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Frontiers in Endocrinology 2023Diabetic kidney disease (DKD) is a severe diabetic complication that affects up to half of the individuals with diabetes. Elevated blood glucose levels are a key... (Review)
Review
Diabetic kidney disease (DKD) is a severe diabetic complication that affects up to half of the individuals with diabetes. Elevated blood glucose levels are a key underlying cause of DKD, but DKD is a complex multifactorial disease, which takes years to develop. Family studies have shown that inherited factors also contribute to the risk of the disease. During the last decade, genome-wide association studies (GWASs) have emerged as a powerful tool to identify genetic risk factors for DKD. In recent years, the GWASs have acquired larger number of participants, leading to increased statistical power to detect more genetic risk factors. In addition, whole-exome and whole-genome sequencing studies are emerging, aiming to identify rare genetic risk factors for DKD, as well as epigenome-wide association studies, investigating DNA methylation in relation to DKD. This article aims to review the identified genetic and epigenetic risk factors for DKD.
Topics: Humans; Diabetic Nephropathies; Genome-Wide Association Study; Diabetes Complications; Risk Factors; Epigenesis, Genetic; Diabetes Mellitus
PubMed: 37324271
DOI: 10.3389/fendo.2023.1163001 -
Nutrients Sep 2019The Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD) conducted a review of existing systematic reviews and... (Review)
Review
The Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD) conducted a review of existing systematic reviews and meta-analyses to explain the relationship between different dietary patterns and patient-important cardiometabolic outcomes. To update the clinical practice guidelines for nutrition therapy in the prevention and management of diabetes, we summarize the evidence from these evidence syntheses for the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), Portfolio, Nordic, liquid meal replacement, and vegetarian dietary patterns. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. We summarized the evidence for disease incidence outcomes and risk factor outcomes using risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs), respectively. The Mediterranean diet showed a cardiovascular disease (CVD) incidence (RR: 0.62; 95%CI, 0.50, 0.78), and non-significant CVD mortality (RR: 0.67; 95%CI, 0.45, 1.00) benefit. The DASH dietary pattern improved cardiometabolic risk factors ( < 0.05) and was associated with the decreased incidence of CVD (RR, 0.80; 95%CI, 0.76, 0.85). Vegetarian dietary patterns were associated with improved cardiometabolic risk factors ( < 0.05) and the reduced incidence (0.72; 95%CI: 0.61, 0.85) and mortality (RR, 0.78; 95%CI, 0.69, 0.88) of coronary heart disease. The Portfolio dietary pattern improved cardiometabolic risk factors and reduced estimated 10-year coronary heart disease (CHD) risk by 13% (-1.34% (95%CI, -2.19 to -0.49)). The Nordic dietary pattern was correlated with decreased CVD (0.93 (95%CI, 0.88, 0.99)) and stroke incidence (0.87 (95%CI, 0.77, 0.97)) and, along with liquid meal replacements, improved cardiometabolic risk factors ( < 0.05). The evidence was assessed as low to moderate certainty for most dietary patterns and outcome pairs. Current evidence suggests that the Mediterranean, DASH, Portfolio, Nordic, liquid meal replacement and vegetarian dietary patterns have cardiometabolic advantages in populations inclusive of diabetes.
Topics: Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Diet; Diet, Mediterranean; Diet, Vegetarian; Dietary Approaches To Stop Hypertension; Humans; MEDLINE; Meta-Analysis as Topic; Metabolic Diseases; Nutrition Therapy; Risk Factors; Scandinavian and Nordic Countries; Systematic Reviews as Topic
PubMed: 31540227
DOI: 10.3390/nu11092209 -
Reviews in Endocrine & Metabolic... Mar 2020The association between diabetes mellitus (and its micro- and macro-vascular complications) and erectile dysfunction is widely known and the presence of hypogonadism may... (Review)
Review
The association between diabetes mellitus (and its micro- and macro-vascular complications) and erectile dysfunction is widely known and the presence of hypogonadism may further complicate sexual dysfunction and quality of life, given the association between hypogonadism and reduced libido, ejaculatory disorders, and depressive symptoms. However, the recent introduction of novel antidiabetic agents with a wide range of mechanism of action may have a significant impact both on male and female sexuality directly (by inducing side effects as urinary tract infections) and indirectly (improving metabolic status and reducing diabetes complications behind sexual dysfunctions). To date only few papers are reporting the sexual effects of these treatments and, often, these are not comparable in their results. Conversely, female sexual dysfunctions are somehow under-investigated. Data on prevalence is heterogeneous and specific pathogenic mechanisms, as well as the burden of psychological factors, are still heatedly debated. The aim of this narrative review is to summarize current knowledge and stressing out the need to diagnose male and female sexual dysfunctions also in light of the impact of treatments with novel antidiabetic agents. This would highlight the still unmet needs for sexual care in a diabetes care setting and could represent an incentive for future discussions, as well as a required theoretical starting point for studies on this subject.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Erectile Dysfunction; Female; Humans; Hypoglycemic Agents; Hypogonadism; Libido; Male; Sexual Dysfunction, Physiological
