Risk Factors for Ocular Surface Irritation Symptoms in Inactive Mild and Moderate-to-Severe Graves' Orbitopathy.

INTRODUCTION: This study aims to analyze risk factors for ocular surface irritation symptoms in patients with non-corneal-damage inactive mild and moderate-to-severe Graves' orbitopathy (GO). METHODS: This retrospective study enrolled 307 patients with non-corneal-damage inactive GO admitted to Sun Yat-sen Memorial Hospital from April 2017 to September 2023. The activity and severity of GO were evaluated using the Clinical Activity Score (CAS) and the European Group on Graves' Orbitopathy (EUGOGO) classification, respectively. Multivariate logistic regression analysis was performed to analyze risk factors for ocular surface irritation symptoms. RESULTS: Among patients with inactive GO, for mild cases, CAS (P < 0.001), upper eyelid lag (P = 0.049), and extraocular muscle involvement (P = 0.019) in the symptomatic group were greater than those in the asymptomatic group, and multivariate logistic regression analysis demonstrated that upper eyelid lag (P = 0.048), CAS 1 (P < 0.001), CAS 2 (P = 0.005), and extraocular muscle involvement (P = 0.029) were risk factors for ocular surface irritation symptoms; for moderate-to-severe cases, CAS (P = 0.004), extraocular muscle involvement (P < 0.001), marginal reflex distance 1 (MRD1) (P = 0.030), and thyroid-stimulating hormone (TSH) (P = 0.034) in the symptomatic group were greater than those in the asymptomatic group, while multivariate logistic regression analysis indicated that extraocular muscle involvement (P = 0.018) and MRD1 (P = 0.012) were risk factors for ocular surface irritation symptoms. CONCLUSION: In non-corneal-damage inactive mild and moderate-to-severe GO, eyelid malposition and periocular muscle inflammation are risk factors for ocular surface irritation symptoms.

Graves' orbitopathy is the most common outward sign of Graves' disease. Patients with inactive Graves' orbitopathy often complain of ocular surface irritation symptoms. This study retrospectively collected clinical data from 307 patients with inactive Graves' orbitopathy and no concurrent corneal damage. The aim was to analyze risk factors for ocular surface irritation symptoms. Upper lid lag, eye movement disorder, and the Clinical Activity Score were found to be risk factors for mild cases. Eye movement disorder and the distance between the upper eyelid margin and corneal reflection point were risk factors for moderate-to-severe cases. To reduce symptoms, it may be helpful to treat inflammation around the eyes and address any eyelid abnormalities.

The Counteracting Effects of Ang II and Ang-(1-7) on the Function and Growth of Insulin-secreting NIT-1 Cells.

INTRODUCTION: China now has the highest number of diabetes in the world. Angiotensin II (Ang II) causes insulin resistance by acting on the insulin signaling pathway of peripheral target tissues. However, its effect on islet ß-cells remains unclear. The possible role of Angiotensin-(1-7) [Ang-(1-7)] as an antagonist to the effects of Ang II and in treating diabetes needs to be elucidated. OBJECTIVES: To assess the effects of Ang II and Ang-(1-7) on the function and growth of islet ß cell line NIT-1, which is derived from the islets of non-obese diabetic/large T-antigen (NOD/LT) mice with insulinoma. METHODS: NIT-1 cells were treated with Ang II, Ang-(1-7) and their respective receptor antagonists. The impact on cell function and growth was then evaluated. RESULTS: Ang II significantly reduced insulin-stimulated IR-ß-Tyr and Akt-Ser; while Ang-(1-7), saralasin (an Ang II receptor antagonist), and diphenyleneiodonium [DPI, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) antagonist] reversed the inhibiting effect. Conversely, Ang II significantly increased insulin-stimulated intracellular H2O2 and P47 phox, while saralasin and DPI reverted the effect. Furthermore, Ang-(1-7) reduced the elevated concentrations of ROS and MDA while increasing the proliferation rate that was reduced by high glucose, all of which were reversed by A-779, an antagonist of the Mas receptor (MasR). CONCLUSION: Angiotensin II poses a negative regulatory effect on insulin signal transduction, increases oxidative stress, and may inhibit the transcription of insulin genes stimulated by insulin in NIT-1 cells. Meanwhile, angiotensin-(1-7) blocked these effects via MasR. These results corroborate the rising potential of the renin-angiotensin system (RAS) in treating diabetes.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

