Metabolic and endocrine correlates of cognitive function in healthy young women.

OBJECTIVE: Obesity has been associated with cognitive decline in longitudinal studies of older individuals. We hypothesized that the cognitive sequelae of obesity may be detectable in the reproductive years. In addition, we explored the hypothesis that these associations may be mediated by the hormonal milieu. DESIGN AND METHODS: Of 49 young healthy lean and overweight women aged 20-45, we investigated the association between performance on a battery of cognitive tests, body composition parameters [body mass index, total fat, abdominal (visceral, subcutaneous, and total) adipose tissue, and muscle], and hormone levels (insulin, adiponectin, leptin, insulin-like growth factor 1 (IGF-1), estrogen, testosterone, and vitamin D). RESULTS: We found a significant negative association between both visceral adiposity and muscle, and performance in the domain of verbal learning and memory, after controlling for age and education. Other body composition parameters showed similar trends (0.05 < P < 0.10). Additionally, the degree of insulin resistance was negatively associated with executive function domain. None of the associations between the other hormones examined (adipokines, IGF-1, gonadal hormones, and vitamin D) and cognitive function were significant. CONCLUSION: These preliminary findings suggest a possible association between obesity and cognitive function in healthy young women of reproductive age. More research is warranted into the potential modulatory effect of insulin resistance on this association.

Effects of growth hormone withdrawal in obese premenopausal women.

OBJECTIVE: We previously reported improved body composition and cardiovascular risk markers plus a small decrease in glucose tolerance with GH administration vs placebo for 6 months to abdominally obese premenopausal women. The objective of this study was to determine whether the effects of GH treatment on cardiovascular risk markers, body composition and glucose tolerance in obese women persist 6 months after GH withdrawal. DESIGN AND PATIENTS: Fifty abdominally obese premenopausal women completed a trial of rhGH vs placebo for 6 months; thirty-nine women completed a subsequent 6-month withdrawal observation period. MEASUREMENTS: IGF-I, body composition by CT, (1) H-MRS and DXA, serum cardiovascular risk markers, oral glucose tolerance test (OGTT). RESULTS: IGF-I standard deviation scores (SDS) within the GH group were -1.7 ± 0.1 (pretreatment),-0.1 ± 0.3 (after 6 months of GH) and -1.7 ± 0.1 (6 months post-GH withdrawal). Six months after GH withdrawal, total abdominal and subcutaneous adipose tissue, total fat, trunk fat, trunk/extremity fat, hsCRP, apoB, LDL, and tPA were higher than at the 6-month (GH discontinuation) timepoint (P ≤ 0.05). All body composition and cardiovascular risk markers that had improved with GH returned to baseline levels by 6 months after GH discontinuation, as did fasting and 2-h OGTT glucose levels. CONCLUSION: The effects of GH administration to abdominally obese premenopausal women have a short time-course. The beneficial effects on body composition and cardiovascular risk markers, and the side effect of altered glucose tolerance returned to pretreatment levels after GH withdrawal. There was no suppression of endogenous IGF-I levels, which returned to baseline after GH withdrawal.

Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity.

CONTEXT: Chronic starvation is characterized by GH resistance, and obesity is characterized by decreased GH secretion. In both extremes, IGF1 levels may be low and androgen levels may be abnormal. OBJECTIVE: To investigate the determinants of IGF1 and GH across the weight spectrum in women. DESIGN: Cross-sectional study. SETTING: Clinical research center. STUDY PARTICIPANTS: In total, 32 women had participated in the study: 11 women with anorexia nervosa (AN), 11 normal-weight women, and 10 obese women of comparable mean age. INTERVENTION: None. MAIN OUTCOME MEASURES: Pooled hourly overnight serum samples assayed for IGF1, GH, estradiol (E(2)), testosterone, SHBG, insulin, free fatty acids, and trunk fat. RESULTS: Free testosterone was higher in obese women and lower in women with AN than in normal-weight women, and was the only independent (and positive) predictor of IGF1 levels, accounting for 14% of the variability (P=0.032) in the group as a whole. This relationship was stronger when obese women were excluded, with free testosterone accounting for 36% of the variability (P=0.003). Trunk fat accounted for 49% of the variability (P<0.0001) of GH, with an additional 7% of the variability attributable to E(2) (P=0.042) in the group as a whole, but was not a significant determinant of GH secretion when obese women were excluded. CONCLUSIONS: Free testosterone is a significant determinant of IGF1 levels in women across the body weight spectrum. In contrast, GH secretion is differentially regulated at the extremes of the weight spectrum.

Bioactive insulin-like growth factor-I in obesity.

CONTEXT: In obesity, total IGF-I is not reduced to the degree predicted by low GH levels, and free IGF-I levels are normal to high. Total and free IGF-I may not reflect IGF-I biological activity because immunoassays cannot account for the modifying effects of IGF binding proteins on interactions between IGF-I and its receptor. OBJECTIVE: The aim of the study was to investigate the biological activity of IGF-I in obesity. DESIGN AND SETTING: We conducted a cross-sectional study at a General Clinical Research Center. STUDY PARTICIPANTS: Thirty-four healthy women (11 lean, 12 overweight, and 11 obese) of comparable age (overall mean, 30.7 +/- 1.3 yr) participated in the study. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: We measured bioactive IGF-I (as measured by a kinase receptor activation assay), IGFBP-1, and GH using 6-h pools of serum collected every 10 min for 24 h, and fasting IGF-I and IGFBP-3. RESULTS: Mean 24-h GH (R = -0.76; P < 0.0001), total IGF-I (R = -0.36; P = 0.040), and IGFBP-1 (R = -0.41; P = 0.017) levels were inversely associated with BMI, whereas bioactive IGF-I and IGFBP-3 levels were not. Mean bioactive IGF-I was similar in the groups [2.72 +/- 0.22 (lean), 3.10 +/- 0.32 (overweight), and 2.43 +/- 0.23 [corrected] (obese) microg/liter; overall P = 0.22]. Percentage bioactive IGF-I [(bioactive/total IGF-I) x 100] was higher in obese subjects than both lean and overweight subjects (P = 0.039). CONCLUSIONS: Despite low GH secretion in obesity and decreasing IGFBP-1 with increasing BMI, 24-h mean bioactive IGF-I levels are not reduced in obese women and do not correlate with BMI or IGFBP-1 levels. This argues against elevated bioactive IGF-I as the etiology of reduced GH secretion through a feedback mechanism in obesity.