Comparison of laser and traditional lancing devices for capillary blood sampling in patients with diabetes mellitus and high bleeding risk.

PURPOSE: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. METHODS: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. RESULTS: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. CONCLUSION: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value.

Concurrent Subacute Thyroiditis and Graves' Disease After COVID-19: A Case Report.

There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves' disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.

Impact of urinary iodine concentration on blood glucose levels and blood pressure: a nationwide population-based study.

PURPOSE: Iodine is a vital trace element for systemic metabolic control as well as thyroid hormone synthesis. Though iodine has significant antioxidant and anti-inflammatory effects, reports on its effects on metabolic disorders are limited and inconsistent. METHODS: Impact of urinary iodine concentrations (UICs) on fasting blood glucose (FBG) levels and blood pressure (BP) in the general Korean population was evaluated adjusting for covariates including thyrotropin level and presence of thyroid diseases. RESULTS: The median UIC was 302.3 µg/L in all participants and was significantly lower in those with dysglycemia (303.6 µg/L in normal participants, 285.1 µg/L in participants with FBG levels of 100-125 mg/dL, and 261.8 µg/L in participants with FBG levels ≥ 126 mg/dL; p = 0.002). Similarly, the UIC was lower in participants with higher BP (311.6 µg/L in normal participants, 288.7 µg/L in prehypertensive participants, and 265.8 µg/L in hypertensive participants; p < 0.001). The multiple linear regression model showed a negative correlation between the UIC and FBG levels (p = 0.002), and the UIC and systolic BP (p < 0.001). One standard deviation increase in the UIC showed odds ratios of 0.84 (95% confidence interval [CI] = 0.73-0.98) for elevated FBG levels (≥ 100 mg/dL) and 0.94 (95% CI = 0.88-0.99) for elevated SBP (≥ 120 mm Hg) after full adjustment. CONCLUSION: Higher UICs were associated with lower FBG and BP levels, independent of thyroid function and other confounding factors in Korea, an iodine-replete country.

Prognostic role of the lymphocyte-to-monocyte ratio for clinical outcomes of patients with progressive radioiodine-refractory differentiated thyroid carcinoma treated by sorafenib.

OBJECTIVES: The lymphocyte-to-monocyte ratio (LMR) reflects the status of tumour-infiltrating immune cells and host immunity. The LMR has been reported as a prognostic marker in various cancers. The present study evaluated the role of the LMR as a prognostic marker in patients with progressive radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC). DESIGN: Retrospective cohort study. PATIENTS: Forty patients with progressive RAIR DTC who were treated by sorafenib with available baseline complete blood cell count data. MEASUREMENTS: We assessed the response rate, progression-free survival (PFS) and overall survival (OS). RESULTS: The patients were divided into low and high LMR groups based on their baseline LMRs (<4, n = 22, 55% and ≥4, n = 18, 45%, respectively). There were no significant differences in baseline characteristics between the groups. The OS curves differed significantly based on the LMR. The median OS of the low LMR group was 24.3 months and that of the high LMR group was not reached until the end of observation period (P = .015). The PFS curves and median PFS also differed significantly based on the LMR values (P = .019). In multivariate analysis, low LMR was an independent risk factor for all-cause mortality in patients with progressive RAIR DTC (hazard ratio, 2.64; 95% confidence interval: 1.04-6.72, P = .041). CONCLUSION: A low LMR was associated with poor response rate, PFS and OS in patients with progressive RAIR DTC treated with sorafenib. Thus, LMR could be a simple prognostic biomarker in patients with progressive RAIR DTC.

Modified risk stratification based on cervical lymph node metastases following lobectomy for papillary thyroid carcinoma.

OBJECTIVE: Evidence for American Thyroid Association (ATA) risk stratification stems largely from studies involving patients undergoing total thyroidectomy. We aimed to assess the risk of recurrence according to the present ATA risk stratification system in patients who underwent lobectomy. DESIGN: Retrospective cohort study. PATIENTS: Patients who underwent thyroid lobectomy for 1-4 cm-sized papillary thyroid carcinoma (n = 571). MEASUREMENTS: Disease-free survival (DFS) was compared according to the ATA risk stratification, and specific lymph node (LN) characteristics were evaluated to modify the ATA criteria with a higher predictability for recurrence. RESULTS: Based on the ATA risk stratification, 439 patients (61.1%) were classified into intermediate- or high-risk group, and consideration for completion thyroidectomy is suggested by ATA guidelines for these patients. However, no significant differences were found in DFS among the low-, intermediate- and high-risk groups (P = .9). In contrast, when patients were stratified according solely to the LN criteria from the ATA risk stratification, only 127 patients (22.2%) had intermediate risk (intermediate-N1a) and exhibited significantly poorer DFS than those with N0 disease (P = .035). Modifying the intermediate-N1a criteria by adding the extranodal extension (ENE) status and omitting the clinical nodal disease enabled the subclassification of 19 patients (3%) with a high risk for recurrence. CONCLUSIONS: The present study suggests that risk stratification based solely on LN metastases is more reasonable for predicting structural persistence/recurrence following lobectomy than that based on the overall ATA criteria. Considering the ENE status can assist in selecting patients with a high risk of recurrence to minimize further treatments.

The value of preoperative antithyroidperoxidase antibody as a novel predictor of recurrence in papillary thyroid carcinoma.

The link between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is widely recognized. Considering the strong association between raised antithyroidperoxidase antibody (TPOAb) and CLT, we postulated that the preoperative TPOAb can predict the prognosis of PTC, particularly for recurrence. A total of 2,070 patients who underwent total thyroidectomy for classical type PTC with tumor size ≥1 cm and with available data on preoperative TPOAb and TgAb were enrolled to compare disease-free survival (DFS) according to the presence of preoperative TPOAb, TgAb, and coexistent CLT. Patients with positive preoperative TPOAb had a significantly better DFS compared to patients without positive preoperative TPOAb (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.30-0.94, p = 0.028) while no difference in DFS was found according to preoperative TgAb status. Positive preoperative TPOAb was an independent prognostic factor for structural persistent/recurrent disease after adjustment for major preoperative risk factors such as age, sex, and tumor size (HR 0.52, 95% CI 0.28-0.99, p = 0.048). Although the coexistence of CLT lowered the risk for structural persistence/recurrence in univariate analysis (HR 0.52, 95% CI 0.31-0.86, p = 0.012), it was not an independent favorable prognostic factor by multivariate analysis (HR 0.65, 95% CI 0.38-1.10, p = 0.106). However, when coexistent CLT was combined with positive preoperative TPOAb, it indicated an independent protective role in structural persistent/recurrent disease (HR 0.39, 95% CI 0.16-0.98, p = 0.045). Our study clearly showed that presence of preoperative TPOAb can be a novel prognostic factor in predicting structural persistence/recurrence of PTC.

Clinical Significance of Gross Invasion of Strap Muscles in Patients With 1- to 4-cm-Sized Papillary Thyroid Carcinoma Undergoing Lobectomy.

BACKGROUND: Given the emerging evidence supporting the lack of prognostic significance of gross extrathyroidal extension invading only strap muscles (strap-gETE), this study investigated whether lobectomy is feasible for patients with strap-gETE. METHODS: A retrospective cohort study was conducted with 636 patients who had 1- to 4-cm-sized papillary thyroid carcinoma (PTC) treated with thyroid lobectomy. Patients with gross invasion of perithyroidal organs other than strap muscles or synchronous distant metastasis were excluded from the study. Disease-free survival (DFS) was compared according to the presence of strap-gETE. RESULTS: Strap-gETE was present in 50 patients (7.9%), with the remaining 586 patients (92.1%) showing no evidence of gETE. During the median follow-up period of 7.4 years, 6% of the patients with strap-gETE and 5.1% of the patients without gETE experienced structural persistent/recurrent disease (p = 0.99). No differences in DFS were observed between the two groups (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.38-4.08; p = 0.720). After adjustment for five major risk factors (age, gender, tumor size, multifocality, and cervical lymph node metastasis status) in the multivariate analysis, the presence of strap-gETE did not exhibit an independent role in the development of structural persistent/recurrent disease (HR 1.05; 95% CI 0.24-4.53, p = 0.950). CONCLUSIONS: Strap-gETE did not increase the risk of structural persistent/recurrent disease for the patients who underwent lobectomy for 1- to 4-cm-sized PTC. The study data support the limited role of strap-gETE in clinical outcomes and may broaden the indications for lobectomy for patients with PTCs.

Influence of coexistent Hashimoto's thyroiditis on the extent of cervical lymph node dissection and prognosis in papillary thyroid carcinoma.

OBJECTIVE: Previous studies did not focus on the differences in the extent of cervical lymph node (LN) dissection according to coexistent Hashimoto's thyroiditis (HT) in patients with papillary thyroid carcinoma (PTC) and its clinical impact. We aimed to determine whether extensive cervical LN dissection is responsible for favourable clinical outcomes in PTC patients with HT and whether the coexistence of HT itself has an independent protective effect regardless of LN status. DESIGN: Retrospective cohort study. PATIENTS: 1369 patients with PTC who underwent total thyroidectomy with central compartment neck dissection. MEASUREMENTS: Metastatic LN ratio, defined as number of metastatic LNs divided by number of removed LNs, was used to evaluate the extent of LN dissection as well as the status of LN metastasis. Disease-free survival and dynamic risk stratification were compared for clinical outcomes. RESULTS: Presence of HT did not lower the risk of cervical LN metastasis (61.6% in patients with HT vs 65.1% in patients without HT, P = .292). Patients with HT had significantly larger numbers of removed LNs than patients without HT (11 vs 8, respectively, P < .001). Accordingly, metastatic LN ratio was smaller in patients with HT (P = .002), which was independently associated with structural persistent/recurrent disease (hazard ratio [HR] 2.33, 95% confidence interval [CI] 1.30-4.16, P = .004). HT itself was negatively associated with structural persistent/recurrent disease after adjustment for other clinicopathological factors (HR 0.39, 95% CI 0.18-0.87, P = .020). CONCLUSIONS: Coexistence of HT itself is an independent factor associated with favourable outcome in PTC patients, regardless of the extent of LN dissection.

Vincristine-associated Neuropathy With Antifungal Usage: A Kaiser Northern California Experience.

The dose-limiting toxicity for vincristine is peripheral neuropathy which can be potentiated with concurrent usage of azole antifungals. The current retrospective study assessed the incidence of concurrent vincristine and azole antifungal usage to determine if it led to increased neurotoxicity for the Kaiser Northern California pediatric acute lymphoblastic leukemia (ALL) and Hodgkin lymphoma patient population. Data were obtained from the electronic medical record (2007 to 2014). In total, 130 subjects received at least one dose of vincristine for ALL or Hodgkin lymphoma (median age 9, 88% ALL, 58% male, 47% Caucasian). Thirty one percent of patients received concurrent antifungal usage (fluconazole, 78%; voriconazole, 10%; fluconazole/voriconazole, 12%); however, concurrent antifungal usage accounted for <15% of vincristine doses. Grade 2 or greater neuropathy occurred in 51% of patients; grade 3 neuropathy was present in 8% of patients. No difference in the incidence of grade 2 or greater neuropathy was observed with the concurrent use of antifungal therapy (P=0.35), sex (P=0.59), type of cancer (P=0.41), ethnicity (P=0.29), or age (P=0.39), but was higher with increasing amount of vincristine doses (P=0.004). These results suggest that concurrent azole antifungal usage with vincristine for patients with ALL and Hodgkin lymphoma was low in the Kaiser Northern California population and limited usage as needed may be reasonable and safe.

Remnant cholesterol is an independent risk factor for the incidence of chronic kidney disease in newly-diagnosed type 2 diabetes: A nationwide population-based study.

AIMS: To evaluate the impact of remnant cholesterol (remnant-C) on chronic kidney disease (CKD) incidence in newly-diagnosed type 2 diabetes. METHODS: This retrospective cohort study used Korean National Health Insurance Service data on 212,836 patients with newly-diagnosed type 2 diabetes between 2009 and 2014. We conducted cox regression analysis to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for developing CKD according to remnant-C tertile. RESULTS: During a median follow-up duration of 5.23 years, 6,850 CKD cases developed. In the fully adjusted model, HRs and 95 % CIs for incident CKD increased in the highest tertile of baseline remnant-C compared to the lowest (HR [95 % CI]; 1.234 [1.159-1.314]). This association was more prominent in patients with hypertension or low-income status (P for interaction < 0.05). Increased HRs in the highest tertile of remnant-C was sustained in type 2 diabetes patients within target range of conventional lipid profile such as low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL and < 70 mg/dL (1.165 [1.041-1.304] and 1.308 [1.063-1.609]), high-density lipoprotein cholesterol (HDL-C) (1.243 [1.155-1.338]) and triglyceride (1.168 [1.076-1.268]), respectively. CONCLUSIONS: In newly-diagnosed type 2 diabetes patients, higher remnant-C is independently associated with CKD incidence, even when conventional lipid values are well-controlled.

