Plasma phospholipid transfer protein (PLTP): review of an emerging cardiometabolic risk factor

Plasma phospholipid transfer protein (PLTP) is a lipid transfer glycoprotein that binds to and transfers a number of amphipathic compounds. In earlier studies, the attention of the scientific community focused on the positive role of PLTP in high-density lipoprotein (HDL) metabolism. However, this potentially anti-atherogenic role of PLTP has been challenged recently by another picture: PLTP arose as a pro-atherogenic factor through its ability to increase the production of apolipoprotein B-containing lipoproteins, to decrease their antioxidative protection and to trigger inflammation. In humans, PLTP has mostly been studied in patients with cardiometabolic disorders. Both PLTP and related cholesteryl ester transfer protein (CETP) are secreted proteins, and adipose tissue is an important contributor to the systemic pools of these two proteins. Coincidently, high levels of PLTP and CETP have been found in the plasma of obese patients. PLTP activity and mass have been reported to be abnormally elevated in type 2 diabetes mellitus (T2DM) and insulin-resistant states, and this elevation is frequently associated with hypertriglyceridemia and obesity. This review article presents the state of knowledge on the implication of PLTP in lipoprotein metabolism, on its atherogenic potential, and the complexity of its implication in obesity, insulin resistance and T2DM.     

Non-alcoholic fatty liver syndrome: a hepatic consequence of common metabolic diseases

BACKGROUND AND AIMS: The association of liver steatosis with a number of common metabolic conditions has been suggested. The aim of the present study was to evaluate the clinical features of subjects with different severities of steatosis. METHODS: The present study was performed in 282 consecutive patients with 'bright liver' at ultrasonography and in 58 subjects without steatosis. They had no history of alcohol abuse and negative tests for the presence of hepatitis B and C virus. Patients underwent clinical examination, anthropometry, laboratory tests and routine liver ultrasonography. Steatosis was graded as absent, mild, moderate and severe. RESULTS: A progressive increase in the prevalence of obesity (P < 0.001), type 2 diabetes (P < 0.001), alanine aminotransferase (ALT) elevation (P < 0.001) and hypertriglyceridemia (P < 0.001), and a decrease of hypercholesterolemia (P < 0.05) was observed from the control group to the groups with mild, moderate and severe steatosis. More than half the subjects with liver steatosis had insulin resistance metabolic syndrome. Obesity, diabetes and hypertriglyceridemia were more common by 5.3-fold, 4.0-fold, and 6.7-fold, respectively, in subjects with severe steatosis, as compared to controls. Prevalence of obesity, diabetes and hyperlipidemia was significantly higher in subjects with fatty liver and ALT elevation. CONCLUSION: Fatty liver can be considered as the hepatic consequence of common metabolic diseases.     

The dietary inflammatory index,obesity, type 2 diabetes,and cardiovascular risk factors and diseases

An unhealthy diet is a recognized risk factor in the pathophysiology of numerous chronic noncommunicable diseases (NCD), including obesity, type 2 diabetes (T2DM), and cardiovascular diseases (CVD). This is, at least in part, due to unhealthy diets causing chronic low-grade inflammation in the gut and systemically. To characterize the inflammatory potential of diet, we developed the Dietary Inflammatory Index (DII®). Following this development, around 500 papers have been published, which examined the association between the DII, energy-adjusted DII (E-DII?), and the children's DII (C-DII?) and many chronic NCDs including obesity and cardiometabolic diseases. Although a previous narrative review published in 2019 briefly summarized the evidence in this area, there was a significant increase in papers on this topic since 2020. Therefore, the purpose of this narrative review is to provide an in-depth updated review by including all papers until July 2021 on DII and its relationship with obesity, T2DM, and CVD. Furthermore, we aim to identify potential gaps in the literature and provide future directions for research. Most studies found that DII was associated with an increased risk of obesity, T2DM, and CVD with some relationships being sex-specific. However, we identified the paucity of papers describing associations between dietary inflammation and T2DM and its risk factors. Few studies used gold-standard measures of cardiometabolic risk factors. We also identified the lack of interventional studies designed to change the inflammatory potential of diets and study its effect on cardiometabolic risk factors and diseases. We recommend that such interventional studies are needed to assess if changes in DII, representing the inflammatory potential of diet, independently of changes in body composition can modulate cardiometabolic risk factors and diseases.     

