Electrogastrography in children and adolescents with type 1 diabetes: weak correlation with metabolic control parameters

AIM: To evaluate gastric myoelectrical activity with respect to duration and metabolic control of type 1 diabetes mellitus (T1DM). METHODS: 172 children and adolescents with T1DM (mean 14.4+/-3.7 y), divided into subgroups depending on diabetes duration (< 5 and > 5 y), and 35 healthy controls (mean 13.93+/-3.59 y) were examined. All subjects underwent electrogastrography (EGG) performed after overnight fasting. In subjects with T1DM, haemoglobin A1c (HbA1c) and blood glucose levels during EGG records were measured. RESULTS: 15.69% of T1DM patients and 91.42% of the controls fulfilled normal EGG criteria (p < 0.001). T1DM subjects had a lower percentage of fasting normogastria (34.56+/-27.35% vs 69.84+/-18.16%, p = 0.0001) and higher bradygastria (51.97+/-30.24% vs 19.11+/-15.01%, p = 0.0001) compared to controls. In diabetic patients, an increase in postprandial normogastria (60.37+/-23.96% vs 76.68+/-12.38, p < 0.05) and a decrease in bradygastria percentage (25.67+/-21.01% vs 9.58+/-7.13%, p < 0.05) was observed. In children with disease < 5 y, diabetes duration correlated with power ratio (r = - 0.27, p = 0.01), postprandial normogastria (r = - 0.24, p = 0.03) and tachygastria (r = 0.25, p = 0.02). Weak correlations between EGG parameters and glucose (preprandial dominant frequency r = - 0.19, p < 0.05; postprandial normogastria r = 0.23, p < 0.01) and HbA1c levels (preprandial bradygastria r = 0.19, postprandial dominant power r = 0.23; p < 0.05) were observed. CONCLUSION: Gastric myoelectrical rhythm derangement is present in a large proportion of young diabetic patients. Bradygastria is the most prominent EGG abnormality. Weak correlation was found between EGG parameters and diabetes metabolic control.     

Role of hemoglobin A1c, duration and puberty on bone mineral density in diabetic children

BACKGROUND: The aim of the present was to determine bone mineral density (BMD) in type 1 diabetic children and the roles of hemoglobin A(1c), disease duration and pubertal stage on BMD changes. METHODS: Fifty-eight patients were investigated: 16 had been newly diagnosed (Diabetes(New)) and 42 were already on follow up (Diabetes(Follow up)). BMD of the lumbar vertebrae, HbA1c(HbA1c(last)), Ca, P, Mg were measured. Mean HbA1c of the previous year (HbA1c(1year)), the whole duration of diabetes (HbA1c(whole)), and diabetic impact index (HbA1c(whole) x diabetes duration) were calculated in the Diabetes(Follow up) group. RESULTS: Mean BMD-Z score (-0.61 +/- 0.99 g/cm(2)) of the whole group was significantly lower than zero. Osteopenia was present in 14 (24.1%), and osteoporosis in three (5.2%). HbA1c(whole) was the most important determinant effecting BMD-Z (r = -0.35, P < 0.05) with the cut-off for osteopenia and osteoporosis being 9.8% and 12.1%, respectively. The cut-off of diabetes duration for osteopenia was 3.6 years and it was more predictive for osteopenia compared to HbA1c(whole). In the Diabetes(New) group, the BMD-Z score of the early pubertal group was significantly lower than those in other pubertal groups. CONCLUSION: BMD is affected in diabetic children, and HbA1c(whole) and diabetes duration are the most important determinants. Pubertal stage is another determinant of BMD, especially in newly diagnosed patients.     

Low risk of overt nephropathy after 24 yr of childhood-onset type 1 diabetes mellitus (T1DM) in Norway

