Surrogate indices of insulin resistance using the Matsuda index as reference in adult men-a computational approach.

Background: Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men. Methods: A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust. Results: The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01). Conclusions: The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

A longitudinal study of free leptin index in pre-eclamptic pregnancies.

The ratio between circulating levels of leptin and soluble leptin receptor (sOB-R), the free leptin index (FLI), is used as a marker of leptin resistance. Therefore, the aim of our study was to investigate the FLI in mild pre-eclamptic pregnancies in a nested case-control study within a prospective observational study. Circulating levels of leptin and sOB-R levels rise significantly during pregnancy in healthy (p < 0.05) (n = 46) and pre-eclamptic pregnancies (p < 0.05) (n = 20). Serum levels of leptin were significantly higher in pre-eclamptic compared to healthy pregnancies at second and third trimesters of pregnancy (p < 0.05). Additionally, serum levels of sOB-R were significantly lower in pre-eclamptic pregnancies during the second and third trimesters of pregnancy compared to healthy pregnancies (p < 0.05). Moreover, we found that FLI did not vary significantly during pregnancy in healthy women (p > 0.05), while it increases in pre-eclamptic pregnancies (p < 0.05). Indeed, FLI was significantly higher at second and third trimesters of pregnancy in pre-eclamptic compared to healthy pregnancies (p < 0.05). In addition, FLI was significantly higher in the luteal phase compared with the follicular phase of the menstrual cycle in eumenorrheic women (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed the ability of leptin (AUC = 0.72) and FLI (AUC = 0.67) as a reliable predictor for mild pre-eclampsia during the second trimester of pregnancy. In conclusion, our findings show that FLI were significantly increased in mild pre-eclamptic pregnancies and allowed us to hypothesize that this rise might alter leptin bioavailability and bioactivity which might lead to the sympathetic hyperactivity and the hypertensive disorders during pregnancy.

Maternal Serum Angiopoietin-Like 3 Levels in Healthy and Mild Preeclamptic Pregnant Women.

Objective: Angiopoietin-like protein 3(ANGPTL3) is an important regulator of lipoprotein metabolism in the fed state by inhibiting the enzyme lipoprotein lipase in oxidative tissues. However, the possible role of ANGPTL3 throughout gestation and its relationship with hormonal and biochemical variables are still unknown. The aim of this study was to determinate serum ANGPTL3 level in healthy non-pregnant women, during healthy and preeclamptic pregnancy and postpartum. Methods: Serum ANGPTL3 was analyzed by enzyme-linked immunosorbent assay (ELISA), in a prospective cohort of healthy pregnant women (n = 52) and women with mild preeclampsia (n = 21), and women at three months postpartum (n = 20) and healthy non-pregnant women (n = 20). The results obtained were correlated with biochemical, hormonal and anthropometric variables and insulin resistance indices. Results: Levels of ANGPTL3 were not different between the follicular and the luteal phases of the cycle in healthy non-pregnant women. There was a significant reduction in serum ANGPTL3 levels from the first to the third trimester in healthy pregnant women compared with healthy non-pregnant and postpartum women (p <0.01). ANGPTL3 levels do not differ significantly during the three trimesters of pregnancy neither in healthy women nor in preeclamptic women. The serum levels of ANGPTL3 in women who developed preeclampsia are not statistically different from those observed in healthy pregnant women in each trimester of pregnancy. A significant lineal positive correlation was observed between serum ANGPTL3 levels and triglyceride (P =0.0186, r =0.52), very low-density lipoprotein cholesterol (P =0.0224, r =0.50), and total cholesterol levels (P =0.0220, r =0.50) in healthy non-pregnant women (P 0.05). Besides, there were no significant correlations between serum ANGPTL3 and body mass index (BMI), high-density lipoprotein cholesterol, glucose, insulin, leptin, or HOMA-IR (P >0.05). Conclusions: We describe for the first time the profile of ANGPTL3 throughout pregnancy and postpartum as well as and discussed about explore their potential contribution interactions with lipoprotein metabolism throughout pregnancy and postpartum. Thus, low levels of ANGPTL3 during pregnancy might favor lipid uptake in oxidative tissues as the main maternal energy source, while may helping to preserve glucose for use by the fetus and placenta.

