Cardiovascular events associate with diabetes status rather than with early basal insulin treatment for the prevention of post-transplantation diabetes mellitus.
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SUBMITTER: Topitz D
PROVIDER: S-EPMC7056949 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Cardiovascular events associate with diabetes status rather than with early basal insulin treatment for the prevention of post-transplantation diabetes mellitus.
Topitz David D Schwaiger Elisabeth E Frommlet Florian F Werzowa Johannes J Hecking Manfred M
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20200301 3
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Project description:BackgroundPost-transplantation diabetes mellitus (PTDM) might be preventable.MethodsThis open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant.ResultsIn the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24.ConclusionsAt low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study.Clinical Trial registration number: NCT03507829.
| S-EPMC8455276 | biostudies-literature
Project description:Diabetes mellitus (DM) after transplantation remains a crucial clinical problem in kidney transplantation. To obtain insights into molecular mechanisms underlying the development of post-transplant diabetes mellitus (PTDM) and its early impact on glomerular structures, here we comparatively analyze the proteome of histologically normal appearing glomeruli from patients with PTDM from normoglycemic (NG) transplant recipients, and from recipients with pre-existing type 2 DM (PTDM)
2023-10-24 | PXD042188 | Pride
Project description:No effective interventions to reduce risk for new-onset diabetes after transplantation (NODAT), a condition associated with postoperative hyperglycemia and reduced patient and graft survival, have been established. In this 1-year, proof-of-concept clinical trial, we randomly assigned 50 renal transplant recipients to immediate-postoperative isophane insulin for evening blood glucose ≥140 mg/dl (treatment group) or short-acting insulin and/or oral antidiabetic agents for blood glucose ≥180-250 mg/dl (standard-of-care control group). We included only patients without a history of diabetes who received tacrolimus. By the third postoperative evening, all patients in the treatment group had blood glucose ≥140 mg/dl and were subsequently treated with basal insulin; during the first 3 weeks after transplantation, the mean ± SD daily insulin dosage was 17±11 IU/d. Among controls, 23 (92%) of 25 had blood glucose ≥200 mg/dl and 18 (72%) of 25 received standard-of-care antihyperglycemic treatment. Asymptomatic hypoglycemia occurred five times in the treatment group and once in the control group. Throughout follow-up, the treatment group had 73% lower odds of NODAT (odds ratio, 0.27) than the control group, and hemoglobin A1c was on average 0.38% lower in the treatment group than the control group. Twelve months after transplantation, all patients in the treatment group were insulin-independent, whereas 7 (28%) of 25 controls required antidiabetic agents. The groups did not differ for insulin sensitivity, but the treatment group showed better β-cell function throughout the 1-year follow-up. In conclusion, this study suggests regimens that include basal insulin significantly reduce the odds for NODAT after renal transplantation, presumably via insulin-mediated protection of β cells.
| S-EPMC3312499 | biostudies-literature
Project description:BackgroundDespite the progressive aging of the population in industrialized countries, few studies have focused on the natural history of cardiovascular disease in the very old, and recommendations on prevention of cardiovascular disease in this population are lacking. We aimed to analyze all-cause mortality and cardiovascular events according to prevalent type 2 diabetes mellitus and established cardiovascular disease in nonagenarians from a Mediterranean population.MethodsWe analyzed the primary health records of all nonagenarians living in the Community of Madrid (N = 59,423) and collected data for 4 groups: Group 1, individuals without T2DM or established CVD (T2DM-, CVD-); Group 2, individuals without T2DM but with established CVD (T2DM-, CVD +); Group 3, individuals with T2DM but without established CVD (T2DM + , CVD-); and Group 4, individuals with both T2DM and established CVD (T2DM + , CVD +), taking into account the influence of sex on the outcomes. Follow-up was 2.5 years. The primary outcomes were cumulative incidence and incidence density rates for all-cause mortality, non-fatal myocardial infarction, non-fatal stroke (the first composite primary outcome [CPO1]), combined with heart failure (CPO2). We evaluated the adjusted effect of each group on all-cause mortality (Cox regression).ResultsMean age was 93.3 ± 2.8 years (74.2% women). Hypertension, dyslipidemia, heart failure, albuminuria, and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were significantly more prevalent in G4 than in the other groups (all p values < 0.001). We observed significantly higher cumulative incidence rates for all-cause mortality, CPO1, and CPO2 in participants belonging to G4 (all p values ≤ 0.001). People in G2 presented higher rates of all-cause mortality, heart failure, CPO1, and CPO2 than people in G3 (all p values ≤ 0.001). In the fully adjusted model, G4 independently predicted all-cause mortality (HR = 1.48 [95% CI, 1.40 to 1.57] vs reference G1 [p < 0.01]). In addition, significant HRs were recorded for cardiovascular disease alone (G2) and type 2 diabetes mellitus alone (G3) (1.13 and 1.14, respectively; both p values < 0.01).ConclusionsIn Spanish nonagenarians, established cardiovascular disease and type 2 diabetes mellitus conferred a modest risk of all-cause mortality. However, the simultaneous presence of both conditions conferred the highest risk of all-cause mortality.
