1.High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction
Shun-ichiro ASAHARA ; Hiroyuki INOUE ; Yuka IHARA ; Kyoko TERUYAMA ; Asuka IMAI ; Chisako HARA ; Mizuki HARA ; Masako SEIKE ; Aisha YOKOI ; Nozomi KIDO ; Hirotaka SUZUKI ; Ayumi KANNO ; Yuka INABA ; Hitoshi WATANABE ; Go SHIOI ; Maki KIMURA-KOYANAGI ; Michihiro MATSUMOTO ; Hiroshi INOUE ; Keiichi I. NAKAYAMA ; Wataru OGAWA ; Masato KASUGA ; Yoshiaki KIDO
Diabetes & Metabolism Journal 2026;50(1):77-89
Background:
The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe.
Methods:
We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass.
Results:
In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass.
Conclusion
This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.
2.Implications of the diagnosis of locomotive syndrome stage 3 for long-term care
Koichiro IDE ; Yu YAMATO ; Tomohiko HASEGAWA ; Go YOSHIDA ; Mitsuru HANADA ; Tomohiro BANNO ; Hideyuki ARIMA ; Shin OE ; Tomohiro YAMADA ; Yuh WATANABE ; Kenta KUROSU ; Hironobu HOSHINO ; Haruo NIWA ; Daisuke TOGAWA ; Yukihiro MATSUYAMA
Osteoporosis and Sarcopenia 2024;10(2):89-94
Objectives:
Locomotive syndrome stage 3 (LS3), which has been established recently, may imply a greater need for care than LS stage 0 (LS0), LS stage 1 (LS1), and LS stage 2 (LS2). The relationship between LS3 and long-term care in Japan is unclear. Therefore, this study aimed to examine this relationship.
Methods:
A total of 531 patients (314 women and 217 men; mean age, 75 years) who were not classified as requiring long-term care and underwent musculoskeletal examinations in 2012 were grouped according to their LS stage. Group L comprised patients with LS3 and Group N comprised those with LS0, LS1, and LS2. We compared these groups according to their epidemiology results and long-term care requirements from 2013 to 2018.
Results:
Fifty-nine patients (11.1%) were diagnosed with LS3. Group L comprised more patients (50.8%) who required long-term care than Group N (17.8%) (P < 0.001). Group L also comprised more patients with vertebral fractures and knee osteoarthritis than Group N (33.9% vs 19.5% [P = 0.011] and 78% vs 56.4% [P < 0.001], respectively). A Cox proportional hazards model and Kaplan–Meier analysis revealed a significant difference in the need for nursing care between Groups L and N (log-rank test, P < 0.001; hazard ratio, 2.236; 95% confidence interval, 1.451–3.447).
Conclusions
Between 2012 and 2018, 50% of patients with LS3 required nursing care. Therefore, LS3 is a highrisk condition that necessitates interventions. Approaches to vertebral fractures and osteoarthritis of the knee could be key.
3.Preoperative Less Right Shoulder Elevation Had a Higher Risk of Postoperative Shoulder Imbalance When Main Thoracic Curve Shows Higher Correction Regardless of the Upper Instrumented Vertebra Level for Patients with Adolescent Idiopathic Scoliosis Lenke Type 1
Tomohiro BANNO ; Yu YAMATO ; Tomohiko HASEGAWA ; Go YOSHIDA ; Hideyuki ARIMA ; Shin OE ; Yuki MIHARA ; Koichiro IDE ; Yuh WATANABE ; Kenta KUROSU ; Keiichi NAKAI ; Yukihiro MATSUYAMA
Asian Spine Journal 2023;17(1):166-175
Methods:
We examined the data of AIS patients with Lenke type 1 curves who underwent posterior fusion surgery in a retrospective manner. PSI was defined as a 2-year postoperative absolute radiographic shoulder height (RSH) of ≥2 cm. Patients were divided into two groups based on the presence of PSI and the level of their upper instrumented vertebra (UIV) (UIV at T2 or T3 [U-UIV] or UIV below T3 [L-UIV]). The radiographic parameters and clinical outcomes were compared, and the cutoff values of risk factors were identified by multivariate analysis.