Serum angiopoietin-like 3 levels are elevated in obese non diabetic men but are unaffected during an oral glucose tolerance test.

This study aimed to determine ANGPTL3 serum levels in healthy young lean and obese non-diabetic men during an oral glucose tolerance test (OGTT) and correlate them with anthropometric, biochemical and hormonal parameters. A case-control study was carried out and 30 young obese non-diabetic (23.90 ± 3.84 years and BMI 37.92 ± 4.85 kg/m2) and 28 age-matched healthy lean (24.56 ± 3.50 years and BMI of 22.10 ± 1.72 kg/m2) men were included in this study. The primary outcome measures were serum basal ANGPTL3 and ANGPTL3-area under the curve (AUC) levels. The percentage of body fat was measured by dual-energy X-ray absorptiometry and biochemical, hormonal and insulin resistance indices were determined. Basal ANGPTL3 and ANGPTL3-AUC levels were significantly elevated (p < 0.05) in young obese subjects compared with lean subjects and were positively and significantly associated with different anthropometric measurements. Fasting ANGPTL3 serum levels were positively correlated with fasting insulin, leptin, Leptin/Adiponectin index and triglyceride-glucose index. Moreover, ANGPTL3-AUC was negatively correlated with Matsuda index. In this regard, chronically high ANGPTL3 levels in young obese subjects might favor triglyceride-rich lipoprotein clearance to replenish triglyceride stores by white adipose tissue rather than oxidative tissues.

Inhibidores de dipeptidil dipeptidasa-IV: de la teoría a la práctica / Dipeptidil dipeptidase-IV inhibidors: from the theory to the practice

Esta revisión de los inhibidores de dipeptidil peptidasa-IV busca motivar el uso racional de tal grupo farmacológico en la práctica diaria. Este grupo es una nueva opción terapéutica en monoterapia o terapia combinada para el tratamiento de los pacientes con diabetes mellitus tipo 2. En Colombia, se encuentran disponibles: sitagliptina, vildagliptina, saxagliptina y linagliptina. Si bien todas las gliptinas tienen el mismo mecanismo de acción-aumentan la vida media del péptido similar al glucagón-, esta revisión presenta las diferencias entre sus propiedades farmacológicas, eventos adversos y perfil de seguridad. Estos medicamentos son de segunda o tercera línea para el tratamiento oral de los pacientes con diabetes mellitus tipo 2, o primera línea en los pacientes intolerantes a la metformina. Además, algunas de las ventajas que tienen son que: generan menor riesgo de hipoglucemia, tienen efecto neutro sobre el peso, son seguros en adultos mayores, disminuyen la variabilidad de la glucemia y, adicionalmente, se pueden utilizar en la enfermedad renal crónica avanzada, con o sin terapia de reemplazo renal, y en la insuficiencia hepática.

This review of dipeptidyl peptidase-IV inhibitors seeks to encourage the rational use of these drugs in daily practice; this group is a new therapeutic option in monotherapy or combination therapy for the treatment of patients with diabetes mellitus type 2. Sitagliptin, vildagliptin, saxagliptin and linagliptin are available in Colombia. While all gliptins have the same mechanism of action-they increase the average life of glucagon-like peptide-, this review presents the differences among their pharmacological properties, adverse events and safety profile. These drugs are second or third-line for the oral treatment of patients with diabetes mellitus type 2, or first-line in patients intolerant to metformin. They also have some advantages like lower risk of hypoglycemia, neutral effect on weight, safety for the elderly, reduction of glycaemia variability; additionally, they can be used in advanced chronic kidney disease, with or without renal replacement therapy, and in liver failure.