OBJECTIVE—To evaluate whether homeostasis model assessment-estimated insulin resistance (HOMA-IR) is an independent predictor of cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND METHODS—Conventional CVD risk factors (sex, age, smoking, plasma lipids, blood pressure, and metabolic control) and insulin resistance (estimated by HOMA) were evaluated at baseline in 1,326 patients with type 2 diabetes examined within the Verona Diabetes Complications Study. At baseline and after a mean follow-up of 4.5 years, CVD was assessed by medical history, physical examination, electrocardiography, and echo-Doppler of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were carefully scrutinized to identify cardiovascular deaths. In statistical analyses, CVD was an aggregate end point including both fatal and nonfatal coronary, cerebrovascular, and peripheral vascular disease as well as ischemic electrocardiographic abnormalities and vascular lesions identified by echo-Doppler. RESULTS—At baseline, 441 subjects were coded positive for CVD (prevalent cases). Incident cases numbered 126. Multiple logistic regression analyses showed that, along with sex, age, smoking, HDL/total cholesterol ratio, and hypertension, HOMA-IR was an independent predictor of both prevalent and incident CVD. A 1-unit increase in (log)HOMA-IR value was associated with an odds ratio for prevalent CVD at baseline of 1.31 (95% CI 1.10–1.56, P = 0.002) and for incident CVD during follow-up of 1.56 (95% CI 1.14–2.12, P < 0.001). CONCLUSIONS—HOMA-IR is an independent predictor of CVD in type 2 diabetes. The improvement of insulin resistance might have beneficial effects not only on glucose control but also on CVD in patients with type 2 diabetes.

In this review, after a general introduction devoted to show the importance of the role played by C ₂-symmetry chiral auxiliaries to provide high levels of stereoselection, a complete survey of the preparation and use of optically active 1,1′-binaphthyl derivatives as chiral auxiliaries in asymmetric synthesis is attempted. 1. Introduction 2. Synthesis and Applications of [1,1′-binaphthyl]-2,2′-diol (1) and Derivatives 2.1. Synthesis 2.2. Applications 2.2.1. Enantioselective Reduction of Prochiral Ketones 2.2.2. Enantioselective Addition of Chiral Titanium Reagents to Aromatic Aldehydes 2.2.3. Asymmetric Diels-Alder Reactions 2.2.4. Asymmetric Hydrogenation of Prochiral Unsaturated Acids and Esters 2.2.5. Asymmetric Alkylation of Racemic Allylic Substrates 2.2.6. Crown Ethers Containing 1,1′-Binaphthylic Units 2.2.7. Stereoselective Polymerization 2.2.8. Asymmetric Ullmann Coupling Reactions 2.2.9. Asymmetric Alkylation of Arylacetic Acids 2.2.10. Asymmetric Cyclization 3. Synthesis and Applications of [1,1′-Binaphthyl]-2,2′-dithiol (2) 3.1. Synthesis 3.2. Applications 4. Synthesis and Applications of 2,2′-Bis(diarylphosphino)-1,1′-binaphthyls (BINAPs) 4.1. Synthesis 4.2. Applications 4.2.1. Rh(I)-BINAP Complexes 4.2.1.1. Asymmetric Hydrogenation of α-Acylaminoacrylic Acids 4.2.1.2. Asymmetric Isomerization of Double Bonds 4.2.1.3. Asymmetric Hydroboration of Styrenes 4.2.2. Ru(II)-BINAP Complexes 4.2.2.1. Asymmetric Hydrogenation of α,β- and β,γ-Unsaturated Acids 4.2.2.2. Asymmetric Hydrogenation of (Z)-2-Acyl-1-benzylidene-1,2,3,4-tetrahydroisoquinolines 4.2.2.3. Asymmetric Hydrogenation of Prochiral Allylic Alcohols 4.2.2.4. Asymmetric Hydrogenation of Chiral Allylic Secondary Alcohols 4.2.2.5. Asymmetric Hydrogenation of Prochiral Functionalized Ketones 4.2.2.6. Asymmetric Hydrogenation of β-Oxoesters 4.2.2.7. Asymmetric Hydrogenation of 1,3-Diketones 4.2.3. Pd-BINAP Complexes 5. Synthesis and Applications of [1,1′-Binaphthyl]-2,2′-diamine (4) and its Analogues 5.1. Synthesis 5.2. Applications 5.2.1. Enantioselective Reduction of Ketones 5.2.2. Asymmetric Hydrogenation of Acylaminoacrylic Acids 5.2.3. Asymmetric Synthesis of Lactones 5.2.4. Asymmetric Alkylation of Aromatic Aldehydes Mediated by N,N,N′,N′-Tetramethyl[1,1′-binaphthyl]-2, 2′-diamine (51) 6. Some Other 1,1′-Binaphthyl Derivatives with C ₂-Symmetry 6.1. 1,1′-Binaphthylic Substituted Tetramethylethylenediamine 6.2. 2,2′-Bis[(diphenylphosphino)methyl]-1,1′-binaphthyl [(S)-(-)-NAPHOS(1,1′)] 6.3. Miscellanea 7. Conclusions

3-iodothyronamine (T1AM) is a novel relative of thyroid hormone, able to interact with specific G protein-coupled receptors, known as trace amine-associated receptors. Significant functional effects are produced by exogenous T1AM, including a negative inotropic and chronotropic effect in cardiac preparations. This work was aimed at estimating endogenous T1AM concentration in different tissues and determining its cardiac metabolism. A novel HPLC tandem mass spectrometry assay was developed, allowing detection of T1AM, thyronamine, 3-iodothyroacetic acid, and thyroacetic acid. T1AM was detected in rat serum, at the concentration of 0.3±0.03 pmol/ml, and in all tested organs (heart, liver, kidney, skeletal muscle, stomach, lung, and brain), at concentrations significantly higher than the serum concentration, ranging from 5.6±1.5 pmol/g in lung to 92.9±28.5 pmol/g in liver. T1AM was also identified for the first time in human blood. In H9c2 cardiomyocytes and isolated perfused rat hearts, significant Na+-dependent uptake of exogenous T1AM was observed, and at the steady state total cellular or tissue T1AM concentration exceeded extracellular concentration by more than 20-fold. In both preparations T1AM underwent oxidative deamination to 3-iodothyroacetic acid. T1AM deamination was inhibited by iproniazid but not pargyline or semicarbazide, suggesting the involvement of both monoamine oxidase and semicarbazide-sensitive amine oxidase. Thyronamine and thyroacetic acid were not detected in heart. Finally, evidence of T1AM production was observed in cardiomyocytes exposed to exogenous thyroid hormone, although the activity of this pathway was very low.