Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)-study protocol for a phase 2, randomized, placebo controlled trial.

BACKGROUND: Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. METHODS: This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. DISCUSSION: This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. TRIAL REGISTRATION: ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. CLINICALTRIALS: gov NCT04774224. Registered on 01 March 2021.

Behaviour and metabolic control in children with Type 1 diabetes mellitus on insulin pump therapy: 2-year follow-up.

AIMS: This study investigated whether continuous subcutaneous insulin infusion is associated with sustained improvement in behaviour and metabolic control. METHODS: Children with Type 1 diabetes mellitus (n = 27, 8-18 years old) who had been assessed previously prior to commencing continuous subcutaneous insulin infusion, and 6-8 weeks later, were re-evaluated 2 years after commencing insulin pump therapy. Behaviour was reassessed using the Behavioral Assessment System for Children-2nd edition (BASC-2) and current HbA(1c) levels were recorded. RESULTS: Two years after commencing continuous subcutaneous insulin infusion, parent-reported internalizing and externalizing symptoms were significantly lower than pre-insulin pump therapy commencement levels. Self reports of internalizing and externalizing problems did not differ significantly across the three assessment points. There was no significant difference between pre-insulin pump therapy HbA(1c) and HbA(1c) after 2 years on continuous subcutaneous insulin infusion, despite an initial improvement 6-8 weeks after commencing the therapy. CONCLUSIONS: Children with Type 1 diabetes mellitus showed sustained improvements in parent-reported behaviour, but not in self reports of behaviour or in metabolic control 2 years after commencement of continuous subcutaneous insulin infusion.

Poor adherence to integral daily tasks limits the efficacy of CSII in youth.

INTRODUCTION/AIMS: Many young people experience improved glycemia with continuous subcutaneous insulin infusion (CSII) regimens; however, sustained glycemic benefit eludes a significant proportion. Our aims were to assess adherence to recommended CSII-related behaviors in a representative pediatric cohort and to identify potentially modifiable behaviors that impact on HbA1c in youth. RESEARCH DESIGN AND METHODS: Data uploaded from insulin pump devices of 100 youth with type 1 diabetes were analyzed. RESULTS: Ability to translate recommended behaviors into daily self-management varied widely in youth. Mean bolus frequency was 6.1/d; however, 69/100 entered <4 blood glucose levels (BGL)/d. HbA1c decreased by 0.2% for each additional BGL (p=0.001) and bolus event (p<0.001) per day. Prandial insulin omission was common and associated with significantly increased HbA1c. On average, if breakfast insulin was missed ≥4 times per fortnight, HbA1c increased 1.0% (p<0.001). If one or more days per fortnight with ≤2 food boluses/d were recorded, then HbA1c increased 0.8% (p=0.001). Increasing age and duration of CSII correlated with poorer adherence to recommended behaviors. CONCLUSIONS: Glycemic advantage obtained with CSII regimens is closely related to the manner in which CSII is employed. Poor adherence to integral CSII-related tasks is frequently encountered in adolescents and limits the efficacy of CSII in these youth.

Psychological adjustment of well siblings of children with Type 1 diabetes.

AIMS: Studies of siblings of children with Type 1 diabetes (Type 1 DM) have shown either increased levels of maladjustment or, alternatively, increased levels of pro-social behaviour according to whether the sibling or parent was interviewed. The purpose of this study was to examine the psychological adjustment of Type 1 DM siblings using both parent and sibling report and to assess the concordance between child and parent reports. METHODS: Ninety-nine siblings aged 11-17 years and parents of children with Type 1 DM treated at the Royal Children's Hospital, Melbourne were recruited sequentially. The Strengths and Difficulties Questionnaire (SDQ) was used to assess well siblings' emotional and behavioural functioning using data collected within a semi-structured interview. SDQ data between the sibling cohort and normative data sample were compared using independent-samples t-tests. Sibling reports and parent reports were compared using a series of paired-sample t-tests and correlation analyses. RESULTS: Type 1 DM siblings did not report greater emotional or behavioural maladjustment or more pro-social behaviour than norms. Parents rated siblings' pro-social behaviour as being comparable with that of youth from the general community; however, parents rated healthy siblings as having lower levels of maladjustment; specifically, significantly fewer conduct problems, hyperactive behaviour and peer-related problems (all P < 0.01). There were no significant differences between parent ratings and sibling ratings on peer-related problems or pro-social behaviour. CONCLUSIONS: Type 1 DM siblings did not report increased behavioural or emotional dysfunction relative to children in the general population and, according to their parents, were even better adjusted than their peers.

Improving glycaemic control in children and adolescents: which aspects of therapy really matter?

In paediatric diabetes, the concept of intensive therapy in the post-Diabetes Control and Complications Trial period has become subverted by a pharmaco-technological paradigm at the expense of other aspects of care such as goal-setting and psychosocial support. This review examines which patients benefit most from intensive therapy in terms of glycaemic control (HbA1c). It also reviews published controlled trial and observational data relating to the impact of various insulin types and delivery systems on glycaemic control and canvasses the literature dealing with the impact of patient support, philosophy of care, goal setting and treating team dynamic on HbA1c. Taking into account the characteristics of those patients who benefit most from intensive therapy, the quantum of HbA1c change and the persistence of changes that have been reported in selected and non-selected patient groups, it appears that there is a clear hierarchy in aspects of therapy that improve glycaemic control for children and adolescents with Type 1 diabetes. Prime issues appear to be patient support, team cohesion and goal setting. The reported glycaemic benefits achieved by an isolated emphasis upon a pharmaco-technological paradigm are limited in children and adolescents. It appears that only after the prime issues have been first considered will the potential benefits of the insulin types and regimens then be realized.

Is bedtime supper necessary for older children with diabetes using glargine insulin in multiple daily injection regimens?

AIMS: Current guidelines for dietary management of Type 1 diabetes in children recommend a carbohydrate supper before bed. However, with the introduction of insulin analogues such as glargine (with a basal insulin profile), supper may be unnecessary. The purpose of this study was to investigate whether supper is required to prevent nocturnal hypoglycaemia when using multiple daily injections, with glargine as the basal insulin and rapid-acting insulin pre-meals, in older children with Type 1 diabetes. METHODS: Thirty-five children aged 10-18 years with Type 1 diabetes were recruited to a randomized cross-over trial (supper vs. no supper). Each phase consisted of three consecutive days of wearing a continuous glucose-monitoring system (CGMS) to record nocturnal blood glucose levels in the home setting. The supper phase included one 15-g carbohydrate dairy snack consumed before bed. The evening meals were standardized. Activity was restricted. RESULTS: Valid CGMS data were obtained for 163 nights (85 supper, 78 no supper). Nocturnal hypoglycaemia rates were similar in the supper and no-supper groups (32.9% vs. 33.3% of nights; P = 0.96). CONCLUSIONS: This study suggests that supper is not necessary for all children to prevent nocturnal hypoglycaemia when using glargine insulin. The recommendation for inclusion of supper should be individually tailored and not mandatory.

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.

OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: 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). CONCLUSIONS: 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.

Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy. METHODS: An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic (< or =3.9 mmol/l) and hyperglycaemic (> or =10.1 mmol/l) ranges and glycaemic variability. RESULTS: Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI -5.37 to 8.81), hypoglycaemic (0.54; 95% CI -3.48 to 4.55) or hyperglycaemic (-2.18; 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29; 95% CI -0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in participants with sensor use > or =70% compared with participants with sensor use <70% (95% CI -0.98 to -0.04, p = 0.04). Five episodes of device malfunction occurred. CONCLUSIONS/INTERPRETATION: Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, frequent use of this technology (> or =70%) was not universally acceptable. TRIAL REGISTRATION: ACTRN12606000049572

Improvements in cognition, mood and behaviour following commencement of continuous subcutaneous insulin infusion therapy in children with type 1 diabetes mellitus: a pilot study.

