Publications by authors named "Anne Rod"

10 Publications

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Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series.

J Diabetes 2020 Jan 10;12(1):48-57. Epub 2019 Jul 10.

Department of Endocrinology and Diabetology, Caen University Hospital, Caen, France.

Background: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics.

Methods: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology.

Results: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies.

Conclusions: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.
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January 2020

Joint impact of gestational diabetes and obesity on perinatal outcomes.

J Gynecol Obstet Hum Reprod 2018 Nov 25;47(9):469-476. Epub 2018 Aug 25.

CHU de Caen, Service de Gynécologie Obstétrique et Médecine de la Reproduction, Cote de Nacre, France.

Objective: Gestational diabetes and obesity are independent risk factors for obstetric and neonatal complications. The purpose of our study was to evaluate the impact of their association on pregnancy outcomes.

Material And Methods: Monocentric retrospective cohort study including patients with obesity and gestational diabetes (GDM), those with GD without obesity, and those with obesity without GDM, who gave birth between 01 January 2012 and 31 December 2014, and whose GDM was exclusively monitored at our centre. The diagnostic criteria and management modalities of GDM were based on the 2010 CNGOF (Collège National des Gynécologues et Obstétriciens Français [French national college of obstetricians and gynaecologists]) Clinical Practice Recommendations. Obesity was defined as having a body mass index ≥30 Kg/m.

Results: A total of 1,484 patients were included, 259 with GDM and obesity, 549 with GDM without obesity, 676 with obesity without GDM. In the GDM + obesity group, GDM was treated earlier and was more uncontrolled and more often treated with insulin in relation to non-obese women with GDM. These patients also presented a higher risk of caesarean section (OR 2.92, CI 95% 2.04-4.16, P<0.001), preeclampsia (OR 4.62, CI 95% 1.31-16.32, P=0.017), maternal morbidity (OR 2.05, CI 95% 1.37-3.04, P<0.001) and large foetus for gestational age (OR 1.91, CI 95% 1.26-2.88, P=0.002). Obesity alone was a risk factor in its own right for preeclampsia (OR 7.32, CI 95% 2.50-21.45, P<0.001) and macrosomia (OR 3.55, IC 95% 2.24-5.62, P<0.001), compared to non-obese patients with GDM. Uncontrolled GDM was associated independently of obesity with the risk of induced labour and large foetus for gestational age.

Conclusion: Obesity on its own is a risk factor for obstetric complications and its association with GDM strongly impacts on pregnancy outcomes.
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November 2018

Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial.

JAMA 2018 05;319(17):1773-1780

Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, Université Paris-Sud, Université de Versailles Saint-Quentin-en-Yvelines, INSERM, Villejuif, France.

Importance: Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes.

Objective: To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes.

Design, Settings, And Participants: The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation.

Interventions: Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations.

Main Outcomes And Measures: The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval.

Results: Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19).

Conclusion And Relevance: This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment.

Trial Registration: Identifier: NCT01731431.
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May 2018

Sustained Efficacy of Insulin Pump Therapy in Type 2 Diabetes: 9-Year Follow-up in a Cohort of 161 Patients.

Diabetes Care 2016 06 8;39(6):e74-5. Epub 2016 Apr 8.

Department of Endocrinology, University of Caen, Côte de Nacre Regional Hospital Center, Caen, France

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June 2016

Potential Insulin Underdelivery from Prefilled and Reusable Insulin Pens in Cases of Premature Needle Withdrawal: A Laboratory Evaluation.

Diabetes Technol Ther 2015 Oct 5;17(10):712-6. Epub 2015 Jun 5.

Diabetes Care Unit, University Hospital of Caen , Caen, France .

Background: Devices for the treatment of diabetes are not always used as recommended in good practice. Our aim was to evaluate potential insulin underdelivery in cases of premature needle withdrawal after injection with insulin pens, which is a commonly observed misuse, especially in young type 1 diabetes patients.

Materials And Methods: Potential insulin underdelivery was evaluated using five prefilled insulin pens (lispro Kwikpen(®) [Eli Lilly, Indianapolis, IN], aspart Flexpen(®) [Novo Nordisk, Bagsvaerd, Denmark], glulisine Solostar(®) [Sanofi, Paris, France], detemir Flexpen(®) [Novo Nordisk], and glargine Solostar(®) [Sanofi]) and three reusable insulin pens (Humapen(®) Luxura HD with lispro cartridge [Eli Lilly], Novopen(®) Echo with aspart and detemir cartridge [Novo Nordisk], and JuniorSTAR(®) with glulisine and glargine cartridge [Sanofi]) in a laboratory. For each pen and insulin, we simulated premature needle withdrawal 2 and 3 s after an insulin injection of 5 and 10 units, respectively.

