Christina Daousi

Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes

Aims  A cross‐sectional study has been performed in order to estimate the prevalence, severity, and current treatment of chronic painful peripheral neuropathy (CPPN) in people with diabetes in the community.

Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors

Aims: To determine the prevalence of overweight and obesity among patients with type 1 and type 2 diabetes mellitus attending a secondary care diabetes clinic in the United Kingdom, and to assess the impact of overweight and obesity on glycaemic control and cardiovascular risk factors in patients with type 2 diabetes. Methods: 3637 patients with diabetes were identified from the hospital electronic diabetes register, 916 with type 1 diabetes (mean (SD) age 40.4 (15.1) years, 496 male) and 2721 with type 2 diabetes (mean (SD) age 62.5 (11.8) years, 1436 male). Data on body mass index (BMI), glycaemic control, lipid profiles, and blood pressure were extracted. Results: Of patients with type 1 diabetes, 55.3% were overweight (BMI ⩾25 kg/m2), 16.6% were obese (BMI ⩾30 kg/m2), and 0.4% had morbid obesity (BMI ⩾40 kg/m2). In contrast, 86% of patients with type 2 diabetes were overweight or obese, 52% were obese, and 8.1% had morbid obesity. Obese patients with type 2 diabetes were younger, had poorer glycaemic control, higher blood pressures, worse lipid profiles, and were more likely to be receiving antihypertensive and lipid lowering drugs compared with patients with BMI <30 kg/m2. Conclusions: Obesity is the rule among patients attending this hospital diabetes clinic, with 86% of those with type 2 diabetes overweight or obese. Obesity is associated with significantly worse cardiovascular risk factors in this patient group, suggesting that more active interventions to control weight gain would be appropriate.

Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months’ GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA1c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m2 (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA1c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy (1H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA1c reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (−59.3, −16.5%). The relative reduction in IHL correlated with that in HbA1c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism.

Polycystic Ovary Syndrome with Hyperandrogenism Is Characterized by an Increased Risk of Hepatic Steatosis Compared to Nonhyperandrogenic PCOS Phenotypes and Healthy Controls, Independent of Obesity and Insulin Resistance

CONTEXT Nonalcoholic fatty liver disease may be evident in women with polycystic ovary syndrome (PCOS), both conditions being associated with obesity and insulin resistance. However, few studies have accounted for the high prevalence of obesity in PCOS. OBJECTIVE The aim of this study was to determine whether PCOS is independently associated with hepatic steatosis, compared with healthy controls of similar age and body mass index (BMI), and whether steatosis is associated with hyperandrogenemia. DESIGN AND SETTING We conducted a cross-sectional, case-control study at two tertiary referral centers. PATIENTS Twenty-nine women with PCOS diagnosed by the Rotterdam criteria [aged 28 yr; 95% confidence interval (CI), 26-31; BMI, 33 kg/m2; 95% CI, 31-36] and 22 healthy controls (aged 29 yr; 95% CI, 28-31; BMI, 30 kg/m2; 95% CI, 28-33) were studied. METHODS Proton-magnetic resonance spectroscopy quantified hepatic and skeletal muscle fat; whole body magnetic resonance imaging quantified internal, visceral, and sc adipose tissue volumes. Differences were assessed between PCOS and controls using t tests, and between hyperandrogenic (HA) PCOS, PCOS with normal androgens (NA), and controls using analysis of covariance. RESULTS After statistical adjustment for BMI, HA-PCOS had significantly higher liver fat vs. NA-PCOS (3.7%; 95% CI, 0.6-13.1) and vs. controls (2.1%; 95% CI, 0.3-6.6). Similarly, after adjustment for homeostasis model assessment for insulin resistance, internal and visceral adipose tissue volumes, liver fat remained significantly greater in HA-PCOS compared to NA-PCOS and controls. CONCLUSION These data suggest that HA-PCOS is associated with hepatic steatosis, independent of obesity and insulin resistance.

Electrical spinal cord stimulation in the long‐term treatment of chronic painful diabetic neuropathy

Aims  Electrical spinal cord stimulation (ESCS) is a technique for the management of chronic painful diabetic neuropathy (CPDN) affecting the lower limbs. We assessed the efficacy and complication rate of ESCS implanted at least 7 years previously in eight patients.

The natural history of chronic painful peripheral neuropathy in a community diabetes population

Aims  To examine the natural history of chronic painful diabetic neuropathy (CPDN).

Presentation, management and outcomes in acute pituitary apoplexy: a large single-centre experience from the United Kingdom

To study the presentation, management and outcomes and to apply retrospectively the Pituitary Apoplexy Score (PAS) (United Kingdom (UK) guidelines for management of apoplexy) to a large, single‐centre series of patients with acute pituitary apoplexy.

The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency

BACKGROUND Adult GHD syndrome is associated with clustering of adverse cardiovascular (CV) risk factors such as abnormal body composition, dyslipidemia, insulin resistance and abnormal haemostatic factors. There is a wealth of evidence linking CV events with elevated levels of inflammatory markers (hs-CRP and IL-6) in the general population; however data on their abnormalities in GHD and specially the effects of GH replacement (GHR) on these inflammatory markers are limited. OBJECTIVE To study the effects of GHR on inflammatory markers, glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease. DESIGN Fifteen hypopituitary adults (11 males, mean age 48.5 years) with recently diagnosed, severe GHD were recruited. Patients received GHR (in addition to other pituitary hormone replacements) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels. Weight, waist hip ratio (WHR), body composition, fasting plasma glucose and insulin, insulin resistance index (HOMA-IR), fasting serum lipid levels, hs-CRP, IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR. RESULTS GHR resulted in a physiological increase in IGF-1 SDS [median -0.6 to +0.39, P<0.0001], improved quality of life (mean pre-treatment AGHDA score 16 vs. post-treatment score 7, P<0.0001) and reduction in WHR (0.94 vs. 0.92, P=0.01). There were no significant changes in body weight and composition. Levels of hs-CRP (log transformed, mean (SD)) were significantly reduced following GHR (pre 1.21 (0.9) vs. post 0.27 (0.9), P<0.0001) but TNF-alpha and IL-6 levels remained unchanged. Fasting glucose (mmol/L) [4.6 (0.1) vs. 5.1 (0.1), P=0.003], fasting insulin (muU/mL) [9.4 (8.1) vs. 12.1 (9.2), P=0.03] and HOMA-IR [1.2 (1.0) vs. 1.5 (1.1) P=0.02] (all pre-GHR vs. post-GHR and mean (SD)) significantly increased following GHR indicating increased insulin resistance. Significant improvements were noted in fasting LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels following GHR [3.4 (0.9) vs. 2.9 (0.7), P=0.03 and 1.2 (0.2) vs. 1.3 (0.2), P=0.02, respectively] (all pre-GHR vs. post-GHR and mean (SD)). Levels of total cholesterol and triglycerides did not change following GHR. CONCLUSIONS Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD resulted in favourable changes in hs-CRP, WHR, fasting LDL-C and HDL-C levels all of which are recognised CV risk markers. However, there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR, monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population.

Pituitary adenomas in childhood, adolescence and young adulthood: presentation, management, endocrine and metabolic outcomes

OBJECTIVE To elucidate the long-term outcomes of pituitary adenomas diagnosed in childhood and adolescence, knowledge of which remains sparse. DESIGN AND METHODS A retrospective review of patients aged ≤21 years at diagnosis of pituitary adenoma, attending a neuroendocrine service in Liverpool, UK, between 1984-2009. RESULTS There were 41 patients (33 female), mean age at diagnosis 17.3 years (range 11-21) and mean follow-up 9.6 years; 29 patients had prolactinomas (15 macroprolactinomas), 6 non-functioning pituitary adenomas (NFPAs), 5 Cushings disease (CD) and 1 acromegaly. All prolactinoma patients received dopamine agonists (DAs) and three also underwent pituitary surgery. Furthermore, ten patients underwent surgery: five with CD, one with acromegaly and four with NFPA. Four received radiotherapy after surgery. Another ten patients received hormone replacement: nine hydrocortisone, five thyroxine, seven sex steroids and five GH; another seven had severe asymptomatic GH deficiency. Three female patients were treated for infertility (two successfully). Thirteen patients gained significant weight (body mass index (BMI) increase >2 kg/m(2)) since diagnosis and 16 in total are now obese (BMI>30 kg/m(2)). Five were treated with orlistat and one attended a weight management service. Two received antihypertensive medications, two had type 2 diabetes and four were treated for dyslipidaemia. CONCLUSIONS This is one of the largest reviews of patients aged 21 or younger at diagnosis of pituitary adenoma followed up by a single service. Two-thirds had prolactinomas, all were treated with DAs and three underwent surgery. Increased cardiovascular risk factors (obesity and dyslipidaemia) and infertility are important sequelae and active identification and treatment are necessary.

Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide 1 and ghrelin in obese patients with Type 2 diabetes mellitus.

Diabet. Med. 29, e205–e210 (2012)