Greater changes in insulin sensitivity after intake of an isoenergetic HCF than after intake of an HP diet might help to explain the diverse effects of these diets on diabetes risk. This trial is registered at clinicaltrials.gov as NCT00579657.

WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix–associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine. Human adipocyte differentiation was associated with increased WISP1 expression and secretion. Stimulation of human macrophages with WISP1 led to a proinflammatory response. Circulating WISP1 and WISP1 subcutaneous adipose tissue expression were regulated by weight changes in humans and mice. WISP1 expression in visceral and subcutaneous fat tissue was associated with markers of insulin resistance and inflammation in glucose-tolerant subjects. In patients with nonalcoholic fatty liver disease, we found no correlation among disease activity score, liver fat content, and WISP1 expression. Insulin regulated WISP1 expression in adipocytes in vitro but had no acute effect on WISP1 gene expression in subcutaneous fat tissue in overweight subjects who had undergone hyperinsulinemic clamp experiments. The data suggest that WISP1 may play a role in linking obesity to inflammation and insulin resistance and could be a novel therapeutic target for obesity.

Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR). Pigment epithelium-derived factor (PEDF) has been shown to be a major antiangiogenic growth factor in the mammalian eye. PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease. However, whether this concept of a reduced angiogenesis inhibitor holds true in humans is as yet unclear. In this study, we analyzed the in vivo regulation of PEDF in patients with and without hypoxic eye disease. We used immunoblots to measure PEDF in ocular fluids obtained from 64 nondiabetic and diabetic patients. In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy. The PEDF concentrations in patients with PDR (P < 0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P < 0.001) were lower than in control patients. Levels of PEDF were replenished in PDR patients with previous retinal scatter photocoagulation compared with PDR patients without previous photocoagulation (P ‫؍‬ 0.01). Immunohistochemistry revealed an interstitial staining pattern as expected for a secreted protein, with an intense staining in retinas of patients without proliferative eye disease. However, in patients with PDR, little or no staining was detectable. Our data strongly support the concept that retinal angiogenesis is induced by loss of the major angiogenesis inhibitor in the eye, PEDF, in combination with an increased expression of angiogenic growth factors such as vascular endothelial growth factor. Our findings suggest that substitution of angiogenesis inhibitors may be an effective approach in the treatment of PDR. Diabetes 50: [2641][2642][2643][2644][2645] 2001 T he control of retinal angiogenesis is of critical importance for the preservation of vision. Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR), which is still one of the most common causes of blindness worldwide. Retinal ischemia induces intraocular neovascularization, presumably by stimulating the expression of angiogenic growth factors and by inhibiting the release of antiangiogenic cytokines (1,2). Vitreal levels of angiogenic growth factors have been shown to be directly associated with the degree of retinal angiogenesis (3,4). The ability to monitor and grade retinal angiogenesis within the eye as well as the ability to aspirate vitreous, which is known to contain retina-derived growth factors in direct association to the stage of retinal angiogenesis, makes the eye an ideal setting in which to investigate the delicate balance of new vessel growth and the influence of specific growth factors in vivo in humans.Pigment epithelium-derived factor (PEDF) protects cerebellar granule cells against neurotoxic agents (5) and is also called early population doubling level cDNA-1 (EPC-1), reflecting its upregulation during cell cycle ...

