Does Insulin Like Growth Factor-1 (Igf-1) Deficiency Have a “Protective” Role in the Development of Diabetic Retinopathy in Thalassemia Major Patients?

Abstract

RationaleBoth insulin and IGF-1 have been implicated in the control of retinal endothelial cell growth, neovascularization and diabetic retinopathy. Recent findings have established an essential role for IGF-1 in angiogenesis and demonstrated a new target for control of retinopathy that explains why diabetic retinopathy initially increases with the onset of insulin treatmentObjectiveThis cross-sectional study was designed to give insights into relationship between Insulin-Growth-Factor 1 (IGF-1) levels and diabetic retinopathy (DR) in a sample of thalassemia major (TM) patients with insulin dependent diabetes mellitus (IDDM). This relation was not previously evaluated, despite the fact that both diseases co-exist in the same patient. The study also describes the clinical and biochemical profile of the associated complications in TM patients with and without IDDM.DesignA population-based cross-sectional study.ParticipantsThe study includes 19 consecutive TM patients with IDDM and 31 age- and sex-matched TM patients without IDDM who visited our out-patient clinics for an endocrine assessmentMethodsAn extensive medical history, with data on associated complications and current medications, was obtained. Blood samples were drawn in the morning after an overnight fast to measure the serum concentrations of IGF-1, glucose, fructosamine, free thyroxine (FT4), thyrotropin (TSH) and biochemical analysis. Serologic screening assays for hepatitis C virus seropositivity (HCVab and HCV-RNA) were also evaluated; applying routine laboratory methods. Plasma total IGF-1 was measured by a chemiluminescent immunometric assay (CLIA) method. Ophthalmology evaluation was done by the same researcher using stereoscopic fundus biomicroscopy through dilated pupils. DR was graded using the scale developed by the Global Diabetic Retinopathy Group. Iron stores were assessed by direct and indirect methods.ResultsEighteen TM patients with IDDM (94.7 %) and ten non-diabetic patients (32.2 %) had IGF-1 levels below the 2.5th percentile of the normal values for the Italian population. The mean serum IGF-1 concentrations were significantly lower in the diabetic versus the non-diabetic TM groups (p < 0.001). DR was present in 4 (21 %) of 19 TM patients with IDDM and was associated with the main classical risk factors, namely inefficient glycemic control and duration of the disease but not hypertension. Using the scale developed by the Global Diabetic Retinopathy Group, the DR in our patients was classified as non proliferative diabetic retinopathy (NPDR). Only a few numbers of microaneurysms [1–3] were detected. Our data also confirm the strong association of IDDM in TM patients with other endocrine and non-endocrine complications.

Genetic risk variants for metabolic traits in Arab populations

“…Recent study on IGF1 deficient mice showed elevated levels of triglyceride28; and another study on IGF1 treatment in healthy individuals showed reduced levels of fasting and postprandial triglyceride29. IGF1 deficiency has been reported to be involved in the development of diabetic retinopathy in Thalassemia major patients from Italy30 and in the development of metabolic syndrome in a British cohort31.…”

Diabetes and Glucose Metabolism in Thalassemia Major: An Update

“…Although the incidence of retinopathy and nephropathy in thalassemic patients with diabetes is lower than in patients affected by type 1 DM [55] (Table 3), evaluation of kidney function, proteinuria and fundus imaging should be performed in these patients for early diagnosis of complications. ACE inhibitors should be used for primary renal protection in diabetics.…”

Pro‐apoptotic effects of micro‐ribonucleic acid‐365 on retinal neurons by targeting insulin‐like growth factor‐1 in diabetic rats: An in vivo and in vitro study

“…miR‐365 is a potential therapeutic target for diabetes mellitus, because of its ability to act like an endocrine signaling molecule and potential disease biomarker. The neurotrophic insulin‐like growth factor‐1 (IGF‐1), which regulates glucose and participates in retinal endotheliocyte proliferation and neovascularization, is heavily involved in DR pathogenesis through many different pathways. IGF‐1 is an attributing factor in controlling neuronal excitability, as well as the metabolism and survival of neurons.…”