Occurrence Of New-onset Diabetes Research Articles

The Questionable Burden of AB0 Incompatible Kidney Transplantation

Abstract Background AB0 incompatible kidney transplantation has become a genuine treatment for end-stage renal disease. Non-inferiority in long term graft function compared to AB0 compatible transplantation has been shown. However, the assumed burden due to complications owing to increased immunosuppression inherent to AB0 incompatible transplantation has not yet been quantified. Aims The aim of the study was to determine if AB0 incompatible recipients have additional morbidity and whether this burden is justified or whether kidney paired donation programs should be advocated. Methods From January 2000 to March 2020 46 AB0 incompatible living kidney transplantations were performed. Patients were matched with AB0 compatible recipients according to sex, age, underlying disease, year of transplantation, and duration of dialysis. Number and duration of readmissions, surgical complication rates according to Clavien-Dindo and its comprehensive complication index (CCI), kidney function, occurrence of new onset diabetes, as well as tumor incidence were analyzed. Results Readmission rate was not higher in AB0 incompatible recipients. The median difference in length of hospital stay for readmissions, CCI during primary hospital stay, and CCI for readmissions at 3, 6, 12 and >12 months after transplantation were comparable. Incidence of tumor and new onset diabetes after transplantation was not increased in incompatible recipients. Conclusions AB0 incompatible recipients do not suffer from a higher burden compared to AB0 compatible recipients. We currently recommend not delaying transplantation in AB0 incompatible pairs.

The incidence, risk factors, and outcome of new-onset diabetes among post-COVID-19 patients: A single-center study

Background: Coronavirus disease 2019 (COVID-19) infection may elevate the risk of hyperglycemia and other complications in patients with and without prior diabetes history. It is not clear whether the virus induces type 1 or type 2 diabetes or instead causes a novel form of diabetes. Precise mechanism of diabetes onset in COVID-19 patients remains unresolved. Aims and Objectives: The aims of this study were to know the incidence, risk factors, and outcome of new-onset diabetes among post-COVID-19 patients and association of disease severity and occurrence of new-onset diabetes in post-COVID-19 Patients. Materials and Methods: Patients age more than 18 years, not known diabetic, tested positive with rapid antigen test or reverse transcription polymerase chain reaction admitted to a tertiary care hospital were included in the present prospective observational study. The patients who developed new-onset diabetes during the 3 months follow-up and, the risk factors associated with new-onset diabetes are assessed. Patients with hemoglobin (HbA1c) >6.5% were diagnosed with new-onset diabetes. Results: Total 246 patients were non-diabetics at admission, at 1 week 188 were non-diabetics and 49 were diabetics, and nine were prediabetics. Patients were within the age range of 21–95 years with mean age of 49.46±17.02 years and male predominance (59.76%). Out of 188 non-diabetics, 19 (10.10%) developed new-onset diabetes, and 2 (1.06%) developed new-onset prediabetes after 3 months. Out of 49 diabetics, 19 (38.77%) became non-diabetic, 30 (61.22%) remained diabetic, and out of nine prediabetes 2 (22.22%) developed new-onset diabetes, 5 (55.55%) reversed to non-diabetic, and 2 (22.22%) remained prediabetic after 3 months. In total, from HbA1c at admission and 3 months, 51 subjects had new-onset diabetes (20.73%). Most common risk factors found with occurrence of new-onset diabetes were those on high dose of steroid (P=0.0001), family history of diabetes mellitus (DM) (P=0.001), over weight and obesity (P=0.0001), fungal infection (P=0.0001), and need of oxygen and intensive care unit requirement (P=0.0001). The patient with increased laboratory markers of inflammation such as ferritin, neutrophil leukocyte ratio, lactate dehydrogenase, and C-reactive protein D-dimer had strong association with occurrence of new-onset diabetes (P=0.0001). Conclusion: COVID-19 infection confers an increased risk for type 2 diabetes. Patients of all ages and genders had an elevated incidence and risk for occurrence of new-onset diabetes. Moreover, it was strongly associated with overweight and obesity, steroid dosage, and its duration, disease severity, positive family history of DM, and increased laboratory markers of inflammation. Hence, particular attention should be paid during the first 3 months after COVID-19 infection and patients need to be under follow-up for blood glucose monitoring.

Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion.

Lipid-lowering is a central theme in the management of patients with atherosclerotic cardiovascular disease (ASCVD)and heterozygous familial hypercholesterolemia (HeFH), with statins being currently used as the first-line lipid-lowering agent (LLAs). Bempedoic acid (BA) has been recently approved for lipid management in ASCVD/HeFH patients. This expert opinion paper brings out the essential conceptto assess the current place of BA in the Indian population. Here we highlight that the majority of the patients with clinical ASCVD may not be receiving the optimal dose of statin, thereby failing to achieve their lipid targets. The addition of BA to statin results in a significant reduction in low-density lipoprotein cholesterol (LDL-C) along with substantial reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) levels. For patients who do not achieve LDL-C targets, BA can be an effective add-on alternative to choose among non-statin LLAs. BA is a good choice for statin-intolerant cases, especially in combination with ezetimibe. Given the lack of effect of worsening hyperglycemia or any increase in the occurrence of new-onset diabetes, BA can be used without hesitation in patients with diabetes. The small risk of hyperuricemia could be mitigated with appropriate patient selection and monitoring of serum uric acid levels in patients at high risk of hyperuricemia. We believe BA is an excellent non-statin therapy that is efficacious, well-tolerated, and cost-effective for lipid management in ASCVD, HeFH, and statin-intolerant patients in India.

SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes.

Evidence suggests an association between severe acute respiratory syndrome–cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immunolocalization in pancreatic cells of SARS-CoV-2–infected NHPs and patients who had died from coronavirus disease 2019 (COVID-19). We report expression of ACE2 in pancreatic islet, ductal, and endothelial cells in NHPs and humans. In pancreata from SARS-CoV-2–infected NHPs and COVID-19 patients, SARS-CoV-2 infected ductal, endothelial, and islet cells. These pancreata also exhibited generalized fibrosis associated with multiple vascular thrombi. Two out of 8 NHPs developed new-onset diabetes following SARS-CoV-2 infection. Two out of 5 COVID-19 patients exhibited new-onset diabetes at admission. These results suggest that SARS-CoV-2 infection of the pancreas may promote acute and especially chronic pancreatic dysfunction that could potentially lead to new-onset diabetes.

Assessment of Association between Antihypertensive Drug Use and Occurrence of New-onset Diabetes in South Indian Patients.

Objective:The objective of this study was to determine the association between antihypertensive drug use and new-onset diabetes (NOD) in patients with hypertension (HTN).Materials and Methods:A retrospective observational study was conducted in a tertiary care hospital located in south India. Patients diagnosed with HTN and HTN with diabetes between January 2012 and December 2016, were identified and studied. Medical records of these patients from Medical Record Department were evaluated by medical record review method, and relevant data were recorded in a case record form. Statistical evaluation by chi-square method and odds ratio (OR) was carried out to appraise the incidence of NOD in patients taking antihypertensive medications.Results:A total of 1250 patients with HTN were screened, and based on inclusion and exclusion criteria, 952 patients were enrolled in the study; among which, 537 were patients with HTN and 415 were patients with diabetic HTN. The majority of the patients with HTN and patients with diabetic HTN were from the age-group of above 60 years. The most commonly prescribed drugs observed in our study population were amlodipine in 94 (22.7%) patients. OR was calculated and it was observed that the combination therapy has a fivefold risk for the development of NOD in patients with HTN, followed by Angiotensin II receptor blockers (2.06) (confidence interval [CI]: 1.56–2.73), diuretics (1.33) (CI: 0.95–1.85), non-Dihydropyridine calcium channel blockers (DHP CCBs) (1.3) (CI: 0.51–3.30), vasodilators (1.13) (CI: 0.40–3.15), and Angiotensin converting enzyme inhibitors (1.06) (0.68–1.64).Conclusion:Patients on non-DHP CCBs, diuretics, and combination antihypertensives showed more chances of developing NOD.

Immune phenotype predicts new onset diabetes after kidney transplantation

Few data are available concerning immune factors involved in the occurrence of new onset diabetes after transplantation (NODAT). Our objective was to determine an immune profile associated with the subsequent development of NODAT. The secondary objective was to build a predictive model of NODAT. We studied a prospective cohort of incident kidney transplant patients to determine whether pre-transplant immune characteristics could be associated with the occurrence of NODAT. 818 patients were included. We observed a significant inverse correlation between BMI and recent thymic emigrants (RTE) % at transplant time (p < 0.001). 177 (17.3%) of 677 non-diabetic patients experienced NODAT in the first year post-transplant. In multivariate analysis, age, body mass index (BMI), use of Tacrolimus, use of anti-thymocyte globulins (ATG), higher B cell count, and lower recent thymic emigrants (RTE) % were associated with NODAT. A differential effect of immune profile was observed in ATG-treated patients and non-ATG-treated patients. B cell count predicts NODAT only in non-ATG-treated patients whereas lower RTE% was associated with NODAT only in ATG-treated patients. Tacrolimus sparing and B cell depletion may efficiently prevent NODAT in selected patients. We identified an immune profile associated with the occurrence of post-transplant diabetes. Further studies should better precise the exact mechanisms involved in this association. Trial registration NCT02843867, registered July 8, 2016 – retrospectively registered https://clinicaltrials.gov/ct2/show/record/NCT02843867.

New-onset diabetes after transplant: Incidence, risk factors and outcome.

The outcome of renal transplantation depends on achieving effective immunosuppression while minimising the consequences of such treatment. The occurrence of new-onset diabetes in the post-transplant period has been associated with several risk factors including some immunosuppressive medication. Better understanding of the clinical and genetic risk factors associated with new-onset diabetes after transplant (NODAT) could enable risk stratification of patients in the pre-transplant period, with the goal of applying measures that will reduce the incidence. To ascertain the incidence of and clinical and genetic risk factors that predispose to NODAT, and to examine its effect on the outcome of renal transplantation. We performed a retrospective cohort review of all renal transplants at Groote Schuur Hospital, Cape Town, South Africa, between 2004 and 2008. Patients who were lost to follow-up or had pre-transplant diabetes or primary non-function were excluded. A subset of the cohort who gave informed consent was enlisted for genetic tests. We identified 111 patients who met the inclusion criteria. The incidence of NODAT was 18.0% (n=20 patients). Risk factors for NODAT included age at transplant (p=0.03), body weight (p=0.04), treatment for acute cellular rejection (p=0.02) and polycystic kidney disease as the cause of renal failure (p=0.005). None of the genes investigated (TCF7L2 rs11196205, rs12255372 and rs7903146 and HNF1β rs1800575, rs121918671 and rs121918672) was found to be significantly associated with the risk of NODAT. The genotype frequencies for the single-nucleotide polymorphisms studied were closer (although not identical) to those reported for Caucasians than to those reported for the Yoruba (black) population in West Africa. Overall patient survival was 78% at five years, while graft survival was 72%. There was no significant difference in patient or graft survival between the group with NODAT and the group without. NODAT was common in renal transplant recipients. Some risk factors predate transplant and could be used to risk-stratify patients to determine appropriate risk-reduction strategies. The genetic determinants for NODAT in this population may differ from those reported elsewhere. NODAT had no impact on patient or graft survival in this cohort.

Correlating pancreatic parenchymal remnant volume following pancreaticoduodenectomy with occurrence of new-onset diabetes using multidetector row computed tomography (MDCT) imaging volumetry

Correlating pancreatic parenchymal remnant volume following pancreaticoduodenectomy with occurrence of new-onset diabetes using multidetector row computed tomography (MDCT) imaging volumetry

Long-Term Safety and Efficacy of Triple Combination Ezetimibe/Simvastatin Plus Extended-Release Niacin in Patients With Hyperlipidemia

