AP/HP Pôle 1

- Diabétologie -

Réponses affichées : 12

Lien PubMed Resistance to leptin-replacement therapy in Berardinelli-Seip congenital lipodystrophy: an immunological origin
BELTRAND J, LAHLOU N, LE CHARPENTIER T, SEBAG G, LEKA S, POLAK M, TUBIANA-RUFI N, LACOMBE D, DE KERDANET M, HUET F, ROBERT JJ, CHEVENNE D, GRESSENS P, LEVY-MARCHAL C
2010 - Eur J Endocrinol 162(6):1083-91
CONTEXT: Recently, in a 4-month proof-of-concept trial, beneficial metabolic effects were reported in non-diabetic children with Berardinelli-Seip congenital lipodystrophy (BSCL); this information prompted us to hypothesize that long-term leptin-replacement therapy might improve or reverse the early complications of the disease in these patients. PATIENTS AND METHODS: A 28-month trial was implemented in eight patients. Efficacy assessment was based on a decrease in serum triglyceride concentrations, and/or a decrease in liver volume and/or an increase in insulin sensitivity of at least 30% respectively. The response was defined as follows: total (3/3 positive criteria), partial (1 or 2/3), or negative (0/3). Anti-leptin antibodies were measured with a radiobinding assay, and a neutralizing effect was assessed in primary cultures of embryonic neurons incubated with an apoptotic agent (N-methyl-D-aspartate) and the patient serum, with or without leptin. RESULTS: A negative or partial response to treatment was observed in five of eight patients even when leptin dosages were increased. A displaceable leptin binding was detectable in all patients after 2 months of treatment. At 28 months, binding was higher in the patients with a negative response than in the total responders, and it paralleled both the increase in leptin dosage and serum leptin concentrations. Co-incubation of embryonic neurons with serum from two patients with a negative response inhibited the neuroprotective effect of leptin. CONCLUSION: Under leptin therapy, patients with BSCL may develop a resistance to leptin, which could be partly of immunological origin, blunting the previously reported beneficial effects.
Unité(s) : Diabétologie Pédiatrique, Endocrinologie Pédiatrique et Gynécologie
 
Lien PubMed Growth hormone: health considerations beyond height gain
ROSS J, CZERNICHOW P, BILLER BM, COLAO A, REITER E, KIESS W
2010 - Pediatrics 125(4):e906-18
The therapeutic benefit of growth hormone (GH) therapy in improving height in short children is widely recognized; however, GH therapy is associated with other metabolic actions that may be of benefit in these children. Beneficial effects of GH on body composition have been documented in several different patient populations as well as improvements in lipid profile. Marked augmentation of bone mineral density also seems evident in many pediatric populations. Some of these benefits may require continued therapy past the acquisition of adult height. With long-term therapy of any kind, the adverse consequences of treatment should also be considered. Fortunately, long-term GH treatment seems to be safe and well-tolerated. This review describes the long-term metabolic effects of GH treatment in the pediatric population and considers how these may benefit children who are treated with GH.
Unité(s) : Diabétologie Pédiatrique
 
Lien PubMed Effect of insulin detemir dose frequency on clinical outcomes in patients with diabetes in PREDICTIVE
FONTAINE P, GIN H, PINGET M, THIVOLET C, HANAIRE H, ROBERT JJ, MARRE M, VENKATANARASIMHACHAR S
2009 - Adv Ther 26(5):535-51
INTRODUCTION: The aim was to compare clinical outcomes by different dosing frequencies of insulin detemir (detemir) used over 52 weeks in various regimens. Methods: This analysis involved French patients enrolled in PREDICTIVE (a large-scale, multinational, observational study of empirical use of detemir in everyday clinical practice) for whom data have been collected over 52 weeks. Three cohorts were considered: patients with type 1 diabetes; patients with type 2 diabetes using detemir in a basal insulin plus oral antidiabetic drug (OAD) regimen; patients with type 2 diabetes using detemir as part of basal-bolus insulin therapy. In each cohort, data were stratified according to detemir dosing frequency at the beginning and end of 52 weeks: once daily (o.d.) at the beginning and end; twice daily (b.i.d.) at the beginning and end; o.d. at the beginning, but b.i.d. at the end. Endpoints assessed included glycated hemoglobin, fasting plasma glucose, hypoglycemia, weight, and insulin dose. RESULTS: There were improvements in glycemic control and tolerability in all subgroups. Patients completing on o.d. dosing tended to have better outcomes than those completing on b.i.d. dosing in all cohorts, and o.d. administration was associated with lower insulin dosing. There was little evidence that switching from o.d. to b.i.d. dosing influenced outcomes other than insulin dose. However, there were some baseline differences between subgroups selected for o.d. and b.i.d. dosing that might have influenced outcomes: many patients appeared to have been continued on previous basal dosing frequencies; for others, b.i.d. detemir dosing seemed to be used to intensify previous therapy. CONCLUSIONS: With the caveat that empirical choices of dose frequency were made, this analy-sis shows that empirical use of o.d. detemir produces results at least as good as empirical use of b.i.d. detemir in basal-bolus-treated type 1 and type 2 diabetes, and in basal plus OAD-treated type 2 diabetes.
Unité(s) : Diabétologie Pédiatrique
 
