Determinants of blood glucose variability in adolescents with insulin-dependent diabetes mellitus

Metabolic control and blood glucose variability in children with insulin-dependent diabetes mellitus (IDDM) during and after puberty were studied. Seventy-two children (43M, 29F), aged 10-19 years, with a 2-16-year duration of IDDM participated in the study. Fourteen of the patients were prepubertal (Tanner stage 1), 27 pubertal (Tanner 2-4) and 31 postpubertal (Tanner 5). They performed self-monitoring of blood glucose (SMBG) five times daily, every 2 days for 4 weeks. The SD (SDbg) for all values in each patient was calculated as a measure of blood glucose variability. Weight-length index, linear growth velocity and Tanner stage were recorded. Hemoglobin (Hb)A_Ic, alkaline phosphatase and sex hormone levels in serum were analyzed. Subjectively experienced hypoglycemic episodes were recorded. HbA_Ic levels showed no relation to Tanner stage. SDbg was lower in stage 5 than in stages 2-4 ( p = 0.02). There was no significant correlation between HbA _lc and SDbg, but the variability was significantly lower in individuals with mean blood glucose in the lower quartile compared with those in the upper three quartiles ( p < 0.001). Alkaline phosphatase concentration, as a measure of growth velocity, was the main independent determinant of SDbg ( r = 0.35, p < 0.005). There was an inverse correlation between levels of sex hormones and SDbg. We conclude that blood glucose variability is lower after than during puberty. This variability seems to be related to linear growth velocity or its biochemical marker.     

A prospective, longitudinal study examining the development of retinopathy in children with diabetes

A prospective longitudinal study of 182 children and adolescents with diabetes revealed that during a follow-up of 2.5 ± 0.5 years the prevalence of retinopathy increased from 10.8% to 28.0%, corresponding to an annual increase of 7%. Retinopathy was diagnosed at a mean age of 15.3 years (95% CI, 14.8–15.8 years) after a mean duration of diabetes of 8.9 years (95% CI, 8.0 9.7 years). Prepubertal years of diabetes contributed to the risk of developing retinopathy. The initial signs of retinopathy were microaneurysm(s) in 56%, microaneurysm(s) and haemorrhage(s) in 30%, and haemorrhage(s) in 10%. A combination of microaneurysm, haemorrhage and cotton-wool spot was observed in 2%, and microaneurysms, haemorrhage and an IRMA lesion were seen in 2%. Most of the initial lesions disappeared during the follow-up period, but at the same time new lesions developed elsewhere in the retina in all but 2 cases. In 8 patients (15% of patients with retinopathy) aged 13.7 19.8 years and having had diabetes for 3.7–14.8 years, retinal changes progressed from mild to a more advanced background retinopathy. A higher glycated haemoglobin level during puberty was the only factor which differentiated these patients from control patients matched for sex, age, puberty and duration of diabetes.     

Continuous subcutaneous insulin injection for self-care of young patients with insulin-dependent diabetes mellitus

Continuous subcutaneous insulin injection was used for the self-care of five patients aged 10–18 years with insulin-dependent diabetes mellitus. After an introduction to the concept and procedures for continuous subcutaneous injection, the patients soon became familiar with self-care using an insulin pump at home and at school. Three months later, the control of blood glucose improved with smaller doses of insulin in four cases and milder hypoglycemia was observed compared to when using multiple injections. Significantly decreased variations and lowered means of early morning blood glucose values were observed and seemed to explain the reason for better glycemic control. Buffered regular insulin continuously injected by pumps brought a more stable nocturnal blood glucose level compared to isophane insulin injected at bedtime, the absorption of which seemed to vary considerably. On the contrary, unbuffered regular insulin injected by pumps brought frequent nocturnal hypoglycemia, sudden worsening of glycemic control and skin infections and thus, was deemed inadequate for continuous subcutaneous injection.     

Calcitonin secretion in children with insulin-dependent diabetes mellitus

To test the hypothesis that calcitonin (CT) deficiency may contribute to bone mineral loss in insulin-dependent diabetes mellitus (IDDM), we studied basal and calcium stimulated (2 mg/kg body wt. in 5 min) CT levels in 15 children with IDDM and osteopenia. Ten age-sex matched healthy children were studied as controls. Since extractable CT (exCT) allows more sensitive and specific measurement of CT monomer, we measured both total serum CT (tCT) and exCT. Diabetic children had slightly but significantly (P<0.05) higher basal levels of both tCT (24.5±7.1 ng/l) and exCT (5.6±1.6 ng/l) than controls (tCT: 18.7±5.4 ng/l; exCT: 4.3±1.2 ng/l). Calcium stimulation test pointed out significant increase (P<0.001) of tCT and exCT in both groups with peak values not significantly different in IDDM in respect to controls. However, diabetic children showed a reduced CT reserve evidenced by a lower peak/basal ratio (diabetics: tCT 1.68, exCT 1.84; controls: tCT 2.49, exCT 2.88) and by a more rapid decrease in CT levels. We conclude that CT deficiency is not a causative factor of diabetic osteopenia. The slightly higher basal CT values suggest that an increased bone reabsorption may be operative in IDDM and it stimulates CT secretion. This chronic C cell stimulation may induce the reduction in CT reserve observed employing the calcium infusion test.     

HLA system in Chinese children with insulin-dependent diabetes mellitus

ABSTRACT. HLA in 12 unrelated Chinese paediatric patients with insulin dependent diabetes mellitus (IDDM) were found to have an increased frequency of BW22, B17 and AW33.
BW22 was observed in 5/12 (41.7%) of IDDM patients compared to 40/330 normal unrelated Chinese controls (p < 0.005, RR = 5.2). AW33 and B17 were observed in 6/12 (50.0%) and 7/12 (58.3%) of IDDM patients respectively, compared to 36/330 and 46/330 in the normal controls respectively (AW33: corrected p < 0.0026, RR = 8.2, B17: corrected p < 0.0026, RR = 8.6). HLA B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of this study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states.     

Rapid onset of severe retinopathy, cataracts and neuropathy in young patients with diabetes mellitus

It is rare for young diabetic patients to develop severe complications in the first years of their disease. We describe three patients, aged 14-23 years who developed cataracts and severe retinopathy within one to five years of diagnosis of diabetes. During the same period, one patient developed peripheral neuropathy and a second severe autonomic neuropathy. Rapid development of chronic complications in these patients raises the possibility that there may be a subset of patients with unusual susceptibility to complications. We re-emphasize the need for vigilant monitoring for complications in young diabetic patients, even in the first few years of their disease. In particular, young patients with visual complaints should be evaluated carefully for evidence of treatable eye disease.     

Annotation Microvascular complications of insulin-dependent diabetes: Risk factors, screening and intervention

The ability to detect subclinical signs of the microvascular complications of diabetes during adolescence and our increased understanding of risk factors for their development provide an opportunity to prevent irreversible organ damage. Glycaemic control makes a major contribution to the risk and progression of microvascular complications. However, the unique psychological and physiological changes of childhood and adolescence present a considerable challenge for those attempting to reduce the burden of adult microvascular disease.     

Higher drive for thinness in adolescent males with insulin-dependent diabetes mellitus compared with healthy controls

Eating behaviour in adolescent males with insulin-dependent diabetes mellitus (IDDM) living in central Sweden was compared with that of healthy age-matched male controls using the Eating Disorder Inventory for Children and an interview. The patients were heavier than controls (p = 0.004) and had higher Drive for Thinness scores (p = 0.002). None was diagnosed as having a current eating disorder. Conclusion: The results of the study may indicate an increased risk of future eating disorders in males with IDDM.     