Results:
Of 104 patients, 21 (20.2%) had left shoulder elevation PSI. The PSI group had a significantly greater preoperative RSH (−5.1 mm vs. −14.3 mm) and main thoracic (MT) curve correction rate (77.3% vs. 69.1%) than the non-PSI group. The PSI incidence did not differ between the U-UIV and L-UIV groups. Multivariate analysis identified preoperative RSH and the MT curve correction rate as independent risk factors for PSI. The receiver operating characteristic curve analysis identified the preoperative RSH cutoff value as −6.5 mm and MT curve correction rate cutoff value as 76.9%.
Conclusions
Even in AIS patients with Lenke type 1 curves, the incidence of PSI was relatively high (20.2%). Patients with preoperative lower right shoulder elevation (i.e., RSH >−6.5 mm) had a higher risk of PSI regardless of UIV level when the MT curve showed a higher correction rate (i.e., correction rate >76.9%).
4.Change in Line of Sight after Corrective Surgery of Adult Spinal Deformity Patients: A 2-Year Follow-up
Ken Jeffrey MAGCALAS ; Shin OE ; Yu YAMATO ; Tomohiko HASEGAWA ; Go YOSHIDA ; Tomohiro BANNO ; Hideyuki ARIMA ; Yuki MIHARA ; Hiroki USHIROZAKO ; Tomohiro YAMADA ; Koichiro IDE ; Yuh WATANABE ; Yukihiro MATSUYAMA
Asian Spine Journal 2023;17(2):272-284
Methods:
This retrospective study includes 295 corrective surgery patients with ASD. Subjects were divided into two groups after propensity age matching analysis: cranial malalignment (McGS <−8 or >13) and normal cranial alignment (−8≤ McGS ≤13). Lumbar lordosis (LL), pelvic tilt (PT), TK, cervical lordosis (CL), and sagittal vertical axis (SVA) were evaluated between the two groups.
Results:
SVA (95–56 mm) and PT (34°–25°) decreased and LL (19°–41°) increased 2 years after surgery (p <0.05), but McGS (−1.1° to −0.5°) and CL (21°–19°) did not change. Conversely, in the group with cranial malalignment, SVA (120–64 mm), PT (35°–26°), and LL (12°–41°) showed similar results to the normal cranial parameter group 2 years after surgery, but in contrast, McGS (−13° to −2°) and CL (24°–18°) improved significantly.
Conclusions
Severe ASD adversely affects to maintain horizontal gaze but can be improved by spinal corrective surgery.
5.How Is Degenerative Lumbar Scoliosis Associated with Spinopelvic and Lower-Extremity Alignments in the Elderly
Jili WANG ; Hiroki USHIROZAKO ; Yu YAMATO ; Koichiro IDE ; Tomohiko HASEGAWA ; Go YOSHIDA ; Tomohiro BANNO ; Shin OE ; Hideyuki ARIMA ; Yuki MIHARA ; Yuh WATANABE ; Keiichi NAKAI ; Kenta KUROSU ; Hironobu HOSHINO ; Yukihiro MATSUYAMA
Asian Spine Journal 2023;17(2):253-261
Methods:
Adult volunteers aged over 50 years were included in the study after participating in the screening program. Characteristic data and standing radiographic parameters were assessed. A propensity score model was established with adjustments for age and sex after a preliminary analysis, and cases were divided into DLS (Cobb angle >10°) and non-DLS (Cobb angle ≤10°) groups.
Results:
There were significant differences in age, sex, C2 sagittal vertical axis (C2-SVA), C7-SVA, T1 pelvic angle (TPA), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), PI minus LL (PI–LL), knee angle, ankle angle, pelvic shift, C7-center sacral vertical line, L4 tilt, femur-tibia angle, and hip-knee-ankle angle (all p <0.05) using a preliminary analysis of 261 cases (75 DLS and 186 non-DLS). A one-to-one propensity score-matched analysis was used after 70 pairs of cases were selected. There were no significant differences in the characteristic data for lower extremity parameters. There were still significantly higher values of C2-SVA, TPA, PI, PT, and PI–LL in DLS group than in non-DLS group (all p <0.05).
Conclusions
This study showed an important relationship between DLS and sagittal spinal deformity. However, DLS was not associated with the sagittal and coronal lower extremity alignments.
