Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial.

AIM: Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D). METHODS: 64 patients (T1D since <4 months, age 10-17.99, fasting sC-peptide ≥0.12 nmol/l, GADA-positive) were randomized into Day(D) 1-90 400 mg/day Ibuprofen, D1-450 vitamin D 2000 IU/day, D15, 45 sc. 20 µg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40 µg GAD-alum D15, 45; placebo. RESULTS: Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24 h with change in C-peptide AUC at 15 months (r = -0.776, p < 0.0001). CONCLUSION: Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov).

Randomised controlled trial of a person-centred transition programme for adolescents with type 1 diabetes (STEPSTONES-DIAB): a study protocol.

INTRODUCTION: Adolescence is a critical period for youths with chronic conditions, when they are supposed to take over the responsibility for their health. Type 1 diabetes (T1D) is one of the most common chronic conditions in childhood and inadequate self-management increases the risk of short-term and long-term complications. There is a lack of evidence regarding the effectiveness of transition programmes. As a part of the Swedish Transition Effects Project Supporting Teenagers with chrONic mEdical conditionS research programme, the objective of this study is to evaluate the effectiveness and experiences of different transitional care models, including a person-centred transition programme aiming to empower adolescents with T1D to become active partners in their health and care. METHODS AND ANALYSIS: In this randomised controlled trial, patients are recruited from two paediatric diabetes clinics at the age of 16 years. Patients are randomly assigned to either the intervention group (n=70) where they will receive usual care plus the structured transition programme, or to the control group (n=70) where they will only receive usual care. Data will be collected at 16, 17 and 18.5 years of age. In a later stage, the intervention group will be compared with adolescents in a dedicated youth clinic in a third setting. The primary outcome is patient empowerment. Secondary outcomes include generic, diabetes-specific and transfer-specific variables. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Review Board in Stockholm (Dnr 2018/1725-31). Findings will be reported following the Consolidated Standards of Reporting Trials statement and disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT03994536.

Successful treatment of a cohort of infants with neonatal diabetes using insulin pumps including data on genetics and estimated incidence.

AIM: Neonatal diabetes is rare, and treatment is challenging. We present aspects on treatment, genetics and incidence. METHOD: This was a prospective cohort study including all cases in our study area in Sweden. We compared with data from the National Diabetes Registry, the Neonatal Quality Register and the National Patient Register. RESULTS: In the 19-year study period January 1, 1998 to December 31, 2016, we treated seven infants, five of them boys. Six patients used a subcutaneous insulin pump, and the smallest patient started at a weight of 938 g. Most important was for the pump to deliver minute doses of insulin and the design of cannulas and tubing. All patients could stop insulin treatment at 17-145 days of age. One patient relapsed at age 4.5 years. Four patients used the insulin pump after discharge. A mutation was identified in five patients, and this included all patients born after 30 weeks of gestation. The incidence of neonatal diabetes was 2/1 00 000, higher than previously estimated for Europe. Similar but lower incidences were reported in the registries. CONCLUSION: Insulin pumps were safe in neonatal diabetes. All seven cases were transient. Neonatal diabetes was more common in our area than reported from Europe.

Self- and parent-reported executive problems in adolescents with type 1 diabetes are associated with poor metabolic control and low physical activity.

BACKGROUND: Management of diabetes is demanding and requires efficient cognitive skills, especially in the domain of executive functioning. However, the impact of impaired executive functions on diabetes control has been studied to a limited extent. The aim of the study is to investigate the association between executive problems and diabetes control in adolescents with type 1 diabetes. MATERIALS AND METHODS: Two hundred and forty-one of 477 (51%) of 12- to 18-year-old adolescents, with a diabetes duration of >2 years in Stockholm, Uppsala, and Jönköping participated. Parents and adolescents completed questionnaires, including Behavioral Rating Inventory of Executive Function (BRIEF), Attention-Deficit/Hyperactivity Disorder (ADHD)-Rating Scale (ADHD-RS) and demographic background factors. Diabetes-related data were collected from the Swedish Childhood Diabetes Registry, SWEDIABKIDS. Self-rated and parent-rated executive problems were analyzed with regard to gender, glycosylated hemoglobin (HbA1c), frequency of outpatient visits, and physical activity, using chi-square tests or Fisher's test, where P-values <.05 were considered significant. Furthermore, adjusted logistic regressions were performed with executive problems as independent variable. RESULTS: Executive problems, according to BRIEF and/or ADHD-RS were for both genders associated with mean HbA1c >70 mmol/mol (patient rating P = .000, parent rating P = .017), a large number of outpatient visits (parent rating P = .015), and low physical activity (patient rating P = .000, parent rating P = .025). Self-rated executive problems were more prevalent in girls (P = .032), while parents reported these problems to a larger extent in boys (P = .028). CONCLUSION: Executive problems are related to poor metabolic control in adolescents with type 1 diabetes. Patients with executive problems need to be recognized by the diabetes team and the diabetes care should be organized to provide adequate support for these patients.

