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.     

Urinary oxidative stress markers in young patients with type 1 diabetes

BACKGROUND: Involvement of oxidative stress in the pathogenesis of diabetic vascular complications has been proposed. However, there are few methods to determine the status of oxidative stress both directly and quantitatively in young patients with type 1 diabetes. METHODS: A total of 27 young patients with type 1 diabetes (mean age +/- SD, 12.6 +/- 4.2 years) with normal renal function and 38 healthy control subjects (13.0 +/- 4.6 years) were investigated. Early morning voiding urine samples were collected. The concentrations of acrolein-lysine adducts, 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined using competitive enzyme-linked immunosorbent assay, and nitric oxide metabolites were measured using the colorimetric, non-enzymatic assay. RESULTS: Urinary concentrations of 8-OHdG, but not acrolein-lysine adducts and nitric oxide metabolites, were significantly increased in the diabetic group. For diabetic patients, microalbuminuria was significantly correlated with higher concentrations of all three markers. Hemoglobin A(1c) values were significantly correlated with 8-OHdG values. CONCLUSIONS: These findings indicate that increased oxidative stress and the risk of vascular complications may be present at early stages of type 1 diabetes.     

Microvascular complications in children and adolescents with type 1 diabetes mellitus in Assiut governorate,Egypt

Background

Type 1 diabetes mellitus (T1DM) carries a long-term burden of increased microvascular complications in the form of nephropathy, retinopathy, and neuropathy. As the incidence of T1DM continues to rise, the burden of microvascular complications will also increase and negatively influence the prognosis of young patients. Microalbuminuria (MA) represents the earliest clinical indication of diabetic nephropathy and is a predictor of increased cardiovascular morbidity and mortality. Our study’s aim was to determine the prevalence of microvascular complications among type 1 diabetic patients in Assiut University Children Hospital, Upper Egypt and to find out its correlation with various risk factors.

Erythrocyte indicators of oxidative stress in gestational diabetes

Foetuses born to mothers with gestational diabetes are at increased risk of developing respiratory distress, foetal macrosomia, foetal anomalies and platelet hyperaggregability. High blood glucose level induces oxidative stress and decreases antioxidant defences. The present study discusses the possibility of lipid peroxidation and protein oxidation in both maternal and foetal erythrocytes as an indicator of oxygen radical activity. The level of lipid peroxidation and protein oxidation in erythrocytes was estimated in 20 mothers with gestational diabetes and their newborns. The maternal age varied between 19 and 42 y and foetal age ranged between 34 and 39 weeks. The proteolytic activities in the erythrocyte lysates obtained from mothers with gestational diabetes and their newborns were significantly greater [(mean ± SD) 24.41 ± 9.05 and 16.70 ± 3.36μM of amino groups/g haemoglobin, n = 20, respectively] than those from control group (10.18 ± 4.84 and 14.64 ± 6.21 μM amino groups/g haemoglobin, n = 15, respectively; p < 0:05 in both cases). Similarly erythrocyte malondialdehyde levels were significantly elevated in babies born to mothers with gestational diabetes (10.11 ±2.21 nM/g haemoglobin) when compared to controls (6.8 ± 3.75 nM/g haemoglobin) (p < 0:05). In the erythrocytes of mothers with gestational diabetes, malondialdehyde levels correlated significantly with glycated haemoglobin levels (p < 0:01). The results of this study indicate that the oxidative stress induced by gestational diabetes manifests as increased lipid peroxidation and protein oxidative damage in the erythrocytes of both mothers with gestational diabetes and their newborn infants.     

Initial insulin therapy in children and adolescents with type 1 diabetes mellitus

Weitzel D, Pfeffer U, Dost A, Herbst A, Knerr I, Holl R. Initial insulin therapy in children and adolescents with type 1 diabetes mellitus. Objective: The aim of the study was to define parameters that influence the initial insulin dosage in young subjects with type 1 diabetes regarding the amount of daily insulin, the ratios of basal and prandial insulin, and the insulin/carbohydrate ratios. Study design: We used a computer‐based registry (with prospectively collected data) in Germany and Austria, a software for the management and data documentation of diabetic patients (DPV), to analyze the initial insulin therapy in 2247 children with newly diagnosed type 1 diabetes to identify factors that influence diabetes therapy within the first 10 d. Results: For both genders, glucosylated hemoglobin A1c (HbA1c), blood pH at diabetes onset, and pubertal status are the major factors determining the initial insulin dosage calculated as the amount of daily insulin per kilogram body weight (kg), the basal and prandial insulin dose per kilogram, and day and the insulin/carbohydrate ratios for meals. The frequency of hypoglycemia correlated with increasing quotient of applied to calculated insulin dosage. Conclusion: The predictive factors of insulin requirement may exert beneficial effects on the assessment and adjustment of insulin therapy in young diabetic subjects at disease onset. On the basis of a multiple, linear regression, we suggest a formula to calculate the initial insulin therapy.     

Ambulatory blood pressure monitoring (ABPM) in normotensive adolescents with type 1 diabetes

Abstract: Objective: To evaluate 24‐h ambulatory blood pressure monitoring (ABPM) for early detection of hypertension in adolescents with type 1 diabetes mellitus (DM1). Design: Patients underwent fundoscopy, albuminuria determinations, two repeated autonomic cardiovascular tests, heart rate (HR) variation during deep breathing and blood pressure (BP) variation during sustained handgrip. Twenty‐four hour BP measurements were taken automatically by an oscillometric portable monitor. Setting: A specialty pediatric diabetes clinic and subjects' homes. Participants: Eighteen children aged 10–17 yr with 2+ yr of DM1, without long‐term complications, and 34 controls. Results: Higher ambulatory HR during the day than at night did not differ between DM1 subjects and controls. Mean systolic (s) and diastolic (d) BP in patients during the daytime were not significantly different from the control values. During the night, both sBP and dBP mean values in patients differed from those of controls. Statistical analysis of day and night HR and BP measurements were not different in both groups. The percentage decrease during the night in sBP and dBP was significantly smaller in patients than in controls. There were no differences by gender or duration of diabetes > or < 5 yr or by HbA1 above and below 10%. No difference in nocturnal sBP or dBP decline was observed between patients with or without abnormal autonomic test results. Conclusion: ABPM is more reliable than casual BP measurement in detecting early BP alterations during the night, before the appearance of microalbuminuria, in young patients with DM1.     

Improved glycemic control in adolescents with type 1 diabetes mellitus who attend diabetes camp.

OBJECTIVE: Diabetes camp has become a common part of medical practice worldwide. Although patients' knowledge and self-management of diabetes may improve after camp, improved glycated hemoglobin A1c (HbA1c) levels have not been consistently demonstrated. RESEARCH DESIGN AND METHODS: We performed a retrospective study of medical records at the Children's Medical Center Dallas Endocrinology Center for adolescents with type 1 diabetes aged 12-18 yr. We compared patients who did (n = 77) or did not (n = 106) attend Camp Sweeney, a regional 20-d diabetes camp. Some patients (n = 82) and their parents also completed measures of adherence, depression, and quality of life. RESULTS: HbA1c decreased over time in patients who attended diabetes camp {mean [+/-standard deviation (SD)] at baseline, (T1) = 8.6% (+/-1.8%) and at follow-up, (T2) = 8.3% (+/-1.6%)}, whereas it increased in those who did not attend [mean (+/-SD) at T1 = 8.4% (+/-2.1%) and at T2 = 8.9% (+/-2.3%)] (p < 0.005). Seven months after camp (T3), there were still significant differences in HbA1c between the camp and control groups (p = 0.04), with the difference because of persistent improvement for girls but not for boys. Patients' adherence (p < 0.05) and adjustment (p < 0.05) improved by parental report in those who attended camp; parents of patients who did not attend did not report the change. CONCLUSIONS: Attending Camp Sweeney is associated with improved glycemic control and parent-reported adherence and adjustment in adolescents with type 1 diabetes. Additional studies are needed to determine whether these findings can be generalized to other diabetes camps.     