6.Association between Pelvic Parameters and Vaginal Delivery
Tomohiro YAMADA ; Yu YAMATO ; Tomohiko HASEGAWA ; Go YOSHIDA ; Tatsuya YASUDA ; Tomohiro BANNO ; Hideyuki ARIMA ; Shin OE ; Yuki MIHARA ; Hiroki USHIROZAKO ; Koichiro IDE ; Yuh WATANABE ; Hironobu HOSINO ; Yukihiro MATSUYAMA
Asian Spine Journal 2022;16(2):248-253
Methods:
As part of a 2016 health screening, 320 female volunteers underwent whole-spine radiographs. Age-matched healthy women were grouped according to the number of vaginal deliveries (0, 1–2, or ≥3). Demographic variables and spinopelvic parameters were compared among the three groups.
Results:
Of the 320 volunteers, 213 were enrolled (mean age, 71.1±7.2 years). The mean number of vaginal deliveries was 2.2. The average pelvic incidence (PI) was 55.6°±11.1° and was significantly higher in the 90 women with three or more vaginal deliveries than in the other two groups (p<0.001). The average sacral slope was 33.4°±11.1° and was significantly higher in the women with three or more vaginal deliveries than in the 18 who did not deliver vaginally (p<0.001). The 105 women with one or two vaginal deliveries had significantly higher PIs and sacral slopes than did those who did not deliver vaginally (p<0.001).
Conclusions
This is the first study documenting an association between vaginal delivery and pelvic parameters. Bony birth canal realignment during vaginal delivery can affect postnatal PI. Our study helps in understanding the PI changes over a woman’s life span.
7.Revision Surgery for a Rod Fracture with Multirod Constructs Using a Posterior-Only Approach Following Surgery for Adult Spinal Deformity
Yu YAMATO ; Tomohiko HASEGAWA ; Go YOSHIDA ; Tomohiro BANNO ; Shin OE ; Hideyuki ARIMA ; Yuki MIHARA ; Hiroki USHIROZAKO ; Tomohiro YAMADA ; Yuh WATANABE ; Koichiro IDE ; Keiichi NAKAI ; Kenta KUROSU ; Yukihiro MATSUYAMA
Asian Spine Journal 2022;16(5):740-748
Methods:
We retrospectively reviewed the medical records of 404 patients who underwent corrective fusion surgery for ASD with a minimum 2-year follow-up. We studied cases of reoperation for postoperative rod fractures and investigated surgical procedure, intraoperative findings, clinical course, and rod refracture following revision surgery.
Results:
Rod fracture was observed in 88 patients (21.8%). Fifty-three patients (average age, 68.3 years; average blood loss, 502.2 mL [% estimated blood volume=16.4%]; and operation time, 203.3 minutes) who suffered from a rod fracture at an average of 28.3 months after the primary operation underwent reoperation. Surgical invasiveness had no significant differences in total or partial rod replacement; however, the procedures with and without an anterior bone graft significantly differed. The replaced rod refractured at an average of 35.3 months after the revision surgery of five patients. The rod also refractured at a level outside multiple rods in two patients and with traumatic episodes in three patients. Three patients had bone grafts in the anterior column.
Conclusions
Revision surgery involving a multirod with a posterior-only approach for a rod fracture that occurred after ASD was performed successfully. Bone grafting in the anterior column is unnecessary for patients without massive bone defects.
8.Selective Angiography to Detect Anterior Spinal Artery Stenosis in Thoracic Ossification of the Posterior Longitudinal Ligament
Go YOSHIDA ; Hiroki USHIROZAKO ; Tomohiko HASEGAWA ; Yu YAMATO ; Tatsuya YASUDA ; Tomohiro BANNO ; Hideyuki ARIMA ; Shin OE ; Yuki MIHARA ; Tomohiro YAMADA ; Koichiro IDE ; Yuh WATANABE ; Takasuke USHIO ; Yukihiro MATSUYAMA
Asian Spine Journal 2022;16(3):334-342
Methods:
This study prospectively examined nine T-OPLL patients who underwent posterior thoracic decompression with kyphosis correction and instrumented fusion at Hamamatsu University School of Medicine between 2017 and 2019. All underwent preoperative selective angiography to detect and evaluate the Adamkiewicz artery and ASA. Intraoperative neuromonitoring and Doppler ultrasonography were performed to analyze neurological complications and spinal cord blood flow.
