And Type Diabetes

As outlined throughout this chapter, prolonged exposure to elevated FFAs contributes to insulin resistance and to the many metabolic manifestations of the insulin resistant state and type 2 diabetes. It follows, therefore, that a sustained reduction in FFA flux from adipose tissue would theoretically be predicted to result in improvement in the metabolic abnormalities. Therapies that directly or indirectly improve insulin sensitivity, such as weight reduction, exercise, oral hypoglycemic agents, and insulin, are indeed associated with a reduction in FFAs and improvement in many of the metabolic disturbances of insulin resistance and type 2 diabetes, but the exact mechanism of improvement may or may not be a consequence of the reduction in FFAs per se. More specific therapies that primarily target abnormalities of FFA metabolism would need to be tested to address the hypothesis that reduction of plasma FFAs improves insulin sensitivity and its associated metabolic abnormalities.

The antilipolytic agent nicotinic acid and its longer acting analogues have been used to investigate the metabolic and clinical effects of reducing FFAs (248,249). Acute administration of the long-acting nicotinic acid analog, acipimox, has been shown by numerous investigators to reduce plasma FFAs, fatty acid oxidation, and gluco-neogenesis, and to increase glucose oxidation rates, with some but not all studies showing suppression of endogenous glucose production, increased insulin-mediated suppression of glucose production, insulin-mediated glucose uptake, and decreased intramuscular LCFA-CoA content (250-256). In addition, the lipoprotein profile is modified to a less atherogenic one (reduced VLDL particle production, increased LDL particle size, lowered plasma TGs and elevated HDL-cholesterol) in hyperlipidemic patients. Insulin secretion was potentiated within one week of acipimox treatment (257). Nicotinic acid and analogs act through a newly discovered G-protein coupled "nicotinic acid" receptor, which is expressed in adipose tissue and also in macrophages. Their HDL-cholesterol raising properties may be owing to additional effects on the ABCA1-mediated cholesterol efflux from peripheral tissues and its transport back to the liver. There is, however, an escape from the beneficial effects of acipimox and a rebound elevation of FFAs, which occurs with prolonged acipimox treatment and limits its potential therapeutic benefit (164,250) .

The insulin sensitizing PPAR7 activators thiazolidinediones (TZDs) have been successfully used in the management of type 2 diabetes (258). They ameliorate muscle and liver insulin sensitivity, and have been suggested to improve ^-cell function. Despite an overall increase in adiposity, they induce a beneficial fat redistribution from visceral to subcutaneous fat depots, and the differentiation of new insulin-sensitive adipocytes (259). Preliminary studies have also demonstrated a reduction in liver fat, with consequent improvements in hepatic inflammation and fibrosis (260). The effects of TZDs on plasma fasting FFAs are variable in humans (more consistently decreased in animals), being decreased by 20-25% in some studies (261-263), but barely lowered despite insulin sensitization in another (264). In the latter, postprandial FFAs were decreased by TZD treatment. TZDs also increase plasma adiponectin levels, suppress the release of pro-inflammatory cytokines, and exert other pleiotropic effects directly at the level of the vascular wall (265). PPARa is expressed at higher levels in tissues exhibiting high rates of fatty acid ^-oxidation, i.e., muscle and liver. PPARa activation decreases plasma TGs and FFAs, partly via enhanced fatty acid uptake and oxidation by the liver. Therefore, PPARa/7 co-agonists may have substantial advantages and offer an attractive therapeutic option. In animal models of genetically or diet-induced insulin resistance, PPARa/7 dual agonists improve glucose and lipid tolerance (266) and enhance insulin action (267,268). They have also been shown to increase glucose stimulated insulin secretion in diabetic db/db mice (269).

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment