Caron P.J.,Center Hospitalier University Larrey |
Bevan J.S.,Royal Infirmary |
Petersenn S.,Center for Endocrine Tumors |
Flanagan D.,Derriford Hospital |
And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Context: Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation. Objective: The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas. Design: PRIMARYS was a 48-week, multicenter, open-label, single-arm study. Setting: The study was conducted at specialist endocrine centers. Patients: Treatment-nave acromegalic patients with GH-secretingmacroadenomas participated in the study. Intervention: Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration). Outcome Measures: The primary endpoint was the proportion of patients with clinically significant (20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0 ) for the primary endpoint was that the proportion with TVRwas-55%. Secondary endpointsincluded: TVR at other time points, GH andIGF-1, acromegalic symptoms, quality of life (QoL), and safety. Results: Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9 -75.3% in sensitivity (n89) and secondary analyses (n63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance. Conclusions: Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor volume, GH and IGF-1, and acromegalic symptoms, and improves QoL. Copyright © 2014 by the Endocrine Society.
Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus
Shima T.,Saiseikai Suita Hospital |
Uto H.,Kagoshima University |
Ueki K.,University of Tokyo |
Takamura T.,Kanazawa University |
And 11 more authors.
Journal of Gastroenterology | Year: 2013
Background The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. Methods In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. Results Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥ 60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy- two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. Conclusions Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/ nonalcoholic steatohepatitis. © Springer 2012.
Reach G.,Diabetes and Metabolic Diseases |
Reach G.,University of Paris 13
Diabetes and Metabolism | Year: 2013
Aim: Diabetic patients often do not adjust their insulin doses using the algorithms that they have been taught. While this behavior may intuitively have a number of causes, such as the complexity of the decision or the fear of hypoglycaemia, we propose in this article a more general, "psychophysical", explanation based on behavioral economics concepts used to describe decisions made under uncertainty and risk. The concepts discussed herein may not be familiar to clinicians, who will find here an introduction to theories that may be helpful in understanding some aspects of non-adherence to medical prescriptions. Results: 1) The Prospect Theory of Kahneman and Tversky proposes that choices made in the context of risk are subject to loss aversion. 2) Decisions under uncertainty use mental short cuts called "heuristics", which can lead to biases; for instance, overestimating the probability of the risk. 3) To understand the very concept of risk, emotions must be considered with a special focus on anticipated regret. 4) Finally, selection difficulty is an important determinant of the preference for the status quo. Conclusion: These concepts may be relevant for understanding a preference for the status quo in decisions made in a context of uncertainty and risk, such as insulin dose adjustment. We suggest that these mental mechanisms may also be involved in other aspects of patients' non-adherence. As other common human behaviors, non-adherence may actually often be a consequence of biases resulting from our ways of thinking, being both cognitive and emotional, and, according to Kahneman, more often "fast" than "slow" Empirical studies are needed to support this hypothesis. © 2012 Elsevier Masson SAS.
Emanuele E.,University of Pavia |
Minoretti P.,University of Pavia |
Altabas K.,University of Zagreb |
Gaeta E.,University of Pavia |
Altabas V.,Diabetes and Metabolic Diseases
International Journal of Dermatology | Year: 2011
Background Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. Methods A total of 15 lean (body mass index [BMI] <25kg/m2) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. Results Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6±3.1AU versus 16.6±4.1AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3±7.3μg/ml) and without (19.3±6.1μg/ml) cellulite (P=0.69). Conclusions Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue. © 2011 The International Society of Dermatology.
Altabas V.,Diabetes and Metabolic Diseases
Current Clinical Pharmacology | Year: 2013
The metabolic syndrome is a constellation of risk factors for cardiovascular diseases including: abdominal obesity, a decreased ability to metabolize glucose (increased blood glucose levels and/or presence of insulin resistance), dyslipidemia, and hypertension. Patients who have developed this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Genetic factors and the environment both are important in the development of the metabolic syndrome, influencing all single components of this syndrome. The goals of therapy are to treat the underlying cause of the syndrome, to reduce morbidity, and to prevent complications, including premature death. Lifestyle modification is the preferred first-step treatment of the metabolic syndrome. There is no single effective drug treatment affecting all components of the syndrome equally known yet. However, each component of metabolic syndrome has independent goals to be achieved, so miscellaneous types of drugs are used in the treatment of this syndrome, including weight losing drugs, antidiabetics, antihypertensives, antilipemic and anticlothing drugs etc. This article provides a brief insight into contemporary drug treatment of components the metabolic syndrome. © 2013 Bentham Science Publishers.