OBJECTIVEThe development of periarticular thickening of skin on the hands and limited joint mobility (cheiroarthropathy) is associated with diabetes and can lead to significant disability. The objective of this study was to describe the prevalence of cheiroarthropathy in the well-characterized Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort and examine associated risk factors, microvascular complications, and the effect of former DCCT therapy (intensive [INT] vs. conventional [CONV]) on its development.RESEARCH DESIGN AND METHODSThis cross-sectional analysis was performed in 1,217 participants (95% of the active cohort) in EDIC years 18/19 after an average of 24 years of follow-up. Cheiroarthropathy—defined as the presence of any one of the following: adhesive capsulitis, carpal tunnel syndrome, flexor tenosynovitis, Dupuytren's contracture, or a positive prayer sign—was assessed using a targeted medical history and standardized physical examination. A self-administered questionnaire (Disabilities of the Arm, Shoulder and Hand [DASH]) assessed functional disability.RESULTSCheiroarthropathy was present in 66% of subjects (64% of the INT group and 68% of the CONV group; P = 0.1640) and was associated with age, sex, diabetes duration, skin intrinsic fluorescence, HbA1c, neuropathy, and retinopathy (P < 0.005 for each). DASH functional disability scores were worse among subjects with cheiroarthropathy (P < 0.0001).CONCLUSIONSCheiroarthropathy is common in people with type 1 diabetes of long duration (∼30 years) and is related to longer duration and higher levels of glycemia. Clinicians should include cheiroarthropathy in their routine history and physical examination of patients with type 1 diabetes because it causes clinically significant functional disability.

Background and Aims After the Diabetes Control and Complications Trial (DCCT), the Epidemiology of Diabetes Interventions and Complications (EDIC) study continued to demonstrate persistent benefit of prior intensive therapy on neuropathy, retinopathy, and nephropathy in type 1 diabetes mellitus (DM)., The relationship between control of glycemia and gastric emptying (GE) is unclear. Methods We assessed GE with a 13C-spirulina breath test and symptoms in 78 participants with type 1 diabetes at year 20 of EDIC. The relationship between delayed GE and HbA1c, complications of DM, and gastrointestinal symptoms were evaluated. Results GE was normal (37 participants, 50%), delayed (35 participants, 47%), or rapid (2 participants, 3%). The latest mean HbA1c was 7.7%. In univariate analyses, delayed GE was associated with greater DCCT baseline HbA1c and duration of DM prior to DCCT (P ≤ 0.04), greater mean HbA1c over an average of 27 years of follow up (during DCCT-EDIC, P = 0.01), lower R-R variability during deep breathing (P=0.03) and severe nephropathy (P=0.05) and a greater composite upper gastrointestinal symptom score (P<0.05). In multivariate models, retinopathy was the only complication of DM associated with delayed GE. Separately, DCCT baseline HbA1c (OR 1.6, 95% CI 1.1–2.3) and duration of DM (OR 1.2, 95%CI 1.01–1.3) prior to DCCT entry and mean HbA1c during DCCT-EDIC (OR 2.2, 95%CI 1.04–4.5) were independently associated with delayed GE. Conclusions In the DCCT/EDIC study, delayed GE was remarkably common and associated with gastrointestinal symptoms and with measures of early and long-term hyperglycemia. ClinicalTrials.gov numbers NCT00360815 and NCT00360893.

No abstract

Immunopurification of doping control samples is a mandatory necessity in erythropoietin (EPO) analysis during a confirmation procedure; moreover, it has become common practice to also immunopurify samples for the initial testing procedure. Typically used materials (e.g., Stemcell purification plate and MAIIA purification kit) rely on anti‐EPO antibodies for purification. Also, the detection of EPO after electrophoretic separation and western blotting is based on a monoclonal anti‐EPO antibody, clone AE7A5, directed against a 26 amino acid sequence of the N‐terminal region of human EPO. While the electrophoretic separation and blot transfer efficiency can be monitored with reference standards and quality control samples, it is presently not possible to monitor the functionality of the entire sample preparation procedure. The reliance on antibodies for both purification and detection has complicated the implementation of an internal standard (ISTD). In this study, customized EPO‐polyethylene glycol (PEG) conjugates were synthesized as potential ISTDs and assessed as to their compatibility with existing sample preparation procedures for urine and blood sample analysis using the most common immunopurification techniques. Moreover, probing for the impact of the ISTD on sodium N‐lauroylsarcosinate (“sarcosyl”) polyacrylamide gel electrophoresis (SAR‐PAGE)‐based EPO analysis concerning potential interference with target analytes was conducted. The presented data demonstrate that a 12‐kDa PEG residue attached to human EPO represents a particularly useful construct to serve as ISTD for erythropoietin‐receptor agonist (ERA) analysis. The conjugate is applicable to both urine and blood testing using the commonly employed purification techniques, supporting and improving result interpretations especially concerning specimens where the natural abundance of human EPO is low.

No abstract