Increasing the complexity of lipoprotein characterization for cardiovascular risk in type 2 diabetes.

The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates in their arteries, in part, due to persistent atherogenic dyslipidaemia characterized by elevated triglycerides, remnant cholesterol, smaller LDL particles and reduced HDL cholesterol. The causal link between dyslipidaemia and atherosclerosis in T2DM is complex, and our contention is that a deeper understanding of lipoprotein composition and functionality, the vehicle that delivers cholesterol to the artery, will provide insight for improving our understanding of the hidden cardiovascular risk of diabetes. This narrative review covers three levels of complexity in lipoprotein characterization: 1-the information provided by routine clinical biochemistry, 2-advanced nuclear magnetic resonance (NMR)-based lipoprotein profiling and 3-the identification of minor components or physical properties of lipoproteins that can help explain arterial accumulation in individuals with normal LDLc levels, which is typically the case in individuals with T2DM. This document highlights the importance of incorporating these three layers of lipoprotein-related information into population-based studies on ASCVD in T2DM. Such an attempt should inevitably run in parallel with biotechnological solutions that allow large-scale determination of these sets of methodologically diverse parameters.

Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes.

Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90-95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as the primary cause of morbidity and mortality, placing a substantial burden on healthcare systems due to the potential for macrovascular and microvascular complications. In this context, leptin, an adipocyte-derived hormone, plays a fundamental role. This hormone is essential for regulating the cellular metabolism and energy balance, controlling inflammatory responses, and maintaining CV system homeostasis. Thus, leptin resistance not only contributes to weight gain but may also lead to increased cardiac inflammation, greater fibrosis, hypertension, and impairment of the cardiac metabolism. Understanding the relationship between leptin resistance and CV risk in obese individuals with type 2 DM (T2DM) could improve the management and prevention of this complication. Therefore, in this narrative review, we will discuss the evidence linking leptin with the presence, severity, and/or prognosis of obesity and T2DM regarding CV disease, aiming to shed light on the potential implications for better management and preventive strategies.

Niveles de ALT y respuesta hipoglucemiante al tratamiento con agonistas del receptor de GLP-1 / Baseline ALT levels as a marker of glycemic response to treatment with GLP-1 receptor agonists

Antecedentes y objetivo: Evaluar si los niveles de ALT, como marcador de esteatosis hepática no alcohólica, pueden determinar la respuesta hipoglucemiante al tratamiento con agonistas del receptor GLP-1 (AR-GLP1). Pacientes y métodos: Estudio analítico longitudinal retrospectivo. Se incluyeron pacientes con diabetes tipo 2 (DM2) tratados sin interrupción con AR-GLP1 (85% liraglutida) durante un año. Se clasificó a los pacientes en 2 grupos según niveles iniciales de ALT, con punto de corte en la mediana (24 U/l). La variable dependiente fue el cambio (final-inicial) de HbA1c. El valor predictivo de niveles de ALT > 24 U/l y del cambio en ALT fue analizado con regresión lineal multivariante ajustada para edad, género, evolución de DM2, tipo y dosis de AR-GLP1, niveles iniciales de HbA1c, índice de masa corporal (IMC) y cambio de IMC. Resultados: Se incluyeron 117 pacientes (48% mujeres) con edad media de 58,6 (DE 9,6) años. El tratamiento estuvo asociado con un cambio en ALT de −4,3 U/l (p = 0,041) y un cambio en HbA1c de −1,1% (p < 0,0001). Tanto el descenso de HbA1c (−1,41% vs −0,76%; p = 0,045) como el de ALT (−9,25 vs 0,46 U/l; p = 0,002) fueron significativamente más marcados en pacientes con ALT por encima de la mediana. En análisis multivariante tanto niveles de ALT > 24 U/l (b = −0,74; IC 95%: −1,31 a −0,18; p = 0,011) como el cambio en ALT (b = 0,028; IC 95%: 0,010 a 0,046; p = 0,003) fueron factores predictivos de respuesta. Conclusiones: Niveles elevados de transaminasas y su descenso se asocian a una respuesta hipoglucemiante favorable a AR-GLP1 (AU)

Background and objectives: This study aimed to assess if ALT levels, as a marker of non-alcoholic fatty liver disease, may predict HbA1c response to treatment with GLP-1 receptor agonists (GLP-1 RAs). Patients and methods: A retrospective, longitudinal, analytical study was conducted including patients with type 2 diabetes mellitus continuously treated with GLP-1 agonists (85% with liraglutide) for one year. Patients were divided into two groups according to baseline ALT levels, with 24 U/L (the median of the distribution) as the cut-off point. The dependent variable was HbA1c change (one-year follow-up minus baseline). The predictive value of ALT levels above 24 U/L and ALT change was analyzed using multivariate linear regression adjusted to age, gender, diabetes duration, type and dose of GLP-1 RA, baseline HbA1c, baseline body mass index (BMI), and change in BMI. Results: A total of 117 patients (48% females) aged 58.6 (SD 9.6) years were enrolled into the study. Treatment was associated with a change in ALT of −4.3 U/L (p = 0.041) and a change in HbA1c of −1.1% (p < 0.0001). Decreases in HbA1c (−1.41% vs −0.76%; p = 0.045) and ALT (−9.25 vs 0.46 U/L; p = 0.002) were significantly higher in patients with ALT levels above the median. In the multivariate analysis, both ALT > 24 U/L (b = −0.74; 95% CI: −1.31 to −0.18; p = 0.011) and ALT change (b = 0.028; 95% CI: 0.010 to 0.046; p = 0.003), were significant response predictors. Conclusions: Elevated baseline transaminase values and decreased transaminase levels during follow-up are associated to a favorable glycemic response to GLP-1 RAs (AU)

Baseline ALT levels as a marker of glycemic response to treatment with GLP-1 receptor agonists.

BACKGROUND AND OBJECTIVES: This study aimed to assess if ALT levels, as a marker of non-alcoholic fatty liver disease, may predict HbA1c response to treatment with GLP-1 receptor agonists (GLP-1 RAs). PATIENTS AND METHODS: A retrospective, longitudinal, analytical study was conducted including patients with type 2 diabetes mellitus continuously treated with GLP-1 agonists (85% with liraglutide) for one year. Patients were divided into two groups according to baseline ALT levels, with 24 U/L (the median of the distribution) as the cut-off point. The dependent variable was HbA1c change (one-year follow-up minus baseline). The predictive value of ALT levels above 24 U/L and ALT change was analyzed using multivariate linear regression adjusted to age, gender, diabetes duration, type and dose of GLP-1 RA, baseline HbA1c, baseline body mass index (BMI), and change in BMI. RESULTS: A total of 117 patients (48% females) aged 58.6 (SD 9.6) years were enrolled into the study. Treatment was associated with a change in ALT of -4.3 U/L (p=0.041) and a change in HbA1c of -1.1% (p<0.0001). Decreases in HbA1c (-1.41% vs -0.76%; p=0.045) and ALT (-9.25 vs 0.46 U/L; p=0.002) were significantly higher in patients with ALT levels above the median. In the multivariate analysis, both ALT>24 U/L (b=-0.74; 95%CI: -1.31 to -0.18; p=0.011) and ALT change (b=0.028; 95%CI: 0.010 to 0.046; p=0.003), were significant response predictors. CONCLUSIONS: Elevated baseline transaminase values and decreased transaminase levels during follow-up are associated to a favorable glycemic response to GLP-1 RAs.

The impact of processing meat and fish products on phosphorus intake in chronic kidney disease patients.

INTRODUCTION AND OBJECTIVES: The use of phosphate additives in meat and fish processing leads to a phosphorus overload that we cannot quantify through labelling or food composition tables. We analysed this increase by measuring phosphorus content in these products by spectrophotometry. MATERIALS AND METHOD: We determined the phosphorus/protein ratio in fresh meat and fish products with varying degrees of processing by spectrophotometry (phosphorus) and the Kjeldahl method (proteins). We contrasted these results with those reflected in the food composition tables. RESULTS: The phosphorus/protein ratio was higher in processed meat products (15.83 mg/g) than in battered (11.04 mg/g) and frozen meat products (10.5mg/g), and was lower in fresh (8.41 mg/g) and refrigerated meat products (8.78 mg/g). Fresh white fish had a phosphorus/protein ratio of 8.58mg/g, while it increased by 22% (10.3mg/g) in frozen white fish and by 46% (12.54 mg/g) in battered fish. The information in the tables was poor and confusing, and no reference is made to the brands tested. CONCLUSIONS: Processing meat and fish products poses a serious obstacle to the reduction of phosphorus intake. The current regulatory framework does not assist us in the objective of reducing phosphorus additives, since it considers them safe for public consumption. Overcoming these barriers requires a coordinated effort to demonstrate that a high intake of these additives may be harmful to the general population and it should be more closely examined by regulators.

Ability of retinopathy to predict cardiovascular disease in patients with type 2 diabetes mellitus.

