Hyporesponsiveness to intradermal administration of hepatitis B vaccine in insulin dependent diabetes mellitus

The immune response to intradermal or intramuscular hepatitis B vaccine in 18 children with insulin dependent diabetes mellitus (IDDM) compared with 24 healthy children was studied. Patients were divided into responders, hyporesponders, and non-responders according to their antihepatitis B serum concentrations after hepatitis B vaccination. We also studied HLA class II antigen distribution and did delayed type hypersensitivity (DTH) tests on children with IDDM and controls.
No difference in the immune response (antihepatitis B surface antigen antibody titres) was found with intramuscular administration, whereas with intradermal administration a statistically lower immune response (p < 0.001) was observed in children with IDDM v controls. This hyporesponsiveness cannot be attributed to HLA class II antigen distribution because their frequency was the same in both groups of children with IDDM.
It is suggested that the poor immune response to intradermal hepatitis B vaccine may be due to impaired macrophage activity resulting in failure of antigen presentation, which may be of importance in the immune dysfunction in children with IDDM. This hypothesis is suggested by a significantly lower score on a DTH test to a battery of antigens in the IDDM group when compared with controls. It is therefore suggested that when the hepatitis B vaccination is offered to children with IDDM it may be preferable to give it intramuscularly.

     

Reduced immune response to hepatitis B vaccine in children with insulin dependent diabetes

Twenty-four patients with moderately controlled insulin dependent diabetes with a duration of diabetes ranging from 2 to 10 years as well as 17 control subjects were vaccinated against hepatitis B virus using Gen Hevac B vaccine. The vaccine was injected 0.5 mL intramuscularly into the deltoid region on three separate occasions at intervals of 1 month. If subjects were still negative for anti-hepatitis B surface antigen (HBs) or had inadequate antibody after the third injection, a fourth administration of vaccine was given 3 months later. The mean anti-HBs titer was 243.3 ± 97.2 mi.u./mL in control subjects and 39.8 ± 53.2 in diabetic patients (P < 0.001). In the control group optimal protection was obtained in 100% of subjects, whereas 11 diabetic patients (45.8%) had low anti-HBs titer (< 10 mi.u./mL). All of 11 diabetic patients showed adequate (> 10 mi.u./mL) anti-HBs titer after the fourth dose of vaccine. In diabetic patients the most striking feature was the reduced CD4/CD8 ratio which was significantly lower (P < 0.001) than that of the control group. We conclude that diabetic children have an impaired immune response to hepatitis B vaccine. It is suggested that diabetic children should be vaccinated against hepatitis B virus with four injections instead of three.     

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.     

Residual insulin secretion in insulin dependent diabetes mellitus.

The residual insulin secretory capacity of 244 children with insulin dependent diabetes mellitus was determined by measurement of their 24 hour urinary C peptide excretion. An inverse linear relation was found between the residual B cell secretion and the duration of diabetes. The age at onset of diabetes did not affect the residual B cell function significantly.     

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.     

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.     

Indwelling cannula for insulin administration in diabetes mellitus.

Experience with an indwelling subcutaneous Teflon cannula for insulin delivery to 10 children with diabetes mellitus is described. There were no significant complications during a one year trial period. The device may particularly benefit children during the early phase after diagnosis and for those with true needle phobia.     

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.     

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.     

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.     

Safety of neonatal hepatitis B vaccine administration.

OBJECTIVE: To determine whether hepatitis B vaccination of newborns increases the incidence of fever and/or suspected sepsis. METHODS: A prospective clinical study was undertaken at the Kaiser Permanente San Francisco Medical Center involving normal full term newborns born between November 1, 1991, and April 30, 1994. During this time 3302 infants were vaccinated within 21 days of birth with hepatitis B vaccine, and 2353 were not. Clinical and demographic data were collected from Kaiser Permanente's existing clinical information systems, and laboratory data for blood and cerebrospinal fluid (CSF) cultures were obtained from the comprehensive automated regional laboratory reporting system. RESULTS: There were no significant differences between vaccinated and unvaccinated newborns in the proportion of infants who received care for fever (0.8% vaccinated and 1.1% unvaccinated, P = 0.28), allergic reactions, seizures or other neurologic events in the first 21 days of life. Vaccinated newborns were significantly less likely to undergo microbiologic evaluation for possible sepsis. Among vaccinated newborns 4.0% had blood cultures and 1.6% had CSF cultures. Among infants who were not vaccinated 8.3% had blood cultures and 1.6% had CSF cultures (P <0.001 for both tests). CONCLUSION: This study found no evidence that newborn hepatitis B vaccination is associated with an increase in the number of febrile episodes, sepsis evaluations or allergic or neurologic events. In addition our data did not support any increase in medical procedures attributed to receipt of hepatitis B vaccine.     

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.     

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.     

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.