Incidence Of New-onset Diabetes Research Articles

Pancreatic surgery and tertiary pancreatitis services warrant provision for support from a specialist diabetes team

Pancreatic surgery units undertake several complex operations, albeit with considerable morbidity and mortality, as is the case for the management of complicated acute pancreatitis or chronic pancreatitis. The centralisation of pancreatic surgery services, with the development of designated large-volume centres, has contributed to significantly improved outcomes. In this editorial, we discuss the complex associations between diabetes mellitus (DM) and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis, highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services. Type 3c pancreatogenic DM, refers to DM developing in the setting of exocrine pancreatic disease, and its identification and management can be challenging, while the glycaemic control of such patients may affect their course of treatment and outcome. Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period. The incidence of new onset diabetes after pancreatic resection is widely variable in the literature, and depends on the type and extent of pancreatic resection, as is the case with pancreatic parenchymal loss in the context of severe pancreatitis. Early involvement of a specialist diabetes team is essential to ensure a holistic management. In the current era, large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery, with inclusion of provisions for optimisation of the perioperative glycaemic control, to improve outcomes. While various guidelines are available to aid perioperative management of DM, auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement. The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined, a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis. Therefore, pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams. With the ongoing accumulation of evidence, it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.

Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial.

Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.

Effect of Genetic Polymorphism on Clinical Efficacy of Tacrolimus in Adult Living Donor-Liver Transplant Patients

Background and Aim The influence of genetic polymorphism on the clinical outcome including response and safety of immunosuppression in liver transplant (LT) recipients remains controversial among different races and ethnicities, especially for calcineurin inhibitors (CNIs). This study aims to evaluate the effect of different genotypes of the single nucleotide polymorphism (SNP) in the genes encoding CYP3A5 on the therapeutic response to the widely used calcineurin inhibitor; tacrolimus. Method In 49 living donor liver transplant (LDLT) recipients with tacrolimus as the backbone immunosuppressive, the rejection, delayed graft function, laboratory evidenced nephrotoxicity, new onset diabetes and hypertension rates were considered the primary therapeutic and safety outcomes of tacrolimus. The biochemical parameters of tacrolimus response and safety as evidence by the status of liver functions, renal functions, complete blood counts and serum electrolytes, as well as the need for Mycophenolate mofetil (MMF) were considered the secondary outcomes. Results the rejection and delayed graft function rates didn’t differ significantly among different genotypes (p = 1), similarly; the incidence of new onset diabetes and hypertension didn’t differ significantly among different genotypes (p = 1, and 0.4143 respectively). Moreover; laboratory evidenced nephrotoxicity rates didn’t differ significantly among different genotypes (p = 0.5040). No significant intergenotype differences were observed in the all biochemical outcomes. However the need for MMF was significantly higher among carriers of the CYP3A5*3 allele. Conclusion different genotypes did not offer an advantage over one another in predicting therapeutic response or toxicity of tacrolimus among LDLT recipients.

Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD)

ObjectiveWe aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population.SettingPopulation-based retrospective cohort study using annual health check-up data...

Clonal hematopoiesis as a novel risk factor for type 2 diabetes mellitus in patients with hypercholesterolemia.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with atherosclerosis and cardiovascular disease. It has been suggested that CHIP may be related to diabetes, so we investigated the association between CHIP and new-onset type 2 diabetes. This study included 4,047 subjects aged >=40 years without diabetes. To detect CHIP, targeted gene sequencing of genomic DNA from peripheral blood cells was performed. The incidence of new-onset type 2 diabetes during the follow-up period was evaluated. Of the total subjects, 635 (15.7%) had CHIP. During the median follow-up of 5.1 years, the incidence of new-onset diabetes was significantly higher in CHIP carriers than in subjects without CHIP (11.8% vs. 9.1%, p = 0.039). In a univariate analysis, CHIP significantly increased the risk of new-onset diabetes (HR 1.32, 95% CI 1.02-1.70, p = 0.034), but in a multivariate analysis, it was not significant. The CHIP-related risk of new onset diabetes differed according to LDL cholesterol level. In the hyper-LDL cholesterolemia group, CHIP significantly increased the risk of diabetes (HR 1.64, 95% CI 1.09-2.47, p = 0.018), but it did not increase the risk in the non-hyper-LDL cholesterolemia group. The subjects with CHIP and hyper-LDL-cholesterolemia had approximately twice the risk of diabetes than subjects without CHIP and with low LDL cholesterol (HR 2.05, 95% CI 1.40-3.00, p < 0.001). The presence of CHIP was a significant risk factor for new-onset type 2 diabetes, especially in subjects with high LDL cholesterol. These results show the synergism between CHIP and high LDL cholesterol as a high-risk factor for diabetes.

