Uridine correlates with the concentration of fructosamine and HbA1c in children with type 1 diabetes

Aim: Treating uridine as a product of UTP degradation and hypoxanthine as a degradation product of ATP, we assessed the concentration of uridine and hypoxanthine in the blood of children with newly diagnosed type 1 diabetes. We also sought to define the relationship between indicators of the degree of metabolic control of diabetes (fructosamine, HbA1c) and the concentration of the tested catabolites. Methods: This study was carried out on 33 children aged 12.26 ± 4.49 with newly diagnosed type 1 diabetes during their first hospitalization. The concentration of uridine and hypoxanthine was determined by high‐performance liquid chromatography (HPLC). Results: The results showed significantly elevated levels of hypoxanthine and uridine in the blood. We further show that blood uridine level is associated with purine metabolism and hyperglycaemia, and we demonstrate a significant positive correlation between the concentration of uridine and (i) the percentage of HbA1c and (ii) fructosamine levels, which indicate the role of hyperglycaemia in the pathogenesis of pyrimidine nucleotide metabolism in type 1 diabetes prior to diagnosis. Conclusion: The results confirm the existence of a relationship between the degree of metabolic control of diabetes and pyrimidine metabolism. Presumably, the analysis of uridine could be used as an adjunct marker of the severity of diabetic complications in newly diagnosed patients.     

Frequency of SMBG correlates with HbA1c and acute complications in children and adolescents with type 1 diabetes

Ziegler R, Heidtmann B, Hilgard D, Hofer S, Rosenbauer J, Holl R; for the DPV‐Wiss‐Initiative. Frequency of SMBG correlates with HbA1c and acute complications in children and adolescents with type 1 diabetes. The aim of this study was to correlate the frequency of self‐monitoring of blood glucose (SMBG) to the quality of metabolic control as measured by hemoglobin A1c (HbA1c), the frequency of hypoglycemia and ketoacidosis, and to see whether the associations between SMBG and these outcomes are influenced by the patient's age or treatment regime. We analyzed data from the DPV‐Wiss‐database of 26 723 children and adolescents aged 0–18 yr with type 1 diabetes recorded during 1995–2006. Variables evaluated were gender, age at visit, diabetes duration, therapy regime, insulin dose, body mass index–standard deviation scores (BMI–SDS), HbA1c, rate of hypoglycemia, and ketoacidosis. In the youngest age group of children under the age of 6 yr, the frequency of SMBG was the highest compared with that in children aged 6–12 yr or children aged > 12 yr: 6.0/d vs. 5.3/d vs. 4.4/d (p < 0.001). Frequency of SMBG differed significantly also in the different groups of treatment (p < 0.001), but only for the continuous subcutaneous insulin infusion (CSII) group the frequency was considerably higher: 5.3/d (CSII) vs. 4.7/d (multiple daily injections) vs. 4.6/d (conventional therapy). Adjusted for age, gender, diabetes duration, year of treatment, insulin regimen, insulin dose, BMI‐SDS, and center difference, SMBG frequency was significantly associated with better metabolic control with a drop of HbA1c of 0.20% for one additional SMBG per day (p < 0.001). Increasing the SMBG frequency above 5/d did not result in further improvement of metabolic control. A higher frequency of SMBG measurements was related to better metabolic control. But only among adolescents aged > 12 yr, metabolic control (HbA1c) improved distinctively with two or more blood glucose measurements.     

Seasonal variation of haemoglobin A1 in children with insulin-dependent diabetes mellitus

The results of three controlled trials performed on children with insulin-dependent diabetes mellitus were examined for evidence of seasonal variation in concentrations of glycosylated haemoglobin (HbA1). All three studies showed lower levels during the summer months. Multiple regression analysis showed that the month of sampling accounted for a significant proportion of the total variance in HbA1 levels (P<0.001 in all three studies). We suggest that exercise, dietary changes and the frequency of minor illnesses may all contribute to this fluctuation which has important implications for the design of clinical trials in childhood diabetes.Abbreviation HbA1 acid stable glycosylated haemoglobin     

Hemoglobin A1c (HbA1c) in children with long standing and newly diagnosed diabetes mellitus.

In 35 children with long-standing diabetes mellitus, a significant correlation was found between the hemoglobin A1c (HbA1c)--and the 24-hour urinary glucose excretion. By contrast, 11 newly diagnosed diabetic children had grossly elevated HbA1c-concentrations, but no correlations could be established between the levels of HbA1c and the duration of symptoms, blood glucose, glycosuria, ketonuria and the acid--base status. However, HbA1c and C-peptide were significantly correlated. The elevated HbA1c-concentrations decreased towards normal in all of these 11 children after 2--3 months following adequate therapy. The results suggest that the determination of HbA1c may serve as a valuable metabolic control index in children with long-standing diabetes mellitus, but adds little information in newly diagnosed patients. For the individual diabetic child during the early treatment period, HbA1c may be the index of choice for adequacy of metabolic control.     

Seasonal variation of birth month and breastfeeding in children with diabetes mellitus

OBJECTIVE: As breastfeeding is suggested to protect against diabetes mellitus we decided to investigate whether the seasonal variation of month of birth of diabetic children, with more diabetes in children born in summer, can be explained to some extent by a seasonal variation of exclusive breastfeeding. PATIENTS: A population-based group of 297 children who had been diagnosed with diabetes mellitus before the age of 15 years was compared with 792 matched healthy subjects. RESULTS: There was no difference in duration of breast-feeding between children who later got diabetes and the controls. Children (both diabetics and controls) born during the summer were exclusively breastfed for a mean period of 2.2 months. Corresponding figures for children born during winter were 2.8 months (p<0.04), spring 2.5 months (n.s.) and autumn 2.7 months (p<0.05). Seasonality was most pronounced in children who developed diabetes between the ages of 10 and 15 years. CONCLUSION: These results indicate that children born during the summer, who have increased risk of developing diabetes mellitus, have also been exclusively breastfed for a shorter time.     

