Physical activity and overweight in children and adolescents using intensified insulin treatment

Aim:  To describe physical activity and inactivity and parameters associated with overweight in a population-based study of children and adolescents on intensive insulin treatment.
Methods:  Physical activity and inactivity were evaluated in 723 type 1 diabetic subjects, 240 children aged 6–10 yr and 483 adolescents aged 11–19 yr, using a questionnaire that can estimate total amount of time spent on inactivity and light, moderate and vigorous activity.
Results:  Overall, 54% of the participants do not fulfil the international recommendations of 60 min of moderate-to-vigorous activity per day. Girls are less active than boys in childhood (70 vs. 88 min/d, p = 0.01) and in adolescence (47 vs. 57 min/d, p = 0.02). Furthermore, this study shows that those who are more active are also those who seldom skip meals (p < 0.001). Forty-three percent of the participants watch TV for more than 2 h a day, and TV viewing was found to be related to overweight in children and adolescents with type 1 diabetes [OR: 2.5 (1.40–4.54), p = 0.002]. No statistical differences in physical activity were noted between the different intensified insulin regimens. Patients wearing insulin pumps were not less active.
Conclusion:  To increase physical activity to recommended level and limit TV viewing should be an important issue in education of all children and adolescents with type 1 diabetes, independent of insulin regimen.     

Effect of Carelink, an internet-based insulin pump monitoring system, on glycemic control in rural and urban children with type 1 diabetes mellitus

Objective:  To determine whether use of the internet-based insulin pump monitoring system, Carelink, improved glycemic control in rural and urban children treated with insulin pump therapy.
Research design:  We reviewed records of 94 children treated with insulin pump therapy between the years 2004 and 2007 and compared glycemic control, diabetes self-care measures, frequency of clinic visits, and geographic location associated with Carelink use.
Results:  Carelink users showed improvement in hemoglobin A1c (HbA1c) levels [8.0 ± 0.1 (SE) vs. 7.7 ± 0.1 (SE), p = 0.002]. Carelink users uploaded pump and glucometer data 2.2 ± 1.8 (SD) times per month over 0.8 ± 0.4 (SD) yr. Patients who had no access to carelink software and were followed in a conventional manner showed no change in HbA1c levels [8.0 ± 0.2 (SE) vs. 8.1 ± 0.2 (SE), p = 0.17] during the study period. Carelink non-users, defined as patients who had Carelink access but did not use it, had a higher HbA1c level at the start of the study and did not change over the study period [8.9 ± 0.2 (SE) vs. 9.0 ± 0.3 (SE), p = 0.82]. Rural Carelink users showed improvement in HbA1c levels following Carelink use [7.9 ± 0.2 (SE) vs. 7.4 ± 0.2 (SE), p = 0.001], yet had significantly fewer clinic visits per year compared with urban patients [2.8 ± 0.2 (SE) vs. 3.5 ± 0.1 (SE), p = 0.001].
Conclusion:  Use of the Carelink system was associated with improved glycemic control in children with type 1 diabetes on insulin pump therapy.     

Young children (<5 yr) and adolescents (>12 yr) with type 1 diabetes mellitus have low rate of partial remission: diabetic ketoacidosis is an important risk factor

Objective:  To determine whether there are different rates of partial remission in preschool, school-age children, and adolescents with type 1 diabetes mellitus (T1DM) and to identify clinical characteristics that are associated with increased rate of partial remission.
Design/methods:  A total of 152 consecutive patients with newly diagnosed T1DM in 2004 were studied. Clinical characteristics at diagnosis, hemoglobin A1C (HbA1C), and total daily insulin dose (TDD) at 3-month interval follow-up for 1 yr were analyzed in each age-group (group 1, aged <5 yr; group 2, aged 5–12 yr; and group 3, aged >12 yr). Partial remission was defined as TDD <0.5 units/kg/d with HbA1C <8% assessed at 6 months after diagnosis.
Results:  Young children (group 1, 26.8%) and adolescents (group 3, 29%) had low rates of partial remission compared with school-age children (group 2, 56%, p = 0.002). There were no differences in the rates of diabetic ketoacidosis (DKA), autoantibody frequency, and HbA1C at diagnosis between age-groups. DKA at diagnosis was associated with less likelihood of having partial remission (p < 0.001). There were no associations between gender, autoantibodies, and HbA1C at diagnosis and the rate of partial remission.
Conclusions:  Young children and adolescent children with T1DM had a low rate of partial remission. Metabolic control was poorest in young children, whereas higher dose insulin in adolescents because of insulin resistance contributes to less likelihood of having partial remission. DKA at diagnosis was associated with low rate of partial remission. It is possible that the low frequency of honeymoon phase in young children reflects more aggressive beta-cell destruction in young children.     

Glycemic control in adolescents with type 1 diabetes mellitus improves lipid serum levels and oxidative stress

Introduction:  Atherosclerosis begins in childhood, and diabetes is a risk factor for coronary heart disease. Dyslipidemia is prevalent in children with type 1 diabetes mellitus (T1DM), with an association between elevated hemoglobin A1c (HbA1c), serum lipid levels, and oxidative stress. Our aim was to examine the effect of metabolic control on serum lipid levels and oxidative stress in adolescents with T1DM.
Methods:  Twenty-six adolescents (13 boys and 13 girls), aged 15.65 ± 1.5 yr, with disease duration of 5.9 ± 2.8 yr and average HbA1c 10.8 ± 1.9% were assigned to intensive insulin therapy for 3 months. Comparisons for HbA1c, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, total triglycerides (TG), total cholesterol (TC), apolipoprotein AI, apolipoprotein AII, apolipoprotein B (ApoB), and thiobarbituric acid reactive substances (TBARS) were done between patients whose HbA1c improved by 0.5% or more (GR1) and the rest of the cohort (patients whose HbA1c improved by <0.5%, did not change, or increased) (GR2).
Results:  ApoB (p = 0.047) and TBARS (p = 0.01) were significantly lower at the end of the study in GR1. In GR2, TC (p = 0.01) and LDL (p = 0.03) were significantly higher at study end. Overall, significant beneficial changes in TC (p = 0.006), TG (p = 0.04), LDL (p = 0.02), ApoB (p = 0.015), and oxidative stress (p = 0.001) were found in GR1 compared with GR2.
Conclusions:  We provide direct evidence for the beneficial effect of tight metabolic control on serum lipids and oxidative stress in adolescents with T1DM, indicating that tight metabolic control may reduce cardiovascular risk in these patients.     

Basal insulin and total daily insulin dose in children with type 1 diabetes using insulin pumps

Objective:  To assess the contribution of basal insulin to the total daily dose (CBITDD) and to identify the determinant factors in children with type 1 diabetes mellitus.
Study design:  Cross-sectional study in which the basal insulin requirement was established based on a memory read-out of insulin delivery from pumps. Factors such as glycated haemoglobin A1c (HbA1c), fasting C-peptide, standard deviation score of body mass index (sdsBMI) and demographic data were determined during routine hospital visits. Study group included a total of 90 well-controlled diabetic children with the mean HbA1c 6.6 ± 0.7 (5.2–7.9), age 10.4 ± 4.4 yr (1.1–17.9 yr), diabetes duration 3.0 ± 2.6 yr (0.3–10.9 yr) and sdsBMI 0.08 (−2.27 to 1.79), excluding patients with ketoacidosis or infectious diseases.
Results:  Correlations between CBITDD and age (r = 0.39 and p < 0.005) and diabetes duration (r = 0.61 and p < 0.0001) and an inverse correlation with C-peptide (r = −0.41 and p = 0.0001) were found. C-peptide-positive patients had a significantly lower percentage of basal insulin compared with C-peptide-negative patients (20.6 ± 11 vs. 31.6 ± 11.0%, respectively; p = 0.0004); yet, no significant difference in total insulin daily dose (0.65 ± 0.3 vs. 0.78 ± 0.2 U/kg/d, respectively) was observed.
Conclusions:  The percentage of basal insulin in diabetic children is below 50% and in well-controlled diabetic children is related to the fasting C-peptide level, age of patient and diabetes duration but not to HbA1c and sdsBMI.     

