RESEARCH PROJECT
Managing Adult
Onset Diabetes
with Testosterone

Researcher:

Edward M. Lichten, M.D., F.A.C.S.
189 Townsend Street- second floor
Birmingham, MI 48009

248.593.9999

Project Number:609-97 Providence Hospital, Southfield, Michigan


Overview:  In this pilot research study performed more than 10 years ago with James Sowers, M.D., professor and chairman of Endocrinology and Metabolism at Wayne State University College of Medicine, Lichten established that:

1. All diabetic men are hypogonadal (low in testosterone) either as an absolute measurement of total testosterone less than 450 ng/dl or a Free Androgen Index less than 0.4 calculated by the formula of DC Anderson [Science 1972]

2. Testosterone replacement with either 450-750 mg of testosterone as pellets or divided up into weekly injections, proved safe and effective in reducing both insulin and hypoglycemic medications measured concombinantly as lower hemoglobin A1c.

3. Miscellaneous observations included: lowering of total cholesterol, reduced triglycerides, reduced weight, reduced waist measurement, impor ed energy and sex performance.

4. Testosterone was effective at preventing coma induced by profound hypoglycemia.


The new 2008 research proposal will include multiple sites, 200 patients, and a double blind study.

I will personally review the supplied information. The patient will be billed for a consultation (insurance participating) and will receive an initial evaluation and authorization number. A copy will be faxed back to the physician as well. The physician will order the testosterone and placebo from the designated pharmacy. Blood samples will be drawn in the physician's office, spun, decanted, and frozen in plastic tubes for shipment back to Southfield, Michigan.


Introduction:
Testosterone supplementation may or maynot improve glucose metabolism as the only reference to such is antedotal [1]. Studies with other compounds [available as prescription medications] have not been shown to change the course of the disease.[2] Since small vessel disease characteristic of Type II diabetes may limit tissue levels of testosterone, the question is raised whether previous replacement dosing for decreased libido may have been inadequate to effect glucose metabolism. Therefore, we seek to standardize testosterone serum levels to the upper limits documented in previous treatments of normal men to see if we can improve glucose, insulin usage and overall well being. [3-4]
Jens Moller in 1984 [1] reported that testosterone could improve circulation through small vessel disease without changing circulation in large feeder vessels. Diabetes is a disease typified by small vessel dysfunction. And since 50 percent of diabetic men report problems of erectile performance, the study seeks to establish if the tesetosterone levels reached with testosterone injections or pellets can offer any improvement in sexual performance. [5-6]
Studies with high dose testosterone replacement have been performed in a large number of longitudinal studies. Pellet placement for a number of years in men have shown no negative effects on lipid metabolism or side-effects. [7-8] Since testosterone is indicated and FDA approved for treatment of hypogonadal men[9], [those whose testosterone levels are under 400 ng/dl, a free testosterone <10 mg/ml, or meeting define criteria and without prostatic hypertrophy, cancer or elevated PSA levels], its use is acceptable in our clincal research propulation.

Summary of Research Proposal:
Selection:
Fifty men volunteers with 1) adult onset diabetes mellitus [and low testosterone levels] will be offered participation in this study. Those who qualify and agree to the study will be randomized into one group with active compound and a second with a placebo (blank). The study plan will continue for 3 months, then off for less than one month, then on to the alternative therapy.
Those who decline testosterone replacement, those with elevated PSA and those with prostatic disease can enter a separate 'control' group to serve as a second control group. They will have the opportunity for laboratory testing but receive no treatment.

Restrictions:
All men will need to have a PSA test, prostate examination, and specific blood tests prior to admission into this study for the use of testosterone injections or pellets. This is mandatory to document the status of any prostatic conditon. Testing will be repeated at the end of 3 months and at the end of the study. Your physician will of course perform any tests he feels are warranted and you are to report any side-effects or problems to him immmediately.

Initial Selection:
Once selected, the initial treatment will be with either 2cc of 200mg/cc Testosterone Enanthate intramuscular injection every week for 10 weeks or sesame oil (placebo). These individuals will have a blood draw at the beginning and 12 weeks later. These spun and decanted samples will be frozen and send back to Dr. Lichten for processing with the authorization number. Only after the serum has been received will the patient and doctor receive a second authorization number to use the alternative therapy for the next 10 weeks. Two weeks after the last injection, the serum will be redrawn, processed accordingly and sent back to Doctor Lichten. The serial log of weight, blood pressure, and anthropologic measurements will be requested at that time.

For those individuals who are able to travel to Southfield, Michigan, a suburb of Detroit, Michigan (a Northwest Airline' hub), testosterone pellets will be placed every 12 weeks. These are more convenient and the laboratory testing will be performed in Doctor Lichten's office.


References:
  1. Moller Jens.Cholesterol: Interactions with Testosterone and Cortisol in Cardiovascular Diseases. Springer-Verlag, Berlin, 1987.
  2. Ando S, Rubens R, Tottiers R. Androgen plasma levels in male diabetics. Jorunal of Endocrinological Investigation. 1984; Feb; 71(2):21-4.
  3. Goodman and Gilman. The Pharmacological Basis of Therapeutics. 4th edition. 1970
  4. Bhasin S, Storer TW, Berman N, Callegari C, et al. The Effects of Supraphysiologic Doses of Testosterone on Muscle Size and Strength in Normal Men. The New England Journal of Medicine 1996 July 4; 335(1):1-7.
  5. Jockenhovel F, Vogel E, Kreutzer M, Reinhardt W, et al. Pharmacokinetics and phamacodynamics of subcutaneous testosterone implants in hypogonadal men. Clinical Endocrinology. 1996; 45: 61-7`.
  6. Jensen SB, Hagen C, Froland A, Pederseon PB. Sexual function and pituitary axis in insulin treated diabetic men. Acta Medica Scandinavia- Suppl 1979; 624: 65-8/
  7. Bagatell CJ, Heiman JR, Rivier JE, Bremner WJ. Effects of Endogenous Testosterone and Estradiol on Sexual Behavior in Normal Young Men. Journal of Clinical Endocrinology and Metabolism 1992; 175:1326-32.
  8. Handelsman DJ, Conway AJ, Boylan LM. Suspension of Human Spermatogenesis by Testosterone Implants.Journal of Clinical Endocrinology and Metabolism. 1992;175:1326-1332.
  9. Anderson RA, Wu FCW. Comparision between testosterone indued azoospermia and oligozoospermia in a Male Contraceptive Study II. Pharmacokinetics and Pharmacodynamics of Once Weekly Adminsitration of Testosterone Enanthate. Journal of Clinical Endocrinology and Metabolism 1996;81:896-901.
  10. Androderm C-III. Ciba-Geigy. 1995

Installed: March 15,2000
Revisited; January 1, 2008