Endocrine Journal Impact Factor & Information

Publisher: Nihon Naibunpi Gakkai

Journal description

Current impact factor: 2.02

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.019
2012 Impact Factor 2.228
2011 Impact Factor 2.027
2010 Impact Factor 1.952
2009 Impact Factor 1.806
2008 Impact Factor 1.6
2007 Impact Factor 1.572
2006 Impact Factor 1.14
2005 Impact Factor 1.037
2004 Impact Factor 0.848
2003 Impact Factor 1.045
2002 Impact Factor 0.847
2001 Impact Factor 0.869
2000 Impact Factor 0.779
1999 Impact Factor 0.532
1998 Impact Factor 0.656
1997 Impact Factor 0.818
1996 Impact Factor 0.715
1995 Impact Factor 1.341
1994 Impact Factor 1.006
1993 Impact Factor 0.428

Impact factor over time

Impact factor
Year

Additional details

5-year impact 2.10
Cited half-life 5.70
Immediacy index 0.26
Eigenfactor 0.01
Article influence 0.60
Website Endocrine Journal website
Other titles Endocrine journal (Online)
ISSN 0918-8959
OCLC 53816300
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Insulinoma and insulin or insulin receptor (IR) autoantibodies are the main causes of hyperinsulinemic hypoglycemia in adults, but the exact cause in other cases remains obscure. This study is to determine the genetic basis of hyperinsulinemic hypoglycemia in two cases without the above abnormalities. Sequence analysis of IR gene in two patients with adult-onset hyperinsulinemic hypoglycemia and their relatives were performed, and the mutant gene observed in one case was analyzed. Both cases had normal levels of fasting plasma glucose (FPG), fasting hyperinsulinemia, low insulin sensitivity, and hypoglycemia with excessive insulin secretion during oral glucose tolerance test (OGTT). Both reported adult-onset postprandial hypoglycemic symptoms. In one patient, a missense mutation (Arg256Cys) was detected in both alleles of the IR gene, and his parents had the same mutation in only one allele but no hypoglycemia. The other had a novel nonsense mutation (Trp1273X) followed by a mutation (Gln1274Lys) in one allele, and his 9-year old son had the same mutation in one allele, together with hyperinsulinemic hypoglycemia during OGTT. Overexpression experiments of the mutant gene found in Case 1 in mammalian cells showed abnormal processing of the IR protein and demonstrated reduced function of Akt/Erk phosphorylation by insulin in the cells. In two cases of hyperinsulinemic hypoglycemia in adults, we found novel mutations in IR gene considered to be linked to hypoglycemia. We propose a disease entity of adult-onset hyperinsulinemic hypoglycemia syndrome associated with mutations in IR gene.
    Endocrine Journal 03/2015; 62(4). DOI:10.1507/endocrj.EJ14-0547
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    ABSTRACT: There is evidence that betatrophin, a hormone derived from adipose tissue and liver, affects the proliferation of pancreatic beta cells in mice. The aim of this study was to examine circulating betatrophin concentrations in Japanese healthy controls and patients with type 1 and type 2 diabetes. A total of 76 subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were enrolled in the study. Circulating betatrophin was measured with an ELISA kit and clinical parameters related to betatrophin were analyzed statistically. Circulating betatrophin (Log transformed) was significantly increased in patients with diabetes compared with healthy subjects (healthy controls, 2.29 ± 0.51; type 1 diabetes, 2.94 ± 0.44; type 2 diabetes, 3.17 ± 0.18; p<0.001, 4.1 to 5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log triglyceride were strongly associated with Log betatrophin in all subjects (n=76) in correlation analysis. In type 1 diabetes, there was a correlation between Log betatrophin and Log CPR. These results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes. The findings of this pilot study also suggest a possibility of association between the level of betatrophin and the levels of glucose and triglycerides.
