Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy

Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus

Evidence based diabetology : strategies to prevent macrovascular disease and to reduce mortality

Diabetes mellitus (DM) is the most common metabolic disease worldwide and the number of newly diagnosed cases is increasing. DM is strongly associated with a number of devastating chronic late complications, including retinopathy, nephropathy and neuropathy (microvascular complications), as well as cardiac, cerebrovascular and peripheral vascular disease (macrovascular complications). Despite lots of progress in therapeutic possibilities during the last decades, mortality risk due to macrovascular complications is still increased in patients with DM when compared to non diabetic individuals. It has also been suggested that specific risk factors influence macrovascular risk differentially in persons with and without DM. In addition, there is still uncertainty whether the effectiveness of certain treatment forms differs between patients with and without DM, and in the patients with DM, between type 1 and type 2. The focus of my thesis was on prevention and therapy of macrovascular disease in patients with type 1 and type 2 DM, as well as on comparisons with patients without DM. Three studies (Studies A-C) investigated the effectiveness of specific treatment forms on macrovascular disease by means of systematic reviews and meta-analyses, whereas two studies (Studies D and E) evaluated novel risk indicators using survival analysis based on data from the 'Swiss Cohort of the World Health Organisation (WHO) Multinational Study of Vascular Disease in Diabetes'. The aim of Study A (published in Am Heart J 2006 Jul;152(1):27-38) was to assess the effect of improved glycaemic control on cardiac, cerebrovascular and peripheral vascular complications in type 1 and type 2 DM. Outcomes included the incidence rate ratios (IRRs) for any macrovascular event, cardiac events, stroke, and peripheral arterial disease. Results showed a 62% (95% Confidence Interval (CI) 44-74%) and 19% (95% CI 9-27%) reduction in macrovascular risk for improved glycaemic control in type 1 and type 2 DM, respectively. In type 1 DM the effect was mainly based on a reduction of cardiac and peripheral vascular events. In type 2 DM it was due to reductions in stroke and peripheral vascular events. The effects appeared to be particularly important in younger patients with shorter duration of DM. Study B (published in Curr Med Res Opin 2006 Mar;22(3):617-23) examined the effectiveness of fibrates (peroxisome proliferator activated receptor α-agonists) in the prevention of coronary heart disease in type 2 DM. The primary outcome of this meta-analysis was the IRR for coronary heart disease (CHD) events (a combination of non fatal myocardial infarction and death due to CHD). Secondary endpoints were death due to CHD, fatal and non fatal myocardial infarction, and fatal and non fatal stroke. The results of Study B showed a 16% risk reduction for CHD events (95% CI 4-26%) in patients with type 2 DM when treated with fibrates compared to placebo. For the secondary endpoints a tendency towards reduction in risk was found, although this did not reach conventional levels of statistical significance. Coronary stenting is established as a treatment of coronary heart disease. The aim of Study C (published in Heart 2006 May;92(5):650-7) was to indirectly compare the effects of polymer based sirolimus versus paclitaxel eluting coronary stents and to examine whether they are equally effective in the prevention of restenosis in patients with and without DM. The indirect comparisons were performed by calculating the ratio of incidence rate ratios (RIRR) of studies comparing sirolimus eluting stents versus conventional bare metal stents and studies comparing paclitaxel eluting versus bare metal stents. The overall study population and patients with and without DM were analysed separately. Outcomes included in-stent- and in-segment restenosis, target lesion revascularisation, and major adverse cardiac events. The results of this study showed that rates of revascularisation procedures are reduced by sirolimus as well as paclitaxel eluting stents when compared to bare metal stents independent of the study population. However, in persons without DM a superiority of the sirolimus eluting stent to the paclitaxel eluting stent was found for all endpoints under investigation. In contrast, for persons with DM no statistically significant differences between the two drug eluting stents were found. A meta-regression analysis confirmed a difference between individuals with and without DM. Study D (published in Diabetologia 2006, DOI 10.1007/s00125-006-0483-1) evaluated the long-term association of two parameters with mortality, namely QT interval and resting heart rate (rHR) in patients with type 1 and type 2 DM. Based on the 23-year follow up of the 'Swiss Cohort of the WHO Multinational Study of Vascular Disease in Diabetes', the prognostic values of these two risk factors were examined on all-cause, cardiovascular and cardiac mortality and mortality due to ischaemic heart disease using a Cox proportional hazards model. Results showed an association of prolonged QT interval (corrected for heart rate, QTc) with an increased mortality risk due to all causes, as well as cardiovascular and cardiac disease in type 1 DM, whereas no association was found for rHR. In contrast, in patients with type 2 DM elevated rHR but not QTc was associated with an increased risk of all-cause mortality as well as death due to cardiovascular, cardiac and ischaemic heart disease. Study E (published in J Intern Med 2006 Sep;260(3):272-80) was based on an 15- year follow up of the 'Swiss Cohort of the WHO Multinational Study of Vascular Disease in Diabetes'. This study evaluated the long-term association of apolipoprotein B (apo B) with mortality risk in patients with type 1 DM. Compared to Study D, follow up was shorter due to the fact that apo B was only measured later in the course of the study. Analyses were performed for all-cause and cardiac mortality and mortality due to ischaemic heart disease, using a parametric proportional hazards model based on the Weibull distribution. Apo B was found to be positively related to all-cause and cardiac mortality, and mortality due to ischaemic heart disease. An apo B >0.96 g/L translated into a doubling of overall mortality, and a sevenfold increase of mortality due to cardiac disease or ischaemic heart disease. In conclusion, this thesis showed that: • The incidence of macrovascular events is reduced by improved glycaemic control, both in type 1 and type 2 DM. Although effects on specific manifestations of macrovascular disease are different between the two types of DM, in absolute terms benefits are comparable. • CHD events are substantially reduced in patients with type 2 DM when treated with fibrates. Nevertheless, their exact role in lipid lowering treatment needs to be investigated further. • Compared to bare metal stents, sirolimus as well as paclitaxel eluting stents are effective in reducing the rates of revascularisation procedures. Based on indirect evidence, stents eluting sirolimus appear to be superior to paclitaxel eluting stents in patients without DM but not in patients with DM. • Prolongation of QTc is related to an increased mortality risk in patients with type 1 DM, whereas elevated rHR is associated with higher mortality risk in patients with type 2 DM. • Increased apo B levels are consistently associated with mortality risk in type 1 DM. In addition to these conclusions, two general statements can be made: • The effectiveness of therapeutic interventions may be different in persons with compared to persons without DM. • Within the group of patients with DM, the effectiveness of specific interventions may vary between type 1 and type 2 DM

