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Nature Reviews. Nephrology Jul 2020Diabetes is one of the fastest growing diseases worldwide, projected to affect 693 million adults by 2045. Devastating macrovascular complications (cardiovascular... (Review)
Review
Diabetes is one of the fastest growing diseases worldwide, projected to affect 693 million adults by 2045. Devastating macrovascular complications (cardiovascular disease) and microvascular complications (such as diabetic kidney disease, diabetic retinopathy and neuropathy) lead to increased mortality, blindness, kidney failure and an overall decreased quality of life in individuals with diabetes. Clinical risk factors and glycaemic control alone cannot predict the development of vascular complications; numerous genetic studies have demonstrated a clear genetic component to both diabetes and its complications. Early research aimed at identifying genetic determinants of diabetes complications relied on familial linkage analysis suited to strong-effect loci, candidate gene studies prone to false positives, and underpowered genome-wide association studies limited by sample size. The explosion of new genomic datasets, both in terms of biobanks and aggregation of worldwide cohorts, has more than doubled the number of genetic discoveries for both diabetes and diabetes complications. We focus herein on genetic discoveries for diabetes and diabetes complications, empowered primarily through genome-wide association studies, and emphasize the gaps in research for taking genomic discovery to the next level.
Topics: Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Humans
PubMed: 32398868
DOI: 10.1038/s41581-020-0278-5 -
Bulletin of Experimental Biology and... May 2021The review presents modern views about the role of oxidative stress reactions in the pathogenesis of types 1 and 2 diabetes mellitus and their complications based on the... (Review)
Review
The review presents modern views about the role of oxidative stress reactions in the pathogenesis of types 1 and 2 diabetes mellitus and their complications based on the analysis of experimental and clinical studies. The sources of increased ROS generation in diabetes are specified, including the main pathways of altered glucose metabolism, oxidative damage to pancreatic β-cells, and endothelial dysfunction. The relationship between oxidative stress, carbonyl stress, and inflammation is described. The significance of oxidative stress reactions associated with hyperglycemia is considered in the context of the "metabolic memory" phenomenon. The results of our studies demonstrated significant ethnic and age-related variability of the LPO-antioxidant defense system parameters in patients with diabetes mellitus, which should be considered during complex therapy of the disease. Numerous studies of the effectiveness of antioxidants in diabetes mellitus of both types convincingly proved that antioxidants should be a part of the therapeutic process. Modern therapeutic strategies in the treatment of diabetes mellitus are aimed at developing new methods of personalized antioxidant therapy, including ROS sources targeting combined with new ways of antioxidant delivery.
Topics: Animals; Antioxidants; Diabetes Complications; Diabetes Mellitus; Humans; Oxidative Stress; Reactive Oxygen Species
PubMed: 34173093
DOI: 10.1007/s10517-021-05191-7 -
Endocrine Reviews Jun 2016The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM... (Review)
Review
The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM is more frequently diagnosed at lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Generally, large sex-ratio differences across countries are observed. Diversities in biology, culture, lifestyle, environment, and socioeconomic status impact differences between males and females in predisposition, development, and clinical presentation. Genetic effects and epigenetic mechanisms, nutritional factors and sedentary lifestyle affect risk and complications differently in both sexes. Furthermore, sex hormones have a great impact on energy metabolism, body composition, vascular function, and inflammatory responses. Thus, endocrine imbalances relate to unfavorable cardiometabolic traits, observable in women with androgen excess or men with hypogonadism. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome. Overall, psychosocial stress appears to have greater impact on women rather than on men. In addition, women have greater increases of cardiovascular risk, myocardial infarction, and stroke mortality than men, compared with nondiabetic subjects. However, when dialysis therapy is initiated, mortality is comparable in both males and females. Diabetes appears to attenuate the protective effect of the female sex in the development of cardiac diseases and nephropathy. Endocrine and behavioral factors are involved in gender inequalities and affect the outcome. More research regarding sex-dimorphic pathophysiological mechanisms of T2DM and its complications could contribute to more personalized diabetes care in the future and would thus promote more awareness in terms of sex- and gender-specific risk factors.
Topics: Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Male
PubMed: 27159875
DOI: 10.1210/er.2015-1137 -
Advanced Science (Weinheim,... Sep 2021Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep... (Review)
Review
Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep the blood glucose levels under control, these medications are not without side effects. More importantly, once diagnosed diabetes is rarely reversible. Dysfunctions in the kidney, retina, cardiovascular system, neurons, and liver represent the common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, the molecular mechanisms of how type 2 diabetes develops and leads to irreparable organ damage remain elusive. This review particularly focuses on novel targets that may play role in pathogenesis of type 2 diabetes. Further research on these targets may eventually pave the way to novel therapies for the treatment-or even the prevention-of type 2 diabetes along with its complications.
