Quality Control Measures over 30 Years in a Multicenter Clinical Study: Results from the Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study.

Implementation of multicenter and/or longitudinal studies requires an effective quality assurance program to identify trends, data inconsistencies and process variability of results over time. The Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study represent over 30 years of data collection among a cohort of participants across 27 clinical centers. The quality assurance plan is overseen by the Data Coordinating Center and is implemented across the clinical centers and central reading units. Each central unit incorporates specific DCCT/EDIC quality monitoring activities into their routine quality assurance plan. The results are reviewed by a data quality assurance committee whose function is to identify variances in quality that may impact study results from the central units as well as within and across clinical centers, and to recommend implementation of corrective procedures when necessary. Over the 30-year period, changes to the methods, equipment, or clinical procedures have been required to keep procedures current and ensure continued collection of scientifically valid and clinically relevant results. Pilot testing to compare historic processes with contemporary alternatives is performed and comparability is validated prior to incorporation of new procedures into the study. Details of the quality assurance plan across and within the clinical and central reading units are described, and quality outcomes for core measures analyzed by the central reading units (e.g. biochemical samples, fundus photographs, ECGs) are presented

Anti-Müllerian hormone and its relationships with subclinical cardiovascular disease and renal disease in a longitudinal cohort study of women with type 1 diabetes

Abstract Background Reproductive age may be a risk factor for vascular disease. Anti-Müllerian hormone (AMH) is produced by viable ovarian follicles and reflects reproductive age. We examined whether AMH concentrations were associated with markers of subclinical cardiovascular disease (CVD) and kidney disease among women with type 1 diabetes. Methods We performed a cross-sectional analysis of the Epidemiology of Diabetes Interventions and Complications Study. Participants included women with type 1 diabetes and ≥1 AMH measurement (n = 390). In multivariable regression models which adjusted for repeated measures, we examined the associations between AMH with CVD risk factors, estimated glomerular filtration rate, and albumin excretion ratio. We also examined whether initial AMH concentrations were associated with the presence of any coronary artery calcification (CAC) or carotid intima media thickness (cIMT). Results After adjustment for age, AMH was not associated with waist circumference, blood pressure, lipid profiles, or renal function. Higher initial AMH concentrations had borderline but non-significant associations with the presence of CAC after adjustment for age (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.00, 1.16) which were minimally altered by addition of other CVD risk factors, although women in the 3rd quartile of AMH had lower odds of CAC than women in the lowest quartile (OR 0.40, 95% CI 0.17, 0.94). After adjustment for age, higher AMH was associated with statistically significant but only slightly higher cIMT (0.005 mm, p = 0.0087) which was minimally altered by addition of other CVD risk factors. Conclusions Among midlife women with type 1 diabetes, AMH has slight but significant associations with subclinical measures of atherosclerosis. Future studies should examine whether these associations are clinically significant. Trial registration NCT00360815 and NCT00360893 Study Start Date April 1994.https://deepblue.lib.umich.edu/bitstream/2027.42/138004/1/40695_2017_Article_23.pd

Assessment of Circulating Insulin Using Mass Spectrometry During Insulin Glargine Treatment in Type 2 Diabetes: Implications for Estimating Insulin Sensitivity and β-cell Function