Visceral adipose tissue area is an independent risk factor for hepatic steatosis

Background and Aim:  Recent data indicate that hepatic steatosis is associated with insulin resistance, dyslipidemia and obesity (especially central body fat distribution). There have been few studies on the correlation between biopsy-proven hepatic steatosis and the above factors in a disease-free population. The aim of the present study was to evaluate the relation between hepatic steatosis assessed by biopsy and clinical characteristics including regional fat distribution measured by computed tomography (CT) in living liver donors.
Methods:  Laboratory data, liver/spleen Hounsfield ratio (L/S ratio), regional fat distribution by CT and liver status by biopsy were evaluated retrospectively in a total of 177 living liver donors without a history of alcohol intake.
Results:  The unpaired t -test showed that age, triglycerides (TG), high density lipoprotein, total cholesterol, alanine aminotransferase, body mass index, L/S ratio, visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) were associated with hepatic steatosis. In the multiple logistic regression analysis, VAT (odds ratio 1.031, 95% CI 1.013–1.048, P  < 0.01) and TG (odds ratio 1.012, 95% CI 1.004–1.020, P  < 0.01) were independent risk factors of hepatic steatosis. Subgroup analysis also showed that VAT was an independent risk factor in men (odds ratio 1.022, 95% CI 1.003–1.041, P  < 0.05) and women (odds ratio 1.086, 95% CI 1.010–1.168, P  < 0.05).
Conclusion:  Our results suggest that visceral abdominal adiposity is correlated with hepatic steatosis in healthy living liver donors.     

Chrononutrition in cardiometabolic diseases: Current evidence and future perspectives

Chrononutrition is the field of nutritional science that investigates the relationship between food intake, timing of food intake, and their effects and influence on circadian rhythms and overall health. By aligning eating patterns with body's internal clock, optimisation of metabolic processes, improvements of various aspects of health can be achieved. Cardiovascular (CV) and metabolic diseases remain the leading cause of morbidity and mortality worldwide. Notably, in the US alone, approximately half of all cardiometabolic deaths are attributed to modifiable dietary factors, suggesting that dietary changes could result in dramatic increases in lifespan and its related quality of life. Social media have also a great impact on chrononutrition and their role cannot be neglected. The impact of social media on chrononutrition can be multifaceted: information dissemination, influence on eating habits, digital detox challenges, cultural influence and social jet lag. This special issue will provide novel insights and clarifications on chrononutrition, but also on additional controversial topics. The articles we selected should promote future preclinical and clinical studies to ultimately identify the most appropriate approaches to reduce the unacceptable high burden of CV and metabolic diseases.     

Association of obstructive sleep apnea with cardiometabolic diseases and cardiovascular mortality

Background

Obstructive sleep apnea (OSA) is one of the leading respiratory disorders, increasing the risk of cardiometabolic diseases. In the study, we investigated the association between OSA and the risk of cardiometabolic diseases and all-cause and cardiovascular mortality in adults.

Methods

Participants were enrolled in the National Health and Nutrition Examination Survey. The baseline covariates were compared between participants with and without OSA status. Multivariable logistic regression was performed to explore the association between OSA and cardiometabolic diseases, while Cox proportional regression was performed for all-cause and cardiovascular mortality.

Results

OSA status was positively associated with higher risks of cardiometabolic diseases, including hypertension (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.14–1.45; p < 0.001), diabetes (OR 1.46, 95% CI 1.22–1.76; p < 0.001), and cardiovascular diseases (OR 1.29, 95% CI 1.08–1.54; p = 0.006) after adjusting for numerous covariates. However, no associations of OSA with all-cause or cardiovascular mortality were observed.

Conclusion

OSA was associated with a higher risk of hypertension, diabetes, and cardiovascular diseases, but had no significant association with all-cause or cardiovascular mortality in adults.     

Ectopic fat and cardiometabolic and vascular risk

Given that the variation in how regional adipose tissue handles and stores excess dietary energy has substantial cardiometabolic implications, ectopic fat distribution might be an important predictor of cardiometabolic and vascular risk, in addition to overall obesity itself.     

Diabetes and cancer: two diseases with obesity as a common risk factor

There is a growing body of evidence to support a connection between diabetes (predominantly type 2), obesity and cancer. Multiple meta‐analyses of epidemiological data show that people with diabetes are at increased risk of developing many different types of cancers, along with an increased risk of cancer mortality. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinaemia, enhanced inflammatory processes, dysregulation of sex hormone production and hyperglycaemia. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Indeed, obesity is associated with an increased risk of cancer and diabetes. Abdominal adiposity has been shown to play a role in creating a systemic pro‐inflammatory environment, which could result in the development of both diabetes and cancer. Here, we examine the relationship between diabetes, obesity and cancer, and investigate the potential underlying causes of increased cancer risk in individuals with diabetes. Current treatment recommendations for reducing the overall disease burden are also explored and possible areas for future research are considered.     

