A case for late autoimmune diabetes of the adult?
Jan Ruxer, MD, PHD, Michal Mozdzan, MD, Leszek Czupryniak, MD, PHD and Jerzy Loba, MD, PHD
Type 1 diabetes is a well-defined condition requiring life-saving insulin replacement therapy immediately after diagnosis (1). It is also a well-known fact from the natural course of the disease that soon after the insulin therapy has been initiated, insulin requirements decrease, sometimes rapidly, and patients who stopped taking insulin shortly after diabetes diagnosis have been reported (2). However, this so-called “honeymoon period” usually starts several weeks after the diagnosis and rarely exceeds several months’ duration. It is believed, however, and has been unfortunately shown in the past, e.g., during wartime, that insulin discontinuation in a long-standing type 1 diabetic patient poses a serious threat to health and life (3,4). We describe a case of a patient with a definite diagnosis of autoimmune diabetes who, 2 years after having been diagnosed with diabetes, stopped insulin treatment for a period of 17 months and did not develop ketoacidosis.
In April 2000, a 19-year-old woman was admitted to the Metabolic Diseases Department due to profound weakness, dizziness, and increased thirst, as well as a 10-kg weight loss in 6 months. The symptoms occurred several months earlier but became more severe within the previous 8 weeks.
The patient was diagnosed with type 1 diabetes in November 1998. Her symptoms at the time gradually developed for 4 months and included increased thirst, polyuria, weight loss, and mild ketoacidosis. At the time of diagnosis, her blood glucose was 17.8 mmol/l. She was positive for islet cell autoantibodies (ICAs), with a titer of 90 JDF units, as well as positive for antibodies against GAD (anti-GAD, 80 units/ml). The treatment on discharge consisted of an intensive insulin regimen: short-acting insulin before meals and long-acting insulin twice daily; the daily requirement of insulin was 46 units.
The patient continued with her treatment for the next 2 years. She was compliant with physician recommendations, adhered to a prescribed diet, and performed self-monitoring of blood glucose four to six times daily. Her mean daily blood glucose ranged from 5.6 to 11.1 mmol/l. However, in November 2000, the patient stopped taking insulin and went on a free diet. The immediate cause of the sudden change of her behavior was a deep conflict with her parents, which eventually led to her leaving home for 13 months. During this time, she, using her words, “was well and completely forgot about her diabetes.” In December 2001, she returned to her parents, although she refused to restart insulin therapy or to have a therapeutic session with a psychologist.
When she was admitted to our department in April 2002, her blood glucose was 29.8 mmol/l. It was established that she had not been taking insulin for the previous 17 months, nor had she been measuring her glucose or following any diet. Her body mass was 53 kg, height 165 cm, BMI 19.5 kg/m2, and blood pressure 120/80 mmHg. No abnormalities in physical examination were found. Her acid-base balance was pH 7.44, serum bicarbonate 20 mmol/l, and base excess −2.8 mmol/l; she also had a trace of ketones in her urine. Her HbA1c was 10.6% and C-peptide 0.21 nmol/l (reference range 0.17–1.2). As at diabetes diagnosis, she was positive for ICAs and anti-GAD, although the titers of these autoantibodies were distinctly lower: 10 JDF units and 5.8 units/ml, respectively. In the beginning, she was treated with intravenous insulin infusion with a mean daily insulin requirement of ∼90 units and, after 3 days, transferred to a basal-bolus insulin regimen. At discharge, she was taking 70 units of insulin daily; she was well and accepted reinitiated insulin therapy.
We present a case of a patient diagnosed with type 1 diabetes in whom long-term insulin discontinuation did not result in acute hyperglycemic crises. The diagnosis of type 1 diabetes seems to be valid, because the immunologic tests confirmed that autoimmunologic processes developed in the patient (1). However, lack of severe (or, for that matter, any clinically significant) ketoacidosis during discontinuation of insulin is somewhat surprising. The clinical course of the diabetes was typical of type 2 rather than type 1 diabetes (5). Seventeen months free of insulin therapy suggested that the patient still had residual insulin secretion sufficient to maintain effective glucose metabolism. It is particularly worth noting that autoantibody assays failed to identify that she required insulin to maintain her life. The period of not taking insulin cannot be, however, labeled a “honeymoon period” since the patient was treated with stable doses of insulin for the previous 2 years. The clinical course of the disease is probably most typical of late autoimmune diabetes of the adult (LADA), which probably should have been diagnosed in the patient (6). LADA has recently gained considerable interest among both researchers and clinicians, probably due to increasing availability of immunological assays (7,8). However, its clinical identification is still unclear, as even the issue of insulin requirement at diagnosis is still a matter of dispute (9,10). The results of several studies indicate that LADA patients might constitute up to one-third of the alleged type 2 diabetic population (6,7,9), and the aberrant course of diabetes should always make one consider LADA as a possible diagnostic option, particularly in younger subjects (7–9).
