Background
Nonalcoholic fatty liver disease (NAFLD) is linked to a raised risk of cardiovascular diseases (CVD), although the underlying mechanisms are not completely known. A reduced myocardial ...mechano‐energetic efficiency (MEE) has been found to be an independent predictor of CVD.
Objective
To evaluate the association between NAFLD and a compromised MEE.
Methods
Myocardial MEE was assessed by a validated echocardiography‐derived measure in 699 nondiabetic individuals subdivided into two groups according to ultrasonography defined presence of NAFLD.
Results
Subjects with NAFLD displayed higher levels of systolic (SBP) and diastolic blood pressure (DBP), triglycerides, fasting and postload glucose, high‐sensitivity C‐reactive protein (hsCRP), insulin resistance (IR) estimated by HOMA‐IR and liver IR index, and lower values of high‐density lipoprotein (HDL) in comparison with those without NAFLD. Presence of NAFLD was associated with increased levels of myocardial oxygen demand and reduced values of MEE. MEE was negatively correlated with male sex, age, BMI, waist circumference, SBP, DBP, total cholesterol, triglycerides, fasting and postload glucose, HOMA‐IR and liver IR index, hsCRP and positively with HDL levels. In a multivariable regression analysis, presence of NAFLD was associated with MEE regardless of several cardio‐metabolic risk factors such as age, gender, waist circumference, SBP, DBP, total and HDL cholesterol, triglycerides, glucose tolerance and hsCRP (β = −0.09, P = 0.04), but not independently of IR estimates.
Conclusion
Ultrasound‐defined presence of NAFLD is associated with a decreased MEE, a predictor of adverse cardiovascular events. The relationship between NAFLD and a compromised MEE is dependent of IR.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
To compare the effect of liraglutide, sitagliptin and insulin glargine added to standard therapy on left ventricular function in post-ischemic type-2 diabetes mellitus patients.
Methods
We ...evaluated 32 type-2 diabetes mellitus Caucasians with history of post-ischemic chronic heart failure NYHA class II/III and/or left ventricular ejection fraction ≤45 %. Participants underwent laboratory determinations, electrocardiogram, echocardiogram, Minnesota Living with Heart Failure questionnaire and 6 min walking test at baseline and following 52 weeks treatment. Patients were treated with standard therapy for chronic heart failure and were randomized to receive liraglutide, sitagliptin and glargine in addition to metformin and/or sulfonylurea.
Results
Liraglutide treatment induced an improvement in left ventricular ejection fraction from 41.5 ± 2.2 to 46.3 ± 3 %;
P
= 0.001). On the contrary, treatment with sitagliptin and glargine induced no changes in left ventricular ejection fraction (41.8 ± 2.6 vs. 42.5 ± 2.5 % and 42 ± 1.5 vs. 42 ± 1.6 %, respectively;
P
= NS). Indexed end-systolic LV volume was reduced only in liraglutide-treated patients (51 ± 9 vs. 43 ± 8 ml/m
2
;
P
< 0.05). Liraglutide treatment induced also a significant increase in the anterograde stroke volume (39 ± 9 vs. 49 ± 11 ml;
P
< 0.05), whereas no differences were observed in the other two groups. Cardiac output and cardiac index showed a significant increase only in liraglutide-treated patients (4.4 ± 0.5 vs. 5.0 ± 0.6 L/min;
P
< 0.05 and 1.23 ± 0.26 vs. 1.62 ± 0.29 L/m
2
;
P
= 0.005, respectively).
Liraglutide treatment was also associated with an improvement of functional capacity and an improvement of quality of life.
Conclusions
These data provide evidence that treatment with liraglutide is associated with improvement of cardiac function and functional capacity in failing post-ischemic type-2 diabetes mellitus patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Objective To examine whether individuals with normal glucose tolerance (NGT), whose 1-h post-load plasma glucose is ≥155 mg/dl, or with impaired glucose tolerance (IGT) have an increased ...carotid intima–media thickness (IMT), as compared with NGT individuals with 1-h post-load plasma <155 mg/dl. Methods Atherosclerosis risk factors, oral glucose tolerance test (OGTT), and ultrasound manual measurement of IMT were analyzed in 400 non-diabetic Caucasians. Results As compared with individuals with a 1-h post-load plasma glucose <155 mg/dl, NGT individuals with a 1-h post-load plasma glucose ≥155 mg/dl exhibited higher hsCRP (2.0 ± 1.5 vs. 1.5 ± 1.0, P = 0.008), and IMT (0.82 ± 0.20 vs. 0.71 ± 0.16; P = 0.006), and lower insulin sensitivity (71 ± 39 vs. 105 ± 57; P < 0.0001), and IGF-1 levels (214 ± 88 vs. 176 ± 49; P < 0.03). No significant differences were observed in metabolic and cardiovascular risk factors between IGT and NGT subjects with a 1-h post-load glucose ≥155 mg/dl. Of the three glycemic parameters, 1-h and 2-h post-load glucose, but not fasting glucose, were significantly correlated with IMT. In a stepwise multivariate regression analysis in a model including age, gender, and a variety of atherosclerosis risk factors, the three variables that remained significantly associated with IMT were age ( P < 0.0001), BMI ( P < 0.0001), and 1-h post-load glucose ( P = 0.02) accounting for 20.2% of its variation. Conclusions NGT subjects with a 1-h post-load glucose ≥155 mg/dl have an atherogenic profile similar to IGT individuals. These data suggest that a cutoff point of 155 mg/dl for the 1-h post-load glucose during OGTT may be helpful in the identification of NGT subjects at increased risk for cardiovascular disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Aims/hypothesis Minimal model analysis for insulin sensitivity has been validated against the glucose clamp and is an accepted method for estimating insulin sensitivity from IVGTT. However minimal ...model analysis requires a 3 h test and relevant expertise to run the mathematical model. The aim of this study was to suggest a simple predictor of minimal model analysis index using only 1 h IVGTT. Methods We studied participants with different clinical characteristics who underwent 3 h regular (n = 336) or insulin-modified (n = 160) IVGTT, or 1 h IVGTT and euglycaemic-hyperinsulinaemic clamp (n = 247). Measures of insulin sensitivity were insulin sensitivity index estimated by minimal model analysis (SI) and the mean glucose infusion rate (clamp) (M). A calculated SI (CSI) predictor, graphic removed , was suggested, based on the calculation of the rate of glucose disappearance K G and the suprabasal AUC of insulin concentration ΔAUCINS over T = 40 min. For all the participants, α was assumed equal to the regression line slope between K G/(ΔAUCINS/T) and SI in control participants. Results CSI and SI showed high correlation (R ² = 0.68-0.96) and regression line slopes of approximately one in the majority of groups. CSI tended to overestimate SI in type 2 diabetic participants, but results were more reliable when CSI was computed with insulin-modified rather than regular IVGTT. CSI showed behaviours similar to SI as regards relationships with BMI, acute insulin response and sex. CSI showed good correlation with M (R ² = 0.82). Conclusions/interpretation A short test can achieve a good approximation of minimal model analysis and clamp insulin sensitivity. The importance of a method such as CSI is that it allows analysis of IVGTT datasets with samples limited to 1 h.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A link between increased blood viscosity and type 2 diabetes has been previously reported. Herein, we investigated the association of blood viscosity with prediabetes, identified by glycated ...hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria, and subclinical atherosclerosis.
The study cohort includes 1136 non-diabetic adults submitted to anthropometrical evaluation, an oral glucose tolerance test and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood viscosity was estimated using a validated formula based on hematocrit and total plasma proteins.
After adjusting for age, and gender, individuals with HbA1c-defined prediabetes (HbA1c 5.7–6.4% 39–47 mmol/mol) exhibited significantly higher values of hematocrit, and predicted blood viscosity as compared with controls. Increased levels of IMT were observed in subjects with HbA1c-defined prediabetes in comparison to controls. Predicted blood viscosity was positively correlated with age, waist circumference, blood pressure, cholesterol, triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load glucose levels, fasting insulin, IMT and inversely correlated with HDL and Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e. HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant correlation with predicted blood viscosity (β = 0.054, P = 0.04) in a multivariate regression analysis model including multiple atherosclerosis risk factors.
The study shows that individuals with HbA1c-defined prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion may be helpful to capture individuals with an increased risk of diabetes and cardiovascular disease who may benefit from an intensive lifestyle intervention.
•Subjects with HbA1c-defined prediabetes have increased blood viscosity and hematocrit.•HbA1c is an independent contributor of blood viscosity and hematocrit.•Blood viscosity and hematocrit are associated with carotid intima-media thickness.•Carotid intima-media thickness is increased in subjects with HbA1c-defined prediabetes.•A HbA1c value of 5.7–6.4% may identify subjects with increased cardio-metabolic risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Carotid Intima-Media Thickness (C-IMT) is a reliable predictor of cardiovascular events. We examined if increased C-IMT was associated with defects in glucose metabolism in ...non-diabetic subjects independently of age. Methods In 366 Caucasian non-diabetic subjects of the CARAMERIS study, we measured glucose response during a 75 g-Oral Glucose Tolerance Test (OGTT), insulin sensitivity index (ISI, by Matsuda Index), Liver Insulin Resistance Index (Liver-IR), insulin secretion by ΔAUC Ins0-120 /Glu0-120 (ΔI/ΔG) and beta cell function (Disposition Index, DI). Results Subjects were divided in two groups according to the median age (AGE1 ≤ 45 y; AGE2 > 45 y). Only 5 subjects in AGE1 and 32 in AGE2 had C-IMT > 0.9 mm. Compared to AGE1, AGE2 had a worse cardio-metabolic profile, increased cholesterol, glucose and insulin concentrations, blood pressure and C-IMT. Both ΔI/ΔG ratio and DI were significantly reduced in AGE2. By considering tertiles of C-IMT in each AGE group (G1-G3, where G3 comprised the highest C-IMT), we found that G3 showed increased OGTT glucose profiles and Liver IR, decreased ISI and DI, compared to G1 in each AGE group. Conclusions Increased C-IMT, but within normal ranges, is associated independently of age with altered postprandial glucose profile, increased peripheral and hepatic insulin resistance, decreased b-cell function. C-IMT measurement should become a routine analysis even in younger subjects to predict the risk of cardio-metabolic disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Context: CDKAL1 is a recently discovered susceptibility gene for type 2 diabetes.
Objective: Our objective was to investigate the impact of rs7754840 of CDKAL1 on insulin secretion, insulin ...sensitivity, and risk of type 2 diabetes.
Design and Settings: Study 1 (the EUGENE2 study) was a cross-sectional study including subjects from five white populations in Europe (Denmark, Finland, Germany, Italy, and Sweden). Study 2 is an ongoing prospective study of Finnish men.
Participants: In study 1, 846 nondiabetic offspring of type 2 diabetic patients (age 40 ± 10 yr; body mass index 26.7 ± 5.0 kg/m2) participated. In study 2, subjects included 3900 middle-aged men (533 type 2 diabetic and 3367 nondiabetic subjects).
Interventions: Interventions included iv glucose-tolerance test (IVGTT), oral glucose-tolerance test (OGTT), and euglycemic-hyperinsulinemic clamp in study 1 and OGTT in study 2.
Main Outcome Measures: Parameters of insulin secretion, insulin resistance, and glucose tolerance status were assessed.
Results: In study 1, carriers of the GC and CC genotypes of rs7754840 had 11 and 24% lower first-phase insulin release in an IVGTT compared with that in carriers of the GG genotype (P = 0.002). The C allele was also associated with higher glucose area under the curve in an OGTT (P = 0.016). In study 2, rs7754840 was significantly associated with type 2 diabetes (P = 0.022) and markers of impaired insulin release insulinogenic index (IGI), P = 0.012 in 2405 men with normal glucose tolerance.