The safety and efficacy of combination ezetimibe/simvastatin (E/S) plus extended-release niacin was assessed in 942 patients with type IIa/IIb hyperlipidemia for 64 weeks in a randomized, double-blind study. Patients received E/S (10/20 mg) plus niacin (to 2 g) or E/S (10/20 mg) for 64 weeks, or niacin (to 2 g) for 24 weeks and then E/S (10/20 mg) plus niacin (2 g) or E/S (10/20 mg) for an additional 40 weeks. The primary end point, the safety of E/S plus niacin, included prespecified adverse events (ie, liver, muscle, discontinuations due to flushing, gallbladder-related, cholecystectomy, fasting glucose changes, new-onset diabetes). The secondary end points included the percentage of change from baseline in high-density lipoprotein (HDL) cholesterol, triglycerides, non-HDL cholesterol, and low-density lipoprotein cholesterol, other lipids, lipoprotein ratios and high-sensitivity C-reactive protein. The anticipated niacin-associated flushing led to a greater rate of study discontinuations with the E/S plus niacin regimen than with E/S alone (0.7%, p <0.001). The rate of liver and muscle adverse events was low (<1%) in both groups. Four patients had gallbladder-related adverse events; 1 patient in the E/S and 1 in the E/S plus niacin group underwent cholecystectomy. The occurrence of new-onset diabetes was 3.1% for the E/S and 4.9% for the E/S plus niacin group. The fasting glucose levels increased to greater than baseline during the first 12 weeks (E/S, 3.2 mg/dl; E/S plus niacin, 7.7 mg/dl) and gradually decreased to pretreatment levels by 64 weeks in both groups. E/S plus niacin significantly improved HDL cholesterol, triglycerides, non-HDL cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and A-I, and lipoprotein ratios compared with E/S (p <or=0.004). The changes in high-sensitivity C-reactive protein were comparable for both groups. In conclusion, the combination of E/S plus niacin was generally well tolerated, aside from niacin-associated flushing, and was significantly superior to E/S alone in improving several lipoprotein parameters during a 64-week trial in patients with hyperlipidemia. E/S plus niacin provided a broad, lipid-altering therapeutic option for these patients, even in the presence of diabetes with glucose monitoring.

Tissue ACE Inhibitors for Secondary Prevention of Cardiovascular Disease in Patients With Preserved Left Ventricular Function: A Pooled Meta-analysis of Randomized Placebo-controlled Trials

A pooled meta-analysis of published, randomized placebo-controlled clinical trials to evaluate the role of tissue angiotensin-converting enzyme (ACE) inhibitors in secondary prevention of cardiovascular disease in patients with preserved left ventricular function. Peer-reviewed journals listed in Index Medicus/MEDLINE, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews. Randomized placebo-controlled clinical trials of at least 12 months' duration, in patients with a prior cardiovascular event or at high risk for cardiovascular events, were analyzed. DATA SYNTHESIS AND ANALYSIS: A total of 31,555 patients (136,882 patient-years) from 4 trials were selected for the meta-analysis. Relative risk estimations were made using data pooled from these trials, and statistical significance was determined using the chi2 test. The number of patients needed to treat was also calculated for each outcome. Tissue ACE inhibitors significantly reduced the risk of all-cause mortality, cardiovascular mortality, acute myocardial infarction, and stroke (P < .001 for each). The need for invasive coronary revascularization was reduced (P = .03), as was the risk of hospitalization for congestive heart failure (P = .001). The occurrence of new-onset diabetes was also significantly reduced (P < .001), but the risk of hospitalization for angina was not significantly affected (P = .677). Treating about 100 patients for about 4.5 years would prevent 1 death, 1 non-fatal myocardial infarction, 1 cardiovascular death, or 1 invasive coronary revascularization. Tissue ACE inhibitors have demonstrated benefit when used for secondary prevention of cardiovascular disease in patients with preserved left ventricular function in randomized placebo-controlled clinical trials.

Hypertension Treatment Guidelines: Is It Time for an Update?

Hypertension Treatment Guidelines: Is It Time for an Update?

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Is New‐Onset Diabetes of Clinical Significance in Treated Hypertensive Patients?—Con

There is little doubt that diabetes is more common in hypertensive than normotensive individuals. There are also some data suggesting that the use of certain antihypertensive agents, i.e., diuretics and more specifically some beta blockers will increase the occurrence of new onset diabetes (NOD) when compared to other medications, especially angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The clinical significance of this 1%-3.5% difference, however, has not been established. Different studies report different outcomes. In large outcome trials the occurrence of NOD did not effect mortality or morbidity outcomes. Although one study reported that NOD had the same prognosis as pretreatment diabetes, another did not. At present, data are insufficient to suggest that NOD is of important clinical significance or that present treatment recommendations, especially regarding the use of diuretics, should be changed.