Philippe Oriot

One-year metabolic outcomes in patients with type 2 diabetes treated with exenatide in routine practice.

AIM The study objective was to analyze, in everyday practice, the long-term metabolic effects of exenatide (for 9 and 12 months) in patients with type 2 diabetes not responding to treatments with metformin and sulphonylurea at maximum dosages. METHODS A total of 299 type 2 diabetics were recruited from 14 centres specializing in diabetes care across Belgium. Main study endpoints were changes in HbA(1c), weight and waist circumference, and tolerability and compliance. Two patient cohorts were analyzed for effectiveness, with data available at 9 (n=90) and 12 (n=94) months of follow-up. RESULTS Significant decreases in HbA(1c) of -1.3% and -1.6% were observed in the 9- and 12-month cohorts, respectively (P<0.001). The decrease in HbA(1c) was greater in patients with higher baseline levels (P<0.001), and the response was independent of baseline weight, body mass index (BMI), age, gender and diabetes duration. A progressive reduction of weight (4.9 kg) was also observed in the two cohorts at 9 and 12 months (P<0.001), with greater weight loss in patients with higher baseline BMI (P=0.046) and in female subjects (P=0.025). Waist circumference also decreased from baseline to endpoints. A correlation was observed between reduction in HbA(1c) and weight loss (P=0.019). Side effects, mainly of gastrointestinal origin, were reported in 33% (93/284 patients in the safety cohort). The rate of hypoglycaemia was 3.5%. Treatment was discontinued in 27% of patients (n=77) mainly due to drug inefficacy (53%, n=41) or adverse events (26%, n=20), or both (8%, n=6). CONCLUSION Exenatide leads to long-term improvement of glycaemic control as well as weight loss in a majority of patients not responding to combined oral drug therapy in real-world clinical practice. However, no baseline factors predictive of response could be identified. Exenatide can be considered an effective treatment option in such patients, including those with high baseline HbA(1c) and long duration of diabetes.

Exenatide improves weight loss insulin sensitivity and β-cell function following administration to a type 2 diabetic HIV patient on antiretroviral therapy

The use of retroviral drugs in the treatment of infection by human immunodeficiency virus (HIV) is associated, especially for first generations, with side effects such as lipodystrophy, fatty liver and insulin resistance, which may trigger secondary diabetes or worsen existing diabetes. The use of Glucagon-Like Peptide-1 in obese patients with type 2 diabetes on HIV retroviral as an alternative to insulin therapy is not documented; we report the case of a 47-year-old treated with exenatide when insulin was discontinued. During the first year of treatment, exenatide, in combination with metformin and repaglinide, led to a weight loss of 14 kg and fat mass and waist circumference were respectively reduced from 31 to 25.5% and from 114 to 103 cm. Homeostatic model assessment (HOMA) was used to calculate β-cell secretion which increased from 50 to 78% and insulin sensitivity which increased from 28 to 51%, reflecting a decrease in HbA(1c) by 1.9%. Exenatide may be a new therapeutic option for HIV-infected type 2 diabetes patients undergoing retroviral therapy.

Assessing the incidence of gestational diabetes and neonatal outcomes using the IADPSG guidelines in comparison with the Carpenter and Coustan criteria in a Belgian general hospital

Abstract We have conducted a systematic universal screening for gestational diabetes mellitus (GDM) since 2008, following the criteria outlined by the International Association of Diabetes and Pregnancy Study Group (IADPSG) since 2011. However, we recently replaced the IADPSG standards with those established by the Belgian French Language Gynecologists and Obstetricians Group (GGOLFB). These new criteria indicate GDM when fasting plasma glucose (FPG) is ⩾0·92 g/l at the beginning of pregnancy or when an orally provoked hyperglycaemia test (75 g of glucose) between the twenty-fourth and twenty-eighth week results in an FPG of ⩾0·92 g/l and/or ⩾1·80 g/l after 1 hour and/or ⩾1·53 g/l after 2 hours. The goal of this retrospective study was to evaluate the incidence of GDM, neonatal outcomes, and the use of insulin therapy 21 months post-implementation of the IADPSG criteria within our centre. A total of 393 patients were diagnosed with GDM from January 2009 to December 2012. After applying the new criteria, the incidence of GDM rose significantly from 8 to 23% (P<0·0001). However, there were no significant changes in the proportion of GDM patients requiring insulin therapy (34·2% versus 34·7%) or the rate of foetal large for gestational age (11·2% versus 8·8%). In addition, the ⩾90% percentile decreased non-significantly from 96·3±0·6% to 94·3±0·70% (P = 0·057), whereas the lower quartiles and the proportion of cesarean deliveries (27·0% versus 25·6%) did not change significantly. Therefore, non-targeted screening significantly increased the incidence of GDM in our centre without significantly decreasing large for gestational age or the number of cesarean deliveries.

