-
Cardiovascular Diabetology Jul 2023Type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic kidney disease (CKD), are recognized among the most disruptive public health issues of the current... (Review)
Review
Type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic kidney disease (CKD), are recognized among the most disruptive public health issues of the current century. A large body of evidence from epidemiological and clinical research supports the existence of a strong interconnection between these conditions, such that the unifying term cardio-metabolic-renal (CMR) disease has been defined. This coexistence has remarkable epidemiological, pathophysiologic, and prognostic implications. The mechanisms of hyperglycemia-induced damage to the cardio-renal system are well validated, as are those that tie cardiac and renal disease together. Yet, it remains controversial how and to what extent CVD and CKD can promote metabolic dysregulation. The aim of this review is to recapitulate the epidemiology of the CMR connections; to discuss the well-established, as well as the putative and emerging mechanisms implicated in the interplay among these three entities; and to provide a pathophysiological background for an integrated therapeutic intervention aiming at interrupting this vicious crosstalks.
Topics: Humans; Diabetes Mellitus, Type 2; Cardio-Renal Syndrome; Kidney; Cardiovascular Diseases; Renal Insufficiency, Chronic; Metabolic Diseases
PubMed: 37525273
DOI: 10.1186/s12933-023-01937-x -
Circulation Nov 2023A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular... (Review)
Review
A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.
A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.
Topics: United States; Humans; Cardiovascular Diseases; Metabolic Syndrome; American Heart Association; Risk Factors; Kidney; Renal Insufficiency, Chronic
PubMed: 37807920
DOI: 10.1161/CIR.0000000000001186 -
Progress in Lipid Research Jul 2023Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid... (Review)
Review
Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid metabolism are responsible for the development of various pathologies comprising metabolic syndrome, obesity, and type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative in most cells of our body, coordinate temporal aspects of lipid homeostasis. In this review we summarize current knowledge on the circadian regulation of lipid digestion, absorption, transportation, biosynthesis, catabolism, and storage. Specifically, we focus on the molecular interactions between functional clockwork and biosynthetic pathways of major lipid classes comprising cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, and sphingomyelins. A growing body of epidemiological studies associate a socially imposed circadian misalignment common in modern society with growing incidence of metabolic disorders, however the disruption of lipid metabolism rhythms in this connection has only been recently revealed. Here, we highlight recent studies that unravel the mechanistic link between intracellular molecular clocks, lipid homeostasis and development of metabolic diseases based on animal models of clock disruption and on innovative translational studies in humans. We also discuss the perspectives of manipulating circadian oscillators as a potentially powerful approach for preventing and managing metabolic disorders in human patients.
Topics: Animals; Humans; Lipid Metabolism; Circadian Rhythm; Circadian Clocks; Diabetes Mellitus, Type 2; Energy Metabolism; Metabolic Diseases; Lipids
PubMed: 37187314
DOI: 10.1016/j.plipres.2023.101235 -
International Journal of Obesity (2005) Jul 2023A bidirectional relationship exists between adipose tissue metabolism and iron regulation. Total body fat, fat distribution and exercise influence iron status and... (Review)
Review
A bidirectional relationship exists between adipose tissue metabolism and iron regulation. Total body fat, fat distribution and exercise influence iron status and components of the iron-regulatory pathway, including hepcidin and erythroferrone. Conversely, whole body and tissue iron stores associate with fat mass and distribution and glucose and lipid metabolism in adipose tissue, liver, and muscle. Manipulation of the iron-regulatory proteins erythroferrone and erythropoietin affects glucose and lipid metabolism. Several lines of evidence suggest that iron accumulation and metabolism may play a role in the development of metabolic diseases including obesity, type 2 diabetes, hyperlipidaemia and non-alcoholic fatty liver disease. In this review we summarise the current understanding of the relationship between iron homoeostasis and metabolic disease.
Topics: Humans; Glucose; Iron; Diabetes Mellitus, Type 2; Obesity; Liver; Lipid Metabolism
PubMed: 37029208
DOI: 10.1038/s41366-023-01299-0 -
Journal of Hepatology Dec 2023While the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with obesity and insulin resistance is widely appreciated, there are a host of... (Review)
Review
While the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with obesity and insulin resistance is widely appreciated, there are a host of complex interactions between the liver and other endocrine axes. While it can be difficult to definitively distinguish direct causal relationships and those attributable to increased adipocyte mass, there is substantial evidence of the direct and indirect effects of endocrine dysregulation on the severity of MASLD, with strong evidence that low levels of growth hormone, sex hormones, and thyroid hormone promote the development and progression of disease. The impact of steroid hormones, e.g. cortisol and dehydroepiandrosterone, and adipokines is much more divergent. Thoughtful assessment, based on individual risk factors and findings, and management of non-insulin endocrine axes is essential in the evaluation and management of MASLD. Multiple therapeutic options have emerged that leverage various endocrine axes to reduce the fibroinflammatory cascade in MASH.