Lipoprotein(a), metabolic profile and new-onset type 2 diabetes in patients with familial combined hyperlipidemia: A 9 year follow-up study

Lipoprotein(a) [Lp(a)] appears to have an inverse association with the risk of type 2 diabetes mellitus in the general population. This study aimed to investigate the prognostic role of Lp(a) regarding the development of type-2 diabetes in the special population of subjects with familial combined hyperlipidemia (FCH). This cohort study included 474 patients (mean age 49.7±11.3 years, 64% males) with FCH, without diabetes at baseline who were followed for a mean period of 8.2±6.8 years. At baseline evaluation venous blood samples were obtained for the determination of lipid profile and Lp(a) levels. The endpoint of interest was the development of diabetes. Patients with increased Lp(a) levels ≥30mg/dl compared to those with low Lp(a) levels <30mg/dl had lower levels of triglycerides (238±113 vs 268±129 mg/dl, p=0.01), greater levels of high-density lipoprotein (HDL) cholesterol (44±10 vs 41±10 mg/dl, p=0.01) and hypertension in a greater percentage (42% vs 32%, p=0.03). The incidence of new-onset diabetes during the follow-up period was 10.1% (n=48). Multiple Cox regression analysis revealed that increased Lp(a) is an independent predictor of lower diabetes incidence (HR 0.39, 95% CI 0.17-0.90, p=0.02) after adjustment for confounders. Among subjects with FCH those with higher Lp(a) levels have lower risk for the development of type 2 diabetes. Moreover, the presence of increased Lp(a) seems to differentiate the expression of metabolic syndrome characteristics in patients with FCH, as increased Lp(a) is related to lower levels of triglycerides, greater prevalence of hypertension and higher levels of HDL cholesterol.

Long-term outcomes in lean and non-lean NAFLD patients: a systematic review and meta-analysis.

Although nonalcoholic fatty liver disease (NAFLD) commonly occurs in overweight or obese individuals, it is increasingly being identified in the lean population. The association between lean and an increased risk of all-cause mortality among patients with NAFLD remains controversial. We aimed to perform a systematic review and meta-analysis of the literature to evaluate this association and compare the long-term outcomes of lean NAFLD patients and non-lean NAFLD patients. For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang, and Chinese Biomedical Literature Database (CBM) from inception to October 15, 2021, for relevant original research articles without any language restrictions. Our primary outcome was to compare the all-cause mortality in lean NAFLD patients and non-lean NAFLD patients by qualitative synthesis. Relative risks (RRs) and corresponding 95% confidential intervals (CIs) were pooled with a random effect model. Heterogeneity was evaluated using I-squared (I²) statistics while publication bias was determined using Egger's tests. Subgroup and sensitivity analyses were performed. As for secondary outcomes, we estimated total, cardiovascular, and liver-related mortality, as well as the incidence of diabetes, hypertension, cirrhosis, and cancer in lean and non-lean individuals with NAFLD by quantitative synthesis. Person-years of follow-up were used as the denominator to estimate the mortality and incidence. We identified 12 studies (n = 26,329), 7 of which (n = 7924) were used to evaluate the risk of all-cause mortality between lean and non-lean NAFLD patients. Lean patients with NAFLD were found to be at an elevated risk of death compared to non-lean patients (RR = 1.39, 95% CI 1.08-1.82, heterogeneity: I² = 43%). Among the lean NAFLD population, all-cause mortality was 13.3 (95% CI: 6.7-26.1) per 1000 person-years, 3.6 (95% CI: 1.0-11.7) for liver-related mortality, and 7.7 (95% CI: 6.4-9.2) for cardiovascular-related mortality. The incidence of new-onset diabetes was 13.7 (95% CI 8·2-22.7) per 1000 person-years, new-onset hypertension was 56.1 (95% CI: 40.2-77.9), cirrhosis was 2.3 (95% CI: 1.0-5.0), and cancer was 25.7 (95% CI: 20.3-32.4). Lean patients with NAFLD had a higher risk of all-cause death than non-lean patients. Body mass index (BMI) should not be used as a criterion to determine whether further observation and therapy of patients with NAFLD are warranted.

