Insulin-dependent Diabetes Mellitus In Children Research Articles

Dyslipidemia in insulin dependent diabetic children

Background: Children and adolescents with insulin-dependent diabetes mellitus (IDDM) are at high risk of metabolic disorders that may interfere with lipid metabolism and predispose to dyslipidemia. Objective: To detect the incidence of dyslipidemia and associated factors in children with IDDM in Diyala. Patients and Methods: This was a case-control study that included a total of 100 children with type 1 diabetes mellitus(T1DM) and 100 age- and gender-matched non-diabetic children who presented to the Pediatric Department/Al-Batool Teaching Hospital during the period from April 2022 to April 2023. Demographic data included the child's age, gender, weight, mother’s educational level, mother's job, child's educational level, school attendance, and physical activity. Clinical data included systolic and diastolic blood pressure, HbA1c, family history of illness, disease duration, type of insulin, and insulin dose. Fasting lipid profile and hemoglobin A1c investigations were done for the study groups, and the data were statistically analyzed. Results: The overall dyslipidemia in IDDM children and controls was 46% and 8%, respectively, with a highly significant difference. The mean age and weight in diabetic patients with dyslipidemia were 8.23±3.63 years and 28.96±13.31 kg, respectively, which was higher than that of normolipidemic diabetic patients (10.72±3.23 years and 34.22±12.14 kg, respectively) with significant differences. Furthermore, 28.26% of mothers of dyslipidemia-.diabetic patients were employed, compared with only 11.11% of normolipidemic-diabetic patients, a significant difference. A family history of DM was reported in 47.83% and 27.78% of dyslipidemic and normolipidemic diabetic patients, respectively, with a significant difference. Conclusion: The incidence of dyslipidemia among diabetic children in Diyala is 46%. Older age, increased body weight, and a mother’s job as an employer are significantly associated with the development of dyslipidemia in insulin-dependent diabetes mellitus patients. Keywords: Dyslipidemia, Diabetes mellitus, Children, Diyala.

Dyslipidemia in insulin dependent diabetic children

Background: Children and adolescents with insulin-dependent diabetes mellitus (IDDM) are at high risk of metabolic disorders that may interfere with lipid metabolism and predispose to dyslipidemia. Objective: To detect the incidence of dyslipidemia and associated factors in children with IDDM in Diyala. Patients and Methods: This was a case-control study that included a total of 100 children with type 1 diabetes mellitus(T1DM) and 100 age- and gender-matched non-diabetic children who presented to the Pediatric Department/Al-Batool Teaching Hospital during the period from April 2022 to April 2023. Demographic data included the child's age, gender, weight, mother’s educational level, mother's job, child's educational level, school attendance, and physical activity. Clinical data included systolic and diastolic blood pressure, HbA1c, family history of illness, disease duration, type of insulin, and insulin dose. Fasting lipid profile and hemoglobin A1c investigations were done for the study groups, and the data were statistically analyzed. Results: The overall dyslipidemia in IDDM children and controls was 46% and 8%, respectively, with a highly significant difference. The mean age and weight in diabetic patients with dyslipidemia were 8.23±3.63 years and 28.96±13.31 kg, respectively, which was higher than that of normolipidemic diabetic patients (10.72±3.23 years and 34.22±12.14 kg, respectively) with significant differences. Furthermore, 28.26% of mothers of dyslipidemia-.diabetic patients were employed, compared with only 11.11% of normolipidemic-diabetic patients, a significant difference. A family history of DM was reported in 47.83% and 27.78% of dyslipidemic and normolipidemic diabetic patients, respectively, with a significant difference. Conclusion: The incidence of dyslipidemia among diabetic children in Diyala is 46%. Older age, increased body weight, and a mother’s job as an employer are significantly associated with the development of dyslipidemia in insulin-dependent diabetes mellitus patients.