Lien PubMed Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE study in a cohort of French patients with type 1 or type 2 diabetes
MARRE M, PINGET M, GIN H, THIVOLET C, HANAIRE H, ROBERT JJ, FONTAINE P
2009 - Diabetes Metab 35(6):469-75
AIM: PREDICTIVE (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n=1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes. METHODS: Patients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA(1c), fasting blood glucose and variability of fasting blood glucose) and weight change. RESULTS: The incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P<0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA(1c), by -0.6% and -0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by -1.4mmol/L and -1.9mmol/L respectively; and FBG variability, by -0.8mmol/L and -0.3mmol/L, respectively (P<0.0001 for all). CONCLUSION: Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.
Unité(s) : Diabétologie Pédiatrique
 
Lien PubMed Alimentation, plaisir et diabete de l'enfant
MOSSER F
2009 - Soins Pediatr Pueric 248(.):29-31
Unité(s) : Diabétologie Pédiatrique
 
  Glucose tolerance and insulin secretion, morbidity, and death in patients with cystic fibrosis
BISMUTH E, LABORDE K, TAUPIN P, VELHO G, RIBAULT V, JENNANE F, GRASSET E, SERMET-GAUDELUS I, DE BLIC J, LENOIR G, ROBERT JJ
2008 - J. Pediat. 152(4):540-545
OBJECTIVES: To describe the history, mechanisms, and consequences of cystic fibrosis (CF)-related diabetes, from childhood to early adulthood. STUDY DESIGN: Pancreatic beta-cell function was estimated from the plasma insulin/glucose ratios during oral glucose tolerance test (total area under the curve and deltaI(30-0min)/G(30min), homeostasis model assessment [HOMA]%B), insulin sensitivity with the HOMA%S index, in 237 children with CF (109 boys, 128 girls). Progression of glucose metabolism abnormalities was evaluated by analysis for interval censored data; rates of pulmonary transplantation and death by Kaplan-Meier analysis. RESULTS: Impaired glucose tolerance was found in 20% of patients at 10 years, 50% at 15 years, 75% at 20 years, 82% at 30 years; for diabetes, >20% at 15 year, 45% at 20 years, 70% at 30 years; for insulin treatment, 30% at 20 years, 40% at 30 years. Early impairment was associated with lower survival rates and higher rates of lung transplantation. The area under the curve(glucose) correlated with decreased body mass index and height. Decrease in early insulin secretion (deltaI(30-0min)/G(30min)) was associated with impaired glucose tolerance, in all estimates of insulin secretion with diabetes. HOMA%S did not differ between the groups. Increased inflammation correlated with insulin resistance and impaired glucose tolerance. CONCLUSIONS: CF-related diabetes, mainly because of beta-cell deficiency, is frequent early in life and associated with impaired nutritional state and growth, increased rates of terminal respiratory failure, and death.
Unité(s) : Biostatistique, Diabétologie Pédiatrique, Explorations Fonctionnelles, Génétique Médicale Pédiatrique, Pneumologie et Asthmologie Pédiatriques
 
