Background Obesity is closely associated with various cardiovascular diseases ( CVD s). Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of CVD . This study aimed to evaluate whether the 2 most abundant adipokines, adipocyte‐fatty acid binding protein (A‐ FABP ) and adiponectin, are independent risk factors predisposing to CVD . Method and Results We investigated prospectively the 12‐year development of CVD in relation to the baseline levels of A‐ FABP and adiponectin in a population‐based community cohort comprising 1847 Chinese subjects recruited from the H ong K ong C ardiovascular R isk F actors P revalence S tudy 2 ( CRISPS 2) cohort without previous CVD . Baseline serum levels of A‐ FABP , adiponectin, and C ‐reactive protein ( CRP ), an established biomarker predictive of CVD , were measured. In all, 182 (9.9%) of the 1847 Chinese subjects developed CVD during a median follow‐up of 9.4 years. The CVD group had more traditional risk factors, higher baseline levels of A‐ FABP and CRP (both P <0.001), but similar adiponectin levels ( P =0.881) compared with the non‐ CVD group. In C ox regression analysis including both biomarkers, the adjusted HR for A‐ FABP and CRP for subjects above the optimal cutoff values were 1.57 (95% CI , 1.14 to 2.16; P =0.006) and 1.60 (95% CI , 1.12 to 2.27; P =0.01), respectively, after adjustment for traditional risk factors. The category‐free net reclassification index, but not the c‐statistic, showed improvement in predictive performance by the addition of A‐ FABP to the traditional risk factor model ( P =0.017). Conclusions Circulating A‐ FABP level predicts the development of CVD after adjustment for traditional risk factors in a community‐based cohort. Its clinical use for CVD prediction warrants further validation.
Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly expressed in adipose tissue and liver. Several recent studies demonstrated that ANGPTL4 is the target gene of peroxisome proliferation activators, the agonists of which are widely used as the antidiabetic and lipid-lowering drugs. Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Adenovirus-mediated expression of ANGPTL4 potently decreased blood glucose and improved glucose tolerance, whereas it induced hyperlipidemia, fatty liver, and hepatomegaly in C57 mice. In db/db diabetic mice, ANGPTL4 treatment reduced hyperglycemia to a normal level, and markedly alleviated glucose intolerance and hyperinsulinemia. Ex vivo studies on primary rat hepatocytes revealed that ANGPTL4 significantly decreased hepatic glucose production and enhanced insulin-mediated inhibition of gluconeogenesis. Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance. In patients with type 2 diabetes, serum levels of ANGPTL4 were significantly lower than those in healthy subjects, suggesting that the decreased ANGPTL4 could be a causative factor of this disease. These results collectively indicate that ANGPTL4 exerts distinct effects on glucose and lipid metabolism, and that its beneficial effect on glucose homeostasis might be useful for the treatment of diabetes.
To investigate the association between raised blood pressure and dysglycemia.We studied the association between raised blood pressure and dysglycemia in 1,862 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. We determined the factors predicting the development of diabetes and hypertension in 1,496 subjects who did not have either condition at baseline.Diabetes and hypertension were both related to age, obesity indexes, blood pressure, glucose, HDL cholesterol, and triglycerides. Of subjects with diabetes, 58% had raised blood pressure. Of subjects with hypertension, 56% had dysglycemia. BMI and blood glucose 2 h after a 75-g oral glucose load were independent predictors of new-onset diabetes. Age, systolic blood pressure, and 2-h glucose were independent predictors of new-onset hypertension. BMI, systolic blood pressure, and 2-h glucose were independent predictors of the development of diabetes and hypertension together.Diabetes and hypertension share common etiological factors. Patients with diabetes or hypertension should be screened and managed for the precursor of the other condition.
A 73 year old woman was referred because of hypophosphataemia and raised serum alkaline phosphatase. She was a chronic hepatitis B carrier and regular monitoring had shown a persistently raised alkaline phosphatase (415-495 U/l; normal range 47-124). All other liver enzymes were within the normal range, and ultrasound of the liver was unremarkable.
Further assessment showed low serum phosphate (0.51-0.63 mmol/l; 0.88-1.45), but normal albumin adjusted calcium (2.53-2.63 mmol/l; 2.24-2.63) and creatinine (40 µmol/l; normal 49-82). Her serum parathyroid hormone was extremely high at 689 ng/l (normal 9-52), serum calcidiol (25-hydroxyvitamin D) was low at 23.5 nmol/l (normal >50), and serum calcitriol (1,25-dihydroxycalciferol) was raised at 240.5 pmol/l (60.2-158.6).
