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Akira Kurozumi Yosuke Okada Hiroko Mori Tadashi Arao Yoshiya Tanaka 《Journal of diabetes investigation.》2013,4(4):393-398
Aims/Introduction
The combination therapy of dipeptidyl‐peptidase (DPP)‐4 inhibitor and α‐glucosidase inhibitors (α‐GIs) is highly effective in suppressing postprandial hyperglycemia. The aim of the present study was to compare the effects of voglibose and miglitol on glucose fluctuation, when used in combination with DPP‐4 inhibitor by using continuous glucose monitoring (CGM).Materials and Methods
In a randomized cross‐over study, 16 patients with type 2 diabetes who presented with postprandial hyperglycemia despite alogliptin (25 mg) were treated with voglibose (0.9 mg) or miglitol (150 mg). We measured standard deviation (SD); mean amplitude of glycemic excursions (MAGE), and mean, minimum and maximum glucose measured by CGM during three phases (alogliptin monotherapy, dual therapy of alogliptin and voglibose, and dual therapy of alogliptin and miglitol). The primary outcome measure was SD between α‐GIs.Results
SD was significantly improved by the addition of either voglibose (18.9 ± 10.1) or miglitol (19.6 ± 8.2) to alogliptin monotherapy (36.2 ± 8.7). MAGE improved significantly with the addition of either voglibose (57.5 ± 26.1, P < 0.01) or miglitol (64.6 ± 26.2, P < 0.01) to alogliptin monotherapy (101.5 ± 21.5). There was no significant difference in glucose fluctuation between α‐GIs. There were no differences between two groups in mean (132.6 ± 21.4 and 138.7 ± 25.4) and maximum (184.3 ± 48.7 and 191.9 ± 38.3). The minimum glucose under alogliptin plus voglibose (94.9 ± 20.2) was significantly lower than that under alogliptin and miglitol (105.3 ± 21.0).Conclusions
Glucose fluctuation was improved by the addition of voglibose or miglitol to alogliptin. Glucose fluctuations and postprandial hyperglycemia were similar between α‐GIs. This trial was registered with the University Hospital Medical Information Network (no. UMIN R000010028). 相似文献3.
Minoru Iwata Yumi Matsushita Kazuhito Fukuda Tatsurou Wakura Keisuke Okabe Yukiko Koshimizu Yasuo Fukushima Chikaaki Kobashi Yu Yamazaki Hisae Honoki Hikari Suzuki Mika Kigawa Kazuyuki Tobe 《Journal of diabetes investigation.》2014,5(5):570-580
Aims/Introduction
The objective of the present study was to clarify the validity of β‐cell function‐related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients.Materials and Methods
In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross‐sectional study examining the relationship between the homeostasis model assessment of β‐cell function (HOMA‐β) and C‐peptide‐based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several β ‐cell function‐related indices using a receiver operating characteristic (ROC) curve analysis.Results
The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA‐β, followed by the fasting serum C‐peptide immunoreactivity index (CPI); the fasting serum C‐peptide immunoreactivity itself (F‐CPR) had the least correlation. The CPI, HOMA‐β and SUIT were significantly lower in the insulin‐requiring group than in the non‐insulin‐requiring group, even after adjustments for confounding factors (P < 0.01). The areas under the ROC curve for insulin requirement were 0.622, 0.774, 0.808, and 0.759 for F‐CPR, CPI, SUIT, and HOMA‐β, respectively. The cut‐off values of SUIT, CPI, and HOMA‐β for an over 80% specificity for the prediction of insulin therapy were 23.5, 1.00, and 14.9, respectively.Conclusions
The present study shows that SUIT is the best predictor of insulin requirement among these β‐cell function‐related markers. 相似文献4.
