Diabetic ketoacidosis in children newly diagnosed with type 1 diabetes mellitus: Role of demographic, clinical, and biochemical features along with genetic and immunological markers as risk factors. A 20-year experience in a tertiary Belgian center.

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). Little is known about the association between genetic and immunological markers and the risk for DKA at onset of T1D. The aim of this study was to create a model foreseeing the onset of DKA in newly diagnosed patients. METHODS: This retrospective study included 532 T1D children (aged <18 years at diagnosis) recruited in our hospital, from 1995 to 2014. DKA and its severity were defined according to the criteria of ISPAD. Genetic risk categories for developing T1D were defined according to the Belgian Diabetes Registry. Multivariate statistical analyses were applied to investigate risk factors related to DKA at diagnosis. RESULTS: Overall 42% of patients presented DKA at diagnosis. This study outlined the major risk of DKA at diagnosis for younger children (<3 years) and for those belonging to ethnic minorities. Children carrying neutral genotypes had a 1.5-fold increased risk of DKA at diagnosis than those with susceptible or protective genotypes, a paradoxical observation not previously reported. Only solitary positive IA-2A increased the risk of DKA at diagnosis. The proposed model could help to predict the probability of DKA in 70% of newly diagnosed cases. CONCLUSIONS: This was the first reported implication of IA-2A positivity and neutral genotypes predisposing to DKA at diagnosis regardless of its severity. Earlier diagnosis through genetic and immunological screening of high-risk children could decrease DKA incidence at diabetes onset.

Targets and teamwork: Understanding differences in pediatric diabetes centers treatment outcomes.

OBJECTIVE: The reason for center differences in metabolic control of childhood diabetes is still unknown. We sought to determine to what extent the targets, expectations, and goals that diabetes care professionals have for their patients is a determinant of center differences in metabolic outcomes. RESEARCH DESIGN AND METHODS: Children, under the age of 11 with type 1 diabetes and their parents treated at the study centers participated. Clinical, medical, and demographic data were obtained, along with blood sample for centralized assay. Parents and all members of the diabetes care team completed questionnaires on treatment targets for hemoglobin A1c (HbA1c) and recommended frequency of blood glucose monitoring. RESULTS: Totally 1113 (53% male) children (mean age 8.0 ± 2.1 years) from 18 centers in 17 countries, along with parents and 113 health-care professionals, participated. There were substantial differences in mean HbA1c between centers ranging from 7.3 ± 0.8% (53 mmol/mol ± 8.7) to 8.9 ± 1.1% (74 mmol/mol ± 12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health-care professionals that reported lower targets and more frequent testing, and (3) teams with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. CONCLUSIONS: The diabetes care teams' cohesiveness and perspectives on treatment targets, expectations, and recommendations have an influence on parental targets, contributing to the differences in pediatric diabetes center outcomes.

HLA-DQ genotypes - but not immune markers - differ by ethnicity in patients with childhood onset type 1 diabetes residing in Belgium.

AIM: The aim of this study was to compare genetic (HLA-DQ) and immune markers in a large population of type 1 diabetic (T1D) children and adolescents residing in the same environment, but of different ethnic origin: European Caucasians (EC), Moghrabin Caucasians (MC), Black Africans (BA) and of Mixed Origin (MO). METHODS: Retrospective study, including 452 patients with T1D aged 0.1-17.5 yr at diagnosis recruited at the Diabetology Clinic of the University Children's Hospital Queen Fabiola from May 1995 to March 2013. HLA-DQ genotyping, diabetes-associated autoantibodies, organ-specific autoantibodies, and other markers of autoimmunity were studied. RESULTS: The proportion of the different ethnic groups was: 55% EC, 35% MC, 6% BA, and 4% MO. Between these four groups, there were no significant differences concerning age, hemoglobin A1c (HbA1c), presence of diabetic ketoacidosis, random C-peptide level at diagnosis and 2 yr later. The two most frequent haplotypes were DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302 with a significant higher prevalence in MC and EC (p = 0.002 and 0.03, respectively). The high-risk heterozygous genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 was more frequent in EC than in MC, whereas the homozygous genotype DQA1*0501-DQB1*0201/DQA1*0501-DQB1*0201 was more prevalent in MC (p = 0.019). These susceptible genotypes were more frequent in youngest patients (p = 0.003). Diabetes-associated autoantibodies, organ-specific autoantibodies, and other immune markers did not statistically differ between ethnic groups. CONCLUSIONS: These observations in a large population of T1D children and adolescents of different ethnic groups residing in Belgium show significant differences in HLA-DQ status, but not in diabetes-associated autoantibodies, organ-specific autoantibodies, or other immune markers.

Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009.

OBJECTIVE: To investigate whether center differences in glycemic control are present in prepubertal children <11 yr with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: This cross-sectional study involved 18 pediatric centers worldwide. All children, <11 y with a diabetes duration ≥12 months were invited to participate. Case Record Forms included information on clinical characteristics, insulin regimens, diabetic ketoacidosis (DKA), severe hypoglycemia, language difficulties, and comorbidities. Hemoglobin A1c (HbA1c) was measured centrally by liquid chromatography (DCCT aligned, range: 4.4-6.3%; IFFC: 25-45 mmol/mol). RESULTS: A total of 1133 children participated (mean age: 8.0 ± 2.1 y; females: 47.5%, mean diabetes duration: 3.8 ± 2.1 y). HbA1c (overall mean: 8.0 ± 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p < 0.001 resp. p = 0.179). Language difficulties showed a negative relationship with HbA1c (8.3 ± 1.2% vs. 8.0 ± 1.0%; p = 0.036). Frequency of blood glucose monitoring demonstrated a significant but weak association with HbA1c (r = -0.17; p < 0.0001). Although significant different HbA1c levels were obtained with diverse insulin regimens (range: 7.3-8.5%; p < 0.001), center differences remained after adjusting for insulin regimen (p < 0.001). Differences between insulin regimens were no longer significant after adjusting for center effect (p = 0.199). CONCLUSIONS: Center differences in metabolic outcomes are present in children <11 yr, irrespective of diabetes duration, age, or gender. The incidence of severe hypoglycemia is lower than in adolescents despite achieving better glycemic control. Insulin regimens show a significant relationship with HbA1c but do not explain center differences. Each center's effectiveness in using specific treatment strategies remains the key factor for outcome.

Screening for diabetic retinopathy with fluorescein angiography in patients with type 1 diabetes from adolescence to adult life. A retrospective study of the past 30 years of clinical practice in a tertiary Belgian centre.

BACKGROUND: The aim of the present study was to describe the prevalence and progression of DR diagnosed by fluorescein angiography (FA) in patients with type 1 diabetes (T1D) during a 30-year follow-up, and the relationship with glycated haemoglobin (HbA1c). MATERIALS AND METHODS: We included 4325 FA reports representing 851 patients with T1D with a mean age at diagnosis of 10.4 years (range: 0.0-49.9) and followed between 1986 and 2015. Clinical characteristics of the population were collected from patients' files. The HbA1c level was measured within a maximum period of ±1 year from the date of FA. Descriptive statistics were realized to study prevalence and progression of DR. RESULTS: At diagnosis of incipient abnormalities, mean age was 22.8 years (range 13.7-46.9) and mean diabetes duration was 13 years (range: 4.3-29.6). Lesions requiring treatment were observed in 5.9% of the patients at a mean age of 32.4 years (range: 30.4-34.3) and a mean diabetes duration of 23.8 years (range: 19.4-28.1). On average, it took 12.9 years (range: 12.2-13.5) to progress from an incipient abnormality to a lesion requiring treatment. Mean HbA1c ± SD was 7.8 ± 1.5% over a period of 30 years. CONCLUSIONS: While it could have been expected to observe a higher prevalence of DR, our study described by far the lowest results of prevalence comparing to similar studies, probably due to a good average HbA1c over 30 years.

[Pediatric diabetology at the University Children's Hospital Queen Fabiola in Brussels is 40 years old]. / La diabétologie pédiatrique de l'ULB a 40 ans.

