First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes.

OBJECTIVE: To determine the relationship between first-phase (1 minute + 3 minutes) insulin production during the intravenous glucose tolerance test (IV-GTT) and risk factors for developing type 1 diabetes. STUDY DESIGN: Relatives of persons with type 1 diabetes (n = 59,600) were screened for islet cell antibodies (ICAs). Subjects who had positive screening results underwent IV-GTT (> or =2 times), repeat ICA screening, insulin autoantibody (IAA) screening twice, and an oral glucose tolerance test. RESULTS: Of the 59,600 subjects in the study, 2199 (3.69%) had positive findings on initial ICA test. IV-GTTs were performed in 1622 subjects, with children <8 years having the lowest first-phase insulin release (FPIR) and subjects 8 to 20 years of age having the highest FPIR. The FPIR was lower for subjects with a confirmed positive ICA test result or a positive IAA test result, subjects with higher titers of ICA or IAA, and subjects who had an abnormal (impaired or diabetic) oral glucose tolerance test result. CONCLUSION: FPIR in the IV-GTT correlates strongly with risk factors for development of type 1 diabetes.

First-phase insulin release in normal children.

Normal values for the first-phase insulin release during an intravenous glucose tolerance test are not yet well defined for children and adolescents. In this study, 69 normal subjects (aged 7 to 22 years) who had no family history of type I diabetes, a normal glycohemoglobin value, and a negative islet cell antibody test result underwent a standard intravenous glucose tolerance test. The mean (+/- SEM) first-phase insulin release increased with age and pubertal status: 7 to 10 years, 93 +/- 10.1 mIU/L; 11 to 15 years, 172.7 +/- 22.3 mIU/L; and 16 to 22 years, 163 +/- 28.5 mIU/L. The mean intraindividual variability in 11 subjects who underwent a second test was 23.6%. Acute stress, as estimated by observer assessment or by blood catecholamine levels, did not significantly correlate with first-phase insulin release. We conclude that first-phase insulin release is markedly lower in prepubertal children than in adolescents and young adults.

Prediction of the course of pre-type I diabetes.

To increase knowledge on the predictability of the onset of insulin-dependent diabetes mellitus (IDDM; type I), we followed 38 subjects less than 18 years of age who had positive results on two or more islet-cell antibody tests and one identical twin who had positive results on one islet-cell antibody test. All 39 patients had longitudinal intravenous glucose tolerance tests to determine the first-phase insulin response (FPIR). Insulin dependence has developed in 10 untreated subjects less than 18 years of age. Of the 10 subjects, insulin dependence developed in eight a mean of 4.6 months after their FPIR fell to less than 30 microU/ml and a mean of 14 months after it fell to less than 46 microU/ml. Nine of the untreated subjects had an FPIR less than 67 microU/ml on at least two occasions and became insulin dependent a mean of 19 months after the value first fell below this level (95% confidence limit = 66.4% to 100%). All but one of the 10 subjects in whom IDDM developed initially had islet-cell antibody levels of greater than 80 JDF units. Insulin autoantibody values at onset were available for 9 of the 10 subjects and were positive (greater than 39 nU/ml) in six. We conclude that the combination of positive results on two islet-cell antibody tests and two diminished FPIRs (less than 67 microU/ml) in subjects less than 18 years of age reliably predicts the onset of IDDM. These data should permit intervention studies to be planned.

Diagnosis of pre-type I diabetes.

Islet cell antibodies were found in 71 of 1169 first-degree relatives (6.1%) from 448 families who had a proband with type I diabetes. Seven children have since become insulin dependent. All had islet cell antibodies and were followed up prospectively with measurement of first-phase insulin production during intravenous glucose tolerance testing. In this group the statistical probability of developing type I diabetes within 12 months with 95% confidence was found to be 59% to 100% when the first-phase insulin secretion was less than 25 microU/mL. The identification of the prediabetes time period should allow an opportunity for intervention in the underlying disease process to determine if the onset of type I diabetes can be altered.

Low vitamine A and zinc concentrations in Mexican-American migrant children with growth retardation.

Nutritional evaluations were undertaken on 102 Mexican-American preschool children who were below the 3rd percentile for height, weight, or head circumference. Serum vitamin A concentrations were low in 36 of 102 children (35%). Hair zinc concentrations were low in 28 of 96 children (29%) and plasma zinc concentrations were low in 35 of 94 children (37%). Children with only low height had a mean hair zinc level of 87.5 microgram/g, whereas those with only low weight had a mean level of 108.6 microgram/g and those with only low head circumference had a mean level of 100.1 microgram/g. There was no correlation of height percentiles with plasma zinc, hair zinc, or serum vitamin A. However, further studies are needed to determine if there is a relationship between growth retardation and zinc and/or vitamin A status in this population.

Cystic fibrosis and malnutrition.

Cystic fibrosis as a specific disease entity has been known to be associated with malnutrition for almost half a century. The importance of the malnutrition in the disease process remains unknown, as does much information about specific nutritional deficiencies in CF. Supplements for children with CF should include extra energy as fat or carbohydrate, a form of linoleic acid that can be absorbed, hydrolyzed protein, fat-soluble vitamins with vitamins A and E in a water emulsion, vitamin B12, probably B vitamins and vitamin C, and trace minerals. Routine measurements of nutritional status, particularly in children with growth failure, should be made at regular intervals and should include a three-day diet record and a simultaneous 72-hour stool fat determination. If fat malabsorption is not controlled by pancreatic enzymes, the use of antacids or cimetidine should be considered. The true role of nutrition in patients with CF will not be known until the appropriate studies are completed.

Increased prostaglandin synthesis in childhood diabetes mellitus.

Prostaglandins are synthesized from the fatty acids, linoleic and arachidonic acids, and are associated with increased platelet aggregation as has been found in blood from patients with diabetes mellitus. In the present study blood was obtained from 40 children with diabetes and from 20 control children for measurements of fatty acid and PGE1, PGE2, and PGF2alpha levels. The production of PGE2 and PGF2alpha was significantly elevated in blood from the children with diabetes at all times measured. The mean quantitative plasma linoleic acid levels were also higher in the patients. The increased PG synthesis may be related to the vascular problems that occur in patients with diabetes.