Progressive Hyperglycemia across the Glucose Tolerance Continuum in Older Obese Adults Is Related to Skeletal Muscle Capillarization and Nitric Oxide Bioavailability
Open Access
- 1 May 2011
- journal article
- other
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 96 (5), 1377-1384
- https://doi.org/10.1210/jc.2010-2069
Abstract
Context: Reduced tissue nutrient exposure may aid in the progression of glucose intolerance. Objective: The aim of the study was to examine peripheral tissue glucose disposal in relation to muscle capillarization and plasma nitric oxide bioavailability. Design: Participants were carefully matched for age, adiposity, and lipid status and stratified into normal (n = 20), impaired (n = 20), and type 2 diabetic (n = 20) glucose-tolerant groups. Setting: The study was conducted in an outpatient setting at a Clinical Research Unit. Participants: Older, obese men and women (n = 60; age, 65 ± 1 yr; body mass index, 32.7 ± 0.5 kg/m2) participated in the study. Intervention: We performed a cross-sectional study. Main Outcome Measures: Body composition, energy metabolism, aerobic fitness (maximum oxygen consumption), insulin sensitivity (glucose clamp), vastus lateralis muscle morphology, and plasma nitric oxide were assessed. Results: Although subjects were identical with respect to age, body composition, energy expenditure, and lipid status, insulin-stimulated glucose disposal and maximum oxygen consumption showed progressive decline with increasing glucose intolerance. Muscle fiber type composition and mitochondrial density were not different between groups. However, capillary density markedly declined with advancing glucose intolerance (1.86 ± 0.31, 1.70 ± 0.28, 1.42 ± 0.24 capillary/fiber; P < 0.05), a trend that was mirrored by fasting plasma nitric oxide concentrations (26.3 ± 3.6, 19.8 ± 2.3, 15.2 ± 2.1 μmol/liter; P < 0.05). Furthermore, skeletal muscle capillary density correlated with insulin sensitivity (r = 0.65; P < 0.001). Conclusions: Impaired muscle capillarization and reduced nutrient exposure to the metabolizing tissue may play a major role in the progression of insulin resistance across the glucose tolerance continuum, independent of age, adiposity, lipid status, and resting energy metabolism. These data also highlight plasma nitric oxide as a potential surrogate marker of these impairments and may be indicative of the progression toward type 2 diabetes.Keywords
This publication has 40 references indexed in Scilit:
- Diagnosis and Classification of Diabetes MellitusDiabetes Care, 2010
- Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxideClinical Science, 2009
- Randomized trial on the effects of a 7-d low-glycemic diet and exercise intervention on insulin resistance in older obese humansThe American Journal of Clinical Nutrition, 2009
- Infusing Lipid Raises Plasma Free Fatty Acids and Induces Insulin Resistance in Muscle MicrovasculatureJournal of Clinical Endocrinology & Metabolism, 2009
- Obesity Blunts Microvascular Recruitment in Human Forearm Muscle After a Mixed MealDiabetes Care, 2009
- From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes MellitusDiabetes, 2009
- Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adultsJournal of Applied Physiology, 2008
- Patients with type 2 diabetes have normal mitochondrial function in skeletal muscleDiabetologia, 2007
- Exercise Restores Skeletal Muscle Glucose Delivery But Not Insulin-Mediated Glucose Transport and Phosphorylation in Obese SubjectsJournal of Clinical Endocrinology & Metabolism, 2006
- The Microvasculature in Insulin Resistance and Type 2 DiabetesSeminars in Vascular Medicine, 2002