Yuichi Sato Shimpei Fujimoto Eri Mukai Hiroki Sato Yumiko Tahara Kasane Ogura Gen Yamano Masahito Ogura Kazuaki Nagashima Nobuya Inagaki 《Journal of diabetes investigation.》2014,5(1):19-26
Aims/Introduction
Chronic hyperlipidemia impairs pancreatic β‐cell function, referred to as lipotoxicity. We have reported an important role of endogenous reactive oxygen species (ROS) overproduction by activation of Src, a non‐receptor tyrosine kinase, in impaired glucose‐induced insulin secretion (GIIS) from diabetic rat islets. In the present study, we investigated the role of ROS production by Src signaling in palmitate‐induced dysfunction of β‐cells.Materials and Methods
After rat insulinoma INS‐1D cells were exposed to 0.6 mmol/L palmitate for 24 h (palmitate exposure); GIIS, ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity were examined with or without exposure to10 μmol/L 4‐amino‐5‐(4‐chlorophenyl)‐7‐(t‐butyl)pyrazolo[3,4‐d]pyrimidine (PP2), a Src inhibitior, for 30 or 60 min.Results
Exposure to PP2 recovered impaired GIIS and decreased ROS overproduction as a result of palmitate exposure. Palmitate exposure increased activity of NOX and protein levels of NOX2, a pathological ROS source in β‐cells. Palmitate exposure increased the protein level of p47phox, a regulatory protein of NOX2, in membrane fraction compared with control, which was reduced by PP2. Transfection of small interfering ribonucleic acid of p47phox suppressed the augmented p47phox protein level in membrane fraction, decreased augmented ROS production and increased impaired GΙIS by palmitate exposure. In addition, exposure to PP2 ameliorated impaired GIIS and decreased ROS production in isolated islets of KK‐Ay mice, an obese diabetic model with hyperlipidemia.Conclusions
Activation of NOX through Src signaling plays an important role in ROS overproduction and impaired GΙIS caused by chronic exposure to palmitate, suggesting a lipotoxic mechanism of β‐cell dysfunction of obese mice. 相似文献5.
Seo Hee Lee Yong‐ho Lee A Ra Choi Youngki Lee Byung‐Wan Lee Eun Seok Kang Chul Woo Ahn Bong Soo Cha Hyun Chul Lee 《Journal of diabetes investigation.》2014,5(5):517-524
Aims/Introduction
Type 2 diabetes is characterized by progressive deterioration of β‐cell function. Recently, it was suggested that the C‐peptide‐to‐glucose ratio after oral glucose ingestion is a better predictor of β‐cell mass than that during fasting. We investigated whether postprandial C‐peptide‐to‐glucose ratio (PCGR) reflects β‐cell function, and its clinical application for management of type 2 diabetes.Materials and Methods
We carried out a two‐step retrospective study of 919 Korean participants with type 2 diabetes. In the first step, we evaluated the correlation of PCGR level with various markers for β‐cell function in newly diagnosed and drug‐naïve patients after a mixed meal test. In the second step, participants with well‐controlled diabetes (glycated hemoglobin <7%) were divided into four groups according to treatment modality (group I: insulin, group II: sulfonylurea and/or dipeptityl peptidase IV inhibitor, group III: metformin and/or thiazolidinedione and group IV: diet and exercise group).Results
In the first step, PCGR was significantly correlated with various insulin secretory indices. Furthermore, PCGR showed better correlation with glycemic indices than homeostatic model assessment of β‐cell function (HOMA‐β). In the second step, the PCGR value significantly increased according to the following order: group I, II, III, and IV after adjusting for age, sex, body mass index and duration of diabetes. The cut‐off values of PCGR for separating each group were 1.457, 2.870 and 3.790, respectively (P < 0.001).Conclusions
We suggest that PCGR might be a useful marker for β‐cell function and an ancillary parameter in the choice of antidiabetic medication in type 2 diabetes. 相似文献6.
