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Most Cited Articles (Vol. 63)

May 2018

1st

Serum irisin and its regulation by hyperinsulinemia in women with polycystic ovary syndrome

Agnieszka Adamska, Monika Karczewska-Kupczewska, Agnieszka Lebkowska, Robert Milewski, Maria Górska, Elzbieta Otziomek, Agnieszka Nikolajuk, Slawomir Wolczynski, Irina Kowalska

Vol 63 No. 12

Abstract

Irisin is an adipokine/myokine which could be connected with insulin sensitivity. Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, hyperandrogenism and insulin resistance. The aim of the present study was to determine the relationship between serum irisin concentration and insulin sensitivity (Mffm) as well as the effect of insulin infusion on circulating irisin levels in PCOS women as compared with healthy controls. Seventy seven women were enrolled in the study - 57 with PCOS and 20 healthy controls matched for BMI and age. Hyperinsulinemic euglycemic clamps were performed in all of the study participants. The serum concentrations of irisin at baseline and after the clamp, as well as changes of serum irisin concentration in response to insulin supplied during the clamp (Δ irisin), were estimated. The mean serum concentrations of irisin at baseline and after hyperinsulinemia were higher in PCOS women in comparison to the control group (p=0.01; p=0.006, respectively). Insulin infusion resulted in a decrease of serum irisin concentration only in the PCOS group (p=0.007). In the control group, Δ irisin positively correlated with Mffm (r=0.56, p=0.009). In the entire group, multiple regression analysis showed that Δ irisin (β=0.70, p=0.0002), FFAs 60’ during the clamp study (β=-0.22, p=0.01), SHBG (β=0.54, p<0.0001) and the interaction between Δ irisin and PCOS (β=-0.67, p=0.0004) were significantly associated with Mffm. The higher serum irisin concentrations at baseline and in response to insulin infusion might be secondary to insulin resistant conditions in PCOS women.

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1st

Expression of EAP1 and CUX1 in the hypothalamus of female rats and relationship with KISS1 and GnRH

Jing Xu, Pin Li

Vol 63 No. 8

Abstract

Using a combination of high throughput and bioinformatics strategies, in combination with a system biology approach, a group of related genes including EAP1 and CUX1 whose expression increased at the time of female puberty were singled out from the hypothalamus of nonhuman primates and rats. It was hypothesized that EAP1 and CUX1 genes may be required for the timely initiation of female puberty by regulating the expression of KISS1 gene. Therefore, we measured the hypothalamic expression of EAP1 and CUX1 genes of female SD rats in mRNA and protein levels along with the numbers of respective immunoreactive cells at three different development stages (juvenile, early puberty and adult). Besides, we investigated the distribution of their immunoreactive cells. Although there was no changes in the mRNA levels of EAP1 and CUX1 in the hypothalamus during the different sexual development stages, the protein expression of EAP1 in the early-puberty group was significantly higher than that in the juvenile group. Moreover, we found that EAP1 and CUX1 genes were localized in neuronal nuclei. Both were prominent in cells of the the arcuate nucleus (ARC) of the rat hypothalamus which was also the main localization of KISS1 gene. Especially, CUX1 gene was co-expressed in the kisspeptin neurons. Furthermore, the number and percentage of EAP1 immunoreactive cells in the early-puberty group were both significantly more than the juvenile group. Above results indicate that EAP1 gene may be involved in the neuroendocrine control of female puberty in correlation with the kisspeptin signaling.

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1st

Pathological characteristics of low-risk papillary thyroid microcarcinoma with progression during active surveillance