PubMed: 31863254
DOI: 10.1007/s11154-019-09535-7 -
Cells May 2021Diabetic retinopathy is one of the most important microvascular complications associated with diabetes mellitus, and a leading cause of vision loss or blindness... (Review)
Review
Diabetic retinopathy is one of the most important microvascular complications associated with diabetes mellitus, and a leading cause of vision loss or blindness worldwide. Hyperglycaemic conditions disrupt microvascular integrity at the level of the neurovascular unit. In recent years, zebrafish have come into focus as a model organism for various metabolic diseases such as diabetes. In both mammals and vertebrates, the anatomy and the function of the retina and the neurovascular unit have been highly conserved. In this review, we focus on the advances that have been made through studying pathologies associated with retinopathy in zebrafish models of diabetes. We discuss the different cell types that form the neurovascular unit, their role in diabetic retinopathy and how to study them in zebrafish. We then present new insights gained through zebrafish studies. The advantages of using zebrafish for diabetic retinopathy are summarised, including the fact that the zebrafish has, so far, provided the only animal model in which hyperglycaemia-induced retinal angiogenesis can be observed. Based on currently available data, we propose potential investigations that could advance the field further.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetic Retinopathy; Disease Models, Animal; Retina; Zebrafish
PubMed: 34070439
DOI: 10.3390/cells10061313 -
BMC Endocrine Disorders May 2021Recent studies have reported that HbA1c and lipid variability is useful for risk stratification in diabetes mellitus. The present study evaluated the predictive value of... (Observational Study)
Observational Study
INTRODUCTION
Recent studies have reported that HbA1c and lipid variability is useful for risk stratification in diabetes mellitus. The present study evaluated the predictive value of the baseline, subsequent mean of at least three measurements and variability of HbA1c and lipids for adverse outcomes.
METHODS
This retrospective cohort study consists of type 1 and type 2 diabetic patients who were prescribed insulin at outpatient clinics of Hong Kong public hospitals, from 1st January to 31st December 2009. Standard deviation (SD) and coefficient of variation were used to measure the variability of HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride. The primary outcome is all-cause mortality. Secondary outcomes were diabetes-related complications.
RESULT
The study consists of 25,186 patients (mean age = 63.0, interquartile range [IQR] of age = 15.1 years, male = 50%). HbA1c and lipid value and variability were significant predictors of all-cause mortality. Higher HbA1c and lipid variability measures were associated with increased risks of neurological, ophthalmological and renal complications, as well as incident dementia, osteoporosis, peripheral vascular disease, ischemic heart disease, atrial fibrillation and heart failure (p < 0.05). Significant association was found between hypoglycemic frequency (p < 0.0001), HbA1c (p < 0.0001) and lipid variability against baseline neutrophil-lymphocyte ratio (NLR).
CONCLUSION
Raised variability in HbA1c and lipid parameters are associated with an elevated risk in both diabetic complications and all-cause mortality. The association between hypoglycemic frequency, baseline NLR, and both HbA1c and lipid variability implicate a role for inflammation in mediating adverse outcomes in diabetes, but this should be explored further in future studies.
Topics: Adult; Aged; Blood Glucose; Computer Simulation; Diabetes Complications; Diabetes Mellitus; Female; Glycated Hemoglobin; Hong Kong; Humans; Lipids; Machine Learning; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Survival Analysis
PubMed: 33947391
DOI: 10.1186/s12902-021-00751-4 -
Acta Diabetologica Nov 2020The COronaVirus DISease 19 (COVID-19) is a pandemic infectious disease caused by the novel coronavirus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2).... (Review)
Review
The COronaVirus DISease 19 (COVID-19) is a pandemic infectious disease caused by the novel coronavirus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Older age and presence of comorbidities, including diabetes, were shown to be associated with a more severe course and a higher fatality rate. Studies from the most affected countries, including China, United States and Italy, seem to indicate that prevalence of diabetes among patients affected by COVID-19 is not higher than that observed in the general population, thus suggesting that diabetes is not a risk factor for SARS-CoV-2 infection. However, a large body of evidence demonstrate that diabetes is a risk factor for disease progression towards critical illness, development of acute respiratory distress syndrome, need for mechanical ventilation or admission to intensive care unit, and ultimately death. The mechanisms underlying the relationship between COVID-19 and diabetes remain to be elucidated. In particular, it is still unresolved whether is diabetes per se, especially if poorly controlled, or rather the various comorbidities/complications associated with it that predispose patients with COVID-19 to a worse prognosis. In fact, conditions that cluster with diabetes in the context of the metabolic syndrome, such as obesity and hypertension, or complicate chronic hyperglycemia, such as cardiovascular disease and chronic kidney disease, have also been associated with poor prognosis in these individuals and the available studies have not consistently shown that diabetes predict disease severity independently of them.
Topics: Betacoronavirus; COVID-19; Comorbidity; Coronavirus Infections; Diabetes Complications; Diabetes Mellitus; Disease Progression; Humans; Pandemics; Pneumonia, Viral; Prognosis; Risk Factors; SARS-CoV-2; Severity of Illness Index
PubMed: 32865671
DOI: 10.1007/s00592-020-01586-6 -
Journal of Diabetes and Its... Nov 2019Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid... (Review)
Review
Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid gastric emptying also is a frequent and important diabetic complication. In contrast, acute hyperglycemia causes slow gastric emptying, and acute hypoglycemia causes rapid gastric emptying. Rapid gastric emptying is frequent in T2DM; however, it may also occur in T1DM, particularly in the early stages of the disease, but may persist even into late stages. Recent studies suggest that usually, the stomach restricts the emptying of nutrients to 1-4 kcals/min. This restriction is due to the action of the gastric 'braking' hormones such as GLP-1, leptin, and amylin acting via the gastric inhibitory vagal motor circuit (GIVMC). Disruption of this braking system leads to rapid gastric emptying. Acute hyperglycemia also slows gastric emptying by stimulating the GIVMC, while acute hypoglycemia causes rapid gastric emptying by stimulating the gastric excitatory vagal motor circuit (GEVMC). In contrast, chronic hyperglycemia causes rapid gastric emptying by inducing oxidative stress in the stomach wall that disrupts inhibitory neuromuscular transmission and increases the contractility of the smooth muscle, while chronic hyperglycemia may also cause slow gastric emptying via severe inflammatory stress caused by proinflammatory macrophages and reduce contractility of the smooth muscle. There is a bidirectional relationship between blood glucose and gastric emptying. Thus, rapid gastric emptying may lead to a sizeable postprandial spike, and slow gastric emptying may blunt it. Postprandial hyperglycemia is involved in the development, progression, and complications of DM. Correction of fast gastric emptying involves agents that activate GIVMC and the use of gastric 'braking' hormones or their analogs. Recognition and treatment of rapid gastric emptying may contribute to better management of postprandial hyperglycemia and prevention of some diabetic complications.
Topics: Blood Glucose; Diabetes Complications; Diabetes Mellitus; Gastric Emptying; Gastroparesis; Humans; Hyperglycemia; Postprandial Period; Prognosis; Stomach Diseases
PubMed: 31439470
DOI: 10.1016/j.jdiacomp.2019.107414 -
Biomedicine & Pharmacotherapy =... Sep 2023Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable... (Review)
Review
Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation.
Topics: Humans; Aged; Glycemic Control; Diabetes Mellitus; Constipation; Hyperglycemia; Gastrointestinal Diseases; Diabetes Complications
PubMed: 37506579
DOI: 10.1016/j.biopha.2023.115202 -
Hormone and Metabolic Research =... Jul 2022The development and progression of the complications of chronic diabetes mellitus are attributed not only to increased blood glucose levels but also to glycemic... (Review)
Review
The development and progression of the complications of chronic diabetes mellitus are attributed not only to increased blood glucose levels but also to glycemic variability. Therefore, a deeper understanding of the role of glycemic variability in the development of diabetic complications may provide more insight into targeted clinical treatment strategies in the future. Previously, the mechanisms implicated in glycemic variability-induced diabetic complications have been comprehensively discussed. However, endothelial dysfunction and platelet hyperactivation, which are two newly recognized critical pathogenic factors, have not been fully elucidated yet. In this review, we first evaluate the assessment of glycemic variability and then summarise the roles of endothelial dysfunction and platelet hyperactivation in glycemic variability-induced complications of diabetes, highlighting the molecular mechanisms involved and their interconnections.
Topics: Blood Glucose; Diabetes Complications; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Vascular Diseases
PubMed: 35835141
DOI: 10.1055/a-1880-0978 -
Endocrinology and Metabolism (Seoul,... Feb 2024Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial... (Review)
Review
Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved β-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Diabetes Complications; Combined Modality Therapy; Hyperglycemia
PubMed: 38031401
DOI: 10.3803/EnM.2023.1816