New classes of modified teleparallel gravity models

New classes of modified teleparallel theories of gravity are introduced. The action of this theory is constructed to be a function of the irreducible parts of torsion $f(T_{\rm ax},T_{\rm ten},T_{\rm vec})$, where $T_{\rm ax},T_{\rm ten}$ and $T_{\rm vec}$ are squares of the axial, tensor and vector components of torsion, respectively. This is the most general (well-motivated) second order teleparallel theory of gravity that can be constructed from the torsion tensor. Different particular second order theories can be recovered from this theory such as new general relativity, conformal teleparallel gravity or $f(T)$ gravity. Additionally, the boundary term $B$ which connects the Ricci scalar with the torsion scalar via $R=-T+B$ can also be incorporated into the action. By performing a conformal transformation, it is shown that the two unique theories which have an Einstein frame are either the teleparallel equivalent of general relativity or $f(-T+B)=f(R)$ gravity, as expected.Comment: v2: 10 pages, accepted for publication in PLB; for a detailed derivation of the field equations see Appendix A in v

Teleparallel Theories of Gravity: Illuminating a Fully Invariant Approach

Teleparallel gravity and its popular generalization $f(T)$ gravity can be formulated as fully invariant (under both coordinate transformations and local Lorentz transformations) theories of gravity. Several misconceptions about teleparallel gravity and its generalizations can be found in the literature, especially regarding their local Lorentz invariance. We describe how these misunderstandings may have arisen and attempt to clarify the situation. In particular, the central point of confusion in the literature appears to be related to the inertial spin connection in teleparallel gravity models. While inertial spin connections are commonplace in special relativity, and not something inherent to teleparallel gravity, the role of the inertial spin connection in removing the spurious inertial effects within a given frame of reference is emphasized here. The careful consideration of the inertial spin connection leads to the construction of a fully invariant theory of teleparallel gravity and its generalizations. Indeed, it is the nature of the spin connection that differentiates the relationship between what have been called good tetrads and bad tetrads and clearly shows that, in principle, any tetrad can be utilized. The field equations for the fully invariant formulation of teleparallel gravity and its generalizations are presented and a number of examples using different assumptions on the frame and spin connection are displayed to illustrate the covariant procedure. Various modified teleparallel gravity models are also briefly reviewed.Comment: v2: 72 pages, revised version, references added, matches published versio

Muscle Mitochondrial ATP Synthesis and Glucose Transport/Phosphorylation in Type 2 Diabetes

BACKGROUND: Muscular insulin resistance is frequently characterized by blunted increases in glucose-6-phosphate (G-6-P) reflecting impaired glucose transport/phosphorylation. These abnormalities likely relate to excessive intramyocellular lipids and mitochondrial dysfunction. We hypothesized that alterations in insulin action and mitochondrial function should be present even in nonobese patients with well-controlled type 2 diabetes mellitus (T2DM). METHODS AND FINDINGS: We measured G-6-P, ATP synthetic flux (i.e., synthesis) and lipid contents of skeletal muscle with (31)P/(1)H magnetic resonance spectroscopy in ten patients with T2DM and in two control groups: ten sex-, age-, and body mass-matched elderly people; and 11 younger healthy individuals. Although insulin sensitivity was lower in patients with T2DM, muscle lipid contents were comparable and hyperinsulinemia increased G-6-P by 50% (95% confidence interval [CI] 39%–99%) in all groups. Patients with diabetes had 27% lower fasting ATP synthetic flux compared to younger controls (p = 0.031). Insulin stimulation increased ATP synthetic flux only in controls (younger: 26%, 95% CI 13%–42%; older: 11%, 95% CI 2%–25%), but failed to increase even during hyperglycemic hyperinsulinemia in patients with T2DM. Fasting free fatty acids and waist-to-hip ratios explained 44% of basal ATP synthetic flux. Insulin sensitivity explained 30% of insulin-stimulated ATP synthetic flux. CONCLUSIONS: Patients with well-controlled T2DM feature slightly lower flux through muscle ATP synthesis, which occurs independently of glucose transport /phosphorylation and lipid deposition but is determined by lipid availability and insulin sensitivity. Furthermore, the reduction in insulin-stimulated glucose disposal despite normal glucose transport/phosphorylation suggests further abnormalities mainly in glycogen synthesis in these patients

Noninvasive in vivo magnetic resonance measures of glutathione synthesis in human and rat liver as an oxidative stress biomarker.

UNLABELLED: Oxidative stress (OS) plays a central role in the progression of liver disease and in damage to liver by toxic xenobiotics. We have developed methods for noninvasive assessment of hepatic OS defenses by measuring flux through the glutathione (GSH) synthesis pathway. (13) C-labeled GSH is endogenously produced and detected by in vivo magnetic resonance after administration of [2-(13) C]-glycine. We report on a successful first-ever human demonstration of this approach as well as preclinical studies demonstrating perturbed GSH metabolism in models of acute and chronic OS. Human studies employed oral administration of [2-(13) C]-glycine and (13) C spectroscopy on a 3T clinical magnetic resonance (MR) imaging scanner and demonstrated detection and quantification of endogenously produced (13) C-GSH after labeled glycine ingestion. Plasma analysis demonstrated that glycine (13) C fractional enrichment achieved steady state during the 6-hour ingestion period. Mean rate of synthesis of hepatic (13) C-labeled GSH was 0.32 ± 0.18 mmole/kg/hour. Preclinical models of acute OS and nonalcoholic steatohepatitis (NASH) comprised CCl4 -treated and high-fat, high-carbohydrate diet-fed Sprague-Dawley rats, respectively, using intravenous administration of [2-(13) C]-glycine and observation of (13) C-label metabolism on a 7T preclinical MR system. Preclinical studies demonstrated a 54% elevation of GSH content and a 31% increase in flux through the GSH synthesis pathway at 12 hours after acute insult caused by CCl4 administration, as well as a 23% decrease in GSH content and evidence of early steatohepatitis in the model of NASH. CONCLUSION: Our data demonstrate in vivo (13) C-labeling and detection of GSH as a biomarker of tissue OS defenses, detecting chronic and acute OS insults. The methods are applicable to clinical research studies of hepatic OS in disease states over time as well as monitoring effects of therapeutic interventions

Comparing the efficacy, safety, and utility of intensive insulin algorithms for a primary care practice

Diabetes management is firmly based within the primary care community. Landmark randomized, controlled trials have demonstrated that even modest reductions in glycated hemoglobin (HbA1c) can yield improvements in economic and medical end-points. Diabetes is a chronic, progressive disease associated with loss of pancreatic β-cell function. Therefore, most patients will eventually require insulin therapies in order to achieve their individualized targeted HbA1c as their β-cell function and mass wanes. Although clinicians understand the importance of early insulin initiation, there is little agreement as to when to introduce insulin as a therapeutic option. Once initiated, questions remain as to whether to allow the patients to self-titrate their dose or whether the dosing should be tightly regulated by the clinician. Physicians have many evidence-based basal insulin protocols from which to choose, all of which have been shown to drive HbA1c levels to the American Diabetes Association target of ≤7%. This article will discuss ways by which insulin therapies can be effectively introduced to patients within busy primary care practices. Published evidence-based basal insulin protocols will be evaluated for safety and efficacy