Glucose Metabolism Indices and the Development of Chronic Kidney Disease: A Cohort Study of Middle-Aged and Elderly Chinese Persons.

Objective: Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD. Methods: We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß and the development of CKD. Results: With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31). Conclusion: HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.

The Outcomes of Balanced Orbital Decompression for Dysthyroid Optic Neuropathy: Focusing on Choroiretinal Folds with and without Optic Disc Edema.

Purpose: To assess the outcomes of balanced orbital decompression for chorioretinal folds (CRFs) with and without optic disc edema (ODE) in dysthyroid optic neuropathy (DON). Method: A retrospective, interventional study was performed at Sun Yat-sen Memorial Hospital from April 2018 to November 2021. We collected the medical records of 13 patients (24 eyes) with DON and CRFs. Then, we divided them into the ODE group (15 eyes, 62.5%) and the non-ODE group (NODE group, 9 eyes, 37.5%). The valid ophthalmic examination parameters of 8 eyes in each group after balanced orbital decompression were compared at the 6-month follow-up. Results: The mean best corrected visual acuity (BCVA, 0.29 ± 0.27) and visual field-mean deviation (VF-MD, -6.55 ± 3.71 dB) in the ODE group were significantly worse than those in the NODE group (0.06 ± 0.15 and -3.49 ± 1.56 dB; all p < 0.01). Six months after orbital decompression, all parameters were found to have significantly improved in both groups, including BCVA and VF-MD (all p < 0.05). Moreover, the improvement amplitude of BCVA (p = 0.020) in the ODE group was significantly greater than that in the NODE group. There was no difference in BCVA between the ODE group (0.13 ± 0.19) and the NODE group (0.10 ± 0.13). The disc edema of all eyes (8/8 eyes, 100%) in the ODE group was completely mitigated after orbital decompression. The CRF resolution of 2 eyes (2/8 eyes, 25%) in the ODE group and no eyes in the NODE group was mitigated. Conclusions: Balanced orbital decompression can significantly improve visual functions and eliminate optic disc edema in DON patients, whether CRF relieves or not.

Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet ß Cells.

BACKGROUND: The RAS system is involved in the regulation of islet function, but its regulation remains unclear. OBJECTIVE: This study investigates the role of an islet-specific miR-375 in the effect of RAS system on islet ß-cells. METHODS: miR-375 mimics and inhibitors were transfected into insulin-secreting MIN6 cells in the presence or absence of RAS component. RESULTS: Compared to control, in Ang II-treated MIN6 cells, miR-375 mimic transfection results in a decrement in cell viability and Akt-Ser levels (0.739±0.05 vs. 0.883±0.06 and 0.40±0.04 vs. 0.79±0.04, respectively), while the opposite occurred in miR-375 inhibitor-transfected cells (1.032±0.11 vs. 0.883±0.06 and 0.98±0.05 vs. 0.79±0.04, respectively, P<0.05). Mechanistically, transfection of miR- 375 mimics into Ang II-treated MIN6 cells significantly reduced the expression of Mapkap1 protein (0.97±0.15 vs. 0.63±0.06, P<0.05); while miR-375 inhibitor-transfected cells elevated Mapkap1 expression level (0.35±0.11 vs. 0.90±0.05, P<0.05), without changes in mRNA expression. Transfection of miR-375 specific inhibitors TSB-Mapkap1 could elevate Mapkap1 (1.62±0.02 vs. 0.68±0.01, P<0.05), while inhibition of Mapkap1 could significantly reduce the level of Akt-Ser473 phosphorylation (0.60±0.14 vs. 1.80±0.27, P<0.05). CONCLUSION: The effects of Ang II on mouse islet ß cells were mediated by miR-375 through miR- 375/Mapkap 1 axis. This targeted regulation may occur by affecting Akt phosphorylation of ß cells. These results may provide new ideas and a scientific basis for further development of miRNA-targeted islet protection measures.

