[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To investigate whether center differences in glycemic control are present in prepubertal children <11 yr with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: This cross-sectional study involved 18 pediatric centers worldwide. All children, <11 y with a diabetes duration ≥12 months were invited to participate. Case Record Forms included information on clinical characteristics, insulin regimens, diabetic ketoacidosis (DKA), severe hypoglycemia, language difficulties, and comorbidities. Hemoglobin A1c (HbA1c) was measured centrally by liquid chromatography (DCCT aligned, range: 4.4-6.3%; IFFC: 25-45 mmol/mol). RESULTS: A total of 1133 children participated (mean age: 8.0 ± 2.1 y; females: 47.5%, mean diabetes duration: 3.8 ± 2.1 y). HbA1c (overall mean: 8.0 ± 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p < 0.001 resp. p = 0.179). Language difficulties showed a negative relationship with HbA1c (8.3 ± 1.2% vs. 8.0 ± 1.0%; p = 0.036). Frequency of blood glucose monitoring demonstrated a significant but weak association with HbA1c (r = -0.17; p < 0.0001). Although significant different HbA1c levels were obtained with diverse insulin regimens (range: 7.3-8.5%; p < 0.001), center differences remained after adjusting for insulin regimen (p < 0.001). Differences between insulin regimens were no longer significant after adjusting for center effect (p = 0.199). CONCLUSIONS: Center differences in metabolic outcomes are present in children <11 yr, irrespective of diabetes duration, age, or gender. The incidence of severe hypoglycemia is lower than in adolescents despite achieving better glycemic control. Insulin regimens show a significant relationship with HbA1c but do not explain center differences. Each center's effectiveness in using specific treatment strategies remains the key factor for outcome.
[Show abstract][Hide abstract] ABSTRACT: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control.
Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally.
A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001).
Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.
[Show abstract][Hide abstract] ABSTRACT: This report describes the general outline and progress of a multicentre study on risk factors of coronary heart disease and their determinants in children and adolescents. “Cardiovascular Risk in Young Finns” comprises a cross-sectional study of 3 to 18-year old subjects in 1980, and follow-up studies in 1983 and 1986 in various parts of Finland, and in 1989 in one of the study areas (Turku). The number of participants in 1980 was 3596 (83.1%) of those invited. In 1983 and 1986 83.2% and 77.8% of them, respectively, participated. The study programme has comprised questionnaire data on, for example, general health and living conditions, physical activity, eating habits, smoking, and psychological variables. The physical examination covered height, weight, skinfold thickness, pubertal stages and blood pressure. Blood specimens were obtained to assess concentrations of serum lipids and insulin, and in 1986 also for possible genetic markers of hypercholesterolemia. A 48 hour recall on nutrient intake was obtained from some of the subjects. The follow-up studies have enabled a study of the tracking phenomenon. Other important questions under study include, for example, the possible clustering of risk factors and their determinants. The cohorts studied provide a valuable research basis for the future, with emphasis on enabling a long-term follow-up of the subjects.
Annals of Medicine 07/2009; 23(1). DOI:10.3109/07853899109147928 · 4.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The question of whether blood pressure is one of the main risk factors for cardiovascular diseases in childhood has been evaluated in a Study of Cardiovascular Risk in Young Finns. In the second follow-up study, carried out in 1986, blood pressure was successfully measured in 2500 individuals aged nine to 24 years using a random zero sphygmomanometer. The mean systolic blood pressure in girls rose from 102 mmHg (95th percentile 119 mmHg) at age nine to 116 mmHg (138 mmHg) at age 24 and that in boys from 102 mmHg (95th percentile 121 mmHg) to 128 mmHg (148 mmHg). Diastolic blood pressure was more often measurable using Korotkoff's 5th than the 4th phase. The values observed were similar to those reported by the Second Task Force on Blood Pressure Control in Children, but owing to differences in the methods used to measure blood pressure it cannot be reliably concluded that the blood pressures were similar in the two series. Even in childhood blood pressure measurement is important, and since it changes with the physical size of the child, observations should be compared with normal values such as those reported here. No data are yet available to suggest that children with blood pressure values in the high normal range would benefit from interventions. Thus normal blood pressure value curves should be applied with caution when assessing children.
