Experimental studies have suggested that ghrelin plays a role in glucose homeostasis and in the regulation of blood pressure (BP). We therefore assessed the hypothesis that a low ghrelin concentration may be a risk factor for type 2 diabetes and hypertension. We also characterized the effect of the ghrelin Arg51Gln and Leu72Met mutations on ghrelin concentrations in the population-based hypertensive (n ‫؍‬ 519) and control (n ‫؍‬ 526) cohorts of our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. The fasting plasma ghrelin concentrations of 1,040 subjects were analyzed using the radioimmunoassay method. Insulin sensitivity was assessed using the quantitative insulin sensitivity check index (QUICKI). Ghrelin concentrations were negatively associated with fasting insulin (P < 0.001), systolic (P ‫؍‬ 0.026) and diastolic BP (P ‫؍‬ 0.018), and the prevalence of type 2 diabetes (P ‫؍‬ 0.015) and insulin resistance (P < 0.001) in the multivariate models. In the control cohort, low ghrelin was associated with hypertension (BP >140/90 mmHg) (P ‫؍‬ 0.031). The subjects with the ghrelin 51Gln allele had lower ghrelin concentrations than the Arg51Arg homozygotes (P ‫؍‬ 0.001). We conclude that low ghrelin is independently associated with type 2 diabetes, insulin concentration, insulin resistance, and elevated BP. Therefore, it might have some role in the etiology of type 2 diabetes and the regulation of BP. The ghrelin Arg51Gln mutation is associated with low plasma ghrelin concentrations. Diabetes 52:2546 -2553, 2003 G hrelin is a recently discovered peptide hormone secreted mainly from the stomach (1). It has a very potent growth hormone (GH)-releasing effect both in animal models and humans (1-3). In addition, it probably has effects independent of GH secretion (4). It is a somatotrophic orexigenic adipogenic hormone that links the regulatory systems for growth and energy balance (5). The effects of ghrelin are mediated through the GH secretagogue receptor, which is widely distributed in the body (6).The role of ghrelin in glucose and insulin metabolism has been studied actively. In experimental settings, glucose administration or food intake have been shown to decrease plasma ghrelin concentrations (7-9). Studies of the effects of ghrelin on insulin secretion have shown both stimulatory (10 -12) and inhibitory effects (13,14). In human subjects, insulin infusion has been shown to decrease ghrelin concentrations (15,16), whereas parenteral administration of insulin had no effect on ghrelin concentrations (17). On contrary, administration of insulin and leptin induced the increase of ghrelin mRNA in rats (18).Ghrelin exerts beneficial hemodynamic effects in humans by reducing cardiac afterload and increasing cardiac output (19). The vasodilatory effect is possibly mediated through a GH/IGF-I/nitric oxide-independent mechanism (20).Based on these recent studies, it appears that ghrelin might have a role in glucose and insulin metabolism and it also may influence blood pressure (BP) levels. Therefore, chang...

Adiponectin is a novel polypeptide that is highly specific to adipose tissue. In contrast to other adipocytokines, adiponectin levels are decreased in obesity and associated comorbidities, such as type 2 diabetes. Decreased expression of adiponectin is correlated with insulin resistance. It has been suggested that several agents, such as tumor necrosis factor alpha, could mediate their effects on insulin metabolism through modulating adiponectin secretion from adipocytes. The mechanisms for the development of atherosclerotic vascular disease in obese individuals are largely unknown. Several findings support the interesting hypothesis that adiponectin could be a link between obesity and related atherosclerosis. First, adiponectin levels are lower in patients with coronary artery disease. Second, adiponectin modulates endothelial function and has an inhibitory effect on vascular smooth muscle cell proliferation. Moreover, adiponectin is accumulated more preferably to the injured vascular wall than intact vessels and has been shown to suppress macrophage-to-foam cell transformation. Adiponectin may also be involved in the modulation of inflammation. Thiazolidinediones, antiatherogenic and other effects have been explained by their direct enhancing effect on adiponectin. In conclusion, adiponectin has anti-inflammatory and antiatherogeneic effects as well as multiple beneficial effects on metabolism. Therefore it is not a surprise that adiponectin therapy has been tested in animal models of obesity, and it has been shown to ameliorate hyperglycemia and hyperinsulinemia without inducing weight gain or even inducing weight loss in some studies. Unlike agents that exert their effects centrally, adiponectin's effects seem to be peripherally mediated. The evidence of an association between adiponectin and the metabolic and cardiovascular complications of obesity is growing all the time.

