American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity.

Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed NAFLD treatment is also reviewed with a focus on lipid-lowering drugs Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered

Non-alcoholic fatty liver disease and dyslipidemia: An update

Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer

Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal–obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism.

Testosterone and obesity.

Introduction: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events.Areas covered: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed.Expert opinion: The present systematic review and meta-analysis does not support a causal role between TS and adver...

Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis

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

Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with Type 2 Diabetes but Not in Men with Coexisting Depression: The BLAST Study

BACKGROUND

The association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established. Current Endocrine Society and European Association of Urology guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes and in men suffering from erectile dysfunction. It is recognised that a range of physical symptoms appear as the testosterone level falls but few studies have addressed the threshold at which symptoms improve with physiological replacement. We report the first double-blind placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess the metabolic changes with testosterone replacement.

METHODS

The type 2 diabetes registers of seven general practices were screened to establish the prevalence of low testosterone and the associations with diabetes control. Of 550 eligible patients approached, 488 men (mean age 62.6) consented to take part in screening with a morning testosterone level, assessed between 8 and 11 am. This identified 211 patients for a double-blind placebo-controlled study of long acting testosterone undecanoate (TU) 1000 mg lasting 30 weeks followed by 52 weeks of open label use. The population was divided into a SEVERE group with either total testosterone (TT) of 8 nmol/l or less or free testosterone (FT) 180 pmol/l or less or a MILD group with TT 8.1-12 nmol/l or FT 181-250 pmol/l.

RESULTS

Men in the SEVERE group increased mean through TT from 7.73 nmol/l at baseline to 9.93 at 30 weeks and the MILD group from 10.47 to 11.94. The SEVERE group showed marked improvement in sexual function, but no significant improvement in metabolic parameters. The MILD group showed no improvement in sexual function, but significant improvement in weight, body mass index, waist circumference and Hospital Anxiety and Depression Scale. Improvement was seen in all parameters during 52 weeks open label treatment where trough TT levels approached 15 nmol/l. Baseline prostate-specific antigen (PSA) was lower in the SEVERE group and increased with TU for 30 weeks and then stabilised. There was no increase in PSA with treatment in the MILD group.

CONCLUSIONS

Testosterone undecanoate significantly improves sexual parameters and Ageing Male Symptom Score, but not metabolic factors at 30 weeks in men with SEVERE testosterone deficiency syndrome (TDS). In men with MILD TDS, significant improvements in metabolic but not sexual parameters were seen, suggesting that there are threshold levels for response to testosterone replacement therapy and that trials of therapy need to achieve sustained therapeutic levels to be effective. PSA showed minor rises, but only for 30 weeks in the SEVERE group.

The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study).

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. We wished to study changes seen in LFTs (GGT, ALT and ALP) following fibrate therapy and then determine associated factors. 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). Of the study population 106 patients were on fenofibrate; the remaining on bezafibrate. Significant lowering of GGT (p  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). 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.

/pdf/effect-of-fibrate-treatment-on-liver-function-tests-in-43akbwhdck.pdf

Mithun Bhartia

Papers

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

Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with Type 2 Diabetes but Not in Men with Coexisting Depression: The BLAST Study

The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study).

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

Drugs and the Peroxisome Proliferator Activated Receptors