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‣ The “Perfect Storm” for Type 1 Diabetes: The Complex Interplay Between Intestinal Microbiota, Gut Permeability, and Mucosal Immunity

Vaarala, Outi; Atkinson, Mark A.; Neu, Josef
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
Publicado em /10/2008 Português
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It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involving facets related to the gut, one where individual factors that, upon their interaction with each another, form a “perfect storm” critical to the development of type 1 diabetes. This trio of factors includes an aberrant intestinal microbiota, a “leaky” intestinal mucosal barrier, and altered intestinal immune responsiveness. Studies examining the microecology of the gastrointestinal tract have identified specific microorganisms whose presence appears related (either quantitatively or qualitatively) to disease; in type 1 diabetes, a role for microflora in the pathogenesis of disease has recently been suggested. Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased-risk for the disease. Finally, an altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance, resulting in the autoimmunity that underlies type 1 diabetes. Herein...

‣ Self-Monitoring of Blood Glucose as Part of the Integral Care of Type 2 Diabetes

Boutati, Eleni I.; Raptis, Sotirios A.
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
Publicado em /11/2009 Português
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Results from landmark diabetes studies have established A1C as the gold standard for assessing long-term glycemic control. However, A1C does not provide “real-time” information about individual hyperglycemic or hypoglycemic excursions. Real-time information provided by self-monitoring of blood glucose (SMBG) represents an important adjunct to A1C, because it can differentiate fasting, preprandial, and postprandial hyperglycemia; detect glycemic excursions; identify hypoglycemia; and provide immediate feedback about the effect of food choices, physical activity, and medication on glycemic control. The importance of SMBG is widely appreciated and recommended as a core component of management in patients with type 1 or insulin-treated type 2 diabetes, as well as in diabetic pregnancy, for both women with pregestational type 1 and gestational diabetes. Nevertheless, SMBG in management of non–insulin-treated type 2 diabetic patients continues to be debated. Results from clinical trials are inconclusive, and reviews fail to reach an agreement, mainly because of methodological problems. Carefully designed large-scale studies on diverse patient populations with type 2 diabetes with the follow-up period to investigate long-term effects of SMBG in patients with type 2 diabetes should be carried out to clarify how to make the best use of SMBG...

‣ The Reality of Type 2 Diabetes Prevention

Kahn, Richard; Davidson, Mayer B.
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.320454%
Efforts to reduce the burden of type 2 diabetes include attempts to prevent or delay the onset of the disease. Landmark clinical trials have shown that lifestyle modification programs focused on weight loss can delay the onset of type 2 diabetes in subjects at high risk of developing the disease. Building on this knowledge, many community-based studies have attempted to replicate the trial results and, simultaneously, payers have begun to cover diabetes prevention services. This article focuses on the evidence supporting the premise that community prevention efforts will be successful. Unfortunately, no study has shown that diabetes can be delayed or prevented in a community setting, and efforts to replicate the weight loss achieved in the trials have been mostly disappointing. Furthermore, both the clinical trials and the community-based prevention studies have not shown a beneficial effect on any diabetes-related clinical outcome. While the goal of diabetes prevention is extremely important, the absence of any persuasive evidence for the effectiveness of community programs calls into question whether the use of public funds or national prevention initiatives should be supported at this time.

‣ Levels of Oxidized LDL and Advanced Glycation End Products–Modified LDL in Circulating Immune Complexes Are Strongly Associated With Increased Levels of Carotid Intima-Media Thickness and Its Progression in Type 1 Diabetes

Lopes-Virella, Maria F.; Hunt, Kelly J.; Baker, Nathaniel L.; Lachin, John; Virella, G.; Nathan, David Matthew; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.320454%
OBJECTIVE High cholesterol levels in circulating immune complexes (IC), surrogate markers of modified LDL, are associated with increased carotid intima-media thickness (IMT) and cardiovascular events in type 1 diabetes. Different modifications of LDL are involved in IC formation, but which of these are predictive of vascular events is not known. Therefore, we measured oxidized LDL (oxLDL), advanced glycation end products–modified LDL (AGE-LDL), and malondialdehyde-modified LDL (MDA-LDL) in IC and determined their relationship with increased carotid IMT and compared the strength of the association with that observed with conventional risk factors. RESEARCH DESIGN AND METHODS Levels of oxLDL, AGE-LDL, and MDA-LDL were measured in circulating IC isolated from sera of 479 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, collected at baseline. Internal and common carotid IMT were measured 8 and 14 years later by DCCT/EDIC. RESULTS OxLDL, AGE-LDL, and MDA-LDL levels in circulating IC were significantly correlated with diabetes duration, BMI, and lipid and blood pressure, but not with age. Multivariate logistic regression models indicated that individuals in the highest versus lowest quartile of oxLDL and AGE-LDL in IC had a 6.11-fold [confidence interval (CI) 2.51–14.8] and a 6.4-fold (CI 2.53–16.2) increase in the odds of having high carotid IMT...

