Persistently high glucose levels in young children with type 1 diabetes.

OBJECTIVES: The aim of the study was to characterize glucose levels and variability in young children with type 1 diabetes (T1D). METHODS: A total of 144 children of 4-10 yr old diagnosed with T1D prior to age 8 were recruited at five DirecNet centers. Participants used a continuous glucose monitor (CGM) every 3 months during an 18-month study. Among the 144 participants, 135 (mean age 7.0 yr, 47% female) had a minimum of 48 h of CGM data at more than five of seven visits and were included in analyses. CGM metrics for different times of day were analyzed. RESULTS: Mean hemoglobin A1c (HbA1c) at the beginning and end of the study was 7.9% (63 mmol/mol). Fifty percent of participants had glucose levels >180 mg/dL (10.0 mmol/L) for >12 h/d and >250 mg/dL (13.9 mmol/L) for >6 h/d. Median time <70 mg/dL (3.9 mmol/L) was 66 min/d and <60 mg/dL (3.3 mmol/L) was 39 min/d. Mean amplitude of glycemic excursions (MAGE) was lowest overnight (00:00-06:00 hours). The percent of CGM values 71-180 mg/dL (3.9-10.0 mmol/L) and the overall mean glucose correlated with HbA1c at all visits. There were no differences in CGM mean glucose or coefficient of variation between the age groups of 4 and <6, 6 and <8, and 8 and <10. CONCLUSIONS: Suboptimal glycemic control is common in young children with T1D as reflected by glucose levels in the hyperglycemic range for much of the day. New approaches to reduce postprandial glycemic excursions and increase time in the normal range for glucose in young children with T1D are critically needed. Glycemic targets in this age range should be revisited.

Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program.

AIMS: To determine if the presence of diabetes autoantibodies predicts the development of diabetes among participants in the Diabetes Prevention Program. METHODS: A total of 3050 participants were randomized into three treatment groups: intensive lifestyle intervention, metformin and placebo. Glutamic acid decarboxylase (GAD) 65 autoantibodies and insulinoma-associated-2 autoantibodies were measured at baseline and participants were followed for 3.2 years for the development of diabetes. RESULTS: The overall prevalence of GAD autoantibodies was 4.0%, and it varied across racial/ethnic groups from 2.4% among Asian-Pacific Islanders to 7.0% among non-Hispanic black people. There were no significant differences in BMI or metabolic variables (glucose, insulin, HbA(1c), estimated insulin resistance, corrected insulin response) stratified by baseline GAD antibody status. GAD autoantibody positivity did not predict diabetes overall (adjusted hazard ratio 0.98; 95% CI 0.56-1.73) or in any of the three treatment groups. Insulinoma-associated-2 autoantibodies were positive in only one participant (0.033%). CONCLUSIONS: These data suggest that 'diabetes autoimmunity', as reflected by GAD antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes is not a clinically relevant risk factor for progression to diabetes.

Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT).

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type 1 diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. STUDY DESIGN: Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until EDIC year 4 were assessed. RESULTS: In contrast to the 7.4 years of the DCCT, during which mean hemoglobin A(1c) levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76%; P <.0001), the subsequent first 4 years of EDIC had mean hemoglobin A(1c) levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P <.001) and 78% (P <.007), respectively, in the former intensive therapy group compared with the former conventional group. CONCLUSIONS: These findings provide further support for the DCCT recommendation that most adolescents with type 1 diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications.

Influence of family structure on health among youths with diabetes.

Type 1 diabetes mellitus is a chronic metabolic disorder and is one of the most common chronic diseases in childhood. The study discussed in this article examined the extent to which family structure is significantly associated with health in youths with Type 1 diabetes. A convenience sample of 155 children with diabetes and their mothers completed face-to-face interviews; multiple regression analyses were conducted. Findings demonstrated that family structure remains a significant predictor of youths' health when statistically controlling for race, child's age, family socioeconomic status, and adherence. Social workers in outpatient medical settings are in a unique position to develop family-oriented strategies targeting this neglected area of primary care.

Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects.

OBJECTIVE: This study reports 6- and 12-month follow-up for the families of adolescents with diabetes who participated in a trial of Behavioral-Family Systems Therapy (BFST). RESEARCH DESIGN AND METHODS: A total of 119 families of adolescents with type 1 diabetes were randomized to 3 months of treatment with either BFST, an education and support (ES) group, or current therapy (CT). Family relationships, adjustment to diabetes, treatment adherence, and diabetic control were assessed at baseline, after 3 months of treatment, and 6 and 12 months later. This report focuses on the latter two evaluations. RESULTS: Compared with CT and ES, BFST yielded lasting improvements in parent-adolescent relationships and diabetes-specific conflict. Delayed effects on treatment adherence emerged at 6- and 12-month follow-ups. There were no immediate or delayed effects on adolescents' adjustment to diabetes or diabetic control. CONCLUSIONS: BFST yielded lasting improvement in parent-adolescent relationships and delayed improvement in treatment adherence, but it had no effect on adjustment to diabetes or diabetic control. A variety of adaptations to BFST could enhance its impact on diabetes outcomes.

