Initiation of the Fixed Combination IDegLira in Patients with Type 2 Diabetes on Prior Injectable Therapy: Insights from the EASY French Real-World Study.

INTRODUCTION: Combining basal insulin (BI) with glucagon-like peptide-1 receptor agonist (GLP-1RA) is recognized as a relevant option to optimize glucose control in type 2 diabetes (T2D). The EASY real-world study aimed to evaluate the modalities of initiation and the effectiveness of the insulin Degludec plus Liraglutide (IDegLira) fixed-ratio combination in the French health care system. METHODS: A retrospective analysis included all patients with T2D and prior injectable therapy (GLP1-RA and/or insulin) who started treatment with IDegLira from September 2016 to December 2017 in 11 French diabetes centers. Baseline characteristics, reasons for IDegLira initiation, and modes of implementation were collected from the medical records. Changes in HbA1c and body weight were determined in patients with available follow-up data (nearest 6-month visit). RESULTS: IDegLira was initiated in 629 patients previously treated with GLP-1RA alone (11.6%), insulin alone (31.5% including 16.5% with BI and 14.9% with multiple daily injections [MDI]) or a free combination of GLP-1RA and insulin (56.9% including 44.8% with BI and 12.1% with MDI), associated or not with oral agents. IDegLira starting dose (mean of 29 ± 11 dose steps) most often exceeded the recommended dose, and was significantly correlated with prior BI but not GLP-1RA dosage. At initiation, mean age, body mass index (BMI) and HbA1c were 60.1 ± 10.2 years, 33.4 ± 6.2 kg/m2 and 8.8 ± 1.7%, respectively. In 461 patients with available follow-up (median 178 days), HbA1c decreased in all subgroups submitted to treatment intensification (- 1.7 ± 1.8% [p < 0.0001], - 1.2 ± 1.8% [p < 0.001] and - 0.8 ± 1.8% [p = 0.0026] in patients with prior GLP-1RA, BI or MDI therapy, respectively) but also in those switching from BI and GLP-1RA free combination (- 0.2 ± 0.9%, p = 0.0419). Significant body weight gain occurred in patients previously treated with GLP-1RA alone (+ 1.5 ± 5.8 kg, p = 0.0572) or combined to BI (+ 1.0 ± 3.1 kg, p < 0.0001) while those on BI (- 1.4 ± 4.6 kg, p = 0.0139) or MDI (- 1.4 ± 5.0 kg, p = 0.0484) experienced weight loss. CONCLUSIONS: While providing new information on the use of IDegLira in the French healthcare system, these data confirm the effectiveness of this fixed-ratio combination in the management of T2D.

Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp.

AIMS: Apelin is a recently identified adipokine known to improve glucose tolerance and insulin sensitivity in murine models. This study was dedicated to the proof of concept that apelin administration also enhances insulin sensitivity in humans. MATERIALS AND METHODS: Healthy overweight men were enrolled in this randomized, double-blind, placebo-controlled, cross-over study that successively considered the efficacy and the tolerance of 2 doses of (pyr1)-Apelin-13. A first group of subjects received 9 nmol/kg (n = 8) of (pyr1)-Apelin-13 and, after examination of safety data, a second group received 30 nmol/kg (n = 8). Each volunteer underwent 2 hyperinsulinaemic-euglycaemic clamps where the basal level of glucose infusion rate (GIR) was measured from the 90th to the 120th minute (level 1). Continuous intravenous administration of apelin or placebo was ongoing for 2 hours and GIR was finally evaluated from the 210th to the 240th minute (level 2). Primary evaluation endpoint was the difference in GIR between level 2 and level 1 (ΔGIR). RESULTS: A slight increase in ΔGIR was observed with the low apelin dose (0.65 ± 0.71 mg/kg/min, P = .055) whereas the highest dose significantly improved insulin sensitivity (0.82 ± 0.71 mg/kg/min, P = .033). Cardiovascular monitoring and safety reports did not reveal any side effect of apelin administration. CONCLUSION: As the first demonstration of the insulin-sensitizing action of apelin in humans, alongside numerous studies in rodents, this trial confirms that the apelin/APJ pathway should be considered as a new target to design alternative therapeutic strategies to control insulin resistance in type 2 diabetic patients.

Glucose Profiles in Pregnant Women After a Gastric Bypass : Findings from Continuous Glucose Monitoring.