Insulin-related metabolism following hematopoietic stem cell transplantation in childhood

Objectives:  To assess insulin-related metabolism following hematopoietic stem cell transplantation (HSCT) in childhood.
Study design:  Thirty-four patients who underwent HSCT were compared with 21 patients with similar diseases who were not transplanted. Median follow-up was 3.6 yr after HSCT. Anthropometric parameters, fasting plasma glucose and insulin levels, hemoglobin A_1c (HbA_1c) and lipid profile were measured and compared.
Results:  HbA_1c was significantly higher (p = 0.001) in the study group. Two (5.8%) patients in the study group developed type 2 diabetes mellitus. Among thalassemic patients, significantly lower insulin resistance indices (p = 0.05) and fasting plasma insulin levels (p = 0.033) were found in the study group compared with the control group.
Conclusions:  Attentive follow-up of insulin-related metabolism following HSCT in children is needed. The significance of the higher HbA1c values in the study group remains to be evaluated in a larger cohort of patients.     

Use of a subcutaneous injection port to improve glycemic control in children with type 1 diabetes

Objective:  To determine if use of an injection port, the Insuflon™, would help to improve glycemic control in youth with type 1 diabetes (TID) who were in suboptimal glycemic control (hemoglobin A1c, HbA1c >8.0%).
Study design:  A three-arm randomized protocol was used to study the effects of the Insuflon (a subcutaneous injection port) vs. an alarmable blood glucose meter vs. a control group on glycemic control in 66 youth with T1D. All participants used insulin glargine™ as their basal insulin and the NovoPen^® Junior with insulin aspart™ as their rapid-acting insulin. Participants were randomized into control, alarm, or Insuflon groups. HbA1c levels were the primary outcome with values at baseline, 3, and 6 months.
Results:  Initial parameters were similar in the three groups. HbA1c values were significantly lower for youth who used the Insuflon than for the control group at 3 and 6 months (p = 0.025). The HbA1c values (in %) for youth using the Insuflon decreased significantly from 9.4 at screening to 8.7 at 3 months (p < 0.001) and 8.5 at 6 months (p < 0.001). There were no significant reductions (p ≥ 0.05) in the HbA1c values within the other two groups.
Conclusion:  The Insuflon injection port helps some youth with T1D to improve glycemic control.     

Intramyocellular lipid, adiposity, and muscle oxygen supply in prepubertal type 1 diabetes

Abstract:  Background: In the non-diabetic population, intramyocellular lipid (IMCL) accumulation is associated with obesity and poor muscle oxygen supply. IMCL levels are increased in type 1 diabetes, but their significance is less clear.
Methods:  We studied a group of 16 prepubertal boys (age 6.4–9.9 yr) with type 1 diabetes and a range of glycemic control [hemoglobin A1c (HbA1c) 6.4–10.2%]. Children's adiposity was assessed by anthropometry, muscle oxygen supply by near-infrared spectroscopy (NIRS), abdominal and IMCL content by magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS).
Results:  IMCL content did not associate with muscle reoxygenation rate, abdominal adiposity, duration of diabetes, or recent glycemic control. Muscle reoxygenation rate correlated with percentage body fatness (r² = 0.46, p = 0.004), visceral (r² = 0.45, p = 0.007) and abdominal subcutaneous fat volume (r² = 0.63, p = 0.0004), and dietary fat intake (r² = 0.27, p = 0.03) but not with the duration of diabetes nor HbA1c. HbA1c was significantly related to dietary fat intake only (r² = 0.28, p = 0.03).
Conclusion:  While causality cannot be inferred, interventions aimed at improving muscle oxygen supply, or preventing its deterioration, might reduce the development of adiposity in children with type 1 diabetes.     

Improved glycemic control and lower frequency of severe hypoglycemia with insulin detemir; long-term experience in 105 children and adolescents with type 1 diabetes

