Search

Type 2 diabetes mellitus (T2DM) is characterized by tissue-specific insulin resistance and pancreatic β-cell dysfunction, which result from the interplay of local abnormalities within different tissues and systemic dysregulation of tissue crosstalk. The main local mechanisms comprise metabolic (lipid) signalling, altered mitochondrial metabolism with oxidative stress, endoplasmic reticulum stress and local inflammation. While the role of endocrine dysregulation in T2DM pathogenesis is well established, other forms of inter-organ crosstalk deserve closer investigation to better understand the multifactorial transition from normoglycaemia to hyperglycaemia. This narrative Review addresses the impact of certain tissue-specific messenger systems, such as metabolites, peptides and proteins and microRNAs, their secretion patterns and possible alternative transport mechanisms, such as extracellular vesicles (exosomes). The focus is on the effects of these messengers on distant organs during the development of T2DM and progression to its complications. Starting from the adipose tissue as a major organ relevant to T2DM pathophysiology, the discussion is expanded to other key tissues, such as skeletal muscle, liver, the endocrine pancreas and the intestine. Subsequently, this Review also sheds light on the potential of multimarker panels derived from these biomarkers and related multi-omics for the prediction of risk and progression of T2DM, novel diabetes mellitus subtypes and/or endotypes and T2DM-related complications. Inter-organ crosstalk is increasingly understood as an important mechanism contributing to insulin resistance and β-cell failure, the key features of type 2 diabetes mellitus. This Review discusses mediators of inter-organ crosstalk in type 2 diabetes mellitus, its pathogenesis and its related complications. Key points: Crosstalk between adipose tissue, liver, skeletal muscle, pancreas and intestine plays a key role in pathogenesis of insulin resistance and β-cell dysfunction, both of which characterize type 2 diabetes mellitus (T2DM). Among metabolic mediators, bioactive lipids such as diacylglycerols and ceramides are the best described inhibitors of insulin signalling, but fatty acids such palmitic acid and myristic acid, also contribute to metabolic alterations via post-translational protein modification. The current concept of the pathogenesis of T2DM postulates that adipose tissue dysfunction initiates insulin resistance and ectopic lipid storage, but also contributes to pancreatic β-cell dysfunction via long-term excessive exposure to fatty acids and glucose. Multi-omics studies based on previously identified crosstalk mediators have proposed multimarker signatures, which could, in the future, help improve the prediction of risk and progression of T2DM and its subtypes, and the risk of complications. Mendelian randomization studies have identified causal associations between established and novel biomarkers and the risk of T2DM and its complications, but are also critically revising previously accepted roles of several crosstalk mediators, underlining the concept of reverse causality. Current studies also focus on the relevance of crosstalk mediators in understanding the subtypes of prediabetes and diabetes mellitus and for the subtype-specific differences in diabetes mellitus-related comorbidities and complications to pave the way for future precision diabetology. [ABSTRACT FROM AUTHOR]

Osteoporosis and atherosclerosis are significant public health problems that often coexist, especially in the elderly. Although some studies have reported an age-dependent relationship, others have suggested a causal relationship between osteoporosis and atherosclerosis. The aim of our study was to evaluate the cardiovascular risk in a population of patients with osteoporosis by measuring carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cf-PWV). A total of 58 patients with osteoporosis and an equal number of healthy control subjects were enrolled. All subjects underwent (1) a bone densitometry examination using dual X-ray absorptiometry, (2) a vascular evaluation for the measurements of cIMT and cf-PWV and (3) a blood sample for the evaluation of lipids and phosphocalcic metabolism. Patients with osteoporosis had a significant increase in cIMT and cf-PWV. There was also a significant inverse correlation between the femoral neck BMD and cf-PWV values. In conclusion, osteoporotic outpatients have earlier vascular ageing, with an increase of arterial stiffness. These data support a possible association between osteoporosis and atherosclerosis independent of age. [ABSTRACT FROM AUTHOR]