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Stephen L Atkin

Publications and source records attributed to Stephen L Atkin.

15 recordsLinked to original sources
PubMed2026

Metabolic Stress Testing Reveals Persistent Lipid-Handling Dysfunction in Women With Polycystic Ovary Syndrome Despite Exercise Training.

AIM: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and metabolic dysfunction, yet baseline metabolomic studies show inconsistent findings. We investigated whether metabolic abnormalities in PCOS emerge under physiological stress and how these responses are modified by exercise training. MATERIALS AND METHODS: Twelve women with PCOS and 10 controls completed hyperinsulinaemic-euglycaemic clamps with randomised saline or lipid infusion, before and after 8 weeks of supervised exercise. Plasma metabolomics (163 metabolites) were measured at baseline, post-infusion and post-clamp. Linear mixed-effects models assessed Group × Timepoint × Intervention interactions. RESULTS: No baseline metabolite differences were observed between groups. A significant three-way interaction (p = 0.008) indicated condition-dependent trajectory divergence. Post hoc analysis revealed a specific divergence during post-exercise lipid challenge (p = 0.048). Women with PCOS showed reduced suppression of ether-linked phosphatidylcholines during insulin-stimulated lipid loading (PC ae C44:4, p = 0.031), despite exercise-induced improvements in fitness and normalisation of amino acid profiles. Exploratory metabolite ratios suggested impaired substrate coordination under stress. CONCLUSIONS: Metabolic defects in PCOS are stress-dependent and not detectable at rest. Exercise training improves resting metabolism but reveals persistent impairment in adaptive lipid handling during combined insulin and lipid challenges, suggesting impaired coordination of substrate supply during metabolic stress. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ISRCTN42448814.

Humans↗
PubMed2025

Shared and divergent acute cardiovascular risk protein responses to lipid infusion in women with and without PCOS.

AIMS: Elevated circulating lipids are linked to cardiovascular disease (CVD), especially in insulin-resistant states like polycystic ovary syndrome (PCOS), but their effects on cardiovascular risk proteins (CVRPs) remain unclear. This study used a two-step approach to examine acute cardiovascular proteomic responses to lipid-induced metabolic stress. We first identified proteins altered by lipids and insulin in healthy control (HC) women, then assessed whether these responses were similar or divergent in women with PCOS. METHODS: In a randomised cross-over study, 10 healthy controls and 12 women with PCOS underwent 5-h saline (control) or intralipid infusions. After 3&#x2009;h, a 2-h hyperinsulinemic-euglycemic clamp was initiated. Plasma CVRP expression was assessed at baseline, post-lipid (180&#x2009;min) and post-clamp (300&#x2009;min) using SOMAscan proteomics. STRING and pathway enrichment analyses were performed to explore functional associations. RESULTS: In the HC group, lipid infusion altered the expression of 11 out of 54 CVRPs including increases in RANK, IL2RA, TACI, SLAF5 and DCN (p <0.05) and decreases in THPO, BOC, SOD2, FGF23, and AgRP (p <0.05). Most changes reversed with insulin, but BOC, SOD2, MMP12, FGF23, and DCN remained dysregulated. In PCOS, responses mirrored the HC group except for lower AgRP following lipid infusion (p <0.01), and persistent elevation of SLAF5 and DCN following insulin (p <0.05). Enrichment analysis linked altered proteins to immune activation, cell proliferation, and cytokine-receptor signalling. CONCLUSION: Acute lipid infusion revealed shared and phenotype-specific proteomic responses linked to early vascular stress. In PCOS, persistent dysregulation suggests reduced metabolic adaptability, with exploratory signals that may complement established biomarkers of early cardiovascular risk.

Humans↗
PubMed2006

The effect of thyroid dysfunction on N-terminal pro-B-type natriuretic peptide concentrations.