Long-term cardiovascular and non-cardiovascular mortality in women and men with type 1 and type 2 diabetes mellitus: a 30-year follow-up in Switzerland

While studies from other countries have shown an excess mortality in diabetic individuals when compared with the general population, comparable long-term data is not available for Switzerland

Self-monitoring of blood glucose in non-insulin treated patients with type 2 diabetes: a systematic review and meta-analysis

To assess the effect of self-monitoring of blood glucose (SMBG) on glycaemic control in non-insulin treated patients with type 2 diabetes by means of a systematic review and meta-analysis

Continuous subcutaneous insulin infusion therapy: effects on quality of life

To compare the diabetes-specific quality of life in subjects with type 1 diabetes treating their diabetes with multiple daily injections (MDI) to that of subjects on continuous subcutaneous insulin infusion (CSII)

Exercise-induced Growth Hormone Secretion in the Assessment of Growth Hormone Deficiency in Adult Individuals

The role of exercise testing in the assessment of GH deficiency (GHD) in adult patients is currently unclear. This study aimed at evaluating the diagnostic value of exercise-induced GH levels in the detection of severe GHD in adult patients

Dehydroepiandrosterone sulfate in the assessment of the hypothalamic-pituitary-adrenal axis

The role of dehydroepiandrosterone-sulfate (DHEA-S) in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with suspected insufficiency is uncertain

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials

To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus