A case of thyroid storm caused by Graves' disease misdiagnosed as panic attack due to panic disorder.

BACKGROUND: Graves' disease is characterized by hyperthyroidism and its symptoms often overlap with those of panic disorder, which may make it difficult to distinguish between the two conditions. In this report, we describe how proper diagnosis of thyroid disease in patients with mental illness can lead to appropriate treatment. CASE PRESENTATION: We encountered a 34-year-old woman in whom thyroid crisis from Graves' disease was misdiagnosed as panic attack. The patient was being managed as a case of panic disorder and bipolar disorder in a psychiatric outpatient setting. About 6 months before presentation she had lost about 16 kg in weight, and a month before presentation she developed several unpleasant symptoms as her condition worsened. Several weeks before she had had severe palpitations, tachycardia, and discomfort in her throat. She became unable to eat solids, ate only yogurt and gelatin, and felt it difficult to take psychiatric drugs. She visited our emergency outpatient department on a Sunday morning, presenting with nausea, severe tachycardia, fever, and restlessness with anxiety. We treated her as panic disorder with fever, but noted proptosis and considered the possibility of Graves' disease. Thyroid function tests were performed even though data from her clinic was not available because it was a weekend. Because there was no improvement in her condition after her first visit, she returned to our hospital early the next morning. We had misdiagnosed her as having severe panic attacks due to panic disorder, and after a diazepam injection had allowed her to go home. Later that day, the thyroid function test results became available, and her symptoms and the results strongly indicated a thyroid storm. The endocrinology department was consulted immediately, and she was referred for hospitalization the next day. During hospitalization, she was treated with steroid and radioactive iodine therapy and was discharged from hospital in 3 weeks. CONCLUSION: Psychiatrists and doctors engaged in psychosomatic medicine need to consider the possibility of severe hyperthyroidism as a differential diagnosis of panic disorder.

Near-infrared Spectroscopy of Vastus Lateralis Muscle during Incremental Cycling Exercise in patients with Type 2 Diabetes.

PURPOSE: It is clinically important to elucidate the precise mechanism of exercise intolerance in patients with type 2 diabetes (T2DM). The aim of this study was to examine whether there is a difference in the time course change of the oxygenation in the vastus lateralis (VL) muscle during submaximal incremental cycling exercise between patients with T2DM and age-matched healthy subjects. METHODS: Nine elderly men with T2DM and 10 age-matched healthy men (CON) participated in this study. All participants performed an incremental cycling exercise.Total, deoxygenated and oxygenated hemoglobin/myoglobin in the VL muscle were assessed using near-infrared spectroscopy, and cardiorespiratory response was also evaluated during the exercise. RESULTS: There were no significant differences in the time course changes of deoxygenated hemoglobin/myoglobin between groups ( p > 0.05). However, the oxygenated hemoglobin/myoglobin in T2DM was significantly higher than that in CON at an intensity above ventilatory threshold during the incremental cycling exercise ( p< 0.05). CONCLUSION: This study suggests that patients with T2DM had early limitation of oxygen extraction and lower capacity of oxygenated myoglobin dissociation in the VL muscle. The fact that patients with T2DM showed different oxygen kinetics in a peripheral tissue from healthy subjects may partly explain the potential mechanisms of exercise intolerance in T2DM.

Family history of diabetes in both parents is strongly associated with impaired residual ß-cell function in Japanese type 2 diabetes patients.

AIMS/INTRODUCTION: The objective of the present study was to clarify the association of the type and number of first-degree family history of diabetes (FHD) with the clinical characteristics, especially with residual ß-cell function, in type 2 diabetes patients. MATERIALS AND METHODS: A total of 1,131 type 2 diabetes patients were recruited and divided into four groups according to FHD information as follows: (i) patients without FHD (FHD-); (ii) those with at least one sibling who had diabetes without parental diabetes (FHD+); (iii) those with one parent (FHD++); or (iv) those with both parents (FHD+++) who had diabetes with or without a sibling with diabetes. RESULTS: The percentages of the FHD-, FHD+, FHD++ and FHD+++ groups were 49.4%, 13.4%, 34.0% and 3.2%, respectively. Patients in the FHD++ and FHD+++ groups were significantly younger at the time of diabetes diagnosis (P < 0.001) than those in the FHD- and FHD+ groups, even after adjusting for confounding factors. In addition, the levels of insulin secretion were significantly lower in the patients in the FHD+, FHD++ and FHD+++ groups than those in the FHD- group (P < 0.05) after adjusting for confounding factors, and the patients in the FHD+++ group presented with the lowest levels of insulin secretion among the four groups. CONCLUSIONS: Our results showed that in type 2 diabetes patients, the degree of the associations between FHD and clinical characteristics differs according to the number and the type of FHD. In particular, FHD in both parents is most strongly associated with impaired residual ß-cell function.

Ratio of low molecular weight serum adiponectin to the total adiponectin value is associated with type 2 diabetes through its relation to increasing insulin resistance.

AIM: Among the three adiponectin isoforms, a lower ratio of high molecular weight (HMW) adiponectin to total adiponectin (TA) is well known to cause insulin resistance and type 2 diabetes (T2D). However, how the levels of other adiponectin isoforms, such as the middle molecular weight (MMW) and low molecular weight (LMW) isoforms, and their relative ratio to TA change in T2D subjects has not been determined. Therefore, we investigated the association of these adiponectin-related parameters with T2D. METHODS: We examined the associations between adiponectin-related parameters and diabetes in a group of 394 T2D subjects and 374 controls (1st group) randomly selected from among the participants in our previous study. The associations between these parameters and the HOMA-IR in a 2nd group, consisting of the subjects remaining in the 1st group after the exclusion of subjects receiving diabetic medication, were also examined. RESULT: In the 1st group, after adjusting for confounding factor, the levels of all the adiponectin isoforms and the HMW/TA ratio were significantly lower among the diabetic subjects than among the controls (all P values < 0.01). On the contrary, the LMW/TA ratio was significantly higher among the diabetic subjects (P < 0.01) and was positively associated with T2D (odds ratio = 8.64, P < 0.01). In the 2nd group, the HMW/TA ratio was inversely associated with the HOMA-IR; however, the LMW/TA ratio was positively associated with the HOMA-IR (ß for LMW/TA ratio = 0.89, SE = 0.24, P < 0.001), similar to the association with T2D. The MMW/TA ratio was not associated with T2D or the HOMA-IR. CONCLUSION: The current investigation demonstrated that, unlike the reduction in the levels of all the adiponectin isoforms and the HMW/TA ratio, an increased LMW/TA ratio was associated with T2D through its relation to insulin resistance.

Non-locomotive physical activity intervention using a tri-axial accelerometer reduces sedentary time in type 2 diabetes.

OBJECTIVES: The purpose of this study is to examine whether the use of a tri-axial accelerometer can reduce sedentary time and increase non-locomotive physical activity (N-LPA), and to investigate the effect of this intervention on parameters of glucose and fat metabolism in patients with type 2 diabetes. METHODS: Thirty-eight patients with type 2 diabetes (Age: 61.8 ± 1.4 years, BMI: 24.8 ± 0.6, HbA1c: 6.6 ± 0.1 %) participated in this 12-week randomized controlled study, and 31 patients were included in the final analyses. Patients were randomly assigned to one of three groups: control, N-LPA or locomotive physical activity (LPA). Patients in the N-LPA and LPA groups were asked to increase their N-LPA and LPA, respectively, using tri-axial accelerometer feedback. Glucose and fat metabolic parameters were evaluated before and after 12-week intervention. RESULTS: Only the N-LPA intervention significantly reduced sedentary time (p < 0.05) and increased N-LPA (p < 0.05). However, these changes were insufficient to improve parameters associated with glucose and fat metabolism (p > 0.05), despite a significant positive correlation between the change in sedentary time and HbA1c levels (p < 0.05). CONCLUSION: Our results showed that the N-LPA intervention using a tri-axial accelerometer successfully reduced sedentary time in patients with type 2 diabetes, however that induced no significant improvement of glucose and fat metabolism. Further research is required to determine the degree of reduction in sedentary time and increase in N-LPA needed to improve glucose and fat metabolism.

FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men.

AIM: Several studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population. METHODS: We genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMImax) before or at the time of diagnosis and 693 control individuals with information regarding their BMImax. RESULTS: The BMImax showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMImax and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMImax and age. CONCLUSIONS: These results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMImax before or at the time of diagnosis.

Jogging Therapy for Hikikomori Social Withdrawal and Increased Cerebral Hemodynamics: A Case Report.

Severe social withdrawal, called hikikomori, has drawn increased public attention. However, an optimal clinical approach and strategy of treatment has not been well established. Here, we report a case of hikikomori for which an exercise intervention using jogging therapy was effective, showing cerebral hemodynamic improvement. The patient was a 20 year old Japanese male who was hospitalized in order to evaluate and treat severe social withdrawal. Although depressive and anxiety symptoms partially subsided with sertraline alone, social withdrawal persisted due to a lack of self confidence. With his consent, we implemented exercise therapy with 30 minutes of jogging three times a week for three months. We did not change the pharmacotherapy, and his social withdrawal remarkably improved with continuous jogging exercise. Using near infrared spectroscopy to evaluate hemodynamic alteration, bilateral temporal hemodynamics considerably increased after the three-month jogging therapy. Regarding exercise therapy for mental illness, numerous studies have reported the effectiveness of exercise therapy for major depression. This case implied, however, that the applicability of exercise therapy is not limited to major depressive disorder. Jogging therapy may contribute to reinforcing self confidence associated with "resilience" in conjunction with neurophysiological modulation of neural networks.

