OBJECTIVE-The effect of glycemic variability (GV) on cardiovascular risk has not been fully clarified in type 2 diabetes. We evaluated the effect of GV, blood pressure (BP), and oxidative stress on intima-media thickness (IMT), left ventricular mass index (LVMI), flow-mediated dilation (FMD), and sympathovagal balance (low frequency [LF]/high frequency [HF] ratio) in 26 type 2 diabetic patients (diabetes duration 4.41 6 4.81 years; HbA 1c 6.70 6 1.25%) receiving diet and/or metformin treatment, with no hypotensive treatment or complications.RESEARCH DESIGN AND METHODS-Continuous glucose monitoring (CGM) data were used to calculate mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA)-2, mean blood glucose (MBG), mean postprandial glucose excursion (MPPGE), and incremental area under the curve (IAUC). Blood pressure (BP), circadian rhythm, and urinary 15-F2t-isoprostane (8-iso-prostaglandin F 2a [PGF 2a ]) were also evaluated. Subjects were divided into dipper (D) and nondipper (ND) groups according to DBP.RESULTS-IMT and LVMI were increased in ND versus D (0.77 6 0.08 vs. 0.68 6 0.13 [P = 0.04] and 67 6 14 vs. 55 6 11 [P = 0.03], respectively). MBG, MAGE, and IAUC were significantly associated with LF/HF ratio at night (r = 0.50, P = 0.01; r = 0.40, P = 0.04; r = 0.41, P = 0.04, respectively), MPPGE was negatively associated with FMD (r = 20.45, P = 0.02), and CONGA-2 was positively associated with LVMI (r = 0.55, P = 0.006). The Dsystolic BP was negatively associated with IMT (r = 20.43, P = 0.03) and with LVMI (r = 20.52, P = 0.01). Urinary 8-iso-PGF 2a was positively associated with LVMI (r = 0.68 P , 0.001).CONCLUSIONS-An impaired GV and BP variability is associated with endothelial and cardiovascular damage in short-term diabetic patients with optimal metabolic control. Oxidative stress is the only independent predictor of increased LV mass and correlates with glucose and BP variability.

We have recently reported, in a small cohort of subjects, that acrosome reaction (AR) and intracellular free calcium ([Ca2+]i) increase in response to progesterone were significantly correlated with in-vitro fertilization (IVF) rate. In the present study we extended these results to 90 subjects undergoing IVF. We confirm that both parameters were highly significantly correlated with the fertilization rate (P < 0.001). In particular, significantly lower responses to progesterone were detected in subjects with a fertilization rate < 50%, further enlightening the functional significance of sperm responsiveness to progesterone with respect to the process of fertilization. Moreover, we report here that both tests are highly discriminant of fertilization success, with positive predictive values > 90% for [Ca2+]i values which increase by > 1.2-fold and AR inducibility > 7% (cut-off values). Conversely, AR following challenge with the calcium ionophore A23187 was less significantly correlated with the percentage fertilization rate (P < 0.05), and showed lower predictive values than response to progesterone. All these tests ([Ca2+]i increase in response to progesterone, AR in response to progesterone and to A23187) appear highly sensitive and moderately specific. The positive predictive value may rise to > 95% when the combination of two tests ([Ca2+]i and inducibility of AR in response to progesterone) is considered. No correlation with fertilization rate has been found for spontaneous AR or basal [Ca2+]i. In conclusion, we propose that assessment of human sperm responsiveness to progesterone may be clinically useful in predicting fertilizing ability in vitro.

Neurovascular coupling (NVC) and dynamic cerebral autoregulation (dCA) are both impaired in the acute phase of ischemic stroke, but their reciprocal interactions are difficult to predict. To clarify these aspects, the present study explored NVC in a healthy volunteer population during a surrogate state of impaired dCA induced by hypercapnia. This study aimed to test whether hypercapnia leads to a depression of NVC through an impairment of dCA. Continuous recordings of middle cerebral arteries cerebral blood flow velocity (CBFv), blood pressure (BP), heart rate, and end-tidal CO2 were performed in 19 right-handed subjects (aged >45 yr) before, during, and after 60 s of a passive paradigm during normocapnia and hypercapnia. The CBFv response was broken down into subcomponents describing the relative contributions of BP (VBP), critical closing pressure (VCrCP), and resistance area product (VRAP). VRAP reflects myogenic activity in response to BP changes, whereas VCrCP is more indicative of metabolic control. The results revealed that hypercapnia significantly affected NVC, with significant reductions in the relative contribution of VCrCP to the paradigm-induced increase in CBFv. The present study suggests that hypercapnia impairs both dCA and NVC, probably acting through an impairment of the metabolic component of CBF control.

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PaCO2 affects cerebral blood flow (CBF) and its regulatory mechanisms, but the interaction between neurovascular coupling (NVC), cerebral autoregulation (CA), and cerebrovascular reactivity to CO2 (CVR), in response to hypercapnia, is not known. Recordings of cerebral blood flow velocity (CBFv), blood pressure (BP), heart rate, and end‐tidal CO2 (EtCO2) were performed in 18 subjects during normocapnia and 5% CO2 inhalation while performing a passive motor paradigm. Together with BP and EtCO2, a gate signal to represent the effect of stimulation was used as input to a multivariate autoregressive‐moving average model to calculate their separate effects on CBFv. Hypercapnia led to a depression of dynamic CA at rest and during stimulation in both hemispheres (P <0.02) as well as impairment of the NVC response, particularly in the ipsilateral hemisphere (P <0.01). Neither hypercapnia nor the passive motor stimulation influenced CVR. Dynamic CA was not influenced by the motor paradigm during normocapnia. The CBFv step responses to each individual input (BP, EtCO2, stimulation) allowed identification of the influences of hypercapnia and neuromotor stimulation on CA, CVR, and NVC, which have not been previously described, and also confirmed the depressing effects of hypercapnia on CA and NVC. The stability of CVR during these maneuvers and the lack of influence of stimulation on dynamic CA are novel findings which deserve further investigation. Dynamic multivariate modeling can identify the complex interplay between different CBF regulatory mechanisms and should be recommended for studies involving similar interactions, such as the effects of exercise or posture on cerebral hemodynamics.