Effect of Intranasal Insulin on LH Concentrations in Man

Phase 1

Completed

Brief Summary: Over the last few years, studies have shown that men with type 2 diabetes sometimes develop a condition called hypogonadotrophic hypogonadism (HH). People with this condition produce little or no sex hormones. Obesity and metabolic syndrome are also associated with HH. Research suggests that insulin in the brain may benefit the glands that release these hormones. During this study, subjects will spray a small amount of insulin into their nose.This will increase insulin concentrations in the brain. The purpose of this study is to find out the effect of one dose of intranasal insulin on release of LH (a sex hormone) in obese diabetic men with HH.

Detailed Description: Studies over the last few years have clearly established that at least 25% of men with type 2 diabetes have subnormal free testosterone (T) concentrations in association with inappropriately low leutinizing hormone (LH) and FSH (follicle stimulating hormone) concentrations. These patients thus suffer from hypogonadotrophic hypogonadism (HH). Obesity and metabolic syndrome are also associated with HH. Animal studies and in vitro data have shown that insulin action and insulin responsiveness in the brain are necessary for the maintenance of the functional integrity of the hypothalamo-hypophyseal-gonadal axis. Insulin concentrations can be increased in the brain by delivering insulin intranasally with vianase device. The aim of this project is to study the effect of one dose of intranasal insulin on release of LH in obese diabetic men with HH. 15 obese men with type 2 diabetes and low free T along with normal LH concentrations will be recruited for the study. The study will be carried out at the clinical center of Texas Tech (Odessa campus). There will be two study visits, each comprising of blood tests every 15 minutes over 6 hours. 40 IU of intranasal insulin or saline will be given after a baseline period of blood sampling of 2 hours. Student's t-test will be used to compare the change in LH concentrations after intranasal saline or insulin.

Recruitment & Eligibility

Inclusion Criteria

Males age 18 to 75 years
Obesity (BMI ≥30 kg/m2)
Type 2 diabetes
Hypogonadotropic hypogonadism defined as calculated free testosterone concentrations below 7 ng/dl along with normal or low LH concentrations

Exclusion Criteria

HbA1c>8.5%
Use of preprandial insulin therapy
Use of testosterone currently or in the past 4 months
Use of over the counter health supplements which contain androgens
Use of corticosteroids or narcotics in the past 3 months
Coronary event or procedure(myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous twelve weeks
Type I Diabetes
Currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious or inflammatory condition
Hepatic disease (transaminase > 3 times normal) or cirrhosis
Renal impairment (defined as glomerular filtration rate<30)
HIV or Hepatitis C positive status
Any other life-threatening, non-cardiac disease
History of untreated severe obstructive sleep apnea(defined as apnea-hypopnea index ≥30)
currently suffering from symptomatic depression, with or without treatment
Use of an investigational agent or therapeutic regimen within 30 days of study
Participation in any other concurrent clinical trial
Pituitary tumor/damage/ other trophic hormone deficiency

Arm && Interventions

Group	Intervention	Description
control	placebo (intranasal saline)	All patient will receive insulin at one visit and saline at another visit
diabetes	intranasal insulin	All patient will receive insulin at one visit and saline at another visit
diabetes	placebo (intranasal saline)	All patient will receive insulin at one visit and saline at another visit
control	intranasal insulin	All patient will receive insulin at one visit and saline at another visit

Primary Outcome Measures

Name	Time	Method
LH	4 hours	Luteinizing hormone (LH) concentrations after intranasal insulin as compared to placebo (intranasal saline). This endpoint was measured in both arms

Secondary Outcome Measures