Cancer Risk in Graves Disease with Radioactive 131I Treatment: A Nationwide Cohort Study.

Radioactive 131I (RAI) therapy has potential effects for the treatment of Graves disease (GD). However, whether RAI therapy for GD increases cancer risk remains controversial in medicine and public health. We aimed to investigate whether the risk of cancer increases in patients with GD receiving RAI therapy compared with those who did not. Methods: We used the Korean National Health Insurance Service's National Health Information Database from 2004 to 2020 and defined GD as prescribing antithyroid drugs, RAI, or thyroidectomy as a treatment for GD (International Classification of Diseases, 10th revision, E05 group). We investigated the hazard ratios (HRs) of overall and site-specific cancers associated with RAI in patients with GD. Subsequent cancer was defined as a primary malignancy treated at least 1 y after RAI therapy. Results: In total, 10,737 patients with GD who received RAI therapy (7,193 women, 67.0%; mean age, 43.7 ± 13.4 y) were matched to 53,003 patients with GD who had never received RAI treatment (35,471 women, 66.9%; mean age, 43.8 ± 13.2 y) in a 1:4-5 ratio by age, sex, and health checkup data. The median follow-up duration was 8.7 y (interquartile range, 5.2-12.1 y), and the median cumulative RAI dose was 555 MBq (interquartile range, 370-630 MBq) in the RAI therapy group. During 2004-2020, the overall subsequent cancer rates were 5.66 and 5.84 per 1,000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted HR of 0.97 (95% CI, 0.88-1.06); this remained at 0.96 (95% CI, 0.83-1.10) after adjustment for multiple clinical confounding factors. For cancer subtypes, the risk of leukemia was significantly increased, with an HR of 2.39 (95% CI, 1.17-4.91). However, a loss of statistical significance was observed after adjusting for confounding factors, which may be attributed to the limited number of absolute events. Moreover, cancer-specific mortality was not different between the RAI and the non-RAI groups, with an adjusted HR of 0.99 (95% CI, 0.66-1.47). Conclusion: This study identified that the overall cancer risk in patients with GD who received RAI therapy compared with those who did not was not significant in Korea. Further long-term studies are needed to determine the risks and advantages of RAI therapy in patients with GD.

Impact of diabetes on emergency care of acute myocardial infarction patients during the coronavirus disease 2019 pandemic: a nationwide population-based study.

Background: Although acute myocardial infarction (AMI) requires timely intervention, limited nationwide data is available regarding the association between disruption of emergency services and outcomes of patients with AMI during the coronavirus disease 2019 (COVID-19) pandemic. Moreover, whether diabetes mellitus (DM) adversely affects disease severity in these patients has not yet been investigated. Methods: This nationwide population-based study analyzed 45,648 patients with AMI, using data from the national registry of emergency departments (ED) in Korea. Frequency of ED visits and disease severity were compared between the COVID-19 outbreak period (year 2020) and the control period (the previous year 2019). Results: The number of ED visits by patients with AMI decreased during the first, second, and third waves of the outbreak period compared to the corresponding time period in the control period (all p-values < 0.05). A longer duration from symptom onset to ED visit (p = 0.001) and ED stay (p = 0.001) and higher rates of resuscitation, ventilation care, and extracorporeal membrane oxygen insertion were observed during the outbreak period than during the control period (all p-values < 0.05). These findings were exacerbated in patients with comorbid DM; Compared to patients without DM, patients with DM demonstrated delayed ED visits, longer ED stays, more intensive care unit admissions (p < 0.001), longer hospitalizations (p < 0.001), and higher rates of resuscitation, intubation, and hemodialysis (all p-values < 0.05) during the outbreak period. While in-hospital mortality was similar in AMI patients with and without comorbid DM during the two periods (4.3 vs. 4.4%; p = 0.671), patients with DM who had other comorbidities such as chronic kidney disease or heart failure or were aged ≥ 80 years had higher in-hospital mortality compared with those without any of the comorbidities (3.1 vs. 6.0%; p < 0.001). Conclusion: During the pandemic, the number of patients with AMI presenting to the ED decreased compared with that of the previous year, while the disease severity increased, particularly in patients with comorbid DM.

Ischaemic stroke in patients with diabetes requiring urgent procedures during the COVID-19 pandemic in South Korea: a retrospective, nationwide, population-based cohort study using data from the National Emergency Department Information System.