AIM: To estimate the risk of diabetic nephropathy and associated risk factors in a nationwide cohort of childhood-onset type 1 diabetes mellitus (T1DM) and 19-30 yr of diabetes duration. METHODS: Patients diagnosed with childhood-onset T1DM (<15 yr) from 1973 through 1982, who previously (1989-1990) participated in a clinical examination to assess diabetic complications, were invited for a new examination in 2002-2003. Of 355 eligible patients, 299 participated (84.2%), and complete urine samples for evaluation of albuminuria were obtained from 295 patients, with a mean age of 33 yr (range 20.9-44.0) and mean diabetes duration of 24 yr (range 19.3-29.9). Persistent microalbuminuria and overt nephropathy [albumin excretion rate (AER) 15-200 microg/min and AER > 200 microg/min, respectively] in at least two out of three consecutive overnight urine samples were defined as diabetic nephropathy. RESULTS: Overt nephropathy was found in 7.8% [95% confidence interval (CI) 4.7-10.9] and persistent microalbuminuria in 14.9% (95% CI 10.8-19.0) of the subjects. Hemoglobin A1c (HbA1c) (p = 0.001), systolic blood pressure (BP) (p = 0.002), total cholesterol (p = 0.019), and C-reactive protein (CRP) (p = 0.019) were associated with diabetic nephropathy. Significant predictors in 1989-1990 for the development of diabetic nephropathy in 2002-2003 were HbA1c (p < 0.001), AER (p = 0.007), and cholesterol (p = 0.022). CONCLUSIONS: In a subgroup of patients diagnosed with childhood-onset T1DM in 1973-1982, 7.8% had overt nephropathy after 19-30 yr of diabetes duration, which is low compared with studies from other countries. HbA1c, systolic BP, total cholesterol, and CRP were each independently associated with diabetic nephropathy.     

Prevalence of EGG derangement in newly diagnosed type 1 diabetes in childhood

OBJECTIVE: To evaluate gastric myoelectrical activity in children with newly diagnosed type 1 diabetes melliltus (T1DM) in relation to blood glucose control and visceral neuropathy. METHODS: Percutaneous electrogastrograpy (EGG) was performed on 42 children (20 F; mean age 12.9 +/- 3.1 years) with T1DM of <1 year's duration and on 35 healthy controls (18 F; mean age 13.4 +/- 3.6 years). After overnight fasting, a 30-minute EGG recording was followed by test meal consumption and then a 60-minute postprandial EGG aquisition. Fasting and postprandial periods were analyzed for gastric dysrhythmias, dominant frequency (DF) and additional parameters. In T1DM patients, HbA1c and blood glucose levels were measured and tests for visceral neuropathy were performed. RESULTS: In 41 T1DM patients (98%), cardiovascular neuropathy tests were negative. In 12 of those patients (29%) and in 32 healthy controls (91%), electrogastrograms were normal. The percentages of fasting and postprandial gastric dysrhythmias were significantly higher in T1DM patients compared to controls (P < 0,05). In T1DM children after feeding, some normalization of gastric myoelectrical rhythm was observed: normogastria increased nearly 2-fold to 72.6 +/- 22.9% and bradygastria decreased to 20.8 +/- 20.4% from 52.3 +/- 32.4% (P < 0.05). The percentages of fasting bradygastria and normogastria were correlated with glycemia level (r = -0.55 and r = 0.51, respectively; P < 0.05), as was postprandial DF (r = 0.41; P < 0.05). There was no correlation between HbA1c levels and EGG parameters. CONCLUSIONS: Derangement of the gastric myoelectrical activity is present in 71% of children with early stage T1DM. Glucose levels influence gastric myoelectrical activity, whereas long-term glucose control (HbA1c level) does not correlate with EGG parameters.     

Optimal control of type 1 diabetes mellitus in youth receiving intensive treatment

OBJECTIVE: To investigate the impact of factors that might interfere with optimal glycemic control in youth with type 1 diabetes mellitus (T1DM) in the current era of intensive management, including the interplay of race/ethnicity and socioeconomic status (SES) on HbA1c levels. STUDY DESIGN: This study comprised a database review of all patients under age 18 years with T1DM for at least 6 months duration. Sex, age, race/ethnicity, duration of diabetes, mode of insulin administration (pump vs injection), body mass index, SES, and HbA1c level were recorded at each patient's most recent visit between January and September 2003. RESULTS: Mean HbA1c level for the 455 patients was 7.6% +/- 1.4%; only 31% of patients failed to meet the therapeutic goal of < 8.0%. Multiple linear regression analysis identified female sex (P = .02), older age (P = .001), longer duration of diabetes (P < .001), injection therapy (P < .001), and lower SES (P = .001) as significantly associated with higher HbA1c level. After adjustment for SES, race/ethnicity was not a determinant of HbA1c level. CONCLUSIONS: Low SES had a greater association with poor metabolic control than did race/ethnicity, which was not associated with differences in HbA1c level after controlling for SES. Most children were able to attain glycemic targets at least as good as the Diabetes Control and Complications Trial recommendations in a large clinical practice.     

