Cholesterol Efflux Capacity and Cardiovascular Disease: The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

(1) Background and Aims: Efforts to reduce coronary artery disease (CAD) by raising high-density lipoprotein (HDL) cholesterol (HDL-C) have not been uniformly successful. A more important factor than HDL-C may be cellular cholesterol efflux mediated by HDL, which has been shown to be associated with CAD. In this report, we analyzed the influence of cardiovascular biomarkers and risk factors on cholesterol efflux in a prospective observational study of patients referred to coronary angiography. (2) Methods: HDL-mediated efflux capacity was determined for 2468 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who were referred to coronary angiography at baseline between 1997 and 2000. Median follow-up time was 9.9 years. Primary and secondary endpoints were cardiovascular and all-cause mortality, respectively. (3) Results: Cholesterol efflux strongly correlated with HDL-related markers including HDL cholesterol, HDL phospholipids, and apolipoproteins AI and AII, as well as HDL particle concentration, which was not seen for low density lipoprotein (LDL) markers including LDL cholesterol and apoB. Cholesterol efflux was associated negatively with C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), and serum amyloid A. Cardiovascular mortality was higher in patients in the lowest cholesterol efflux quartile. This association was weakened, but not fully abolished, after adjustment for HDL cholesterol. (4) Conclusions: We demonstrate that cholesterol efflux was associated with HDL-composition as well as inflammatory burden in patients referred for coronary angiography, and that this inversely predicts cardiovascular mortality independently of HDL cholesterol.

Data on the impact of peripheral artery disease and of type 2 diabetes mellitus on the risk of cardiovascular events.

Here, we provide additional data addressing the individual and combined associations of type 2 diabetes (T2DM) and of peripheral artery disease (PAD) with future cardiovascular events in a prospective cohort study including 338 PAD patients and 711 patients who did not have PAD. Subgroup analyses regarding patient age as well as additional Cox regression models taking into account medications are presented. This data article is related to a research article titled "Single and combined effects of peripheral artery disease and of type 2 diabetes mellitus on the risk of cardiovascular events: a prospective cohort study" (Saely et al., 2018).

Single and combined effects of peripheral artery disease and of type 2 diabetes mellitus on the risk of cardiovascular events: A prospective cohort study.

BACKGROUND AND AIMS: The individual and combined effects of type 2 diabetes (T2DM) and peripheral artery disease (PAD) on future cardiovascular events are unknown and are addressed in the present investigation. METHODS: Cardiovascular events were prospectively recorded in 1049 subjects, encompassing 4 groups: 558 with neither PAD nor diabetes, 153 with T2DM but without PAD, 192 with PAD but without T2DM and 146 with the combination of PAD and T2DM. RESULTS: Over a mean follow-up period of 7.2 ±â€¯2.6 years, the cardiovascular event rate was lowest in patients with neither PAD nor T2DM (16.7%). Compared to this group the event rate was not significantly increased in T2DM patients without PAD (22.2%, p = 0.077) but higher in non-diabetic patients with PAD (52.6%; p < 0.001) and further increased in patients with both PAD and T2DM (71.2%; p < 0.001). Nondiabetic PAD patients were at a higher cardiovascular risk than T2DM patients without PAD (p < 0.001). Compared to those with neither PAD nor T2DM, hazard ratios after multivariate adjustment were 1.26 [0.84-1.91]; p = 0.267, 4.17 [2.97-5.85]; p < 0.001, and 7.82 [5.49-11.12]; p < 0.001 for those with T2DM only, for those with PAD only and for those with the combination of PAD plus diabetes, respectively. CONCLUSIONS: PAD is a stronger risk factor for future cardiovascular events than T2DM, but T2DM in PAD patients accelerates atherothrombotic disease and strongly increases the incidence of cardiovascular events.

FREE THYROID HORMONES AND MORTALITY IN CAUCASIANS UNDERGOING ANGIOGRAPHY: THE LUDWIGSHAFEN RISK AND CARDIOVASCULAR HEALTH (LURIC) STUDY.