应用胰岛素泵治疗儿童及青少年1型糖尿病对糖代谢的影响

为观察应用胰岛素泵治疗儿童及青少年1型糖尿病(T1DM)对糖代谢的影响 ,随访10例胰岛素泵治疗的T1DM患儿 ,分别观察胰岛素泵治疗前、后6个月的糖化血红蛋白值(HbA1c)、胰岛素用量、严重低血糖及酮症酸中毒发生次数的变化情况。结果显示 ,胰岛素泵治疗6个月后HbA1c 显著下降 ,治疗前为8.97 %±1.69 %,治疗后为7.51 %±1.17 % (t=2.52 ,P<0.05) ;胰岛素用量无显著下降 ;未发生严重低血糖和酮症酸中毒。表明胰岛素泵治疗可有效控制血糖 ,明显降低HbA1c,减少低血糖及酮症酸中毒的发生 ,是儿童及青少年T1DM常规治疗的较好选择。     

Signal-averaged electrocardiogram in children and adolescents with insulin-dependent diabetes mellitus

We report on the potential usefulness of the signal-averaged electrocardiogram (SA-ECG) in young patients with insulin-dependent diabetes mellitus (IDDM) to predict subclinical cardiovascular complications. Sixteen patients with IDDM and 18 age-matched healthy subjects were studied. The IDDM group included 4 males and 12 females, aged 7 to 20 y (mean 14.2 +/- 3.8 y, +/- SD). The duration from the onset of IDDM to the study ranged from 1.2 to 9.8 y (mean 5.4 +/- 3.8 y), and HbAlc value ranged from 6.6 to 12.4% (mean, 10.0 +/- 1.8%). SA-ECG was recorded and analyzed using the methods described by Simson. Values of filtered QRS duration (f-QRS), root mean square voltage (RMS), the duration of low amplitude signal (LAS) and late duration (LD) were calculated and compared between the groups. These parameters were not significantly different between the IDDM and control groups. However, in patients with poor glycemic control (HbAlc >10%), f-QRS was long and RMS was significantly low (p < 0.05, each) compared with the control group. Three patients with IDDM were positive for ventricular late potentials, although none had ventricular tachyarrhythmia. None of the control subjects showed ventricular late potentials. CONCLUSION: Certain parameters of SA-ECG showed abnormal values in IDDM patients with poor glycemic control. Thus, SA-ECG is a potentially useful and non-invasive method for the assessment of subclinical cardiac impairment in diabetic children and adolescents.     

Telemedical support to improve glycemic control in adolescents with type 1 diabetes mellitus

Introduction In this paper, we evaluated the feasibility of a telemedical (TM) support program and its effect on glycemic control in adolescents with type 1 diabetes mellitus (T1DM). Thirty-six adolescents (m=20, median age at the start of the study: 15.3 years (range: 10.7–19.3 years), median age at diagnosis: 9.3 years (2.1–13.8 years), median duration of disease: 6.4 years (1.0–12.8 years), HbA1c>8%, all on intensified insulin therapy) were randomized in a crossover trial over 6 months (3 months with TM, 3 months with conventional support and paper diary (PD)). During the TM phase, the patients sent their data (date, time, blood glucose, carbohydrate intake, insulin dosage) via mobile phone, at least daily, to our server and diabetologists sent back their advice via short message service (SMS) once a week.Results Glycemic control improved during the TM phase, while it deteriorated during the PD phase: TM-PD group HbA1c (%, median (range)): 9.05 (8–11.3) (at 0 months), 8.9 (6.9–11.3) (at 3 months), and 9.2 (7.4–12.6) (at 6 months), and PD-TM group: 8.9 (8.3–11.6), 9.9 (8.1–11), and 8.85 (7.3–11.7) (p<0.05). Patients rated the TM support program to be a good idea. Technical problems with General Packet Radio Service (GPRS) data transmission led to data loss and decreased patient satisfaction.Conclusion Our telemedical support program, VIE-DIAB, proved to be feasible in adolescents and helped to improve glycemic control.     

