Search

Authors and colleagues have continued clinical diabetic research in the light of Continuous Glucose Monitoring (CGM) and M value. M value is calculated from the daily profile of blood glucose, and it indicates the total numerical value of two factors, which are average blood glucose and mean amplitude of glycemic excursions (MAGE). The case is 53 years old female with Type 1 diabetes mellitus (T1DM), who was on multiple daily insulin injection (MDI). Using FreeStyle Libre, blood glucose was studied for 14 days. Average blood glucose in a day was 169 mg/dL, 163 mg/dL, 164 mg/dL and 166 mg/dL in day 3,5,9,11, respectively with almost same level. In contrast, the levels of the M value distributed widely from 12.5 to 98.3. A discrepancy of HbA1c was found between estimated value and laboratory data on out clinic, which was 7.4% and 8.0%, respectively. These results suggest that there would be rather large difference in MAGE even though the average blood glucose was almost the same in the 4 days. Furthermore, this investigation would be beneficial for check the detail blood glucose variability associated with various activities, and for better and stable control of blood glucose in T1DM.

Glycative stress is a conception of a state that causes an excess of carbohydrate-derived or fatty acid-derived short-chain aldehydes in the body. Short-chain aldehydes, which are highly reactive, undergo a carbonylation process with lysine and arginine residues in proteins and form advanced glycation endproducts (AGEs). When postprandial hyperglycemia occurs, open-ring glucose with exposed aldehyde groups (-CHO) increases and various carbohydrate-derived aldehydes are formed simultaneously (this phenomenon is named “aldehyde sparks”). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is an enzyme abundant intracellularly as the keystone of defense against glycative stress and plays a role in metabolizing highly toxic glyceraldehyde, however, under diabetic conditions, the enzyme activity is markedly reduced by forming S-(2-succinyl) cysteine-GAPDH. We also found that a high-fat diet reduced GAPDH activity and increased glyceraldehyde and methylglyoxal. High animal fat diets in particular require caution because they increase preference dependence on animal fat. In the lipid-rich brain, they promotes the formation of lipid-derived AGEs formed by methylglyoxal and acrolein providing evidence of their close association with amyloid cascade, ultimately leading to the onset of Alzheimer-type dementia. Through the process of amylod beta (Aβ) glycation modification and cross-linking, Aβ polymerization is promoted and deposited in the brain. Thus, neurotoxicity is aggravated. Furthermore, Aβ progresses toward being persistent and Aβ clearance is reduced. Tau proteins similarly undergo glycation modification and trigger polymerization. methylglyoxal or acrolein-derived glycated Aβ clearance by primary microglia cultured cells reduced significantly compared to the unglycated Aβ provides evidence of the reduced clearance upon glycation. It was also shown that melatonin, which promotes glycolytic cross-linking degradation, may promote microglial Aβ phagocytosis. We next plan to examine the potential of plant extracts that promote glycation cross-linking degradation to improve Aβ phagocytosis. Advanced Alzheimer-type dementia with a disoriented neural network hardly recovers with treatment. In this review article, we discussed possible future therapeutic strategies for Alzheimer-type dementia by increasing Aβ clearance from the early stage such as the prevention of Aβ-glycation and the promotion of glycated-Aβ degradation, which may be a paradigm shift.

Diabetes has been a crucial medical and social problem worldwide. For adequate nutritional therapy, there have been discussions concerning Calorie Restriction (CR) and Low Carbohydrate Diet (LCD). We have investigated glucose variability of diabetic patients applying CR, LCD, continuous glucose monitoring (CGM) and applied FreeStyle Libre which is flash glucose monitoring (FGM). The patient is a 40-year-old female with type 2 diabetes mellitus (T2DM), who showed BMI 20.7, postprandial blood glucose 257 mg/dL. HbA1c 12.1%, Glycoalbumin 31.6% (11.6-16.4), serum C-peptide 2.0 ng/ml and unremarkable data of liver function, renal, lipids. She was provided the intervention of three stages, which are i) CR with 60% carbohydrate in Day 1-2, ii) LCD meal with 12% carbohydrate in Day 3-5; iii) LCD + Sodium-glucose cotransporter 2 (SGLT2) inhibitor (Ipragliflozin L-Proline 50mg) in Day 6-12. The glucose profile was measured by FreeStyle Libre Pro (Abbott) for 14 days. The daily profile of blood glucose was abruptly decreased on Day 6. Time percentage of satisfactory blood glucose 70-180 mg/dL (/24h) was 0%, 0%, 2%, 14%, 0%, 54%, 100% in Day 1-7, respectively. These results suppose the acute clinical efficacy of SGLT2 inhibitor, and this report would become a reference for future diabetic practice and research.

Post-fermented tea (dark tea) is produced from enzyme-inactivated fresh tea leaves by microbial fermentation. Batabata tea and Awaban tea are two major dark teas fermented under aerobic and anaerobic conditions, respectively. However, how their chemical compositions and functionalities change during different post-fermentation processes remains unclear. Nuclear magnetic resonance (NMR)-based analyses showed that (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) decreased in Batabata tea during post-fermentation with aerobic molds. In contrast, EGC and EC increased, and pyrogallol was produced in Awaban tea during post-fermentation with lactic acid bacteria (LAB). The anti-glycation activities of two dark teas were investigated using an in vitro assay system with human serum albumin (HSA). The anti-glycation activity decreased in Batabata tea, but it was retained in Awaban tea during post-fermentation. Our results showed that post-fermentation with LAB was an efficient way to enhance phenol content and that pyrogallol contributed to anti-glycation activity of Awaban tea.

Background: Authors have continued research for meal tolerance test (MTT) by calorie restriction diet (CRD) and low carbohydrate diet (LCD), besides M value and glucose variability. Methods: Subjects were 38 patients of two groups. Group-1 has 19 patients (57.6±12.9 years) with type 2 diabetes mellitus (T2DM) and positive glutamic acid decarboxylase antibody (GADA), which is possible to latent autoimmune diabetes in adults (LADA). Group-2 has recruited 19 cases with T2DM and negative GADA, who showed age, sex, glucose variability-matched subjects. They were given CRD on day 1-2, and LCD day 3-14, and biomarkers were compared between Group-1 and Group-2. Results: Average values of the daily profile of blood glucose on day2(CRD)/day4(LCD) in Group-1 vs 2 were studied. Obtained data were 202/148 mg/dL vs 205/143 mg/dL, respectively with similarity. However, M value showed 174/58 vs 179/22, respectively with difference. There were significant correlations of M value between day2 and day4 in Group-1 vs Group-2. Further, both showed contrast tendency, associated with wide distribution vs narrow distribution, respectively. Conclusions: These results suggested that Group-1 with positive GADA may have insufficient pancreas secretion compared with that of Group-2, and these data may become a basal reference for future study of LADA.