[Show abstract][Hide abstract] ABSTRACT: A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n=3554) and the apolipoproteins A-l and B measured (n=1355). Two follow-up studies were carried out in 1983 (n=2851) and 1986 (n=2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-l and B were measured again in 1986 (n=1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980′s from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9-to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3–24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.
Annals of Medicine 07/2009; 23(1):53-59. DOI:10.3109/07853899109147931 · 4.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).
[Show abstract][Hide abstract] ABSTRACT: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome.
Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally.
A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively.
This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).
[Show abstract][Hide abstract] ABSTRACT: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries.
Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood.
A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen.
Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres.
Diabetic Medicine 04/2008; 25(4):463-8. DOI:10.1111/j.1464-5491.2008.02399.x · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To reevaluate the persistence and stability of previously observed differences between pediatric diabetes centers and to investigate the influence of demography, language communication problems, and changes in insulin regimens on metabolic outcome, hypoglycemia, and ketoacidosis.
This was an observational cross-sectional international study in 21 centers, with clinical data obtained from all participants and A1C levels assayed in one central laboratory. All individuals with diabetes aged 11-18 years (49.4% female), with duration of diabetes of at least 1 year, were invited to participate. Fourteen of the centers participated in previous Hvidoere Studies, allowing direct comparison of glycemic control across centers between 1998 and 2005.
Mean A1C was 8.2 +/- 1.4%, with substantial variation between centers (mean A1C range 7.4-9.2%; P < 0.001). There were no significant differences between centers in rates of severe hypoglycemia or diabetic ketoacidosis. Language difficulties had a significant negative impact on metabolic outcome (A1C 8.5 +/- 2.0% vs. 8.2 +/- 1.4% for those with language difficulties vs. those without, respectively; P < 0.05). After adjustement for significant confounders of age, sex, duration of diabetes, insulin regimen, insulin dose, BMI, and language difficulties, the center differences persisted, and the effect size for center was not reduced. Relative center ranking since 1998 has remained stable, with no significant change in A1C.
Despite many changes in diabetes management, major differences in metabolic outcome between 21 international pediatric diabetes centers persist. Different application between centers in the implementation of insulin treatment appears to be of more importance and needs further exploration.
Diabetes care 10/2007; 30(9):2245-50. DOI:10.2337/dc07-0475 · 8.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Assessment of quality of life (QOL) in adolescents with diabetes requires patient, parent and health professional input. Psychometrically robust instruments to assess parent and professional perspectives are required.
Questionnaires concerning adolescent QOL were developed for completion by parents and health professionals. In an international study assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10-18; from 17 countries including Europe, Japan and North America), parents and health professionals completed their respective questionnaires between March and August 1998.
Feasibility and acceptability of the new questionnaires were indicated by high questionnaire completion rates (adolescents 92%; parents 89%; health professionals 94%). Internal consistency was confirmed (Cronbach's alpha coefficients 0.80 parent; 0.86 health professional). Correlations of Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and health professional global QOL ratings were generally low (r ranging from 0.12 to 0.36). Parent-rated burden decreased incrementally across adolescence, particularly for girls. Professional-rated burden followed a similar profile but only after age 15 years. Until then, burden was rated as uniformly high. Clinically relevant discrepancies in parent and professional burden scores were noted for one-parent families and families where adolescents had been referred for psychological help. In both cases, health professionals but not one-parent families perceived these as high burden situations. The clinical significance of this relates to the significantly poorer metabolic control recorded for adolescents in both situations.
Parent and health professional questionnaires were found to have adequate internal consistency, and convergent and discriminant validity in relation to key clinical and QOL outcomes. The questionnaires are brief, easy to administer and score. They may also enable comparisons across countries and languages to facilitate development of international health outcome parameters. The inclusion of the parent and health professional perspectives completes a comprehensive assessment of adolescent QOL relevant to diabetes.