Topics: Humans; Insulin Resistance; Metabolic Diseases; Fatty Liver; Adipocytes
PubMed: 37730124
DOI: 10.1016/j.jhep.2023.08.030 -
The Journal of Clinical Investigation Jun 2023Cell senescence (CS) is at the nexus between aging and associated chronic disorders, and aging increases the burden of CS in all major metabolic tissues. However, CS is... (Review)
Review
Cell senescence (CS) is at the nexus between aging and associated chronic disorders, and aging increases the burden of CS in all major metabolic tissues. However, CS is also increased in adult obesity, type 2 diabetes (T2D), and nonalcoholic fatty liver disease independent of aging. Senescent tissues are characterized by dysfunctional cells and increased inflammation, and both progenitor cells and mature, fully differentiated and nonproliferating cells are afflicted. Recent studies have shown that hyperinsulinemia and associated insulin resistance (IR) promote CS in both human adipose and liver cells. Similarly, increased CS promotes cellular IR, showing their interdependence. Furthermore, the increased adipose CS in T2D is independent of age, BMI, and degree of hyperinsulinemia, suggesting premature aging. These results suggest that senomorphic/senolytic therapy may become important for treating these common metabolic disorders.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Cellular Senescence; Aging; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Obesity
PubMed: 37317964
DOI: 10.1172/JCI169922 -
Nutrition, Metabolism, and... Jul 2023A comprehensive review comparing the effect of vegetarian (V) and non-vegetarian (NV) diets on the major cardiometabolic diseases' outcomes was performed. (Review)
Review
AIMS
A comprehensive review comparing the effect of vegetarian (V) and non-vegetarian (NV) diets on the major cardiometabolic diseases' outcomes was performed.
DATA SYNTHESIS
We performed literature research (up to December 31, 2022) of the evidence separately for vascular disease (VD), obesity (OB), dyslipidemia (Dysl), hypertension (HPT), type 2 diabetes (T2D), metabolic syndrome (MetS), analyzing only cohort studies and randomized controlled studies (RCTs) and comparing the effect of V and NV diets. Cohort studies showed advantages of V diets compared to NV diets on incidence and/or mortality risk for ischemic heart disease, overweight and OB risk. Most cohort studies showed V had lower risk of HPT and lower blood pressure (BP) than NV and V diets had positive effects on T2D risk or plasma parameters. The few cohort studies on the risk of MetS reported mixed results. In RCTs, V diets, mainly low-fat-vegan ones, led to greater weight loss and improved glycemic control than NV diets and in the only one RCT a partial regression of coronary atherosclerosis. In most RCTs, V diets significantly reduced LDL-C levels (but also decreased HDL-C levels) and BP.
CONCLUSIONS
In this comprehensive review of the association between V diets and cardiometabolic outcomes, we found that following this type of diet may help to prevent most of these diseases. However, the non-uniformity of the studies, due to ethnic, cultural, and methodological differences, does not allow for generalizing the present results and drawing definitive conclusions. Further, well-designed studies are warranted to confirm the consistency of our conclusions.
Topics: Humans; Diet, Vegetarian; Obesity; Hypertension; Metabolic Syndrome; Diabetes Mellitus, Type 2; Diet, Fat-Restricted
PubMed: 37217433
DOI: 10.1016/j.numecd.2023.04.005 -
Nature Communications Oct 2023Obesity is a risk factor for type 2 diabetes and cardiovascular disease. However, a substantial proportion of patients with these conditions have a seemingly normal body...
Obesity is a risk factor for type 2 diabetes and cardiovascular disease. However, a substantial proportion of patients with these conditions have a seemingly normal body mass index (BMI). Conversely, not all obese individuals present with metabolic disorders giving rise to the concept of "metabolically healthy obese". We use lipidomic-based models for BMI to calculate a metabolic BMI score (mBMI) as a measure of metabolic dysregulation associated with obesity. Using the difference between mBMI and BMI (mBMIΔ), we identify individuals with a similar BMI but differing in their metabolic health and disease risk profiles. Exercise and diet associate with mBMIΔ suggesting the ability to modify mBMI with lifestyle intervention. Our findings show that, the mBMI score captures information on metabolic dysregulation that is independent of the measured BMI and so provides an opportunity to assess metabolic health to identify "at risk" individuals for targeted intervention and monitoring.
Topics: Humans; Diabetes Mellitus, Type 2; Body Mass Index; Obesity; Risk Factors; Cardiovascular Diseases; Metabolic Syndrome
PubMed: 37805498
DOI: 10.1038/s41467-023-41963-7 -
Cardiovascular Diabetology Sep 2023Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the... (Review)
Review
Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.
Topics: Humans; Endothelial Cells; Vascular Diseases; Diabetes Mellitus; Hyperglycemia; Oxidative Stress
PubMed: 37660030
DOI: 10.1186/s12933-023-01965-7 -
Frontiers in Endocrinology 2023
Topics: Humans; Environmental Exposure; Air Pollution; Metabolic Diseases
PubMed: 37867520
DOI: 10.3389/fendo.2023.1298687