Fasting hyperinsulinemia associates with increased sub-clinical inflammation in first-degree relatives normal glucose tolerant women independently of the metabolic syndrome.
BACKGROUND
To evaluate the influence of gender on the relationship between inflammation and hyperinsulinemia in first-degree relatives of type 2 diabetic patients independently of metabolic syndrome.


METHODS
Study group consisted in 217 first-degree relatives with normal glucose tolerance after an oral glucose tolerance test. A logistic analysis, adjusted for age, sex and all the components of the metabolic syndrome, was used to determine the relationship between interleukin-6 (IL-6) and leptin and tertiles of fasting insulin, and to take into account the influence of gender.


RESULTS
In the whole cohort, IL-6 and leptin were significantly higher and adiponectin significantly lower in the III tertile when corrected for age, body mass index (BMI) and metabolic syndrome components. In women, but not in men, IL-6 and leptin remained significantly higher when corrected for metabolic syndrome. In the whole cohort and in women, univariate correlations between IL-6 concentrations and the parameters under evaluation showed that IL-6 and leptin were positively correlated with age, BMI, waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, fasting insulin, Delta AUC insulin area, triglyceride (TG), free fatty acids (FFA) and monocyte chemoattractant protein-1 (MCP-1) and inversely correlated with HDL cholesterol (HDL-C) and adiponectin. In women a forward stepwise linear regression analysis in a model including age, BMI, features of metabolic syndrome, fasting insulin, Delta AUC insulin and insulin sensitivity index (ISI) index revealed that only IL-6 and leptin were independently associated with fasting insulin levels.


CONCLUSIONS
In first-degree relatives normal glucose tolerant women, fasting hyperinsulinemia, independently of the presence of metabolic syndrome, is associated with elevated IL-6 and leptin levels, suggesting an increased cardiovascular risk.
Setola
Emanuela
E
Cardio-Metabolic and Clinical Trials Unit and Cardiodiabetes & Core-Lab, Metabolic and Cardiovascular Science Division and Internal Medicine Department, San Raffaele Scientific Institute, Milan, Italy.
Monti
Lucilla D
LD
Lucotti
Pietro
P
Galluccio
Elena
E
Oldani
Matteo
M
Bosi
Emanuele
E
Piatti
PierMarco
P
D052242:Adiponectin / Q000097:blood; D000328:Adult; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications* / Q000235:genetics; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000235:genetics; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D012727:Sex Characteristics
D052242:Adiponectin; D007328:Insulin; D015850:Interleukin-6