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BACKGROUND: We developed a simple and new insulin resistance index derived from a glucose clamp and a meal tolerance test (MTT) in Japanese patients with type 2 diabetes mellitus. METHODS: Fifteen patients [mean age: 53 years, fasting plasma glucose (FPG) 7.7 mmol/L, HbA1c 7.1% (54 mmol/mol), body mass index 26.8 kg/m(2)] underwent a MTT and a glucose clamp. Participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum C-peptide immunoreactivity (CPR) was measured at 0 (fasting; F-CPR) and 120 min. Homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices (ISI) were calculated from the MTT results. The glucose infusion rate (GIR) was measured during hyperinsulinemic-euglycemic glucose clamps. RESULTS: The mean GIR in all patients was 5.8 mg·kg(-1)·min(-1). The index 20/(F-CPR × FPG) was correlated strongly with GIR (r = 0.83, P < 0.0005). HOMA-IR (r = -0.74, P < 0.005) and ISI (r = 0.66, P < 0.01) were also correlated with GIR. In 10 patients with mild insulin resistance (GIR 5.0-10.0 mg·kg(-1)·min(-1)), 20/(F-CPR × FPG) was very strongly correlated with GIR (r = 0.90, P < 0.0005), but not with HOMA-IR and ISI (r = -0.49, P = 0.15; r = 0.20, P = 0.56, respectively). In patients with mild insulin resistance, plasma adiponectin (r = 0.65, P < 0.05), but not BMI or waist circumstance, was correlated with GIR. CONCLUSIONS: 20/(F-CPR × FPG) is a simple and effective index of insulin resistance, and performs better than HOMA-IR and ISI in Japanese patients with type 2 diabetes mellitus. Our results suggest that 20/(F-CPR × FPG) is a more effective index than HOMA-IR in Japanese patients with mild insulin resistance.
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Glucemia/metabolismo , Péptido C/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Ayuno/sangre , Resistencia a la Insulina/fisiología , Adulto , Anciano , Pueblo Asiatico/etnología , Diabetes Mellitus Tipo 2/etnología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
[This corrects the article DOI: 10.33160/yam.2020.08.009.].
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome, which can progress to liver cirrhosis. Standard medication has not been established. Pemafibrate is a selective peroxisome proliferator-activated receptor (PPAR) α modulator. We retrospectively evaluated the efficacy of pemafibrate in patients with NAFLD. METHODS: We retrospectively enrolled 17 patients (ten men, seven women; median age, 63 years; range, 27-81 years). They were all proven to have fatty liver through imaging and had little or no history of drinking (ethanol consumption of < 20 g/day for women and < 30 g/day for men). They were administered pemafibrate from October 2018 to June 2020. RESULTS: After administration, serum triglyceride (TG) tended to be decreased (300.5 ± 22.5 to 239.5 ± 34.3 mg/dL, P = 0.06). Serum high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels did not change. ALT was significantly decreased (-47.4%) for six months (57.5 ± 8.8 to 30.3 ± 5.8 U/L, P < 0.01). The values of serum GGT significantly decreased (-48.7%) for sixth months (63.9 ± 10.3 to 32.8 ± 6.6 U/L, P < 0.01). Aspartate aminotransferase (AST) to platelet ratio (APRI), a fibrosis marker, also was significantly decreased in the sixth month (0.7 ± 0.1 to 0.4 ± 0.1, P < 0.05). Body mass index (BMI) and hemoglobin A1c (HbA1c) showed no significant change. CONCLUSION: Pemafibrate dramatically ameliorated the values of liver function tests and APRI in patients with NAFLD.
