The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study

Ohkura, Tsuyoshi; Inoue, Kazuoki; Fujioka, Yohei; Nakanishi, Risa; Shiochi, Hideki; Sumi, Keisuke; Yamamoto, Naoya; Matsuzawa, Kazuhiko; Izawa, Shoichiro; Ohkura, Hiroko; Kato, Masahiko; Yamamoto, Kazuhide; Taniguchi, Shin‐ichi

doi:10.1186/1756-0500-6-453

Cited by 13 publications

(9 citation statements)

References 26 publications

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“…In our study, galectin-3 had a weak tendency towards negative correlation with the insulinogenic index, and a positive correlation with the proinsulin/insulin ratio. The proinsulin/insulin ratio is a marker of beta cell stress [ 12 ]. Galectin-3−/− mice were relatively resistant to diabetogenesis as evaluated by glycemia, quantitative histology and insulin content in streptozotocin induced diabetes [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

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Low serum galectin-3 concentrations are associated with insulin resistance in patients with type 2 diabetes mellitus

Ohkura

Fujioka

Nakanishi

et al. 2014

Diabetol Metab Syndr

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BackgroundGalectin-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.MethodsThis was a cross-sectional study. Twenty patients (mean fasting plasma glucose 7.6 mmol/L, HbA1c 7.2%, BMI 28.1 kg/m2) 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.ResultsThe 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.ConclusionsThese results suggest that low levels of serum galectin-3 are associated with insulin resistance in patients with type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

“…Plasma insulin was defined as immunoreactive insulin (IRI). This method, using the meal tolerance test (MTT), is a well-established method in our hospital [ 11 , 12 ].…”

Section: Methodsmentioning

confidence: 99%

Low serum galectin-3 concentrations are associated with insulin resistance in patients with type 2 diabetes mellitus

Ohkura

Fujioka

Nakanishi

et al. 2014

Diabetol Metab Syndr

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“…The glucose clamps were conducted as previously described [ 16 – 18 ]. Briefly, the patients fasted overnight from 21:00 to 09:00 h before each test and visited the clinic in the morning.…”

Section: Methodsmentioning

confidence: 99%

“…The MTT was conducted as previously described [ 16 – 18 ] on a different day, generally 2–3 days before the glucose clamp. Briefly, the patients were fasted overnight from 21:00 to 09:00 h before each test.…”

Section: Methodsmentioning

confidence: 99%

Bezafibrate improves insulin resistance evaluated using the glucose clamp technique in patients with type 2 diabetes mellitus: a small-scale clinical study

Shiochi

Ohkura

Fujioka

et al. 2014

Diabetol Metab Syndr

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BackgroundBezafibrate is mainly used to treat hypertriglyceridemia. Studies have reported that bezafibrate also improves type 2 diabetes mellitus, but the mechanism has not been fully elucidated. We performed euglycemic hyperinsulinemic clamps (glucose clamp) and meal tolerance tests (MTT) to examine the effects of bezafibrate on insulin resistance in patients with type 2 diabetes mellitus.MethodsTwelve Japanese patients with type 2 diabetes mellitus and dyslipidemia (mean age: 59.5 years; fasting plasma glucose: 7.95 mmol/L; hemoglobin A1c [HbA1c]: 7.3%; body mass index: 26.5 kg/m2) underwent a glucose clamp and MTT before and after 12 weeks of treatment with 400 mg/day bezafibrate. The glucose infusion rate was measured during the glucose clamp. The patients took a test meal (460 kcal) in the MTT. Plasma glucose and immunoreactive insulin levels were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum C-peptide immunoreactivity, serum lipids, and liver function markers were also measured during the MTT.ResultsBezafibrate significantly increased the mean glucose infusion rate from 5.78 ± 1.94 to 6.78 ± 2.52 mg/kg/min (p < 0.05). HbA1c improved from 7.30 ± 0.55% to 7.02 ± 0.52% (p < 0.05). In the MTT, fasting plasma glucose decreased from 7.95 ± 1.15 to 6.98 ± 1.07 mmol/L (p < 0.05). The area under the plasma glucose curve from 0 to 180 min decreased significantly from 29.48 ± 5.07 to 27.12 ± 3.98 mmol/h/L (p < 0.05), whereas immunoreactive insulin was unchanged. Furthermore, bezafibrate also significantly improved serum lipids, with decreases in triglyceride levels from 1.84 ± 0.88 to 1.14 ± 0.41 mmol/L (p < 0.05), low-density lipoprotein cholesterol levels from 3.56 ± 0.83 to 2.92 ± 0.55 mmol/L (p < 0.05), and remnant-like particle cholesterol levels decreased from 0.25 ± 0.16 to 0.14 ± 0.06 mmol/L (p < 0.05), and increases in high-density lipoprotein cholesterol levels from 1.50 ± 0.24 to 1.66 ± 0.29 mmol/L (p < 0.05).ConclusionsBezafibrate improved glucose intolerance and peripheral insulin resistance in these Japanese patients with type 2 diabetes mellitus and dyslipidemia. Therefore, bezafibrate could be used to treat insulin resistance in patients with type 2 diabetes mellitus and dyslipidemia.Trial registrationUniversity Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000012462.

