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It is known that glucose disturbances contribute to micro- and macrovascular complications and vascular aging. Telomere length is considered to be a cellular aging biomarker. It is important to determine the telomere length role in vascular structural and functional changes in patients with diabetes mellitus. We conducted a cross-sectional observational study in a high-risk population from Moscow, Russia. The study included 50 patients with diabetes and without clinical cardiovascular disease and 49 control group participants. Glucose metabolism assessment tests, measuring intima–media complex thickness and determining the presence of atherosclerotic plaques, pulse wave velocity measurement, and telomere length measurement were administered to all participants. Vascular changes were more dramatic in patients with diabetes than in the control group, and the telomeres were shorter in patients with diabetes. Significant differences were found in the vascular wall condition among diabetes patients, and there were no substantial differences in the arterial structure between patients with ‘long’ telomeres; however, there were statistically significant differences in the vascular wall condition between patients with ‘short’ telomeres. Vascular ageing signs were more prominent in patients with diabetes. However, despite diabetes, vascular changes in patients with long telomeres were very modest and were similar to the vascular walls in healthy individuals. Thus, long lymphocyte telomeres may have a protective effect on the vascular wall and may prevent vascular wall deterioration caused by glucose metabolism disorders.
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Morbid Obesity Centre, Department of Nutrition, Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Gynecology, Institute of Clinical Medicine, Department of Endocrinology, Vestfold Hospital Trust, PO Box 2168, 3103 Tønsberg, Norway
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Morbid Obesity Centre, Department of Nutrition, Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Gynecology, Institute of Clinical Medicine, Department of Endocrinology, Vestfold Hospital Trust, PO Box 2168, 3103 Tønsberg, Norway
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Morbid Obesity Centre, Department of Nutrition, Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Gynecology, Institute of Clinical Medicine, Department of Endocrinology, Vestfold Hospital Trust, PO Box 2168, 3103 Tønsberg, Norway
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We aimed to examine whether a whole-grain crispbread (CB) low-fructose, low-calorie diet (LCD) might be superior to a traditional LCD based on fructose-rich liquid meal replacements (LMRs) with respect to improvement of various cardiometabolic risk factors and reproductive hormones. Parallel-group randomised controlled clinical trial. Morbidly obese women with polycystic ovarian syndrome (PCOS) were randomised to either an 8-week CB-LCD or LMR-LCD (900–1100 kcal/day, fructose 17 g/day or 85 g/day). A total of 51 women completed the study. Body weight, fat mass and waist circumference reduced by mean (s.d.) 10.0 (4.8) kg, 7.4 (4.2) kg and 8.5 (4.4) cm, with no significant differences between groups. Total-cholesterol, HDL-cholesterol and Apo-A1 were significantly reduced within both groups (all P values <0.01), with no significant between-group differences. The triacylglycerol and LDL-cholesterol levels were reduced within the LMR group only, with no significant between-group differences. Blood pressure and most measures of glucose metabolism improved significantly in both diet groups, with no significant between-group difference. Uric acid levels rose by 17.7 (46.4) and 30.6 (71.5) μmol/l in the CB and LMR group, respectively, with no significant difference between groups. Gastrointestinal discomfort was significantly and equally reduced in both intervention groups. Free testosterone index was reduced in both groups, with no significant difference between groups. Morbidly obese women with PCOS who underwent either an 8-week low or high-fructose LCD-diet had similar changes in various cardiometabolic risk factors and reproductive hormones. Registration at ClinicalTrials.gov: NCT00779571.
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The aim of this study was to estimate the prevalence of metabolic syndrome (MS) and its components in obese Mexican adolescents and to compare the clinical, anthropometric, and biochemical characteristics between patients with and without MS by sex. We conducted a cross-sectional study with a sample of 110 obese adolescents (boys and girls) from 8 to 16 years old (BMI ≥95th percentile), who were recruited in the pediatric obesity clinic of a third-level care hospital. A frequency analysis was used to estimate the prevalence of MS and its components, and the assessments were compared between the sexes and between the groups with and without MS using the Kruskal–Wallis test. The prevalence of MS was 62%. In order of prevalence, the following components of MS were observed in the sample: abdominal obesity (88%), high triglycerides (TG) (85%), low HDL-C (60%), hypertension (35%), and hyperglycemia (5%). In the groups with MS, hypertension (P<0.001), waist circumference (P=0.003), and TG (P=0.012) were significantly higher, and HDL-C (P<0.001) was significantly lower. In conclusion the prevalence of MS and its components is high among obese Mexican-Hispanic children. These findings show the importance of preventing and treating obesity in the early stages of life in order to decrease the incidence rates of cardiovascular disease and type 2 diabetes mellitus.
