Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that regulates fundamental cellular processes such as proliferation, migration, apoptosis, and differentiation through five cognate G protein-coupled receptors (S1P1-S1P5). However, little is known about the role of S1P in obesity formation. We previously demonstrated that blockade of S1P2 signaling in S1P2-deficient mice attenuates high-fat diet-induced adipocyte hypertrophy and glucose intolerance and a S1P2-specific antagonist JTE-013 inhibits, whereas an S1P1/S1P3 dual antagonist (VPC23019) activates adipogenic differentiation. In this study, we examined whether an S1P1-specific agonist SEW-2871 and VPC23019 act on obesity and glucose intolerance in ob/ob mice. The oral administration of SEW-2871 and JTE-013 induced significant reductions in body weight gains and epididymal/inguinal fat adipocyte sizes and improved glucose intolerance and adipocyte inflammation in ob/ob mice but not in their control C57BL/6J mice. Both SEW-2871 and JTE-013 decreased mRNA levels of tumor necrosis factor-α and CD11c, whereas increased those of CD206 and adiponectin in the epididymal (not inguinal) fats isolated from ob/ob mice but not in control mice with no changes in the levels of peroxisome proliferator activated receptor gamma and its regulated genes. By contrast, VPC23019 did not cause all such alterations in these mice, however co-administration of SEW-2871 and VPC23019 abolished the effect of SEW-2871 on ob/ob mice. In conclusion, the S1P1 agonist SEW-2871 acted like the S1P2 antagonist JTE-013 to reduce body and improve glucose tolerance in obese mice. Therefore, endogenous S1P could promote obesity/type 2 diabetes through the S1P2, whereas exogenous S1P could act against them through the S1P1. Disclosure M. Asano: None. M. Fuwa: None. I. Mori: None. H. Morita: None. K. Kajita: None. T. Ishizuka: None.

The role of mitochondria in white adipocytes (WAs) has not been fully explored. A recent study revealed that brown adipocytes contain functionally distinct mitochondrial fractions, cytoplasmic mitochondria, and peridroplet mitochondria. However, it is not known whether such a functional division of mitochondria exists in WA. Herein, we observed that mitochondria could be imaged and mitochondrial DNA and protein detected in pellets obtained from the cytoplasmic layer and oil layer of WAs after centrifugation. The mitochondria in each fraction were designated as cytoplasmic mitochondria (CMw) and peridroplet mitochondria (PDMw) in WAs, respectively. CMw had higher beta-oxidation activity than PDMw, and PDMw was associated with diacylglycerol acyltransferase 2. Therefore, CMw may be involved in beta-oxidation and PDMw in droplet expansion in WAs. White adipocytes contain two mitochondrial fractions: cytoplasmic mitochondria (CMw) and peridroplet mitochondria (PDMw). The formation of PDMw is partially regulated by perilipin 1 (PLIN1). CMw is responsible for beta-oxidation, whereas PDMw is associated with diacylglycerol acyltransferase 2 (DGAT2) and contributes to the supply of triglycerides to lipid droplets. image

One of the major global health and welfare issues is the treatment of obesity and associated metabolic disorders, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease. Obesity, caused by the excessive accumulation of triglycerides in adipose tissues, induces adipocyte dysfunction, followed by inflammation, in adipose tissues and lipotoxicity in nonadipose tissues. Several studies have shown that obesity and glucose homeostasis are influenced by sphingolipid mediators, including ceramide and sphingosine 1-phosphate (S1P). Cellular accumulation of ceramide impairs pancreatic β-cell survival, confers insulin resistance in the liver and the skeletal muscle, and deteriorates adipose tissue inflammation via unknown molecular mechanisms. The roles of S1P are more complicated, because there are five cell-surface S1P receptors (S1PRs: S1P1–5) which have altered functions, different cellular expression patterns, and inapparent intracellular targets. Recent findings, including those by our group, support the notable concept that the pharmacological activation of S1P1 or S1P3 improves obesity and associated metabolic disorders, whereas that of S1P2 has the opposite effect. In addition, the regulation of S1P production by sphingosine kinase (SphK) is an essential factor affecting glucose homeostasis. This review summarizes the current knowledge on SphK/S1P/S1PR signaling in and against obesity, insulin resistance, and associated disorders.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that regulates fundamental cellular processes such as proliferation, migration, apoptosis, and differentiation through 5 cognate G protein-coupled receptors (S1P1-S1P5). We previously demonstrated that blockade of S1P2 signaling in S1P2-deficient mice attenuates high-fat diet-induced adipocyte hypertrophy and glucose intolerance and an S1P2-specific antagonist JTE-013 inhibits, whereas an S1P1/S1P3 dual antagonist (VPC23019) activates, adipogenic differentiation of preadipocytes. Based on those observations, this study examined whether an S1P1-specific agonist, SEW-2871, VPC23019, or their combination acts on obesity and glucose intolerance in leptin-deficient ob/ob mice. The oral administration of SEW-2871 or JTE-013 induced significant reductions in body/epididymal fat weight gains and epididymal/inguinal fat adipocyte sizes and improved glucose intolerance and adipocyte inflammation in ob/ob mice but not in their control C57BL/6J mice. Both SEW-2871 and JTE-013 decreased messenger RNA levels of tumor necrosis factor-α and CD11c, whereas they increased those of CD206 and adiponectin in the epididymal fats isolated from ob/ob mice with no changes in the levels of peroxisome proliferator activated receptor γ and its regulated genes. By contrast, VPC23019 did not cause any such alterations but counteracted with all those SEW-2871 actions in these mice. In conclusion, the S1P1 agonist SEW-2871 acted like the S1P2 antagonist JTE-013 to reduce body/epididymal fats and improve glucose tolerance in obese mice. Therefore, this study raises the possibility that endogenous S1P could promote obesity/type 2 diabetes through the S1P2, whereas exogenous S1P could act against them through the S1P1.

Abstract Disclosure: I. Mori: None. T. Ishizuka: None. H. Morita: None. K. Kajita: None. White adipocytes (WAs) are involved in the formation of obesity and insulin resistance, but little is known about the role of WAs mitochondria. A recent study revealed that the mitochondria of brown adipocytes (BAs) consist of cytoplasmic mitochondria CM), which is responsible for β-oxidation, and peridroplet mitochondria (PDM), which supplies triglyceride to lipid droplets. However, it is unclear whether such a functional division exist in WA mitochondria. In this study, we examined whether the pellets obtained from cytoplasmic and oil layers of WAs of C57/BL/J mice by centrifugation were mitochondria. Since mitochondrial DNA, mitochondrial protein, Mitotracker Red staining, and mitochondrial images in electron microscope were detected in both fractions, they were considered to be cytoplasmic mitochondria (CMw) and peridroplet mitochondria (PDMw) in WAs, respectively. The amount of CMw and PDMw were greater in epididymal fat than in inguinal fat. CMw had higher β-oxidation activity than PDMw. PDMw was associated with perilipin 1/3 and diacylglycerol acyltransferase 2. The amount of PDMw was elevated in epididymal fat of mice fed a high-fat diet (HFD) for 2 and 4 weeks compared to normal chew-fed mice. These results suggested that CMw was involved in β-oxidation, and PDMw in droplet expansion. Although numerous researches have been shown that amount of mitochondria is suppressed in obese WAs, our results revealed that PDMw might be involved in the early stage of obesity formation. Presentation: 6/1/2024

Introduction & Objective: Glucocorticoid (GC) treatments have widely contributed to induction and maintenance therapies. However, GC-induced hyperglycemia cannot be predicted by fasting plasma glucose and HbA1c alone. The aim of the study was to identify the risk factors for GC-induced hyperglycemia and have developed and validated a novel scoring system for predicting the need for hypoglycemic agents during GC treatment. Methods: In a developing set, 508 adults receiving prednisolone (PSL) for the first time were divided into two groups based on their treatment with or without hypoglycemic agents. Their clinical and laboratory parameters were compared, and risk factors were identified using logistic regression analysis after performing univariate analyses between the two groups. A point-addition scoring system with several categories and their coefficients in each risk factor was constructed to predict the need for hypoglycemic agents. The scoring system was then applied and validated on two validation sets, A and B. Results: Older age and higher HbA1c percentages, body mass index, and initial PSL dosage were identified as risk factors. The sensitivity, specificity, and accuracy of the scoring system were 70.6%, 81.9%, and 77.1% in the developing set, 75.8%, 78.4%, and 77.4% in the validation set A, 79.4%, 73.9%, and 75.3% in the validation set B, respectively. Conclusion: The scoring system is a valid and reliable tool for predicting the need for hypoglycemic agents in advance during GC treatment. Disclosure A. Kato: None. M. Fuwa: None. M. Asano: None. I. Mori: None. H. Morita: None. Funding JSPS KAKENHI (23K06864)

Background: The use of serum soluble interleukin 2 receptor (sIL-2R) for the diagnosis of febrile illnesses has not been examined. In this study, febrile patients were classified according to etiology and disease, and serum sIL-2R levels were evaluated. We determined whether serum sIL-2R is a useful marker for differentiating between malignant lymphoma (ML) and non-ML patients and between patients with ML and Kikuchi disease, which present similar clinical manifestations. Methods: This study was a cross-sectional study and included 344 patients with uncomplicated hemophagocytic syndrome, who had a fever of 38 °C or higher within 1 week of admission to our institution. Patient serum sIL-2R was measured, and the serum sIL-2R values are shown as median and IQR. Results: Serum sIL-2R increased above the upper reference limit in all disease groups with fever. The serum sIL-2R level in ML patients (n = 13) was 4760 (2120–6730) U/mL and significantly higher (p < 0.001) than the level of 998 (640–1625) U/mL in non-ML patients (n = 331). The serum sIL-2R level in ML patients (n = 13) was also significantly higher (p < 0.001) compared with that in patients with Kikuchi disease (n = 20; 705 (538–1091) U/mL). Conclusions: Serum sIL-2R tends to exceed the upper reference limit in patients with febrile illnesses. We conclude that the measurement of serum sIL-2R is useful for differentiating ML from non-ML and ML from Kikuchi disease.

BACKGROUND:Glucocorticoid (GC) treatments are often used. There is limited information on the prediction of hyperglycaemia after GC administration. AIMS:This study aimed to identify the risk factors for hyperglycaemia after glucocorticoid (GC) administration and the need for hypoglycaemic agents to correct it and to develop and validate a novel scoring system for predicting GC-induced hyperglycaemia. METHODS:In a development set, 508 adults receiving prednisolone (PSL) for the first time were divided into two groups based on treatment with or without hypoglycaemic agents. Clinical and laboratory parameters were compared, and risk factors were identified using logistic regression analysis after performing univariate analyses between the two groups. A point-addition scoring system with several categories and coefficients for each risk factor was constructed to predict the need for hypoglycaemic agents. The scoring system was then applied and validated on two validation sets: A and B. RESULTS:Older age, higher glycated haemoglobin percentage, body mass index and initial PSL dosage were identified as risk factors. The sensitivity, specificity and accuracy of the scoring system were 70.6%, 81.9% and 77.1% in the development set; 75.8%, 78.4% and 77.4% in validation set A; and 79.4%, 73.9% and 75.3% in validation set B respectively. By fitting the total score in the development set and the probability of hyperglycaemia to a logistic curve, a figure was created to show the probability of GC-induced hyperglycaemia in patients scheduled to receive GC. CONCLUSION:This scoring system is a novel, valid and reliable tool for predicting GC-induced hyperglycaemia and the need for hypoglycaemic agents to correct it.

Mitochondria play various roles for biological maintenance in adipocytes. As for lipid metabolism, mitochondria have the opposite function of burning fatty acid by β-oxidation and supplying triglyceride (TAG) to lipid droplet. Recent study revealed that brown adipocytes (BA) contain cytoplasmic mitochondria (CM), which have high β-oxidation ability, and peridroplet mitochondria (PDM), which adhere lipid droplet, have high ability to generate ATP to synthesize and supply TAG to lipid droplet. On the other hand, Mitofusin 2 (Mfn2) and Mitoguardin 2 (MIGA2), and diacylglycerol acyltransferase 2 (DGAT2) are speculated to involved in interaction between mitochondria, endoplasmic reticulum and lipid droplet to promote TAG synthesis and expansion of lipid droplet. However, little is known about such mitochondrial fractions in white adipocytes (WA). In this study, we investigated whether WA isolated from mice adipose tissue may have mitochondria fractions corresponding to CM/PDM in BA. Cytoplasmic mitochondria and peridroplet mitochondria in WA (CMw/PDMw) were separated by centrifugation. Mitochondrial DNA, mitochondrial protein, incorporation of MitoTracker Red, and citrate synthase activity were detected in PDMw, as well as CMw. Electron microscopy showed larger size of mitochondria were observed in PDMw, than in CMw. Immunoblot analysis showed that Perilipin (Plin) 1 and Plin3 were detected in PDMw, but not in CMw. In addition, MIGA2 was detected in both CMw and PDMw, whereas Mfn2 and DGAT2 in PDMw. Immunoprecipitation study revealed that co-precipitation of Plin1/3 and MIGA2/Mfn2/DGAT2 was observed in the PDMw fraction. Our data indicated that mitochondria adhering lipid droplet was detected, which bind to Plin1/3. Moreover, the immunoprecipitation study suggested that mitochondria in the PDMw fraction may support TAG synthesis and expansion of lipid droplet. These results suggested that CMw and PDMw might play different roles in lipid metabolism in WA. Disclosure M.Fuwa: None. M.Asano: None. I.Mori: None. H.Morita: None. K.Kajita: None. T.Ishizuka: None.