Quality of Life Research 09/2006; 15(6):1033-42. DOI:10.1007/s11136-006-0042-8 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The optimal insulin regimen for paediatric patients with type 1 diabetes remains controversial. Therefore this multicentre study was performed in adolescents over a 3-year period to assess metabolic control, severe hypoglycaemia, and weight gain in relation to insulin injection regimens. Out of 2873 children and adolescents in an international survey in 1995, 872 adolescents (433 boys, 439 girls, mean age in 1995 11.3+/-2.2 years) were restudied in 1998, relating insulin regimens to HbA(1c) measured in a central laboratory. In addition, the daily dose of insulin, changes in body mass index (BMI), and events of severe hypoglycaemia were evaluated. Over 3 years, the use of multiple injection regimens increased from 42% to 71%: 251 patients remained on twice daily insulin, 365 remained on multiple injections and 256 shifted from twice daily insulin to multiple injections. In all three subgroups an increase in insulin dose, a deterioration of metabolic control, and an increase in BMI were observed. Metabolic control deteriorated less than expected over 3 years during adolescence (HbA(1c) 1995: 8.7+/-1.6%; 1998 observed: 8.9+/-1.6%, HbA(1c) expected for 1998: 9.0%). BMI increased more than expected, the increase was greatest in patients switching from twice daily to multiple injections, and higher in females compared to males. CONCLUSION: in this international study, metabolic control was unsatisfactory in many adolescents with type 1 diabetes irrespective of the insulin regimen. No improvement in metabolic control was observed in this cross-sectional survey, over 3 years in any of the subgroups. Even the group switching from twice to multiple injections did not improve blood glucose control and the increase in body mass index was most pronounced in this group. Conclusive evidence, however, should be based on prospectively planned, randomised therapeutic trials in paediatric patients.
European Journal of Pediatrics 02/2003; 162(1):22-9. DOI:10.1007/s00431-002-1037-2 · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families.
The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires.
Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores.
In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.
Diabetes Care 12/2001; 24(11):1923-8. DOI:10.2337/diacare.24.11.1923 · 8.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period.
Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years).
Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia.
This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.
Diabetes Care 09/2001; 24(8):1342-7. DOI:10.2337/diacare.24.8.1342 · 8.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross-sectional, non-population-based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4-6.3%, mean 5.4%). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 +/- 1.3% (mean +/- SD) compared with 8.9 +/- 1.8% in those aged 12-18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg(-1) 24 h(-1)) in children aged 2-9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37% (n = 1071) used three or more. Of those on two or three injections daily, 37% used pre-mixed insulins, either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on pre-mixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbA1c was related to use of more short-acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few.
Diabetic Medicine 09/1998; 15(9):752-9. DOI:10.1002/(SICI)1096-9136(199809)15:9<752::AID-DIA678>3.0.CO;2-W · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although existence of islet cell antibodies (ICA) is regarded as secondary to beta cell death, islet cell surface antibodies (ICSA) might play a role in the disease process. We have collected information from nine European clinics to determine whether ICSA are more common in diabetic children or their relatives in geographical areas or time periods of high incidence of insulin-dependent diabetes mellitus (IDDM). In Finland and Sweden ("North group") with a high incidence of IDDM during childhood, 36% of the patients were positive or weakly positive for ICSA at diagnosis compared with 24% in France (p = 0.1), 11% in Berlin-Vienna (p < 0.01), and 14% in Italy (p < 0.01). This difference was seen in all age groups but was most pronounced in the youngest (0-4 y). This geographical difference was also seen among family members of whom 46% were positive or weakly positive in the North group, 25% in France (p < 0.001), 21% in Berlin-Vienna (p < 0.001), and 16% in Italy (p < 0.001). Of several analyzed antibodies (ICA, gastric parietal cell, thyroglobulin, and thyroid microsomal), only ICSA showed simultaneous positivity in all family members (r = 0.32, p < 0.01). ICSA were most common in family members of patients with short (< 8 d) duration of symptoms (p < 0.05) and showed a similar seasonality, both in patients and relatives, as the incidence of IDDM. We conclude that the geographical difference in incidence of childhood IDDM in Europe may be associated to similar geographical differences in occurrence of ICSA both in newly diagnosed diabetic children and in their relatives. Simultaneous existence of ICSA in both patients and family members and a similar seasonality for ICSA and incidence of IDDM suggest that ICSA may reflect an ongoing disease process.