| S-EPMC8931574 | biostudies-literature
Project description:ObjectiveOur objectives were to describe the basal insulin treatment regimens most widely used in a real-world setting in France and to estimate the associated treatment costs in people with type 2 diabetes mellitus (T2DM).MethodsA cross-sectional observational study was conducted (November 2017-February 2018) among adult patients with T2DM requiring basal insulin therapy for their own use in a representative sample of pharmacies. Costs were compared between patients treated with three recently marketed insulins (glargine 300 U/ml [Gla-300], biosimilar glargine 100 U/ml [Gla-100] and a fixed-ratio combination of insulin degludec and liraglutide) and those treated with three established basal or intermediate insulins: branded glargine 100 U/ml, insulin detemir and neutral protamine Hagedorn insulin [NPH]).ResultsOverall, 1933 patients were analysed. Gla-300 accounted for 59.9% of novel basal insulin prescriptions, and branded Gla-100 accounted for 67.9% of established insulin prescriptions. Recent insulins were more frequently associated with glucagon-like peptide-1 (GLP-1) analogues. Results confirmed a lower rate of severe hypoglycaemia with Gla-300 than with Gla-100. On average, weekly total costs of treatment with all basal insulins were not significantly different, except with detemir, where they were higher.ConclusionNew basal insulins are expected to be integrated into clinical practice. This analysis shows that their use does not impact upon the management cost of insulin therapy in people with T2DM.
| S-EPMC8160062 | biostudies-literature
Project description:ObjectiveTo review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM).Materials and methodsData sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies.ResultsIn pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time-action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6-12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%-17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300.ConclusionClinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities.
| S-EPMC5501629 | biostudies-literature
Project description:BackgroundMigraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes.Research design and methodsA total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20 years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status.ResultsMigraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age.ConclusionsIn this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.
| S-EPMC9737987 | biostudies-literature
Project description:BackgroundThe effect of gestational diabetes mellitus (GDM) on cardiovascular diseases (CVD) is not assessed within the first 10 years postpartum, regardless of subsequent diabetes. The aim of this study was to determine the risk of CVD events related to GDM within 7 years of postpartum.MethodsThis nationwide population-based study of deliveries in 2007 and 2008 with a follow-up of 7 years was based on data from the French medico-administrative database. Two groups were formed: women with a history of GDM and women without GDM or previous diabetes. CVD included angina pectoris, myocardial infarction, stroke, heart bypass surgery, coronary angioplasty, carotid endarterectomy and fibrinolysis. Hypertensive disease was assessed separately. Determinants studied included age, obesity, subsequent diabetes mellitus and hypertensive diseases during pregnancy. Adjusted odds ratios for outcomes were calculated using multiple logistic regressions.ResultsThe hospital database recorded 1,518,990 deliveries in 2007 and 2008. Among these, 62,958 women had a history of GDM. After adjusting for age, DM, obesity and hypertensive disorders in pregnancy, GDM was significantly associated with a higher risk of CVD (adjusted Odds Ratio aOR = 1.25 [1.09-1.43]). Considering each variable in a separate model, GDM was associated with angina pectoris (aOR = 1.68 [1.29-2.20]), myocardial infarction (aOR = 1.92 [1.36-2.71]) and hypertension (aOR = 2.72 [2.58-2.88]) but not with stroke.ConclusionsA history of GDM was identified as a risk factor of CVD, especially coronary vascular diseases, within the 7 years postpartum. A lifestyle changes from postpartum onwards can be recommended and supported.
