Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

Potential role of fibroblast growth factor 21 in the deterioration of bone quality in impaired glucose tolerance.

PURPOSE: Findings on trabecular bone score (TBS), an index of bone quality, have been reported in prediabetes defined by impaired fasting glucose or HbA1c. Here, we assessed the bone mineral density (BMD) and TBS in prediabetes individuals with impaired glucose tolerance (IGT), and investigated the association of these bone parameters with serum levels of fibroblast growth factor 21 (FGF21), a hormone implicated in bone metabolism and with higher levels in IGT. METHODS: Chinese postmenopausal women aged 55-80 years, without diabetes, were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study in 2016-2018. Normal glucose tolerance (NGT) was defined by fasting glucose < 5.6 mmol/L and 2-h plasma glucose (2hG) < 7.8 mmol/L, and IGT by 2hG 7.8-11 mmol/L. Serum levels of FGF21 and other bone metabolism regulators were measured. Insulin sensitivity was assessed by the Matsuda index. Independent determinants of TBS were evaluated using multivariable stepwise linear regression. RESULTS: 173 individuals with NGT and 73 with IGT were included. TBS was lower in those with IGT compared to those with NGT, while BMD was comparable. Individuals with IGT had significantly higher serum FGF21 levels, which in turn showed an independent inverse relationship with TBS, attenuated after inclusion of the Matsuda index. Serum FGF21 levels, however, did not correlate with BMD. CONCLUSION: Among Chinese postmenopausal women, bone quality was worse in IGT, despite comparable bone density. FGF21 levels showed a significant independent inverse relationship with TBS, partly attributed to insulin resistance. Whether FGF21 contributes to the impaired bone quality in IGT remains speculative.

HbA1c variability, in addition to mean HbA1c, predicts incident hip fractures in Chinese people with type 2 diabetes.

Type 2 diabetes is associated with an increased risk of hip fractures. We hypothesize that long-term glycemic variability predicts incident hip fractures. We demonstrated that HbA1c variability predicted incident hip fractures independent of mean HbA1c, suggesting the potential benefits of minimizing glycemic variability in addition to optimizing mean glycemia for bone health. INTRODUCTION: Type 2 diabetes is associated with an increased risk of hip fractures, and a linear relationship between HbA1c levels and hip fracture incidence has been observed. We hypothesize that HbA1c variability also predicts incident hip fractures in type 2 diabetes. METHODS: Chinese individuals with type 2 diabetes aged ≥ 60 years were identified from electronic health records in Hong Kong between 2008 and 2012 and observed for incident hip fractures. Hip fracture was defined by the International Classification of Diseases (Ninth Revision) code 820. HbA1c variability was determined using standard deviation, adjusted standard deviation, and coefficient of variation of HbA1c measurements in the 5 years preceding the entry date. Multivariable Cox regression analysis was used to evaluate associations between HbA1c variability and incident hip fractures. RESULTS: A total of 83,282 participants were included. Their mean age was 71.3 ± 7.5 years, duration of diabetes 11.7 ± 7.7 years, baseline HbA1c 56.6 ± 13.5 mmol/mol (7.33 ± 1.23%), and median follow-up 6.8 years. All indices of HbA1c variability were significant independent predictors of incident hip fractures, with an adjusted hazard ratio of up to 1.29 (all p < 0.001), and remained to be independent predictors across groups of different intensity of glycemic control. Mean HbA1c ≥ 64 mmol/mol (8.0%) was associated with a 25% increase in incident hip fractures compared with mean HbA1c < 53 mmol/mol (7.0%). CONCLUSION: HbA1c variability is an independent positive predictor of hip fracture in type 2 diabetes, across the spectrum of varying degree of glycemic control, while a high HbA1c is also not advisable from the perspective of bone health.

Obesity, adipokines and cancer: an update.

Obesity causes dysfunction of adipose tissue, with resultant chronic inflammation and adverse interplay of various adipokines, sex steroids and endocrine hormones. All these drive tumourigenesis and explain the epidemiological link between obesity and cancer. Over the past decade, the associations among obesity, adipokines and cancer have been increasingly recognized. Adipokines and their respective signalling pathways have drawn much research attention in the field of oncology and cancer therapeutics. This review will discuss the recent advances in the understanding of the association of several adipokines with common obesity-related cancers and the clinical therapeutic implications.