OBJECTIVE: Alterations in thyroid hormone functions are associated with mortality and morbidity. Data on euthyroid individuals are very limited and controversial. We therefore investigated the relationship between circulating thyroid hormones and all-cause and cardiovascular (CV) mortality in participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and their association with morbidity. METHODS: LURIC, a prospective, observational study of a hospital-based cohort of Caucasians, was recruited between June 1997 and May 2001 at the Ludwigshafen General Hospital, Ludwigshafen, Germany. Mortality was recorded for a follow-up period of 10 years. The current investigation includes 2,507 patients without overt thyroid disease who all underwent coronary angiography. Blood was drawn before angiography. We evaluated the association between thyroid hormone concentrations and mortality. RESULTS: Low free triiodothyronine (FT3) (hazard ratio [HR], 1.00 versus 0.54; lowest versus highest quartile) and high free thyroxine (FT4) (HR, 1.52 versus 1.00; highest versus lowest quartile) were significant predictors of all-cause and CV mortality, independent of age and sex. Thyroid-stimulating hormone showed no consistent correlation with mortality. CONCLUSION: High FT4 and low FT3 concentrations are significantly related to all-cause and CV mortality. These findings suggest that free thyroid hormones should be measured and considered in patients at intermediate to high risk of coronary heart disease. ABBREVIATIONS: BMI = body mass index CAD = coronary artery disease CCI = Charlson Comorbidity Index CI = confidence interval CV = cardiovascular eGFR = estimated glomerular filtration rate FT3 = free triiodothyronine FT4 = free thyroxine HR = hazard ratio T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.

Impact of cardiovascular risk factors on severity of peripheral artery disease.

OBJECTIVE: The development of peripheral artery disease is affected by the presence of cardiovascular risk factors. It is unclear, whether particular risk factors are leading to different clinical stages of peripheral artery disease. The aim of this retrospective cross-sectional study was to assess the association of cardiovascular risk factors with the presence of critical limb ischaemia. METHODS: The study cohort was derived from a consecutive registry of patients undergoing endovascular therapy in a tertiary referral centre between January 2000 and April 2014. Patients undergoing first-time endovascular intervention for chronic peripheral artery disease of the lower extremities were included. Univariate and multivariate logistic regression models were used to assess the association of age, sex, diabetes mellitus, hypertension, dyslipidaemia, smoking, and renal insufficiency with critical limb ischaemia vs. intermittent claudication. RESULTS: A total of 3406 patients were included in the study (mean age 71.7 ± 11.8 years, 2075 [61%] male). There was a significant association of age (OR 1.67, 95%-CI 1.53-1.82, p < 0.001), male gender (OR 1.23, 95%-CI 1.04-1.47, p = 0.016), diabetes (OR 1.99, 95%-CI 1.68-2.36, p < 0.001) and renal insufficiency (OR 1.62, 95%-CI 1.35-1.96, p < 0.001) with the likelihood of critical limb ischaemia. Smoking was associated with intermittent claudication rather than critical limb ischaemia (OR 0.78, 95%-CI 0.65-0.94, p = 0.010), while hypertension and dyslipidaemia did not show an association with critical limb ischaemia. CONCLUSIONS: In peripheral artery disease patients undergoing first-time endovascular treatment, age, male gender, diabetes, and renal insufficiency were the strongest predictors for the presence of critical limb ischaemia.

Cardiovascular Safety of Plant Sterol and Stanol Consumption.

Plant sterols and stanols as components of functional foods are widely used for cholesterol lowering. The regular intake of these functional foods is associated with a decrease in low density lipoprotein cholesterol of about 10 % and an increase in plasma plant sterol or stanol concentrations by about a factor of 2. There is no doubt that a decrease in low density lipoprotein cholesterol is beneficial to cardiovascular health. However, due to the concomitant increase in circulating plant sterols safety issues associated with the intake of plant sterol containing functional foods have been raised. Herein, we will review and evaluate those arguments raised against the use of plant sterols and stanols.

Prevalence of type 2 diabetes is higher in peripheral artery disease than in coronary artery disease patients.

Type 2 diabetes mellitus and pre-diabetes are risk factors for atherosclerosis and are highly prevalent in patients with coronary artery disease. However, the prevalence of impaired glucose metabolism in patients with peripheral artery disease is not as well elucidated. We aimed at comparing prevalence rates of type 2 diabetes mellitus and pre-diabetes, which were diagnosed according to the current American Diabetes Association criteria, among 364 patients with peripheral artery disease, 529 patients with coronary artery disease and 383 controls. The prevalence of type 2 diabetes mellitus in peripheral artery disease patients was 49.7%. It was significantly higher in these patients than in coronary artery disease patients (34.4%; p < 0.001) and controls (21.4%; p < 0.001). Adjusted for sex, age and body mass index, odds ratios for type 2 diabetes mellitus were 2.0 (95% confidence interval 1.5-2.6) comparing the peripheral artery disease group with the coronary artery disease group (p < 0.001) and 4.0 (2.8-5.8) comparing the peripheral artery disease group with controls (p < 0.001). The prevalence of pre-diabetes among non-diabetic subjects was high in all three study groups (64.5% in peripheral artery disease patients, 63.4% in coronary artery disease patients and 61.8% in controls), without significant between-group differences. In conclusion, the prevalence of type 2 diabetes mellitus is even higher in peripheral artery disease patients than in coronary artery disease patients. This observation underlines the need to consider impaired glucose regulation in the management of peripheral artery disease.

Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.

OBJECTIVES: This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. BACKGROUND: AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. METHODS: We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). RESULTS: We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements. CONCLUSIONS: The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity.

Toward individualized cholesterol-lowering treatment in end-stage renal disease.

There is broad evidence that lowering low-density lipoprotein (LDL) cholesterol will reduce cardiovascular risk. However, in patients on maintenance hemodialysis treatment, lowering LDL cholesterol is not as effective in preventing cardiovascular complications as in the general population. Cholesterol is either endogenously synthesized or absorbed from the intestine. It has been suggested that the benefit of using statins to prevent atherosclerotic complications is less pronounced in people with high absorption of cholesterol. Recent data indicate that patients on hemodialysis have high absorption of cholesterol. Therefore, these patients may benefit from dietary counseling to reduce cholesterol intake, from functional foods containing plant sterols and stanols, and from drugs that interfere with intestinal absorption of sterols (i.e., ezetimibe, bile acid resins, and sevelamer). This review discusses cholesterol homeostasis and the perspective of personalized treatment of hypercholesterolemia in hemodialysis.

Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease: results from the Ludwigshafen risk and cardiovascular health study.

BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable coronary artery disease (CAD). METHODS: sST2 plasma concentrations were measured in 1345 patients with stable CAD referred for coronary angiography at a single tertiary care center. The primary endpoint was all-cause mortality. RESULTS: During a median follow-up time of 9.8 years, 477 (36%) patients died. The median sST2 plasma concentration at baseline was significantly higher among decedents than survivors (21.4 vs 18.5 ng/mL; P < 0.001). In multivariate Cox proportional hazards regression analysis, sST2 was an independent predictor of all-cause mortality (risk ratio 1.16 per 1-SD increase in log-transformed values; 95% CI 1.05-1.29; P = 0.004). In the same multivariate analysis, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were also independent predictors, whereas galectin-3 was not. Patients with sST2 in the highest quartile (>24.6 ng/mL) displayed a 2-fold increased risk of death in univariate analysis, which was attenuated but remained significant in a fully adjusted model (risk ratio 1.39; 95% CI 1.10-1.76; P = 0.006). Further analysis showed that the prognostic impact of sST2 was additive to NT-proBNP and hs-cTnT. Using a multibiomarker approach combining these 3 complementary makers, we demonstrated that patients with all 3 biomarkers in the highest quartiles had the poorest outcome. CONCLUSIONS: In this cohort of patients with stable CAD, increased sST2 was an independent predictor of long-term all-cause mortality and provided complementary prognostic information to hs-cTnT and NT-proBNP.

High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular mortality.

AIMS: High-density lipoprotein (HDL) cholesterol is a strong predictor of cardiovascular mortality. This work aimed to investigate whether the presence of coronary artery disease (CAD) impacts on its predictive value. METHODS AND RESULTS: We studied 3141 participants (2191 males, 950 females) of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean ± standard deviation age of 62.6 ± 10.6 years, body mass index of 27.5 ± 4.1 kg/m², and HDL cholesterol of 38.9 ± 10.8 mg/dL. The cohort consisted of 699 people without CAD, 1515 patients with stable CAD, and 927 patients with unstable CAD. The participants were prospectively followed for cardiovascular mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A total of 590 participants died from cardiovascular diseases. High-density lipoprotein cholesterol by tertiles was inversely related to cardiovascular mortality in the entire cohort (P = 0.009). There was significant interaction between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In stratified analyses, HDL cholesterol was strongly associated with cardiovascular mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18-0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95% CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI) = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in 3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER cohort, and by a meta-analysis comprising all three cohorts. CONCLUSION: The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patients.

Evaluation of 9 biomarkers for predicting 10-year cardiovascular risk in patients undergoing coronary angiography: findings from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study.

BACKGROUND: Conventional factors do not fully explain the distribution of cardiovascular outcomes. Biomarkers are known to participate in well-established pathways associated with cardiovascular disease, and may therefore provide further information over and above conventional risk factors. This study sought to determine whether individual and/or combined assessment of 9 biomarkers improved discrimination, calibration and reclassification of cardiovascular mortality. METHODS: 3267 patients (2283 men), aged 18-95 years, at intermediate-to-high-risk of cardiovascular disease were followed in this prospective cohort study. Conventional risk factors and biomarkers were included based on forward and backward Cox proportional stepwise selection models. RESULTS: During 10-years of follow-up, 546 fatal cardiovascular events occurred. Four biomarkers (interleukin-6, neutrophils, von Willebrand factor, and 25-hydroxyvitamin D) were retained during stepwise selection procedures for subsequent analyses. Simultaneous inclusion of these biomarkers significantly improved discrimination as measured by the C-index (0.78, P = 0.0001), and integrated discrimination improvement (0.0219, P<0.0001). Collectively, these biomarkers improved net reclassification for cardiovascular death by 10.6% (P<0.0001) when added to the conventional risk model. CONCLUSIONS: In terms of adverse cardiovascular prognosis, a biomarker panel consisting of interleukin-6, neutrophils, von Willebrand factor, and 25-hydroxyvitamin D offered significant incremental value beyond that conveyed by simple conventional risk factors.

C-peptide levels are associated with mortality and cardiovascular mortality in patients undergoing angiography: the LURIC study.

OBJECTIVE: C-peptide is a proinsulin cleavage product released from the pancreas in amounts equimolar to insulin, and elevated levels of C-peptide have been found in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest that C-peptide could play a causal role in the pathophysiology of vascular disease, but nothing is known about the prognostic value of C-peptide concentrations in the circulation. RESEARCH DESIGN AND METHODS: We examined whether C-peptide is associated with cardiovascular and total mortality in 2,306 patients from the Ludwigshafen Risk and Cardiovascular Health Study who underwent coronary angiography at baseline (1997-2000). RESULTS: During a mean follow-up of 7.6 years, 440 deaths (19.1%) occurred, 252 (10.9%) of which were due to cardiovascular causes. Age- and sex-adjusted hazard ratios (HRs) in the third compared with the first tertile of C-peptide were 1.46 (95% CI 1.15-1.85; P = 0.002) for all cause and 1.58 (1.15-2.18; P = 0.005) for cardiovascular mortality. After further adjustment for common risk factors as well as markers of glucose metabolism, these HRs remained significant at 1.46 (1.10-1.93; P = 0.008) and 1.55 (1.07-2.24; P = 0.022), respectively. Moreover, patients in higher tertiles of C-peptide exhibited higher levels of markers of endothelial dysfunction and atherosclerosis as well as a more severe extent of coronary lesions. CONCLUSIONS: In patients undergoing coronary angiography, C-peptide levels are independently associated with all cause and cardiovascular mortality as well as presence and severity of coronary artery disease. Further studies are needed to examine a potential causal role of C-peptide in atherogenesis in humans.

Isolated post-challenge hyperglycaemia predicts increased cardiovascular mortality.

OBJECTIVE: The American Diabetes Association (ADA) has revised the criteria for the diagnosis of diabetes in 2010. Glycated haemoglobin at a cut-point of ≥6.5% has been included in the diagnostic algorithm. We aimed to investigate whether there is still the need to perform oral glucose tolerance tests (OGTT). METHODS: We studied 2002 people referred for angiography who did not have a history of diabetes. OGTT were performed in all 1772 subjects with fasting glucose <126 mg/dl. Participants were prospectively followed for all-cause and cardiovascular mortality over a mean duration (±standard deviation) of 7.7 ± 2.0 years. RESULTS: Using the ADA 2010 criteria 618 individuals were categorised as having new-onset type 2 diabetes. Among these, 167 had isolated post-challenge hyperglycaemia. A total of 346 participants died during follow-up. Cardiovascular death occurred in 202 cases. Those with elevated fasting glucose ≥126 mg/dl and/or glycated haemoglobin ≥6.5% had increased all-cause (hazard ratio [HR]: 1.63, 95% confidence interval [95%CI]: 1.28-2.08, p < 0.001) and cardiovascular mortality (HR: 1.66, 95%CI: 1.21-2.29, p = 0.002) compared to subjects without diabetes according to the ADA 2010 definition. Isolated elevation of post-challenge glucose independently predicted increased cardiovascular mortality (HR: 1.57, 95%CI: 1.02-2.43, p = 0.041). All-cause and cardiovascular mortality were not significantly different between subjects with increased fasting glucose and/or glycated haemoglobin and those with isolated elevation of post-challenge glucose. CONCLUSIONS: Performing OGTT will identify a high risk group for cardiovascular mortality undetected by fasting glucose or glycated haemoglobin.

Duration of type 2 diabetes strongly predicts all-cause and cardiovascular mortality in people referred for coronary angiography.

OBJECTIVE: Type 2 diabetes represents a major cardiovascular risk factor. However, few studies have addressed the impact of the disease duration on mortality. Thus, we aimed to investigate the predictive value of diabetes duration for all-cause and cardiovascular mortality in subjects undergoing coronary angiography. METHODS: We studied 2455 participants of the LUdwigshafen RIsk and Cardiovascular health study (1768 males/687 females). They had a mean ± standard deviation (SD) age of 63.1 ± 9.0 years (range: 40.0-79.9) and a mean ± SD body mass index of 27.7 ± 4.0 kg/m(2). 704 subjects were newly diagnosed with type 2 diabetes according to the 2010 criteria of the American Diabetes Association and 446 subjects had a known history of type 2 diabetes. The mean ± SD duration of the follow-up for all-cause and cardiovascular mortality was 7.4 ± 2.3 years. RESULTS: A total of 543 deaths occurred during the follow-up. Among these, 343 were accounted for by cardiovascular diseases. The duration of type 2 diabetes was strongly and positively correlated with all-cause and cardiovascular mortality (both P<0.001). The multivariate adjusted hazard ratios (95% confidence intervals) for cardiovascular mortality compared to subjects without diabetes were 1.76 (1.34-2.32), 2.86 (2.00-4.08), 2.96 (1.85-4.74), and 4.55 (3.24-6.39) for subjects with new onset type 2 diabetes and subjects with known type 2 diabetes (duration ≤ 5, >5 and ≤ 10, >10 years), respectively. CONCLUSIONS: The data emphasise the need to consider the diabetes duration for the prediction of mortality in subjects at intermediate to high cardiovascular risk.