Astaxanthin is a carotenoid that is present in high quantities in the meat of fish like salmon and the shells of shrimp and crab. It exhibits free radical scavenging antioxidant activity when consumed di- etarily. Astaxanthin is absorbed by the small intestine before exerting its antioxidant effect; however, a portion of dietary intake remains unabsorbed in the digestive tract and reaches the large intes- tines . We hypothesized that astaxanthin may exert its antioxidant action in the large intestine to influence the gut microbiota. In this review we introduce the results of two studies of astaxanthin. Firstly, a clinical trial targeting post-menopausal women screened for high oxidative stress burden. Astaxanthin was administered orally for eight weeks in order to examine its effects and safety, and subjects were surveyed for any changes in subjective symptoms. Secondly, in a mouse model, real time PCR (polymerase chain reaction) was used to examine the ability of astaxanthin to prevent changes in the enteric flora induced by a high-fat diet. When fat intake increases due to changes in diet, the equilibrium between the various species that constitute the intestinal flora is altered. As a result, degenerative changes in lifestyle-related disease and aging of the host are promoted. Here we find that the intake of astaxanthin was able to inhibit these changes in the gut microbiota of mice induced by a high-fat diet. Even in humans, it is highly probably that the unabsorbed astaxanthin that remains in the intestinal tract exerts a positive effect against disturbance of the intestinal flora caused by a high-fat diet., Astaksantin je karotenoid prisutan u velikom količinama u mesu riba poput lososa i oklopima kozica i rakova. Kada se uzima kao hrana ispoljava svoju sposobnost hvatanja slobodnih radikala i antioksidativnog djelovanja. Prije no što započne svoje antioksidativno djelovanje apsorbira se preko tankog crijeva, međutim , dio ostaje neapsorbiran i dospijeva u debelo crijevo. Razmatrali smo mogućnost da astaksantin pomoću svojih antioksidativnih svojstava može utjecati na crijevnu mikrobiotu. U okviru ovog preglednog rada osvrnut ćemo se na rezultate dvaju istraživanja. Prvo je kliničko ispitivanje usmjereno na postmenopauzalne žene koje su prošle screening na opterećenost oksidativnim stresom. Astaksantin su dobivale oralno kroz 8 tjedana kako bi se procijenili njegovi učinci i sigurnost, a ispitanice su anketirane vezano za promjene u subjektivnim simptomima. Dru- gi, mišji model, koristio je PCR (Lančanu reakciju polimeraze) u pravom vremenu kako bi ispitao potencijal astaksantina u sprječavanju promjena u crijevnoj flori induciranih dijetom bogatom mas- tima. Pri dijeti bogatoj mastima povećava se unos masti što narušava ravnotežu raznih vrsta koje sačinjavaju intestinalnu floru. Posljedična neravnoteža rezultira degenerativnim promjenama i boles- tima vezanima za način života. U ovom istraživanju nalazimo da unos astaksantina može spriječiti promjena u mikrobioti miševa izazvane prehranom bogatom mastima. Čak i u ljudi je za vjerovati da neapsorbirani astaksantin koji ostaje u debelom crijevu ima pozitivan učinak protiv poremećaja uzrokovanih prehranom bogatom mastima.

Background: Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) have been on discussion for years. Authors have continued diabetic research about LCD, CR, Morbus (M) value and insulin secretion. In this study, homeostasis model assessment (HOMA) was investigated. Subjects and Methods: Subjects enrolled were 52 patients with type 2 diabetes mellitus (T2DM) (average 62.3 years). Methods included the measurement of fasting glucose and immunoreactive insulin (IRI), daily profile of blood glucose and M value. Results: The obtained data were as follows: average HbA1c 8.0%, average glucose of daily profile 222 mg/dL. Median data were M value 151, HOMA-R 1.07, HOMA-β 11.1. Divided into 4 groups due to M value, the levels of HOMA-R and HOMA-β in each group were 0.68, 1.08, 1.64, 1.38 and 16.9, 16.3, 10.2, 5.3, respectively. Significant correlation were observed between M value and HOMA-R (p

Background Concerning diabetic nutritional therapy, Calorie Restriction (CR) and Low Carbohydrate Diet (LCD) have been on discussion. Authors continue clinical research related to CR, LCD, Morbus(M) value and insulin secretion. Subjects and Methods Subjects were 42 patients (63.4 years on average) with type 2 diabetes mellitus (T2DM) with its immunoreactive insulin (IRI) =

The passage number of cells refers to the number of subculturing processes that the cells have undergone. The effect of passage number on morphological and phenotypical characteristics of cells is of great importance. Advanced glycation end products have also been associated with cell functionality and characteristics. Murine monocyte RAW 264.7 cells differentiate into osteoclasts upon receptor activation caused by nuclear factor-kappa-Β ligand (RANKL) treatment. This study aims to identify the role of passage number on intracellular advanced glycation end products (AGEs) formation and osteoclastogenic differentiation of RAW 264.7 cells. Western blotting was performed to check intracellular AGE formation along with fluorometric analysis using a microplate reader. Tartrate-resistant acid phosphatase (TRAP) staining was performed to check osteoclastogenic differentiation, and qPCR was realized to check the responsible mRNA expression. Immunofluorescence was used to check the morphological changes. Intracellular AGE formation was increased with passaging, and the higher passage number inhibited multinucleated osteoclastogenic differentiation. Osteoclastogenic gene expression also showed a reducing trend in higher passages, along with a significant reduction in F-actin ring size and number. Lower passages should be used to avoid the effects of cell subculturing in in vitro osteoclastogenesis study using RAW 264.7 cells.

Background: Arguments have continued about Low Carbohydrate Diet (LCD) and Calorie Restriction (CR). Authors have reported clinical research of LCD and Morbus (M) value. Subjects and Methods: Subjects enrolled are 84 patients with Type 2 diabetes mellitus (T2DM), 60.9 ± 10.9 years. The protocol were as follows: 1) CR diet on day 1, 2 with 60% carbohydrates, and LCD on day 3-14 with 12% carbohydrates, 2) Daily profile of blood glucose 7 times a day on day 2 (CR) and day 4 (LCD), 3) urinary C-Peptide radioimmunoassay (u-CPR) excretion, 4) M value calculation, 5) investigation of these data with correlation. Results: Subjects were classified into 4 groups according to M value, which were .4–21, 23–66, 29–192, 200–728, respectively. HbA1c value was 6.2, 8.0, 7.8, 9.2 %, respectively. Blood glucose in median from day 2 to day 4 were 123 to 107 mg/dL, 164 to 130 mg/dL, 193 to 156 mg/dL, 277 to 201 mg/dL, respectively. M value in median from day 2 to 4 was 6.3 to 9, 41 to 7, 108 to 16, 367 to 88, respectively. u-CPR was 88 to 58, 53 to 35, 65 to 52, 74 to 64, respectively. There were significant correlations among among glucose, M value and u-CPR. Discussion and Conclusion: Average glucose, M value and u-CPR decreased remarkably on day 4. As average glucose and M value were higher, decrease degree were larger. These results suggested that carbohydrate in meal would influence glucose variability in T2DM. Our data would become basic data for pathophysiological analysis of glucose variability research in the future.

