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Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies

The incidence of type 1 diabetes (T1D) has increased explained by changes in environment or lifestyle. In modern society dissemination of heavy metals has increased. As the autoimmune process usually starts already, we hypothesized that exposure to toxic metals during fetal life might contribute to development of T1D in children. We analysed arsenic (AS), aluminium (Al), cadmium (Cd), lithium (Li), mercury (Hg), lead (Pb), in cord blood of 20 children who later developed T1D (probands), and in 40 age-and sex-matched controls. Analysis of heavy metals in cord blood was performed by ALS Scandinavia AB (Luleå, Sweden) using the ‘ultrasensitive inductively coupled plasma sector field mass spectrometry method’ (ICP-SFMS) after acid digestion with HNO3. Most children had no increased concentrations of the metals in cord blood. However, children who later developed T1D had more often increased concentrations (above limit of detection; LOD) of aluminium (p = 0.006) in cord blood than the non-diabetic controls, and also more often mercury and arsenic (n.s). Our conclusion is that exposure to toxic metals during pregnancy might be one among several contributing environmental factors to the disease process if confirmed in other birth cohort trials.

Summary of surgical procedure codes used in the analysis. (PDF 86 kb)

Summary of ICD codes used for ulcerative colitis and Crohn’s disease. (PDF 36 kb)

Summary of codes used for extra-intestinal manifestations/comorbidities. (PDF 151 kb)

Summary of codes used for medical treatment/prescribed drugs. (PDF 47 kb)

Summary of paediatric prevalence studies – by year of publication. (PDF 107 kb)

The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P 0.05), HSP60 and IA-2 (IL-10, P 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity.

We determined A/H1N1-HA antibodies in relation to HLA-DQ genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7-18 years old type 1 diabetes patients diagnosed April 2009 - December 2010. Antibodies to (35) S-methionine-labeled A/H1N1 hemagglutinin were determined in a radiobinding assay in patients diagnosed before (n=325), during (n=355) and after (n=461) the October 2009 - March 2010 Swedish A(H1N1)pdm09 vaccination campaign, along with HLA-DQ genotypes and autoantibodies against GAD, insulin, IA-2 and ZnT8 transporter. Before vaccination, 0.6% patients had A/H1N1-HA antibodies compared to 40% during and 27% after vaccination (p

AIMS/HYPOTHESIS: The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. METHODS: Blood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). RESULTS: At type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p < 0.0001). GADA was positively associated with TPOAb (p < 0.001) and with TGAb (p < 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p c) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p c = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. CONCLUSIONS/INTERPRETATION: GADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.

The prevalence of atopy was studied in 61 children with type I insulin-dependent diabetes mellitus (IDDM) and 72 age- and sex-matched control subjects. The two groups had a similar prevalence of atopic disease and did not differ significantly with respect to history, clinical findings, skin prick test results, total serum IgE levels, or presence of circulating IgE antibodies to allergen. We also studied delayed-type hypersensitivity reactions in 37 of the children with IDDM and 46 of the control subjects. Children with IDDM, as compared with those without IDDM, more often had other autoimmune diseases in their family histories (p0.01). They also had significantly stronger delayed hypersensitivity reactions than the control subjects, as determined with tetanus toxoid (p0.05) and mumps antigen (p0.01). The reactivity to purified protein derivate of tuberculin and Candida antigen was similar in the two groups. The study does not confirm previous suggestions of an inverse relationship between IDDM and atopic disease but does not confirm previous suggestions of an inverse relationship between IDDM and atopic disease but does confirm that IDDM is associated with other immunologic disturbances. The different genetic and immunologic traits do not prevent allergic manifestations in children with diabetes.

The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on chemokines and their receptors.Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex.Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group.Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity.

The aim of this study was to explore the association between pedometer-determined physical activity versus measures of obesity, inflammatory markers and arterial stiffness in people with Type 2 diabetes.We analysed data from 224 men and 103 women with Type 2 diabetes, aged 54-66 years. Physical activity was measured with waist-mounted pedometers during three consecutive days and the number of steps/day were calculated and classified in four groups:5000 steps/day, 5000-7499 steps/day, 7500-9999 steps/day and ≥ 10000 steps/day. Blood samples were analysed for lipids, HbA(1c), inflammatory markers including C-reactive protein and interleukin-6. Nurses measured blood pressure and anthropometrics. Aortic pulse wave velocity was measured with applanation tonometry over the carotid and femoral arteries.Mean steps/day was 7683 ± 3883 (median 7222, interquartile range 4869-10,343). There were no differences in age, diabetes duration, blood pressure, lipids or glycaemic control between the four groups of pedometer-determined physical activity. Subjects with higher steps/day had lower BMI (28.8 vs. 31.5 kg/m(2), P0.001), waist circumference (101.7 vs. 108.0 cm, P0.001), lower levels of C-reactive protein (1.6 vs. 2.6 mg/l, P = 0.007), lower levels of interleukin-6 (1.9 vs. 3.8 pg ml, P0.001) and lower pulse wave velocity (10.2 vs. 11.0 m/s, P = 0.009) compared with less physically active people.We conclude that physical activity measured with pedometer was associated not only with less abdominal obesity, but also with decreased systemic low-grade inflammation as well as with low arterial stiffness, in people with Type 2 diabetes.

