Highlights • Day-to-day glucose variability and oxidative stress correlation in T2DM is reported. • Daily and day-to-day glucose variability is associated with oxidative stress. • Glucose variability ...and oxidative stress increase in tandem.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Organ bath experiments are conventionally used to investigate the physiological actions and effects of hormones and drugs on organ responses. We developed an experimental method to reproduce insulin ...secretion from isolated rat pancreas preparations, to investigate substances that promote insulin secretion ex vivo. 1,5-anhydro-D-glucitol (1,5-AG) is found in foods, and exists in humans and rodents; however, whether 1,5-AG stimulates insulin secretion remains unclear. This study aimed to assess the effects of short-term 1,5-AG stimulation on insulin secretion in both ex vivo and in INS-1E (rat-derived) cells in vitro. Our results indicated that 1,5-AG had no potency to increase the proportion of insulin outflow both in ex vivo and in vitro experiments. Insulin outflow significantly increased upon stimulation with 10 μM glimepiride, a member of the sulfonylurea class of drugs, ex vivo. Glucose-stimulated insulin secretion was observed not only in INS-1E cells but also in rat pancreatic preparations. Our findings demonstrated that short-term exposure to 1,5-AG had no effect on insulin secretion in rats.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To investigate substances related to insulin secretion, we reported a convenient experimental method to reproduce insulin secretion from isolated rat pancreas preparations using an organ bath. While ...the method has experimental utility for investigating insulin secretion, optimization of the experimental design is still needed. The level of insulin outflow in the control decreased over time in our previous study. Decreasing serum 1,5-anhydroglucitol (1,5-AG) levels is also known to be shown in patients with worsening glycemic control. There is one in vitro report demonstrated that 1,5-AG induced insulin release. It appears that discussion needs to be deepened further on it. In this study, we investigated the effect of 1,5-AG on insulin secretion through to optimize the condition of endocrine function using the ex vivo organ bath technique. The level of insulin outflow in the control and 1,5-AG groups decreased over time in the organ bath experiment. To analyze the effect of trypsin on reduced insulin secretion, pancreas preparation was treated with soybean trypsin inhibitor (TI). Insulin outflow levels of the TI group were significantly higher than the control group. An enzyme indicator of tissue damage tended to be lower in the TI group. There was no significant enhancement of insulin secretion by 1,5-AG. The present study demonstrated the utility of TI application for the organ bath technique. This finding supported the development of an organ bath technique for the assessment of the effects of novel therapeutics on insulin secretion.
Background/Aim: We developed an experimental method to reproduce insulin secretion from isolated rat pancreas preparations using an organ bath system. However, secretion of trypsin, another ...pancreatic enzyme, interferes with insulin production in such systems. We aimed to ascertain the minimum trypsin inhibitor (TI), dose for obtaining a sustained, stable rate of insulin secretion. Materials and Methods: The action of TI (1-10 μg/ml) on pancreatic preparations of male Wistar-Imamichi rats in organ bath experiments was assessed by measuring insulin, amylase, and trypsin activity. Results: The level of insulin outflow remained steady in the TI-treated samples, in contrast to that in the untreated control, where insulin secretion decreased over time. The level of amylase outflow did not change significantly. Trypsin activity was significantly lower in the TI-treated samples than in the control. Conclusion: Even low concentrations of TI can maintain insulin secretion by inhibiting trypsin activity in organ bath experiments.
Aim: To evaluate long‐term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes ...patients.
Methods: Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years.
Results: There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P < 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non‐fatal events between the two groups. Composite events were also similar in the two groups.
