W. Dahms

Impact of diabetes and its treatment on cognitive function among adolescents who participated in the Diabetes Control and Complications Trial.

OBJECTIVE—The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13–19 years at entry in the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS—This was a longitudinal study involving 249 patients with type 1 diabetes who were between 13 and 19 years old when they were randomly assigned in the DCCT. Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study, ∼18 years later, were compared with baseline performance. We assessed the effects of the original DCCT treatment group assignment, mean A1C values, and frequency of severe hypoglycemic events on eight domains of cognition. RESULTS—There were a total of 294 reported episodes of coma or seizure. Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain. As in a previous analysis of the entire study cohort, higher A1C values were associated with declines in the psychomotor and mental efficiency domain (P < 0.01); however, the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis. CONCLUSIONS—Despite relatively high rates of severe hypoglycemia, cognitive function did not decline over an extended period of time in the youngest cohort of patients with type 1 diabetes.

Psychological Adjustment of Children Evaluated for Short Stature: A Preliminary Report

Since synthetic growth hormone became available in the mid-1980s, there has been debate about its use for non-growth-hormone-deficient short children. Justification for this use of growth hormone often is based on a presumed association of short stature with significant psychosocial maladjustment. However, systematic evaluation of psychosocial functioning in short children has been limited, and our understanding of this area is scant. In this study, we have used a combination of interview and self-report measures to examine self-esteem, personality characteristics, affective functioning, coping style, and stature-related stresses in 41 children (5 to 16 years) referred to a pediatric endocrinology service because of short stature. Parent-report and child measures of self-esteem and psychological functioning indicated no evidence of maladjustment in comparison with norms. Furthermore, within the subject sample, the degree of short stature was not related to poor psychological functioning. We found limited evidence linking increased age with increased distress, suggesting that short stature may pose greater difficulties for children as they enter adolescence. Taken as a whole, however, the results do not support the contention that short stature is generally associated with psychosocial maladjustment in children referred for evaluation of their short stature.

Urea synthesis, nitrogen balance, and glucose turnover in growth-hormone-deficient children before and after growth hormone administration

We measured the effect of human growth hormone (hGH) on urea synthesis, nitrogen retention, and glucose turnover in ten euthyroid growth hormone (GH)-deficient children before and after seven daily injections of 0.1 U/kg hGH. The patients were fed a weight-maintaining diet with 9% of energy derived from protein. Following an overnight fast, urea synthesis and glucose turnover were determined using a primed constant infusion of [15N2] urea and a constant infusion of [6,6-2H2] glucose. Human growth hormone produced a decrease in urea nitrogen synthesis from 6.8 +/- 0.5 to 4.2 +/- 0.4 mg/kg.h; (P less than .01), while plasma urea nitrogen decreased from 13.1 +/- 0.8 to 7.4 +/- 0.8 mg/dL; (P less than .01). The decrease in urea synthesis was reflected in a corresponding decrease in urine urea nitrogen excretion (-2.8 mg/kg.h). There was a significant correlation between plasma urea nitrogen and urea synthesis rate both before (r = 0.85, P less than .01) and after (r = 0.79, P less than .01) hGH treatment. In response to hGH, there was a rise in both plasma glucose (81.4 +/- 2.2 v 89.8 +/- 2.3 mg/dL; P less than .05) and insulin (5.7 +/- 0.8 v 13.1 +/- 3.0 microU/mL; P less than .05), however, glucose turnover remained unchanged (4.7 +/- 0.3 v 4.6 +/- 0.6 mg/kg.min). After seven days of growth hormone treatment, the patients were placed on 0.1 U/kg of hGH three times a week for 6 months, and their growth rate was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of urinary albumin-creatinine ratio and albumin excretion rate in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study

BACKGROUND AND OBJECTIVES The objective of this study was to compare random urine albumin-creatinine ratio (ACR) with timed urine albumin excretion rate (AER) in patients with type 1 diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 1186 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study provided spot urine specimens concurrent with 4-hour timed urine collections. ACR and AER were compared using Bland-Altman plots, cross-classification of albuminuria status and its change over time, and within-person variability. RESULTS Despite moderate correlation (r=0.62), ACR levels (mg/g) were lower than AER levels (mg/24 hr). This difference was greatest for men. Gender-specific estimated AER (eAER) values were empirically derived from ACR. Comparing the eAER with measured AER, agreement of prevalent microalbuminuria and macroalbuminuria classification was fair to moderate, and classification of change in albuminuria status over time was different. Intraclass correlations were 0.697 for ACR and 0.803 for AER. Effects of DCCT intensive versus conventional diabetes therapy on urine albumin excretion or classification of albuminuria were similar using the eAER versus measured AER, as were the effects of the previous glycosylated hemoglobin. CONCLUSIONS Systematic differences exist between urine ACR and AER, related to gender and other determinants of muscle mass. Use of ACR (or eAER) versus AER yields differences in classification of prevalent albuminuria states and changes in albuminuria states over time. These findings support the use of consistent ascertainment methods over time and further efforts to standardize and optimally interpret measurement of urine albumin excretion.

The associations of apolipoprotein E and angiotensin-converting enzyme polymorphisms and cognitive function in Type 1 diabetes based on an 18-year follow-up of the DCCT cohort.

Diabet. Med. 27, 15–22 (2010)

The control of food intake: effects of dieting and intestinal bypass.

Individuals who undergo intestinal bypass surgery decrease their food intake after the operation. Bypass patients also have a reduced preference for sweet tasting foods and greater sensitivity to caloric preloads before meals. The significant metabolic changes seen after intestinal bypass but not after dieting may account for the reduced food intake, or other mechanisms may be responsible.

Glycemic Control and Hypoglycemia: Is the Loser the Winner?: Response to Perlmuter et al.

The editorial by Perlmuter et al. (1) in the October 2008 issue of Diabetes Care commented on the long-term effects of severe hypoglycemia and raised concerns about our study (2), which reported that within the cohort of subjects who entered the Diabetes Control and Complications Trial (DCCT) during adolescence, there was no relationship between subsequent episodes of severe hypoglycemia and cognitive performance measured ∼20 years after study entry. Below, we outline their five major concerns and provide supporting information. One concern of Perlmuter et al. was the exclusion of potential participants from the DCCT if they had a history of severe hypoglycemia, thus limiting generalizability. However, a history of severe hypoglycemia was not an absolute exclusion criterion for participation in the DCCT. Indeed, 24% of the 175 participants had previously experienced 1–5 episodes of severe hypoglycemia with loss of consciousness before entry …