Prevalence of microalbuminuria in young patients with type 1 and type 2 diabetes mellitus

This study was designed to determine the prevalence of microalbuminuria and the associated risk factors in patients with childhood-onset diabetes mellitus (DM). One hundred and sixty-three patients (141 with type 1 DM [DM1] and 22 with type 2 DM [DM21), aged 8 to 28 years, were evaluated for albumin excretion rate and HbA(1c). The mean duration of DM was 8.1 +/- 3.4 and 5.5 +/- 3.9 years in DM1 and DM2, respectively. Persistent microalbuminuria and macroalbuminuria were observed in 11.3% and 2.8% of patients with DM1, and 18.2% and 4.5% in patients with DM2, respectively. In DM1, the duration of DM, age of onset, and HbA(1c) levels were significant predictors of microalbuminuria. Our observations suggest that screening for microalbuminuria should be started from early adolescence in patients with DM1 and DM2.     

The role of diabetes duration, pubertal development and metabolic control in growth in children with type 1 diabetes mellitus

OBJECTIVE: To investigate whether pubertal development, duration of type 1 diabetes mellitus (DM1), or metabolic control play some role in the anomalies in growth observed in diabetic children. PATIENTS: We conducted a prospective evaluation of 83 patients (37 female, 46 male) who were followed from the onset of DM1 at the prepubertal stage until they reached final height. All patients were treated with a conventional regimen of insulin. METHODS: Height SDS, weight SDS, BMI SDS, duration of DM1 in years, and values of HbA1c were the study variables. RESULTS: In prepubertal (P1) girls (data for the initial vs the intermediate evaluations): weight SDS was -0.14 +/- 0.19 vs 0.11 +/- 0.20, p = ns; BMI SDS -0.25 +/- 0.15 vs 0.01 +/- 0.13, p = ns. In postpubertal (P3) girls, weight SDS was 0.49 +/- 0.2 vs 1.2 +/- 0.32, p <0.01; BMI SDS 0.09 +/- 0.16 vs 1.03 +/- 0.24, p <0.01, whereas in P1 boys, height SDS was 0.16 +/- 0.30 vs -0.20 +/- 0.27, p <0.05; and in P3 boys: 0.09 +/- 0.21 vs -0.28 +/- 0.26, p <0.05. Thus pubertal development influenced changes observed in girls with DM1, but did not do so in boys. The anomalies described in children with DM1 were observed from the third year of DM1 duration in both girls and boys. We did not observe any correlation between HbA1c values with height SDS, weight SDS or BMI SDS. CONCLUSIONS: The anomalies in growth observed in girls with DM1 are related to pubertal development, but this is not the case in boys. Alterations in children with DM1 were found from the third year of DM1 duration. Furthermore, the present data also indicate that the degree of metabolic control observed in our patients treated with modern but conventional regimen did not play a major role in the anomalies observed.     

Urinary cytokine response to asymptomatic bacteriuria in type 1 diabetic children and young adults

It has been reported that urinary interleukin-6 (IL-6) and IL-8 levels are decreased in adult diabetic women with asymptomatic bacteriuria (ASB) when compared with non-diabetic women with ASB. Such impaired cytokine excretion might play a role in the higher prevalence of ASB among diabetic subjects. The aim of this study was to examine the urinary IL profile in children and young adults with type 1 diabetes mellitus (T1DM) with and without ASB. Midstream clean voiding urine samples were collected and cultured from 133 patients with T1DM (age: 15.6 +/- 5.7 yr) and 178 controls (14.1 +/- 4.7 yr) for two consecutive days. ASB was diagnosed in the case of >or=10(5) bacteria/mL. The urinary IL-6 and IL-8 concentrations were determined, and the presence of leukocyturia was also recorded. The prevalence of ASB was 16.5% in diabetic subjects and 2.8% in controls (p = 0.001). There was no difference between the diabetic and the control groups in the prevalence of 'IL-6-uria' (21.9 vs. 18.0%; p = 0.41), but IL-8 was more frequently detectable in the diabetic group (47.4 vs. 27.5%; p = 0.001). In individuals with ASB, the IL-8 level was similar in the diabetic (median: 70.0 pg/mg creatinine) and control group (42.3 pg/mg creatinine; p = 0.8). Indeed, the IL-8 levels were higher in diabetic subjects with ASB as compared with those without it (70.0 vs. <3.1 pg/mg creatinine; p = 0.001), and there was a significant association between the urinary IL-8 concentration and the bacterial count (p = 0.001). Diabetic patients with leukocyturia had higher IL-8 concentration than those without it (20.9 vs. <3.1 pg/mg creatinine; p = 0.003). Weak significant correlation was found between urinary IL-8 and hemoglobin A1c (HbA1c) (r = 0.4; p = 0.002). The sensitivity and specificity of leukocyturia were 50 and 89.9% in the whole population and those of IL-8 were 74.1 and 67.5%, respectively. In diabetic patients, 36.4% of the bacteriuria were gram-negative and 63.6% gram-positive. Our results suggest that diabetic children with ASB mount an IL-8 response to pathogens, which is comparable to non-diabetic children with bacteriuria. Thus, early in the natural history of diabetes, there are no significant changes in the IL response of children with ASB, as previously reported in adults.     