    Endocrine Journal 03/2015; DOI:10.1507/endocrj.EJ14-0525
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    ABSTRACT: Obesity has reached global epidemic proportions and is associated with multiple comorbidities, including cardiovascular disease. A novel predictor of cardiovascular disease is elevated central systolic blood pressure. In fact, lifestyle modifications have been shown to decrease the central systolic blood pressure in overweight and obese men. The mechanism underlying these changes has yet to be fully elucidated. Interestingly, testosterone has been found to have cardioprotective effects. Moreover, serum testosterone levels are lower in obese men than in normal weight men. However, it is still unclear whether testosterone participates in the decrease of central blood pressure in overweight and obese men following lifestyle modifications. So, the purpose of the present study was to investigate the effect of testosterone on central systolic blood pressure in overweight and obese men before and after the 12-week lifestyle modification program. Forty-four overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and dietary modifications). For all participants, central systolic blood pressure and serum testosterone levels were measured before and after the program. After the program, central systolic blood pressure was significantly decreased while serum total testosterone levels were significantly increased in overweight and obese men. Moreover, we also found a significant negative relationship between the change in serum testosterone levels and that in central systolic blood pressure. The present study suggests that increased serum testosterone levels likely contribute to a decrease in central blood pressure in overweight and obese men.
    Endocrine Journal 03/2015; DOI:10.1507/endocrj.EJ14-0555
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    ABSTRACT: There is little information on direct comparison between metformin and glucagon-like peptide-1 (GLP-1) receptor agonists in the Asian population. This study examined the efficacy and safety of liraglutide monotherapy compared with metformin monotherapy in overweight/obese Japanese patients with type 2 diabetes (T2DM). The study was a 24-week, open-labeled, randomized controlled study. Overweight or obese patients with T2DM aged 20-75 years with suboptimal glycemic control were randomized to liraglutide or metformin monotherapy. The primary endpoint was change in HbA1c at week 24. Secondary endpoints included changes in daily glycemic profile, body weight, incidence of hypoglycemia and other adverse events. The study, which was originally planned to enroll 50 subjects in each group, was ended with insufficient recruitment. A total of 46 subjects completed the study, and analysis was conducted in this cohort. Reduction in HbA1c at week 24 was comparable between the metformin (n = 24) and liraglutide (n = 22) groups (-0.95 ± 0.80% vs. -0.80 ± 0.88%, p = 0.77), while the liraglutide group reached maximal reduction more rapidly than did the metformin group. There was no significant difference in weight gain or incidence of hypoglycemia between the groups. Diarrhea was more frequent in the metformin group, while constipation was more frequent in the liraglutide group. There was no significant difference in treatment satisfaction between the groups. In conclusion, liraglutide and metformin monotherapy showed similar reduction in HbA1c during 24 weeks, with no difference in weight gain or incidence of hypoglycemia in overweight or obese Japanese patients with T2DM.
    Endocrine Journal 02/2015; DOI:10.1507/endocrj.EJ14-0602
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    ABSTRACT: The effects and possible mechanisms of adipose-derived stem cells (ASC) infusion on type 2 diabetic rats were investigated in this study. Twenty normal male Sprague-Dawley rats were included in normal control group, and 40 male diabetic rats were randomly divided into diabetic control group and ASC group (which received ASC infusion). After therapy, levels of fasting plasma glucose (FPG), HbA1c, serum insulin and C-peptide, recovery of islet cells, inflammatory cytokines, and insulin sensitivity were analyzed. After ASC infusion, compared with diabetic control group, hyperglycemia in ASC group was ameliorated in 2 weeks and maintained for about 6 weeks, and plasma concentrations of insulin and C-peptide were significantly improved (P<0.01). Number of islet β cells and concentration of vWF in islets in ASC group increased, while activity of caspase-3 in islets was reduced. Moreover, concentrations of TNF-α, IL-6 and IL-1β in ASC group obviously decreased (P<0.05). The expression of GLUT4, INSR, and phosphorylation of insulin signaling molecules in insulin target tissues were effectively improved. ASC infusion could aid in T2DM through recovery of islet β cells and improvement of insulin sensitivity. Autologous ASC infusion might be an effective method for T2DM.
