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Title: Immune and metabolic changes leading to diabetes
Author: Hawa, Mohammed Iqbal
ISNI:       0000 0004 2734 3660
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2012
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Environmental factors are strong determinants of diabetes-predictive biomarkers. We found these environmentally-determined biomarkers included, advanced glycation end-product serum carboxymethyl lysine (CML), a glycotoxin and diabetes-associated autoantibodies, are largely determined by familial shared and non-familial non-shared effects respectively. Serum CML emerges as an additional diabetes-risk determinant additional to autoimmunity. Low-risk non-diabetic identical twins failed to identify an alteration in insulin secretion or sensitivity predisposing to type 1 diabetes (T1D). Antigen-specific antibodies in autoimmune T1D are also found in adults presenting with non-insulin requiring diabetes known as latent autoimmune diabetes of adult onset (LADA). Antigen specific antibodies in childhood and adult onset diabetes are similar with the same dominant isotype. European LADA patients compared with ‘type 2 diabetes’ patients are usually non-insulin requiring, younger, leaner and female. LADA is more prevalent than T1D, yet neither encompasses all adult-onset autoimmune diabetes. Prevalence of Metabolic Syndrome is significantly higher, in ‘type 2 diabetes’ than in adults with LADA or T1D. Excluding glucose as a variable, Metabolic Syndrome is not more prevalent in autoimmune diabetes than in controls. Metabolic Syndrome is not a characteristic of autoimmune diabetes. Our evidence indicated that autoimmune diabetes is more prevalent in adulthood (9.7% of 6156 patients) than childhood and that presentation with non-insulin requiring diabetes is the norm, not the exception. 4 Autoantibodies to CD38 antigen reported as a feature of non-insulin requiring diabetes, are not so in childhood onset diabetes and do not add to the panel of diabetes associated auto-antigens. This thesis suggests that autoimmune T1D of adult onset is prevalent, initially usually non-insulin requiring. Moreover T1D is, in part, non-genetically determined, likely involving more than one non-genetic effect and includes a broad clinical spectrum of severity, not overlapping with ‘type 2 diabetes’. The precise cause or initiating factor of the disease still remains a mystery.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine