Physical Activity, Insulin Sensitivity, and Hypertension among US Adults: Findings from the Insulin Resistance Atherosclerosis Study

Abstract Context There is evidence demonstrating variation in insulin sensitivity across the menstrual cycle. However, to date, research has yielded inconsistent results. Objective This study investigated variation in insulin sensitivity across the menstrual cycle and associations with BMI, physical activity and cardiorespiratory fitness. Design Data from 1906 premenopausal women in NHANES cycles 1999-2006 were analysed. Main outcome measures Menstrual cycle day was assessed using questionnaire responses recording days since last period. Rhythmic variation of plasma glucose, triglyceride and insulin, homeostatic model of insulin resistance (HOMA-IR) and adipose tissue insulin resistance index (ADIPO-IR) across the menstrual cycle were analysed using cosinor rhythmometry. Participants were assigned low or high categories of BMI, physical activity and cardiorespiratory fitness and category membership included in cosinor models as covariates. Results Rhythmicity was demonstrated by a significant cosine fit for glucose (p= 0.014) but not triglyceride (p= 0.369), insulin (p= 0.470), HOMA-IR (p=0.461) and ADIPO-IR (p= 0.335). When covariates were included, rhythmicity was observed when adjusting for: 1. BMI: glucose (p< 0.001), triglyceride (p< 0.001), insulin (p< 0.001), HOMA-IR (p< 0.001) and ADIPO-IR (p< 0.001); 2. Physical activity: glucose (p< 0.001), triglyceride (p= 0.006) and ADIPO-IR (p= 0.038); 3. Cardiorespiratory fitness: triglyceride (p= 0.041), insulin (p= 0.002), HOMA-IR (p= 0.004) and ADIPO-IR (p= 0.004). Triglyceride amplitude, but not acrophase, was greater in the high physical activity category compared to low (p=0.018). Conclusions Rhythmicity in insulin sensitivity and associated metabolites across the menstrual cycle are modified by BMI, physical activity and cardiorespiratory fitness.

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Vascular dysfunction and insulin stimulated blood flow : impact of physical inactivity and type 2 diabetes

10.32469/10355/48201 ◽

2014 ◽

Author(s):

◽

Leryn J. Boyle

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Blood Flow ◽

Insulin Sensitivity ◽

Endothelial Function ◽

Physical Inactivity ◽

Vascular Dysfunction ◽

Insulin Stimulation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.

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Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides

International Journal of Molecular Sciences ◽

10.3390/ijms21041514 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1514 ◽

Cited By ~ 4

Author(s):

Paul T. Reidy ◽

Ziad S. Mahmassani ◽

Alec I. McKenzie ◽

Jonathan J. Petrocelli ◽

Scott A. Summers ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

Muscle Contraction ◽

Contractile Activity ◽

Skeletal Muscle Insulin Resistance ◽

Ceramide Content ◽

Subcellular Compartmentalization ◽

Skeletal Muscle Insulin Sensitivity

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

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Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study

Diabetes Care ◽

10.2337/diacare.22.4.562 ◽

1999 ◽

Vol 22 (4) ◽

pp. 562-568 ◽

Cited By ~ 185

Author(s):

S. M. Haffner ◽

R. D'Agostino ◽

L. Mykkanen ◽

R. Tracy ◽

B. Howard ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Risk ◽

Insulin Sensitivity ◽

Cardiovascular Risk Factors ◽

Insulin Resistance Atherosclerosis Study

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Changes Induced by Physical Activity and Weight Loss in the Morphology of Intermyofibrillar Mitochondria in Obese Men and Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0002 ◽

2006 ◽

Vol 91 (8) ◽

pp. 3224-3227 ◽

Cited By ~ 77

Author(s):

Frederico G. S. Toledo ◽

Simon Watkins ◽

David E. Kelley

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Weight Loss ◽

Insulin Sensitivity ◽

Lifestyle Modification ◽

Vastus Lateralis ◽

Vastus Lateralis Muscle ◽

Mitochondrial Content ◽

The Mean

Abstract Context: In obesity, skeletal muscle insulin resistance may be associated with smaller mitochondria. Objective: Our objective was to examine the effect of a lifestyle-modification intervention on the content and morphology of skeletal muscle mitochondria and its relationship to insulin sensitivity in obese, insulin-resistant subjects. Design: In this prospective interventional study, intermyofibrillar mitochondrial content and size were quantified by transmission electron microscopy with quantitative morphometric analysis of biopsy samples from vastus lateralis muscle. Systemic insulin sensitivity was measured with euglycemic hyperinsulinemic clamps. Setting: The study took place at a university-based clinical research center. Participants: Eleven sedentary, overweight/obese volunteers without diabetes participated in the study. Intervention: Intervention included 16 wk of aerobic training with dietary restriction of 500-1000 kcal/d. Main Outcome Measures: We assessed changes in mitochondrial content and size and changes in insulin sensitivity. Results: The percentage of myofiber volume occupied by mitochondria significantly increased from 3.70 ± 0.31 to 4.87 ± 0.33% after intervention (P = 0.01). The mean individual increase was 42.5 ± 18.1%. There was also a change in the mean cross-sectional mitochondrial area, increasing from a baseline of 0.078 ± 0.007 to 0.091 ± 0.007 μm2 (P < 0.01), a mean increase of 19.2 ± 6.1% per subject. These changes in mitochondrial size and content highly correlated with improvements in insulin resistance (r = 0.68 and 0.72, respectively; P = 0.01). Conclusions: A combined intervention of weight loss and physical activity in previously sedentary obese adults is associated with enlargement of mitochondria and an increase in the mitochondrial content in skeletal muscle. These findings indicate that in obesity with insulin resistance, ultrastructural mitochondrial plasticity is substantially retained and, importantly, that changes in the morphology of mitochondria are associated with improvements in insulin resistance.

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Low Insulin Sensitivity (Si = 0) in Diabetic and Nondiabetic Subjects in the Insulin Resistance Atherosclerosis Study: Is it associated with components of the metabolic syndrome and nontraditional risk factors?

Diabetes Care ◽

10.2337/diacare.26.10.2796 ◽

2003 ◽

Vol 26 (10) ◽

pp. 2796-2803 ◽

Cited By ~ 45

Author(s):

S. M. Haffner ◽

R. D'Agostino ◽

A. Festa ◽

R. N. Bergman ◽

L. Mykkanen ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Insulin Sensitivity ◽

The Metabolic Syndrome ◽

Insulin Resistance Atherosclerosis Study

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An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women: Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants (Preprint)

10.2196/preprints.9098 ◽

2017 ◽

Author(s):

Julia H Goedecke ◽

Amy E Mendham ◽

Louise Clamp ◽

Pamela A Nono Nankam ◽

Melony C Fortuin-de Smidt ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

South African ◽

Exercise Intervention ◽

African Women ◽

Control Group ◽

Intravenous Glucose ◽

Black South African ◽

Causal Pathways

BACKGROUND The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D. OBJECTIVE The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women. METHODS A total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks. RESULTS The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05). CONCLUSIONS The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention. CLINICALTRIAL Pan African Clinical Trial Registry PACTR201711002789113; http://www.pactr.org/ATMWeb/ appmanager/atm/atmregistry?_nfpb=true&_pageLabel=portals_app_atmregistry_portal_page_13 (Archived by WebCite at http://www.webcitation.org/6xLEFqKr0)

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