    Endocrine Journal 02/2015; 62(4). DOI:10.1507/endocrj.EJ14-0584
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    ABSTRACT: The analogue insulin glulisine (Glu) shows both more rapid onset and shorter duration of action compared with the other rapid-acting insulin analogues. The current study investigates these properties in regard to the occurrence of hypoglycemia related to exercise. A randomized, single-center, open-label, crossover study was conducted in 12 hospitalized type 2 diabetes patients (all male, mean ± SD age of 51.9 ± 11.3 years; BMI: 25.5 ± 3.9 kg/m(2); HbA1c: 11.2 ± 2.4 %). Glu or insulin aspart (Asp) was subcutaneously administered just before breakfast. Insulin dosage was determined as the usual dose of pre-prandial rapid-acting insulin for patients treated with insulin therapy or as 0.1 unit/kg for patients treated with oral anti-hyperglycemic agents. Sixty min after the start of eating, the patients began aerobic exercise on a bicycle ergometer for 30 min at 50% of maximum heart rate. Hypoglycemic episodes (plasma glucose level < 70 mg/dL with or without symptoms) were observed more frequently in Asp group (p < 0.05). Post-exercise plasma glucose levels at 90, 120, and 150 min were significantly lower in Asp group (p < 0.05). In patients with BMI < 25 kg/m(2) (n = 6), post-exercise blood glucose levels were significantly lower in Asp group (p < 0.05), while in patients with BMI ≥ 25 kg/m(2) (n = 6) the difference was not significant. Glu may therefore be a suitable choice of rapid-acting insulin for patients with type 2 diabetes who are at high risk of post-exercise hypoglycemia.
    Endocrine Journal 02/2015; DOI:10.1507/endocrj.EJ14-0610
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    ABSTRACT: In this study, we present a case of developmental delay, epilepsy and neonatal diabetes (DEND) syndrome in a young male patient with the R50P mutation located in the Kir6.2 subunit of the ATP-sensitive K(+) (KATP) channel. Whereas most patients with DEND syndrome are resistant to sulfonylurea therapy, our patient was responsive to sulfonylurea, lacked the most common neurological symptoms, such as epilepsy, but refused to drink water. His serum electrolytes and plasma osmolarity were normal but the serum vasopressin level was increased. To investigate the underlying mechanism of his water intake disorder, a 5 μl aliquot of 340 μM KATP channel opener diazoxide or 100 μM KATP channel inhibitor glibenclamide was injected into the third ventricle of the rat brain, and water intake was monitored. Although the injection of glibenclamide had no effect, injection of diazoxide significantly increased water intake by about 1.5 fold without affecting food intake. This result indicates that the KATP channel activity in the brain may have an influence on water intake. Here, we present the first case of a DEND syndrome-afflicted patient with water intake disorder and increased serum vasopressin level, possibly related to altered KATP channel activity.
    Endocrine Journal 02/2015; 62(4). DOI:10.1507/endocrj.EJ14-0392
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    ABSTRACT: Agents that stimulate human pancreatic beta cell proliferation are needed to improve diabetes mellitus treatment. Recently, a small molecule, WS6, was observed to stimulate human beta cell proliferation. However, little is known about its other effects on human islets. To better understand the role of WS6 as a possible beta cell regenerative therapy, we carried out in-depth phenotypic analysis of WS6-treated human islets, exploring its effects on non-beta cell proliferation, beta cell differentiation, and islet cell viability. WS6 not only stimulated beta cell proliferation in cultured human islets (in agreement with previous reports), but also human alpha cell proliferation, indicating that WS6 is not a beta cell-specific mitogen. WS6 did not change the proportion of insulin-positive beta cells or the expression of beta cell-specific transcription factors, suggesting that WS6 does not alter beta cell differentiation, and WS6 had no effect on human islet cell apoptosis or viability. In conclusion, WS6 stimulates proliferation of both human beta and alpha cells while maintaining cellular viability and the beta cell differentiated phenotype. These findings expand the literature on WS6 and support the suggestion that WS6 may help increase human islet mass needed for successful treatment of diabetes.