Predictors of glucose control in children and adolescents with type 1 diabetes mellitus

AIMS: To evaluate the glucose control [(as measured by hemoglobin A1c (HbA1c)], the factors associated with glycemic control, and possible explanations for these associations in a sample of children and adolescents with type 1 diabetes. METHODS: Data were collected on 155 children and adolescents, with type 1 diabetes mellitus, attending a multidisciplinary diabetes clinic in Portland, OR. Patients' hospital charts were reviewed to determine demographic factors, disease-related characteristics, and HbA1c level. RESULTS: Mean percent HbA1c was 9.3. Adolescents between the ages of 14 and 18 yr were in poorer metabolic control (adjusted mean percent HbA1c 0.56 higher than children 2-8 yr). Children who attended the clinic three to four times in the previous year were in better control (adjusted mean percent HbA1c 0.46 lower than those who visited two or fewer times and 1.11 lower than those who attended five or more times). Children with married parents were in better glycemic control than those of single, separated, or divorced parents (adjusted mean percent HbA1c 0.47 lower for children of married parents). This effect appeared to be mediated, in part, by the number of glucose checks performed per day. CONCLUSIONS: This study suggests that adolescents should be targeted for improved metabolic control. Diabetes team members need to be aware of changing family situations and provide extra support during stressful times. Regular clinic attendance is an important component of intensive diabetes management. Strategies must be developed to improve accessibility to the clinic and to identify patients who frequently miss appointments.     

Treatment of hypertension and microalbuminuria in children and adolescents with type 1 diabetes mellitus

Abstract: Nephropathy is the main cause of morbidity and mortality in patients with type 1 diabetes and, in adults, persistent microalbuminuria is the best marker of the consequent risk for its development. In the pediatric population, puberty represents the most important risk factor for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. As many as 50% of subjects may revert to normoalbuminuria. Hypertension is a further risk factor and may accelerate the progression of micro- and macrovascular complications. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects – hence they represent the drug of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific, they may become the obvious treatment choice in the near future. There is no consensus as to who should be treated and when treatment with renoprotective drugs should begin in the pediatric population, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review some models and controversial aspects of this issue are presented and discussed.     

Autonomic blood pressure control in children and adolescents with type 1 diabetes mellitus

Introduction:  Increased daytime blood pressure and reduced nocturnal dipping can already be found in children with type 1 diabetes mellitus. We hypothesized that impaired baroreflex sensitivity can cause this abnormal blood pressure behavior in children and adolescents with type 1 diabetes, reflecting an early stage of diabetic autonomic neuropathy.
Methods:  In the present study, we monitored beat-to-beat blood pressure and pulse interval non-invasively with portapres© in 38 patients with type 1 diabetes (7–18 yr) and 14 non-diabetic subjects (5–17 yr). The Trigonometric Regressive Spectral Analysis was used to assign spontaneous oscillations of blood pressure and pulse interval to defined frequency bands between 0.003 and 1.0 Hz and to calculate baroreflex sensitivity. Correlations with diabetes-specific data like hemoglobin A1c (HbA1c) and with 24-h blood pressure measurements were calculated.
Results:  The diabetic subjects displayed significantly less variance of blood pressure and pulse interval in the high frequency (HF) bands and a lower BRS. BRS decreased with higher HbA1c and daily insulin dose. We also saw significant changes in spectral variance of blood pressure and pulse interval with these parameters. Patients with higher sympathetic activity (LF/HF-ratio) during daytime measurements displayed more nocturnal dipping.
Conclusion:  Our data evidence impaired baroreflex sensitivity in children and adolescents with type 1 diabetes mellitus. We suggest spectral analysis of spontaneous blood pressure and pulse interval oscillations during night sleep to further pursue the role of baroreflex sensitivity in the etiology of the non-dipping phenomenon in diabetic patients.