title: Does mitochondrial genome mutation in subjects with maternally inherited diabetes and deafness decrease severity of diabetic retinopathy?
abstract: Two types of retinopathy, diabetic and pigmentary, may be seen in subjects with maternal inheritance diabetes and deafness. The potential for interactions between the two retinopathies has not been explored. The mitochondrial mutation may affect development of diabetic retinopathy in subjects with MIDD by altering normal pathways of glucose metabolism. We identified five unrelated MIDD kindreds with 61 living maternal line family members. Twenty-three of the family members, 12 with diabetes mellitus and 11 without volunteered to be studied. Subjects were graded for severity of diabetic retinopathy and presence or absence of pigmentary retinopathy after slit lamp biomicroscopy, retinal photography of seven standard fields and fluorescein angiography. Blood was taken, in the fasted state, from MIDD subjects (duration of diabetes 17.0+/-6.9 yr) and non-diabetic subjects with the mutation, for assay of sorbitol and glucose and values compared with diabetic and non-diabetic control subjects without the mutation. Diabetic retinopathy was absent in 9/12 subjects (75%), with 3 having mild non-proliferative retinopathy. No one had cataract. Red blood cell sorbitol levels, adjusted for ambient blood glucose, were significantly lower in MIDD subjects compared with diabetic subjects (1.16+/-0.5 cf. 2.03+/-1.1, x 10(-3) g mmol(-1), p=0.04). Pigmentary retinopathy was present in 15 of 23 subjects, of whom 13 had some abnormality of glucose tolerance. Abnormal glucose tolerance was strongly associated with the development of pigmentary retinopathy (odds ratio 19.5, p=0.008). In conclusion, there appears to be a decreased prevalence of diabetic retinopathy and cataract in MIDD, which we propose is due to reduced glucose metabolism by the polyol pathway. Abnormal glucose tolerance increases the clinical expression of pigmentary retinopathy in subjects with a mitochondrial genome mutation. A greater understanding of the metabolic effects of mitochondrial DNA mutations has the potential to give insight into the mechanisms of diabetic retinopathy and other complications of diabetes mellitus.
authors.affiliation: Department of Diabetes and Endocrinology, Westmead Hospital, NSW, Australia. janeh@westmed.wh.usyd.edu.au
authors.forename: D J
authors.initials: DJ
authors.lastname: Holmes-Walker
authors.forename: P
authors.initials: P
authors.lastname: Mitchell
authors.forename: S C
authors.initials: SC
authors.lastname: Boyages
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism; D018392:Genomic Imprinting; D006019:Glycolysis; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D017354:Point Mutation; D012356:RNA, Transfer, Leu / Q000235:genetics*; D012016:Reference Values; D013012:Sorbitol / Q000097:blood
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; D013012:Sorbitol