Arterial Stiffness, BMI, Dipping Status and ACE D/I Polymorphism in Type 1 Diabetic Children.

THE AIM: of the study was to investigate clinical and genetic determinants of arterial stiffness in children and adolescents with type 1 diabetes mellitus. MATERIAL AND METHODS: 122 patients (mean age: 16.0±2.35 years), with an average diabetes duration of 5.0 years and without evidence of arterial hypertension were recruited. Ambulatory arterial stiffness index (AASI) was assessed with 24-h automatic blood pressure monitoring. Body weight, height, HbA1c and plasma lipids were measured. Angiotensin I converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism was analysed. RESULTS: Mean AASI equalled 0.22±0.20 and showed significant, positive correlation with age and BMI-SDS. No association was found between AASI and gender, diabetes duration, daily insulin dose, HbA1c and blood lipids concentration. AASI was higher in non-dippers compared to dippers (0.26±0.18 vs. 0.19±0.18, respectively; p=0.04). In a multivariate model AASI was significantly associated with II homozygosity of ACE gene (p=0.007). CONCLUSIONS: In type 1 diabetic children and adolescents AASI is correlated with age and BMI-SDS. Non-dipping status and I-allele were associated with higher arterial stiffness.

Glycemic variability in patients with Wolfram syndrome is lower than in type 1 diabetes.

AIMS: Wolfram syndrome (WFS) is diagnosed as coexistence of diabetes mellitus and optic atrophy, where pancreatic beta cell destruction is associated with neurodegeneration. Typically, WFS necessitates insulin treatment similar to type 1 diabetes (T1D), but the mechanism of beta cell mass reduction leading to hyperglycemia is different. METHODS: The aim of the study was to assess glycemic variability using the continuous glucose monitoring (CGM) system in seven pediatric patients with genetically confirmed WFS and compare the results with data obtained from 21 propensity score-matched patients with T1D. The "GlyCulator" application was used for the calculation of glycemic variability indices. RESULTS: CGM recordings showed similarities in glycemic variability among WFS patients, but differing from those of the T1D group. Coefficient of variation (%CV), CONGA4h, and GONGA6h were significantly (p < 0.05) lower in WFS patients (28.08 ± 7.37, 54.96 ± 11.92, and 55.99 ± 10.58) than in T1D patients (37.87 ± 14.24, 74.12 ± 28.74, p = 0.02, and 80.26 ± 35.05, respectively). In WFS patients, the percentage of values above 126 mg/dL was 69.79 (52.08-77.43), whereas in patients with T1D, the percentage was significantly lower-47.22 (35.07-62.85, p = 0.018). Curiously, a tendency toward a lower percentage of measurements below 70 mg/dL was noted in the WFS group [0 (0-7.29)] in comparison with the T1D group [6.25 (0-18.06), p = 0.122]. WFS patients had a significantly higher C-peptide level (0.31 ± 0.2 ng/mL) than T1D patients (0.04 ± 0.04 ng/mL; p = 0.006). CONCLUSIONS: Patients with WFS show smaller glycemic variability than individuals with T1D, and this may be associated with persistent residual insulin secretion.

Bilirubin is an independent factor inversely associated with glycated hemoglobin level in pediatric patients with type 1 diabetes.

OBJECTIVE: Bilirubin is a potent antioxidant, and serum total bilirubin (STB) concentrations correlate negatively with cardiovascular risk. In adult diabetic patients and in healthy adults, a negative correlation between STB and glycated hemoglobin (HbA1c) has been reported. We investigated whether there is such an association in children and adolescents with type 1 diabetes mellitus. METHODS: The study group included 224 patients with type 1 diabetes duration of more than 12 months. Patients with suspected or confirmed hemolytic anemia or liver dysfunction were excluded. RESULTS: A statistically significant negative correlation was found between STB and HbA1c (R = -0.15; p = 0.024), which retained its significance in multivariate analysis (ß = -0.18, p = 0.005). Patients' age and daily insulin dose were positively correlated with HbA1c levels, whereas other variables included in the multivariate analysis [sex, diabetes duration, insulin regimen, C-peptide, hemoglobin, mean corpuscular hemoglobin concentration (MCHC), alanine transaminase (ALT), and aspartate transaminase (AST)] did not correlate with HbA1c. The mean HbA1c level in patients with STB >1.2 mg/dL (>21 µmol/L; the threshold for clinical diagnosis of Gilbert's syndrome) was lower than in patients with STB ≤1.2 mg/dL (≤21 µmol/L), and the mean difference was 0.63% (6.9 mmol/mol; 95% CI: 0.11-1.16%). CONCLUSIONS: These results show that in young patients with type 1 diabetes, STB concentration is an independent factor inversely associated with HbA1c level. Further studies should investigate the background and long-term effects of this association.

