Autoimmune markers and neurological complications in non-insulin-dependent diabetes mellitus

Morano, Susanna; Tiberti, Claudio; Cristina, G.; Sensi, M.; Cipriani, R; Guidobaldi, Leo; Torresi, P; Medici, Francesco; Anastasi, Emanuela; Mario, U. Di

doi:10.1016/s0198-8859(99)00051-8

Cited by 14 publications

(9 citation statements)

References 26 publications

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“…The pathogenesis of diabetic neuropathy is still not fully understood and may involve multiple mechanisms. In the literature, controversial data regarding the association markers autoantibodies and diabetic neuropathy have been reported [12,[19][20][21]40]. To verify whether autoimmune markers of T1D are associated with subclinical neuropathy, we examined the levels of anti-GAD 65 antibodies, IAA and IA-2A in T1D neuropathic patients.…”

Section: Discussionmentioning

confidence: 99%

“…The potential role of auto reactive T-and B-cells sensitized to nervous tissue components in the development of autonomic neuropathy is supported by a report of Kaufman et al, [19] describing autoantibodies to GAD 65 in all the five diabetic patients with neuropathy in their study, but in none of the four patients with T1D of comparable duration and no complications. In contrast, many correspondences dispute this association [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Farhan¹,

Alghasham²,

Zafar³

et al. 2013

J Diab Res Clin Met

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Background: Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease with autoantibodies against glutamic-aciddecarboxylase (GAD)65, insulin and tyrosine phosphatase (TP) as a feature of disease. The correlations of these autoantibodies with disease severity remain to be explored. Here we investigate the status and contribution of autoantibodies against GAD65, insulin and TP in T1D patients and to explore whether these antibodies have a role in T1D progression and in T1D associated neuropathy. Methods: Sera from 57 T1D patients with varying levels of disease activities and 42 age-and sex-matched healthy controls were evaluated for anti-GAD65-antibodies, anti-insulin-antibodies and anti-TP-antibodies. Results: Serum analysis showed T1D patients contain 42% of anti-GAD65-antibodies, 76% of anti-insulin-antibodies and 34% of anti-TP-antibodies. Interestingly, not only was there an increased number of subjects positive for these antibodies, but also levels of these antibodies were significantly higher among T1D patients whose ages were >35 years as compared with younger T1D patients (age ≤35 years). In addition, significant correlation was observed between the levels of these antibodies and glycosylated haemoglobin (HbA 1c ). Furthermore, T1D neuropathic patients had higher levels of these antibodies compared with T1D patients without neuropathy. Conclusions: Our data support an association between these markers autoantibodies and severity of T1D. The stronger response observed in patients with uncontrolled T1D suggests that these antibodies may be useful biomarkers in evaluating the progress of T1D and in elucidating the mechanisms of disease pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Farhan¹,

Alghasham²,

Zafar³

et al. 2013

J Diab Res Clin Met

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“…The presence of autoimmune immunoglobulins against intracellular proteins such as glutamic acid decarboxylase, islet cell antibodies and insulinomaassociated antibodies have been described in the sera of patients with type 1 and type 2 diabetes and diabetic rats [2][3][4][5][6][7]. Their potential role on cell function and pathophysiology, however, remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes with neuropathy: autoantibody stimulation of autophagy via Fas

et al. 2008

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We reported previously that sera from patients with type 2 diabetes and neuropathy induce autophagy in human neuroblastoma (SH-SY5Y) cells. Here we report that enriched immunoglobulin fractions from a subpopulation of these patients induce autophagy and colocalization with Fas-activated death domain (FADD), a component of the Fas-activated death domain receptor signaling pathway. These effects were replicated by treatment of SY5Y cells with Fas ligand, tumor necrosis factor alpha and an agonist anti-Fas antibody. Preincubation of these sera with a soluble Fas receptor chimera (extracellular domain) markedly decreased the stimulation of autophagy. The results suggest that sera from subset of individuals with type 2 diabetes and neuropathy contain autoantibodies that activate the Fas cascade.

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“…31,32 Other studies have observed raised antinuclear antibodies and a presence of anti-insulin antibodies in individuals with type 1 and 2 diabetes with nerve dysfunction. 33,34 Secondly, insulin resistance within the peripheral nervous system has been reported in animal models of type 2 diabetes. 35 Insulin is a potent neurotrophic factor that supports axonal growth as well as Schwann cell physiology and receptors for insulin are abundantly expressed on peripheral nerves, at the node of Ranvier, and on Schwann cell membranes.…”

Section: Discussionmentioning

confidence: 99%

Altered peripheral nerve structure and function in latent autoimmune diabetes in adults

Issar

Yan

Kwai

et al. 2019

Diabetes Metabolism Res

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Aim The present study was undertaken to investigate mechanisms of peripheral nerve dysfunction in latent autoimmune diabetes in adults (LADA). Materials and methods Participants with LADA (n = 15) underwent median nerve ultrasonography and nerve excitability to examine axonal structure and function, in comparison to cohorts of type 1 diabetes (n = 15), type 2 diabetes (n = 23) and healthy controls (n = 26). The LADA group was matched for diabetes duration, glycaemic control, and neuropathy severity with the type 1 and type 2 diabetes groups. A validated mathematical model of the human axon was utilized to investigate the pathophysiological basis of nerve dysfunction. Results The most severe changes in nerve structure and function were noted in the LADA group. The LADA cohort demonstrated a significant increase in nerve cross‐sectional area compared to type 1 participants and controls. Compared to type 1 and 2 diabetes, measures of threshold electrotonus, which assesses nodal and internodal conductances, were significantly worse in LADA in response to both depolarising currents and hyperpolarising currents. In the recovery cycle, participants with LADA had a significant increase in the relative refractory period. Mathematical modelling of excitability recordings indicated the basis of nerve dysfunction in LADA was different to type 1 and 2 diabetes. Conclusions Participants with LADA exhibited more severe changes in nerve function and different underlying pathophysiological mechanisms compared to participants with type 1 or 2 diabetes. Intensive management of risk factors to delay the progression of neuropathy in LADA may be required.

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Autoimmune markers and neurological complications in non-insulin-dependent diabetes mellitus

Cited by 14 publications

References 26 publications

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Type 2 diabetes with neuropathy: autoantibody stimulation of autophagy via Fas

Altered peripheral nerve structure and function in latent autoimmune diabetes in adults

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