Effects of GH and Lirglutide on AgRP

Inclusion Criteria

HEALTHY SUBJECTS

• 40 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 subjects
• No prescription medication or other drug use
• On 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 contraception
• Current non-smoker

GH DEFICIENT SUBJECTS

• 24 patients with isolated GH deficiency:12 males, 12 females.
• Ages 18-45 years
• Diagnosis of isolated GH deficiency based on accepted, BMI-appropriate GH stimulation test cut offs within 12 months of enrollment
• No prior GH therapy within 12 months of study enrollment
• Normal thyroid, adrenal and gonadal function documented by accepted stimulation test and clinical criteria
• Premenopausal women: use of nonhormonal method of contraception

Exclusion Criteria

HEALTHY SUBJECTS

• History of malignancy, diabetes, thyroid cancer or pancreatitis
• Recent dieting, weight change >5%, pregnancy or lactation or heavy exercise
• Use of glucocorticoids, hormonal supplements or medications that could affect GH or IGF-1 or for weight loss within 6 months of enrollment

GH DEFICIENT SUBJECTS

• DM requiring medication
• HbA1C > 7.5
• Malignancy, pancreatitis or thyroid cancer history.
• Deficiency of other pituitary hormones, liver or renal disease
• Use of glucocorticoids, hormonal supplements or medications that could affect GH or IGF-1 or for weight loss within 6 months of enrollment

• Recent dieting, weight change > 5%, pregnancy, lactation or heavy exercise 6. Current smoking