By the end of medical school at the Free University of Brussels (ULB) in 1969, I began my specialization in pediatrics. Immediately, my mentor, Professor Helmut Loeb led me into pediatric diabetes which was non-existent in Belgium. Forty years later, the diabetes clinic for children and adolescents at the University Children's Hospital Queen Fabiola in Brussels has the largest number of young patients in Belgium, social medical activities and clinical research, with the best protective glycated hemoglobin levels (proven in international comparisons from Hvidøre Study Group on Childhood Diabetes) in relation to potentially invalidating complications in the short and long term. Nevertheless, this wasn't obvious, because to stay humanistic, the fight was very hard. Over four decades, hospital life changed: balkanisation of pediatrics at ULB and competition in the same field; overrun by administrative and political power at the expense of medical freedom; weakening of the medical status at university hospitals in order to dominate and break solidarity; emphasis of financial gain instead of better quality of care and treatment. Fortunately, despite all of these pitfalls, some doctors and administrators are still able to maintain non-profit quality care for all and in our interests as a whole. Moreover, Belgian Social Security has recognized pediatric diabetic centers and subsidizes the pluridisciplinary teams of which the standards have been fairly defined. If type 1 diabetes occurs in younger and younger children, the future of pediatric diabetology will also include type 2 diabetes whose rates are exponential in countries where "fast food" reigns along with little physical exercise. Belgium is about 10 years behind what's happening in the United States....

[(R)evolution in pediatric diabetology]. / (R)evolution de la diabétologie pédiatrique.

Before the discovery of insulin 87 years ago, all diabetic children died within a few weeks or months following diagnosis. Since then, improvements in the treatment and live of young diabetics have sometimes occurred in (r)evolutions that have caused debate among physicians. They are briefly reviewed in this paper. Today's young diabetics, properly trained in self-monitoring and self-treatment, are as competitive physically and intellectually as their non-diabetic peers provided their glycemic control (i.e., their glycated hemoglobin levels) is kept close to normal. They escape the potentially incapacitating complications associated with chronic hyperglycemia of several decades' duration: blindness, renal failure, amputations, excess cardiovascular mortality, etc. To achieve this favourable outcome, diabetic children should be followed by multidisciplinary teams that include pediatric diabetologists and have a large enough case load to acquire a high level of expertise. Quality of care and patient well-being should be compared across teams with the goal of optimizing both these parameters. Any dogmatism must be avoided. The international comparisons of the Hvidøre Study Group on Childhood Diabetes have shown that diabetic children and adolescents on twice-daily free-mix regimens have significantly lower HbA1c than those on basal-bolus, pumps or twice-daily premixed/insulin regimens. Attempts to prevent type 1 diabetes are under way: vitamin D supplementation, avoidance of beta-casein (cow's milk hypothesis), etc. A definitive cure for type 1 diabetes mellitus is difficult to foresee.

[Management of type 1 diabetes (insulin, diet, sport): "Dorchy's recipes"]. / Stratégie thérapeutique dans le diabète de type 1 (insuline, alimentation, sport): "Dorchy's recipes".

The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications by maintaining blood glucose concentrations close to the normal range and an HbA1c level under 7%. The number of daily insulin injections, 2 or > or = 4, by itself does not necessarily give better results, but the 4-injection regimen allows greater freedom, taking into account that the proper insulin adjustment is difficult before adolescence. Successful glycemic control in young patients depends mainly on the quality and intensity of diabetes education. Any dogmatism must be avoided. Due to their pharmakokinetic characteristics, fast-acting and long-acting insulin analogues have specific indications in both the twice-daily injection regimen and the basal-bolus insulin therapy. They improve quality of life, without necessarily reducing HbA1c. Dietary recommendations issued over the last few years are the same for diabetic and non-diabetic individuals in order to avoid degenerative diseases. In the twice-daily free-mix regimen, the allocation of carbohydrates throughout the day is essential. There is no linear correlation between the metabolization of x grams of glucose by y units of insulin and carbohydrate counting is a piece of nonsense. Glycamic changes during exercise depend largely on blood insulin levels. In the young diabetic, during insulin deficiency, and therefore in a poor degree of metabolic control, i.e. hyperglycemic and ketotic, exercise accentuates hyperglycemia and ketosis, leading to extreme fatigue. If the insulin dosage is too high, the increase in muscular assimilation, combined with the shutdown of liver glucose production, may result in a severe hypoglycemia. During the recovery period, the repletion of muscular and hepatic glycogen stores may also provoke an hypoglycemia during hours after the cessation of muscular work.

