Downregulation of serum IGF-1 for treatment of early worsening of diabetic retinopathy: a long-term follow-up of two cases.
ABSTRACT In 2003, we reported on 2 cases of nonproliferative and proliferative diabetic retinopathy, subsequent to HbA1c reduction by intensive insulin therapy (so-called early worsening of diabetic retinopathy). This acute condition could partly be reversed by discontinuation of intensive insulin therapy, whereby glycemia increased and serum IGF-1 concentration decreased [Ophthalmologica 2003;217:373-377]. On review 7 years later, both type-2 diabetic patients were on insulin therapy but had failed to achieve good glycemic control. One patient had mild background retinopathy on both eyes, with visual acuity of 1.0 and 0.7 after cataract extraction plus intravitreal triamcinolone injection. The 2nd patient was blind in one eye from secondary glaucoma due to vitrectomy and silicone oil filling; the fellow eye displayed residual retinal neovascularization with a hyaloid membrane and a visual acuity of 0.5. Hence, early worsening as opposed to late worsening of diabetic retinopathy seems to benefit from therapeutic suppression of growth factor action.
- American journal of ophthalmology 01/2009; 146(6):974; author reply 974-5. · 3.83 Impact Factor
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ABSTRACT: Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib-sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (chi(2) = 658.14, df = 20; P < 0.0001). The sib-sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection.Investigative ophthalmology & visual science 09/2008; 49(9):3839-45. · 3.43 Impact Factor
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ABSTRACT: It is well known that intensified insulin treatment of poorly controlled type 1 diabetic patients may worsen an existing diabetic retinopathy (DR). This observation has been explained by an insulin-induced stimulation of the GH/IGF-I axis. Here, we report on three cases, where the progression of DR during intensified metabolic control was treated with manipulation of insulin therapy and/or by administration of octreotide. Serum concentrations of IGF-I, IGFBP-3, insulin, cystatin C, creatinine, endogenous creatinine clearance and HbA1c-levels were assessed by routine laboratory methods; serum IGF-I bioactivity was estimated by a highly specific kinase receptor activation assay. Visual acuity and retinopathy stage was assessed by established clinical methods including fluorescein angiography. After glycaemic control was improved by intensified insulin therapy, serum IGF-I levels acutely increased. Subsequently, DR progressed to an advanced stage ("florid retinopathy"), with macular edema, and proliferation of new vessels (in two cases). Immediate reduction of insulin dosage and administration of octreotide lowered serum total IGF-I levels (and IGF-I bioactivity as measured in one patient). Subsequently, macular edema resolved partly, and visual acuity improved, allowing laser photocoagulation to be performed. In conclusion, in poorly controlled type 1 diabetic patients, intensified insulin therapy is able to cause florid DR with acute macular edema. These sight-threatening changes may improve by short-term reduction of insulin dosage or by administration of octreotide, and we speculate that this may be related to down-regulation of (serum) IGF-I.Growth Hormone & IGF Research 05/2005; 15(2):130-5. · 2.26 Impact Factor