Highlights from the 38th Annual Meeting of ISPAD, Istanbul, Turkey

Neil H. White, MD, CDE (USA)
Natalia Marek-Trzonkowska, PhD. (Poland)
Scott Williamson, MD (United Kingdom)

ISPAD 2012 - Gallery

The 38th Annual Meeting of the International Society of Pediatric and Adolescent Diabetes (ISPAD) was held 10-13 October 2012 at the Lütfi Kirdar International Convention and Exhibition Center in Istanbul, Turkey.  The meeting was chaired and hosted by Şükran Darcan, MD, and Damla Gökşen, MD, from Izmir, Turkey. The program covered recent advances in pediatric diabetes combining basic science and clinical and translational research achievements. The meeting attracted 1,329 participants (1,008 non-ISPAD members) from 90 countries. Seventy-one oral presentations and 316 posters reflected research diversity and clinical innovations at the field of pediatric and adolescent diabetes around the world. Abstracts of the Oral and Poster Sessions can be found in a recent supplement of Pediatric Diabetes 2012;12(Suppl. 17):1-173. In the current report we present some highlights from the plenary sessions, symposia, oral presentations and selected poster sessions.

At the meeting, ISPAD gave its four primary awards to:
1.    ISPAD Prize for Achievement  to Mark Sperling, MD (Pittsburgh, USA);
2.    Lestradet Award for Education and Advocacy to Mohammed A. Abdullah, MD, (Sudan);
3.    Young Investigator Award to Natalia Marek-Trzonkowska, PhD (Poland);
4.    Prize for Innovation in Paediatric Diabetes Care to Exeter Monogenic Diabetes Clinical Team and Laboratory (United Kingdom).

Wednesday, 10 October 2012

Opening lecture:  Dr David Beran (Switzerland) "Global Challenges for Integrated Pediatric Diabetes Care: Do We Need to Redefine the Health System for Diabetes?"
Dr. Beran, an expert in health care management, opened the meeting with a challenge to expand our concept of health systems outside of direct medical care and consider more the concept of integrated care. Comparisons were made between the health care systems in the developed world and the developing world and the need for an integrated health care system in both areas. The developed world is possibly close to reaching the limits of medical care provided by the health care systems and has seen life expectancy in type 1 diabetes mellitus (T1D) increasing to become similar to the rest of the population in recent years. Factors outside the influence of current health systems are therefore now significantly more influential on patients health in the developed world. On the other hand, in some areas of the developing world, life expectancy after diagnosis is still as low as one year due to lack of resources and access to insulin. While resources are poor, the health system based on a medical perspective cannot address this. An integrated health care system goes beyond the traditional medical perspective of health care to address the wider issues of the patient which impact on their diabetes care, e.g., employment, social circumstances and political influences on their society.

Plenary Session I: New Ideas in the Development of Type 1 Diabetes
Prof. Bart Roep (Netherlands) gave an interesting lecture regarding new insights into immunology in the pancreas in type 1 diabetes. Prof. Roep showed that many people with type 1 diabetes still have β-cells full of insulin as long as >10 years since the disease onset, which is associated with ongoing insulitis. These observations make intervention therapies conceivable even in long lasting autoimmune diabetes. Prof. Roep underlined the extremely heterogeneous pathology of type 1 diabetes between the patients and showed limitations of C-peptide as the marker of β-cell mass. In addition, Prof. Roep demonstrated that analysis of authoreactive CD8+ T-cells specific to various β-cell antigens is a valuable method for the prediction of outcome and insulin independence in diabetic patients after allogeneic islet transplantation. At the end of the lecture Prof. Roep discussed the idea of immune tolerance induction in diabetic patients with tolerogenic dendritic cells cultured in presence of vitamin D.
Prof. Anand Hardikar (Australia) showed that small non-coding RNAs (microRNAs; miRNA) play a critical role in development and function of pancreatic β-cells. Prof. Hardikar reported that one of the most important known miRNAs involved in biology of β-cells is miR-375. This miRNA not only plays a role in β-cell development but also regulates glucose-induced responses in these cells and maintains normal pancreatic α- and β-cell mass. Release of islet specific miRNAs is observed upon β-cell damage and can be detected in human plasma. Therefore, Prof. Hardikar concluded that miRNAs represent a new class of biomarkers which can be used as predictors of development of type 1 diabetes, progression of type 2 diabetes and biomarkers for the follow-up of diabetic patients subjected to interventional therapies.
Symposium I: Psychological Interventions
Clinical Psychologists Jon Haug (Norway) and Deborah Christie (United Kingdom) presented their views and understanding on the problem of insulin omission amongst the children and adolescents they see with T1D. There is no one solution for the problem of insulin omission, but the children themselves will have the solution within them. Dr. Haug outlined from his experience the necessity for the person with T1D to have a self-guiding and regulating system within themselves for insulin injections, which works at a conscious level and provides them with positive emotions and not negative ones regarding injections. This is required to replace the automatic hidden mechanism of insulin regulation, which has been lost. If emotions and feelings regarding insulin use are negative, so too is the prime power which drives insulin regulation and insulin omission will result. The great challenge for health professionals is then to help that child to change its drive for insulin use from a negative to a positive one. Dr Haug used the example of a study in Oslo of teenagers whose HbA1c improved with the motivation of money, but the effect was short lived. For long term change and improvement, he stated that internal and not external rewards were required, and this depends on creating internal feelings of worth, meaning and significance.
Dr. Christie suggested that by using the techniques of motivational interviewing (MI), the child or adolescent can be aided in identifying their own reason for insulin omission, and begin the process of addressing it themself. Dr Christie outlined the principles of MI, which involve moving from a consultation in which we tell individuals what to do to a conversation where the individual is helped to become their own expert at finding the answer and to develop a desire to change. This takes more time, and a skill at using open questions, listening well, reflecting and summarising within an interview, but finding an individual's solution to insulin omission always requires time and effort from the health care provider.

