CFH I62V as a Putative Genetic Marker for Posner-Schlossman Syndrome.

Objective: Posner-Schlossman syndrome (PSS), also known as glaucomatocyclitic crisis, is an ocular condition characterized by recurrent attacks of anterior uveitis and raised intraocular pressure. Previous studies by our team and others have identified the genetic association of complement pathway genes with uveitis and glaucoma. This study aimed to investigate the complement genes in PSS patients with the view of elucidating the genetic background of the disease. Methods: A total of 331 subjects (56 PSS patients and 275 controls) were recruited for this study. We selected 27 variants in six complement pathway genes (SERPING1, C2, CFB, CFH, C3, and C5) and detected them using TaqMan single nucleotide polymorphism (SNP) Genotyping Assays. Univariate SNP association analysis, haplotype-based association analysis, gene-gene interaction analysis among complement genes, and genotype-phenotype correlation analysis were performed. Results: Among the 27 variants of six complement pathway genes, the functional variant I62V (rs800292) at the CFH gene was found to be significantly associated with PSS; there was a significant increase in the frequency of A allele and AA homozygosity in PSS patients than in controls (P = 1.79 × 10-4; odds ratio (OR) 2.18, 95% CI: 1.44-3.29; P = 4.65 × 10-4; OR 3.66, 95% CI: 1.70-7.85, respectively). The additive effect of CFH-rs800292 and SERPING1-rs3824988 was identified with an OR of 12.50 (95% CI: 2.16-72.28). Genotype-phenotype analysis indicated that the rs800292 AA genotype was associated with a higher intraocular pressure and higher frequency of recurrence. Unlike a high proportion of human leukocyte antigen (HLA)-B27 positivity in anterior uveitis, only 3 in 56 (5.36%) PSS patients were HLA-B27 positive. In addition, one haplotype block (GC) in the SERPING1 gene showed a nominal association with PSS with an increased risk of 2.04 (P = 0.01; 95% CI: 1.18-3.53), but the P-value could not withstand the Bonferroni correction (Pcorr > 0.05). Conclusion: This study revealed a genetic association of a CFH variant with PSS as well as its clinical parameters, implying that the alternative complement pathway might play an important role in the pathogenesis of PSS. Further studies to enrich the understanding of the genetic background of PSS and the role of the complement system in ocular inflammation are warranted.

Associations of Insulin Levels and Insulin Resistance With Urine Glucose Excretion Independent of Blood Glucose in Chinese Adults With Prediabetes and Newly Diagnosed Diabetes.

Several studies have demonstrated that renal glucose reabsorption is increased in patients with type 2 diabetes. However, the increased renal glucose reabsorption may contribute to the progression of hyperglycemia. Therefore, promoting urine glucose excretion (UGE) by suppression of renal glucose reabsorption is an attractive approach for the treatment of diabetes. Insulin resistance is identified as a major characteristic in the pathogenesis of type 2 diabetes. Thus, our aim was to evaluate the association of UGE with serum insulin levels and insulin resistance in subjects with glucose abnormalities, including prediabetes and newly diagnosed diabetes (NDD). The present study included 1129 subjects, 826 individuals with prediabetes and 303 individuals with NDD. Urine samples were collected within 2 h of oral glucose loading for the measurement of glucose. Fasting serum insulin was measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was assessed. Multiple linear regression analysis and multivariate logistic regression analysis were performed to determine the association of UGE with insulin levels and HOMA-IR. A negative association between serum insulin levels and UGE was observed. The relationship remained significant after adjustment for potential confounders, including age, gender, blood pressure and glucose (ß = -5.271, 95% CI: -9.775 to -0.767, p = 0.022). Furthermore, multivariable logistic regression model showed that increased insulin levels were associated with a decreased risk for high UGE after multivariable adjustment. In addition, similar correlation was also observed between HOMA-IR and UGE. HOMA-IR was negatively correlated with UGE after controlling for potential confounders. Moreover, an independent inverse relationship between HOMA-IR and the risk of high UGE was found (OR = 0.85, 95% CI: 0.78-0.93, p < 0.001). In conclusion, insulin levels and HOMA-IR were negatively correlated with UGE after adjusting for potential confounders. Subjects with increased insulin levels or IR were at a decreased risk of high UGE independent of blood glucose. The study suggests that insulin might affect UGE through other ways, in addition to the direct blood glucose-lowering effect, thereby resulting in reduced UGE.

Identification of Newly Diagnosed Diabetes and Prediabetes Using Fasting Plasma Glucose and Urinary Glucose in a Chinese Population: A Multicenter Cross-Sectional Study.