Results:
All nine patients showed ASA stenosis in the area of T-OPLL. In all patients, the Adamkiewicz artery was located between T7 and L2 and the area of ASA stenosis corresponded to the level of T-OPLL and greatest spinal cord compression; intraoperative Doppler ultrasonography confirmed the ASA defect at the same spinal level. The number of spinal levels from the Adamkiewicz artery to the most compressive OPLL lesion was greater in the two patients who developed postoperative neurological deficit compared to those who did not (5.5 vs. 2.3, p=0.014).
Conclusions
This is the first study to report detection of ASA stenosis in patients with T-OPLL. Maintaining spinal cord blood flow is important in these patients to avoid neurological deterioration.
9.Impact of Spinal Correction Surgeries with Osteotomy and Pelvic Fixation in Patients with Kyphosis Due to Osteoporotic Vertebral Fractures
Tomohiko HASEGAWA ; Hiroki USHIROZAKO ; Yu YAMATO ; Go YOSHIDA ; Tatsuya YASUDA ; Tomohiro BANNO ; Hideyuki ARIMA ; Shin OE ; Tomohiro YAMADA ; Koichiro IDE ; Yuh WATANABE ; Yukihiro MATSUYAMA
Asian Spine Journal 2021;15(4):523-532
Combination of retrospective and prospective study. We aimed to compare the clinical outcomes between local fixation surgery and spinopelvic fixation surgery for the treatment of kyphosis secondary to osteoporotic vertebral fractures with spinopelvic malalignment. The clinical characteristics of patients with rigid kyphosis due to osteoporotic vertebral fracture differ from that of middle-aged patients with vertebral fractures in terms of bone fragility and presence of spinopelvic malalignment. Little is known about the surgical strategies for these deformities, most especially the extent of fusion of vertebra involved. We analyzed 24 patients with vertebral osteotomy at the level of the fracture and spinal fixation without pelvic fixation (local group), and 22 patients with vertebral osteotomy and pelvic fixation (pelvic group). Radiographic parameters, the incidence of proximal junctional kyphosis (PJK), distal junctional kyphosis (DJK), rod fractures, and the Oswestry Disability Index (ODI) were compared between the two groups over a 2-year follow-up period. In the pelvic group, postoperative spinopelvic parameters significantly improved, with the improvements maintained. No remarkable changes in spinopelvic parameters were seen in the local group. The mean ODI scores 2 years after surgery were 45.3 and 33.0 in the local and pelvic group, respectively ( For patients with rigid kyphosis due to osteoporotic vertebral fractures, better spinopelvic alignment and health-related quality of life can be achieved through extensive corrective surgery with pelvic fixation.
10.Impact of Spinal Correction Surgeries with Osteotomy and Pelvic Fixation in Patients with Kyphosis Due to Osteoporotic Vertebral Fractures
Tomohiko HASEGAWA ; Hiroki USHIROZAKO ; Yu YAMATO ; Go YOSHIDA ; Tatsuya YASUDA ; Tomohiro BANNO ; Hideyuki ARIMA ; Shin OE ; Tomohiro YAMADA ; Koichiro IDE ; Yuh WATANABE ; Yukihiro MATSUYAMA
Asian Spine Journal 2021;15(4):523-532
Combination of retrospective and prospective study. We aimed to compare the clinical outcomes between local fixation surgery and spinopelvic fixation surgery for the treatment of kyphosis secondary to osteoporotic vertebral fractures with spinopelvic malalignment. The clinical characteristics of patients with rigid kyphosis due to osteoporotic vertebral fracture differ from that of middle-aged patients with vertebral fractures in terms of bone fragility and presence of spinopelvic malalignment. Little is known about the surgical strategies for these deformities, most especially the extent of fusion of vertebra involved. We analyzed 24 patients with vertebral osteotomy at the level of the fracture and spinal fixation without pelvic fixation (local group), and 22 patients with vertebral osteotomy and pelvic fixation (pelvic group). Radiographic parameters, the incidence of proximal junctional kyphosis (PJK), distal junctional kyphosis (DJK), rod fractures, and the Oswestry Disability Index (ODI) were compared between the two groups over a 2-year follow-up period. In the pelvic group, postoperative spinopelvic parameters significantly improved, with the improvements maintained. No remarkable changes in spinopelvic parameters were seen in the local group. The mean ODI scores 2 years after surgery were 45.3 and 33.0 in the local and pelvic group, respectively ( For patients with rigid kyphosis due to osteoporotic vertebral fractures, better spinopelvic alignment and health-related quality of life can be achieved through extensive corrective surgery with pelvic fixation.

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