Immunogenicity of different brands of human insulin and rapid-acting insulin analogs in insulin-naïve children with type 1 diabetes.

AIMS: To determine (i) whether insulin preparations produced by three companies induce the same immune responses in insulin-naïve children with type 1 diabetes (T1DM); (ii) if switching from human insulin to rapid-acting insulin analogs influences this immune response; and (iii) if different insulin brands produce different clinical results during the first 2 yr after T1DM diagnosis. METHODS: Insulin antibodies (IA) were measured for 140 patients aged 1.4-17.6 yr. Regular human insulin, neutral protamine Hagedorn (NPH) human insulin, and rapid-acting insulin analogs (lispro or aspart) taken by the patients were produced by one of three companies: Bioton, Poland (A), Eli Lilly, USA (B) and NovoNordisk, Denmark (C). RESULTS: Positive IA levels were found in 112 patients (80.0%) at baseline and in 137 (97.9%) at 6 and at 24 months after T1DM diagnosis. There was no difference in IA levels among patients taking insulin preparations produced by different companies at 6 months (mean ± SD, A 27.8 ± 15.7%; B 25.3 ± 15.4%; C 24.5 ± 14.2; p = 0.54) or at 24 months (A 25.6 ± 17.8%; B29.6 ± 17.0%; C 26.2 ± 17.0%; p = 0.52); HbA(1c) and daily insulin dose did not differ significantly either. After 24 months, IA levels were similar for those who had used human insulin (mean ± SD, 25.7 ± 17.2%) and for those that had added rapid-acting analogs (28.1 ± 17.3%, p = 0.41). CONCLUSIONS: Three brands of insulin preparations did not differ with respect to immunogenicity. Rapid-acting analogs did not increase IA levels in patients previously treated with human insulin only. Patients using insulin preparations of different brands did not differ with respect to daily insulin dose or HbA(1c) .

HbA(1c) levels in schoolchildren with type 1 diabetes are seasonally variable and dependent on weather conditions.

AIMS/HYPOTHESIS: We evaluated seasonal HbA(1c) changes in children with type 1 diabetes and its relation with measures of weather conditions. METHODS: HbA(1c) changes over more than 3 years were evaluated in type 1 diabetic patients who were younger than 18 years and had diabetes duration of more than 12 months, and correlated with measures of weather conditions (ambient temperature, hours of sunshine and solar irradiance). After comparison of autocorrelation patterns, patterns of metabolic control and meteorological data were evaluated using Spearman rank correlation. RESULTS: A total of 3,935 HbA(1c) measurements in 589 school (≥ 7 years) and 88 preschool (<7 years) children were analysed. Mean (± SD) HbA(1c) level for the whole study period was 7.65 ± 1.12%. The lowest HbA(1c) levels were observed in late summer and the highest in winter months, with differences consistently exceeding 0.44%. Autocorrelation analysis of HbA(1c) levels in schoolchildren showed a sine-wave pattern with a cycle length of roughly 12 months, which mirrored changes in ambient temperature. Strong negative correlations of HbA(1c) with ambient temperature (R = -0.56; p = 0.0002), hours of sunshine (R= -0.52; p = 0.0007) and solar irradiance (R = -0.52; p = 0.0006) were present in schoolchildren, but not in preschoolers (p ≥ 0.29 for each correlation). CONCLUSIONS/INTERPRETATION: Seasonal changes of HbA(1c) levels in schoolchildren with type 1 diabetes are a significant phenomenon and should be considered in patient education and diabetes management. They may potentially affect the results of clinical trials using HbA(1c) levels as their primary outcome, as well as HbA(1c)-based diagnosis of diabetes.

