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André Scheen - One of the best experts on this subject based on the ideXlab platform.
Current Diabetes Reports, 2018Co-Authors: André ScheenAbstract:
In patients with preDiabetes or Type 2 Diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset Diabetes. These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-Type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and Type 2 Diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents. Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in Type 2 Diabetes and of new-onset Diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with Type 2 Diabetes and hypertension.
Current Diabetes Reports, 2018Co-Authors: André ScheenAbstract:
Purpose of Review In patients with preDiabetes or Type 2 Diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset Diabetes. Recent Findings These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-Type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and Type 2 Diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents. Summary Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in Type 2 Diabetes and of new-onset Diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with Type 2 Diabetes and hypertension.
Acta Clinica Belgica, 2003Co-Authors: André ScheenAbstract:
Type 2 Diabetes mellitus is a heterogeneous syndrome characterized by abnormalities in carbohydrate and fat metabolism. The causes of Type 2 Diabetes are multi-factorial and include both genetic and environmental elements that affect beta-cell function and tissue (muscle, liver, adipose tissue, pancreas) insulin sensitivity. Although there is considerable debate as to the relative contributions of beta-cell dysfunction and reduced insulin sensitivity to the pathogenesis of Diabetes, it is generally agreed that both these factors play important roles. However, the mechanisms controlling the interplay of these two impairments are unclear. A number of factors have been suggested as possibly linking insulin resistance and beta-cell dysfunction in the pathogenesis of Type 2 Diabetes. A majority of individuals suffering from Type 2 Diabetes are obese, with central visceral adiposity. Therefore, the adipose tissue should play a crucial role in the pathogenesis of Type 2 Diabetes. Although the predominant paradigm used to explain this link is the portal/visceral hypothesis giving a key role in elevated non-esterified fatty acid concentrations, two new emerging paradigms are the ectopic fat storage syndrome (deposition of triglycerides in muscle, liver and pancreatic cells) and the adipose tissue as endocrine organ hypothesis (secretion of various adipocytokins, i.e. leptin, TNF-alpha, resistin, adiponectin, implicated in insulin resistance and possibly beta-cell dysfunction). These two paradigms constitute the framework for the study of the interplay between insulin resistance and beta-cell dysfunction in Type 2 Diabetes as well as between our obesogenic environment and Diabetes risk in the next decade.
Markku Laakso - One of the best experts on this subject based on the ideXlab platform.
Endocrine development, 2016Co-Authors: Alena Stančáková, Markku LaaksoAbstract:
Genetic and environmental factors as well as their interactions contribute to the pathogenesis of Type 2 Diabetes. Linkage analysis, candidate gene approaches, genome-wide association studies, and sequencing have been used in the identification of common, low-frequency and rare variants for Type 2 Diabetes. Genome-wide association studies have identified >80 common variants for Type 2 Diabetes, with small effect sizes (risk of Type 2 Diabetes increased by 5-40%). Almost all of these variants regulate insulin secretion, and only a few regulate insulin sensitivity. Common variants capture only ∼10% of the heritability of Type 2 Diabetes. Low-frequency and rare variants with large effects have also been identified, but their contribution to 'missing heritability' at the population level is limited. Gene-environment and gene-gene interactions and epigenetics are likely to contribute to the missing heritability of Type 2 Diabetes. Epigenetic factors (DNA methylations and histone modifications) are especially important because they might mediate the effects of environmental exposures on the risk of Type 2 Diabetes. Although understanding of the genetics of Type 2 Diabetes has exhibited great progress in the past few years, a substantial amount of additional work will be required to identify causal variants/genes and molecular mechanisms via which the association signals found confer Diabetes risk.
Dyslipidemias, 2015Co-Authors: Henna Cederberg, Markku LaaksoAbstract:
Type 2 Diabetes is associated with microvascular and macrovascular complications. More than 70 % of these patients die of cardiovascular disease (CVD). Dyslipidemia in Type 2 Diabetes is characterized by elevated levels of plasma total and very-low-density lipoprotein triglycerides and postprandial triglyceride-rich lipoprotein remnants, abundance of small dense low-density lipoprotein (LDL) particles, low levels of HDL cholesterol, and elevated levels of apolipoprotein B. High levels of LDL cholesterol is the most important modifiable risk factor for CVD in Type 2 Diabetes, and therefore statin treatment, in addition to diet, is the basis of lipid-lowering treatment. Statin treatment is evidence-based in the prevention of CVD mortality and morbidity in individuals with Type 2 Diabetes
Endocrinología y Nutrición, 2009Co-Authors: Markku LaaksoAbstract:
Diabetes affects currently about 5% of world’s populations, and its prevalence is rapidly increasing particularly in elderly subjects. Because over 80% of all diabetic subjects have Type 2 Diabetes, the increase in the number of diabetic individuals implies an epidemic of Type 2 Diabetes. Although microvascular disease is also common in patients with Type 2 Diabetes, cardiovascular disease (CVD), particularly coronary heart disease (CHD), is a major complication of this disease, and over 50% of all patients die of CHD1. Type 2 Diabetes is usually preceded by a long period of asymptomatic hyperglycemia which may last for years. Both insulin resistance and Type 2 Diabetes are characterized by dyslipidemia, which increases the risk for CVD2. Although several mechanisms are likely to contribute to accelerated atherosclerosis and increased risk of CVD observed in patients with Type 2 Diabetes mellitus, dyslipidemia is perhaps the most important single risk factor among all risk factors3.
Seminars in vascular medicine, 2002Co-Authors: Markku LaaksoAbstract:
Type 2 Diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although Type 2 Diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in Type 2 Diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with Type 2 Diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with Type 2 Diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.
