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      Hypothalamic–pituitary–adrenal axis activity, personality traits, and BCL1 and N363S polymorphisms of the glucocorticoid receptor gene in metabolically obese normal-weight women

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          Abstract

          We sought associations among metabolic profiles, copeptin levels, emotional control, personality traits, and hypothalamic–pituitary–adrenal axis activity in metabolically obese normal-weight young women (MONW). We assessed body composition, including fat-free mass; body fat (BF) and android and gynoid fat depots; fasting blood glucose, insulin, copeptin, cortisol (baseline and after dexamethasone), adrenocorticotropin (ACTH), triglycerides, total cholesterol, low- (LDL) and high-density (HDL) lipoproteins; and the BCL1 and N363S polymorphisms of the glucocorticoid receptor gene in 59 MONW and 71 healthy women aged 20–40 years. We also evaluated personality traits using the NEO-Five Factor Inventory and the subjective extent of emotional suppression by the Courtauld Emotional Control Scale. Compared to the controls, MONW had significantly higher insulin, cholesterol, LDL, triglycerides, and waist circumference, but lower HDL. MONW also had increased BF (>30 % of weight) and unfavorable regional fat distribution with excess android fat. The android/BF ratio was 8.29 % (MONW) versus 7.89 % (controls) ( p = 0.005), while the gynoid/BF ratio was 31.99 versus 34.1 %, respectively ( p = 0.008). Despite similar ACTH levels in both groups, MONW had higher cortisol levels both at the baseline ( p < 0.001) and in the dexamethasone suppression test ( p = 0.003). Copeptin levels and the distribution of glucocorticoid receptor polymorphisms were similar in both groups. There were also no significant differences in psychological features between MONW and controls. In conclusion, the MONW phenotype was associated with hypothalamic–pituitary–adrenal axis dysregulation, unfavorable metabolic profiles, and fat accumulation, but normal distribution of glucocorticoid receptor gene polymorphisms and copeptin levels, and no significant differences in psychological features between MONW and controls.

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          Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women.

          We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, and impaired glucose tolerance (IGT). A total of 2,964 elderly men and women (mean age 73.6 years) were recruited for cross-sectional comparisons of diabetes or glucose tolerance, generalized obesity with dual-energy X-ray absorptiometry, and regional body fat distribution with computed tomography. RESULTS-Approximately one-third of men with type 2 diabetes and less than half of women with type 2 diabetes were obese (BMI > or =30 kg/m(2)). Despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and IGT than in subjects with normal glucose tolerance (NGT) (11.2 +/- 9.4, 10.3 +/- 5.8, and 9.2 +/- 5.9 cm(2) for men; 12.1 +/- 6.1, 10.9 +/- 6.5, and 9.4 +/- 5.3 cm(2) for women; both P < 0.0001). Visceral abdominal fat was also higher in men and women with type 2 diabetes and IGT than in subjects with NGT (172 +/- 79, 163 +/- 72, and 145 +/- 66 cm(2) for men; 162 +/- 66, 141 +/- 60, and 116 +/- 54 cm(2) for women; both P < 0.0001 across groups). Higher rates of intermuscular fat and visceral abdominal fat were associated with higher fasting insulin in normal-weight (BMI <25 kg/m(2)) men (r = 0.24 for intermuscular fat, r = 0.37 for visceral abdominal fat, both P < 0.0001) and women (r = 0.20 for intermuscular fat, r = 0.40 for visceral abdominal fat, both P < 0.0001). These associations were not found in obese subjects. Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat.
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            Metabolic syndrome in normal-weight Americans: new definition of the metabolically obese, normal-weight individual.

