Protein-bound homocyst(e)ine in normal subjects and in patients with homocystinuria

A method was developed to quantitate protein-bound homocyst(e)ine using 2-mercaptoethanol. Protein-bound homocyst(e)ine was discovered in the plasma from normal individuals, ranging from 0.5--2.2 nmole/ml. In two obligatory heterozygotes for classical homocystinuria, plasma protein-bound homocyt(e)ine was 3.5 and 4.8 nmole/ml, respectively. Untreated homozygotes showed approximately a 40-fold increase of plasma protein-bound homocyst(e)ine. Furthermore, using conventional methods, no free homocystine was detectable in the supernatant of plasma precipitate from two classical homocystinuric patients treated with pyridoxine, but plasma protein-bound homocyst(e)ine showed a 10-fold increase. Protein-bound homocyst(e)ine was also demonstrated in the liver, kidney, and brain tissues from a patient with methylenetetrahydrofolate reductase deficiency.     

Longitudinal growth in children and adolescents with type 1 diabetes

Objective

To study longitudinal growth in children with type 1 diabetes mellitus.

Methods

Anthropometry, disease duration, insulin regimens and HbA1C recorded from patients with diabetes enrolled in a specialty clinic.

Results

160 children (75 boys; mean (SD) age 9.4 (3.3) y) were enrolled. 35% children had low (<25^th centile) height velocity. Disease duration and HbA1C affected height velocity (adjusted for puberty). Children on basal-bolus had higher height velocity Z scores than those on a split mix regimen [(0.5(1.6) vs. -0.3(1.4), P<0.05)]. Children diagnosed before 5 years of age had lowest height velocity. Of the children who reached final height, 53% remained below target height.

Conclusion

Children with type 1 diabetes mellitus have lower height velocity compared to healthy children; those diagnosed at younger age were at higher risk for growth failure.

     

Monitoring for retinopathy in children and adolescents with type 1 diabetes

In children with an average diabetes onset at 11 y of age, the first retinal changes can be expected after a median diabetes duration of 9y, while the median time until clinically relevant background retinopathy is 14 y. Periodic examinations of the retinal status become necessary with the onset of puberty or after 5y of diabetes duration. Only sensitive methods should be used for retinopathy screening; the minimum recommended standard is a stereoscopic slit-lamp biomicroscopic examination in mydriasis. The degree of glycaemic control, both before and after puberty, appears to be of outstanding importance for the development of retinopathy, but the contribution of other factors (arterial blood pressure, lipid abnormalities, sex steroids, smoking and genetic factors) may be of varying relevance in the individual patient. Thus, to improve the long-term prognosis for children with diabetes appropriate screening for retinopathy and associated risk factors is mandatory.     

Individualized insulin therapy in children and adolescents with type 1 diabetes

The most important point about individualized therapy is to make it flexible to fit the needs of the patient. These needs are determined by age, pubertal status, treatment schedule, exercise, intelligence, education and socioeconomic status. In addition, major emphasis should be placed on the dietary needs, attitude and ability of the patient. Aspects of insulin regimens that can be adjusted include number of injections per day, timing of injections and the type of insulin used. Several factors that affect insulin action should also be considered, including the presence of insulin antibodies, the amount of subcutaneous fat, injection technique and muscular activity. Insulin pump therapy in childhood and adolescence may also be considered in certain cases. Controversial areas in childhood diabetes therapy include the number of daily injections, whether porcine insulin has any advantages, use of multiple doses of intermediate- and long-acting insulin, mixing regular insulin and short-acting insulin analogues, strategies to prevent hypoglycaemia and the importance of choice of injection sites in childhood.     

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.     

Vulvovaginal candidiasis in children and adolescents with type 1 diabetes mellitus

In this prospective study we investigated the frequency of vulvovaginal candidiasis, the results of yeast cultures and detection of ketoconazole resistance in female children and adolescents with type 1 diabetes mellitus (DM1). The study consisted of 35 patients with DM1 (age 1.7-20 years) and 22 controls (age 1.5-18 years). Age, duration of DM1 and evidence of genital symptoms were recorded initially. After a pelvic examination, two separate swabs and samples for blood glucose and hemoglobin A1c (HbA1c) were taken. One of the swabs was used for direct examination and the second was placed on Sabouraud's dextrose agar and incubated. In vitro susceptibility of Candida species to ketoconazole was established by using Etest (AB B1ODISC). Candida species were isolated in 32 of 61 (52.5%) swabs of patients with DM1 and five of 22 (18.2%) of the control group. The predominant Candida species isolated from patients with DM1 were C. albicans (72.7%), C. glabrata (22.7%), C. tropicalis (2.3%), and C. parapsilosis (2.3%). The mean HbA1c in diabetic patients from whom Candida species were isolated was significantly higher than that of patients without Candida infection (p = 0.002). Most of the C. glabrata isolates were significantly resistant to ketoconazole. During the follow-up of patients with DM1, genital candidiasis is generally overlooked. It should not be forgotten that species other than C. albicans might cause genital candidiasis.     

