Does Insulin Resistance Drive the Association between Hyperglycemia and Cardiovascular Risk?

被引:16
作者
Faerch, Kristine [1 ]
Bergman, Bryan [2 ]
Perreault, Leigh [2 ]
机构
[1] Steno Diabet Ctr, DK-2820 Gentofte, Denmark
[2] Univ Colorado, Aurora, CO USA
基金
美国国家卫生研究院;
关键词
IMPAIRED GLUCOSE-TOLERANCE; CORONARY-HEART-DISEASE; ALL-CAUSE; MORTALITY; PIOGLITAZONE; EVENTS; COMPLICATIONS; PROGRESSION; PREVENTION; FRAMINGHAM;
D O I
10.1371/journal.pone.0039260
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Several studies have shown associations between hyperglycemia and risk of cardiovascular disease (CVD) and mortality, yet glucose-lowering treatment does little to mitigate this risk. We examined whether associations between hyperglycemia and CVD risk were explained by underlying insulin resistance. Methods: In 60 middle-aged individuals without diabetes we studied the associations of fasting plasma glucose, 2-hour post oral glucose tolerance test plasma glucose, insulin sensitivity as well as body fat percentage with CVD risk. Insulin sensitivity was measured as the glucose infusion rate during a euglycemic hyperinsulinemic clamp, body fat percentage was measured by dual X-ray absorptiometry, and CVD risk was estimated using the Framingham risk score. Associations of fasting plasma glucose, 2-hour plasma glucose, insulin sensitivity and body fat percentage with the Framingham risk score were assessed in linear regression models. Results: Both fasting and 2-hour plasma glucose levels were associated with higher Framingham risk score (fasting glucose: r(2) = 0.21; 2-hour glucose: r(2) = 0.24; P<0.001 for both), and insulin sensitivity with lower Framingham risk score (r(2) = 0.36; P<0.001). However, adjustment for insulin sensitivity and 2-hour glucose made the effect of fasting glucose non-significant (P = 0.060). Likewise, when adjusting for insulin sensitivity and fasting glucose, the association between 2-hour glucose and Framingham risk score disappeared (P = 0.143). In contrast, insulin sensitivity was still associated with Framingham risk score after adjusting for glucose levels (P<0.001). Body fat was not associated with Framingham risk score when taking insulin sensitivity into account (P = 0.550). Conclusion: The association between plasma glucose levels and CVD risk is mainly explained by insulin resistance, which raises the question of whether glucose lowering per se without changes in the processes that underlie hyperglycemia should be the sole clinical paradigm in the treatment of type 2 diabetes or its prevention.
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页数:6
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