Contrasting features of insulin dependent diabetes mellitus associated with neuroectodermal defects and classical insulin dependent diabetes mellitus

The Wolfram, or DIDMOAD, syndrome is a rare congenital disease that is associated with diabetes insipidus, insulin dependent diabetes mellitus of an early onset, bilateral optic atrophy and deafness. Urological disorders are usually present as well. We have studied nine patients belonging to five different families. All of the family members were HLA typed (including DR), and islet cell as well as antinuclear antibody determinations were carried out. Although individuals with insulin dependent diabetes mellitus are very prone to have either HLA-DR3 or -DR4 antigens, none of our patients had DR3 antigens and only one was DR4 positive. On the other hand, three of our patients were typed as HLA-DR2 positive. This antigen is uncommon in classical insulin dependent diabetes. In one of the families, the affected siblings did not share the same HLA haplotype. Islet cell and antinuclear antibodies were not found in any of the cases and six of the patients had a small, but significant, insulin secretory reserve. On the basis of some of the clinical features it was also possible to further distinguish between the DIDMOAD syndrome and the classical insulin dependent diabetes mellitus. The differences encountered between classical and DIDMOAD insulin dependent diabetes mellitus--the presence/absence of HLA linkage, HLA-DR2, -DR3 and -DR4 associations, islet cell or antinuclear antibodies, the tendency to ketosis and diabetic retinopathy--indicate that their etiopathogenies are triggered by distinct mechanisms.     

Autonomic dysfunction and severe hypoglycaemia in insulin dependent diabetes mellitus.

The aims of the present study were to investigate the relationship between severe hypoglycaemia and autonomic dysfunction in diabetic children, and to assess the glycaemic response to an insulin infusion test. In a one year period, 12 of 69 diabetic patients (17%) experienced at least one severe episode of hypoglycaemia, defined as an event which required outside assistance. All patients underwent five cardiovascular autonomic tests. Seven of the hypoglycaemic patients showed three or more abnormal autonomic tests. Among the 57 non-hypoglycaemic diabetics, there was no patient with three or more abnormal tests. In hypoglycaemic diabetics with and without autonomic dysfunction, and in eight healthy age matched subjects an insulin infusion test was performed. A pronounced blood glucose decline and a subnormal increase in heart rate during insulin infusion were obtained in patients with autonomic dysfunction. Thus, severe hypoglycaemia may be due to impaired defence mechanisms against blood glucose decline in diabetic children with autonomic dysfunction.     

Leptin levels in children with insulin dependent diabetes mellitus

Leptin, a product of the ob gene, is a polypeptide hormone produced in adipose tissue that informs the brain about the amount of energy storage of body fat. It has very important effects on neuroendocrine functions and energy expenditure. The aim of our study was to determine leptin levels of children with insulin dependent diabetes mellitus (IDDM), which is known to affect body metabolism, and to investigate the relationship between duration of the disease, insulin dosage, HbA1c levels, body mass index (BMI), serum lipids and IGF-1 levels. Sixteen patients with IDDM (chronological age 13.8 +/- 2.6 years) whose HbAlc levels were 10.2 +/- 1.9 %, BMI 21.2. +/- 2.7 kg/m2, insulin dosage 0.9 +/- 0.4 U/kg/day and duration of the disease 6.7 +/- 2.6 years, and 12 healthy controls (13.4 +/- 2.6 years) were included in the study. Fasting plasma leptin levels were measured by radioimmunoassay method. The mean plasma leptin levels of the patient and the control groups were 19.1 +/- 7.6 ng/ml and 6.1 +/- 2.9 ng/ml, respectively, and significant difference was found between the two groups (p < 0.05). No correlation was found between leptin values and IGF-1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride levels, atherogenic index, insulin dosage or HbA1c levels in the patient group. A weak statistical correlation was determined between BMI and leptin levels in the IDDM group (r = 0.28, p < 0.05). A positive correlation was also found between leptin levels and the duration of the disease (r = 49, p < 0.05). As a result, it seems that leptin levels of children with IDDM differed from the levels of the control group significantly, and that the duration of insulin therapy was responsible for this difference.     

Thyroid hormones and thyroglobulin autoantibodies in insulin dependent diabetes mellitus

Serum T4, FT4, T3, and TSH were measured in a group of children with insulin dependent diabetes mellitus and a control group. In the insulin dependent diabetes mellitus group, serum T3 concentration was significantly lower than the control values. Serum T4, FT4 and TSH level did not differ. The difference in serum T3 concentration was significant between diabetic children with good or poor control. Thyroglobulin antibodies were investigated in diabetic children by Serono's "hTg antibodies" kit. Thyroglobulin antibodies were present in 14.5%. TSH concentration did not differ in antibody positive and negative cases, but one child with diabetes had evidence of moderately impaired thyroid reserve.     