It is important identify patients with very high cardiovascular risk to intensify their therapy. Our aim was to assess the association between retinopathy and incident cardiovascular events (cardiovascular disease [CVD]) in patients with type 2 diabetes mellitus (DM). Patients were included if they had type 2 DM and a visible fundus. Baseline clinical and biochemical variables, including urinary albumin excretion rate, were collected. Clinical end points were nonfatal or fatal cardiovascular events (unstable angina including revascularization, nonfatal or fatal myocardial infarction, transient ischemic attack, nonfatal or fatal stroke, lower-leg amputation, terminal chronic heart failure, sudden death). Cox multivariate regression models were used to evaluate the risk associated with each variable and the independent contribution of baseline retinopathy. A total of 458 patients were included, with mean follow-up time of 6.7 +/- 2.6 years. Incident CVD rates were 30.7 per 1,000 patient-years in patients with a normal fundus, 56.7 in patients with nonproliferative retinopathy, and 90.7 in patients with proliferative retinopathy (p <0.0001). In multivariate analysis, nonproliferative retinopathy (hazard ratio 1.71, 95% confidence interval 1.1 to 2.66, p = 0.017) and proliferative retinopathy (hazard ratio 2, 95% confidence interval 1.1 to 3.56, p = 0.019) were significantly associated with incident CVD. In conclusion, retinopathy proved to be an independent risk marker for CVD in patients with type 2 DM.

[Microalbuminuria accounts for the increased vascular disease risk in diabetic patients with metabolic syndrome]. / La microalbuminuria explica el incremento de riesgo vascular en pacientes con diabetes y síndrome metabólico.

The aim of this study was to determine the impact of the metabolic syndrome on vascular disease risk in patients with type-2 diabetes. A prospective cohort study was carried out. The main dependent variable was the combination of coronary disease, stroke and lower leg amputation. Cox regression modeling was used. In total, 317 patients were followed for a mean of 7.7 years. The prevalence of metabolic syndrome was 87%. Multivariate analysis identified the following as predictors of incident vascular disease: age (relative risk [RR] =1.06, 95% confidence interval [CI], 1.02-1.1; P=.0003), baseline cardiovascular disease (RR=1.8; 95% CI, 1.1-3.0; P=.017), and the simultaneous presence of four metabolic risk factors (RR=5.8; 95% CI, 1.8-18; P=.003). The most predictive factor was microalbuminuria (chi2=5.9; P=.015). Microalbuminuria accounts for the increased risk of vascular disease in patients with metabolic syndrome. In evaluating vascular disease risk in patients with type-2 diabetes, it is more important to consider the total number of metabolic risk factors than the presence of metabolic syndrome alone.

La microalbuminuria explica el incremento de riesgo vascular en pacientes con diabetes y síndrome metabólico / Microalbuminuria accounts for the increased vascular disease risk in diabetic patients with metabolic syndrome

El objetivo fue evaluar la importancia pronóstica del síndrome metabólico (SM) en el riesgo vascular en diabetes mellitus tipo 2 (DM2). Se realizó estudio de cohortes prospectivo. La variable dependiente, enfermedad cardiovascular (ECV), fue una combinación de eventos coronarios, cerebrovasculares y amputación de extremidades inferiores. Se utilizó modelo de regresión de Cox. Se incluyó a 317 pacientes seguidos durante 7,7 años. La prevalencia de SM fue del 87%. Los predictores de ECV incidente en análisis multivariable fueron: edad (riesgo relativo [RR] = 1,06; intervalo de confianza [IC] del 95%, 1,02-1,1; p = 0,0003), ECV prevalente (RR = 1,8; IC del 95%, 1,1-3; p = 0,017), y presentar simultáneamente 4 factores de riesgo metabólicos (RR = 5,8; IC del 95%, 1,8-18; p = 0,003). El componente más predictivo fue la microalbuminuria (χ2 = 5,9; p = 0,015). La microalbuminuria explica el poder predictivo del SM para la aparición de ECV. Es más importante considerar el número de factores de riesgo metabólico que el SM al evaluar el riesgo vascular del paciente con DM2 (AU)

The aim of this study was to determine the impact of the metabolic syndrome on vascular disease risk in patients with type-2 diabetes. A prospective cohort study was carried out. The main dependent variable was the combination of coronary disease, stroke and lower leg amputation. Cox regression modeling was used. In total, 317 patients were followed for a mean of 7.7 years. The prevalence of metabolic syndrome was 87%. Multivariate analysis identified the following as predictors of incident vascular disease: age (relative risk [RR] =1.06, 95% confidence interval [CI], 1.02-1.1; P=.0003), baseline cardiovascular disease (RR=1.8; 95% CI, 1.1-3.0; P=.017), and the simultaneous presence of four metabolic risk factors (RR=5.8; 95% CI, 1.8-18; P=.003). The most predictive factor was microalbuminuria (χ2=5.9; P=.015). Microalbuminuria accounts for the increased risk of vascular disease in patients with metabolic syndrome. In evaluating vascular disease risk in patients with type-2 diabetes, it is more important to consider the total number of metabolic risk factors than the presence of metabolic syndrome alone (AU)

[Metabolic syndrome as a cardiovascular risk factor in patients with type 2 diabetes]. / Influencia del sídrome metabólico en el cardiovascular de pacientes con diabetes tipo 2.

INTRODUCTION AND OBJECTIVES: To assess the cardiovascular risk associated with the presence of metabolic syndrome in patients with type 2 diabetes. Patients and method. Prospective cohort study of patients with type 2 diabetes. The baseline presence of components of metabolic syndrome as defined by the World Health Organization was determined. The main dependent variable was a combination of coronary events (onset angina, fatal or nonfatal myocardial infarction) and cerebrovascular events (transient ischemic attack, fatal or nonfatal stroke and lower limb amputation). Secondary end points were coronary events and stroke. We calculated the predictive power of the presence of metabolic syndrome and of different numbers of its component features. RESULTS: 318 patients were included. Mean duration of follow-up was 4.6 years (SD 1.5 years). The prevalence of metabolic syndrome was 77.0%. The rates of cardiovascular events, coronary events and stroke, expressed per 1000 patient-years, were 14.0, 5.6, and 8.4 respectively in patients without metabolic syndrome, and 33.3, 20.7, and 11.7 respectively in patients with metabolic syndrome (P=.058 cardiovascular events; P=.05 coronary events). In the multivariate analysis, the simultaneous presence of all four metabolic syndrome components significantly increased the global cardiovascular disease risk (RR=5.0; 95% CI, 1.6-15.9; P=.006) and the risk of coronary heart disease (RR=7.4; 95% CI, 1.3-41.1; P=.02), but not the risk of stroke. CONCLUSIONS: The simultaneous presence of all four metabolic syndrome components is associated with an increase in the risk of cardiovascular events in patients with type 2 diabetes.

Mild renal insufficiency as a cardiovascular risk factor in non-proteinuric type II diabetes.

OBJECTIVES: To evaluate cardiovascular risk according to baseline renal function in a group of non-proteinuric type II diabetic patients. MATERIAL AND METHODS: Prospective study with a follow-up of 423 non-proteinuric type II diabetic patients with creatinine <150 micromol/l for an average of 4.7 years (S.D. 1.55). Creatinine clearance (CC) was estimated using the Cockcroft-Gault formula and expressed in millilitre per minute. The hazard ratio (HR) associated with each millilitre per minute decrease in baseline CC on fatal or non-fatal cardiovascular events and total mortality was evaluated using the Cox regression model. RESULTS: Baseline creatinine was 89 micromol/l (S.D. 15.9) and CC was 69.5 ml/min (S.D. 20). There were 63 cardiovascular events (15 unstable angina, 10 non-fatal myocardial infarctions, 25 non-fatal strokes, two amputations, nine fatal myocardial infarctions and two fatal strokes) and 39 total deaths (11 for cardiovascular causes). The cardiovascular event rate was 31.7/1000 patient-years and the total mortality rate was 19.6/1000 patient-years. The independent predictors of cardiovascular events were: CC (HR=1.035; confidence interval (CI) 95% 1.02-1.05; P<0.0001), total cholesterol/HDL cholesterol ratio (HR=1.25; CI 95% 1.1-1.4; P=0.0008), baseline coronary heart disease (HR=2.05; CI 95% 1.07-3.9; P=0.04) and baseline microalbuminuria (HR=2.3; CI 95% 1.3-3.8; P=0.003). The independent total mortality predictors were: CC (HR=1.04; CI 95% 1.02-1.08; P<0.0001), male (HR=2.1; CI 95% 1.1-4; P=0.027) and baseline microalbuminuria (HR=2.1; CI 95% 1.1-4;P=0.03). CONCLUSIONS: Mild renal insufficiency increases cardiovascular risk in non-proteinuric patients with type II diabetes.

Fasting plasma glucose variability as a risk factor of retinopathy in Type 2 diabetic patients.

AIMS/HYPOTHESIS: The purpose of this study was to determine whether plasma glucose variability, irrespective of glycated hemoglobin (HbA1c), was able to predict the onset of retinopathy in Type 2 diabetic patients. METHODS: The study was based on a cohort of 130 Type 2 diabetic patients without retinopathy recruited from June 1994 to June 1998. The fundus was reexamined between November 2000 and June 2001, with a mean follow-up period of 5.2 years. Fasting plasma glucose (FPG) variability was measured by its variation coefficient (VC). Stratified and multivariate models were used to estimate the effect of FPG variability and mean HbA1c during follow-up on cumulative incidence (IP) of retinopathy. RESULTS: The IP of retinopathy was 36.2% and increased all along the quartiles of FPG variability (P=.001). In multivariate analyses, only the last quartile of the distribution of VC (OR=3.68; 95% confidence interval (CI) 1.01-13.4; P=.049) was significant. The term of interaction between mean HbA1c and VC was not significant. CONCLUSIONS/INTERPRETATION: FPG variability fulfills criteria to be considered a risk factor for retinopathy: A statistically significant association exists after adjustment for confounders, time sequence, dosage response gradient, and biological plausibility.