2005 Abstracts

 

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

Fourlanos S, Harrison LC

Pediatr Diabetes 6:3-4 (2005)

In this issue, Reinehr et al. report on insulin resistance and its relationship to adiposity in children with type 1 diabetes (T1D). The total study population consisted of 8156 children aged 4–20 yr, but they focused on 4124 children with satisfactory glycemic control, defined by a hemoglobin A1c (HbA1c) of <8.0%. Insulin action was assumed to be related to the total daily insulin dose, which was calculated in three ways: dose per weight (ID/kg), dose per body surface area (ID/m2), and dose per ideal body weight (ID/ideal kg). Adiposity was estimated as body mass index (BMI). The relationship between insulin resistance and adiposity was analyzed in three ways. First, children with satisfactory (HbA1c < 8.0%) and poor (HbA1c ≥ 8.0%) glycemic control were compared. The children with poor glycemic control had a higher BMI and daily insulin doses. Second, children with satisfactory glycemic control were divided into tertiles according to BMI; the highest tertile had a lower ID/kg but a higher ID/m2 compared to the lowest tertile. These findings were confirmed in a multivariate analysis, with BMI having a significant weak inverse correlation with ID/kg and a weak positive correlation to ID/m2. Third, children with satisfactory glycemic control were categorized by daily insulin dose into insulin resistant (ID/kg ≥ 1.0 units, n = 882) and insulin sensitive (ID/kg < 1.0 unit, n = 3242) groups. BMI was not significantly different between the groups. The authors concluded that children with "T1D with insulin resistance based on ID/kg are not more overweight than insulin-sensitive children with T1D" and "ID/m2 seems to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1D".

[Visit article page on Pediatr Diabetes website]

 

Latent autoimmune diabetes in adults (LADA) should be less latent

Fourlanos S, Dotta F, Greenbaum CJ, Palmer JP, Rolandsson O, Colman PG, Harrison LC

Diabetologia 48:2206-2212 (2005)

'Latent autoimmune diabetes in adults' (LADA) is the term coined to describe adults who have a slowly progressive form of autoimmune or type 1 diabetes that can be treated initially without insulin injections. The diagnosis of LADA is currently based on three clinical criteria: (1) adult age at onset of diabetes; (2) the presence of circulating islet autoantibodies, which distinguishes LADA from type 2 diabetes; and (3) insulin independence at diagnosis, which distinguishes LADA from classic type 1 diabetes. The prevalence of LADA in adults presenting with non-insulin-requiring diabetes is approximately 10%. Recognition of LADA expands the concept and prevalence of autoimmune diabetes, but LADA remains poorly understood at both a clinical and research level. In this perspective, we review the nomenclature, diagnostic criteria, genetics, pathology and therapy of LADA, to arrive at recommendations that might advance knowledge and management of this form of diabetes.

[Visit article page on Diabetologia website]

 

The prospect of vaccination to prevent type 1 diabetes

Harrison LC

Hum Vaccin 1:143-150 (2005)

Type 1 diabetes (T1D) is an autoimmune disease in which genes and environment contribute to cell-mediated immune destruction of insulin-producing beta cells in the pancreatic islets. Primary prevention by traditional 'positive' vaccination awaits evidence that infectious agents trigger T1D. The pre-clinical phase of T1D, in which at-risk individuals can be infected by the presence of autoantibodies to islet antigens, is a window for secondary prevention. The Holy Grail of therapy is 'negative' vaccination to induce immune tolerance against disease-specific autoantigens that drive immune-mediated pathology. This can be achieved by administering autoantigen via a 'tolergenic' (e.g., muscosal, intradermal) route, cell (e.g., resting dendritic cell), mode (e.g., with blockade of c0-stimulation molecules) or form (as an 'altered peptide ligand'). Although effective in rodent models of autoimmune disease, these strategies have so far been disappointing in humans. This review discusses the prospects of vaccination to prevent T1D, focusing on autoantigen-specific mucosal tolerance..

[View free full-text article on Hum Vaccin website]

 

Substance abuse in young patients with type 1 diabetes: easily neglected in complex medical management

Lee P, Nicoll AJ, McDonough M, Colman PG

Intern Med J 35:359-361 (2005)

The use of recreational drugs has become increasingly popular among young people. As a centre caring for a large group of young patients with type 1 diabetes, we have become concerned about the number of patients presenting with drug-related metabolic problems. We present a case series highlighting the issues of substance abuse in young patients with type 1 diabetes.

