Progressive hyperglycemia across the glucose tolerance continuum in older obese adults is related to skeletal muscle capillarization and nitric oxide bioavailability.

contextReduced tissue nutrient exposure may aid in the progression of glucose intolerance.

objectiveThe aim of the study was to examine peripheral tissue glucose disposal in relation to muscle capillarization and plasma nitric oxide bioavailability.

designParticipants 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.

settingThe study was conducted in an outpatient setting at a Clinical Research Unit.

participantsOlder, obese men and women (n = 60; age, 65 ± 1 yr; body mass index, 32.7 ± 0.5 kg/m(2)) participated in the study.

interventionWe performed a cross-sectional study.

main outcome measuresBody composition, energy metabolism, aerobic fitness (maximum oxygen consumption), insulin sensitivity (glucose clamp), vastus lateralis muscle morphology, and plasma nitric oxide were assessed.

resultsAlthough 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).

conclusionsImpaired 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.