Background: As to nutritional therapy, continuous discussions were observed concerning calorie restriction (CR) and low-carbohydrate diet (LCD). Authors and colleagues have applied LCD for lots of diabetic patients and reported the detail relationship with ketone bodies and Morbus (M) value. Methods: Ninety-three patients with type 2 diabetes mellitus (T2DM) were considered as subjects in the study, among which 51 were male and 52 were female, 58.3±13.2 years old on average, 60 years old in median. Methods were as follows: 1) patients were admitted and provided formular diet, which included CR diet (60% carbohydrates, 1400 kcal/day) on day 1-2, and LCD (12% carbohydrate, 1400 kcal/day) on day 3-14; 2) several biomarkers on fasting were measured on day 2, 4 and 14; 3) daily profile of blood glucose were done on day 2 and day 4. Results: According to the M-value, subjects were classified into 4 groups, which were less than 25, 26-100, 101-250, more than 251, and number was 24, 24, 24, 21, respectively. The average HbA1c in 4 groups were 6.6%, 7.4%, 8.5% and 9.5% respectively. The median M-values decreased from day 2 to 4, which were 10.4 to 9.1, 53.5 to 7.7, 150 to 19.1 and 438 to 87, respectively. The average uric acid in each group revealed significant increase from day 2 to day 14. There were significant correlation between uric acid increment and creatinine increment, and among creatinine, creatinine clearance (CCr) and Cystatin C. Conclusion: LCD showed efficacy for glucose variability with significant decrease in glucose and M-value. Renal study showed increase of serum uric acid. In addition to correlations of Cystatin C and biomarkers, current results would be from some dehydrated state and/or relative decrease of total calorie intake. These findings would become the fundamental data of efficacy of LCD and its physiological influences for renal function.

Background: Debate between the Calorie Restriction (CR) and Low-Carbohydrate Diet (LCD) has been continued for several years. We have started LCD therapy for diabetic patients since 1999, and experienced good response to control hyperglycemia. Recently the risk of postprandial hyperglycemia for cardiovascular events is reported, and the range of glucose level is focused. Morbus (M) value is proposed to be a good index to show the range of glucose fluctuation. Usefulness of LCD and usefulness of M-value were shown by combined analysis. Methods: Twenty-six patients with Type 2 Diabetes Mellitus (T2DM), who admitted to the Takao Hospital, were the subjects. They were 12 males and 14 females, and their age ranged from 38 to 78 years old. A few patients were new patients, but mostly referred from other hospitals to receive LCD treatment. All patients started from CR therapy with 60% carbohydrate for 2 days, and then carried out LCD dietary therapy with 12% carbohydrates for 10-12 days. On day 2 and 12, blood glucose level was measured at 7 points a day to see the fluctuation from morning to night. Blood and urinary samples were corrected on the same day to get ordinary biochemical data and metabolic marker. Results: To know the effect of LCD on different level of HbA1c, the patients were grouped to low (L; 6.1±0.5%), middle (M; 7.9±0.4%) and high (H; 9.2±0.7%) by HbA1c value. The M-values after 2 day CR were 26.1 (L), 94.1 (M) and 343 (H), respectively. The LCD therapy decreased M-value to 10.4 (L), 18.8 (M) and 84.2 (H), respectively. The significant reduction of M-values was a reflection of the improved postprandial glucose level. LCD was effective even in the bad controlled diabetic patients. In addition to the decreased triacylglycerol and 24 hr urinary C-peptide, uric acid increased in all patients. Conclusion: Ten to 12 day-dietary therapy with LCD was quite effective to improve blood glucose profile. Patients with high HbA1c could be safely treated by LCD. Blood glucose improvement was well correlated to the M-value.

In the anti-aging medicine, we recommend to assess the skin aging by five categories: wrinkle age, spot age, yellow tint age, elasticity age, and moisture age. Photo-aging (oxidative stress) and glycative stress are major causes of age-related deterioration in the skin. Gly- cative stress finally causes skin accumulation of advanced glycation end products(AGEs), inducing yellow tint, and cross linkage between collagen fibers inducing less elastic skin. Oxidative stress causes skin dark spots through the various processes; excess pigment forma- tion and DNA damages. It also causes wrinkle formation associated with matrix metallopro- teinase(MMP) activation and degeneration of collagen and elastin fibers. Study of oxidative and glycative stress may help identify new anti-aging treatments so that we can achieve the skin rejuvenation.

Piceatannol has been reported to have a wide variety of effects on the skin, including promoting collagen production, inhibiting melanin synthesis, inducing the antioxidant glutathione, and eliminating reactive oxygen species. In this study, a randomized, placebo-controlled, double-blind trial was conducted to clinically evaluate the effects of piceatannol-rich passion fruit seed extract on the skin of healthy Japanese women (age, 35-54 y). Thirty-two women with dry skin received either passion fruit seed extract (5 mg piceatannol) or a placebo (dextrin) for 8 wk. Skin hydration and other parameters on the face were assessed at 0, 4, and 8 wk by using specialized equipment. Furthermore, questionnaire interviews were conducted regarding the physical condition of subjects at 0, 4, and 8 wk. The results showed that consumption of passion fruit seed extract led to significant increases in the moisture content of human skin after 4 and 8 wk compared with that before the trial. The amount of transepidermal water loss decreased over time, although the differences were not significant. Moreover, a stratified analysis of subjects with moisture values of ≤200 μS revealed increased moisture content in the passion fruit seed extract group as compared with the placebo group. Furthermore, the results of questionnaires showed significant reductions in "perspiration" and "fatigue" in the passion fruit seed extract group as compared with the placebo group. These results indicate that oral intake of passion fruit seed extract that is rich in piceatannol could improve the moisture of dry skin and reduce fatigue.

Aim Growth hormone (GH) deficiency may be associated with histological progression of non-alcoholic fatty liver disease (NAFLD) which includes non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Insulin-like growth factor 1 (IGF-1) is mainly produced by hepatocytes and its secretion is stimulated by GH. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of IGF-1 in Japanese patients. Methods Serum samples were obtained in 199 Japanese patients with biopsy-proven NAFLD and in 2911 sex- and age-matched healthy people undergoing health checkups. The serum levels of IGF-1 were measured using a commercially available immunoradiometric assay. The standard deviation scores (SDS) of IGF-1 according to age and sex were also calculated in NAFLD patients. Results The serum IGF-1 levels in NAFLD patients were significantly lower (median, 112 ng/mL) compared with the control population (median, 121 ng/mL, P

We assessed the relationship between the number of daily steps and changes in cardiovascular disease (CVD) risk factors in a year-long pedometer-based walking program for physically active older people. A total of 36 physically active older people (68.3 ± 5.8 years) completed this 59-week program. The CVD risk parameters were measured at baseline and at weeks 21 and 59. The mean number of steps increased by week 21 and was maintained at week 59 (approximately 10 000 steps, increase in 1500 steps from the baseline; P < .05). Following a significant reduction in body mass index at week 21, systolic blood pressure levels were significantly reduced, and high-density lipoprotein cholesterol levels were significantly increased at week 59 ( P < .05). In summary, even active older people can achieve further protection against CVD risks by minor, but sustained, physical activity using pedometers for a period of more than 1 year.