Cholesterol synthesis is associated with hepatic lipid content and dependent on fructose/glucose intake in healthy humans.

Visceral obesity and fatty liver have been related to high synthesis and low absorption of cholesterol. This study aimed to investigate the associations of cholesterol metabolism with liver and visceral fat content in healthy humans. Another objective was to explore the effects of very-high-fructose and very-high-glucose diets on cholesterol homeostasis. We report on a cohort of 20 people (12 males, 8 females; age 30.5 ± 2.0 years; body mass index 25.9 ± 0.5 kg/m(2)) who completed a four-week dietary intervention study. Between the baseline and the followup examination the study participants in addition to a balanced weight-maintaining diet received 150 g of either fructose or glucose per day. Visceral and liver fat were measured with magnetic resonance (MR) imaging and (1)H-MR spectroscopy, respectively. Cholesterol absorption and synthesis were estimated from the serum noncholesterol sterol concentrations. Performing cross-sectional analyses the lanosterol and desmosterol to cholesterol ratios were positively correlated with visceral and liver fat content (all P < .03). The lathosterol to cholesterol ratio decreased in response to high-fructose diet (P = .006) but not in response to high-glucose diet. To conclude, visceral and liver fat content are associated with cholesterol synthesis in healthy humans. Furthermore, cholesterol synthesis appears to be dependent on fructose/glucose intake.

Additional use of glycated hemoglobin for diagnosis of type 2 diabetes in people undergoing coronary angiography reveals a subgroup at increased cardiovascular risk.

OBJECTIVE: To study the prognosis of people with newly diagnosed type 2 diabetes as per the American Diabetes Association (ADA) 2010 definition but without diabetes as per the ADA 2009 definition. RESEARCH DESIGN AND METHODS: A total of 2,002 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study without a history of diabetes were studied. RESULTS: During the follow-up of a mean duration ± SD of 7.7 ± 2.0 years, 346 people died (202 cardiovascular deaths). Subjects with type 2 diabetes as per the ADA 2009 definition (n = 468) had significantly increased all-cause and cardiovascular mortality compared with people without diabetes as per the ADA 2010 definition (both P ≤ 0.003). Subjects with type 2 diabetes as per the ADA 2010 definition but without diabetes as per the ADA 2009 definition (n = 150) were at significantly increased risk to die of cardiovascular diseases (P = 0.029). CONCLUSIONS: Use of the ADA 2010 diabetes definition may be instrumental in improving cardiovascular risk stratification in people undergoing coronary angiography.

Glycated hemoglobin predicts all-cause, cardiovascular, and cancer mortality in people without a history of diabetes undergoing coronary angiography.

OBJECTIVE: Glycated hemoglobin has been suggested to be superior to fasting glucose for the prediction of vascular disease and death from any cause. The aim of the present work was to analyze and compare the predictive value of glycated hemoglobin and fasting glucose on all-cause and cause-specific mortality in subjects who underwent coronary angiography. RESEARCH DESIGN AND METHODS: We studied 2,686 participants of the Ludwigshafen Risk and Cardiovascular health study without a history of diabetes. The majority of this cohort had coronary artery disease. Glycated hemoglobin was measured at the baseline examination. The mean (± SD) duration of the follow-up for all-cause, cardiovascular, and cancer mortality was 7.54 ± 2.1 years. RESULTS: A total of 508 deaths occurred during the follow-up. Of those, 299 were accounted for by cardiovascular diseases and 79 by cancer. Baseline glycated hemoglobin was predictive of all-cause, cardiovascular, and cancer mortality. The multivariable-adjusted hazard ratios (HR) (95% CI) for glycated hemoglobin values of <5.0, 5.0-5.4, 5.5-5.9, 6.0-6.4, 6.5-7.4, and ≥7.5% for all-cause mortality were 1.36 (0.85-2.18), 1.00 (0.76-1.32), 1.00 (reference), 1.11 (0.88-1.41), 1.39 (1.07-1.82), and 2.15 (1.32-3.53), respectively. Similar J-shaped relationships were found between glycated hemoglobin and cardiovascular and cancer mortality. The associations of glycated hemoglobin with all-cause and cardiovascular mortality remained significant after inclusion of fasting glucose as a covariate. However, fasting glucose was not significantly related to mortality when adjusting for glycated hemoglobin. CONCLUSIONS: Glycated hemoglobin significantly and independently of fasting glucose predicts all-cause and cardiovascular mortality in whites at intermediate to high cardiovascular risk.

Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon-like peptide 1.

BACKGROUND: Variants in TCF7L2 have been associated with the age at onset of type 2 diabetes in Mexican Americans. However, there is a lack of data on this relationship in Caucasians. Furthermore, risk alleles in TCF7L2 have been suggested to account for decreased conversion of proinsulin to insulin and decreased expression of GLP-1. We investigated the effect of the allelic variants rs1225537 and rs7903146 in TCF7L2 on the age at onset of type 2 diabetes, the plasma concentrations of proinsulin and GLP-1, and the ratio of proinsulin to insulin in a German cohort. METHODS: We studied 3185 participants of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. Among these, 1021 subjects had type 2 diabetes. Data on age at onset of diabetes were available in 925 subjects. OGTTs were performed in a subgroup not previously known to have diabetes. RESULTS: Carriers of the risk alleles in rs1225537 and rs7901346 had increased risk of type 2 diabetes and elevated HbA(1c) (all p < 0.001). The risk alleles were also associated with early onset of type 2 diabetes, decreased insulin secretion and markedly increased proinsulin and proinsulin to insulin ratio (all p < 0.03). GLP-1 was not significantly related to the TCF7L2 genotype. CONCLUSIONS: Our data demonstrate that TCF7L2 variants are associated with an early age of onset of type 2 diabetes in Caucasians and affects the conversion of proinsulin to insulin. However, TCF7L2 is not consistently associated with fasting GLP-1.

Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial.

An increasing amount of fructose in the diet is suggested to play a causal role in the pathogenesis of the metabolic syndrome, type 2 diabetes and fatty liver. Our aim was to investigate and compare the effects of very high fructose and very high glucose in hyperenergetic diets on glucose and lipid metabolism and on fat depots in healthy humans. We conducted an exploratory, prospective, randomised, single-blinded, intervention trial. Participants in addition to a balanced weight-maintaining diet received 150 g of fructose or glucose/d for 4 weeks. Insulin sensitivity was estimated from oral glucose tolerance tests. Visceral and subcutaneous abdominal fat was determined with MRI. Liver fat and intramyocellular lipids of the tibialis anterior muscle were measured with (1)H magnetic resonance spectroscopy. A total of twenty healthy subjects (fructose group n 10 and glucose group n 10; twelve males and eight females) completed the study. They had a mean age of 30·5 (SEM 2·0) years and a mean BMI of 25·9 (SEM 0·5) kg/m(2). Insulin sensitivity appeared to decrease both in the fructose and glucose groups. TAG markedly increased in the fructose group. No strong alterations or treatment effects were found for liver fat, visceral fat, subcutaneous abdominal fat and intramyocellular lipids of the tibialis anterior muscle. In conclusion, the effects of very high fructose and very high glucose in hyperenergetic diets on glucose metabolism and body fat composition were not different in the healthy participants of the present study. However, elevation of plasma TAG seemed to be fructose-specific.