| S-EPMC4728938 | biostudies-literature
Project description:BackgroundTo identify possible differences in cardiovascular (CV) risk among different insulin therapies, we performed pre-specified meta-analyses across the clinical program for basal insulin peglispro (BIL), in patients randomized to treatment with BIL or comparator insulin [glargine (IG) or NPH].MethodsOne phase 2 (12-week) and 6 phase 3 (26 to 78-week) randomized studies of BIL compared to IG or NPH, in patients with type 1 or type 2 diabetes, were included. The participants were diverse with respect to demographics, baseline glycemic control, and concomitant disease or medications, but treatment groups were comparable in each study. For any potential CV or neurovascular event, relevant medical information was provided to a blinded external clinical events committee (C5Research, Cleveland Clinic, Cleveland, OH, USA) for adjudication. Cox regression analysis was used to compare treatment groups. The primary endpoint was a composite of adjudicated MACE+ [CV death, myocardial infarction (MI), stroke, or hospitalization for unstable angina].ResultsThe pooled population included 5862 patients in the safety evaluation, with randomization to BIL:IG:NPH of 3578:2072:212. Mean age was 54.1 years, 27 % had type 1 diabetes, 56 % were male, and 88 % were white. Baseline demographic and clinical characteristics, including use of statins or other lipid-lowering drugs, were comparable between BIL and comparators. A total of 83 patients experienced at least 1 MACE+ and 70 patients experienced at least 1 MACE (CV death, MI, or stroke). Overall, there were no treatment-associated differences in time to MACE+ [hazard ratio (HR) for BIL versus comparator insulin (95 % CI): 0.82 (0.53-1.27)] or MACE [0.83 (0.51-1.33)]. In 4297 patients with type 2 diabetes, there were 71 MACE+ events [HR: 1.02 (95 % CI: 0.63-1.65), p = 0.94]. In 1565 patients with type 1 diabetes, there were only 12 MACE+ [0.24 (0.07-0.85), p = 0.027]. There were no differences in all-cause death between BIL and comparators. Sub-group analyses did not identify any sub-population with increased risk with BIL versus comparator insulins.ConclusionsTreatment with BIL versus comparator insulin in patients with type 1 diabetes or type 2 diabetes was not associated with increased risk for major CV events in the studies analyzed.
| S-EPMC4869328 | biostudies-literature
Project description:Aims/introductionInsulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). The present study investigated the pharmacodynamic properties of IDegAsp in Japanese patients with type 1 diabetes mellitus.Materials and methodsIn this randomized, double-blind, two-period, cross-over trial, 21 Japanese patients with type 1 diabetes mellitus received single doses of 0.5 U/kg IDegAsp and biphasic insulin aspart 30 in a randomized sequence (13-21 days washout between treatments). The pharmacodynamic response was evaluated in a 26-h euglycemic glucose clamp (target 5.5 mmol/L). Single-dose IDegAsp glucose infusion rate (GIR) profiles were extrapolated to steady state using modeling.ResultsThe IDegAsp single-dose GIR profile showed a clear distinction between the effects of the bolus (IAsp) and basal (IDeg) components in IDegAsp. When simulated to steady state, the GIR profile of IDegAsp was shifted upwards compared with the single-dose profile, and showed a rapid onset of action and a distinct peak from the IAsp component followed by a separate and sustained basal action from the long-acting IDeg component. For biphasic insulin aspart 30, the initial shape of the GIR profile was similar to IDegAsp, but GIR continuously decreased from maximum and reached zero 18-20 h post-dosing. The characteristics of the GIR profile for IDegAsp were retained when simulated to steady state in a twice-daily dosing regimen.DiscussionIn Japanese patients with type 1 diabetes mellitus, the pharmacodynamic profile of IDegAsp is characterized by distinct prandial and basal effects from the IAsp and IDeg components, consistent with what has been reported previously in Caucasian patients with type 1 diabetes mellitus.
| S-EPMC4931208 | biostudies-literature