Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity.

Background & Aims: Hepatic mitochondrial respiration is higher in steatosis, but lower in overt type 2 diabetes. We hypothesized that hepatic oxidative phosphorylation (OXPHOS) capacity increases with a greater degree of insulin resistance in obesity, independent of other metabolic diseases.

Methods: We analyzed 65 humans without diabetes (BMI 50 ± 7 kg/m, hemoglobin A1c 5.

Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis.

Aims/hypothesis: To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death.

Methods: This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included.

Metabolic surgery-induced changes of the growth hormone system relate to improved adipose tissue function.

Aims: Body weight loss improves insulin resistance and growth hormone secretion in obesity, which may be regulated by leptin according to preclinical studies. How changes in leptin, lipids and insulin sensitivity after bariatric (metabolic) surgery affect the human growth hormone system is yet unclear.

Participants And Methods: People with obesity (OBE, n = 79, BMI 50.

Skin advanced glycation end products as a screening tool of neuropathy in type 2 diabetes mellitus.

Aim Of The Study: To examine the diagnostic utility of skin advanced glycation end products (AGEs) as screening tool of neuropathy in type 2 diabetes mellitus (T2DM).

Patients And Methods: We included 132 participants (88 men) with a mean age of 64.57 years and median T2DM duration of 14.

Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease.

Background & Aims: Adipose tissue dysfunction is involved in the development of insulin resistance and is responsible for excessive lipid delivery to other organs such as the liver. We tested the hypothesis that impaired mitochondrial function is a common feature of subcutaneous (SAT) and visceral adipose tissue (VAT), but may differently contribute to adipose tissue insulin resistance (IR) in obesity, non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH).

Methods: In this cross-sectional study, we analyzed tissue-specific insulin sensitivity using stable isotope dilution and hyperinsulinemic-normoglycemic clamp tests.

Correlation Between Skin Advanced Glycation End Products and Cardiac Autonomic Neuropathy Among Subjects with Type 2 Diabetes Mellitus.

Introduction: Advanced glycation end products (AGEs) are frequently increased in the skin of subjects with type 2 diabetes mellitus (T2DM). This study aimed to examine the correlation of AGEs with cardiac autonomic neuropathy (CAN) in T2DM.

Methods: To this aim, 132 participants (88 men) with a mean age of 64.

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.

Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes.

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM.

Skin Advanced Glycation End Products among Subjects with Type 2 Diabetes Mellitus with or without Distal Sensorimotor Polyneuropathy.

Materials And Methods: We included 132 subjects (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years.

Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis.

Aims/hypothesis: Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death.

Methods: This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity.

Novel molecular markers of cardiovascular disease risk in type 2 diabetes mellitus.

Diabetes represents the leading risk factor for the development of cardiovascular disease (CVD). Chronic hyperglycemia and/or acute post-prandial changes in blood glucose determine an increase in reactive oxygen species (ROS), which play a fundamental role in endothelial dysfunction and in the nuclear transport of pro-atherogenic transcription factors that activate the "inflammasome". In addition, the glycemic alteration favors the formation and stabilization of atherosclerotic plaque through the mechanism of non-enzymatic glycation of different molecules, with the establishment of the so-called "advanced glycosylation end products" (AGE).

Considerations for single- versus multiple-drug pharmacotherapy in the management of painful diabetic neuropathy.

Introduction: The efficacy of monotherapy to reduce pain from diabetic peripheral neuropathy (DPN) is frequently not satisfactory and guidelines do not provide unanimous treatment options. In this context, multiple drug pharmacotherapy may provide benefit.

Areas Covered: The aim of the present review is to describe the clinical trials addressing the pharmacotherapy of painful DPN.

Skin AGEs and diabetic neuropathy.

Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for measurement of tissue-bound AGEs is tissue biopsy.

Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans.

Background: Nonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge, mainly due to the worldwide obesity and diabetes epidemics.

Scope Of Review: This review summarizes the knowledge on the pathogenesis underlying NAFLD by focusing on studies in humans and on hypercaloric nutrition, including effects of saturated fat and fructose, as well as adipose tissue dysfunction, leading to hepatic lipotoxicity, abnormal mitochondrial function, and oxidative stress, and highlights intestinal dysbiosis.

Metabolic liver disease in diabetes - From mechanisms to clinical trials.

Non-alcoholic fatty liver disease (NAFLD) comprises fatty liver (steatosis), non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis and may lead to end-stage liver failure or hepatocellular carcinoma. NAFLD is tightly associated with the most frequent metabolic disorders, such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Both multisystem diseases share several common mechanisms.

Clinical Tools for Peripheral Neuropathy to Exclude Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Mellitus.

Introduction: Assessment for cardiovascular autonomic neuropathy (CAN) remains difficult in everyday clinical practice. We sought to examine the diagnostic utility of various simple tools for diabetic peripheral neuropathy (DPN) in the detection of CAN in type 2 diabetes mellitus.

Methods: We examined 153 type 2 diabetes mellitus subjects by various DPN tools (vibration perception threshold, 10 g Semmes-Weinstein monofilament, Ipswich touch test, NC-stat/DPNCheck, neuropathy disability score) for the detection of CAN.

Current Pharmacological Treatment of Painful Diabetic Neuropathy: A Narrative Review.

: Distal symmetrical polyneuropathy (DSPN) is one of the most common chronic complications of diabetes mellitus. Although it is usually characterized by progressive sensory loss, some patients may develop chronic pain. Assessment of DSPN is not difficult, but the biggest challenge is making the correct diagnosis and choosing the right treatment.

The Diagnostic Utility of VibraTip for Distal Symmetrical Polyneuropathy in Type 2 Diabetes Mellitus.

Introduction: The aim of this study was to assess the performance of VibraTip, a device used to test a person's vibration perception during routine checks for peripheral neuropathy, against two thresholds of the Neuropathy Disability Score (NDS) for diagnosing distal symmetrical polyneuropathy (DSPN) in patients with type 2 diabetes mellitus (T2DM).

Methods: One hundred consecutive subjects with T2DM were enrolled in the study, of whom 54 were men. The mean age was 62.

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.

Mean platelet volume and coronary artery disease.

Purpose Of Review: To critically review the literature describing links between mean platelet volume (MPV) and cardiovascular disease (CVD). We will focus on coronary artery disease (CAD). The MPV is measured routinely as part of a routine blood count.

Advances in pharmacological treatment of type 1 diabetes during pregnancy.

Introduction: In women with type 1 diabetes mellitus (T1DM), pregnancy is associated with a potential risk of maternal, foetal and neonatal outcomes. Stringent metabolic control is required to improve these outcomes.

Areas Covered: In this review, the authors summarise the current evidence from studies on the pharmacological therapy and on monitoring of T1DM during pregnancy.