Aims To compare levels of insulin antibodies in children and adolescents after initiation of insulin therapy using either insulin aspart (IAsp) or human insulin (HI) in combination with Neutral Protamine Hagedorn (NPH) insulin, and to investigate the relationships between insulin antibodies and HbA1c and insulin dose. Methods IAsp-specific antibodies (IAsp-Ab) and antibodies cross-reacting with HI and IAsp (HI-cross-Ab) were analysed by radioimmunoassay at diagnosis of diabetes and every 3–6 months for 30 months. Seventy-two patients (HI = 30, IAsp = 42) with Type 1 diabetes, aged 2–17 years were included. Data on HbA1c, insulin dose and serious adverse events (SAEs) were collected retrospectively. Results IAsp-Ab levels remained low throughout the study. After 9 months, the level of HI-cross-Ab increased [mean (sd) HI, 48.8% (21.53); IAsp, 40.2% (17.92)] and remained elevated. Repeated measurement analysis of HI-cross-Ab levels showed no significant difference between treatments (P = 0.16). HI-cross-Ab were significantly associated with total insulin dose (U/kg) (P = 0.001) and time (P

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

To examine the risk of low birthweight (2500 g, LBW), intrauterine growth retardation (IUGR) and preterm birth (gestational age37 wk) in relation to milk intake.Observational study in southeast Sweden. Questionnaires were used to collect data on milk consumption during pregnancy and infant birthweight from mother-infant pairs during a 2-y period as part of the ABIS (All Babies in Southeast Sweden) study. Data on IUGR were obtained through the Swedish medical birth registry.Adjusting for confounders, low milk intake during pregnancy was associated with an increased risk of IUGR (p = 0.019; n = 12880). LBW (p = 0.191) and preterm birth (p = 0.921) were not associated with milk intake during pregnancy.This study indicates that low milk intake in the pregnant mother may be associated with IUGR of the newborn. We cannot exclude the possibility that the correlation found between milk consumption and intrauterine growth may be due to undetected confounders. Hence, further research is needed to evaluate the relationship between low milk intake, birthweight and risk of IUGR.

Screening to predict serious diseases in the general population has been regarded as unethical as it is supposed to make people anxious. Therefore we have evaluated whether mothers become anxious when their babies participate in a project to predict diabetes in the general child population. Out of 21 700 newborn children, 16 300 (75%) entered the ABIS project (All Babies in South-east Sweden). The parents (usually the mothers) answered a questionnaire at the child's birth and then again after 1 yr. A total of 10 868 representative birth questionnaires had been analyzed. To the question, 'How do you feel when you know that your child is participating in this study?', only 2.5% of mothers of children with type 1 diabetes in the family answered 'more anxious/much more anxious', and even fewer (1.5%) of the mothers in the general population (p0.01). A total of 52.5% of the general population answered 'calmer/more reassured' (29.3% 'calmer' and 23.2% 'much calmer'), while 43.3% felt unaffected. Those 1.5% of mothers who reported becoming more anxious were more likely to be in an unstable social situation (unemployed, p0.001; born abroad, p0.001; low education, p0.001). At the 1-yr follow-up, 4948 unselected questionnaires had been analyzed. Only 1.2% of the mothers felt 'more anxious', while the overwhelming majority felt either unaffected (58.7%) or calmer (38.6%). At this follow-up, most of those who had felt 'more anxious' at birth did not feel that way any longer, and none of those with diabetes in the family. We conclude that large-scale screening studies for the prediction of diabetes in the general population can be performed without causing increased anxiety. A few parents, most often found in the group with known social problems, might need extra information and support.