Short night-time sleep duration is associated with thyroid nodules: A community-based survey from Guangzhou, China.

BACKGROUND: Sleep plays a critical role in maintaining human health. This study aimed to explore the association between sleep status and thyroid nodules. METHODS: A total of 2414 individuals aged 18 or older with euthyroidism were enrolled in this community-based survey. Sleep status was self-reported. Thyroid ultrasonography was performed to measure nodules. Multiple logistic analyses were applied to adjust for confounding factors. RESULTS: The percentages of thyroid nodules among individuals who slept <5 hours, 5-8 hours, and >8 hours per night were 57.79% (115/199), 44.19% (833/1885) and 42.73% (141/330), respectively (p = 0.001). Individuals who slept <5 hours per night had a significantly higher percentage of thyroid nodules than those who slept 5-8 hours per night (57.79% vs. 44.19%, p = 0.001) or >8 hours per night (57.79% vs. 42.73%, P < 0.001). However, no similar result was shown between individuals who slept >8 hours and 5-8 hours per night (42.73% vs. 44.19%, p = 0.621). Multiple logistic analysis showed that a sleep duration of <5 hours per night was significantly associated with thyroid nodules (odds ratio (OR) 1.643, 95% confidence interval (CI) 1.084-2.490, p = 0.019) when compared to a sleep duration of >8 hours per night. However, a sleep duration of <5 hours per night was not associated with thyroid nodules compared to a sleep duration of 5-8 hours (OR 1.294, 95% CI 0.918-1.824, p = 0.141). Similarly, no significant differences were seen among sleep duration per day, time of falling asleep, habit of daytime napping or thyroid nodules in multiple logistic analyses (all p > 0.05). CONCLUSIONS: Short nighttime sleep duration was associated with thyroid nodules in our community-based population. Screening for thyroid nodules among these individuals is recommended.

Development and validation of a nomogram for assessing risk of isolated high 2-hour plasma glucose.

A tool was constructed to assess need of an oral glucose tolerance test (OGTT) in patients whose fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are normal. Data was collected from the longitudinal REACTION study conducted from June to November 2011 (14,686 subjects, aged ≥ 40 y). In people without a prior history of diabetes, isolated high 2-hour plasma glucose was defined as 2-hour plasma glucose ≥ 11.1 mmol/L, FPG < 7.0 mmol/L, and HbA1c < 6.5%. A predictive nomogram for high 2-hour plasma glucose was developed via stepwise logistic regression. Discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test; performance was externally validated in Northeast China. Parameters in the model included gender, age, drinking status, marriage status, history of hypertension and hyperlipidemia, waist-to-hip ratio, FPG, and HbA1c. All variables were noninvasive, except FPG and HbA1c. The AUC of the nomogram for isolated high 2-hour plasma glucose was 0.759 (0.727-0.791) in the development dataset. The AUCs of the internal and externally validation datasets were 0.781 (0.712-0.833) and 0.803 (0.778-0.829), respectively. Application of the nomogram during the validation study showed good calibration, and the decision curve analysis indicated that the nomogram was clinically useful. This practical nomogram model may be a reliable screening tool to detect isolated high 2-hour plasma glucose for individualized assessment in patients with normal FPG and HbA1c. It should simplify clinical practice, and help clinicians in decision-making.

Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: a cross-sectional study.