Screening for dysglycaemia by oral glucose tolerance test should be recommended in all women with polycystic ovary syndrome.

STUDY QUESTION: Should fasting glucose (FG) or an oral glucose tolerance test (OGTT) be used to screen for dysglycaemia in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: A full OGTT should be recommended as the screening method for dysglycaemia in women with PCOS, regardless of BMI or family history of diabetes mellitus (DM). STUDY DESIGN, SIZE, DURATION: A cross-sectional study on 467 Chinese women diagnosed with PCOS by the Rotterdam criteria between January 2010 to December 2013. PARTICIPANTS, SETTING, METHODS: The study was done at a university hospital in Hong Kong. All subjects underwent a 75 g OGTT after overnight fasting. We evaluated the performance of FG alone, when compared with the full OGTT, in identifying subjects with dysglycaemia (prediabetes or DM, according to the 2010 diagnostic criteria of the American Diabetes Association). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 467 subjects, 58 (12.4%) had dysglycaemia, among which 46 (9.8%) had prediabetes and 12 (2.6%) had DM, including 4 with known DM. Of the 46 subjects with prediabetes, 25 (54.3%) had normal FG and of the 8 subjects with screened DM in this study, 1 (12.5%) had normal FG. The sensitivity of FG alone in screening for prediabetes, DM and overall dysglycaemia were 45.7, 87.5 and 48.1%, respectively, i.e. missing 54.3% of prediabetes and 12.5% of DM cases as defined by the OGTT. Among the 54 subjects with screened dysglycaemia, 20 (37.0%) had BMI < 25 kg/m(2) and 35 (64.8%) had no family history of DM. LIMITATIONS, REASONS FOR CAUTION: We only reported on the biochemical diagnosis of DM based on a single time point. In clinical practice, confirmatory results at another time point is required for definitive diagnosis in asymptomatic subjects. WIDER IMPLICATIONS OF THE FINDINGS: There is an ongoing debate as to whether FG or an OGTT should be used as a screening method for dysglycaemia in women with PCOS. Some guidelines also recommend glucose screening only in those who are overweight and/or having family history of diabetes (DM). There have been scarce data on this issue in the Chinese population, which the current study aims at addressing. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a research grant from the Hong Kong Obstetrical and Gynaecological Trust Fund, as well as internal research funding of the Department of Obstetrics and Gynaecology, The University of Hong Kong. All authors have no competing interests.

Cardiometabolic risk profile of participants with prediabetes diagnosed by HbA1c criteria in an urban Hong Kong Chinese population over 40 years of age.

AIMS: To investigate the usefulness of the additional measurement of HbA1c , compared with performing only the oral glucose tolerance test (OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. METHODS: All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c , according to American Diabetic Association 2010 criteria. RESULTS: Based on OGTT criteria alone, 3.5% of the study cohort (N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c , in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia (N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index (HOMA-IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia (N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance (N = 249; all P < 0.01). CONCLUSION: The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention.

Genetics of Apparently Sporadic Pheochromocytoma and Paraganglioma in a Chinese Population.

Identification of germline mutation in patients with apparently sporadic pheochromocytomas and paragangliomas is crucial. Clinical indicators, which include young age, bilateral or multifocal, extra-adrenal, malignant, or recurrent tumors, predict the likelihood of harboring germline mutation in Caucasian subjects. However, data on the prevalence of germline mutation, as well as the applicability of these clinical indicators in Chinese, are lacking. We conducted a cross-sectional study at a single endocrine tertiary referral center in Hong Kong. Subjects with pheochromocytomas and paragangliomas were evaluated for the presence of germline mutations involving 10 susceptibility genes, which included NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, TMEM 127, MAX, and FH genes. Clinical indicators were assessed for their association with the presence of germline mutations. Germline mutations, 2 being novel, were found in 24.4% of the 41 Chinese subjects recruited and 11.4% among those with apparently sporadic presentation. The increasing number of the afore-mentioned clinical indicators significantly correlated with the likelihood of harboring germline mutation in one of the 10 susceptibility genes. (r=0.757, p=0.026). The presence of 2 or more clinical indicators should prompt genetic testing for germline mutations in Chinese subjects. In conclusion, our study confirmed that a significant proportion of Chinese subjects with apparently sporadic pheochromocytoma and paraganglioma harbored germline mutations and these clinical indicators identified from Caucasians series were also applicable in Chinese subjects. This information will be of clinical relevance in the design of appropriate genetic screening strategies in Chinese populations.