Absence of occult hepatitis B virus infection in sera of diabetic children and adolescents following hepatitis B vaccination

Background The prevalence of occult hepatitis B (HB) infection (OBI) in HB-vaccinated diabetic children has not yet been tested. Here, we aimed to determine the prevalence of OBI among HB-vaccinated children and adolescents with insulin-dependent diabetes mellitus (IDDM).Results Eighty-seven (51.2%) children had a titer for antibodies to HB surface antigen (anti-HBs) of <10 IU/L. These included 44 (70%) IDDM children and 43 (40.2%) healthy children. Eighty-three (48.8%) children had an anti-HBs titer of ≥10 IU/L; they included 19 (30%) with IDDM and 64 (59.8%) healthy children. None of the enrolled children (n = 170) were reactive for total antibody to HB core antigen (anti-HBc) as determined by enzyme-linked immunosorbent assay. HB virus DNA was not detected in HB-vaccinated IDDM or healthy children and adolescents.Method An amount of 170 HBsAg-negative sera samples from HB-vaccinated children and adolescents was included. They were classified into the IDDM group (n = 63) and the healthy control group (n = 107). HBsAg, anti-HBc, and anti-HBs were tested by enzyme-linked immunosorbent assay, and HB virus DNA was tested by nested polymerase chain reaction using 3 pairs of surface, core, and X genes.In Conclusion Primary HB vaccination confers long-term protection against OBI in Egyptian diabetic children and adolescents. However, the number of cases tested in this study was relatively low, and further studies and long-term follow-up of large populations are needed to draw solid and convincing conclusions.

Antibody levels against hepatitis B virus after hepatitis B vaccination in Egyptian diabetic children and adolescents

Background: The remarkable effectiveness of universal infantile hepatitis B (HB) vaccination is well documented in many countries. Nevertheless, the influence of insulin-dependent diabetes mellitus (IDDM) on the sero-protective level of antibody to hepatitis B surface antigen (anti-HBs) after HB vaccination has not been investigated in Egyptian children. The aim of this study was to investigate long-term anti-HBs sero-protective levels after infantile HB vaccination in Egyptian IDDM children.Results: The mean age of the healthy children was 10.86 ± 1.21 y (range, 5.5–15 y); 49 (45.8%) were boys and 58 (54.2%) were girls. The mean age of the IDDM children was 10.29 ± 3.04 y (range, 4–17 y); 32 (50.8%) were boys and 31 (49.2%) were girls. There were no significant differences between the healthy and IDDM children with respect to age and sex (p > 0.05). Among the 107 healthy children, 43 (40%) did not have a protective anti-HBs level (anti-HBs < 10 IU/L) and 64 (60%) had a protective level (anti-HBs ≥ 10 IU/L). In contrast, among the IDDM children, 44 (69.8%) and 19 (30.2%) did not and did have protective anti-HBs levels, respectively. This difference in anti-HBs concentration between healthy and diabetic children was highly significant (p < 0.001). None of the vaccinated healthy or IDDM children was reactive to HBsAg or total anti-HBc.Patients and Methods: A total of 170 children (81 boys, 89 girls) who had been routinely vaccinated against HB were included. Their mean age was 10 ± 2.1 y. The enrolled children were divided into healthy (n = 107) and IDDM (n = 63) cohorts. Body Mass Index and levels of hepatitis B surface antigen (HBsAg), total antibody to hepatitis B core antigen (anti-HBc), and anti-HBs were evaluated in all children. In addition, the duration of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) were measured in IDDM children.Conclusion: Our results are alarming. It appears that the majority of Egyptian diabetic children vaccinated against HB may not have sufficient anti-HBs levels to protect them from HB. Moreover, this study emphasizes the need for a population-based strategy for the management of patients without an anti-HBs protective level after HB vaccination and justifies the need to elucidate the heritability of those children.

Linear Association Between Household Income and Metabolic Control in Children With Insulin-Dependent Diabetes Mellitus Despite Free Access to Health Care

In health care systems with a user fee, the impact of socioeconomic factors on pediatric insulin-dependent diabetes mellitus (IDDM) control could be due to the cost of accessing care. There is a linear association between household income and the average glycosylated hemoglobin (HbA1c) of children and adolescents with IDDM despite free access to health care. We used a linear regression model to examine the association between normalized average HbA1c of 1766 diabetic children (diagnosed at our institution from 1980 to 2011 before 17 years of age) and the median household income of their neighborhoods (obtained from Statistics Canada, 2006 Census data). We found a negative linear association (P < .001; r = -0.2) between the level of income and metabolic control assessed by HbA1c after controlling for sex, age at diagnosis, duration of diabetes, ethnicity, geographical factors, frequency of visits, current age (as a proxy for change in practice over time), and change of measurement methods of HbA1c across time. For every increase of $15,000 in annual income, HbA1c decreased by 0.1%. We report a linear association of household income with metabolic control of IDDM in childhood. Given that Canada has a system of free universal access to health care, confounding by access to care is unlikely. Considering the impact of poorly controlled IDDM in childhood on the development of long-term complications, our findings suggest that the higher complication rate found in adults of low socioeconomic status might originate from the poor control that they experienced in childhood. Support for the care of IDDM children from low-income neighborhoods should be increased.

Occurrence of microalbuminuria among children and adolescents with insulin-dependent diabetes mellitus

Microalbuminuria precedes the onset of diabetic nephropathy in insulin-dependent diabetes mellitus (IDDM) pediatric patients. Its prevention is among the most important challenges in managing IDDM. We attempted to determine the occurrence of microalbuminuria among IDDM Saudi children and adolescents and its associated risk factors. This is a retrospective cross-sectional study conducted on 409 IDDM children and adolescents attending the pediatric clinic at King Abdul-Aziz University Hospital from 2006 to 2010. Their ages ranged from 1 to 18 years and the mean ± standard deviation (mean ± SD) was 12.3 ± 4.1 years. Twenty-four-hour urinary albumin excretion (on two separate occasions or more, 3 - 6 months apart each), HbA1c, duration of IDDM, Tanner staging and body mass index (BMI) were reviewed. Prevalence of microalbuminuria in our cohort was 11.3%. IDDM duration was ≥2 years in 55.8% of our patients; of them, 15.6% had microalbuminuria while 45.2% had IDDM duration <2 years (6% had microalbuminuria) (P <0.01). The prevalence of microalbuminuria was higher among the post-pubertal subjects (50%) than that among the pre-pubertal (8.7%) and pubertal (41.5%) subjects. Furthermore, microalbuminuria was present in 16.7% of those with elevated blood pressure, but only in 8.5% among those with normal blood pressure (P <0.05). The enrolled overweight and obese subjects showed a higher prevalence of microalbuminuria (14%) when compared with that among those with a normal BMI (6.6%) (P <0.05). In our cohort, duration of IDDM, pubertal status, hypertension and BMI affected the prevalence of microalbuminuria. Annual screening for microalbuminuria in IDDM children and adolescents is imperative.

The effects of sera obtained from children with insulin-dependent diabetes mellitus on cultivated islet cells: cytotoxicity and insulin release.

Sera were obtained from 24 patients with newly-diagnosed insulin-dependent diabetes mellitus (IDDM) and 14 children with a high risk of diabetes. The influence of the decomplementated sera on basal and stimulated insulin secretion was studied in a mixed culture of newborn rat islet cells. In addition, complement-dependent antibody-mediated cytotoxicity (C'AMC) was measured by 51Cr-release from pre-labelled islet cells. Incubation of the islet cells with sera from ten IDDM patients did not affect the basal insulin release. Sera from other children with IDDM (n = 14) either significantly increased (n = 7) or inhibited (n = 7) basal IRI secretion was compared with the sera of control donors. Nearly half of the sera from the high-risk children was found to be insulin-stimulating. Preincubation of islet cells with sera from IDDM children caused a significant decrease of insulin response to 16.5 mM glucose plus 5 mM theophylline (P less than 0.001). Sera from the high-risk children did influence the response of pancreatic cells to secretagogues. C'AMC was found in 45% of the patients with IDDM and in 33% of the high-risk children, however, there was no correlation between C'AMC and serum effect upon basal insulin secretion. These results suggest the presence of B-cytotropic factors in serum from children with IDDM or with a risk of diabetes. Opposite effects of different sera on insulin secretion may reflect the variety of pathogenetic mechanisms involved in islet cell destruction.

Nutritional Intake of Children and Adolescents with Insulin-Dependent Diabetes Mellitus in Crete, Greece

Background/Aims: The incidence of childhood insulin-dependent diabetes mellitus (IDDM) is rapidly increasing in Greece. The aim of this study was to examine nutrient patterns of children and adolescents with IDDM in Crete. Methods: A case-control survey of eating habits was conducted among 41 children and adolescents, aged 6–17 years, with IDDM (cases) and healthy sex- and age-matched controls, recruited from Heraklion University Hospital and the village of Rouvas, Crete, respectively. Dietary data was based on 24-hour recall records. Results: Dietary intake was similar between the groups. Both groups exceeded the recommendations for total and saturated fat and consumed lower than recommended amounts of dietary fibre and total carbohydrates. Children with IDDM consumed more dairy products and vegetables and less meats and cereals. Vegetables were consumed by a relatively high proportion of children and adolescents in both groups, but there was a higher proportion of fruit consumers amongst the IDDM group. For those who ate fruit and vegetables, intake approximated current recommendations of 400 g/day. Conclusions: The need to increase complex carbohydrates and reduce the consumption of total and saturated fat, in order to approach the traditional dietary pattern of Crete for this population, should be addressed via appropriate nutrition education programmes.

Transient insulin-dependent diabetes mellitus in children with steroid-dependent idiopathic nephrotic syndrome during tacrolimus treatment

Despite the availability of immunosuppressive drugs such as prednisone, cyclophosphamide, cyclosporine A (CyA) and mycophenolate mofetil for the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS), medication-free remission is not achieved in a number of patients. To avoid excessive steroid toxicity, the use of tacrolimus (Tac) has been discussed. We report on five children diagnosed with SDNS on the histological basis of minimal change glomerulopathy or focal segmental glomerulosclerosis. Following the failure of other medications to achieve sustained remission, Tac was administered to these patients who varied in age from 10.5 to 13.5 years. Only one patient showed a substantial reduction in the number of relapses with the Tac treatment. Two boys, after 9 and 44 months on therapy, respectively, developed insulin-dependent diabetes mellitus (IDDM), necessitating the withdrawal of Tac and the daily use of insulin for 3 and 6 months. In both patients hyperglycemia had occurred during prednisone-based relapse therapy of SDNS. The patients had low serum protein concentrations, presumably increasing the free active Tac fraction, while trough levels of the drug remained unchanged. Both of the affected patients had additional risk factors for impaired glucose tolerance, such as morbid obesity (patient 1; BMI: 41.6 kg/m(2)) and African American origin (patient 2). Our case reports demonstrate that the use of Tac in patients with SDNS may be associated with an increased risk for IDDM, especially during relapse of NS, and particularly if additional risk factors are present. Moreover, Tac does not appear to substantially increase the success of treatment.

Applying the Transactional Stress and Coping Model to Sickle Cell Disorder and Insulin-Dependent Diabetes Mellitus: Identifying Psychosocial Variables Related to Adjustment and Intervention

This review paper examines the literature on psychosocial factors associated with adjustment to sickle cell disease and insulin-dependent diabetes mellitus in children through the framework of the transactional stress and coping (TSC) model. The transactional stress and coping model views adaptation to a childhood chronic illness as mediated by several psychosocial factors. This review examines the utility of the model in explaining adjustment in two different childhood diseases, identifies needed research and intervention targets, as well as highlights potential changes to the model. The major conclusions of this review suggest that, in addition to child-specific factors, family functioning is an area that interventions should address in sickle cell disease and insulin-dependent diabetes mellitus.

Circulating acylated and total ghrelin and galanin in children with insulin‐treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development

To study the circulating levels of two gut-derived peptides in children with type 1 (insulin-dependent) diabetes mellitus (IDDM). Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP-1, body mass and pubertal development were evaluated in 91 children, aged 11.1 +/- 2.7 years, affected by IDDM and treated with insulin. Ninety-one healthy children were selected as controls. Body mass index (BMI)-adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP-1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI-adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects. The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.

Gluten sensitivity in a subset of children with insulin dependent diabetes mellitus.

The association between celiac disease and insulin dependent diabetes mellitus (IDDM) is well established. Rectal gluten challenge has been used in patients with celiac disease and in first degree relatives as a tool to assess the mucosal immune response to gluten. The aim of this study was to assess the mucosal immune response to gluten in IDDM children by rectal gluten challenge. Rectal biopsy specimens were obtained from 19 children with IDDM before and 6 h after rectal challenge with 2 g of a peptic tryptic digest of gliadin. A total of 16 treated celiac patients and 10 control subjects were also investigated. Epithelium and lamina propria CD3(+) and gamma delta(+) lymphocytes were counted with reference to a standard reference area of muscularis mucosae (10(4) microm(2)). After a local instillation of gliadin, a significant (>mean + 1 SD) percentage increment of lamina propria and epithelium CD3(+) and of lamina propria and epithelium gamma delta(+) lymphocytes was observed in five IDDM children, as compared to 11 and 13 celiac patients and one and two controls, respectively. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis classified four of 19 IDDM children in the group of celiac patients. The positivity was associated with normal serology (antigliadin antibody, antiendomysial antibody, and antitissue transglutaminase antibodies) and a morphologically normal jejunal mucosa. All four patients had HLA-DQ alleles associated with celiac disease. Approximately 20% of IDDM children react to rectal instillation of gliadin. Long term follow-up is necessary to establish whether these subjects are at increased risk for developing celiac disease.

