The geoepidemiology of type 1 diabetes

Borchers, Andrea T.; Uibo, Raivo; Gershwin, M. Eric

doi:10.1016/j.autrev.2009.12.003

Cited by 217 publications

(161 citation statements)

References 88 publications

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“…Second, themembranes were incubated for another 15 min with the ethanolamine/glycine buffer containing Tween 20 (0.14%) and gelatin hydrolysate (5 g/l). 7,36 After membranes were cut into 5 mm wide strips, the strips were incubated on a shaker overnight at 4 uC with sera or plasma and diluted 1 : 50 for IgA and 1 : 100 for IgG antibody assay in an incubating buffer composed of 1.25 g/l gelatin hydrolysate, 0.25 g/l Tween 20, 6.1 g/l NaCl (Merck and Co.) and 0.06 g/l Tris Base (SigmaAldrich). Strips were incubated with secondary anti-human IgA or anti-human IgG (diluted 1 : 500; DAKO) antibodies labeled with horseradish peroxidase for 1 h at room temperature; subsequent substrate reaction with carbazole in 50 nm sodium acetate buffer (pH 5.0) in the presence of hydrogen peroxide (0.04% 3-amino-9-ethylcarbazole and 0.015% hydrogen peroxide) was performed for 30 min.…”

Section: Detection Of Serum Antibodiesmentioning

confidence: 99%

“…Among these, the common susceptibility loci of HLA and other immune system-related genes, 3 permeability changes in the small-bowel mucosa, 4 and association with wheat consumption 4,5 are prominent. Both diseases are increasing in most regions of the world, 6,7 as are several other autoimmune diseases, but the actual cause of the disease remains unknown. However, several recent studies have highlighted the role of environmental and social changes that have taken place over the last several decades.…”

Section: Introductionmentioning

confidence: 99%

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Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

et al. 2011

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Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions. INTRODUCTIONWith an approximate prevalence of 1.0% in Western countries, celiac disease (CD) is one of the most common lifelong chronic disorders. 1 CD and type 1 diabetes (T1D) form a significant sector of childhood diseases with high rate of co-occurrence. 2 Both diseases are autoimmune in origin and develop as a result of complex pathological mechanisms, involving several common genetic, environmental and immunological factors. Among these, the common susceptibility loci of HLA and other immune system-related genes, 3 permeability changes in the small-bowel mucosa, 4 and association with wheat consumption 4,5 are prominent. Both diseases are increasing in most regions of the world, 6,7 as are several other autoimmune diseases, but the actual cause of the disease remains unknown. However, several recent studies have highlighted the role of environmental and social changes that have taken place over the last several decades. 8,9 The central event in the pathogenesis of CD is damage to the small intestinal mucosa that occurs after ingestion of gluten or related prolamins in genetically susceptible individuals. During this process, several morphological and immunological alterations have been demonstrated in the small-bowel mucos...

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Section: Detection Of Serum Antibodiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

et al. 2011

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“…Regrettably, for reasons yet to be understood, the incidence of T1D has been increasing at an alarming annual rate of ∼3%, thus indicating that the number of patients with T1D is predicted to rise significantly in the future (1). T1D occurs as a consequence of pancreatic β-cell destruction leading to insulin deficiency, a defect that causes hyperglycemia, hyperglucagonemia, cachexia, ketoacidosis, and other abnormalities (2,3).…”

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confidence: 99%

Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice

Fujikawa

Chuang

Sakata

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

182

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Leptin monotherapy reverses the deadly consequences and improves several of the metabolic imbalances caused by insulindeficient type 1 diabetes (T1D) in rodents. However, the mechanism(s) underlying these effects is totally unknown. Here, we report that intracerebroventricular (icv) infusion of leptin reverses lethality and greatly improves hyperglycemia, hyperglucagonemia, hyperketonemia, and polyuria caused by insulin deficiency in mice. Notably, icv leptin administration leads to increased body weight while suppressing food intake, thus correcting the catabolic consequences of T1D. Also, icv leptin delivery improves expression of the metabolically relevant hypothalamic neuropeptides proopiomelanocortin, neuropeptide Y, and agouti-related peptide in T1D mice. Furthermore, this treatment normalizes phosphoenolpyruvate carboxykinase 1 contents without affecting glycogen levels in the liver. Pancreatic β-cell regeneration does not underlie these beneficial effects of leptin, because circulating insulin levels were undetectable at basal levels and following a glucose overload. Also, pancreatic preproinsulin mRNA was completely absent in these icv leptin-treated T1D mice. Furthermore, the antidiabetic effects of icv leptin administration rapidly vanished (i.e., within 48 h) after leptin treatment was interrupted. Collectively, these results unveil a key role for the brain in mediating the antidiabetic actions of leptin in the context of T1D.brain | leptin monotherapy | glucose homeostasis | glucagon suppression A ccording to the Juvenile Diabetes Research Foundation, type 1 diabetes (T1D) afflicts 1-3 million people in the United States alone. Regrettably, for reasons yet to be understood, the incidence of T1D has been increasing at an alarming annual rate of ∼3%, thus indicating that the number of patients with T1D is predicted to rise significantly in the future (1). T1D occurs as a consequence of pancreatic β-cell destruction leading to insulin deficiency, a defect that causes hyperglycemia, hyperglucagonemia, cachexia, ketoacidosis, and other abnormalities (2, 3). T1D is a deadly condition if not treated. Current life-saving interventions include daily insulin administration; insulin therapy reduces hyperglycemia, glycosylated hemoglobin, and cachexia and prevents or delays some T1D-associated morbidities (3, 4). However, even with insulin therapy, T1D secondary complications include debilitating and long-lasting conditions, such as heart disease, neuropathy, and hypertension (5-7). Moreover, probably because of insulin's lipogenic and cholesterologenic actions, longterm insulin treatment is suspected to underlie the increased ectopic lipid deposition (i.e., in nonadipose tissues) (8) and incidence of coronary artery disease (>90% after the age of 55 y) (9, 10) seen in patients with T1D. Furthermore, in part attributable to insulin's potent, fast-acting, glycemia-lowering effects, intensive insulin therapy significantly increases the risk for hypoglycemia, an event that is disabling and can even be fatal (3,(11...

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“…Si bien, tanto la frecuencia de agentes virales, como la polución ambiental resultan hipótesis plausibles, y existe un alto riesgo de obtener asociaciones espurias, en este sentido los estudios de modelamiento para estudios temporales podrían prestar gran utilidad. Dada la considerable variabilidad geográfica de la DM1 en todo el mundo, es necesario estudiar posibles nuevas asociaciones que permitan explicar las grandes diferencias regionales en los nuevos patrones epidemiológicos [32][33][34][35] que permitan validar y confirmar la posible implicancia de estos factores ambientales con la agrupación espacio-temporal de la DM1.…”

Section: Discussionunclassified

Estudio temporal de diabetes mellitus tipo 1 en Chile: asociación con factores ambientales durante el período 2000-2007

Torres-Avilés

et al. 2013

Rev. méd. Chile

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The geoepidemiology of type 1 diabetes

Cited by 217 publications

References 88 publications

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice

Estudio temporal de diabetes mellitus tipo 1 en Chile: asociación con factores ambientales durante el período 2000-2007

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