80歳，男性．発熱を主訴に精査入院となり，血液検査，腎生検の結果から，顕微鏡的多発血管炎（microscopic polyangiitis：MPA）の診断に至った．入院時から，心電図で完全房室ブロックがあり，ペースメーカー留置を検討していた．しかし，MPAに対する寛解導入治療によって，完全房室ブロックは1度房室ブロックに改善した．小型血管炎ではそれに伴う心筋虚血によって完全房室ブロックが引き起こされ，治療によって改善する可能性を念頭に置く必要がある．

Neurosarcoidosis is a rare disease and is often difficult to diagnose. Herein, we report a case of neurosarcoidosis in a patient with a history of Ewing's sarcoma of the brain. He presented with fever of unknown origin, and a pathological diagnosis was obtained via biopsy of a normal-sized inguinal lymph node with fluorodeoxyglucose (FDG) accumulation on positron emission tomography/computed tomography (PET/CT). The condition could not have been diagnosed without FDG-PET/CT.

Objective: The objective of this study was to explore the feasibility of monitoring actively dying patients hospitalized in a palliative care unit using a nonwearable sheet-type monitor that measured the state of sleep and vital signs per minute. In addition, we aimed to clarify the incidence of increased respiratory rate and its relationship with survival time. Design and Measurement: This study was conducted at a 51-bed palliative care unit in Japan from April 2018 through October 2019. Actively dying patients hospitalized in the palliative care unit were eligible to participate. Increased respiratory rate was measured by Nemuri SCAN, and patient's information was extracted from their medical records. Results: In this study, 23 patients were monitored until death; 19 patients with an observational period of 7 days or longer (163 patient days in total) were included in this analysis. There were no adverse events due to use of the nonwearable device. The cumulative incidence of increased respiratory rate (defined as more than 30 respiratory rate per minute) was 63.16% during the observational period, and the mean time between appearance of increased respiratory rate and death was 4.17 ± 4.04 days. Conclusion: This study clearly shows that hospitalized actively dying patients can be monitored using a nonwearable sheet-type monitor that measures sleeping state and vital signs per minute. Further studies are needed to utilize these noninvasive continuous monitoring devices in daily clinical practice.

Male, 41 years old (yo) had been complaining of severe arthralgia. Past History indicated obstruction of intestinal tract at 12 yo and gastric ulcer at 13 yo. He had been suffered from polyarthralgia especially at PIP and MP joints of both hands from 38 yo. Finally, he complained severe arthralgia at PIP and MP joints with clubbed fingers without swelling. Biochemical finding indicated negative rheumatoid factor and anti-CCP antibody and normal MMP-3 level, but slightly increased CRP and ESR levels. Radiological finding indicated periostosis of long bone without bone erosion and osteoporosis. His facial appearance was acromegalic with cutaneous manifestation of pachydermia and cutis vertices gyrate without abnormal growth hormone response. Histological findings of skin indicated oedema and hyperplasia of sebaceous glands with infiltration of lymphocytes around small blood vessels compatible with pachydermoperiostosis. In this case mutation of SLCO2A1 gene, which coded prostaglandin transport protein, was identified. The mutation c.940 + 1G > A of SLCO2A1 gene results in deletion of exon 7 and truncation of PG transporter (p.Arg288Glyfs*7). We suggest that severe arthralgia was originated from over production of prostaglandin E2. Further studies will be required.

A 47 years old man who had been diagnosed as malignant pheochromocytoma with metastases of lumbar spines at 21 years old. He had received partial tumor abscission, radiotherapy and 131I-MIBG treatment, He had been suffered from gait disturbance for spinal compression by the metastasis of vertebral spines at 42 years old. CVD treatment and 5-FU+CBDCA treatment had been performed for 13 cycles. After treatment with 5-FU and CBDCA, MRI imaging showed brain abscess and drainage for brain abscess had been done. Nocardia farcinica was identified in his brain abscess. Treatment with ST combination vanished brain abscess by MRI imaging.