Effect of serum 25‐hydroxyvitamin D3 on insulin resistance and β‐cell function in newly diagnosed type 2 diabetes patients
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Mingjing Bao Limei Liu Yang Xian Jichuan Wu Pengqiu Li 《Journal of diabetes investigation.》2016,7(2):226-232
Aims/Introduction
To evaluate serum 25‐hydroxyvitamin D3 (25(OH)D3) in newly diagnosed type 2 diabetes patients and to explore the associations of 25(OH)D3 with insulin resistance and β‐cell function.Materials and Methods
A total of 97 newly diagnosed type 2 diabetes patients and 69 healthy controls were recruited. Serum 25(OH)D3 was determined using high‐pressure liquid chromatography. Insulin resistance was measured using a homeostasis model assessment of insulin resistance (HOMA‐IR). β‐Cell function was determined using the HOMA β‐cell function index (HOMA‐β), early‐phase insulin secretion index (ΔI30/ΔG30) and area under the insulin curve (AUCins). Correlation analysis was carried out using Pearson''s correlation and multiple stepwise regression analysis.Results
Serum 25(OH)D3 was much lower in patients with newly diagnosed type 2 diabetes (t = −13.00, P < 0.01), and the prevalence of hypovitaminosis 25(OH)D3 was 62.9% (61/97) in diabetic patients. Among the diabetic patients, patients with hypovitaminosis 25(OH)D3 showed higher glycosylated hemoglobin and AUCglu (P < 0.01) as well as lower HOMA‐β, ΔI30/ΔG30 and AUCins. Serum 25(OH)D3 was independently positively correlated with ΔI30/ΔG30 and AUCins (P < 0.05), but was not significantly correlated with either HOMA‐IR or HOMA‐β. Only triglycerides, glycosylated hemoglobin and ΔI30/ΔG30 emerged as independent factors associated with serum 25(OH)D3 in both diabetes patients and the health control group.Conclusions
The present results further showed a low serum 25(OH)D3 concentration in patients with newly diagnosed type 2 diabetes. 25(OH)D3 deficiency is associated with disturbances in glucose metabolism and lipid metabolism. Serum 25(OH)D3 is not correlated with basal insulin resistance or β‐cell function, but is significantly positively correlated with glucose‐stimulated insulin secretion and β‐cell function. 相似文献7.
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Efficacy and safety of 40 mg or 60 mg duloxetine in Japanese adults with diabetic neuropathic pain: Results from a randomized, 52‐week,open‐label study
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Hitoshi Yasuda Nigishi Hotta Masato Kasuga Atsunori Kashiwagi Ryuzo Kawamori Tadaaki Yamada Yuko Baba Levent Alev Ko Nakajo 《Journal of diabetes investigation.》2016,7(1):100-108
Introduction
To examine the long‐term efficacy and safety of duloxetine in the treatment of Japanese patients with diabetic neuropathic pain, we carried out a 52‐week, randomized, open‐label extension of a 12‐week, double‐blind, placebo‐controlled study.Materials and Methods
Japanese adults with diabetic neuropathic pain who completed the double‐blind study were eligible for this long‐term study, carried out at 71 sites in Japan (March 2008 to March 2010). Participants (n = 258) were re‐randomized (1:1) to 40 mg/day or 60 mg/day duloxetine. Pain (Brief Pain Inventory severity and interference), quality of life (Patient''s Global Impression of Improvement), and safety (primary outcome; adverse events, vital signs, metabolic measures) were measured.Results
Significant (P < 0.0001) and sustained improvements (change ± standard deviation; n = 257) were observed in Brief Pain Inventory severity (average pain score −2.1 ± 1.7). Improvements were also seen in Brief Pain Inventory interference (mean of subscores −0.96 ± 1.52) and Patient''s Global Impression of Improvement (−0.9 ± 1.1) scores; these scores decreased significantly (P < 0.0001) during the long‐term study. Frequently reported adverse events included somnolence (13.6%), constipation (13.2%) and nausea (10.5%). Increases were observed in plasma glucose, glycosylated hemoglobin and total cholesterol levels, and in bodyweight and heart rate; however, none of these were clinically meaningful. Overall, there were no clinically significant safety concerns.Conclusions
This is the first publication of a long‐term study carried out in Asia with an entirely Japanese patient population to suggest that long‐term duloxetine therapy for diabetic neuropathic pain is effective and has an acceptable safety profile. 相似文献9.
Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: A randomized, 52‐week,open‐label,parallel‐group trial
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Kohei Kaku Arihiro Kiyosue Yuri Ono Toshihiko Shiraiwa Shizuka Kaneko Keiji Nishijima Heidrun Bosch‐Traberg Yutaka Seino 《Journal of diabetes investigation.》2016,7(1):76-84
Introduction
The safety and efficacy of liraglutide in combination with an oral antidiabetic drug (OAD) compared with combination of two OADs were assessed in Japanese patients with type 2 diabetes.Materials and Methods
This was a 52‐week, open‐label, parallel‐group trial in which patients whose type 2 diabetes was inadequately controlled with a single OAD (glinide, metformin, α‐glucosidase inhibitor or thiazolidinedione) were randomized 2:1 to either pretrial OAD in combination with liraglutide 0.9 mg/day (liraglutide group; n = 240) or pretrial OAD in combination with an additional OAD (additional OAD group; n = 120). The primary outcome measure was the incidence of adverse events (AEs).Results
Overall, 86.3% of patients in the liraglutide group and 85.0% of patients in the additional OAD group experienced AEs; these were similar in nature and severity. Adverse event rates were 361 and 331 per 100 patient‐years of exposure, respectively. Confirmed hypoglycemia was rare (seven episodes in two patients on liraglutide, and two in two patients on additional OAD). There were no reported pancreatitis events, and no unexpected safety signals were identified. Mean reductions in glycosylated hemoglobin were significantly greater in the liraglutide group than the additional OAD group [estimated mean treatment difference −0.27% (95% confidence interval (CI) −0.44, −0.09; P = 0.0026)]; reductions in mean fasting plasma glucose levels were also greater with liraglutide [estimated mean difference −5.47 mg/dL (−0.30 mmol/L; 95% CI: −10.83, −0.10; P = 0.0458)].Conclusions
Liraglutide was well tolerated and effective as combination therapy with an OAD in Japanese patients with type 2 diabetes. 相似文献10.
Katarzyna Kusińska Karolina Bukowska‐Strakova Przemysław Witek Teresa Koblik Alicja Józkowicz Józef Dulak 《Journal of diabetes investigation.》2014,5(1):99-107
Aims/Introduction
Type 2 diabetes is often complicated by diabetic foot syndrome (DFS). We analyzed the circulating stem cells, growth factor and anti‐oxidant gene expression profiles in type 2 diabetes patients without or with different forms of DFS.Materials and Methods
Healthy volunteers (n = 13) and type 2 diabetes patients: (i) without DFS (n = 10); or with (ii) Charcot osteoneuropathy (n = 10); (iii) non‐infected (n = 17); (iv) infected (n = 11); and (v) healed ulceration were examined (n = 12). Peripheral blood endothelial progenitor cells (EPC), mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and very small embryonic‐like (VSEL) cells were phenotyped using flow cytometry. Plasma cytokine concentrations and gene expressions in blood cells were measured by Luminex and quantitative real‐time polymerase chain reaction assays, respectively.Results
Patients with non‐complicated type 2 diabetes showed reduced HMOX1 expression, accompanied by HMOX2 upregulation, and had less circulating EPC, MSC or HSC than healthy subjects. In contrast, VSEL cells were elevated in the type 2 diabetes group. However, subjects with DFS, even with healed ulceration, had fewer VSEL cells, more CD45‐CD29+CD90+MSC, and upregulated HMOX1 when compared with the type 2 diabetes group. Patients with Charcot osteopathy had lowered plasma fibroblast growth factor‐2. Elevated plasma tumor necrosis factor‐α and decreased catalase expression was found in all diabetic patients.Conclusions
Patients with type 2 diabetes and different forms of DFS have an altered number of circulating stem cells. Type 2 diabetes might also be associated with a changed plasma growth factor and anti‐oxidant gene expression profile. Altogether, these factors could contribute to the pathogenesis of different forms of DFS. 相似文献11.
