CHD Risk Minimization through Lifestyle Control: Machine Learning Gateway

Studies on the influence of a modern lifestyle in abetting Coronary Heart Diseases (CHD) have mostly focused on deterrent health factors, like smoking, alcohol intake, cheese consumption and average systolic blood pressure, largely disregarding the impact of a healthy lifestyle in mitigating CHD risk. In this study, 30+ years' World Health Organization (WHO) data have been analyzed, using a wide array of advanced Machine Learning techniques, to quantify how regulated reliance on positive health indicators, e.g. fruits/vegetables, cereals can offset CHD risk factors over a period of time. Our research ranks the impact of the negative outliers on CHD and then quantifies the impact of the positive health factors in mitigating the negative risk-factors. Our research outcomes, presented through simple mathematical equations, outline the best CHD prevention strategy using lifestyle control only. We show that a 20% increase in the intake of fruit/vegetable leads to 3-6% decrease in SBP; or, a 10% increase in cereal intake lowers SBP by 3%; a simultaneous increase of 10% in fruit-vegetable can further offset the effects of SBP by 6%. Our analysis establishes gender independence of lifestyle on CHD, refuting long held assumptions and unqualified beliefs. We show that CHD risk can be lowered with incremental changes in lifestyle and diet, e.g. fruit-vegetable intake ameliorating effects of alcohol-smoking-fatty food. Our multivariate data model also estimates functional relationships amongst lifestyle factors that can potentially redefine the diagnostics of Framingham score-based CHD-prediction

Clinical and Cost Implications of Insulin Degludec in Patients with Type 1 Diabetes and Problematic Hypoglycemia:A Quality Improvement Project

Introduction To assess the real-life clinical benefits and cost implications of switching from another basal insulin to insulin degludec (degludec) in patients with type 1 diabetes (T1D) on basal–bolus regimens with recurrent hypoglycemia and/or hypoglycemia unawareness. Methods Patients with T1D who were aged ≥ 18 years, were on a basal–bolus regimen, and had switched to degludec plus bolus insulin for at least 6 months were included. Patients had to have switched to degludec as a result of recurrent hypoglycemia and/or hypoglycemia unawareness. Results Six months of follow-up data were available for 42 patients. At 6 months, there was a significant reduction in median (interquartile range) HbA1c, from 8.6 (8.0–9.3)% [70 (64–78) mmol/mol] to 8.4 (7.9–8.9)% [68 (63–74) mmol/mol]; p < 0.05. Median daily basal insulin dose reduced significantly from 30.0 (14.7–45.0) to 25.5 (14.0–30.2) units; p < 0.0001. Data from hospital records showed reductions in the frequency of episodes of severe hypoglycemia from eight in the 6 months preceding degludec initiation to two in the 6 months following initiation. In the same period, diabetic ketoacidosis (DKA) episodes reduced from two before degludec initiation to no episodes after initiation. No patients reported worsening treatment satisfaction after switching to degludec. Considering the reductions in the basal dose required and the frequency of hypoglycemia episodes, we estimate that switching such patients to degludec from other basal insulins could provide significant savings in direct healthcare costs. Conclusion In patients with T1D, switching to degludec was associated with an improvement in HbA1c and reductions in basal insulin dose, severe hypoglycemia, and DKA. When used in appropriate patients, degludec could lead to significant cost savings

Renal Protection with SGLT2 Inhibitors: Effects in Acute and Chronic Kidney Disease

Purpose of Review: This review offers a critical narrative evaluation of emerging evidence that sodium-glucose co-transporter-2 (SGLT2) inhibitors exert nephroprotective effects in people with type 2 diabetes. Recent Findings: The SGLT2 inhibitor class of glucose-lowering agents has recently shown beneficial effects to reduce the onset and progression of renal complications in people with and without diabetes. Randomised clinical trials and ‘real world’ observational studies, mostly involving type 2 diabetes patients, have noted that use of an SGLT2 inhibitor can slow the decline in glomerular filtration rate (GFR), reduce the onset of microalbuminuria and slow or reverse the progression of proteinuria. Summary: The nephroprotective effects of SGLT2 inhibitors are class effects observed with each of the approved agents in people with a normal or impaired GFR. These effects are also observed in non-diabetic, lean and normotensive individuals suggesting that the mechanisms extend beyond the glucose-lowering, weight-lowering and blood pressure-lowering effects that accompany their glucosuric action in diabetes patients. A key mechanism is tubuloglomerular feedback in which SGLT2 inhibitors cause more sodium to pass along the nephron: the sodium is sensed by macula cells which act via adenosine to constrict afferent glomerular arterioles, thereby protecting glomeruli by reducing intraglomerular pressure. Other effects of SGLT2 inhibitors improve tubular oxygenation and metabolism and reduce renal inflammation and fibrosis. SGLT2 inhibitors have not increased the risk of urinary tract infections or the risk of acute kidney injury. However, introduction of an SGLT2 inhibitor in patients with a very low GFR is not encouraged due to an initial dip in GFR, and it is prudent to discontinue therapy if there is an acute renal event, hypovolaemia or hypotension

Ethnic differences in health related quality of life for patients with type 2 diabetes

Background - The objective of this study was to investigate the association between ethnicity and health related quality of life (HRQoL) in patients with type 2 diabetes. Methods - The EuroQol EQ-5D measure was administered to 1,978 patients with type 2 diabetes in the UK Asian Diabetes Study (UKADS): 1,486 of south Asian origin (Indian, Pakistani, Bangladeshi or other south Asian) and 492 of white European origin. Multivariate regression using ordinary least square (OLS), Tobit, fractional logit and Censored Least Absolutes Deviations estimators was used to estimate the impact of ethnicity on both visual analogue scale (VAS) and utility scores for the EuroQol EQ-5D. Results - Mean EQ-5D VAS and utility scores were lower among south Asians with diabetes compared to the white European population; the unadjusted effect on the mean EQ-5D VAS score was −7.82 (Standard error [SE] = 1.06, p < 0.01) and on the EQ-5D utility score was −0.06 (SE = 0.02, p < 0.01) (OLS estimator). After controlling for socio-demographic and clinical confounders, the adjusted effect on the EQ-5D VAS score was −9.35 (SE = 2.46, p < 0.01) and on the EQ-5D utility score was 0.06 (SE = 0.04), although the latter was not statistically significant. Conclusions - There was a large and statistically significant association between south Asian ethnicity and lower EQ-5D VAS scores. In contrast, there was no significant difference in EQ-5D utility scores between the south Asian and white European sub-groups. Further research is needed to explain the differences in effects on subjective EQ-5D VAS scores and population-weighted EQ-5D utility scores in this context

Insights for Care:The Healthcare Utilisation and Cost Impact of Managing Type 2 Diabetes-Associated Microvascular Complications

Introduction: The increasing prevalence of type 2 diabetes (T2DM) in the UK imposes a significant burden on the National Health Service (NHS). Despite the availability of effective treatments, the loss of glycaemic control over time results in significant comorbidities, including nephropathy, neuropathy and retinopathy. The cost of treating these microvascular complications has not been well documented, and this study aimed to provide an accurate assessment of the healthcare resource utilisation (HCRU) associated with managing T2DM and its complications. Methods: This retrospective cohort study utilised electronic medical records from patients with T2DM from the Heart of England Foundation Trust (HEFT), which captures data from patients using secondary care services. Patients were diagnosed with microvascular complications based on ICD-10 or OPCS codes. HCRU over a 2-year period was based on NHS Tariffs for healthcare services for inpatient, accident and emergency, and dialysis clinic usage. Results: The study cohort comprised 26,629 patients with T2DM who used HEFT services during the study period, 22.6%, 20.8% and 3.1% of whom had comorbid nephropathy, retinopathy or neuropathy, respectively. While the prevalence of diabetes in the overall HEFT population was reported to be 7% in 2012, diabetes and its associated complications accounted for more than 30% of secondary care costs. Furthermore, while patients with diabetes represent only 17% of HEFT inpatients, they account for more than 20% of service usage. The economic burden of microvascular complications increased substantially with the severity of the condition, with the overall cost exceeding £70 million over the 2-year period. Conclusion: This study of patients with T2DM in a typical secondary care provider in the UK showed that avoiding the progression of microvascular complications could provide substantial cost savings through targeted interventions that improve outcomes and lower resource use. Funding: Merck Sharp & Dohme Limited

