The associations between maternal pre-pregnancy body mass index or gestational weight change during pregnancy and body mass index of the child at 3 years of age.

OBJECTIVE: To estimate the associations between maternal pre-pregnancy body mass index (BMI) or gestational weight change (GWC) during pregnancy and offspring BMI at 3 years of age, while taking several pre-and postnatal factors into account. DESIGN: The Norwegian Mother and Child Cohort Study is a population-based pregnancy cohort study of women recruited from all geographical areas of Norway. SUBJECTS: The study includes 31 169 women enrolled between 2000 and 2009 through a postal invitation sent to women at 17-18 weeks of gestation. Data collected from 5898 of the fathers were included. MAIN OUTCOME MESURES: Offspring BMI at 3 years was the main outcome measured in this study. RESULTS: Mean maternal pre-pregnancy BMI was 24.0 kg m(-2) (s.d. 4.1), mean GWC in the first 30 weeks of gestation was 9.0 kg (s.d. 4.1) and mean offspring BMI at 3 years of age was 16.1 kg m(-2) (s.d. 1.5). Both maternal pre-pregnancy BMI and GWC were positively associated with mean offspring BMI at 3 years of age. Pre-pregnancy BMI and GWC also interacted, and the strength of the interaction between these two factors was strongly associated with the increase in offspring BMI among mothers who gained the most weight during pregnancy and had the highest pre-pregnancy BMI. Our findings show that results could be biased by not including pre-pregnant paternal BMI. CONCLUSION(S): This large population-based study showed that both maternal pre-pregnancy BMI and GWC were positively associated with mean offspring BMI at 3 years of age.

Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families.

The main genetic predisposition to type 1 diabetes (T1D) is known to be conferred by the HLA-DRB1, -DQA1 and -DQB1 genes in the major histocompatibility complex (MHC). Other genetic factors within this complex are known to contribute, but their identity has often been controversial. This picture is shared with several other autoimmune diseases (AIDs). Moreover, as common genetic factors are known to exist between AIDs, associations reported with other AIDs may also be involved in T1D. In this study, we have used these observations in a candidate gene approach to look for additional MHC risk factors in T1D. Using complementary conditional methods (involving conditional logistic regression and family-based haplotype tests) and analyses of linkage disequilibrium (LD) patterns, we confirmed association for alleles of the HLA-A and HLA-B genes and found preliminary evidence for a novel association of a single-nucleotide polymorphism (rs2259571) in the AIF1 gene, independent of the DRB1-DQA1-DQB1 genes and of each other. However, no evidence of independent associations for a number of previously suggested candidate polymorphisms was detected. Our results illustrate the importance of a comprehensive adjustment for LD effects when performing association studies in this complex.

A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma.

Type 1 diabetes (T1D) and allergic asthma are immune-mediated diseases. Pattern recognition receptors are proteins expressed by cells in the immune system to identify microbial pathogens and endogenous ligands. Toll-like receptors (TLRs) and CD14 are members of this family and could represent a molecular link between microbial infections and immune-mediated diseases. Diverging hypotheses regarding whether there exists a common or inverse genetic etiology behind these immune-mediated diseases have been presented. We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. Allele and haplotype frequencies were analyzed in relation to diseases and in addition transmission disequilibrium test analyses were performed in the family material. Both T1D and allergic asthma were significantly associated with the TLR2 rs3804100 T allele and further associated with the haplotype including this SNP, possibly representing a susceptibility locus common for the two diseases. Neither TLR4 nor CD14 were associated with T1D or allergic asthma.

The FCRL3 -169T>C polymorphism is associated with rheumatoid arthritis and shows suggestive evidence of involvement with juvenile idiopathic arthritis in a Scandinavian panel of autoimmune diseases.