Results: With prefilled pens, mean potential insulin underdelivery was 0.43±0.30 and 0.44±0.32 units after injection of 5 and 10 units, respectively. With reusable pens, mean potential insulin underdelivery was lower (0.29±0.13 and 0.29±0.12 units after injection of 5 and 10 units, respectively; P<0.001). The results were heterogeneous across pens, ranging from 2.6%/1.6% to 20.2%/8.6% of the selected insulin dose for prefilled/reusable pens, respectively (P<0.001).

Conclusions: Potential insulin underdelivery varies across prefilled and reusable insulin pens but may represent up to one-fifth of the total injected dose. Clinicians should be aware of the potential consequences of premature needle withdrawal and should reinforce insulin injection education.
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October 2015

Neuromuscular electrostimulation and insulin sensitivity in patients with type 2 diabetes: the ELECTRODIAB pilot study.

Acta Diabetol 2015 Apr 9;52(2):285-91. Epub 2014 Aug 9.

Diabetes Care Unit, University Hospital of Caen, Caen, France,

Aim: Physical activity (PA) improves insulin sensitivity and is particularly important for type 2 diabetes (T2D) management; however, patient adherence is poor. Neuromuscular electrostimulation (NMES) is widely used for rehabilitation issues, but the metabolic impact of provoked involuntary muscular contractions has never been investigated.

Materials And Methods: ELECTRODIAB is a prospective, bi-centric, and 4-week-long pilot study that enrolled 18 patients with T2D who did not require insulin treatment. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp before and after (1) a single NMES session and (2) a week of daily NMES training. Energy expenditure (EE) at baseline and during NMES was evaluated by indirect calorimetry. Dietary and background PA were monitored to avoid bias.

Results: After a single session (T1) or a week (T2) of NMES training, insulin sensitivity (M value) increased by 9.3 ± 38.2 % (ns) and 24.9 ± 35.8 % (p = 0.009), respectively, compared with the baseline (T0). Insulin sensitivity increased up to 46.2 ± 33.8 % (p = 0.002) at T2 in the more insulin-resistant subjects (baseline M value ≤4 mg/Kg/min, n = 10). The NMES session-generated EE was 1.42 ± 9.27 kcal/h, which was not significantly increased from the baseline.

Conclusions: Insulin sensitivity was significantly improved in patients with T2D after 1 week of daily NMES training, with very low EE. NMES could be an alternative to conventional PA, but the putative mechanisms of action must still be investigated.
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April 2015

Cross-sectional survey and retrospective analysis of a large cohort of adults with type 1 diabetes with long-term continuous subcutaneous insulin infusion treatment.

J Diabetes Sci Technol 2014 Sep 27;8(5):1005-10. Epub 2014 May 27.

Endocrinology Department, Caen University Hospital, Caen, France University of Caen (UNICAEN), Caen, France.

Background. Continuous subcutaneous insulin infusion (CSII) is an established modality for intensive insulin treatment of type 1 diabetes (T1D), but long-term data concerning satisfaction, CSII function use, safety, and efficacy in real-life conditions are scarce. Methods. We analyzed a cohort of adult patients with T1D treated with CSII for more than 1 year in a single diabetes center. We performed a cross-sectional survey in 2010 (tolerance/satisfaction and behavior forms) and a retrospective analysis of medical records (including HbA1c level, hospitalization, and catheter infections). The primary objective was to assess long-term tolerance/satisfaction, and secondary objectives were safety and efficacy. Results. There were 295 patients analyzed. After a median duration of CSII use of 5 years, overall satisfaction was high for about 90% of patients. Mean CSII-related discomfort scores were low for work, recreation, and sleep and moderate for sport and sexual activity (2.5 ± 1.9, 2.6 ± 1.8, 2.6 ± 2.1, 3.4 ± 2.3, and 4.0 ± 2.9 of 10, respectively). Despite a high level of diabetes education, only one third of patients were using advanced CSII functions. During long-term follow-up, the safety of CSII treatment was good; the hospitalization rate was 0.18 patients/year, and catheter infections were scarce. The HbA1c level dropped about -0.5% independently from CSII duration (P < .05). Conclusions. In this adult cohort, satisfaction and tolerance, together with safety, of CSII were maintained at long-term follow up. The sole basic functions of CSII were currently used by patients. A 0.5% decrease in the HbA1c level was maintained during the study period.
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September 2014

Autonomy of patients with type 2 diabetes with an insulin pump device: is it predictable?

J Diabetes Sci Technol 2014 Jul 30;8(4):760-5. Epub 2014 Apr 30.

Endocrinology and Diabetes Department, CHU Côte de Nacre, Caen Cedex, France.

Background: Insulin pump therapy may be offered to patients with type 2 diabetes that is not controlled by multiple daily injections. Patients with type 2 diabetes may suffer from unrecognized cognitive disabilities, which may compromise the use of a pump device.