Symposium II:  JDRF / ISPAD Symposium / Microbiota and Type 1 Diabetes
Mark Atkinson (USA) discussed “The Role of the Gut Microbiome in Type 1 Diabetes:  EARLY Lessons from Humans and Animal Models”.  He pointed out the expanding role of environment in the etiology of T1D in the form of an environmental inciting event and also the potential of prenatal programming.  He discussed the increasing incidence of T1D in many areas around the world and the increasing incidence in “HLA-not-at-risk” subjects.  After summarizing potential causes as viruses, dietary factors during infancy (formula feeding, less breast feeding, early introduction of cereal into the diet) and omega-3 fatty acids, he introduced the idea of a role of injudicious antibiotic use on the gut microbiome.  The gut microbiome changes in response to lifestyle changes.  In BB rats and NOD mice, changes in diet and antibiotics change the incidence of diabetes suggesting that changes in the gut microbiome could play a role.  Additionally, it has been shown that the the autoimmune microbiome for T1D may be distinctly different from that found in healthy children and the TEDDY Study showed differences in the gut microbiome by region.  Dr. Atkinson pointed out that the mechanisms of an association between the gut microbiome and diabetes are unknown.  He concluded that this research is promising but is currently only in its infancy.  There is a need to study more populations in more regions to better understand the bacterial species involved and study the metabolic pathways of these various bacteria species.
Anette-Gabriele Ziegler (German) in her presentation entitled “Microbiota and Short Chain Fatty Acids in Human Diabetes” then discussed the BABYDIAB Study.  Stool samples are being collected overtime to assess the changes in microbiome in children who develop autoimmune diabetes.  Although the results are not yet significant, there seems to be an increase in bacteria that produce short chain fatty acids and a decrease in lactate producers associated with the development of autoimmunity.
Mark Atkinson (USA) then presented on behalf of Richard Insel (USA; JDRF) who was unable to attend the meeting.  This presentation, entitled “Can Type 1 Diabetes be Prevented by Intestinal Microbiota Induced Immunoregulation?”, concentrated on factors influencing the development of the gut microbiome and potential mechanisms by which alteration in this process could affect the rate of development of autoimmunity and T1D.  The concept of the “Hygiene Hypothesis” was discussed.  As the immune system spends less effort fighting infection, it spends additional effort developing autoimmunity.  The Juvenile Diabetes Research Foundation (JDRF) is working along with NIH to create a Microbiome Consortium to create a network of investigators and centers to more aggressively study the gut microbiome and its role in diabetes.  

Oral Session 1: Diabetes Genetics, Immunology and New Insulins and Pharmacologic Agents
Dr. Natalia M. Marek-Trzonkowska (Poland) presented results of the first clinical study on cellular vaccine based on regulatory T-cells (Tregs) against type 1 diabetes. The therapy has been conducted at the Medical University of Gdansk in Poland and is addressed to recently-diagnosed diabetic children with high C-peptide level. The study in children was preceded by multiple animal experiments and human trial in adults with graft versus host disease non-responsive to standard treatment which confirmed the safety of Treg administration. Dr. Marek-Trzonkowska reported that therapy is associated with no adverse effects. In addition, treated patients are characterized by higher C-peptide level than individuals who did not receive Treg therapy. These results are clinically relevant as patients who received Tregs require lower doses of insulin than non-treated individuals. Eleven (11) months since diagnosis of type 1 diabetes, 2 out of 11 treated individuals do not require exogenous insulin. These initial results are very promising, but Dr. Marek-Trzonkowska underlines the need for the consolidation of this therapy which is a point of the new study that her team starts at the end of this year.
Prof. Johnny Ludvigsson (Sweden) discussed the approach of tolerance induction in type 1 diabetes with glutamic acid decarboxylase 65 kDa isoform (GAD65), a major autoantigen in the disease pathogenesis. Although alum-formulated GAD65 (GAD-alum) induced preservation of residual insulin secretion in a previous Phase II clinical trial, recent Phase II and Phase III trials failed to reach their primary end-points. Therefore, the European Phase III trial was closed after 15 months, and the 30 months follow-up period was completed only for a minority of the patients. However, the analysis of this group revealed that patients in the Phase III trial treated with 2 doses of GAD-alum had less decline of both fasting (p=0.040) and stimulated C-peptide (p=0.012) after 30 months, and a larger proportion of these patients preserved >25% of their initial C-peptide after a mixed meal tolerance test compared to placebo (p=0.012). Therefore, positive Phase II trial plus positive effects according to exploratory analyses of Phase III support the concept of GAD treatment. At the end Prof. Ludvigsson opined that in research on type 1 diabetes we need to learn from development of allergy, immunotherapy and cancer combination therapies, rather than dismiss a treatment that does not reach a certain fixed endpoint.
Prof. Maria Craig (Australia) on behalf of A.S. Al-Shabeeb presented the study regarding association between enterovirus infection and miRNA levels in type 1 diabetes with inflammation and pancreatic islet cell death. Prof. Craig’s group identified 21 miRNAs that increased at least 10-fold and six that decreased at least 10-fold in human islets following infection with coxsackievirus B (CVB) 3, 4 and 5 in vitro compared with the not infected control islets. Of the up-regulated miRNAs, 19 were associated with genes involved in immune regulation (e.g., IL-2, IL-10, PTPN22, GPR183 and TAGAP), five were transcription regulators (e.g., AFF3, IL2RA and RGS1) and four were in the HLA region (e.g., HLADRB1 and HLADQB1). The down-regulated miRNAs were associated with T-cell activation (e.g., CD69) and immune response (e.g., CCR5). Studies of Prof. Craig identified a specific miRNA signature during CVB infection of human islets, with marked differential expression of multiple miRNAs associated with type 1 diabetes candidate genes. Functional analysis of these miRNAs may expand our understanding of the mechanisms underlying CVB-induced type 1 diabetes.
Prof. Marian Rewers (USA) discussed metabolic profiles predicting islet autoimmunity leading to type 1 diabetes. Longitudinal profiles of 382 metabolites were investigated at 4 time points in 25 high-risk children who developed diabetes (T1D group), 25 with persistent islet autoimmunity but not T1D, and 25 controls matched for HLA DR/DQ, sex, and age. The major novel finding was that lower levels of vitamin C in the infancy predict development of anti-islet autoantibodies. Secondary bile acids, glycodeoxycholate, glycolithocholate sulfate, and taurolithocholate 3-sulfate, were also significantly higher in both T1D patients and non-diabetic individuals positive for islet antibodies compared to the controls. Prof. Rewers’ study also defined biochemicals associated with gut microbiome (3-indoxyl sulfate, phenylacetylglutamate, p-cresol) which may serve as predictors of T1D in children. These results suggest that altered gut microbial activity and/or lower ascorbate levels in early childhood are significant predictors of islet autoimmunity leading to T1D.
Dr. B. Michaud (France) showed results regarding analysis of various autoantibodies against non-islet cell antigens in type 1 diabetic children (T1D). 6.1% of investigated T1D children had anti-H+/K+ ATPase autoantibodies and only 2 of these patients had clinical signs of autoimmune gastritis. Around one-quarter of patients positive for anti-H+/K+ ATPase autoantibodies had at least one other autoantibody, such as anti-TPO, anti-TG, anti-transglutaminase or anti-ASCA antibodies. These results demonstrate that in some patients the loss of immune tolerance associated with T1D spreads to involve other tissues. Although asymptomatic, the presence of multiple autoantibodies reflects an upstream process revealing a loss of immune tolerance to a larger repertoire of autoantigens.
Dr. Andreina Baj (Italy) discussed the intrafamilial spread of enterovirus (EV) infections at the time of clinical onset of T1D. Despite the fact that the obtained results did not prove a causal relationship between EV and T1D, 96% of investigated children were positive for EV genomes and clusters of T1D were detected, each involving 2-4 families that shared the same EV species. During 1-year of follow-up, 25% of siblings of investigated diabetic individuals developed T1D and they all were EV positive.
Dr. Ondrej Cinek (Czech Republic) discussed that Interferon-Induced Helicase (IFIH1) polymorphism rs1990760 influences the rate of enterovirus viraemia. 1,001 blood samples from infants or toddlers (646 with the highest-risk HLA genotype for T1D) were analyzed. The results presented suggest an increased risk of viraemia in the IFIH1 946Ala/Thr heterozygotes relative to the Ala/Ala homozygotes, while there was no difference in viraemia between the Thr/Thr and Ala/Ala homozygocity. These observations indicate that the rs1990760 polymorphism, previously confirmed to be associated with the risk of T1D, may affect the likelihood of enterovirus viraemia.
Dr. B. Okere (Italy) presented a method for isolation of multipotent insulin secreting cells. It was observed that serum-free medium sustained stem cell growth and potential. Preliminary pancreatic induction revealed expression of the stemness marker NESTIN which characterizes pancreatic progenitor cells, and pancreatic markers INSULIN and PDX1 in the cultured placental cells. These data indicate that placenta-derived stem cells might be a reliable and ethical-free source of insulin-producing cells in clinical applications.

