pre-operatively. At 2-year follow-up, 36% non-diabetic and 57% pre-diabetic patients had developed NODM. Appropriate pre-operative diabetic assessment is warranted for all patients undergoing pancreatic resections.

SNPs Within the MTOR Gene Are Associated With an Increased Risk of Developing De Novo Diabetes Mellitus Following the Administration of Everolimus in Liver Transplant Recipients

BackgroundThe impact of immunosuppressive drugs in patients following liver transplantation (LT) is very individual. Despite the multiple beneficial effects of the mammalian target of rapamycin (mTOR) inhibitor everolimus (EVR) in LT recipients, some patients do not benefit from EVR administration. We investigated whether the presence of common single-nucleotide polymorphisms (SNPs) in the mTOR gene are predictive for adverse events following the introduction of EVR after LT. Materials and MethodsThe feasibility and efficacy of EVR in 127 liver transplant recipients who were converted to EVR-based immunosuppression was documented retrospectively. Blood samples of these patients were analyzed for the occurrence of 4 SNPs in the mTOR promoter region (mTOR3099/rs2295079 C>G, mTOR3162/rs2295080 A>C) and the mTOR 3′ untranslated regio (mTOR8167/rs12139042 C>T, mTOR8600/rs2536 A>G); the specific allele variants were also associated with the incidence of adverse events (AEs). ResultsOf all patients, 21 (16.5%) did not tolerate the medication and had to discontinue. Of those patients who continued, 37% developed signs of reduced tolerance within the first 6 months, resolving after 12 months. When the cohort was divided according to genotype and allele frequency, patients with the mTOR3162/rs2295080 CC variant had a significantly higher risk (odds ratio = 5.89; 95% confidence interval = 1.48–23.40; P = .012) of developing new-onset diabetes mellitus following EVR treatment than AA or AC genotype carriers. ConclusionOur results suggest that the SNP mTOR3162/rs2295080 CC genotype is associated with the development of new-onset diabetes mellitus following EVR treatment.

Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjögren syndrome.

To determine whether taking hydroxychloroquine (HCQ) could prevent the development of new-onset diabetes mellitus (DM) among patients with Sjögren syndrome (SS). This is a nationwide, population-based, retrospective cohort study utilizing the Taiwan National Health Insurance Research Database (NHIRD). Data were collected from 1 January 1999, through 31 December 2013, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. In total, 7774 patients newly diagnosed with SS by at least three outpatient visits or one inpatient admission were selected from the NHIRD as participants. Patients who had previously been diagnosed with DM and whose follow-up durations shorter than 90 days were excluded. HCQ exposure group includes patients who had been diagnosed with SS no longer than 180 days previously, and had been prescribed HCQ for the first time for at least 90 days. The diagnosis of DM was defined as at least two outpatient visits or one inpatient admission with anti-diabetic medication prescription. Patients with SS treated with HCQ had a significantly lower cumulative incidence of new-onset DM than those not treated with HCQ (adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.96, P < 0.05). HCQ use for 3 years or more had favorable protective effects (adjusted hazard ratio: 0.22, CI: 0.05-0.92). HCQ reduced the incidence of DM in a time and dose-dependent manner. Patients with SS who had taken HCQ for 3 years or more exhibited significant protective effects against developing new-onset DM.

Calcium channel blocker monotherapy versus combination with renin-angiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients.

BackgroundIn real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods.MethodsA total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI).ResultsAfter propensity score-matched (PSM) analysis, two propensity-matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years.ConclusionsThe use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.

119Angiotensin converting enzyme inhibitor versus angiotensin receptor blockers on the top of calcium channel blocker in development of new-onset diabetes mellitus in hypertensive Korean patients

119Angiotensin converting enzyme inhibitor versus angiotensin receptor blockers on the top of calcium channel blocker in development of new-onset diabetes mellitus in hypertensive Korean patients