Circulating thyroid antibodies and thyroid function studies in children and adolescents with insulin-dependent diabetes mellitus

Significant high titres (1400–125,600) of circulating thoroid microsomal antibodies (MCHA) were found in the sera of 5 out of 59 non-ketoacidotic, insulin-dependent diabetic (IDDM) patients (mean age 14.5 years). Among these five patients (four females, one male), all of whom were over 11 years, two also had thyroglobulin antibodies. Increased thyrotropin (TSH) response to TRH was found in 3/5 MCHA positive patients and in 3/54 without circulating MCHA. Serum thyroxine (T₄) and free T₄ (FT₄) average values were significantly lower (P<0.01 and P<0.001) in diabetics (7.1±1.8g/dl and 10.2±3.1 pg/ml, x±SD) as compared to normal sex and age matched controls (8.9±1.9 g/dl and 12.2±2.2 pg/ml, respectively). T₄ and FT₄ values were inversely related to the duration of the disease. Subnormal T₄ values were found in six (five females and one male) patients, four of whom had subnormal FT₄ values. No patient had low triiodothyronine (T₃) and high reverse T₃ (rT₃) values, i.e. none displayed the biochemical pattern of the low T₃ syndrome described with ketoacidotic status. This indicates also a satisfactory compensation of IDDM in all the patients. At the time of study no patient (including also those with circulating MCHA and TGHA and with TSH hyper-response to TRH) showed either thyroid size enlargement or clinical features of thyroid dysfunction including impaired growth and bone age retardation.Abbreviations MCHA thyroid microsomal antibodies - IDDM insulin-dependent diabetes mellitus - TSH thyrotropin - T₄ serum thyroxine - FT₄ free T₄ - T₃ triiodo thyronine - FT₃ free T₃ - rT₃ reverse T₃ - TGHA thyroglobulin antibodies - TRH thyrotrophin releasing hormone     

Delayed menarche in young German women with type 1 diabetes mellitus: recent results from the DPV diabetes documentation and quality management system

Background  Findings have been inconsistent regarding the effect of T1DM (type 1 diabetes) on age at menarche. Objective  The purpose was to investigate in young German women with T1DM menarcheal age and factors potentially affecting menarche, including glycemic control, BMI (body mass index), relative T1DM duration (proportion of life with diabetes), insulin dose, and insulin therapy intensity. Initiated in 1990, the DPV program is an ongoing, prospective long-term longitudinal follow-up study to benchmark the quality of care provided to pediatric and, more recently, adult diabetes patients. Two hundered two German diabetes centers participated in nationwide data collection. Based on ethnicity and the availability of menarche and T1DM onset data as the main inclusion criteria, 643 young German women were selected from 11,629 female T1DM patients aged <20 years, recruited by referral, clinic or hospital ascertainment, or self report. Mean age at menarche (±SD) was 13.22 ± 1.31 years, representing a delay of 0.52 years (p < 0.001) relative to the general population. Significant delay (p < 0.05) was also found for relative T1DM duration, BMI SD score, insulin dose, and HbA1c level, with a 1% increase in HbA1c resulting in a delay in menarche by 0.07 years. Conclusions  Age at menarche is delayed in type 1 diabetes mellitus. The delay increases with relative T1DM duration and poor quality of glycemic control.     

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     

Anticardiolipin antibodies in children and adolescents with insulin-dependent diabetes mellitus

Anticardiolipin antibodies were determined in 29 diabetic children and adolescents, aged 3.9–26.8 years, with disease duration from 1 month to 19 years. Anti-islet cell antibodies (ICA-IgG and CF-ICA), anti-insulin antibodies (IAA), antithyroid antibodies and non organ-specifc (NOSA) antibodies were also determined. Patients were grouped according to insulin-dependent diabetes mellitus (IDDM) duration: group I (n=11)<6 months, and group II (n=18)>5 years. Eleven of group II patients showed precocious signs of micro-angiopathic complications. Forty-two age- and sex-matched healthy subjects served as controls. IgG and IgM anticardiolipin antibodies were evaluated by ELISA and their results expressed as arbitrary units (AU). IgG anticardiolipin antibodies were found in 7 patients (24%), while IgM anticardiolipin antibodies were absent in all. IgG anticardiolipin antibodies were more frequent in IDDM patients than in controls (P<0.005) and group I (in 6 out of 11 patients; 54.5%) than in group II (in 1 out of 18 patients; 5.5%) (P<0.025). In five out of six group I patients with IgG anticardiolipin antibodies, ICA-IgG and/or CF-ICA were also found. No correlation was observed between anticardiolipin and other auto-antibodies, micro-angiopatic complications, and HLA typing.     