Oral Session 2: Diabetes Acute and Chronic Complications
Dr Kim Donaghue (Australia) presented a study of cardiac autonomic variables in adolescents with T1D.  Those in the group with higher albumin:creatinine ratios  (ACR) had increased baseline heart rate and increased lower:higher frequency ratio, suggesting that higher sympathetic tone may be putting them at risk of early renal disease.  
Dr. J. Couper (Australia) studied carotid intima thickness (cIMT) and aortic intima thickness (aIMT) (both are factors associated with accelerated atherosclerosis) in 356 adolescents.  Multiple regression analysis showed that aIMT was associated with ACR, suggesting that higher urinary albumin excretion before the development of microalbuminuria, relates to early atherosclerosis in adolescents with T1D.  
Dr. J. Nazim (Poland) presented a prospective study of 438 children and adolescents from Poland, looking at the prevalendce and course of microalbuminuria.  MA was found to be reversible in the majority of patients, including 58.6% of cases of persistent MA (where MA was present for >= 2 consecutive years during the study).  
R. Hoffman (USA) found, in 16 adolescents with T1D, a correlation between poor diabetes control and endothelial dysfunction using venous occlusion plethysmography, suggesting that poor glycaemic control may cause poor tissue blood flow and future complications.

Oral Session 3: Diabetes and Obesity
This session included presentations of 8 oral abstracts, including four from the Early Bird study in the UK.  Dr. Streeter (United Kingdom) found that, despite pathophysiologic considerations that would suggest that insulin resistance (IR) would be associated with a reduced bone mass, in a study of 347 healthy children 5-16 years old, IR (by HOMA-IR) did not correlate with lower bone mineral density.  
Dr. M.B.A. Mostazir (United Kingdom) showed that redistribution of body fat, as suggested by changes in skin folds and waist circumference, predicted IR and other metabolic consequences that were not reflected in the BMI.  
J. Hosking (United Kingdom) reported HbA1c to be a poor indicator of impaired fasting glucose (IFG) and was not diagnostically useful in youth.  Hosking also reported that in 55 children, those who developed IFG had lower β-cell function, as determined by HOMA-B, than those that did not develop IFG.  This lower β-cell function was present as early as 5 years of age even though IFG did not develop until later, mostly after 11 years old.
S.P. Garnett (Australia), representing the RESIST Study Group, reported preliminary results for a randomized controlled trial comparing a high carbohydrate, low fat compared to a modest carbohydrate, moderate protein diet, along with metformin and exercise in both groups.  At 6 months, there was no difference between groups in weight loss, reduction of BMI z-score or insulin resistance (measured as insulin:glucose ratio).  
C. Marcus (Germany), presenting for E. Hagman, reported results from a registry-based study in Germany and Sweden.  After adjusting for age, sex and obesity, impaired fasting glucose (IFG) by ADA and WHO criteria was greater in Sweden than in Germany.  
Z. Gray (United Kingdom) reported that among youth with type 2 diabetes in the UK, white subjects tended to be older and more obese at diagnosis than those of South African or African-Caribbean origin.  Whites also tended to have lower HbA1c and higher fasting C-peptide.
Fröhlich-Reiterer (Austria) reported data from the DPV multicenter survey.  This analysis included 12,774 patients from 248 centers in Germany and Austria.  12.8% were overweight and 2.8% obese.  Multiple regression analysis revealed that female gender, longer duration, pubertal onset, more intensive therapy and higher insulin doses were associated with higher BMI-SDS.

Thursday, 11 October 2012

Pleanary Session II: Biomarkers and Pathogenisis of Diabetes Complications
Josephine Forbes (Australia) gave a fascinating presentation on AGEs (Advanced Glycation Endproducts) in which she discussed the effects of orally administered and endogenously produced AGEs in animal studies. Mice fed on low AGE diets have a lower rate of diabetic nephropathy and rodents fed a high AGE diet have impaired kidney function. Mice that overexpress receptors for AGE (RAGE) develop bad nephropathy. When activated, AGE receptors on cells lead to downstream signalling leading ultimately to apoptosis.
 
Professor Kristian Hanssen (Norway) expanded on the subject of AGEs with a presentation on the numerous different types of AGEs and what is currently known about their long-term effects. AGEs are involved in the pathology of vascular thickening and AGE levels correlate with mean intima thickness. It appears that evidence of the pathological effects of AGEs on cells may be present many years before the development of late complications of T1D, suggesting that patients with T1D need to keep their HbA1c low from diagnosis, and keep it low.
 
Hilary Keenan (USA) presented some of the statistics of the Joslin medal cohort (subjects with T1DM for >50yrs who have volunteered for clinical research).  A large percentage of theses patients are using insulin pumps, have low HbA1c, and exhibit a lower rate of complications than expected for the duration of their diabetes.

Oral session 4: Diabetes Care, Education, Psychosocial Issues
T. Kawamura (Japan) presented a small pilot study of MI. Parents were taught MI and the effect of this on their child's diabetes was assessed by HbA1c anfter 6 months. There was a significant reduction in HbA1c at 6 and 12 months.
Nienke Maas-van-Schaaijk (Netherlands) presented work looking at stress levels in parents of adolescents with T1DM, and found that fathers of children with T1DM have significantly more stress than fathers of children without.  
H. McGuire ( International Diabetes Federation) presented data from the 3C study, comparing the Beijing and Shantou areas in China. In Beijing the average HbA1c was 7.9%, compared to 10% in the poorer Shantou area.
B. Haliloglu (Turkey) presented the findings of a survey of school children with T1DM in Istanbul, which outlined difficulites for many children in diabetes care in the school environment.
A. Delamater (USA) found that in minority youths with T1DM, measures of intrinsic motivation (IM) are related to regimen adherence and glycaemic control, suggesting that interventions increasing intrinsic motivation may improve glycaemic control.

Oral Session 5: Diabetes Acute and Chronic Complications II
Dr. F.J. Cameron (Australia) presented data regarding association between uncomplicated diabetic ketoacidosis (DKA) and brain morphology and function. DKA and non-DKA groups did not differ in demographic variables at baseline. However, the total cortical grey matter volume was lower in the DKA group on day 1 and increased over 6 months; total cortical white matter volume was increased in the DKA group on day 1 and decreased over 6 months; white matter swelling was apparent in the frontal, temporal and parietal cortices on day 1 in the DKA group. In addition, the DKA group was characterized by lower levels of a marker of neuronal density/activity (NAA/Creatine) on day 1 in the frontal grey matter and basal ganglia. The DKA group also showed lower mental state scores on days 1 and 5 while changes in total and regional brain volumes in the first 5 days were associated with delayed memory recall, and focused, sustained, and divided attention at 6 months. The aforementioned outcomes were strongly correlated with pH and age at the time of presentation.
Dr. P. Barat (France) presented a method of indirect quantification of advanced glycation end-products (AGEs) by measuring of skin autofluorescence (SAF). The method was used for the assessment of correlation between AGE consumption and its accumulation in skin reflected by SAF. AGE intake was associated with poor metabolic control, but no association between AGE intake and AGE burden quantified with SAF was observed in the current study.
Dr. Lukasz Szmygel (Poland) presented a novel diagnostic tool for the assessment of newly-diagnosed T1D children. Dr. Szmygel showed that ultrasound measurement of the optic nerve sheath diameter (ONSD) can be a very useful and noninvasive method for monitoring of dehydration and metabolic acidosis. In the investigated group there was a significant difference between ONSD on admission and after normalization of biochemical parameters.
In children with newly-diagnosed T1D with compensated metabolic acidosis on admission, average ONSD was increased (3.64 ± 0.40 mm) in comparison with the control group (3.39 ± 0.32 mm). The highest ONSD (3.74 ± 0.96 mm) was observed in children admitted in the state of diabetic ketoacidosis.
Dr. M. El Samahy (Egypt) showed results regarding frequency of peripheral blood T-CD4+CD25high cells expressing CD62L and tumor necrosis factor- receptor 2 (TNFR2) in T1D. Dr. El Samahy observed that percentage of CD4+CD25high and CD4+CD25highCD62Lhigh cells was significantly lower in T1D patients than in control individuals. In addition, T1D was associated with elevated numbers of CD4+CD25highTNFR2+ T-cells. These trends were the most pronounced in patients with complications. Further analysis revealed that HbA1c, urinary albumin excretion, and CRP were negatively associated with the percentage of CD4+CD25high T-cells in T1D patients. The presented data indicate that alterations in the frequency of CD4+CD25high cells expressing CD62L or TNFR2 are associated with increased inflammation, poor glycemic control and increased risk of vascular complications in T1D patients.
Dr. J. Cusumano (Australia) discussed the transition outcomes in young adults. The patients completed a current health care questionnaire and were examined for the diabetic complications. Dr. Cusumano concluded that young adults transitioned from paediatric care did not have good recall of previously taught screening recommendations or their current measure of glycaemic control. It is a concern that some do not access a constant health provider and have worse glycaemic control increasing risk for poorer long term health outcomes.
Dr. L.A. McLaren (United Kingdom) showed that the 5-year period following transition from paediatric to adult diabetes care was associated with significant mortality, frequent hospital admissions predominately with DKA and high rates of microvascular complications.
Dr. J. Rosenbauer (Germany) discussed the problem of mortality in children and adolescents with recent-onset T1D in the German population. The main conclusion of the study was that no significant excess mortality exists following early-onset of type 1 diabetes in childhood prior to the onset of late complications.

Oral Sesson 6: Monogenic Diabetes Forms and Their Treatment
This session included 8 presentations of abstracts related to monogenic diabetes.  
W. Fendler (Poland) presented on behalf of a the Poland group  their experience with the MODY Probability Calculator (MPC; see Diabetologia (2012) 55:1265–1272 or http://www.diabetesgenes.org/content/mody-probability-calculator).  Utilizing 617 children, suspected of having MODY, 73% of those selected for genetic testing on clinical grounds were also identified based on the MPC.  However, relying on the MPC alone with the original cut-off 0.4, 36 of the MODY cases would not have been tested; using the higher cut-off (0.61), 45 would have been missed.  Using a combination of clinical criteria and the MPC gave better positive predictive value (PPV) and negative predictive value (NPV).  Two-stage screening reduced the number of unnecessary MODY genetic tests by 27% or 45% depending on the MPC cut-off used.  The authors concluded that using the MPC plays a supportive role in selecting cases for testing, but should not be used in the absence of clinical criteria.  
J. Lebl (Czech Republic) presented the 13-year Czech experinece in 1,698 subjects referred for MODY testing. 603 (36%) subjects from 265 (42% of families) had MODY.  It was estimated that 0.08% of all diabetic patients had MODY.  The most common forms were MODY1 (HNF4α; 9%), MODY2 (GCK; 67%) and MODY3 (HNF1α; 18%).  
Rubio-Cabezas (Spain), working with the group from Exeter, UK, described deficiency of neurogenin-3 as a cause of mild diabetes with variable age of onset and severe diarrhea with malabsorption.  
A. Farmer (United Kingdom) presented on behalf of the Euro-WABB Registry.  The Registry has collected data on 36 cases of Wolfram Syndrome, 26 cases of Alstrom Syndrome and 21 cases of Bardet Biedl Syndrome.  
N. Unanue (Chile) reported the Chilean experience in testing for neonatal diabetes.  14 of 17 (82%) children with the onset of diabetes before 6 months of age had a mutation identified.  In those with permanent neonatal diabetes (PND), 7 of 8 had KCNJ11 or ABCC8 mutation. In the 4 with transient neonatal diabetes (TND), only 1 of 4 had an ABCC8 mutation and 3 had abnormality on chromosome 6q24.  For those with PND and extrapancreatic manifestations (N=5), 2 had neurogenin-3 deficiency, one had a GATA6 mutation along with hypothyroidism and 2 had no mutation identified.  
T. Urakami (Japan) reported their experience using the GLP-1 receptor agonist (GLP-1 RA; laraglutide) in one subject with MODY3 and one with mitochondrial diabetes (MD).  GLP-1 RA resulted in good control (MODY3) and improved control (MD) even without the use of sulfonylurea.  
P. Dusatkova (Czech Republic) reported their experience in 3 differenct cohorts with HNF1β mutations (MODY5).  Both patients with diabetes and renal cysts had HNF1β mutations whereas only 8 out of 116 (=6.9%) with renal cysts alone and 2 out of 30 (6.7%; both from the same family) with a MODY picture and no renal abnormality had HNF1β mutations.  
Finally, C. Marcus (Sweden), working along with the Exeter group, reported the Swedish MODY experience.  Between 2005 & 2010, 3,966 children were diagnosed with diabetes and of these 392 (=9.8%) were Ab negative. Of these, 28 were already known to have MODY and 309 of the others were sequenced for the MODY genes.  One percent (1%) of all and  13% of Ab negative subjects had MODY1, 2 or 3.  Five (5) out of 30 with MODY mutations had no parent with diabetes.