Comparison of fingerstick hemoglobin A1c levels assayed by DCA 2000 with the DCCT/EDIC central laboratory assay: results of a Diabetes Research in Children Network (DirecNet) Study

BACKGROUND: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) high-performance liquid chromatography (HPLC) method for measuring hemoglobin A1c (HbA1c) serves as a reference standard against which other assays are compared. The DCA 2000 + Analyzer (Bayer Inc., Tarrytown, NY, USA), which uses an immunoassay, is a very popular device for measuring HbA1c levels in pediatric diabetes practices. OBJECTIVE: To determine how HbA1c values measured with the DCA 2000 in a multisite, pediatric diabetes clinic setting compare with corresponding HbA1c values measured in the DCCT/EDIC laboratory. DESIGN/METHODS: To examine this question, the Diabetes Research in Children Network (DirecNet) used the DCA 2000 in five clinical centers to measure baseline HbA1c levels in 200 youth with type 1 diabetes mellitus (T1DM) (aged 12.5 +/- 2.8 yr) who were participating in an outpatient clinical trial. At the same visit, an additional blood sample was obtained, refrigerated, and shipped to the DCCT/EDIC central laboratory for determination of HbA1c values. RESULTS: The central laboratory HbA1c value averaged 8.0 +/- 0.9% (mean +/- SD), with a median (25th and 75th quartiles) of 7.8% (7.3 and 8.5%, respectively). The DCA 2000 HbA1c values were strongly correlated (r = 0.94, p < 0.001), but significantly higher than DCCT/EDIC central laboratory values with a mean difference of +0.2% (95% confidence interval +0.14 to 0.23%, p < 0.001). There was some variation in the differences between DCA 2000 and central laboratory values at the five clinical centers (p < 0.001) with mean differences ranging between 0.0 and 0.3%, but differences between the two methods did not vary significantly by age or gender. CONCLUSION: Measurements of HbA1c by the DCA 2000 compare favorably with the DCCT/EDIC central laboratory method, albeit with slightly higher values.     

Postprandial chylomicron clearance rate in late teenagers with diabetes mellitus type 1

A delayed chylomicron (CM) clearance rate, a known risk factor for atherosclerosis, has been described in adults with diabetes type 1 (DM1). We determined the CM clearance rate in late teenagers with DM1, and the relationship between CM clearance rate and elevated plasma lipid concentrations in DM1 teenagers in poor metabolic control (as characterized by HbA(1c) percentage). Plasma lipids and CM clearance were determined in nine patients with DM1 (mean age +/- SD: 17.5 +/- 0.6 y) and four healthy controls (mean age +/- SD: 20.1 +/- 0.8 y), by measuring breath (13)CO(2), plasma triglyceride, retinyl palmitate, and (13)C-labeled oleic acid concentrations, after oral administration of a fat-rich meal together with vitamin A and (13)C-oleic acid. In patients with DM1, fasting triglyceride and cholesterol concentrations were positively correlated with HbA(1c) percentage (p < 0.05). Neither in DM1 patients, nor in controls, was an elevated triglyceride concentration (above 1.7 mmol/L) found. Yet, in 22% of DM1 patients, cholesterol concentration was above 5.2 mmol/L, but not in any of the controls. CM clearance rate in DM1 patients was similar to that in controls and did not significantly correlate with HbA(1c) percentage. Fasting lipid concentrations in DM1 patients were not significantly correlated with CM clearance rate. Present data indicate that elevated lipid concentrations in late teenagers with DM1 are not attributable to a delay in CM clearance rate. A delayed CM clearance rate at late teenager age is not a risk factor contributing to the increased risk for atherosclerosis in DM1.     

