Dyslipidemia is one of the key risk factors for cardiovascular disease (CVD) in diabetes mellitus. Despite the mounting clinical trial data, the management of dyslipidemia other than lowering the low density lipoprotein cholesterol (LDL-c) continues to be controversial. The characteristic features of diabetic dyslipidemia are high plasma triglyceride concentration, reduced high density lipoprotein cholesterol (HDL-c) concentration, and increased concentration of small dense LDL particles. These changes are caused by increased free fatty acid flux secondary to insulin resistance and aggravated by increased inflammatory adipokines. The availability of several lipid-lowering drugs and nutritional supplements offers novel and effective options for achieving target lipid levels in people with diabetes. While initiation of drug therapy based on differences in the lipid profile is an option, most practice guidelines recommend statins as first-line therapy. Although the evidence for clinical utility of combination of statins with fibrates or nicotinic acid in reducing cardiovascular events remains inconclusive, the preponderance of evidence suggests that a subgroup who have high triglycerides and low HDL-c levels may benefit from combination therapy of statins and fibrates. The goal of therapy is to achieve at least 30-40 % reduction in LDL-c levels. Preferably the LDL-c should be less than 100 mg/dL in low-risk people and less than 70 mg/dL in those at high risk, including people with established CVD.
Several new pharmacological agents have recently been developed to optimise the management of type 2 (non-insulin-dependent) diabetes mellitus. The aim of this article is to briefly review the various therapeutic agents available for management of patients with type 2 diabetes mellitus and to suggest a potential approach to drug selection. There are three general therapeutic modalities relevant to diabetes care. The first modality is lifestyle adjustments aimed at improving endogenous insulin sensitivity or insulin effect. This can be achieved by increased physical activity and bodyweight reduction with diet and behavioural modification, and the use of pharmacological agents or surgery. This first modality is not discussed in depth in this article. The second modality involves increasing insulin availability by the administration of exogenous insulin, insulin analogues, sulphonylureas and the new insulin secretagogue, repaglinide. The most frequently encountered adverse effect of these agents is hypoglycaemia. Bodyweight gain can also be a concern, especially in patients who are obese. The association between hyperinsulinaemia and premature atherosclerosis is still a debatable question. The third modality consists of agents such as biguanides and thiazolidinediones which enhance insulin sensitivity, or agents that decrease insulin requirements like the alpha-glucosidase inhibitors. Type 2 diabetes mellitus is a heterogeneous disease with multiple underlying pathophysiological processes. Therapy should be individualised based on the degree of hyperglycaemia, hyperinsulinaemia or insulin deficiency. In addition, several factors have to be considered when prescribing a specific therapeutic agent. These factors include efficacy, safety, affordability and ease of administration.
There is ample empiric evidence to indicate that oxidative stress contributes to the pathogenesis of coronary artery disease and has a key role in the onset and progression of diabetes and its complications. Diabetes leads to depletion of the cellular antioxidant defense system and is associated with an increase in the production of free radicals. Oxidative stress can be the result of multiple pathways. Some of these are related to substrate-driven overproduction of mitochondrial reactive oxygen species, advanced glycation end product formation, glucose autoxidation, and depletion of micronutrients and cellular elements with antioxidative properties. There are numerous observational studies in the literature showing a beneficial outcome of the consumption of antioxidant vitamins. However, the interventional trials portray a different picture. The divide between the robust experimental evidence of the pathogenetic role of increased oxidative load in diabetes and the overwhelming failure of antioxidants to show any health benefits in clinical trials may well be characterized as the "antioxidant paradox."
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