Non-Q wave myocardial infarction: Identification of high and low risk subsets by clinical variables

[This corrects the article DOI: 10.1371/journal.pone.0160243.]

Effect of high-salt diet on blood pressure and body fluid composition in patients with type 1 diabetes: randomized controlled intervention trial

INTRODUCTION: Patients with type 1 diabetes are susceptible to hypertension, possibly resulting from increased salt sensitivity and accompanied changes in body fluid composition. We examined the effect of a high-salt diet (HSD) in type 1 diabetes on hemodynamics, including blood pressure (BP) and body fluid composition. RESEARCH DESIGN AND METHODS: We studied eight male patients with type 1 diabetes and 12 matched healthy controls with normal BP, body mass index, and renal function. All subjects adhered to a low-salt diet and HSD for eight days in randomized order. On day 8 of each diet, extracellular fluid volume (ECFV) and plasma volume were calculated with the use of iohexol and 125I-albumin distribution. Hemodynamic measurements included BP, cardiac output (CO), and systemic vascular resistance. RESULTS: After HSD, patients with type 1 diabetes showed a BP increase (mean arterial pressure: 85 (5) mm Hg vs 80 (3) mm Hg; p<0.05), while BP in controls did not rise (78 (5) mm Hg vs 78 (5) mm Hg). Plasma volume increased after HSD in patients with type 1 diabetes (p<0.05) and not in controls (p=0.23). There was no significant difference in ECFV between diets, while HSD significantly increased CO, heart rate (HR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in type 1 diabetes but not in controls. There were no significant differences in systemic vascular resistance, although there was a trend towards an HSD-induced decrease in controls (p=0.09). CONCLUSIONS: In the present study, patients with type 1 diabetes show a salt-sensitive BP rise to HSD, which is accompanied by significant increases in plasma volume, CO, HR, and NT-proBNP. Underlying mechanisms for these responses need further research in order to unravel the increased susceptibility to hypertension and cardiovascular disease in diabetes. TRIAL REGISTRATION NUMBERS: NTR4095 and NTR4788

Microvascular and macrovascular complications in type 2 diabetes Ghanaian residents in Ghana and Europe: The RODAM study.

AIMS: To compare microvascular and macrovascular complication rates among Ghanaians with type 2 diabetes (T2D) living in Ghana and in three European cities (Amsterdam, London and Berlin). METHODS: Data from the multicenter Research on Obesity and Diabetes among African Migrants (RODAM) study were analyzed. 650 Ghanaian participants with T2D (206 non-migrant and 444 migrants) were included. Logistic regression analyses were used to determine the association between migrant status and microvascular (nephropathy and retinopathy) and macrovascular (coronary artery disease (CAD), peripheral artery disease (PAD) and stroke) complications with adjustment for age, gender, socioeconomic status, alcohol, smoking, physical activity, hypertension, BMI, total-cholesterol, and HbA1c. RESULTS: Microvascular and macrovascular complications rates were higher in non-migrant Ghanaians than in migrant Ghanaians (nephropathy 32.0% vs. 19.8%; PAD 11.2% vs. 3.4%; CAD 18.4% vs. 8.3%; and stroke 14.5% vs. 5.6%), except for self-reported retinopathy (11.0% vs. 21.6%). Except nephropathy and stroke, the differences persisted after adjustment for the above-mentioned covariates: PAD (OR 7.48; 95% CI, 2.16-25.90); CAD (2.32; 1.09-4.93); and retinopathy (0.23; 0.07-0.75). CONCLUSIONS: Except retinopathy, the rates of microvascular and macrovascular complications were higher in non-migrant than in migrant Ghanaians with T2D. Conventional cardiovascular risk factors did not explain the differences except for nephropathy and stroke

Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome

There is significant interest in altering the course of cardiometabolic disease development via gut microbiomes. Nevertheless, the highly abundant phage members of the complex gut ecosystem -which impact gut bacteria- remain understudied. Here, we show gut virome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease, in 196 participants by combined sequencing of bulk whole genome and virus like particle communities. MetS gut viromes exhibit decreased richness and diversity. They are enriched in phages infecting Streptococcaceae and Bacteroidaceae and depleted in those infecting Bifidobacteriaceae. Differential abundance analysis identifies eighteen viral clusters (VCs) as significantly associated with either MetS or healthy viromes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of participants. The identification of the temperate Ca. Heliusviridae provides a starting point to studies of phage effects on gut bacteria and the role that this plays in MetS

Association between C reactive protein and microvascular and macrovascular dysfunction in sub-Saharan Africans with and without diabetes: the RODAM study.

INTRODUCTION: Although inflammation assessed by elevated C reactive protein (CRP) concentration is known to be associated with risk of cardiovascular disease, its association with microvascular and macrovascular dysfunction in diabetes and non-diabetes remains unclear. We examined the association between CRP and diabetes and associated microvascular and macrovascular dysfunction in sub-Saharan Africans with and without diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional analyses of baseline data from the multicenter RODAM study (Research on Obesity and Diabetes among African Migrants) including 5248 Ghanaians (583 with diabetes, 4665 without diabetes) aged 25-70 years were done. Logistic regression analyses were used to examine the associations between CRP Z-scores and diabetes and microvascular (nephropathy) and macrovascular (peripheral artery disease (PAD)) dysfunction, with adjustments for age, sex, site of residence, smoking, body mass index, systolic blood pressure, and low-density lipoprotein cholesterol. RESULTS: In the fully adjusted models, higher CRP concentration was significantly associated with diabetes (adjusted OR 1.13; 95% CI 1.05 to 1.21, p=0.002). In participants with diabetes, higher CRP concentration was associated with PAD (1.19; 1.03 to 1.41, p=0.046) but not nephropathy (1.13; 0.97 to 1.31, p=0.120). Among participants without diabetes, higher CRP concentration was associated with higher odds of PAD (1.10; 1.01 to 1.21, p=0.029) and nephropathy (1.12; 1.04 to 1.22, p=0.004). CONCLUSIONS: In this study, higher CRP concentration was associated with higher odds of diabetes in sub-Saharan Africans. Also, higher CRP concentration was associated with higher odds of nephropathy and PAD in non-diabetes and higher odds of PAD in diabetes. CRP may be an important marker for assessment of risk of diabetes and risk for PAD and nephropathy in sub-Saharan Africans with and without diabetes

Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction

Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.Peer reviewe

Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide

Background Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0±0.0 and SMase: 0.6±0.1 mN/mm; n = 9, p Conclusions Hypertension is associated with marked alterations in vascular sphingolipid biology such as elevated ceramide levels and signaling, that contribute to increased vascular tone

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

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe