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"Diabetes Complications"
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Glycemia Reduction in Type 2 Diabetes — Microvascular and Cardiovascular Outcomes
In a secondary analysis comparing the effect of insulin glargine, glimepiride, liraglutide, and sitagliptin, added to metformin, on the incidences of microvascular complications and death, no material between-group differences were seen.
Journal Article
Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus
A multicenter, randomized trial involving participants with diabetes and no evident cardiovascular disease at trial entry showed that aspirin led to a lower risk of serious vascular events than placebo but also caused a higher risk of major bleeding.
Journal Article
Effects of Bilio-Pancreatic Diversion on Diabetic Complications: A 10-year follow-up
OBJECTIVE: The surgical option could represent a valid alternative to medical therapy in some diabetic patients. However, no data are available on long-term effects of metabolic surgery on diabetic complications. We aimed to determine whether patients with newly diagnosed type 2 diabetes who underwent bilio-pancreatic diversion (BPD) had less micro- and macrovascular complications than those who received conventional therapy. RESEARCH DESIGN AND METHODS: This was an unblinded, case-controlled trial with 10-years' follow-up, conducted from July 1998 through October 2009 at the Day Hospital of Metabolic Diseases, Catholic University, Rome, Italy. A consecutive sample of 110 obese patients (BMI >35 kg/m²) with newly diagnosed type 2 diabetes was enrolled. The study was completed by 50 subjects. The main outcome measure was long-term effects (10 years) of BPD versus those associated with conventional therapy on microvascular outcome, micro- and macroalbuminuria, and glomerular filtration rate (GFR). Secondary measures included macrovascular outcomes, type 2 diabetes remission, glycated hemoglobin, and hyperlipidemia. RESULTS: Ten-year GFR variation was -45.7 ± 18.8% in the medical arm and 13.6 ± 24.5% in the surgical arm (P < 0.001). Ten-year hypercreatininemia prevalence was 39.3% in control subjects and 9% in BPD subjects (P = 0.001). After 10 years, all BPD subjects recovered from microalbuminuria, whereas microalbuminuria appeared or progressed to macroalbuminuria in control subjects. Three myocardial infarctions, determined by electrocardiogram, and one stroke occurred in control subjects. After the 10-year follow-up, coronary heart disease (CHD) probability was 0.22 ± 0.10 and 0.05 ± 0.04 in the medical and surgical groups, respectively (P < 0.001). Remission from type 2 diabetes was observed in all patients within 1 year of surgery. Surgical and medical subjects had lost 34.60 ± 10.25 and 0.38 ± 6.10% of initial weight at the 10-year follow-up (P < 0.001). CONCLUSIONS: Renal and cardiovascular complications were dramatically reduced in the surgical arm, indicating long-term benefits of BPD on diabetic complications, at least in the case of morbid obesity with decompensated type 2 diabetes.
Journal Article
Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications
Type 2 diabetes mellitus (T2DM), a prevalent chronic disease affecting over 400 million people globally, is driven by genetic and environmental factors. The pathogenesis involves insulin resistance and β-cell dysfunction, mediated by mechanisms such as the dedifferentiation of β-cells, mitochondrial dysfunction, and oxidative stress. Treatment should be based on non-pharmacological therapy. Strategies such as increased physical activity, dietary modifications, cognitive-behavioral therapy are important in maintaining normal glycemia. Advanced therapies, including SGLT2 inhibitors and GLP-1 receptor agonists, complement these treatments and offer solid glycemic control, weight control, and reduced cardiovascular risk. Complications of T2DM, such as diabetic kidney disease, retinopathy, and neuropathy, underscore the need for early diagnosis and comprehensive management to improve patient outcomes and quality of life.
Journal Article
Effects of Different Modes of Exercise Training on Glucose Control and Risk Factors for Complications in Type 2 Diabetic Patients: A meta-analysis
OBJECTIVE:--We sought to meta-analyze the effects of different modes of exercise training on measures of glucose control and other risk factors for complications of diabetes. RESEARCH DESIGN AND METHODS--The 27 qualifying studies were controlled trials providing, for each measure, 4-18 estimates for the effect of aerobic training, 2-7 for resistance training, and 1-5 for combined training, with 1,003 type 2 diabetic patients (age 55 ± 7 years [mean ± between-study SD]) over 5-104 weeks. The meta-analytic mixed model included main-effect covariates to control for between-study differences in disease severity, sex, total training time, training intensity, and dietary cointervention (13 studies). To interpret magnitudes, effects were standardized after meta-analysis using composite baseline between-subject SD. RESULTS:--Differences among the effects of aerobic, resistance, and combined training on HbA₁c (A1C) were trivial; for training lasting >=12 weeks, the overall effect was a small beneficial reduction (A1C 0.8 ± 0.3% [mean ± 90% confidence limit]). There were generally small to moderate benefits for other measures of glucose control. For other risk factors, there were either small benefits or effects were trivial or unclear, although combined training was generally superior to aerobic and resistance training. Effects of covariates were generally trivial or unclear, but there were small additional benefits of exercise on glucose control with increased disease severity. CONCLUSIONS:--All forms of exercise training produce small benefits in the main measure of glucose control: A1C. The effects are similar to those of dietary, drug, and insulin treatments. The clinical importance of combining these treatments needs further research.
Journal Article
Hypoxia and hypoxia-inducible factors in diabetes and its complications
Hypoxia-inducible factors (HIFs) are the key regulators of oxygen homeostasis in response to hypoxia. In diabetes, multiple tissues are hypoxic but adaptive responses to hypoxia are impaired due to insufficient activation of HIF signalling, which results from inhibition of HIF-1α stability and function due to hyperglycaemia and elevated fatty acid levels. In this review, we will summarise and discuss current findings about the regulation of HIF signalling in diabetes and the pathogenic roles of hypoxia and dysregulated HIF signalling in the development of diabetes and its complications. The therapeutic potential of targeting HIF signalling for the prevention and treatment of diabetes and related complications is also discussed.
Journal Article
Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus
To investigate the associations of serum α-Klotho and β-Klotho levels with type 2 diabetes mellitus (T2DM) progression.
We evaluated 106 healthy controls and 261 cases of T2DM with or without diabetic complications (range: 45–84years). Serum α-Klotho and β-Klotho levels were analyzed using enzyme-linked immunosorbent assays.
Compared to the healthy controls, α-Klotho and β-Klotho levels were significantly lower among patients with T2DM and with or without diabetic complications (P<0.05). Furthermore, α-Klotho levels were lower in the microalbuminuric and macroalbuminuric groups, compared to the normoalbuminuric group. However, β-Klotho levels were only lower in the macroalbuminuric group (P<0.05). Multiple linear regression analyses revealed that α-Klotho and β-Klotho levels were positively correlated with the creatinine clearance rate, and negatively correlated with the urinary albumin to creatinine ratio and randomly sampled serum levels of creatinine, blood urea nitrogen, and blood glucose. Moreover, α-Klotho and β-Klotho levels were positively correlated among patients with T2DM (r=0.693, P<0.001).
Serum levels of α-Klotho and β-Klotho are down-regulated in patients with T2DM. Thus, these proteins may participate in the pathological mechanism of diabetes, and the positive correlation of α-Klotho and β-Klotho levels indicates that they might have similar mechanisms in T2DM.
Journal Article
Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its Complications and Therapeutic Approaches to Correction
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.
Journal Article
Haemoglobin glycation index and risk for diabetes-related complications in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial
Aims/hypothesisPrevious studies have suggested that the haemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications in individuals with type 1 and type 2 diabetes. We investigated whether HGI was a predictor of adverse outcomes of intensive glucose lowering and of diabetes-related complications in general, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.MethodsWe studied participants in the ADVANCE trial with data available for baseline HbA1c and fasting plasma glucose (FPG) (n = 11,083). HGI is the difference between observed HbA1c and HbA1c predicted from a simple linear regression of HbA1c on FPG. Using Cox regression, we investigated the association between HGI, both categorised and continuous, and adverse outcomes, considering treatment allocation (intensive or standard glucose control) and compared prediction of HGI and HbA1c.ResultsIntensive glucose control lowered mortality risk in individuals with high HGI only (HR 0.74 [95% CI 0.61, 0.91]; p = 0.003), while there was no difference in the effect of intensive treatment on mortality in those with high HbA1c. Irrespective of treatment allocation, every SD increase in HGI was associated with a significant risk increase of 14–17% for macrovascular and microvascular disease and mortality. However, when adjusted for identical covariates, HbA1c was a stronger predictor of these outcomes than HGI.Conclusions/interpretationHGI predicts risk for complications in ADVANCE participants, irrespective of treatment allocation, but no better than HbA1c. Individuals with high HGI have a lower risk for mortality when on intensive treatment. Given the discordant results and uncertain relevance beyond HbA1c, clinical use of HGI in type 2 diabetes cannot currently be recommended.
Journal Article