Testosterone obesity and diabetes

Description

Dr. Jones presents the main recent findings on testosterone, obesity and diabetes. He highlights that age - surprisingly enough - only has a relatively small effect on the age-related reduction in testosterone levels. The main causes are obesity and comorbidities.1 Dr. Jones continues by introducing the metabolic syndrome and insulin resistance, which is central to all the manifestations of the metabolic syndrome; hyperglycemia, hypertension, dyslipidemia, thrombosis and microalbuminuria (an indicator of endothelial dysfunction). Acknowledging that lifestyle and genetics contribute to insulin resistance, he points out that testosterone deficiency also is a major contributor to insulin resistance.

Dr. Jones notes that insulin resistance is an independent predictor of cardiovascular disease, and confers a risk similar to that of smoking 2, and that visceral fat accumulation is associated with increased insulin, glucose and C-peptide levels and decreased testosterone levels.3 Notably, even after adjusting for age, body mass index, and visceral fat area, levels of free testosterone are still negatively correlated with glucose, insulin, and C-peptide levels.3

Since 1982, studies have consistently shown that men with type 2 diabetes have low testosterone levels.4 As many as 42% of diabetic men have free testosterone <0.255 nmol/L.5 It is notable that while BMI and waist circumference are both significantly negatively correlated with testosterone levels, the association is stronger for waist circumference.5 One important link between low testosterone and diabetes is visceral adiposity, as reflected in a larger waist circumference.5 Dr. Jones presents data on weight loss and elevations in testosterone levels; a weight loss of 10% may results in an elevation of testosterone levels by 1.5 to 6 nmol/L.6 However, he notes that it is hard for obese/diabetic men to lose this amount of weight.

Testosterone replacement therapy may improve several cardiovascular risk factors; visceral obesity, insulin resistance, hypercholesterolemia, hypertension, coagulation and inflammation. Dr. Jones supports this by presenting the results from several studies. The TIMES2 (Testosterone replacement In hypogonadal men with either MEtabolic Syndrome or type 2 diabetes) study found beneficial effects of testosterone replacement therapy on body fat, waist circumference, insulin resistance, total and LDL-cholesterol, Lp(a), and sexual function in hypogonadal men with type 2 diabetes and/or MetS.7 The Moscow study found that testosterone treatment with testosterone undecanoate injections for 30 weeks significantly decreases weight, BMI and waist circumference.8 In addition, levels of leptin, insulin, IL-1β, TNF-α and CRP also significantly decreased.8 He underscores the results from the long-term registry studies by Dr. Saad and colleagues, which found substantial and continuous improvements in anthropometric parameters; reduction in waist circumference, weight and percent weight loss of 8.5 cm, 15.3 kg and 13.6%, respectively.9-14 As a 10% weight loss is necessary in order to achieve improvements in heart disease and cancer risk, this finding is clinically significant. It is also notable that testosterone replacement results in a 15% improvement in insulin resistance 7, which is of similar magnitude as that seen with metformin treatment.

Dr. Jones ends by presenting mortality outcomes of testosterone replacement therapy. Diabetic men with testosterone levels of <10.4 nmol/L have been found twice as likely to be dead 7 years later, compared to diabetic men treated with testosterone (multivariate-adjusted HR for decreased survival in the untreated group was 2.3).15 Specifically, 20% of non-treated diabetic men were dead at a mean follow-up of 5.8 years, whereas only 8.6% of testosterone treated diabetic men died. Notably, the death rate of testosterone treated diabetic men was similar to that seen in non-diabetic men with normal testosterone levels.15

In summary, testosterone deficiency is associated with visceral obesity, insulin resistance, diabetes, erectile dysfunction, cardiovascular risk and mortality. Testosterone replacement therapy reduces body fat, body weight, insulin resistance and inflammation. It also prevents overspill of lipid into visceral fat and arterial walls, and thereby protects against hepatic steatosis and atherosclerosis. Ultimately, testosterone replacement therapy may increase longevity in diabetic men with testosterone deficiency.

Resume Dr. Jones
Consultant Physician in General Internal Medicine, Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust Barnsley and

Honorary Professor of Andrology, Hormone and Vascular Biology Research Group, Academic Unit of Diabetes, Endocrinology and Metabolism, Department of Human Metabolism, University of Sheffield Medical School.

Address:
Centre for Diabetes and Endocrinology,
Barnsley District General Hospital,
Gawber Road, Barnsley, UK
Academic Unit of Diabetes Endocrinology and Metabolism,
Department of Human Metabolism
University of Sheffield Medical School,
Beech Hill Road, Sheffield, UK

QUALIFICATIONS:
1975 - BSc with Honours in Biochemistry, University of Sheffield
1980 - MB ChB, University of Sheffield
1984 - MRCP (UK)
1990 - MD University of Sheffield: ‘Studies on the Hypothalamic and Paracrine Control of Anterior Pituitary Hormone Secretion’
2001 - FRCP (London)
ICP GCP for Investigators 2010– The Institute of Clinical Research

ACCREDITATION RCP:
General Medicine, Endocrinology and Diabetes Mellitus (1993)

ADMINISTRATIVE APPOINTMENTS:
Programme Director for Training of Specialist Registrars in Diabetes, Endocrinology and General Internal Medicine to the South Yorkshire and South Humber Deanery Rotational Training Scheme 200-2010.
Chair of Specialist Education Committee for spR’s in Diabetes and Endocrinology for Leicester, Nottingham and South Yorkshire and South Humber Deaneries2003-2010

Society for Endocrinology (UK):
Lead Convener for Special Interest Group in Andrology
Committee member Corporate Liaison Group
Associate Editor Therapeutic Advances in Endocrinology and Metabolism
Sub-section Editor Journal of Men Health

Editorial Board:
Clinical Endocrinology
Nature Scientific Reports
American Journal of Men's Health

PREVIOUS APPOINTMENTS:

Aug. 1980 - Jan. 1981:
House Officer in General Medicine, Royal Hallamshire and Lodge Moor Hospitals, Sheffield.

Feb 1981 - Jul 1981:
House Officer in General Surgery (University Department of Surgery) Northern General Hospital, Sheffield.

Aug. 1981 - Mar 1983:
Senior House Officer in General Medicine, Diabetes and Endocrinology. Barnsley District General Hospital.

Mar 1983 - Mar 1985:
Medical Registrar (Rotating). Royal Hallamshire Hospital, Sheffield Neurology, General Medicine with Cardiothoracic Disorders, General Medicine, Endocrinology and Diabetes.

Mar 1985 – Dec 1987:
Research Fellow, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School.

May 1987 - Jul 1987:
Medical Registrar in General Medicine, Cardiovascular disease and Hypertension (University Department of Therapeutics).

Jan 1988 - Jan 1994:
Lecturer and Honorary Senior Registrar in Medicine, Diabetes and Endocrinology, Northern General and Royal Hallamshire Hospitals, Sheffield.

Feb 1994 - April 1997: Consultant Physician in General Medicine and Endocrinology at the Royal Hallamshire Hospital, Sheffield.

May 1997 - July 1997 Senior Clinical Research Fellow, Metabolic Bone Unit, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield.

Aug 1997 - Jan 1998:
Consultant Physician in General Medicine, Diabetes and Endocrinology, Rotherham District General Hospital, Rotherham.

MEMBERSHIP OF LEARNED SOCIETIES:
Royal College of Physicians of London
Society for Endocrinology
Endocrine Society of America
The International Pituitary Pathologists Club
International Society for the Study of the Aging Male (ISSAM)
International Society for Men’s Health
Association of British Clinical Diabetologists
Diabetes UK


 

Speakers

Dr. Morgentaler

Prof. Dr. Hugh Jones
Centre for Diabetes & Endocrinology,
Barnsley Hospital NHS Foundation Trust &
Academic Unit of Diabetes,
Endocrinology & Metabolism,
University of Sheffield, UK

References

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  • Seidell JC, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt R. Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism. 1990;39(9):897-901. Return to content
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  • Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur. J. Endocrinol. 2013;169(6):725-733. Return to content