A triad of high triglycerides, low high-density lipoprotein (HDL) cholesterol, and elevated small dense low-density lipoprotein particles occurring in a patient with type 2 diabetes is referred to atherogenic diabetic dyslipidemia (ADD). Despite statin therapy, a significant residual risk remains potentially attributable to increased triglyceride concentration and low HDL cholesterol, a characteristic hallmark of ADD. Current therapeutic options in reducing this residual risk include nicotinic acid, omega 3 fatty acids, and selective peroxisome proliferator-activated receptor-alpha (PPAR) agonists (fibrates). These drugs are limited in their potential either by lack of evidence to support their role in reducing cardiovascular events or due to their side effects. This review details their current status and also the role of new glitazar, saroglitazar adual PPARα/γ agonist with predominant PPARα activity in the management of ADD.

Severe hypertriglyceridaemia (HTG) is recognised as the third most common cause of acute pancreatitis. While secondary causes of HTG such as excess alcohol, obesity and diabetes are well recognised, identification and treatment of primary genetic disorders such as lipoprotein lipase (LPL) deficiency remain a challenge. HTG secondary to such genetic disorders does not respond to established medical therapy, resulting in recurrent episodes of acute pancreatitis. A very low fat diet remains first-line therapy in the treatment of severe HTG secondary to LPL deficiency, and in resistant cases insulin, heparin and plasma apheresis are used with some success. Viral vector-delivered gene therapy is a novel treatment option that is currently being tested in patients with LPL deficiency with promising results.

The metabolic syndrome is intricately linked to type 2 diabetes and in fact may be a prodrome of that condition. Both exhibit characteristic perturbations of the lipid profile namely raised triglycerides (>1.7 mmol/l) and reduced HDL cholesterol (<1 mmol/l in men and <1.3 mmol/l in women) [1]. Other conditions characterized by a degree of insulin resistance, for example, the polycystic ovarian syndrome (PCOS) also exhibit similar changes in the full lipid profile [2].Dysregulation of lipoprotein metabolism in these circumstances is caused by a combination of overproduction of VLDL-apo B 100, decreased catabolism of apo B-containing particles, and increased catabolism of apo A-I containing HDL particles [3]. Reduction in the number of apo B-containing particles using LDL cholesterol as a surrogate marker is a widely established strategy for reducing cardiovascular risk with an extensive evidence base. However, despite significant proven benefits from statin therapy, considerable residual risk remains, which is potentially attributable to increased triglyceride-rich lipoproteins and reduced levels of HDL cholesterol.A meta-analysis of 17 prospective studies showed that after adjusting for variables such as HDL cholesterol, total cholesterol, and other risk factors, the relative risk for coronary heart disease with a 1 mmol/l increase in triglyceride was 1.14 [95% confidence interval (CI) 1.05-1.28] for men and 1.37 (95% CI 1.13-1.66) for women [4]. Findings from the PROCAM study similarly support the idea that elevated triglycerides are an independent cardiovascular risk factor [5]. Thus, the potential benefits of adjunctive therapy (e.g., with fibric acid derivatives) to monotherapy with statins, particularly in those patients with triglyceriderich dyslipidemia as seen in patients with diabetes and/or the metabolic syndrome should be demonstrable following well designed randomized controlled trials.Fibrates are peroxisome proliferators activated receptor a (PPAR-a) agonists that work by transcriptionally regulating genes involved in lipid metabolism resulting in lower plasma triglycerides and elevated levels of HDL. The clinical utility of therapy with fibric acid derivatives (either as monotherapy or as adjunctive therapy with statin therapy) has been the subject of controversy for several decades. Unlike statins, which are effective throughout the range of LDL cholesterol, it appears that fibric acid derivatives may only lower cardiovascular disease events in diabetic patients with 'atherogenic dyslipidemia', characterized by elevated triglycerides and reduced levels of HDL cholesterol. Two trials involving the use of fenofibrate either as monotherapy or in combination with statin therapy have reported this in the last few years. The FIELD trial [6] was disappointingly negative with respect to cardiovascular outcomes, the potential explanation being 'drop-in' statin therapy as a confounding issue. More recently, in the ACCORD-lipid arm [7], overall, after a mean of 4.5 years, the combination of fenofibrate and s...

SummaryThe authors present a case of an 84-year-old patient who presented to the emergency department with sudden onset abdominal pain radiating to the neck. The patient's medication included warfarin, and alendronate, which was started by the general practitioner 2 days prior to presentation. Initial systemic examination and investigations, including chest x-ray, were unremarkable. Within 24 h of presentation the patient developed bilateral pneumonia with effusions. Due to continued clinical deterioration over the next 48 h, a CT thorax was performed that showed evidence of large oesophageal perforation with mediastinitis and gas in the mediastinum. The patient was treated with an expandable metal stent, bilateral chest drains, broad spectrum antibiotics, antifungals and total parenteral nutrition. Over a period of 8 weeks the patient made an excellent recovery. This rare case illustrates the importance of vigilance for the life-threatening complication of oesophageal perforation with alendronate treatment. BACKGROUND