    Endocrine Journal 02/2015; 62(4). DOI:10.1507/endocrj.EJ14-0449
  • Endocrine Journal 01/2015; 62(3). DOI:10.1507/endocrj.EJ14-0566
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    ABSTRACT: A 39-year-old Japanese woman presented with typical clinical symptoms of Cushing's syndrome, including amenorrhea and hirsutism, for 2 years. The results of her initial endocrine evaluation were consistent with ACTH-independent Cushing's syndrome due to bilateral adrenal masses (diameters of 3.1 cm and 2.4 cm on the right and left, respectively). Serum dehydroepiandrosterone levels were 6,901 ng/mL (normal range 230-2,660 ng/mL). Bilateral laparoscopic adrenalectomies were performed (left adrenalectomy first and right adrenalectomy 3 months later). Following the left adrenalectomy, the results of the endocrine evaluations were still consistent with a diagnosis of ACTH-independent Cushing's syndrome. Serum dehydroepiandrosterone sulphate levels, however, were below the normal range (143 ng/mL). Unexpectedly, the patient's menstruation resumed 2.5 months after the left adrenalectomy. Pathological examination of the resected glands showed bilateral adrenocortical adenomas, one on the left with a diameter of 3 cm, and two on the right with diameters of 0.7 cm and 1.3 cm. Immunohistochemical analysis revealed side chain cleavage, 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, and 21-hydroxylase immunoreactivity in each adenoma. Dehydroepiandrosterone-sulfotransferase immunoreactivity was pronounced in the left adenoma, less pronounced in one of the right adenoma and weak in the other right adenoma. These results were consistent with clinical endocrine findings. Ours is the first case of a patient with bilateral cortisol-secreting adenomas with unilateral oversecretion of dehydroepiandrosterone sulphate. Resumption of menstruation after the correction of the dehydroepiandrosterone-sulphate excess, despite persistent cortisol excess, indicates the importance of adrenal androgens for the regulation of the menstrual cycle.
    Endocrine Journal 01/2015; 62(3). DOI:10.1507/endocrj.EJ14-0552
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    ABSTRACT: We recently established 2 mouse lines with different susceptibilities (prone and resistant) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-prone [SDG-P] and -resistant [SDG-R], respectively). In the present study, we analyzed transgenerational changes in metabolic phenotypes in these 2 mouse colonies to explore how the distinct phenotypes have emerged through the repetitive selection. Using C57BL/6, C3H, and AKR as background strains, mice showing inferior and superior glucose tolerance after HFD feeding were selected and bred repetitively over 20 generations to produce SDG-P and SDG-R, respectively. In addition to the blood glucose levels, HFD intake and body weight were also measured over the selective breeding period. As the generations proceeded, SDG-P mice became more susceptible to HFD-induced glucose intolerance and body weight gain, whereas SDG-R mice had gradually reduced HFD intake. The differences in fasting and post-glucose challenge blood glucose levels, body weight, and HFD intake became more evident between the 2 colonies through the selective breeding, mainly due to the HFD-induced glucose metabolism impairment and body weight gain in SDG-P mice and the reduction of HFD intake in SDG-R mice. These transgenerational changes in the metabolic phenotypes suggest that the genetic loci associated with the quantitative traits have been selectively enriched in SDG-P and SDG-R.