Methods: To predict patient autonomy, we evaluated 39 patients with type 2 diabetes from our database (n = 143) after continuous subcutaneous insulin infusion (CSII) initiation using (1) an autonomy questionnaire evaluating the patient's cognitive and operative capacities for CSII utilization, (2) the Montreal Cognitive Assessment (MOCA) for the detection of mild cognitive disabilities, (3) the Hospital Anxiety and Depression Scale (HADS) for the detection of anxiety and depression, and (4) the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Patients were selected to constitute 3 groups matched for age, with different degrees of autonomy at discharge after the initial training program: complete (n = 13), partial (n = 13), or no autonomy (n = 13).

Results: The satisfaction level with the pump device was high. At the last follow-up visit, only 23% of patients did not reach complete autonomy. The autonomy score correlated fairly with the MOCA score (R = 0.771, P < .001). A receiver operating characteristic (ROC) analysis showed that at a cut-off score of 24, the MOCA identified autonomous versus dependent patients at long-term follow-up (area under the ROC curve [AUC], 0.893; sensitivity, 81%; specificity, 81%). The HADS correlated negatively with the autonomy score, and the sociocultural level also influenced autonomy with pump utilization.

Conclusion: Patients with type 2 diabetes with partial autonomy at discharge may progress to complete autonomy. The MOCA and HADS may help predict a patient's ability to manage with a pump device.
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July 2014

Efficacy of continuous subcutaneous insulin infusion in type 2 diabetes mellitus: a survey on a cohort of 102 patients with prolonged follow-up.

Diabetes Technol Ther 2010 Dec;12(12):931-6

Department of Medicine, Department of Endocrinology, Caen University Hospital, Caen, France.

Objectives: We evaluated the long-term efficacy of continuous subcutaneous insulin infusion (CSII) for treating type 2 diabetes patients uncontrolled by multiple daily injections.

Research Design And Methods: All 102 type 2 diabetes patients who began insulin pump therapy at Caen University Hospital (Caen, France) between January 1998 and August 2008 were included in a retrospective observational study. Ninety-three percent of the patients were previously treated by insulin with a mean duration of 5.6 years.

Results: The median duration of follow-up with CSII was 24 months. A1c glycated hemoglobin (HbA1c) improved from baseline (9.3 ± 1.8%) to the 1-year evaluation (7.8 ± 1.4%) (P < 0.001). The magnitude of HbA1c improvement was highly dependent on (1) pretreatment HbA1c level, (2) degree of patient's autonomy, and (3) previous antidiabetes treatment. HbA1c decreased by 0.9 ± 1.6% (P = 0.002) in the group previously treated by a basal-bolus regimen. HbA1c decrease was maintained at follow-up until 6 years (P < 0.05). Mean body weight gain was 3.9 ± 8.6 kg at 1 year (P < 0.001) and remained stable at follow-up. No significant change in insulin requirement was observed.

Conclusions: The use of CSII in patients with type 2 diabetes is safe and effective for improving glycemic control, particularly in those patients with baseline HbA1c above 8%. Such beneficial effect of CSII may persist until 6-year follow-up, suggesting the durability of CSII efficacy in our study population.
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December 2010

Cushing's syndrome associated with a nested stromal epithelial tumor of the liver: hormonal, immunohistochemical, and molecular studies.

Eur J Endocrinol 2009 Nov 18;161(5):805-10. Epub 2009 Aug 18.

Unité Fonctionnelle d'Endocrinologie et Maladies Métaboliques, Department of Medicine, CHU Côte de Nacre, 14033 Caen Cedex, France.

Context: Ectopic ACTH syndrome (EAS) is principally associated with aggressive malignant tumors but also with neuroendocrine tumors of good prognosis. Recently, rare nonhepatocytic nested stromal and epithelial tumors (NSET) were characterized by their possible association with Cushing's syndrome of which biochemical and physiopathological features were still incompletely studied.

Objective: To describe the clinical and hormonal characteristics of an EAS originating from a liver NSET and further understand the mechanism of cortisol overproduction.

Design And Setting: This is a clinical case report from the Endocrinology Department of Caen University Hospital, France.

Patient And Intervention: A 17-year-old female patient was found to have a large liver NSET with mild Cushingoid clinical features and intense biological hypercortisolism but moderate ACTH secretion. Resection of the tumor was curative with a 30-month follow-up.

Results: The epithelial component of the tumor coexpressed ACTH mildly, corticotropin-releasing hormone (CRH) strongly, and 11beta-hydroxysteroid dehydrogenase at a level comparable with normal human hepatocytes.

Conclusions: Liver NSET is a new cause of EAS, which may evoke hypercortisolism by multiple biochemical pathways.
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November 2009