Anti-CD38 autoimmunity in children with newly diagnosed type 1 diabetes mellitus

AIMS: To test for anti-CD38 autoimmunity in children with newly-diagnosed type 1 diabetes mellitus (DM1). METHODS: Serum anti-CD38 autoantibodies were detected by Western blot in 270 children (130 girls, 140 boys, mean age 8 +/- 4 years) with newly-diagnosed DM1 and 179 gender- and age-matched non-diabetic children. In 126 diabetic children, another blood sample was obtained 15 +/- 4 months after the diagnosis. RESULTS: Anti-CD38 autoantibody titers at least 3 SD above the mean value for the control group were found in 4.4% of children with DM1 vs 0.6% of controls (chi2 = 5.8, p <0.016). No statistical differences were observed between anti-CD38 positive and negative patients in terms of phenotype. At follow-up, of six diabetic children who were positive for anti-CD38 antibodies, two were new cases. A positive correlation was found between the antibody titer of diabetic sera at diagnosis and follow up (r = 0.46, p <0.0001). CONCLUSION: An autoimmune reaction against CD38, a protein expressed in human islets, is associated with newly-diagnosed DM1. In children with DM1, CD38 autoimmunity increases with time and persists.     

Increased prevalence of overweight in adolescent girls with type 1 diabetes mellitus

Height and weight were measured in young patients with type 1 diabetes up to the age of 22 y. We found no difference between birth length standard deviation scores (SDS), final height SDS and target height SDS. The study group of 89 diabetic boys and girls did not differ in final height from age- and sex-matched healthy controls. SDS for height at diagnosis, +0.17 +/- 1.10, exceeded that for final height, -0.06 +/- 0.97 (p = 0.037). Height SDS decreased between the ages of 11 and 18 (p < 0.01). In diabetic girls, but not boys, final height SDS was significantly related to mean HbA1c during puberty (r = -0.40; p = 0.025). Weight gain occurred from age of menarche in girls with type 1 diabetes. At the age of 18, diabetic girls were 6.5 kg heavier and had 2.7 kg/m2 higher body mass index (BMI) than control girls (p < 0.001). Diabetic boys were not heavier than control boys. There was a significant relationship between mean HbA1c during puberty and BMI at the age of 18 in diabetic girls (r = 0.47; p = 0.009). In diabetic females, body weight remained unchanged, HbA1c improved and the dose of insulin was significantly reduced between 18 and 22 y of age. The HbA1c improvement was most marked in patients with poor metabolic control. In conclusion, although mean final height was normal in young patients with type 1 diabetes, growth was increased before diagnosis and pubertal growth spurt was reduced. Adolescent overweight was overrepresented; it related to poor metabolic control in females with diabetes, but showed no further acceleration in early adulthood.     

Autonomic function testing in children and adolescents with diabetes mellitus

Cardiac autonomic neuropathy (CAN) is a common complication in type 1 diabetes mellitus (T1DM) and associated with an increased mortality. Early detection of CAN would be desirable for a better individual risk stratification. The aim of this study was to determine whether autonomic dysfunction can be diagnosed in young patients with a recent history of T1DM. Autonomic function was assessed in 20 pediatric patients with T1DM, aged 10-19 yr, and a control group of 136 non-diabetic patients using four cardiorespiratory reflexes: heart rate and blood pressure response in standing position, deep breathing, and Valsalva maneuver. Furthermore, power spectral analyses of the low- and high-frequency band of heart rate variability (HRV) and baroreflex sensitivity (BRS) were tested with the non-invasive Task force monitor (CNSystems, Graz, Austria). Cardiorespiratory reflexes were pathologic for at least one item in 75% of the diabetic and 60% in the healthy control group. A reduced BRS was always combined with abnormal HRV. We found this pattern in 30% of diabetic patients and never in the control group. In patients with impaired BRS, mean hemoglobin A1c (HbA1c) was 7.7% and duration of diabetes 6.5 yr. This did not differ from the overall value of the diabetic group: HbA1c level 8.4% and diabetes duration 7.3 yr. In conclusion, signs of autonomic dysfunction are not uncommon in an early stage of diabetes in young patients. Classical cardiorespiratory reflexes seem to be less specific than HRV and BRS as testing methods.     

