1.
Enteral nutritional support and use of diabetes-specific formulas for patients with diabetes: a systematic review and meta-analysis.
Elia, M, Ceriello, A, Laube, H, Sinclair, AJ, Engfer, M, Stratton, RJ
Diabetes care. 2005;(9):2267-79
Abstract
OBJECTIVE The aim of this systematic review was to determine the benefits of nutritional support in patients with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS Studies utilizing an enteral nutritional support intervention (oral supplements or tube feeding) were identified using electronic databases and bibliography searches. Comparisons of interest were nutritional support versus routine care and standard versus diabetes-specific formulas (containing high proportions of monounsaturated fatty acids, fructose, and fiber). Outcomes of interest were measures of glycemia and lipid status, medication requirements, nutritional status, quality of life, complications, and mortality. Meta-analyses were performed where possible. RESULTS A total of 23 studies (comprising 784 patients) of oral supplements (16 studies) and tube feeding (7 studies) were included in the review, and the majority compared diabetes-specific with standard formulas. Compared with standard formulas, diabetes-specific formulas significantly reduced postprandial rise in blood glucose (by 1.03 mmol/l [95% CI 0.58-1.47]; six randomized controlled trials [RCTs]), peak blood glucose concentration (by 1.59 mmol/l [86-2.32]; two RCTs), and glucose area under curve (by 7.96 mmol.l(-1).min(-1) [2.25-13.66]; four RCTs, i.e., by 35%) with no significant effect on HDL, total cholesterol, or triglyceride concentrations. In addition, individual studies reported a reduced requirement for insulin (26-71% lower) and fewer complications with diabetes-specific compared with standard nutritional formulas. CONCLUSIONS This systematic review shows that short- and long-term use of diabetes-specific formulas as oral supplements and tube feeds are associated with improved glycemic control compared with standard formulas. If such nutritional support is given long term, this may have implications for reducing chronic complications of diabetes, such as cardiovascular events.
2.
New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy.
Ceriello, A
Diabetes care. 2003;(5):1589-96
Abstract
Evidence implicates hyperglycemia-derived oxygen free radicals as mediators of diabetic complications. However, intervention studies with classic antioxidants, such as vitamin E, failed to demonstrate any beneficial effect. Recent studies demonstrate that a single hyperglycemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain seems to be the first and key event in the activation of all other pathways involved in the pathogenesis of diabetic complications. These include increased polyol pathway flux, increased advanced glycosylation end product formation, activation of protein kinase C, and increased hexosamine pathway flux. Superoxide overproduction is accompanied by increased nitric oxide generation, due to an endothelial NOS and inducible NOS uncoupled state, a phenomenon favoring the formation of the strong oxidant peroxynitrite, which in turn damages DNA. DNA damage is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose) polymerase. Poly(ADP-ribose) polymerase activation in turn depletes the intracellular concentration of its substrate NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, and produces an ADP-ribosylation of the GAPDH. These processes result in acute endothelial dysfunction in diabetic blood vessels that, convincingly, also contributes to the development of diabetic complications. These new findings may explain why classic antioxidants, such as vitamin E, which work by scavenging already-formed toxic oxidation products, have failed to show beneficial effects on diabetic complications and may suggest new and attractive "causal" antioxidant therapy. New low-molecular mass compounds that act as SOD or catalase mimetics or L-propionyl-carnitine and lipoic acid, which work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such a strategy, and preliminary studies support this hypothesis. This "causal" therapy would also be associated with other promising tools such as LY 333531, PJ34, and FP15, which block the protein kinase beta isoform, poly(ADP-ribose) polymerase, and peroxynitrite, respectively. While waiting for these focused tools, we may have other options: thiazolinediones, statins, ACE inhibitors, and angiotensin 1 inhibitors can reduce intracellular oxidative stress generation, and it has been suggested that many of their beneficial effects, even in diabetic patients, are due to this property.