Are Insulin Autoantibodies Markers for Insulin-Dependent Diabetes Mellitus?

Atkinson, Mark A.; Maclaren, Noel K.; Riley, William J.; Winter, William E.; Fisk, Diann; Spillar, Rebecca

doi:10.2337/diab.35.8.894

Cited by 108 publications

(58 citation statements)

References 9 publications

(15 reference statements)

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“…It is also noteworthy that despite lower insulin levels during the IVGTT, the relatives of diabetic patients -especially these with positive autoantibodies -had significantly higher fasting insulin concentrations and higher HOMA-IR index than had the controls. Moreover, a positive correlation between IAA levels and HOMA-IR was found in the study group, confirming the previous observations suggesting that not only decreased beta-cell secretory reserve, but also increased insulin resistance, impact upon the progression of the autoimmune process, especially in subjects with auto-antibodies directed against pancreatic islet antigens [17][18][19]. Abnormal sensitivity to insulin in patients with type 1 diabetes was shown for the first time by Ginsberg in the 1970s [20].…”

Section: Prace Oryginalnesupporting

confidence: 88%

Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Siewko¹,

Popławska-Kita²,

Telejko³

et al. 2014

Endokrynologia Polska

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Introduction: The aim of this study was to evaluate beta-cell function and insulin resistance in relation to the occurrence of anti-islet antibodies in first degree relatives of patients with type 1 diabetes (T1D). Material and methods:The group studied consisted of 90 relatives and 60 healthy individuals without a family history of diabetes. An intravenous glucose tolerance test (IVGTT) was performed in all participants and the first phase insulin response index (FPIR) was calculated. Serum concentrations of GADA, IAA and IA-2A were measured by RIA. HOMA-IR and HOMA%B indices were calculated using a computer calculator from website. Results: At least one positive antibody was found in 28 relatives (31.1%) but in none of the controls. The most frequently detected antibodies were IAA (22.2%). The relatives of diabetic patients had significantly higher fasting insulin level (p), significantly lower FPIR index (p), as well as higher HOMA-IR (p) and lower HOMA%B (p) compared to the controls. A positive correlation between IAA concentration and HOMA-IR (r = 0.287, p < 0.005) and a negative correlation between IAA level and HOMA%B (r = -0.226, p < 0.05) were also shown. Conclusions: Our results confirmed that more than 30% of the first-degree relatives of diabetic patients have positive markers of autoimmune beta-cell destruction. The study showed also that these individuals, in spite of normal glucose tolerance, have markedly decreased beta-cell secretory reserve and decreased sensitivity to insulin action, strongly suggesting an increased risk for developing diabetes later in life.

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Section: Prace Oryginalnesupporting

confidence: 88%

Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Siewko¹,

Popławska-Kita²,

Telejko³

et al. 2014

Endokrynologia Polska

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“…In addition to autoantibodies directed against islet cell proteins (Bottazzo et al, 1980) and glutamic acid decarboxylase (Baekkeskov et al, 1982(Baekkeskov et al, , 1990Kaufman et al, 1992) the IAA are useful in the investigation diagnosis of IDDM (Palmer et al, 1983;Atkinson et al, 1986;Dean et al, 1986;Wilkin, 1990). In newly diagnosed IDDM patients the frequency of IAA is about 40% in children, but only 4% in adults (Karjalainen et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Recombinant human preproinsulin expression, purification and reaction with insulin autoantibodies in sera from patients with insulin-dependent diabetes mellitus

Berg¹,

Walter

Mauch³

et al. 1993

Journal of Immunological Methods

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A novel prokaryotic expression vector pGEX-6T was designed for high-level expression of recombinant fusion protein with a histidine-hexapeptide and glutathione-S-transferase at its N-terminus and the recombinant human preproinsulin at its C-terminus. Efficiency of expression was investigated in the Escherichia coli strain CAG456. The synthesized protein was sequestered in an insoluble form in inclusion bodies and was purified to homogeneity by one-step affinity chromatography based on the specific complex formation of the histidine-hexapeptide and a chelating matrix which was charged with Ni 2+ ions. The antigenic nature of the purified recombinant preproinsulin fusion protein was evaluated by ELISA screening for insulin autoantibodies in selected sera from patients with recent-onset type 1 (insulin-dependent) diabetes mellitus classified by the existence of additional autoantibodies reactive against glutamic acid decarboxylase. 14% of the tested sera (n = 43) contained insulin autoantibodies which strongly recognized the recombinant human preproinsulin. Comparable measurements with both recombinant human preproinsulin and mature insulin suggested that the observed autoantigenicity of preproinsulin was mediated by the C-peptide or/and signal peptide.

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“…Anti-insulin autoantibodies (IAAs) were the first specific ICAs to be identified and this was done in 1983 by Palmer et al [27] who performed seminal studies in this area using serum from patients who have not been challenged by exogenous insulin at the time of sample collection. Subsequent research have addressed the insulin levels after glucose challenge and it was concluded that insulinopenia was more prevalent in subjects possessing both, ICAs and IAAs, compared to those being positive just for ICAs [28] . However, this marker has a relatively low sensitivity, being even less than 40% [29] .…”

Section: Immunological Characteristicsmentioning

confidence: 99%

Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

Pipi

Marketou

Tsirogianni

2014

WJD

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Ever since its first appearance among the multiple forms of diabetes, latent autoimmune diabetes in adults (LADA), has been the focus of endless discussions concerning mainly its existence as a special type of diabetes. In this mini-review, through browsing important peer-reviewed publications, (original articles and reviews), we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity. A unique combination of immunological, clinical and metabolic characteristics has been identified in this group of patients, namely persistent islet cell antibodies, high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte antigen haplotypes, progressive loss of beta cells, adult disease onset, normal weight, defective glycaemic control, and without tendency to ketoacidosis. Although anthropomorphic measurements are useful as a first line screening, the detection of C-peptide levels and the presence of glutamic acid decarboxylase (GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria and guidelines still puzzle the physicians, who struggle between early diagnosis and correct timing for insulin treatment.

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Are Insulin Autoantibodies Markers for Insulin-Dependent Diabetes Mellitus?

Cited by 108 publications

References 9 publications

Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Recombinant human preproinsulin expression, purification and reaction with insulin autoantibodies in sera from patients with insulin-dependent diabetes mellitus

Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

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