departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
Aging in the male is associated with both a higher incidence of type 2
diabetes and hypogonadism. However, little information is available about the
complex of symptoms and hormonal changes related to partial androgen
deficiency in aging (called andropause) in type 2 diabetic men. Here, for the
first time, we used a combination of clinical and hormonal criteria to define
andropause and to analyze the relationships between the androgen environment
and glucose metabolism in 55 type 2 diabetic men (63.6 +/- 7.9 years, mean +/-
SD). Low plasma levels of total testosterone (< or =3.4 ng/mL) and free
testosterone (< or =11 pg/mL) were found in 20% and 54.5%, respectively, of
the diabetic men. The fraction of diabetic men with subnormal levels of total
testosterone increased with aging: 14.2% (50 to 59 years), 17.4% (60 to 69
years) and 36% (> 70 years). The corresponding figures for subnormal values of
free testosterone were 38%, 69.6%, and 54.5%, respectively. In the whole group
of type 2 diabetic men, no significant linear correlations between total or
free testosterone with fasting plasma glucose, insulin, C-peptide, or
fructosamine values could be established. Total testosterone was positively
correlated with glycosylated haemoglobin (HbA(1c)) levels (r =.322, P =.01).
Although fasting plasma glucose was marginally higher in aging type 2 diabetic
patients with andropause than in those without andropause (162 +/- 6.9 v 139
+/- 8.9, mean +/- SEM, P =.05), there were no differences between both
subgroups for plasma fasting insulin, C-peptide, fructosamine, or HbA(1c)
levels. Replacement therapy (150 mg intramuscular [IM] of enanthate of
testosterone every 14 days for 6 months) was applied in 10 type 2 diabetic men
with clinical features of andropause associated with subnormal concentrations
of serum testosterone. The treatment induced significant increases in total
plasma testosterone (baseline: 3.9 +/- 0.3; at 6 months: 7.1 +/- 0.9 ng/mL,
mean +/- SEM, P =.003) and free testosterone (baseline: 9.3 +/- 0.6; at 6
months 17.6 +/- 2.4 pg/mL, P =.003), but had a neutral effect on overall
glycemic control. These data show a high prevalence of andropause in aging
type 2 diabetic men and suggest that the endogenous androgen environment, as
well as correction of the partial androgen deficiency, do not have a
meaningful effect on glycemic control.
Endocrinology Clinic, Alexandrovska Hospital, Medical University of Sofia,
Sofia, Bulgaria.
The objective of this study was to assess the effects of oral testosterone
supplementation therapy on glucose homeostasis, obesity and sexual function in
middle-aged men with type 2 diabetes and mild androgen deficiency. Forty-eight
middle-aged men, with type 2 diabetes, (visceral) obesity and symptoms of
androgen deficiency, were included in this open-label study. Twenty-four
subjects received testosterone undecanoate (TU; 120 mg daily, for 3 months);
24 subjects received no treatment. Body composition was analyzed by
bio-impedance. Parameters of metabolic control were determined. Symptoms of
androgen deficiency and erectile dysfunction were scored by self-administered
questionnaires. TU had a positive effect on (visceral) obesity: statistically
significant reduction in body weight (2.66%), waist-hip ratio (-3.96%) and
body fat (-5.65%); negligible changes were found in the control group. TU
significantly improved metabolic control: decrease in blood glucose values and
mean glycated hemoglobin (HbA1c) (from 10.4 to 8.6%). TU treatment
significantly improved symptoms of androgen deficiency (including erectile
dysfunction), with virtually no change in the control group. There were no
adverse effects on blood pressure or hematological, biochemical and lipid
parameters, and no adverse events. Oral TU treatment of type 2 diabetic men
with androgen deficiency improves glucose homeostasis and body composition (decrease
in visceral obesity), and improves symptoms of androgen deficiency (including
erectile dysfunction). In these men, the benefit of testosterone
supplementation therapy exceeds the correction of symptoms of androgen
deficiency and also includes glucose homeostasis and metabolic control.
The effect of testosterone supplement on insulin
sensitivity, glucose effectiveness, and acute insulin response after glucose
load in male type 2 diabetics.
Division of Endocrinology and Metabolism, Department of Internal Medicine,
Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Our understanding of the effect of androgens on insulin action and glucose
metabolism is incomplete. Several different models and methods have been used
to study androgen effects, with some studies indicating that higher
testosterone levels are associated with increased insulin resistance. In
polycystic ovary syndrome, where high testosterone levels are frequently found,
affected patients have a higher risk of diabetes. In contrast, increased
insulin resistance was found in both hypergonadotropic and hypogonadotropic
men with hypoandrogenism, patients with Klinefelter's syndrome and men with
idiopathic gonadotropin deficiency. Insulin resistance is considered to be one
of the cornerstones in the state that ultimately leads to clinically
established type 2 diabetes mellitus. In addition, men with type 2 diabetes
have relative hypogonadism. Therefore, supplementation with testosterone might
play a role in improving both insulin resistance and hypogonadism. The study
population consisted of 11 male patients with type 2 diabetes. Their mean age
was 57.7 +/- 3.41 years, the body mass index (BMI) was 24.4 +/- 1.02 kg/m2,
and the waist-to-hip ratio (W/H) was 0.91 +/- 0.05. The patients were all
treated with oral hypoglycemic agents. The men received androgen injections
every 3 weeks intramuscularly for 12 weeks. The injections were testosterone
depot 100 mg/3 weeks. Insulin sensitivity, glucose effectiveness and area
under acute insulin response were calculated from "minimal model" algorithms.