OBJECTIVES: The COVID-19 pandemic resulted in suboptimal care for ischaemic stroke. Patients with diabetes mellitus (DM), a high-risk group for stroke, had compromised routine care during the pandemic, which increases the chance of stroke. We examined influence of the COVID-19 pandemic on the management of ischaemic stroke in patients with DM in South Korea. DESIGN: Retrospective, nationwide, population-based cohort study. SETTING: Data from the National Emergency Department Information System. PARTICIPANTS: We analysed 11 734 patients diagnosed with acute ischaemic stroke who underwent intravenous thrombolysis or endovascular thrombectomy between 2019 (the reference year) and 2020 (the pandemic year). Among them, 1014 subjects with DM were analysed separately. OUTCOME MEASURES: The frequency of emergency department (ED) visits, time from symptom onset to ED, from ED visit to admission and in-hospital mortality were compared between two periods in the overall population and in patients with DM. RESULTS: During the pandemic, the incidence of ischaemic stroke requiring urgent procedures increased by 7.57% in total and by 9.03% in patients with DM. Time delay from symptom onset to ED (reference vs pandemic, total: 1.50 vs 1.55 hours; p<0.01) and from ED visit to admission (total: 3.88 vs 3.92 hours; p=0.02) occurred during the pandemic in the overall population, but not significantly in patients with DM specifically. Older patients with DM showed higher chances of intensive care unit (ICU) admission during the pandemic: 53.5% vs 62.8% in age 70-79, 60.5% vs 71.9% in age 80-89 and 20.0% vs 70.8% in age ≥90 years (all p=0.01). There was no significant difference in in-hospital mortality between two periods (total: 8.2% vs 8.4%, p=0.65; DM: 8.1% vs 6.7%, p=0.25). CONCLUSIONS: During the COVID-19 pandemic, the incidence of ischaemic stroke requiring urgent procedures increased, and older patients with DM showed a higher ICU admission rate. However, the pandemic was not associated with an increased in-hospital stroke mortality.

Additive impact of diabetes and sarcopenia on all-cause and cardiovascular mortality: A longitudinal nationwide population-based study.

OBJECTIVE: Diabetes mellitus (DM) and sarcopenia (SP) are growing public health concerns in an aging society, which share common pathophysiological mechanisms and are associated with serious health consequences. We investigated the impact of DM and SP on all-cause and cardiovascular mortalities in a longitudinal nationwide population-based study. METHODS: The study analyzed data from the Korea National Health and Nutrition Examination Survey conducted between 2008 and 2011, including information on appendicular skeletal muscle mass data. Mortality data up to December 2020 were retrieved from the National Death Registry. RESULTS: Among the 17,920 participants, 14,737 (82.2 %) had neither DM nor SP (DM-/SP-), 1349 (7.5 %) had only DM (DM+/SP-), 1425 (8.0 %) had only SP (DM-/SP+), and 409 (2.3 %) had both DM and SP (DM+/SP+). Compared to the DM-/SP- group, the DM-/SP+ and DM+/SP+ groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.47 (95 % confidence interval [CI]: 1.14-1.89) and 1.85 (95 % CI: 1.28-2.69), respectively, while the DM+/SP- group did not (HR 1.29, 95 % CI: 0.97-1.74). The DM+/SP+ group demonstrated the highest risk of overall mortality (p-for-trend <0.001). Compared to the DM-/SP- group, only the DM+/SP+ group demonstrated increased cardiovascular mortality with HRs of 2.10 (95 % CI: 1.11-4.00) while the DM+/SP- (HR 1.35, 95 % CI: 0.79-2.30) and DM-/SP+ (HR 1.42, 95 % CI: 0.84-2.43) groups did not. CONCLUSIONS: The coexistence of DM and SP additively increased the risk of all-cause and cardiovascular mortality. Individuals with either disease may require more careful management to prevent the development of the other disease to reduce mortality.

AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner.

BACKGRUOUND: G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress. METHODS: Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium. RESULTS: In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2-related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer-binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner. CONCLUSION: GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.

Comparison of Laser and Conventional Lancing Devices for Blood Glucose Measurement Conformance and Patient Satisfaction in Diabetes Mellitus.

Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.

Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults.

