Diabetes Mellitus, Autoimmunity, and Ageing

Whittingham, Senga; Mathews, John D.; Mackay, I. R.; Stocks, A.E.; Ungar, Berta; Martin, F. I. R.

doi:10.1016/s0140-6736(71)91212-8

Cited by 74 publications

(27 citation statements)

References 9 publications

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“…Previous reports have found either an increase, decrease or no clear relation in the frequencies of thyrogastric autoantibodies with duration of Type I diabetes [8][9][10]. These studies dealt mainly with older patients ( > 20 years of age), whereas our study consisted of patients who developed Type 1 diabetes before the age of 20 years and who were usually less than 40 years of age at the time of study.…”

Section: Discussionmentioning

confidence: 90%

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Coincident presence of thyro-gastric autoimmunity at onset of Type 1 (insulin-dependent) diabetes

1983

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Summary.We have determined thyroid microsomal and gastric parietal cell autoantibodies in 972 patients with onset of Type 1 (insulin-dependent) diabetes before age 20 years. In a cross sectional study, the frequencies of these autoantibodies did not change significantly over the ensuing 20 years following diagnosis of diabetes. In a longitudinal study of 424 patients with Type 1 diabetes followed up to 5.3 years, few new patients with thyro-gastric autoantibodies were identified. Whereas the frequencies of these autoantibodies among the diabetic patients were more than fivefold greater than for age, sex and race matched controls, they resembled those seen in the non-diabetic general population (n=1524) for the over 60 year age group. We conclude that in patients with thyrogastric autoantibodies and Type 1 diabetes, the onset of autoimmune processes affecting the thyroid, gastric mucosa and pancreatic islets tend to be simultaneous, although the resultant diseases have different natural histories.

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Section: Discussionmentioning

confidence: 90%

“…Human blood group 0 tissues were obtained surgically, snap frozen and used unfixed as tissue substrates [10]. Thyroid tissue used was from a patient with Graves' disease.…”

Section: Methodsmentioning

confidence: 99%

Coincident presence of thyro-gastric autoimmunity at onset of Type 1 (insulin-dependent) diabetes

1983

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“…among diabetics may be as high as 30%, is most severe during poor metabolic control, and is most evident in insulin-dependant diabetes mellitus. 23 Although diabetic patients with hypothyroidism may be at increased risk of cardiovascular morbidity and mortality, 50 this risk may be further intensified by hypertension.…”

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confidence: 99%

Insulin, thyroid hormone, and heart function of diabetic spontaneously hypertensive rat.

Davidoff

Rodgers

1990

Hypertension

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Diabetes impairs cardiac performance more extensively in hypertensive rats than it does in nonhypertensive strains. A "low thyroid state" may contribute to the adverse cardiovascular effects of diabetes in spontaneously hypertensive rats (SHR). We tested this hypothesis by comparing the effects of thyroid hormone with those of insulin treatment on cardiac performance of diabetic SHR. Diabetes was induced with streptozotocin (45 mg/kg). Subsets of diabetic rats were treated with either insulin (10-20 units/kg/day) or triiodothyronine (8-10 /ig/kg/day). Heart rate and systolic arterial pressure were obtained at weekly intervals. After 8 weeks, cardiac function was assessed using an isolated working heart preparation. Diabetes reduced arterial pressure and heart rate in vivo and markedly depressed cardiac performance under volume and pressure loading conditions ex vivo, confirming previous observations. As 4 Chemically induced diabetes in hypertensive rats has a more profound effect on cardiac function than it does in normotensive models. -7Collectively, the data suggest that pressure loadinduced left ventricular hypertrophy increases the susceptibility of the myocardium to diabetes-related derangements.

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“…GAD65 conformational Catalytic region [223] Catalytic region [222] GAD65 N-terminal linear None ascertained [210,224] Amino acids 4-22 [210,224,225] GAD65 C-terminal linear Rare Amino acids 475-585 [222] GAD67 conformational GAD67 or GAD65 [216] GAD67 specific [210,224] Cross-inhibition (see text) b96.11 > b78 [226] b78 > b96.11 [210] Anti-GAD65 transfer to animals (see text) Diabetes: no Not recorded Neurological: yes [227][228][229][230][231] Other autoimmune diseases Thyrogastric cluster [232] Diabetes 30%-60% Thyrogastric cluster [207,208] IvIg Plasmapheresis Rituximab ……..…”

Section: Type 1 Diabetes Spsmentioning

confidence: 99%

The Role of Pathogenic Autoantibodies in Autoimmunity

Rowley

Whittingham

2015

Antibodies

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Abstract:The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID). Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb) show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig) class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

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Diabetes Mellitus, Autoimmunity, and Ageing

Cited by 74 publications

References 9 publications

Coincident presence of thyro-gastric autoimmunity at onset of Type 1 (insulin-dependent) diabetes

Coincident presence of thyro-gastric autoimmunity at onset of Type 1 (insulin-dependent) diabetes

Insulin, thyroid hormone, and heart function of diabetic spontaneously hypertensive rat.

The Role of Pathogenic Autoantibodies in Autoimmunity

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