As the 21^st century advances, evidence-based medicine (EBM) has come to be regarded as essential in all field of medical sciences and practical medicine. Creating medicines have been searching for based on EBM and development of new medicine has been carried out.In Japan the number of diabetic patients has increased to 129% during recent 10 years. The number of diabetic complications has also increased and hemodyalysis has been introduced in approximately 16,000 patients/year with diabetic nephropathy in Japan in 2008.Additinally many diabetic patients are suffering from numbness, cold sensation and pains in extremities derived from diabetic neuropathy. Therefore reduction of diabetic complications is one of the most important considerations in the field of diabetic patient care.Diabetes mellitus is equivalent to wasting-thirst in Jomgiiyaolue.We have reported the effectiveness of Goshajinkigan (GJG) for the treatment of nembness associated with diabetic neuropathy for the first time in Japan in 1984.In controlled comparative study, GJG showed significantly higher rates of improvement of this symptom versus mechobalamin.Insulin resistance has an important role on the occurrence of type 2 diabetes and metabolic syndrome.We have studies the effects of Kampo medicine on the insulin resistance using the euglycemic clamp and molecular biological techniques.1) Animal experimental studies: The improvement of insulin resistance in STZ rats by the administration of GJG might be via NO pathway and due, at least in part, to correct in the abnormal early steps of insulin signaling pathway in skeletal muscle.2) Clinical Studies: Effects of GJG on insulin resistance in patients with type 2 diabetes were investigated. HOMA-R was significantly decreased after GJG treatment (P=0.019). On the other hand, HOMA-R in the control group did not show significant difference. HOMA-R returned to the pre GJG treatment level1month after GJG discontinuation (P=0.018). The high-dose clamp resulted in a significantly increased insulin action (MCR levels) after GJG treatment.These animal experimental and clinical studies suggest that GJG might be effective for improving insulin resistance in the patients with type 2 diabetes.Kampo formulations might be useful not only for the prevention and the treatment of diabetic complications but also effective for the prevention and treatment of type 2 diabetes.In conclusion GJG has been used for the treatment of numbness and dysnuria since the statement in Yanshijishengfang. We have found the effectiveness of GJG on the treatment of diabetic neuropathy and on the prevention and the treatment of type 2 diabetes. We would like to continue these scientific activities.

Recently in Japan, the numbers of diabetic patients have been increased to 7.4 million and to 16.2 millions if the subjects of impaired glucose tolerance are added. Most Japanese diabetic patients are type 2 (non-insulin dependent). Decreased secretion of insulin and insulin resistance play important roles on the occurrence and progression of type 2 diabetes.
Long-established systems of traditional medicine have evolved from systematic recordings of human evidence for more than 3 thousands years. In addition the traditional Chinese medicinal philosophy is one of the oldest medical sciences in the world and has a long-standing history in the usage of herbal medicinals. Nowadays the use of complementary/alternative medicine and especially the consumption of botanicals has been increasing rapidly worldwide.
1. Clinical Studies
The management of diabetic neuropathy is one of the most difficult clinical problems. Among 65 patients with diabetic neuropathy who suffered from numbness of lower extremities 43 (66.2%) experienced some degree of improvement after oral administration of Goshajinkigan (GJG). Following our first report, more than 10 papers were published in Japan and almost same results were obtained. In a well-controlled comparative study, the efficacy of GJG and mecobalamin in diabetic neuropathy was estimated. After oral administration of GJG, the general improvement rate was 80.0%, while it was 48.1% in mecobalamin. The difference between the two groups was statistically significant (P<0.01). These results suggested that GJG is a useful medicine for amelioration of numbness due to diabetic neuropathy.
2. Animal experimental studies
Regular physical training has been known to be beneficial in the prevention and the treatment of life-style related diseases such as type 2 diabetes. However, it is very difficult for diabetic patients to continue physical exercise training for a long time. Troglitazone has insulin-sensitizing actions but it withdrew because of severe fatal hepato-toxic actions. Therefore development of insulin-sensitizing medicine without significant side-effects have been expected.
Chinese herbal medicine has less frequent side effects when compared to modern western medicine.
In the present study, the effect of GJG on insulin resistance in streptozotocin (STZ, 50mg kg^-1 BW, ivy.)-induced diabetic rats was examined by means of the euglycemic clamp procedure.
The improvement of impaired insulin action in STZ-diabetic rats by single and repeated administration of GJG may be due, at least in part, to enhance insulin signaling, and subsequent ameliorated production of NO. In conclusion,
(1) Diagnosis and primary treatment to reduce blood glucose including diet, exercise, oral hypoglycemic agents and insulin should be practiced by western style medical sciences. (2) Kampo medication is useful for the prevention and treatment of diabetic complications. (3) Kampo medicine has the possibility of prevention of type 2 diabetes.