[Screening for subclinical complications in children and adolescents with type 1 diabetes: experience acquired in Brussels]. / Dépistage des complications subcliniques chez les jeunes diabétiques de type 1: expérience bruxelloise.

Clinical studies conducted since the 1970s by the pediatric diabetology group of the Free University of Brussels have demonstrated that screening for subclinical retinopathy, neuropathy, and nephropathy should be started at puberty and at least 3 years after the diabetes diagnosis with the goal of detecting early abnormalities responsible for subclinical disorders that can be reversed by improved metabolic control, thus preventing the occurrence of irreversible potentially incapacitating lesions. A 1974 retinal fluorescein angiography study showed that the development of microaneurysms, which are irreversible lesions, could be preceded by fluorescein leakage due to disruption of the blood-retinal barrier. Risk factors for early retinopathy include: duration of diabetes, age at diagnosis (with younger children having longer times to retinopathy), puberty and sex (with onset one year earlier in girls than in boys), long-term bad metabolic control over several years, high cholesterol levels and excessive body mass index (2002). On the other hand, rapid improvement of diabetic control may worsen diabetic retinopathy (1985). Minimal EEG abnormalities were found in relationship with frequent and severe hypoglycemic comas and/or convulsions, and retinopathy (1979). Desynchronization of action potentials in distal nerve fibers preceded conduction velocity slowing (1981). A single high glycated hemoglobin value was associated with peroneal motor nerve conduction slowing (1985), which was not observed in the femoral nerve (1987). Sympathetic skin response (1996) and statistical analysis of heart rate variability (2001) could have some interest for the diagnosis of early diabetic autonomic neuropathy. Early microproteinuria is of mixed origin, being both glomerular (microalbumin) and tubular (beta2-microglobulin). Exercise testing to exhaustion did not provide additional information than the basal excretion (1976). Microtransferrinuria (1984) and urinary acid glycosaminoglycans output (2001) could also be predictive markers of glomerular dysfunction. Physical training reduced exercise-related proteinuria by half (1988). High levels of serum lipoprotein (a) were not associated with the presence of subclinical complications (1996). On the other hand, ultra sensitive C-reactive protein could be an interesting indicator for the risk of developing early complications (2005). Poor metabolic control was associated with higher levels of triglycerides, total cholesterol, LDL cholesterol, and apolipoprotein B (1990). Decreased gluthatione peroxidase, gluthatione reductase, and of vitamin C levels, denoting moderate oxidative stress, were found (1996), although there was no evidence of increased LDL cholesterol peroxidation (1998). Erythrocytes exhibited increased glycolytic activity, and neutrophils decreased migration, in relationship with metabolic control (1992). The degree of metabolic control influenced serum triiodothyronine levels (1985), magnesium concentrations (1999). Helicobacter pylori infection and eradication are not related to HbA1c levels (2007). Insulin therapy could activate the complement pathway if intermediate and long-acting insulin preparations without protamine sulphate are used (1992), and provoke higher BMI in adolescents on 4 insulin injections (1988). Well-being was inversely related to glycated hemoglobin levels (1997). Family cohesiveness and parental alexithymia predict glycemic control (2008). Alexithymia factor explains 11.5% of the HbA1c total variance (2010).

[Félicien Rops and phosphatous diabetes in the 19th century]. / Félicien Rops et le diabète phosphateux au 19e siècle.