There were no significant differences in the value of BMI, W/H ratios, plasma
lipid concentrations, testosterone, homeostasis model assessment (HOMA) of
insulin sensitivity, and beta-cell function, before and after supplementation
of testosterone. Furthermore, the insulin sensitivity (SI) (1.04 +/- 0.25,
1.11 +/- 0.36 x 10(-5) min(-1/)pM; p = 0.43), glucose effectiveness (EG)
(0.018 +/- 0.003, 0.017 +/- 0.002 min(-1); p = 0.29), and acute insulin
response (AIR) after a glucose load (45.7 +/- 24.3, 50.1 +/- 32.5 pM; p =
0.45) did not change significantly after supplmentation with testosterone. In
our study, there was no improvement of SI, EG, and AIR after 3 months of
Testosterone Depot treatment in type 2 diabetes, but we believe that duration
and dosage of the androgen therapy might play an important role in improving
insulin sensitivity. The mechanisms by which testosterone causes insulin
resistance is unknown, and larger studies on androgen treatment in type 2
diabetic patients are necessary.
Androgen-replacement therapy depresses the ex vivo
production of inflammatory cytokines by circulating antigen-presenting cells
in aging type-2 diabetic men with partial androgen deficiency.
Servicio de Endocrinologia, Hospital Universitario de Salamanca, Paseo de San
Vicente 58-182, 37007 Salamanca, Spain. corrales@usal.es
Androgens are considered to have immunomodulatory effects but their cellular
mechanisms of action remain largely unknown. In the present study we
prospectively analyzed the serial effects of androgen-replacement therapy on
both the distribution of peripheral blood lymphocytes, monocytes and dendritic
cells as well as on the production of interleukin (IL)-1beta, IL-6 and tumor
necrosis factor alpha (TNFalpha) inflammatory cytokines by circulating
monocytes and CD33 myeloid, CD16 and plasmacytoid dendritic cell subsets, the
most potent antigen-presenting cells (APCs) in type-2 diabetic men with
partial androgen deficiency. Analyses were performed before therapy and at 1,
3, 6 and 12 months after treatment with 150 mg testosterone enanthate every 2
weeks in a group of 13 type-2 diabetic men. Our results show for the first
time that testosterone-replacement therapy is associated with a reduction or
complete abrogation of spontaneous ex vivo production of IL-1beta, IL-6 and
TNFalpha by APCs. Meanwhile, the in vitro production of inflammatory cytokines
by these cells after stimulation with lipopolysaccharide plus recombinant
human interferon-gamma remained unchanged, suggesting that APCs preserve their
constitutive machinery to produce inflammatory cytokines under androgen
treatment. These results confirm and extend previous observations about the
anti-inflammatory effects of androgen therapy on APCs in a new, previously
unexplored model of androgen deficiency; namely, aging type-2 diabetic men. A
decreased production of inflammatory cytokines by APCs might have important
consequences for sex differences in susceptibility to autoimmune diseases,
inflammatory response to injury and atheromatosis.
The University of Auckland, Department of Sport and Exercise Science, Auckland,
New Zealand. j.baldi@auckland.ac.nz
The purpose of this investigation was to determine whether moderate intensity
resistance training (RT) improves glycaemic control in obese, type 2 diabetic
men. Eighteen subjects were randomly assigned to a 10-week RT program, or a
non-training control group (C). Glycosylated haemoglobin (HbA 1c ), fasting
glucose and insulin, glucose and insulin 120 minutes (2h) after a 75 g oral
glucose load, body composition and muscular strength and endurance were
measured before and after the 10-week experimental period. In the RT group
fasting glucose and insulin decreased with training (p < 0.05) and decreases
in HbA 1c approached significance (p = 0.057). 2-h glucose and insulin did not
change in either group. Fat free mass (FFM) increased by 3.5 % after RT but
was unchanged in the controls. Fat mass (FM) increased 6.9 % in C but was
unchanged in RT. Percent body fat was unchanged in both groups. Muscular
strength and endurance increased by 25 to 52 % in the RT group but was
unchanged in controls. Changes in fasting glucose and HbA 1c were inversely
related to changes in FFM. These results suggest that RT is an effective form
of exercise training which modestly improves glycaemic control and lowers
fasting insulin levels in obese type 2 diabetics.
National Center for Diabetes Endocrinology and Genetics, Jordan University
Hospital, Amman, Jordan.
OBJECTIVE: Metformin, an oral hypoglycemic agent, has several other metabolic
and hormonal effects. This study aims at identifying the metabolic effect of
metformin on androgens in diabetic men. METHODS: The study was conducted at
The National Center for Diabetes Endocrinology and Genetics, Jordan University
Hospital, Amman, Jordan from April 2001 to September 2001. We studied 15 men
with type 2 diabetes mellitus by measuring fasting serum glucose, insulin,
glycosylated hemoglobin, total and free testosterone, sex hormone binding
globulin, dehydroepiandrosterone sulphate, 17-OH progesterone, luteinizing
hormone, and follicle stimulating hormone before and after a short course of
metformin. RESULTS: There was a significant decrease in fasting serum glucose
and glycosylated hemoglobin and increase in the level of 17-OH progesterone.
The remainder of the measured parameters did not show any significant change.
Although serum glucose and glycosylated hemoglobin decreased insulin levels
were not changed. CONCLUSION: In contrast to normal men there was no change in
androgen levels in diabetics but the 17-OH progesterone was elevated.
