Familial hyperproinsulinemia associated with NIDDM. A case study

• Published in: Diabetes care Vol. 16; no. 10; pp. 1340 - 1346
• Main Authors: OOHASHI, H, OHGAWARA, H, NANJO, K, TASAKA, Y, QIU-PING CAO, SHU JIN CHAN, RUBENSTEIN, A. H, STEINER, D. F, OMORI, Y
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.1993
• Subjects: Adolescent; Adult; Aged; Associated diseases and complications; Biological and medical sciences; Blood Glucose - analysis; C-Peptide - blood; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA Primers; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Exons; Female; Glucose Intolerance - genetics; Glucose Tolerance Test; Humans; Hyperinsulinism - blood; Hyperinsulinism - genetics; Insulin - genetics; Male; Medical sciences; Molecular Sequence Data; Polymerase Chain Reaction; Proinsulin - blood; Proinsulin - genetics; Endocrinopathy; Human; Proinsulin; Family study; Non insulin dependent diabetes
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.16.10.1340

Familial hyperproinsulinemia associated with NIDDM. A case study. H Oohashi , H Ohgawara , K Nanjo , Y Tasaka , Q P Cao , S J Chan , A H Rubenstein , D F Steiner and Y Omori Diabetes Center, Tokyo Women's Medical College, Japan. Abstract OBJECTIVE--To report studies on an elderly patient with moderate NIDDM associated with marked fasting hyperinsulinemia. RESEARCH DESIGN AND METHODS--The propositus and several family members were studied by a combination of clinical, biochemical, and molecular genetic approaches to define the underlying genetic defect. RESULTS--Fasting levels of contrainsulin hormones were normal, and resistance to exogenous insulin was absent. Gel filtration and reverse-phase high-performance liquid chromatography revealed elevated amounts of a structurally abnormal proinsulin intermediate (AC proinsulin). A study of the family of the propositus showed the same abnormality in 4 of 5 members in 3 successive generations. Genetic analysis revealed a point mutation affecting residue 65 of human proinsulin (Arg-->His) in one allele of the insulin gene in the propositus, a defect similar to that described previously in 3 other apparently unrelated lineages. CONCLUSIONS--This family exhibits a clear-cut relationship between increasing age and metabolic decompensation in all the hyperproinsulinemic members, suggesting that (inherited) metabolic stress and age both contribute to development of diabetes mellitus.