Hisazumi Araki Yuki Tanaka Syohei Yoshida Yoshikata Morita Shinji Kume Keiji Isshiki Shin‐ichi Araki Takashi Uzu Atsunori Kashiwagi Hiroshi Maegawa 《Journal of diabetes investigation.》2014,5(4):435-441
Aims/Introduction
In Japan, liraglutide was recently approved for patients with type 2 diabetes. To our knowledge, there are no markers predicting successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type 2 diabetes and renal impairment. We therefore assessed clinical characteristics predicting successful switching.Materials and Methods
We analyzed 21 patients with type 2 diabetes and estimated glomerular filtration rates <60 mL/min/1.73 m2 receiving long‐term insulin in Shiga University of Medical Science Hospital, Otsu, Shiga, Japan. Their β‐cell function was assessed by measuring urinary C‐peptide and C‐peptide immunoreactivity (CPR) index, along with glucagon loading and oral glucose tolerance tests. Blood glucose concentration and blood pressure were measured daily before and after switching from insulin to liraglutide, and glycated hemoglobin (HbA1c; National Glycohemoglobin Standardization Program) was assessed 12 weeks after switching to liraglutide.Results
Baseline HbA1c was significantly lower in successfully switched than in unsuccessfully switched patients. CPR index, urinary C‐peptide concentration and 6‐min post‐glucagon increment in CPR (ΔCPR) did not differ significantly in the two groups. ΔCPR 120 min after 75 g oral glucose was significantly higher in successfully than unsuccessfully switched patients. Mean blood glucose concentrations before breakfast, after breakfast, before lunch and after dinner were significantly lower in successfully switched patients. HbA1c did not change significantly in either group.Conclusions
Measurement of oral glucose‐stimulated ΔCPR120 min is recommended when considering switching Japanese type 2 diabetes patients with renal impairment from insulin to liraglutide monotherapy. 相似文献12.
Sunghwan Suh Hyung‐Doo Park Sang‐Man Jin Hye Jeong Kim Ji Cheol Bae So Young Park Mi Kyoung Park Duk Kyu Kim Nam H Cho Moon‐Kyu Lee 《Journal of diabetes investigation.》2013,4(6):546-551
Aims/Introduction
Small dense low‐density lipoprotein (sdLDL) has been suggested to be a potential risk factor for cardiovascular diseases (CVD).Materials and Methods
We carried out a prospective nested case–control study in the Korean Health and Genome Study. Participants were men and women aged 40–69 years who developed CVD (n = 313), and were matched by age and sex to controls who remained free of CVD (n = 313) during the 8‐years follow‐up period (from 2001 to 2009). LDL subfractions were analyzed in frozen samples collected from the 626 participants using polyacrylamide tube gel electrophoresis.Results
Patients with CVD had a significantly higher glycated hemoglobin level compared with the controls (5.72 vs 5.56). The proportion of patients with diabetes mellitus (DM) was higher in those who developed CVD during follow up (8.0% vs 1.9%). The frequency of CVD according to each tertile of LDL particle size and the number of metabolic syndrome components did not differ significantly. In the multivariate analysis, DM (odds ratio 4.244, 95% confidence interval 1.693–10.640, P = 0.002) was the only independent predictive factor of CVD. LDL particle size was not associated with the risk for future CVD.Conclusions
Small dense LDL might not be a significant predictor of CVD in this Korean community‐based prospective cohort study. 相似文献13.
