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The effect of SGLT2 inhibitors on drug-naive obese type 2 diabetes mellitus patients
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211
of SGLT2 inhibitors. Thus, it is controversial whether we should continue SGLT2 inhibitor administration in the long term after having obtained the expected beneficial metabolic effects. We therefore examined the 1-year clinical course of patients with type 2 diabetes mellitus after discontinuation of the SGLT2 inhibitor tofogliflozin. Methods: Twenty-one patients with type 2 diabetes mellitus who were treated with 20 or 40 mg/day tofogliflozin for 52 weeks participated in this study (monotherapy, n = 9; combination therapy with sulfonylureas, n = 12). All the patients were involved in the Phase 3 clinical study of tofogliflozin in Japanese patients with type 2 diabetes mellitus. After discontinuation of tofogliflozin, changes in clinical parameters including body weight, HbA1c, serum lipid concentrations and liver enzymes were observed for the following year. Results: Patient body weight decreased an average of 3.1 kg after tofogliflozin administration for 52 weeks, but increased 2.1 kg on average in the 3 months following tofogliflozin discontinuation. Furthermore, body weight returned to the level before treatment within one year. HbA1c levels also decreased an average of 1.1% after tofogliflozin administration, but increased 0.4% in the first 3 months after discontinuation of the drug, and interventions with other classes of hypoglycemic agents were performed in 19 of the 21 patients. Similarly, alanine aminotransferase and γ-glutamyltransferase significantly decreased during the tofogliflozin treatment period, but increased again after discontinuation of tofogliflozin. Conclusion: The pharmacological effect of the SGLT2 inhibitor tofogliflozin disappeared immediately following drug discontinuation, and increases in body weight, HbA1c and the liver enzymes were observed within 3 months in most cases. Therefore, careful assessment of patients, including behavioral changes and their metabolic condition, is necessary for making a decision on continuation/discontinuation of SGLT2 inhibitors. PD-37 The effect of rice-bran dietary fiber on postprandial blood glucose for Type II diabetic patients TzuYing WU1 *, WenHuy CHEN1. 1Nutrition & Dietetics Division of the Lukang Branch of Changhua Hospital, Taiwan Dietary fiber has important role in the management of postprandial blood glucose (PBG) control for diabetic patients. The rice bran that is left over from the rice refinement process has a large amount of dietary fiber. Therefore, the effect of rice-bran dietary fiber (RDF) on PBG among Type II diabetic patients was investigated. A total of nine volunteering Type II diabetic patients were enrolled in this study. The patients were given, on two separate days, the same breakfasts (including 60 grams carbohydrates) that were with RDF (10 g) or RDF-free. Fasting and postprandial blood was collected at intervals of 30 min for 180 min to determine whole blood glucose. The results indicated that the use of RDF can significantly reduce the area under the curve (AUCglucose) for the PBG plot (36360 ± 6073 vs. 32560 ± 5546.7 mg/dL × min, P < 0.05) as well as shortened the PBG peak values and peak time. In conclusion, rice bran dietary fiber can be used to improve PBG for Type II Diabetic Patients. PD-38 The effect of SGLT2 inhibitors on drug-naive obese type 2 diabetes mellitus patients Shinji CHIKAZAWA1, Yuki MATSUHASHI2 *, Yusuke TANDO2, Makoto DAIMON2. 1Tsugaru General Hospital, 2Hirosaki University Graduate School of Medicine, Japan We administered sodium glucose cotransporter 2 (SGLT2) inhibitors to drug-naive obese type 2 diabetes mellitus (T2D) patients for 3 or 4 months. We report changes in blood sugar