Res. 2002;10: 782-791. Objective: Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERI-TAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. Research Methods and Procedures: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. Results: Arg51Gln QFS subjects (n ϭ 6) had lower ghrelin concentrations (p ϭ 0.007) than Arg51Arg subjects (n ϭ 14). White preproghrelin Met72Met subjects in HERI-TAGE had the lowest BMI (p ϭ 0.020), and those in the QFS cohort had the lowest FM (p Ͻ 0.001). Met72 carrier status (Met72ϩ) was associated with lower FM (p ϭ 0.026) and higher insulin-like growth factor-1 levels (p ϭ 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p ϭ 0.002) and a lower fasting respiratory quotient (p ϭ 0.037). HERITAGE Met72ϩ white subjects also showed lower exercise respiratory quotient (p ϭ 0.030) and higher maximal oxygen uptake (p ϭ 0.023). Furthermore, the prevalence of Met72ϩ was higher (19.2%; p Ͻ 0.05) in SOS subjects whose BMI was Յ25 kg/m 2 than in those with BMI Ͼ25 kg/m 2 (14.8%). SOS Met72ϩ obese women had a lower (11.4%; p ϭ 0.032) prevalence of hypertension than noncarriers (23.9%). Discussion: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.

We conclude that age was the most important factor, followed by BMI, race and lifestyle factors in explaining steroid hormone variability.

Objectives: Resistin is a newly described hormone with a suggested role in insulin resistance. In humans, inflammatory cells seem to be the major source of resistin. The aim of this study was to find out whether plasma resistin concentration associates with carotid artery atherosclerosis and the risk factors of atherosclerosis.Methods: Plasma resistin concentrations were measured in 525 Finnish middle-aged subjects among our population-based cohort. Intima-media thickness was measured from the internal carotid artery, the bifurcation enlargement, and the common carotid artery.Results: Among all the subjects, the median resistin concentration was 7.07 ng/ml (interquartile range, 5.82-8.84), women having higher levels than men (P Ͻ 0.001) with median values of 7.56 ng/ml (6.18 -9.19) and 6.67 ng/ml (5.63-8.31), respectively. Resistin level correlated negatively with mean intima-media thickness, internal carotid artery, and common carotid artery, but the association did not remain significant after adjustments. Plasma resistin concentration was associated positively with leukocytes (P Ͻ 0.001), highly sensitive C-reactive protein (P ϭ 0.009), and IGF binding protein 1 (P Ͻ 0.001), but not with plasma insulin or glucose levels in analysis of covariance after adjustments for age, sex, and body mass index. Conclusions:The results imply that inflammatory factors are more important in the determination of plasma resistin concentration than plasma insulin or glucose values. Resistin is associated with proatherogenic inflammatory markers but not independently with early atherosclerosis.

Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are widespread diseases and have multiple common risk factors and comorbidities. No studies of association between ultrasonography-diagnosed NAFLD and AF exist in other than diabetic population. The goal of this prospective study was to study the value of NAFLD as a predictor of atrial fibrillation. This study had 958 subjects from the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort, and the mean follow-up time was 16.3 years. NAFLD was diagnosed if the subject had fatty liver in ultrasonography and no excess alcohol intake. AF was followed in the National Registers. In this study 249 subjects (26.0%) had NAFLD and 37 (14.9%) of these had AF whereas only 56 (7.9%) of those without NAFLD experienced AF during the follow-up time (p = 0.001). In the multiple Cox regression analysis including potential confounders (age, sex, study group, diabetes, body mass index (BMI), waist circumference, alcohol consumption, smoking, serum alanine aminotransferase concentration (ALT), systolic blood pressure, quick index, left ventricular mass index, left atrial diameter, coronary artery disease (CAD), atrial natriuretic peptide (ANP) and high sensitive C-reactive protein (hs-CRP)), NAFLD remained as an independent predictor of AF (Adjusted OR, 1.88 (95% Confidence interval (CI) 1.03–3.45)). In conclusion, our data shows that NAFLD is independently associated with the risk of AF.

No abstract

Lumbar radicular pain is a fairly common health problem, yet its risk factors are far from clear. There are no published systematic reviews on associations between cardiovascular or lifestyle risk factors and lumbar radicular pain or sciatica. The aim of this systematic literature review was to assess associations between these risk factors and lumbar radicular pain or sciatica. We conducted a systematic search of the Medline database for all original articles on lumbar radicular pain or sciatica published until August 2006. Twenty-two papers from 19 studies were included in the review. Overweight or obesity was associated with sciatica in most of the casecontrol and cohort studies. Some studies showed an increased risk of lumbar radicular pain in smokers with a long smoking history or in those with high levels of physical activity. A few case-control studies showed an association between serum C-reactive protein and sciatica. No consistent associations were found for serum lipids levels or high blood pressure. In summary, the associations of overweight, long smoking history, high physical activity and a high serum C-reactive protein level with lumbar radicular pain or sciatica were substantiated by the present review. However, more prospective studies are needed in order to further clarify these associations and the mechanisms of action.