Pediatric Research 12/1996; 40(5):695-701. DOI:10.1203/00006450-199611000-00008 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children.
Archives of Disease in Childhood 11/1996; 75(5):410-5. DOI:10.1136/adc.75.5.410 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied associations of 24-h serum insulin profiles with insulin dose, age, gender, haemoglobin A1c (HbA1c) and C-peptide values, as well as blood glucose profiles in 77 consecutive children-nine aged 2-4, 14 aged 5-8, 26 aged 9-12, and 28 aged 13-17 years--2 years after the onset of insulin-dependent diabetes mellitus (IDDM). Mean weight-based insulin doses in the four age groups were similar (0.7 +/- 0.2 U.kg-1.day-1 in all); body surface-area-based doses differed. Insulin doses correlated significantly with the 24-h mean and area-under-the-curve (AUC) values, and with mean values at 03.00 hours of serum insulin in the children aged 5-8 and 13-17 years. The mean insulin concentrations of the age groups (95% confidence intervals) increased with age [6.1 (3.8, 9.7), 7.6 (5.9, 9.8), 10.4 (8.6, 12.4), and 14.0 (11.6, 16.8) mU/l; p < 0.0002]. The 24-h mean of serum insulin together with HbA1c concentration predicted 32% of the variation of mean blood glucose concentrations. Of children aged less than 9 years, 50% had insulin values less than 5 mU/l (healthy subjects' lower reference limit), and 14% were of less than 2 mU/l (detection limit of the assay) at 03.00 hours. At 07.00 hours, 82% had insulin values of less than 5 mU/l, and 36% were of less than 2 mU/l, respectively. Some young children had night-time hypoglycaemia with simultaneous hypoinsulinaemia. Insulin profiles correlated poorly with the HbA1c and peak C-peptide values.(ABSTRACT TRUNCATED AT 250 WORDS)
[Show abstract][Hide abstract] ABSTRACT: To learn more about the preclinical phase of IDDM we observed for a median period of 46.5 months (range 0.5–69 months) a group of 57 siblings positive for ICA and/or IAA when first screened within 6 months of the diagnosis of the proband. Sequential blood samples and IVGTTs were obtained at intervals of 6–12 months. Seventeen siblings (29.8%) presented with IDDM during the observation period. The duration of the known preclinical period ranged from 0.5 to 51 months (median 29 months). The converters were younger than the other siblings (P<0.05) and had higher initial ICA levels (P<0.01). In addition they had a lower FPIR in the first IVGTT (P<0.001). On all subsequent tests the converters had higher ICA levels and a lower FPIR (P<0.05 or less), a lower glucose elimination rate from the third test onwards (P<0.01 or less) and higher IAA levels at 3 years (P<0.05). Some variation could be observed in the FPIR in the converters with an initial increase and subsequent decrease (P<0.05 for both). Their levels of complement-fixing ICA increased up to 18 months (P<0.05) and IAA levels up to 3 years (P<0.01). Those high risk siblings who progress to clinical IDDM are characterized by young age, strong and increasing signs of islet-cell specific autoimmunity, reduced insulin secreting capacity and emerging glucose intolerance. The present observations seem to be incompatible with the hypothesis of beta-cell destruction occurring at a constant, predictable rate.
[Show abstract][Hide abstract] ABSTRACT: Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date-and sex-matched population-based control children in the nationwide Childhood Diabetes in Finland study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.
[Show abstract][Hide abstract] ABSTRACT: Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3–4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference in incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden (North) and Pittsburgh were younger (PPP20 mmol/l;PPP