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OBJECTIVE To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL−1 (Gla-300) and degludec 100 units ⋅ mL−1 (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Subjects with T1D (N = 22, 11 men, age 44.3 ± 12.4 years, disease duration 25.5 ± 11.7 years, A1C 7.07 ± 0.63% [53.7 ± 6.9 mmol ⋅ mL−1], BMI 22.5 ± 2.7 kg · m−2), naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34 ± 0.08 units ⋅ kg−1) and Deg-100 (0.26 ± 0.06 units ⋅ kg−1), dosing at 2000 h, after 3 months of optimal titration of basal (and bolus) insulin. RESULTS At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0–24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIR[0–24 h]) was equivalent for the two insulins (ratio 1.04, 90% CI 0.91–1.18). Suppression of endogenous glucose production, free fatty acids, glycerol, and β-hydroxybutyrate was 9%, 14%, 14%, and 18% greater, respectively, with Gla-300 compared with Deg-100 during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 versus Deg-100 (ratio 0.77, 90% CI 0.63–0.92). CONCLUSIONS In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects.

OBJECTIVE To prove equivalence of individual, clinically-titrated basal insulin doses of Gla-300 and Deg-100 under steady-state conditions in a single-blind, randomized, crossover study, on the glucodynamics (PD) in people with type 1 diabetes (T1DM). RESEARCH DESIGN AND METHODS T1DM subjects [N=22, 11 males M, age 44.3±12.4 years, disease duration 25.5±11.7 years, A1C 7.07±0.63% (53.7±6.9 mmol/mol), BMI 22.5±2.7 kg/m2], naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34±0.08 U.Kg-1) and Deg-100 (0.26±0.06 U.Kg-1), (dosing at 20.00h), after 3 months of optimal titration of basal (and bolus) insulin. RESULTS At the end of 3 months, Gla-300 and Deg-100 reduced slightly and similarly A1C vs baseline. Clamp average plasma glucose (0-24h) was euglycemic with both insulins. The area under curve of glucose infused [AUC-GIR(0-24h)] was equivalent for the two insulins (ratio 1.04, 90% CIs 0.91, 1.18). Suppression of endogenous glucose production, free fatty acids (FFA), glycerol and b-hydroxybutyrate was 9%, 14%, 14% and 18% greater respectively, with Gla-300 as compared with Deg-100, during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 vs Deg-100 (ratio 0.77, 90% CI 0.63, 0.92). CONCLUSIONS In T1DM, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady-state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 as compared with Deg-100 are higher, and associated with quite similar even 24h distribution of PD and anti-lipolytic effects.

Obesity leads to sarcopenia and poor physical function with aging. Evidence in animals and in middle-age humans suggests that the pituitary hormone oxytocin reduces appetite, promotes weight loss, and improves glucose tolerance while preserving lean muscle mass. We studied oxytocin’s effect on body mass index (BMI), glucose tolerance, muscle mass, and physical function in an older adult population with sarcopenic obesity. Twenty-one older (≥60 yrs), obese (30-43 kg/m2), sedentary ( In conclusion, this preliminary data suggests that oxytocin leads to improvement in whole body lean mass. Future studies are needed in a larger population to determine whether older adults with sarcopenic obesity may benefit from treatment with oxytocin to improve lean muscle mass. Further work is needed to determine whether these improvements ultimately lead to improved physical function and other parameters of healthspan with aging. Disclosure S.E. Espinoza: None. J. Lee: None. C. Wang: None. D.J. MacCarthy: None. V. Ganapathy: None. C. Pascucci: None. N. Musi: None. Funding Claude D. Pepper Older Americans Independence Centers (University of Texas Health Science Center at San Antonio; University of Texas Medical Branch Galveston); Clinical Translational Science Award Programs (University of Texas Health Science Center at San Antonio; University of Texas Medical Branch Galveston); University of Texas Health Science Center at Houston

To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mLSubjects with T1D (At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0-24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIRIn T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects.