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“…From the above, it is speculated that the rate of change of HbA1c levels tended to be low in the glimepiride group, because the effect of glimepiride to suppress postprandial hyperglycemia is smaller than that of mitiglinide/voglibose fixed-dose combination and thereby daily fluctuations in blood glucose levels were greater in the glimepiride group. The blood glucose AUC has been reported to be lower in a mitiglinide group than in a glimepiride group, and it seems reasonable that the concomitant administration of voglibose, which has a strong effect of suppressing postprandial hyperglycemia, would further decrease the blood glucose AUC [21,22].…”

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confidence: 99%

Differences between Mitiglinide/Voglibose Fixed-dose Combination and Glimepiride in Modifying Low-density Lipoprotein Heterogeneity in Japanese Type-2 Diabetic Patients: A Pilot Study

2015

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Purpose: The purpose of this study was to compare the effects of mitiglinide/voglibose fixed-dose combination and glimepiride on low-density lipoprotein (LDL)-heterogeneity in type-2 diabetic patients with unstable glycemic control after treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods: This was an open-label pilot study in which type-2 diabetic patients were randomly assigned to the mitiglinide/voglibose (fixed-dose combination of mitiglinide 10?mg and voglibose 0.2?mg, n=14) or glimepiride (0.5?mg, n=16). Results: In the glimepiride group, serum LDL cholesterol (LDL-C) and small-dense (sd) LDL levels decreased significantly (?8.5% and ?9.0%), while sd-LDL/LDL-C and an indicator of LDL-particle size, LDL-C/apoB, did not change significantly. In the mitiglinide/voglibose group, serum LDL-C levels did not change, while sd-LDL levels and sd-LDL/LDL-C decreased significantly (?8.6% and ?7.9%) and LDL-C/apoB increased significantly (5.8%). Fasting blood glucose levels tended to be reduced to a greater extent in the glimepiride group than in the mitiglinide/voglibose group (?13.9% vs. ?8.4%, p=0.08), while the rate of reduction of HbA1c levels tended to be higher in the mitiglinide/voglibose group than in the glimepiride group (?6.9% vs. ?3.4%, p=0.09), suggesting differences in fluctuating blood glucose levels between the 2 groups. Conclusion: There were differences in the effects of mitiglinide/voglibose fixed-dose combination and glimepiride in addition to DPP-4 inhibitors on LDL-metabolism, and this may be related to fluctuations in blood glucose levels after treatment with these agents.

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The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study

Cited by 13 publications

References 26 publications

Low serum galectin-3 concentrations are associated with insulin resistance in patients with type 2 diabetes mellitus

Low serum galectin-3 concentrations are associated with insulin resistance in patients with type 2 diabetes mellitus

Bezafibrate improves insulin resistance evaluated using the glucose clamp technique in patients with type 2 diabetes mellitus: a small-scale clinical study

Differences between Mitiglinide/Voglibose Fixed-dose Combination and Glimepiride in Modifying Low-density Lipoprotein Heterogeneity in Japanese Type-2 Diabetic Patients: A Pilot Study

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