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Cardiovascular risk assessment remains difficult in elderly patients. We examined whether chromogranin A (CgA) measurement in plasma may be valuable in assessing risk of death in elderly patients with symptoms of heart failure in a primary care setting. A total of 470 patients (mean age 73 years) were followed for 10 years. For CgA plasma measurement, we used a two-step method including a screening test and a confirmative test with plasma pre-treatment with trypsin. Cox multivariable proportional regression and receiver-operating curve (ROC) analyses were used to assess mortality risk. Assessment of cardiovascular mortality during the first 3 years of observation showed that CgA measurement contained useful information with a hazard ratio (HR) of 5.4 (95% CI 1.7–16.4) (CgA confirm). In a multivariate setting, the corresponding HR was 5.9 (95% CI 1.8–19.1). When adding N-terminal proBNP (NT-proBNP) to the model, CgA confirm still possessed prognostic information (HR: 6.1; 95% CI 1.8–20.7). The result for predicting all-cause mortality displayed the same pattern. ROC analyses in comparison to NT-proBNP to identify patients on top of clinical variables at risk of cardiovascular death within 5 years of follow-up showed significant additive value of CgA confirm measurements compared with NT-proBNP and clinical variables. CgA measurement in the plasma of elderly patients with symptoms of heart failure can identify those at increased risk of short- and long-term mortality.
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The concept of the heart as an endocrine organ arises from the observation that the atrial cardiomyocytes in the mammalian heart display a phenotype that is partly that of endocrine cells. Investigations carried out between 1971 and 1983 characterised, by virtue of its natriuretic properties, a polypeptide referred to atrial natriuretic factor (ANF). Another polypeptide isolated from brain in 1988, brain natriuretic peptide (BNP), was subsequently characterised as a second hormone produced by the mammalian heart atria. These peptides were associated with the maintenance of extracellular fluid volume and blood pressure. Later work demonstrated a plethora of other properties for ANF and BNP, now designated cardiac natriuretic peptides (cNPs). In addition to the cNPs, other polypeptide hormones are expressed in the heart that likely act upon the myocardium in a paracrine or autocrine fashion. These include the C-type natriuretic peptide, adrenomedullin, proadrenomedullin N-terminal peptide and endothelin-1. Expression and secretion of ANF and BNP are increased in various cardiovascular pathologies and their levels in blood are used in the diagnosis and prognosis of cardiovascular disease. In addition, therapeutic uses for these peptides or related substances have been found. In all, the discovery of the endocrine heart provided a shift from the classical functional paradigm of the heart that regarded this organ solely as a blood pump to one that regards this organ as self-regulating its workload humorally and that also influences the function of several other organs that control cardiovascular function.
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Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, parastatin, and serpinin and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular, and the immune systems and by affecting the glucose or calcium homeostasis. As some peptides exert similar effects, but others elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.
The Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK
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Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK
Diabetes and Endocrinology Department, Kettering General Hospital NHS Foundation Trust, Kettering, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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The Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK
Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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The Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK
Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Aims
Physical activity has been proposed to be an effective non-pharmacological method of reducing systemic inflammation and therefore may prove particularly efficacious for women with polycystic ovary syndrome (PCOS) who have been shown to have high levels of inflammation and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Therefore, the aim of the present study was to assess whether modest changes in daily step count could significantly reduce levels of inflammatory markers in women with PCOS.
Subjects and Methods
Sixty-five women with PCOS were assessed at baseline and again at 6 months. All had been provided with an accelerometer and encouraged to increase activity levels. Multivariate linear regression analyses (adjusted for age, ethnicity, baseline step count, change in BMI and change in accelerometer wear-time) were used to assess changes in daily step count against clinical and research biomarkers of inflammation, CVD and T2DM.
Results
Mean step count/day at baseline was 6337 (±270). An increase in step count (by 1000 steps) was associated with a 13% reduction in IL6 (β: −0.81 ng/L; 95% CI, −1.37, −0.25, P = 0.005) and a 13% reduction in CRP (β: −0.68 mg/L; 95% CI, −1.30, −0.06, P = 0.033). Additionally, there was a modest decrease in BMI (β: 0.20 kg/m2; 95% CI, −0.38, −0.01, P = 0.038). Clinical markers of T2DM and CVD were not affected by increased step count.
Conclusions
Modest increases in step count/day can reduce levels of inflammatory markers in women with PCOS, which may reduce the future risk of T2DM and CVD.
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Objective
Primary aldosteronism (PA) is divided into two major subtypes, aldosterone-producing adenoma (APA) and bilateral idiopathic hyperplasia (IHA) and is associated with a higher risk of cardiovascular events. However, the nature of vascular function in PA patients remains to be determined. The aim of this study was to determine the vascular function and investigate the implications of vascular function assessments in the patients.
Methods
Flow-mediated dilation (FMD), as an index of endothelial function, and cardio-ankle vascular index (CAVI), as an index of arterial stiffness, were retrospectively compared between 42 patients with APA, 37 patients with IHA, and 42 patients with essential hypertension (EH). These values were also compared with background factors, KCNJ5 mutation and clinical outcome in terms of blood pressure reduction after adrenalectomy in the APA group.
Results
FMD was significantly lower in the APA group (4.8 ± 2.1%) and IHA group (4.1 ± 1.9%) than in the EH group (5.7 ± 2.1%). CAVI did not differ significantly among groups. Although no significant correlations were seen between FMD and background factors in the IHA group, FMD correlated negatively with BMI and plasma aldosterone concentration in the APA group (rs = −0.313, rs = −0.342, respectively). KCNJ5 mutational status was not associated with FMD value. High FMD was associated with blood pressure normalization after adrenalectomy in the APA group.
Conclusions
Patients with PA displayed impaired endothelial function. Complete clinical success after adrenalectomy was associated with preserved endothelial function. This study provides a better understanding of FMD assessment in patients with PA.
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Introduction
Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM.
Objectives
In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored.
Patients and methods
A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests, and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000–2000 mg metformin daily add-on insulin (MET group, n = 34) or insulin (non-MET group, n = 31). After, baseline measurements were repeated.
Results
The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with non-MET group (–1.58 (–3.35, 0.31) mmol/L vs 1.36 (–1.12, 2.24) mmol/L, P = 0.004). In parallel, the largest amplitude of glycemic excursions (–2.83 (–5.47, –0.06) mmol/L vs 0.45 (–1.29, 4.48) mmol/L, P = 0.004), the s.d. of blood glucose (–0.85 (–1.51, 0.01) mmol/L vs –0.14 (–0.68, 1.21) mmol/L, P = 0.015), and the coefficient of variation (–6.66 (–15.00, 1.50)% vs –1.60 (–6.28, 11.71)%, P = 0.012) all demonstrated improvement in the MET group, compared with the non-MET group. Significant reduction in insulin dose, BMI, and body weight was observed in patients in MET, not those in non-MET group.
Conclusion
Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as an adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.
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Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China
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Background
Lower extremity arterial disease (LEAD) is highly prevalent in people with diabetes in China, but half of cases are underdiagnosed due to diversities of clinical presentations and complexities of diagnosis approaches. The purpose of this study was to develop a risk score model for LEAD to facilitate early screening among type 2 diabetes (T2DM) patients.
Methods
A total of 8313 participants with T2DM from the China DIA-LEAD study, a multicenter, cross-sectional epidemiological study, were selected as the training dataset to develop a risk score model for LEAD by logistic regression. The area under receiver operating characteristic curve (AUC) and bootstrapping were utilized for internal validation. A dataset of 287 participants consecutively enrolled from a teaching hospital between July 2017 and November 2017 was used as external validation for the risk score model.
Results
A total of 931 (11.2%) participants were diagnosed as LEAD in the training dataset. Factors including age, current smoking, duration of diabetes, blood pressure control, low density lipoprotein cholesterol, estimated glomerular filtration rate, and coexistence of cardio and/or cerebrovascular disease correlated with LEAD in logistic regression analysis and resulted in a weighed risk score model of 0–13. A score of ≥5 was found to be the optimal cut-off for discriminating moderate–high risk participants with AUC of 0.786 (95% CI: 0.778–0.795). The bootstrapping validation showed that the AUC was 0.784. Similar performance of the risk score model was observed in the validation dataset with AUC of 0.731 (95% CI: 0.651–0.811). The prevalence of LEAD was 3.4, 12.1, and 27.6% in the low risk (total score 0–4), moderate risk (total score 5–8), and high risk (total score 9–13) groups of LEAD in the training dataset, respectively, which were 4.3, 19.6, and 30.2% in the validation dataset.
Conclusion
The weighed risk score model for LEAD could reliably discriminate the presence of LEAD in Chinese with T2DM aged over 50 years, which may be helpful for a precise risk assessment and early diagnosis of LEAD.
