QTc and autonomic neuropathy in diabetes: effects of acute hyperglycaemia and n-3 PUFA.

BACKGROUND AND AIMS: Autonomic function is also regulated by glycaemia and exerts a crucial role in the control of blood pressure and cardiac function. The disruption of this physiological mechanism impacts deeply on cardiovascular mortality in diabetes. We investigated the influence of autonomic dysfunction on QTc interval and on sympatho-vagal balance (LF/HF), in response to acute hyperglycaemia and to membrane electrical stabilization (n-3 PUFA). METHODS AND RESULTS: Twenty-four type 2 diabetic patients, without (N-: n=13) or with (N+: n=11) autonomic neuropathy and 13 healthy subjects (C) underwent BP and ECG monitoring during a 24-h period and during a 2-h hyperglycaemic clamp. Delta QTc during the night was blunted in diabetics (0.5+/-2.5 vs. C: 2.9+/-2.5%, p=0.001), and Delta LF/HF was decreased in N+ (-2.8+/-38.2 vs. C=34.8+/-28.1%, p=0.02). During hyperglycaemia, QTc increased in C; LF/HF significantly increased in C and N-. A 6-month treatment with n-3 PUFA partially restored Delta LF/HF and Delta QTc (2.1+/-1.40, p=0.04 vs. basal) only in N-. CONCLUSION: Hyperglycaemia increases QTc interval and sympathetic activity; electrical membrane stabilization improves autonomic function only in the absence of overt autonomic neuropathy. Strategies to prevent the disruption of autonomic function with newer approaches, other than just glucose control, should be implemented.

Early autonomic dysfunction in glucose-tolerant but insulin-resistant offspring of type 2 diabetic patients.

In type 2 diabetes, both insulin resistance and hyperglycemia are considered responsible for autonomic dysfunction, but the specific role of these two abnormalities is not clear. To test the specific role of insulin resistance on autonomic dysfunction, we studied 69 glucose-tolerant offspring of type 2 diabetic patients, comparing the most insulin-resistant tertile (IR) with the most insulin-sensitive tertile (IS) and comparable control subjects, all undergoing the oral glucose tolerance test, impedentiometry, 24-hour blood pressure and ECG monitoring, and an intravenous glucose tolerance test (IVGTT) followed by a euglycemic hyperinsulinemic clamp, with continuous blood pressure and ECG measurements. Sympathovagal balance was evaluated as low- to high-frequency ratio (LF:HF) by spectral analysis on R-R intervals. The change of systolic and diastolic blood pressure was calculated as [(day-night/d)]x100. In IR, the changes of systolic and diastolic blood pressure were significantly lower versus IS (9.2+/-5.0% versus 12.4+/-3.6%, P<0.02; 13.2+/-6.5% versus 17.4+/-5.2%, P<0.02). During the night, LF:HF fall was reduced in IR (43.1+/-21.0 versus 61.4+/-16.9, P<0.02). Hyperinsulinemia (IVGTT) rapidly and significantly increased LF:HF in IR (4.9+/-3.3 versus basal: 2.3+/-1.4, P=0.03) but not in IS. In offspring of type 2 diabetic patients with normal glucose tolerance and normal blood pressure values, insulin resistance is associated with abnormal control of blood pressure and sympathetic activation. Insulin resistance may therefore be responsible for some early derangements of the autonomic nervous tone control and thus contributes to increase the incidence of arterial hypertension and/or diabetes.