Prevalence and spectrum of SDHx mutations in pheochromocytoma and paraganglioma in patients from Belgium: an update

Since the early 2000s, the prevalence and spectrum of mutations in genes encoding subunits of succinate dehydrogenase (SDHx) were reported in large cohorts of patients with pheochromocytoma (PC) and paraganglioma (PGL) from most Western countries. Unfortunately, in Belgium, no equivalent work was performed thus far. Therefore, the aim of the work was to look for mutations in SDHx genes and genotype-phenotype correlations in patients with PC and/or PGL from Belgium. Screening of the coding parts of SDHx genes and deletion search were performed in all patients with PC and/or PGL referred to the -Cliniques Universitaires Saint-Luc from 05/2003 to 05/2011. Genetic screening was performed in 59 unrelated head and neck (hn)PGLs (8 fami-lial) and 53 PCs (7 extra-adrenal; 3 metastatic). In hnPGLs, 10 different SDHD mutations (3 substitutions, 5 deletions, 2 splice site mutations) were detected in 16 patients, including 7 familial cases and 9 apparently sporadic cases. In the same subset, we found 8 different SDHB mutations (5 substitutions, 1 splice site mutation, 1 deletion, 1 duplication) in 10 patients with sporadic hnPGL without evidence of malignancy. No SDHx mutation was detected in patients harboring PCs and no SDHC mutation whatsoever. In conclusion, in our multicentric database of PC-PGLs from Belgium, (i) the prevalence of SDHx mutations was high in hnPGLs (44% in the whole subset, 37% of apparently sporadic cases); (ii) in sporadic cases, the prevalence of SDHB mutations was high (20%), similar to that of SDHD (18%); and (iii) no SDHx mutation was found in a subset of mostly adrenal, benign PCs.

Fibrosis of the thyroid gland caused by an IgG4-related sclerosing disease: three years of follow-up

Abstract Immunoglobulin G4-related sclerosing disease (IgG4-RSD) represents a recently identified inflammatory disorder in which infiltration of IgG4 plasma cells causes fibrosis in organs. While IgG4-RSD is well documented in the pancreas and other organs, it is poorly characterized in the thyroid gland. We report a case of a 48-year-old female with a fibrotic thyroid mass associated with a retroperitoneal fibrosis. Diagnosed early as Riedel disease, the high serum IgG4, immunohistopathology and decreased fibrosis with corticosteroid therapy, finally confirm for the first time, the origin of IgG4-RSD fibrosis of the thyroid.

Nodular sclerosing Hodgkin's disease mimicking Riedel's invasive fibrous thyroiditis.

Riedels thyroiditis appears in the form of a hard cervical mass with rapid onset, and it is associated with extensive fibrosis that compresses nearby structures, such as the trachea and supra-aortic vessels; its diagnosis is essentially histopathological. Although its histological characteristics have been well established, there are some diagnostic pitfalls. We report here the case of a 37-year-old woman, with clinical and histopathological data suggesting Riedels disease. Fibrosis regressed after treatment with corticosteroids, relieving the compressed airways. However, in contrast with the latest knowledge on this disease, the IgG4 serum levels were consistently normal, and positron emission tomography in search of extensive fibrosis revealed an abnormal metabolic activity of the bone marrow. The final diagnosis revised by the histopathologist was that of nodular sclerosing Hodgkins lymphoma. This case allows us to review the diagnostic approach when facing a thyroid mass with extremely rapid evolution.

Outcomes of glycemic control in type 1 diabetic patients switched from basal insulin glargine 100 U/ml to glargine 300 U/ml in real life

