Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones.

The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT.

Correlation of cardiac autonomic neuropathy with small and large peripheral nerve function in type 2 diabetes mellitus.

AIMS: To analyse the correlation of cardiac autonomic neuropathy (CAN), sympathetic and parasympathetic dysfunction with the different diagnostic tools for large and small peripheral nerve fibres in type 2 diabetes mellitus (T2DM). METHODS: We included 153 T2DM subjects (92 men) with mean age of 64.4 years. CAN, as well as sympathetic and parasympathetic dysfunction were diagnosed by the Ewing's cardiovascular reflex tests. Vibration perception threshold (VPT), monofilament, Ipswich Touch test, automated sural nerve conduction study and neuropathy disability score (NDS) evaluated large and small peripheral nerve fibre function. RESULTS: CAN (adjusted odds ratio [aOR]: 44.57), parasympathetic (aOR: 18.40) and sympathetic dysfunction (aOR: 5.50) correlated with measures of small fibre function evaluated by pinprick sensation and temperature perception. Among tools for large nerve fibres, positive correlation was shown between: (1) CAN and abnormal VPT (aOR: 16.78), (2) parasympathetic dysfunction and abnormal VPT (aOR: 39.47). CONCLUSIONS: CAN and parasympathetic dysfunction correlate with peripheral neuropathy, especially when the latter is assessed through VPT and measures of small fibre function as evaluated by pinprick sensation and temperature perception. The latter additionally correlate with sympathetic nervous system impairment.

The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes.

INTRODUCTION: There is now an abundance of anti-diabetic agents. However, only few patients achieve glycemic targets. Moreover, current glucose-lowering agents mainly depend upon insulin secretion or function. Sodium glucose co-transporter type 2 (SGLT2) inhibitors present a novel glucose-lowering therapy, inducing glycosuria in an insulin-independent fashion. AREAS COVERED: In this review, the authors discuss the key efficacy and safety data from phase II clinical trials in type 2 diabetes mellitus (T2DM) of the main SGLT2 inhibitors approved or currently in development, and provide a rationale for their use in T2DM. EXPERT OPINION: Despite the very promising characteristics of this new therapeutic class, a number of issues await consideration. One important question is what to expect from head-to-head comparison data. We also need to know if dual inhibition of SGLT1/SGLT2 is more efficacious in reducing HbA1c and how this therapy affects metabolic and cardiovascular parameters. Additionally, several SGLT2 agents that have not yet come to market have hitherto been evaluated in Asian populations, whereas approved SGLT2 inhibitors have been frequently studied in other populations, including Caucasian subjects. Thus, we need more information on the potential role of ethnicity on their efficacy and safety.