Association between insulin resistance and c-reactive protein among Peruvian adults

<p>Abstract</p> <p>Objective</p> <p>Insulin resistance (IR), a reduced physiological response of peripheral tissues to the action of insulin, is one of the major causes of type 2 diabetes. We sought to evaluate the relationship between serum C-reactive protein (CRP), a marker of systemic inflammation, and prevalence of IR among Peruvian adults.</p> <p>Methods</p> <p>This population based study of 1,525 individuals (569 men and 956 women; mean age 39 years old) was conducted among residents in Lima and Callao, Peru. Fasting plasma glucose, insulin, and CRP concentrations were measured using standard approaches. Insulin resistance was assessed using the homeostasis model (HOMA-IR). Categories of CRP were defined by the following tertiles: <0.81 mg/l, 0.81-2.53 mg/l, and >2.53 mg/l. Logistic regression procedures were employed to estimate odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Elevated CRP were significantly associated with increased mean fasting insulin and mean HOMA-IR concentrations (p < 0.001). Women with CRP concentration >2.53 mg/l (upper tertile) had a 2.18-fold increased risk of IR (OR = 2.18 95% CI 1.51-3.16) as compared with those in the lowest tertile (<0.81 mg/l). Among men, those in the upper tertile had a 2.54-fold increased risk of IR (OR = 2.54 95% CI 1.54-4.20) as compared with those in the lowest tertile.</p> <p>Conclusion</p> <p>Our observations among Peruvians suggest that chronic systemic inflammation, as evidenced by elevated CRP, may be of etiologic importance in insulin resistance and diabetes.</p

Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance?

BACKGROUND: The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. PRESENTATION OF THE HYPOTHESIS: We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. TESTING THE HYPOTHESIS: Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10) increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. IMPLICATIONS OF THE HYPOTHESIS: If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier

Endothelial derived vasoactive factors and leukocyte derived inflammatory mediators in subjects with asymptomatic atherosclerosis

To clarify relationships between the (endothelial vasodilatory and vasoconstrictive function) and leukocyte inflammatory mediators in subjects with asymptomatic atherosclerosis, we measured (intraplatelet cyclic 3', 5' guanosine monophosphate [cGMP] and cyclic 3', 5' adenosine monophosphate [cAMP]), plasma endothelin (ET-1), and plasma neopterin in 197 subjects with asymptomatic atherosclerosis (median age 63 years, range 49-69 years). We measured neutrophil protease 4 (NP4), tumor necrosis factor (TNFμ), soluble tumor necrosis factor receptor-1 (sTNFR-1), and neutrophil gelatinase associated lipocalin (NGAL) in 152 of the 197 subjects. Intraplatelet cGMP correlated inversely with plasma ET-1 (r=-0.22; p=0.01), which confirms earlier in vitro data of the inhibitory effect of ET-1 on NO production and/or the cGMP mediated inhibitory effect of NO on ET-1 production. Plasma neopterin as well as NP4 correlated directly with intraplatelet cGMP (r=0.24; p<0.01 and r=0.33; p<0.001, respectively). Intraplatelet cAMP correlated directly with plasma TNFμ (r=0.17; p<0.05) and sTNFR-1 (r=0.20; p<0.05). The relationship between leukocyte derived inflammatory mediators and intraplatelet cyclic nucleotides suggest an antiaggregating effect of leukocytes upon platelets, which may constitute a negative feedback mechanism that inhibits platelet activation during the atherosclerotic inflammatory process