Insulin resistance is an independent factor to determine an exaggerated pressor response to ischemic rhythmic handgrip in non–diabetic older adults
Authors: Hotta Norio , Hori Amane , Okamura Yukiko , Baba Reizo , Watanabe Hidehiro , Sugawara Jun , Kim Han-Kyul , Ishizawa Rie , Iwamoto Gary A , Vongpatanasin Wanpen , Mitchell Jere H , Smith Scott A , Mizuno Masaki 
Published: April 2020

Patients with type 2 diabetes display an exaggerated blood pressure (BP) response during exercise. However, the mechanism(s) underlying this abnormal exercise BP is poorly understood. A previous study demonstrated that the increase in muscle sympathetic nerve activity during post–exercise muscle ischemia (PEMI) is significantly associated with glucose control and insulin resistance markers such as fasting glucose, hemoglobin A1c (HbA1c), and hemoglobin model assessment of insulin resistance (HOMA‐IR) in middle aged type 2 diabetic patients. To date, evidence supporting a similar relationship between the pressor response to exercise and insulin resistance–related factors in non–diabetic older adults remains to be elucidated. It was hypothesized that exercise BP is associated with insulin resistance–related factors in non–diabetic older adults.PURPOSETo investigate the relationship between cardiovascular responses to handgrip exercise and insulin resistance–related factors in non–diabetic older adults.METHODSHealthy male (n=23) and female (n=23) older adults over 60 years without diabetes, chronic heart, kidney, or liver disease, or peripheral arterial disease volunteered to participate. Baseline measurements included: 1) insulin resistance–related factors (fasting blood glucose, HbA1C, insulin, and HOMA‐IR), 2) fasting lipid and lipoprotein levels (triglycerides, LDL and HDL cholesterols), 3) indexes of oxidative stress (derivatives of reactive oxygen metabolite and biological antioxidant potential), 4) oxygen uptake efficiency slope (OUES), an index of cardiorespiratory fitness, and 5) arterial stiffness (heart‐ankle pulse wave velocity: haPWV). We assessed heart rate and BP responses to 1) isometric handgrip of 30% MVC, 2) PEMI induced by tourniqueting the arm after isometric handgrip, 3) passive movement of the wrist during PEMI, and 4) rhythmic dynamic handgrip (RHG) with minimal effort during PEMI.RESULTSDiastolic BP (DBP) response to RHG with PEMI was significantly correlated with males (r=0.44, P=0.02), HbA1c (r=0.33, P=0.03), haPWV (r=0.45, P<0.01), and systolic BP at rest. A forward stepwise multi‐regression analysis revealed that sex (β=0.508) and HbA1c (β=0.341) were significant determinants explaining the variance of DBP response to RHG with PEMI. We also found that DBP response to RHG with PEMI in abnormal HOMA‐IR group (2.5 ≤) (Δ33±3 mmHg) was significantly (P<0.01) greater than that of normal HOMA‐IR group (< 1.6) (Δ22±2 mmHg). No correlation between systolic BP responses and insulin resistance–related factors was found. No correlation between exercise BP and OUES was found.CONCLUSIONSThese data suggest that insulin resistance is significantly associated with the pressor response to exercise, especially ischemic exercise, in non–diabetic older adults.Support or Funding InformationSupported by JSPS KAKENHI JP17K01769, Health Science Center Foundation, and UTSW SHP Interdisciplinary Research Grant Program.