Increased risk of new-onset diabetes in patients with COVID-19: a systematic review and meta-analysis.

There is growing evidence that patients with COVID-19 are at increased risk of new-onset diabetes. The limited preliminary studies do not provide strong evidence. To assess the association of the SARS-CoV-2 virus with new-onset diabetes and to characterize the population. Search PubMed, Embase, Cochrane Library, and Web of Science electronic databases for a limited period from December 2019 to July 2022. Two independent reviewers conducted a thorough review of eligible articles and extracted relevant information. Pooled proportions, risk ratios (RR), and 95% confidence intervals (95% CI) indicated the incidence and risk ratios of events. The incidence of new-onset diabetes and hyperglycemia in patients with COVID-19 was 5% (P < 0.001) (3 and 30% for new-onset diabetes and hyperglycemia, respectively), with age, ethnicity, time of diagnosis, and study type all having an impact on the incidence (P < 0.05). New-onset diabetes and hyperglycemia were 1.75 times higher in COVID-19 patients than in non-COVID-19 patients. In new-onset diabetes and hyperglycemia population, the percentage of men is 60% (40% for women), with a mortality rate of 17%. The proportion of new-onset diabetes and hyperglycemia after infection with COVID-19 was 25% in men and 14% in women. The incidence and relative risk of new-onset diabetes and hyperglycemia are elevated after COVID-19 infection, especially in the early COVID-19 and male populations. PROSPERO registration no.: CRD42022382989 https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=382989.

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Atorvastatin

Predictors of New-Onset Diabetes in Hospitalized Patients with SARS-CoV-2 Infection.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is one of the world’s most disruptive health crises. The presence of diabetes plays an important role in the severity of the infection, and a rise in newly diagnosed diabetes cases has been identified. The aim of this retrospective study was to determine the incidence of new-onset diabetes (NOD) and predictive factors with their cut-off values for patients hospitalized with COVID-19. All patients (n = 219) hospitalized for COVID-19 during three consecutive months were included. NOD was diagnosed in 26.48% of patients. The severity of the infection, hospital admission values for fasting plasma glucose, lactate dehydrogenase (LDH), PaO2/FiO2 ratio, the peak values for leucocytes, neutrophils, C-reactive protein, triglycerides, and the need for care in the intensive care unit were predictors for the occurrence of NOD in univariate analysis, while only LDH level remained a significant predictor in the multivariable analysis. In conclusion, the results of the study showed a high incidence of NOD in patients hospitalized with COVID-19 and identified LDH levels at hospital admission as a significant predictor of NOD during SARS-CoV-2 infection. However, the persistence of NOD after the COVID-19 infection is not known, therefore, the results must be interpreted with caution.