Comparison of single-mother and two-parent families on metabolic control of children with diabetes.

OBJECTIVE: To understand the impact of family structure on the metabolic control of children with diabetes, we posed two research questions: 1) what are the differences in sociodemographic, family, and community factors between single-mother and two-parent families of diabetic children? and 2) to what extent do these psychosocial factors predict metabolic control among diabetic children from single-mother and two-parent families? RESEARCH DESIGN AND METHODS: This cross-sectional study included 155 diabetic children and their mothers or other female caregivers. The children were recruited if they had been diagnosed with diabetes for at least 1 year, had no other comorbid chronic illnesses, and were younger than 18 years of age. Interviews and self-report questionnaires were used to assess individual, family, and community variables. RESULTS: The findings indicate that diabetic children from single-mother families have poorer metabolic control than do children from two-parent families. Regression models of children's metabolic control from single-mother families indicate that age and missed clinic appointments predicted HbA1c levels; however, among two-parent families, children's ethnicity and adherence to their medication regimen significantly predicted metabolic control. CONCLUSIONS: This study suggests that children from single-mother families are at risk of poorer metabolic control and that these families have more challenges to face when raising a child with a chronic illness. Implications point to a need for developing strategies sensitive to the challenges of single mothers.

First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes.

OBJECTIVE: To determine the relationship between first-phase (1 minute + 3 minutes) insulin production during the intravenous glucose tolerance test (IV-GTT) and risk factors for developing type 1 diabetes. STUDY DESIGN: Relatives of persons with type 1 diabetes (n = 59,600) were screened for islet cell antibodies (ICAs). Subjects who had positive screening results underwent IV-GTT (> or =2 times), repeat ICA screening, insulin autoantibody (IAA) screening twice, and an oral glucose tolerance test. RESULTS: Of the 59,600 subjects in the study, 2199 (3.69%) had positive findings on initial ICA test. IV-GTTs were performed in 1622 subjects, with children <8 years having the lowest first-phase insulin release (FPIR) and subjects 8 to 20 years of age having the highest FPIR. The FPIR was lower for subjects with a confirmed positive ICA test result or a positive IAA test result, subjects with higher titers of ICA or IAA, and subjects who had an abnormal (impaired or diabetic) oral glucose tolerance test result. CONCLUSION: FPIR in the IV-GTT correlates strongly with risk factors for development of type 1 diabetes.

Reproductive health beliefs and behaviors in teens with diabetes: application of the Expanded Health Belief Model.

OBJECTIVE: To identify significant correlates among constructs of the Expanded Health Belief Model (EHBM) with reproductive health behaviors [preventing an unplanned pregnancy and seeking preconception counseling (PC)] and metabolic control in teenaged women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eighty adolescent women with type 1 diabetes participated in a multisite, exploratory, case-control study. Subjects (only cases, and not controls, were used for the analyses of this paper) had a single, 1-h structured phone interview with a trained, same gender research assistant. Variables of interest were awareness, knowledge, health beliefs, attitudes, intention and behaviors regarding diabetes and reproductive health. RESULTS: Several major constructs of the EHBM were significantly correlated in the expected direction with reproductive health behaviors and metabolic control of adolescents with type 1 diabetes. In particular, perceived susceptibility, barriers, threat, intention, and self-efficacy with birth control (BC) use, and motivational cue (initial awareness of PC) with seeking PC. CONCLUSIONS: Being told by a health care professional to seek out PC is a motivational cue that triggers action. The timing of this message would seem to play an important role in preventing an unplanned pregnancy. Therefore, interventions focusing on changing health beliefs and on increasing awareness may be effective in promoting positive reproductive health behaviors in adolescent females with diabetes.

Validation of a structured interview for the assessment of diabetes self-management.