BACKGROUND: Both obesity and subclinical hypothyroidism (SCH) have adverse effects on human body, but the relationship between these two conditions remains inconsistent. The presence of thyroid autoantibodies influences thyroid hormone levels, and may further mediate the interaction between obesity and SCH. This study aimed to explore the association among obesity, SCH and thyroid autoantibodies. METHODS: This study was a cross-sectional survey of 2505 subjects. Obesity was defined as a body mass index ≥28 kg/m2. Serum concentrations of thyroid hormones, thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were examined. Logistic analysis was used to explore the relation among obesity, SCH and thyroid autoantibodies. RESULTS: A proportion of 11.54% (289/2505) subjects were obese, and 165 subjects had SCH. The positive rates of thyroid autoantibodies, TPO-Ab and Tg-Ab were 17.64% (442/2505), 11.02% (276/2505) and 14.13% (354/2505), respectively. The proportion of SCH was significantly higher in obese than nonobese subjects among those with positive thyroid autoantibodies [22.41% (13/58) vs. 11.72% (45/384), p = 0.025, χ2 test]. Moreover, obesity was significantly associated with SCH in the presence of thyroid autoantibodies after adjusting for confounding factors (OR 2.212, 95% CI 1.103 to 4.433, p = 0.025). A higher proportion of subjects with obesity had Tg-Ab positivity [17.99% (52/289) vs. 13.63% (302/2216), p = 0.045, χ2 test], and obesity remained significantly associated with Tg-Ab positivity by multiple logistic analysis (OR 1.504, 95% CI 1.077 to 2.101, p = 0.017). CONCLUSIONS: Obesity was associated with SCH in the presence of thyroid autoantibodies. Examination of SCH is recommended in obese subjects with thyroid autoantibody positivity.

PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study.

BACKGROUND: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. METHODS: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). RESULTS: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. CONCLUSION: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03944109.

Iodine nutritional status, the prevalence of thyroid goiter and nodules in rural and urban residents: a cross-sectional study from Guangzhou, China.

OBJECTIVES: A variety of factors differed between rural and urban areas may further influence iodine status and thyroid structure. Hence, this study compared iodine nutrition, the prevalence of thyroid goiter, and nodules between rural and urban residents in Guangzhou, a southern coastal city of China. METHODS: A total of 1211 rural residents and 1305 urban residents were enrolled in this cross-sectional study. A questionnaire regarding personal characteristics was administered. Urinary iodine concentration (UIC) was examined. Ultrasonography of the thyroid was performed to evaluate thyroid goiter and nodules. Multiple logistic analysis was used to identify the potential associated factors. RESULTS: The median UIC was significantly lower in rural residents than in urban residents (120.80 µg/L vs 136.00 µg/L, P < 0.001). Although the coverage rate of iodized salt was much higher in rural residents than in urban residents (99.59% vs 97.29%, P < 0.001), the percentages of seafood intake (8.60% vs 29.29%, P < 0.001), iodine-containing drug consumption (0.33% vs 1.24%, P = 0.011), and iodine contrast medium injection (0.58% vs 1.87%, P = 0.004) were lower in rural residents than in urban residents. Both the prevalence of thyroid goiters and nodules was significantly higher in rural residents than in urban residents (goiter: 8.06% vs 1.20%, P < 0.001; nodules: 61.89% vs 55.04%, P = 0.023). Living in rural areas was associated with thyroid goiter (OR 5.114, 95% CI 2.893-9.040, P < 0.001). CONCLUSIONS: There were differences in iodine nutrition and the prevalence of thyroid goiter and nodules in rural and urban residents in Guangzhou. Differentiated and specialized monitoring is recommended in our area.

The association of adiponectin with risk of pre-diabetes and diabetes in different subgroups: cluster analysis of a general population in south China.

