Background-The aim of this study was to elucidate the effect of repetitive fluctuations in blood glucose concentrations on monocyte adhesion to the aortic endothelium. Methods and Results-Nonobese type 2 diabetes, Goto-Kakizaki (GK) rats were fed twice daily to induce repetitive postprandial glucose spikes. Then, we compared the number of monocytes adherent to the endothelium of thoracic aorta in these rats with that in rats fed ad libitum. To suppress the glucose spikes, rats were injected with an inhibitor of sodium-glucose transporter, phloridzin, just before each meal for 12 weeks. GK rats fed twice daily showed significantly lower HbA 1c than GK rats fed ad libitum. However, the former group showed markedly higher number of monocytes adherent to the endothelium than the latter, together with increased arterial intimal thickening. Phloridzin significantly reduced the number of adherent monocytes in GK rats fed twice daily. Conclusion-Our

Taste and smell perception, particularly taste perception, were associated with a greater risk of frailty in community-dwelling elderly people. These results suggest that lower taste and smell perception may be an indicator of frailty in old age.

There is a growing body of evidence that postprandial hyperglycaemia plays an important role in accelerated atherosclerosis and may be a therapeutic target for preventing cardiovascular disease (CVD) in diabetes. However, there is no convenient biomarker that could reflect cumulative postprandial hyperglycaemia in diabetes. We have recently found that glyceraldehyde can rapidly react with amino groups of proteins to form glyceraldehyde-derived advanced glycation end products (AGEs), which evoke vascular inflammation and endothelial dysfunction, thereby being implicated in accelerated atherosclerosis in diabetes. In this study, we examined whether glyceraldehyde-derived AGEs were a biomarker that could reflect cumulative postprandial hyperglycaemia in Goto-Kakizaki (GK) rats fed twice a day. GK rats at 8 weeks of age were divided into 2 groups; either the vehicle (VEH) or 50 mg/kg of nateglinide (NAT) was administered twice daily just before each meal. After 6 weeks, nateglinide treatment was found to not only prevent postprandial hyperglycaemia, but also reduce glyceraldehyde-derived AGE levels in GK rats fed twice a day. However, there was no significant difference in HbA1c or glucose-derived AGE levels between the two groups. The present study demonstrated for the first time that glyceraldehyde-derived AGEs, but not HbA1c or glucose-derived AGEs, were a biomarker that could reflect cumulative postprandial hyperglycaemia in diabetic rats. Glyceraldehyde-derived AGEs may be a novel therapeutic target for preventing CVD in diabetes.

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Background Multisite pain, including low-back and knee pain, is a major health issue that greatly decreases quality of life. Objectives This study analyzed the effects of l-serine, which provides necessary components for nerve function, and EPA, which exerts anti-inflammatory properties, on pain scores of adults with pain in at least the low back and knee for ≥3 mo. Methods This was a randomized, double-blind, placebo-controlled, parallel-group study. The Japan Low Back Pain Evaluation Questionnaire (JLEQ) and Japanese Knee Osteoarthritis Measure (JKOM) were applied as primary outcomes. The Brief Pain Inventory (BPI) and safety evaluation were secondary outcomes. We enrolled 120 participants aged ≥20 y (36 men and 84 women: mean ± SD age = 40.8 ± 10.9 y). The participants were randomly allocated to either the active group (daily ingestion of 594 mg l-serine and 149 mg EPA) or placebo group. The study period consisted of 8-wk dosing and 4-wk posttreatment observation. ANCOVA between groups for each time point was conducted using the baseline scores as covariates. Results The JLEQ scores (active compared with placebo: 14.2 ± 11.2 compared with 19.0 ± 10.2) at week 8 were lower in the active group (P < 0.001). The JKOM scores at week 4 (11.7 ± 9.0 compared with 13.9 ± 7.9), week 8 (10.4 ± 7.9 compared with 13.1 ± 7.1), and week 12 (10.3 ± 7.4 compared with 13.8 ± 7.5) were lower in the active group (P ≤ 0.04). Additionally, the active group had 11–27% better scores compared with the placebo group for BPI1 (worst pain), BPI3 (average pain), and BPI5D (pain during moving) at week 4 (P ≤ 0.028) and week 8 (P ≤ 0.019), respectively, and BPI5D was 23% better in the active group at week 12 (P = 0.007). No adverse events were observed. Conclusions l-Serine and EPA were effective for pain relief in adults with low-back and knee pain after multiplicity adjustment. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000035056.

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Abnormalities in early insulin secretion are closely associated with the pathogenesis of various disease conditions that combine to characterize type 2 diabetes, suggesting that normalizing early insulin response in portal blood represents an important treatment not only for postprandial hyperglycaemia but also for postprandial hyperlipidaemia.