Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers.

Wound healing, including re-epithelialization, is delayed in diabetes. Growth factors influence the healing process and amongst these, insulin-like growth factor (IGF) has been shown to stimulate keratinocyte proliferation in vitro. Monoclonal antibodies to insulin-like growth factors 1 and 2 (IGF1 and IGF2) were used to investigate their distribution in diabetic foot ulcers and surrounding tissues by immunohistochemistry, compared with diabetic and non-diabetic uninjured skin. IGF2 was found throughout the epidermis (stratum granulosum, spinosum, and basale) in all three groups. Staining for IGF2 was intense in both normal and diabetic skin as well as in diabetic foot ulcers, being greatest at the ulcer edge. IGF1, in comparison, was found throughout the epidermis of non-diabetic skin; expression was restricted to the stratum granulosum and spinosum of uninjured diabetic skin and was absent in the basal layer at the ulcer edge. A similar absence of IGF1 in dermal fibroblasts was found in tissue sections from diabetic patients. This lack of expression of IGF1 within the basal layer and fibroblasts may contribute to retarded wound healing in diabetes mellitus.

A substitution model of dietary manipulation is an effective means of optimising lipid profile, reducing C-reactive protein and increasing insulin-like growth factor-1.

There are two key methods in which fat intake may be manipulated; the 'substitution model' and the 'reduction model'. However insufficient information is known about the mechanisms of dietary fat reduction in individuals who have successfully reduced their fat intake, to be clear as to which strategy offers the greatest chance of success. Our objective was to ascertain the most effective dietary intervention for improving cardiovascular risk profile. Eighty female volunteers (high fat consumers) were recruited. Each subject was randomly allocated into one of the following groups. Substitution of high-fat foods was made with reduced-fat products, by the reduction of high-fat foods, by a combination of substitution and reduction strategies, or no advice was given. Each intervention lasted 3 months. Anthropometric measures and fasting blood samples were taken at baseline and follow-up. The substitution intervention resulted in weight loss (mean -1.4 (95 % CI -2.4, -0.2) kg) and reduced percentage body fat (mean -1.3 (95% CI -2.0, -0.5)%). There was no significant weight change with the other interventions. Fasting triacylglycerols (-0.2 (SEM 0.07) mm; P=0.04), cholesterol and C-reactive protein (CRP) levels (0.8 (SEM 0.2) mg/l; P=0.04) fell with the substitution intervention, but not with the other interventions. Insulin-like growth factor-1 increased with both substitution and reduction (P=0.02). There was no significant change in fasting insulin or glucose with any intervention. The substitution model of dietary intervention is effective even over a relatively short interval of time in reducing fasting total cholesterol, triacylglycerols and CRP. Although the group size for the present study was small and involved females only, it has significant implications for population intervention strategies.