Objective:  To assess the effect of the insulin analog detemir on glycemic control and severe hypoglycemia in children and adolescents with type 1 diabetes.
Research design and methods:  A retrospective chart analysis was performed in 105 patients with type 1 diabetes after switching to insulin detemir between 2004 and 2007. In children below 12 yr of age (n = 53), evening neutral protomin hagedorn (NPH) insulin was replaced by insulin detemir if therapeutic goals were not reached and blood glucose levels were unpredictable or hardly controllable. In adolescents above 12 yr of age (n = 52), insulin detemir was started when changing to intensified insulin therapy.
Results:  In children below 12 yr of age, hemoglobin A1c (HbA1c) at start was 8.3 ± 0.8% and after 12 months of treatment with insulin detemir significantly lowered (7.6 ± 0.6%, p < 0.001). In the age-group above 12 yr of age at the start of the study, the improvement of HbA1c after 12 months of treatment was less pronounced (8.0 ± 1.2 vs. 7.6 ± 1.0%) but still significant (p < 0.01). The risk for severe hypoglycemia was significantly decreased compared with patients attending the outpatient clinic between 1995 and 2003 (4.8/100 patient years vs. 7.6/100 patient years, p = 0.003). From the beginning to the end of the follow-up period, body mass index dropped significantly in children below 12 yr of age but no effect was observed in adolescents.
Conclusions:  Use of insulin detemir allows a safe nocturnal glycemic control in children and adolescents with type 1 diabetes and is associated with significantly improved HbA1c levels and fewer severe hypoglycemic events. This makes insulin detemir a most valuable new tool for the treatment of children and adolescents with type 1 diabetes.     

A randomized prospective study of insulin pump vs. insulin injection therapy in very young children with type 1 diabetes: 12-month glycemic, BMI, and neurocognitive outcomes

Objective:  To compare glycemic control, body mass index (BMI), neurocognitive function, and parenting stress for preschool-aged diabetic children randomized to treatment either with continuous subcutaneous insulin infusion (CSII) or with intensive insulin injection therapy (IIT).
Methods:  Children <5 yr of age diagnosed with type 1 diabetes mellitus for at least 12 months were randomized to either CSII (n = 21) or IIT (n = 21) for 6 months. After 6 months, the IIT group began CSII therapy and the CSII group continued on pumps. Hemoglobin A1c (HbA1c) and BMI percent were collected at baseline, 3, 6, 9, and 12 months. Neurocognitive assessments (Developmental Test of Visual–Motor Integration and Stanford–Binet Intelligence Scale: Fourth Edition) were administered to children, and parenting and child behavior assessments (Parenting Stress Index and Child Behavior Checklist) were completed by parents and at baseline, 6, and 12 months.
Results:  Thirty-five children completed the study. Mean HbA1c decreased significantly over the study period (8.9% ± 0.6 vs. 8.5% ± 0.7, p = 0.006). Initiation of CSII resulted in an HbA1c decrease of 0.4% after 3 months (p = 0.002); however, in the CSII first group, the HbA1c at 12 months was not significantly different from study start (8.8% ± 0.6 vs. 8.5% ± 0.6; p = 0.4). There were no significant changes in BMI%, neurocognitive, parenting, and child behavior measures between groups.
Conclusion:  Initiation of CSII vs. continuing IIT does not significantly influence HbA1c, BMI, neurocognitive, or parenting stress parameters in a research study setting.     

Carbohydrate intake, serum lipids and apolipoprotein E phenotype show association in children

Aim:  To study the association between carbohydrate intake and serum lipids in children, and influence of apolipoprotein E phenotype (apoE) on the association.
Subjects/methods:  A total of 644 children from a prospective, randomized atherosclerosis prevention trial (STRIP) participated in this longitudinal study at age 5 (n = 644), 7 (n = 585) and 9 (n = 550) years. ApoE phenotype, fasting triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations and 4-day food records were analysed.
Results:  An increase in the total carbohydrate intake by 1 E% (percentage of total daily energy intake) associated with a decrease in HDL cholesterol by 0.006 mmol/L (p < 0.001) when adjusted for saturated, monounsaturated and polyunsaturated fatty acid, age, gender, body mass index and STRIP study group. The inverse association between total carbohydrate intake and HDL cholesterol was evident in children with apoE3 (p < 0.001) or apoE4 (p < 0.001), but not in those with apoE2 (p = 0.78). An increase in total carbohydrate intake by 1 E% increased triglycerides by 0.02 mmol/L (p < 0.001) independently of apoE phenotype, while 1 E% increase in sucrose intake increased triglycerides by 0.01 mmol/L (p < 0.001).
Conclusion:  Carbohydrate intake has a relatively small effect on serum lipids in children. Children with the apoE3 or E4 but not with E2 phenotype show reduction in HDL cholesterol with increasing carbohydrate intake indicating that genetic and environmental factors interact with children's lipoprotein metabolism.     