Adiponectin as a protective factor in hepatic steatosis

AIM: Obesity and insulin resistance (IR) are closely related to hepatic steatosis (HS), and adiponectin is a hepatic insulin sensitizer that has important effects in liver function. This study aims at investigating the relationship between serum adiponectin concentration and the presence of HS. METHODS: We carried out a cross-sectional study in a check-up unit of a University Hospital in Mexico City. We enrolled 196 subjects, comprising 98 subjects with HS (27 women, 71 men) and 98 controls (37 women and 61 men). Anthropometric, metabolic and biochemical variables were measured in the two groups. Serum adiponectin and leptin concentrations were determined, their association with grade of HS tested, and concentrations, according to quartiles, compared between cases and controls. X2 analysis for linear trends was used to test for a dose-response relationship and logistic regression analysis was conducted to test for a protective effect of adiponectin. RESULTS: The HS subjects were older and more obese than controls, with a central obesity pattern. In the fourth quartile of adiponectin concentrations, HS was less common and severe. In a multivariate model of the fourth quartile of the adiponectin concentrations, we observed a protective effect (OR = 0.17, 95%CI: 0.04-0.67, P= 0.01). In subjects with more severe HS, we observed higher leptin concentrations, and caloric intakes, total fat and iron consumption were higher than in controls. CONCLUSION: The results of the present study suggest that a high serum concentration of adiponectin is associated with a protective effect against HS.     

The cardiometabolic syndrome as a cardiovascular risk factor

The cardiometabolic syndrome (CMS) is associated with cardiovascular disease (CVD) and includes a constellation of risk factors such as central obesity, hypertension, insulin resistance, dyslipidemia, microalbuminuria, and hypercoagulability. Collectively, these risk factors increase CVD endpoints such as stroke, congestive heart failure, chronic kidney disease (CKD), and overall mortality. The CMS is associated with endothelial dysfunction, inflammation, abnormal thrombolysis, and increased oxidative stress that accentuate progression of CVD. We will review how the varying components of the CMS relate to an increased CVD and renal disease risk.     

Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: A six-month,randomized, placebo-controlled,double-blind clinical trial

Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin-induced improvements in cardiometabolic health remains to be clarified. Thus, we investigated the way in which lorcaserin treatment may alter cardiovascular disease risk, either independently or through changes in body weight. We measured, for the first time, lipid particle quantification, lipid peroxidation, appetite-regulating hormones and mRNA expression of the 5-hydroxytryptamine 2c receptor (5-HT2c receptor). A total of 48 obese participants were enrolled in this six-month, randomized (1:1), placebo-controlled, double-blinded clinical trial. Lorcaserin treatment reduced fat mass (P < 0.001), the fatty liver index (P < 0.0001) and energy intake (P < 0.03) without affecting energy expenditure or lean mass. Total low-density lipoprotein (LDL) (P < 0.04) and small LDL particles (P < 0.03) decreased, while total high-density lipoprotein (HDL) P < 0.02) increased and heart rate significantly decreased with lorcaserin treatment. No mRNA expression of the 5-HT2c receptor was observed in peripheral organs. These data suggest that lorcaserin treatment for six months improves cardiometabolic health in obese individuals, acting mainly through the brain.     

Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality

Abstract Aims/hypothesis. The aim of this study was to examine the possible link between isolated post-challenge hyperglycaemia (2-h post-challenge plasma glucose ≥ 11.1 mmol/l, and fasting plasma glucose < 7.0 mmol/l) and mortality. Methods. The data from three population based longitudinal studies (in Mauritius, Fiji and Nauru) were pooled and mortality rates were determined in 9179 people who were followed for between 5 and 12 years. Results. There were 595 people with previously diagnosed diabetes, and 799 with newly diagnosed diabetes, of whom 243 (31) had isolated post-challenge hyperglycaemia. In comparison with people without diabetes, people with isolated post-challenge hyperglycaemia had an increased risk of all-cause mortality [Cox proportional hazards ratio (95 % CI): 2.7 (1.8–3.9) – men; 2.0 (1.3–3.3) – women], and of cardiovascular mortality [2.3 (1.2–4.2) – men; 2.6 (1.3–5.1) – women]. In addition, men with isolated post-challenge hyperglycaemia had a high risk of cancer death [8.0 (3.6–17.9)]. Conclusion/interpretation. These data show that isolated post-challenge hyperglycaemia, which can only be identified by the 2-h glucose, is common, and at least doubles the mortality risk. This should be considered in the design of screening programmes that use only fasting glucose [Diabetologia (1999) 42: 1050–1054] Received: 18 March 1999 and in revised form: 27 May 1999     

Visceral fat accumulation as an important risk factor for obstructive sleep apnoea syndrome in obese subjects

Objectives. It is well known that obstructive sleep apnoea (OSA) is frequently associated with obesity. In the current study, we investigated the correlation between abdominal visceral fat accumulation and the presence of OSA in obese subjects.
Subjects. A consecutive series of 37 patients (17 men and 20 women) with primary obesity who were admitted to the Second Department of Internal Medicine, Osaka University Hospital, were investigated. Patients with OSA were designated as those whose apnoea index (number of apnoea h⁻¹ of sleep) was more than 5.
Main outcome measures. The distribution of body fat was determined using computed tomographic sections. The upper airway dimensions were evaluated with indices obtained by cephalometry in both inspiratory and expiratory phases.
Results. Visceral adipose tissue (AT) area which was measured at the level of the umbilicus, and its ratio to total AT area were both significantly greater in OSA patients as compared with those in non-OSA patients. All subjects whose visceral AT area measured more than 220 cm² manifested OSA. These two parameters also closely correlated with an increase in apnoea index. A multiple linear regression analysis revealed that the visceral AT area significantly correlated to apnoea index when age, AT mass and lean body mass were taken into account. The fluctuations of the upper airway were significantly greater in the large visceral fat group than in the small visceral fat group.
Conclusions. These results suggest that visceral fat accumulation is an important risk indicator for OSA in obese subjects.     

Incretin mimetics as a novel therapeutic option for hepatic steatosis.

BACKGROUND: Fat accumulation in the liver or non-alcoholic fatty liver disease (NAFLD) is regarded as a key pathogenic factor and component of the metabolic syndrome. It was reported that administration of the incretin mimetic exenatide reversed hepatic steatosis in an obese mouse model. We had the opportunity to study the effect of additional exenatide administration on liver fat content in a patient with type 2 diabetes. CASE REPORT: A 59-year-old male with poorly controlled type 2 diabetes was treated with exenatide in addition to metformin monotherapy. Following 44 weeks of exenatide therapy, mean the liver fat measured by liver spectroscopy declined from 15.8% to 4.3%. This dramatic decrease in liver fat was accompanied by significant beneficial changes in several cardiovascular disease risk factors and improvement of all liver enzymes, in particular alanine aminotransferase, the most important marker of liver steatosis. CONCLUSION: This case report suggests that the incretin mimetic exenatide decreases hepatic fat accumulation and may play a role in the future treatment of NAFLD, and the associated insulin resistance and cardiovascular risk factors in an ever-growing high-risk population.     

Cardiovascular risk factors of airport visitors in India: results from a nation‐wide campaign

Cardiovascular diseases have become the major cause of death in India, but overall awareness is still low. Therefore, the initiative was undertaken to set up health care screening booths at eight airports and one hospital throughout India to increase awareness and to determine cardiovascular risk factors. Participants were screened for hypertension (systolic blood pressure (BP) ≥140 mmHg or diastolic BP≥90 mmHg), diabetes [fasting blood glucose (FBG) level ≥126  or ≥200 mg/dL for random blood glucose (RBG)], and body mass index (BMI). Among 100 107 participants screened (46 ± 13 years; 17% women), prevalence of diabetes was 12 571 (15%), hypertension: 30 345 (33%) and overweight: 61 219 (65%). Diabetes was treated more often than hypertension (44% vs 11%). Hypertension and diabetes prevalence values were relatively high in young obese adults; BMI correlated significantly (p < .001) stronger to both systolic BP and RBG for subjects younger than 40 years than for those who were older (r = 0.27 vs r = 0.06 and r = 0.15 vs r = 0.03, respectively). Among obese women aged 60 years and older the hypertension prevalence was higher than 40%, in obese men this prevalence value was already seen from the group of 30 to 40 years old. For participants older than 50 years with hypertension, diabetes prevalence was 20%. These results show that screening initiatives like these are highly needed to increase the overall awareness of diabetes and particularly of hypertension. Systematic screening programs also help to identify specific patient populations and cope with undertreatment of those at the highest cardiovascular risk. The fact that women were underrepresented in the present screening campaign suggests actions are needed to encourage them to participate in health care programs.