Continuous subcutaneous insulin infusion in toddlers and children with type 1 diabetes mellitus is safe and effective

OBJECTIVE: The aim of this study was to investigate the safety and efficacy of continuous subcutaneous insulin infusion (CSII) for type 1 diabetes mellitus (T1DM) in toddlers and children. RESEARCH DESIGN AND METHODS: Seventy children who began CSII at the age of 12 yr or younger (youngest 2 yr old) and who were maintained on CSII for at least 6 months were studied by a retrospective chart review. A pre- or postintervention comparison approach was used to assess the impact of CSII on the measured variables. The control period was defined as 1 yr prior to beginning CSII. Charts were reviewed for hemoglobin A1c (HbA1c) reports of severe hypoglycemia, diabetic ketoacidosis (DKA), height and weight, and range of blood glucoses reported at each visit. Mean values for HbA1c, body mass index (BMI) z-score, and range of blood glucose were computed for each subject over all pre-CSII visits, and again over all post-CSII visits. RESULTS: The mean HbA1c decreased significantly during CSII [7.8 +/- 0.8% pre-CSII vs. 7.3 +/- 0.7% on CSII, p < 0.0001]. Hypoglycemic episodes decreased with CSII in the 10- to 12-yr-old group (p < 0.02) and demonstrated a strong trend (mean of 0.46-0.22 events per patient year, p < 0.06) overall. Two episodes of DKA occurred in the CSII period and none in the control period (p = NS). BMI z-scores increased to 0.21 in the 5- to 9-yr-age group (p < 0.008) and averaged 0.13 overall. The range of blood glucoses decreased during CSII (p < 0.005) in the middle and oldest age groups. CONCLUSIONS: This study supports CSII as a safe and effective alternative to managing T1DM, with no increase in hypoglycemia and a trend to improve control, even in the youngest patients.     

Continuous subcutaneous insulin infusion benefits quality of life in preschool-age children with type 1 diabetes mellitus

OBJECTIVE: To compare medical, nutritional, and psychosocial outcomes of continuous subcutaneous insulin infusion (CSII) therapy and multiple daily insulin injections (MDI) in preschoolers with type 1 diabetes mellitus (T1DM) in a randomized controlled trial. STUDY DESIGN: Sixteen children (mean age 4.4 +/- 0.7 yr, range 3.1-5.3 yr) with T1DM were randomly assigned to CSII or MDI. Hemoglobin A1c (HbA1c) was measured monthly for 6 months. Glucose variability was measured at baseline and at 6 months using continuous blood glucose sensing. Quality of life, adverse events, and nutrition information were assessed. RESULTS: Parents of the CSII group reported a significant decrease in diabetes-related worry, while parents of the MDI group reported an increased frequency of stress associated with their child's medical care. Mean HbA1c levels from baseline (CSII 8.3 +/- 1.4%, MDI 8.0 +/- 0.8%) to 6 months (CSII 8.4 +/- 0.8%, MDI 8.2 +/- 0.4%) remained stable, and group differences were not significant. There were no significant group differences in duration of hypo- or hyperglycemic events or frequency of adverse events. CONCLUSION(S): For young children with T1DM, CSII therapy is comparable to MDI therapy with regard to glucose control but is associated with higher treatment satisfaction and improved quality of life.     

Angiotensin-converting enzyme gene polymorphism and lipid profiles in Kuwaiti children with type 1 diabetes

METHODS: We studied angiotensin-converting enzyme (ACE) gene polymorphism and lipid profiles in Kuwaiti children with uncomplicated type 1 diabetes. A total of 125 children with type 1 diabetes were matched in a case-control study on age and gender to 125 non-diabetic children as controls. Serum lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL; low-density lipoprotein cholesterol, LDL-c; triglycerides, TG; apolipoprotein A1 and B, apo A1 and B; lipoprotein(a), Lp(a)); and glycated hemoglobin, HbA1c were evaluated according to ACE genotypes. RESULTS: Genotype distributions were found to be similar in cases [ACE insertion/insertion (II) 9.6%, ACE insertion/deletion (ID) 38.4%, ACE deletion/deletion (DD) 52.0%], and controls (II 8.8%, ID 43.2%, DD 48.0%), and were characterized by higher frequencies of DD, ID, and lower frequencies of II. Diabetic children with DD genotype showed significantly higher levels of TC (p < 0.01), HDL (p < 0.001), and apo A1 (p < 0.001) than controls. There was a higher proportion of diabetic children with family history of cardiovascular disease (CVD) in the DD genotype group (51.9%) than those with II genotype group (11.1%) (p < 0.001). Also, there was a significant increase in the frequency of diabetic children with Lp(a) > 30 mg/dL in children with a family history of CVD (p = 0.008). Lp(a) levels were correlated with HbA1c in the diabetic group (r = 0.239, p = 0.019), but when patients with poor glycemic control (HbA1c > 9%) were excluded, the significant correlation disappeared (r = 0.127, p = 0.381). After adjusting confounding between variables, the logistic regression analysis showed that the two significantly related variables with the rise in Lp(a) were increasing TC level and poor glycemic control. CONCLUSIONS: In children with type 1 diabetes, the role of ACE polymorphism as a probable contributor to CVD seems to be partially mediated through other factors such as poor glycemic control, TC, and Lp(a) level. A longitudinal study is recommended with a larger number of patients in each ACE genotype group in order to assess such associations.     