Lipoprotein composition in children and adolescents with type 1 diabetes mellitus

Atherosclerotic cardiovascular diseases are the major causes of morbidity and mortality in patients with diabetes mellitus. Both quantitative and qualitative abnormalities of lipo-proteins are associated with the development of atherogenesis. In this study, the prevalence of dyslipidemia and the relative levels of glycosylated lipoproteins in 20 children and adolescents with type 1 diabetes mellitus were determined. Lipid profile, apolipoproteins A-I and B, Lp(a) and LpA-I in plasma were assayed. LpB and glycosylated HDL and LDL were evaluated by ELISA. Diabetic patients and controls had normal lipid profiles, but the diabetic group showed significantly higher LpA-I and lower LpA-I:A-II concentrations than controls. The diabetic group showed a significantly higher glycosylation level of HDL than controls and did not show a statistical difference for glycosylated LDL. No significant correlation between glycosylated lipoproteins, glycemia or HbA1c was found. In conclusion, these results suggest that type 1 diabetic patients develop important qualitative lipid abnormalities.     

Plasma homocysteine levels in children and adolescents with type 1 diabetes

OBJECTIVE: Hyperhomocysteinemia has been established as a risk factor for cardiovascular disease. The objective was to investigate total plasma homocysteine concentrations in children and adolescents with type 1 diabetes and a control group. METHOD: Twenty-seven children with type 1 diabetes and 27 subjects of an age- and sex-matched control group were recruited. Fasting samples were collected for plasma total homocysteine, serum vitamin B12, folate, and creatinine. RESULTS: Fasting total homocysteine concentrations showed no difference between patients and controls (5.6 +/- 2.9 micromol/L vs 5.7 +/- 2.2 micromol/L; p greater than 0.05). The diabetic patients had significantly higher serum folate than the healthy controls (11.4 +/- 3.3 ng/mL vs 9.4 +/- 4.1 ng/mL; P = 0.02 and higher serum B12 than the control group (282.8 +/- 119 pg/mL vs 228.5 +/- 50.9 pg/mL; P = 0.03). Total plasma homocysteine concentration correlated with age (r = 0.44, P = 0.02), weight (r = 0.56, P = 0.002), body mass index (r = 0.57, P = 0.002), folate (r = -0.48, P = 0.01), and creatinine (r = 0.41, P = 0.03) in diabetic patients. In stepwise multivariate regression model for diabetics, the independent correlates for total plasma homocysteine concentration was folate (P = 0.002). CONCLUSION: We concluded that fasting plasma total homocysteine concentrations were within normal limits in children and adolescents with type 1 diabetes who were without any clinical evidence of microvascular and macrovascular complications.     

儿童青少年1型糖尿病患者胃动力调查结果分析

目的探讨不同病程1型糖尿病患儿胃动力变化及血糖对胃动力的影响。方法正常对照组（A组）24例。1型糖尿病组49例,其中B组为新诊断者28例,平均病程1.5个月;C组为病程3年以上者21例,平均病程6.3年。对上述对象做胃电图检查。糖尿病组进行钡条胃排空试验,同时测定空腹和餐后2h血糖。问卷调查消化道症状。结果问卷调查显示,B组仅1例有消化道症状（占3.6%）,C组有消化道症状10例（占47.6%）,两组差异有统计学意义（P=0.001）。B组有4例出现胃排空延迟,C组有1例,两组差异无统计学意义（P=0.54）。两组胃电图与正常对照组相比,餐前、餐后,胃窦、胃体振幅差异无统计学意义;B组胃体餐后频率低于A组（P〈0.01）;C组胃窦、胃体餐后频率均低于A组（P〈0.05）;B组胃窦餐前振幅低于C组（P〈0.05）。未发现血糖水平、糖化血红蛋白（HbA1c）与胃排空、胃电参数的相关性（P〉0.05）。结论糖尿病组尤其是长病程组消化道症状发生率显著高于正常对照组。儿童青少年1型糖尿病患者病程早期可见胃排空延迟,糖尿病患儿餐后胃电频率下降,提示儿童青少年1型糖尿病患者早期即可出现胃动力异常。     

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.