            To determine the prevalence rates and likelihood of the metabolic syndrome and its individual components in normal-weight and slightly overweight individuals (BMI 18.5-26.9 kg/m(2)). There were a total of 7,602 adult participants of the Third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey. Prevalence and odds ratios (ORs) of the metabolic syndrome, defined according to National Cholesterol Education Program Adult Treatment Panel III criteria, were computed according to 2.0- to 2.5-unit increments in BMI. Depending on ethnicity and sex, the prevalence of the metabolic syndrome increased in a graded fashion from 0.9-3.0% at BMI 18.5-20.9 kg/m(2) to 9.6-22.5% at BMI 25.0-26.9 kg/m(2). Compared with men with BMI 18.5-20.9 kg/m(2), the odds for the metabolic syndrome were 4.13 (95% CI 1.57-10.87) for men with BMI 21-22.9 kg/m(2), 5.35 (2.41-11.86) for men with BMI 23-24.9 kg/m(2), and 9.08 (4.23-19.52) for men with BMI 25-26.9 kg/m(2) after controlling for age, ethnicity, education, income, physical activity, smoking status, and alcohol and total fat, saturated fat, carbohydrate, and fiber intakes. The corresponding ORs in women were 4.34 (2.08-9.07), 7.77 (3.95-15.26), and 17.34 (9.29-32.38). Individuals in the upper normal-weight and slightly overweight BMI range have a relatively high prevalence and are at increased risk of having the metabolic syndrome. Therefore, screening in individuals with normal or slightly elevated BMI is important in the prevention of diabetes and cardiovascular disease.
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              Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome?

              Recent studies have shown that reduced fetal growth is associated with the development of the insulin resistance syndrome in adult life. The mechanisms are not known. However increased activity of the hypothalamic-pituitary-adrenal axis (HPAA) may underlie this association; the axis is known to be reset by fetal growth retardation in animals, and there is evidence in humans of an association between raised HPAA activity and the insulin resistance syndrome. We have, therefore, examined the relations among size at birth, plasma cortisol concentrations, and components of the insulin resistance syndrome in a sample of healthy men. We measured 0900 h fasting plasma cortisol and corticosteroid-binding globulin levels in 370 men who were born in Hertfordshire, UK, between 1920-1930 and whose birth weights were recorded. Fasting plasma cortisol concentrations varied from 112-702 nmol/L and were related to systolic blood pressure (P = 0.02), fasting and 2-h plasma glucose concentrations after an oral glucose tolerance test (P = 0.0002 and P = 0.04), plasma triglyceride levels (P = 0.009), and insulin resistance (P = 0.006). Plasma cortisol concentrations fell progressively (P = 0.007) from 408 nmol/L in men whose birth weights were 5.5 lb (2.50 kg) or less to 309 nmol/L among those who weighed 9.5 lb (4.31 kg) or more at birth, a trend independent of age and body mass index. These findings suggest that plasma concentrations of cortisol within the normal range could have an important effect on blood pressure and glucose tolerance. Moreover, this study provides the first evidence that intrauterine programming of the HPAA may be a mechanism underlying the association between low birth weight and the insulin resistance syndrome in adult life.
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                Author and article information

                Contributors
                +48-91-4253550 , +48-91-4253552 , miazgowski@interia.pl
                Journal
                Endocrine
                Endocrine
                Endocrine
                Springer US (Boston )
                1355-008X
                1559-0100
                18 February 2014
                18 February 2014
                2014
                : 47
                : 1
                : 315-321
                Affiliations
                [ ]Department of Hypertension and Internal Medicine, Pomeranian Medical University, 71252 Szczecin, Poland
                [ ]Department of Biochemistry & Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
                [ ]West Pomeranian Institute of Psychotherapy, Szczecin, Poland
                Article
                187
                10.1007/s12020-014-0187-0
                4145218
                24535466
                7cf6ec91-ef1d-43e5-8f7b-3de837ee5dab
                © The Author(s) 2014

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 23 December 2013
                : 25 January 2014
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media New York 2014

                Endocrinology & Diabetes
                cortisol,copeptin,personality traits,glucocorticoid receptor gene,metabolically obese normal-weight

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