Age‐dependent decline of β‐cell function in type 1 diabetes after diagnosis: a multi‐centre longitudinal study

Barker, Adam; Lauria, Angelo; Schloot, Nanette C.; Hosszúfalusi, Nóra; Ludvigsson, Johnny; Mathieu, Chantal; Mauricio, Dı́dac; Nordwall, Maria; Schueren, Bart Van der; Mandrup-Poulsen, Thomas; Scherbaum, Werner A.; Weets, Ilse; Gorus, Frans; Wareham, Nicholas J.; Leslie, Richard; Pozzilli, Paolo

doi:10.1111/dom.12216

Cited by 90 publications

(116 citation statements)

References 41 publications

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“…Similarly, combined data from TrialNet studies described insulin secretion in adults and pediatric subjects entered in type 1 diabetes clinical trials, but only within 2 years of diagnosis (8). As in our current study, Barker et al (15) reported differences in C-peptide according to age at diagnosis. While involving a large number of subjects, that study involved only subjects within 5 years of diagnosis and used noncentralized measurements of fasting Cpeptide.…”

Section: Discussionsupporting

confidence: 73%

“…This study included a highly selective cohort of survivors from an era prior to present management paradigms and thus may not be characteristic of a general, current type 1 diabetes population. Others have also reported on the presence of residual insulin secretion in type 1 diabetes; these studies tested selected cohorts (11)(12)(13), small numbers of participants (14), or individuals with a limited duration of disease (15). In addition to the presence of diabetes-related autoantibodies, history of other autoimmune diseases, and family history of type 1 diabetes, the absence or presence of endogenous insulin secretion is often used to classify patients as having type 1 diabetes versus type 2 diabetes.…”

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confidence: 99%

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Prevalence of Detectable C-Peptide According to Age at Diagnosis and Duration of Type 1 Diabetes

Davis¹,

et al. 2014

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OBJECTIVE It is generally accepted that complete β-cell destruction eventually occurs in individuals with type 1 diabetes, which has implications for treatment approaches and insurance coverage. The frequency of residual insulin secretion in a large cohort of individuals at varying ages of diagnosis and type 1 diabetes duration is unknown. RESEARCH DESIGN AND METHODS The frequency of residual insulin secretion was determined by measurement of nonfasting serum C-peptide concentration in 919 individuals with type 1 diabetes according to prespecified groups based on age at diagnosis and duration of disease (from 3 to 81 years' duration). Stimulated C-peptide was measured in those with detectable nonfasting values and a group of those with undetectable values as control. RESULTS The overall frequency of detectable nonfasting C-peptide was 29%, decreasing with time from diagnosis regardless of age at diagnosis. In all duration groups, the frequency of C-peptide was higher with diagnosis age >18 years compared with ≤18 years. Nineteen percent of those with undetectable nonfasting C-peptide were C-peptide positive upon stimulation testing. CONCLUSIONS The American Diabetes Association’s definition of type 1 diabetes as “usually leading to absolute insulin deficiency” results in clinicians often considering the presence of residual insulin secretion as unexpected in this population. However, our data suggest that residual secretion is present in almost one out of three individuals 3 or more years from type 1 diabetes diagnosis. The frequency of residual C-peptide decreases with time from diagnosis regardless of age at diagnosis, yet at all durations of disease, diagnosis during adulthood is associated with greater frequency and higher values of C-peptide.

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Section: Discussionsupporting

confidence: 73%

mentioning

confidence: 99%

Prevalence of Detectable C-Peptide According to Age at Diagnosis and Duration of Type 1 Diabetes

Davis¹,

et al. 2014

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“…Rapid weight gain during the first years of life has been found to increase the incidence of type 1 diabetes (7) and a number of studies have also shown a positive correlation between the year of onset of type 1 diabetes and BMI (8,9,10). More recently, we have shown that the decline in fasting C-peptide is more rapid in those patients with an earlier age of onset of type 1 diabetes, and that the factors influencing the decline in fasting C-peptide following diagnosis differ substantially according to the age of onset (11). Several studies have reported data showing that the age of onset of type 1 diabetes is inversely related with BMI, with children diagnosed at younger ages typically being heavier than those diagnosed later (9,12,13,14).…”

Section: Introductionmentioning

confidence: 67%

“…In each study centre, type 1 diabetes was diagnosed according to ADA and WHO criteria. A detailed description of the cohort has been published elsewhere (11).…”

Section: Subjectsmentioning

confidence: 99%

BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children

Lauria

Barker

Schloot

et al. 2015

European Journal of Endocrinology

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Objective: Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. Design: Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. Methods: Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (!5 years, nZ126; O5 years !10 years, nZ295; O10 years !18 years, nZ421; O18 years, nZ410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. Results: In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed O18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (b 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m 2 higher baseline BMI (PZ0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (bZ0.026, 95% CIZ0.0097, 0.042; PZ0.002). Conclusions: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of b-cell function in type 1 diabetes.

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“…Classic type 1 diabetes clinical progression is thought to eventually reach a state of absolute insulin deficiency, and the rate at which this state is reached is dependent on many factors, most notably glycemic control and age at onset; however, more literature on long-term insulin microsecretors is emerging (2,3,10). We wondered why this patient had such severe comorbidities, presumed rapid disease progression, and early death despite the presence of insulin-positive b-cells, appreciable C-peptide, and HLA associated with protection against type 1 diabetes.…”

mentioning

confidence: 99%

Presumptive Type 1 Diabetes With Comorbidities and Rapid Progression Despite Numerous Insulin-Positive Islets

et al. 2016

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Age‐dependent decline of β‐cell function in type 1 diabetes after diagnosis: a multi‐centre longitudinal study

Cited by 90 publications

References 41 publications

Prevalence of Detectable C-Peptide According to Age at Diagnosis and Duration of Type 1 Diabetes

Prevalence of Detectable C-Peptide According to Age at Diagnosis and Duration of Type 1 Diabetes

BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children

Presumptive Type 1 Diabetes With Comorbidities and Rapid Progression Despite Numerous Insulin-Positive Islets

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