on behalf of DiOGenes Background-We sought to separately examine the effects of either weight loss or diets varying in protein content and glycemic index without further changes in body weight on cardiovascular risk factors within the Diet, Obesity, and Genes study (DiOGenes). Methods and Results-DiOGenes is a pan-European controlled dietary intervention study in 932 overweight adults who first lost body weight on an 8-week low-calorie diet and were then randomized to 1 of 5 ad libitum diets for 26 weeks. The diets were either high or low protein or high or low glycemic index in 4 combinations or control. Weight loss (Ϫ11.23 kg; 95% confidence interval, Ϫ11.54 to Ϫ10.92; PϽ0.001) reduced high-sensitivity C-reactive protein (Ϫ1.15 mg/L; 95% confidence interval, Ϫ1.30 to Ϫ0.41; PϽ0.001), low-and high-density lipoprotein cholesterol, triglycerides, and blood pressure. During the 26-week weight maintenance period in the intention-to-treat analysis, the further decrease of high-sensitivity C-reactive protein blood levels was Ϫ0.46 mg/L greater (95% confidence interval, Ϫ0.79 to Ϫ0.13) in the groups assigned to low-glycemic-index diets than in those on high-glycemic-index diets (PϽ0.001).Groups on low-protein diets achieved a Ϫ0.25 mg/L greater reduction in high-sensitivity C-reactive protein (95% confidence interval, Ϫ0.59 to Ϫ0.17) than those on high-protein diets (PϽ0.001), whereas lipid profiles and blood pressure were not differently affected. Conclusions-This large-scale intervention study clearly separates weight loss from dietary composition-related effects.Low-glycemic-index carbohydrates and, to a lesser extent, low-protein intake may specifically reduce low-grade inflammation and associated comorbidities in overweight/obese adults. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique identifier: NCT00390637.

Objective: The syndrome of polycystic ovaries (PCOS) is a known risk factor for type 2 diabetes. It is not known, however, whether the increase in diabetes risk is related to endocrine abnormalities associated with PCOS such as hyperandrogenemia, or whether it is a consequence of the anthropometric or metabolic alterations frequently observed in PCOS women. Design: Since markers of inflammation are supposed to predict type 2 diabetes, interleukin-6 (IL-6) and C-reactive protein (CRP) in combination with parameters of obesity, insulin resistance and hyperandrogenism were determined in 57 PCOS women and in 20 age-matched healthy controls. In addition, the C-174G IL-6 promoter polymorphism was analyzed as a determinant in influencing IL-6, obesity, and androgen levels in women. Results: Neither CRP nor IL-6 were significantly elevated in lean or obese PCOS women compared with age-matched lean or obese controls. In PCOS patients, variables of body composition (body mass index (BMI), waist to hip ratio, dual-energy X-ray-absorptiometry fat mass) and of insulin resistance were correlated with IL-6 or CRP, while parameters of hyperandogenism were not. Multivariate linear regression analysis revealed that obesity is the dominant force, thus explaining 18% and 24% of the IL-6 or CRP levels, respectively, in PCOS women. No association of IL-6 or BMI to a certain genotype at C-174G could be demonstrated in 50 PCOS patients. The heterozygous GC genotype, however, was associated with lower androstendione levels. Metformin treatment of 9 obese, insulin-resistant PCOS patients over a period of 6 months caused a significant decrease in body weight, body fat mass and total testosterone, but showed no significant decline in IL-6 or CRP concentrations. Conclusions: In PCOS women, plasma levels of IL-6 and CRP were not increased when compared with age-and BMI-matched controls. BMI was, however, the parameter most strongly related to IL-6 and CRP in PCOS; thus PCOS-related endocrine abnormalities do not appear to activate inflammatory parameters thereby enhancing the risk of diabetes. In PCOS, the type 2 diabetes risk may, therefore, be confined to those with obesity and/or metabolic alterations rather than affecting all women suffering from the syndrome.European Journal of Endocrinology 150 525-532

No abstract

In euthyroidism, subjects with a TSH in the upper normal range (2.5-4.5 mU/l) were more obese, had higher triglycerides, and had an increased likeliness for the metabolic syndrome. Therefore, a TSH below 2.5 mU/l is associated with a favourable metabolic profile. Whether lowering TSH to levels below 2.5 mU/l improves metabolism needs to be investigated in intervention trials.

Aims/hypothesis: Insoluble dietary fibre intake is associated, by unknown mechanisms, with a reduced risk of type 2 diabetes. We investigated whether a shortterm dietary intervention with purified insoluble fibres influences acute and delayed responses of glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1. Methods: Fourteen healthy women with NGT were studied for 300 min on six to eight occasions. Subjects consumed three matched portions of control (C) or fibre-enriched bread (10.