AIMS/HYPOTHESIS: Anecdotally, parents and teachers of children with type 1 diabetes mellitus report improvements in behaviour and learning following the commencement of continuous subcutaneous insulin infusion (CSII). This study aimed to investigate changes in cognition, mood and behaviour following commencement of CSII in children with type 1 diabetes. METHODS: Children (n = 32) with type 1 diabetes aged 6-16 years and starting CSII at two Australian centres underwent behavioural, cognitive and glycaemic assessments prior to the commencement of CSII and 6-8 weeks after its start. A comprehensive cognitive test battery was administered, comprising measures of intelligence, attention, processing speed and executive skills. Behaviour and mood were assessed using the Behaviour Assessment System for Children--Second Edition. Continuous glucose monitoring was performed over a 72 h period and HbA(1c) was measured at both time-points. RESULTS: After commencement of CSII, there were significant improvements in HbA(1c), a reduction in hyperglycaemia and blood glucose variation and an increase in normoglycaemia. Significant improvements were observed in perceptual reasoning, selective attention, divided attention, cognitive flexibility and working memory. Fewer mood-related symptoms were reported (parent, teacher and self-report) and fewer behavioural problems (parent reports) CONCLUSIONS/INTERPRETATION: In this uncontrolled pilot study, children with type 1 diabetes demonstrated significant improvements in measures of metabolic control, mood and behaviour and in some complex cognitive skills after commencing CSII therapy.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Twice-daily variable insulin regimens: proportions of insulin types have little impact on glycaemic control in primary school-aged children.

AIM: To ascertain the relationship between glycaemic outcome and proportions and timing of insulin admixture in a cohort of primary school-aged children who were receiving insulin in a twice-daily regimen. METHODS: Children aged 4-10 years with Type 1 diabetes of > 2 years duration and on twice-daily variable insulin regimens were eligible for inclusion in this study, which took place over a 12-month period. Characteristics of insulin regimen [total daily dose (TDD), proportion of total daily dose given in the morning and proportion of the TDD given as intermediate-acting insulin] were compared with parameters of glycaemia including glycated haemoglobin (HbA(1c)) and continuous glucose monitoring measures (mean glucose, per cent time in various glycaemic ranges, and intra- and inter-day glycaemic variation). RESULTS: Forty-nine children completed the study. Participants were all prepubertal at the start of the study and representative of the local diabetes population aged 4-10 years (mean age 8.2 years, mean duration of diabetes 3.5 years, mean HbA(1c) 8.1%). The mean TDD was 0.9 units/kg/day (range 0.6-1.3). The TDD, percentage of TDD given as intermediate-acting insulin and the percentage of TDD given as the morning dose were not associated with HbA(1c), mean continuous glucose monitoring system glucose, per cent time in various glycaemic ranges or intra- and inter-day glycaemic variation. CONCLUSIONS: Insulin proportions in twice-daily, variable insulin regimens are not associated with any short- or medium-term glycaemic outcomes.

Major increase in Type 1 diabetes: no support for the Accelerator Hypothesis.

BACKGROUND: The Accelerator Hypothesis postulates that the apparent increase in incidence of Type 1 diabetes mellitus (T1DM) is related to an acceleration of disease onset by weight-related insulin resistance. Our diabetes clinic has experienced a major recent increase in newly diagnosed diabetes. The Accelerator Hypothesis predicts that this increase should be associated with younger age and increased body mass at diagnosis, with youngest children having the highest body mass index (BMI). AIM: To test the Accelerator Hypothesis in the context of the major increase in T1DM at our centre. METHODS: Data from all young people diagnosed with T1DM between 1992 and 2003 were reviewed. Height and weight measurements from initial outpatient review were used to calculate BMI. RESULTS: The mean increase in BMI standard deviation score (SDS) is 0.03 per year (P = 0.01). Age at diagnosis has also increased by a mean of 0.11 years annually (P = 0.003). There was no association between BMI SDS and age at diagnosis (P = 0.7). A significant difference in BMI SDS between age-banded subgroups was evident (P = 0.04); however, youngest children had the lowest SDS. CONCLUSION: Our results do not support increased body mass as an accelerator of diabetes presentation.

Social consumption of alcohol in adolescents with Type 1 diabetes is associated with increased glucose lability, but not hypoglycaemia.

AIM: To determine the effects of social consumption of alcohol by diabetic adolescents on glycaemic control. METHODS: Fourteen (five male) patients aged > 16 years were recruited from the diabetes clinic at the Royal Children's Hospital. The continuous glucose monitoring system (CGMS) was attached at a weekend when alcohol consumption was planned for one night only. For each patient, the 12-h period from 18.00 h to 06.00 h for the night with alcohol consumption (study period) was compared with the same period with non-alcohol consumption (control period) either 24 h before or after the alcohol study night. Thus, each subject was his/her own control. Glycaemic outcomes calculated from continuous glucose monitoring included mean blood glucose (MBG), percentage of time spent at low glucose levels (CGMS < 4.0 mmol/l), normal glucose levels (CGMS 4.0-10.0 mmol/l) and high glucose levels (> 10.0 mmol/l) and continuous overall net glycaemic action (CONGA). RESULTS: The mean number of standard alcohol drinks consumed during the study period was 9.0 for males and 6.3 for females. There was no difference in percentage of time at high and normal glucose levels in the study and control periods. During the control period, there was a higher percentage of time with low glucose levels compared with the study period (P < 0.05). There was an increased level of glycaemic variation during the study time when compared with the control period. CONCLUSIONS: In an uncontrolled, social context, moderately heavy alcohol consumption by adolescents with Type 1 diabetes appears to be associated with increased glycaemic variation, but not with low glucose levels.

Interventions to promote optimal health outcomes in children with Type 1 diabetes--are they effective?

The incidence of Type 1 diabetes is increasing worldwide, imposing enormous public health costs, as well as profoundly affecting individual quality of life. There is evidence that psychological problems are increased in children with diabetes and this morbidity is often associated with poor metabolic control. Specific risk factors for this dual morbidity are emerging from empirical studies. The next challenge is to identify effective interventions for use with children at risk for adverse mental and physical health outcomes. The intervention literature is reviewed. It is noted that most studies have used diabetes-specific, unstandardized interventions in groups of adolescents, with few interventions trialled with younger children. No study has targeted a specific psychological disorder such as behaviour problems or depression, both of which are known to be increased in children with diabetes and for which effective standardized interventions are available. Attention is drawn to methodological limitations in many of the studies conducted to date and suggestions made to reduce these in future interventions attempting to reduce the burden of illness in children with diabetes.

Insights into the acute cerebral metabolic changes associated with childhood diabetes.

AIMS: Type 1 diabetes is a prevalent chronic disease in childhood with the commonest single cause of death being cerebral oedema in the context of diabetic ketoacidosis (DKA). The nature of the alterations in cerebral metabolism that may result in vulnerability to neuronal injury remains unknown. The aim of this study was to analyse the magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) brain data from eight children with diabetes following acute presentation with hyperglycaemia with or without ketoacidosis, to determine the nature and timing of any alterations in cerebral structure and metabolism. METHODS: This study used MRI and MRS to investigate regional cerebral abnormalities in a small series of diabetic patients with and without DKA. Changes were compared with the clinical and biochemical features of the patients studied. RESULTS: Our small series of patients all demonstrated abnormal signal changes in the frontal region on fluid attenuated inversion recovery (FLAIR) MR imaging, suggestive of oedema, and spectroscopic abnormalities of increased taurine, myoinositol and glucose levels. The MR abnormalities varied in severity but did not correlate with any clinical or biochemical parameters. CONCLUSIONS: These changes indicate that many diabetic children, particularly at presentation, may have alterations in cerebral metabolism with implications for the pathogenesis and treatment of the cerebral complications of DKA. In addition, our findings suggest that increased taurine may be one of the important differentiating factors in the response of the brain of diabetic children to DKA that may reflect an increase in their vulnerability to cerebral oedema compared with diabetic adults.

A novel approach to continuous glucose analysis utilizing glycemic variation.

BACKGROUND: Various methodologies have been proposed for analysis of continuous glucose measurements. These methods have mainly focused on the proportion of low or high glucose readings and have not attempted to analyze other dimensions of the data obtained. This study proposes an algorithm for analysis of continuous glucose data including a novel method of assessing glycemic variability. METHODS: Mean blood glucose and mean of daily differences (MODD) assessed the degree that the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge, CA) trace was representative of the 3-month glycemic pattern. Percentages of times in low, normal, and high glucose ranges were used to assess marked glycemic excursion. Continuous overall net glycemic action (CONGA), a novel method developed by the authors, assessed intra-day glycemic variability. These methods were applied to 10 CGMS traces chosen randomly from those completed by children with type 1 diabetes from the Royal Children's Hospital, Melbourne, Victoria, Australia and 10 traces recorded by healthy volunteer controls. RESULTS: The healthy controls had lower values for mean blood glucose, MODD, and CONGA. Patients with diabetes had higher percentages of time spent in high and low glucose ranges. There was no overlap between the CONGA values for patients with diabetes and for controls, and the difference between controls and patients with diabetes increased markedly as the CONGA time period increased. CONCLUSIONS: We advocate an approach to the analysis of CGMS data based upon a hierarchy of relevant clinical questions alluding to the representative nature of the data, the amount of time spent in glycemic excursions, and the degree of glycemic variation. Integrated use of these algorithms distinguishes between various patterns of glycemic control in those with and without diabetes.

Childhood precursors of adolescent outcomes in type 1 diabetes mellitus.

Contemporary outcome measures of chronic illnesses such as type 1 diabetes mellitus are broader than those clinical outcomes traditionally assessed in therapeutic encounters. A holistic approach emphasises quality of life and emotional well-being as well as the achievement of optimal disease management. This paper reviews current knowledge about growth, metabolic control, diabetes complications, neurocognitive and psychological outcomes as well as health-related quality of life in childhood diabetes mellitus. It is suggested that the antecedents of adverse diabetes and psychological outcomes in adolescence lie in the years prior to adolescence. The model of care in childhood diabetes mellitus must be focussed on earlier screening and intervention if adverse outcomes are to be reduced.

Rates of diabetes mellitus-related complications in a contemporary adolescent cohort.

BACKGROUND: Ten years after the Diabetes Control and Complications Trial there is a paucity of data as to what are current rates of diabetes-related complications in adolescence. OBJECTIVE: To assess the incidence of diabetes-related complications in a contemporary cohort of adolescents with type 1 diabetes mellitus. DESIGN: Retrospective cross-sectional survey. PATIENTS: Adolescents aged >10 years with type 1 diabetes mellitus for >5 years from the Royal Children's Hospital, Melbourne Diabetes Clinic. RESULTS: 382 patients were studied (191 male). The mean HbA1c for males was 8.72% and for females was 8.80%. The rates of hypothyroidism and hypercholesterolaemia were 1.5% and 22% respectively. Twenty-five patients (8%) had intermittent microalbuminuria and six (2%) had persistent microalbuminuria. Only one patient had macroalbuminuria (0.3%). Only two patients (0.7%) with mild non-were diagnosed proliferative diabetic retinopathy. Coeliac disease was diagnosed in 6% of patients. CONCLUSIONS: In this representative and contemporary cohort of diabetic adolescents the incidence of microvascular diabetes-related complications is quite low.