Lower HbA1c after 1 year, in children with type 1 diabetes treated with insulin glargine vs. NPH insulin from diagnosis: a retrospective study

Salemyr J, Bang P, Örtqvist E. Lower HbA1c after 1 year, in children with type 1 diabetes treated with insulin glargine vs. NPH insulin from diagnosis: a retrospective study. Objective: Insulin glargine offers sustained insulin delivery for 24 h. Change to glargine treatment consistently results in lower fasting glucose and fewer hypoglycemic episodes in children with type 1 diabetes compared to continuation of NPH, although glargine has not been shown to improve HbA1c in randomized trials. Studies comparing glargine and NPH in multiple injection therapy in children treated from diagnosis of type 1 diabetes are lacking. Methods: HbA1c and insulin requirement were compared in a retrospective study of children (7–17 yr of age) with type 1 diabetes treated from diagnosis with basal insulin glargine (n = 49) or NPH (n = 49) in a multiple injection therapy (MIT) regimen with a rapid‐acting insulin analogue. Patients were followed every third month for 1 yr. HbA1c, insulin dose, and weight data were retrieved. Results: HbA1c (mean ± SD) was lower at 3–5 months (5.5 ± 0.89 vs. 6.2 ± 0.89%, p < 0.05) and 6–9 months (5.6 ± 1.14 vs. 6.6 ± 0.99%; p < 0.001) in glargine treated. After 12 months, HbA1c was significantly lower in glargine treated (6.3 ± 1.56 vs. 7.1 ± 1.28; p < 0.01). Reported total insulin doses were similar at nadir (0.5 U/kg BW × 24 h), but significantly lower at 12 months in glargine treated (0.64 ± 0.23 vs. 0.86 ± 0.3 U/kg BW × 24 h; p < 0.001). Conclusions: HbA1c 1 yr from diagnosis was lower in children treated with glargine from start as compared with those on NPH. This observation should be viewed in the light of a significantly lower dose of total daily insulin in the glargine group.     

Insulin pump treatment in children and adolescents with type 1 diabetes

Within children and adolescents with type 1 diabetes insulin pump treatment is of increasing interest. Frequency of insulin pump therapy shows a rapid and steep increase in toddlers and young children. Insulin pumps allow a close to physiologic insulin delivery due to basal rates programmed over 24 hours with circadian rhythms taken into account. Furthermore, another advantage of technical devices as insulin pumps is the application of extremely small amounts of insulin, as needed in very young children, with the possibility of titration of infusion rates down to 0.01E/h. Dawn Phenomenon and hypoglycemic events are main indications for insulin pump treatment in children and adolescents. A significant reduction of severe hypoglycemia, especially nocturnal hypoglycemia was shown, whereas a reduction of HbA1c and an improvement of metabolic control has been reported in short term and in some but not all long term studies. Ketoacidosis rate did not increase in insulin pump therapy. Complications due to continuous subcutaneous insulin infusion, like local infections and dermatological changes are frequent but were not associated with glycemic control and did not lead to discontinuation of insulin pump treatment. Pump discontinuation rate in general is low, varying from 1% in very young children up to 6% in pubertal adolescent girls. Insulin pump treatment was shown to be safe and efficient and the simplicity of handling the devices as well as an improvement of quality of life may explain the rapid increase of pump treatment in young children and adolescents with type 1 diabetes.     

Utility of immediate hemoglobin A1c in children with type I diabetes mellitus

Agus MSD, Alexander JL, Wolfsdorf JI. Utility of immediate hemoglobin A1c in children with type I diabetes mellitus. Objective: Immediate feedback (IFB) of hemoglobin A1c (HbA1c) results to adults with type 1 and 2 diabetes allows more appropriate care decisions at the clinic visit and may improve glycemic control. Our objective is to determine whether IFB of HbA1c results to children with type 1 diabetes will improve patient care and glycemic control. Methods: In this prospective randomized controlled trial, children under 18 years of age were randomly assigned to receive HbA1c results during their diabetes clinic visit by point‐of‐care fingerstick testing (immediate) or several days after by venipuncture and laboratory assessment (conventional). HbA1c levels, therapy changes, and painfulness of testing were recorded at baseline and every follow‐up appointment for a year. Results: The 215 patients studied had similar baseline characteristics including initial HbA1c (7.90 ± 1.24% vs. 7.81 ± 1.13%, p = 0.25). IFB improved HbA1c at 3 months (?0.20 ± 0.66%, p = 0.005) with a return to baseline for the remainder of the study. Subjects receiving conventional feedback had increased HbA1c results at 12 months (+0.27 ± 1.05%, p = 0.048). Less frequent patient–clinician communication between visits was reported with IFB (0.29 ± 0.48 vs. 0.38 ± 0.49 contacts/visit, p = 0.043). Subjects rated fingersticks as less painful than conventional venipuncture (0.30 ± 0.66 vs. 3.9 ± 2.6, p < 0.001). Conclusions: IFB of HbA1c is a more acceptable method of HbA1c determination in children with type 1 diabetes mellitus. Although sustained improvements in glycemic control did not result from this intervention alone, IFB testing resulted in more efficient patient–clinician communication and was less painful.     

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.     

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.