Abstract
BackgroundSeveral 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.MethodsIn 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.ResultsBoth fasting and 2-hour plasma glucose levels were associated with higher Framingham risk score (fasting glucose: r2 = 0.21; 2-hour glucose: r2 = 0.24; P<0.001 for both), and insulin sensitivity with lower Framingham risk score (r2 = 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).ConclusionThe 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.
Highlights
Type 2 diabetes significantly increases the risk for cardiovascular disease (CVD) and all-cause mortality
Using the euglycemic hyperinsulinemic clamp in 60 middleaged individuals without diabetes, we examined whether associations between hyperglycemia and CVD risk were explained by underlying insulin resistance
Clinical characteristics Clinical characteristics of the study population are shown in Plasma glucose levels and Framingham risk score Both fasting and 2-hour glucose levels were highly significantly related to the Framingham risk score (P,0.001 for both; Figure 1A–B); the correlations were not very strong
Summary
Type 2 diabetes significantly increases the risk for cardiovascular disease (CVD) and all-cause mortality. A meta-analysis of several observational studies showed that the association of CVD risk with post-challenge glucose concentration is stronger than that of fasting plasma glucose [5] These data are supported by the Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe (DECODE), which showed that 2-hour glucose, but not fasting glucose, predicts CVD mortality in individuals with glucose levels within the normal range [6]. It is still unknown which underlying metabolic abnormalities that cause the increased CVD risk in people with elevated 2-hour glucose. We examined whether associations between hyperglycemia and CVD risk were explained by underlying insulin resistance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