Pre-HbA1c in children with insulin dependent diabetes mellitus

Day-to-day fluctuations in blood concentration of the glycosylated hemoglobin, HbA1c or HbA1, are mainly due to variations in content of the intermediate aldimide form, preHbA1c. Using electrofocusing we have studied this component adjacent to the HbA1c band, which represents the stable ketoamine form. The fraction of preHbA1c present rapidly increases upon incubation of erythrocytes in 20 mM glucose at +37 degrees C, and the reaction is fully reversible if glucose is removed. In children with insulin-dependent diabetes mellitus with different degrees of metabolic control, levels of preHbA1c varied between 0.2 and 3.7% of total hemoglobin (median value 1.3%, N = 25). A clear correlation was found between preHbA1c and urinary glucose concentrations during the 12 hours preceding blood sampling (r = 0.75, p less than 0.001, df = 18). As expected, pre-HbA1c did not correlate to HbA1c or glycosylated albumin, which reflect long- and medium-term diabetic control.     

Incidence of insulin dependent diabetes mellitus in Karachi, Pakistan

OBJECTIVES: To determine the incidence of insulin dependent diabetes mellitus (IDDM) among children aged up to 16 years residing in the city of Karachi, Pakistan, during the five years from 1989 to 1993. DESIGN: Retrospective study of incidence using hospital and clinic records. SETTING: The city of Karachi, Pakistan. SUBJECTS: Children satisfying standard criteria for the diagnosis of IDDM, attending treatment facilities for the first time during the study period. MAIN OUTCOME MEASURES: The incidence of IDDM in this population and its variation by age and sex. RESULTS: The incidence of IDDM in this population is 1.02/100000 per year, which is one of the lowest incidence rates yet reported. CONCLUSIONS: The very low incidence of IDDM, contrasted with the substantially higher incidence among migrants, supports the view that environmental factors are the major determinants of variations in the incidence of this condition between populations.     

Helicobacter pylori infection in children with insulin dependent diabetes mellitus

To assess the seroprevalence of Helicobacter pylori (HP) in children with insulin dependent diabetes mellitus, a serological test for Helicobacter pylori (anti-HP IgG with ELISA) was performed in 88 diabetic and 42 healthy control children. Anti-HP IgG was positive in 49/88 (55.6%) of diabetics and 13/42 (30.9%) of controls (p<0.01). Diabetic children were divided into two groups according to HP status: HP(+) and HP(-). The two groups were compared for age, gender, duration of diabetes, diabetic control (HbA1c), SDS for height and gastric emptying time. Seroprevalence of HP was higher in IDDM patients than in healthy controls. Duration of diabetes was the only factor which correlated significantly with HP status. HP status was not related to gastric emptying time.     

Islet autoantibodies and insulin dependent diabetes mellitus in cystic fibrosis

Cystic fibrosis-related diabetes mellitus (CF-DM) is thought to be secondary to beta-cell destruction by fibrous tissue replacing the exocrine pancreas. The aim of this study was to investigate the hypothesis that other factors may also be responsible. Glutamic acid decarboxylase (GAD) and islet cell (IA-2) antibodies were measured by quantitative ELISA in a group of patients with CF (n=30) in comparison to a group of newly diagnosed DM type 1 (IDDM) patients (n=30) and normal subjects (n=30). GAD antibodies were positive (>32 ng/ml) in 50% of the CF, 93% of the IDDM and 0% of the control group. IA-2 antibodies were detected (>0.9 U/ml) in 40% of the CF, 93% of the IDDM and 0% of the control group. Among the fifteen CF patients with positive GAD and IA-2 antibodies, four already had IDDM and another five abnormally low (<45 mU/l) first phase insulin response (FPIR) indicating a prediabetic state. We conclude that factors other than mechanical may be involved in the development of CFDM. The presence of autoantibodies predicting IDDM supports the hypothesis that CF-DM may have a multifactorial pathogenesis.     

Early markers of the renal complications of insulin dependent diabetes mellitus.

We investigated the associations between albuminuria, metabolic control, glomerular filtration, blood pressure, and platelet function in children with insulin dependent diabetes mellitus. The geometric mean (95% tolerance levels) albumin excretion (expressed as the geometric mean albumin to creatinine ratio on two overnight urine collections (UA/UC], in 60 diabetic children was 0.72 (0.80-6.9) mg/mmol, significantly greater than in 45 normal children (geometric mean 0.41 (0.14-1.17]. Mean (SD) glomerular filtration rate, measured by 51Cr edetic acid clearance during constant infusion, was significantly greater in diabetic children (129 (20) ml/min/1.73 m2) compared with normal controls (109 (13]. Mean (SD) renal length for height standard deviation score was +0.25 (1.1); systolic blood pressure standard deviation score was 0.15 (0.65), and diastolic blood pressure was 0.51 (0.82). Spontaneous platelet aggregation, expressed as percentage fall in platelet count in stirred whole blood after 2 minutes was 17.8 (9.2)% in the diabetic compared with 12.3 (7.9)% in normal children. UA/UC correlated with renal length and of the children with UA/UC above the normal range, 70% also had a glomerular filtration rate above the normal range. There was a weak correlation between UA/UC and glycated haemoglobin (HbA1c). All children with spontaneous platelet aggregation above normal had had diabetes for more than seven years. These cross sectional data define some of the early markers and inter-relationships that may be important in the development of nephropathy.     

