Association between one-hour post-load plasma glucose levels and vascular stiffness in essential hypertension

Objectives: Pulse wave velocity (PWV) is a surrogate end-point for cardiovascular morbidity and mortality. A plasma glucose value $155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes (T2D) and for subclinical organ damage. Thus, we addressed the question if 1-hour post-load plasma glucose levels, affects PWV and its central hemodynamic correlates, as augmentation pressure (AP) and augmentation index (AI). Methods: We enrolled 584 newly diagnosed hypertensives. All patients underwent OGTT and measurements of PWV, AP and AI. Insulin sensitivity was assessed by Matsuda-index. Results: Among participants, 424 were NGT and 160 had impaired glucose tolerance (IGT). Of 424 NGT, 278 had 1-h postload plasma glucose ,155 mg/dl (NGT,155) and 146 had 1-h post-load plasma glucose$155 mg/dl (NGT$155). NGT$155 had a worse insulin sensitivity and higher hs-CRP than NGT,155, similar to IGT subjects. In addition, NGT $155 in comparison with NGT,155 had higher central systolic blood pressure (134612 vs 131610 mmHg), as well as PWV (8.463.7 vs 6.761.7 m/s), AP (12.567.1 vs 9.865.7 mmHg) and AI (29.4611.9 vs 25.1612.4 regression analysis, 1-h post-load plasma glucose resulted the major determinant of all indices of vascular stiffness. Conclusion: Hypertensive NGT$155 subjects, compared with NGT,155, have higher PWV and its hemodynamic correlates that increase their cardiovascular risk profile

Insulin sensitivity, β-cell function, and incretin effect in individuals with elevated 1-hour postload plasma glucose levels

OBJECTIVE: Individuals with normal glucose tolerance (NGT), whose 1-h postload plasma glucose is ≥155 mg/dL (NGT 1h-high), have an increased risk of type 2 diabetes. The purpose of this study was to characterize their metabolic phenotype. RESEARCH DESIGN AND METHODS: A total of 305 nondiabetic offspring of type 2 diabetic patients was consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. RESULTS: Compared with individuals with a 1-h postload plasma glucose <155 mg/dL (NGT 1h-low), NGT 1h-high individuals exhibited lower insulin sensitivity after adjustment for age, sex, and BMI. Insulin secretion estimated from the OGTT did not differ between the two groups of individuals. By contrast, compared with NGT 1h-low individuals, the acute insulin response during an IVGTT and the disposition index were significantly reduced in NGT 1h-high individuals after adjustment for age, sex, and BMI. Incretin effect, estimated as the ratio between total insulin responses during OGTT and IVGTT, was higher in NGT 1h-high individuals compared with NGT 1h-low individuals. CONCLUSIONS: NGT 1h-high individuals may represent an intermediate state of glucose intolerance between NGT and type 2 diabetes characterized by insulin resistance and reduced β-cell function, the two main pathophysiological defects responsible for the development of type 2 diabetes. Postload hyperglycemia is the result of an intrinsic β-cell defect rather than impaired incretin effec

Elevated hemoglobin glycation index identify non-diabetic individuals at increased risk of kidney dysfunction

Hemoglobin glycation index (HGI), calculated as the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose concentration, is a measure of the individual tendency toward non-enzymatic hemoglobin glycation which has been found to be positively associated with nephropathy in subjects with diabetes. In this cross-sectional study we aimed to evaluate whether higher HGI levels are associated with impaired kidney function also among nondiabetic individuals. The study group comprised 1505 White nondiabetic individuals stratified in quartiles according to HGI levels. Estimated glomerular filtration rate (eGFR) was calculated by using the MDRD equation. Individuals in the intermediate and high HGI groups exhibited a worse metabolic phenotype with increased levels of visceral obesity, total cholesterol, triglycerides, inflammatory biomarkers such as hsCRP and white blood cells count and lower values of HDL and insulin sensitivity assessed by Matsuda index in comparison to the lowest quartile of HGI. Subjects in the intermediate and high HGI groups displayed a graded decrease of eGFR levels in comparison with the lowest quartile of HGI. In a logistic regression analysis individuals in the highest quartile of HGI exhibited a significantly 3.6-fold increased risk of having chronic kidney disease (95% CI: 1.13-11.24, P = 0.03) and a significantly 1.6-fold increased risk of having a mildly reduced kidney function (95% CI: 1.19-2.28, P = 0.003) in comparison to individuals in the lowest HGI group. In conclusion HGI may be a useful tool to identify nondiabetic individuals with an increased risk of having kidney dysfunction

Sympathovagal balance and 1-h postload plasma glucose in normoglucose tolerant hypertensive patients.