Background: The discussion concerning calorie restriction (CR) and low carbohydrate diet (LCD) has been continued for long yeas. As to LCD, we have reported lots of experience and research for glucose variability and ketone bodies. Subjects and methods: Three cases with type 2 diabetes mellitus (T2DM) were on LCD and studied. Methods included 3 patterns of LCD meal which are super, standard and petit LCD, with including carbohydrate ratio 12%, 26% and 40%, respectively. Case 1 (61, M) showed hyperglycemia about 150 mg/dL to 300 mg/dL in daily profile with 12.5% in HbA1c. Starting super LCD therapy, the glucose profile decreased to less than 150 mg/dL and HbA1c decreased to 6.7% in 3 months. Case 2 (53, M) revealed HbA1c 8.3%, weight 110 kg and body mass index 34.5. By super LCD, his weight was decreased 17 kg in 5 months, with normalized HbA1c and elevated serum 3-hydroxybutyric acid (3-OHBA). Case 3 (72, M) had always extremely elevated fasting triglyceride for 5 years. Starting petit LCD for 2 years, triglyceride and weight were decreased moderately. Successively, changing to standard LCD for 1 year, weight was decreased 6 kg, and triglyceride was normalized. Discussion and conclusion: Each case suggests the characteristic beneficial effect of LCD. From our clinical experience and research, super LCD method, which is one of the very low-carbohydrate ketogenic diet (VLCKD), has evident efficacy of weight reduction. Super-LCD is characterized by strictly limitation for carbohydrate. Standard-LCD and petit-LCD method can be useful and applicable in response to the status of the patients. Thus, LCD treatment have beneficial effects for patients with various status.

Background: There have been discussion for years concerning Calorie Restriction (CR) and low carbohydrate diet (LCD). As to LCD, we have reported clinical experience and research for glucose variability and ketone bodies. Case and results: The patient was 41 yo man with type 2 diabetes mellitus (T2DM). His data includes height 186 cm, BMI 31.2, fasting blood glucose 151 mg/dL, HbA1c 9.4%. He was on super LCD diet with 12% of carbohydrate, and has continued aerobics exercise and muscle training. Average glucose level on day 2,4 and 10 was 161 mg/dL, 117 mg/dL and 102 mg/dL, respectively. Body weight decreased from 107 kg to 100 kg in 4 weeks. As ketone body, 3-hydroxybutyric acid (3-OHBA) was elevated to 2350 μmol/L (-85). Lipid profiles from day 2 to day 28 showed that Triglyceride 215 to 46, HDL 32 to 44, LDL 89 to 93. Discussion and conclusion: Authors have proposed 3 types of LCD so far, which are petit, standard and super, with 12%, 26%, 40% of carbohydrate ratio. Continuing super-LCD usually brings elevated ketone bodies and significant weight reduction. As for successful result, influenced factors would be application of super LCD, aerobics and anaerobic exercise, understanding and adequate continuation, adequate support of co-medicals.

The purpose of this study was to investigate anthropometric factors for the patients with Type 2 Diabetes Mellitus (T2DM). Subjects were 80 T2DM patients with 67.7 ± 12.9 years old. Methods included basal blood test including HbA1c and measured height, body weight, waist circumference (WC) and thigh circumference (TC). Several factors were calculated and investigated the correlation among Body Mass Index (BMI), HbA1c. WC, TC, Waist to Height ratio (WHtR), Thigh to Height ratio (THtR) and Thigh to Waist ratio (TWaR). Results were as follows: 1) Average BMI was 25.1 kg/m2 and average HbA1c was 7.2%, 2). There was significant correlation between WC and TC (p

Background: Discussion has been continued concerning Calorie Restriction (CR) and Low Carbohydrate Diet (LCD). For years, authors have investigated LCD associated with lipids, renal function and Ketone Bodies (KB) for clinical application of super LCD formular meal. In this study, 3-hydroxybutyric acid (3-OHBA) and acetoacetic acid (AcAc) was measured. Subjects and Methods: The subjects were 105 patients with type 2 diabetes mellitus (T2DM), (M/F 47/58, 62.7 years. in average) they were admitted for treatment of T2DM. The protocol consists of 3 steps. 1. Calorie Restriction (CR) diet was given on day 1 and 2 with 60% of carbohydrates. 2. Low Carbohydrate Diet (LCD) was given after day 3 with 12% of carbohydrates which is super-LCD formula meal. 3. Total ketone bodies (T-KB), 3-OHBA and AcAc were measured, and investigated the value and ratio of these markers. Results: Median T-KB was 349, 415, 486, 415, 445 μmol/L, in day 4-6, 7-9, 10-11, 12-15, 21-30, in 5 groups. Discussion and Conclusion: Hyperketonemia is due to continuation of LCD, which is physiological ketosis without clinically hazardous acidosis. As value of 3-OHBA increased, the ratio of 3-OHBA/T-KB increased. These results may become the fundamental data for clarifying the pathophysiological role of 3-OHBA and AcAc in hyperketonemia from carbohydrate restriction. respectively. There was significant correlation between value of 3-OHBA and ratio of 3-OHBA/T-KB (p

Aim The purpose of anti-aging medical checkups is to evaluate the functional age of the patient, aiming to prevent functional aging and rejuvenate the functional age. In this study, a comparison of the medical checkup results was conducted in elderly groups with different levels of activities of daily living (ADL). Methods There were three groups of subjects; and an independent group that included 43 independently-living subjects (68.9±6.3 years) in the Kyoto Yurin area, a support-requiring group that included 31 subjects (77.8±7.2 years) routinely visiting a day care center and a nursing-requiring group that included 19 subjects (83.7±6.8 years) who were living in a medical care facility for the elderly. We conducted anti-aging medical checkups, and the following five factors were evaluated: muscle mass by the bioelectric impedance method (Physion MD), bone strength by an ultrasonic wave method (A-1000: Yokogawa, AOS-100NW: Aloka), fingertip pulse wave analysis (SDP-100: Fukuda), cognitive function (Wisconsin card sorting test) and the serum insulin-like growth factor-I and dehydroepiandrosterone-sulfate (DHEA-s) level. To calculate the functional age of the subjects, we used the Age Management Check (Ginga Kobo, Nagoya), and the Δage (functional age-chronological age) was analyzed and compared between the groups. Results The functional ages in the independent group were muscle age, 55.5±7.0; blood vascular age, 65.4±8.5; neural age, 63.6±14.8; hormone age, 70.4±7.6 and bone age, 60.2±14.6 years. As a result of an increase in 1,506 daily steps based on walking instruction with pedometer monitoring, the subjects significantly improved their body weight, BMI, waist size, fasting plasma glucose level and serum DHEA-s in six months. By showing them their functional age, their motivation to participate in the health promotion program was increased, and the compliance was high, with an omission rate of less than 20% in 2.5 years. The support- and nursing-requiring groups showed muscle ages of 58.8±3.3 and 61.9±4.0, blood vascular ages of 75.5±12.6 and 71.8±11.1, neural ages of 86.5±8.8 and 88.5±5.8 and bone ages of 81.0±12.0 and 75.7±12.3, respectively. The Δage analysis in the three groups revealed that the Δneural age increased as the ADL decreased. Conclusions The Δage analysis indicated that the decreased ADL in the elderly may be mainly associated with their neural function in the factors examined. Anti-aging medical checkups are high in terms of their cost-performance ratio and are easily accepted by the elderly, and are thus recommended for elderly with all grades of ADL.