Félicien Rops was among the 19th century's finest draughtsmen and Belgium's most sulphurous artist. Rops was also a prolific letter-writer. In his correspondence, he complained of real or imaginary diseases among which phosphatous diabetes. Causes and treatments of diabetes at that time are described.

[Growth in type 1 diabetic children]. / Croissance de l'enfant diabétique.

Despite the fact that height in diabetic children has extensively been studied, many controversies remain. The aim of this study is to review growth in type 1 diabetes. Height at diagnosis is probably not increased compared with appropriate reference data. Later loss of height is observed due to a reduced peak height velocity during puberty. The poor pubertal growth can be linked to abnormalities of the growth hormone--insulinlike growth factor-I axis. It has also been showed that good metabolic control is necessary to allow normal growth in diabetic children. Metabolic control and the age at onset of type 1 diabetes are reported to be significant factors influencing final height. Careful monitoring of height and weight in diabetic patients must be made and good glycemic control has to be maintained to allow normal growth and development in diabetic patients.

[Neonatal diabetes: a case of pancreatic beta cell agenesis and a 38-year follow-up of a permanent neonatal diabetes mellitus]. / Diabètes néonatals: un cas d'agénésie des cellules beta et suivi pendant 38 ans d'un diabète néonatal permanent.

Neonatal diabetes, transient (TND) or permanent (PND) is a rare disease, with a reported frequency of 1/300,000. If establishing a diagnosis is quite easy, treatment remains challenging during childhood. Understanding of physiopathology increased this last decade, as many mutations in genes playing critical roles in the development of pancreas, have been described: the most common are chromosome 6q anomalies in the case of TND, and mutations in KCNJ11 and ABCC8 genes encoding the subunit of the insulin cell potassium channel in the case of PND. We report on 2 peculiar stories: the first one is the unique case of a newborn with isodisomy of chromosome 6, methylmalonic acidemia and pancreatic beta cell agenesis, who died on the 16th day of life. The second one is the longest follow-up ever described, 38-year, of a permanent neonatal diabetes mellitus without complications, except for rare micro-aneurysms, in spite of insufficient metabolic control.

[(Pre)type 2 diabetes and MODY: pediatric diabetology future]. / (Pré)diabète de type 2 et MODY: l'avenir de la diabétologie pédiatrique.

Type 2 diabetes mellitus (T2D) is no longer a disease only of adults. In some American locations and populations, incidence and prevalence of T2D are much higher than those of type 1 diabetes, because of increased calorie and fat intake, and decreased exercise. The increasing prevalence of T2D in the United States has closely paralleled the increase in childhood obesity noted there, but now across the Western world. Besides obesity, the other youth risk factors for T2D are: ethnicity, family history, puberty, female, metabolic syndrome, acanthosis nigricans and polycystic ovary syndrome. Any feature or condition associated with insulin resistance/hyperinsulinemia should alert to screen youth at increased risk for (pre)T2D. T2D should be differenciated from monogenic diabetes (Maturity Onset Diabetes of the Young or MODY). Treatment goals are to decrease weight and increase exercise, to normalize insulinemia, glycemia and HbA1c, to control hypertension and hyperlipidemia. The aim of the pharmacological therapy is to decrease insulin resistance, namely by metformin. Sometimes, insulin therapy is necessary.

[Biological variation of glycation and mean blood glucose have greater influence on Hba1c levels in type 1 young diabetic patients than glucose instability]. / La variation biologique de la glycation et la moyenne glycémique ont une plus grande influence sur l'HbA1c des jeunes diabétiques de type 1 que l'instabilité glycémique.

The aim of the study was to assess the relative influence of mean blood glucose (MBG), glucose instability (GI) and biological variation of glycohemoglobin (BVG) on HbA1c. The study included 378 unselected young type 1 diabetic patients with a diabetes duration > 1 year. There were 1,409 visits with simultaneous HbA1c determinations and self-monitoring of BG meter downloads. GI was quantified by measuring the standard deviation (SD) of the recorded BG values. A statistical model was developed to predict HbA1c from MBG. Hemoglobin glycation index (HGI) was calculated (HGI = observed HbA1c--predicted HbA1c) for each visit to assess BVG based on the directional deviation of observed HbA1c from that predicted by MBG in the model. Afterwards, the population was divided by thirds into high-, moderate-, and low-HGI groups, i.e. high-, moderate-, and low-glycators, reflecting BVG. A total of 246,000 preprandial BG measurements were analysed, with a mean of 177 per visit. Grand MBG +/- SD was 171 +/- 40 mg/dl. Predicted HbA1c was calculated from the equation: 3.8399 + 0.0242 x MBG (r = 0.66; p < 0.0001). A MBG change of 40 mg/dl corresponded to 1% change in HbA1c, within the range 6-12%. Multiple regression analysis showed no significant relationship between SD and HbA1c, after adjustment for MBG. MBG was 10 times more important than SD to predict HbA1c. MBG was not statistically different between the high- and low glycators, but HbA1c was significantly different. Multiple linear regression was used to predict HbA1c from MBG, SD and BVG (measured by HGI), adjusted for age, duration, gender and ethnic origin. BVG and MBG had large influences on HbA1c, the impact of BVG being 84% of the impact of MBG. On the other hand, GI had only 17% of the impact of MBG. In conclusion the effect of BVG on HbA1c is independent and much greater that the influence attributable to GI. Hemoglobin glycation phenotype, responsible for BVG, may be important for the clinical assessment of diabetic patients in order to avoid complications.

[Severe hypoglycemia in children and adolescents with type 1 diabetes: risks factors and management]. / Hypoglycémies sévères chez les jeunes diabétiques de type 1: facteurs de risque et traitement.

Hypoglycemia is one of the most common acute complications in the treatment of type 1 diabetes. It is the result of a mismatch between insulin dose, food consumed, and recent exercise. Hypoglycemia occurs more frequently in younger children and with lower HbA1c levels. Symptoms of hypoglycemia result from autonomic (adrenergic) activation and/or neurological dysfunction (neuroglycopenia). Severe hypoglycemia means that the child is having altered mental status and cannot assist in his care, is semiconscious or unconscious, or in coma--convulsions and may require parenteral therapy (glucagon or i.v. glucose). The blood glucose threshold for symptoms may be affected by antecedent hypoglycemia, duration of diabetes with decrease in neurohormonal counterregulatory responses. This phenomenon is termed hypoglycemia unawareness and is an important cause of severe hypoglycemia. Fortunately, there is absence of adverse effects of severe hypoglycemia on cognitive function in children with diabetes over 18 months, even if some controversies exist. Severe hypoglycemia is rapidly reversed by injection of glucagon 0.5 mg if < 25 kg, 1.0 mg if > 25 kg. In the hospital, intravenous infusion of glucose should be administered, e.g. glucose 10%, 2-5 mg/kg/min (1.2-3.0 ml/kg).

[Diabetic ketoacidosis: diagnosis, management, prevention]. / L'acidocétose diabétique: diagnostic, prise en charge, prévention.

Diabetic ketoacidosis results from relative or absolute deficiency of insulin and is a frequent metabolic emergency. It occurs in previously undiagnosed diabetes, in half of the cases in Europe, or is the consequence of a severe unbalance in a well-known diabetic patient, who, deliberately or not, does not take enough or not at all insulin. In population studies, the mortality rate in children ranges from 0,15% to 0,30%, cerebral edema accounts for 60% to 90%. Three stages are described: ketosis, ketoacidosis, ketoacidotic coma. This paper summarizes the physiopathology as well as the clinical and biological signs. It opens up an algorithm for the management of diabetic ketoacidosis and its complications and indicates prevention methods.

[Helicobacter pylori infection and eradication are not related to glycosylated hemoglobin levels (HbA1c) in young patients with type 1 diabetes]. / L'infection par Helicobacter pylori et son éradication ne sont pas liées aux taux d'hémoglobine glyquée des jeunes diabétiques de type 1.