Continuous subcutaneous insulin infusion in children and adolescents with diabetes mellitus: decreased HbA1c with low risk of hypoglycemia

AIM: To evaluate blood glucose and HbA1c levels, insulin dosage, hypoglycemia rate and body mass index (BMI) at baseline, and at 3 and 6 months after initiation of continuous subcutaneous insulin infusion (CSII) in children and youth with type 1 diabetes mellitus (DM). METHODS: A 6-month trial of pump therapy was carried out in 40 patients with type 1 DM and one with cystic fibrosis (CF) induced DM (25 males), aged 4-25 years (mean 13.5 +/- 4.2 [SD]; 4-8 years, n = 6; 8-10 years, n = 8; 10-12 years, n = 4; 12-15 years, n = 11; >15 years, n = 12). RESULTS: HbA1c was significantly reduced from 9.5 +/- 1.7% to 8.6 +/- 1.2% at 3 months (p < 0.03), and at 6 months 8.8 +/- 1.5% (p < 0.05). The mean daily values of blood glucose, as well as individual mean values of blood glucose at fasting and before lunch, also exhibited a significant reduction (p < 0.05) at 3 and 6 months. There was a significant reduction in the number of hypoglycemic events (level of plasma glucose <3.3 mmol/l, calculated as number of events per patient/30 days) at 3 months (6.5 +/- 5.5 vs 2.8 +/- 3.3; p = 0.02) and at 6 months (6.5 +/- 5.5 vs 3.5 +/- 3.0; p = 0.04). The insulin requirement dropped by 27.2% (1.03 +/- 0.30 U/kg/day before starting CSII; 0.75 +/- 020 U/kg/day on insulin pump therapy onset; 0.76 +/- 0.18 U/kg/day at 3 months; 0.75 +/- 0.21 U/kg/day at 6 months). During the follow-up 0.10 events of diabetic ketoacidosis/patient/year were recorded. The patients exhibited no increase in BMI during the 6 months of follow-up. CONCLUSION: CSII was safe and effective in improving short- and medium-term metabolic control in young adults, adolescents and younger children with DM.     

Continuous subcutaneous glucose monitoring in children with type 1 diabetes mellitus: a single-blind, randomized, controlled trial

BACKGROUND: Tight glycemic control delays the long-term complications of type 1 diabetes mellitus (T1DM) but increases the risk for hypoglycemia. The continuous glucose-monitoring system (CGMS) provides blood glucose (BG) readings every 5 min, and its accuracy and reliability has been established in adults. However, there are limited data on its efficacy and safety in children. The purpose of this study was to determine if CGMS use improves metabolic control in children with T1DM. METHODS: Twenty-seven children (12 male) with T1DM participated in this single-blind, randomized, controlled trial. Participants (age: 11.4 +/- 3.7 (mean +/- SD) yr, range: 7-17 yr) were randomized to an intervention group (n = 18) or a control group (n = 9). Both groups wore the CGMS for 72-h periods at 0, 2, and 4 months. Adjustments in therapy for the intervention group were based on both CGMS and self-monitoring of BG (SMBG) data, while only SMBG data were used for the control group. Hemoglobin A1c (HbA1c) was determined at 0, 2, 4, and 6 months. The change in HbA1c from 0 to 6 months (HbA1c(Delta1-4)) and mean daily area under the CGMS curve for glucose <70 mg/dL area under the curve (AUC(<70)) were compared between groups. RESULTS: At study entry, HbA1c levels were similar in the intervention and control groups (8.4 +/- 0.98 and 8.8 +/- 0.86%, respectively; p = 0.12) but were significantly lower in the intervention group compared with the control group at study completion (7.8 +/- 0.88 and 8.6 +/- 0.95%, respectively; p = 0.02). The decrease in HbA1c of 0.61 +/- 0.68% in the intervention group was statistically significant (p = 0.03), whereas the decrease in HbA1c of 0.28 +/- 0.78% in the control group was not. Nonetheless, the differences in HbA1c(Delta1-4) between groups did not reach statistical significance (p = 0.13). There was no statistically significant difference in AUC(<70) between study groups (p = 0.18). CONCLUSION: CGMS use may improve metabolic control in children with T1DM without increasing the risk for hypoglycemia.     