To investigate pain, leakage and bleeding when injecting insulin with different diameters of needles.Sixty children and adolescents aged 9-21 yrs participated in study A and 40 aged 8-20 yrs in study B. Both were double-blind and randomized. In study A, we evaluated the pain when injecting with three needles [Novo 27G/13 mm (N27), B-D MicroFine IV 28G/13 mm (B28), NovoFine 28G/12 mm (N28)] and in study B, with three needles [NovoFine 28G/12 mm (N28), B-D MicroFine+ 29G/13 mm (B29), NovoFine 30G/8 mm (N30)] and one placebo injection (no needle mounted). Abdominal and thigh injections were given in a 45 degrees angle with a lifted two-finger skinfold on two different visits, scoring pain on a 10-cm visual analog scale (VAS), and in study B faces were added to the scale.The median VAS scores in study A were 1.2 cm (N27), 1.2 cm (B28) and 1.0 cm (N28) for abdominal injections, and 1.2 cm (N27), 0.7 cm (B28) and 1.1 cm (N28) (n.s.) for thigh injections. The median VAS scores in study B were 2.5 cm (N28), 2.3 cm (B29) and 2.8 cm (N30) (n.s.) for abdominal injections, and 2.0 cm (N28), 1.5 cm (B29) and 1.9 cm (N30) (n.s.) for thigh injections. The overall median score of placebo injections was 0.1 cm (p=0.0001). Bleedings were less common with the B29 needle (35.5%) than with the N28 needle (48.1%) (p=0.028) but with no difference compared to the N30 needle (39.2%). Leakage of insulin was found in 14% of abdominal and 25% of thigh injections (p=0.0001) with no difference between the needles. VAS scores were higher in study B which may be explained by the facial VAS scale increasing the range of answers.We found no difference in injection pain, preference, bleeding or insulin leakage between the needles. Decreasing the needle diameter from 0.4 to 0.3 mm (27-30G) does not seem to decrease pain perception in this age group.

Due to the potential ethical and psychological implications of screening, and especially in regard of screening on children without available and acceptable therapeutic measures, there is a common view that such procedures are not advisable. As part of an independent research- and bioethical case study, our aim was therefore to explore and describe bioethical issues among a representative sample of participant families (n = 17,055 children) in the ABIS (All Babies In South-east Sweden) research screening for Type 1 diabetes (IDDM). The primary aim is the identification of risk factors important for the development of diabetes and other multifactorial immune-mediated diseases. Four hundred, randomly chosen, participant mothers were asked to complete a questionnaire exploring issues of information, informed consent, bio-material, confidentiality and autonomy, and of prevention/intervention. 293 completed the questionnaire, resulting in a response rate of 73.3%. The majority of questions had the form of 6-point Likert-type response scales (1-6). We found that the majority of respondents felt calm in in regard of samples and written material, and also concerning the possibility of their child in the future being identified as having high risk of developing Type 1 diabetes. An important finding concerning access and control of mainly biological data was indicated, with the respondents expressing concern for potential future use. We believe our findings indicate that this kind of empirical studies can substantially contribute to our understanding of bioethical issues of medical research involving genetics. Issues, such as safeguards ensuring the ethical criteria of autonomy and respect, were emphasised by our respondents. We believe the issues brought up may promote further discussion, and do suggest issues for consideration by, among others, researchers, bioethicists and Institutional Review Boards.

Even a minor decrease in birthweight predisposes to adult disease. Inflammatory bowel disease (IBD) in the mother is a risk factor for low birthweight and preterm infants. This study investigated the effect of IBD in the mother or father, adjusting for confounders, on the newborn infant, with the focus on birthweight and pregnancy duration. A total of 10399 single-birth mother-infant pairs was prospectively enrolled within the ABIS project (All Babies In Southeast Sweden). Outcome measures included birth week, preterm birth (37 wk), birthweight, low birthweight (2500 g), birth length, caesarean section and neonatal hospital care. Ulcerative colitis (UC) in the mother was associated with lower birthweight in the infant (adjusted difference: -330 g, adjusted 95% confidence interval: -509 to -150 g, p0.001), and with even lower birthweight when the mother was treated with Mesalazine or steroids. No decrease in birthweight was seen in infants whose mother suffered from Crohn's disease (CD) (adjusted difference: -65 g, adjusted 95% confidence interval: -354 to 224 g, p0.05). Maternal UC or CD did not affect the pregnancy duration. The neonatal outcome of infants whose father suffered from UC and CD did not differ from the control group.UC in the mother affects the birthweight of the infant, which may predispose to future disease in the infant. Most women and men with UC and CD can, however, expect a healthy child with neither preterm birth nor low birthweight.

The incidence of nephropathy in Type 1 diabetes mellitus has declined during the past decade, probably as a result of improved glycaemic control. We wanted to investigate whether the incidence of severe retinopathy has changed during the same time period and to evaluate the importance of glycaemic control in relation to the development of severe retinopathy and nephropathy. All 213 patients in whom Type 1 diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in southeastern Sweden were studied. Ninety-two per cent of the patients were followed from the onset of diabetes to 1991 or to death. The cumulative incidence of severe retinopathy was not significantly different between the patients with diabetes onset 1961-65, 1966-70, 1971-75, and 1976-80. The risk of developing severe retinopathy or nephropathy was higher in patients with very poor glycaemic control (HbA1cor = 8.4%) vs patients with poor control (HbA1cor = 7.28.4%; p0.001). Patients with poor control had an increased risk of developing severe retinopathy vs patients with good control (HbA1c7.2%; p0.008) but there was no difference in the risk of nephropathy. No patients with good control developed nephropathy and only one patient developed severe retinopathy during 25 years of diabetes.