Change in glycemic control predicts change in weight in adolescent boys with type 1 diabetes

Abstract: Objective:  To characterize the intraindividual relationships between changes in weight, glycosylated hemoglobin (HbA1c) levels, and reported total daily insulin dose between clinic visits in adolescent boys with type 1 diabetes (T1D).
Research design and methods:  Intraindividual changes in HbA1c, anthropometric data, and reported total daily insulin dose between consecutive visits for 94 adolescent boys with T1D were analyzed.
Results:  Average quarterly weight gain was 2.8 kg during periods of improving, 1.5 kg during periods of minimal change, and 0.8 kg during periods of worsening glycemic control (improving vs. minimal change p < 0.001; minimal change vs. worsening p = 0.11; improving vs. worsening p < 0.001). Analyzing the quarterly weight velocity according to change in reported total daily dose of insulin, we found significantly greater weight gain during intervals when the family reported a decreasing insulin dose compared to intervals when the family reported no change in insulin dose (p = 0.003). Conversely, weight change during periods of reported increasing insulin dose was similar to that when the family reported that the boy's insulin dose did not change.
Conclusions:  Quarterly weight velocity was correlated with degree of change in glycemic control between visits in adolescent boys with T1D. When weight loss or inadequate weight gain and worsening glycemic control occur, the possibility of insulin omission must be explored. Reviewing the adolescent's growth data and then the division of responsibilities for diabetes management within the family, clinicians must reconcile discrepancies between weight velocity and a reportedly adequate dose of insulin.     

Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes

Background:  Insulin glargine is a long-acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes.
Objective:  We evaluated the clinical course of diabetes in children and adolescents who were switched from NPH to insulin glargine.
Methods:  Between August 2003 and November 2004, a total of 76 subjects were switched to glargine in our clinic, treating 340 children with type 1 diabetes. All the subjects had been receiving insulin NPH, and their serum C-peptide levels had been non-detectable for at least 1 yr. Data were collected retrospectively, and 12–18 months after the change, experiences with glargine were inquired using a questionnaire. Seven subjects (9.2%) discontinued glargine before 12 months, and seven refused to participate.
Results:  Data for 62 subjects were analyzed. At the switch (0 months), their mean age was 12.7 yr (range 5.1–17.5), mean duration of diabetes was 6.7 yr (range 1.8–14.3), and mean hemoglobin A1c was (HbA1c) 9.2%. Twelve months later (+12 months), the mean HbA1c remained similar (9.2%), the proportion of long-acting insulin was smaller (47.7 vs. 58.1%; p < 0.001), and the daily insulin dose was lower (0.97 vs. 1.05 IU/kg; p < 0.001). The number of injections was lower at +12 months (17.7% with more than five injections vs. 64.5%; p < 0.001). No differences were seen in weight for height or the number of severe hypoglycemias. Most subjects who continued with glargine for ≥12 months considered glargine better than NPH.
Conclusions:  A switch to insulin glargine retains a similar glycemic control and does not change the number of severe hypoglycemias.     

The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

Objective:  To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM)
Research design and methods:  Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10–18 yr, puberty (≥Tanner breast stage 2 or testicular volume >4 mL), insulin dose ≥1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests.
Results:  Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (−0.3 vs. −0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone.
Conclusion:  The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM.     

Treatment of Danish adolescent diabetic patients with CSII – a matched study to MDI

Objective:  To compare two intensified insulin therapy regimens – continuous subcutaneous insulin infusion (CSII) against multiple daily insulin injection (MDI) – in Danish adolescents examined in a prospective, matched controlled study design.
Research design and methods:  Thirty type 1 diabetic adolescents at CSII and 26 matched MDI controls were included in this open intention-to-treat study. Actrapid was used in both groups. Before study entry, all participants followed a brush-up course in order to minimize study effect. At each visit, the following parameters were recorded: hemoglobin A1c (HbA1c), insulin dose, weight, number of hypoglycemic and diabetic ketoacidosis (DKA) events, and the time resources used. At entry and exit of the study, diet registration and validated quality-of-life (QoL) questionnaires were filled by the participants.
Results:  A non-significant decline in HbA1c was seen in both groups (p = 0.468); HbA1c decreased from 9.5 to 8.9% and from 9.7 to 9.5% in the CSII and MDI group, respectively. The insulin dose and the number of severe hypoglycemic events per patient were lower (non-significant) in the CSII group. Both groups showed increased body mass index – highest in the CSII group – and mild to moderate DKA episodes were only seen among CSII users. No differences could be demonstrated within the QoL or diet registrations.
Conclusions:  CSII treatment is beneficial as an intensified insulin therapy for selected type 1 diabetic patients and both MDI and CSII can be offered by the professional diabetes team to better tailor therapy. In future, there is a strong need to identify the characteristics of responders to CSII treatment in order to increase the efficacy and safety of CSII treatment.     

