PCSK9 critically controls LDLR expression in pancreas perhaps contributing to the maintenance of a proper physiological balance to limit cholesterol overload in beta cells. This effect is independent of circulating PCSK9 and is probably related to locally produced PCSK9.

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Objective: The role of resistin in insulin sensitivity and obesity is controversial. Some authors suggest that increased serum resistin levels are associated with obesity, visceral fat, insulin resistance, type 2 diabetes and inflammation, while others failed to observe such correlations. The aim of the present study was to investigate the relationship of plasma resistin levels with markers of the metabolic syndrome and atherosclerosis in a large population-based study. Design and patients: Plasma resistin levels were determined in 1090 subjects free of any medication selected from the PLIC study (designed to verify the presence of atherosclerotic lesions and progression intimamedia thickness (IMT) in the common carotid artery in the general population) and related to the presence of obesity, metabolic syndrome, metabolic abnormalities, cardiovascular risk, and progression of IMT. Results: Plasma resistin levels were highly positively correlated with triglycerides, waist circumference, waist/hip ratio, systolic blood pressure, and ApoAI/ApoB ratio, while they were inversely correlated with high density lipoprotein and ApoAI levels. This finding was gender specific (mainly in women). Plasma resistin levels were significantly higher in women with the metabolic syndrome compared with controls (4.90 (0.24) ng/ml vs 3.90 (0.11) ng/ml; P!0.01), while no difference was observed in obese subjects. Finally, plasma resistin levels were significantly correlated with cardiovascular risk calculated according to the Framingham algorithm (P!0.01). Conclusion: Plasma resistin levels are increased in presence of the metabolic syndrome and are associated with increased cardiovascular risk.European Journal of Endocrinology 156 279-284

Background and Purpose-The evaluation of the leptin:adiponectin ratio (L:A) has been suggested as an atherosclerotic index in patients with type 2 diabetes and a useful parameter to assess insulin resistance in patients with and without diabetes. Methods-We investigated, therefore, the relationship between L:A ratio and intima media thickness (IMT), an independent predictor of cardiovascular disease, in 110 healthy males. Results-L:A ratio was significantly correlated to body mass index, waist, hip, waist-to-hip ratio, systolic blood pressure, IMT, high-density lipoprotein, apolipoprotein A-I, glucose, and the homeostasis model of insulin resistance-revised. No significant correlation was observed with age, diastolic blood pressure, low-density lipoprotein, triglycerides, apolipoprotein B, ApoB/ApoA-I ratio, insulin, alanine transaminase, ␥-glutamyl-transferase, and resistin. In addition, when the relationship between IMT and adiponectin or leptin alone was analyzed, only leptin plasma levels significantly associated with IMT (rϭ0.301, PϽ0.01). In a multiple regression analysis including in the statistical model the risk factors known to affect IMT (age, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, total cholesterol, body mass index, glucose, and L:A ratio), we observed that only age, L:A, and glucose were independent predictors of IMT. As expected, obese subjects (body mass index Ͼ30 kg/m 2 ) showed a significantly higher L:A ratio compared with nonobese subjects (1.20 versus 0.42, respectively, PϽ0.001); in addition, subjects with the metabolic syndrome showed a significantly higher L:A ratio level (0.79) compared with subjects without (0.52) (PϽ0.01). Conclusions-We show here that the L:A ratio is a powerful independent predictor of IMT in healthy subjects and correlates with several anthropometric, metabolic, and clinical parameters better than each single adipokine. (Stroke.