Aim: Although previous studies have shown that consumption of green tea catechins (GTC) and walking might prevent development of cardiovascular disease (CVD), the effects of GTC supplementation on CVD risk in active older people are unknown. Methods: A total of 52 older adults (male/female 20/32, mean age 69.1 ± 5.9 years) participating in a pedometer-based walking program were randomly assigned to a GTC group with an intake of 630.9 mg GTC daily (n = 26) or a control group (n = 26) for 14 weeks. Cardiovascular risk markers were measured before and after this trial. Results: In the GTC group, values of the following markers were significantly reduced (P

糖化は蛋白とグルコースのような還元糖との間におきる糖化最終産物(AGEs)を生成する非酵素的な反応である。糖化ストレスは老化の危険因子として考えられるが、この反応に関する情報は限られている。今回、我々は牛皮を2mol/Lグルコースに浸透し、60℃、6日間インキュベートした糖化反応のモデルを作製した。牛皮の硬さ(ヤング率)はビーナストロンで測定した。Nε-(carboxymethyl)lysine (CML)と蛍光性AGEsの定量は、酵素免疫測定法と蛍光分光法によって測定した。牛皮の色の変化は時間経過とともに白色調から黄褐色に変化した。硬さは反応前の73.2kPaから6日後の275.1kPaに上昇、蛋白あたりのCMLは0.017μgから0.142μgに増加した。蛍光分光法による解析の結果、励起光365~370nmのとき、438~491nmの間に最大値457nmのピークを認め、インキュベート期間が長くなるにつれ蛍光強度は増加した。結論として、AGEs生成阻害物質や糖化による皮膚劣化を防ぐ素材を探索するために、本モデルが役立つ可能性がある。, Glycation is a non-enzymatic reaction between a protein and a reducing sugar, such as glucose, that forms advanced glycation end products (AGEs). Glycation stress is thought as a risk factor of aging; however, information regarding this reaction is limited. Here, we developed a model of glycation reaction by using a bovine skin incubated with 2mol/L glucose at 60°C for 6 days. Hardness (Young's modulus) of the bovine skin was measured by the Venus TRON. Levels of Nε-(carboxymethyl) lysine (CML) and fluorescent AGEs were measured by an enzyme-linked immunoassay (ELISA) and fluorescent spectroscopy. The skin color changed from white to yellowish-brown with time. The hardness elevated from 73.2kPa before reaction to 275.1kPa after 6 days, while CML per protein increased from 0.017μg to 0.142μg. Fluorescent spectroscopy showed that, at the time of excitation with 365~370nm wave length, there was a peak in 438~491nm with the maximum value of 457nm, and the intensity increased as incubation period became longer. In conclusion, this model may be useful to detect effective ingredients that can inhibit the formation of AGEs and prevent skin deterioration during glycation reactions.

混合ハーブ抽出物(MHE)は抗糖化作用が既に報告されている。HMEはローマカミツレ・セイヨウサンザシ・ドクダミ・ブドウ葉の熱水抽出物である。HMEは漢方薬とみなすことができる。漢方薬では、構成生薬の追加が元の効能を変化させることが知られている。HMEに生薬である生姜・山椒を加えカプセルに充填した試験食を作成し、それが抗糖化作用を示すか調べた。またQOLへの影響を調べた。対象者は12名で、血糖正常群8名(男:女1:7、平均年齢47歳)と糖尿病・高血糖群4名(男:女3:1、平均年齢51歳、HbA1c 5.7～7.0)の2群に分けられた。両群とも、HMEはエキス固形分240mgと生姜・山椒一定量を1日量として4カプセル・12週間摂取した。また各群の1名ずつは80週間摂取を継続した。抗糖化作用は皮膚AGEs蓄積を非侵襲的に測定し皮膚自発蛍光(AF)として示すAGE reader™により評価した。皮膚弾力はCutometerにより評価した。 抗加齢QOL共通問診表により「便秘」、「冷え性」、「体重減少」が有意(p=0.043)の改善または変化を認めた。皮膚AFは8週・12週にて両群とも減少し、血糖正常群では12週で有意(p=0.020)な低下を認めた。80週までの継続摂取では皮膚AF減少は継続した。12週での摂取終了は皮膚AFの悪化を認めた。皮膚弾力は糖尿病・高血糖群の12週でR2に若干の改善を認めた。MHEに2つの生薬を追加配合した処方は皮膚AGEs蓄積を抑制した。試験食の継続摂取は安全で有用な抗糖化法と考えられることが示唆された。, The anti-glycation effect of mixed herbal extract (MHE) was already reported. HME was produced using hot water extraction from Anthemis nobilis (Roman chamomile), Crataegus oxyacantha (hawthorn berry), Houttuynia cordata (dokudami), and Vitis vinifera (grape leaf). MHE can be regarded as a Chinese herbal remedy. In Chinese herbal remedy, it is well known that a little of additional crude drugs can change the original effects. We assessed whether a capsulated novel remedy of MHE with Zingiber officinale (syouga) and Zanthoxylum piperitum (sansho) showed an anti-glycation effect. We also assessed its effects on one's quality of life (QOL). The subjects consisted of 12 volunteers divided into two groups, the Normal Blood Sugar (NBS) Group (male: 1; female: 7; age: 47.3 ± 10.2 years) and the Diabetes Mellitus / Impaired Fasting Glycaemia (DM/IFG) Group (male: 3; female: 1; age: 51.5 ± 12.7 years) with HbA1c 5.7～7.0. Both of the Groups were administered 240 mg of MHE (solid substance) with certain amounts of Zingiber officinale (syouga) and Zanthoxylum piperitum (sansyo) in 4 capsules per day for 12 weeks. Two individuals - one of NBS Group and the other of DM/IFG Group - were administered continuously for 80 weeks. The inhibition of glycation was assessed by AGE reader™, non-invasively measuring the advanced glycation endproducts (AGEs) as skin auto fluorescence (AF). Also the skin elasticity was assessed by Cutometer. The analysis using the Anti-Aging QOL Common Questionnaire (AAQol) showed that the score for the parameters, “constipation", “cold skin", and “weight loss; thin" were significantly improved or changed (p=0.043). The skin AF decreased in the both Groups after 8 and 12 weeks respectively, and significant variation (p=0.020) was observed in the NBS Group after 12 weeks. Continuous intake for 80 weeks revealed continuing low values of skin AF. Stopping the intake at 12 weeks resulted in a deterioration of skin AF. The skin elasticity index R2 in the DM/IFG Group showed a slight improving tendency after 12 weeks. The novel remedy of MHE with additional two crude drugs inhibited the accumulation of AGEs in the skin. These results suggest that a continuous supplementation of the test product was considered to be a safe anti-glycation method.

