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      Changes in insulin resistance indicators, IGFs, and adipokines in a year-long trial of aerobic exercise in postmenopausal women

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          Abstract

          Physical activity is a known modifiable lifestyle means for reducing postmenopausal breast cancer risk, but the biologic mechanisms are not well understood. Metabolic factors may be involved. In this study, we aimed to determine the effects of exercise on insulin resistance (IR) indicators, IGF1, and adipokines in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial was a two-armed randomized controlled trial in postmenopausal, inactive, cancer-free women. A year-long aerobic exercise intervention of 225 min/week ( n=160) was compared with a control group asked to maintain usual activity levels ( n=160). Baseline, 6- and 12-month serum levels of insulin, glucose, IGF1, IGF-binding protein 3 (IGFBP3), adiponectin, and leptin were assayed, and after data collection, homeostasis model assessment of IR (HOMA-IR) scores were calculated. Intention-to-treat analyses were performed using linear mixed models. The treatment effect ratio (TER) of exercisers to controls was calculated. Data were available on 308 (96.3%) women at 6 months and 310 (96.9%) women at 12 months. Across the study period, statistically significant reductions in insulin (TER=0.87, 95% confidence interval (95% CI)=0.81–0.93), HOMA-IR (TER=0.86, 95% CI=0.80–0.93), and leptin (TER=0.82, 95% CI=0.78–0.87), and an increase in the adiponectin/leptin ratio (TER=1.21, 95% CI=1.13–1.28) were observed in the exercise group compared with the control group. No significant differences were observed for glucose, IGF1, IGFBP3, adiponectin or the IGF1/IGFBP3 ratio. Previously inactive postmenopausal women who engaged in a moderate-to-vigorous intensity exercise program experienced changes in insulin, HOMA-IR, leptin, and adiponectin/leptin that might decrease the risk for postmenopausal breast cancer.

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          Glucose clamp technique: a method for quantifying insulin secretion and resistance.

          Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.
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            Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

            The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin). An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). At 1 year, ILI resulted in clinically significant weight loss in people with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.
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              Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans.

              Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-alpha). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m2, n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m2, n = 19) compared with lean men (mean BMI: 23.4 kg/m2, n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-alpha on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% (P < 0.05) increase in plasma adiponectin and a 45% (P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% (P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-alpha (P < 0.01) and IL-6 plus its soluble receptor (P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL-6) and insulin resistance and atherosclerosis.
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                Author and article information

                Journal
                Endocr Relat Cancer
                ERC
                Endocrine-Related Cancer
                Society for Endocrinology (Bristol )
                1351-0088
                1479-6821
                June 2011
                11 April 2011
                : 18
                : 3
                : 357-369
                Affiliations
                [1 ]simpleDepartment of Population Health Research simpleAlberta Health Services - Cancer Care Calgary, AlbertaCanadaT2N 4N2
                [2 ]simpleDepartments of Oncology and Community Health Sciences, Faculty of Medicine simpleUniversity of Calgary Calgary, AlbertaCanadaT2N 4N2
                [3 ]simplePerinatal Epidemiology Research Unit, Departments of Obstetrics and Gynaecology and Pediatrics simpleDalhousie University Halifax, Nova ScotiaCanadaB3K 6R8
                [4 ]simplePrevention Center simpleFred Hutchinson Cancer Research Center Seattle, Washington, 98109USA
                [5 ]simpleApplied Research Program, Division of Cancer Control and Population Sciences simpleNational Cancer Institute Bethesda, Maryland, 20892USA
                [6 ]simpleDepartment of Medicine, Faculty of Medicine simpleUniversity of Calgary Calgary, AlbertaCanadaT2N 4N2
                [7 ]simpleDepartment of Obstetrics and Gynecology, Keck School of Medicine simpleUniversity of Southern California Los Angeles, California, 90033USA
                [8 ]simpleDepartment of Statistics simpleUniversity of British Columbia Vancouver, British ColumbiaCanadaV6T 1Z2
                [9 ]simpleDepartment of Public Health Sciences simpleUniversity of Alberta Edmonton, AlbertaCanadaT6G 2T4
                [10 ]simpleDepartment of Epidemiology and Public Health simpleYale University New Haven, Connecticut, 06520-8034USA
                [11 ]simpleDepartment of Physical Therapy simpleUniversity of British Columbia Vancouver, British ColumbiaCanadaV6T 1Z3
                [12 ]simpleDepartments of Physical Therapy and Oncology simpleUniversity of Alberta Edmonton, AlbertaCanadaT6G 2G4
                [13 ]simpleDepartment of Exercise and Sports Science simpleEast Carolina University Greenville, North Carolina, 27858USA
                [14 ]simpleFaculty of Physical Education and Recreation simpleUniversity of Alberta Edmonton, AlbertaCanadaT6G 2H9
                Author notes
                (Correspondence should be addressed to C Friedenreich at Department of Population Health Research, Alberta Health Services-Cancer Care; Email: christine.friedenreich@ 123456albertahealthservices.ca )
                Article
                ERC100303
                10.1530/ERC-10-0303
                3111235
                21482635
                a6fd26e0-83ec-4010-b78a-3c5c1ff1d79d
                © 2011 Society for Endocrinology

                This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 March 2011
                : 11 April 2011
                Funding
                Funded by: Canadian Breast Cancer Research Alliance
                Award ID: #017468
                Funded by: Alberta Cancer Foundation
                Award ID: #22170
                Categories
                Regular Papers

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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