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Clinical Studies |
Department of Medicine, University of Texas Health Science Center (S.M.H., H.M.), San Antonio, Texas 78284-7873; and the Department of Medicine, Kuopio University Hospital (H.M., P.K., L.M., M.L.), Kuopio, Finland
Address all correspondence and requests for reprints to: Dr. Steven M. Haffner, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7873.
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Abstract |
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Leptin levels were significantly correlated with free testosterone (r = -0.14; P < 0.05), sex hormone-binding globulin (r = -0.26; P < 0.05), total testosterone (r = -0.32; P < 0.01), and cortisol(r = -0.09; P = NS). However, after adjustment for body mass index (or, alternatively, waist or hip circumference), leptin concentrations were not significantly related to sex hormones or cortisol. Our data suggest that in men, sex hormones are not important independent modifiers of leptin concentrations.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Currently, no data exist on whether sex hormones affect the concentrations of leptin in men. To explore this issue, we examined sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-SO4), estradiol, and cortisol in relation to leptin concentrations in normoglycemic men. We have previously shown in these subjects that low sex hormone-binding globulin (SHBG) and testosterone concentrations are associated with insulin resistance and/or adverse body fat distribution (9).
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Subjects and Methods |
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Weight and height were measured in light-weight clothing without shoes. BMI (calculated as weight divided by height squared, kg/m2) and waist and hip circumferences were used as indexes of overall adiposity. Waist circumference was measured at the level of the umbilicus with the subject standing and breathing normally. Hip circumference was measured at the level of the greatest hip girth. Waist to hip ratio and waist circumference were used as measures of body fat distribution.
The subjects selected for the study were admitted to the metabolic ward for 2 days. On day 1, an oral glucose tolerance test (75 g glucose) was performed, and samples for plasma glucose, lipid, lipoprotein, and insulin measurements were obtained. On day 2, the euglycemic clamp (11) was performed. These methods have been previously described (10). Plasma glucose in the fasting state and during glucose clamp studies was measured by the glucose oxidase method. Plasma insulin was determined by RIA (Pharmacia Diagnostics, Uppsala, Sweden).
Aliquots of fasting serum specimens were saved as contingency samples and frozen at -70 C. This sample was not thawed until the analyses were performed for sex hormones and cortisol in the laboratory of Dr. Steven Haffner (San Antonio, TX). Estradiol, total testosterone, and DHEA-SO4 were measured with solid phase commercial RIAs (Diagnostic Products Corp., Los Angeles, CA) (9). Free testosterone (Diagnostic Products Corp.) and SHBG (Diagnostic Systems Laboratory, Webster, TX) were measured by commercial double antibody systems (9). Serum cortisol was analyzed by a solid phase RIA (Diagnostic Products Corp.).
Leptin concentrations were measured by a commercial RIA (Linco Research, St. Louis, MO) (8, 12, 13). The within-assay coefficient of variation ranged from 3.4–8.3%, and the between-assay coefficient of variation ranged from 3.6–6.2%.
All calculations were performed using SAS statistical software (SAS
Institute, Cary, NC). Data are presented as the mean ±
SE (Table 1
). The following statistical
tests were performed: Spearman correlation, partial correlation
analysis (nonparametric; see Tables 2 and 3), and multiple linear regression analysis. Partial
parametric correlations were performed by substituting the ranks of the
observations for the actual value. As BMI and waist circumference were
very highly correlated (P = 0.82), they were not
entered in the same correlation model. BMI was used in preference to
waist circumference and waist/hip ratio because BMI explained a larger
proportion of the variance in leptin in these data.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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describes the clinical and metabolic characteristics of
the subjects. The mean age was 54.2 yr, and the mean BMI was 26.3
kg/m2. Table 2 shows Spearman correlations (nonparametric)
for sex hormones, leptin, and overall adiposity. Leptin was
significantly correlated with lower levels of free testosterone (r
= -0.14), SHBG (r = -0.26), and total testosterone (r =
-0.32) and higher levels of fasting insulin (r = 0.62) and BMI
(r = 0.52), waist circumference (r = 0.66), and hip
circumference (r = 0.50). A high BMI was significantly associated
with lower levels of free testosterone (r = -0.23), SHBG (r
= -0.35), total testosterone (r = -0.38), and cortisol (r =
-0.33) and higher levels of fasting insulin (r = 0.48). Similar
correlations were observed for waist and hip circumferences and sex
hormones. The scatterplots of leptin with SHBG and total testosterone
are shown in Figs. 1 and 2,
respectively.
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shows the correlations of leptin with sex hormones and cortisol
after adjustment for BMI and waist or hip circumference. The
correlations of leptin with sex hormones were not statistically
significant. However, leptin continued to be weakly correlated with
fasting insulin. We also examined whether alterations in sex hormones could explain the association between leptin concentrations and fasting insulin or BMI by multiple linear regression analysis in which leptin concentrations were the dependent variable and fasting insulin, BMI, and sex hormones were independent variables. However, the relation between leptin and insulin or BMI was only slightly modified by including sex hormones in the regression model (data not shown).
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Discussion |
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Previous studies of leptin concentrations in men and women have shown higher leptin levels in women than in men (6, 7, 8, 12, 13, 14, 15, 16). In some (6, 7), but not all (12, 13, 14, 15, 16), studies, adjustment for adiposity eliminates the gender difference in leptin concentrations. Our data suggest that higher testosterone levels in men are not likely to be major determinants of leptin concentrations after taking account of adiposity.
A number of studies have suggested correlations between leptin concentrations and insulin concentrations or insulin resistance (7, 17, 18). During the hyperinsulinemic euglycemic clamp (17, 19), insulin infusion did not increase leptin concentrations. However, during a 72-h insulin infusion, leptin levels rose during the last 24 h (19). These observations suggest a lack of acute effect of insulin on leptin concentrations, but hyperinsulinemia and/or insulin resistance could have a long term effect on leptin concentrations. It might be argued that this relation could be due in part to the effect of sex hormones, as sex hormones are related to insulin resistance, overall adiposity, and an adverse body fat distribution (9). Our data, however, suggest that the relation between fasting insulin and leptin is only moderately attenuated by adjustment for sex hormones.
One limitation of the present proposal is that we do not have data from a direct measurement of overall adiposity, such as underwater weighing or dual energy x-ray absortiometry. We used a number of surrogates for overall adiposity, including waist and hip circumference and body mass index, which show relatively similar relations to leptin.
In conclusion, we have shown only modest inverse correlations between leptin concentrations and levels of SHBG and total and free testosterone in men. These associations appeared to be explained by the association of obesity with both sex hormones and leptin.
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Footnotes |
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Received September 23, 1996.
Revised December 5, 1996.
Accepted February 18, 1997.
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References |
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