Bariatric Surgery-induced High-density Lipoprotein Functionality Enhancement Is Associated With Reduced Inflammation.

Background: Emerging evidence suggests an association between impaired high-density lipoprotein (HDL) functionality and cardiovascular disease (CVD). HDL is essential for reverse cholesterol transport (RCT) and reduces inflammation and oxidative stress principally via paraoxonase-1 (PON1). RCT depends on HDL's capacity to accept cholesterol (cholesterol efflux capacity [CEC]) and active transport through ATP-binding cassette (ABC) A1, G1, and scavenger receptor-B1 (SR-B1).

Methylation Status of Exon IV of the Brain-Derived Neurotrophic Factor (BDNF)-Encoding Gene in Patients with Non-Diabetic Hyperglycaemia (NDH) before and after a Lifestyle Intervention.

BDNF signalling in hypothalamic neuronal circuits is thought to regulate mammalian food intake. In light of this, we investigated how a lifestyle intervention influenced serum levels and DNA methylation of BDNF gene in fat tissue and buffy coat of NDH individuals. In total, 20 participants underwent anthropometric measurements/fasting blood tests and adipose tissue biopsy pre-/post-lifestyle (6 months) intervention.

Androgen receptor-reduced sensitivity is associated with increased mortality and poorer glycaemia in men with type 2 diabetes mellitus: a prospective cohort study.

Introduction: Hypogonadism is associated with poorer glycaemic outcomes/increased all-cause and cardiovascular morbidity/mortality in type 2 diabetes mellitus (T2DM). Increasing CAG repeat number within exon-1 of the androgen receptor (AR) gene is associated with increased AR resistance/insulin resistance.

Methods: We determined in a long-term 14-year follow-up cohort of 423 T2DM Caucasian men, the association between baseline androgen status/CAG repeat number (by PCR then Sequenom sequencing) and metabolic/cardiovascular outcomes.

Genetically defined favourable adiposity is not associated with a clinically meaningful difference in clinical course in people with type 2 diabetes but does associate with a favourable metabolic profile.

Aims: Change in weight, HbA , lipids, blood pressure and cardiometabolic events over time is variable in individuals with type 2 diabetes. We hypothesised that people with a genetic predisposition to a more favourable adiposity distribution could have a less severe clinical course/progression.

Methods: We involved people with type 2 diabetes from two UK-based cohorts: 11,914 individuals with GP follow-up data from the UK Biobank and 723 from Salford.

Circulating microRNA changes in patients with impaired glucose regulation.

We analysed if levels of four miRNAs would change after a lifestyle intervention involving dietary and exercises in prediabetes. MiRNAs previously shown to be associated with diabetes (Let-7a, Let-7e, miR-144 and miR-92a) were extracted from serum pre- and post-intervention. mRNA was extracted from fat-tissue for gene expression analyses.

Lifestyle intervention in individuals with impaired glucose regulation affects Caveolin-1 expression and DNA methylation.

Aims: We investigated whether a lifestyle intervention could influence expression and DNA methylation of diabetes-related genes in patients with impaired glucose regulation (IGR), the results were compared to bariatric surgery, considering it an intensive change.

Methods: Twenty participants with IGR had adipose tissue biopsy and blood collected pre- and post-lifestyle (6 months) intervention; 12 obese patients had subcutaneous fat taken before and after bariatric surgery. RNA/DNA was extracted from all samples and underwent qPCR.

Male hypogonadism: 14-year prospective outcome in 550 men with type 2 diabetes.

Introduction: Hypogonadism is more prevalent in men with type 2 diabetes (T2DM) (25%-40%) than in men without T2DM. Hypogonadism has been associated with poorer glycaemic outcomes and increased cardiovascular morbidity/mortality. We report a 14-year follow-up study to evaluate the influence of baseline testosterone level on T2DM outcomes.

Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme.

We investigated biological determinants that would associate with the response to a diet and weight loss programme in impaired glucose regulation (IGR) people using sequential window acquisition of all theoretical fragment ion spectra (SWATH) mass spectrometry (MS), a data acquisition method which complement traditional mass spectrometry-based proteomics techniques. Ten women and 10 men with IGR underwent anthropometric measurements and fasting blood tests. SWATH MS was carried out with subsequent immunoassay of specific peptide levels.

Assessment of global long interspersed nucleotide element-1 (LINE-1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2DM) individuals.

Introduction: Recent studies have indicated that methylation of the LINE-1 elements is associated with an increased risk of worsening carbohydrate metabolism. It has been shown that overall DNA methylation of LINE-1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors.

Methods: A total of 794 T2DM individuals from Salford, UK were included in this study (60% men n = 470).

Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation.

The rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development.

Placental alkaline phosphatase de-phosphorylates insulin-like growth factor (IGF)-binding protein-1.

Background: Insulin-like growth factors (IGF) regulate fetal growth through their effects on placenta. Their actions are influenced by IGF binding protein-1. Phosphorylated IGFBP-1 (pIGFBP-1) has high affinity for IGF-I and usually inhibits IGF-I activity but during pregnancy, it is de-phosphorylated to generate lower affinity isoforms and consequently, increased IGF bioavailability.

Insulin-like growth factor-II and insulin-like growth factor binding protein-2 prospectively predict longitudinal elevation of HDL-cholesterol in type 2 diabetes.

Introduction: Associations of insulin-like growth factor-II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) with cardiovascular risk have been inadequately studied. We hypothesized that IGF-II and IGFBP-2 associate with longitudinal trends in lipid profiles in type 2 diabetes patients.

Subjects And Methods: Four hundred and eighty nine subjects with type 2 diabetes (age 27-87 years) from the Salford Diabetes Cohort were studied.

IGFBP2 is a biomarker for predicting longitudinal deterioration in renal function in type 2 diabetes.

Objective: Insulin-like growth factors are implicated in the development of diabetic nephropathy. IGF-binding protein 2 (IGFBP2) and IGF2 are expressed in the kidney, but their associations with diabetic nephropathy are unclear. We therefore tested the hypothesis that circulating levels of IGF2 and IGFBP2 predict longitudinal renal function in individuals with type 2 diabetes.

IGF2 gene polymorphisms and IGF-II concentration are determinants of longitudinal weight trends in type 2 diabetes.

The hypothesis of the study was that IGF2 gene polymorphisms were associated with longitudinal trends in weight through modification of IGF-II concentration.Observational study that explored associations of the IGF2 gene and baseline circulating IGF-II concentration with 'real-world' longitudinal trends in body-mass index in a type 2 diabetes population.26 haplotype tagging single nucleotide polymorphisms (SNPs) from the IGF2 and H19 genes were studied in 485 Caucasian individuals in the Salford Longitudinal Diabetes Cohort.

Interactions of the IGF System with Diabetes and its Vascular Complications.

The insulin-like growth factor (IGF) system is an evolutionarily conserved group of important proteins that are fundamental to life. Indeed, insulin can be viewed as simply a specialized arm of the IGF system that has evolved to regulate primarily metabolic functions. The main purpose of the IGF system is to form a highly refined mechanism for the control of cellular growth, metabolism and survival.

Atorvastatin administration is associated with dose-related changes in IGF bioavailability.

Objective: IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins.

Design And Methods: We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (S.

Reverse cardiac remodelling and renal functional improvement following bilateral renal artery stenting for flash pulmonary oedema.

Acute flash pulmonary oedema (AFPO) is a life-threatening syndrome almost unique to patients with atheromatous renovascular disease (ARVD). Although recurrent AFPO is a widely accepted indication to consider renal revascularization, this is based on a number of case reports/series describing a successful outcome post-procedure. There is limited literature on the pathophysiological mechanisms and treatment effects of revascularization to support this clinical decision making.

Apposite insulin-like growth factor (IGF) receptor glycosylation is critical to the maintenance of vascular smooth muscle phenotype in the presence of factors promoting osteogenic differentiation and mineralization.

Vascular calcification is strongly linked with increased morbidity and mortality from cardiovascular disease. Vascular calcification is an active cell-mediated process that involves the differentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. Several inhibitors of this process have been identified, including insulin-like growth factor-I (IGF-I).

Reduced pericellular sensitivity to IGF-I in fibroblasts from girls with Turner syndrome: a mechanism to impair clinical responses to GH.

Girls with Turner syndrome (TS) are treated with supraphysiological doses of growth hormone (GH) to improve final height; however in some girls, the growth response can be poor. This may reflect aberrations in GH and/or IGF-I actions at the cellular level, and thus this study compared the response of skin fibroblasts from normal children (n = 5) and girls with TS (n = 8) to GH, IGF-I, or a combination, by assessing the IGF binding protein (IGFBP) profile of conditioned medium harvested over 7 d. The two cell types had a comparable IGFBP profile; IGFBP-3 and IGFBP-4 were the most abundant species.

Inflammatory markers and growth in South Asian and European origin infants in Britain: the Manchester Children's Growth and Vascular Health Study.

Objective: Given the high risk of cardiovascular disease in South Asians and the importance of inflammation in coronary heart disease we tested the hypothesis that circulating C-reactive protein (CRP) and interleukin 6 (IL-6) would be higher in healthy British born infants of South Asian origin than in infants of European origin in the first 2 years of life.

Study Design And Setting: Infants of South Asian (n=74) and European (n=129) origin were followed prospectively from birth. Anthropometry and fasting CRP and IL-6 concentrations were measured at one or more of 3, 6, 12 and 24 months of age.

Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome.

Aims/hypothesis: IGFs and their binding proteins are increasingly recognised as important in understanding the pathogenesis of cardiovascular disease. Low IGFBP-1, particularly coupled with low IGF-I, is associated with increased cardiovascular risk. In relation to structural and regulatory parallels between IGFBP-1 and - 2 we have now examined the hypothesis that IGFBP-2 may be a marker for cardiovascular risk.

Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake.

Background: The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease.

Objective: We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate.

Design, Subjects And Setting: Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n=205) compared with people still resident in the same villages of origin in India (n=246).

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India.

Aims/hypotheses: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system.

Materials And Methods: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246).

The effect of atorvastatin on serum lipoproteins in acromegaly.

Objective: Acromegaly is associated with long-term adverse effects on cardiovascular mortality and morbidity. Reducing growth hormone secretion improves well-being and symptoms, but may not significantly improve the lipoprotein profile. An additional approach to cardiovascular risk reduction in acromegaly may therefore be to target lipoprotein metabolism directly.

A substitution model of dietary manipulation is an effective means of optimising lipid profile, reducing C-reactive protein and increasing insulin-like growth factor-1.

There are two key methods in which fat intake may be manipulated; the 'substitution model' and the 'reduction model'. However insufficient information is known about the mechanisms of dietary fat reduction in individuals who have successfully reduced their fat intake, to be clear as to which strategy offers the greatest chance of success. Our objective was to ascertain the most effective dietary intervention for improving cardiovascular risk profile.