AIMS: Normoglucose tolerant (NGT) subjects with a 1-h postload plasma glucose (PLPG) value ≥155 mg/dL have an increased risk of type-2 diabetes and subclinical organ damage. Heart rate variability (HRV) reflects cardiac autonomic balance, frequently impaired in course of diabetes. At this time, no data support the association between 1-h PLPG and HRV; thus, we investigated the possible association between 1-h PLPG and HRV. METHODS: We enrolled 92 never-treated hypertensive subjects (56 women, 36 men), aged 55 ± 9.8 years. During OGTT, the patients underwent electrocardiographic recordings to evaluate HRV in the time domain (SDNN). Insulin sensitivity was assessed by Matsuda index. RESULTS: Among participants, 56 were NGT, 20 had impaired glucose tolerance (IGT), and 16 had type-2 diabetes. According to the 1-h PLPG cutoff point of 155 mg/dL, we divided NGT subjects into: NGT &lt; 155 (n = 38) and NGT ≥ 155 (n = 18). Glucose tolerance status was associated with a significant (P &lt; 0.0001) increase in PLPG and insulin and the reduction in Matsuda index. In all groups, the SDNN values significantly (P &lt; 0.0001) decreased during the first hour of OGTT. A complete recovery in NGT groups was observed at the end of the second hour; in IGT and type-2 diabetes, SDNN remained significantly lower with respect to baseline values. At multiple regression analysis, Matsuda index resulted in the only determinant of SDNN modification, explaining the 12.3 % of its variability. CONCLUSIONS: Our data demonstrate that during OGTT, sympathovagal balance is acutely affected by both glucose and insulin modifications. Particularly, NGT ≥ 155 subjects behave in the same way of IGT and type-2 diabetes patients

Cerebral oxygen desaturation occurs frequently in patients with hypertension undergoing major abdominal surgery

Hypertensive patients are more likely to experience latent cerebral ischemia causing regional cerebral oxygen saturation (rSO2) decrease during general anesthesia. The aim of this prospective observational study was to assess the incidence of decreased rSO2 in hypertensive patients undergoing major abdominal surgery and the perioperative factors affecting this change in rSO2. A total of 41 hypertensive patients were enrolled and stratified according to their hypertension as controlled and uncontrolled. The intraoperative rSO2 and physiological data were routinely collected. The Mini-Mental State Exam (MMSE) was used to test cognitive function before surgery and after 4 days. Cerebral desaturation was defined as a decrease in rSO2 of more than 20% of the baseline value. There were 20 patients (49%) suffering intraoperative cerebral desaturation classified into cerebral desaturation group (group D) and those 21 without intraoperative desaturation classified into normal group (group N). The area under the curve below 90 and 80% of baseline (AUCrSO2 <90% of baseline and AUCrSO2 <80% of baseline) was lower in patients of group N (2752.4 ± 1453.3 min% and 0.0 min%) than in patients of group D (6264.9 ± 1832.3 min% and 4486.5 ± 1664.9 min%, P < 0.001). Comparing the two groups, the number of uncontrolled hypertensive individuals in group D (12/20) was significantly more than group N (4/21) (P = 0.007). A significant correlation was observed between relative decrease in MAP and relative decrease in rSO2 (r2 = 0.495, P < 0.001). Moreover, nine patients (45%) in group D occurred early postoperative cognitive function decline were more than three patients (14.3%) in group N (P = 0.031). This pilot study showed a large proportion of hypertensive patient experienced cerebral desaturation during major abdominal surgery and uncontrolled hypertension predisposed to this desaturation. NCT02147275 (registered at http://www.clinicaltrials.gov)

Elevated hemoglobin glycation index identify non-diabetic individuals at increased risk of kidney dysfunction