Plasma level of ATPase inhibitory factor 1 (IF1) is associated with type 2 diabetes risk in humans: A prospective cohort study

AimMitochondrial dysfunction is associated with the development of type 2 diabetes mellitus (T2DM). It is thus of clinical relevance to identify plasma biomarkers of mitochondrial dysfunction associated with the risk of T2DM.ATPase inhibitory factor 1 (IF1) endogenously inhibits mitochondrial ATP synthase activity. Here, we analyzed association of the plasma IF1 level with markers of glucose homeostasis and with the conversion to new-onset diabetes (NOD) in individuals with prediabetes. MethodsIn the IT-DIAB prospective study, the baseline plasma level of IF1 was measured in 307 participants with prediabetes. The primary outcome was the incidence of NOD within five years of follow-up. Cross-sectional analysis of the IF1 level was also done in two independent interventional studies. Correlations between plasma IF1 and metabolic parameters at baseline were assessed by Spearman's correlation coefficients, and the association with the risk of NOD was determined using Cox proportional‐hazards models. ResultsIn IT-DIAB, the mean IF1 plasma level was lower in participants who developed NOD than in those who did not (537 ± 248 versus 621 ± 313 ng/mL, P = 0.01). The plasma IF1 level negatively correlated with clinical variables associated with obesity and insulin resistance, including the body mass index (r = −0.20, P = 0.0005) and homeostasis model assessment of insulin resistance (HOMA-IR). (r = −0.37, P < 0.0001). Conversely, IF1 was positively associated with plasma markers of cardiometabolic health, such as HDL-C (r = 0.63, P < 0.0001) and apoA-I (r = 0.33, P < 0.0001). These correlations were confirmed in cross-sectional analyses. In IT-DIAB, the IF1 level was significantly associated with a lower risk of T2DM after adjustment for age, sex, and fasting plasma glucose (HR [95% CI] per 1 SD = 0.76 [0.62; 0.94], P = 0.012). ConclusionWe identified for the first time the mitochondrial-related biomarker IF1 as being associated with the risk of T2DM.

Tacrolimus treatment after short-term intravenous methylprednisolone in incipient minimal change disease for adults: A retrospective analysis

The present study aimed to investigate the efficacy and safety of tacrolimus for treating incipient minimal change disease in adults. The clinical data of 52 adult patients with minimal change disease of nephrotic syndrome diagnosed by renal biopsy in the First affiliated hospital of Zhengzhou University between August 2013 and August 2015 were retrospectively analyzed. According to the treatment plan, the patients were divided into a tacrolimus group and a glucocorticoid group. The efficacy and safety of tacrolimus in the treatment of minimal change disease in adult patients was analyzed and compared with that of glucocorticoids. The results revealed that the baseline characteristics of the two groups were similar (P>0.05). At 24 weeks, there was a significant difference in serum albumin between the two groups (P<0.01). The serum albumin levels of tacrolimus group was higher compared with the glucocorticoid group. In addition, the complete remission rates in the tacrolimus and glucocorticoid groups were 93.75 and 77.8%, respectively (P=0.095), and the mean complete remission time was 6.33±4.21 and 5.14±2.45 weeks, respectively (P=0.175). The relapse rate was 12.5 and 22.2% in the tacrolimus and glucocorticoid groups, respectively (P=0.368). During the follow-up, in tacrolimus group, the incidence of new onset diabetes or impaired glucose tolerance, osteoporosis, infection, abnormal liver function, Cushing's syndrome, acne and gastrointestinal symptoms were significantly less than those of glucocorticoids (P<0.05). In conclusion, tacrolimus treatment after short-time intravenous methylprednisolone is an effective treatment option with fewer adverse effects in adult onset minimal change disease.