AIMS: Given the potential effect of cross-reactivity of insulin glargine U-100 and its metabolites in the insulin immunoassay, we determined the impact on insulin sensitivity and β-cell measures in GRADE participants with type 2 diabetes receiving the analog. MATERIALS AND METHODS: Using liquid chromatography mass spectrometry (LC-MS), we measured concentrations of endogenous insulin, glargine, and its two metabolites (M1 and M2) in fasting and OGTT-stimulated plasma from 19 participants and fasting specimens from another 97 participants 12 months after randomization to receive the insulin glargine. The last dose of glargine was administered before 10:00 pm the night before. Insulin was also measured on these specimens using an immunoassay. We used fasting specimens to calculate insulin sensitivity (HOMA2-S%; QUIKI index, PREDIM index) and β-cell function (HOMA2-B%). Using specimens following glucose ingestion, we calculated insulin sensitivity (Matsuda ISI[comp] index) and β-cell response (insulinogenic index [IGI], and total incremental insulin response [iAUC] / iAUC glucose). RESULTS: In plasma, glargine was metabolized to form the M1 and M2 metabolites that were quantifiable by LC-MS; however, the analog and its metabolites cross-reacted \u3c100% in the insulin immunoassay. This incomplete cross-reactivity resulted in a systematic bias of fasting based measures. In contrast, as M1 and M2 did not change following glucose ingestion, a bias was not observed for IGI and iAUC insulin. CONCLUSIONS: Despite glargine metabolites being detected in the insulin immunoassay, dynamic insulin responses can be used to assess β-cell responsiveness. However, given the cross-reactivity of the glargine metabolites in the insulin immunoassay, fasting-based measures of insulin sensitivity and β-cell function are biased. This article is protected by copyright. All rights reserved

Quality Control Measures over 30 Years in a Multicenter Clinical Study: Results from the Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study.

Implementation of multicenter and/or longitudinal studies requires an effective quality assurance program to identify trends, data inconsistencies and process variability of results over time. The Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study represent over 30 years of data collection among a cohort of participants across 27 clinical centers. The quality assurance plan is overseen by the Data Coordinating Center and is implemented across the clinical centers and central reading units. Each central unit incorporates specific DCCT/EDIC quality monitoring activities into their routine quality assurance plan. The results are reviewed by a data quality assurance committee whose function is to identify variances in quality that may impact study results from the central units as well as within and across clinical centers, and to recommend implementation of corrective procedures when necessary. Over the 30-year period, changes to the methods, equipment, or clinical procedures have been required to keep procedures current and ensure continued collection of scientifically valid and clinically relevant results. Pilot testing to compare historic processes with contemporary alternatives is performed and comparability is validated prior to incorporation of new procedures into the study. Details of the quality assurance plan across and within the clinical and central reading units are described, and quality outcomes for core measures analyzed by the central reading units (e.g. biochemical samples, fundus photographs, ECGs) are presented

Certification and Standardized Processes in the DCCT/EDIC Study.

<p>Certification and Standardized Processes in the DCCT/EDIC Study.</p

Methods in the DCCT/EDIC Study.

<p>Methods in the DCCT/EDIC Study.</p

Quality Control Monitoring in the DCCT/EDIC Study.

<p>^a Data analyzed at the central reading units (e.g. CBL, CORU, CERC);</p><p>^b EDIC-specific quality assessments</p><p>^c Height: two measurements within 1 cm; if not, measure twice more</p><p>^d Weight: two measurements within 0.2 kg; if not, measure twice more</p><p>Quality Control Monitoring in the DCCT/EDIC Study.</p

Data Flow in the DCCT/EDIC Study.

<p>The CERC was located at the University of Minnesota, Minneapolis, MN between 1983–2004, and at Wake Forest University, Winston Salem, NC from 2005-present.</p

Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in GRADE: A Randomized Clinical Trial

Objective: We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. Research Design and Methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study of adults with T2DM of < 10 years duration, HbA1c of 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, glucagon-like peptide-1 receptor agonist liraglutide, or dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean[SD] age, 58.0[10.2] years; 32% female; 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every six months. Analyses examined differences at one year and over the 3-year follow-up. Results: Across treatments, diabetes distress (-0.24, p<0.0001) and depressive symptoms (-0.67, p<0.0001) decreased over one year. Diabetes distress was lower at one year for glargine compared to the other groups combined (-0.10, p=0.002). Diabetes distress was also lower for liraglutide compared to glimepiride or sitagliptin (-0.10, p=0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms. Conclusions: Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress; glargine lowered diabetes distress modestly at one year rather than increasing it. Liraglutide also reduced diabetes distress at one year. Results can inform treatment decisions for adults with early T2DM.</p