Context. Dyspnea is one of the most distressing symptoms for terminally ill cancer patients and a predictor of poor prognosis. Identification of simple clinical signs, such as heart rate, indicating clinical course of each patient is of value. Objectives. To explore the potential association between heart rate and reversibility of the symptom, treatment response to palliative intervention, and survival in terminally ill cancer patients with dyspnea at rest. Methods. This is a secondary analysis of a multicenter prospective cohort study of patients with advanced cancer to validate multiple prognostic tools. In the patients with dyspnea at rest at the baseline, we examined a potential association between heart rate and the reversibility of dyspnea and refractoriness to palliative treatment using logistic regression analysis. Survivals were compared using the Cox proportional hazards model among four groups with different levels of the heart rate (<= 74, 75-84, 85-97, and >= 98). Results. A total of 2298 patients were enrolled, and 418 patients (18%) had dyspnea at rest. Reversibility of dyspnea was significantly higher in the patients with lower heart rate (P for trend = 0.008), and the refractoriness to palliative treatment tended to be higher in the patients with higher heart rate (P for trend = 0.101). The median survival for each heart rate quartile groups was significantly higher in the lower heart rate group (24 vs. 21 vs. 14 vs. 9 days; heart rate <= 74, 75-84, 85-97, and >= 98, respectively; log-rank P < 0.001). Conclusion. Heart rate may help clinicians to make the prediction of the patient's clinical course more accurate. (C) 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Association between TNFα and IL-6 and glucose tolerance has been reported. However, it is not clear that TNFα and IL-6 affect on glucose tolerance. Recently, biologic agents such as TNF and IL-6 inhibitors have been appeared in the treatment of RA. We have examined comparative effects of TNF αand IL-6 inhibitors on glucose tolerance and lipid metabolism in patients with rheumatoid arthritis. Registered 589 patients with RA have been screened by HbA1c level (more than 5.6%), treatment with methotrexate (MTX) and treatment with biologic agents with or without MTX. We have excluded the patients with RA who are treated with insulin, and selected 30 cases of RA patients who were able to follow-up for 12 months (M). Patients with RA were divided to 3 groups by the treatments as follows: TNF inhibitors with MTX (TNF+MTX), IL-6 with and without MTX (IL-6±MTX) and MTX alone. Body weight, HbA1c, LDL-C, HDL-C, LDL-C/HDLC(L/H) and disease activity score (DAS) were measured before and after 6 and 12 M. There were no differences of DAS between each group before and after 6 and 12 M. DAS in each group was a significantly decreased compared with before (P < 0.05-0.001). HbA1c levels in TNF+MTX were not significantly different (before 6.08%, 6 M 5.92%, 12M 5.91%), but those in MTX alone and IL-6±MTX were significantly improved (before 6.42% and 6.2%, 6M 5.87% and 5.78%, P< 0.05, 12M 5.82%, P< 0.05 and 5.81%, P< 0.01), respectively. There were no significant differences of body weight between each group. HDL-C and LDL-C in IL-6±MTX were significantly (P< 0.01) increased (before 58.2 mg/dl and 123.2 mg/dl, 6M 71.7 mg/dl and 148.5 mg/dl, 12M 63.4 mg/dl and 144.2 mg/dl), respectively. L/H in TNF+MTX was significantly (P<0.05) decreased. In conclusion, effect of glucose tolerance in IL-6 inhibitors was better than TNF inhibitors in RA patients with glucose intolerance. However, TNF inhibitor in lipid metabolism was better than IL-6 inhibitors. Disclosure T. Ishizuka: None. K. Fujioka: None. I. Mori: None. T. Takeda: None. S. Inui: None.

