Abstract
Hypoglycemia is associated with increased risk of cardiovascular adverse clinical outcomes. There is evidence that impaired glucose tolerance (IGT) is associated with cardiovascular morbidity and mortality. Whether IGT individuals have asymptomatic hypoglycemia under real-life conditions that are related to early atherosclerosis is unknown. To this aim, we measured episodes of hypoglycemia during continuous interstitial glucose monitoring (CGM) and evaluated their relationship with early manifestation of vascular atherosclerosis in glucose tolerant and intolerant individuals. An oral glucose tolerance test (OGTT) was performed in 79 non-diabetic subjects. Each individual underwent continuous glucose monitoring for 72 h. Cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. IGT individuals had a worse cardiovascular risk profile, including higher IMT, and spent significantly more time in hypoglycemia than glucose-tolerant individuals. IMT was significantly correlated with systolic (r = 0.22; P = 0.05) and diastolic blood pressure (r = 0.28; P = 0.01), total (r = 0.26; P = 0.02) and LDL cholesterol (r = 0.27; P = 0.01), 2-h glucose (r = 0.39; P<0.0001), insulin sensitivity (r = −0.26; P = 0.03), and minutes spent in hypoglycemia (r = 0.45; P<0.0001). In univariate analyses adjusted for gender, minutes spent in hypoglycemia were significantly correlated with age (r = 0.26; P = 0.01), waist circumference (r = 0.33; P = 0.003), 2-h glucose (r = 0.58; P<0.0001), and 2-h insulin (r = 0.27; P = 0.02). In a stepwise multivariate regression analysis, the variables significantly associated with IMT were minutes spent in hypoglycemia (r2 = 0.252; P<0.0001), and ISI index (r2 = 0.089; P = 0.004), accounting for 34.1% of the variation. Episodes of hypoglycemia may be considered as a new potential cardiovascular risk factor for IGT individuals.
Highlights
Hypoglycemia is a well-known side effect of glucose-lowering therapy in both type 1 and type 2 diabetes mellitus, and becomes more prevalent with treatment intensification [1,2]
In univariate analyses adjusted for gender, minutes spent in hypoglycemia were significantly correlated with age (r = 0.26; P = 0.01), waist circumference (r = 0.33; P = 0.003), 2h post-load plasma glucose (r = 0.58; P,0.0001), and 2-h post-load insulin (r = 0.27; P = 0.02)
In univariate analyses adjusted for gender and age, carotid intima–media thickness (IMT) was significantly correlated with systolic and diastolic blood pressure, total and LDL cholesterol, 2h post-load plasma glucose, insulin sensitivity, and minutes spent in hypoglycemia (Table 2)
Summary
Hypoglycemia is a well-known side effect of glucose-lowering therapy in both type 1 and type 2 diabetes mellitus, and becomes more prevalent with treatment intensification [1,2]. Subjects with IGT are characterized by a late insulin response to an oral glucose tolerance test (OGTT), that results in a progressive raise of plasma insulin from 60 to 120 min [10,11]. In these subjects, a persistent increase in insulin levels after a meal may result in late postprandial hypoglycemia. Whether IGT individuals have asymptomatic hypoglycemia under real-life conditions that are related to early atherosclerosis is unknown. We measured episodes of hypoglycemia during continuous interstitial glucose monitoring (CGM) and evaluated their relationship with a early manifestation of vascular atherosclerosis, assessed as carotid intima–media thickness (IMT) in glucose tolerant and intolerant individuals
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