Impact of prior cerebrovascular disease and glucose status on incident cerebrovascular disease in Japanese.

BACKGROUND: Although both a history of cerebrovascular disease (CVD) and glucose abnormality are risk factors for CVD, few large studies have examined their association with subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose status, and their combinations on subsequent CVD using real-world data. METHODS: This is a retrospective cohort study including 363,627 men aged 18-72 years followed for ≥ 3 years between 2008 and 2016. Participants were classified as normoglycemia, borderline glycemia, or diabetes defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD (i.e. ischemic stroke, transient ischemic attack, and non-traumatic intracerebral hemorrhage) were identified according to claims using ICD-10 codes, medical procedures, and questionnaires. RESULTS: Participants' mean age was 46.1 ± 9.3, and median follow up was 5.2 (4.2, 6.7) years. Cox regression analysis showed that prior CVD + conferred excess risk for CVD regardless of glucose status (normoglycemia: hazard ratio (HR), 8.77; 95% CI 6.96-11.05; borderline glycemia: HR, 7.40, 95% CI 5.97-9.17; diabetes: HR, 5.73, 95% CI 4.52-7.25). Compared with normoglycemia, borderline glycemia did not influence risk of CVD, whereas diabetes affected subsequent CVD in those with CVD- (HR, 1.50, 95% CI 1.34-1.68). In CVD-/diabetes, age, current smoking, systolic blood pressure, high-density lipoprotein cholesterol, and HbA1c were associated with risk of CVD, but only systolic blood pressure was related to CVD risk in CVD + /diabetes. CONCLUSIONS: Prior CVD had a greater impact on the risk of CVD than glucose tolerance and glycemic control. In participants with diabetes and prior CVD, systolic blood pressure was a stronger risk factor than HbA1c. Individualized treatment strategies should consider glucose tolerance status and prior CVD.

Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation of the sodium-glucose cotransporter-2 inhibitor tofogliflozin.

Sodium-glucose cotransporter-2 inhibitors (SGLT2) are drugs that have been reported to have several effects through the regulation of plasma volume, for example, antihypertensive effects. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2 inhibitor tofogliflozin on estimated plasma volume (ePV), brain natriuretic peptide (BNP) and the relationship between changes in ePV, BNP and body weight (BW). Data from 157 participants with type 2 diabetes receiving tofogliflozin monotherapy in a phase 3 study were analysed. Changes in variables or correlations among them during a 52-week administration and a 2-week post-treatment period were investigated. Percent change in ePV was calculated using the Strauss formula. Significant decreases in BW, ePV and ln-transformed BNP (ln-BNP) were noted by week 52. %ΔBW was not significantly correlated with %ΔePV and Δln-BNP, while %ΔePV was significantly correlated with Δln-BNP. Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased. %ΔBW was significantly correlated with %ΔePV and Δln-BNP. Furthermore, ePV and BNP were significantly higher than baseline levels.

Neural basis of stimulus-angle-dependent motor control of wind-elicited walking behavior in the cricket Gryllus bimaculatus.

Crickets exhibit oriented walking behavior in response to air-current stimuli. Because crickets move in the opposite direction from the stimulus source, this behavior is considered to represent 'escape behavior' from an approaching predator. However, details of the stimulus-angle-dependent control of locomotion during the immediate phase, and the neural basis underlying the directional motor control of this behavior remain unclear. In this study, we used a spherical-treadmill system to measure locomotory parameters including trajectory, turn angle and velocity during the immediate phase of responses to air-puff stimuli applied from various angles. Both walking direction and turn angle were correlated with stimulus angle, but their relationships followed different rules. A shorter stimulus also induced directionally-controlled walking, but reduced the yaw rotation in stimulus-angle-dependent turning. These results suggest that neural control of the turn angle requires different sensory information than that required for oriented walking. Hemi-severance of the ventral nerve cords containing descending axons from the cephalic to the prothoracic ganglion abolished stimulus-angle-dependent control, indicating that this control required descending signals from the brain. Furthermore, we selectively ablated identified ascending giant interneurons (GIs) in vivo to examine their functional roles in wind-elicited walking. Ablation of GI8-1 diminished control of the turn angle and decreased walking distance in the initial response. Meanwhile, GI9-1b ablation had no discernible effect on stimulus-angle-dependent control or walking distance, but delayed the reaction time. These results suggest that the ascending signals conveyed by GI8-1 are required for turn-angle control and maintenance of walking behavior, and that GI9-1b is responsible for rapid initiation of walking. It is possible that individual types of GIs separately supply the sensory signals required to control wind-elicited walking.