A Poster Tour held the following day (Friday, 12 October) expanded on the monogenic diabetes theme.  Albada et al (Netherlands) reported on the presentation and phenotype of four patients with MODY5 (HNF-1β mutation and emphasized the association with renal disease and Tatsi et al (Greece) discussed the characteristics of MODY3 (HNF-1 mutation) in the Greek population and reported that 12% of those referred for MODY testing based on clinical characteristics had mutations in the HNF-1 gene.  Fitas et al (Portugal), Kocova et al (Macedonia), and Zmyslowska et al (Poland) discussed their experience with Wolfram Syndrome and pointed out the variability of the presenting features, even among a pair of siblings with the same genotype.  Wajda-Cuszlag et al (Poland) reported a case of permanent neonatal diabetes mellitus (PNDM) presenting with hyperglycemia on the first day of life that resulted from compound heterozygocity (S384L from mother and T207M from father) of the glucokinase (GCK) gene and Catli et al (Turkey and Exeter, UK) reported a case of PNDM due to a novel heterozygous missense mutation L30Q of the INS gene.  Data reported by Tihonovich et al (Russian Federation) and Techmanska et al (Poland) reported their experience with identifying PNDM associated with mutations in KCNJ11, ABCC8 and GCK and recommended that children diagnosed before 6 months (Tihonovich et al) or 2 years (Techmanska et al) should have genetic testing, especially if there are no immunologic markers.  In a provocative case report by Obermannova et al (Czech Republic), a girl with developmental delay, epilepsy and neonatal diabetes (DEND syndrome) due to a C166G mutation in the KCNJ11 gene was treated with glibenclamide starting at the age of 10 years.  Although glibenclamide improved diabetes control, it did not result in insulin independence; however, it did result in improvement of her EEG and her psychomotor development.

Symposium IV: VIDIS Symposium / Viruses and Diabetes
Prof. Francesco Dotta (Italy) discussed the topic of islet inflammation, viral infection and innate immunity in T1D.  Prof. Dotta underlined the complexity and heterogeneity of pathogenic mechanisms leading to T1D in different patients. Such heterogeneity regards the strength of the autoimmune attack and, as a consequence, the residual β-cell mass at diagnosis. Increasing evidence has shown that viruses may, on one hand, infect pancreatic β-cells thereby inducing β-cell dysfunction and contributing to islet inflammation and damage or, on the other hand, may modulate the immune response. Prof. Dotta concluded that in the light of such a correlation and heterogeneity in T1D pathogenesis, the existence of a single viral strain to be considered as “the diabetogenic” virus seems unlikely. Current studies suggest that viruses may indeed participate to T1D pathogenesis, but their role is strongly influenced by the genotype of the host, the serotype of the virus, the timing of infection and the characteristics of the ongoing autoimmune response.
Dr. Ken Coppieters (Belgium) explained how antiviral CTLs seek and destroy -cells in T1D. Dr. Coppieters described a novel technique that allows for the in vivo visualization of diabetogenic CD8 T-cell responses within mouse pancreatic islets. This approach was employed to determine the dynamic behavior of a CD8+ T-cell population that was activated and expanded as a result of a peripheral viral infection. Dr. Coppieters’ group found that upon viral clearance, these cells primarily arrested in the postcapillary vessels in close proximity to the pancreatic islets. Following extravasation, the diabetogenic CTLs efficiently migrated through the exocrine pancreas and were able to traffic between anatomically nearby islets. The islet-infiltrating CD8 T-cells rarely arrested or contacted β-cells directly and induction of β-cell death required the presence of hundreds of CTLs in the immediate vicinity of an islet. These data offer direct insight into the infiltration kinetics of virally expanded CD8 T-cells in pancreatic islets during autoimmune diabetes development.
Dr. Luis Sarmiento (Cuba) discussed the protective and deleterious association between viral infections and diabetes in the tropics. Dr. Sarmiento demonstrated that epidemics of meningitis in Cuba due to echoviruses (E) were associated with appearance of islet cell antibodies (ICA) in convalescent stage of the infection. The prevalence of ICA in infected patients varied depending on the virus strain responsible for the infection. Interestingly, although the prevalence of ICA in the children infected with strains dominating in 2000 and 2001 (E16 and E30) was high, there was no patient positive for ICA-related autoantibodies during the epidemics developed T1D ten years later. Dr. Sarmiento concluded that it is reasonable to assume that while the β-cell autoimmunity may be triggered upon exposure to diabetogenic enterovirus, the regulatory mechanisms could halt islet destruction and eventually abort the autoimmune process. Further studies are needed to assess the capability of enteroviruses to generate protective immune mechanism in human.

Symposium V:  SWEET Symposium
Presentations on behalf of the SWEET group reviewed the heterogeneity of diabetes care among the EU countries.  
Z. Sumnik (Czech Republic) summarized the 27-country results of a questionnaire about diabetes care.  Insulin analogs and blood glucose strips 3 times a day are covered in all countries, and glucose strips more than 3 times a day and  insulin pumps are covered in most countries.  However, coverage for CGM is variable and the care between EU countries is variable.  
H. Veeze (Netherlands) summarized the cost of diabetes care in EU countries.  Overall, CSII costs about twice and sensor-augmented pump about three times standard MDI care.  
M. Witsch (Luxembourg) reviewed the outcomes at the SWEET Centers of Reference and B. Aschemeier (Germany) reviewed how to become a Center of Reference.

Symposium VI: Diabetes Care in School
This symposium included three speakers Şükrü Hatun (Turkey), Linda Siminerio (USA), and Angie Middlehurst (Australia) discussing programs for dealing with diabetes in a school setting in their respective countries.  Hatun discussed the Diabetes Program at School developed by the Turkish Society of Pediatric Endocrinology and Diabetes in coorperation with the Ministry of National Education and the Ministry of Health.  Siminerio reviewed the American Diabetes Association’s Safe at School campaign.

Friday, 12 October 2012

Plenary Session III:  The Brain and Glucose Metabolism
The opening session on Friday started with the Lestradet Lecture in which Mohammed A. Abdullah from the University of Khartoum in Sudan discussed the changing course of diabetes care in Sudan since 2003 and the changes that have taken place since 2005 when he began to spread the word about using a multidisciplinary team approach to diabetes care.  The Lestradet Lecture was followed by lectures from Rory McCrimmon (UK) and Ana Maria Arbeláez (USA) related to the role of the brain in glucose metabolism.