The effect of daily walking on body fat distribution was investigated using an electronic pedometer and ultrasonography. Subjects were 77 women, aged 31 to 72 years. They were divided into four groups according to the average number of steps they walked per day(I<7, 500, 7, 500≤II<10, 000, 10, 000≤III<12, 500, 12, 500≤IV). Subcutaneous fat in the trunk and limbs, and the minimum thickness of subcutaneous fat(Smin) and the maximum thickness of preperitoneal fat(Pmax) below the xiphoid process were measured by ultrasonography. Abdominal wall fat index (AFI) reflecting the intra−abdominal fat accumulation was obtained by dividing Pmax by Smin. Fat distribution was analyzed by ANCOVA, controlled for age, body mass index(BMI), percent body fat, and menopausal status. Energy and macronutrient intake were obtained through a nutritional survey. There were no significant differences in anthropometric variables, energy and macronutrient intake, and subcutaneous fat thickness in trunk and limbs. Pmax of Group I was significantly higher than Group IV. Furthermore. Group I showed significantly higher AFI than the other three Groups (II, III, IV). The results of this study suggested that women who walked less than 7, 500 steps per day tend to have significantly increased intra−abdominal fat accumulation.
Fatty acid glycerol esters ; Group I ; Walking ; Roman Numeral IV ; Amniotic Fluid Index

The purpose of the present study is to investigate protein metabolism during rapid weight reduction. Six male boxing players put on a restricted diet of their own accord for two weeks. Body weight changes were observed and a biochemical analysis was made of their urine and blood. The initial body weight of 66.1±3.0kg (mean±SE) decreased to 63.6±3.2 kg after two weeks (P<0.01) . The changes in lean body mass (LBM) by weight reduction were not significant, but the LBM tended to decrease after two weeks. The mean caloric intake was 2, 791±728 kcal before the study and 1, 643±548 kcal after two weeks. The reduction of carbohydrate consumption is much more than that of fat and protein consumption. The 3-Me/Cr in urine increased significantly after two weeks (348.1 ± 37.0 μol/g to 508.1 f 45.6 μmol/g, P<0.01) and the increase of Urea-N/Cr in urine (8.4±0.5mg/mg creatinine to 13.7±1.3mg/mg creatinine, P<0.01) was also significant after two weeks. Urine volume decreased significantly after two weeks (P<0.01) . There was no significant difference in the blood components during the weight reduction period. These results might suggest that rapid weight reduction and massive decrease of carbohydrate intake accelerate protein catabolism.