She was diagnosed with vitamin D insufficiency with secondary hyperparathyroidism and was prescribed cholecalciferol 800 IU/day. After three months of treatment, serum phosphate remained persistently low at 0.52 mmol/l and she had developed hypercalcaemia (albumin adjusted calcium 2.73 mmol/l). Her 24 hour urine for calcium was normal (7.1 mmol/day; 2.0-7.4) and parathyroid hormone remained raised at 691 ng/l.
### 1 What is the most likely diagnosis?
#### Short answer
The patient has primary hyperparathyroidism; vitamin D replacement seemed to unmask the hypercalcaemia.
#### Long answer
Primary hyperparathyroidism is a common endocrine disorder. Up to 80% of patients have no symptoms of hypercalcaemia and only a small proportion present with associated complications such as hypercalciuria, renal stones, osteoporosis, and fractures.
Vitamin D insufficiency is also a common problem worldwide, which often goes unrecognised. A serum calcidiol concentration of below 50 nmol/l is suggestive of vitamin D insufficiency. Recently, the National Institute of Health of the United States recommended a calcidiol value of greater than 75 nmol/l to reduce fracture risk, improve lower extremity function, and protect against development of colorectal cancer. …
The F11 receptor (F11R, also known as junctional adhesion molecule A (JAM-A)) plays a role in the development of hypertension in rat. Genetic variants in the human F11R gene were demonstrated to influence systolic blood pressure. In the present study, we investigated the relationship between F11R and hypertension by examining the levels of a circulating soluble form of F11R (sF11R) in hypertensive patients.Plasma sF11R was measured by enzyme-linked immunosorbent assay in 152 hypertensive and 166 normotensive subjects in whom seven tagging single-nucleotide polymorphisms (SNPs) in the F11R gene had been genotyped.Plasma sF11R levels were significantly higher in hypertensive subjects than in normotensive subjects (median (interquartile) range): 162.8 (85.5-293.2) vs. 116.5 (74.1-194.8) pg/ml, P = 0.004), which remained significantly higher after adjusting for age, sex, body mass index (BMI), and homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.028). In stepwise multiple logistic regression, sF11R level (log-transformed) (P = 0.040), triglycerides (log-transformed) (P = 0.024), and HOMA-IR (log-transformed) (P < 0.001) were independently associated with hypertension. Plasma sF11R level correlated with systolic and diastolic blood pressures (r = 0.15, P < 0.001, and r = 0.13, P = 0.024, respectively). In stepwise multiple linear regression, hypertension (P = 0.013) and fibrinogen levels (P = 0.027) were significant independent predictors of sF11R level. A seven-locus haplotype, present in 2.1% of the subjects, was associated with higher sF11R level (P = 0.024).These results further support a role of F11 receptor in the pathophysiology of human hypertension.
Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 gene (APOA5) are associated with hypertriglyceridaemia in our population. We studied the associations of SNPs in APOA5 with the metabolic syndrome (MetS) in the Hong Kong and Guangzhou Chinese.We genotyped five tagging SNPs in 1330 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort with follow-up after a median interval of 6·4 years; 1952 subjects from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort were used to replicate the findings. The MetS was defined according to the consensus criteria proposed jointly by several organizations in 2009.The SNP rs662799 (-1131T>C) was associated with the MetS (odds ratio = 1·47, P = 0·00082) and the number of its components present (regression coefficient = 0·204, P = 4·6 × 10(-5) ) after adjusting for age, sex, smoking, drinking and education in Hong Kong subjects at baseline. Similar association of this SNP was found in Hong Kong subjects at follow-up (P = 0·010 and 0·00021, respectively) and in Guangzhou subjects (P = 0·0041 and 0·017, respectively). The association of rs662799 with the number of the MetS components was significant regardless of age, sex, obesity and alcohol drinking, but almost disappeared after further adjusting for plasma triglycerides.Our results showed that the -1131T>C polymorphism in APOA5 was associated with the MetS because of its strong effect on plasma triglycerides. This may partly explain the higher cardiovascular risk in people with this polymorphism.
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