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control of 3 patients. Case 1: 20 mg tohogliflozin for 4 months was administered to 47 year-old female whose duration of diabetes mellitus (DM) was about 3 years. Body weight (BW) was reduced from 85.9 kg to 71.1 kg. Blood sugar levels before meals ( preprandial) were lowered from 166 mg/dL to 97 mg/dL. HbA1c was improved from 8.7% to 5.3%. Imunoreactive insulin (IRI) levels decreased from 7.49 mcIU/mL to 4.89 mcIU/mL. Serum C-peptide reactivity (S-CPR) decreased from 2.54 ng/mL to 1.75 ng/mL. Case 2: 50 mg ipragliflozin for 4 months was administered to 64 year-old male whose duration was about 4 years. BW was reduced from 79.3 kg to 75.8 kg. Preprandial blood sugar was lowered from 202 mg/dL to 162 mg/dL. HbA1c was improved from 10.7% to 7.6%. IRI increased from 3.06 mcIU/mL to 7.39 mcIU/mL. S-CPR increased from 1.73 ng/ ml to 2.65 ng/mL. Case 3: 5 mg dapagliflozin for 3 months was administered to 43 year-old male whose duration was about 1 month. BW was reduced from 95.3 kg to 83.5 kg. Preprandial blood sugar was lowered from 134 mg/dL to 96 mg/ dL. HbA1c was improved from 7.9% to 5.7%. IRI decreased from 11.86 mcIU/mL to 8.94 mcIU/mL. S-CPR decreased from 2.13 ng/mL to 1.61 ng/mL. The improvements of their clinical condition were much due to the loss of their body weight. Insulin resistance could be reduced by the loss of body weight. Insulin resistance is the essential of T2D. Adiponectin levels were slightly increased in Case 1 and Case 2. Free fatty acid was decreased in Case 3. These phenomena indicated that SGLT 2 inhibitor could increase one of insulin sensitivity enhancers, and decrease one of induction factors of insulin resistance. In Case 1 and in Case 3, the patients took care of their BW, and they stopped snacking. As the patient of Case 2 could not stop snacking, neither IRI nor S-CPR were improved. When SGLT2 inhibitors are administered to drug-naïve obese T2D patients who observe the compliance to dietary, we may expect the improvement of their insulin resistance and SGLT2 inhibitors could cure the essential of T2D. PD-39 Plasma serpinB1 levels are strongly correlated with circulating ANGPTL8 levels in patients with type 2 diabetes Shinsuke TOKUMOTO1 *, Akihiro HAMASAKI1, Emi OKAMURA1, Yukiko KAWASAKI1, Sachiko HONJO1, Yoshiyuki HAMAMOTO2 . 1Centre for Diabetes and Endocrinology, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, 2Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, Japan Background and aims: SerpinB1, a protease inhibitor secreted by the liver, has recently been described as a potent stimulator that increases beta cell proliferation in mice and humans. While we previously reported that ANGPTL8 correlated with insulin secretion capacity, the pathophysiological role of SerpinB1 in patients with type 2 diabetes mellitus (T2DM) remains poorly understood. The aim of the study was to evaluate the relationship between plasma SerpinB1 levels and other biomarkers including ANGPTL8. Materials and methods: Overnight fasting plasma samples from 8 healthy subjects and 69 T2DM patients were collected. HbA1c, fasting plasma glucose, total cholesterol, triacylglycerol, and creatinine clearance (CrCl) calculated by 24-hour urine collection were measured in all T2DM patients. Plasma levels of serpinB1 (Cusabio, Catalogue No. CSB-EL021065HU) and ANGPTL8 (Eiaab, Catalogue No. E11644h) were determined by enzyme-linked immunosorbent assay according to the manufacturer’s protocol. Correlations were evaluated by Spearman’s rank test. P values <0.05 were considered statistically significant. Results: Plasma serpinB1 levels were significantly higher in T2DM patients (0.53 ± 0.28 ng/mL) than in healthy subjects (0.21 ± 0.16 ng/mL; p < 0.05). In T2DM patients, plasma serpinB1 levels showed a significant positive association with ANGPTL8 (r = 0.47 p < 0.001). Both serpinB1 and ANGPTL8 levels
of SGLT2 inhibitors. Thus, it is controversial whether we should continue SGLT2 inhibitor administration in the long term after having obtained the expected beneficial metabolic effects. We therefore examined the 1-year clinical course of patients with type 2 diabetes mellitus after discontinuation of the SGLT2 inhibitor tofogliflozin. Methods: Twenty-one patients with type 2 diabetes mellitus who were treated with 20 or 40 mg/day tofogliflozin for 52 weeks participated in this study (monotherapy, n = 9; combination therapy with sulfonylureas, n = 12). All the patients were involved in the Phase 3 clinical study of tofogliflozin in Japanese patients with type 2 diabetes mellitus. After discontinuation of tofogliflozin, changes in clinical parameters including body weight, HbA1c, serum lipid concentrations and liver enzymes were observed for the following year. Results: Patient body weight decreased an average of 3.1 kg after tofogliflozin administration for 52 weeks, but increased 2.1 kg on average in the 3 months following tofogliflozin discontinuation. Furthermore, body weight returned to the level before treatment within one year. HbA1c levels also decreased an average of 1.1% after tofogliflozin administration, but increased 0.4% in the first 3 months after discontinuation of the drug, and interventions with other classes of hypoglycemic agents were performed in 19 of the 21 patients. Similarly, alanine aminotransferase and γ-glutamyltransferase significantly decreased during the tofogliflozin treatment period, but increased again after discontinuation of tofogliflozin. Conclusion: The pharmacological effect of the SGLT2 inhibitor tofogliflozin disappeared immediately following drug discontinuation, and increases in body weight, HbA1c and the liver enzymes were observed within 3 months in most cases. Therefore, careful assessment of patients, including behavioral changes and their metabolic condition, is necessary for making a decision on continuation/discontinuation of SGLT2 inhibitors. PD-37 The effect of rice-bran dietary fiber on postprandial blood glucose for Type II diabetic patients TzuYing WU1 *, WenHuy CHEN1. 1Nutrition & Dietetics Division of the Lukang Branch of Changhua Hospital, Taiwan Dietary fiber has important role in the management of postprandial blood glucose (PBG) control for diabetic patients. The rice bran that is left over from the rice refinement process has a large amount of dietary fiber. Therefore, the effect of rice-bran dietary fiber (RDF) on PBG among Type II diabetic patients was investigated. A total of nine volunteering Type II diabetic patients were enrolled in this study. The patients were given, on two separate days, the same breakfasts (including 60 grams carbohydrates) that were with RDF (10 g) or RDF-free. Fasting and postprandial blood was collected at intervals of 30 min for 180 min to determine whole blood glucose. The results indicated that the use of RDF can significantly reduce the area under the curve (AUCglucose) for the PBG plot (36360 ± 6073 vs. 32560 ± 5546.7 mg/dL × min, P < 0.05) as well as shortened the PBG peak values and peak time. In conclusion, rice bran dietary fiber can be used to improve PBG for Type II Diabetic Patients. PD-38 The effect of SGLT2 inhibitors on drug-naive obese type 2 diabetes mellitus patients Shinji CHIKAZAWA1, Yuki MATSUHASHI2 *, Yusuke TANDO2, Makoto DAIMON2. 1Tsugaru General Hospital, 2Hirosaki University Graduate School of Medicine, Japan We administered sodium glucose cotransporter 2 (SGLT2) inhibitors to drug-naive obese type 2 diabetes mellitus (T2D) patients for 3 or 4 months. We report changes in blood sugar
S103
control of 3 patients. Case 1: 20 mg tohogliflozin for 4 months was administered to 47 year-old female whose duration of diabetes mellitus (DM) was about 3 years. Body weight (BW) was reduced from 85.9 kg to 71.1 kg. Blood sugar levels before meals ( preprandial) were lowered from 166 mg/dL to 97 mg/dL. HbA1c was improved from 8.7% to 5.3%. Imunoreactive insulin (IRI) levels decreased from 7.49 mcIU/mL to 4.89 mcIU/mL. Serum C-peptide reactivity (S-CPR) decreased from 2.54 ng/mL to 1.75 ng/mL. Case 2: 50 mg ipragliflozin for 4 months was administered to 64 year-old male whose duration was about 4 years. BW was reduced from 79.3 kg to 75.8 kg. Preprandial blood sugar was lowered from 202 mg/dL to 162 mg/dL. HbA1c was improved from 10.7% to 7.6%. IRI increased from 3.06 mcIU/mL to 7.39 mcIU/mL. S-CPR increased from 1.73 ng/ ml to 2.65 ng/mL. Case 3: 5 mg dapagliflozin for 3 months was administered to 43 year-old male whose duration was about 1 month. BW was reduced from 95.3 kg to 83.5 kg. Preprandial blood sugar was lowered from 134 mg/dL to 96 mg/ dL. HbA1c was improved from 7.9% to 5.7%. IRI decreased from 11.86 mcIU/mL to 8.94 mcIU/mL. S-CPR decreased from 2.13 ng/mL to 1.61 ng/mL. The improvements of their clinical condition were much due to the loss of their body weight. Insulin resistance could be reduced by the loss of body weight. Insulin resistance is the essential of T2D. Adiponectin levels were slightly increased in Case 1 and Case 2. Free fatty acid was decreased in Case 3. These phenomena indicated that SGLT 2 inhibitor could increase one of insulin sensitivity enhancers, and decrease one of induction factors of insulin resistance. In Case 1 and in Case 3, the patients took care of their BW, and they stopped snacking. As the patient of Case 2 could not stop snacking, neither IRI nor S-CPR were improved. When SGLT2 inhibitors are administered to drug-naïve obese T2D patients who observe the compliance to dietary, we may expect the improvement of their insulin resistance and SGLT2 inhibitors could cure the essential of T2D. PD-39 Plasma serpinB1 levels are strongly correlated with circulating ANGPTL8 levels in patients with type 2 diabetes Shinsuke TOKUMOTO1 *, Akihiro HAMASAKI1, Emi OKAMURA1, Yukiko KAWASAKI1, Sachiko HONJO1, Yoshiyuki HAMAMOTO2 . 1Centre for Diabetes and Endocrinology, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, 2Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, Japan Background and aims: SerpinB1, a protease inhibitor secreted by the liver, has recently been described as a potent stimulator that increases beta cell proliferation in mice and humans. While we previously reported that ANGPTL8 correlated with insulin secretion capacity, the pathophysiological role of SerpinB1 in patients with type 2 diabetes mellitus (T2DM) remains poorly understood. The aim of the study was to evaluate the relationship between plasma SerpinB1 levels and other biomarkers including ANGPTL8. Materials and methods: Overnight fasting plasma samples from 8 healthy subjects and 69 T2DM patients were collected. HbA1c, fasting plasma glucose, total cholesterol, triacylglycerol, and creatinine clearance (CrCl) calculated by 24-hour urine collection were measured in all T2DM patients. Plasma levels of serpinB1 (Cusabio, Catalogue No. CSB-EL021065HU) and ANGPTL8 (Eiaab, Catalogue No. E11644h) were determined by enzyme-linked immunosorbent assay according to the manufacturer’s protocol. Correlations were evaluated by Spearman’s rank test. P values <0.05 were considered statistically significant. Results: Plasma serpinB1 levels were significantly higher in T2DM patients (0.53 ± 0.28 ng/mL) than in healthy subjects (0.21 ± 0.16 ng/mL; p < 0.05). In T2DM patients, plasma serpinB1 levels showed a significant positive association with ANGPTL8 (r = 0.47 p < 0.001). Both serpinB1 and ANGPTL8 levels