Summary
Glucose tolerance and insulin secretion were studied in two groups of non-diabetic identical twins of recently-diagnosed Type 1 (insulin-dependent) diabetic patients: (1) a group of 5 twins with islet cell antibodies, and (2) a group of 6 twins without. Despite similar fasting glucose, insulin and C-peptide concentrations both groups of twins had significantly higher fasting proinsulin concentrations than the control group (p<0.05). The twins with complement-fixing islet cell antibodies had reduced glucose tolerance and clearance, whilst the twins without islet cell antibodies did not. Neither group of twins showed any abnormality in insulin, C-peptide or proinsulin response to oral or intravenous glucose. We conclude that increased fasting proinsulin levels precede abnormalities of insulin secretion, and are an early indication of minor B-cell damage in these twins irrespective of their risk of developing diabetes.
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Alviggi L, Johnston C, Hoskins PJ, Tee DEH, Pyke DA, Leslie RDG, Vergani D (1984) Pathogenesis of insulin-dependent diabetes: a role for activated T-lymphocytes. Lancet II: 4–6
Millward BA, Alviggi L, Hoskins PJ, Johnston C, Heaton DA, Bottazzo GF, Vergani D, Leslie RDG, Pyke DA (1986) Immune changes associated with insulin-dependent diabetes can remit without causing the disease: a study in identical twins. Br Med J 292: 793–796
Srikanta S, Garda OP, Gleason RE, Jackson RA, Soeldner JS, Eisenbarth GS (1984) Pre-type 1 diabetes. Linear loss of beta cell response to intravenous glucose. Diabetes 33: 717–720
Heaton DA, Millward BA, Gray P, Tun Y, Hales CN, Pyke DA, Leslie RDG (1987) Evidence of B cell dysfunction which does not lead on to diabetes: a study of identical twins of insulin dependent diabetics. Br Med J 294: 145–146
Barnett AH, Eff C, Leslie RDG, Pyke DA (1981) Diabetes in identical twins: a study of 200 pairs. Diabetologia 20: 87–95
Wilkin TJ, Nicholson S, Casey CR (1985) A micro-enzyme linked immuno-absorbant assay for insulin autoantibodies in serum. J Immunol Methods 76: 185–194
Morgan DR, Lazarow A (1963) Immunoassay of insulin: two antibody system. Diabetes 20: 1–9
Gray IP, Siddle K, Frank BH, Hales CN (1987) Characterization and use in immunoradiometric assays of monoclonal antibodies directed against human proinsulin. Diabetes 36: 684–688
Rosenbloom AL, Hunt SS, Rosenbloom EK, Maclaren NK (1982) Ten year prognosis of impaired glucose tolerance in siblings of patients with insulin-dependent diabetes. Diabetes 31: 385–387
Tarn AC, Smith CP, Spencer KM, Bottazzo GF, Gale EAM (1987) Type1 (insulin-dependent) diabetes: a disease of slow clinical onset? Br Med J 294: 342–344
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Heaton, D.A., Millward, B.A., Gray, I.P. et al. Increased proinsulin levels as an early indicator of B-cell dysfunction in non-diabetic twins of Type 1 (insulin-dependent) diabetic patients. Diabetologia 31, 182–184 (1988). https://doi.org/10.1007/BF00276853
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DOI: https://doi.org/10.1007/BF00276853