Given that ovarian function declines with age, older women occasionally experience health or fertility problems. Functional change is influenced by physical, mental, oxidative, and glycation stresses, which may lead to a decline in the secretion of hormones, such as melatonin, growth hormone/insulin-like growth factor-I, and dehydroepiandrosterone (DHEA). Many different factors influence the degradation of ovarian function, and the proper treatment depends on the accurate identification of each patient’s condition. Potential degradation mechanisms include the accumulation of advanced glycation end products (AGEs) by glycation stress, and the activation of receptors for AGEs. Accumulated evidence has suggested that in vitro fertilization success rate can be increased on administration of melatonin and DHEA, or glycation stress therapy, to patients with poor ovarian function. The provision of advanced medical technology to rejuvenate ovarian function should be combined with prophylactic lifestyle guidance, such as that developed by Anti-Aging Medicine, to treat the underlying causes of ovarian functional decline. Here, we review the application of Anti-Aging Medicine to aspects of reproductive medicine.

グルコースと蛋白質の非酵素的な糖化反応により,蛋白糖化最終生成物(advanced glycation end products: AGEs)が生成される.AGEsの生体内蓄積は糖尿病合併症や加齢に伴う疾患に関与しているため,近年では抗糖化は健康増進,疾患予防,アンチエイジングなどの分野で注目されている。本研究ではクマイザサ抽出物(Sasa senanensis Rehder)の抗糖化作用を検討し,「抗糖化」をキーワードとした健康食品・化粧品素材しての可能性を模索することを目的とした.今回,ヒト血清アルブミン(human serum albumin; HSA)とグルコースを反応させたin vitro実験系において,蛍光性AGEs,3-デオキシグルコソン(3DG),ペントシジン(Pent),カルボキシメチルリジン(CML)をAGEsとして評価し,陽性対照として塩酸アミノグアニジン(AG)を用い,蛍光測定法・ELISA法・HPLC法にてAGEsの測定を行った。抗糖化活性としてIC50(50%生成阻害濃度)を算出した。蛍光性AGEsに関してクマイザサ(粉末)の抗糖化活性のIC50はAGと同等であった.クマイザサ(熱水抽出物)の抗糖化活性のIC50はAGと比べ極めて小さかった.3DG生成阻害活性に関して,クマイザサ(熱水抽出物)のIC50はアミノグアニジンと同等であった.クマイザサ(粉末)のIC50はAGよりも極めて小さかった.Pent生成阻害活性に関して,AGと比較してクマイザサ(粉末)および(熱水抽出物)のIC50は極めて小さかった.CML生成阻害率に関して,AGと比較してクマイザサ(粉末)および(熱水抽出物)のIC50は極めて小さかった.クマイザサについては初めて糖化物生成抑制作用が確認され,健康食品・化粧品素材としての可能性が期待される., Non-enzymatic reaction between glucose and protein leads to the formation of advanced glycation end products (AGEs), and its accumulation has been linked to the development of diabetic complications, as well as to the progression of age-related diseases. In recent years, attention has been paid to the effect of inhibiting AGE formation in the body for the purposes of anti-aging, health promotion, and lifestyle-disease prevention. In the present study, we evaluated the anti-glycation effects of Kumaizasa (Sasa senanensis Rehder) and the potential of its use as an anti-glycation product. Using an in vitro method with glucose and human serum albumin (HSA), we analyzed the inhibition of the formation of AGEs; specifically fluorescent AGEs, 3-deoxyglucosone (3DG), Pentosidine (Pent), and Nε-(carboxymethyl) lysine (CML) by Kumaizasa utilizing fluorescence spectroscopy, HPLC, and enzyme linked immunoassay (ELISA). We analyzed its anti-glycation effects by comparing the 50% inhibitory concentration (IC50) against these glycated products with aminoguanidine, a known inhibitor of glycation. IC50 of fluorescent AGEs by Kumaizasa (powder form) and aminoguanidine were almost equal concentrations, while IC50 against 3DG, Pent, and CML were significantly lower for Kumaizasa (powder form) than that of aminoguanidine. IC50 of 3DG by Kumaizasa (hot water extraction) and aminoguanidine were almost equal concentrations, while IC50 against fluorescent AGEs, Pent, and CML were significantly lower for Kumaizasa (hot water extraction) than that of aminoguanidine. These results suggest that Kumaizasa strongly inhibits glycation and may be useful for anti-glycation products, including health foods and cosmetics.

This article reviews glycation stress as a factor linked to age-related diseases and functional and structural alterations of the skin. Photo-aging and glycation stress are major causes of skin deterioration. Glycation occurs when a reducing sugar, such as glucose or fructose, combines with a protein in a non-enzymatic reaction forming a glycated protein. Further reactions form advanced glycation end products (AGEs), which may accumulate in tissue. AGEs may also bind to a receptor for AGEs (RAGE), thus inducing inflammatory changes in skin and other tissues. The concept of glycation stress includes cellular and tissue responses to reducing sugars and aldehydes, not just to the production of AGEs. Glycation stress may be induced and affected by many factors, including exposure to ultraviolet light, which drastically intensifies AGE accumulation. AGEs modify skin collagen by reducing skin elasticity, and one result is wrinkle formation. AGEs accumulated in skin may be detected using auto-fluorescence (AF); our data from 136 healthy Japanese females shows the AF level is correlated with age. Glycation stress, and subsequently skin aging, may be reduced by managing levels of blood glucose, low-density lipoprotein cholesterol, and triglyceride through an appropriate diet, lifestyle, and intake of anti-glycation materials such as AGE generation inhibitors, AGE decomposers, and AGE receptor antagonists. Study of glycation stress may help identify new anti-aging treatments.

Objective: Previous epidemiological surveys of diet indicated a potential relationship between fruit intake and the pathogenesis of lifestyle-related disease. Recent reports indicate grapefruit (GF) may affect sugar metabolism. The present study measured glucose, triglyceride and insulin levels in human blood after GF ingestion with and without other foods.Methods: Twelve healthy, non-smoking female volunteers, non-obese (age 40.5 ± 4.2 years old, BMI 22.0 ± 0.9) were provided with five different breakfasts on successive days: GF, bread or fried vegetables alone, GF + bread, GF + fried vegetables. In meals that included GF, the GF was eaten before the bread or fried vegetables. Blood samples were taken after meals to measure plasma glucose, immuno reactive insulin (IRI), triglyceride and vitamin C.Results: Plasma glucose following a meal of bread or fried vegetables or a meal of bread and fried vegetables with GF was similar. Insulin secretion was slower after a meal of GF alone compared to bread alone (p < 0.001) and the area under curve (AUC) of glucose per carbohydrate intake was lower when GF was eaten prior to bread or fried vegetables than after a single intake of bread or fried vegetables alone (p < 0.001). The AUC of triglyceride after a prior intake of GF before fried vegetables was slower than that after an intake of fried vegetables alone (p < 0.05). Blood vitamin C concentration increased after GF intake (p < 0.001).Conclusion: GF contains saccharides and a variety of dietary elements, including fiber, vitamins, citric acid, naringenin and bergamottin. It is possible that these compounds may affect sugar and lipid metabolism.