  Long-term follow-up of OGTT-derived glucose tolerance, insulin secretion and insulin sensitivity indices in subjects with glucokinase mutations (MODY2
MARTIN D, BELLANNE-CHANTELOT C, DESCHAMPS I, FROGUEL P, ROBERT JJ, VELHO G
2008 - Diabetes Care 31(7):1321-1323
Objective We investigated the natural history of MODY2, notably the factors associated with deterioration of hyperglycemia over time. Research Design And Methods We report an 11-year follow-up of glucose tolerance and of indices of insulin secretion and insulin sensitivity derived from oral glucose tolerance tests in 33 MODY2 subjects. Results The variation between tests of glucose tolerance (expressed as the area under the glucose curve) was 6.9+/-3.2% (m+/-SEM), but individual results ranged from -20% to 61%. Deterioration of glucose tolerance between tests was associated with decreased insulin sensitivity, while insulin secretion remained stable. Conclusions Glucose tolerance can remain stable over many years in subjects with MODY2, due to the relative stability of the glucokinase-related beta-cell defect. However, the development of insulin resistance may have an important role in the deterioration of the glucose tolerance and in the long-term evolution of the disorder.
Unité(s) : Diabétologie Pédiatrique
 
  What's new in metabolic and genetic hypoglycaemias: diagnosis and management
VALAYANNOPOULOS V, ROMANO S, MENTION K, VASSAULT A, RABIER D, POLAK M, ROBERT JJ, KEYZER Y, DE LONLAY P
2008 - Eur. J. Pediat. 167(3):257-265
Hypoglycaemia in children can be a life-threatening situation that needs to be assessed rigorously in order to treat efficiently and avoid relapse that can be responsible for cerebral damage. The diagnosis of impairment in glucose homeostasis requires the knowledge of the mechanisms regulating blood glucose concentration. The clinical history and presentation, when available, especially the timing of hypoglycaemia with respect to the last meal and some simple clinical and biological tests may allow diagnosing the vast majority of patients presenting with hypoglycaemia. Recently, new metabolic and endocrinologic genetic causes of hypoglycaemia have been identified that may give new insight to the complex mechanisms of glucose regulation and thus contribute to the discovery of new genes regulating glucose homeostasis. New diagnostic tests such as the 18-fluoro-Dopa PET-scan have also been recently developed.
Unité(s) : U781, Biochimie Métabolique, Métabolisme, Endocrinologie Pédiatrique et Gynécologie, Diabétologie Pédiatrique
 
  Neonatal hyperinsulinism: clinicopathologic correlation
DE LONLAY P, SIMON A, GALMICHE-ROLLAND L, GIURGEA I, VERKARRE V, AIGRAIN Y, SANTIAGO-RIBEIRO MJ, POLAK M, ROBERT JJ, BELLANNE-CHANTELOT C, BRUNELLE F, NIHOUL-FEKETE C, JAUBERT F
2007 - Hum. Pathol. 38(3):387-399
Neonatal hyperinsulinism is a life-threatening disease that, when treated by total pancreatectomy, leads to diabetes and pancreatic insufficiency. A more conservative approach is now possible since the separation of the disease into a nonrecurring focal form, which is cured by partial surgery, and a diffuse form, which necessitates total pancreas removal only in cases of medical treatment failure. The pathogenesis of the disease is now divided into K-channel disease (hyperinsulinemic hypoglycemia, familial [HHF] 1 and 2), which can mandate surgery, and other metabolic causes, HHF 3 to 6, which are treated medically in most patients. The diffuse form is inherited as a recessive gene on chromosome 11, whereas most cases of the focal form are caused by a sulfonylurea receptor 1 defect inherited from the father, which is associated with a loss of heterozygosity on the corresponding part of the mother's chromosome 11. The rare bifocal forms result from a maternal loss of heterozygosity specific to each focus. Paternal disomy of chromosome 11 is a rare cause of a condition similar to Beckwith-Wiedemann syndrome. A preoperative PET scan with fluorodihydroxyphenylalanine and perioperative frozen-section confirmation are the types of studies done before surgery when needed. Adult variants of the disease are less well defined at the present time.
Unité(s) : Chirurgie Viscérale Pédiatrique, Métabolisme, Radiologie Pédiatrique, Endocrinologie Pédiatrique et Gynécologie, Anatomie Pathologique, Diabétologie Pédiatrique
 