Mitsuyoshi Hirokawa, Takumi Kudo, Hisashi Ota, Ayana Suzuki, Akira Miyauchi

Vol 63 No. 9

Abstract

Papillary thyroid microcarcinoma (PTMC) is generally an indolent disease and active surveillance is conducted for low-risk cases. This study was carried out to clarify the pathological characteristics of PTMC cases that exhibited enlarged nodules or nodal metastasis during the surveillance period. A total of 188 PTMC cases that underwent surgery after active surveillance for ≥ 1 year were examined. Ki-67 labeling indices of > 5% and > 10% were detected in 50.0% and 22.2% of enlarged cases, respectively, values that were significantly higher than those in non-enlarged cases. Intraglandular dissemination and psammoma bodies in normal thyroid tissue were associated with new occurrence of nodal metastasis. Ultrasonographic macrocalcification and follicular variants were observed in 13.8% and 10.6% of non-enlarged cases, respectively, but not in enlarged or nodal metastatic cases. Intraglandular dissemination and psammoma bodies were ultrasonographically detected in 50.0% and 40.0% of cases, which was confirmed by microscopy. Thus, high Ki-67 labeling index, intraglandular metastasis, and psammoma bodies in normal thyroid tissue are indicators of progressive PTMC, and may be identified cytologically or ultrasonographically. In PTMC cases with ultrasonographic macrocalcification, active surveillance can be proactively implemented.

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Most Cited Articles (Vol. 62)

May 2018

1st

Lifestyle modification increases serum testosterone level and decrease central blood pressure in overweight and obese men

Hiroshi Kumagai, Asako Zempo-Miyaki, Toru Yoshikawa, Takehiko Tsujimoto, Kiyoji Tanaka, Seiji Maeda

Vol 62 No. 5

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.

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2nd

Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

Yi X. Chan, Matthew W. Knuiman, Joseph Hung, Mark L. Divitini, David J. Handelsman, John P. Beilby, Brendan McQuillan, Bu B. Yeap

Vol 62. No. 9

Abstract

Clarifying the relationship of sex hormones to preclinical atherosclerosis could illuminate pathways by which androgens are associated with cardiovascular events and mortality. Our aim was to determine hormone profiles associated with carotid intima-media thickness (CIMT) and carotid atheroma, in men with and without known coronary artery disease (CAD). We included 492 community-based men aged 20-70 years (Group A) and 426 men with angiographically proven CAD aged <60 years (Group B). Fasting early morning sera were assayed for testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) using mass spectrometry. CIMT and carotid plaque were assessed ultrasonographically. Mean (±SD) age was Group A: 53.8±12.6 and Group B: 49.6±5.1 years. Higher T was associated with reduced CIMT (-0.011 mm per 1-SD increase, p=0.042) and lower prevalence of carotid plaque (odds ratio [OR] per 1-SD increase, 0.68, p=0.012) in Group A, but not B. E2 was associated with increased CIMT in Group A (0.013 mm, p=0.011) but not B. Higher DHT and E2 were associated with reduced carotid plaque in Group B (DHT: OR=0.77, p=0.024; E2: OR=0.75, p=0.008), but not A. In community-dwelling men, higher T is associated with favourable CIMT and lower prevalence of carotid plaque, while higher E2 is associated with worse CIMT. In men with CAD, higher DHT or E2 are associated with less carotid plaque. T, DHT and E2 are differentially associated with preclinical carotid atherosclerosis in a cardiovascular phenotype-specific manner. Interventional studies are needed to examine effects of exogenous T and its metabolites DHT and E2, on atherogenesis.

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3rd

A 1-year safety study of dulaglutide in Japanese patients with type 2 diabetes on a single oral hypoglycemic agent: an open-label, nonrandomized, phase 3 trial

Masanori Emoto, Yasuo Terauchi, Akichika Ozeki, Tomonori Oura, Masakazu Takeuchi, Takeshi Imaoka

Vol 62. No. 12

Abstract

The goal of this study was to assess the safety and efficacy of 0.75 mg of dulaglutide, a once weekly glucagon-like peptide-1 receptor agonist, in Japanese patients with type 2 diabetes (T2D) on a single oral hypoglycemic agent (OHA). In this phase 3, nonrandomized, open-label, parallel-group, 52-week study, safety and efficacy of once weekly dulaglutide 0.75 mg were assessed in Japanese patients with T2D on a single OHA (sulfonylureas [SU], biguanides [BG], α-glucosidase inhibitors [AGI], thiazolidinedione [TZD], or glinides [GLN]). A total of 394 patients were treated with study drug, and 92.9% completed the 52-week treatment period. The most frequent treatment-emergent adverse events were nasopharyngitis and gastrointestinal disorders, including constipation, diarrhea, and nausea. Incidences of hypoglycemia varied across the combination therapy groups: incidence was greater in patients receiving SU compared with other combinations. No severe hypoglycemic episodes occurred during the study. Increases from baseline in pancreatic and total amylase, lipase, and pulse rate were observed in all 5 combination therapy groups. Significant reductions from baseline in HbA1c were observed in all 5 combination therapy groups (-1.57% to -1.69%, p < 0.001 for all). Mean body weight changes from baseline varied across the combination therapy groups: a significant increase was observed in combination with TZD, there were no significant changes in combination with SU or GLN, and significant reductions were observed in combination with BG or AGI. Once weekly dulaglutide 0.75 mg in combination with a single OHA was overall well tolerated and improved glycemic control in Japanese patients with T2D.

