Is hypoxia vulnerability in fishes a by-product of maximum metabolic rate?

ABSTRACT The metabolic index concept combines metabolic data and known thermal sensitivities to estimate the factorial aerobic scope of animals in different habitats, which is valuable for understanding the metabolic demands that constrain species' geographical distributions. An important assumption of this concept is that the O2 supply capacity (which is equivalent to the rate of oxygen consumption divided by the environmental partial pressure of oxygen: ) is constant at O2 tensions above the critical O2 threshold (i.e. the where O2 uptake can no longer meet metabolic demand). This has led to the notion that hypoxia vulnerability is not a selected trait, but a by-product of selection on maximum metabolic rate. In this Commentary, we explore whether this fundamental assumption is supported among fishes. We provide evidence that O2 supply capacity is not constant in all fishes, with some species exhibiting an elevated O2 supply capacity in hypoxic environments. We further discuss the divergent selective pressures on hypoxia- and exercise-based cardiorespiratory adaptations in fishes, while also considering the implications of a hypoxia-optimized O2 supply capacity for the metabolic index concept.

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10–18 and h2 = 0.58, P = 1 × 10–7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (− 0.22), waist circumference (− 0.25), triglycerides (− 0.18), fat mass (− 0.23), fasting glucose (− 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (− 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Gravicentric approach to Type 2 Diabetes therapy. The success prediction. A proof-of-concept

This study is the proof-of-concept of our "Gravicentric" theory. This concept is based on several fundamental points: obesity as the main foe; rapid reversibility of the disease; as well as a new perspective on the roles different pharmacological classes play in general, and the role of insulin and GLP-1 analogs, in particular. The paper presents and discusses our experience of the implementation of insulin and GLP-1 analogs. The possibility of "insulin weaning"; the therapeutic approach for over-treated patients; and physiological dosing of insulin is also discussed therein. Objectives Primary: To evaluate the long-term efficacy of GLP-1 analogs in insulin-treated Type 2 Diabetes Mellitus (T2DM) patients. Secondary: To analyze which patient would most likely benefit from this combined treatment. Methods In 54 T2DM patients with a mean disease duration of 17.5 years and a mean extent of insulin therapy of 4.5 years, additional GLP-1 analogs therapy was prescribed. Mean duration of GLP-1 treatment was 25.8 months (2.15 years). During the intervention, clinical, biochemical, and anthropometric parameters were analyzed. Compliance, Hypoglycemia and Metabolic Index (MI) assessments were implemented. Results Mean Glycated hemoglobin (HbA1C) decreased from 9.28 1.43 to 8.54 1.4% on GLP-1 analogs, p 0.01. Total Daily dose of Insulin (TDI) showed considerable reduction: 80.6 42.7 U/day before starting GLP-1 vs.41.0 30.7 U/day on GLP-1, p 0.01. These changes were directly linked to weight loss: BMI has dropped from 35.1 4.8 kg/cm2 before, to 32.8 5.0 kg/cm2 on GLP-1 analogs, with patients losing 6.7 kg on average. Moreover, 13 (24%) participants discontinued at least one kind of insulin, while 7 (13%) stopped taking insulin completely, with simultaneous improvement in diabetes control. No clinically significant hypoglycemia was observed. Post-hoc, the participants were categorized according to each patients ability to reduce TDI by more than 20 U/day, and then split into two groups. Group A 34 patients (64.2%) who successfully reduced TDI; Group B 19 patients (35.8%) who failed to do so. The comparison of the two groups showed the following: Significantly larger virtually twice as large baseline TDI in Group A (97.440.4 U/day vs. 52.231.0 U/day), p 0.001. Very effective BMI reduction (BMI 3.3 2.4 kg/cm2 0.9 1.2 kg/cm2, p 0.001) and much better compliance (1.4 1.1 vs. 2.2 1.0, p 0.02) in Group A. A considerable decline of insulin requirements in group A, on GLP-1 therapy (TDI on GLP-1 was -62.4 31.9 U/day) with no TDI reduction in Group B (TDI on GLP-1 was +0.03 14.1 U/day, p 0.001). Thus, in spite of the fact that on GLP1 therapy HbA1C has declined to the same levels in both groups, patients from group A became much leaner and metabolically healthier. We suggest overtreatment as the critical factor of obesity in Group A. Conclusions Adding GLP-1 analogs to insulin in poorly controlled, insulin-treated T2DM patients resulted in an impressive weight (BMI) reduction with significant improvements in glucose control. This provided for a further decline in insulin resistance and insulin requirements. We suggest that the best candidate for successful GLP-1 analogs therapy is an obese, overtreated and compliant T2DM person. Changes in Metabolic Index (MI) rather than surrogate glycemic parameters (HbA1C) are better predictors of a successful T2DM therapy. Neither the duration of diabetes nor the length of insulin therapy in the past is likely to have a critical role in predicting success. These findings are proof-of-concept of our Gravicentric theory in T2DM.

Multimodal FDG-PET and EEG assessment improves diagnosis and prognostication of disorders of consciousness

ABSTRACTThe complex diagnosis of disorders of consciousness (DoC) diagnosis increasingly relies on brain-imaging techniques for their ability to detect residual signs of consciousness in otherwise unresponsive patients. However, few of these techniques have been validated on external datasets. Here, we show that the FDG-PET glucose metabolic index of the best preserved hemisphere has robust in-sample and out-sample performances to diagnose DoC, slightly outperforming EEG-based classification. We further show that a multimodal assessment combining both FDG-PET and EEG not only improved diagnostic performances, but also allowed to identify covert cognition and to predict 6-month responsiveness in initially unresponsive patients. Lastly, we show that DoC heterogeneity reflects a sum of regional cortical metabolic differences, and their corresponding behavioral patterns, rather than a binary contrast between conscious and unconscious states. In total, we show that FDG-PET and EEG provide complementary information on DoC physiopathology and that their combination improves DoC diagnosis and prognostication.

Which Metabolic Index is Appropriate for Predicting Non-alcoholic Steatohepatitis?

BACKGROUND There are controversial ideas about the application of metabolic indices for the prediction of nonalcoholic steatohepatitis (NASH). In this study, we evaluated some novel metabolic indices for the screening of NASH. METHODS This prospective case-control study was performed in a gastroenterology outpatient clinic. Consecutively selected patients with persistently elevated aminotransferase levels and evidence of fatty liver in ultrasonography were enrolled. Those with other etiologies of aminotransferase elevation were excluded. The remaining was presumed to have NASH. The control group consisted of age and sex-matched subjects with normal liver function tests and liver ultrasound examinations. RESULTS Finally, 94 patients with steatohepatitis and 106 controls were included in the project. The mean liver fat content (LFC), aspartate aminotransferase, and alanine aminotransferase levels were significantly lower in the control group than in the NASH group. LFC was independently associated with the presence of NASH in logistic regression analysis. LFC had a good area under the curve for the prediction of NASH in ROC (receiver operating characteristic curve) analysis. CONCLUSION LFC seems to be a reliable metabolic index for the detection of patients with NASH.