BACKGROUND: B-type natriuretic peptides and N-terminal pro-B-type natriuretic peptides (NT-proBNP) have been suggested as being useful for the diagnosis of congestive heart failure. We have shown previously that changes in thyroid function are associated with changes in concentrations of other low molecular weight molecules. Therefore, the aim of this study was to assess whether similar changes occurred with NT-proBNP concentrations following treatment of thyroid dysfunction. METHODS: Seventeen patients (12 female, 5 male, age range 24-77 years) with newly diagnosed hypothyroidism and 21 patients (16 female, 5 male, age range 21-66 years) with newly diagnosed hyperthyroidism had NT-proBNP measured at baseline and when they subsequently became euthyroid. RESULTS: NT-proBNP levels were not significantly different in the hyperthyroid group from the hypothyroid, either before (P = 0.706) or after treatment to euthyroidism (P = 0.170). The hypothyroid group showed a rise in NT-proBNP after treatment (P < 0.001). There was a marginally significant fall in the NT-proBNP levels in the hyperthyroid group (P = 0.05). However, these changes were within the expected wide range of biological variability of NT-proBNP shown in earlier studies. CONCLUSIONS: Hypothyroidism alters NT-proBNP concentrations, but the magnitude of this effect may be lost in the wide biological variability of natriuretic peptides and this statistically significant finding is not likely to be of clinical relevance.

Adult↗
PubMed2006

The LH/FSH ratio has little use in diagnosing polycystic ovarian syndrome.

BACKGROUND: The luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is often requested to help diagnose polycystic ovarian syndrome (PCOS) despite a recent consensus recommending against its use. This study aimed to compare the variability of the LH/FSH ratio in PCOS with that of normal menstruating women over a full cycle in order to establish the diagnostic utility, or otherwise, of the test. METHODS: Twelve women with PCOS and 11 matched controls had blood collected at four-day intervals on 10 consecutive occasions over a complete menstrual cycle. RESULTS: The median LH/FSH ratio for individual subjects did not differ significantly between the PCOS and the non-affected group (1.6 versus 1.2, P = 0.14). Only 7.6% of samples from PCOS patients had an LH/FSH ratio above three, compared with 15.6% of samples from normal subjects. CONCLUSION: This study confirms that measurement of the LH/FSH ratio is of limited use in the diagnosis of PCOS.

Adult↗
PubMed2006

The effect of glucose variability on the risk of microvascular complications in type 1 diabetes.

OBJECTIVE: It is not known whether glycemic instability may confer a risk of microvascular complications that is in addition to that predicted by the mean blood glucose (MBG) value alone. This study has analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of glucose variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Pre- and postprandial seven-point glucose profiles were collected quarterly during the DCCT in 1,441 individuals. The mean area under the curve glucose and the SD of glucose variability within 24 h and between visits were compared with the risk of retinopathy and nephropathy, having adjusted for age, sex, disease duration, treatment group, prevention cohort, and phase of treatment. RESULTS: Multivariate Cox regression showed that within-day and between-day variability in blood glucose around a patient's mean value has no influence on the development or progression of either retinopathy (P = 0.18 and P = 0.72, respectively) or nephropathy (P = 0.32 and P = 0.57). Neither preprandial (P = 0.18) nor postprandial (P = 0.31) glucose concentrations preferentially contribute to the probability of retinopathy. CONCLUSIONS: This study has shown that blood glucose variability does not appear to be an additional factor in the development of microvascular complications. Also, pre- and postprandial glucose values are equally predictive of the small-vessel complications of type 1 diabetes.

Adolescent↗
PubMed2005

Neuropilin-1 and VEGF correlate with somatostatin expression and microvessel density in ovarian tumours.

