Association between hemoglobin glycation index with insulin resistance and carotid atherosclerosis in non-diabetic individuals

Abstract

Hemoglobin glycation index (HGI), defined as the difference between the observed HbA1c value and the value of HbA1c predicted from plasma glucose levels, represents a measure of the degree of non-enzymatic glycation of hemoglobin and it has been found to be positively associated with micro- and macro-vascular complications in subjects with type 2 diabetes. To investigate the pathophysiological abnormalities responsible for the increased cardiovascular risk of patients with higher HGI, we evaluated the association of HGI with cardio-metabolic characteristics in nondiabetic offspring of type 2 diabetic individuals. Insulin sensitivity, measured by a hyperinsulinemic-euglycemic clamp, cardio-metabolic risk factors including lipid profile, uric acid and inflammatory factors, and ultrasound measurement of carotid intima–media thickness (IMT) were assessed in 387 nondiabetic individuals. Participants were stratified in tertiles according to HGI (high, moderate and low). As compared with subjects with low HGI, those with high HGI displayed an unfavorable cardio-metabolic risk profile having significantly higher values of BMI, waist circumference, triglycerides, uric acid, fasting insulin, inflammatory markers, such as high sensitivity C reactive protein, erythrocytes sedimentation rate, complement C3, fibrinogen, and white blood cell count, and carotid IMT, and lower HDL and insulin-stimulated glucose disposal. In a linear regression analysis model including several atherosclerotic risk factors such as gender, age, BMI, inflammatory factors, lipid profile, insulin-stimulated glucose disposal, fasting insulin, uric acid, and blood pressure, HGI was the major predictor of IMT (β = 0.35; P = 0.001). In a logistic regression analysis adjusted for confounders, individuals with high HGI showed a 2.7-fold increased risk of vascular atherosclerosis (OR 2.72, 95%CI 1.01–7.37) as compared with subjects with low HGI. The present findings support the notion that HGI may be a useful tool to identify a subset of nondiabetic individuals conceivably harboring a higher risk of cardiovascular disease.

Association between hemoglobin glycation index and hepatic steatosis in non-diabetic individuals

“…An increased HGI level, calculated using fasting plasma glucose concentration to predict HbA1c value, has been recently shown to identify a subgroup of the ACCORD population with a greater risk of diabetic complications, hypoglycemia and total mortality [22]. Moreover we have recently found that higher HGI levels may identify subjects with an increased risk of vascular atherosclerosis also among individuals without diabetes [27]. In the present cross-sectional study, for the first time, we report an association between HGI and liver steatosis in subjects not affected by diabetes.…”

“…The design of the CATAMERI study has been previously reported [14,[25][26][27]. The study cohorts include 2055 participants used to estimate the linear relationship between fasting plasma glucose and HbA1c in the study population to calculate the predicted HbA1c value, and 1120 individuals in whom hepatic steatosis was assessed by ultrasonography.…”

“…The study cohorts include 2055 participants used to estimate the linear relationship between fasting plasma glucose and HbA1c in the study population to calculate the predicted HbA1c value, and 1120 individuals in whom hepatic steatosis was assessed by ultrasonography. All participants were consecutively recruited at the Department of Medical and Surgical Sciences of the University ''Magna Graecia" of Catanzaro [14,[25][26][27]. Exclusion criteria included: history of type 1 or type 2 diabetes mellitus, heart failure, end stage renal disease, haemoglobinopathies or anemia, history of malignant disease, gastrointestinal diseases associated with bleeding or malabsorption, autoimmune diseases, acute or chronic infections, positivity for antibodies to hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg), accumulation diseases such as amyloidosis and hemochromatosis, history of drug abuse, self-reporting alcohol consumption of >20 g/day, and history of treatments known to induce liver injury including tamoxifen, glucocorticoids, tetracycline, estrogens, methotrexate, and amiodarone.…”

“…A predicted value of HbA1c was calculated by inserting fasting plasma glucose concentration into the sub-sample linear regression equation (HbA1c = 0.0158 * fasting glucose levels (mg/dl) +4.0311). HGI was calculated by subtracting the predicted value of HbA1c from the observed HbA1c level for all participants, as previously described [22,27]. Study participants (1120 subjects) were stratified into quartiles according to their HGI value.…”

“…Nevertheless, no studies have been carried out to assess the correlation between HGI and NAFLD in subjects without type 2 diabetes. To address this issue, we sought to evaluate whether HGI is associated with hepatic steatosis and related biomarkers in a large cohort of adult White subjects participating to the CATAnzaro MEtabolic RIsk factors (CATAMERI) study [14,[25][26][27].…”