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BACKGROUND: In mitochondrial diabetes, apoptosis of ß-cells caused by mitochondrial stress plays an important role in impaired insulin secretion. Several studies have reported that coenzyme Q10 (CoQ10) has therapeutic effects on mitochondrial diabetes, but no reports have examined the fundamental effectiveness or mechanism of CoQ10 in mitochondrial diabetes. We previously reported in a Japanese article that CoQ10 has protective effects on pancreatic ß-cells against mitochondrial stress using mouse pancreatic ß-cell line MIN6 and staurosporine (STS). Here, we report that CoQ10 protects MIN6 cells against apoptosis caused by STS and describe the more detailed apoptotic cascade. METHODS: Apoptosis of MIN6 cells was induced by 0.5 µM STS treatment for specific periods with or without 30 µM CoQ10. The apoptosis cascade in MIN6 cells was then investigated using WST-8 assays, annexin-V staining, western blotting, and DNA degradation analysis. RESULTS: Sixteen hours of 0.5 µM STS treatment led to 47% cell viability, but pretreatment with 30 µM CoQ10 resulted in significantly higher viability of 76% (P < 0.01). CoQ10 also prevented translocation of phosphatidylserine from the inner leaflet to the outer leaflet of the cell membrane. CoQ10 prevented cytochrome c release from mitochondria and activation of caspase-3. CONCLUSION: We concluded that CoQ10 protects pancreatic ß-cells through anti-apoptotic effects against STS treatment.
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AIMS/INTRODUCTION: The aim of the present study was to evaluate the properties of the glucagon stimulation test (GST) and the normal meal tolerance test (NMTT) in patients with type 2 diabetes. MATERIALS AND METHODS: We enrolled 142 patients with type 2 diabetes, and carried out a GST and a NMTT. We carried out the NMTT using a calorie-controlled meal based on an intake of 30 kcal/kg ideal bodyweight/day. We calculated the change in C-peptide immunoreactivity (ΔCPR) by subtracting fasting CPR from the CPR 6 min after the 1-mg glucagon injection (GST) or 120 min after the meal (NMTT). RESULTS: Mean ΔCPR for the GST was 2.0 ng/mL, and for the NMTT was 3.1 ng/mL. A total of 104 patients had greater ΔCPR in the NMTT than the GST, and the mean ΔCPR was significantly greater in the NMTT than the GST (P < 0.05). To exclude any influence of antidiabetic drugs, we examined 42 individuals not taking antidiabetic agents, and found the mean ΔCPR was significantly greater in the NMTT than the GST (GST 2.4 ng/mL, NMTT 4.3 ng/mL; P < 0.05). To consider the influence of glucose toxicity, we carried out receiver operating characteristic analyses with fasting plasma glucose and glycated hemoglobin. The optimal cut-off levels predicting GST ΔCPR to be larger than NMTT ΔCPR were fasting plasma glucose 147 mg/dL and glycated hemoglobin 9.0% (fasting plasma glucose: sensitivity 0.64, specificity 0.76, area under the curve 0.73; glycated hemoglobin: sensitivity 0.56, specificity 0.71, area under the curve 0.66). CONCLUSIONS: The NMTT is a reliable insulin secretion test in patients with type 2 diabetes, except for those in a hyperglycemic state.
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Péptido C/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Glucagón/administración & dosificación , Glucemia/análisis , Estudios Transversales , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posprandial , Estudios Retrospectivos , Sensibilidad y EspecificidadAsunto(s)
Glucemia/análisis , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Triglicéridos/sangre , Anciano , Ayuno , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , Población Rural , Sensibilidad y Especificidad , Accidente Cerebrovascular/prevención & controlRESUMEN
INTRODUCTION: Several studies have shown that dipeptidyl peptidase-4 (DPP-4) inhibitors improve insulin secretion during oral glucose tolerance tests. However, the effects of DPP-4 inhibitors on impaired acute insulin responses in the postprandial state in real-world settings are unknown. Therefore, we evaluated the effects of sitagliptin on the acute insulin responses in Japanese patients with type 2 diabetes mellitus (T2DM) using meal tolerance tests. METHODS: Twenty-one patients with T2DM were given a test meal (460 kcal), and plasma glucose and insulin were measured at 0, 30, 60, 120, and 180 min after the meal. The insulinogenic index of all of these patients was below 43.2. The postprandial profiles were assessed at baseline and after 3 months of treatment with 50 mg/day sitagliptin after a meal (n = 11) or were untreated (control group; n = 10). This study was a prospective, open-label, non-blinded, non-randomized, clinical study. RESULTS: Sitagliptin significantly decreased the plasma glucose levels at 60, 120, and 180 min, and significantly increased the plasma insulin levels at 0 and 30 min. There were no significant changes in glucose or insulin in the control group. The insulinogenic index increased significantly in the sitagliptin group compared with the control group (+16.7 vs. +0.1, P < 0.005). However, homeostasis model assessment of insulin resistance and the insulin sensitivity index were not significant different between the two groups. CONCLUSION: Administration of sitagliptin at 50 mg/day after a meal improved the impaired acute insulin response and suppressed postprandial hyperglycemia. Whereas the study is rather small and the design is suboptimal as it is not randomized and not blinded, these results suggest that sitagliptin is effective in Japanese patients with T2DM, many of whom display impaired acute insulin responses after a meal.