[View article page on Intern Med J website]

 

The insulin A-chain epitope recognized by human T cells is posttranslationally modified

Mannering SI, Harrison LC, Williamson NA, Morris JS, Thearle DJ, Jensen KP, Kay TW, Rossjohn J, Falk BA, Nepom GT, Purcell AW

J Exp Med 202:1191-1197 (2005)

The autoimmune process that destroys the insulin-producing pancreatic beta cells in type 1 diabetes (T1D) is targeted at insulin and its precursor, proinsulin. T cells that recognize the proximal A-chain of human insulin were identified recently in the pancreatic lymph nodes of subjects who had T1D. To investigate the specificity of proinsulin-specific T cells in T1D, we isolated human CD4(+) T cell clones to proinsulin from the blood of a donor who had T1D. The clones recognized a naturally processed, HLA DR4-restricted epitope within the first 13 amino acids of the A-chain (A1-13) of human insulin. T cell recognition was dependent on the formation of a vicinal disulfide bond between adjacent cysteine residues at A6 and A7, which did not alter binding of the peptide to HLA DR4. CD4(+) T cell clones that recognized this epitope were isolated from an HLA DR4(+) child with autoantibodies to insulin, and therefore, at risk for T1D, but not from two healthy HLA DR4(+) donors. We define for the first time a novel posttranslational modification that is required for T cell recognition of the insulin A-chain in T1D.

[View free full-text article on J Exp Med website]

 

Immunology of type 1 diabetes

Narendran P, Estella E, Fourlanos S

QJM 98:547-556 (2005)

The incidence of type 1 diabetes in the UK is 20 per 100 000 and increasing, particularly in the under-5-years age group. It comes with the burden of daily insulin injection and blood testing, as well as both short- and long-term complications, and this can include premature death. The standardized mortality ratio for type 1 diabetes has been estimated as 4-fold for females and 2.7-fold for males in the UK. Even with tight glucose control, there is a significant risk of neuropathy, retinopathy and nephropathy, as well as a 3-fold increase in the risk of severe hypoglycaemia.
Understanding the pathology of type 1 diabetes may help improve management. Type 1 diabetes is characterized by an absolute loss of insulin secretion, and results from an autoimmune process that destroys insulin-producing beta cells within the pancreatic islet. This review will focus on the immunology of type 1 diabetes, and how this understanding may influence the clinical management, and development of new treatments for this disease.

[View free full-text article at QJM website]

 

Creation of a multidisciplinary, evidence based, clinical guideline for the assessment, investigation and management of acute diabetes related foot complications

Wraight PR, Lawrence SM, Campbell DA, Colman PG

Diabet Med 22:127-136 (2005)

AIMS: To design a multidisciplinary, evidenced-based, clinical guideline for the assessment, investigation and management of inpatients with acute diabetes related foot complications.
METHODS: A systematic search of both published (identified by searching all major electronic databases and hand searching key journals) and unpublished literature (derived from national and internationally recognized experts) identified 266 articles specific to diabetes related foot complications. Of these, 126 (47%) were assessed to be methodologically sound and clinically relevant. A narrative summary with the articles tabulated according to their level of evidence was prepared. A multidisciplinary expert group of health professionals, with a known interest and recognized expertise in diabetes related foot complications, was established to assess the evidence.
RESULTS: The multidisciplinary expert group used the identified literature and clinical experience to create a comprehensive, evidence-based, clinical guideline for the assessment, investigation and management of acute diabetes related foot complications. Included within the guideline is a novel, diabetes specific classification system, which codes for the presence/absence and severity of the four principle causative factors (Neuropathy, Vascular compromise, Ulceration and Infection) in the development of acute diabetes related foot complications.
CONCLUSION: Through the creation and implementation of this evidence-based clinical guideline, specific for acute diabetes related foot complications, it is hoped that health professionals will be better equipped to make informed decisions for this patient population. This may benefit the individual and health system through reductions in amputation rate, length of hospital stay and health expenditure.

[Visit article page on Diabet Med website]

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