Gluten sensitivity in a subset of children with insulin dependent diabetes mellitus

Objectives The association between celiac disease and insulin dependent diabetes mellitus (IDDM) is well established. Rectal gluten challenge has been used in patients with celiac disease and in first degree relatives as a tool to assess the mucosal immune response to gluten. The aim of this study was to assess the mucosal immune response to gluten in IDDM children by rectal gluten challenge. Methods Rectal biopsy specimens were obtained from 19 children with IDDM before and 6 h after rectal challenge with 2 g of a peptic tryptic digest of gliadin. A total of 16 treated celiac patients and 10 control subjects were also investigated. Epithelium and lamina propria CD3 + and γδ + lymphocytes were counted with reference to a standard reference area of muscolaris mucosae (10 4 μm 2). Results After a local instillation of gliadin, a significant (>mean + 1 SD) percentage increment of lamina propria and epithelium CD3 + and of lamina propria and epithelium γδ + lymphocytes was observed in five IDDM children, as compared to 11 and 13 celiac patients and one and two controls, respectively. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis classified four of 19 IDDM children in the group of celiac patients. The positivity was associated with normal serology (antigliadin antibody, antiendomysial antibody, and antitissue transglutaminase antibodies) and a morphologically normal jejunal mucosa. All four patients had HLA-DQ alleles associated with celiac disease. Conclusions Approximately 20% of IDDM children react to rectal instillation of gliadin. Long term follow-up is necessary to establish whether these subjects are at increased risk for developing celiac disease.

Effects of metabolic control on vitamin E nutritional status in children with type 1 diabetes mellitus

Objective: To evaluate the effects of the metabolic control of the insulin-dependent diabetes mellitus (IDDM) on the nutritional status of vitamin E. Methods: A total of 47 children with IDDM and a mean age of 11.91±1.60 (mean±SD) years were studied, matched for age and sex with 16 healthy children (11.75±1.83 years). Following the American and British Associations for IDDM, we used a classification of ‘good’, ‘moderate’ or ‘poor’ control of the illness: (a) good control [glycosilated haemoglobin (HbAlc) ≤7%]; (b) moderate control (7%< HbAlc ≤8%); and (c) poor control (HbAlc>8%). Serum concentrations of total cholesterol (CHOL), triglycerides (TG), high-density lipoproteins-cholesterol (HDLc), very low- and low-density lipoproteins cholesterol (VLDLc and LDLc), plasma and erythrocyte vitamin E (Vit Ep and Vit Ee) and plasma vitamin A (Vit Ap) were measured in all children. Results: The children with ‘poor’ metabolic control of the illness presented significantly higher plasma concentrations of CHOL, LDLc, VLDLc, LDLc/HDLc, (VLDL+LDL)c/HDLc, TG and Vit Ep; higher indices Vit Ep/Vit Ee and Vit Ep/Vit Ap relative to those with a ‘good’ control of the illness. Direct-linear correlations were found between Vit Ep and the percentage of HbAlc and with the markers of atherogenic risk in the IDDM children. Conclusion: There is a significant rise in Vit Ep concentrations as metabolic control of the illness worsens, whereas Vit Ee remained unchanged. These results suggest that vitamin E maintains its nutritional status despite a poor control of the IDDM during childhood.

Projected number of diabetic renal disease patients among insulin-dependent diabetes mellitus children in Japan using a Markov model with probabilistic sensitivity analysis.