Child abuse suspicion masquerading new onset insulin dependent diabetes mellitus

The identification and diagnosis of child abuse is a challenging task to the pediatrician. The increased awareness among both the public and medical personnel, while improving attentiveness to this important subject, can sometimes result in misdiagnosing medical conditions, thus causing distress and delay in required treatment. Numerous reports have described conditions mimicking non-accidental injuries; most of these include dermatological findings related to skin diseases, medical conditions causing pathological fractures, and rare diseases with unusual physical findings. We present a case of a 9.5-year-old child in which the workup for a suspected abusive event led to a delay in the diagnosis of insulin dependent diabetes mellitus later presented as diabetic ketoacidosis.     

Plasma and erythrocyte vitamin E levels in children with insulin dependent diabetes mellitus.

Vitamin E is considered to be one of the most important antioxidants. There is a trend today to supply diabetic children with vitamin E in order to prevent microvascular complications. In this study, our objective was to demonstrate validity of plasma and erythrocyte vitamin E levels in diabetic children. This study was conducted on twenty-five diabetic patients aged from 7-16 years and ten non-diabetic, age-matched healthy subjects as the control group. Vitamin E levels were measured by high-performance liquid chromatography. There was no significant difference between the mean plasma vitamin E levels of diabetic and control groups, 870.80 +/- 220.51 micrograms/dl and 891 +/- 221.21 micrograms/dl, respectively (p > 0.05). The mean erythrocyte vitamin E levels of diabetic and control groups were significantly different: 183.12 +/- 62.58 micrograms/dl and 246.90 +/- 68.26 micrograms/dl, respectively (p < 0.05). Erythrocyte vitamin E levels were significantly lower than plasma vitamin E levels in both groups. We further investigated whether a correlation exists between plasma and erythrocyte vitamin E levels and duration of diabetes, insulin dose and HbA1c measurements. However no correlation was found. In conclusion, measurement of erythrocyte vitamin E levels may be considered to be more valuable than plasma vitamin E levels in diabetic children and supplementation may be provided according to erythrocyte levels rather than plasma levels.     

Foot pathology in insulin dependent diabetes.

OBJECTIVES--Foot pathology is a major source of morbidity in adults with diabetes. The aim of this study was to determine if children with insulin dependent diabetes have an increased incidence of foot pathology compared with non-diabetic children. DESIGN--Questionnaire, clinical examination, and biomechanical assessment. SUBJECTS--67 diabetic children and a comparison group matched for age, sex, and social class. RESULTS--We found significantly more foot pathology in the children with diabetes (52 children) than the comparison group (28 children); with more biomechanical anomalies (58 children with diabetes, 34 comparison group); and a higher incidence of abnormal skin conditions (53 children with diabetes, 27 comparison group). Forty two children with diabetes had received foot health education compared with 27 in the comparison group, but the study revealed ignorance and misconceptions among the diabetic group, and previous contact with a podiatrist was minimal. CONCLUSIONS--The survey suggests that children with diabetes have an increased incidence of foot pathology justifying greater input of podiatric care in the hope of preventing later problems.     

Urinary C-peptide excretion at onset of insulin dependent diabetes mellitus in children

The 24-hour urinary excretion of C-peptide and the plasma C-peptide concentration were measured at the onset of insulin dependent diabetes mellitus (IDDM) in children. The excretion of C-peptide was twice as high as that found in normal control subjects, whereas the plasma C-peptide values were markedly lower, indicating increased urinary leakage of C-peptide in this phase of the disease. In the diabetic children under seven years of age the mean value of C-peptide excretion was clearly lower than in the older children.     

Residual insulin secretion in adolescent diabetics after remission.

Twenty four hour blood glucose profiles were compared in two groups of insulin dependent adolescent diabetic patients who were beyond their initial partial remission phase. In the group with persistent endogenous insulin secretion, blood glucose profiles were significantly lower but the difference was small and not reflected in average 24 hour concentrations of glucose nor glycosylated haemoglobin. Endogenous insulin secretion must be considered in studies of metabolic control after the remission period but the effect on overall glucose control is probably clinically unimportant.