Skeletal muscle-specific overproduction of constitutively activated c-Jun N-terminal kinase (JNK) induces insulin resistance in mice.

AIMS/HYPOTHESIS: Although skeletal muscle insulin resistance has been associated with activation of c-Jun N-terminal kinase (JNK), whether increased JNK activity causes insulin resistance in this organ is not clear. In this study we examined the metabolic consequences of isolated JNK phosphorylation in muscle tissue. METHODS: Plasmids containing genes encoding a wild-type JNK1 (WT-JNK) or a JNK1/JNKK2 fusion protein (rendering JNK constitutively active; CA-Jnk) were electroporated into one tibialis anterior (TA) muscle of C57Bl/6 mice, with the contralateral TA injected with an empty vector (CON) to serve as a within-animal control. RESULTS: Overproduction of WT-JNK resulted in a modest (~25%) increase in phosphorylation (Thr(183)/Tyr(185)) of JNK, but no differences were observed in Ser(307) phosphorylation of insulin receptor substrate 1 (IRS-1) or total IRS-1 protein, nor in insulin-stimulated glucose clearance into the TA muscle when comparing WT-JNK with CON. By contrast, overexpression of CA-Jnk, which markedly increased the phosphorylation of CA-JNK, also increased serine phosphorylation of IRS-1, markedly decreased total IRS-1 protein, and decreased insulin-stimulated phosphorylation of the insulin receptor (Tyr(1361)) and phosphorylation of Akt at (Ser(473) and Thr(308)) compared with CON. Moreover, overexpression of CA-Jnk decreased insulin-stimulated glucose clearance into the TA muscle compared with CON and these effects were observed without changes in intramuscular lipid species. CONCLUSIONS/INTERPRETATION: Constitutive activation of JNK in skeletal muscle impairs insulin signalling at the level of IRS-1 and Akt, a process which results in the disruption of normal glucose clearance into the muscle.

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.

AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.

Plasma amyloid-ß oligomers level is a biomarker for Alzheimer's disease diagnosis.

Amyloid beta (Aß), especially Aß oligomers, is important in Alzheimer's disease (AD) pathogenesis. We studied plasma Aß(40), Aß(42), and Aß oligomers levels in 44 AD patients and 22 non-demented controls. Cognitive functions were assessed by Chinese version of mini-mental state examination (MMSE), Abbreviated Metal Test (AMT), Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog). Plasma Aß monomers and oligomers levels were measured by ELISA. We found that the median plasma Aß(40) and Aß(42) levels were similar between AD and controls, and without significant correlation with cognition. Plasma Aß oligomers level was higher in AD than controls (642.54 ng/ml [range 103.33-2676.93] versus 444.18 ng/ml [range 150.19-1311.18], p=0.047), and negatively correlated with cognition. In multivariate logistic regression analysis, the highest tertile of Aß oligomers levels showed an increased risk of AD than the combined group of middle and lowest tertiles (OR=8.85, p=0.013), after adjustment of gender, age and APOE4 genotype. Increased plasma Aß oligomers level was associated with decreased MMSE and AMT scores (p=0.037, p=0.043, respectively) and increased ADAS-cog score (p=0.036), suggesting negative correlation with cognitive function. We concluded that plasma Aß oligomers level is an useful biomarker for AD diagnosis.

Evaluation of the combined use of adiponectin and C-reactive protein levels as biomarkers for predicting the deterioration in glycaemia after a median of 5.4 years.

AIMS/HYPOTHESIS: Hypoadiponectinaemia and raised C-reactive protein (CRP) level are obesity-related biomarkers associated with glucose dysregulation. We evaluated the combined use of these two biomarkers in predicting the deterioration of glycaemia in a prospective study after a median of 5.4 years. METHODS: In total 1,288 non-diabetic participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, with high-sensitivity CRP (hsCRP) and total adiponectin levels measured were included. OGTT was performed in all participants. Two hundred and six participants had deterioration of glycaemia at follow-up, whereas 1,082 participants did not. RESULTS: Baseline age, hsCRP and adiponectin levels were significant independent predictors of the deterioration of glycaemia in a Cox regression analysis after adjusting for baseline age, sex, BMI, hypertension, triacylglycerols, 2 h post-OGTT glucose and homeostasis model assessment of insulin resistance index (all p < 0.01). The introduction of hsCRP or adiponectin level to a regression model including the other biomarker improved the prediction of glycaemic progression significantly in all participants, especially in women (all p < 0.01). The combined inclusion of the two biomarkers resulted in a modest improvement in model discrimination, compared with the inclusion of either one alone. Among participants with impaired fasting glucose/impaired glucose tolerance (IFG/IGT) at baseline, hsCRP and adiponectin levels were not predictive of progression or improvement of glycaemic status. CONCLUSIONS/INTERPRETATION: Adiponectin and hsCRP levels are independent factors in predicting the deterioration of glycaemia, supporting the role of adiposity-related inflammation in the development of type 2 diabetes. Their combined use as predictive biomarkers is especially useful in women, but not in participants with IFG/IGT.

A randomised controlled trial of nasal continuous positive airway pressure on insulin sensitivity in obstructive sleep apnoea.

The effects of treatment of obstructive sleep apnoea (OSA) on glucose metabolism have been investigated previously with conflicting results. This study evaluated the impact of nasal continuous positive airway pressure (nCPAP) treatment of OSA on insulin sensitivity. Males with moderate/severe OSA and no significant comorbidity were randomised to a therapeutic or sham nCPAP treatment group for 1 week and then reassessed. Those who received therapeutic nCPAP were further evaluated at 12 weeks. Insulin sensitivity (K(itt)) was estimated by the short insulin tolerance test. Other evaluations included blood pressure, metabolic profile, urinary catecholamines and intra-abdominal fat. In total, 61 Chinese subjects were randomised. 31 subjects receiving therapeutic nCPAP showed an increase in K(itt) (6.6+/-2.9 to 7.6+/-3.2 % x min(-1); p = 0.017), while the 30 patients on sham CPAP had no significant change, and the changes in K(itt) were different between the two groups (p = 0.022). At 12 weeks, improvement in K(itt) was seen in 20 subjects with BMI >or=25 kg x m(-2) (median (interquartile range) 28.3 (26.6-31.5); p = 0.044), but not in the nine subjects with BMI<25 kg x m(-2), or the entire group. The findings indicate that therapeutic nCPAP treatment of OSA for 1 week improved insulin sensitivity in nondiabetic males, and the improvement appeared to be maintained after 12 weeks of treatment in those with moderate obesity.

Relationship between symptoms of androgen deficiency and psychological factors and quality of life among Chinese men.

Androgen deficiency in the ageing male (ADAM) was proposed to characterize a symptom cluster of decrease in sexual function and strength, dysphoria and osteopenia in ageing men with decreased levels of androgens. Unlike menopause, literature on the topic is scarce and focuses mainly on the physiological aspects of the problem. However, men with ADAM also face a milieu of psychosocial stressors which may adversely affect their mental health. It is pertinent to examine ADAM within a psychological context. This study aims to determine the prevalence of symptoms of ADAM among Chinese men, and to examine their relationship with psychological distress and quality of life. A cross-sectional design was employed with standardized questionnaires to assess symptoms of ADAM and related psychological factors. The ADAM questionnaire, Hospital Anxiety and Depression Scale, Perceived Stress Scale, General Health Questionnaire and Short Form Health Survey-12 were administered to a community sample of 311 Chinese men (aged 40-80) attending a family medicine clinic in Hong Kong. Demographic information was also collected. A total of 87.8% of the sample was screened ADAM positive using the ADAM questionnaire. Age, duration of marriage, occupation, household income and physical health were found to be significantly associated with ADAM status. ADAM positive individuals were found to have higher anxiety and depression scores, higher stress level, higher psychiatric morbidity and poorer physical and mental quality of life compared with their ADAM negative counterparts. Symptoms of ADAM are prevalent among the Chinese. ADAM positivity as measured by the ADAM questionnaire is associated with poorer psychological well-being and quality of life in the ageing population. Further research and clinical attention to the psychological needs of this population is warranted.

Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance.

Obstructive sleep apnoea (OSA) is associated with insulin resistance and metabolic syndrome. There is evidence that adipocyte-fatty acid binding protein (A-FABP) may be involved in the development of cardiometabolic dysfunction. The present authors hypothesise that A-FABP is upregulated in OSA. A total of 124 males without hypertension, diabetes mellitus, hyperlipidaemia or cardiovascular disease were recruited and underwent polysomnography. Serum A-FABP levels showed significant positive correlations with duration of oxygen desaturation and minimal oxygen saturation, fasting insulin and insulin resistance index by homeostasis model assessment. When subjects were divided into tertiles according to apnoea/hypopnoea index (AHI), serum A-FABP levels were significantly higher in the group with AHI >/=34.4 events.h(-1) than the groups with AHI 13.2-34.4 events.h(-1) or with AHI <13.2 events.h(-1). Serum A-FABP levels were significantly higher in the AHI >/=34.4 group than obesity-matched subjects with AHI <34.4 events.h(-1). Serum adipocyte-fatty acid binding protein levels correlated with obstructive sleep apnoea and insulin resistance, independently of obesity, and were significantly higher in severe obstructive sleep apnoea. Adipocyte-fatty acid binding protein may play a role in obstructive sleep apnoea and metabolic dysfunction.

Association of F11 receptor gene polymorphisms with central obesity and blood pressure.

OBJECTIVES: F11 receptor, also known as junctional adhesion molecule-1, in the autonomic nervous system is implicated in the development of hypertension in spontaneous hypertensive rats. We investigated the association of single nucleotide polymorphisms (SNPs) in the F11 receptor gene (F11R) with hypertension and central obesity in Hong Kong Chinese. METHODS: Seven tagging SNPs were identified in the HapMap database. Genotyping was performed using Sequenom MassArray in 263 hypertensive subjects and 393 normotensive controls, of whom 263 matched the cases in age and sex. RESULTS: When subjects on anti-hypertensive medication were excluded, rs790056 and rs2774276 were associated with lower systolic blood pressure (TT:124.8 +/- 18.3 mmHg vs. TC + CC: 120.2 +/- 15.5 mmHg, P = 0.004 and CC: 124.7 +/- 18.5 mmHg vs. CG+GG: 120.5 +/- 15.1 mmHg, P = 0.007 respectively). Comparing 213 subjects with central obesity with 213 controls matched for sex and age, rs2481084 and rs3737787 were associated with lower odds of central obesity (odds ratio = 0.516, P = 0.002 and odds ratio = 0.540, P = 0.005 respectively). All these associations remained significant after correction for multiple testing. Analysis of statistically similar SNPs suggested that the causative variants for systolic blood pressure were located in F11R, whilst those for central obesity could be due to causative variants in the transcription factor 1 gene immediately upstream. CONCLUSIONS: F11 receptor plays a role in blood pressure regulation, not only in rats but also in man. The link between F11 receptor and central obesity merits further investigation.

Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis.

OBJECTIVE: Adipocyte fatty acid-binding protein (A-FABP) has been shown to be an important player in atherosclerosis in animal models. However, the clinical relevance of these findings is still unknown. This study aims to examine the relationship between serum A-FABP level and carotid intima-media thickness (IMT), an indicator of atherosclerosis in humans. METHODS AND RESULTS: The study cohort included 479 Chinese subjects who underwent carotid IMT measurement. Serum A-FABP levels were determined by enzyme-linked immunosorbent assays. Serum A-FABP levels positively correlated with carotid IMT in both men (r=0.211, P=0.001) and women (r=0.435, P<0.001). In women, but not in men, the presence of plaques was associated with significantly higher serum A-FABP levels (P<0.001 versus women without plaques). Stepwise multiple regression analysis showed that serum A-FABP level was independently associated with carotid IMT in women (P=0.034), together with age and hypertension (both P<0.001). CONCLUSIONS: A-FABP is an independent determinant of carotid atherosclerosis in Chinese women, but not in men. This gender difference may be attributed to the lower serum A-FABP levels in men, and the effect of other risk factors, such as smoking, among our male participants. Our results have provided clinical evidence supporting the role of A-FABP in the development of atherosclerosis.