OBJECTIVE: Adiponectin is an adipocyte-derived hormone with an important role in glucose metabolism. The present study explored the effect of adiponectin in diverse population groups on pre-diabetes and newly diagnosed diabetes. METHODS: A total of 3300 individuals were enrolled and their data were collected in the analyses dataset from December 2018 to October 2019. Cluster analysis was conducted based on age, BMI, waistline, body fat, systolic blood pressure, triglycerides, and glycosylated hemoglobin 1c. Cluster analysis divided the participants into four groups: a young-healthy group, an elderly-hypertension group, a high glucose-lipid group, and an obese group. Odds ratio (OR) and 95% CIs were calculated using multivariate logistic regression analysis. RESULTS: Compared with the first quartile of adiponectin, the risk of pre-diabetes of fourth quartile was decreased 61% (aOR = 0.39, 95% CI (0.20-0.73)) in the young-healthy group; and the risk of diabetes of fourth quartile was decreased 85% (aOR = 0.15, 95% CI (0.02-0.67)) in the obese group. There were no significant correlations between the adiponectin level and diabetes/pre-diabetes in the other two groups. Additionally, receiver operating characteristic curve analysis indicated that adiponectin could significantly improve the diagnosis based on models in the young-healthy group (from 0.640 to 0.675) and the obese group (from 0.714 to 0.761). CONCLUSIONS: Increased adiponectin levels were associated with decreased risk of pre-diabetes in the young-healthy population, and with a decreased the risk of diabetes in the obese population. An increased adiponectin level is an independent protective factor for pre-diabetes and diabetes in a specific population in south China.

The Risk Threshold for Hemoglobin A1c Associated With Albuminuria: A Population-Based Study in China.

Background: Diabetic kidney disease (DKD) is a kind of common microvascular complication of diabetes. This study aims to explore the possible links between blood sugar level and albuminuria, providing the exact cut point of the "risk threshold" for blood glucose with DKD. Methods: The relationship between blood glucose and albuminuria was modeled using linear and logistic regression in the REACTION study cohorts (N= 8932). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. Two-slope linear regression was used to simulate associations between blood glucose and ACR. Results: We found that the increase in ACR was accompanied by increased HbA1c, with a turning point at 5.5%. The positive correlation remained highly significant (P<0.001) when adjusted for age, sex, marital status, education, smoking status, drinking status, BMI, waistline, SBP and DBP. In subgroup analyses including gender, obesity, hypertension, and smoking habits, the relationship was significant and stable. Conclusions: We determined a risk threshold for HbA1c associated with albuminuria in a Chinese population over the age of 40. HbA1c ≥ 5.5% was positively and independently associated with ACR. These results suggest the necessity of early blood glucose control and renal function screening for DKD in at-risk populations.

Association between uric acid lowering and renal function progression: a longitudinal study.

BACKGROUND: This study aimed to explore the association between uric acid lowering and renal function. MATERIALS AND METHODS: We conducted a population-based cohort study with 1,534 subjects for 4 years from 2012 to 2016. The population was divided into four groups according to the interquartile range of changes in serum uric acid with quartile 1 representing lower quarter. Renal function decline was defined as eGFR decreased more than 10% from baseline in 2016. Renal function improvement was defined as eGFR increased more than 10% from baseline in 2016. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the adjusted Cox regression models, compared to quartile 4, quartile 1 (HR = 0.64, 95% CI [0.49-0.85]), quartile 2 (HR = 0.65, 95% CI [0.50-0.84]) and quartile 3 (HR = 0.75, 95% CI [0.58-0.96]) have reduced risk of renal function decline. An increasing hazard ratio of renal function improvement was shown in quartile 1 (HR = 2.27, 95% CI [1.45-3.57]) and quartile 2 (HR = 1.78, 95% CI [1.17-2.69]) compared with quartile 4. CONCLUSIONS: Uric acid lowering is associated with changes in renal function. The management of serum uric acid should receive attention in clinical practice and is supposed to be part of the treatment of chronic kidney disease.

Associations of GDF-15 and GDF-15/adiponectin ratio with odds of type 2 diabetes in the Chinese population.

PURPOSE: We elucidate the effect of Growth differentiation factor-15(GDF-15)/adiponectin ratio in improving the assessment value for odds of type 2 diabetes. METHODS: Cross-sectional design. A total of 405 participants (135 patients with newly diagnosed type 2 diabetes, 135 age- and sex-matched participants with prediabetes, and 135 healthy controls) were collected from Guangzhou and Dongguan, China. The serum GDF-15 and adiponectin levels were measured by ELISA and latex-enhanced immunoturbidimetry. Logistic regression analysis and restricted cubic splines were used to evaluate the associations between diabetes and the indicators. RESULTS: The low level of adiponectin and high GDF-15/adiponectin ratio were significantly associated with increased odds of type 2 diabetes, but not for GDF-15. Three clusters were identified based on the K-means clustering analysis. Compared to the lowest quartiles of adiponectin, the OR and 95% CI of the highest adiponectin with type 2 diabetes was 0.24 (0.07-0.74, p trend = 0.004) after adjusting for sex, age, BMI, and DBP only in cluster 1. After adjusting for confounding factors, subjects with the highest GDF-15/adiponectin ratio quartiles had 3.9 times (OR = 3.85, 95% CI = 0.76-24.25) and 3.8 times (OR = 3.80, 95% CI = 1.02-14.68) higher odds of type 2 diabetes in cluster 2 and cluster 3, respectively. The association between the GDF-15/adiponectin ratio and type 2 diabetes was attenuated, but still remarkable (OR = 3.18, 95% CI = 1.11-10.18), in cluster 1. CONCLUSIONS: Higher GDF-15/adiponectin ratio is independently associated with increased odds of type 2 diabetes for all study populations, suggesting that the GDF-15/adiponectin ratio may be a better indicator of type 2 diabetes.

The Clinical Features of Graves' Orbitopathy with Elevated Intraocular Pressure.

BACKGROUND: To investigate the clinical characteristics of Graves' orbitopathy (GO) with elevated intraocular pressure (IOP) using the European Group of Graves' Orbitopathy (EUGOGO) system. METHODS: In this retrospective study, the clinical data of GO patients with elevated IOP (≥21 mmHg) were collected in Sun Yat-sen Memorial Hospital from January 2010 to June 2016. The demographic characteristics, clinical history of thyroid disease and GO, and ocular examination data were evaluated, and the activity and severity of GO were classified. RESULTS: Data were collected from 58 eyes of 39 patients. The durations of thyroid disease and GO were 15.9 ± 18.9 months and 7.5 ± 6.2 months, respectively. The average IOP was 24.8 ± 5.3 mmHg (range: 21-55 mmHg). No significant difference in IOP was observed between active and inactive eyes. Eight eyes (13.8%), 29 eyes (50.0%), and 21 eyes (36.2%) were graded as mild, moderate-severe, and sight-threatening disease, respectively, according to the EUGOGO classification. The IOP was not significantly different among the three EUGOGO grades. No glaucomatous optic nerve damage or visual field defects were found. CONCLUSION: Increased IOP was evident for every grade of GO severity and activity of the EUGOGO system. IOP, glaucomatous optic nerve damage, and visual fields must be evaluated regularly during follow-up evaluations, regardless of the degree of activity and severity of GO.

Interactions among endotoxin, uric acid, and lactate in relation to the risk of type 2 diabetes: A population-based study.

BACKGROUND: Blood levels of endotoxin, uric acid (UA), or lactate (LAC) are associated with type 2 diabetes mellitus (T2DM). Thus, we explored the interactions among blood endotoxin, UA, and LAC levels and the risk of T2DM. METHODS: This population-based cross-sectional study included 2520 Chinese adults. Fasting blood endotoxin, UA, and LAC levels were determined and the cut-off values were obtained from the receiver operating characteristic curve analysis. The study population was classified into two or four subgroups based on low or high, or both low and high levels of endotoxin, UA, and LAC, respectively. RESULTS: The odds ratios (ORs) for T2DM (all P < .05) were higher in the high groups than the low groups of endotoxin, UA, or LAC, respectively. Participants in the groups with high levels of both endotoxin and UA, endotoxin and LAC, or UA and LAC, had 4.71 (95% CI 3.01-7.37), 5.13 (95% CI 3.29-7.99), or 3.73 (95% CI 2.34-5.94) times higher risk for T2DM compared to those in groups with low levels of both endotoxin and UA, endotoxin and LAC, or UA and LAC (all P < 0.05), respectively. In the interaction analysis, an interactive effect between endotoxin and UA (P < .05), or endotoxin and LAC (P < .05), but not UA and LAC, was observed that contributed to an increased risk of T2DM. CONCLUSIONS: The interaction between levels of endotoxin and UA or levels of endotoxin and LAC was related to an increased risk of T2DM in the Chinese population.

