Abstract
Prediabetes is a strong predictor of type 2 diabetes and its associated cardiovascular complications, but few studies explore sexual dimorphism in this context. Here, we aim to determine whether sex influences physiological response to high-fat high-sucrose diet (HFS) and myocardial tolerance to ischemia-reperfusion injury. Male and female Wistar rats were subjected to standard (CTRL) or HFS diet for 5 months. Then, ex-vivo experiments on isolated perfused heart model were performed to evaluate tolerance to ischemia-reperfusion injury. HFS diet induced fasting hyperglycemia and increased body fat percent to a similar level in both sexes. However, glucose intolerance was more pronounced in female HFS. Cholesterol was increased only in female while male displayed higher level of plasmatic leptin. We observed increased heart weight to tibia length ratio only in males, but we showed a similar decrease in tolerance to ischemia-reperfusion injury in female and male HFS compared with respective controls, characterized by impaired cardiac function, energy metabolism and coronary flow during reperfusion. In conclusion, as soon as glucose intolerance and hyperglycemia develop, we observe higher sensitivity of hearts to ischemia-reperfusion injury without difference between males and females.
Highlights
According to the American Diabetes Association, prediabetes can be defined as elevated fasting plasma glucose 100–125 mg/dL (5.6–6.9 mmol/L), 2-h plasma glucose140–199 mg/dL (7.8–11.0 mmol/L), or HbA1c 5.7–6.4% (39–46 mmol/mol) [1,2]
We previously showed that five months high-fat high-sucrose (HFS) diet induced prediabetes in female Wistar rats [18], defined by mild hyperglycemia and glucose intolerance
F-HFS (p < 0.001) indicating that males are more prone to gain weight than females. In line with these results, we showed an increase in plasma level of leptin at 5 months (Figure 2D)
Summary
According to the American Diabetes Association, prediabetes can be defined as elevated fasting plasma glucose 100–125 mg/dL (5.6–6.9 mmol/L), 2-h plasma glucose. 140–199 mg/dL (7.8–11.0 mmol/L), or HbA1c 5.7–6.4% (39–46 mmol/mol) [1,2] This is a reversible condition preceding well-established type 2 diabetes [3], highly related to sedentary lifestyle and consumption of high fat and/or high sucrose diet. It is estimated that 5 to 10% of the prediabetic population will develop type 2 diabetes annually, while the risk in the normoglycemic population is around 0.7% [1]. People without type 2 diabetes but with the highest post-challenge blood glucose level have 27% greater risk for CV diseases than patients with the lowest post-challenge blood glucose level [7]. Type 2 diabetes affects differently men and women regarding the associated
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