Dermatological side effects and complications of continuous subcutaneous insulin infusion in preschool-age and school-age children

Objective:  The objective of this study was to evaluate whether very young children develop more dermatological complications during insulin pump treatment compared with school children.
Study design:  Cross-sectional study in 78 consecutive children using insulin pump treatment >4 months.
Results:  Children in group A [n = 40, 28 males (M) and 12 females (F)] were 2.3 ± 1.3 yr (±SD) and those in group B (n = 38, 13 M and 25 F) were 11.0 ± 2.9 yr old at the start of continuous subcutaneous insulin infusion (CSII). The mean duration of CSII was similar in both groups (23.6 ± 16.5 months in group A and 21.8 ± 16.1 in group B). The most common dermatological complications were scars <3 mm (50% in group A vs. 71% in group B, p < 0.05) and lipohypertrophic areas at the insertion sites (45% in group vs. 47% in group B). Local abscesses and blisters were rare findings in both groups (7.5–12%), none leading to interruption or stop of CSII.
Conclusions:  Dermatological side effects during CSII are not more frequent or severe in very young diabetic children compared with diabetic children in school age.     

Variation within the PPARG gene is associated with residual beta-cell function and glycemic control in children and adolescents during the first year of clinical type 1 diabetes

Context:  Conflicting evidence exists as to whether the Pro12Ala single nucleotide polymorphism of the type 2 diabetes susceptibility gene peroxisome proliferator-activated receptor gamma ( PPARG ) also confers risk for type 1 diabetes (T1D).
Objective:  The objective of this study was to investigate the PPARG gene in relation to residual beta-cell function and glycemic control in newly diagnosed T1D.
Design:  Prospective, non-interventional, 12-month follow-up study, conducted in 18 centers in 15 countries.
Patients:  Two hundred and fifty-seven children and adolescents (aged <16 yr) with newly diagnosed T1D.
Main outcome measures:  Beta-cell function was determined as 90-min meal-stimulated C-peptide (Boost test) 1, 6, and 12 months after diagnosis. Hemoglobin A1c (HbA1c) and daily insulin dose (IU/kg/d) were recorded at 1, 3, 6, 9, and 12 months after diagnosis. Haplotypes within PPARG were estimated by SNPH ap program. Statistical analyses were performed in a repeated measurements model.
Results:  Five haplotypes within PPARG were generated (h1, 68.4%; h2, 16.3%; h3, 8.3%; h4, 3.5%; and hx, 3.5%). Compared with the most frequent h1 haplotype, the haplotypes h3 and h4 of the PPARG associated with residual beta-cell function during the first year of clinical disease: h3 with a 27% lower C-peptide (p = 0.02) and h4 with a 39% lower C-peptide (p = 0.01). Haplotype h4 also associated with a 0.86% (absolute) higher HbA1c, after adjustment for the insulin dose (p = 0.02).
Conclusion:  Variation in the PPARG locus may influence disease progression during the first year after the presentation of T1D.     