OBJECTIVE: The authors developed and validated a semi-structured interview; the Diabetes Self-Management Profile (DSMP), to measure self-management of type 1 diabetes. The DSMP includes the following regimen components: exercise, management of hypoglycemia, diet, blood glucose testing, and insulin administration and dose adjustment. RESEARCH DESIGN AND METHODS: Families of youths with type 1 diabetes (n = 105) who were entering a controlled trial of intensive therapy (IT) versus usual care (UC) were administered the DSMP Analyses assessed the reliability and validity of the DSMP, including its associations with HbA1c and quality of life. RESULTS: The DSMP total score has adequate internal consistency (Cronbach's alpha 0.76), 3-month test-retest reliability (Pearson correlation, r = 0.67), inter-interviewer agreement (r = 0.94), and parent-adolescent agreement (r = 0.61). DSMP total scores (r = -0.28) and 3 subscales correlated significantly with HbA1c (diet [r = -0.27], blood glucose testing [r = -0.37], and insulin administration and dose adjustment [r = -0.25 ]). Adolescents' reports of self-management did not differ from parental reports. Higher DSMP scores were associated with more favorable quality of life for mothers and youths. CONCLUSIONS: The DSMP is a convenient measure that yields a reliable and valid assessment of diabetes self-management. Compared with extant similar measures, the DSMP is more strongly correlated with HbA1c.

Randomized, controlled trial of behavior therapy for families of adolescents with insulin-dependent diabetes mellitus.

OBJECTIVE: To describe the short-term results of a controlled trial of Behavioral Family Systems Therapy (BFST) for families of adolescents with diabetes. METHODS: We randomized 119 families of adolescents with diabetes to 3 months' treatment with either BFST, an education and support Group (ES), or current therapy (CT). Family relationships, psychological adjustment to diabetes, treatment adherence and diabetic control were assessed at baseline, after 3 months of treatment (reported here), and 6 and 12 months later. RESULTS: Compared with CT and ES, BFST yielded more improvement in parent-adolescent relations and reduced diabetes-specific conflict. Effects on psychological adjustment to diabetes and diabetic control were less robust and depended on the adolescent's age and gender. There were no effects on treatment adherence. CONCLUSIONS: BFST yielded some improvement in parent-adolescent relationships; its effects on diabetes outcomes depended on the adolescent's age and gender. Factors mediating the effectiveness of BFST must be clarified.

Defective insulin receptors in Rabson-Mendenhall syndrome cause complete peripheral insulin resistance but minimal hepatic insulin response remains.

In Rabson-Mendenhall syndrome, severe insulin resistance is caused by defective insulin receptors. The patient studied lacks insulin receptor binding due to a truncation mutation of one allele and a point mutation of the other allele of the insulin receptor alpha-subunit. He developed pulmonary hypertension and cor pulmonale, and was considered for organ transplantation. A trial of prednisone 1.2 mg/kg/d was initiated to determine if he could tolerate immunosuppressive therapy without deterioration of his pre-existing, difficult to control diabetes mellitus. Insulin responsiveness was measured prior to and after 4 d of glucocorticoid administration ('Before GC' and 'After GC') using the hyperinsulinemic glucose clamp and stable isotope tracer dilution techniques. After a 12-h fast and 24 h of intravenous insulin, a primed continuous infusion of 6,6-(2)H(2)-glucose was administered during a 2-h tracer equilibration period followed by a 2-h insulin-deficient period, and a 2-h hyperinsulinemic glucose clamp period during which insulin was infused at 7 u/kg/h. Blood glucose concentrations during the basal periods, while no insulin was infused, were 245+/-7 and 138+/-8 mg/dL in the studies Before GC and After GC, respectively. During both hyperinsulinemic glucose clamp periods, the blood glucose was 171+/-1 and 167+/-5 mg/dL, respectively. Hepatic glucose production (HGP) was higher during the basal period Before GC than during the same period After GC (7.86+/-0.23 vs. 5.31+/-0.19 mg/kg/min). HGP rate was suppressed by insulin to 1.48+/-0.45 mg/kg/min Before GC, but was not suppressed After GC (4.19+/-0.81 mg/kg/min). The hyperinsulinemic glucose clamp did not increase the glucose utilization rate nor the glucose clearance rate over basal in either Before GC or After GC, indicating complete peripheral insulin resistance. In summary, the liver showed some response to insulin in the absence of insulin receptors but the peripheral tissues had no response to insulin. Glucocorticoids worsened insulin resistance in the liver in this patient.

Diabetic ketoacidosis in children.

Diabetic ketoacidosis is a serious condition that warrants immediate and aggressive intervention. Even with appropriate intervention, DKA is associated with significant morbidity and possible mortality in diabetic patients in the pediatric age group. With appreciation of its severity, proper understanding of the pathophysiology, and careful attention to the details of management and close monitoring, most cases will have a satisfactory outcome. Because treatment is costly and because the risk for morbidity remains even under the best of circumstances, prevention of DKA must be a major goal in the treatment of type 1 diabetes mellitus. Involvement and close follow-up by a multidisciplinary team of health care professionals with experience in dealing with diabetes in children and adolescents is the best way to avoid DKA.

Performance evaluation of the MiniMed continuous glucose monitoring system during patient home use.

BACKGROUND: The recent availability of a continuous glucose monitor offers the opportunity to match the demands of intensive diabetes management with a period of equally intensive blood glucose monitoring. The present study evaluates the performance of the MiniMed continuous glucose monitoring system (CGMS) in patients with diabetes during home use. METHODS: Performance data and demographic information were obtained from 135 patients who were (mean +/- SD) 40.5+/-14.5 years old, had an average duration of diabetes of 18.0+/-9.8 years, 50% were female, 90% were Caucasian, and 87% of whom had been diagnosed with type 1 diabetes. Patients were selected by their physician, trained on the use of the CGMS and wore the device at home for 3 days or more. The performance of the CGMS was evaluated against blood glucose measurements obtained using each patient's home blood glucose meter. Evaluation statistics included correlation, linear regression, mean difference and percent absolute difference scores, and Clarke error grid analysis. RESULTS: The CGMS values were compared to 2477 SMBG tests (r = 0.91, slope = 0.93, intercept = 14.5 mg/dL, mean absolute difference = 18.0%+/-19.8%). Clarke error grid analysis showed 96.2% of the data pairs falling within the clinically acceptable regions (zones A and B). CONCLUSIONS: These results demonstrate the agreement of the CGMS to blood glucose meter values, under conditions of home use, in patients selected by their physicians as candidates for continuous monitoring. The detailed glucose information provided by the CGMS should make successful management of diabetes more easily achieved.

Conventional versus intensive diabetes therapy in children with type 1 diabetes: effects on memory and motor speed.

OBJECTIVE: Severe hypoglycemia may impair medial temporal-mediated cognitive skills, such as the ability to recall past events explicitly (delayed declarative memory). The objective of this study was to determine whether delayed declarative memory deficits are present in a group of diabetic children with an increased risk of severe hypoglycemia. RESEARCH DESIGN AND METHODS: Nondiabetic children (n = 16) and children with type 1 diabetes who had been randomly assigned to either intensive (IT) (n = 13) or conventional (CT) (n = 12) diabetes therapy at the time of diagnosis participated in the study. All episodes of severe hypoglycemia were prospectively ascertained. All children were tested on memory tasks that have been closely linked to medial temporal functioning and on reaction time measures. RESULTS: Our results demonstrated that the IT group had a threefold higher rate of severe hypoglycemia, performed less accurately on a spatial declarative memory task, and performed more slowly, but not less accurately, on a pattern recognition task than did the CT group or control subjects. In addition, both groups of type 1 diabetic children were significantly impaired on a motor speed task compared with their nondiabetic peers. CONCLUSIONS: These results indicate a selective relative memory impairment associated with IT that is consistent with the effects of severe hypoglycemia and medial temporal damage or dysfunction. If larger prospective studies determine that severe hypoglycemia is the mediating factor for this memory impairment, extreme caution in imposing overly strict standards for glucose control in young patients with type 1 diabetes would be indicated because of the increased risk of hypoglycemia associated with IT regimens.

Disparity in glycemic control and adherence between African-American and Caucasian youths with diabetes. Family and community contexts.

OBJECTIVE: To describe sociodemographic, family, and community factors that contribute to the glycemic control of African-American and Caucasian youths with diabetes, we investigated two questions: 1) Is there a disparity in glycemic control between African-American and Caucasian youths with diabetes, and if so, what sociodemographic, family, and community factors explain the disparity? and 2) Is there a difference in the adherence to treatment between African-American and Caucasian youths with diabetes, and if so, what sociodemographic, family, and community factors explain the difference? RESEARCH DESIGN AND METHODS: This cross-sectional study included 146 youths with diabetes (95 Caucasians and 51 African-Americans) and their mothers. The youths were invited to participate if they had been diagnosed with diabetes at least 1 year before the study, did not have another chronic illness, and were < 18 years of age. RESULTS: The findings indicate that African-American youths with diabetes are in significantly poorer metabolic control than their Caucasian counterparts (1.5% difference in HbA1c levels). Single-parent household status and lower levels of adherence partially account for the poorer glycemic control. Examination of the adherence subscales indicates that African-Americans report significantly lower adherence to diet and glucose testing than Caucasian youths. CONCLUSIONS: This study suggests that African-American youths with diabetes may be at greater risk for poor glycemic control due to the higher prevalence of single parenting and lower levels of adherence found in this population.