Utility of the NIH Toolbox Cognition Battery in middle to older aged adults with longstanding type 1 diabetes: The DCCT/EDIC study.

Objective: Adults with type 1 diabetes (T1D) face an increased risk for cognitive decline and dementia. Diabetes-related and vascular risk factors have been linked to cognitive decline using detailed neuropsychological testing; however, it is unclear if cognitive screening batteries can detect cognitive changes associated with aging in T1D. Method: 1,049 participants with T1D (median age 59 years; range 43-74) from the Diabetes Control and Complications Trial (DCCT), and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, completed the NIH Toolbox Cognition Battery (NIHTB-C) and Montreal Cognitive Assessment (MoCA). Neuropsychological assessments, depression, glycated hemoglobin levels (HbA1c), severe hypoglycemia, T1D complications, and vascular risk factors were assessed repeatedly over 32 years to determine associations with current NIHTB-C performance. Available cognitive data was clinically adjudicated to determine cognitive impairment status. Results: NIHTB-C scores had moderate associations (r = 0.36-0.53) with concurrently administered neuropsychological tests. In multivariate models, prior severe hypoglycemic episodes, depression symptoms, nephropathy, lower BMI, and higher HbA1c and LDL cholesterol were associated with poorer NIHTB-C Fluid Cognition Composite scores. The NIHTB-C adequately detected adjudicated cognitive impairment (Area Under the Curve = 0.86; optimal cut score ≤90). The MoCA performed similarly (Area Under the Curve = 0.83; optimal cut score ≤25). Conclusions: The NIHTB-C is sensitive to the cognitive effects of diabetes-related and vascular risk factors, correlated with neuropsychological testing, and accurately detects adjudicated cognitive impairment. These data support its use as a screening test in middle to older aged adults with T1D to determine if referral for detailed neuropsychological assessment is needed.

Cognitive performance declines in older adults with type 1 diabetes: results from 32 years of follow-up in the DCCT and EDIC Study.

BACKGROUND: With improved treatment, individuals with type 1 diabetes are living longer but there is limited information on the effects of type 1 diabetes on cognitive ability as they become older adults. We followed up individuals with type 1 diabetes to identify independent risk factors for cognitive decline as people age. METHODS: 1051 participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. Participants completed cognitive assessments at baseline (median age 27 years) and 2, 5, 18, and 32 years later (median age 59). HbA1c levels, frequency of severe hypoglycaemia, non-glycemic risk factors such as elevated blood pressure, and microvascular and macrovascular complications were assessed repeatedly. We examined the effects of these on measures of memory and psychomotor and mental efficiency. These studies are registered with clinicaltrials.gov, NCT00360815 (DCCT) and NCT00360893 (EDIC). FINDINGS: Over 32 years of follow-up, we found substantive declines in memory and psychomotor and mental efficiency. Between 18 and 32 years of follow-up, the decline in psychomotor and mental efficiency was five times larger than the change from baseline to year 18. Independent of the other risk factors and comorbidities, exposure to higher HbA1c levels, more episodes of severe hypoglycaemia, and elevated systolic blood pressure were associated with greater decrements in psychomotor and mental efficiency that was most notable by year 32 (p<0·0001). The combined effect of the presence of these three risk factors is the equivalent to an additional 9·4 years of age. INTERPRETATION: Cognitive function declines with ageing in type 1 diabetes. The association of glycaemia and blood pressure levels with cognitive decline suggests that better management might preserve cognitive function. FUNDING: United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease.

Residual ß cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia.

BACKGROUNDWe investigated residual ß cell function in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study participants with an average 35-year duration of type 1 diabetes mellitus (T1DM).METHODSSerum C-peptide was measured during a 4-hour mixed-meal tolerance test. Associations with metabolic outcomes and complications were explored among nonresponders (all C-peptide values after meal <0.003 nmol/L) and 3 categories of responders, classified by peak C-peptide concentration (nmol/L) as high (>0.2), intermediate (>0.03 to ≤0.2), and low (≥ 0.003 to ≤0.03).RESULTSOf the 944 participants, 117 (12.4%) were classified as responders. Residual C-peptide concentrations were associated with higher DCCT baseline concentrations of stimulated C-peptide (P value for trend = 0.0001). Residual C-peptide secretion was not associated with current or mean HbA1c, HLA high-risk haplotypes for T1DM, or the current presence of T1DM autoantibodies. The proportion of subjects with a history of severe hypoglycemia was lower with high (27%) and intermediate (48%) residual C-peptide concentrations than with low (74%) and no (70%) residual C-peptide concentrations (P value for trend = 0.0001). Responders and nonresponders demonstrated similar rates of advanced microvascular complications.CONCLUSIONß Cell function can persist in long-duration T1DM. With a peak C-peptide concentration of >0.03 nmol/L, we observed clinically meaningful reductions in the prevalence of severe hypoglycemia.TRIAL REGISTRATIONClinicalTrials.gov NCT00360815 and NCT00360893.FUNDINGDivision of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (DP3-DK104438, U01 DK094176, and U01 DK094157).

Evolution of the study coordinator role: the 28-year experience in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC).

BACKGROUND: The role of the study coordinator (SC) in multicenter studies of long duration has received limited attention. PURPOSE: To describe the evolution of the SC's role during the 28-year Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. METHODS: The evolution of the SC's position from the traditional role of protocol implementation to that of research collaborator and co-investigator, based on personal experience and observation, is described in detail. Findings from a survey regarding professional demographics and job satisfaction, completed by all 28 SCs in 2010, provided additional information. We used dimensions of the SC's role specific to DCCT/EDIC to construct a classification schema of functions and responsibilities that describe the SC's role. RESULTS: Among the 28 SCs, 24 were nurses, 12 held bachelor's degrees, 11 had a master's degree, 19 were certified diabetes educators (CDEs), 12 had worked with DCCT/EDIC for more than 20 years, and 5 had been with the study since its inception (>26 years). Responses confirmed a high degree of functional consistency across sites with data acquisition, performing study procedures, recruitment and consent for additional ancillary studies, regulatory management, scheduling, clinical consultation, and ongoing contact with study participants frequently reported. Study-wide leadership activities, a category not generally included in the usual SC role, were reported by approximately 30% of the SCs. The level of professional satisfaction was high with two-thirds being very satisfied, one-third moderately to quite satisfied, and none dissatisfied. LIMITATIONS: The limitations include a relatively small sample size, self-reported data, and a single long-term multicenter trial and observational follow-up study on which we based our findings and conclusions. CONCLUSIONS: By optimizing their organizational and scientific contributions to the overall research endeavor, SCs in DCCT/EDIC have made major contributions to the unprecedented success of the study and report high job satisfaction. The efforts of the SCs have been integral to the remarkably high participant retention and data completion rates. The DCCT/EDIC experience may serve as a model for the role of the SC in future diabetes and other multicenter clinical trials.