Conclusions: This study showed no significant differences in fatal or non‐fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 7–17.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The authors assessed the association between the ratio of urinary activity of N‐acetyl‐β‐D‐glucosaminidase (NAG) to creatinine and the brachial‐ankle pulse wave velocity (baPWV) in patients without ...overt diabetes mellitus (DM). This was a cross‐sectional study of 233 patients who had an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and no history of kidney disease. Patients were divided into two groups: high NAG group (>5.8 U/g creatinine) and low NAG group (≤5.8 U/g creatinine). Mean baPWVs of the high NAG group were significantly higher than those of the low NAG group in both the eGFR ≥30 and <60 tertiles and the eGFR ≥60 and <90 tertiles. The baPWV was positively correlated with NAG in all patients (r=0.341, P<.001). Stepwise multivariate regression analysis showed that the baPWV was significantly related with NAG, age, and systolic blood pressure. Elevated NAG is related to elevated arterial stiffness in patients without DM.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes complicated by hypercholesterolemia. Aim: To examine the mechanism by which colestimide ...decreases plasma glucose levels in the above patients. Methods: A total of 16 inpatients with type 2 diabetes complicated by hypercholesterolemia received colestimide for 1 week after their plasma glucose levels stabilized. We measured plasma glucose, serum immunoreactive insulin (IRI), serum lipid, plasma glucagon, and plasma glucagon-like peptide-1 (GLP-1) levels. These variables at baseline and 1 week of colestimide administration were compared. Results: Preprandial plasma glucose levels (baseline: 132 ± 33 mg/dL vs. completion: 118 ± 43 mg/dL, P=0.073) tended to decrease after colestimide administration, while 1-hr postprandial plasma glucose levels (baseline: 208 ± 49 mg/dL vs. completion: 166 ± 30 mg/dL, P<0.001) and 2-hr postprandial plasma glucose levels (baseline: 209 ± 56 mg/dL vs. completion: 178 ± 39 mg/dL, P=0.015) decreased significantly at 1 week of colestimide administration. The 2-hr postprandial plasma GLP-1 level was significantly (P=0.015) higher at 1 week of colestimide administration as compared with the baseline level, while there were no significant changes in preprandial and 1-hr postprandial plasma GLP-1 levels. Conclusions: The GLP-1-increasing activity of colestimide may explain, at least in part, the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes complicated by hypercholesterolemia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. ...We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals.
Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.
Percentage decreases from FMD0 to FMD60 were significantly greater in the TM group (-21.19% ± 17.90%; P < 0.001) and the OG group (-17.59% ± 26.64%) than in the control group (6.46% ± 9.17%; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group (-18.91% ± 16.58%) than in the control group (6.78% ± 11.43%; P < 0.001) or the TM group (5.22% ± 37.22%; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = -0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = -0.462; P < 0.05) and the AUC of IRI (r = -0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables.
Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Postprandial hyperglycemia is an independent risk factor for cardiovascular disease-related morbidity and mortality, not only in diabetes mellitus (DM) but also in impaired glucose tolerance. ...Postprandial glycemic levels have been difficult to monitor, but recently 1,5-anhydroglucitol (1,5-AG) levels have proven to be beneficial for this purpose. In humans, 1,5-AG, a 1-deoxy-glucopyranose, is a major and abundant polyol, of which 90% is derived from ingested food, and little is produced from glycogen in the liver. Nearly all 1,5-AG is reabsorbed in normoglycemia, but the reabsorption rate decreases in proportion to the degree of hyperglycemia above the renal threshold for glucosuria, which is 160 to 180 mg/dL. Glucosuria appears if the level of blood glucose rises above this level. The renal reabsorption of 1,5-AG is competitively inhibited by glucosuria. The 1,5-AG level appears to be well suited for monitoring glucose homeostasis in subjects with near-normoglycemia or with postprandial hyperglycemia without fasting hyperglycemia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aims: To evaluate the association of low‐density lipoprotein, high‐density lipoprotein and non‐high‐density lipoprotein cholesterol with the risk of stroke, diabetes‐related vascular events and ...mortality in elderly diabetes patients.
Methods: This study was carried out as a post‐hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry.
Results: During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes‐related deaths and 113 diabetes‐related events. High low‐density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non‐high‐density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes‐related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non‐high‐density lipoprotein cholesterol were 1.010 (1.001–1.018, P = 0.029) for stroke, 1.019 (1.007–1.031, P < 0.001) for diabetes‐related death and 1.008 (1.002–1.014; P < 0.001) for total diabetes‐related events.
Conclusions: Higher non‐high‐density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes‐related mortality and total events in elderly diabetes patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 18–28.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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