correlation between measures of metabolic control and plasma IGF-1 levels [113]. There

have been others that have not found such a relationship, but they may have had

insufficient power to detect a relationship or there may have been confounding factors

[114]. Interventions which improve glycemic control have been shown to increase

circulating IGF-1 levels [115]. The study of laboratory animals with streptozotocin

(STZ) induced diabetes have supported the theory of reduced IGF-1 levels in diabetes

and an inverse relationship with metabolic control [116].

 The long term complications of diabetes include microangiopaty retinopathyy,

nephropathy, neuropathy, and periodontal disease) and macroangiopathy which results in

an increased incidence of cardiovascular disease [113]. Diabetes is associated with

vascular smooth muscle cell and endothelial cell disfunction [117]. Abnormalities

include impairment of vasodilatory responses, increased levels of endothelium-derived

von Willebrand's factor, and decreased levels of prostacyclin and plasminogen factor.

Vascular basement membrane thickening and increased vascular permeability are present

in diabetic patients and animals models [117]. Endothelial cells have IGF receptors and

secrete IGF binding proteins. They are exposed to circulating IGFs and to IGFs

synthesized by vascular smooth muscle cells [118]. IGFs have metabolic and trophic

effects on endothelial cells and vascular smooth muscle cells [117]. A potential role of

IGFs in the development of retinopathy and nephropathy as well as other tissues has been

investigated. The specific role of IGFs in the development of periodontal disease

associated with diabetes has not been investigated at this time.

 IGF-1 binding to IGF-1 receptors and IGF-1 stimulated tyrosine kinase activity are

unimpaired in red blood cells in type 2 diabetics [119]. IGF-1 receptor number and basal