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Current Cardiology Reviews 2020The globalization of the Western lifestyle has resulted in increase of diabetes mellitus, a complex, multifactorial disease. Diabetes mellitus is a condition often... (Review)
Review
The globalization of the Western lifestyle has resulted in increase of diabetes mellitus, a complex, multifactorial disease. Diabetes mellitus is a condition often related to the disorders of the cardiovascular system. It is well established that three quarters of diabetics, aged over 40, will die from cardiovascular disease and are more likely than non-diabetics to die from their first cardiovascular event. Therefore, it is of paramount importance to individualize treatment via risk stratification. Conditions that increase cardiovascular risk in people with diabetes include age more than 40 years, male gender, history of relative suffering from premature CHD, blood pressure and high LDL levels, presence of microalbuminuria, obstructive sleepapnea, erectile dysfunction and other conditions. Several models have been developed in order to assess cardiovascular risk in people with and without diabetes. Some of them have been proven to be inadequate while others are widely used for years. An emerging way of risk assessment in patients with diabetes mellitus is the use of biomarkers but a lot of research needs to be done in this field in order to have solid conclusions.
Topics: Adult; Biomarkers; Cardiovascular Diseases; Diabetes Complications; Female; Heart Disease Risk Factors; Humans; Male; Risk Assessment; Risk Factors
PubMed: 31713488
DOI: 10.2174/1573403X15666191111123622 -
Metabolic and Metabo-Clinical Signatures of Type 2 Diabetes, Obesity, Retinopathy, and Dyslipidemia.Diabetes Feb 2022Macro- and microvascular complications of type 2 diabetes (T2D), obesity, and dyslipidemia share common metabolic pathways. In this study, using a total of 1,300...
Macro- and microvascular complications of type 2 diabetes (T2D), obesity, and dyslipidemia share common metabolic pathways. In this study, using a total of 1,300 metabolites from 996 Qatari adults (57% with T2D) and 1,159 metabolites from an independent cohort of 2,618 individuals from the Qatar BioBank (11% with T2D), we identified 373 metabolites associated with T2D, obesity, retinopathy, dyslipidemia, and lipoprotein levels, 161 of which were novel. Novel metabolites included phospholipids, sphingolipids, lysolipids, fatty acids, dipeptides, and metabolites of the urea cycle and xanthine, steroid, and glutathione metabolism. The identified metabolites enrich pathways of oxidative stress, lipotoxicity, glucotoxicity, and proteolysis. Second, we identified 15 patterns we defined as "metabo-clinical signatures." These are clusters of patients with T2D who group together based on metabolite levels and reveal the same clustering in two or more clinical variables (obesity, LDL, HDL, triglycerides, and retinopathy). These signatures revealed metabolic pathways associated with different clinical patterns and identified patients with extreme (very high/low) clinical variables associated with extreme metabolite levels in specific pathways. Among our novel findings are the role of N-acetylmethionine in retinopathy in conjunction with dyslipidemia and the possible roles of N-acetylvaline and pyroglutamine in association with high cholesterol levels and kidney function.
Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Dyslipidemias; Female; Humans; Insulin Resistance; Male; Metabolome; Metabolomics; Middle Aged; Obesity; Prognosis; Qatar; Regression Analysis
PubMed: 34732537
DOI: 10.2337/db21-0490 -
Acta Medica Portuguesa Dec 2021
Topics: Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans
PubMed: 32456770
DOI: 10.20344/amp.13111 -
Journal of Diabetes and Its... Oct 2022Urologic complications such as bladder and sexual dysfunction among men and women with diabetes have received relatively little attention. This is despite emerging... (Review)
Review
Urologic complications such as bladder and sexual dysfunction among men and women with diabetes have received relatively little attention. This is despite emerging evidence that demonstrates that urologic complications increase with age in the general population and are more common in individuals with diabetes compared to those without diabetes. Here we summarize the latest information about the epidemiology of urologic complications in the setting of diabetes and the most recent findings regarding pathophysiology. In addition, we identify knowledge gaps and need for future funding to address these gaps that will reduce the burden of urologic complications in diabetes and optimize quality of life for all individuals affected by it.
Topics: Diabetes Complications; Diabetes Mellitus; Female; Humans; Male; Quality of Life; Sexual Dysfunction, Physiological
PubMed: 36088680
DOI: 10.1016/j.jdiacomp.2022.108288 -
PloS One 2020To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function... (Randomized Controlled Trial)
Randomized Controlled Trial
Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data.
OBJECTIVES
To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes.
METHODS
Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial.
PARTICIPANTS
Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey.
INTERVENTION
Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function.
RESULTS
One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%.
CONCLUSIONS
ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes.
REGISTRATION
- ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.
Topics: Aged; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Double-Blind Method; Europe; Female; Galvanic Skin Response; Humans; Hyperglycemia; International Cooperation; Life Style; Linagliptin; Male; Metformin; Microcirculation; Middle Aged; Patient Selection; Research Design; Risk Factors
PubMed: 32282852
DOI: 10.1371/journal.pone.0231196 -
Diabetes Care Feb 2020The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia,...
2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: ) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium-glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA or individualized HbA target; ) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and ) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to ≤60 mL min [1.73 m] or urinary albumin-to-creatinine ratio >30 mg/g, particularly >300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death.
Topics: Cardiovascular Diseases; Consensus; Diabetes Complications; Diabetes Mellitus, Type 2; Europe; History, 21st Century; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Renal Insufficiency, Chronic; Societies, Medical; Sodium-Glucose Transporter 2 Inhibitors; United States
PubMed: 31857443
DOI: 10.2337/dci19-0066 -
The Journal of Clinical Investigation Oct 2020Hypoxia can be defined as a relative deficiency in the amount of oxygen reaching the tissues. Hypoxia-inducible factors (HIFs) are critical regulators of the mammalian... (Review)
Review
Hypoxia can be defined as a relative deficiency in the amount of oxygen reaching the tissues. Hypoxia-inducible factors (HIFs) are critical regulators of the mammalian response to hypoxia. In normal circumstances, HIF-1α protein turnover is rapid, and hyperglycemia further destabilizes the protein. In addition to their role in diabetes pathogenesis, HIFs are implicated in development of the microvascular and macrovascular complications of diabetes. Improving glucose control in people with diabetes increases HIF-1α protein and has wide-ranging benefits, some of which are at least partially mediated by HIF-1α. Nevertheless, most strategies to improve diabetes or its complications via regulation of HIF-1α have not currently proven to be clinically useful. The intersection of HIF biology with diabetes is a complex area in which many further questions remain, especially regarding the well-conducted studies clearly describing discrepant effects of different methods of increasing HIF-1α, even within the same tissues. This Review presents a brief overview of HIFs; discusses the range of evidence implicating HIFs in β cell dysfunction, diabetes pathogenesis, and diabetes complications; and examines the differing outcomes of HIF-targeting approaches in these conditions.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Diabetes Complications; Diabetes Mellitus; Glucose; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Models, Biological; Tissue Distribution
PubMed: 32809974
DOI: 10.1172/JCI137556 -
International Journal of Molecular... Jun 2022Type 2 diabetes mellitus (T2DM) can result in microvascular complications such as neuropathy, retinopathy, nephropathy, and cerebral small vessel disease, and contribute... (Review)
Review
Type 2 diabetes mellitus (T2DM) can result in microvascular complications such as neuropathy, retinopathy, nephropathy, and cerebral small vessel disease, and contribute to macrovascular complications, such as heart failure, peripheral arterial disease, and large vessel stroke. T2DM also increases the risks of depression and dementia for reasons that remain largely unclear. Perturbations in the cytochrome P450-soluble epoxide hydrolase (CYP-sEH) pathway have been implicated in each of these diabetes complications. Here we review evidence from the clinical and animal literature suggesting the involvement of the CYP-sEH pathway in T2DM complications across organ systems, and highlight possible mechanisms (e.g., inflammation, fibrosis, mitochondrial function, endoplasmic reticulum stress, the unfolded protein response and autophagy) that may be relevant to the therapeutic potential of the pathway. These mechanisms may be broadly relevant to understanding, preventing and treating microvascular complications affecting the brain and other organ systems in T2DM.
Topics: Animals; Cytochrome P-450 Enzyme System; Diabetes Complications; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; Epoxide Hydrolases; Inflammation
PubMed: 35682911
DOI: 10.3390/ijms23116232 -
Frontiers in Endocrinology 2020
Topics: Diabetes Complications; Diabetes Mellitus; Humans; Lung Diseases; Obesity
PubMed: 32765427
DOI: 10.3389/fendo.2020.00462 -
Frontiers in Endocrinology 2022There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher... (Review)
Review
There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.
Topics: COVID-19; Causality; Comorbidity; Diabetes Complications; Diabetes Mellitus; Humans; Patient Acuity; Risk Factors; SARS-CoV-2
PubMed: 35250853
DOI: 10.3389/fendo.2022.780663