Effect of fibrate treatment on liver function tests in patients with the metabolic syndrome.

BACKGROUND: Fibrates are used especially in patients with hypertriglyceridaemia, a feature of the metabolic syndrome. Elevated LFTs are often observed in these patients perhaps related to fatty infiltration. AIM: We wished to study changes seen in LFTs (GGT, ALT and ALP) following fibrate therapy and then determine associated factors. METHODS: This was a retrospective observational study in which data was collected from case notes of patients started on fibrates (n = 118, 2002-2008) in the lipid clinic at Good Hope Hospital and pre/post-fibrate lipid and LFT values were obtained. All biochemistry was performed on the Roche P-Unit using supplied reagents. Statistical analyses included t tests and regression analyses (factorised when quartiles were compared). RESULTS: Of the study population 106 patients were on fenofibrate; the remaining on bezafibrate. Significant lowering of GGT (p < 0.0001), ALT (p = 0.0014) and ALP (p < 0.0001) levels were observed following fibrate treatment. Baseline lipid (cholesterol, triglycerides and HDL) concentrations, alcohol intake, length of treatment, gender, concurrent statin treatment and diabetes did not correlate with these changes in LFT in a multiple regression analysis. Higher pre-fibrate GGT (p < 0.0001), ALT (p < 0.0001) and ALP (p < 0.0001) concentrations were associated with larger decreases in each of these tests respectively with the highest 2 quartiles (GGT > 57 IU/l, ALT > 34 IU/l and ALP > 94 IU/l) significantly different to the lowest quartile. The above associations remained significant even when the regression analyses were corrected for changes in lipid values (which did not show an association). CONCLUSIONS: Fibrate treatment led to improvements in LFT, the greatest benefit seen in patients with higher baseline LFT values. It appears that baseline and changes in lipid values post fibrate treatment were not associated with change in LFT.

Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study.

INTRODUCTION: The association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established and current endocrine society guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes or erectile dysfunction. AIM: We report the first double-blind, placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess metabolic changes with long-acting testosterone undecanoate (TU). METHODS: The type 2 diabetes registers of seven general practices identified 211 patients for a 30-week double-blind, placebo-controlled study of long-acting TU 1,000 mg followed by 52 weeks of open-label use. Because of the established impact of age, obesity, and depression on sexual function, these variables were also assessed for influence on metabolic parameters. MAIN OUTCOME MEASURE: Changes in glycated hemoglobin (HbA1c) and the level of testosterone at which response are achieved. RESULTS: Treatment with TU produced a statistically significant reduction in HbA1c at 6 and 18 weeks and after a further 52 weeks of open-label medication most marked in poorly controlled patients with baseline HbA1c greater than 7.5 where the reduction was 0.41% within 6 weeks, and a further 0.46% after 52 weeks of open-label use. There was significant reduction in waist circumference, weight, and body mass index in men without depression, and improvements were related to achieving adequate serum levels of testosterone. There were no significant safety issues. CONCLUSIONS: Testosterone replacement therapy significantly improved HbA1c, total cholesterol, and waist circumference in men with type 2 diabetes. Improvements were less marked in men with depression at baseline, and therapeutic responses were related to achieving adequate serum testosterone levels. Current advice on 3- to 6-month trials of therapy may be insufficient to achieve maximal response. Patients reported significant improvements in general health.

Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes.

INTRODUCTION: Sexual dysfunction, particularly erectile dysfunction (ED), is common in men with type 2 diabetes, occurring in up to 75% of cases. The prevalence of hypogonadism is also high in men with diabetes and low testosterone is associated with both sexual dysfunction and a reduced response to oral therapy for ED. AIM: This study aimed to determine the effect of testosterone replacement with long-acting Testosterone Undecanoate (TU) on sexual function, mood and quality of life vs. placebo over a treatment period of 30 weeks followed by 52 weeks of open-label medication. The study was conducted in a primary care population of men with type 2 diabetes attending their primary care physician for routine visits. METHODS: The male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L or less. Two hundred eleven men were screened. A double-blind placebo-controlled study was conducted in 199 men with type 2 diabetes and hypogonadism treated for 30 weeks with either 1,000 mg of TU or matching placebo followed by 52-week open-label follow on. MAIN OUTCOME MEASURES: The primary outcome measure, International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression Scale, and Global Efficacy Question were used as secondary outcome measures to assess mood and self-reported quality of life. RESULTS: Testosterone replacement therapy with long-acting TU improved all domains of sexual function at 30 weeks (erectile function [EF], P = 0.005; intercourse satisfaction, P = 0.015; sexual desire, P = 0.001; overall satisfaction, P = 0.05; and orgasm, P = 0.04), with benefit as early as 6 weeks. Improvements in AMS score were significant in men without depression (P = 0.02) and the presence of depression at baseline was associated with marked reduction in response to both sexual function and psychological scores. All responses in sexual function continued to improve significantly up to 18 months with an improvement in EF score of 4.31 from baseline. In a small cohort of 35 men taking phosphodiesterase type 5 inhibitors, there was no change during the double-blind phase but a nine-point improvement in EF domain during 52-week open-label treatment. After 30 weeks, 46% vs. 17% of patients on active therapy vs. placebo felt that the treatment had improved their health, reaching 70% after open-label therapy. Less obese and older patients responded better to testosterone therapy. There were no significant adverse events. CONCLUSION: TU significantly improved all domains of the IIEF and patient reported quality of life at 30 weeks and more significantly after 52-week open-label extension. Improvement was most marked in less obese patient and those without coexisting depression. In men with type 2 diabetes, trials of therapy may need to be given for much longer than 3-6 months suggested in current guidelines.

Postprandial reactive hypoglycaemia: varying presentation patterns on extended glucose tolerance tests and possible therapeutic approaches.

Reactive hypoglycemia is a state characterised by sympathetic or neuroglycopenic symptoms associated with hypoglycaemia in the postprandial state resulting in considerable distress to the patient. It is our practice to carry out either extended glucose tolerance tests (eGTTs) or mixed meal tests in these patients. We describe two patients who experienced hypoglycaemic symptoms early and late during eGTT. The patient who experienced symptoms early, in contrast to the patient who presented with late symptoms, did not possess any characteristics of the metabolic syndrome. Based on clinical symptoms, glucose, insulin, and free fatty acid (FFA) levels, we speculate on possible mechanisms that may have accounted for each of their presentation patterns. We then discuss low glycaemic index diet which will be the mainstay of management.

Fibrates and estimated glomerular filtration rate: observations from an outpatient clinic setting and clinical implications.

BACKGROUND: Previous studies have demonstrated that fibrates have an effect on creatinine concentrations. The pattern of change with fibrates in estimated glomerular filtration rate (eGFR), widely used in clinical practice, has not been previously described. METHODS: Data was retrospectively collected from 132 consecutive case notes of patients started on fibrates in a lipid clinic between 2002 and 2008. Pre- and post-fibrate creatinine concentrations were measured and eGFR measurements were obtained. RESULTS: Of the 79 patients with both pre and post-treatment eGFR values <90 ml/min/1.73 m(2), a significant mean eGFR reduction of 8.2 ml/min/1.73 m(2) was noted. Of these patients, 50% demonstrated a reduction in eGFR >8 ml/min/1.73 m(2), 25% demonstrated a reduction >16 ml/min/1.73 m(2), and 10% demonstrated a reduction >21 ml/min/1.73 m(2). CONCLUSIONS: The authors demonstrate a significant effect of fibrates on eGFR in clinical practice. Awareness of the pattern of eGFR change is important for decisions regarding the continued use of fibrate therapy and/or commonly co-prescribed diabetic drugs and renal specialist referrals.

Significant increase in high-density lipoprotein cholesterol with fibrates is associated with low pretreatment high-density lipoprotein cholesterol: findings from an outpatient clinic setting.

BACKGROUND: Change in high-density lipoprotein cholesterol (HDL-C) observed in large randomized controlled trials using fibrates has varied. Inconsistent cardiovascular outcomes have also been the common theme of these trials. Subgroup analysis of even the negative trials, however, reveals significant reduction in cardiovascular disease in patients with low HDL-C and high triglycerides. We wished to study HDL-C change following fibrate therapy in our lipid clinic and determine the factors associated with HDL-C change. METHODS: Data were collected from case notes of patients started on fibrates (n=248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in HDL-C. RESULTS: Linear regression analysis revealed that HDL-C change was associated with pretreatment HDL-C (P<0.001), diabetes (P=0.004) and treatment duration (P=0.036). Multiple regression analysis with all of the factors in the model suggested that they were independent. Patients with a baseline HDL-C <1.0 mmol/L showed a greater HDL-C increase when compared to patients with a baseline HDL-C ≥1.0 mmol/L; HDL-C <1.0 mmol/L (increase of 0.15 mmol/L, linear regression: c=0.14, 95% confidence interval 0.05-0.30, P<0.001) and HDL-C ≥1.0 (increase of 0.002 mmol/L, linear regression: reference category). A similar relationship between change in HDL-C and baseline HDL-C was observed within groups stratified by patient characteristics (apart from those on concurrent statin therapy and females). CONCLUSIONS: Our results may explain the discrepancies observed in some randomized controlled trials whereby subgroup analysis of patients with the metabolic syndrome appeared to show benefit whereas this was absent in the total cohort. Thus, future interventional studies using fibrates should perhaps focus on patients with low HDL-C levels.