Rory McCrimmon (United Kingdom) from the University of Dundee gave a lecture entitled “Another Piece of the Jigsaw: How the Brain Regulates Pancreatic Endocrine Function” in which he summarized his in vitro work on glucose sensing in the brain.  Dr. McCrimmon outlined a proposed mechanism by which, similar to that of the β-cell and involving glucokinase and the SUR-1/KATP-channel, glucose excitory and inhibitory neurons in the ventromedial nucleus of the hypothalamus release neurotransmitters in response to changing glucose and control the α-cell release of glucagon and the release of epinephrine in response to hypoglycemia and also affects the β-cell release of insulin.  

 Ana Maria Arbeláez (USA) from Washington University in St. Louis, USA, then gave a talk entitled “Neural Circuits Involved in Hypoglycemia Counterregulation” in which she reviewed the methods and summarized results from her studies in humans using positron emission tomography (PET) and pulsatile arterial spin labelling (PASL) MRI to study the CNS mechanisms of hypoglycemia-associated autonomic failure (HAAF).  The thalamus appears to play an inhibitory role in the hypothalamic response to hypoglycemia, and perhaps to other stress-related stimuli as well.  She suggested that a cerebral network of interconnecting brain regions modulates the response to hypoglycemia.  Whether or not other fuels (such as lactate or ketones) modify these pathways is currently under study.

Oral Session 7: Diabetes Care, Education, Psychosocial Issues II
A. Cotterill (Australia) presented the details of a project developed in Queensland, Australia, aimed at improving the management of children with HbA1c>10% and psychosocial co-morbidities, using frequent video conference support for the health care team by a child psychiatrist. Staff felt it made a difference to their practice and team morale.
In a small observational study, F. Mehta (United Kingdom) followed 31 patients after commencing the use of an automated bolus calculator (ABC) and found a reduction in their median HbA1c over 6 months, and an increase in numbers achieving target HbA1c. It was suggested that an RCT, with larger patient numbers, would be required to determine whether this effect was due to the ABC or other factors.
Another observational study of ABCs was presented by I. Rabonne (Italy). Children were categorised by their carbohydrate counting experience, including a control group which did not use the ABC. After 18 months the only group with significantly improved HbA1c were those on the ABC who had been using carbohydrate counting from the onset of their diabetes.
D.H. Froisland (Norway) presented the results of a survey of health-related  quality of life (HRQOL) in children with diabetes in Norway. 978 children responded to the survey (48% of 8-19 year olds in Norway with T1D). No significant differences were found in quality of life score between children on pumps and those on injections.
J. Ludvigson( Sweden), presenting for R.E.J. Besser, showed that although mixed meal tollerance test is the best measure of determining residual insulin secretion, because peak of C-peptide at 90 minutes is consistent, a single test at that time could replace multiple testing and reduce the complexity of the test.
E. Cengiz (USA) used the US T1D exchange database to compare characteristics of children with excellent control (HbA1c <7%) to those with poorer control (HbA1c >9%) and found that children with excellent control were more likely to be non-hispanic white, have private insurance and were more likely to practice more complex diabetes management behaviours such as  glucometer downloading and bolus dose fine tuning.
J. Pennisi (Australia) presented a qualitative study using focus groups of adolescents aged 13-14 to identify 'enablers' and 'challenges' to living with diabetes. Peer support and positive parental support were identified as enablers, and challenges were the appropriate attitude towards independence within the context of diabetes.
Dr. A.A. Elsharkawy (Egypt) presented compelling evidence supporting the safe involvement of children with T1D older than 10 years in fasting during Ramadan. 41 children were studied who were on differing insulin regimes. With modulation of their insulin, and food offered outside the fast, they were able to fast safely for the majority of the month.

Oral Session 8:  Pumps and Sensors
This session included oral abstract presentations related to insulin pumps and continuous glucose monitors (GMs).
C. Ziegler (Germany) spoke on behalf of the DREAM project and reported that in 18 adolescents already using CSII who used a “closed loop” system for one night in a controlled supervised setting, 89% stated that they would like to use the system again, but 78% commented that it was too big.  
K.A. Gajewska (Poland) reported that those who followed the guidelines of the Warsaw School of Pump Therapy (WSPT) related to the use of square or dual wave bolus doses had better HbA1c than those who were non-adherent to these guidelines.  
F. Sundberg (Sweden) reported that in children <7 years old with T1D, only a minority of hypoglycemic episodes were symptomatic and that CGM detected events that would have otherwise been missed.  
I. M. Overgaard Larsen (Denmark) reported the characteristics of those who responded favorably to CSII therapy compared to those who did not.  Young age (<6 years old) was associated with a high rate of responders (47%) compared to only 23-25% of those 6-19 years old.  Other than age, only a higher HbA1c and >7 boluses and/or blood glucoses (SBGM) >5 per day were associated with a higher response rate.  
B.S. Olsen (Denmark) reported similar results from a national registry of children diagnosed with T1D.  Again, younger age, more boluses and more SBGM were associated with better response to CSII therapy.  
R.H. Slover (USA) reported results from the Medtronic-sponsored ASPIRE study, in which the Veo® insulin pump, which suspends insulin delivery if the glucose (determined by CGM) falls to <70 mg/dL overnight, was used.  After exercise to induce overnight hypoglycemia, the Veo® pump was associated with shorter duration of overnight hypoglycemia than on the control night without the automatic suspension mode.  Slover also reported their experience with the Medtronic mySentry® device in 35 children with T1D.  Families found the device easy to use and acceptable, but no analysis was done related to overnight blood glucoses.  

Oral session 9: Diabetes Epidemiology
Dr. Wojciech Fendler (Poland) presented a study regarding changes in the prevalence of different types of diabetes in paediatric populations in Poland in 2005-2011. Epidemiologic data (PolPeDiab Collaboration) and nationwide genetic test results (TEAM Programme) were used for the assessment of prevalence of T1D, T2D, cystic fibrosis-related diabetes (CFRD) and monogenic diabetes (MD). MD included: MODY, neonatal diabetes, Wolfram and Alström syndromes. The study revealed significant increase in prevalence of T1D (96   →138/100,000 children), T2D and CFRD (0.3→1.01/100,000; 0.1→0.95/100,000, respectively). The prevalence of MD was stable ( 4.2-4.6/100,000) accounting for 3.1-4.2% of children with diabetes. Glucokinase (GCK)-MODY was found to be the most frequent type. Dr. Fendler concluded that the prevalence of MD in a paediatric population with a low prevalence of obesity is nearly 5-fold higher than that of T2DM and CFRD, justifying a need for increased access to genetic diagnostic procedures in diabetic children.
Dr. I.M. Sorensen (Norway) discussed the influence of antibiotic administration in early childhood on the risk of T1D onset in Norwegian population. It has been previously shown that exposure to compounds that influence gut immunity may affect the tolerance. (see Symposium II above)  Therefore, children born between January 1, 2004 and December 31, 2010 were examined. No association between use of antibiotics in early childhood and development of T1D was found.
Dr. J. Yates (Australia) showed that a younger age at diagnosis and a higher baseline HbA1c independently predict a shorter honeymoon in children with T1DM. These findings underline the need for strict monitoring and intensive treatment of younger patients with a high initial HbA1c (>10%) as a shortened honeymoon is associated with an increased risk of complications.
Dr. A. Parkkola (Finland) presented the data regarding prevalence of tissue transglutaminase antibodies (TGA) and celiac disease (CD) in children with resent-onset T1D and their first-degree relatives. The cross-sectional observation study included 745 newly-diagnosed children with T1D and their 2,692 first-degree relatives from the nationwide Finnish Pediatric Diabetes Register.  The results showed that in children with newly-diagnosed T1D and in first-degree relatives, TGAs were six-fold more common than was known CD. This suggests a considerable proportion of possibly silent CD.
Dr. J.M. Lawrence (USA) discussed the results of SUPREME-DM Project, regarding use of electronic health record to estimate 5-year incidence of diabetes among Health Maintenance Organization (HMO) members <20 years of age. The study revealed that age- and sex-adjusted DM incidence rate ranged from a low of 30.2/100,000 in 2008 to a high of 34.3/100,000 in 2005.  The SUPREME-DM project reported higher DM incidence rates for 10-14 and 15-19 year olds than other US studies. Dr. Lawrence suggested that this could result from inclusion of some undiagnosed type 2 diabetes cases in the estimate of total DM incidence.
Dr. C. Choleau (France) discussed the high frequency of ketoacidosis at onset of T1D in children and adolescents in France. The study was conducted during one year and 1,299 children were examined. It was found that severe ketoacidosis was more common when the child was hospitalized at the initiative of the family (26.6%) than by a general practitioner (7.6%) or a pediatrician (5.1%). Dr Choleau concluded that the age, the route to diagnosis and knowledge regarding diabetes are the main factors influencing the prevalence of ketoacidosis. These data support the implementation of a campaign to prevent ketoacidosis at diagnosis.
Dr. A.-L. Ponsonby (Australia) showed the results of population-based investigation of the role of life course factors in the onset of T1D. Interestingly, it was found that TD1 patients had different skin phenotype than healthy controls. T1D children were characterized by sun sensitive phenotype: fair skin, blue/green eyes and blonde/red hair. Dr Ponsonby also reported that the modification of past sun exposure by the melanocortin-1 receptor genotype provides further support that UV radiation or derivatives such as vitamin D may be causally related to a reduced risk of T1D. In addition, they presented data suggesting that ambient UV radiation 6 weeks prior to birth may affect vitamin D levels at birth and at the time of first T1D presentation.
Dr. J. Wolfsdorf (USA), presenting for M. Quinn, compared the presentation, family history, and biochemical status at diagnosis of diabetes mellitus (DM) in children under age 6 years who presented in the decade of the 1990's in comparison to children presenting with DM in 2000-2009. It was observed that over 2 decades, the proportion of children <6 years with DM presenting diabetic ketoacidosis (DKA) decreased by 1.5% per annum. In both decades approximately 10% of patients had a first degree relative with T1D. Children who had a first degree relative with T1D were less likely to present in DKA. Dr. Wolfsdorf concluded that despite the decreasing percentage of young children with the new-onset DM presenting with DKA, the frequency of DKA remains unacceptably high.

Symposium VII: Nutrition
Professor Jennie Brand-Miller (Australia) gave a presentation on her extensive experience using the Glycaemic Index (GI). Various studies have shown that consumption of lower GI food is associated with lower mean BG, and foods with the same carbohydrate content but different GI have been shown to produce markedly different glucose profiles. In the context of intensive insulin therapy, Prof. Brand-Miller suggested that the glycaemic load (carbohydrate content x GI/100) can be used to more accurately estimate the insulin bolus in individuals with T1D. Prof. Brand-Miller also described the food insulin index and its possible future use. This is based not on the glucose response to an individual food, but the insulin response, so may more accurately predict how much insulin is required.
Francesca Annan (United Kingdom), who is both a paediatric diabetes dietitian and a qualified sports dietitian, discussed the nutritional needs of young athletes with T1D. These are not extensively covered in current guidelines. In young athletes 50-60% of the diet should be carbohydrates, with each meal at least 1g/kg CHO. In some children, upwards of 400g/day may be required, and extra CHO is needed if exerecise is >45minutes. Many children take less CHO than their bodies require, resulting in a loss of performance and symptoms of fatigue.
Dr. Susana Patton (USA) gave a presentation on the challenges of providing adequate nutrition to toddlers with diabetes. Young children with T1D in the USA have slightly higher intakes of fat than recommended, and eat more processed grains and less vegetables than recommended. Strategies to improve young childrens’ diets were discussed, including the principle of presenting a child with a food on multiple occasions before withdrawing it from their repertoire. Setting rules for children around mealtimes, with elimination of distractions and release from the table as soon as they are finished, are strategies which can help parents overcome some of the challenges of the 'picky eater'.

Symposium VIII:  Unusual Forms of Diabetes:  Basic Science and the Role of Registries
Andrew Hattersley (United Kingdom) reviewed the history and the progress of the ISPAD rare diabetes collection from its beginnings as a discussion with Jan Bruining (Netherlands) in 2000 to the present day when the service (available at www.diabetesgenes.org) offers free diagnositic testing for all patients diagnosed with diabetes before 9 months of age.  This endeavor has resulted in over 500 patients now successfully controlled off insulin and the identification of 20 different type of neonatal diabetes.
T. Barrett (United Kingdom) presented their experience with the Euro-WABB Registry, which is collecting cases from the EU of Wolfram, Alstrom, and Bardet-Biedl syndromes.  A consensus set of clinical and molecular diagnostic data fields has been established by a group of experts in each syndrome.  The database enables entry of up to 370 data fields to document detailed phenotyping on suspected or known patients with these syndrome.  44 fields are used to define the syndromes.  There were currently (as of the presentation) 140  patient entries from 7 EU states.  More information is available at www.euro-wabb.org.
F. Urano (USA) from Washington University is St. Louis discussed the work in his laboratory related to endoplasmic reticulum (ER) stress and Wolfram Syndrome (WS).  ER are involved in protein folding, steroid synthesis, calcium storage and regulating cell death.  The protein product of the WFS1 gene, wolframin, is expressed in the ER of β-cells and neurons and reduces ER stress.  Dr. Unano’s lab is currently working to better understand the molecular/cellular mechanism(s) of cell death in β-cells and neurons in animal models of WS, and has developed a model system to screen potential compounds/drugs that might protect against ER stress in WS.  A few compounds are currently being studied in vitro.  In addition, Dr. Urano’s lab has collected 24 skin biopsies from WS patients and controls to isolate fibroblasts and transform them into pluripotent stem cells (iPSCs) that can then be transformed in neurons and β-cells that can be studied in vitro.  These biopsies were obtained from subjects enrolled in the Washington University Wolfram Syndrome registry (http://wolframsyndrome.dom.wustl.edu)  and who participated in the Wolfram Syndrome Research Clinic at Washington University.