BACKGROUND AND OBJECTIVES: The Fc receptor-like 3 (FCRL3) gene -169T>C single nucleotide polymorphism (SNP) has been reported to be associated with several autoimmune diseases (AIDs) in Japanese populations. However, association results in other populations have been conflicting. Therefore, we investigated this SNP in a Scandinavian panel of AIDs. METHODS: We genotyped patients with rheumatoid arthritis (RA; n = 708), juvenile idiopathic arthritis (JIA; n = 524), systemic lupus erythaematosus (SLE; n = 166), ulcerative colitis (UC; n = 335), primary sclerosing cholangitis (PSC; n = 365), Crohn disease (CD; n = 149), a healthy control group (n = 1030) and 425 trio families with type 1 diabetes (T1D). Statistical analysis consisted of case-control and family-based association tests. RESULTS: RA was associated with the C allele (odds ratio (OR) = 1.16, 95% CI 1.01 to 1.33) and the CC genotype (OR = 1.30, 95% CI 1.01 to 1.67) of the FCRL3 -169T>C SNP in our material. Suggestive evidence for association was also found for JIA (CC genotype: OR = 1.30, 95% CI 0.99 to 1.70), and clinical subgroup analysis indicated that this was connected to the polyarticular subgroup. No significant association was found with SLE, UC, CD, PSC or T1D. In patients with RA, we found no significant interaction between the FCRL3 -169T>C and PTPN22 1858C>T SNPs, nor between the FCRL3 -169CC genotype and IgM-rheumatoid factor or anti-cyclic citrullinated peptide titre levels. CONCLUSION: We found an association between the FCRL3 -169T>C SNP and RA, and suggestive evidence for involvement with JIA, in a Norwegian population. These findings lend support for a role for this SNP in RA across ethnically diverse populations, and warrant follow-up studies in JIA.

Sweets, snacking habits, and skipping meals in children and adolescents on intensive insulin treatment.

AIM: To examine the association between skipping meals and snacking events and dietary and clinical characteristics in children and adolescents using modern insulin treatment. METHODS: Dietary intake was recorded for 4 d in food diaries in 655 young diabetic patients. Number of meals and snacking events was recorded in a separated questionnaire, while clinical data were obtained from case record forms. Skipping meals refer to consuming a main meal (e.g., breakfast) five times a week or less. RESULTS: Modern insulin treatment may favor a more flexible lifestyle. This study shows that there are fewer young diabetic patients who skip meals than non-diabetic controls (p < 0.001) even when using modern intensified insulin treatment. However, skipping meals among young diabetic patients was associated with negative characteristics such as having suboptimal hemoglobin A1c (HbA1c) (OR 4.7, p = 0.02), higher low-density lipoprotein (LDL) cholesterol levels (OR 4.0, p < 0.001), watching more TV (OR 3.6, p < 0.001), being overweight (OR 2.8, p = 0.03), as well as having a higher intake of added sugar (OR 2.1, p = 0.01) and lower intake of fiber (OR 0.2, p = 0.04) compared with those not skipping meals. Having more than two snacking events during the day was associated with higher HbA1c, higher intake of added sugar and sweets, and spending more hours in front of the TV or personal computer. CONCLUSIONS: In general, fewer children and adolescents with type 1 diabetes skip meals compared with healthy peers. Those who skip meals and have more snacking events have poorer glycemic control and less healthy dietary and leisure habits.

HLA class II alleles in Norwegian patients with coexisting type 1 diabetes and celiac disease.

BACKGROUND: Type 1 diabetes (T1D) and celiac disease (CeD) are 2 distinct diseases, but there is an increased risk of developing CeD for T1D patients. Both diseases are associated with HLA-class II alleles, such as DQB1 *02:01 and DQB1 *03:02; however, their risk contribution vary between the diseases. MATERIALS AND METHODS: We genotyped HLA-DRB1 and - DQB1 in 215 patients with coexisting T1D and CeD identified from a T1D cohort, and compared them to patients with T1D (N = 487) and CeD (N = 327), as well as healthy controls (N = 368). RESULTS: The patients with coexisting T1D and CeD had an intermediate carrier frequency (72.8%) of the DRB1 *03:01- DQB1 *02:01- DQA1 *05:01 haplotype compared to T1D (64.1%) and CeD (88.7%) patients. The DRB1 *03:01- DQB1 *02:01- DQA1 *05:01/ DRB1 *04- DQB1 *03:02- DQA1 *03 haplotype combination, encoding DQ2.5 and DQ8 molecules, was equally frequent among patients with both T1D and CeD (52.6%) and T1D patients (46.8%) but significantly lower in CeD patients (9.5%). CONCLUSION: Overall, the patients with coexisting T1D and CeD had an HLA profile more similar to T1D patients than CeD patients.

Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes.

OBJECTIVES: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. DESIGN: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. RESULTS: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. CONCLUSIONS: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.

Increase in insulin antibodies during continuous subcutaneous insulin infusion and multiple-injection therapy in contrast to conventional treatment.

Forty-five insulin-dependent diabetics were randomized to 1 yr treatment with either continuous subcutaneous insulin infusion (CSII), multiple insulin injections (MI), or continued conventional treatment. The CSII group used regular insulin only, the MI group used 4-6 premeal injections of regular insulin and intermediate insulin at night, and the conventional group used two daily injections of combined regular and intermediate insulin. Only highly purified porcine insulin was used. Near normoglycemia was obtained during CSII and MI but not during conventional treatment. Antibodies against insulin were measured in serum samples by measuring the binding of iodinated porcine insulin to serum after removal of free and antibody-bound insulin from the samples by acid charcoal. The percent binding of 125I-labeled insulin increased significantly during MI and CSII, in contrast to conventional treatment. Nineteen patients had sufficient binding capacity for Scatchard analysis. In the CSII and MI groups, high- or low-affinity antibodies or both were induced. When insulin was administered subcutaneously during MI or CSII for 1 yr, the insulin antibody production increased, in contrast with conventional treatment.

HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection.

Recent studies have shown that the risk conferred by the high-risk DQA1*03-DQB1*0302 (DQ8) haplotype is modified by the DRB1*04 allele that is also carried by this haplotype. However, many of these studies suffer from lack of sufficient numbers of DQ-matched control subjects, which are necessary because there is a strong linkage disequilibrium between genes in the HLA complex. In the present study, using a large material of IDDM patients and DQ-matched control subjects, we have addressed the contribution of DR4 subtypes to IDDM susceptibility. Our data, together with recent data from others, clearly demonstrate that some DR4-DQ8 haplotypes are associated with disease susceptibility, while others are associated with protection, depending on the DRB1*04 allele carried by the same haplotype. In particular, our data demonstrate that DRB1*0401 confers a higher risk than DRB1*0404. Based on combined available data on the genetic susceptibility encoded by various DR4-DQ8 haplotypes and the amino acid composition of the involved DRbeta*04 chains as well as the ligand motifs for these DR4 subtypes, we have developed a unifying hypothesis explaining the different risks associated with different DR4-DQ8 haplotypes. We suggest that disease susceptibility is mainly conferred by DQ8 while DR4 subtypes confer different degrees of protection. Some DR4 subtypes (i.e., DRB1*0405, 0402, and 0401) confer little or no protection, while others (i.e., DRB1*0404, 0403, and 0406) cause an increasing degree of protection, possibly by binding a common protective peptide. Features of a protective peptide that fit such a model are briefly discussed.

No independent associations of LMP2 and LMP7 polymorphisms with susceptibility to develop IDDM.

Results from a recent study suggested that polymorphisms within the HLA class II genes LMP2 and LMP7 were associated with the susceptibility for developing IDDM, and that this association could not be explained by linkage disequilibrium to HLA-DR or -DQ genes. We typed 285 IDDM patients and 337 HLA-DRB1-DQA1-DQB1 genotypically matched control subjects from an ethnically homogeneous population for both the G/T polymorphism in intron 6 of the LMP7 gene and the Arg-His polymorphism in the LMP2 gene. In addition, we typed IDDM families in which at least one parent was homozygous for a DRB1-DQA1-DQB1 haplotype and performed a transmission/disequilibrium test of these LMP polymorphisms. Our data suggest that none of these LMP2 or LMP7 polymorphisms are independently associated with IDDM susceptibility, in contrast to what has been previously reported by others. Further, our results suggest that one partial explanation for the previously reported independent association between IDDM and these LMP polymorphisms may have been that patients and control subjects were not matched for DRB1*04 subtypes. Our results emphasize the need for a complete matching for DRB1, DQA1, and DQB1 alleles between patients and control subjects when attempting to detect independent effects of other polymorphisms in the HLA complex on IDDM susceptibility or protection.