BackgroundFMF is recessive systemic auto inflammatory disorder characterized by recurrent fever, peritonitis, pleuritis, pericarditis and arthritis accompanied with skin rash. Mutation of MEFV gene encoding pyrin resulted in inflammasome activation and the uncontrolled production of IL-1β. Overview of pathogenesis, clinical features and management in Japanese patients with FMF had been reported1. However, the differences of clinical features between mutated and non-mutated of MEFV still remain unclear.ObjectivesWe have analyzed 20 Japanese patients with FMF to clarify the association between various clinical features and mutation of MEFV.MethodsGenomic DNA were purified from white blood cells in 20 FMF patients, and mutated MEFV has been explored. We have analyzed MEFV, TNFRSF1A, MVK and NLRP3 genes in 20 patients with FMF. Therefore, we excluded another autoinflammatory diseases such as TNF receptor-associated syndrome (TRAPS), mevalonate kinase deficiency and cryopyrin-associated periodic syndrome. Clinical symptoms and laboratory data were analyzed around onset time. Each patient had been treated with colchicine (0.5-2 mg).ResultsCharacteristics of Patients with FMF (13 female/7 male) were as follows; Onset time were 0-53 years old (17.5 ±12.2), and teen aged patients were most. Frequencies of clinical symptoms such as periodic fever, headache, arthralgia, abdominal pain, chest pain, myalgia, and cervical lymph nodes swelling were 20/20, 7/20, 6/20, 5/20,4/20,2/20 and 1/20, respectively (double symptoms were observed). Patients with FMF were divided to 3 groups as follows; Patients with typical compound heterozygous mutations of MEFV (E148Q/M694I) which indicated exon 10 mutation, were 3 cases (group 1). Patients with atypical mutations, except for mutations in exon 10, such as exon 1 (E84K, L110P), 2 (E148Q), 3(P369S, R408Q), 5(S503C) and 9(I591M) were 8 cases (group 2). Patients with no mutations in MEFV gene were 9 cases (group 3). There were no significant differences of age at first visiting hospital (FV), onset age of fever attack (O), duration of fever attack (D) and frequency of fever attack (FF) between group 1, group2 and group 3 ( FV: 22.3 ± 4.5, 26.8 ± 14.6 years old (yo) and 29.5 ± 8.7 yo, O: 11.6 ± 2.4 yo, 18.5 ± 13.8 yo and 18.5 ± 12.0 D: 3.0 ± 1.4 hrs, 6.3 ± 3.2 hrs, and 8.1 ± 8.5 hrs, FF: 1.2 ± 0.2/month (M), 1.2 ± 1.1/M, and 1.1 ± 0.2/M), respectively. Laboratory examinations such as WBC, CRP and serum amyloid A (SAA) were not significantly different between 3 groups. All of those patients were effective for colchicine treatment except for 2 patients in group 1 because of severe diarrhea and alopecia. Finally, 2 patients in group 1 received canakinumab treatment. Mutations of E148Q were found in 9 patients (45%).ConclusionWe have examined association between clinical features and mutations of MEFV in 20 Japanese patients, suggesting no positive findings in Japanese patients with FMF. Mutations of E148Q in exon 2 were observed in 16-23 % of normal Japanese patients1, indicating that E148Q is the polymorphism or accelerating factor.References[1] K. Migita et al, Familial Mediterranean fever : overview of pathogenesis, clinical features and management. Immunological Medicine 41:2, 55-61, 2018Disclosure of InterestsNone declared

Insulin is often administered for glucocorticoid (GC) -induced hyperglycemia. We have developed and validated a scoring system to predict insulin requirement for optimal control of hyperglycemia during GC treatment through retrospective studies. The Developing set: 303 adults out of 2718 patients, undergoing their first treatment of prednisolone (PSL) with a dosage of 5 mg/day or more for 4 weeks at least, were divided into 2 groups depending on with or without administration of insulin during GC treatment. Risk factors for insulin requirement were identified by a stepwise logistic regression analysis after univariate analyses of clinical parameters before GC treatment between the 2 groups. We constructed a point-addition scoring system, consisting of several categories and their coefficients in each risk factor, derived from another multivariate analysis. We validated it to validation sets A (n=44) and B (n=77) in another two facilities, respectively. Male, FPG, HbA1c, serum CRE, and an initial dose of PSL were identified as the risk factors. The AUC by ROC analysis of the total scores when the Developing set was scored, showed 0.94. The sensitivity, specificity, and accuracy were 90%, 88%, and 88%; 88%, 67%, and 71%; 83%, 76%, and 77% in the Developing set, Validation set A, and B, respectively if the cut off value of the total scores was defined as 19 points. The scoring system: Table is useful. Disclosure M. Kawashima: None. Y. Kitada: None. K. Kajita: None. I. Mori: None. T. Ishizuka: None. D. Murakami: None. H. Okada: None. H. Morita: None. Funding Sanofi; Eli Lilly Japan K.K.