IDegLira fixed-ratio combination in the real world: a retrospective observational single-center Italian experience.

OBJECTIVE: An improvement of type 2 diabetes treatment is represented by the recent availability of a fixed-ratio combination of slow insulin degludec and GLP-1 RA liraglutide (IDegLira), which shows encouraging clinical trial results. This work represents a real-world evidence study to evaluate if the obtained clinical results are also confirmed in the clinical practice, in an Italian type 2 diabetes patients' population. PATIENTS AND METHODS: This retrospective observational study was conducted in the Diabetology Service of the Umbria local sanitary agency (USL Umbria 1) in Perugia. The study investigated all diabetic patients >18 years, who underwent anti-diabetic treatment with basal insulin with or without the concomitant consumption of one or more oral anti-diabetic agent (BOT group) or GLP-1 RA or rapid-acting insulin bolus (BB group), with unsatisfactory glycemic control for either hypoglycemic episodes or weight gain. The observation period was February 2018 to April 2019. RESULTS: IDegLira results to be effective in reducing HbA1c and fasting plasma glucose, especially among GLP-1 RA and BOT subgroup. In BOT group, a statistical difference was noted from the first month of treatment, also for post-prandial glycemia. Obtained results were achieved at a moderate dose of IDegLira reported during the study, which also represents a significant reduction of the amount of basal insulin in BB patients. CONCLUSIONS: Obtained results suggest that in a real-world setting, the switch to IDegLira treatment is a valid option for patients with unsatisfactory glycemic control, or who experienced side effects such as weight gain and hypoglycemia of other insulin therapies.

Early detection of insulin deprivation in continuous subcutaneous insulin infusion-treated patients with type 1 diabetes.

BACKGROUND: This study was performed to define the clinical relevance of early changes of capillary 3beta-hydroxybutyrate (3betaOHB), for detection of metabolic deterioration before occurrence of overt diabetic ketoacidosis following interruption of continuous subcutaneous insulin infusion (CSII). METHODS: An open clinical trial was performed with eight patients with type 1 diabetes on CSII therapy. After an overnight fast, at 8 a.m. (T0) CSII was interrupted for 4 h. At noon (T240) CSII was re-established, and at 4 p.m. (T480) the study was ended. Blood glucose (BG) and capillary and plasma 3betaOHB were measured at 30-min intervals, plasma insulin at 60-min intervals, and urinary ketones at 120-min intervals. RESULTS: After CSII interruption mean BG increased from 149.8+/-54.4 mg/dL at T0 to 224.8+/-56.2 mg/dL at T240 (P<0.05), and mean capillary 3betaOHB increased from 0.1+/-0.1 mmol/L at T0 to 0.9+/-0.6 mmol/L at T240 (P<0.001). The rate of increase of capillary 3betaOHB was faster and significantly more relevant than that of BG (P<0.05). The restoration of CSII produced a significant reduction of mean BG and capillary 3betaOHB (T480, 119.5+/-24 mg/dL and 0.2+/-0.2 mmol/L, respectively; P<0.05 for both vs. T240). The recovery of capillary 3betaOHB was significantly faster than that of BG (P=0.03). CONCLUSIONS: The dynamic evaluation of changes of capillary 3betaOHB levels can represent a useful support to home BG monitoring in the event of CSII interruption, providing faster information on early metabolic deterioration due to insulin deprivation and allowing preventative action for avoiding the evolution towards overt diabetic ketoacidosis. After reintroduction of insulin infusion the monitoring of the faster recovery of 3betaOHB relative to BG can provide useful information for the prevention of late hypoglycemia due to insulin overinfusion.

A dose-response study of growth hormone (GH) replacement on whole body protein and lipid kinetics in GH-deficient adults.

