Age, Lifestyle, Muscle Mechanisms in Insulin Resistance
調査の概要
詳細な説明
Aging is associated with a progressive development of impaired glucose tolerance (IGT), due to an increased peripheral tissue resistance to the action of insulin. Insulin resistance, a common state in both obese and sedentary individuals, eventually leads to the development of glucose intolerance, and type 2 diabetes with aging. Even in the absence of diabetes, insulin resistance is a key feature in various metabolic abnormalities that increase the risk for developing cardiovascular disease (CVD). Previous studies demonstrate improvements in glucose tolerance and glucose utilization following moderate energy restriction coupled with moderate intensity AEX. WL, through behavioral modification of diet and aerobic exercise (AEX), is perhaps the most effective way to treat as well as prevent insulin resistance and its associated metabolic complications of IGT and type 2 diabetes. Although these studies demonstrate the beneficial effect of weight loss (WL) and AEX on glucose tolerance and insulin action, not much is known about the cellular and molecular mechanisms by which these nonpharmacologic treatments improve glucose utilization in high-risk obese older individuals.
This study seeks to determine the cellular mechanisms by which aerobic exercise and weight loss alter skeletal muscle insulin signaling to improve insulin action in older glucose intolerant individuals. A second purpose is to determine whether certain genes (hereditary information) affect the way the body utilizes glucose in response to exercise and weight loss. In addition, adipose tissue is increasingly recognized as more than an inert depot serving not only to accept and store excess energy in the form of triglycerides, but also to secrete hormones and adipokines that have substantial effects on lipid and glucose metabolism. Furthermore, there are depot differences in metabolic function, as well as adipokine content. However, the physiology both underlying and consequential to these observations remains unknown. Thus, a third aim is to examine the effects of obesity on regional adipokine secretion and expression, and the relationship of adipokines to insulin resistance and the metabolic syndrome.
研究の種類
入学 (実際)
段階
- 適用できない
連絡先と場所
研究場所
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Maryland
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Baltimore、Maryland、アメリカ、21201
- University of Maryland
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Baltimore、Maryland、アメリカ、21201
- Baltimore VA Medical Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Men older than 50 yrs of age
- Non-smoking (more than 5 years)
- BMI greater than 25 kg/m2 and less than 50 kg/m2
Exclusion Criteria:
- CAD, CHF, Myocardial infarction within 6 months or other symptomatic heart disease
- History of stroke, peripheral arterial disease
- Currently being treated for active cancer
- On oral agents or insulin therapy for diabetes
- Poorly controlled Dyslipidemia (abnormal concentration of lipids or lipoproteins in the blood)
- Poorly controlled hypertension (BP > 180/95)
- Other systematic disorders that are not medically treated and stable
- Physical impairment limiting normal activity and other contraindications to exercise
- Aerobically conditioned
- Abnormal response to exercise (chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising BP > 240/120)
- Taking warfarin/coumadin
- Taking oral steroids
- Abnormal renal function or liver function
- Chronic pulmonary disease severe enough to require oxygen
- Anemia
- MMSE < 24, dementia
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:防止
- 割り当て:非ランダム化
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的:WL+AEX
Weight loss plus aerobic exercise
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1 hour sessions, once per week, with a registered dietitian on the American Heart Association Step I diet with caloric intake for each volunteer adjusted by the dietitian to elicit a WL of ~0.2-0.4 kg/wk
Moderate aerobic exercise (75-80% HRR for 45 min) at the Baltimore GRECC exercise facility using treadmills 3 times per week for 6 months.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
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Insulin stimulated glucose disposal
時間枠:Baseline and 6 months
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Baseline and 6 months
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Content and activity of insulin signaling proteins from muscle biopsies
時間枠:Baseline and 6 months
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Baseline and 6 months
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Glucose tolerance
時間枠:Baseline and 6 months
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Baseline and 6 months
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二次結果の測定
結果測定 |
時間枠 |
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Aerobic capacity
時間枠:Baseline and 6 months
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Baseline and 6 months
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Body weight/Composition
時間枠:Baseline and 6 months
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Baseline and 6 months
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Cytokines
時間枠:Baseline and 6 months
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Baseline and 6 months
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Other biomarkers (such as glucose, insulin etc)
時間枠:Baseline and 6 months
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Baseline and 6 months
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協力者と研究者
捜査官
- 主任研究者:Lyndon Joseph, PhD、National Institute on Aging (NIA)
出版物と役立つリンク
一般刊行物
- Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
- Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol (1985). 2004 Jan;96(1):101-6. doi: 10.1152/japplphysiol.00707.2003. Epub 2003 Sep 12.
- Prior SJ, Blumenthal JB, Katzel LI, Goldberg AP, Ryan AS. Increased skeletal muscle capillarization after aerobic exercise training and weight loss improves insulin sensitivity in adults with IGT. Diabetes Care. 2014 May;37(5):1469-75. doi: 10.2337/dc13-2358. Epub 2014 Mar 4.
- Deshmukh AS, Hawley JA, Zierath JR. Exercise-induced phospho-proteins in skeletal muscle. Int J Obes (Lond). 2008 Sep;32 Suppl 4:S18-23. doi: 10.1038/ijo.2008.118.
- Catenacci VA, Hill JO, Wyatt HR. The obesity epidemic. Clin Chest Med. 2009 Sep;30(3):415-44, vii. doi: 10.1016/j.ccm.2009.05.001.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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