Impaired Fasting Glucose and Impaired Glucose Tolerance Have Distinct Lipoprotein and Apolipoprotein Changes: The Insulin Resistance Atherosclerosis Study

Division of Clinical Epidemiology (C.L., S.H.), University of Texas Health Science Center, San Antonio, Texas 78229
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 02/2013; 98(4). DOI: 10.1210/jc.2012-3185
Source: PubMed


Context:Cardiovascular risk is increased in individuals with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG); however, those with IGT appear to be at greater risk. Lipoprotein abnormalities occur also in the prediabetic state.Objective:The authors examined lipoprotein composition in IGT and IFG.Design and Setting:Cross-sectional analysis of a large epidemiological study was done.Participants:The Insulin Resistance Atherosclerosis Study had a total of 1107 participants.Main measures:Lipoproteins and apolipoproteins were measured by conventional methods and lipoprotein composition by nuclear magnetic resonance spectroscopy.Results:Compared with normal glucose tolerance, apolipoprotein B (105.2 vs 99.8 mg/dL, P < .05) was high in isolated IFG, triglyceride (1.48 vs 1.16 mmol/L, P < .001) was high in isolated IGT, and high-density lipoprotein cholesterol was low in combined IFG/IGT (1.12 vs 1.26 mmol/L, P < .001). Nuclear magnetic resonance spectroscopy revealed additional changes: increased total low-density lipoprotein (LDL) particles (1190 vs 1096 nmol/L, P < .01) in isolated IFG; increased large very-low-density lipoprotein (3.61 vs 2.47 nmol/L, P < .01) and small LDL subclass particles (665 vs 541 nmol/L, P < .05) and decreased large LDL subclass particles (447 vs 513 nmol/L, P < .01) in isolated IGT; and decreased large high-density lipoprotein subclass particles in combined IFG/IGT (4.24 vs 5.39 μmol/L, P < .001).Conclusions:Isolated IFG is characterized by increased apolipoprotein B and total LDL particles, whereas isolated IGT is associated with increased triglycerides, large very-low-density lipoprotein subclass particles, and structural remodeling of LDL particles. These results may help to explain differences in cardiovascular disease risk in the prediabetic state.

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    • "However, such correlations were not identified in i-IFG subjects, even though the sample size was the largest in this group among the three prediabetes subjects. Similar to the results reported by Lorenzo et al. [20], in our study, TG levels were higher in i-IGT subjects compared with i-IFG subjects. Van der Zijl et al. [21] showed that lipid accumulation in the pancreas was positively associated with TG levels and negatively with HDL-C levels. "
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    ABSTRACT: Background Increased triglycerides (TGs) and decreased high density lipoprotein cholesterol (HDL-C) levels are established as diabetic risks for nondiabetic subjects. The aim of this study was to investigate the relationship among TG, HDL-C, TG/HDL-C ratio, and early-phase insulin secretion in normoglycemic and prediabetic subjects. Methods We evaluated 663 Japanese subjects who underwent the 75-g oral glucose tolerance test. On the basis of these results, the subjects were divided into four groups: those with normal glucose tolerance (NGT; n=341), isolated impaired fasting glucose (i-IFG; n=211), isolated impaired glucose tolerance (i-IGT; n=71), and combined IFG and IGT (IFG+IGT; n=40). Insulin secretion was estimated by the insulinogenic index (IGI) (Δinsulin/Δglucose [30 to 0 minutes]) and disposition index (DI) (IGI/homeostasis model assessment of insulin resistance). Results In prediabetic subjects (i-IFG, i-IGT, and IFG+IGT), linear regression analyses revealed that IGI and DI were positively correlated with HDL-C levels. Moreover, in subjects with i-IGT and (IFG+IGT), but not with i-IFG, the indices of insulin secretion were negatively correlated with the log-transformed TG and TG/HDL-C ratio. In both the subjects with i-IGT, multivariate linear regression analyses revealed that DI was positively correlated with HDL-C and negatively with log-transformed TG and TG/HDL-C ratio. On the other hand, in subjects with NGT, there was no association between insulin secretion and lipid profiles. Conclusion These results revealed that serum TG and HDL-C levels have different impacts on early-phase insulin secretion on the basis of their glucose tolerance status.
    Diabetes & metabolism journal 08/2014; 38(4):294-301. DOI:10.4093/dmj.2014.38.4.294
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    ABSTRACT: Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance, however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT or IFG+IGT is unknown. Twenty-four older (66.7±0.8yr) obese (34.2±0.9kg/m(2)) adults were categorized as IFG (n=8), IGT (n=8), or IFG+IGT (n=8) according to a 75-gram oral glucose tolerance test (OGTT). Subjects underwent 12-weeks of exercise (60 min/d for 5 d/wk at ~85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic-hyperinsulinemic clamp (40 mU/m(2)/min) with [6,6-(2)H]-glucose was used to determine peripheral and hepatic insulin sensitivity. Non-oxidative glucose disposal and metabolic flexibility (insulin-stimulated respiratory quotient [RQ] minus fasting RQ) were also assessed. Glucose incremental area under the curve was calculated from the OGTT (iAUCOGTT). Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than IFG+IGT (P<0.05). Exercise reduced glucose iAUCOGTT in IGT only (P<0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral, but not hepatic, insulin sensitivity (P<0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher non-oxidative glucose disposal (P<0.05). Adults with IFG+IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in post-prandial glucose. Further work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.
    AJP Endocrinology and Metabolism 09/2013; 305(10). DOI:10.1152/ajpendo.00441.2013 · 3.79 Impact Factor
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    ABSTRACT: Impaired glucose tolerance (IGT) is an independent risk factor for atherosclerotic cardiovascular disease. However, due to the lack of appropriate animal models, the underlying mechanisms for IGT-induced atherosclerosis remain to be elucidated in vivo. We recently used selective breeding to establish 2 mouse lines with distinctively different susceptibilities to diet-induced glucose intolerance, designated selectively bred diet-induced glucose intolerance-resistant (SDG-R) and SDG-prone (SDG-P), respectively. Here, we assessed atherosclerotic lesion formation in these mice. Female SDG-R and SDG-P mice were fed an atherogenic diet (AD; 1.25% cholesterol, 0.5% sodium cholate, and 36% energy as fat) for 20 weeks (8-28 weeks of age). Oral glucose tolerance tests were performed during the AD-feeding period. Atherosclerotic lesion formation was quantitatively analyzed in serial aortic sinus sections by oil red O staining. Plasma lipids were measured after the AD-feeding period. Glucose tolerance was impaired in SDG-P mice as compared to SDG-R mice over the 20-week AD-feeding period. No significant differences were observed in any plasma lipid measurement between the 2 mouse lines. Aortic sinus atherosclerotic lesion formation in SDG-P mice was approximately 4-fold greater than that in SDG-R mice. In 2 mouse lines with different susceptibilities to diet-induced glucose intolerance, IGT accelerated atherosclerotic lesion formation. These mice may therefore serve as useful in vivo models for investigating the causal role of IGT in the pathogenesis of atherosclerosis.
    Atherosclerosis 12/2013; 231(2):421-426. DOI:10.1016/j.atherosclerosis.2013.10.009 · 3.99 Impact Factor
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