A new class of drugs in the treatment of cystic fibrosis (CF) includes two agents: lumacaftor, which corrects CFTR channel protein, and ivacaftor, which increases CFTR channel activity. In our previous study we recruited 50 stable adults with CF and 16 of them showed growth hormone deficit (GHD): 7 patients severe and 9 patients partial GHD. We decided to re-evaluate ten patients with the GHRH + arginine test of whom only five were treated with lumacaftor/ivacaftor. All CF patients in therapy with lumacaftor/ivacaftor showed a marked improvement in GHD. Two patients moved from a severe GHD to a normal response to the GH/IGF-1 axis test, and three patients who had partial GHD moved to normal response. The pituitary gland may be damaged by CF disease and could benefit of the action of correcting drugs.

OBJECTIVES: Obesity is associated with sarcopenia in older adults, and weight loss can lead to further muscle mass loss. Oxytocin decreases with age, and animal studies suggest that oxytocin administration has trophic effects on skeletal muscle cells and reduces adiposity. We conducted a clinical trial to examine the safety and preliminary efficacy of intranasal oxytocin for older adults with sarcopenic obesity. DESIGN: A double-blind, placebo-controlled randomized controlled trial of intranasal oxytocin (24 IU 4 times per day) for 8 weeks. SETTING AND PARTICIPANTS: Twenty-one older (67.5 ± 5.4 years), obese (30–43 kg/m(2)), sedentary (

Aim: to compare head-to-head pharmacokinetics (PK), pharmacodynamics (PD), glucose fluxes and lipid metabolism of clinical doses of insulin glargine U300 (Gla-300) and degludec U100 (IDeg) in real life in T1DM. Methods: 22 subjects [(11M, age 44±12, T1DM for 26±12 years, BMI 22.5±3.2 kg/m2, A1C 7.1±0.6% (53.4±7.1 mmol/mol)] on Gla-100, naïve to Gla-300 and IDeg, were studied (24h euglycemic clamp) with individual doses of Gla-300 and IDeg (dosing at 20.0h) after 3 months of optimal titration of basal-bolus insulin (random crossover). Results (at present in 14 of the 22 subjects, PD only, data in progress): preclamp A1C was similar with Gla-300 vs. IDeg. Individual basal insulin dose was greater with Gla-300 vs. IDeg (0.35±0.09 vs. 0.27±0.06 U/kg, p Conclusions. In T1DM, PD of clinical doses of Gla-300 are equivalent to IDeg with a trend for lower within-day variability. Disclosure P. Lucidi: Other Relationship; Self; Abbott, Novo Nordisk A/S. F. Porcellati: Board Member; Self; AstraZeneca, Eli Lilly and Company, Sanofi. Consultant; Self; Medtronic. P. Candeloro: None. P. Cioli: None. C. Pascucci: None. G.B. Bolli: Advisory Panel; Self; Sanofi. Research Support; Self; A. Menarini Diagnostics, Medtronic. C. Fanelli: Advisory Panel; Self; Sanofi. Other Relationship; Self; Menarini Group.

Obese older adults often have sarcopenia with increased functional impairments. Unfortunately, conventional weight loss treatments can lead to further muscle mass loss. Increasing evidence from animal studies suggests that the pituitary hormone oxytocin has trophic effects on skeletal muscle cells and can induce weight loss. We piloted a clinical trial testing whether intranasal oxytocin would decrease adiposity without lowering muscle mass in older adults with sarcopenic obesity. Twenty-one older (≥60years), obese (30-43kg/m2), sedentary (

