Body Weight Control by a High-Carbohydrate/Low-Fat Diet Slows the Progression of Diabetic Kidney Damage in an Obese, Hypertensive, Type 2 Diabetic Rat Model

Obesity is one of several factors implicated in the genesis of diabetic nephropathy (DN). Obese, hypertensive, type 2 diabetic rats SHR/NDmcr-cp were given, for 12 weeks, either a normal, middle-carbohydrate/middle-fat diet (MC/MF group) or a high-carbohydrate/low-fat diet (HC/LF group). Daily caloric intake was the same in both groups. Nevertheless, the HC/LF group gained less weight. Despite equivalent degrees of hypertension, hyperglycemia, hyperlipidemia, hyperinsulinemia, and even a poorer glycemic control, the HC/LF group had less severe renal histological abnormalities and a reduced intrarenal advanced glycation and oxidative stress. Mediators of the renoprotection, specifically linked to obesity and body weight control, include a reduced renal inflammation and TGF-beta expression, together with an enhanced level of adiponectin. Altogether, these data identify a specific role of body weight control by a high-carbohydrate/low-fat diet in the progression of DN. Body weight control thus impacts on local intrarenal advanced glycation and oxidative stress through inflammation and adiponectin levels

Advanced glycation in uraemic toxicity.

The Maillard reaction involves the non enzymatic combination of carbohydrates such as glucose with protein aminogroups to yield schiff bases and Amadori protein adducts evolving into irreversible advanced glycation end products (AGEs). This phenomenon, part of normal ageing, is accelerated in diabetes, as a result of hyperglycaemia, and in renal failure, as a consequence of the accumulation of reactive carbonyl compounds (RCOs). AGEs and RCOs are implicated in uraemic toxicity both at the biochemical and the clinical level (dialysis amyloidosis, atherosclerosis, alterations of peritoneal membrane permeability). Reduction of plasma AGEs and RCOs is an interesting avenue to reduce uraemic toxicity. Therapeutic strategies involve dialysis technique (haemodialysis membranes, daily haemodialysis, ultrapure dialysate, RCO free peritoneal dialysate) as well as drugs inhibiting AGE formation (aminoguanidine and the less toxic angiotensin converting enzyme inhibitors or angiotensin receptor blockers)

Epoetin treatment of the diabetic patient with renal anaemia

Nephrologists are confronted with a rising tide of diabetes, particularly type 2 diabetes with nephropathy, requiring renal replacement therapy. Preventive measures are effective provided that they are implemented early in the course of the disease. Such measures include tight glycaemic control and adequate management of hypertension, relying mainly on angiotensin-converting enzyme inhibitors. Once diabetic nephropathy is overt, these measures can slow the progression towards end-stage renal failure. They are best complemented by control of lipid disorders, a moderate reduction in protein intake and cessation of smoking. Renal anaemia develops earlier and is more severe in diabetic than in non-diabetic patients. Epoetin treatment should thus be initiated early as this slows the progression of renal failure, prevents anaemia-dependent cardiac hypertrophy and improves exercise capacity and quality of life. Furthermore, early intervention may improve the insulin resistance associated with uraemic type 2 diabetes, thereby lessening the effect of associated lipid metabolism disorders. In addition to early correction with epoetin treatment, attention should be paid to the correction of other causes of anaemia often present in elderly malnourished patients, namely iron, folate and vitamin B12 deficiency. Complications associated with epoetin treatment (i.e. hypertension, clotting of vascular access and, possibly, peripheral vascular disorders) require a cautious, progressive approach to anaemia correction that will necessitate close collaboration between general practitioners, diabetologists and an experienced renal team. The benefits of early referral have been demonstrated and are also cost-effective when the prevention of renal disease, the delay in the institution of renal replacement therapy and the improved cardiovascular status are taken into consideration