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.     

桂林市儿童Ⅰ型糖尿病发病率调查

目的　了解桂林市儿童Ⅰ型糖尿病（ＩＤＤＭ） 发病情况。方法　按照ＷＨＯ 儿童糖尿病多国计划（ ＷＨＯ ＤＩＡ ＭＯＮＤ计划）登记方法,采用捕获—再捕获方法,共调查１ ６７２ ２５７ 名儿童。结果　１９８９ 年～１９９８ 年间１５ 岁以下儿童发病率男性为０．５８／１０ 万,女性０ ．６２／１０ 万,总发病率为０．６０／１０ 万。结论　桂林市ＩＤＤＭ 发病率与ＷＨＯＤＩＡＭＯＮＤ 计划获得的多国发病率情况相一致,与东方及中国其它地区的情况也相近。     

Distinctive characteristics of diabetes mellitus after hematopoietic cell transplantation during childhood

We report on six patients who developed diabetes mellitus after hematopoietic cell transplantation (HCT). The prevalence in our cohort of long-term survivors after HCT performed below 18 yr of age was 3%. The median age at onset of diabetes was 22.4 yr (range 11.3-34.4). The median period between HCT and diabetes was 10.1 yr (range 5.6-22.1). Five out of the six patients received total irradiation therapy and five had other endocrinological abnormalities. The onset of diabetes in all patients was insidious and none had diabetic ketoacidosis. Body mass indexes at diabetes onset were within normal levels. The clinical and laboratory features that characterized our patients with diabetes after HCT make it difficult to classify them as having type-1 or type-2 diabetes. The relatively high prevalence of diabetes and its insidious onset in this group of patients, advocate clinicians to evaluate carefully even slight variations in fasting blood glucose, usually included in the routine biochemistry follow-up. These data also suggest that HbA1c and oral glucose-tolerance test should be added to the follow-up program of late complications if fasting blood glucose levels are slightly increased.     

Documented latent coeliac disease in a child with insulin-dependent diabetes mellitus

The histological development of coeliac disease has been documented in a child with insulin-dependent diabetes mellitus (IDDM). Serum antigliadin IgG was temporarily present at the onset of IDDM. It is assumed that IDDM may exert a trigger effect on the development of coeliac disease.     

Non-genetic risk determinants for type 1 (insulin-dependent) diabetes mellitus in childhood

Using the prospective Hungarian childhood diabetes register, a nationwide case-control study was carried out to investigate the possible role of various non-genetic factors as risk determinants for type 1 diabetes in childhood. A questionnaire (covering family characteristics, social status, fetal and perinatal events, breast-feeding habits, infectious diseases and stressful life events) was sent by mail to all incident diabetic children in 1990 ( n = 163) and to two referent children (for each diabetic chdd), matched for age, sex and county. Diabetic children had a tendency to have mothers > 35 years of age (odds ratio (OR) = 3.52; 95% confidence intervals (CI) 0.74–16.79), a lower proportion of their mothers had higher education (OR = 1.69; 95% CI 0.95–3.0) and these children tended to move home more frequently (OR = 1.99; 95% CI 0.97–4.1). Although the duration of exclusive breast feeding was similar in both groups, the proportion of diabetic children who received no breast milk tended to be higher (OR= 1.76; 95% CI 0.91–3.4). A higher proportion of diabetic children reported non-specific infections (OR = 2.94; 95% CI 1.19–7.21) and the number of stressful life events was higher in diabetic children aged 10–14 years (OR = 3.9; 95% CI 1.14–13.27). As the risk determinants for childhood insulin-dependent diabetes mellitus identified in our low-risk population appear to be similar to those detected in the genetically different, high-risk Swedish population, our study strongly supports an etiological role for these non-genetic risk factors in IDDM.     