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3rd

Association of periodontitis with insulin resistance, β-cell function, and impaired fasting glucose before onset of diabetes

SKM Azizul Islam, Minchul Seo, Young-Sil Lee, Seong-Su Moon

Vol 62. No. 11

Abstract

Periodontitis and insulin resistance (IR) show bidirectional relationship. No studies have assessed the associations of periodontitis with IR, impaired β-cell function, and impaired fasting glucose (IFG) in the general population. We investigated these associations in a representative sample of the Korean population. The subjects were 8,248 males and 10,874 females, who were ≥ 20 years of age and participants in the third, fourth, and fifth Korea National Health and Nutritional Examination Surveys (2008-2010). Periodontitis was defined as community periodontal index (CPI) ≥ code 3 according to World Health Organization criteria. Homeostasis model assessments of IR and β-cell function (HOMA-IR and HOMA-β) were calculated. Participants with periodontitis showed a higher prevalence of diabetes than those without periodontitis. Among subjects without diabetes, after adjustment for confounding factors including age, gender, body mass index, systolic blood pressure, serum total cholesterol, smoking status, alcohol consumption, region, and regular exercise, a comparison of participants with periodontitis vs those without showed a significantly higher prevalence of IFG (28.5% vs. 17.7%, p<0.001) and lower HOMA-β (115.2 vs. 130.8, p<0.001). Periodontitis was identified as a risk factor for IFG (OR, 1.301; 95% CI, 1.193∼1.418; p<0.001). Conversely, participants with and without periodontitis had similar HOMA-IR. In conclusion, periodontitis showed an association with decreased β-cell function and increased prevalence of IFG before onset of diabetes as well as increased prevalence of diabetes in the Korean population. Future longitudinal studies are warranted to elucidate the shared pathophysiology between periodontal disease and diabetes mellitus.

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3rd

Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Mitsuyoshi Takahara, Toshihiko Shiraiwa, Taka-aki Matsuoka, Naoto Katakami, Iichiro Shimomura

Vol 62. No. 1

Abstract

It remains to be seen whether pancreatic β cell dysfunction in type 2 diabetic patients can be ameliorated just by correcting hyperglycemia. The current pilot study investigated β cell function after a four-week treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus. Ten participants (age, 51 ± 13 years; hemoglobin A1c levels, 9.4 ± 1.0%) took 50 mg of ipragliflozin L-proline for four weeks and thereafter discontinued the agent for one week. A 75-g oral glucose tolerance test (OGTT) was performed at 0 (baseline), 4 (end of medication), and 5 weeks (end of washout). The β cell function was evaluated using the disposition index, which was calculated as the product of the ΔIns0-120/ΔGlu0-120 and the Matsuda index, where ΔIns0-120/ΔGlu0-120 represents the ratio of the incremental concentrations of insulin to those of glucose during the 0- to 120-min time period of the OGTT. The fasting glucose level was 182 ± 34 mg/dL at 0 week, 137 ± 20 mg/dL at 4 weeks (p < 0.001), and 154 ± 31 mg/dL at 5 weeks (p = 0.001). Compared to baseline, the disposition index was significantly elevated not only at 4 weeks (p < 0.001) but also at 5 weeks (p = 0.008). In conclusion, the current pilot study showed that the β cell function assessed by the OGTT-derived disposition index was significantly improved after a four-week treatment with ipragliflozin in Japanese patients with type 2 diabetes mellitus.

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