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PURPOSE OF REVIEW: Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus. RECENT FINDINGS: Beta cell death is the final event in a series of mechanisms that, up to date, have not been entirely clarified; it represents the pathophysiological mechanism in the natural history of diabetes mellitus. These mechanisms are not limited to an apoptotic process only, which is characteristic of the immune-mediated insulitis in type 1 diabetes mellitus. They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage. SUMMARY: Necroptosis, autophagy, and pyroptosis are molecular mechanisms that modulate the survival of the pancreatic beta cell, demonstrating the importance of the immune system in glucolipotoxicity processes and the potential role for immunometabolism as another component of what once known as the "ominous octet."
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Morte Celular/fisiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Células Secretoras de Insulina/patologia , Estresse Oxidativo/fisiologia , Animais , Apoptose/fisiologia , Autofagia/fisiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called "healthy obese". Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional study with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 5.2% (n=64) corresponded to unhealthy lean subjects, and 17.4% (n=217) to healthy obese subjects. Metabolically unhealthy normal-weight (MUNW) phenotype was found in males in 53.3% in contrast to 51.3% of metabolically unhealthy obese (MUO) phenotype found in females. An association between metabolically unhealthy phenotypes and a higher risk of a coronary event was found, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes exist in Maracaibo city. Related factors may include insulin resistance, basal glucose levels, and triglycerides levels. Lastly, cardiovascular risk exhibited by healthy obese individuals should be classified in categories of major coronary risk related to lean subjects.
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Aim: Visceral obesity is one of the most intensely researched cardiometabolic risk factors in recent years; nonetheless, its accurate assessment remains a challenge in regions were socioeconomic conditions hinder the widespread use of diagnostic methods for this purpose, such as imaging tests. In this setting, Visceral Adiposity Index (VAI) may be a useful tool. Thus, the objective of this study was to determine the VAI cutoff in adult population from Maracaibo City, Venezuela. Methods: This is a descriptive, cross-sectional study with multi-staged sampling; 2026 subjects of both genders aged ≥18 years were selected from this database and had their VAI calculated. In order to determine VAI cutoffs, subsamples of metabolically healthy and sick individuals were determined, with 599 and 286 subjects, respectively. Gender-specific and general ROC curves were plotted in order to identify the most suitable cutoff according to sensitivity and specificity. Results: Median VAI in the selected sample was 1.67 (0.97-2.78). The optimal cutoff was determined to be 1.91, with 70.3% sensitivity, 70.3% specificity [AUC = 0.777 (0.745-0.808)]. No differences were found between genders. Analysis by age revealed VAI to have greater predictive power among subjects aged < 30 years (cutoff: 1.53), 78.6% sensitivity, 72.8% specificity [AUC = 0.797 (0.709-0.884)]. Conclusion: We suggest a VAI cutoff of 1.9 for define dysfunctional adiposity in our population, with age being an important factor in the epidemiologic behavior of this variable, particularly in younger individuals.
Objetivo: La obesidad central es uno de los factores de riesgo cardiometabólicos emergente más evaluado durante los últimos años, sin embargo, su medición de forma precisa resulta un reto en aquellas poblaciones cuyas condiciones económicas dificultan la realización de métodos diagnósticos complejos, como pruebas de imagen. Por ello el objetivo de este estudio es determinar el punto de corte del índice de adiposidad visceral (VAI) en sujetos adultos de la ciudad de Maracaibo, Venezuela. Métodos: Se seleccionó a 2.026 individuos de ambos sexos, mayores de 18 años, de la base de datos del Estudio de prevalencia de síndrome metabólico en la ciudad de Maracaibo, un estudio descriptivo, transversal, con muestreo multietápico. El VAI se calculó para cada sexo y para la estimación del punto corte se seleccionó a 599 sujetos sanos y 286 enfermos, realizándose curvas COR para identificar el mejor valor de acuerdo con la sensibilidad y la especificidad. Resultados: El promedio de VAI en la muestra seleccionada fue 1,67 (0,97-2,78). El punto de corte fue 1,91 (70,3% de sensibilidad y 70,3% de especificidad) con AUC = 0,777 (0,745-0,808), sin diferencias en el punto de corte según sexo. En el análisis por grupos etarios la mayor capacidad predictiva fue para el grupo < 30 años con AUC = 0,797 (0,709-0,884), con un punto de corte de 1,53 (78,6% de sensibilidad y 72,8% de especificidad). Conclusión: El punto de corte indicado para VAI en nuestra población es de 1,9; considerando la edad como un factor importante en su comportamiento, especialmente en los grupos más jóvenes.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome Metabólica/epidemiologia , Obesidade Abdominal/complicações , Venezuela/epidemiologia , Estudos Transversais/estatística & dados numéricos , Obesidade Abdominal/diagnósticoRESUMO
Background: Insulin resistance (IR) evaluation is a fundamental goal in clinical and epidemiological research. However, the most widely used methods are difficult to apply to populations with low incomes. The triglyceride-glucose index (TGI) emerges as an alternative to use in daily clinical practice. Therefore the objective of this study was to determine an optimal cutoff point for the TGI in an adult population from Maracaibo, Venezuela. Methods: This is a sub-study of Maracaibo City Metabolic Syndrome Prevalence Study, a descriptive, cross-sectional study with random and multi-stage sampling. For this analysis, 2004 individuals of both genders ≥18 years old with basal insulin determination and triglycerides < 500 mg/dl were evaluated.. A reference population was selected according to clinical and metabolic criteria to plot ROC Curves specific for gender and age groups to determine the optimal cutoff point according to sensitivity and specificity.The TGI was calculated according to the equation: ln [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2. Results: The TGI in the general population was 4.6±0.3 (male: 4.66±0.34 vs. female: 4.56±0.33, p=8.93x10 -10). The optimal cutoff point was 4.49, with a sensitivity of 82.6% and specificity of 82.1% (AUC=0.889, 95% CI: 0.854-0.924). There were no significant differences in the predictive capacity of the index when evaluated according to gender and age groups. Those individuals with TGI≥4.5 had higher HOMA2-IR averages than those with TGI <4.5 (2.48 vs 1.74, respectively, p<0.001). Conclusions: The TGI is a measure of interest to identify IR in the general population. We propose a single cutoff point of 4.5 to classify individuals with IR. Future studies should evaluate the predictive capacity of this index to determine atypical metabolic phenotypes, type 2 diabetes mellitus and even cardiovascular risk in our population.
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The direct link between lipid metabolism alterations and the increase of cardiovascular risk are well documented. Dyslipidemias, including isolated high LDL-c or mixed dyslipidemia, such as those seen in diabetes (hypertriglyceridemia, high LDL-c or low HDL-c), correlate with a significant risk of cardiovascular and cerebrovascular disease worldwide. This review analyzes the current knowledge concerning the genetic basis of lipid metabolism alterations, emphasizing lipoprotein lipase gene mutations and the HindIII polymorphism, which are associated with decreased levels of triglycerides and LDL-c, as well as higher levels of HDL-c. These patterns would be associated with decreased global morbidity and mortality, providing protection against cardiovascular and cerebrovascular diseases.