ABSTRACT Aims: The objective of this study was to evaluate glycemic control in type 1 diabetic mellitus patients who were switched from glargine 100 U/ml (Gla-100) to glargine 300 U/ml (Gla-300) in real life practice. Methods: Glycemia based on self-monitoring capillary blood glucose, hypoglycemic events and insulin doses were considered during a two-week period before and after transition from Gla-100 to Gla-300 (period 1). Glycated hemoglobin A1c (HbA1c) levels, basal insulin doses and weight were also determined at 12 and 24 weeks after switching (period 2). Results: 116 patients treated with a basal prandial insulin scheme were included. 72% received one injection and 28% two daily injections of Gla-100 before transition to Gla-300. Glycemic control was similar during period 1 . In contrast, the number of nocturnal hypoglycemic events were significantly reduced [22.2% vs 12.2%; relative risk 0.46 (95% CI 0.30 – 0.68); p < 0.0001], as well as the number of patients with nocturnal hypoglycemia per period [30% vs 16%; relative risk 0.53 (95% CI 0.31–0.86); p < 0.01]. At the end of period 2, HbA1c decreased from 8.0 ± 1.0% (65.5 ± 10.5 mmol/mol) to 7.9 ± 1.0% (62.8 ± 10 mmol/mol) (p = 0.03). Insulin doses of Gla-300 were increased in patients treated previously with Gla-100 (+6.5%), but no weight gain was observed. Conclusion: Short term glycemic control was comparable in patients treated with basal insulin Gla-100 or Gla-300 injection. Nocturnal hypoglycemic rate declined quickly after the switch. HbA1c was reduced after six months of Gla-300 treatment versus baseline. Gla-300 doses were moderately higher (vs Gla-100), in particular, in patients treated with one Gla-100 dose before switching. Gla-300 is an alternative therapeutic option of interest.

Cerebral germinoma revealed through a polydipsic polyuric syndrome in a 10-year-old girl: case report

Abstract Cerebral germinoma is rare. Although the imaging of the germinoma is very evocative, it’s very polymorphic clinical expression is at the origin of misguided diagnosis, as illustrated in our case. We report the case of a 10-year-old girl with diabetes insipidus evolving for 12 months associated with a decrease in visual acuity. Brain MRI (Magnetic Resonance Imaging) revealed a tumor process in the suprasellar region. The stereotaxic biopsy of the tumor confirmed the diagnosis of the hypothalamic germinoma, which allowed the patient to be treated by radiotherapy and chemotherapy. The incidence of cerebral germinoma, its clinical (principally diabetes insipidus) and radiological features as well as therapeutic strategies are discussed hereby.

Gestational diabetes mellitus screening according to Carpenter–Coustan and IADPSG criteria: A 7-year follow-up of prevalence, treatment and neonatal complications at a Belgian general hospital

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mardi 7 novembre 2017

Can an electronic glycaemic notebook associated with an insulin calculator improve HbA1c in diabetic patients on a multiple insulin injections regimen? A 26-week observational real-life study.

Background: Automated insulin calculators (AICs) with carbohydrate counting (CHC) have been shown to be effective in improving glycated haemoglobin (HbA1c) levels. By contrast, use of AICs without CHC, with predetermined prandial insulin doses modified according to a correction factor and modulated as a function of glycaemia, has not yet been investigated. Methods: This comparative, retrospective, observational and non-randomized study took place over a 6-month period of routine clinical practice. It evaluated the use of Free-style InsuLinx® and Free-style Neo® Abbott Diabetes Care (AIC) in easy mode (no CHC). All patients performed a basal–prandial insulin dosing schedule, and were not educated as to how to determine carbohydrate intake. Changes in HbA1c and capillary blood glucose levels, insulin therapy, frequency of blood glucose tests and body weight were analyzed 6 months prior to inclusion (T−6), at the time of inclusion (T0) and 6 months later (T+6). From T−6 to T0 (period A), patients used a standard blood glucose meter and adjusted their insulin doses themselves, and from T0 to T+6 (period B), each patient was provided with an AIC on easy mode function. Results: Of the 230 patients, 221 were retained at the end of the study (126 type 1 diabetes mellitus (T1DM) and 95 type 2 diabetes mellitus (T2DM)). At T−6, average (±standard error of mean) HbA1c level was 8.3 ± 0.1%; T1DM: 8.5 ± 0.1% and T2DM: 8.0 ± 0.1%, respectively. At T0, the average HbA1c level was 8.4 ± 0.1% (p = 0.02); T1DM: 8.5 ± 0.1% (ns) and T2DM: 8.2 ± 0.1% (p = 0.004). At T+6, with AIC in easy mode, average HbA1c level decreased significantly to 7.7 ± 0.1% (p < 0.0001); T1DM: 8.0 ± 0.1% (p < 0.0001) and T2DM: 7.5 ± 0.1% (p < 0.0001). At T+6, in all diabetics, blood glucose monitoring frequency increased by 0.4/day (p < 0.0001). Insulin correction amounted to 14% of changes in predetermined prandial insulin doses. Conclusion: Routine clinical use of an AIC without CHC improved self-management of blood glucose and on average, decreased HbA1c levels by 0.52% in T1DM and 0.80% in T2DM after 6 months.