Health-related quality of life in intensively treated young patients with type 1 diabetes

Abstract:  This study aimed to analyse the impact of the disease and treatment on health-related quality of life (HRQOL) in intensively treated young patients with diabetes. Our main hypothesis was that metabolic control, gender, age and socio-economic status predict HRQOL. All children and adolescents (n = 400, 191 girls) and parents in a geographic population of two paediatric clinics in Sweden [mean age 13.2 yr, ±SD 3.9, range 2.6–19.6; mean duration of diabetes 5.1 yr, ±SD 3.8, range 0.3–17.6; yr mean haemoglobin A1c (HbA1c) 7.1%, ±SD 1.2, range 4.0–10.7] received the DISABKIDS questionnaire, a validated combined chronic generic and condition-specific HRQOL measure for children, and the EuroQol-5D questionnaire. Parents as proxy perceived HRQOL lower than their children. Adolescents with separated parents reported lower generic HRQOL (GeHRQOL) and diabetes-specific HRQOL (DiHRQOL) than those with parents living together (p = 0.027 and p = 0.043, respectively). Adolescent girls reported lower GeHRQOL (p = 0.041) and DiHRQOL (p = 0.001) than boys did. Parents of girls <8 yr of age reported lower DiHRQOL (p = 0.047) than did parents of boys <8 yr. In addition, a difference was found in HRQOL between centres. Intensive insulin therapy did not seem to lower HRQOL. If anything, along with better metabolic control, it increased HRQOL. A correlation between DiHRQOL and HbA1c was found in adolescents (r = −0.16, p = 0.046) and boys aged 8–12 yr (r = −0.28, p = 0.045). We conclude that the diabetes team can influence the HRQOL of the patients as there was a centre difference and because HRQOL is influenced by glycaemic control and insulin regimen. Girls seem to need extra support.     

Continuous subcutaneous insulin infusion vs. multiple daily injections in children with type 1 diabetes: a systematic review and meta-analysis of randomized control trials

Objective:  To investigate potential effects of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) on glycemic control in children with type 1 diabetes mellitus (T1DM).
Study design:  Meta-analysis and systematic review of randomized control studies (RCTs). The electronic databases MEDLINE, Cochrane Library, and EMBASE were searched through October 2007.
Results:  Six RCTs involving 165 participants with T1DM met our predefined inclusion criteria. Combined data from all trials showed that the CSII group compared with the MDI group experienced a significant reduction in the level of glycosylated hemoglobin. The pooled weighted mean difference (WMD) was −0.24% [95% confidence interval (95% CI) −0.41 to −0.07, p < 0.001] with a fixed model and remained significant in the random effect model. This effect was reached by slightly decreasing insulin requirement [three RCTs, n = 74, WMD −0.22 IU/kg/d (95% CI −0.31 to −0.14, p < 0.001)]. No differences in the incidences of ketoacidosis and severe hypoglycemic events were found.
Conclusions:  In short-term insulin therapy, CSII compared with MDI is a more effective form of metabolic control and allows reducing the daily insulin requirement. Yet, no conclusions have been made so far whether this effect holds in later years. These results should be approached with caution because of the methodological limitations of the analyzed studies.     

The impact of modifiable family factors on glycemic control among youth with type 1 diabetes

Objective:  To identify modifiable family factors impacting glycemic control in youth with type 1 diabetes (T1DM) beyond the anticipated physical, developmental, and behavioral issues associated with adolescence.
Study design:  In 153 youth (aged 8–16 yr) with T1DM duration of 6.3 ± 3.5 yr and average hemoglobin A1c (HbA1c) of 8.4 ± 1.4%, we examined modifiable family factors that might impact adherence to diabetes management and, in turn, influence glycemic control. Youth and parents completed surveys that assessed diabetes-specific knowledge, negative affect related to blood glucose monitoring (BGM), and parental-perceived burden of diabetes care. Clinician report and chart review provided data on growth, pubertal development, and diabetes management tasks. Glycemic control was measured as HbA1c.
Results:  In bivariate analyses, higher parental diabetes-specific knowledge (p < 0.0001), less youth negative affect related to BGM (p = 0.0005), and less parental-perceived burden (p = 0.0008) were associated with lower HbA1c. In a multivariate model controlling for demographic and diabetes-specific variables, these three factors remained independent and significant predictors of HbA1c (R² = 0.31 and p < 0.0001). Higher parental knowledge, less youth negative affect, and less parental burden predicted lower HbA1c, while youth knowledge and parental negative affect did not.
Conclusion:  To attain optimal glycemic control, treatment programs for youth with T1DM should include ongoing efforts to reinforce parental knowledge of diabetes tasks, promote positive youth affect related to diabetes management, and acknowledge and reduce parental-perceived burden of diabetes management.