    Endocrine Journal 01/2015; 62(4). DOI:10.1507/endocrj.EJ14-0241
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    ABSTRACT: We retrospectively detected overt diabetes during pregnancy (ODMP) using a modified IADPSG definition and assessed whether ODMP increases the risk of developing maternal and neonatal complications and postpartum diabetes in Korean pregnant women. According to the definition of IADPSG, ODMP pregnant women were defined and 71 ODMP, 1781 GDM and 463 non-GDM pregnant women were included in a hospital-based study. Their blood glucose levels were tightly regulated by modifying lifestyles and insulin treatment. The pregnancy outcomes and postpartum glucose tolerances were determined among the non-GDM, GDM and ODMP groups. The ODMP women had higher plasma glucose levels after overnight-fasting and at 2 h after 100 g OGTT challenge as well as higher overnight-fasted plasma insulin and HbA1c levels than GDM women. HbA1c levels at delivery were close to the normal range in both GDM and ODMP groups. Most pregnancy outcomes such as Apgar score and the rate of preterm delivery were not significantly different among three groups. Only the rate of large for gestational age (LGA) was greater in the ODMP group than other groups. However, about 73% of ODMP women remained diabetic at 6-8 week postpartum as compared to 4.3% of GDM. The development of postpartum diabetes was also associated with postpartum waist circumferences and duration of breast feeding. In conclusion, ODMP women in this study maintained tight control of glucose homeostasis and did not experience serious adverse outcomes except for LGA infants; however most ODMP women still had postpartum glucose dysregulation.
    Endocrine Journal 01/2015; 62(4). DOI:10.1507/endocrj.EJ14-0529
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    ABSTRACT: Although several reports have defined normal thyroid volume depending on either age or body surface, there are no sequential reference values on childhood thyroid volume evaluated by using ultrasonography and epidemiological analysis in Japan. The aim of the present study was to establish updated reference values for thyroid volume by ultrasound examination and epidemiological analysis in 0-19 year-old Japanese children. It is based on a cross-sectional study conducted from October 9, 2011 to March 31, 2012. The subjects were 38,063 children who were examined by ultrasonography as the initial preliminary survey of the Fukushima Health Management Survey in October 9, 2011 to March 31, 2012. The width, thickness, and height of each lobe were measured and the volume of each lobe was calculated by the mean of the elliptical shape volume formula. The values of thyroid volume at the 2.5 and 97.5 percentiles of age and body surface area for each gender group were obtained from 0-19 year-old children. Positive correlation was observed between thyroid volume and either age or body surface. The right lobe was significantly larger than the left lobe. The thyroid volume in females was larger than that in males after adjusting body surface area. The reference values of childhood thyroid for each age or body surface area were obtained by this extensive survey using ultrasound. These reference values may be used to define the normal size of thyroid gland by echosonography in Japanese children, although thyroid volume may be affected by dimorphic factors such as sex hormones.
    Endocrine Journal 01/2015; DOI:10.1507/endocrj.EJ14-0478
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    ABSTRACT: Islet autotransplantation (IAT) is a viable treatment for patients with severe chronic pancreatitis, this modality may prevent brittle diabetes mellitus after pancreatectomy. This systematic review and meta-analysis was performed to evaluated the outcomes of IAT after TP and discuss the factors that may affect the efficacy of this procedure. Methods: MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 1977 to 30 April 2014. Cohort Studies reported patients with IAT after TP were included. The studies and data were identified and extracted by two reviewers independently. Data were analyzed using STATA 12.0 and Comprehensive Meta AnalysisV2 software. Random effects model, meta-regression analysis, sensitivity analysis and publication bias were conducted to improve the comprehens ive analysis. Results: Twelve studies reporting the outcomes of 677 patients were included in this review. The insulin independent rate for IAT after TP at last follow-up was 3.72 per 100 person-years (95% CI: 1.00-6.44). The 30-day mortality was 2.1% (95% CI: 1.2-3.8%). The mortality at last follow-up was 1.09 per 100 person-years (95% CI: 0.21-1.97). Factors associated with incidence density of insulin independence in univariate meta-regression analyses included IEQ/kgBW (P=0.026). Conclusions: Our systematic review suggests that IAT is a safe modality for patients with CP need to undergo TP. A significant number of patients will achieve insulin independence for a long time after receiving enough IEQ/kg.