‣ Perceived Impact of Diabetes Genetic Risk Testing Among Patients at High Phenotypic Risk for Type 2 Diabetes

Markowitz, Sarah M.; O’Brien, Kelsey E.; Park, Elyse Richelle; Delahanty, Linda Michele; Grant, Richard W.
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.37005%
Objective: Rapid advances in diabetes genetic epidemiology may lead to a new era of “personalized medicine” based on individual genetic risk assessment. There is minimal experience to guide how best to clinically implement such testing so that results (e.g., “higher” or “lower” relative genetic risk) improve rather than reduce patient motivation for behavior change. Research Design and Methods: Between November 2009 and May 2010, we conducted in-depth interviews with 22 overweight participants at high phenotypic risk for type 2 diabetes to explore perceptions of diabetes genetic risk testing compared with currently available prediction using nongenetic risk factors (e.g., family history, abnormal fasting glucose, obesity). We used hypothetical scenarios to specifically investigate the impact of both “higher” and “lower” relative genetic risk results on participants’ views about diabetes prevention. Results: Many participants conferred a unique value on personal genetic risk information relative to nongenetic risk based on the perceived scientific certainty and durability of genetic results. In contrast, other participants considered their genetic risk within the overall context of their other measured risk factors. Reactions to diabetes genetic test results differed by current motivation levels. Whereas most subjects reported that “higher” risk results would motivate behavior change...

‣ Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration

Asztalos, Bela F.; Schaefer, Ernst J.; Sell, David R.; Strauch, Christopher M.; Monnier, Vincent M.; Sun, Jennifer Katherine; Keenan, Hillary; Cavallerano, Jerry D.; Doria, Alessandro; Aiello, Lloyd Paul; King, George Liang
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.30132%
Objective: To assess complication prevalence and identify protective factors in patients with diabetes duration of (geq)50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. Research Design and Methods: Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for (geq)50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA(_{1c}), lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup. Results: A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. Conclusions: The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications...

‣ Early atherosclerosis relates to urinary albumin excretion and cardiovascular risk factors in adolescents with type 1 diabetes: adolescent type 1 Diabetes cardiorenal Intervention Trial (AdDIT)

Maftei, O.; Pena, A.S.; Sullivan, T.; Jones, T.W.; Donaghue, K.C.; Cameron, F.J.; Davis, E.; Cotterill, A.; Craig, M.E.; Gent, R.; Dalton, N.; Daneman, D.; Dunger, D.; Deanfield, J.; Couper, J.J.
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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OBJECTIVE: The origins of cardiovascular and renal disease in type 1 diabetes begin during childhood. We aimed to evaluate carotid (cIMT) and aortic intima-media thickness (aIMT) and their relationship with cardiovascular risk factors and urinary albumin excretion in adolescents with type 1 diabetes in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT). RESEARCH DESIGN AND METHODS: A total of 406 adolescents with type 1 diabetes, who were 14.1 ± 1.9 years old with type 1 diabetes duration of 6.7 ± 3.7 years, and 57 age-matched control subjects provided clinical and biochemical data and ultrasound measurements of vascular structure (cIMT and aIMT). Vascular endothelial and smooth muscle function was also measured in 123 of 406 with type 1 diabetes and all control subjects. RESULTS: In type 1 diabetic subjects, mean/maximal aIMT (P < 0.006; <0.008), but not mean/maximal cIMT, was greater than in control subjects. Mean/maximal aIMT related to urinary albumin-to-creatinine ratio (multiple regression coefficient [SE], 0.013 [0.006], P = 0.03; 0.023 [0.007], P = 0.002), LDL cholesterol (0.019 [0.008], P = 0.02; 0.025 [0.011], P = 0.02), and age (0.010 [0.004], P = 0.004; 0.012 [0.005], P = 0.01), independent of other variables. Mean/maximal cIMT was greater in males (0.023 [0.006]...