Hemoglobin glycation index (HGI), calculated as the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose concentration, is a measure of the individual tendency toward non-enzymatic hemoglobin glycation which has been found to be positively associated with nephropathy in subjects with diabetes. In this cross-sectional study we aimed to evaluate whether higher HGI levels are associated with impaired kidney function also among nondiabetic individuals. The study group comprised 1505 White nondiabetic individuals stratified in quartiles according to HGI levels. Estimated glomerular filtration rate (eGFR) was calculated by using the MDRD equation. Individuals in the intermediate and high HGI groups exhibited a worse metabolic phenotype with increased levels of visceral obesity, total cholesterol, triglycerides, inflammatory biomarkers such as hsCRP and white blood cells count and lower values of HDL and insulin sensitivity assessed by Matsuda index in comparison to the lowest quartile of HGI. Subjects in the intermediate and high HGI groups displayed a graded decrease of eGFR levels in comparison with the lowest quartile of HGI. In a logistic regression analysis individuals in the highest quartile of HGI exhibited a significantly 3.6-fold increased risk of having chronic kidney disease (95% CI: 1.13-11.24, P = 0.03) and a significantly 1.6-fold increased risk of having a mildly reduced kidney function (95% CI: 1.19-2.28, P = 0.003) in comparison to individuals in the lowest HGI group. In conclusion HGI may be a useful tool to identify nondiabetic individuals with an increased risk of having kidney dysfunction

Association between non-dipping blood pressure pattern and different glucometabolic profile during oral glucose tolerance test

It is known that, a not physiological blood pressure (BP) circadian pattern has been associated with increased risk of organ damage and cardiovascular (CV) event. The aim of this study was to assess the association between circadian BP pattern and glucometabolic phenotypes occurring after oral glucose tolerance test (OGTT). We recruited 810 hypertensive Caucasian patients. All participants underwent to OGTT, laboratory test and 24-h ambulatory BP monitoring (ABPM). The analysis of collected data allowed classifying patients based on nocturnal BP profiles into four categories: dippers, non-dippers, extreme dippers, and reverse dippers. Considering the dipping pattern, the proportion of non-dippers in normal glucose tolerance patients with 1-h glucose &gt;= 155 mg/dL (NGT &gt;= 155) (36.4%) was higher than NGT &lt; 155 (29.6%) and impaired glucose tolerance (IGT) (34.8%), but lower than type 2 diabetes group (T2DM) (52.6%) (p = 0.001). The proportion of dippers was lower in NGT &gt;= 155 (47%) and T2DM (34.6%), when compared with NGT &lt; 155 (53.8%) and IGT (51.2%) (p = 0.017). From logistic regression analysis, 1-h glucose &gt;= 155 increased the risk of a pathological nocturnal drop in BP by 74%, (OR = 1.740, 95% CI 1.254-2.415, p &lt; 0.0001). In addition, the improvement in 1 unit of Matsuda was responsible for a 3.5% risk decrease (OR = 0.965, 95% CI 0.958-0.971, p &lt; 0.0001), while e-GFR determined a 0.9% risk reduction of nocturnal BP drop (OR = 0.991, 95% CI 0.984-0.999, p = 0.020). Our data demonstrated the existence, in newly diagnosed hypertensive patients, of an association between circadian BP profile and altered glycemic response during OGTT, in particular NGT &gt;= 155 subjects are associated with a non-dipper BP pattern, this is clinically relevant because may explain, at least in part, the increased CV risk in this setting of patients

Sex-specific differences in left ventricular mass and myocardial energetic efficiency in non-diabetic, pre-diabetic and newly diagnosed type 2 diabetic subjects

Background: Women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than their male counterparts. However, whether the risk for CVD is higher in prediabetic women than men is still debated. We aimed to determine whether sex-related differences exist in left ventricular mass index (LVMI), and myocardial mechano-energetic efficiency (MEEi) in with normal glucose tolerant (NGT), pre-diabetic and newly diagnosed type 2 diabetic subjects. Methods: Sex-related differences in LVMI and myocardial MEEi, assessed by validated echocardiography-derived measures, were examined among 1562 adults with NGT, prediabetes, and newly diagnosed T2DM, defined according to fasting glucose, 2-h post-load glucose, or HbA1c. Results: Worsening of glucose tolerance in both men and women was associated with an increase in age-adjusted LVMI and myocardial MEEi. Women with newly diagnosed T2DM exhibited greater relative differences in LVMI and myocardial MEEi than diabetic men when compared with their NGT counterparts. Prediabetic women exhibited greater relative differences in myocardial MEEi, but not in LVMI, than prediabetic men when compared with their NGT counterparts. The statistical test for interaction between sex and glucose tolerance on both LVMI (P &lt; 0.0001), and myocardial MEEi (P &lt; 0.0001) was significant suggesting a sex-specific association. Conclusions: Left ventricle is subject to maladaptive changes with worsening of glucose tolerance, especially in women with newly diagnosed T2DM. The sex-specific increase in LVM and decrease in MEEi, both being predictors of CVD, may have a role in explaining the stronger impact of T2DM on the excess risk of CVD in women than in men