    Endocrine Journal 01/2015; DOI:10.1507/endocrj.EJ14-0510
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    ABSTRACT: The aim of this study was to determine the diagnostic efficacy of free metanephrines in plasma samples drawn in the seated position compared with 24-h urinary metanephrines in detecting pheochromocytomas in Asian patients. This prospective study was conducted at Samsung Medical Center between May 2010 and July 2011. The study contained 245 subjects, including 28 patients with histologically-proven pheochromocytoma, 44 with histologically-proven non-pheochromocytoma, 112 controls suspected of having tumors but with negative investigations during two or more years of follow-up, and 45 healthy normotensive volunteers. Plasma-free metanephrines were measured by LC-MS/MS. The cut-off values with optimal sensitivity and specificity for plasma metanephrine and plasma normetanephrine were 0.33 nmol/L and 0.61 nmol/L, respectively. Both the plasma metanephrines measurement and urinary metanephrines measurement had a sensitivity of 96.4% (p = 1.00). However, the urinary metanephrines measurement was significantly more specific than the plasma metanephrines measurement (94.2% vs. 75.6%; p < 0.001). When we applied cut-off values based on BMI, specificity improved from 75.6% to 87.2%, with a comparable gain in sensitivity. From a diagnostic perspective, measurement of free metanephrines in plasma drawn in the seated position is highly sensitive but insufficiently specific when compared with measurement of 24-h urinary fractionated metanephrines. The specificity may be improved by applying cut-off values based on BMI. We suggest that free metanephrines in plasma drawn from seated position can also be used as an initial screening test to ensure pheochromocytomas are not missed in Asian patients.
    Endocrine Journal 12/2014; DOI:10.1507/endocrj.EJ14-0384
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    ABSTRACT: Obesity is associated with increased risk of developing numerous adverse health conditions. Cathepsin k (CTSK) is highly expressed in adipose tissues of obese patients and animal models. Although CTSK has been demonstrated to promote adipocyte differentiation in 3T3-L1 cells, the effects of CTSK selective inhibitor (CKSI) on weight gain and insulin resistance have not been well examined. High-fat diet (HFD) induced obese male C57BL/6 mice were fed a diet with or without CKSI for 8 weeks. The HFD induced increase in adipose tissue weight gain, increase in homeostasis model assessment (HOMA) index as well as accumulation of large adipocytes. After CKSI treatment, all these effects were blunted compared with the HFD control group. A study of the mechanism demonstrated a role for CKSI in significantly down-regulating the expression of two key transcription factors, peroxisome proliferators-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are markers of adipogenic differentiation. These results indicated that the CKSI possesses an anti-obesity effect, possibly involving the inhibition of adipocyte differentiation. CTSK is likely to be a new target of therapeutic intervention for the treatment of obesity.
    Endocrine Journal 11/2014; 62(4). DOI:10.1507/endocrj.EJ14-0336
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    ABSTRACT: The aim of this study is to determine which indicator of chronic kidney disease most closely correlates with 10-year Framingham coronary heart disease (CHD) risk among serum creatinine, serum cystatin C (S-CysC), urine albumin-creatinine ratio (UACR), estimated creatinine-based GFRs (eGFRcre), and estimated CysC-based GFRs (eGFRcys) in patients with obesity and diabetes. Serum creatinine, S-CysC, UACR, and cardio-ankle vascular index (CAVI) were examined in 468 outpatients with obesity and type 2 diabetes, free of severe renal dysfunction or previous history of cardiovascular disease, as a cross-sectional survey using baseline data from the multi-centered Japan Diabetes and Obesity Study. S-CysC and eGFRcys had significantly stronger correlations with the 10-year Framingham CHD risk than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.318; S-CysC, ρ = 0.497; UACR, ρ = 0.174; eGFRcre, ρ = -0.291; eGFRcys, ρ = -0.521; P < 0.01 by Fisher's z-test). S-CysC and eGFRcys had significantly stronger correlations with CAVI than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.198; S-CysC, ρ = 0.383; UACR, ρ = 0.183; eGFRcre, ρ = -0.302; eGFRcys, ρ = -0.444; P < 0.05 by Fisher's z-test). The receiver operating characteristic curves to distinguish the high-risk patients for CHD revealed significantly larger areas under the curve of S-CysC and eGFRcys than those of serum creatinine, UACR, and eGFRcre (serum creatinine, 0.64; S-CysC, 0.75; UACR, 0.56; eGFRcre, 0.63; eGFRcys, 0.76; P < 0.01). The data suggested that eGFRcys can be more predictive of the 10-year CHD risk than eGFRcre in Japanese patients with obesity and diabetes.
