Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

INTRODUCTION: Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. METHODS: In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. RESULTS: The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m(2) but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found. DISCUSSION: We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Evaluation of Quality of Life and Emotional Disturbances in Patients with Diabetic Retinopathy

Diabetes has detrimental effects on many organs, including the kidneys, heart, and the central nervous system, with ophthalmic involvement and Diabetic Retinopathy (DR), specifically, being among the most severe and prominent consequences. Diabetic Retinopathy and especially advanced stages of the disease, have a crucial impact on patients’ quality of life and emotional status. In this context, emotional imbalance, psychological side effects and comorbidities, like anxiety disorders, could emerge, deteriorating the patients’ condition further. A number of questionnaires can be employed in the evaluation of the potential impact of Diabetic Retinopathy on patients’ quality of life, including the Beck Anxiety Inventory (BAI) and The National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). Purpose: The purpose of this study was to evaluate the association of Diabetic Retinopathy (DR) and diabetic macular edema with vision-related quality of life, as well as the potential association between the disease’s severity, emotional status of patients and the manifestation of anxiety and psychological features. Results: Patients with fundoscopic findings had significantly lower scores in all VFQ-25 subscales, indicating worse quality of life in comparison to patients without DR. Severity of DR, greater levels of anxiety, daily sitting time, unemployment and lower education level, were all found to be significantly, negatively associated with a worse quality of life. Regarding emotional status, more years of suffering from diabetes, treatment with insulin and the hours being idle per day were associated with an increased burden of anxiety. In addition, the presence of a concomitant disease, findings in fundoscopy, diabetic macular edema and treatment with anti-VEFG injections, as well as the number of doses, were significantly associated with greater anxiety. Multivariate analysis showed that having Severe Non-Proliferative Diabetic Retinopathy or having Proliferative Diabetic Retinopathy and receiving insulin therapy (alone or in combination with another treatment), were significantly associated with higher levels of anxiety. Conclusion: The well-established impact of DR on the patients’ well-being, quality of life and emotional status render DR and CME prevention, stabilization or delaying progression as a necessity in order to protect patients from developing psychiatric symptoms. On the other hand, the speculated bi-directional association between emotional problems and DR progression highlights the importance of acknowledging and dealing with psychological issues with the aim of delaying DR progression

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Purpose: Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Methods: Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Findings: Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic pituitary adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Implications: Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. (C) 2015 Elsevier HS Journals, Inc. All rights reserved

Diet, life-style and cardiovascular morbidity in the rural, free living population of Elafonisos island

Abstract Background There are about 70 small islands in the Aegean and Ionian Sea, of less than 300 Km2 and 5000 inhabitants each, comprising a total population of more than 75,000 individuals with geographical and socioeconomic characteristics of special interest. The objective of the present study was to assess lifestyle characteristics and the state of cardiovascular risk of the population of a small Eastern Mediterranean island, Elafonisos. Methods PERSEAS (Prospective Evaluation of cardiovascular Risk Surrogates in Elafonisos Area Study) is an ongoing, population-based, longitudinal survey of cardiovascular risk factors, life-style characteristics and related morbidity/mortality performed in a small and relatively isolated island of the Aegean Sea, named Elafonisos. Validated, closed-ended questionnaires for demographic, socio-economic, clinical and lifestyle characteristics were distributed and analyzed. The MedDietScore, a validated Mediterranean diet score was also calculated. In addition, all participants underwent measurement of anthropometric parameters, blood pressure and a full blood panel for glucose and lipids. Results The analysis included 596 individuals who represented 74.5% of the target population. The mean age of the population was 49.5 ± 19.6 years and 48.2% were males. Fifty participants (8.4%) had a history of cardiovascular disease (CVD). The rates of reported diabetes, hypertension, and hypercholesterolemia were 7.7%, 30.9% and 30.9% respectively, with screen-detection of each condition accounting for an additional 4.0%, 12.9%, and 23.3% of cases, respectively. Four hundred and seven individuals (68.3%) were overweight or obese, 25% reported being physically inactive and 36.6% were active smokers. The median MedDietScore was 25 [interquartile range: 6, range 12–47] with higher values significantly associated with older age, better education, increased physical activity, absence of history of diabetes and known history of hypercholesterolemia. Conclusions Obesity and traditional risk factors for CVD are highly prevalent among the inhabitants of a small Mediterranean island. Adherence to the traditional Mediterranean diet in this population is moderate, while physical activity is low. There seems to be a need for lifestyle modification programs in order to reverse the increasing cardiovascular risk trends in rural isolated areas of the Mediterranean basin

Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

Introduction: Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. Methods: In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. Results: The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m(2) but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found. Discussion: We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk