Pretransplantation C-Peptide Level Predicts Early Posttransplantation Diabetes Mellitus and Has an Impact on Survival after Allogeneic Stem Cell Transplantation

Posttransplantation diabetes mellitus (PTDM) is a frequent complication after allogeneic stem cell transplantation (allo-SCT), important for its negative impact on cardiovascular health. Risk factors for PTDM are not well defined. We conducted a prospective study to investigate the risk factors and incidence for PTDM in the first 100 days after allo-SCT. A total of 84 patients completed the study, 60% of whom developed PTDM. In a multivariate logistic regression model, pretransplantation c-peptide level (>3.6 ng/mL; odds ratio [OR], 5.9; 95% confidence interval [CI], 1.77-20.22; P = .004), unrelated donor allo-SCT (OR, 4.3; 95% CI, 1.34-14.2; P = .014), and peak steroid dose >1 mg/kg/day (OR, 5.09; 95% CI, 1.19-23.2; P = .035) were identified as independent predictors of PTDM. In addition, overall survival (OS) was inferior in patients with PTDM compared with those without PTDM (mean survival, 2.26 years vs 2.7 years; P = .021). Pretransplantation c-peptide level greater than the cohort median (>3.6 ng/mL) also was associated with inferior OS (mean, 1.7 years vs 2.9 years; P = .012). In a multivariate Cox proportional hazards model, high-risk disease (hazard ratio [HR], 2.34; 95% CI, 1.09-5.28; P = .029) and pretransplantation c-peptide level >3.6 ng/mL (HR, 1.05; 95% CI, 1.01-1.09; P = .013) were independent predictors of OS when adjusted for systemic steroids and regimen intensity. We suspect that diabetes mellitus in the immediate posttransplantation period may be mediated via an inflammatory pathway that contributes to insulin resistance in the host adipose tissue. Our study is the first to report the risk factors of early PTDM in patients undergoing allo-SCT and identifies pretransplantation c-peptide as an independent predictor of diabetes and survival

Serum urate and cardiovascular events in the DCCT/EDIC study

AbstractIn type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997–2000, and (a) concurrent MetS and (b) incident ‘any CVD’ and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p &lt; 0.0001], and was associated with MetS features in both (men: p = 0.0016; women: p &lt; 0.0001). During follow-up, 110 participants (11%) experienced “any CVD”, and 53 (5%) a MACE. Analyzed by quartiles, SU was not associated with subsequent CVD or MACE. In women, SU as a continuous variable was associated with MACE (unadjusted HR: 1.52; 95% CI 1.07–2.16; p = 0.0211) even after adjustment for age and HbA1c (HR: 1.47; 95% CI 1.01–2.14; p = 0.0467). Predominantly normal range serum urate concentrations in T1D were higher in men than women and were associated with features of the MetS. In some analyses of women only, SU was associated with subsequent MACE. Routine measurement of SU to assess cardiovascular risk in T1D is not merited.Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.</jats:p

Impact of Excessive Weight Gain on Cardiovascular Outcomes in Type 1 Diabetes: Results From the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events. </jats:sec