This study was designed to establish the lower dose of effective GH replacement therapy in severe GH-deficient (GHD) adults. Whole body protein and lipid kinetics were determined in six GHD men in the basal state (B) and after 1 week of treatment with placebo (PL) or 3.3 (GH3.3) or 2 (GH2) micrograms/kg.day recombinant human GH (rhGH). The rates of whole body proteolysis, oxidation, and synthesis were estimated by infusing [1-13C]leucine (prime, 1 mg/kg; infusion rate, 1 mg/kg.h); those of lipolysis (measured in four of the six patients) were estimated by infusing [1,1,2,3,3-D5]glycerol (prime, 1.8 mumol/kg; infusion rate, 0.06 mumol/kg.min). Serum insulin-like growth factor I (IGF-I) concentrations (picograms per mL; mean +/- SE) similarly increased from the basal level (39 +/- 7) after 3.3 (108 +/- 18) or 2 (109 +/- 24) microgram/kg.day rhGH (P < 0.001 vs. basal), whereas they did not change with placebo (41 +/- 8). Leucine Ra was unaffected by the treatments. GH3.3 reduced by 30% the rate of leucine oxidation (P = 0.0069 vs. basal) and increased by 11% nonoxidative leucine disposal (P = 0.0095 vs. basal) and by 21% glycerol Ra (0.0035 vs. basal); GH2 and placebo had no significant effect. In conclusion, 1) at least 3.3 micrograms/ kg.day rhGH are required to increase whole body protein synthesis and lipolysis in male GHD adults; 2) 2 micrograms/kg.day rhGH normalize serum IGF-I concentrations, but do not modify protein and lipid metabolism; and 3) a normal serum IGF-I concentration does not guarantee that rhGH treatment is also effective on intermediate metabolism.

Efficacy and safety of 48 weeks of treatment with octreotide LAR in newly diagnosed acromegalic patients with macroadenomas: an open-label, multicenter, non-comparative study.

The aim of the present multicentric, open-label, non-comparative study was to evaluate the role of octreotide long-acting repeatable (LAR) as primary therapy for the treatment of GH-secreting pituitary macroadenomas. The patients received octreotide LAR 20 mg every 4 weeks for 12 weeks; afterwards the dose was confirmed or adjusted at 30 mg every 4 weeks, for the remaining 12 weeks, for responder or non-responder patients, respectively. Responder patients continued the study until 48 weeks. Twenty-one naive active acromegalic patients were enrolled. In all patients, GH profile, IGF-I levels and magnetic resonance imaging (MRI) were evaluated at baseline and during treatment. The ability of octreotide LAR to decrease mean GH < 2.5 microg/I and/or normalize IGF-I levels, adjusted for age and gender, was defined respectively as total or partial success. Total success was achieved in 5/21 (23.8%), 6/20 (30%) and 4/14 (28.6%) patients after 12, 24 and 48 weeks; partial success in 7/21 (33.3%), 9/20 (45%) and 9/14 (64%) patients at 12, 24 and 48 weeks according to GH levels, while according to IGF-I levels in 7/21 (33.3%), 7/20 (35%) and 5/14 (35.7%) patients at 12, 24 and 48 week. Tumor size was notably decreased after treatment with octreotide LAR: in 16 macroadenoma patients completing the study, the tumor sizes were 1609 +/- 1288, 818 +/- 616 (49.1 +/- 23.7%) and 688 +/- 567 mm3 (54.6 +/- 24.4%) at baseline, 24 and 48 weeks. This study shows that octreotide LAR is effective in suppressing GH/IGF-I secretion and inducing tumor shrinkage in GH-secreting macroadenomas in a 48-week treatment. Octreotide LAR could be used as primary therapy in patients harbouring large pituitary tumors, who are less likely to be cured by neurosurgery.

Pure Leydig cell tumour (hilus cell) of the ovary: a rare cause of virilization after menopause.

A 58-year-old postmenopausal woman with high plasma testosterone levels and virilization, as demonstrated by hirsutism and alopecia, is presented. Urinary 17-ketosteroids and 17-hydroxycorticosteroids as well as the computed axial tomography scan of the adrenal glands were normal. Although no pelvic mass was detected by sonography or pelvic examination, the patient was found to have small pure Leydig cell tumour of the left ovary. Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the patient had regression of the hirsutism, and the plasma testosterone dropped to normal level.