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目的应用动态血糖监测系统(CGMS)观察1型糖尿病患儿血糖控制情况,寻找评价和改善血糖控制的方法。方法收集复旦大学附属儿科医院2003年10月至2004年6月内分泌科门诊随访的儿童1型糖尿病患者28例,男16例,女12例,年龄(13.1±4.5)岁,病程(5.5±3.4)年,其中21例采用每天多次胰岛素注射(MDI),另7例使用胰岛素泵连续胰岛素输注(CSII)治疗。动态监测血糖3d,同时指尖血糖监测≥4次/d。结果(1)研究对象体重指数(BMI)为(19.4±3.0)kg/m2,糖化血红蛋白(HbA1c)为(8.4±1.6)%。CSII组HbA1c(8.2±1.0)%,MDI组HbA1c(8.5±1.8)%,差异有显著性意义(P<0.05);(2)CGMS发现22例77次餐后2h高血糖,CSII组4例(57.1%),每例出现1次,MDI组18例(85.7%),每例出现(4.1±2.5)次,差异显著(P<0.01);(3)CGMS发现17例79次低血糖,持续时间(76.6±92.8)min,而指尖血糖监测仅发现19次低血糖;白天低血糖持续时间(41.5±39.1)min,夜间(112.4±117.1)min,夜间低血糖持续时间显著长于白天(P<0.01)。(4)HbA1c≤8%组餐后高血糖发生率低于HbA1c>8%组(P<0.05),而低血糖的发生率显著升高(P<0.01)。结论1型糖尿病患儿多数存在低血糖和餐后高血糖;动态血糖监测系统是发现血糖异常波动的有效工具。动态血糖监测对指导1型糖尿病治疗,调整胰岛素剂量,从而改善血糖控制有着重要的临床意义。     

分型不明的婴幼儿糖尿病病因学探讨

目的探讨分型不明的婴幼儿糖尿病的病因。方法回顾分析2013年-2016年收治,3岁内起病的自身抗体阴性胰岛素依赖1型糖尿病(T1DM)患儿的临床资料。结果共收集19例患儿,男12例、女7例,起病年龄8个月～3岁;主要症状为乏力、消瘦、多饮、多尿;糖化血红蛋白8.6%～12%,合并酮症酸中毒14例;19例患儿的胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GAD65-Ab)、胰岛素抗体(IAA)均为阴性,胰岛素水平正常偏低。采用二代测序及甲基化MLPA方法检测28个糖尿病相关基因,2例患儿阳性;其中1例携带HNF1A c.1699GA,为已报道的杂合突变,来自其血糖正常的母亲;另1例携带CEL基因的c.2214delT,为尚未见报道的杂合突变,来自其空腹血糖正常的父亲。结论自身抗体阴性T1DM与单基因糖尿病之间存在交叉与重叠,二代测序对早期明确诊断有重要意义。     

Transient focal neurologic deficits associated with hypoglycaemia in children with insulin-dependent diabetes mellitus

We describe 54 transient focal neurologic deficits (TFND) episodes in 44 children under 18 y observed retrospectively during a 5-y period (1991–96). Mean age and duration of insulin-dependent diabetes mellitus (IDDM) were 8.4 and 3.4 y, respectively. None of the children had a history of seizure disorder and only one had a personal history of migraine. Twenty-nine episodes were characterized by right- and 25 by left-sided hemiparesis. Three of six patients who presented more than one event had alternate episodes of right- and left-sided hemiparesis. On 8 occasions the episode was preceded by a brief convulsion, in 39 it was not witnessed, and in 7 it was certainly absent. Hypoglycaemia (<2.77 mmol/l) was documented on 26 occasions. On 18 of these 26 occasions, the episodes did not resolve promptly after sugar administration. The clinical course was benign, all patients remained neurologically normal and none developed migraine at follow up. Episodes of TFND were associated with hypoglycaemia in the majority of our cases and we do not consider invasive investigations to be mandatory, since the long-term prognosis was invariably good.