Aims/Introduction
The goal of this study was to evaluate the effect of Roux‐en‐Y gastric bypass (RYGB) on hyperglycemia and gastrointestinal hormones in Chinese obese type 2 diabetic patients with body mass index (BMI) between 28 and 35 kg/m2.Materials and Methods
A total of eight obese type 2 diabetes patients with BMI 28–35 kg/m2 who underwent RYGB and 10 obese normal glucose tolerance (NGT) patients with no surgery were identified. BMI and blood glucose on baseline, and 2–4 months postoperative, changes of glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic polypeptide (GIP), peptide YY (PYY), and oxyntomodulin (OXM) were recorded. Efficacy of RYGB was defined by the percentage of excess weight loss (%EWL) and amelioration of type 2 diabetes.Results
The %EWL was 53.00 ± 26.25% in 2 month and 63.65 ± 33.71% in 4 month. Glycated hemoglobin changed from 7.2 ± 1.0% preoperative to 6.2 ± 0.9% in 2 month and 6.3 ± 1.2% in 4 month postoperative. The improvement rate of type 2 diabetes 4 months after RYGB was 83.3%. After surgery, area under the curve (AUC) GLP‐1 120 increased with no significance. AUC PYY 120 changed from 10.37 ± 5.45 pmol/L/min preoperative to 22.19 ± 10.61 pmol/L/min in 2 month and 22.04 ± 7.73 pmol/L/min in 4 month postoperative. Postoperative AUC OXM 120 was also higher than that of the preoperative level. AUC GIP 120 decreased from 13.06 ± 8.45 pg/mL/min preoperative to 8.71 ± 3.28 pg/ml/min in 2 month and 6.88 ± 2.33 pg/mL/min in 4 month postoperative.Conclusions
Roux‐en‐Y gastric bypass has a beneficial effect on weight loss and glucose metabolism in obese type 2 diabetes patients with lower BMI. Postoperative concentrations of GLP‐1, PYY and OXM increased, whereas GIP decreased. 相似文献14.
Svetlana N Zykova Ksenia A Balandina Natalia V Vorokhobina Alla V Kuznetsova Rolf Engstad Tatiana A Zykova 《Journal of diabetes investigation.》2014,5(4):392-399
Aims/Introduction
Dysregulated inflammatory response is believed to be an important factor in the pathogenesis of several late complications of diabetes mellitus. β‐Glucans are potent inducers of immune function. The present randomized, double blind, two‐center, placebo‐controlled study was undertaken to explore safety, tolerability and efficacy of soluble β‐1,3/1,6‐glucan (SBG) as a local treatment of diabetic foot ulcers.Materials and Methods
A total of 60 patients with type 1 or 2 diabetes and lower extremity ulcers (Wagner grade 1–2, Ankle/Brachial Index ≥0.7) received SBG or a comparator product (methylcellulose) locally three times weekly up to 12 weeks in addition to conventional management scheme. A total of 54 patients completed the study.Results
A tendency for shorter median time to complete healing in the SBG group was observed (36 vs 63 days, P = 0.130). Weekly percentage reduction in ulcer size was significantly higher in the SBG group than in the methylcellulose group between weeks 1–2, 3–4 and 5–6 (P < 0.05). The proportion of ulcers healed by week 12 was also in favor of SBG (59% vs 37%, P = 0.09), with a significantly higher healing incidence in the SBG group at week 8 (44% vs 17%, P = 0.03). SBG was safe and well tolerated. There was a clinically significant difference regarding the incidence of serious adverse events in favor of the SBG treatment.Conclusions
Local treatment of diabetic lower extremity ulcers with β‐1,3/1,6‐polyglucose shows good safety results. This β‐glucan preparation shows promising potential as a treatment accelerating cutaneous healing. Further studies are required to confirm this effect. This trial was registered with ClinicalTrials.gov (no. ). NCT00288392相似文献15.