Objective: As the concentrations of some hormones are known to decrease with age, the aim of the present study was to develop a method to predict the functional age of the endocrine system.Methods: We retrospectively examined data for blood serum or plasma hormone concentration from 3,313 healthy Japanese (2,006 men and 1,307 women, aged 40-79 years) who gave blood samples between 2005 and 2009. Data for DHEA-s, insulin-like growth factor (IGF-I), cortisol, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were analyzed, and the correlation between concentration of each hormone and age was calculated. In a second stage, data were grouped in 10-year age intervals, subjected to one-way analysis of variance (ANOVA) and evaluated using Tukey’s post-hoc test.Results: In both men and women, TSH was positively correlated with age. IGF-I, DHEA-s and cortisol were negatively correlated with age; in men, age was negatively correlated with FT3. Although correlation coefficients (r) and significance levels differed between sexes and hormones, DHEA-s concentration was highly correlated with age and declined with age in both men and women. An age-structured model was developed from the regression of mean DHEA-s concentration and median age of each group. The confidence limits for the regression were small and imply that the predictions from the model are accurate.Conclusion: We developed an age-structured model of age related to serum DHEA-s concentration. It may be useful as an index for evaluating the functional age of the endocrine system in Japanese men and women.

Objective: To study the relationship between the change in the number of steps taken and brachial-ankle pulse wave velocity (baPWV) during a long-term pedometer-based physical activity program in healthy older adults. Methods: Sixty older adults participated in this 17-week program. Each subject was provided with a pedometer and was given a goal to walk a set number of steps/day. After five subjects were excluded because of insufficient step data, data from 55 subjects (19 men and 36 women; age range: 65–79 years, mean age: 71.3±3.7 years; mean body mass index [BMI]: 24.1±8.8 kg/m 2 ) were analyzed. Subjects were checked before and after the study. Each subject was informed of his or her vascular age, calculated from baPWV, at the start of the study. Results: Subjects were divided into four groups based on the results of baPWV. The group in which baPWV improved above a selected cut-off value (1,700 cm/s) revealed the largest increase in steps/day among groups. This increase (4837.7±1868.7 steps) was larger than in groups in which baPWV remained low (1406.7±2402.1 steps, p=0.036) and high (1678.2±2871.4 steps, p=0.059). In any group, age or initial steps/day did not influence the change in steps. Subjects classified as having an older vascular age than the actual age on the basis of initial baPWV walked further. Conclusion: An increase in steps/day might improve baPWV. Although walking is a low intensity physical activity, it can have an anti-atherosclerosis effect.

Purpose: To examine the relationship between the functional age (FA) and the objectively measured daily physical activity (PA). Methods: The subjects of the present investigation were 15 males and 22 females (68±6 yr.). The Anti-Aging-Dock determined the 5 components of FA (Bone age; BA, Hormone-age; HA, Muscle-age; MA, Nervous system-age; NA, Vascular-age; VA). Each participant wore an electronic pedometer (HJ-720IT, Omron Corporation, Kyoto-city, Kyoto Japan) in order to determine daily number of steps (STEPday) and the time and steps for PA lasting longer >10-min at >60 steps·min –1 of the step rate (Bouttime and Boutstep). The HA was evaluated by using the standard aging curve of serum DHEA-s and IGF-I concentration. Result: Simple correlation coefficient showed that the HA significantly associated with STEP day and Boutstep in female subjects (p 10-min may be an effective PA to protect the age-associated changes in hormonal functions.

Purpose: The purpose of the present investigation was to examine the validity and reliability of the simple moderate to vigorous physical activity (MVPA) monitor (NL-1000; NEWLIFESTYLES, MO) during treadmill walking and running.Methods: A total of 70 men and women, between 22 to 76 years of age, participated in the present investigation. Subjects continuously wore the NL-1000 device on their waist. The NL-1000 calculated the time spent in MVPA corresponding to › 3 METs. All subjects walked at speeds of 40 to 115 m.min-1 and ran at a speed of 130 m.min-1 on a motor driven treadmill for four minutes. Furthermore, eight of all subjects performed a second experiment in order to assess the reliability of NL-1000.Results: The MVPA measured by the NL-1000 (MVPAped) significantly increased at a walking at the speed of faster than 85m.min-1 (p ‹ 0.05). Of the actual exercise time, MVPAped corresponded to › 90% of the actual exercise time in › 85 m.min-1 or faster speed. A multiple regression analysis showed that gender, body mass index, and age did not significantly affect the accuracy of MVPAped, and the treadmill speed came out significant parameter of MVPAped. The MVPAped did not differ significantly within the first and second experiment, furthermore, the results correlated significantly (r = 0.956, p ‹ 0.001).Conclusion: These results indicate that simple MVPA monitor would be a valid instrument to during the treadmill walking and running.

本研究では,若年長距離陸上選手を対象とし乾式遠赤外線低温サウナ浴を用い,陸上競技大会からの筋肉痛回復を検討した.対象者はよく鍛えられた男子陸上選手4名であった.大会後,サウナ浴群(n=2,20.0±1.4歳)またはシャワー浴群(n=2,20.0±0.0歳)は,大会直後(0時間後),そして24,48,72,96,124時間後の計6回,指定されたどちらかの入浴を行った.期間中の測定項目は,身体計測値,採血,MVC,VAS,POMSであった.その結果,高感度C-反応性蛋白(CRP),アルドラーゼ(ALD)が,サウナ群において低値を示す傾向であった.サウナ群において,急性の炎症マーカーが良好な傾向を示したことから,サウナ浴において炎症が抑えられたといえるのかもしれない., This pilot study aimed to examine the effects of far-infrared radiation low temperature sauna bathing on recovery from muscle damage following the race among long-distance runners. The subjects were 4 well-trained male runners. After the running race, the subjects were allocated either the sauna bath group (n=2, aged 20.0±1.4 years) or the shower bath group (n=2, aged 20.0±0.0 years) and bathed 6 times (right after the race, 24, 48, 72, 96 and 120 hours later). The measurements were anthropometrics, blood sampling, maximal voluntary contraction (MVC), visual analogue scale (VAS) concerning muscle soreness and profile of mood states (POMS). In the sauna bath group, C-reactive protein (CRP) and aldolase (ALD) levels tended to be lower compared to the shower bath group. Better results of acute inflammatory markers in the sauna bath group may explain the sauna bathing can suppress the inflammation.