Background The aim of this study was to investigate the relationship between dynamic hyperinflation and daily physical activity (DPA) in adults with cystic fibrosis (CF). Methods Thirty-four clinically stable CF were studied. All patients undertook incremental cardiopulmonary exercise testing (CPET). CPET-related measurements included: oxygen uptake (V’O2), carbon dioxide production (V’CO2), ventilatory profile, work rate (W), inspiratory capacity (IC), end-expiratory lung volume (EELV). PA was assessed using the accelerometer SenseWear Pro3 Armband. Results Exercise tolerance was reduced in most of patients and the mean V’O2,peak value was 75.2% of predicted (28.5 ± 4.8 ml/min/kg). Seventy % of patients responded to CPET with dynamic hyperinflation. Higher incidence of dynamic hyperinflation was found in CF males compared to CF females (p = 0.026). Patients who developed dynamic hyperinflation during CPET had higher vigorous PA (p = 0.01) and more total energy expenditure (p = 0.006) than patients who did not. EELVΔ was related to activities requiring vigorous intensity and total energy expenditure (R = 0.46, p = 0.001; R = 0.57, p

Patients with cystic fibrosis (CF) present with signs and symptoms that overlap with those of adult growth hormone deficiency (GHD) syndrome: loss of muscle mass, bone fragility and lower stress tolerance. In literature, the prevalence of GHD in pediatric CF patients is higher than general population, but these studies have been performed on children with growth delay. To our knowledge, there are no studies on adult patients. The aim of this paper is to evaluate GH–IGF1 axis in an adult CF population. Fifty clinically stable adult patients, 30 males; age 36 ± 2 years; BMI 21.39 ± 0.22 kg/m2 and FEV1 67 ± 4% were studied. Data regarding glycometabolic status and results of pituitary, thyroid, parathyroid, gonadal and adrenal function tests were recorded. All patients underwent a GH releasing hormone (GHRH) + Arginine stimulation test to confirm a GHD. GHRH + Arginine test revealed the presence of GHD in 16 patients (32%); specifically 7 patients had a severe deficiency and 9 a partial deficiency. Adult patients with CF may show GHD. These patients should be followed over time to assess if the GHD could impact the clinical progression of CF.

Objective To report a rare case of a thyrotropin (TSH)-secreting pituitary adenoma associated with thyroid carcinoma. Methods We report the clinical history, imaging studies, and laboratory and pathologic data in a male patient affected by TSH-secreting pituitary adenoma and goiter; histologic evaluation revealed thyroid carcinoma. Results A 50-year-old man complained of years of palpitations, hypertensive crisis, and excessive nervousness that tended to progressively worsen. The basal and dynamic hematologic evaluation showed the presence of high free thyroid hormone levels with inappropriate levels of TSH. The thyroid morphologic study using Doppler ultrasonography showed a gland of increased volume with multiple nodular lesions bilaterally. The nuclear magnetic resonance of the pituitary gland described a microadenoma. A total thyroidectomy was performed followed by neurosurgical treatment of the pituitary lesion. The definitive thyroid histologic examination showed the presence of minimally invasive follicular carcinoma of 17 mm diameter. The patient firmly refused surgical removal of the pituitary adenoma. He was started on replacement therapy with thyroxine. Twelve months later, the hematologic examinations showed normal thyroid hormone levels and a TSH of 6.97 uIU/mL. The pituitary nuclear magnetic resonance showed a stable lesion without difference in size. Conclusion The clinical association between thyroid carcinoma and TSH-producing adenoma is rare, with the removal of the pituitary lesion being mandatory. Pituitary surgery, in this case, is impossible, showing that TSH-producing microadenoma could seldom have an indolent behavior.

Azilsartan medoxomil is a newly approved angiotensin-receptor blocker for the management of hypertension. It is a prodrug that is quickly hydrolyzed to the active moiety azilsartan, a potent and highly selective angiotensin-receptor blocker with estimated bioavailability of ∼ 60%. This new agent induces a potent and long-lasting antihypertensive effect. The effective therapeutic antihypertensive dosages of azilsartan medoxomil in humans vary from 40 to 80 mg/day.The authors review the results of clinical trials published in journals indexed in Medline, Scopus and Google Scholar. Primarily the authors discuss articles that analyze the safety and efficacy of azilsartan in lowering blood pressure.Clinical trials have demonstrated that azilsartan is superior to other angiotensin-receptor blockers in lowering blood pressure. However, the clinical blood pressure trials of azilsartan published to date have been mainly conducted in patients without serious comorbidities and it is not clear if azilsartan has advantages over other angiotensin-receptor blockers in the treatment of these types of hypertensive patients. In addition, it remains to be determined whether the specific pharmacologic and pharmacokinetic characteristics of azilsartan will have a clinically significant impact on long-term cardiovascular outcomes.