Relationship between cows' milk consumption and incidence of IDDM in childhood.

OBJECTIVE: To compare age-standardized incidence rates of diabetes in children 0-14 yr of age and cows' milk consumption in various countries. RESEARCH DESIGN AND METHODS: Ecological correlation study. Only incidence rates from diabetes registries carefully validated by the Diabetes Epidemiology Research International Study Group were used-Finland, Sweden, Norway, Great Britain, Denmark, United States, New Zealand, Netherlands, Canada, France, Israel, and Japan. Data on fluid cows' milk consumption in corresponding countries were obtained from the International Dairy Federation. RESULTS: Correlation between milk consumption and incidence of insulin-dependent diabetes mellitus (IDDM) was 0.96. The data fit a linear regression model, and analysis showed that 94% of the geographic variation in incidence might be explained by differences in milk consumption. CONCLUSIONS: The results support the hypothesis that cows' milk may contain a triggering factor for the development of IDDM.

New semiquantitative dipstick test for microalbuminuria.

OBJECTIVE: We compared a new semiquantitative dipstick test for microalbuminuria (Micral-Test) with a quantitative immunoturbidimetric method. RESEARCH DESIGN AND METHODS: This correlation study was performed at a pediatric and medical outpatient clinic at a university hospital. Overnight urine samples containing less than 200 mg/L albumin from 186 diabetic patients were analyzed. RESULTS: The correlation coefficient between the new semiquantitative method and the immunoturbidimetric reference method was 0.82. Elevated albumin concentration was defined as greater than 20 mg/L albumin in overnight urine, and the prevalence of samples with values above this level was 28%. By this definition, the Micral-Test assay level greater than or equal to 20 mg/L had a sensitivity of 92.3% and a specificity of 82.1%. Of the diabetic subjects, 84.9% were correctly classified as having elevated urinary albumin concentration or not. CONCLUSIONS: The Micral-Test is useful for in-clinic screening for elevated urinary albumin concentration and monitoring the development of urinary albumin excretion in the low microalbuminuric range.

Increased serum levels of advanced glycation end products (AGEs) in children and adolescents with IDDM.

OBJECTIVE: To investigate whether the serum levels of advanced glycation end products (AGEs) are increased in IDDM children and adolescents and to study the effect of puberty on serum levels of AGEs (S-AGEs). RESEARCH DESIGN AND METHODS: A total of 68 children and adolescent IDDM patients (age, 13.3 +/- 4.0 years; duration of diabetes, 5.0 +/- 3.6 years; HbA1c, 8.2 +/- 2.0%; Tanner stage [public hair], 1 vs. 2-5, 24/42) recruited from the pediatric outpatient clinic at Aker University Hospital were compared with 25 healthy nondiabetic control subjects. S-AGEs were measured by a fluoremetric immunoassay. RESULTS: S-AGEs were significantly elevated in the diabetic group when compared with the control group (14.4 +/- 3.5 vs. 11.7 +/- 3.0 U/ml, P < 0.002). A significant correlation (r = 0.26, P < 0.04) was found between S-AGEs and HbA1c in the diabetic group but not in the control group. No significant correlation was found between S-AGEs and the duration of diabetes in the diabetic group or S-AGEs and blood glucose concentration or age in either group. We found no difference between S-AGEs in boys and girls and in prepubertal and pubertal diabetic or control subjects. CONCLUSIONS: S-AGEs are increased in young patients with diabetes before puberty. Since AGEs are linked to the pathogenesis of vascular complications, this observation suggests that the pathological processes leading to diabetic late complications start even before puberty.

