Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes.

Pietropaolo, Massimo; Barinas‐Mitchell, Emma; Pietropaolo, Susan L.; Kuller, Lewis H.; Trucco, Massimo

doi:10.2337/diabetes.49.1.32

Cited by 145 publications

(89 citation statements)

References 26 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Three patients tested positive for GAD antibodies, no patients tested positive for IA-2 antibodies and three patients tested weakly positive for insulin antibodies. Thus, the prevalence rates of antibodies against GAD, IA2 and insulin in the study population are not significantly different from those for the general population [7][8][9] or those for a population of patients with type 2 diabetes [11,12]. Moreover, antibody-positive patients were not diagnosed with diabetes, and none of the subjects tested positive for more than one antibody, a result that is generally considered to be highly predictive of type 1 diabetes.…”

Section: To the Editormentioning

confidence: 68%

Immunological characteristics of diabetes in schizophrenia

2005

View full text Add to dashboard Cite

Abbreviations IA2: insulinoma antigen 2 . LADA: latent autoimmune diabetes of adults To the EditorIn 1899, Henry Maudsley, the first psychiatrist to link diabetes to psychiatric illness, wrote that "diabetes is a disease which often shows itself in families in which insanity prevails" [1]. With this observation, Maudsley suggested that patients with schizophrenia are genetically predisposed to diabetes. The introduction of chlorpromazine (in 1953) and, more recently, the atypical antipsychotics was followed by an increase in the number of cases of new-onset diabetes and the worsening of glycaemic control in cases of existing diabetes in patients with schizophrenia [2]. These findings suggest an iatrogenic, rather than a genetic, origin of diabetes in schizophrenia, in the form of antipsychoticinduced weight gain. However, this debate has not, as yet, been settled.In general, diabetes associated with schizophrenia is classified as type 2 diabetes. However, there are two arguments against this classification. The first argument is the rapid onset of schizophrenia-associated diabetes: over 80% of patients who develop diabetes do so within 6 months of initiating antipsychotic therapy [2]. With such a rapid onset, weight gain is unlikely to be the main stimulus for the development of the diabetes. A prospective randomised trial comparing the classical antipsychotic haloperidol with the three atypicals clozapine, olanzapine and risperidone found no relationship between glucose change and weight gain at endpoint, thereby confirming the independence of these two measures [3]. The second argument is the dramatic clinical presentation of diabetes in schizophrenia. There is an enhanced risk of metabolic complications, such as ketosis, acidosis and ketoacidosis, which are associated with a mortality rate of 26.5% [4][5][6]. These features are suggestive of type 1 diabetes or latent autoimmune diabetes of adults (LADA) rather than type 2 diabetes.Type 1 diabetes and LADA are characterised by diabetes-related antibodies, i.e. antibodies against insulin, GAD and insulinoma antigen 2 (IA2), which are found in over 80% of type 1 diabetic subjects and in fewer than 5% of the general population [7,8]. The aim of this study was to determine the prevalence of the three diabetes-related antibodies in schizophrenic patients, thereby establishing whether autoimmune phenomena play a role in diabetes associated with schizophrenia.Patients (81 men [68.1%], 38 women [31.9%]; mean age 41.5 years [SD=10.9, range 19-65]) gave informed consent to participate in the study, which was approved by the Ethics Committee of the University of Utrecht. The psychiatric diagnosis was based on the shortened version of the

show abstract

Section: To the Editormentioning

confidence: 68%

Immunological characteristics of diabetes in schizophrenia

2005

View full text Add to dashboard Cite

show abstract

“…Hence, there is no basis for assuming that there is a primary role for autoimmunity in diabetes pathogenesis in NZO mice as there clearly is in the NOD mouse model for T cell-mediated type 1 diabetes (Serreze and Leiter, 2001). However, "diabesity" developing in NZO/HlLt males may entail aspects of what is termed "latent autoimmune diabetes of adults or type 1.5 diabetes" (Pietropaolo et al, 2000). We have used Chinese hamster ovary cells stably transfected with the mouse insulin receptor as target cells to confirm the presence of insulin receptor autoantibodies in NZO/HlLt, as originally reported in NZO/ Wehi mice (Harrison and Itin, 1979).…”

Section: Discussionmentioning

confidence: 99%

The Diabetes-Prone NZO/HlLt Strain. I. Immunophenotypic Comparison to the Related NZB/BlNJ and NZW/LacJ Strains