Prevalence and incidence of complications at diagnosis of T2DM and during follow-up by BMI and ethnicity:A matched case-control analysis

Aims To estimate the risk of developing long-term major cardiovascular and renal complications in relation to levels of body mass index (BMI) in a population of White European (WE), African-Caribbean (AC), and South Asian (SA) patients with type 2 diabetes mellitus (T2DM). Materials and methods Patients with new diagnosis of T2DM, aged ≥ 18 years from January 2000 (n = 69,436) and their age-sex-ethnicity matched non-diabetic controls (n = 272,190) were identified from UK primary care database. Incidence rates ratios (IRRs) for non-fatal major cardiovascular events (MACE) and chronic kidney disease (CKD) in patients with T2DM compared to controls were estimated using multivariate Mantel-Cox model. Results Among normal weight patients with T2DM, WEs had significantly higher prevalence of cardiovascular multi-morbidity (95% CI 9.5, 11.3), compared to SAs (95% CI 4.8, 9.5). AC and SA overweight and obese patients had similar prevalence, while obese WEs had significantly higher prevalence. During a median 7 years of follow-up, risk of MACE was significantly higher for overweight (95% CI of IRR 1.50, 2.46) and obese (95% CI of IRR 1.49, 2.43) SAs compared to their WE counterparts. However, similar risk levels were observed for normal weight WEs and SAs, respectively. Risk of CKD was higher and uniform for BMI ≥ 25 kg/m2 amongst WEs and ACs, whereas only overweight patients had significantly higher risk of CKD amongst SA [IRR 2.08 (95% CI 1.49, 2.93)]. Conclusion Risk of MACE/CKD varies over levels of BMI within each ethnic group, with overweight SAs having a disproportionate risk of CKD

Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance:a preliminary study

To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT). Sixty age- and gender- matched White-European adults (30 IGT and 30 normal glucose tolerance -NGT) were recruited for the study. Fasting plasma glucose, lipids and 24-hour blood pressure (BP) was measured in all subjects. Systemic vascular and endothelial function was assessed using carotid-artery intimal media thickness (cIMT) and flow mediated dilation (FMD). Retinal vascular reactivity was assessed by the Dynamic Retinal Vessel Analyser (DVA). Additionally, blood glutathione (GSH, GSSG and tGSH) and plasma von-Willebrand (vWF) factor levels were also measured. Individuals with IGT demonstrated higher BP values (p<0.001), fasting TG and TG:HDL ratios (p<0.001) than NGT subjects. Furthermore, Total:HDL-C ratios and Framingham scores were raised (p=0.010 and p<0.001 respectively). Blood glutathione levels (GSH, GSSG and tGSH) were lower (p<0.001, p=0.039 and p<0.001 respectively) while plasma vWF was increased (p=0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (p=0.017 and p=0.005, respectively) alongside larger brachial artery diameter (p=0.015), lower FMD% (p=0.026) and GTN induced dilation (GID) (p=0.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline fluctuations (BDF) (p=0.026), longer reaction time (RT) (p=0.032) and reduced baseline-corrected flicker response (bFR) (p=0.045). In IGT subjects retinal BDF correlated with and Total:HDL (p= 0.003) and HDL-C (p= 0.004). Arterial RT also correlated with FMD (p=0.017) in IGT but not NGT subjects. In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for CVD. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 μg/mL, n = 9 vs. 1.4 ± 0.3 μg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity