Psycho-social aspects of children and adolescents with diabetes

The diagnosis of diabetes mellitus, a life-long disease with many possible complications, has a dramatic impact upon the entire family, precipitating a state of “shock”. The psychological problems in diabetes should be divided in 3 periods : at diagnosis (other diseases or tension existing in the family and not related to diabetes, socio-economic state); initial adaptation period (acceptance to be “different”, adjustment to rules of control such as daily injection of insulin, self blood glucose monitoring or urine testing, changing of nutritional habits, etc.), and long term coping (self-image, family dynamics, social activities, school achievements, vocational rehabilitation and continuing compliance. Counselling of the psychological problems is an ongoing need and is best delivered when the treating team included psychologists and social workers     

Sulfonylurea challenge test in subjects diagnosed with type 1 diabetes mellitus

Background: Patients with early onset diabetes because of defects in glucose‐stimulated insulin secretion (GSIS) may respond better to sulfonylureas than insulin treatment. Such patients include those with monogenic disorders, who can be differentiated from autoimmune type 1 diabetes mellitus (T1DM) by genetic testing. Genetic testing is expensive and unknown defects in GSIS would not be diagnosed. Aims: We propose a sulfonylurea challenge test to identify patients who have been clinically diagnosed with T1DM, but those who maintain a preferentially sulfonylurea‐responsive insulin secretion. Materials & Methods: A total of 3 healthy controls, 2 neonatal diabetes mellitus (NDM) subjects, 3 antibody‐positive (Ab+T1DM), and 12 antibody‐negative (Ab?T1DM) subjects with type 1 diabetes, were given an intravenous bolus of glucose followed by an oral dose of glipizide. Results: Healthy controls showed a robust C‐peptide increase after both glucose and glipizide, but NDM subjects showed a large increase in C‐peptide only following glipizide. As expected, 2 of 3 Ab+T1DM, as well as 11 of 12 Ab?T1DM showed no response to either glucose or glipizide. However, 1 Ab?T1DM and 1 Ab+T1DM showed a small C‐peptide response to glucose and a marked positive response to glipizide, suggesting defects in GSIS rather than typical autoimmune diabetes. Discussion: These data demonstrate the feasibility of the sulfonylurea challenge test, and suggest that responder individuals may be identified. Conclusions: We propose that this sulfonylurea challenge test should be explored more extensively, as it may prove useful as a clinical and scientific tool.     

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。     

HLA class II genetic association of type 1 diabetes mellitus in Czech children

Abstract:  To examine human leukocyte antigen (HLA) class II association of type 1 diabetes mellitus (DM) in Czech children, we performed a case–control study of 261 patients diagnosed before the age of 15 and 289 non-diabetic control children. Complete HLA-DQA1, DQB1 genotyping and DRB1*04 subtyping were carried out by polymerase chain reactions with sequence-specific primers. The effect of the DRB1*04 subtypes was studied in DRB1*04 alleles carried on DQB1*0302-DQA1*03 haplotypes. The risk was statistically evaluated by testing 2 × 2 tables, considering corrected p-values < 0.05 significant. The DQB1*0302 (odds ratio, OR = 9.0), DQB1*0201 (OR = 3.4) and DQA1*03 (OR = 7.5) alleles were significantly associated with diabetes risk, while the DQB1*0602 (OR = 0.02), DQB1*0301 (OR = 0.08), DQB1*0503 (OR = 0.13), DQB1*0603 (OR = 0.20), DQA1*01 (OR = 0.28) and DQA1*02 (OR = 0.26) alleles were significantly protective. Of the DQA1-DQB1 genotypes, we point out the extremely high risk of OR = 116 conferred by HLA-DQA1*05-DQB1*0201/DQA1*03-DQB1*0302. Among DRB1*04 subtypes, DRB1*0403 was significantly protective (OR = 0.05, CI 95% 0.01–0.45). Since none of the remaining DRB1*04 subtypes was associated with type 1 DM, our study may present another piece of evidence that the DRB1*0401 and DRB1*0404 alleles do not modify type 1 diabetes risk generally in European populations.     

Etiology and outcome of childhood and adolescent diabetes mellitus in North India

The etiology of childhood onset diabetes mellitus (DM) varies between regions and races, and its long-term outcome is affected by social and economic factors. There are scant data on the etiology of childhood DM and outcome of multidisciplinary team management from developing countries. We retrospectively analyzed case records of 160 predominantly middle socio-economic group patients with onset of DM < or =18 years of age for etiology and features at presentation. In addition, we prospectively studied acute and chronic complications and metabolic control in a subset of 67 patients. Type 1 DM comprised 81%, type 2 DM 8%, and fibrocalculous pancreatic DM 9% of patients. Mean HbA1c was 8.0+/-1.5%. Retinopathy was present in 22% and nephropathy in 18% of those with DM duration > or =5 years (mean age 21.2+/-6.8 years, mean duration 10.2+/-4.6 years). The frequency of ketoacidosis and severe hypoglycemia was 5.0 and 3.3 episodes per 100 patient years. Mortality was 7% over 823 person years of follow up. We conclude that fairly good metabolic control is achievable in a middle socio-economic population in India, with the assistance of a diabetes education program. The frequency of microvascular complications is comparable to that in the literature. However, mortality remains unacceptably high.     

Hypoglycemia in diabetes among children and adolescents

Hypoglycemia is one of the most common early complications in insulindependent diabetes mellitus (IDDM). Hypoglycemia in children may be considered a risk factor for brain damage and later intellectual impairment, and carries with it a high degree of child and parental anxiety. Recent studieshave shown that in IDDM patients, and especially in those on intensive therapy,there is a defect in glucose counter-regulation, increased frequency of hypoglycemic episodes, loss of hypoglycemic awareness and responsiveness. Autonomie neuro-pathy, glucagon deficiency and low catecholamine responsewere implied in the pathogenesis of these disorders. In addition, uncontrolled IDDM patients show hypoglycemic symptoms at a higher blood glucose level. These recent observations may suggest that attempts to improve metabolic control may increase the risk of severe hypoglycemia. If so, some alterations in our therapeutic goals must be considered.     

Medication‐induced diabetes mellitus

Epidemiological studies and case reports have demonstrated an increased rate of development of diabetes mellitus consequent to taking diverse types of medication. This review explores this evidence linking these medications and development of diabetes and presents postulated mechanisms by which the medications might cause diabetes. Some medications are associated with a reduction in insulin production, some with reduction in insulin sensitivity, and some appear to be associated with both reduction in insulin production and insulin sensitivity.     

Ocular complications in young adults with insulin-dependent diabetes mellitus since childhood

A cross-sectional study in 80 insulin-dependent diabetic patients born 1963–1968 who experienced the onset of diabetes before 15 years of age showed that at a mean age of 21.6 (range 17–25) years and after a mean duration of diabetes of 13.3 (range 6–24) years, 80% of the patients had retinopathy: 70% had background and 10% proliferative changes. Retinopathy correlated with the duration of the diabetes and poor glucose control at 15 years of age but not with the actual level of glycated haemoglobin. The severity of retinopathy was worse in women than in men. One patient (1.2%) was blind. Two patients had had cataract operations and 66% had myopic refraction in one or both eyes. In 61 patients a further period of ophthalmological follow-up of 3–4 years was included. After 20 years of diabetes, all had retinopathy and 29% had proliferative changes: 33% had received laser treatment after 8–27 (mean 16.1) years of diabetes. Altogether, 2 patients (2.5% of the original series) were blind. For prevention of diabetic retinopathy and blindness, good glucose control from puberty and careful ophthalmological follow-up after transfer of the patient from paediatric to adult diabetes care play major roles.     

Sulfonylurea-responsive diabetes in childhood

We describe a family in which 3/6 siblings had transient, relapsing neonatal diabetes. The father and another sibling had diabetes diagnosed at 20 and 9 years old, respectively. All affected individuals carried the same KCNJ11 gene mutation. In all, sulfonylurea treatment permitted cessation of insulin treatment, with improved glycemic control.     

Clinical picture of childhood type 1 diabetes mellitus in the Eastern Province of Saudi Arabia

Abstract: Aim: Study of the clinical presentation and laboratory data of type 1 diabetes in the Eastern Province of Saudi Arabia.
Methods: The medical records of all affected children during the period 1986–1997 were reviewed for the analysis of clinical and laboratory data.
Results: Type 1 diabetes was diagnosed in 46 children, 27 girls and 19 boys, with a mean age at diagnosis of 9.0 yr. The mean duration of symptoms prior to diagnosis was 12.5 d. Depressed consciousness occurred in 10.8% of the patients (none was comatose) and ketoacidosis in 77%. There was no episode of increased intracranial pressure during treatment, nor was there any death. There was a correlation between the central nervous system depression and the degree of hyperglycemia, and also with the severity of acidosis.
Conclusions: Although more than three quarters of patients with type 1 diabetes had ketoacidosis on presentation, none was comatose or developed clinical cerebral edema during treatment. The presentation of type 1 diabetes in children from Saudi Arabia seems to differ from reports from developed countries.     

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.     

Clinical presentation of childhood type 1 diabetes mellitus in the Al-Madina region of Saudi Arabia

AIM: To describe the clinical pattern and the laboratory characteristics at presentation of childhood type 1 diabetes mellitus in the Al-Madina region of the north-west province of Saudi Arabia. METHODS: The clinical and laboratory data of a total of 230 children who presented with diabetes during a 10-year period (1992-2001) were retrospectively analyzed based on hospital records. RESULTS: Polyuria and polydipsia were by far the most frequent symptoms at presentation (96%); three quarters of the children (76.6%) had weight loss at presentation. One hundred and twenty-seven children (55.2%) of 230 presented with ketoacidosis. The mean age at diagnosis was 6.9 yr. The average duration of presenting symptoms before the hospital encounter was 17.1 d ranging from 3.0 to 45.0 d, with an average of 16.2 d in boys and 17.7 d in girls, a difference which was not significant. CONCLUSION: Polyuria, polydipsia, and weight loss are the most common symptoms at presentation of childhood diabetes mellitus in our region. The frequency of diabetic ketoacidosis was relatively high. The commonly recognized symptoms of diabetes were present in most of the children for a relatively long duration before the diagnosis. This calls for a collaboration of efforts for the early recognition of symptoms by patients and physicians to avoid the more severe types of presentation.     

母乳喂养对妊娠期糖尿病母亲子代儿童期超重的影响

目的：通过对妊娠期糖尿病（GDM）母亲子代的随访,探讨母乳喂养是否可以降低GDM子代发生超重的风险性。方法：对2003年1月至2009年12月GDM母亲子代1189例进行随访,采用logistic回归分析出生后0～3月母乳喂养方式及母乳喂养持续时间对GDM子代超重发生风险的影响。结果：在对孕前BMI、孕期增重、孕期血糖水平、性别、出生体重、年龄及父亲体重等混杂因素进行校正后,0～3月纯母乳喂养组GDM子代儿童期超重发生风险低于人工喂养组（OR：0.479,95%CI：0.256～0.897）;接受0～3月母乳喂养、4～6月母乳喂养及大于6月母乳喂养GDM子代儿童期超重发生风险均低于人工喂养组（分别OR：0.456,95%CI：0.233～0.827;OR：0.29,95%CI：0.103～0.817;OR：0.534,95%CI：0.280～0.970）;接受4～6月母乳喂养GDM子代儿童期超重发生风险低于0～3月母乳喂养组（OR：0.372,95%CI：0.129～0.874）;而接受母乳喂养时间<6月与接受母乳喂养时间≥6月与GDM子代儿童期超重发生风险无相关性（OR：0.769,95%CI：0.4701～1.258）。结论：出生后0～3月母乳喂养,尤其是纯母乳喂养可以降低GDM子代发生超重的风险,且在出生后6月内,随着母乳喂养时间的增加,GDM子代超重发生风险降低,而出生6月以后,延长母乳喂养时间可能并不能降低超重的发生风险。     

HLA‐DRB, ‐DQA,and DQB alleles and haplotypes in Iranian patients with diabetes mellitus type I

Specific alleles at the HLA‐DRB1, ‐DQA1, and ‐DQB1 loci seem to be associated with variable risks of developing type 1 diabetes (T1D). This study assessed the distribution of HLA‐DR and ‐DQ alleles among Iranian T1D patients and healthy controls. In this study, HLA‐DRB1, ‐DQA1, and ‐DQB1 alleles were determined in 100 children with T1D and 100 unrelated healthy controls. The following alleles were found to have a strong positive association with T1D: DRB1*0301, DRB1*0401, DRB1*0402, DQA1*0301, DQA1*0501, DQB1*0201, and DQB1*0302. Meanwhile, protective associations were found for DRB1*1001, DRB1*1101, DRB1*15, DRB1*16, DQA1*0102, DQA1*0103, DQB1*0301, DQB1*0501, and DQB1*0602 alleles. The haplotypes found most frequently among patients with T1D were DRB1*0301‐DQA1*0501‐DQB1*0201, DRB1*0401‐DQA1*0301‐ DQB1*0302, and DRB1*0402‐DQA1*0301‐DQB1*0302, whereas DRB1*1101‐DQA1*0501‐DQB1*0301 and DRB1*16‐DQA1*0102‐ DQB1*0501 haplotypes were negatively associated with the disease. These results confirm the previously reported association of specific HLA‐DR and HLA‐DQ alleles and haplotypes with T1D in Iranian population. The notable difference was the identification of DRB1*16‐DQA1*0102‐DQB1*0501 as a protective haplotype and the absence of a negative association of DRB1*1301‐DQA1*0103‐DRB1*0603 with T1D.     

Management of childhood diseases during the Byzantine period: IV − Juvenile diabetes mellitus

Although Byzantine physicians seemed to recognize the clinical entity and the symptoms of juvenile diabetes mellitus very well, they did not mention many details about the treatment of the disease. Most probably they treated the young patients in the same way as the adults. It is worth mentioning that diabetes was considered a difficult medical problem.     

Recent advances in the management of diabetes mellitus

The Diabetes Control and Complications Trial (DCCT) demonstrated that the improved control of blood glucose levels could delay or prevent long-term complications in patients with insulin dependent diabetes mellitus (IDDM). However, there are questions as to whether this degree of tight control is realistic in community settings. This review will cover new strategies for the management and prevention of IDDM.     

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.