Brain-derived neurotrophic factor (BDNF), an exercise-induced neurotrophin, is an important factor in memory consolidation and cognitive function. This study evaluates the association between plasma BDNF levels and frailty in community-dwelling older adults. Plasma BDNF levels were analyzed in a total of 302 individuals aged 70-84 years from the Korean Frailty and Aging Cohort Study. There were 30 (9.9%) participants with frailty. They were older and had a higher prevalence of dementia and depression than those without frailty. There were no differences in the proportion of male sex between the frail and non-frail groups. Plasma BDNF levels were significantly lower in participants with frailty than in those without frailty. The presence of frailty was significantly associated with plasma BDNF levels (odds ratio 0.508, 95% confidence interval 0.304-0.849) as well as age, hemoglobin, and the presence of dementia, and depression. After adjustment for confounding factors, the significant association between plasma BDNF and frailty was maintained (0.495, 0.281-0.874). This association remained consistent after exclusion of individuals with dementia, depression, stroke, diabetes, and osteoporosis. Plasma BDNF levels were significantly associated with frailty in community-dwelling older adults. Our study may suggest the possible role of BDNF as a novel biomarker of frailty.

Increased Risk of Type 2 Diabetes in Patients With Thyroid Cancer After Thyroidectomy: A Nationwide Cohort Study.

CONTEXT: Abnormal thyroid function after thyroidectomy and subsequent thyroid-stimulating hormone suppression can have detrimental effects on glucose homeostasis in patients with thyroid cancer. OBJECTIVE: To investigate whether thyroidectomy increases the risk of type 2 diabetes in patients with thyroid cancer and to explore the association between levothyroxine dosage and type 2 diabetes risk. METHODS: A retrospective population-based cohort study using the Korean National Health Insurance database. We included 36 377 thyroid cancer patients without known diabetes who underwent thyroidectomy between 2004 and 2013. Matched subjects with nonthyroid cancer were selected using 1:1 propensity score matching. The main outcome measure was newly developed type 2 diabetes mellitus. RESULTS: Patients with thyroid cancer who underwent thyroidectomy had a higher risk of developing type 2 diabetes mellitus than the matched controls (hazard ratio [HR] 1.43, 95% CI 1.39-1.47). Among patients with thyroid cancer, when the second quartile group (in terms of the mean levothyroxine dosage; 101-127 µg/day) was considered the reference group, the risk of type 2 diabetes mellitus increased in the first quartile (<101 µg/day; HR 1.45, 95% CI 1.36-1.54) and fourth quartile groups (≥150 µg/day; HR 1.37, 95% CI 1.29-1.45); meanwhile, the risk decreased in the third quartile group (128-149 µg/day; HR 0.91, 95% CI 0.85-0.97). CONCLUSION: Patients with thyroid cancer who underwent thyroidectomy were more likely to develop type 2 diabetes mellitus than the matched controls. There was a U-shaped dose-dependent relationship between the levothyroxine dosage and type 2 diabetes mellitus risk.

Association Between Visit-to-Visit Fasting Plasma Glucose Variability and Osteoporotic Fractures in Nondiabetic Subjects.

CONTEXT: Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes. OBJECTIVE: We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes. METHODS: Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM). RESULTS: Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results. CONCLUSION: FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.

Implication of thyroid function in periodontitis: a nationwide population-based study.

Possible links between periodontitis and various cardiometabolic and autoimmune diseases have been advocated on the basis of chronic inflammation or oxidative stress. However, the association between periodontitis and thyroid dysfunction is under-researched. Participants without previous thyroid disease or ongoing thyroid-related medication were included from a nationwide population-level survey. Participants were categorized into tertiles of thyroid stimulating hormone (TSH) levels (first tertile < 1.76 mIU/L; second tertile 1.76-2.83 mIU/L; third tertile > 2.83 mIU/L), and periodontal condition was assessed using the Community Periodontal Index. Of the total of 5468 participants, 1423 had periodontitis (26%). A significant difference in the weighted prevalence of periodontitis according to TSH tertiles was observed, with the highest prevalence in the first tertile (26.5%) and the lowest prevalence in the third tertile (20.9%, p = 0.003). Subjects in the first TSH tertile had higher odds for periodontitis than those in the third tertile (OR 1.36, 95% CI 1.10-1.68; p for trend = 0.005) after adjusting for covariates. This association was consistent across subgroups and within sensitivity analyses among subjects without specific factors affecting thyroid function or diseases reported to be related to periodontitis. The present study demonstrated that low TSH levels were associated with significantly higher odds for periodontitis.