Discontinuation of insulin treatment is not an uncommon event in diabetes therapy (11,12). HsinYu et al. (11) recently identified three predictors of ceasing insulin therapy: age >40 years at diabetes diagnosis, severe diabetic ketoacidosis as a first symptom, and excessive body weight. We have raised the issue of infection at the moment of diabetes diagnosis as another possible predictor of nonrequirement for insulin in further therapy (12). However, none of the above factors were present in our patient.
In our opinion, two conclusions can be drawn from the case. First, despite years of intensive research, pathophysiology of diabetes is still far from being clear, as even type 1 diabetes seems to be a heterogenous disease. Our patient was developing diabetic symptoms relatively slowly, and had it not been for her age and slim build, she could well have been regarded as a type 2 diabetic subject. Second, the presence of autoantibodies typical of autoimmune diabetes may not definitely lead to the diagnosis of type 1 diabetes because many patients with type 2 diabetes may also present with some features of autoimmunity. Therefore, finding clear, unequivocal criteria for differentiation between type 1 and type 2 diabetes seems to be the urgent issue of utmost importance.
Footnotes
Address correspondence to Dr. Leszek Czupryniak, Department of Diabetology, University Hospital no. 1, Kopcinskiego 22, 90-153 Lodz, Poland. E-mail: bigosik@poczta.onet.pl.
References
↵ Atkinson MA, Eisenbarth GS: Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358: 221–229, 2001 CrossRefMedline
↵ Agner T, Damm P, Binder C: Remission in IDDM: prospective study of basal C-peptide and insulin dose in 268 consecutive patients. Diabetes Care 10: 164–169, 1987 Abstract/FREE Full Text
↵ Semetkowska-Jurkiewicz E, Jaromczyk-Slisz J, Horoszek-Maziarz S: Analysis of the cause of death in diabetic ketoacidosis based on 5 years of personal observation [article in Polish]. Pol Tyg Lek 44: 484–487, 1989 Medline
↵ Irwin J, Cohle SD: Sudden death due to diabetic ketoacidosis. Am J Forensic Med Pathol 9: 119–121, 1988 Medline
↵ Bell D: Pathophysiology of type 2 diabetes and its relationship to new therapeutic approaches. Diabetes Educ 26 (Suppl.): 4–7, 2000
↵ Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, Lang DA: Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med 11: 299–303, 1994 Medline
↵ Schernthaner G, Hink S, Kopp HP, Muzyka B, Streit G, Kroiss A: Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes). Exp Clin Endocrinol Diabetes 109: S94–S108, 2001
↵ Tan HH, Lim SC: Latent autoimmune diabetes in adults (LADA): a case series. Singapore Med J 42: 513–516, 2001 Medline
↵ Pozzilli P, Di Mario U: Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention (Review). Diabetes Care 24: 1460–1467, 2001 Abstract/FREE Full Text
↵ Szepietowska B, Szelachowska M, Kinalska I: Do latent autoimmune diabetes diabetes of the adult (LADA) patients require insulin at diagnosis? Response to Pozzilli and Di Mario (Letter). Diabetes Care 25: 1662, 2002 FREE Full Text
↵ Hsin Yu E, Guo HR, Wu TJ: Factors associated with discontinuing insulin therapy after diabetic ketoacidosis in adult diabetic patients. Diabet Med 18: 895–899, 2001 CrossRefMedline
↵ Czupryniak L, Ruxer J, Saryusz-Wolska M, Loba J: Discontinuing insulin therapy after diabetic ketoacidosis: is its cause worth considering? Diabet Med. In press
source : http://care.diabetesjournals.org/content/26/4/1314.full
No comments:
Post a Comment