Acute changes of glucose and insulin levels during oral glucose tolerance test are related to changes in LV myocardial deformation, untwisting and coronary flow reserve

Increased arterial stiffness caused by insulin resistance may impair LV function. We investigated whether first degree relatives of diabetics have similar changes of coronary microcirculation and myocardial twisting with diabetics during an oral glucose tolerance test (OGTT). Methods: In 76 subjects, we measured glucose, insulin, pulse wave velocity (PWVa) and augmentation index (AI) (Arteriograph) at 0, 30, 60, 90 and 120 min of OGTT. At 0 and 120 min, we measured a)E', A' and E'/A' mitral annular velocities using tissue Doppler b) LV longitudinal systolic (LGSr-l/s) and diastolic strain rate (LGSrE), twisting (Tw-deg), twisting (Tw–deg/sec) and untwisting (unTw)velocity using speckle tracking echocardiography c) coronary flow reserve (CFR) using Doppler echocardiography. We assessed insulin resistance using insulin sensitivity index (ISI- includes both insulin and glucose throughout OGTT). Results: Thirty-six subjects who were first degree relatives of diabetics had normal OGTT (relatives), 20 had normal OGTT and no family history of diabetes (normals), and 20 had abnormal OGTT (diabetics). Compared to normals, diabetics and relatives had both higher baseline PWVa (9.3±2 vs. 8.1±2 vs. 7.2±1.6), AI (23±9 vs. 24±14, 18±1), insulin (median 14 vs. 15 vs. 10 μU/ml), and lower ISI (50±24 vs. 73.±22 vs. 93±17), E'/A' (0.7±0.2 vs. 0.98±0.2 vs 1.1±0.3) LGSr (-0.95±0.1 vs. -0.94±0.1 vs. -1.1±15) LGSrE (0.98±0.1 vs. 1.±0.1 vs 1.3±15), Tw (15±7 vs. 13±5 vs. 17±7) and unTwvelocity (-95±31 vs. -94±40 vs. 116±36) and lower CFR (2.7±1.1 vs. 2.6±0.9 vs. 3.0±0.6) (p<0.05). Insulin was increased at 120min, to 521% in diabetics, 293% in relatives and 190% in normals (p<0.05). PWVa was increased at 120min to 8.9 (10%) in relatives, was reduced to 6.8 (6%) in normals and remained high (9.4±2m/s) in diabetics (p<0.05). Tw and unTwvelocity at 120min, was increased to 17 (13%) and -105 (10%) in diabetics, to 15 (15%) and -105 (10%) in relatives and was reduced to 13 (24%) and -87 (25%) in normals (p<0.05). CFR was decreased to 2.4 (14%) in diabetics, 2.3 (12%) in relatives and 2.8 (6%) in normals (p<0.05). ISI, insulin and glucose at 120 min were related with PWV, CFR, LGSr, LGSrE, TW,Twvelocity unTwvelocity and E'/A' and PWV was related with LGSr E, Tw, Tw velocity, unTw velocity and E'/ A'(in both diabetics and relatives (p<0.05). Conclusions: Acute hyperglycemia and hyperinsulinemia during OGTT are related with abnormal LV myocardial deformation, twisting and untwisting possibly through increases in arterial stiffness and impairment of coronary microcirculatory function in first degree relatives and diabetics