Weight Gain in Early Life Predicts Risk of Islet Autoimmunity in Children With a First-Degree Relative With Type 1 Diabetes

Couper, Jennifer; Beresford, Sarah; Hirte, Craig; Baghurst, Peter; Pollard, A.C.; Tait, Brian D.; Harrison, Leonard C.; Colman, Peter G

doi:10.2337/dc08-0821

Cited by 88 publications

(79 citation statements)

References 22 publications

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“…The ultimate result is increased insulitis and beta cell apoptosis and, in genetically susceptible individuals, progression to clinical type 1 diabetes transition to a full adaptive immune response [6]. If this hypothesis is correct, it may explain the parallel increase in the prevalence of childhood obesity and type 1 diabetes [55] and the predisposing role for weight gain in early life and insulin resistance in childhood/adolescence for the risk for islet autoimmunity and type 1 diabetes [56,57].…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

2012

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Protein synthesis is increased by several-fold in stimulated pancreatic beta cells. Synthesis and folding of (pro)insulin takes place in the endoplasmic reticulum (ER), and beta cells trigger the unfolded protein response (UPR) to upgrade the functional capacity of the ER. Prolonged or excessive UPR activation contributes to beta cell dysfunction and death in type 2 diabetes, but there is another side of the UPR that may be of particular relevance for autoimmune type 1 diabetes, namely, the crosstalk between the UPR and innate immunity/inflammation. Recent evidence, discussed in this review, indicates that both saturated fats and inflammatory mediators such as cytokines trigger the UPR in pancreatic beta cells. The UPR potentiates activation of nuclear factor κB, a key regulator of inflammation. Two branches of the UPR, namely IRE1/XBP1s and PERK/ATF4/CHOP, mediate the UPR-induced sensitisation of pancreatic beta cells to the proinflammatory effects of cytokines. This can contribute to the upregulation of local inflammatory mechanisms and the aggravation of insulitis. The dialogue between the UPR and inflammation may provide an explanation for the parallel increase in the prevalence of childhood obesity and type 1 diabetes.

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Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

2012

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“…Obesity and insulin resistance may accelerate development of T1D in young predisposed individuals (9)(10)(11). On the other hand, management of T1D in severely obese individuals can be a challenge, with possible deleterious anabolic effects of intensive insulin therapy on body weight, which further exacerbates insulin resistance (11,12).…”

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confidence: 99%

Bariatric Surgery in Obese Patients With Type 1 Diabetes

et al. 2016

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OBJECTIVEThere is a paucity of data on the impact of bariatric surgery in type 1 diabetes (T1D). The aim of this review was to quantify the overall effects of bariatric surgery in obese patients with T1D. METHODSWe searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar from their inception to December 2015 to identify all relevant studies of bariatric surgery in adult obese patients with T1D. RESULTSThe review included 17 studies with 107 individuals, including 10 case series and 7 case reports. Overall, the dominant procedure was gastric bypass (n = 70; 65%). All studies reported a significant reduction in excess weight. A significant reduction in weight-adjusted daily insulin requirements was shown in all case series except one. Pooled mean 6 SD of pre-and postoperative glycated hemoglobin (HbA 1c ) for the entire cohort with available data (n = 96) was 8.4 6 1.3% and 7.9 6 1.1%, respectively (P = 0.01). In addition to common postoperative complications, profound glycemic changes (diabetic ketoacidosis and hypoglycemia) and gastrointestinal dysmotility symptoms (prolonged ileus and acute gastric remnant dilation) have been reported. No surgical mortality was reported. CONCLUSIONSBariatric surgery leads to significant weight loss in severely obese patients with T1D and results in a significant improvement in insulin requirements and glycemic status. The favorable metabolic effects of bariatric surgery may facilitate medical management of and cardiovascular risk reduction in T1D in the setting of severe obesity. Diabetic ketoacidosis and hypoglycemia are potentially serious complications. Short-term results of bariatric surgery in patients with T1D are encouraging, but larger and longer-term studies are needed.Patients with type 1 diabetes (T1D) constitute about 5-10% of all cases of diabetes. Large epidemiologic studies indicate that the worldwide incidence of T1D has been increasing in recent decades (1,2). T1D is associated with serious long-term complications that affect the cardiovascular system, eyes, kidneys, and nervous system and predispose to certain infections (3), which can lead to substantial increased mortality rates compared with the nondiabetic population (4,5).The prevalence of obesity among youth with T1D in the U.S. was found to be 12.6% (6). Overall, approximately 50% of patients with T1D are currently obese or overweight, and between 20 and 40% meet the criteria of metabolic syndrome, depending on the study population and the diagnostic criteria used (7). Excessive

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“…Insulin resistance is usually normal in people with Type 1 diabetes but this is a complicated and unresolved matter [14,15].…”

Section: Aetiology Of Human Type 1 and Type 2 Diabetesmentioning

confidence: 99%

Animal Models for the Evaluation of the Cardiometabolic Therapeutic Potential of Traditional Chinese and Natural Product Medicines

Cao¹,

Kamato²,

Pj³

2017

IJDVR

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Weight Gain in Early Life Predicts Risk of Islet Autoimmunity in Children With a First-Degree Relative With Type 1 Diabetes

Cited by 88 publications

References 22 publications

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

Bariatric Surgery in Obese Patients With Type 1 Diabetes

Animal Models for the Evaluation of the Cardiometabolic Therapeutic Potential of Traditional Chinese and Natural Product Medicines

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