Diabetes, 1999Co-Authors: Markku LaaksoAbstract:
Cardiovascular disease (coronary heart disease, stroke, peripheral vascular disease) is the most important cause of mortality and morbidity among patients with Type 2 Diabetes. Conventional risk factors contribute similarly to macrovascular complications in patients with Type 2 Diabetes and nondiabetic subjects, and therefore, other explanations have been sought for enhanced atherothrombosis in Type 2 Diabetes. Among characteristics specific for Type 2 Diabetes, hyperglycemia has recently been a focus of keen research. A recent meta-analysis of 20 studies on nondiabetic subjects has demonstrated that in the nondiabetic range of glycemia (
Helen R. Murphy - One of the best experts on this subject based on the ideXlab platform.
Current Diabetes Reports, 2014Co-Authors: Niranjala M. Hewapathirana, Helen R. MurphyAbstract:
Over the past decade the prevalence of Type 2 Diabetes in pregnancy has continued to increase. It is vital that health care professionals recognize that preconception care is just as important for mothers with Type 2 Diabetes as it is in Type 1 Diabetes. All women with Type 2 Diabetes should be advised regarding safe effective contraception and the benefits of optimal glycemic control, folic acid supplementation, and avoidance of potentially harmful mediations before attempting pregnancy. Glycemic control is the most important modifiable risk factor for congenital anomaly in women with Type 2 Diabetes, whereas maternal obesity and social disadvantage are associated with large for gestational age neonates. This review aims to bring the reader up to date with the burden of perinatal outcomes and clinical interventions to improve maternal and infant health. It warns that the consequences of Type 2 Diabetes pregnancy do not end at birth.
Best practice & research. Clinical endocrinology & metabolism, 2010Co-Authors: R. C. Temple, Helen R. MurphyAbstract:
The worldwide epidemic in Type 2 Diabetes has been associated with an increased diagnosis in young adults. This has lead to a rapid rise in the number of pregnancies complicated by Type 2 Diabetes. Studies have shown risk of serious adverse outcome, including congenital malformation and perinatal mortality, is the same, or increased, in Type 2 Diabetes compared to Type 1 Diabetes. Despite improved glycaemic control in Type 2 Diabetes compared to Type 1 Diabetes, rates of perinatal morbidity, including preterm birth and macrosomia, appear to be similar. Risk factors associated with poor pregnancy outcome in women with Type 2 Diabetes include obesity, ethnicity and poor pregnancy preparation. This review will cover practical aspects of management of Type 2 Diabetes before, during and after pregnancy, including prepregnancy care, safety of oral hypoglycaemic agents, glycaemic management during labour, and choice of effective contraception.
Wolfgang Rathmann - One of the best experts on this subject based on the ideXlab platform.
Diabetes, 2020Co-Authors: Mohamed A Elhadad, Christian Jonasson, Cornelia Huth, Rory P. Wilson, Christian Gieger, Pamela Matias, Harald Grallert, Johannes Graumann, Valerie Gailus-durner, Wolfgang RathmannAbstract:
With an estimated prevalence of 463 million affected, Type 2 Diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with Type 2 Diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between Type 2 Diabetes and >1000 plasma proteins in the KORA (Cooperative health research in the Region of Augsburg) F4 cohort (n=993, 110 cases), with subsequent replication in the HUNT3 (Third wave of the Nord-Trondelag Health Study) cohort (n=940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status and hypertension. Additionally, we investigated associations with incident Type 2 Diabetes and performed two-sample bi-directional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent Type 2 Diabetes revealed 24 replicated proteins, of which eight are novel. Proteins showing association with incident Type 2 Diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor binding protein-2. Aminoacylase-1 was associated with both prevalent and incident Type 2 Diabetes. MR analysis yielded nominally significant causal effects of Type 2 Diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone-binding globulin on Type 2 Diabetes. In conclusion, our high-throughput proteomics study replicated previously reported Type 2 Diabetes-protein associations, and identified new candidate proteins possibly involved in the pathogenesis of Type 2 Diabetes.
Abbas E Kitabchi - One of the best experts on this subject based on the ideXlab platform.
management of Type 2 Diabetes evolving strategies for the treatment of patients with Type 2 DiabetesMetabolism-clinical and Experimental, 2011Co-Authors: Ebenezer Nyenwe, Terri W Jerkins, Guillermo E Umpierrez, Abbas E KitabchiAbstract:
The prevalence of Type 2 Diabetes continues to increase at an alarming rate around the world, with even more people being affected by preDiabetes. Although the pathogenesis and long-term complications of Type 2 Diabetes are fairly well known, its treatment has remained challenging, with only half of the patients achieving the recommended hemoglobin A1c target. This narrative review explores the pathogenetic rationale for the treatment of Type 2 Diabetes, with the view of fostering better understanding of the evolving treatment modalities. The diagnostic criteria including the role of hemoglobin A1c in the diagnosis of Diabetes are discussed. Due attention is given to the different therapeutic maneuvers and their utility in the management of the diabetic patient. The evidence supporting the role of exercise, medical nutrition therapy, glucose monitoring, and antiobesity measures including pharmacotherapy and bariatric surgery is discussed. The controversial subject of optimum glycemic control in hospitalized and ambulatory patients is discussed in detail. An update of the available pharmacologic options for the management of Type 2 Diabetes is provided with particular emphasis on newer and emerging modalities. Special attention has been given to the initiation of insulin therapy in patients with Type 2 Diabetes, with explanation of the pathophysiologic basis for insulin therapy in the ambulatory diabetic patient. A review of the evidence supporting the efficacy of the different preventive measures is also provided.