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.     

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.     

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.     

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.     

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.     

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.     

Nocturnal hypoglycaemia and sleep disturbances in young teenagers with insulin dependent diabetes mellitus

OBJECTIVE: To determine the effect of nocturnal hypoglycaemia on sleep architecture in adolescents with insulin dependent diabetes mellitus (IDDM). DESIGN: 20 adolescents with IDDM (mean age 12.8 years, mean glycated haemoglobin (HbA1c) 8.9%) were studied on one night. Plasma glucose was measured every 30 minutes and cortisol and growth hormone levels every 60 minutes. Sleep was recorded using standard polysomnographic montages, and sleep architecture was analysed for total sleep time, stages 1-4, rapid eye movement, fragmentation, and arousals. RESULTS: Six subjects (30%) became hypoglycaemic (five subjects < 2.5 mmol/l), with one being symptomatic. There were no differences in age, HbA1c, duration of diabetes, or insulin regimen between hypoglycaemic and non-hypoglycaemic subjects. Hypoglycaemia was not predicted by glucose measurements before bed. There was no detectable rise in plasma cortisol or growth hormone concentrations during hypoglycaemia. Sleep architecture was not disturbed by nocturnal hypoglycaemia with no differences found in sleep stages, fragmentation, or arousals. CONCLUSIONS: Nocturnal hypoglycaemia is a common and usually asymptomatic complication of treatment in adolescents with IDDM. Moderate hypoglycaemia has not been shown to affect sleep architecture adversely. These findings are consistent with, and may explain, the observation that severe hypoglycaemia, with consequent seizure activity, is more common at night than during the day. Counterregulatory hormone responses to nocturnal hypoglycaemia may be less marked than with similar degrees of diurnal hypoglycaemia.     

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.     

Changes in attention with hypo- and hyperglycaemia in children with insulin dependent diabetes mellitus

We compared the results of a computerized attention test (TOVA) in 38 children with insulin dependent diabetes mellitus in relation to various spontaneously occurring blood glucose levels. Testing was performed at the following blood glucose levels: <3.3 mmol/l (hypoglycaemia), 3.3–8.3 mmol/l (normoglycaemia) and >8.3 mmol/l (hyperglycaemia) . The attention (sum of errors and response time) varied significantly with the blood glucose level (P=0.002). The highest number of errors of omission and the longest response time was observed during the test run with hypoglycaemia. Age, sex, age at manifestation of the disease, metabolic control and the results of the intelligence test had no significant influence on these results. We found that attention in children with diabetes was significantly reduced compared to TOVA norms especially during mild hypoglycaemia (P<0.001). Irrespective of the blood glucose levels, reaction time and the variability of the reaction time differed significantly between TOVA norms and diabetic children (P<0.01). Conclusion In children with diabetes mellitus a significant reduction in attention was found at mild hypoglycaemia but as well at low normal blood glucose levels. Attention deficits due to transient lowering of blood glucose may therefore occur in diabetic children even before they are aware of hypoglycaemic symptoms. Received: 24 November 1997 / Accepted: 2 March 1998     

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.