BACKGROUND: Although fasting plasma glucose (FPG) has been highly recommended as the sole test for diabetes screening, the efficacy of FPG alone for diabetes screening is potentially limited due to its low sensitivity. The aim of this study was to improve the efficacy of FPG for diabetes screening using urinary glucose (UG). METHODS: This study was initiated on November 12, 2015, and ended on June 28, 2016. A representative sample of individuals aged between 18 and 65 years, with no history of diabetes, from 6 cities in Jiangsu Province participated in this study. A 75-g oral glucose tolerance test was used to diagnose diabetes. All urine samples were collected within 2 h of oral glucose loading to measure UG. Partial correlation analyses were used to evaluate the associations between UG and other glycemic variables, including FPG, 2-h plasma glucose (2h-PG), and glycated hemoglobin A1c, after adjustment for age. The performance of UG was evaluated using a receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 7485 individuals included, 8% were newly diagnosed with diabetes and 48.7% had prediabetes. The areas under the ROC curves for UG were 0.75 for estimation of 2h-PG ≥7.8 mmol/L and 0.90 for 2h-PG ≥11.1 mmol/L, respectively. The sensitivity and specificity of UG were 52.3% and 87.8%, respectively, for 2h-PG ≥7.8 mmol/L (cutoff point ≥130 mg), and 83.5% and 87.5%, respectively, for 2h-PG ≥11.1 mmol/L (cutoff point ≥178.5 mg). The combination of FPG and UG demonstrated a significantly higher sensitivity than that of FPG alone for the identification of diabetes ([483/597] 80.9% vs. [335/597] 56.1%, χ2 = 85.0, P < 0.001) and glucose abnormalities ([2643/4242] 62.3% vs. [2365/4242] 55.8%, χ2 = 37.7, P < 0.001). CONCLUSIONS: The combination of UG and FPG substantially improves the efficacy of using FPG alone for diabetes screening; this combination might be a practical screening tool and is worth being recommended in the future.

Improving patients' adherence to physical activity in diabetes mellitus: a review.

Regular physical activity (PA) is a key element in the prevention and management of type 2 diabetes mellitus (T2DM). Participation in regular PA improves blood glucose control and can prevent or delay T2DM and its complications, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. However, most people with T2DM are not active and show poor adherence. This paper reviews the possible barriers to PA and strategies to improve the adherence to PA. Based on the currently available literature, it is concluded that self-efficacy and social support from family, friends, and health care providers play the important role in adoption and maintenance of regular PA. Here we also highlight some new modern and innovative interventions that facilitate exercise participation and improve the adherence.

[Value of serum advanced glycation end products-peptide in the screening of diabetes mellitus in a community-based population of high-risk diabetics].

OBJECTIVE: To explore the value of serum advanced glycation end products-peptide (AGE-P) in the screening of diabetes mellitus in a community-based population of high-risk diabetics. METHODS: A total number of 857 adult high-risk diabetics from a community-based population underwent 75 g oral glucose tolerance test (OGTT). Blood samples were drawn to measure the levels of fasting blood glucose (FBG), postprandial blood glucose (2 hPG) and glycosylated hemoglobin A1c (HbA1c). And blood samples were also collected to determine the serum level of AGE-P with the technique of flow injection analysis. Receiver operating characteristic (ROC) curve was plotted to assess the screening value of serum AGE-P in diabetes mellitus. Pearson correlation analysis was conducted to evaluate the association between serum AGE-P and FBG, 2 hPG, HbA1c, body mass index (BMI), waist-to-hip ratio (WHR) and age. RESULTS: Among them, 218 adults were diagnosed with diabetes based on the 2010 American Diabetes Association (ADA) criteria. According to the ROC curve, the optimal cut-point of serum AGE-P for diagnosing diabetes was 10.22 mg/L (a peak height of 25.39 mm) with sensitivity of 84.1%, specificity of 88.3% and positive predictive value of 71%. The area under curve (AUC) of serum AGE-P, FBG, 2 hPG and HbA1c for diagnosing diabetes was 0.924, 0.905, 0.951 and 0.874 respectively. When comparing AUC between serum AGE-P and HbA1c, FBG and 2 hPG, statistical significance was only found in the comparisons between serum AGE-P and HbA1c (P<0.025). Pearson correlation analysis showed that serum AGE-P was highly positively correlated with HbA1c, significantly positively correlated with FBG and 2 hPG and slightly positively correlated with WHR and age (all P<0.05). But there was no correlation with BMI. CONCLUSIONS: Serum AGE-P may be used for the screening of diabetes in the community-based population of high-risk diabetics. And it is even superior to HbA1c.