Is Insulinlike Growth Factor I Associated With Diabetic Retinopathy?

Abstract

Insulinlike growth factor I (IGF-I) is the mediator of the growth-promoting effects of growth hormone and has been suspected of playing a role in the pathogenesis of proliferative diabetic retinopathy (PDR). However, previous attempts to correlate IGF-I levels with PDR have yielded conflicting results. We determined IGF-I levels in a large population-based study of 682 early-onset (diagnosed before 30 yr of age) adult (greater than or equal to 18 yr old) insulin-taking diabetic subjects. PDR was found in 25% of the population. IGF-I levels were measured by radioimmunoassay. The mean serum level of IGF-I was 277 +/- 108 micrograms/L (mean +/- SD). Spearman rank correlations showed statistically significant negative correlations between IGF-I levels and age (r = -0.51, P less than 0.0001), duration of disease (r = -0.36, P less than 0.0001), and glycosylated hemoglobin (r = -0.09, P less than 0.05). There was a significant trend (P less than 0.001) toward decreasing risk of PDR with increasing IGF-I. However, after controlling for duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, and the presence of proteinuria and/or creatinine greater than or equal to 265 microM in a multiple logistic regression model, IGF-I was not significantly associated with PDR. These data suggest that IGF-I may not be a risk factor for the development of PDR.

Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes

“…Jehle et al (12) also found a positive correlation between the dose of insulin and IGF-I, but did not calculate data separately according to sex. Although there could be a sex-speci®c difference in the physiological effect of insulin on the IGF-Igenerating capacity, others (14) did not ®nd any difference in total IGF-I concentrations between male and female patients with diabetes or male and female controls.…”

“…We found low IGF-I in plasma independently of the HbA 1c concentrations. In a large patient population, Dills et al (14) found a very weak negative correlation (r À0.09, P<0.05) between IGF-I and glycated haemoglobin in patients with diabetes of long duration. Tan & Baxter (13) also found a negative correlation between IGF-I and HbA 1c in diabetic patients younger than <50 years, but not in those older than 50 years, in a study in which the duration of the patients' diabetes was not given.…”

“…However, there are few studies on the relationship between glycaemic control and plasma concentrations of IGF-I in adult patients with type 1 diabetes. A negative relationship between glycaemic control and circulating IGF-I has been shown by some investigators (13,14,18) but not by others (19,20). In adult patients with type 1 diabetes with good glycaemic control and without endogenous production of insulin, the plasma concentrations of free insulin are normal or increased in the fasting state and between meals, whereas meal-related insulin peaks are low compared with those in non-diabetic control individuals (21).…”

Adherence to diabetic eye examination guidelines in Australia: the National Eye Health Survey

“…Tissue immunocytochemical studies have localised FGF in patients with diabetic neovascularisation 157;191 . Elevated serum IGF-1 levels have been measured in patients with PDR, both in early-onset 192 and late-onset diabetes 193 . VEGF, a multifunctional cytokine expressed and secreted by many cells, induces angiogenesis and strongly increases vascular permeability 194 .…”

Population PK and PK/PD modelling of microencapsulated octreotide acetate in healthy subjects

“…These pathological effects may occur by either direct GH stimulation or indirectly by the elevation of insulin-like growth factor-1 (IGF-1). For more than 30 years, the importance of GH in the development and progression of diabetic retinopathy has been recognized [7,8]. Recently, there has been a growing interest in IGF-1 and its binding proteins (IGFBP) in proliferative diseases and the potential of altering the course of the disease by reducing IGF-1 concentrations.…”