Summary
It is still a matter of debate whether patients who develop islet-cell antibody positive autoimmune diabetes during adulthood represent slowly evolving Type 1 (insulindependent) diabetes mellitus or a separate subgroup of Type 2 (non-insulin-dependent) diabetes. To address this question, we measured C-peptide response to a test meal, and energy metabolism in the basal state and during a euglycaemic, hyperinsulinaemic clamp in (1) 29 patients with Type 2 diabetes; (2) 10 patients with autoimmune diabetes developing after the age of 40 years; (3) 11 patients with Type 1 diabetes and (4) 15 non-diabetic control subjects. While C-peptide response to a test meal was lacking in Type 1 diabetes and nearly normal in Type 2 diabetes, the C-peptide response in autoimmune diabetes was markedly reduced. Patients with Type 2 diabetes, autoimmune diabetes and Type 1 diabetes showed a 47%, 45% and 42%, respectively, reduction in the rate of non-oxidative glucose metabolism compared with control subjects (p<0.05-0.01). Similarly, patients with Type 2 diabetes (+52%), autoimmune diabetes (+27%) and Type 1 diabetes (+33%) presented with an enhanced basal rate of hepatic glucose production, which was less suppressed by insulin compared with healthy control subjects (p<0.01). However, patients with autoimmune diabetes derived more energy from oxidation of glucose and proteins and less energy from oxidation of lipids than patients with either Type 1 or Type 2 diabetes (p<0.05-0.01). In conclusion, patients who develop autoimmune diabetes during adulthood share the defects in hepatic glucose production and in non-oxidative glucose metabolism with both Type 1 and Type 2 diabetes. Oxidative energy metabolism in autoimmune diabetes, however, differs from that observed in Type 1 and Type 2 diabetes. Given the metabolic characteristics of these patients, it seems justified to consider autoimmune diabetes in adults as a subgroup of diabetes developing in adult age.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Irvine WJ, Gray RS, McCallum CJ, Duncan LJP (1977) Clinical and pathogenetic significance of pancreatic islet antibodies in diabetes treated with oral hypoglycemic agents. Lancet I: 1025–1027
Groop LC, Bottazzo GF, Doniach D (1986) Islet cell antibodies identify latent type 1 diabetes in patients aged 35–75 years at diagnosis. Diabetes 35: 237–241
Groop LC, Miettinen A, Groop P-H, Meri S, Koskimies S, Bottazzo GF (1988) Organ-specific autoimmunity and HLA-DR antigens as markers for β-cell destruction in patients with type II diabetes. Diabetes 37: 99–103
DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237: E214-E223
Ferrannini E (1988) The theoretical basis for indirect calorimetry: a review. Metabolism 37: 287–301
Eriksson J, Franssila-Kallunki A, Ekstrand A, Saloranta C, Widén E, Schalin C, Groop L (1989) Early metabolic defects in individuals at increased risk of developing non-insulin dependent diabetes mellitus. N Engl J Med 321: 337–343
Coleman TG, Manning RD Jr, Norman RA Jr, Guyton AC (1972) Dynamics of water-isotope distribution. Am J Physiol 223: 1371–1375
Hanning I, Home PD, Alberti KGMM (1985) Measurement of free insulin concentrations: the influence of the timing of extraction of insulin antibodies. Diabetologia 28: 831–835
Bottazzo GF, Gleichmann H (1986) Immunology and Diabetes Workshops: report of the first international workshop on the standardization of cytoplasmic islet cell antibodies. Diabetologia 29: 125–126
Miettinen A, Holthöfer H, Kontiainen S, Miettinen M, Andersson LC (1989) Antibodies against gastrointestinal tumours in IDDM. Diabetes 38: 667–669
Radziuk J, Norwich KH, Vranic M (1974) Measurements and validation of non-steady state turnover rates with application to the insulin and glucose systems. Fed Proc 33: 1855–1864
Steele R (1959) Influence of glucose loading and of injected insulin on hepatic glucose output. Ann NY Acad Sci 82: 420–430
Cobelli C, Mari A, Ferrannini E (1987) Non-steady state: error analysis of Steele's model and development for glucose kinetics. Am J Physiol 252: E679-E689
Yki-Järvinen H, Consoli A, Nurjhan N, Young AA, Gerich JE (1989) Mechanism for underestimation of isotopically determined glucose disposal. Diabetes 38: 744–751
Lillioja S, Mott DM, Howard BV, Bennett PH, Yki-Järvinen H, Freymond D, Nyomba BL, Zurlo F, Swinburn B, Bogardus C (1988) Impaired glucose tolerance as a disorder of insulin action Longitudinal and cross-sectional studies in Pima Indians. N Engl J Med 318: 1217–1225
Reaven GM, Sageman WS, Swenson RS (1977) Development of insulin resistance in normal dogs following alloxan-induced insulin deficiency. Diabetologia 13: 459–462
Caruso G, Proietto J, Calenti A, Alford F (1983) Insulin resistance in alloxan-diabetic dogs: evidence for reversal following insulin therapy. Diabetologia 25: 273–279
Unger RH, Grundy S (1985) Hyperglycemia as an inducer as well as a consequence of impaired islet function and insulin resistance: implications of the management of diabetes. Diabetologia 28: 119–121
Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA (1987) Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 79: 1510–1515
Garvey WT, Griffin J, Hamman RF, Kolterman OG (1985) The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes 34: 222–234
Rossetti L, Rothman DL, DeFronzo RA, Shulman GI (1989) Effect of dietary protein on in vivo insulin action and liver glycogen repletion. Am J Physiol 20: E212-E219
Dagenais GT, Tancredi RG, Zierler KL (1976) Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm. J Clin Invest 58: 421–431
Groop LC, Bonadonna RC, Del Prato S, Ratheiser K, Zyck K, Ferrannini E, DeFronzo RA (1989) Glucose and free fatty acid metabolism in non-insulin dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J Clin Invest 84: 205–213
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Groop, L.C., Eriksson, J., Ekstrand, A. et al. Metabolic characteristics of autoimmune diabetes mellitus in adults. Diabetologia 34, 46–51 (1991). https://doi.org/10.1007/BF00404024
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00404024