Gian Piero Carnevale Schianca Gian Paolo Fra Marcello Bigliocca Roberto Mella Luca Rossi Ettore Bartoli 《Journal of diabetes investigation.》2014,5(5):533-538
Aims/Introduction
The conventional oral glucose tolerance test (OGTT) cannot detect future diabetics among isolated impaired fasting glucose (is‐IFG) nor normal glucose tolerant (NGT) groups. By analyzing the relationship between fasting (FPG) and 2‐h plasma glucose (2hPG), the present study identifies is‐IFG subjects liable to worsening glucose homeostasis.Materials and Methods
Oral glucose tolerance test was carried out in 619 patients suffering from obesity, hypertension or dyslipidemia, whose FPG was in the 100–125 mg/dL range. We calculated the percentage increment of 2hPG with respect to FPG (PG%) in these patients using the formula: ([2hPG − FPG] / FPG) × 100. Differences in β‐cell function within is‐IFG patients were assessed by estimated insulin sensitivity index (EISI), first‐phase insulin release (1stPH) and 1stPH/1/EISI (1stPHcorrected).Results
Diabetes was diagnosed in 69 patients (11.2%), combined IFG/impaired glucose tolerance (IGT) in 185 patients (29.9%) and is‐IFG in 365 patients (58.9%). Is‐IFG was subdivided into PG% tertile groups: the percentage of females increased from 25% in the lowest to 45.2% in the highest tertile (χ2 = 18.7, P < 0.001). Moving from the lowest to the highest PG% tertile group, insulin and 2hPG concentrations rose, whereas FPG, EISI, and 1stPHcorrected decreased progressively and significantly. Furthemore, PG% correlated inversely with EISI (r = −0.44, P < 0.0001) and 1stPHcorrected (r = −0.38, P < 0.0001).Conclusions
Oral glucose tolerance test does differentiate the great heterogeneity in metabolic disorders of patients with FPG 100–125 mg/dL. Furthermore, PG% can expand the diagnostic power of OGTT in the is‐IFG range by distinguishing metabolic phenotypes very likely to herald different clinical risks. 相似文献16.
Hitoshi Sugihara Mototsugu Nagao Taro Harada Yasushi Nakajima Kyoko Tanimura‐Inagaki Fumitaka Okajima Hideki Tamura Takeshi Inazawa Takatoshi Otonari Masanobu Kawakami Shinichi Oikawa 《Journal of diabetes investigation.》2014,5(2):206-212
Aims/Introduction
α‐Glucosidase inhibitors (αGIs) are widely used for the primary treatment of type 2 diabetes. We compared the clinical effects of three αGIs (miglitol, acarbose and voglibose) in patients with obese type 2 diabetes.Materials and Methods
Japanese patients (n = 81) with obese type 2 diabetes (body mass index [BMI] ≥25 kg/m2) were enrolled in this multicenter, open‐label study. The participants were randomized into the miglitol (n = 18), acarbose (n = 22), voglibose (n = 19) or control (n = 22) groups. Glycemic control (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI, serum insulin, serum lipids (low‐density lipoprotein and high‐density lipoprotein cholesterol, and triacylglycerols) and adipocytokines (leptin and adiponectin) were evaluated every 4 weeks for 12 weeks.Results
In the miglitol group, HbA1c was improved significantly from the baseline at all points. The changes in HbA1c at 8 and 12 weeks from baseline were greater in the miglitol group than the control group. The voglibose group showed significant improvements in HbA1c at 12 weeks. Bodyweight and BMI were decreased significantly in the miglitol group. In addition, significant correlations were observed between the decrements in HbA1c and bodyweights over 12 weeks in the miglitol (r = 0.759, P < 0.001) and voglibose groups (r = 0.667, P = 0.002). Serum lipid and adipocytokine levels were not altered in any groups.Conclusions
αGIs, especially miglitol, can effectively control blood glucose and bodyweight in obese type 2 diabetes. This study was registered with UMIN (no. UMIN000006465). 相似文献17.
Subject‐driven titration of biphasic insulin aspart 30 twice daily is non‐inferior to investigator‐driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized,open‐label,parallel‐group,multicenter trial
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Wenying Yang Lvyun Zhu Bangzhu Meng Yu Liu Wenhui Wang Shandong Ye Li Sun Heng Miao Lian Guo Zhanjian Wang Xiaofeng Lv Quanmin Li Qiuhe Ji Weigang Zhao Gangyi Yang 《Journal of diabetes investigation.》2016,7(1):85-93
Aims/Introduction
The present study was to compare the efficacy and safety of subject‐driven and investigator‐driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID).Materials and Methods
In this 20‐week, randomized, open‐label, two‐group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self‐mixed human insulin were randomized 1:1 to subject‐driven or investigator‐driven titration of BIAsp 30 BID, in combination with metformin and/or α‐glucosidase inhibitors. Dose adjustment was decided by patients in the subject‐driven group after training, and by investigators in the investigator‐driven group.Results
Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject‐driven group and 14.3 mmol/mol (1.31%) in the investigator‐driven group. Non‐inferiority of subject‐titration vs investigator‐titration in reducing HbA1c was confirmed, with estimated treatment difference −0.26 mmol/mol (95% confidence interval −2.05, 1.53) (–0.02%, 95% confidence interval –0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self‐measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient‐year) was reported in the subject‐driven (1.10) and investigator‐driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject‐driven and investigator‐driven groups, respectively.Conclusions
Subject‐titration of BIAsp 30 BID was as efficacious and well‐tolerated as investigator‐titration. The present study supported patients to self‐titrate BIAsp 30 BID under physicians’ supervision. 相似文献18.