The advanced glycation end product Nepsilon-(carboxymethyl)lysine is increased in serum from children and adolescents with type 1 diabetes.

OBJECTIVE: To investigate whether children and adolescents with type 1 diabetes have increased serum levels of the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) at an early stage of the disease. RESEARCH DESIGN AND METHODS: The serum levels of CML in 38 patients with type 1 diabetes aged 14+/-3.2 (mean+/-SD) years were compared with those in 26 control subjects aged 16+/-1.7 years. The mean duration of diabetes was 5+/-4.7 years, ranging from 0.5 to 15 years. The mean levels of HbA1c were 10.3+/-2.5% in the patient group. The serum levels of CML were measured using a monoclonal anti-CML antibody in a fluoremetric immunoassay. Serum protein levels of advanced glycation end products (AGEs) were assayed using a polyclonal antibody from rabbit immunized with AGE-RNase (pAGE). RESULTS: The serum levels of CML and pAGE were significantly increased in the patient group versus the control group: 1.08 (0.45-2.97) U/ml CML (median 10-90 percentiles) vs. 0.70 (0.36-1.79) U/ml CML, P < 0.03, and 6.6 (5.1-9.9) U/ml pAGE vs. 5.5 (3.7-8.2) U/ml AGEs, P < 0.01. A significant relationship between CML and pAGE was found in the IDDM group, r = 0.76, P < 0.001. The CML levels were not associated with the HbAlc levels (n = 23, r = -0.02, NS), cholesterol levels (n = 21, r = 0.07, NS), age, sex, or diabetes duration. CONCLUSIONS: Serum levels of CML are increased in patients with type 1 diabetes. This increase precedes the development of micro- and macrovascular complications.

HLA associations in insulin-dependent diabetes mellitus: no independent association to particular DP genes.

Genes in the HLA complex are associated with susceptibility to develop insulin-dependent diabetes mellitus (IDDM). Several studies, from different populations, have demonstrated strong associations between particular DR and DQ alleles and disease susceptibility or protection. Whether also particular DP alleles may independently contribute is more controversial. Some studies have found a greater frequency of DPB1*0301 among IDDM patients compared to controls, apparently independently of linkage disequilibrium with high risk DR and DQ alleles. To address this question in an ethnically homogeneous population (Norwegian), we have DPA1 and DPB1 genotyped 237 IDDM patients and 287 DRB1-DQA1-DQB1 matched controls, carrying high risk DR3/4 or DR4/4 genotypes. We were unable to detect any significant independent associations between DP alleles and IDDM susceptibility or protection in this population. Thus, our results do not support previous reports on an independent association between some DP alleles and susceptibility to develop IDDM.

The response of diabetic retinopathy to 41 months of multiple insulin injections, insulin pumps, and conventional insulin therapy.

Forty-five diabetic patients were randomized and treated with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (MI), or conventional insulin treatment (CIT) for 41 months. Near-normoglycemia was obtained with CSII and MI but not with CIT. A transient increase in microaneurysms and hemorrhages was seen at three months in CSII-treated patients. After 41 months, a moderate progression in microaneurysms and hemorrhages was registered, as assessed from fundus photographs, in all treatment groups. Fluorescein angiograms indicated a tendency (not statistically significant) to retarded progression of retinopathy in MI- and CSII-treated patients compared with CIT-treated patients. Soft exudates developed after three to six months of rapid tightening of metabolic control in 50% of patients on CSII and MI regimens. Those patients who had soft exudates had a slower progression of retinopathy three years later than those who did not develop soft exudates. Transient progression of retinopathy may be related to fluctuations in blood glucose levels, although a favorable effect of long-term improved metabolic control was not documented.

Effects of intensified insulin treatment on various lesions of diabetic retinopathy.