OBJECTIVE: Helicobacter pylori (Hp) is a chronic stomach infection common throughout the world. The pediatric diabetes literature on the relation between Hp and HbA1c is sparse and controversial. This study aimed to investigate this relation. METHODS: The study included 100 youth with type 1 diabetes and seropositive for Hp (European Caucasians: n=49; Moghrabin Caucasians: n=51). Mean socioeconomic status was lower among the latter. Hp infection was demonstrated by the (13)C-urea breath test and a gastric biopsy for antibiotic susceptibility testing. HbA1c levels were measured for a year (mean: 6 measurements; upper normal limit: 6.2%) before and after Hp eradication, which was proved by the (13)C-urea breath test. RESULTS: Of 100 Hp-seropositive patients, 49 had active Hp infections and were treated. Mean age+/-SD was 14.2+/-2.8 years, and duration of diabetes at Hp diagnosis was 6.2 +/-2.3 years. Hp infection was eradicated in 38/49 subjects (78%). Eleven (22%) remained infected and required a second treatment. The two subgroups did not differ for age, duration of diabetes or pretreatment HbA1c levels (7.3+/-1.5% versus 7.8+/-0.8%; p=0.16). Mean HbA1c levels in the 49 infected subjects did not differ significantly in the year before and after eradication (7.4+/-1.3% versus 7.9+/-1.1%; p=0.08). Prevalence of infection was higher among youth of North African than European ancestry (47% versus 22%; p<0.001). Their HbA1c levels, however, did not differ (7.3+/-1.5% versus 7.7+/-0.9%; p=0.31), nor did age or duration of diabetes. Among the 100 Hp-seropositive patients, vague abdominal pain was reported by 45 of them; only 24 had active Hp infections. CONCLUSION: Before treatment, patients seropositive for Hp did not differ in HbA1c levels or abdominal complaints according to whether they had active Hp infection. Hp infection was twice as frequent in Moghrabin Caucasians than in European Caucasians, perhaps associated with their lower socioeconomic status. HbA1c levels were similar in patients with and without Hp eradication after one treatment. After a one-year follow-up, Hp eradication had no significant effect on HbA1c levels.

Twenty-Year Progression Rate to Clinical Onset According to Autoantibody Profile, Age, and HLA-DQ Genotype in a Registry-Based Group of Children and Adults With a First-Degree Relative With Type 1 Diabetes.

OBJECTIVE: We investigated whether islet autoantibody profile, HLA-DQ genotype, and age influenced a 20-year progression to diabetes from first autoantibody positivity (autoAb+) in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Persistently islet autoAb+ siblings and offspring (n = 462) under 40 years of age were followed by the Belgian Diabetes Registry. AutoAbs against insulin (IAA), GAD (GADA), IA-2 antigen (IA-2A), and zinc transporter 8 (ZnT8A) were determined by radiobinding assay. RESULTS: The 20-year progression rate of multiple-autoAb+ relatives (n = 194) was higher than that for single-autoAb+ participants (n = 268) (88% vs. 54%; P < 0.001). Relatives positive for IAA and GADA (n = 54) progressed more slowly than double-autoAb+ individuals carrying IA-2A and/or ZnT8A (n = 38; P = 0.001). In multiple-autoAb+ relatives, Cox regression analysis identified the presence of IA-2A or ZnT8A as the only independent predictors of more rapid progression to diabetes (P < 0.001); in single-autoAb+ relatives, it identified younger age (P < 0.001), HLA-DQ2/DQ8 genotype (P < 0.001), and IAA (P = 0.028) as independent predictors of seroconversion to multiple positivity for autoAbs. In time-dependent Cox regression, younger age (P = 0.042), HLA-DQ2/DQ8 genotype (P = 0.009), and the development of additional autoAbs (P = 0.012) were associated with more rapid progression to diabetes. CONCLUSIONS: In single-autoAb+ relatives, the time to multiple-autoAb positivity increases with age and the absence of IAA and HLA-DQ2/DQ8 genotype. The majority of multiple-autoAb+ individuals progress to diabetes within 20 years; this occurs more rapidly in the presence of IA-2A or ZnT8A, regardless of age, HLA-DQ genotype, and number of autoAbs. These data may help to refine the risk stratification of presymptomatic type 1 diabetes.

One center in Brussels has consistently had the lowest HbA1c values in the 4 studies (1994-2009) by the Hvidoere International Study Group on Childhood Diabetes: What are the "recipes"?

The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications (retinopathy, neuropathy, nephropathy, cardiovascular disease, etc.) by maintaining blood glucose concentrations close to normal level. Glycated hemoglobin levels (HbA1c) provide a good criterion of overall glycemic control. The Hvidoere Study Group (HSG) on Childhood Diabetes, founded in 1994, is an international group representing about twenty highly experienced pediatric centers from Europe, North America, Japan and Australia. Four international comparisons of metabolic control (1995, 1998, 2005, 2009) have been performed. The one center that has consistently had the lowest HbA1c values (approximate 7.3% or 56.3 mmol/mol) is my center in Brussels. This is more often obtained with a twice-daily free-mixed regimen with additional supplemental fast insulins ad hoc. The so-called "Dorchy's recipes" are summarized. The conclusion is that the number of daily insulin injections, 2 or ≥ 4, or the use of pumps, by itself does not necessarily give better results. Intensified therapy should not depend upon the number of insulin doses per day, by syringe, pen or pump but rather should be redefined as to intent-to-treat ascertainment (i.e., goals). When there are no mutually agreed upon goals for BG and/or HbA1c, when there is insufficient education and psychosocial support by the medical team or at home, there is likely to be poor outcomes, as shown by the HSG. One of our recipes is not to systematically replace rapid-acting human insulins by fast-acting analogues. Because the multicenter studies of the HSG, performed in developed countries without financial restriction, show that treatment of childhood diabetes is inadequate in general and that levels of HbA1c are very different, diabetes treatment teams should individually explore the reasons for failure, without any prejudice or bias. Any dogmatism must be avoided. Treatment cost vs results must also be taken into account.

Dietary management for children and adolescents with diabetes mellitus: personal experience and recommendations.

Diet has traditionally played an important role in diabetic therapy. Over the years, various diets have been proposed, often without scientific evidence. One of the main errors was (is) to speculate that there exists a direct linear correlation between the injection of x units of insulin and the utilization of y grams of glucose. If this were true, one should give more insulin to practice physical activity. In reality, it is the reverse. Dietary recommendations issued over the last few years are the same for diabetic and non-diabetic individuals in order to avoid degenerative diseases. In many countries, the intake of fat is too high, and that of complex carbohydrates too low. The so-called 'Mediterranean diet', in combination with appropriate insulin therapy, may be optimal. This consists mainly of fiber-rich complex carbohydrates (grain), vegetables, fruits, fish, and olive oil. Explanations of this diet should focus on quality rather than quantity of foodstuffs, and should be given by a multidisciplinary team. Prescription of a highly rigid diet has proved ineffective in producing adequate metabolic control, and increases the risk of deviations from the diet. In our experience, the proper use of the two-injection regimen, in countries where the meal schedule allows correct allocation of diet, may lead to 'intensive conventional therapy' and good metabolic control. It is inadequate to systematically assign the multiple-insulin injection regimen to intensified insulin therapy, and the 'conventional' two-injection regimen to a non-intensified insulin therapy. The proper use of the basal-bolus regimen, with increased flexibility in daily life and dietary freedom, cannot always be applied successfully before adolescence. The adjustment of insulin dosage is more complicated than in the twice-daily injection regimen because dose alteration cannot be made only according to sliding scales based on the glycemia measured immediately before the insulin injection. The simplistic use of these non-physiological sliding scales is the main error in the multiple daily insulin injection regimen. The use of fast-acting insulin analogs in the basal-prandial regimen improves post-prandial glycemia at the expense of an increase in pre-prandial glucose levels, if the period between two meals, and therefore two injections, exceeds 3-4 hours, because of the short duration of action. If there are 4-6 or 7 hours between two meals, it is better to use a rapid-acting insulin. Avoid dogmatism--only objective results (good glycosylated hemoglobin and lipid levels, as well as good quality of life) are important.