BACKGROUND: The diagnosis of gestational diabetes mellitus (GDM) usually requires an oral glucose tolerance test, but this procedure seems inappropriate after gastric bypass surgery (Roux-en-Y gastric bypass (RYGB)) due to specific altered glycemic responses. We aimed here at describing continuous glucose monitoring (CGM) profile of pregnant women after RYGB. METHODS: CGM was performed in 35 consecutive pregnant women after RYGB at 26.2 ± 5 weeks of gestation. RESULTS: After RYGB, pregnant women display high postprandial interstitial glucose (IG) peaks and low IG before and 2 h after meals. The postprandial IG peak is reached early, within 54 ± 9 min. The maximum IG values reach 205 mg/dl, and the percentage of time above 140 mg/dl (6.6 ± 7 %) is similar to what is described in GDM women. CONCLUSIONS: This study is the first to describe CGM profile in pregnant women after RYGB. CGM features are similar to those of non-pregnant post-RYGB patients, characterized by wide and rapid changes in postprandial IG, and high exposure to hyperglycemia. The exposure to hyperglycemia is similar to what is reported in GDM although the time to postprandial peak is shorter. CGM could be an additional useful approach to screen for glucose intolerance during pregnancy after RYGB.

Effect of Nutritional Intervention on Food Choices of French Students in Middle School Cafeterias, Using an Interactive Educational Software Program (Nutri-Advice).

OBJECTIVE: To evaluate the impact of interactive Nutri-Advice kiosks on children's nutritional skills and their ability to apply it to food choices in a middle school cafeteria menu (food choice competencies). DESIGN: Quasi-experimental design; pre/post-test. SETTING: Freestanding interactive computer terminals (kiosks) were installed in three middle schools in Toulouse, France. PARTICIPANTS: A total of 580 children were enrolled into the study (mean age, 13 ± 1 years). INTERVENTION: Each child's physiological profile was stored in a personal barcode card. During 1 school year, once a day, each child could access the kiosk with this card, trying to find the most balanced meal according to his or her profile and the food available on the cafeteria menu. MAIN OUTCOME MEASURES: Children's food choice competency changes and body mass index z-score were evaluated. ANALYSIS: Significance of change in food choice competencies (postintervention vs baseline) was examined using paired t test. RESULTS: Across the study, children chose significantly less cheese and pastry or desserts, and significantly more starchy food and dairy, and tended to choose fruits and vegetables more often. Body mass index z-score decreased significantly during the period. CONCLUSIONS AND IMPLICATIONS: Personalized nutrition counseling through an interactive device has the potential to improve the food choice competencies of children.

French database of children and adolescents with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare multisystem genetic disease leading to severe complications mainly related to obesity. We strongly lack information on the natural history of this complex disease and on what factors are involved in its evolution and its outcome. One of the objectives of the French reference centre for Prader-Willi syndrome set-up in 2004 was to set-up a database in order to make the inventory of Prader-Willi syndrome cases and initiate a national cohort study in the area covered by the centre. DESCRIPTION: the database includes medical data of children and adolescents with Prader-Willi syndrome, details about their management, socio-demographic data on their families, psychological data and quality of life of the parents. The tools and organisation used to ensure data collection and data quality in respect of good clinical practice procedures are discussed, and main characteristics of our Prader-Willi population at inclusion are presented. CONCLUSION: this database covering all the aspects of PWS clinical, psychological and social profiles, including familial psychological and quality of life will be a powerful tool for retrospective studies concerning this complex and multi factorial disease and could be a basis for the design of future prospective multicentric studies. The complete database and the Stata.do files are available to any researcher wishing to use them for non-commercial purposes and can be provided upon request to the corresponding author.

Impaired quality of life of patients with acromegaly: control of GH/IGF-I excess improves psychological subscale appearance.

INTRODUCTION: Acromegaly, a chronic disease caused by GH/IGF-I excess, has a major impact on quality of life (QoL). OBJECTIVE: To evaluate QoL of acromegalic patients in relation to control status of the disease. DESIGN AND METHODS: Single center observational study including 93 patients with acromegaly recruited to complete QoL questionnaire (AcroQol). QoL was evaluated at least 3 months after surgery and/or medical treatment. Patients were divided into two groups: controlled (I) and uncontrolled (II) according to the latest consensus acromegaly 'control' criteria and further subdivided into four subgroups according to the previous pituitary adenoma surgery (Ib and IIb) or without surgery (Ia and IIa). RESULTS: Mean GH (0.81+/-0.47 ng/ml) and IGF-I (195+/-71 ng/ml) values in group I were significantly lower than in group II (GH, 7.01+/-12.05 ng/ml and IGF-I, 513+/-316 ng/ml; P<0.001). There was no difference in total AcroQol score, physical, or psychological scales between groups I and II. However, when adjusted to age and disease duration since diagnosis, patients of group I (63+/-20%) showed an improved psychological subscale appearance than those of group II (58+/-17%; P=0.035). In group II, IGF-I level was lower after surgery (IIa=588+/-353, IIb=410+/-225 ng/ml; P<0.038), and psychological subscale appearance was significantly better in subgroup IIb (64.9+/-18.1%) than in subgroup IIa who had medical treatment (53.9+/-14.3%; P=0.009). CONCLUSION: QoL is severely impaired in acromegalic patients. Control of GH/IGF-I excess by surgery or medical treatment seems to have a positive impact on psychological subscale appearance.