To plan prevention programmes for the diabetic renal disease among insulin-dependent diabetes mellitus (IDDM) children, projections of future trends for the disease is crucial. We projected future trends in the number of diabetic renal disease patients among IDDM children and assessed an impact of treatment dissemination in Japan. We used a Markov model to describe the clinical courses of diabetic renal disease. Future trends in the number of patients with diabetic nephropathy (DN) and end-stage renal disease (ESRD) were projected from the year 1995 to 2015. We made three scenarios for assessing an impact of the dissemination of new treatment. We performed a probabilistic sensitivity analysis for the uncertainty of transition probabilities. The results showed that the number of patients with DN was 790.5 (5th to 95th percentile: 652.5-955.1), ESRD was 253.3 (5th to 95th percentile: 207.3-310.0) in year 2015 on basic scenario. Considering the dissemination of intensive insulin therapy, under the scenario of the gradual increase of the treatment, the result showed that the number of patients with DN was 713.1 (5th to 95th percentile: 546.2-930.6), ESRD was 231.0 (5th to 95th percentile: 176.6-296.2). Under the scenario of the immediate change of the treatment, the results showed that the number of patients with DN in 2015 was 418.9 (5th percentile; 345.4; 95th percentile; 506.1) and with ESRD was 133.4 (5th percentile; 109.0; 95th percentile; 163.8). The results of the projection showed a gradual increase in the number of patients with DMN and ESRD. Examination of three possible scenarios showed that the programme of dissemination of intensive insulin therapy prevented the progression of diabetic renal disease.

HLA alleles and IDDM in children in Hungary: a comparison with Finland

It has been postulated that variation in the distribution of human leukocyte antigen (HLA)-encoded susceptibility alleles for insulin-dependent diabetes mellitus (IDDM) is the genetic basis for variation in the incidence of the disease between populations. The aim of this study was to characterize HLA-encoded susceptibility to IDDM in Hungary and to identify whether HLA-DRB1/DQ-encoded susceptibility could account for the five times lower incidence of disease in Hungary compared with Finland. The haplotypes DRB1∗03-DQA1∗05-DQB1∗02 (DRB1∗03-DQ2) and DRB1∗04-DQA1∗0301-DQB1∗0302 (DRB1∗04-DQ8) were significantly associated with disease in both populations. Three genotypes incorporating either or both of these haplotypes accounted for over 70% of the diabetic population in both races. The combined background frequency and the degree of risk as measured by odds ratios of these HLA-DRB1-DQ genotypes were not significantly different in the two countries. Comparison of the DRB1∗0401-DQ8 haplotype between the two races suggested a role for HLA-B alleles in susceptibility. These data indicate that the susceptibility associated with high risk DRB1-DQ genotypes alone is insufficient to account for the fivefold variation in incidence of IDDM between Hungary and Finland. Other genetic and/or environmental influences must be involved.

Growth and Insulin-Like Growth Factors (IGFs) in Children with Insulin-Dependent Diabetes Mellitus at the Onset of Disease: Evidence for Normal Growth, Age Dependency of the IGF System Alterations, and Presence of a Small (Approximately 18-Kilodalton) IGF-Binding Protein-3 Fragment in Serum

Data on growth of children with insulin-dependent diabetes mellitus (IDDM) before the onset of disease are conflicting, and although the insulin-like growth factor (IGF) system has almost invariably been found altered at diagnosis, most of previous studies are affected by the small number of patients investigated. We studied 60 IDDM children at the onset of disease, comparing their stature with target height, normal growth standards, and height of 102 sex- and age-matched controls. Furthermore, we assessed serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and IGFBP-3 circulating forms. IDDM children were subdivided into 2 groups according to an age above (n = 26) or below (n = 34) 6 yr. The values of endocrine variables of diabetics older than 6 yr were compared with those of 34 age-matched controls. Although the height of diabetics was higher than growth reference values (mean height ± sd, 0.64 ± 1.4 z-score) and their target height (mean target height ± sd, 0.1 ± 0.84 z-score; P < 0.005), no significant difference in height was found between IDDM children and controls (mean height ± sd, 0.64 ± 0.95 z-score) even analyzing the 2 age groups separately. Overall, IDDM children showed reduced levels of IGF-I (mean ± sd,− 0.65 ± 1.9 z-score) and normal levels of IGF-II (mean ± sd, −0.05 ± 1.2 z-score) and IGFBP-3 (mean ± sd, −0.06 ± 1.2 z-score). However, whereas patients younger than 6 yr showed normal values of IGF-I, IGF-II, and IGFBP-3, these peptides were significantly reduced in older subjects compared with either younger IDDM children or controls (P < 0.01). IGFBP-3 immunoblot analysis revealed the presence of an approximately 18-kDa fragment of IGFBP-3 in addition to the major approximately 29-kDa fragment and the intact form (∼42–39 kDa) in 46 of 60 IDDM patients, whereas the approximately 18-kDa band was absent in all 34 control sera. No relationship was found between the endocrine variables and stature at diagnosis. In conclusion, our results indicate that IDDM children at the onset of disease are not taller than healthy peers and have increased IGFBP-3 proteolytic activity. Finally, although the IGF system is normal in younger IDDM children, older patients have reduced IGF levels.