161-LB: Intensive Blood Pressure Lowering and the Risk of New-Onset Diabetes in Patients with Hypertension—A Post Hoc Analysis of the STEP Randomized Trial

Background: The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) trial reported the cardiovascular benefit of intensive blood pressure (BP) control. The objective of this analysis was to evaluate the effect of intensive BP lowering on the new-onset diabetes incidence. Methods: The patients of STEP who had a baseline fasting serum glucose (FSG) &amp;lt;7.0 mmol/L without diabetes history and hypoglycemic medication use were included in the main analysis. The primary outcome was the new-onset diabetes, defined as the time to first occurrence of a FSG ≥7.0 mmol/l. The secondary outcome was the new-onset impaired fasting glucose (IFG: FSG 5.6-6.9 mmol/l) among patients with normoglycemia. The competing risk proportional hazards regression model was used in the main analysis. Results: Over a median follow-up of 3.42 years, 273 (9.6%) in the intensive group and 262 (9.5%) in the standard group developed new-onset diabetes (adjusted HR 1.03; 95% CI 0.87-1.22) . The adjusted hazard ratio for the secondary outcome was 1.05 (95% CI 0.92-1.19) . The mean of the highest FSG was 5.82 mmol/l for intensive group and 5.84 mmol/l for standard group. The sensitivity analyses showed no significant difference with respect to the effect of the treatment arms. Conclusions: Intensive BP lowering (target, 110 to &amp;lt;130 mmHg) , as compared with standard BP lowering (target, 130 to &amp;lt;150 mmHg) , did not increase the risk of new-onset diabetes and IFG in patients with hypertension. Disclosure R. Yang: None. J. Cai: None.

New onset diabetes mellitus in post-COVID-19 patients.

Diabetes, is known to have a bilateral relationship with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Precise mechanism of diabetes onset in COVID-19 patients remains unclear. To analyse the incidence of new onset diabetes (NODM) among COVID-19 patients, as well as the effect of body mass index (BMI), family history, and steroid use on the incidence of the disease. Adult, not known diabetic patients, tested positive with Rapid Antigen Test or RT-PCR admitted to a tertiary care hospital and research institute were included in the present prospective observational study. The patients who developed NODM and NOPD (New Onset Pre-diabetes) during the three months follow-up and the risk factors associated were assessed. Patients with HbA1c >6.4% were diagnosed with NODM. An HbA1c of 5.7% to 6.4% was used to characterize NOPD. Out of 273 previously not known diabetic COVID-19 infected individuals, a total of 100 were studied for three months after consent. Mean age of the patients 48.31 ± 19.07 years with male predominance (67%). Among these, 58% were non-diabetics and 42% were pre-diabetics. 6 (10.3%) of the 58 non-diabetics developed NOPD, and 8 (13.8%) developed NODM. 6 (14.2%) of the 42 pre-diabetics became non-diabetic, and 16.6% (7) developed NODM. Family history of DM (P < 0.001), severity at admission (P < 0.006), diabetic ketoacidosis (P < 0.0275), and persistent symptoms were associated significantly with NODM. Those with NODM had significantly greater BMI, O2 duration, steroid duration, FBS, and PPBS (P < 0.001 for all). Nearly 67% of the patients who developed NOPD had shortness of breath as the common symptom at time of admission (P = 0.0165). The incidence of NODM was strongly influenced by positive family history of DM, higher BMI, steroid dosage, and its duration. Hence, patients with COVID-19 need to be under surveillance for blood glucose screening.