The purpose of the study was to determine whether psychosocial stress during different life periods could be a risk factor in the etiology/pathogenesis of insulin-dependent diabetes mellitus (IDDM) in children.In a population-based sample of 67 case patients 0-14 years of age and 61 matched healthy control subjects, life events during the entire lifespan before the onset of IDDM were recorded as well as measures of child behavior before onset, social support, and family function.Negative life events occurring during the first 2 years of life, life events with difficult adaptation, child behavioral deviances, and a more chaotic family function were more common in the case group. A stepwise logistic regression indicated that negative life events in the first 2 years increased the risk of IDDM and that premorbid child behavior as well as dysfunctional hierarchical family pattern affect the risk.Stress early in life may increase the risk for IDDM, presumably by affecting the autoimmune process. To confirm these results, it is necessary to make a truly prospective study.

Introduction L’isoforme 65 kDa de l’acide glutamique decarboxylase (GAD65) est un antigene majeur dans le diabete de type 1 (DT1). Cet essai a evalue si l’administration de GAD65 (hydroxyde d’alumine de la GAD, GAD-alum) peut preserver la fonction des cellules beta chez les patients ayant un diabete de type 1 recent. Patients et methodes Dans les trois mois suivant le diagnostic de DT1, 334 patients âges de 10–20 ans, ayant un peptide-C a jeun > 0.1 nmol/l et des auto-anticorps seriques anti-GAD65 positifs, ont recu soit quatre injections de GAD-alum, soit deux injections de GAD-alum puis deux injections de placebo, soit quatre injections de placebo. Le critere primaire d’evaluation etait l’evolution du peptide-C apres repas test (Boost), entre le jour de la premiere injection et la consultation 15 mois plus tard. Les criteres secondaires comprenaient l’HbA1c, la dose quotidienne d’insuline, le nombre d’hypoglycemies, et le peptide-C a jeun et maximum apres stimulation. Resultats Le peptide-C apres repas test a diminue de facon identique dans les trois groupes et l’objectif primaire a 15 mois n’a pas ete atteint (p = 0.10). L’administration de GAD-alum n’a pas eu d’effet sur la dose d’insuline, l’HbA1c, ou les hypoglycemies par comparaison avec le placebo. Les effets indesirables (mineurs) ont ete similaires en intensite et en frequence dans les trois groupes. Conclusion La GAD-alum n’a pas freine significativement la baisse du peptide-C apres un repas test et n’a pas ameliore les parametres cliniques sur 15 mois.

Serum selenium concentrations were analysed in 24 children with acute lymphoblastic leukemia and in 152 healthy schoolchildren. Selenium was determined by the energy dispersive X-ray fluorescence technique. Lower median selenium levels were found in children with leukemia, who were on maintenance therapy and who later relapsed, than in controls (p < 0.02) and in children who remained in remission and could have treatment discontinued (p < 0.01). Median observation time for children remaining in continuous complete remission (CCR) was 66 months. There was no significant correlation between low or high serum selenium concentrations on the one hand and either age, sex, weight and height, white blood cell counts (WBC), blood platelets, S-ASAT, S-ALAT, serum protein or serum albumin on the other. Further studies are needed to evaluate the role of selenium for the course of acute lymphoblastic leukemia in children.

Fasting serum C-peptide and total immunoreactive insulin (IRI) were determined in 38 non-diabetic children and adolescents 6–22 years old. C-peptide varied between 0.22–0.73 pmol/ml (mean ± sd, 0.45 ± 0.11). There was a tendency to higher values during puberty. No difference was found between subjects with or without a family history for diabetes. IRI varied between 0–31 μU/ml (mean ± sd, 11.3 ± 6.5). The C-peptide response to glucagon was studied in 10 insulin dependent juvenile diabetics 11–19 years old, who had had measurable amounts of fasting C-peptide on some occasions during the previous years. Duration of diabetes varied between 4–12 years. A slight but significant rise in C-peptide level occurred in 3 patients. Their metabolic control estimated on the basis of daily urinalysis was "excellent" or "good". The results support the hypothesis that even trace remnants of the beta cell function may be of importance for the metabolic control in juvenile diabetes.

Serum insulin, C-peptide and pancreatic polypeptide in response to food and non-food external cues in obese school girls