Topics: Diabetes Complications; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents
PubMed: 34319011
DOI: 10.1002/advs.202100275 -
Cardiovascular Diabetology May 2021Several studies suggest that, together with glucose variability, the variability of other risk factors, as blood pressure, plasma lipids, heart rate, body weight, and... (Review)
Review
Several studies suggest that, together with glucose variability, the variability of other risk factors, as blood pressure, plasma lipids, heart rate, body weight, and serum uric acid, might play a role in the development of diabetes complications. Moreover, the variability of each risk factor, when contemporarily present, may have additive effects. However, the question is whether variability is causal or a marker. Evidence shows that the quality of care and the attainment of the target impact on the variability of all risk factors. On the other hand, for some of them causality may be considered. Although specific studies are still lacking, it should be useful checking the variability of a risk factor, together with its magnitude out of the normal range, in clinical practice. This can lead to an improvement of the quality of care, which, in turn, could further hesitate in an improvement of risk factors variability.
Topics: Diabetes Complications; Diabetes Mellitus; Humans; Prognosis; Risk Assessment; Risk Factors
PubMed: 33962641
DOI: 10.1186/s12933-021-01289-4 -
The Medical Clinics of North America May 2017Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are the most serious and life-threatening hyperglycemic emergencies in diabetes. DKA is more... (Review)
Review
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are the most serious and life-threatening hyperglycemic emergencies in diabetes. DKA is more common in young people with type 1 diabetes and HHS in adult and elderly patients with type 2 diabetes. Features of the 2 disorders with ketoacidosis and hyperosmolality may coexist. Both are characterized by insulinopenia and severe hyperglycemia. Early diagnosis and management are paramount. Treatment is aggressive rehydration, insulin therapy, electrolyte replacement, and treatment of underlying precipitating events. This article reviews the epidemiology, pathogenesis, diagnosis, and management of hyperglycemic emergencies.
Topics: Bicarbonates; Diabetes Complications; Diabetic Ketoacidosis; Emergencies; Fluid Therapy; Hospital Mortality; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Hypoglycemic Agents; Inflammation; Insulin; Oxidative Stress; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 28372715
DOI: 10.1016/j.mcna.2016.12.011 -
Diabetes Care Jan 2011
Topics: Algorithms; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Diabetes, Gestational; Diagnostic Techniques, Endocrine; Female; Humans; Models, Biological; Pregnancy; Risk Factors
PubMed: 21193628
DOI: 10.2337/dc11-S062 -
Diabetes Feb 2017The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a... (Review)
Review
The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, "The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis" on 10-12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment.
Topics: Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Genotype; Humans; Hypoglycemic Agents; Phenotype; Precision Medicine; Prognosis; Risk Factors
PubMed: 27980006
DOI: 10.2337/db16-0806 -
Physical Therapy Nov 2008In 2005, it was estimated that more than 20 million people in the United States had diabetes. Approximately 30% of these people had undiagnosed cases. Increased risk for... (Review)
Review
UNLABELLED
In 2005, it was estimated that more than 20 million people in the United States had diabetes. Approximately 30% of these people had undiagnosed cases. Increased risk for diabetes is primarily associated with age, ethnicity, family history of diabetes, smoking, obesity, and physical inactivity. Diabetes-related complications--including cardiovascular disease, kidney disease, neuropathy, blindness, and lower-extremity amputation--are a significant cause of increased morbidity and mortality among people with diabetes, and result in a heavy economic burden on the US health care system. With advances in treatment for diabetes and its associated complications, people with diabetes are living longer with their condition. This longer life span will contribute to further increases in the morbidity associated with diabetes, primarily in elderly people and in minority racial or ethnic groups. In 2050, the number of people in the United States with diagnosed diabetes is estimated to grow to 48.3 million.
RESULTS
from randomized controlled trials provide evidence that intensive lifestyle interventions can prevent or delay the onset of diabetes in high-risk individuals. In addition, adequate and sustained control of blood sugar levels, blood pressure, and blood lipid levels can prevent or delay the onset of diabetes-related complications in people with diabetes. Effective interventions, at both the individual and population levels, are desperately needed to slow the diabetes epidemic and reduce diabetes-related complications in the United States. This report describes the current diabetes epidemic and the health and economic impact of diabetes complications on individuals and on the health care system. The report also provides suggestions by which the epidemic can be curbed.
Topics: Age Distribution; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Retinopathy; Humans; Incidence; Peripheral Vascular Diseases; Prevalence; Risk Factors; United States
PubMed: 18801858
DOI: 10.2522/ptj.20080020 -
Frontiers in Endocrinology 2021Diabetes mellitus and the associated complications are metabolic diseases with high morbidity that result in poor quality of health and life. The lack of diagnostic... (Review)
Review
Diabetes mellitus and the associated complications are metabolic diseases with high morbidity that result in poor quality of health and life. The lack of diagnostic methods for early detection results in patients losing the best treatment opportunity. Oral hypoglycemics and exogenous insulin replenishment are currently the most common therapeutic strategies, which only yield temporary glycemic control rather than curing the disease and its complications. Exosomes are nanoparticles containing bioactive molecules reflecting individual physiological status, regulating metabolism, and repairing damaged tissues. They function as biomarkers of diabetes mellitus and diabetic complications. Considering that exosomes are bioactive molecules, can be obtained from body fluid, and have cell-type specificity, in this review, we highlight the multifold effects of exosomes in the pathology and therapy of diabetes mellitus and diabetic complications.
Topics: Animals; Biomarkers; Diabetes Complications; Diabetes Mellitus; Exosomes; Humans; Molecular Targeted Therapy
PubMed: 34764939
DOI: 10.3389/fendo.2021.756581