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

BACKGROUND: Insulin resistance is well recognized both in type 1 diabetes mellitus (T1DM) and in obesity. Studies concerning the relation between insulin resistance and overweight in T1DM have not yet been carried out. METHODS: Degree of overweight [standard deviation score-body mass index (SDS-BMI)] and daily insulin doses per weight (ID/kg), per body surface (ID/m2), and per ideal body weight (ID/IW) were recorded in 4124 children aged between 5 and 20 yr with a duration of T1DM of 4-5 yr and an adequate metabolic control [hemoglobin A1c (HbA1c) <8.0%]. SDS-BMI was compared between insulin-resistant (ID/kg > or = 1.0) and insulin-sensitive (ID/kg <1.0) children. The ID/kg, ID/m2, and ID/IW were compared between obese (SDS-BMI >1.9) and non-obese children. Multivariate linear regression analysis was conducted for the dependent variables ID/kg, ID/m2, and ID/IW, including age, gender, SDS-BMI, and HbA1c as independent variables. RESULTS: The 882 insulin-resistant children did not differ significantly (p = 0.447) with respect to SDS-BMI (median +0.38) compared to the 3242 insulin-sensitive children (median SDS-BMI +0.42). The ID/kg was significantly (p = 0.031) lower in the obese children compared to the non-obese children (median 0.80 vs. 0.83), while ID/m2 (median 31.0 vs. 26.2) and ID/IW (median 1.17 vs. 0.85) were significantly (p < 0.001) increased in the obese children. In multivariate linear regression analysis, SDS-BMI was significantly (p < 0.001) associated with an increase in ID/m2 and ID/IW and a decrease in ID/kg. CONCLUSIONS: T1DM children with insulin resistance based on ID/kg are not more overweight than insulin-sensitive children with T1DM. ID/m2 and ID/IW seem to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1DM.     

Early changes in 24-hour ambulatory blood pressure are associated with high normal albumin excretion rate in children with type 1 diabetes mellitus

OBJECTIVE: The relationship between urinary albumin excretion rate (AER) and elevated blood pressure (BP) is unclear as a cause-effect phenomenon in the development of diabetic nephropathy. The aim of this study was to examine the association between AER, HbA1c and BP in children with normoalbuminuria. METHODS: 24-hour ambulatory BP assessment was performed in 78 children with type 1 diabetes mellitus (DM1), age mean +/- SD 13.4 +/- 2.7 yr, range 7.3-18.3 yr, DM1 duration mean +/- SD 6.6 +/- 2.9 yr, range 2.1-11.9 yr. Using generalised linear mixed models with systolic (SBP) and diastolic (DBP) blood pressure as dependent variables, the effects of AER and HbA1c were examined, adjusting for age, gender, DM1 duration and insulin dose. RESULTS: Patients with high normal AER (7-20 microg/min) had higher SBP during daytime and night-time compared to the low normal AER (< or = 7 microg/min) (mean +/- SD 118.20 +/- 7.98 and 110.33 +/- 7.08 mm Hg, p = 0.02; mean +/- SD 108.76 +/- 9.21 and 100.20 +/- 7.75 mm Hg, p = 0.03, respectively). DBP was also higher both during day- and night-time when compared to the < or = 7 microg/min group (mean +/- SD 73.40 +/- 6.50 and 64.86 +/- 5.67 mm Hg, p = 0.002; mean +/- SD 62.50 +/- 6.75 and 56.30 +/- 5.56 mm Hg, p = 0.03 day- and night-time, respectively). CONCLUSION: A rise in SBP and DBP is associated with increased levels of AER even within the normal range.