Assessment of insulin adherence in diabetic outpatients: An observational study.

OBJECTIVES: In the management of diabetic patients on insulin therapy, adherence to medication is a key element for avoiding chronic complications. The purpose of this study was to evaluate diabetic patients' ability to translate glycemic results into an appropriate insulin dose and thus, adherence to insulins. METHODS: This was an observational, retrospective, monocentric pilot study. Diabetic patients on insulin therapy being followed at the metabolic and endocrine diseases department were divided into two groups depending on their mode of glycemic control at home: capillary glycemia (Notebook group) or interstitial glycemia using the FreeStyle Libre® flash system (FSL group). Adherence was assessed based on the rate of compliance in adapting insulin doses to the prescribed protocols (depending on type of insulin, glycemic targets, and patients' characteristics) by a pharmacy resident and a senior diabetologist. Good adherence was defined as a minimum rate of 80% of conforming insulin injections for each patient. RESULTS: A total of 50 patients were included, 35 in the Notebook group and 15 in the FSL group. Two-thirds of patients were non-adherent to insulin. Dose adjustment errors mainly concerned rapid-acting insulin with 51.1% of non- conformities, 10.0% of which were due to underdosing in the Notebook group and 21.7% to overdosing in the FSL group. Hyperglycemia was predominant in both populations with a median time in range of 19.0% in the FSL group and well below recommendations (>70%). CONCLUSIONS: Despite the use of increasingly efficient, easy-to-use devices in diabetes monitoring, insulin non-adherence and glycemic imbalance are unresolved major issues. Diabetic patients require reinforced medical follow-up for optimal insulin management.

[When should we screen for gestational diabetes?]. / Quand dépister le diabète gestationnel?

AIM: Consider the arguments for screening outside the classical period of 24-28 SA. MATERIALS AND METHODS: A literature search between 1990 and 2010 was performed using the Pubmed and Cochrane database. Foreign societies guidelines were also consulted. RESULTS: Screening for gestational diabetes is recommended between 24 and 28 weeks of pregnancy, when glucose tolerance deteriorates. However, for patients with certain risk factors, the increasing prevalence of type 2 diabetes in women of childbearing age requires earlier screening. Fasting blood glucose should be measured at the first visit during pregnancy for these patients. The diagnostics threshold is the same as for patients who are not pregnant, i.e. blood glucose > 1.26 g/L. On the other hand, the interest of screening for gestational diabetes at the beginning of pregnancy in the case of certain risk factors is not supported by prospective studies. It is therefore not recommended to perform an OGTT in early pregnancy in order to diagnose gestational diabetes. The search for a gestational diabetes, regardless of screening policy recommended, has to be performed between 24 and 28 weeks gestational age. There are no reasons to consider a new search for gestational diabetes at later stages.

When should screening be performed for gestational diabetes?

AIM: To consider the arguments for screening outside the standard screening period of 24 to 28 weeks of gestation. MATERIALS AND METHODS: A search of the literature between 1990 and 2010 was performed using the PubMed® and Cochrane® databases. Recommendations from learned societies in diabetology and obstetrics & gynaecology were consulted. RESULTS: Gestational diabetes mellitus screening is classically recommended between weeks 24 and 28 of pregnancy, the period during which glucose tolerance deteriorates. However, the increasing prevalence of type 2 diabetes in women of childbearing age with risk factors requires earlier screening. Fasting blood glucose should be measured at the fi rst visit during early pregnancy for these patients. The diagnostic threshold is the same as for patients who are not pregnant, i.e. blood glucose > 1.26 g/l. However, the benefit of screening for gestational diabetes during early pregnancy for women with risk factors has not been supported by prospective studies. Therefore oral glucose tolerance testing during early pregnancy is not currently recommended for the detection of gestational diabetes. Screening for gestational diabetes, regardless of the recommended screening policy, must be performed between weeks 24 and 28 of pregnancy. There are no reasons to consider subsequent screening for gestational diabetes at a later stage.

A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism.

CONTEXT: LHX4 is a LIM homeodomain transcription factor involved in pituitary ontogenesis. Only a few heterozygous LHX4 mutations have been reported to be responsible for congenital pituitary hormone deficiency. SUBJECTS AND METHODS: A total of 136 patients with congenital hypopituitarism associated with malformations of brain structures, pituitary stalk, or posterior pituitary gland was screened for LHX4 mutations. RESULTS: Three novel allelic variants that cause predicted changes in the protein sequence of LHX4 (2.3%) were found (p.Thr99fs, p.Thr90Met, and p.Gly370Ser). On the basis of functional studies, p.Thr99fs mutation was responsible for the patients' phenotype, whereas p.Thr90Met and p.Gly370Ser were likely polymorphisms. Patients bearing the heterozygous p.Thr99fs mutation had variable phenotypes: two brothers presented somato-lactotroph and thyrotroph deficiencies, with pituitary hypoplasia and poorly developed sella turcica; the youngest brother (propositus) also had corpus callosum hypoplasia and ectopic neurohypophysis; their father only had somatotroph deficiency and delayed puberty with pituitary hyperplasia. Functional studies showed that the mutation induced a complete loss of transcriptional activity on POU1F1 promoter and a lack of DNA binding. Cotransfection of p.Thr99fs mutant and wild-type LHX4 failed to evidence any dominant negative effect, suggesting a mechanism of haploinsufficiency. We also identified prolactin and GH promoters as potential target genes of LHX4 and found that the p.Thr99fs mutant was also unable to transactivate these promoters. CONCLUSIONS: The present report describes three new exonic LHX4 allelic variants with at least one being responsible for congenital hypopituitarism. It also extends the phenotypical heterogeneity associated with LHX4 mutations, which includes variable anterior pituitary hormone deficits, as well as pituitary and extrapituitary abnormalities.

A nationwide study of granulosa cell tumors in pre- and postpubertal girls: missed diagnosis of endocrine manifestations worsens prognosis.

BACKGROUND: There are very few data on the natural history of ovarian granulosa cell tumors (OGCT) in children. The aim of this study was to determine whether early recognition and diagnosis of the initial endocrine signs could improve the outcome of these tumors. METHODS: In a nationwide study from 1990 to 2004, we analyzed the clinical, biological and pathologic data from 40 pre- and postpubertal girls presenting an OGCT. RESULTS: 1. Among the prepubertal girls (n = 29), 17 OGCTs were diagnosed on the basis of precocious pseudopuberty. None of the 17 girls had a peritoneal spread of the tumor (100% FIGO stage Ia). Diagnosis based on a tumoral or acute abdomen (12 cases) was associated with frequent intraperitoneal ruptures of the tumor (50%) and a risk of relapse (2 cases). Of the eight girls who had had a misdiagnosed precocious pseudopuberty, five had a pre- or perioperative tumoral rupture. 2. Among the postpubertal girls (n = 11), endocrine manifestations such as secondary amenorrhea or virilization had been underevaluated in three of them and the diagnosis was established from a tumoral abdomen. This clinical presentation was associated with frequent ruptures of the mass in the peritoneum (80%) and a higher risk of recurrence (30%). 3. A delayed diagnosis of OGCT despite previous endocrine signs (11 cases; 8 pre- and 3 postpubertal) was associated with a high risk of pre- or peri-operative peritoneal tumor spreading (70% FIGO stage Ic or IIc, p <0.05). The mean delay for diagnosis ranged from 3 to 11 months. CONCLUSION: This study highlights the critical role of early diagnosis of OGCT in pre- and postpubertal girls, particularly at the first seemingly banal signs of endocrine disorder. Peritoneal spread of the tumor may thereby be prevented, which improves the prognosis.

[Hypersensitivity to hypoglycemic sulfonylurea compounds. Are there cross-reactions?]. / Allergies aux sulfonylurées hypoglycémiantes. Les réactions croisées existent-elles?

We describe 5 observations of cutaneous reactions or immediate hypersensitivity with different hypoglycemic sulfonylurea: Quincke's oedema with glibornuride, three urticaria (one was followed by bronchospasm and collapsus) with glibenclamide, one bullous dermatitis with carbutamide. With special regard to cross reactions between sulfonylurea: we observe the tolerance of glipizide after glibenclamide induced urticaria, tolerance of glicalazide after glibornuride induced Quincke's oedema and eruption, tolerance of glibornuride after chlorporpamide induced urticaria and Quincke's oedema. In the literature, cross reactions between 1st generation sulfonylurea are noted, but not cross reactions between 1st and 2nd generation.

[Hypothalamic amenorrhea. Diagnostic and therapeutic values of pulsatile administration of gonadorelin]. / Aménorrhée hypothalamique. Intérêts diagnostique et thérapeutique de l'apport pulsatile de gonadoréline.

Hypothalamic amenorrhoea is characterized by deficiency of the pulsatile secretion of the gonadotropin-releasing hormone. In 18 patients with hypogonadotropic hypogonadism a precise topographical diagnosis could be made by pulsatile administration of this hormone using a portable pump, after failure of the simple gonadotropin-releasing hormone test (100 micrograms intravenously). In women wishing to become pregnant, this treatment proved valuable to induce ovulation, being remarkably effective (17 pregnancies in 20 women (85 p. 100) and 2.2 cycles/pregnancy), easy to perform, and safe, as well as less expensive and with less risk of hyperstimulation and multiple pregnancies than the conventional treatment with gonadotropins.