    Endocrine Journal 11/2014; 62(2). DOI:10.1507/endocrj.EJ14-0352
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    ABSTRACT: To assess the total daily inulin dose (TDD) and contribution of basal insulin to TDD and to identify the predictive factors for insulin requirement profiles in subjects with type 2 diabetes, we retrospectively examined insulin requirement profiles of 275 hospitalized subjects treated with basal-bolus insulin therapy (BBT) (mean age, 60.1 ± 12.9 years; HbA1c, 10.2 ± 4.5%). Target plasma glucose level was set between 80 and 129 mg/dL before breakfast and between 80 and 179 mg/dL at 2-hour after each meal without causing hypoglycemia. We also analyzed the relationship between the insulin requirement profiles (TDD and basal/total daily insulin ratio [B/TD ratio]) and insulin-associated clinical parameters. The mean TDD was 0.463 ± 0.190 unit/kg/day (range, 0.16-1.13 unit/kg/day). The mean B/TD ratio was 0.300 ± 0.099 (range, 0.091-0.667). A positive correlation of TDD with B/TD ratio was revealed by linear regression analysis (r=0.129, p=0.03). Stepwise multiple regression analysis identified post-breakfast glucose levels before titrating insulin as an independent determinant of the insulin requirement profile [Std β (standard regression coefficient) = 5.71E-4, p<0.01 for TDD, Std β = -2.39E-4, p <0.01 for B/TD ratio]. The TDD was <0.6 unit/kg/day and the B/TD ratio was <0.4 in the majority (70.2%) of subjects in the present study. These findings may have relevance in improving glycemic control and decreasing the risk of hypoglycemia and weight gain in subjects with type 2 diabetes treated with BBT.
    Endocrine Journal 11/2014; 62(2). DOI:10.1507/endocrj.EJ14-0487
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    ABSTRACT: To assess the significance of ketogenesis in the management of diabetes mellitus, we analyzed the factors associated with the diurnal variation of the plasma ketone body levels. The subjects consisted of 220 patients with type 2 diabetes, aged 60 ± 15 years, without advanced complications. They ate a standardized, low-fat meal at 8:00, 12:00, and 18:00. The plasma levels of 3-hydroxybutyrate (3HB) and free fatty acid (FFA) were increased before breakfast and before dinner. The plasma glucose concentration was almost the same at any blood sampling time point among age quartiles. However, the 3HB levels were significantly decreased with age, which was most obvious before dinner. The FFA levels also decreased with age, but the decline was mild. A multiple regression analysis with stepwise selection revealed that age was an independent, negative contributor and that the pre-breakfast FFA concentration was an independent, positive contributor to the pre-breakfast 3HB levels. Regarding the pre-dinner 3HB levels, in addition to age and the pre-dinner FFA concentration, the uses of sulfonylurea and dipeptidyl peptidase-4 inhibitors were independent negative contributors. The metabolism of ketone bodies is an alternative energy source for the brain under conditions of starvation. While excessive ketogenesis leads to critical ketoacidosis, inadequate ketone body production could be associated with a propensity to develop neurohypoglycemia in elderly patients treated with insulin secretagogues. Because age-related changes in ketogenesis were the most significant before dinner, attention should be paid not only to fasting but also to the pre-dinner levels of 3HB.
    Endocrine Journal 11/2014; DOI:10.1507/endocrj.EJ14-0431