Effects of GH and Lirglutide on AgRP

This is a randomized, placebo-controlled, cross-over study with 4 arms. Healthy and GH deficient adults ages 18-45 years will be studied. Arms will consist of 21-day treatment periods and be separated by 8-week washout periods. Subjects will receive, in random order: i) GH alone, ii) GH with liraglutide, iii) liraglutide alone and iv) placebo. Each phase of the study will consist of a 7-day baseline period including 2 days of testing and 21 days on therapy with visits on days 2, 7, 14 and 21. Testing before, during and at the completion of each arm will include blood sampling and assessments of insulin resistance, energy expenditure and body composition.

Inclusion Criteria:HEALTHY SUBJECTS40 healthy subjects, 20 male, 20 female, ages 18-45 yr.: (i) 20 (10 male, 10 female) who are overweight/Class 1 Obese (BMI 25-34.9) with abdominal fat accumulation (central adiposity) defined by waist circumference (WC) ≥ 102 cm in men, ≥ 88 cm in women, except in East/South Asians for whom the criteria will be WC ≥ 90 men and ≥ 80 women; (ii) 20 (10 male,10 female) who are lean (BMI 19-24.9) and not meeting these WC criteria.No medical conditions except being overweight/obese in half of subjectsNo prescription medication or other drug useOn screening testing: BP<140/<90 mmHg, HbA1c<5.7%, FPG<100 mg/dL, normal IGF-1 and TSH levels.Premenopausal women: use of nonhormonal method of contraceptionCurrent non-smokerGH DEFICIENT SUBJECTS24 patients with isolated GH deficiency:12 males, 12 females.Ages 18-45 yearsDiagnosis of isolated GH deficiency based on accepted, BMI-appropriate GH stimulation test cut offs within 12 months of enrollmentNo prior GH therapy within 12 months of study enrollmentNormal thyroid, adrenal and gonadal function documented by accepted stimulation test and clinical criteriaPremenopausal women: use of nonhormonal method of contraceptionExclusion Criteria:HEALTHY SUBJECTSHistory of malignancy, diabetes, thyroid cancer or pancreatitisRecent dieting, weight change >5%, pregnancy or lactation or heavy exerciseUse of glucocorticoids, hormonal supplements or medications that could affect GH or IGF-1 or for weight loss within 6 months of enrollmentGH DEFICIENT SUBJECTSDM requiring medicationHbA1C > 7.5Malignancy, pancreatitis or thyroid cancer history.Deficiency of other pituitary hormones, liver or renal diseaseUse of glucocorticoids, hormonal supplements or medications that could affect GH or IGF-1 or for weight loss within 6 months of enrollment5. Recent dieting, weight change > 5%, pregnancy, lactation or heavy exercise 6. Current smoking