A systematic review on the impact of diabetes mellitus on the ocular surface.

Diabetes mellitus is associated with extensive morbidity and mortality in any human community. It is well understood that the burden of diabetes is attributed to chronic progressive damage in major end-organs, but it is underappreciated that the most superficial and transparent organ affected by diabetes is the cornea. Different corneal components (epithelium, nerves, immune cells and endothelium) underpin specific systemic complications of diabetes. Just as diabetic retinopathy is a marker of more generalized microvascular disease, corneal nerve changes can predict peripheral and autonomic neuropathy, providing a window of opportunity for early treatment. In addition, alterations of immune cells in corneas suggest an inflammatory component in diabetic complications. Furthermore, impaired corneal epithelial wound healing may also imply more widespread disease. The non-invasiveness and improvement in imaging technology facilitates the emergence of new screening tools. Systemic control of diabetes can improve ocular surface health, possibly aided by anti-inflammatory and vasoprotective agents.

Which creatinine-based estimated glomerular filtration rate equation best predicts all-cause mortality in Chinese subjects with type 2 diabetes?

AIM: In Chinese, ethnicity-based and/or diabetes specific modifications of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been developed for determining estimated glomerular filtrate rate (eGFR). This study aimed to compare the performance of five different creatinine-based eGFR equations in predicting all-cause mortality among Chinese subjects with type 2 diabetes (T2DM). METHODS: A total of 6739 Chinese subjects with T2DM were included. Their eGFR was calculated using the MDRD, CKD-EPI, their respective modified equations for Chinese, and the diabetes specific CKD-EPI Chinese T2DM equations. Multiple Cox regression analysis was used to evaluate the associations of eGFR with all-cause mortality. C-statistics, net reclassification index (NRI) and integrated discrimination index (IDI) were applied to assess the discrimination and reclassification of each eGFR equation in predicting mortality outcome. RESULTS: Over a follow-up of 5.7years, the incidence of all-cause mortality was 12.9% (N=867). The CKD-EPI equation discriminated all-cause mortality better than the MDRD equation (C-statistics: 0.714 vs. 0.689, p<0.0001), and Chinese modification of their respective equations did not improve discrimination. Among the five eGFR equations evaluated, the CKD-EPI Chinese T2DM equation provided the best discrimination in predicting all-cause mortality among Chinese subjects with T2DM, and was the only equation providing a significantly positive NRI and IDI relative to the CKD-EPI equation. CONCLUSIONS: Among Chinese subjects with T2DM, our findings suggested that the CKD-EPI Chinese T2DM equation best predicted all-cause mortality, and relative to the CKD-EPI equation, conferred improved discrimination and reclassification.

Association of hypertension with single nucleotide polymorphisms in the quantitative trait locus for abdominal obesity-metabolic syndrome on chromosome 17.

Genome scan in Chinese revealed an association of blood pressure with the microsatellite marker D17S1303, which lies in a quantitative trait locus for the abdominal obesity-metabolic syndrome (AOMS2) at 17p12 on chromosome 17. We previously reported that D17S1303 was associated with hypertension and obesity. Therefore, we studied 10 single nucleotide polymorphisms (SNP) within 3 kb of D17S1303. One hundred and eighty hypertensive subjects (91 men, 89 women, age 53+/-12 years) and 180 normotensive matched controls (91 men, 89 women, age 52+/-11) were genotyped using the Sequenom genotyping platform. Allelic frequencies in these Chinese subjects differed from those reported for Caucasians. Three SNPs (rs11656507, rs1357926, rs852319) were homozygous in our subjects. The genotype frequencies of rs852320, rs852321 and rs852322 did not differ between hypertensive and normotensive subjects. However, there were significant differences for rs1525402 (P=0.048), rs2692343 (P=0.022), rs2692344 (P=0.017) and rs2321313 (P=0.028). A four-locus haplotype comprising G at rs1525402, C at rs2692343, C at rs2692344 and G at rs2321313 was associated with lower systolic blood pressure (P=0.023) and normotension (P=0.048). Our results provide further evidence that there is a gene, as yet unidentified, influencing blood pressure in the vicinity of D17S1303 in a quantitative trait locus for abdominal obesity-metabolic syndrome at 17p12.