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BACKGROUND: Galectin-3 is a family of soluble beta-galactoside-binding lectins that play many important regulatory roles in inflammation. Galectin-3-deficient mice have been shown to exhibit excess adiposity, hyperglycemia, insulin resistance and systemic inflammation. We investigated the association between serum galectin-3 and insulin resistance in patients with type 2 diabetes using a glucose clamp method. METHODS: This was a cross-sectional study. Twenty patients (mean fasting plasma glucose 7.6 mmol/L, HbA1c 7.2%, BMI 28.1 kg/m(2)) underwent a meal tolerance test and glucose clamp test. Participants were given a test meal and plasma glucose and insulin were measured at 0, 30, 60, 120 and 180 min. The glucose disposal rate was measured during hyperinsulinemic-euglycemic glucose clamps. Serum galectin-3 levels were measured using the enzyme-linked immunosorbent assay method. RESULTS: The mean serum galectin-3 level was 5103 pg/ml. Galectin-3 levels correlated significantly with the glucose disposal rate (R = 0.71, P < 0.001), fasting insulin (R = -0.56, P < 0.01), homeostasis model assessment for insulin resistance (R = -0.52, P < 0.05), and the insulin sensitivity index (R = 0.62, P < 0.005). Galectin-3 levels also positively correlated with the serum adiponectin level (R = 0.61, P < 0.05), but not with the high-sensitive C-reactive protein and interleukin-6 and -10. CONCLUSIONS: These results suggest that low levels of serum galectin-3 are associated with insulin resistance in patients with type 2 diabetes.
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BACKGROUND: An elevated PI/I ratio is attributable to increased secretory demand on ß-cells. However, the effect of postprandial targeting therapy on proinsulin level is unknown. We evaluated the metabolic effect of glinide and sulfonylurea (SU) using the meal tolerance test (MTT). METHODS: MTT was applied to previously untreated Type 2 Diabetes Mellitus (T2DM) subjects. Twenty-two participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum proinsulin and C-peptide immunoreactivity (CPR) were measured at 0 and 120 min. Postprandial profile was assessed at baseline and following 3 months treatment with either mitiglinide or glimepiride. RESULTS: Plasma glucose level at 30, 60, 120, and 180 min was significantly improved by mitiglinide. Whereas, glimepiride showed a significant improve plasma glucose at 0, 180 min. Peak IRI shifted from 120 to 30 min by mitiglinide treatment. The pattern of insulin secretion was not changed by glimepiride treatment. Whereas mitiglinide did not affect the PI/I ratio, glimepiride tended to increase the PI/I ratio. Moreover, although mitiglinide did not affect PI/I ratio as a whole, marked reduction was noted in some patients treated by mitiglinide. PI/I ratio was reduced significantly in the responder group. The responder subgroup exhibited less insulin resistance and higher insulinogenic index at baseline than non-responders. Moreover, the triglyceride level of responders was significantly lower than that of non-responders. CONCLUSIONS: Mitiglinide improved postprandial insulin secretion pattern and thereby suppressed postprandial glucose spike. In T2DM patients with low insulin resistance and low triglyceride, mitiglinide recovered impaired ß-cell function from the viewpoint of the PI/I ratio. TRIAL REGISTRATION UMIN-CTR: UMIN000010467.