Vascular endothelial growth factor (VEGF), is an angiogenic growth factor, expressed more highly in malignant than benign ovarian tumours. Neuropilin-1, which can act as a VEGF receptor has been shown to be associated with tumour angiogenesis in some cancer systems. Somatostatin (SST), a potentially anti-angiogenic factor, acts via somatostatin receptors that are expressed in ovarian cancer. We used immunohistochemistry to demonstrate expression of Neuropilin-1 in 63 malignant and 35 benign ovarian tumours and compared it to VEGF, Flt, Flk, SST expression and tumour microvessel density (MVD). Neuropilin-1 was expressed in 34/63 malignant and 22/35 benign lesions. VEGF, Flt, Flk and SST were expressed more highly in the epithelium of malignant and the vessels of benign lesions. VEGF expression correlated with SST expression in the epithelium (p<0.001) and the vessels (p<0.001), this co-expression was confirmed by dual immunostaining. The MVD for malignant lesions was higher than benign (p<0.001) and positively correlated to epithelial VEGF expression (p=0.001) and negatively correlated to vascular VEGF expression (p=0.025). These results show that Neuropilin-1 is expressed in ovarian tumours and also show that VEGF and SST are co-expressed in the same tissue compartments raising the intriguing possibility that SST may be important in angiogenesis in ovarian cancer.

Adult↗
PubMed2004

Inhibition of endothelial proliferation by the somatostatin analogue SOM230.

OBJECTIVE: Somatostatin (SST) modulates exocrine and endocrine secretion, proliferation and apoptosis via five G protein-linked receptors (SSTRs 1-5). Long-acting SST analogues such as Octreotide, and the new analogue SOM230, have been developed for the treatment of neuroendocrine tumours. Octreotide has previously been reported to inhibit endothelial proliferation. We wished to determine if SOM230 is a more potent inhibitor of endothelial cell proliferation than Octreotide. DESIGN: We have determined the expression of SSTRs in proliferating human umbilical vein endothelial cells (HUVECs) in vitro, and determined their response to the somatostatin analogues SOM230 and Octreotide, following vascular endothelial growth factor (VEGF) stimulation. MEASUREMENTS: Quantitative RT-PCR and western blotting were used to determine the expression of SSTRs 1-5 in proliferating HUVECs. These cells were grown in media containing 200 pg/ml VEGF and treated with 10(-11) to 10(-6) M Octreotide or SOM230. The WST-1 assay was then used to determine the effects of these analogues on HUVEC proliferation. RESULTS: Using quantitative RT-PCR and western blotting, HUVECs were found to express SSTRs 1, 2 and 5. SSTRs 3 and 4 were not detected. Using the WST-1 assay, SOM230 was found to significantly inhibit proliferation by up to 46.0% +/- 9.4% (10(-6)-10(-7) M; P < 0.05), whereas in parallel studies Octreotide failed to inhibit HUVEC proliferation. CONCLUSIONS: The pan SST analogue SOM230 inhibits proliferation of HUVECs, which are unaffected by Octreotide. SOM230 may thus represent a suitable candidate drug for antiangiogenic therapy.

Blotting, Western↗
PubMed2004

Hypopituitarism presenting as a mixed hyperlipidaemia.

A case report is presented of a 37-year-old man who, largely by chance, was found to have a marked mixed hyperlipidaemia. As a teenager he had been treated for apparent idiopathic growth hormone deficiency, but had also never developed secondary sexual characteristics. Pituitary hormone measurement was now consistent with hypopituitarism and magnetic resonance imaging showed hypoplasia of his pituitary stalk as the likely cause. His hyperlipidaemia improved after appropriate hormone replacement. He thus appears to have had a mixed hyperlipidaemia secondary to hypopituitarism, which was secondary to a pituitary stalk abnormality, which in turn may have been associated to the trauma surrounding his normal breech delivery.

Adult↗
PubMed2002

Hyperparathyroidism in elderly osteopenic women.

Raised levels of parathyroid hormones (PTH) predispose to osteoporotic fracture particularly in the elderly. The true prevalence of primary or secondary hyperparathyroidism is unknown, as PTH evaluation is not performed as a screening test in the elderly. We report raised PTH levels in 27 of 190 (14.2%) community living fully mobile postmenopausal women with densitometrically established osteopenia, consuming an average of 645 (+/-191) mg of calcium per day. Twenty-five of the 27 women with raised PTH were normocalcaemic, hypercalcaemia been found only in two. Serum 25 hydroxy vitamin D levels were all within the normal range (above 22 nmol/l). Women with a raised PTH were significantly older and their serum 25 hydroxy vitamin D levels were significantly lower than those women with normal PTH values. These data suggest that in community leaving healthy postmenopausal women, normocalcaemic hyperparathyroidism, in the presence of what are still considered normal vitamin D levels, may be common. This may suggests that widespread supplementation with calcium and vitamin D may be required in postmenopausal women for PTH suppression and preservation of bone mass.

