Type 1 diabetes: pathogenesis and prevention

Department of Clinical Science at North Bristol, University of Bristol, UK.
Canadian Medical Association Journal (Impact Factor: 5.81). 08/2006; 175(2):165-70. DOI: 10.1503/cmaj.060244
Source: PubMed

ABSTRACT Type 1 diabetes results from the autoimmune destruction of insulin-producing beta cells in the pancreas. Genetic and, as yet undefined, environmental factors act together to precipitate the disease. The excess mortality associated with the complications of type 1 diabetes and the increasing incidence of childhood type 1 diabetes emphasize the importance of therapeutic strategies to prevent this chronic disorder. Why is it considered that type 1 diabetes might be preventable? Different strands of diabetes research are coming together to suggest therapeutic targets. Islet cell autoantibody assays make it possible to accurately identify people at risk of future disease. In most cases, a long prodrome provides a window of opportunity to reverse the autoimmune process. Although no current "cure" exists, recent genetic data and preliminary trial results suggest T cells as a target for preventive strategies. Another potentially attainable target is induction of tolerance to the beta-cell proteins such as insulin that are inappropriately recognized. Other strategies involve beta-cell replacement, but currently there are insufficient donor cells available. This may be overcome as the processes controlling the differentiation of pancreatic and nonpancreatic progenitors as well as replication of existing islet beta cells are unravelled.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cutoff point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (í µí±› = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance.
    Journal of Diabetes Research 01/2015; · 3.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mononuclear invasion of Langerhans islet and the ensuing insulitis triggers signal-transduction for the autoimmune mediated pancreatic beta-cell (ß-cell) apoptosis that severely disrupts insulin production resulting in hyperglycemia associated with Type-1 diabetes (T1DM). Today extensive global research is being conducted to eliminate the need for insulin, and even prevent or find a cure for T1DM. The multifactorial combination of autoimmune dysfunction, Langerhans islet hypoxia, and bio-chemical disruption are seen to be contributory factors for ß-cell destruction and the consequential disruption to insulin production. Regeneration of ß-cells back to physiological levels may restore homeostatic insulin levels, reversing T1DM. Evidence suggests that there are still functioning pancreatic ß-cells even in long standing T1DM providing the potential for their regeneration. Although the exact mechanism of ESWT is yet to be fully elucidated, ESWT is seen to influence a complex spectrum of bio-chemical, cellular and neuronal functions (ie. suppression of pro-inflammatory immune response, improved tissue hemodynamics, anti-microbial properties and induction of progenitor cell expression including proangiogenic factors and nitric oxide syntheses). The rationale for the use of extracorporeal shockwaves (ESW) in this instance is attributed to its restorative properties and safety profile demonstrated in cardiology, chronic wounds, osteogenesis, complex pain syndromes, and tendinopathies. ESW may restore autoimmune homeostasis creating a suitable environment for pancreatic ß-cell proliferation that in-turn significantly increases or normalizes endogenous insulin secretion reducing or totally eliminating dependency of exogenous insulin. The devastating complications, morbidity and mortality associated with T1DM warrants the exploration of homeostatic autoimmune restorative treatment (HART) modalities that may partially or fully reverse this disease condition. We present our hypothesis discussing ESW as a potential homeostatic autoimmune restorative treatment (HART) option for T1DM.
    Medical Hypotheses 09/2014; 83(3). DOI:10.1016/j.mehy.2014.05.008 · 1.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study deals with investigating the effects of diabetes and gliclazide –treatment on liver and pancreatic islet β -cell of mother rats and to explain susceptibility of the mentioned organs of their pups as well as of the disease progress. Thirty-six pregnant rats were arranged into four groups (n=9), including control, gliclazide-treatment, diabetic and diabetic receiving gliclazide-treatment. Experimental induction of the diabetes was carried out by intraperitoneal (i.p.) of single dose of 60 mg streptozotocin /kg body weight at 6 th day of gestation. Oral administration of gliclazide (5.2 mg/kg body weight) was done every other day from 6 th day of gestation until parturition. At parturition, the mother rats were euthanized and liver and pancreas specimens were harvested and prepared for light transmission electron microscopy (TEM). The observed findings revealed liver & islet dysfunction in pregnant mother and their pups. Gliclazide –treatment ameliorated the hepatic and pancreatic picture at the light and ultrastructural level. However, mild hepatitis and degranulation of secretory granules of β-cells were still existed. The authors concluded that both maternal diabetes, and their pups were influenced by hepatitis and degranulation of islets β-cells. Gliclazide-treatment showed a sign of amelioration of the liver and pancreatic disease of mother rats and their pups.
    05/2013; 2013(1):22-29. DOI:10.12966/jimr.5.4.2013


1 Download
Available from