The purpose of this study was to clarify various components of walking activities among the high aged people, in relation with physique and heart rates at rest and post exercise recovery period. Subjects are 53 female residents of a care house in Hyogo Prefecture, whose average age being 78.9±0.9 years were tested in various parameters that are relevant to the study, such as height, weight, BMI, resting heart rate, total amount of weekly walking steps (recorded twice, i, e., in September and in October), walking velocity, walking stride, time length for climbing 15 step stairs and self-rate health. the major findings are summarized as follows
(1) Various physical functions that are related to daily activities and therefore related to muscular strength and neuromuscular coordination, were found to decrease significantly upon aging, such as walking velocity and time length for climbing stairs.
(2) The result of multiple correlation regression analysis, taking total amount of weekly walking steps with self-rated health, time length spent for 15 steps of climbing stairs and age were existent.
(3) Walking velocity, walking steps size and stair climbing velocity of good walkers (upper 25% in total amount of weekly walking steps) and it was found that the good walkers walked faster with greater steps size and climbed the stairs faster than the less walking subjects.
(4) The total amount of daily walking steps of various days of the week were compared each other and it was found that the good walkers recorded significantly less amount of walking steps on Thursday than others days. the fact that a large scale shopping center which is located near by the care-house closes on Thursday every week suggests that the amount of walking steps are influenced by social factors, such as shopping behavior.
(5) In terms of the going out behavior outside of care-house, visiting the large scale shopping center (40% of subjects), and hospitals and alike (25%) were recognized. The results suggest that there are certain common elements in the motivation and behavior of out-of- care-house activities.
The above results suggest that the study of walking behavior of the high aged people would be extremely variable not only in assessing the fitness level and physical function of the residents, but also in possible evaluation of efficiencies of the care-house location.

Objective To observe whether nitric oxide (NO) improves high glucose toxicity induced insulin resistance in streptozotocin (STZ) induced diabetic rats. Methods The changes of metabolic clearance rate for glucose (MCR), as the index of insulin effect, were observed in 24 STZ induced diabetic rats and 24 normal rats in awake condition treated by sodium nitroprusside (SNP), N G monomethyl L arginine (LNMMA), adenosine or saline duringeuglycemichyperinsulinemiaclampprocedure.Results MCR in saline treated diabetic rats 〔(7.2?0.8)ml?kg -1 ?min -1 〕 wassignificantlylowerthanthat in normol control rats 〔(18.0?1.8)ml?kg -1 ?min -1 , P

Metabolic syndrome develops because of an accumulation of intra-abdominal fat. In Kampo medicine, an abdominal examination is commonly performed for the diagnosis of diseases. Thus, we examined the relationship between metabolic syndrome and abdominal tension. Our subjects were 999 people (619 males and 380 females) who underwent regular physical check-ups. Metabolic syndrome was diagnosed in 14.5% (21.3% of males and 3.4% of females) and the prevalence rate of subjects with metabolic and pre-metabolic syndromes was 40.8% (55.9% of males and 16.3% of females). In addition, abdominal examinations detected 19.1% of hyperfunction, 64.6% of intermediate function, and 16.3% of hypofunction. Almost subjects with abdominal hyperfunction were classified as metabolic or pre-metabolic syndrome, and neither metabolic nor pre-metabolic syndrome was present in subjects with abdominal hypofunction. In conclusion, assessment of abdominal tension may become an additional valuable screening method for metabolic syndrome.
Syndrome ; Metabolic syndrome ; hypofunction ; hyperfunction ; Abdominal

Medicine, Kampo ; Metabolic ; Therapeutic procedure ; Syndrome

In order to clarify the relationship between acute physical exercise and immunity, the numbers of overall leucocytes, lymphocytes and neutrophils, the concentrations of immunoglo-bulins and complements, the ratios of lymphocyte subsets (OKT 3, 4, 8, Leu 7, OKIa 1) and the levels of lymphocyte transformation response to PHA were measured in nine untrained male subjects (18-22 years old) before, immediately after, along with 24 and 72 hours after acute physical exercise at 50% of VO₂max for 2 hours. Before exercise all components were within normal range. Exercise produced a significant rise in the number of leucocytes and neutrophils overall. The response of lymphocytes to PHA immediately after exercise was significantly lower than before, or 24 hours or 72 hours after exercise.
There was no change in the number of lymphocytes, or in the concentration of immunoglo-bulins and complements before and after exercise. Likewise the ratios of lymphocyte subsets also remained unchanged.
From these results, it can be concluded that acute physical exercise by untrained subjects is one kind of physical stressor and can contribute to T cell dysfunction.