Conclusions: rs7754840 of CDKAL1 was associated with markers of impaired insulin secretion in two independent studies. Furthermore, rs7754840 was associated with type 2 diabetes in Finnish men (study 2). Therefore, CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion.
Abstract Background and aim Weight gain is associated with a decline in insulin sensitivity and a compensatory increase in insulin secretion. IGF-1 is a plausible candidate to explain these divergent ...phenomena. In this cross-sectional study, we analyzed the relationship between IGF-1 levels, insulin sensitivity and secretion in 110 nondiabetic subjects with a wide range of BMI to verify this hypothesis. Methods and results Subjects underwent OGTT, IVGTT and euglycemic-hyperinsulinemic clamp. HOMA-beta, IVGTT-derived and OGTT-derived indexes for first-phase and second-phase insulin secretion were higher in obese as compared with overweight and normal-weight groups, while glucose disposal was lower. IGF-1 levels were negatively correlated with IVGTT-derived and OGTT-derived indexes first-phase and second-phase insulin secretion, and positively correlated with glucose disposal. These correlations were no longer significant after adjustment for BMI. In a multivariate analysis, the variables associated with glucose disposal were IGF-1, age, triglycerides, and 2-h post-load glucose accounting for 23.4% of its variation. When BMI was entered into the model, the variables associated with glucose disposal were triglycerides, 2-h post-load glucose and BMI accounting for 27.2% of variation. In a multivariate analysis, the only variable associated with IVGTT-derived first-phase and second-phase insulin secretion was IGF-1 accounting for 10.4% and 15.1% of variation, respectively. When BMI was entered into the model, it became the only variable associated with both first-phase and second-phase insulin secretion accounting for 25.7% and 37.6% of variation, respectively. Conclusion These data suggest that progressive reduction in IGF-1 levels may be involved in obesity-related changes in both insulin sensitivity and secretion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background and aims Glucose-tolerant subjects who have 1-h post-load glucose levels ≥155 mg dl−1 (normal glucose tolerance (NGT)-1h-high) are at an increased risk of developing type 2 ...diabetes. Prospectively conducted studies indicated that high levels of liver enzymes are predictors of a tendency to develop type 2 diabetes; however, it is unknown whether the NGT-1h-high subjects are at increased risk for secreting higher levels of liver biomarkers. Methods and results In this study, oral glucose tolerance tests (OGTTs) were performed in a cohort of 1000 non-diabetic Caucasians and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were measured in these subjects. The NGT-1h-high subjects had increased levels of ALT and GGT, but not AST, as compared with the NGT-1h-low. Following adjustment for age and gender, the ALT, AST and GGT levels were all found to be significantly correlated with body mass index (BMI), waist circumference, blood pressure, triglycerides as well as fasting and post-challenge glucose and insulin levels. In a logistic regression analysis adjusted for age and gender, NGT-1h-high subjects were found to be at increased risk of having ALT levels in the highest quartile as compared with NGT-1h-low subjects (odds ratio (OR) = 1.71; 95% confidence interval (CI): 1.16–2.52). In addition, NGT-1 h-high subjects exhibited an increased risk for having GGT levels in the highest quartile (OR = 1.50; 95%CI: 1.02–2.17). These associations remained significant after adjustment for BMI, blood pressure and lipids, but were not significant following further adjustment for an insulin sensitivity index. NGT-1h-high subjects were at increased risk of having AST levels in the highest quartile as compared with NGT-1h-low subjects (OR = 1.51; 95%CI: 1.04–2.22). This association ceased to be significant following adjustment for BMI, blood pressure and lipids. Conclusions These data suggest that a 1hPG ≥ 155 mg dl−1 cut-off may facilitate the identification of NGT individuals at risk of developing liver abnormalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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