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CLINICAL RESEARCH: VASCULAR DISEASE AND DIABETES

Abnormal Skeletal Muscle Capillary Recruitment During Exercise in Patients With Type 2 Diabetes Mellitus and Microvascular Complications

Lisa Womack, MS^_*, Dawn Peters, PhD, Eugene J. Barrett, MD, PhD^_*, Sanjiv Kaul, MD, Wendie Price, RN^_* and Jonathan R. Lindner, MD^,_*

^_* General Clinical Research Center and Endocrinology Division, University of Virginia, Charlottesville, Virginia
Division of Cardiovascular Medicine, Oregon Health & Science University, Portland, Oregon

Manuscript received November 12, 2008; revised manuscript received January 29, 2009, accepted February 23, 2009.

^_* Reprint requests and correspondence: Dr. Jonathan R. Lindner, Cardiovascular Division, UHN-62, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239 (Email: lindnerj{at}ohsu.edu).

Objectives: We sought to determine whether skeletal muscle capillary recruitment is impaired in type 2 diabetes mellitus (DM) with and without microvascular complications (MC).

Background: Insulin and exercise each stimulate recruitment of skeletal muscle capillaries. Insulin-mediated recruitment is impaired in insulin-resistant humans and animals, but exercise-mediated recruitment has not been studied.

Methods: We studied 20 control subjects, 22 patients with DM, and 8 patients with DM + MC. With the patients under fasting conditions, contrast-enhanced ultrasound perfusion imaging of the forearm flexor muscles was performed to evaluate capillary blood flow and blood volume at rest and during low- or high-intensity contractile exercise (25% and 80% maximal handgrip). Rheologic parameters of erythrocyte deformability and plasma viscosity were measured.

Results: Muscle capillary responses to exercise were similar between the control and DM groups, but were reduced (p < 0.05) in those with DM + MC. The DM + MC group had a 50% reduction in capillary recruitment and a 60% to 70% reduction in capillary blood flow during both low- and high-intensity exercise compared with the control group. These abnormalities were independent of disease duration. Patients with DM + MC were more insulin resistant than DM patients and had an elevated whole blood viscosity that correlated with plasma glucose (p = 0.001) and C-reactive protein (p = 0.003).

Conclusions: Capillary recruitment during low- and high-intensity exercise is normal in uncomplicated type 2 DM but is impaired in those with microvascular complications. Abnormalities in capillary recruitment may be related to abnormal hemorheology, although larger trials are needed to establish this relation.

Key Words: diabetes mellitus • contrast ultrasound • microvascular dysfunction • muscle perfusion • microbubbles

Abbreviations and Acronyms   CBV = capillary blood volume   CEU = contrast-enhanced ultrasound   CRP = C-reactive protein   DM = diabetes mellitus   DM + MC = diabetes mellitus with microvascular complications   NO = nitric oxide   PI = pulsing interval   VI = video intensity

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