Effects of non-exercise activity and daily exercise activity upon glucose and fat metabolism in type 2 diabetes.

BACKGROUND: The purpose of this study was to disclose the relationship between objectively measured non-exercise activity (NEA) and moderate to vigorous physical activity (MVPA) using triaxial accelerometer and the effect of each activity on glucose and fat metabolism in active type 2 diabetes. Elucidating this relationship and effect would lead to support educational programs for the management of type 2 diabetes. METHODS: Seventy-seven patients with type 2 diabetes who had performed daily programmed walking exercise participated in this cross-sectional study. Physical activity including NEA and MVPA was measured by triaxial accelerometer for 10 consecutive days and the measurements of body composition and glucose and lipid profile were performed. RESULTS: There was no significant correlation between NEA and MVPA in active type 2 diabetes. NEA had a significant inverse correlation with body fat (P<0.05) and higher MVPA manifested a positive influence upon glucose and/or fat metabolism (P<0.05). CONCLUSIONS: This study suggested even patients who performed a routine programmed MVPA remained sedentary other than MVPA, thus, clinicians should counsel patients to not only promote MVPA but to increase NEA by quantification of NEA. The results of this study should be taken into consideration for the development of educational programs and management of type 2 diabetes.

Gender difference in metabolic responses to surface electrical muscle stimulation in type 2 diabetes.

OBJECTIVE: The aim of this study was to examine whether or not there is a gender difference in metabolic responses to surface electrical muscle stimulation (sEMS) in type 2 diabetes (T2DM). METHODS: Ten men and eight women with T2DM participated in two sessions; in both sessions the subjects were investigated after a breakfast and that in one occasion they underwent 30-min sEMS while in the other they were followed while resting. Blood and gas exchange data were compared between genders as to the extent of blood glucose and non-esterified fatty acids responses to sEMS. RESULTS: The time course change of blood glucose concentration after sEMS did not statistically differ between genders while sEMS could attenuate postprandial blood glucose level regardless of gender (p<0.05). Women had a lower respiratory quotient and lactate concentration during sEMS when compared with men (p<0.05). CONCLUSIONS: This study indicated that sEMS might have resulted in lower anaerobic glycolysis in women as compared to men with T2DM. sEMS is expected to be a new exercise method in T2DM. Determining the possible gender differences and precise mechanisms might further shed some light for the efficacy of sEMS use for clinical practice.

Secretory units of islets in transplantation index is a useful predictor of insulin requirement in Japanese type 2 diabetic patients.

AIMS/INTRODUCTION: The objective of the present study was to clarify the validity of ß-cell function-related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients. MATERIALS AND METHODS: In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross-sectional study examining the relationship between the homeostasis model assessment of ß-cell function (HOMA-ß) and C-peptide-based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several ß -cell function-related indices using a receiver operating characteristic (ROC) curve analysis. RESULTS: The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA-ß, followed by the fasting serum C-peptide immunoreactivity index (CPI); the fasting serum C-peptide immunoreactivity itself (F-CPR) had the least correlation. The CPI, HOMA-ß and SUIT were significantly lower in the insulin-requiring group than in the non-insulin-requiring group, even after adjustments for confounding factors (P < 0.01). The areas under the ROC curve for insulin requirement were 0.622, 0.774, 0.808, and 0.759 for F-CPR, CPI, SUIT, and HOMA-ß, respectively. The cut-off values of SUIT, CPI, and HOMA-ß for an over 80% specificity for the prediction of insulin therapy were 23.5, 1.00, and 14.9, respectively. CONCLUSIONS: The present study shows that SUIT is the best predictor of insulin requirement among these ß-cell function-related markers.

Motor unit firing pattern of vastus lateralis muscle in type 2 diabetes mellitus patients.

INTRODUCTION: We investigated the motor unit (MU) firing pattern in type 2 diabetes mellitus (T2DM) patients by means of multichannel surface electromyography (SEMG). METHODS: Eight T2DM patients and 8 age-matched, healthy men performed a ramp-up contraction to 20% of maximal voluntary contraction (MVC). They also performed a sustained contraction at 10% of MVC during isometric knee extension. Multichannel SEMG signals recorded from the vastus lateralis muscle were decomposed with the convolution kernel compensation technique to extract individual MU firing patterns. RESULTS: During the ramp contraction, the extent of MU firing modulation was significantly attenuated in T2DM. Variability of MU firing rate was significantly higher in T2DM at later periods during the sustained contraction. CONCLUSIONS: Our findings suggest that T2DM patients manifest characteristic MU activity patterns due possibly to some degree of neuromuscular impairment affecting the integrity of MU firing modulation.

Type 2 diabetes mellitus patients manifest characteristic spatial EMG potential distribution pattern during sustained isometric contraction.

AIM: The purpose of the present study is to investigate spatial surface electromyography (SEMG) potential distribution pattern in type 2 diabetes mellitus (T2DM) patients. METHODS: Nine T2DM patients and nine age-matched healthy men (CON) performed a sustained isometric knee extension at 10% of maximal voluntary contraction for 120s. Multi-channel SEMG was recorded from the vastus lateralis muscle by means of 64 electrodes. To characterize spatial SEMG potential distribution pattern, modified entropy and correlation coefficients between same electrode locations were calculated at 15, 60 and 120s for the root mean square values. RESULTS: At 60 and 120s, modified entropy in T2DM was significantly lower than those in CON (p<0.05). Correlation coefficients for T2DM were significantly higher than those for CON at 60 and 120s (p<0.05). CONCLUSION: From these results, we suggested that T2DM patients continue to recruit limited and same motor units during the sustained contraction at low force level.

Effect of percutaneous electrical muscle stimulation on postprandial hyperglycemia in type 2 diabetes.

AIMS: The aim of this study was to examine whether percutaneous electrical muscle stimulation (EMS) attenuates postprandial hyperglycemia in type 2 diabetes. METHODS: Eleven patients with type 2 diabetes participated in two experimental sessions; one was a 30-min EMS 30 min after a breakfast (EMS trial) and the other was a complete rest after a breakfast (Control trial). In each trial, blood was sampled before and at 30, 60, 90, and 120 min after the meal. RESULTS: Postprandial glucose level was significantly attenuated in EMS trial at 60, 90, and 120 min after a meal (p<0.05). The C-peptide concentration was also significantly lowered in EMS trial (p<0.01). On the other hand, there was no significant increase in creatine phosphokinase (CPK) concentration in each trial. CONCLUSIONS: The present results provide first evidence indicating that EMS is a new exercise method for treating postprandial hyperglycemia in individuals with type 2 diabetes, especially who cannot perform adequate voluntary exercise because of excessive obesity, orthopedic diseases, or severe diabetic complications.

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice.

Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic ß cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [(14)C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [(14)C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.

Glycemic instability in type 1 diabetic patients: Possible role of ketosis or ketoacidosis at onset of diabetes.

AIMS: In type 1 diabetic patients, some have glycemic instability while others glycemic stability. We have developed criteria for evaluating glycemic instability and investigated the factors responsible. METHODS: Glycemic instability in 52 type 1 diabetic patients was assessed by the mean amplitude of glycemic excursions (MAGE) and M-value, and clinical characteristics of good, fair and poor control groups were compared. RESULTS: The median MAGE and M-value was 6.6mmol/L and 18.7, respectively. Then MAGE >or=6.6mmol/L and M-value >or=18.7 was defined as poor control. In the 32 patients without detectable C-peptide levels, 18 patients (56%) showed poor control. The frequency of ketosis or ketoacidosis at onset of diabetes was dramatically higher in the poor control group not only in the patients as a whole but also in those without detectable C-peptide levels. CONCLUSIONS: A decreased level of C-peptide is a significant factor in glycemic instability. However, some patients have glycemic stability though beta-cell function is completely depleted. The presence of ketosis or ketoacidosis at onset of diabetes may be a factor in later glycemic instability, suggesting the importance of examining patients in detail at onset of diabetes for careful follow-up to prevent progression of acute and chronic complications of diabetes.

Curcumin inhibits glucose production in isolated mice hepatocytes.