β-Thalassemias are a group of hereditary blood disorders characterized by abnormalities in the synthesis of the β hemoglobin (Hb) chains. This disease causes excessive storage of iron in all organs and endocrine glands. Treatment of β-thalassemia major (β-TM) consists of regular blood transfusions, iron chelation and management of secondary complications of iron overload. Endocrine abnormalities are frequently observed. In the last 25 years, the clinical picture of the disease has changed progressively thanks to improvement of treatments. Today, the majority of thalassemic patients reach adult age. The better prognosis and the longer lifespan of affected patients could be responsible for the susceptibility to other concomitant diseases which can manifest during their life. In this context, the possibility and recent literature reports about some cases of malignancy in thalassemic patients open new scenarios for oncoming years. We describe first reports of endocrine malignancies in thalassemic patients.

Background: Dysfunction of GH-IGF-I axis has been described in many patients affected by β-thalassemia major (TM), especially in children and in adolescents. Recent studies have demonstrated the necessity to evaluate adult patients affected by TM to establish the presence of this alteration which could be relevant in the pathogenesis of cardiac and bone disease, frequently present in this hematological condition. The pathogenesis of this alteration, correlated in the past with iron overload, is not yet completely understood. Aim: The aim of this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused β-thalassemic patients (TM) and to correlate the results with transfusional and chelation parameters. Subjects and methods: We performed an arginine plus GHRH stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and liver iron concentration, assessed by a superconducting quantum interference device (SQUID) susceptometer were also determined. Moreover, in each patient we evaluated the bone status by a dual-energy X-ray absorptiometry study. Results: We found the presence of GH deficit in 9 patients (32.1%). There were no significant differences between the two groups regarding the value of ferritin, liver enzymes, and liver iron concentration, assessed by SQUID. The group affected by GH deficit showed a worse bone profile. Conclusions: This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

Introduction CF adult pts complain signs and symptoms that overlap with the GHD: loss of muscle mass, physical function, occurrence of bone fragility, cardiovascular complications and lower stress tolerance. Aim To assess the prevalence of GHD in a cohort of CF adults. Methods 41 pts (30M) with a mean age of 36.9±10.7 yrs were enrolled. Exclusion criteria: liver or lung transplantation, age Results Enrolled subjects had the following characteristics: BMI:21.7±2.8 kg/m 2 FEV1: 61.9±18.3%, FEF25–75 39±23.7%, CVF 78.7±19.5%. All pts with GHD have a severe genotype: have both alleles with mutations of the first 3 classes. Evaluation of the GH-IGF1 axis revealed 34.2% with a GHD: severe in 12.2% and partial in 22%. In severe GHD, mean GH peak was 9.2±1.3 ng/ml and mean IGF1 185.4±51.5 ng/ml, in partial GHD mean GH peak 13.2±1.5, mean IGF1 208±39.7, and in pts with normal GH response, mean GH peak was 51±38.6, mean IGF1 210.6±77.5. All pts with severe GHD showed a ΔF508 mutation (60% in homozygous). We found a significant difference in GHD pts than no GHD: in BMI (23.4±2.4 vs 20.9±2.7) and fasting glucose (115.9±29.1 vs 87.7±13.7) and that these variables are inversely correlated with the GH peak (BMI: R=−0.33, p = 0.04; fasting glucose: R=−0.31, p = 0.05). Discussion To our knowledge there are no studies on the GHD in adults pts CF. You have to follow these pts over time to assess the impact of GHD on general health; should be increased cases in the study to see if this data is confirmed.