  Genetic and epigenetic defects at the 6q24 imprinted locus in a cohort of 13 patients with transient neonatal diabetes: new hypothesis raised by the finding of a unique case with hemizygotic deletion in the critical region
DIATLOFF-ZITO C, NICOLE A, MARCELIN G, LABIT H, MARQUIS E, BELLANNE-CHANTELOT C, ROBERT JJ
2007 - J. Med. Genet. 44(1):31-37
BACKGROUND: Transient neonatal diabetes (TND) is a rare form of diabetes usually present in the first few days after birth that resolves within 1 year but that has a tendency to recur later in life. It can be associated with chromosome 6 paternal uniparental disomy (UPD), paternal duplications or loss of maternal methylation at the 6q24 imprinted locus. OBJECTIVE: To report on a cohort of 13 sporadic TND cases, including five with birth defects (congenital abnormalities of heart, brain and bone) and eight without. RESULTS: The hallmarks of diabetes were similar in patients with or without 6q24 defects. The chromosome 6 abnormalities in our patients (n = 13) included 2 of 13 (approximately 15.4%) cases of paternal UPD6, 2 of 11 (approximately 18%) cases of complete and 3 of 11 (approximately 27%) cases of partial loss of the maternal methylation signature upstream of ZAC1-HYMAI imprinted genes in non-UPD cases, and 1 of 13 (approximately 7.7%) cases of hemizygotic deletion. CONCLUSION: The deletion was found in a patient with severe congenital abnormalities. This genetic lesion was not reported previously. The hypothesis of an effect on regulatory elements critical for imprinting and tissue-specific gene expression in early development by the deletion is raised. The data presented here may contribute to the diagnosis and the understanding of imprinting in the region.
Unité(s) : U781, Diabétologie Pédiatrique
 
  Thyroiditis and gluten intolerance: extrapancreatic auto-immune diseases associated with type 1 diabetes
FAESCH S, JENNANE F, IZEMBART I, CHATENOUD L, TAUPIN P, MARTIN D, POLAK M, ROBERT JJ
2007 - Archives Pédiatrie 14(1):24-30
OBJECTIVES: This study aimed at evaluating the screening of thyroiditis and coeliac disease, in a population of children and adolescents with type 1 diabetes, and at comparing the appearance of antibodies specific for these 2 diseases as a function of age. PATIENTS AND METHODS: The study included 370 children and adolescents, 179 girls and 191 boys, aged 13.8 +/- 4.4 yr and with diabetes for 7.1 +/- 3.8 yr. Auto-immune thyroiditis was screened using antimicrosomal and antithyroglobulin auto-antibodies, at a mean rhythm of 3 tests per patient (1 every 2 yr), associated with dosages of TSH and FT4. Coeliac disease was screened using antigliadin (+/- antiendomysium) auto-antibodies, at a mean rhythm of 2 tests per patient, and was confirmed by duodenojejunal biopsy. Antithyroid auto-antibodies were correlated with age following the << censured data analysis >> type approach. RESULTS: Antithyroid autoantibodies were found in 42 patients (11.4%), of whom 9 were treated for hypothyroidism and 1 for Basedow disease, and coeliac disease autoantibodies were found in 9 patients (3.2% of tested patients). The cumulated frequency of antithyroid auto-antibodies increased regularly with age and was significantly higher in girls, reaching 28% in girls and 12% in boys around 18 yr of age. As a consequence of this evolution, antithyroid auto-antibodies were frequently found at the time of diagnosis of diabetes when it declared after 10 yr of age, while they often became positive secondarily when diabetes occurred before 10 yr of age. Coeliac disease specific auto-antibodies appeared much earlier and were found at the time of diagnosis of diabetes or at the first screening test. CONCLUSION: Antithyroid autoantibodies are increasingly frequent with age in children with type 1 diabetes, and become very elevated in girls. The rhythm for screening should be adapted to this evolution of autoantibodies with age, which is very different between thyroiditis and coeliac disease.
Unité(s) : Métabolisme, Biostatistique, Laboratoire d'Immunologie, Endocrinologie Pédiatrique et Gynécologie, Diabétologie Pédiatrique
 
  Coexistence in the same family of both focal and diffuse forms of hyperinsulinism
VALAYANNOPOULOS V, VAXILLAIRE M, AIGRAIN Y, JAUBERT F, BELLANNE-CHANTELOT C, RIBEIRO MJ, BRUNELLE F, FROGUEL P, ROBERT JJ, POLAK M, NIHOUL-FEKETE C, DE LONLAY P
2007 - Diabetes Care 30(6):1590-1592
Unité(s) : Anatomie Pathologique, Chirurgie Viscérale Pédiatrique, Endocrinologie Pédiatrique et Gynécologie, Métabolisme, Radiologie Pédiatrique, Diabétologie Pédiatrique
 
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