Mild background retinopathy was studied prospectively during long-term strict blood glucose control in insulin-dependent diabetes mellitus. Forty-five subjects (21 women and 24 men with a mean age of 26.3 years and a mean duration of diabetes of 12.8 years) were randomly assigned to continuous subcutaneous insulin infusion, multiple injections, and conventional two-injection treatment. Eyes were examined two months before treatment, at the beginning of treatment, and after three, six, and 12 months. A progressive deterioration was found in the two-injection group during the study, but no significant changes were found in patients receiving multiple injections. A transient deterioration occurred after three months of continuous subcutaneous insulin infusion. Soft exudates appeared in 50% of the patients on the two intensified regimens, but no exudates were found in patients given conventional treatment. The morphologic changes seemed to be related to a large and rapid decrease in mean blood glucose or to an increased frequency of hypoglycemia, or both.

Transient proliferative diabetic retinopathy during intensified insulin treatment.

Two women aged 22 and 19 years who had had diabetes for 11 and four years, respectively, developed proliferative retinopathy after five to seven months of significantly improved metabolic control. They were participants in two separate prospective studies including 97 insulin-dependent patients. At inclusion, one patient showed minimal background retinopathy and the other showed no retinopathy. Their level of glycosylated hemoglobin was initially high (14.3% and 17.5%) but within five to six months had fallen by 5.7% and 7.5%. The improved metabolic control was obtained by home blood glucose monitoring and insulin pump in the older patient and by home blood glucose monitoring only in the other. By maintaining near normoglycemia, regression of the proliferative retinopathy was achieved. Photocoagulation was not performed. After five and two years of follow-up, respectively, only mild background retinopathy has been noted in both patients. We concluded that a significant lowering of blood glucose may provoke proliferative retinopathy and that sustained good metabolic control may reverse this retinopathy without photocoagulation.

Effects of intensified insulin treatment on retinal vessels in diabetic patients.

Forty-five diabetic patients were randomly assigned to treatment with continuous subcutaneous insulin infusion (CSII), multiple injections (MI), and conventional insulin treatment (CIT). They were prospectively followed up for one year. A computerised scanning microdensitometer was applied on fundus photographs of retinal vessels, and we studied changes in calibres of the blood column (W0) and in width (Wr/W0) and intensity (Ir) of the central 'light reflex'. After six months of improved metabolic control the Ir was reduced in both MI and CSII cases compared with CIT cases (p less than 0.01), indicating haemorrheological changes in the retinas. Within these six months cotton-wool spots appeared in half the patients (n = 15) on CSII and MI, but not in CIT patients. Subjects who developed cotton-wool spots, compared with those who did not, had greater intensities of reflection and larger calibres of vessels at the start of the study (p less than 0.01). On intensifying the treatment they were characterised by a larger fall in hemoglobin A1 (p less than 0.01) and by a larger decrease in Ir on arteries (p less than 0.05) and veins (p less than 0.01). The behaviour of the retinal circulation is different in patients developing transient ischaemic lesions on intensified insulin treatment from its behaviour in those who do not.

Decreased serum insulin-like growth factor I during puberty in children with insulin dependent diabetes mellitus (IDDM).

Previous reports concerning insulin-like growth factor-I (IGF-I) in diabetics are conflicting. This study describes IGF-I in children with insulin-dependent diabetes mellitus (IDDM) and healthy controls in relation to pubertal development. Sixty-six children participated (34 girls and 32 boys) of which 33 had IDDM. The mean age in the study population was 14.3 years, (range 7.1 to 19.7). Serum IGF-I was significantly decreased in diabetics. Diabetic girls had a mean IGF-I of 28.3 (14.4; = SD) nmol/l compared with 42.8 (15.0) nmol/l in controls. In diabetic boys the result was 30.0 (16.0) nmol/l compared with 44.1 (23.4) in controls. Growth hormone was measured in only one fasting morning serum sample from each individual. There was no difference between girls, but diabetic boys had higher mean serum concentration of growth hormone than controls (3.5 (4.8) vs. 1.8 (1.5) micrograms/l respectively). Diabetic girls had delayed menarche, corresponding to a slightly delayed bone maturation.