Insulin sensitivity in Type 1 diabetic children and adolescents.

AIM: To estimate insulin sensitivity in Type 1 diabetic children and adolescents, and assess the relationship between insulin sensitivity and clinical markers of adiposity and parameters of the metabolic syndrome. METHODS: A total of 202 patients aged 8-18 years with Type 1 diabetes and disease duration 1.5-15 years participated. Insulin sensitivity was estimated by glucose uptake during an euglycaemic-hyperinsulinaemic clamp and was calculated as the average amount of glucose (M(lbm) = mg/kg(lbm)/min) required to maintain euglycaemia. Blood pressure, glycated haemoglobin (HbA(1c)) and lipid concentrations were measured. RESULTS: The M(lbm )value ranged from 4.14 to 25.25 mg/kg(lbm)/min (mean 9.81 +/- 3.34 mg/kg(lbm)/min). There was a significant relationship between M value and patients' age (r = -0.38, P < 0.0001). Insulin sensitivity decreased significantly with the onset of puberty; hence, it was significantly lower in pubertal and post-pubertal adolescents. Girls were significantly more insulin resistant than boys (9.01 +/- 0.32 vs. 10.43 +/- 0.29 mg/kg(lbm)/min, P = 0.005). Insulin sensitivity correlated with body mass index (r = -0.29, P < 0.001), waist circumference (r = -0.35, P < 0.001), triceps skin fold (r = -0.17, P = 0.018), subscapular skin fold (r = -0.23, P = 0.001) and body fat (r = -0.19, P = 0.006). There was a relationship between M(lbm) value, cholesterol (r = -0.18, P = 0.012), high-density lipoprotein cholesterol (r = 0.15, P = 0.035), low-density lipoprotein cholesterol (r = -0.22, P = 0.002), triglycerides (r = -0.32, P < 0.001) and systolic blood pressure (r = -0.15, P = 0.029). Insulin resistance was related to HbA(1c) (r = -0.18, P = 0.012). Additionally, there was a correlation between M(lbm) value and insulin dose. CONCLUSIONS: Children and adolescents with Type 1 diabetes mellitus have a very wide range of insulin sensitivity, which is determined by sex, age, amount of adipose tissue and glycaemic control.

[Severe hypoglycemia in diabetic children and adolescents: frequency and circumstances of occurrence]. / Czestosc i warunki wystepowania ciezkich hipoglikemii u dzieci i mlodziezy z cukrzyca typu I.

In 103 children and adolescents aged 13.6+/-5.5 years with type I diabetes lasting for 5.9+/-3.1 years, we have retrospectively studied the frequency and circumstances of severe hypoglycemic episodes (coma and/or convulsions). There were 71 severe hypoglycemia during the 5 year follow-up period. One third of patients had one or more severe hypoglycemia during the 5 years, therefore 6.4% of patients had at least one severe hypoglycemia every year. 8.7% of patients had 3 or more hypoglycemia within 5 years. Both glycated hemoglobin and insulin dose were comparable in patients with, or without severe hypoglycemia. Only in one third of the hypoglycemic episodes an apparent cause was found. We conclude that, most often, severe hypoglycemia occur in diabetic children without an identifiable cause and without any direct relationship with the level of glycated hemoglobin (HbA1c).

[Effect of recombinant human growth hormone treatment on glucose metabolism]. / Wplyw leczenia rekombinowanym ludzkim hormonem wzrostu na metabolizm glukozy.

Deciding to administer human growth hormone (hGH, somatotrophin) physicians often consider the possibility of adverse reactions of such a treatment, and among the others, they have regard to its effects on glucose metabolism. The problem is particularly important in patients treated with higher than physiological doses of hGH (children with constitutional short stature, girls with Turner's syndrome). Recent studies suggest, that although the effect of hGH on glucose metabolism is undeniable, replacement doses of this hormone practically do not threaten with diabetes development, but its higher than physiological doses can impair insulin secretion and, in exceptional cases, cause transient diabetes.