353. New-Onset Diabetes as an Acute Complication of COVID-19: A National Population Cohort Analysis

BackgroundDiabetes is emerging as one of the complications of coronavirus disease 2019 (COVID-19), but this is hard to be revealed with cross-sectional studies since it is also known as the major predisposing factor for high-risk COVID-19. Therefore, this study aimed to estimate the risk of new-onset diabetes after COVID-19 through a population follow-up study.MethodsAll COVID-19 confirmed cases in Korea from January 20 to June 4, 2020, were matched with national health insurance data and their health screening data, both provided by the National Health Insurance Service of Korea. Controls were selected as the people who received the PCR test for COVID-19 and showed negative results in the same period and followed up until July 19, 2020. We selected the outcome as the diagnosis of diabetes according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10, E10 – E14). People who were diagnosed with diabetes in the past five years were excluded from both groups. After performing a log-rank test between groups, adjusted incidence rate and hazard ratio were estimated using Cox proportional hazard modeling. Demographic characteristics (age, sex, region, family histories of hypertension/diabetes, and income) and underlying health conditions such as hypertension, dyslipidemia, heart disease, alcohol consumption, cigarette smoking, and BMI were adjusted. Proportional assumptions were tested by the zph test and the sensitivity analysis by excluding each factor in turn and comparing results.ResultsA total of 6,247 COVID-19 patients and 143,594 controls without diabetes in the past were included for the analysis. The number of new-onset diabetes were 759 (12.15%) in COVID-19 patients and 3,465 (2.41%) in controls (P < 0.01). The adjusted incidence of diabetes was 15.34 (95% confidence interval, CI: 14.10 – 16.66) and 11.18 (95% CI: 10.67 – 11.72) per 100 person-year, respectively, with the mean follow-up time as 46.31 (standard deviation: 16.37) days. The adjusted hazard ratio of diabetes in COVID-19 cases was 2.97 (95% CI: 2.44 – 3.63).ConclusionSince COVID-19 patients showed a higher incidence of new-onset diabetes in a short-time follow-up, we should consider diabetes as one of the possible complications of COVID-19. Disclosures All Authors: No reported disclosures

AACE2021-A-1061: A High Incidence of New Onset Diabetes Among Patients with Covid-19 Admitted to Hospital

The early reports of COVID-19 came from Wuhan, China in early December, 2019 with clusters of cases of severe pneumonia (1). Since then, reports of new onset diabetes (NODM) and diabetic ketoacidosis have been published (2, 3). This study aims to estimate the incidence of NODM among patients with COVID-19 admitted to a hospital in Basra, southern Iraq.

Impact of ACLY on type 2 diabetes in UK Biobank: a Mendelian randomisation study

Abstract Background Cholesterol lowering therapies have greatly reduced the burden of cardiovascular disease. Bempedoic acid inhibits ATP citrate lyase (ACLY), a key enzyme in the cholesterol biosynthesis pathway, and has shown promising results in early-phase randomised controlled trials. Targeting this mechanism may therefore provide a further therapeutic option for lowering LDL cholesterol (LDL-C) and cardiovascular risk. In contrast to statin therapy, randomised comparisons suggest that the incidence of new-onset diabetes is lower with bempedoic acid than with placebo. Mendelian randomisation offers the potential to use genetic variants in the ACLY gene to mimic the on-target effects of bempedoic acid. We used this approach to explore the association between genetic inhibition of ACLY and risk of type 2 diabetes (T2DM). Purpose To assess the impact of lifelong genetic inhibition of ACLY associated with lower LDL-C levels on T2DM and glycaemic control (alongside effects on coronary heart disease [CHD]), investigate whether the association varies by background T2DM risk, and explore potential mediating factors. Methods We undertook a 2-sample Mendelian randomisation study of ∼0.3M unrelated White British individuals in UK Biobank, including 26,495 cases of T2DM and 37,272 cases of CHD. Causal effects on these outcomes were estimated using the inverse variance weighted approach, based on 9 independent LDL-C associated ACLY (±500 kb) genetic variants weighted by their LDL-C effects from previously published studies. Results for T2DM and CHD were then meta-analysed with comparable analysis of data from DIAGRAM (n=26,676 T2DM cases) and CARDIoGRAMplusC4D (n=60,801 CHD cases) respectively. Mediation analyses were conducted to explore the relevance of adiposity traits, such as body mass index, on the observed associations. Subgroup analyses considering the effects in individuals at varying risk of T2DM (based on polygenic risk), as well as the effects of ACLY on glycaemic control in those with established diabetes were undertaken. Results Genetic variation in ACLY was associated with a 16% lower risk of T2DM (odds ratio [OR]: 0.84; 95% CI; 0.76–0.92) per 10mg/dL lower ACLY-predicted LDL-C level. The magnitude and direction of this effect was comparable to that observed with CHD (OR: 0.84; 95% CI; 0.77–0.91). There were no differences in the estimated effects of ACLY on T2DM across tertiles of T2DM polygenic risk (p-trend=0.63). Furthermore, the association between ACLY and T2DM was not materially mediated through effects on body mass index. Analyses exploring additional potential mediating factors, the relevance of inflammation, and the effects of ACLY on glycaemic control in individuals with diabetes are also reported. Conclusion This Mendelian randomisation study shows that genetic variants that mimic inhibition of ACLY and are associated with lower LDL-C levels lower the risks of developing T2DM as well as of CHD events. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

The change in the prevalence of obesity and new-onset diabetes in Chinese peritoneal dialysis patients over 25 years.