Childhood diabetes: dietary aspects.

Insulin-dependent diabetes mellitus in children requires a delicate balance between injected insulin and food intake, taking into account physical activity and growth.

High Frequency of HLA-DQB1 Non-Asp57 Alleles in Kuwaiti Children with Insulin-Dependent Diabetes mellitus

The prevalence of polymorphic amino acids at position 57 of the HLA DQB1 in Kuwaiti children with insulin-dependent diabetes mellitus (IDDM) and nondiabetic controls has been determined using a polymerase chain reaction-sequence-specific primers (PCR-SSP) method. Using this approach, 34/55 (62%) IDDM children were found to be homozygous Ala/Ala and 19/55 (35%) were heterozygous with various combinations. Amongst the IDDM children with heterozygous genotype at codon 57 of HLA DQB1, 6/55 (11%) had Asp/Ala, 8/55 (15%) had Ala/Val, 4/55 (7%) had Ala/Ser and 1/55 had Asp/Val allelic combinations. When considered collectively, the nonaspartate (NA) alleles were represented in 87% of the IDDM cases and only 13% cases had Asp⁵⁷ allele in different heterozygous combinations, while none of the IDDM subjects had a homozygous Asp genotype. In nondiabetic controls, homozygous non-Asp (NA) alleles were represented in 44% subjects, 37% of the controls were heterozygous (NA/A) and 19% had a homozygous (A/A) genotype. These differences between the IDDM group and the control group were found to be statistically significant. Our data report one of the highest frequency of NA/NA residues at this locus compared with that from different world populations (Sardinians, Norwegians, US Caucasians, US Blacks and Chinese).

Growth Hormone/Insulin Growth Factor-1 and Growth in IDDM Children and Adolescents.

Diabetes mellitus is a syndrome of disturbed energy homeostasis caused by a deficiency of insulin or of its action and resulting in abnormal metabolism of carbohydrate, protein, and fat. The aim of this study was to study, by use of different anthropometrical parameters, the effect of diabetes mellitus either controlled or non-controlled on the growth pattern of the Egyptian children. At the same time, changes in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in the studied groups were investigated. The study was carried out on 50 healthy normal children and 127 diabetic children with insulin-dependent diabetes mellitus (IDDM) aged 2-18 years. They were classified according to their fasting blood glucose level into controlled <150mg/dl and non-controlled 150-300mg/dl. Then they were subdivided according to their age into three subgroups, 2-9, 10-14, 15-18 years. At the start of the study the 2-9-year-old children had been diabetic since 1.8±0.32 years and the 10-18-year-old children, since 3.96±0.12 years. Clinical and some anthropometrical measurements were made including height and weight; and from them the body mass index (BMI) and Z-score for height and weight were calculated. In addition, mid-arm, wrist, head, and chest circumferences were measured. Radio-immunoassay (RIA) techniques for estimation of serum GH and IGF-1 were performed. The results obtained in this study indicated that the longitudinal growth was the parameter, which was more affected in the IDDM children, especially in those with non-controlled disease. The mean±SEM of the Z-score for their height was -1.16±0.27, -1.047±0.18, and -1.68±0.019 for the age groups 2-9, 10-14, and 15-18 years, respectively. The GH/IGF-1 axis was distributed, and GH concentrations were found to be numerically higher in the different age groups of the non-controlled diabetic children than in those of the normal children. Serum IGF-1 levels were significantly reduced among the diabetic patients when compared with those recorded among their counterpart normal children. The reduction in the IGF-1 levels was pronounced in the non-controlled patients. A significant positive correlation was observed between all the anthropometric measurements and IGF-1 concentrations of the adolescents non-controlled diabetic children aged 10-14 years, defining its role in their growth. Thus the disturbed GH/IGF-1 axis in IDDM children and adolescents might contribute to their growth failure, mainly in the non-controlled patients.