Insulin Secretion in Type 1 Diabetes

Steele, Chynna; Hagopian, William; Gitelman, Stephen E.; Masharani, Umesh; Cavaghan, Melissa K.; Rother, Kristina I.; Donaldson, David; Harlan, David M.; Bluestone, Jeffrey A.; Herold, Kevan C.

doi:10.2337/diabetes.53.2.426

Cited by 152 publications

(142 citation statements)

References 51 publications

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“…We found that patients with autoantibody negative diabetes have a highly preserved beta cell function after 20 years in contrast to antibody positive patients. This is well in line with what has previously been described for T1D [1,2] but in contrast to the general view of progressive beta cell damage in T2D [3].…”

Section: Discussionsupporting

confidence: 92%

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No signs of progressive beta cell damage during 20 years of prospective follow-up of autoantibody-negative diabetes

et al. 2011

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Aims Both type 1 (T1D) and type 2 (T2D) diabetes are considered to be associated with different degrees of progressive beta cell damage. However, few long term studies have been made. Our aim was to study the clinical course of 20 years of diabetes disease, including diabetes progression, co-morbidity and mortality in a prospectively studied cohort of consecutively diagnosed diabetic patients.Methods Among all 233 patients diagnosed with diabetes during 1985-1987 in Malmö, Sweden, 50 of 118 surviving patients were followed-up after 20 years. The age at diagnose was 42.323.1 and 57.513.6 yrs for antibody positive and antibody negative patients, respectively. HbA1c and plasma lipids were analysed with regard to metabolic control.Results Islet antibody negative patients at diagnosis had highly preserved C-peptide levels after 20 years in contrast to antibody positive patients (antibody-negative: C-peptide 0yrs 0.780.47 and 20yrs 0.700.46 (nmol/l), p=0.51 and antibody-positive: C-peptide 0yrs 0.330.35 and 20yrs 0.100.18; p<0.001. Islet antibodies but not age, BMI or C-peptide at diagnosis were predictors of C-peptide levels at 20 years when analysed by logistic regression (p<0.05). HbA1c did not differ between the groups after 20 years. The 20-year mortality was higher among antibody-negative patients, dependent on the higher age at diagnosis in this group (number of deaths: antibody-positive: 18 of 56 vs. antibody-negative: 109 of 188, p<0.001). Of the deceased, 79 % had died from diseases or complications that may be associated to diabetes. ConclusionWe found no progressive beta cell damage in autoantibody negative diabetes at a 20 year follow-up of the clinical course of diabetes.

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Section: Discussionsupporting

confidence: 92%

“…Type 1 and type 2 diabetes are different in terms of aetiology and clinical course but have both been proposed to be associated with progressive beta cell damage [1][2][3]. However, this notion has been questioned.…”

Section: Introductionmentioning

confidence: 99%

No signs of progressive beta cell damage during 20 years of prospective follow-up of autoantibody-negative diabetes

et al. 2011

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“…This disease has an insipid beginning and may take years before it can be recognized as clinical hyperglycemia. While it is traditionally thought that the majority of BCM is destroyed at the time of presentation with diabetes, several recent studies have suggested that there may be significant residual insulin-secretory capacity on diagnosis [3]. Moreover, there is a long preclinical period during which an immunologic assault is believed to occur on the islets of Langerhans and that hyperglycemia only develops when a critical mass of β cells is lost and insulin requirement increases.…”

Section: Introductionmentioning

confidence: 99%

“…Alloxan, however, is a well-known diabetogenic agent itself; thus, the clinical utility of this approach remains unproven [15]. Dithizone and sulfonylurea receptor ligands (e.g., 3 H glibenclamide) have been studied as possible imaging agents [16], but some show broad tissue distributions of uptake contraindicating feasibility [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Visualizing pancreatic β-cell mass with [11C]DTBZ

Simpson

Souza

Witkowski

et al. 2006

Nuclear Medicine and Biology

109

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Abstractβ-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, β-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by β cells, with [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocininduced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in β cells with the use of [ 11 C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes.

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“…In type 1 diabetes, autoimmune destruction of pancreatic beta cells leads to absolute deficiency of insulin secretion with subsequent hyperglycaemia [1]. It is commonly assumed that type 1 diabetes becomes clinically apparent when the remaining beta cell mass (BCM) has decreased to 5-20% [2,3]. Recent studies, however, suggest that patients with type 1 diabetes may still have a large amount of remaining beta cells [4]; in some patients loss of BCM was less than 50% [5].…”

Section: Introductionmentioning

confidence: 99%

Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

et al. 2014

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Aims/hypothesis A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagonlike peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals. MethodsThe targeting of 111 In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq 111 In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq 111 In-labelled exendin in five patients with type 1 Maarten Brom and Wietske Woliner-van der Weg contributed equally to this study. Diabetologia (2014) 57:950-959 DOI 10.1007 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images. Results In rats, 111 In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes. Conclusions/interpretation These studies indicate that 111 Inlabelled exendin may be suitable for non-invasive quantification of BCM.

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Insulin Secretion in Type 1 Diabetes

Cited by 152 publications

References 51 publications

No signs of progressive beta cell damage during 20 years of prospective follow-up of autoantibody-negative diabetes

No signs of progressive beta cell damage during 20 years of prospective follow-up of autoantibody-negative diabetes

Visualizing pancreatic β-cell mass with [11C]DTBZ

Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

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