Atsunori Kashiwagi Kenichi Kazuta Satoshi Yoshida Itsuro Nagase 《Journal of diabetes investigation.》2014,5(4):382-391
Aims/Introduction
In the present dose–response study, we evaluated the efficacy and safety of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium‐dependent glucose cotransporter 2, in Japanese patients with type 2 diabetes mellitus.Materials and Methods
A total of 361 patients from 39 Japanese centers were randomized to receive either once‐daily oral ipragliflozin (12.5, 25, 50 or 100 mg) or a placebo for 12 weeks.Results
All ipragliflozin‐treated groups had clinically significant, dose‐dependent decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose levels compared with placebo‐treated groups. The adjusted mean difference in HbA1c change from baseline to the end of treatment between the placebo and 12.5, 25, 50, and 100 mg ipragliflozin groups were −0.61%, −0.97%, −1.29%, and −1.31%, respectively (P < 0.001). Reductions in HbA1c levels were similar between obese and non‐obese patients, and were larger in patients with baseline HbA1c ≥8.4% than in those with HbA1c <8.4%. Furthermore, bodyweight significantly (P < 0.001) and dose‐dependently decreased among ipragliflozin‐treated groups compared with the placebo group. The incidence of adverse events was similar across all groups. However, mild increases in hematocrit and blood urea nitrogen were found in ipragliflozin treated groups.Conclusions
Once‐daily administration of ipragliflozin was dose‐dependently effective in glycemic control without major adverse effects. Ipragliflozin was equally effective between obese and non‐obese patients, and led to weight loss in both groups. Ipragliflozin was safe and well‐tolerated in Japanese patients with type 2 diabetes mellitus. This trial was registered with ClinicalTrials.gov (no. NCT00621868). 相似文献19.
Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose,lipid profiles and insulin sensitivity in high‐fat diet‐fed mice by modulating expression of genes in peroxisome proliferator‐activated receptor signaling pathway
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Aims/Introduction
Uncoupling protein 2 (UCP2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver‐associated signaling pathway by expression profiling analysis.Materials and Methods
Four‐week‐old male UCP2−/− mice and UCP2+/+ mice were randomly assigned to four groups: UCP2−/− on a high‐fat diet, UCP2−/− on a normal chow diet, UCP2+/+ on a high‐fat diet and UCP2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array.Results
The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β‐cell function were improved in the UCP2−/− group on high‐fat diet. Enhanced insulin sensitivity was observed in the UCP2−/− group. The differentially expressed genes were mapped to 23 pathways (P < 0.05). We concentrated on the ‘peroxisome proliferator‐activated receptor (PPAR) signaling pathway’ (P = 3.19 × 10−11), because it is closely associated with the regulation of glucose and lipid profiles. In the PPAR signaling pathway, seven genes (PPARγ, Dbi, Acsl3, Lpl, Me1, Scd1, Fads2) in the UCP2−/− mice were significantly upregulated.Conclusions
The present study used gene arrays to show that activity of the PPAR signaling pathway involved in the improvement of glucose and lipid metabolism in the liver of UCP2‐deficient mice on a long‐term high‐fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The manipulation of UCP2 protein expression could represent a new strategy for the prevention and treatment of diabetes. 相似文献20.
Difference between old and young adults in contribution of β‐cell function and sarcopenia in developing diabetes mellitus
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