225-LB: Impaired Microvascular Responses May Explain Health Disparities and Impaired Metabolic Flexibility in Hispanic Residents of the Rio Grande Valley

Abstract

Purpose: Impaired skeletal muscle microvascular blood flow (MBF) is one of the earliest pathophysiologies of type 2 diabetes (T2D) . People with a family history of T2D (FH+ are at greater risk for developing T2D than those with no family history (FH-) . Further, we have shown that normoglycemic Caucasian FH+ individuals have impaired skeletal muscle microvascular responses and metabolic flexibility (MF - ability to switch substrate oxidation upon stimulation) to a mixed meal challenge (MMC) when compared with matched FH- (p<0.01) , suggesting early vascular insulin resistance. Mexican Hispanic individuals have the highest prevalence of T2D in the US and make up ∼95% of Hispanic residents of the Rio Grande Valley (HRGV) where T2D diagnosis rates are ∼3x the national average. Therefore, we sought to determine if impaired MBF responses are present in healthy HRGV. Methods: 15 FH- and 13 FH+ HRGV were recruited to assess MF and MBF responses to a MMC. MF was measured via indirect calorimetry and MBF via contrast-enhanced ultrasound while fasting and again 60-min post MMC. Results: No changes in skeletal MBF were noted in FH- (1.21 ± 0.53 SEM and 0.86 ± 0.23 SEM fasting and postprandial MBF respectively) or FH+ (2.17 ± 0.98 SEM and 1.49 ± 0.66 SEM fasting and postprandial MBF respectively) groups. Abdominal adipose MBF responses increased in FH+ (-2.3 ± 0.71 SEM, p=0.004) , but not in FH- (-0.49 ± 0.39 SEM p=0.39) . FH+ display impaired postprandial metabolic flexibility (MF) responses during 60-min of testing post-MMC. Neither blood glucose responses (99.3 ± 1.3 SEM and 102.27 ± 2.1 SEM fasting and post-prandial respectively, p=0.2) nor body composition differed between FH groups. Conclusions: HRGV display impaired skeletal muscle MBF responses, indicating early vascular insulin resistance. Further, the impairment in MF in FH+ may be partially explained by increased adipose MBF responses, as adipose is less metabolically active than skeletal muscle. Disclosure R. D. Russell: None. Y. Tai: None. S. Marupudi: None.