ABSTRACTBackgroundThe global prevalence of both obesity and end-stage kidney diseases (ESKDs) has increased in recent decades. Given the complicated interaction between obesity and ESKD, we examined the change in the prevalence of obesity in incident Chinese peritoneal dialysis (PD) patients over the past 25 years.MethodsWe reviewed the anthropometric measures of incident PD patients in a single Hong Kong center from 1995 to 2019. The results are reported in five 5-year periods. Patients with and without diabetes were analyzed separately, and the incidence of new-onset diabetes after PD was explored.ResultsWe reviewed 1681 patients. Their mean age was 58.4 ± 12.5 years; 931 patients (55.4%) had pre-existing diabetes. From 1995–99 to 2015–19, the prevalence of obesity or overweight at the initiation of PD increased progressively for every 5-year period (from 21.9% to 26.2, 37.9, 42.7 and 47.3%, P < 0.001 for linearity). The increase in the prevalence of obesity or overweight was more pronounced in diabetic patients (from 33.7% to 59.6%) than non-diabetic ones (from 13.2% to 32.3%). Among nondiabetics patients, the incidence of new-onset diabetes after started on PD showed an insignificant rising trend during that period (from 18.0, 19.7, 17.8 and 22.4% to 23.3%, P = 0.106). The incidence of new-onset impaired fasting glucose or diabetes was significantly higher in obese or overweight patients than the others (56.9% versus 51.4%, P < 0.001).ConclusionsThe prevalence of obesity has increased substantially in both diabetic and nondiabetic new PD patients in Hong Kong over the past 25 years. The incidence of new-onset diabetes was significantly higher in new PD patients with pre-existing obesity or overweight than those without obesity. The prognostic implication and impacts on the healthcare system deserve further studies.

Individual and combined contributions of age-specific and sex-specific pulse pressure and brachial-ankle pulse wave velocity to the risk of new-onset diabetes mellitus

IntroductionWe aimed to investigate the individual and combined effects of age-specific and sex-specific pulse pressure (PP) and brachial-ankle pulse wave velocity (baPWV) on the incidence of new-onset diabetes mellitus.Research design...

A Time-Based Meta-Analysis on the Incidence of New Onset Diabetes after Liver Transplantation.

NODAT (new-onset diabetes after transplantation) is an important complication after liver transplant, however, there is variation in the reported incidence of NODAT. Therefore, a meta-analysis was performed to estimate the incidence of NODAT in liver transplant. Electronic databases were searched for articles regarding NODAT incidence after liver transplantation. Incidence of NODAT were analyzed at six different timepoints. Summary statistics were calculated using a generalized linear mixed model in random effects. 28 articles were included and out of a pooled population of 71,257 patients, overall incidence of NODAT was found to be 15.51%, 16.09%, 18.30%, 20.86%, 18.08%, 25.05% for three-months, six-months, one-year, three-year, five-year, and ten-year timepoints respectively. After a sensitivity analysis which only included articles with clear definitions of NODAT, the incidence of NODAT was found to be higher at three-year (21.79%), five-year (25.82%), and ten-year (44.95%) timepoints. Subgroup analysis according to ethnicity found no significant differences for all timepoints. However, studies with predominantly Asian participants generally had a higher incidence of NODAT. In conclusion, this meta-analysis provides a pooled estimate of the incidence of NODAT following liver transplantation. Further studies are required to provide a more comprehensive understanding on how ethnicity can affect the incidence of NODAT.