Association of Estimated Glucose Disposal Rate With the Stenosis Severity of Coronary Artery Disease： A Cross-sectional Study / 中山大学学报(医学科学版)

ObjectiveTo investigate the association between estimated glucose disposal rate （eGDR） and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients （mean age： 62（53-68） years） who underwent coronary angiography for suspected coronary artery disease （53.9% were male）. Insulin resistance level （IR） was calculated according to eGDR formula： eGDR = 21.158 - （0.09 × WC） - （3.407 × hypertension） - （0.551 × HbA1c） ［hypertension （yes = 1 / no = 0）， HbA1c = HbA1c （%）］. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels： no-obstructive CAD group （all coronary stenosis were<50%， n=704）， Single-vessel CAD group （only one involved major coronary artery stenosis≥50%， n=205）， Multi-vessel CAD group （two or more involved major coronary arteries stenosis≥50%， n=349）； Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic （ROC） curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. In multivariate logistic regression models， individuals with the lowest quantile of eGDR （T1） were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR （T3） （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD （P-nonlinear>0.05）. In non-diabetic patients， compared with the reference group （T3）， the T1 group had a significantly increased risk of CAD （OR： 1.42； 95% CI： 1.00~2.01； P<0.05） and multi-vessel CAD （OR： 1.86； 95%CI： 1.21~2.86； P<0.05）. No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis， when eGDR was added to traditional model for CAD， significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR， as a non-insulin measure to assess IR， could be a valuable indicator of CAD severity for population.

Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate

Since the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (T2D). There are also situations where muscle insulin resistance can occur independently from high-fat dietary intake such as sepsis, inflammation, or drug administration though they all may share the same underlying mechanism, i.e., via activation of forkhead box family of transcription factors, and to a lower extent via peroxisome proliferator-activated receptors. The main feature of T2D is a chronic elevation in blood glucose levels. Chronic systemic hyperglycaemia is toxic and can lead to cellular dysfunction that may become irreversible over time due to deterioration of the pericyte cell's ability to provide vascular stability and control to endothelial proliferation. Therefore, it may not be surprising that T2D's complications are mainly macrovascular and microvascular related, i.e., neuropathy, retinopathy, nephropathy, coronary artery, and peripheral vascular diseases. However, life style intervention such as exercise, which is the most potent physiological activator of muscle PDC, along with pharmacological intervention such as administration of dichloroacetate or L-carnitine can prove to be viable strategies for treating muscle insulin resistance in obesity and T2D as they can potentially restore whole body glucose disposal.

The Relationship of Insulin Resistance to High-Sensitivity C-Reactive Protein / 대한임상병리학회지

BACKGROUND: Insulin resistance is known as the common denominator of risk factors of atheros-clerosis as well as the major pathogenic process of type 2 diabetes mellitus (DM). Recently some investigators indicated the relationship of chronic inflammatory reaction to atherosclerosis and insulin resistance. We examined the relationship between insulin resistance and high sensitivity CRP (hs-CRP) in Koreans. METHODS: Twenty-five patients with type 2 DM and eleven healthy men were examined. Glucose disposal rate (GDR, mg/kg/min) was determined as the index of insulin resistance by the euglycemic insulin clamp test with De Fronzo method. The serum hs-CRP level was determined by Behring nephelometric assay, fibrinogen by functional assay, and plasminogen activator inhibitor-1 (PAI-1) by ELISA. We also included 81 healthy subjects to determine the reference range of hs-CRP. RESULTS: The reference range (median) of hs-CRP was 0-5.20 (0.56) mg/L. The hs-CRP concentration was not significantly different between control and DM groups. The GDR of DM (3.8+/-1.7) showed significantly decreased value compared with normal (8.4+/-1.5) group (P<0.001). In all subjects, there was no significant correlation of GDR and hs-CRP. CONCLUSTIONS: There was no significant correlation of GDR and hs-CRP. We think the interventional prospective study with anti-inflammatory drug is warranted to elucidate the independent relationship between insulin resistance and hs-CRP.

CLINICAL STUDY ON THE HYPOGLYCEMIC EFFECT OF GLIPIZIDE IN PATIENTS WITH TYPE II DIABETES MELLITUS / 中华内分泌代谢杂志

Twenty-five type II diabetics failed to be controlled by diet therapy alone were treated with glipizide and followed-up for 6 months. The daily dose of glipizide ranged from 5-30 mg. The excellent or good glycemic control occurred in 88% and 72% of the patients respectively. No hypoglycemia and other side effects were observed. The areas of glipizide-glucose mediated insulin secretion did not show significant change before and after glipizide therapy, but the areas of glucose-mediated insulin secretion, the insulin sensitivity, and the glucose disposal constant(KI)were significantly higher after glipizide therapy. Our study indicated that the hypoglycemic effect of glipizide was not only due to improved islet B cell function in insulin secretion, but also due to enhanced insulin-induced glucose utilization and insulin sensitivity.