Glycemic Variability Is Associated With Reduced Cardiac Autonomic Modulation in Women With Type 2 Diabetes

Abstract

OBJECTIVETo investigate the sex differences in cardiac autonomic modulation in patients with newly diagnosed type 2 diabetes and to determine whether cardiac autonomic modulation is associated with glycemic variability. RESEARCH DESIGN AND METHODSWe investigated a cohort consisting of 48 men and 39 women with non-insulin-treated type 2 diabetes and a known duration of diabetes <5 years. All patients were equipped with a continuous glucose monitoring sensor for 3 days, and the mean amplitude of glycemic excursions (MAGE) was calculated to obtain individual glycemic variability. Cardiac autonomic modulation was quantified by analysis of heart rate variability (HRV) in time and frequency domains and during cardiovascular reflex tests (response to standing [RS], deep breathing [expiration-inspiration], and Valsalva maneuver). RESULTSSex differences in age-and heart rate-adjusted HRV measures were observed in both active and passive tests. Low frequency (LF; P = 0.036), LF/high frequency (HF; P < 0.001), and RS (P = 0.006) were higher in men, whereas expiration-inspiration (P < 0.001), but not HF, was higher in women. In women, reduced cardiac autonomic modulation as assessed by the standard deviation of normal-to-normal intervals (P = 0.001), the root mean square of successive differences (P = 0.018), LF (P < 0.001), HF (P = 0.005), total power (P = 0.008), RS ratio (P = 0.027), and expiration-to-inspiration ratio (P = 0.006) was significantly associated with increased glycemic variability as assessed by MAGE. This was not the case in men. The association in women persisted in a multivariate regression analysis controlling for weight, mean heart rate, blood pressure (systolic), and triglycerides. CONCLUSIONSIn patients with newly diagnosed and well-controlled type 2 diabetes, increased glycemic variability was associated with reduced cardiac autonomic modulation in women but not in men.Evidence points toward a cardioprotective effect of sex hormones (estrogen and progesterone) in premenopausal women, one possibly mediated through improved cardiac autonomic balance both centrally and peripherally by suppression of sympathetic tone and elevation of parasympathetic tone (1,2). The presence of diabetes has been shown to reduce the sex difference and minimize cardioprotection in

Differential Patterns of Impaired Cardiorespiratory Fitness and Cardiac Autonomic Dysfunction in Recently Diagnosed Type 1 and Type 2 Diabetes

“…An explanation for the presence of CAN in recent-onset diabetes could be that HRV is impaired by early subtle glucometabolic disturbances. A recent study reported associations between glycemic variability and reduced cardiac autonomic modulation in patients with newly diagnosed and long-term type 2 diabetes (36). In line with this, nondiabetic hyperinsulinemia was associated with decreased HRV in the Atherosclerosis Risk in Communities (ARIC) study (37).…”

Glycaemic variability in diabetes: clinical and therapeutic implications

“…64,65 A reduced cardiac autonomic modulation is evident in women with T2D with high GV. 66 There is also considerable interest for the emerging association between GV and the decline of cognitive function. 67,68 HbA1c variability appears to predict symptoms of depression in elderly individuals with T2D, 69 including the risk of developing the Alzheimer disease.…”

Glycemic variability and subsequent malignancies among the population without diabetes

“…Although direct research that evaluated the association between hormone variability and the development of cancer was not published, hormonal disturbance may be served as the mediator between development of cancer and glycemic variability. The association between glycemic variability and hormonal disturbance was previously reported, even though it is still in controversy whether change of hormone may cause glycemic disturbance [34,35], or vice versa [36]. In terms of the association between variability in hormone and cancer, it was also previously reported [37].…”