In the presence of obesity, beta-cell mass needs to be increased to compensate for the accompanying demands and maintain euglycemia. However, in Korea, the majority of type 2 diabetic patients are nonobese. We determined the absolute masses, relative volumes, and ratio of alpha- and beta-cell in the pancreas and islets in normal and diabetic Korean subjects to correlate these findings with the clinical characteristics. Whole pancreases procured from organ donors were divided into 24 parts (control 1, n = 9). Tissue was also obtained by surgical resection after 35 partial pancreatectomies: in 25 diabetic patients, 10 age- and body mass index (BMI)-matched patients of benign or malignant pancreatic tumor without diabetes mellitus (DM) (control 2). Morphometric quantifications were performed. In control 1, the relative volume of beta-cells was 2.1 +/- 0.9%, and the total beta-cell mass was 1.3 +/- 0.3 g. The relative volume of beta-cells was found to be variable (control 1, 2.1 +/- 0.9%; control 2, 1.9 +/- 0.7%; DM, 1.4 +/- 1.0%; P < 0.05 DM vs. control 1 and 2) and showed good correlation with BMI (control 1, r(2) = 0.64; DM, r(2) = 0.55; all subjects, r(2) = 0.38; P < 0.05). Notably, in type 2 diabetic patients, the ratio of alpha-cell area to beta-cell area in the islet was higher than in control 1 and 2 (0.81 +/- 0.4 vs. 0.29 +/- 0.2, 0.20 +/- 0.1, P < 0.05). Additionally, significant alpha-cell expansion and a decreased beta-cell fraction were predominantly observed in larger islets (islet area, >6415 micro m(2); P < 0.05) in control 1 and diabetic patients. The relative volume of beta-cell was found to be correlated with BMI in diabetic patients and normal organ donors. Moreover, decreased beta-cell but increased alpha-cell proportion in the islets suggests for a selective beta-cell loss in the pathogenesis of Korean type 2 diabetes.
Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. STEM
It has been suggested that oxidative stress is associated with the pathogenesis of osteoporosis. The objective of this study was to explore the association between a marker of oxidative stress and either bone turnover markers or bone mineral density (BMD) in postmenopausal women. In addition, the effects of oxidative stress on the formation of osteoclasts in human bone marrow cell culture were examined. We performed a cross-sectional analysis in healthy postmenopausal women aged 60-78 years (n = 135, 68.2 +/- 4.9). Oxidative stress was evaluated in the serum by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels. The biochemical markers of bone turnover and areal BMD were measured in all participants. Multivariate linear regression analysis revealed a negative association between 8-OH-dG levels and BMD of the lumbar spine, total hip, femoral neck, and trochanter and positive association with type I collagen C-telopeptide (ICTP) levels. The odds ratio of 8-OH-dG for osteoporosis was 1.54 (1.14-2.31, P = 0.003). In cultures of primary human marrow cells, H2O2 caused concentration-dependent activation of TRAP-positive multinucleated giant cells. H2O2 also increased the area of pits per osteoclast activity assay substrate. RT-PCR showed that H2O2 stimulated the expression of M-CSF and RANKL and increased the RANKL/OPG ratio. The data support the view that oxidative stress is associated with increased bone resorption and low bone mass in otherwise healthy women. In addition, RANKL and M-CSF stimulation induced by oxidative stress may participate in osteoclastogenesis in human bone.
The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.
We report for the first time that a positive serum TgAb test was an independent predictor for thyroid malignancy in thyroid nodules along with serum TSH levels regardless of the presence of AIT. Our results suggest that TgAb measurement could give additional information for predicting malignancy in cytologically indeterminate thyroid nodules in conjunction with clinical risk factors and TSH levels.
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