The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial

in Diabetologia (2012), 55(12), 3155-3162

Aims/hypothesis The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 ... [more ▼]

Aims/hypothesis The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. Methods Children and adults (n = 153) on CSII with HbA1c 7.5–9.5% (58.5–80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months’ washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA1c levels between arms after 6 months. Results Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA1c was –0.43% (–4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI −0.32%, −0.55% [−3.50, −6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA1c reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40). Conclusions/interpretation Continuous glucose monitoring was associated with decreased HbA1c levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects. [less ▲]

The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study: recruitment, intervention and follow-up.

in Diabetologia (2011), 54(3), 627-633

AIMS/HYPOTHESIS: The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study was designed to establish whether weaning to a highly hydrolysed formula in infancy subsequently reduces the risk of type ... [more ▼]

AIMS/HYPOTHESIS: The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study was designed to establish whether weaning to a highly hydrolysed formula in infancy subsequently reduces the risk of type 1 diabetes. METHODS: The study population comprises newborn infants who have first-degree relatives with type 1 diabetes and meet the increased risk HLA inclusion, but not exclusion criteria. The study is being performed in 15 countries in three continents. First-degree relatives of patients with type 1 diabetes were identified from diabetes clinics, diabetes registries, and from other endocrinology or obstetrics offices and websites. HLA typing was performed at birth from cord or heel stick blood, and the results sent to the study's Data Management Unit within 2 weeks for communication of eligibility to the clinical study centre. All mothers recruited were encouraged to breastfeed. The intervention lasted for 6 to 8 months, and weaning formulas based on hydrolysed casein and standard cow's milk were compared. RESULTS: TRIGR recruited 5,606 infants, of whom 2,160 were enrolled as eligible participants, 6% more than the target of 2,032. Of those enrolled, 80% were exposed to the study formula. The overall retention rate over the first 5 years is 87%, with protocol compliance at 94%. The randomisation code will be opened when the last recruited child turns 10 years of age, i.e. in 2017. CONCLUSIONS/INTERPRETATION: The TRIGR experience demonstrates the feasibility and successful implementation of an international dietary intervention study. TRIGR is the first ever primary prevention trial for type 1 diabetes and, if completed successfully, will provide a definite answer to the research question. TRIAL REGISTRATION: ClinicalTrials.gov NCT00179777 FUNDING: The study was funded by the National Institute of Child Health and Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) (grant numbers HD040364, HD042444 and HD051997), Canadian Institutes of Health Research, the Juvenile Diabetes Research Foundation International and the Commission of the European Communities (specific RTD programme 'Quality of Life and Management of Living Resources', contract number QLK1-2002-00372 'Diabetes Prevention'. Other funding came from the EFSD/JDRF/Novo Nordisk Focused Research Grant, Academy of Finland, Dutch Diabetes Research Foundation and Finnish Diabetes Research Foundation). [less ▲]

Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: Reduced insulin antibody titres and preserved beta cell function

in Diabetologia (2006), 49(1), 71-74

Aims/hypothesis: The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin ... [more ▼]

Aims/hypothesis: The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin gene (INS). We investigated the association between INS VNTR class III alleles (-23HphIA/T) and both insulin antibody presentation and residual beta cell function during the first year after diagnosis in 257 children with type 1 diabetes. Materials and methods: To estimate C-peptide levels and autoantibody presentation, patients underwent a meal-stimulated C-peptide test 1, 6, and 12 months after diagnosis. The insulin -23HphIA/T variant was used as a marker of class III alleles and genotyped by PCR-RFLP. Results: The insulin antibody titres at 1 and 6 months were significantly lower in the class III/III and class I/III genotype groups than in the class I/I genotype group (p = 0.01). Class III alleles were also associated with residual beta cell function 12 months after diagnosis and independently of age, sex, BMI, insulin antibody titres, and HLA-risk genotype group (p = 0.03). The C-peptide level was twice as high among class III/III genotypes as in class I/I and class I/III genotypes (319 vs 131 and 166 pmol/l, p=0.01). Furthermore, the class III/III genotype had a 1.1% reduction in HbA1c after adjustment for insulin dose (p = 0.04). Conclusions/interpretation: These findings suggest a direct connection in vivo between INS VNTR class III alleles, a decreased humoral immune response to insulin, and preservation of beta cell function in recent-onset type 1 diabetes. © Springer-Verlag 2005. [less ▲]

Trends in the incidence of childhood onset diabetes in Europe. 1989-1998

in Diabetologia (2001), 44(3), 3-8

AIMS/HYPOTHESIS: To study the epidemiology of childhood-onset (Type I) insulin-dependent diabetes mellitus in Europe, the EURODIAB collaborative group in 1988 established prospective, geographically ... [more ▼]

AIMS/HYPOTHESIS: To study the epidemiology of childhood-onset (Type I) insulin-dependent diabetes mellitus in Europe, the EURODIAB collaborative group in 1988 established prospective, geographically-defined registers of all children diagnosed with Type I diabetes under 15 years of age. This report is based on 24,423 children, registered by 36 centres, with complete participation during the period 1989-1998 and representing most European countries with a population coverage of approximately 20 million children. METHODS: Multiple sources of ascertainment were used to validate the level of ascertainment. Trends in Type I diabetes incidence during the period were analysed using Poisson regression with the results from the 36 centres pooled into nine regions. RESULTS: The standardised average annual incidence rate of Type I diabetes varied more than tenfold between centres. Overall, the annual increase in incidence was 3.2% (95%-CI: 2.7%, 3.7%), being highest for children in the 0-4-year age-group 4.8% (3.8%, 5.9%) and lowest for children in the 10-14-year age group 2.1 % (1.4%, 2.8%). However, the absolute increases in Type I diabetes were roughly similar in the three age-groups of 0-4, 5-9 and 10-14 years. Central Eastern Europe showed the highest increase whereas Sardinia and Northern Europe (except Finland) showed no evidence of an increase. For all age-groups relatively fewer cases had disease onset during the summer months, especially the 10-14-year age-group. CONCLUSION/INTERPRETATION: The extremely large range of incidence rates within Europe has been confirmed. The incidence rate is generally increasing but is more pronounced in some regions than in others. Seasonality at disease onset is apparent even in the youngest age-group. [less ▲]

Correlations between the incidence of childhood onset type 1 diabetes in Europe and HLA genotypes

in Diabetologia (2001), 44(3), 51-59

The Eurodiab Substudy 2 study group. Infections and vaccinations as risk factors for childhood type1(insulin dependent) diabetes mellitus: a multicentre case control investigation

in Diabetologia (2000), 43

Aims/hypothesis. To determine if vaccinations and infections are associated with the subsequent risk of Type I (insulin-dependent) diabetes mellitus in childhood. Method. Seven centres in Europe with ... [more ▼]

Aims/hypothesis. To determine if vaccinations and infections are associated with the subsequent risk of Type I (insulin-dependent) diabetes mellitus in childhood. Method. Seven centres in Europe with access to population-based registers of children with Type I diabetes diagnosed under 15 years of age participated in a case-control study of environmental risk factors. Control children were chosen at random in each centre either from population registers or from schools and policlinics. Data on maternal and neonatal infections, common childhood infections and vaccinations were obtained for 900 cases and 2302 control children from hospital and clinic records and from parental responses to a questionnaire or interview. Results. Infections early in the child's life noted in the hospital record were found to be associated with an increased risk of diabetes, although the odds ratio of 1.61 (95% confidence limits 1.11, 2.33) was significant only after adjustment for confounding variables. None of the common childhood infectious diseases was found to be associated with diabetes and neither was there evidence that any common childhood vaccination modified the risk of diabetes. Pre-school day-care attendance, a proxy measure for total infectious disease exposure in early childhood, was found, however, to be inversely associated with diabetes, with a pooled odds ratio of 0.59 (95% confidence limits 0.46, 0.76) after adjustment for confounding variables. Conclusion/interpretation. It seems likely that the explanation for these contrasting findings of an increased risk associated with perinatal infections coupled with a protective effect of pre-school day care lies in the age-dependent modifying influence of infections on the developing immune system [less ▲]

Familial risk of type 1 diabetes in European children

in Diabetologia (1998), 41

The Fourth International Workshop on the Standardisation of Insulin Autoantibody Measurement

in Diabetologia (1990), 33(10), 638-639

[No abstract available]

The incidence of Type 1 (insulin-dependent) diabetes mellitus in subjects aged 0-19 years in Luxembourg: a retrospective study from 1977 to 1986

in Diabetologia (1988), 31(10), 758-761

A decrease in the incidence of Type 1 (insulin-dependent) diabetes mellitus in the age group 0-14 years has been observed from north to south over north-western Europe. To evaluate whether this trend ... [more ▼]

A decrease in the incidence of Type 1 (insulin-dependent) diabetes mellitus in the age group 0-14 years has been observed from north to south over north-western Europe. To evaluate whether this trend could be found in Luxembourg (a small country between the Netherlands and France) we performed a retrospective study over a period of 10 years. Information concerning all Type 1 diabetic patients (aged 0-19 years at diagnosis), diagnosed between January 1, 1977 and December 31, 1986 was obtained through paediatricians, internists, general practitioners and the Luxembourg Diabetes Association (LDA). The LDA was used as the ascertainment group (to estimate the real number and incidence of Type 1 diabetes mellitus). During the study period 91 Type 1 diabetic patients aged between 0-19 years were diagnosed. An incidence of 11.2 was found in boys (0-19 years). Girls in the same age group showed a considerably lower incidence of 8.8. Standardised incidence (using as standard the world population) revealed an almost similar incidence in the Netherlands and Luxembourg (respectively 10.3 and 10.2) for the age group aged 0-14 years. In France a considerably lower incidence is found (3.6). To what extent different methodology contributes to the differences remains to be clarified. Further prospective studies are necessary to investigate the role of environmental and genetic factors. © 1988 Springer-Verlag. [less ▲]