Haskell

Flurkey

Duffy

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:New Zealand Obese (NZO)/HlLt male mice exhibit a polygenic obesity and approximately 50% develop type 2 diabetes. This strain is known to produce a variety of autoantibodies, including autoantibodies to the insulin receptor. Because of their relatedness to the autoimmune-predisposed New Zealand Black (NZB) and New Zealand White (NZW) inbred strains, we compared NZO to its two related strains for shared hematologic and immunologic characteristics. Comparison of the three strains by serotyping and genotyping methods indicated that NZO shared with NZW the rare (recombinant) H2 z haplotype at the major histocompatibility complex. Similar to the NZB and NZW strains, spleens from NZO mice contained increased numbers of CD19 ϩ CD43 ϩ IgM ϩ B-1 B cells, a phenotype associated with natural autoantibody production. NZO mice developed a progressive microcytic anemia that was distinguished from NZB hemolytic anemia by absence of demonstrable antierythrocyte antibodies in the former. Outcross of NZO females with NZB males accelerated development of obesity and diabetes in F1 males. NZO males made B-lymphocyte-deficient by a disrupted immunoglobulin heavy chain gene did not become diabetic. These results suggest that NZO mice should be useful to investigators interested in studying the genetic contributions to autoimmunity made by the related NZW and NZB strains. Further, these results, combined with the pancreatic histopathology contained in the companion manuscript, suggest that B lymphocytes may be important contributors to diabetes pathogenesis in the NZO mouse. (Lab Invest 2002, 82:833-842).

show abstract

“…It has been shown recently that in subjects with type 2 diabetes, autoimmunity (as indicated by elevated levels of GAD65 and IA-2 autoantibodies) was associated with elevated levels of CRP and fibrinogen (25). Thus, one might speculate that subjects who present with increased levels of inflammatory proteins in the prediabetic state may in fact represent subjects who will eventually develop late-onset type 1 diabetes, with a deterioration of insulin secretion as the primary defect (26).…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes

et al. 2002

View full text Add to dashboard Cite

Elevated serum levels of acute-phase proteins, indicating chronic subclinical inflammation, have been associated with cardiovascular disease as well as the insulin resistance syndrome. Chronic inflammation may also be a risk factor for developing type 2 diabetes. We studied the concentrations of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) in 1,047 nondiabetic subjects in relation to incident diabetes within 5 years in the Insulin Resistance Atherosclerosis Study. Subjects with diabetes at follow-up (n ‫؍‬ 144) had higher baseline levels of fibrinogen (mean ؎ SD; 287. ). It has been hypothesized that atherosclerotic cardiovascular disease and type 2 diabetes arise from a "common soil" (2,3), and chronic inflammation may be such a candidate (4,5). Inflammatory markers, such as high white cell count, high fibrinogen, or low albumin (6), and markers of hemostasis, such as factor VIII (7), have been related to the development of type 2 diabetes. Adipose body mass may be an important mediator to explain these relations (6,7), but pathophysiological mechanisms remain elusive, and no data on the role of insulin resistance are available. This is of particular interest because decreased insulin sensitivity has been linked to incident type 2 diabetes (8), as well as increased levels of inflammatory proteins (9,10) and markers of hemostasis (11,12) and fibrinolysis (11,13).In the present study, we investigated the relation of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) to incident type 2 diabetes during a 5-year period in the Insulin Resistance Atherosclerosis Study (IRAS). Furthermore, we sought to clarify the role of insulin resistance, as directly measured using a frequently sampled intravenous glucose tolerance test. RESEARCH DESIGN AND METHODSThe Insulin Resistance Atherosclerosis Study (IRAS) is a multicenter, epidemiological study aiming to explore relationships among insulin resistance, cardiovascular risk factors, and disease across different ethnic groups and varying states of glucose tolerance. A full description of the design and methods of the IRAS has been published previously (14). The IRAS protocol was approved by local institutional review committees, and all subjects gave informed consent.A total of 1,625 individuals participated in the IRAS. This report includes data on 1,047 subjects, who were nondiabetic at the baseline examination and in whom CRP, PAI-1, and fibrinogen were measured. Subjects were investigated twice following the same protocol. The mean follow-up duration was 5.2 years (range 4.5-6.6). Each of the two IRAS examinations required two visits. Patients were asked before each visit to fast for 12 h, to abstain from heavy exercise and alcohol for 24 h, and to refrain from smoking on the morning of the examination. Race and ethnicity were assessed by self-report. Family history of type 2 diabetes and physical activity were assessed using standard interviewing procedures. A positive family history of diabetes was d...

show abstract

Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes.

Cited by 145 publications

References 26 publications

Immunological characteristics of diabetes in schizophrenia

Immunological characteristics of diabetes in schizophrenia

The Diabetes-Prone NZO/HlLt Strain. I. Immunophenotypic Comparison to the Related NZB/BlNJ and NZW/LacJ Strains

Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes

Contact Info

Product

Resources

About