Aged↗
PubMed2002

Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes.

OBJECTIVE: Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period. RESULTS: Compliance with the dietary supplementation was >90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean +/- SD 8.09 +/- 21.9%, P = 0.006), insulin resistance (6.47 +/- 27.7%, P = 0.003), HbA(1c) (0.64 +/- 3.19%, P = 0.048), total cholesterol (4.07 +/- 8.13%, P = 0.004), LDL cholesterol (7.09 +/- 12.7%, P = 0.001), cholesterol/HDL cholesterol ratio (3.89 +/- 11.7%, P = 0.015), and free thyroxine (2.50 +/- 8.47%, P = 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones. CONCLUSIONS: These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile.

Blood Glucose↗
PubMed2002

Biological variation of homeostasis model assessment-derived insulin resistance in type 2 diabetes.

OBJECTIVE: Individuals with type 2 diabetes are particularly vulnerable to cardiovascular disease. Insulin resistance is a major determinant of this increased risk and is a potential therapeutic target. This study was undertaken to establish the natural biological variation of insulin resistance in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: The biological variation of insulin resistance was assessed by measuring insulin resistance at 4-day intervals on 10 consecutive occasions in 12 postmenopausal women with diet-controlled type 2 diabetes and in 11 weight- and age-matched postmenopausal women without type 2 diabetes. Insulin resistance was derived using the homeostasis model assessment for insulin resistance (HOMA-IR) method. RESULTS: The distribution of HOMA-IR was log Gaussian in the type 2 diabetic study group and Gaussian in the control group. The HOMA-IR in the type 2 diabetic group was significantly greater than that of the control group (mean +/- SD: 4.33 +/- 2.3 vs. 2.11 +/- 0.79 units, P = 0.001). After accounting for analytical variation, the mean intraindividual variation was also substantially greater in the type 2 diabetic group than in the control group (mean 1.05 vs. 0.15, P = 0.001). Consequently, at any level of HOMA-IR, a subsequent sample must increase by >90% or decrease by >47% to be considered significantly different from the first. CONCLUSIONS: HOMA-IR is significantly greater and more variable for individuals with type 2 diabetes. Therefore, this inherent variability needs to be accounted for in studies evaluating therapeutic reduction of HOMA-IR in this group.

Diabetes Mellitus, Type 2↗
PubMed2002

Use of dynamic contrast-enhanced MRI to assess the functional vascular pharmacokinetic parameters of normal human ovaries.

OBJECTIVE: To assess the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to measure functional vascular pharmacokinetic parameters of normal human ovaries in vivo using an open linear two-compartment pharmacokinetic model. STUDY DESIGN: Twenty-one women with no ovarian disease underwent DCE-MRI. Sequential images were acquired during injection of a contrast bolus. Ovarian volumes were calculated and pharmacokinetic data analyzed using a pharmacokinetic model. Ovarian tissue was compared with skeletal muscle to demonstrate the pharmacokinetic parameters. RESULTS: Normal ovarian tissue was found to enhance rapidly and dramatically. When compared with skeletal muscle as a control, ovarian tissue was seen to demonstrate a significantly higher maximum enhancement factor and amplitude of the upslope, although there was no significant difference in the exchange rate. Sample size precluded conclusions about differences due to menstrual cycle or menopausal status. CONCLUSION: The results reflect the vascular physiology of the normal ovary. Definition of the pharmacokinetic properties of normal ovaries will allow DCE-MRI to be applied prospectively to conduct noninvasive, in vivo studies of ovarian angiogenic function, including response to drugs, contraceptive research, assessment of polycystic ovary syndrome, ovarian hyperstimulation syndrome, diagnosis of malignancy and prediction of response to antiangiogenic chemotherapy.

Adolescent↗