Saturday, 13 October 2012

Plenary Session IV:  Type 2 Diabetes in Youth:  Results of the TODAY Study
There were 3 invited presentations on behalf of the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) Study Group.  
Lori Laffel (Boston, USA) reviewed the study design and primary outcome results of the TODAY Study.  699 youth age 10-17 years with T2D for <2 years and HbA1c <8.0% on metformin alone were randomized to 3 groups, metformin alone (M), metformin plus rosiglitazone (M+R) and metformin plus a lifestyle intervention focused on weight loss (M+L) and followed for 2-6 years.  The primary outcome (PO) was treatment failure based primarily on HbA1c >8.0% for 6 months.  The M+R group reached PO less often than the M group (38.6% vs 51.7%; p=0.006).  M+L was intermedicate and not statistically different from M or M+R overall, but was more effective in males.  M+R was least effective in non-Hispanic Blacks and more effective in females than male.  Metformin alone maintained control in only about 50% of subjects, but some maintained control for an extended period of time even if they are non-compliant with treatment.  

Silva Arslanian (Pittsburgh, USA) presented the results of insulin sensitivity and secretion from the TODAY Study.  The beneficial effect of rosiglitazone was mostly during the first 6 months and reduces insulin resistance so there is less burden on the  β-cell.  The best predictor of response to treatment is the β-cell secretory capacity at baseline.  Treatment failure is associated with little change in insulin sensitivity, but is associated with a loss of β-cell function.  

Lynn Levitsky (Boston, USA)  presented the burden of co morbidities in youth from the TODAY Study.  Although the rates of hypertension (33.8%), microalbuminuria (16.6%), and dyslipidemia (↑ LDL cholesterol 10.3%; ↑ triglycerides 28.2%) were high, there was no difference across treatment groups over the duration of the study.  13.7% had non-proliferative diabetic retinopathy and echocardiogram participants had large hearts with increased left atrial size and left ventricular mass.
 
Symposium X: Lessons from Countrywide Diabetes Registries and Organizing National Diabetes Programs
Dr. Justin Warner (United Kingdom) discussed the results from the National Pediatric Diabetes Audit (NPDA), which aims to highlight the main findings on the quality of care for Children and Young People (CYP) with diabetes mellitus (DM) in England and Wales. The NPDA covers the components of the National Service Framework for Diabetes and includes details on the number of CYP with diabetes in England and Wales, the care processes they receive and outcome measures, including inpatient admissions for diabetic ketoacidosis where applicable. In England and Wales, there are 185 centers providing in- and outpatient care for CYP with diabetes and in 2010/11 there were 23,500 submissions to the audit, which represents approximately 90% of the expected number. Dr. Warner concluded that despite a good participation rate, the submission of data on care processes remained poor and outcomes such as HbA1c had remained stable with little year-to-year change. There were large variations in outcome measures across the centers which require investigation to tease out ‘good’ and ‘poor’ practice.
Dr. Reinhard W. Holl (Germany) discussed if diabetes registries impact clinical care using as an example German/Austrian diabetes prospective documentation (DPV) registry. The registry currently includes 63,716 patients with a pediatric onset of diabetes, with 1,273,032 visits contributed by 231 pediatric diabetes centers. It is estimated that 80-90 % of patients in the country are included in the registry, dependent on year and age at onset. Every 6 months, each center receives a comprehensive report, including both cross-sectional comparisons as well as longitudinal graphs reflecting the time-trend in the individual institution compared to the trend in all centers. The data indicate that continuous feedback on process and outcome indicators, together with internal and external discussion of results, continuously improve the quality of care provided at each institution. Improved completeness of control exams following current German/Austrian/ISPAD-guidelines is demonstrated for HbA1c, blood pressure, lipid measurements and immunology, as well as retinal and microalbuminuria exams.

Symposium XI: Diabetes and Sports
This symposium included three presentations.
P. Adolfsson (Sweden) discussed intensified insulin treatment and competitive sports.
Michael Riddle (Canada) provided an evidence-based approach to insulin adjustments and nutritional requirements for exercise and sports.
Phil Southerland (USA), who has type 1 diabetes and is a professional cyclist, reviewed from his personal experiences with the glycemic response to road cycling at the elite athlete level.

Plenary Session V: Genes and Diabetes
During the “Young Investigator Lecture”, Dr. Natalia Marek-Trzonkowska (Poland) presented her study regarding local immunoprotection of human pancreatic islets with live regulatory T-cells (Tregs). The advantage for pancreatic islet transplantation is low invasiveness. However, it does not provide permanent insulin independence and is associated with adverse effects of immunosuppressive therapy required for the islet survival. Therefore, the model proposed by Dr Marek-Trzonkowska aims to overcome these obstacles using viable recipient Treg cells and bioengineering technology for the coating of pancreatic islets. The data presented indicate that the approach does not affect islet and Treg viability and function and may prevent immune-mediated rejection. Local delivery of immunosuppressive Tregs on the surface of pancreatic islets to the engraftment site is a clinically feasible approach. If further animal studies confirm its effectiveness and safety of this approach, it may be utilized for the improvement of islet transplantation in humans.

Prof. Stephen O’Rahilly (United Kingdom) discussed the association between genetics of obesity and insulin resistance. Prof. O’Rahilly explained that the adipocyte triglyceride droplet is a highly regulated organelle and discussed the clinical cases of individuals with genetic abnormalities affecting function of adipose tissue and insulin resistance. It was concluded that traditionally, human monogenic diseases have been viewed as complex qualitative phenotypes (syndromes) with clear inheritance patterns somewhat peripheral to practice of “general medicine” and of limited therapeutic relevance. However, exploration of the extreme ends of the spectrum of continuous human traits is likely to reveal previously unrecognized monogenic disorders. Some of these may be amenable to treatment. These are likely to illuminate physiological pathways relevant to man. Therefore, studies of subtle genetic changes are likely to be important for better understanding of insulin resistance in more common forms of diabetes and obesity.

Prof. Grant Morahan (Australia) reviewed the recent developments in T1D genetics, and discussed the major findings regarding T1D risk gene identification and characterization; shared genetic etiology with related diseases; and disease heterogeneity. Prof. Morahan remarked that despite recent advances in genetic research having led to the identification of over 60 loci that contributed to the susceptibility of developing T1D, the plethora of identified T1D risk genes may have been overwhelming for clinicians as well as for researchers. Therefore, there is a need for a new approach which would test the high level genetic interactions. The group of Prof. Morahan designed a new method which defines 6 genetic subtypes of T1D. The patients fell into various subgroups differ in HLA, sex, auto-antibodies, presence of other autoimmune diseases and risk of diabetic complications. This method seems to be applicable to all other complex genetic diseases as well. The approach could change our understanding of genetic studies in T1D.