Exercise Dose and Metformin for Vascular Health in Adults with Metabolic Syndrome
Exercise Dose and Metformin for Vascular Health in Adults with Metabolic Syndrome
批准号:
10357082
负责人:
Steven K Malin
金额:
$73.23万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-02-01 至 2024-01-31
关键词:
AccelerometerAddressAdherenceAdultAerobic ExerciseAffectAttenuatedBehaviorBlood GlucoseBlood PressureBlood VesselsBody mass indexCarbohydratesCardiovascular systemCause of DeathClinicalClosure by clampDiabetes MellitusDiseaseDoseDouble-Blind MethodDouble-blind trialDrug InteractionsDrug PrescriptionsEarly treatmentEtiologyExerciseExercise TherapyFastingFunctional disorderFutureGlucoseGlucose ClampGlycosylated hemoglobin AGoalsHealthHealthcareHyperglycemiaHypertensionIndirect CalorimetryInflammationInsulinInsulin ResistanceInterventionKnowledgeMeasuresMediatingMetabolicMetabolic syndromeMetforminMicrocirculationMitochondriaMorbidity - disease rateMuscle CellsNitric OxideNon-Insulin-Dependent Diabetes MellitusOGTTObesityOutcomeOxidative StressPatientsPatternPerceptionPeripheralPharmaceutical PreparationsPharmacologyPhysical activityPhysiologic pulsePlacebosPre-Post TestsPublic HealthQuality of lifeRandomizedRecommendationResistanceRoleSignal TransductionSkeletal MuscleTestingTherapeuticTrainingTreesUltrasonographyVascular DiseasesWorkarterial stiffnessarteriolebasecardiometabolismcardiovascular healthcontrast enhanceddisorder preventiondisorder riskendothelial dysfunctionexercise adherenceexercise intensityexercise trainingglucose disposalglucose toleranceglycemic controlhealth organizationimprovedindexinginsightinsulin sensitivitymiddle agemortalityoxidationpost interventionpreventsedentary lifestyletreatment effecttrendtrial design
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Arterial disease is the leading cause of morbidity/mortality in Metabolic syndrome (MetS). This occurs early as
evidenced by arterial dysfunction that, in turn, raises blood pressure and glucose. Health organizations
recommend exercise in an intensity based manner to promote cardiovascular adaptation and prevent disease.
Metformin is a common anti-diabetes medication that reduces future type 2 diabetes and CVD risk. However,
the optimal exercise dose to be combined with metformin for additive effects on vascular function is unknown.
Based on our preliminary work, our overall hypothesis is that metformin blunts adaptation following high
intensity exercise training (HiEx) by lowering mitochondrial derived oxidative stress signaling. We further
hypothesize that low intensity exercise (LoEx) training combined with metformin will promote additive effects
on vascular function compared to LoEx or HiEx+metformin, and maintain/improve non-exercise physical
activity patterns. In this double-blind trial, obese 30-60y MetS patients will be randomized to: 1) LoEx+placebo;
2) LoEx+metformin, 3) HiEx+placebo; or 4) HiEx+metformin for 16 weeks. We will evaluate measures of
arterial stiffness (pulse wave velocity and augmentation index), and nitric oxide-mediated arterial function in
conduit (flow mediated dilation), resistance (post-ischemic flow velocity) and microvascular (contrast enhanced
ultrasound) vessels, before and during a euglycemic clamp pre and post intervention (AIM 1). We will also
assess 24 hr blood pressure as well as determine skeletal muscle metabolic insulin resistance and glucose
tolerance (AIM 2) to address clinical and experimental questions related to health care. Further, we will
examine the effect of metformin on exercise adherence, non-exercise physical activity and quality of life during
the 16 week intervention as well as during an 8 week “free-living” period (Exploratory AIM 3) to improve public
health physical activity recommendations when co-prescribed medication. If these hypothesis are correct, they
will indicate 1) whether and how metformin should be combined with physical activity for CVD prevention, 2)
provide the first indication of whether exercise intensity reduces CVD risk via multi-level vasculature function
vs. metabolic insulin action, 3) provide a rational early treatment for people with MetS. Thus, identification of
the optimal drug to exercise interaction will illuminate how to develop individualized exercise/metformin
prescriptions to correct vascular and ameliorate metabolic insulin resistance that attenuate/prevent progression
to future diabetes and the CV morbidity and mortality.
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Insulin at the Crossroads of Metabolic, Neurologic, and Vasculature Disease.
胰岛素处于代谢、神经和脉管系统疾病的十字路口。
DOI:
10.1249/jes.0000000000000187
发表时间:
2019
期刊:
Exercise and sport sciences reviews
影响因子:
5.7
作者:
[Malin,StevenK]
通讯作者:
Malin,StevenK
DOI:
10.1002/oby.22330
发表时间:
2018-11
期刊:
Obesity (Silver Spring, Md.)
影响因子:
--
作者:
[Malin SK]
通讯作者:
Malin SK
DOI:
10.1210/clinem/dgaa533
发表时间:
2021-01-23
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
[Malin SK]
通讯作者:
Malin SK
DOI:
10.14814/phy2.15039
发表时间:
2021-11
期刊:
Physiological reports
影响因子:
2.5
作者:
[Gilbertson NM, Eichner NZM, Gaitán JM, Khurshid M, Rexrode EA, Kranz S, Hallowell PT, Malin SK]
通讯作者:
Malin SK
DOI:
10.1155/2023/4618215
发表时间:
2023
期刊:
JOURNAL OF DIABETES RESEARCH
影响因子:
4.3
作者:
[Faiz, Habiba, Heiston, Emily M., Malin, Steven K.]
通讯作者:
Malin, Steven K.
共 17 条
Exercise dose and metformin for vascular health in adults with metabolic syndrome
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批准号:9239977
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项目类别:
-
资助金额:$73.97万
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财政年份:2017
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负责人:Steven K Malin
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依托单位:
海外基金