Curcumin is a compound derived from the spice turmeric, and is a potent anti-oxidant, anti-carcinogenic, and anti-hepatotoxic agent. We have investigated the acute effects of curcumin on hepatic glucose production. Gluconeogenesis and glycogenolysis in isolated hepatocytes, and gluconeogenetic enzyme activity after 120 min exposure to curcumin were measured. Hepatic gluconeogenesis from 1 mM pyruvate was inhibited in a concentration-dependent manner, with a maximal decrease of 45% at the concentration of 25 microM. After 120 min exposure to 25 microM curcumin, hepatic gluconeogenesis from 2mM dihydroxyacetone phosphate and hepatic glycogenolysis were inhibited by 35% and 20%, respectively. Insulin also inhibited hepatic gluconeogenesis from 1mM pyruvate and inhibited hepatic glycogenolysis in a concentration-dependent manner. Curcumin (25 microM) showed an additive inhibitory effect with insulin on both hepatic gluconeogenesis and glycogenolysis, indicating that curcumin inhibits hepatic glucose production in an insulin-independent manner. After 120 min exposure to 25 microM curcumin, hepatic glucose-6-phosphatase (G6Pase) activity and phosphoenolpyruvate carboxykinase (PEPCK) activity both were inhibited by 30%, but fructose-1,6-bisphosphatase (FBPase) was not reduced. After 120 min exposure to 25 microM curcumin, phosphorylation of AMP kinase alpha-Thr(172) was increased. Thus, the anti-diabetic effects of curcumin are partly due to a reduction in hepatic glucose production caused by activation of AMP kinase and inhibition of G6Pase activity and PEPCK activity.

The spontaneously diabetic Torii rat with gastroenteropathy.

The spontaneously diabetic Torii (SDT) rat was recently recognized as a new animal model of non-obese type 2 diabetes. As the severe diabetic ocular complications seen in SDT rats already have been investigated, we examined another common diabetic complication, gastroenteropathy. Male SDT rats developed diabetes at 20 weeks and diarrhea at 28 weeks of age. Gastrointestinal motility was evaluated at 28 weeks by measuring the distance of small intestinal transit by oral administration of the non-absorbed marker, arabic gum. SDT rats exhibited greater intestinal transit distance than control SD rats (54.1+/-2.6% versus 43.0+/-1.2%). Insulin treatment of SDT rats begun at 20 weeks of age produced improved stool and reduced intestinal transit distance (41.4+/-0.3%). Morphologically, the SDT rats exhibited longer villi and heavier weight of intestine compared to control SD rats. These results suggest that the SDT rat may be a useful animal model for studies of diabetic gastroenteropathy.

Living donor islet transplantation, the alternative approach to overcome the obstacles limiting transplant.

We performed the world's first successful living donor islet transplantation for unstable diabetes. A total of 408,114 islet equivalents were isolated from half a living pancreas and transplanted immediately to the recipient who was a 27-year-old female. The donor was a 56-year-old female in good health, mother of the recipient. The islets functioned immediately, and the recipient was weaned completely from insulin on the 22nd posttransplant day, and has maintained excellent glycemic control since. The donor was discharged on the 18th postoperative day with normal oral glucose tolerance test and without complications. Living donor islet transplantation could cure one insulin-dependent diabetes mellitus patients with a single donor. There are some advantages in the living donor islet transplantation: (a) living donor can alleviate the issue of donor shortage; (b) highly potent islets can be isolated from a living donor; and (c) the recipient can be treated with immunosuppressant and controlled blood glucose level tightly prior to the transplantation. These are important factors in overcoming the obstacles limiting islet transplantation. We believe that the living donor islet transplantation may become an additional option in treating insulin-dependent diabetes.

Successful islet transplantation from nonheartbeating donor pancreata using modified Ricordi islet isolation method.

BACKGROUND: Current success of islet transplantation has led to donor shortage and the need for marginal donor utilization to alleviate this shortage. The goal of this study was to improve the efficacy of islet transplantation using nonheartbeating donors (NHBDs). METHODS: First, we used porcine pancreata for the implementation of several strategies and applied to human pancreata. These strategies included ductal injection with trypsin inhibitor for protection of pancreatic ducts, ET-Kyoto solution for pancreas preservation, and Iodixanol for islet purification. RESULTS: These strategies significantly improved both porcine and human islet isolation efficacy. Average 399,469+/-36,411 IE human islets were obtained from NHBDs (n=13). All islet preparations met transplantation criteria and 11 out of 13 cases (85%) were transplanted into six type 1 diabetic patients for the first time in Japan. All islets started to secrete insulin and all patients showed better blood glucose control without hypoglycemic loss of consciousness. The average HbA1c levels of the six recipients significantly improved from 7.5+/-0.4% at transplant to 5.1+/-0.2% currently (P<0.0003). The average insulin amounts of the six recipients significantly reduced from 49.2+/-3.3 units at transplant to 11+/-4.4 units (P<0.0005) and five out of six patients reduced to less than half dose. The first patient is now insulin free, the first such case in Japan. CONCLUSION: This demonstrates that our current protocol makes it feasible to use NHBDs for islet transplant into type 1 diabetic patients efficiently.