Interactive association of lipopolysaccharide and free fatty acid with the prevalence of type 2 diabetes: A community-based cross-sectional study.

AIMS/INTRODUCTION: Increased blood lipopolysaccharide (LPS) or free fatty acid (FFA) levels correlate with an increased risk of type 2 diabetes. The purpose of the present study was to evaluate the interactive effect of serum LPS and FFA levels on the prevalence of type 2 diabetes. MATERIALS AND METHODS: This cross-sectional study included 2,553 community-dwelling Chinese adults. Fasting serum LPS levels were determined using the Limulus Amebocyte Lysate Chromogenic Endpoint assay, and FFA levels were determined using an enzymatic method. The participants were divided into three groups according to the tertiles of LPS or FFA levels or nine groups according to the tertiles of LPS and FFA levels. The odd ratios (ORs) for type 2 diabetes were estimated using logistic regression analysis. RESULTS: We found that higher serum LPS or FFA levels were associated with higher high-sensitivity C-reactive protein levels (P < 0.001), homeostatic model assessment of insulin resistance levels (P < 0.001) and ORs for type 2 diabetes (P < 0.01). Meanwhile, there were significant interactions between LPS and FFA in terms of the high-sensitivity C-reactive protein level (P < 0.001), homeostatic model assessment of insulin resistance level (P < 0.001) and ORs for type 2 diabetes (P < 0.001). In the fully adjusted logistic regression model, the OR for participants with type 2 diabetes in the higher LPS and FFA level group were 6.58 (95% confidence interval 3.05-14.18, P < 0.001) compared with that in participants in the lower LPS and FFA level group. CONCLUSIONS: The interaction between LPS and FFA was associated with an increased risk of type 2 diabetes in community-dwelling Chinese adults.

Evaluation of the Graves' Orbitopathy-Specific Quality of Life Questionnaire in the Mainland Chinese Population.

PURPOSE: To study the clinical significance of the Graves' orbitopathy-specific quality of life (GO-QOL) questionnaire in mainland Chinese patients. METHODS: A cross-sectional study was performed at the Ophthalmology Department of the Sun Yat-sen Memorial Hospital from April 2017 to April 2018. Eighty-eight consecutive Graves' orbitopathy (GO) patients completed the two subscales of the GO-QOL questionnaire: visual functioning and appearance. The disease severity of GO was measured by the European Group on Graves' Orbitopathy (EUGOGO) classification, and clinical activity was evaluated by the clinical activity score (CAS). RESULTS: The mean scores of GO-QOL questionnaire for the visual functioning and appearance subscales were 68.4 ± 31.2 and 62.0 ± 27.4, respectively. Lower QOL scores for the visual functioning subscale were significantly correlated with disease severity, the CAS and diplopia (all p < 0.05). Lower QOL scores for appearance were significantly correlated with the CAS (p < 0.05). Although no correlation was found between the appearance subscale scores and disease severity (p=0.407), a downward trend in the appearance subscale scores as the severity of GO increased from mild to sight-threatening GO was found. CONCLUSION: A strong correlation between disease severity and clinical activity has been shown in the GO-QOL questionnaire, suggested by the EUGOGO. The GO-QOL questionnaire is a simple and effective appraisal instrument in the evaluation of health-related QOL in the mainland Chinese patients with GO.