Why were we wrong for so long? The pancreas of type 1 diabetic patients commonly functions for decades

Faustman, Denise L.

doi:10.1007/s00125-013-3104-9

Cited by 14 publications

(13 citation statements)

References 18 publications

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“…It is of historical interest to point out that it had been known since 1902 that occasionally the examination of the pancreas at autopsy of a patient with long‐standing diabetes revealed islets of Langerhans structures. Unfortunately, without accompanying functional data, those islet structures were not known to be functional and thus insulin production was thought to cease for the majority of patients . Our data now additionally show that, not only does C‐peptide production commonly persist, but that prolonged C‐peptide production is more frequent in people with Type 1 diabetes with onset in adulthood rather than in childhood.…”

Section: Discussionmentioning

confidence: 73%

Low levels of C‐peptide have clinical significance for established Type 1 diabetes

Kühtreiber

Washer

Hsu³

et al. 2015

Diabet. Med.

114

119

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Aim To determine whether the low C-peptide levels (<50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. Methods We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n=1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control (n=1273), as well as diabetic complications (n=324) and presence of hypoglycaemia (n=323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. Results C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P<0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P=0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c (P<0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild (P=0.049) or moderate (P=0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol (P<0.0001). Conclusions Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes.

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Section: Discussionmentioning

confidence: 73%

Low levels of C‐peptide have clinical significance for established Type 1 diabetes

Kühtreiber

Washer

Hsu³

et al. 2015

Diabet. Med.

114

119

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“…It has been estimated that approximately only 10% to 30% of normal β-cells exist at the time of clinical diagnosis. [19][20][21] However, our data indicate that β-cell function has been underestimated in a large proportion of patients. Similar results were reported by the T1D China Study Group, which found that more than 76% of 3475 newly diagnosed Chinese T1D patients had FCP levels greater than 200 pM.…”

Section: Discussionmentioning

confidence: 59%

“…There have been few reports on the distribution of β‐cell function in newly diagnosed T1D patients thus far. It has been estimated that approximately only 10% to 30% of normal β‐cells exist at the time of clinical diagnosis . However, our data indicate that β‐cell function has been underestimated in a large proportion of patients.…”

Section: Discussionmentioning

confidence: 64%

“…27 Intriguingly, more than 40 years after diagnosis, patients could still maintain a nonfasting C-peptide concentration of >200 pM. These observations, together with those of the widely known Joslin 50-year Medalist Study, 18 the network for Pancreatic Organ Donors (nPOD)-supported studies, 28 and a series of other studies, 19,[29][30][31] provide strong support for the existence of endogenous C-peptide secretion in patients with longduration T1D.…”

Section: Discussionmentioning

confidence: 77%

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Tapering decay of β‐cell function in Chinese patients with autoimmune type 1 diabetes: A four‐year prospective study

Jin

Huang

et al. 2019

Journal of Diabetes

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Background This study investigated the natural progression of β‐cell function in Chinese autoimmune type 1 diabetic (T1D) patients and clarified factors possibly influencing the course of the disease. Methods The natural progression of β‐cell function of 325 newly diagnosed Chinese autoimmune T1D patients was assessed by fasting and postprandial C‐peptide (FCP and PCP, respectively) levels. β‐Cell function failure was defined as FCP <50 pM and PCP <100 pM, whereas preserved β‐cell function was defined as FCP >200 pM or PCP >400 pM. β‐Cell function that did not meet these criteria was described as residual. Results At initial recruitment, 33.3% of patients had β‐cell function failure, whereas 41.0% and 25.8% of patients had preserved or residual β‐cell function, respectively. The percentage of patients who developed β‐cell function failure during follow‐up at 12, 24, 36, and 48 months after recruitment to the study was 55.8%, 75.6%, 86.7%, and 92.7%, respectively. Moreover, the slope of the β‐cell function curve decreased over time, indicating that the pattern of its decline was non‐linear and tapering. Seven percent of patients did not develop β‐cell function failure within 4 years after diagnosis. Patients with lower initial FCP levels were more likely to develop β‐cell function failure. Conclusions Chinese autoimmune T1D patients have considerable residual β‐cell function at initial diagnosis, and the manner of progression of β‐cell function failure is non‐linear with a tapering decay rate. Furthermore, initial FCP levels may predict β‐cell function failure in Chinese autoimmune T1D patients.

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“…Nevertheless in vivo monitoring of beta cell mass will be an important technique to document beta cell mass loss in newly diagnosed type 1 diabetic patients or autoantibody- positive individuals at high risk of developing overt diabetes. Sensitive C-peptide assays indicate that residual beta cell mass in type 1 diabetic patients may be higher than originally estimated [25], so that accurate quantification of this mass would be a good indicator of possible beta cell regeneration or regain of secretory function.…”

Section: Perspectives and Challengesmentioning

confidence: 99%

Inside the pancreas: progress and challenges of human beta cell mass quantification

Tiedge

2014

Diabetologia

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The accurate quantification of beta cell mass in humans is one of the key challenges in understanding the role of beta cell loss and dysfunction in the pathogenesis of diabetes mellitus. Autopsy studies indicate that beta cell loss is not only a hallmark of autoimmune diabetes but also plays a pivotal role in type 2 diabetes, owing to the toxic effects of lipids, glucose and cytokines. Thus, there is an urgent need for non-invasive clinical techniques for beta cell mass quantification, which should be optimally integrated into standard diagnostic equipment in hospitals. In this issue of Diabetologia (Brom et al DOI 10.1007/s00125-014-3166-3) it is reported that single photon emission computed tomography (SPECT) data with 111 indium-labelled glucagon-like peptide-1 (GLP-1) receptor agonist exendin-3 correlate with the morphometric analysis of beta cell mass in a rat model of alloxan-induced diabetes. With this validation, the authors were able to demonstrate a significant loss of beta cell mass in C-peptidenegative type 1 diabetic patients. Thus, The perfect tracer for non-invasive quantification of beta cell massTracers are chemical compounds with high affinity to specific cell types either through binding to cell surface structures or intracellular accumulation. Coupling with paramagnetic particles, radioisotopes or fluorophores allows in vivo detection by MRI, single photon emission computed tomography (SPECT) or photonsensors. Irrespective of the detection method, the tracer used for labelling beta cells must have certain key features for in vivo quantification of beta cell mass, as detailed in the text box below.• A high sensitivity and affinity for specific structures of the beta cell -through binding to surface structures (e.g. GLP-1 derivatives, DTBZ or single chain antibodies) or -tracer enrichment in beta cells by metabolism (e.g. fluorodeoxyglucose, sulfonylurea derivatives) • No toxic effects • Effective labelling of a high proportion of beta cell mass • Rapid tracer washout to repeat the diagnostic process

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Why were we wrong for so long? The pancreas of type 1 diabetic patients commonly functions for decades

Abstract: The type 1 diabetes field has held firm to the dogma that the pancreas is no longer viable, and thus incapable of producing insulin, within 1 to 2 years of diagnosis for the majority of patients. A new study in this issue of Diabetologia

Cited by 14 publications

References 18 publications

Low levels of C‐peptide have clinical significance for established Type 1 diabetes

Low levels of C‐peptide have clinical significance for established Type 1 diabetes

Tapering decay of β‐cell function in Chinese patients with autoimmune type 1 diabetes: A four‐year prospective study

Inside the pancreas: progress and challenges of human beta cell mass quantification

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