Background: There are discussion of Calorie Restriction (CR) and Low Carbohydrate Diet (LCD). Authors and colleagues have continued research concerning LCD, CR and Morbus (M) value. Furthermore, this study also included homeostasis model assessment (HOMA). Subjects and Methods: Subjects enrolled were 40 type 2 diabetes mellitus (T2DM) cases with more than 10 μU/mL of fasting immunoreacitve insulin (IRI). Methods included fundamental tests such as glucose, IRI, HOMA-R, HOMA-β, average blood glucose on day 2 and 14 during CR and LCD meal. Results: Current data were in the following: average age 56.8 ± 12.3 years old, median values are HbA1c 7.2%, fasting glucose 141 mg/dL, IRI 13.1 μU/mL, HOMA-R 4.6, HOMA-β 57.1. Median values on day 2 vs 14 were average blood glucose 160 vs 120 mg/dL, M value 37.1 vs 7.4, Triglyceride 137 vs 97 mg/dL, respectively. M value showed significant correlation with HOMA-R (p

Aim The biological basis of variability in histological progression of non-alcoholic fatty liver disease (NAFLD) remains unknown. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone, has been shown to influence sensitivity to reactive oxygen species, insulin sensitivity and expression of peroxisome proliferator-activated receptor-α. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA in Japanese patients. Methods Serum samples were obtained in 133 Japanese patients with biopsy-proven NAFLD and in 399 sex- and age-matched healthy people undergoing health checkups. Serum levels of sulfated DHEA (DHEA-S) were measured by chemiluminescent enzyme immunoassay. Results Serum DHEA-S levels in NAFLD patients were similar to those in the control group. Of 133 patients, 90 patients were diagnosed as non-alcoholic steatohepatitis (NASH): 73 patients had stage 0-2, and 17 had stage 3 or 4. Patients with advanced NAFLD (NASH with fibrosis stage 3 or 4) had lower plasma levels of DHEA-S than patients with mild NAFLD (simple steatosis or NASH with fibrosis stage 0-2). The area under the receiver operating characteristic curve for DHEA in separating patients with and without advanced fibrosis was 0.788. A "dose effect" of lower DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 170.4 ± 129.2, 137.6 ± 110.5, 96.2 ± 79.3, 61.2 ± 46.3 and 30.0 ± 32.0 µg/dL for fibrosis stages 0, 1, 2, 3, and 4, respectively. The association between DHEA-S and severity of NAFLD persisted after adjusting for age, sex and insulin resistance. Conclusion Low circulating DHEA-S might have a role in the development of advanced NASH.

Background: Authors and colleagues have undertaken clinical research on Carbohydrate (CR) and Low Carbohydrate Diet (LCD) for years. We have proposed new evaluation method of insulinogenic index-carbohydrate 70g (IGI-carbo70). In similar way, C-peptide index for Carbohydrate-70 (CPI-Carbo70) is proposed in this report. Subjects and methods: The subjects were 37 patients with Type 2 diabetes mellitus (T2DM) and admitted for further evaluation and treatment. CR diet was provided on day 1 and 2, including 60% carbohydrates, 25% lipids and 15% protein with 1400 kcal/day. On day 2, breakfast with 70g of carbohydrate was provided, and glucose and C-peptide values were measured at 0 and 30 minutes. Results: Average HbA1c was 8.1 %, and Morbus (M) value was 70.5 in median. Glucose and C-peptide on 0--30min significantly increased as 163--195 mg/dL, 1.1--1.5μU/mL, respectively. CPI-Carbo70 was 1.94 in average and 1.54 in median. There were significant correlations between increments of glucose and C-peptide, and between HbA1c and CPI-Carbo70. Discussion and conclusion: CPI-Carbo70 was investigated and proposed. It may be useful for evaluating the function of the pancreas. This research would give the fundamental data for this field, and further research development will be expected in the future.

加齢に伴う生活の質(QOL:Quolity of Life)低下により睡眠の質(QOS:Quality of Sleep)は低下する.QOSを良好に保ち健康的な生活習慣を持つことは,労働衛生の面からも重要である.今回我々は企業労働者を対象に腕時計型3次元加速度センサを装着し,QOS及び昼間の身体活動度について非侵襲的評価を試みたので,その結果を報告する.村田機械(株)(愛知県犬山市)に勤める男性従業員のうち検診結果に基づき保健管理センターにより要生活指導と判定された6名(50.5±2.6歳)を対象とした.被検者は抗加齢QOL共通問診票(Anti-Aging QOL Common Questionnaire: AAQol)を記入し,QOSは腕時計型三次元加速度センサ(アクティグラフ Actigraph, A.M.I., USA)を用いて日中及び睡眠時の体動量を計測し評価した.体動測定はセンサを1週間連続装着し行った.結果解析にはアクティグラフ解析ソフトウェア(AW2,A.M.I.,USA)を用いた.自覚症状および生活習慣に問題は認められなかった.睡眠パラメータは各被検者の1週間の身体活動量から算出した.全ての被検者において睡眠効率は90%以上,平均睡眠時間は6時間以上だった.睡眠時活動量,及び中途覚醒は被検者間で差が生じた.観察期間中に腹痛を発症した被検者腹痛前夜の睡眠中活動量及び中途覚醒回数が増大し,睡眠効率が70%程度に低下し,QOSの低下が示唆された.QOS低下に伴い,次日の日中活動量が低下し,居眠り回数が増加した.以上の結果より,3次元加速度センサによる体動量監視はQOS及び昼間活動度の定量評価に有用な方法である., Deterioration in quality of sleep (QOS) according to aging decreases quality of life (QOL). It is important to maintain QOS high and healthy in the lifestyle and also from respect of the occupational health. Here, we tried the noninvasive evaluation of QOS by installing wristwatch-type motion sensors for corporate workers. Subjects were 6 male employees (mean age, 50.5 ± 2.6 years old) of a machine manufacturer located in Inuyama City who underwent a company-wide medical check-up. They were judged by the health management center the needed lifestyle guidance. Subjects undertook the Anti-Aging QOL Common Questionnaire (AAQol) and QOS analysis by using a three-dimension accelerometer (Actigraph, A.M.I., USA). The sensor was continuously installed in the subject for one week and the body motion measurement was performed. The data was analyzed by software AW2 (A.M.I.) referring to the sleep diary described. Problems were not noted in the subjective symptom or their lifestyle by AAQol. Various sleep parameters were calculated from the continuum movement measurements of one week of each subject. The sleep efficiency was more than 90% and the total sleep time 6 hours or more in all subjects. The difference was noted in the amount of the mean activity and number of awakening episodes during sleep. In a subject accompanied abdominal pain during the observation period, the number of awakening episodes increased and the sleep efficiency decreased to less than 70%, indicating low QOS. The daytime mean activity was low with high frequency of the doze the next day of the low QOS sleep. The monitor of the physical movement for 24 hours by an accelerometer may be useful for the quantitative evaluation of QOS and the activity level in daytime.