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Publications
Increase In Plasma Endotoxin Concentrations And The Expression Of Toll Like Receptors And Suppressor Of Cytokine Signaling-3 In Mononuclear Cells Following A High Fat High Carbohydrate Meal: Implications For Insulin Resistance.
Diabetes Care. 2009 Sep 15.
Ghanim H, Abuaysheh S, Sia CL, Korzeniewski K, Chaudhuri A, Fernandez Real JM, Dandona P.
Objective: To compare effect of a high fat high carbohydrate meal (HFHC) with that of a high fiber and fruit meal on the concentrations of endotoxin (LPS), lipopolysaccharide binding protein (LBP), the expression of toll like receptors (TLR) and the suppressor of cytokine signaling-3 (SOCS-3) in mononuclear cells (MNC). Research Design and Methods: Healthy lean subjects were given 910 Calories of either a HFHC meal (n=10) or an American Heart Association (AHA) recommended meal rich in fiber and fruit (n=10) following an overnight fast. Blood was collected before and at 1h, 2h and 3h after the meal. Cellular indices of oxidative and inflammatory stress, the expression of SOCS-3, TLR2 and TLR4 in MNC and plasma concentrations of LPS and LBP were measured. Results: HFHC meal intake induced an increase in plasma LPS concentration and the expression of SOCS-3, TLR2 and TLR4 protein, reactive oxygen species (ROS) generation and nuclear factor kappa B (NFkappaB) binding activity (P<0.05, for all). These increases were totally absent following the AHA meal rich in fiber and fruit. Conclusions: The novel changes described following HFHC meal elucidate further the mechanisms underlying post prandial inflammation and also provide the first evidence explaining the pathogenesis of insulin and leptin resistance mediated by SOCS-3 following such meals. In contrast an AHA meal does not induce these effects.
Hypogonadotropic hypogonadism in men with type 2 diabetes.
Postgrad Med. 2009 May
Dandona P, Dhindsa S, Chandel A, Chaudhuri A.
It has recently been demonstrated that > or = one-third of men with type 2 diabetes mellitus have low testosterone concentrations associated with inappropriately low luteinizing hormone and follicle-stimulating hormone concentrations. Hypogonadotropic hypogonadism in men with type 2 diabetes is associated with obesity but not duration of diabetes, elevated glycosylated hemoglobin, or the presence of microvascular complications of diabetes. Recent data show that hypogonadotropic hypogonadism is also observed frequently in nondiabetics with the metabolic syndrome or obesity, but it is not associated with type 1 diabetes. Low testosterone concentrations in men with type 2 diabetes have also been related to a higher C-reactive protein concentrations, lower hematocrit, increased total and regional adiposity, lower bone mineral density, and erectile dysfunction. This article discusses the pathophysiology of hypogonadotropic hypogonadism in men with type 2 diabetes and its signs and symptoms. Clinical trials are required to determine whether testosterone replacement therapy alleviates insulin resistance, inflammation, and symptoms related to sexual dysfunction care.
Insulin as an anti-inflammatory and antiatherogenic modulator.
J Am Coll Cardiol. 2009 Feb 3
Dandona P, Chaudhuri A, Ghanim H, Mohanty P
Data demonstrate the anti-inflammatory effects of insulin and proinflammatory effects of glucose. These data provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusions in hospitalized patients. Regimens that infuse fixed doses of insulin with high rates of glucose are usually associated with hyperglycemia, which may neutralize the beneficial effects of insulin. Therefore, we propose that such regimens should be avoided and instead replaced by insulin infusions that normalize and maintain blood glucose at a reasonably low level and ensure that plasma insulin is maintained at levels high enough to provide clinically relevant anti-inflammatory and cardioprotective effects. Trials to test this hypothesis are in progress.
Division of Endocrinology, Diabetes, and Metabolism,
State University of New York at Buffalo and Kaleida Health
3 Gates Circle Buffalo, New York 14209, USA.