Widening of foot processes in normoalbuminuric adolescents with type 1 diabetes.

We compared renal morphology in normoalbuminuric adolescents with type 1 diabetes with age-and sex-matched controls. Renal morphological measurements in 46 unselected adolescents with diabetes for approx. 10 years were compared with those in 20 healthy kidney donors. Renal volume estimated by ultra-sound, renal function determined by clearances of inulin and para-aminohippurate, and long-term mean HbA(1c) were measured in the patient group. Basement membrane thickness (BMT), mesangial matrix and capillary volume fractions per glomerulus [V(V)(matrix/glom), V(V)(cap/glom)] were significantly greater in patients than in controls (505 nm, 10.5%, 46.7% vs. 320 nm, 7.9% and 39.3%). The foot processes were wider in patients than in living donors (414 nm vs. 372 nm). There was no difference in mean kidney volume of patients with diabetes and healthy subjects. Glomerular filtration rate, body weight, and slit pore length density explained 60% of the variance in renal volume. After about 10 years' duration of type 1 diabetes, BMT, V(V)(matrix/glom), V(V)(cap/glom), and foot process width were greater in normoalbuminuric adolescents than in healthy controls. This increase in foot processes of normoalbuminuric patients has not been reported before.

Follow-up of kidney biopsies in normoalbuminuric patients with type 1 diabetes.

To study the development of diabetic glomerulopathy, we performed two kidney biopsies after 10.5 and 17 years of type 1 diabetes in 19 normoalbuminuric, normotensive adolescents (10 males). The biopsies were examined with light and electron microscopy. The glomerular filtration rate and effective renal plasma flow, determined with inulin and para-aminohippuric acid clearances, respectively, and ambulatory blood pressure were studied. Between the biopsies, significant increases occurred in glomerular volume, foot process width, mesangial matrix, and mesangial volume fraction/glomerulus. The metabolic control affected the basement membrane thickness, mesangial matrix, and mesangial volume fraction/glomerulus. The mesangial matrix and mesangial volume fraction/glomerulus were higher in female patients on the first biopsy, but on the second biopsy, the levels in males increased to those in females. The night-time systolic and mean arterial blood pressures from the first biopsy seemed to predict the mesangial matrix and mesangial volume fraction/glomerulus, foot process width, and slit pore length on the second biopsy. Despite normoalbuminuria and normal blood pressure, patients with type 1 diabetes have morphological changes of diabetic glomerulopathy that progress. The night-time blood pressure can be used to predict morphological changes of diabetic nephropathy in adolescents who are normoalbuminuric and normotensive.

Nondipping and its relation to glomerulopathy and hyperfiltration in adolescents with type 1 diabetes.

OBJECTIVE: To determine whether there is a relation between dipping/nondipping status and end-organ damage (measured as renal glomerulopathy) and long-term renal function in order to predict the development of nephropathy in normoalbuminuric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Analysis of renal biopsy and ambulatory blood pressure measurements was done in relation to renal function tests performed during a 10-year period. Forty unselected patients (16 girls), with a mean age of 17.7 years and a mean duration of 10.7 years, were studied. The renal biopsies were examined by electron microscopy. Ambulatory blood pressure was monitored (Space Labs 90 207). Systolic nondippers were defined as a <7%, diastolic nondippers as a <14%, and mean arterial blood pressure (MAP) nondippers as a <12% fall in blood pressure during the night. Renal function was evaluated every other year by clearances of inulin (glomerular filtration rate [GFR]) and para-amino hippurate (effective renal plasma flow [ERPF]), and filtration fraction (GFR/ERPF) was calculated. Overnight urinary albumin excretion rate and long-term mean HbA(1c) were measured. RESULTS: MAP (27% of the patients) and diastolic nondippers (12%) had a significantly thicker basement membrane; larger mesangial matrix volume fraction; and higher long-term GFR, nighttime heart rate, and mean HbA(1c) than dippers. CONCLUSIONS: Nondipping status was related to more renal morphological changes and long-term hyperfiltration in normoalbuminuric adolescents and young adults, despite a short duration of type 1 diabetes. Nondipping status may be an early predictor of later nephropathy.