The Connection Between Childhood Pancreatitis and Adult-Onset Diabetes
Research published in Diabetes Care has helped elucidate the relationship between acute pancreatitis and incident diabetes.1
The authors of a nationwide, population-based study of 1,802,110 Israeli adolescents (mean age 17.4 years) with available data linked to the Israeli National Diabetes Registry found that history of acute pancreatitis in childhood with normal pancreatic function in late adolescence is associated with incident type 2 diabetes risk, especially during young adulthood.
Their findings indicated that 13 of 281 (4.6%) patients with resolved pancreatitis developed incident diabetes compared with 44,463 of 1,801,716 (2.5%) among patients without history of pancreatitis. Of note, no cases of diabetes that developed among patients with resolved pancreatitis were identified as type 1 diabetes.
Following adjustment for age, sex, and birth year, the odds ratio (OR) for the association between resolved acute pancreatitis and incident diabetes was 2.23. Findings remained significant following further adjustments for baseline body mass index (BMI) and sociodemographic confounders (OR 2.10).
Childhood pancreatitis was found to be associated with a diabetes diagnosis at a younger age, the researchers said. Approximately 92% of patients with history of childhood pancreatitis who later developed diabetes received their diabetes diagnosis before age 40 years compared with 47% of patients without history of pancreatitis. This association strengthened after limiting the study sample to patients with unimpaired health or normal BMI at baseline.
Consultant360 discussed these findings further with lead author Gilad Twig, MD, PhD, from the Department of Military Medicine at Hebrew University and medical corps of the Israel Defense Forces.
Consultant360: What led you to hypothesize a potential relationship between childhood pancreatitis and incident diabetes in adulthood?
Gilad Twig: Residual damage following acute inflammatory insult may result with reduced activity of the β-cells to support normal glucose levels. The occurrence of β-cell damage during somatic growth might also reduce replication capacity of β-cells and the number of existing islets, as the contribution of new islet formation to the overall increase in β-cell mass from birth to adolescence was estimated to be only 12%. Thus, it could be that inflammation of the exocrine pancreas in pancreatitis collaterally damage β-cells of the endocrine islets, resulting in a reduced islet mass. The fact that the acute insult seems to be clinically resolved, as judged by standard clinical measures, may not necessarily reflect absence of some residual damage to β-cell mass, especially in the first years after injury.
C360: The results of your study showed that, in patients with resolved pancreatitis who developed incident diabetes in adulthood, none of these cases were identified as type 1 diabetes. Was this finding anticipated or surprising?
GT: The observation that none of these cases were identified as type 1 diabetes is in accordance with our primary research hypothesis. We found that the average age of diabetes diagnosis was younger by 4 years among those with a history of acute pancreatitis, even when obesity status was carefully controlled. This may suggest a lower capacity to overcome the individual’s underlying degree of insulin resistance, and that a shorter duration is sufficient to induce β-cells failure and hyperglycemia, supporting the hypothesis that diabetes in young adulthood may be more strongly dependent on β-cell failure than the onset of type 2 diabetes later in life.
C360: How might the findings from your study aid in risk stratification among patients with a history of acute pancreatitis in childhood?
GT: We suggest that history of pancreatitis should be considered as a risk factor, especially during young adulthood. This may be of special importance in individuals with other risk factors.
C360: What clinical takeaway do you hope endocrinologists and other clinicians treating diabetes learn from your study?
GT: Patients with history of acute pancreatitis may require a tighter follow-up and possibly a more aggressive control of other risk factors. Maintaining normal weight is likely central, as most patients with history of pancreatitis were overweight or obese at the time of their diabetes diagnosis.
C360: What is the next step in terms of future research?
GT: We focus our efforts on understanding the critical risk factors for early onset type 2 diabetes, or diabetes onset before age 40 years, as the prevalence of diabetes in this age group has increased disproportionately. There is compelling evidence that incidence of diabetes at such a young age is not only associated with higher financial burden, but also with higher rates of diabetes complications and worse clinical outcomes.
Bendor CD, Bardugo A, Zucker I, et al. Childhood pancreatitis and risk for incident diabetes in adulthood. Diabetes Care. 2019;42(11). https://doi.org/10.2337/dc19-1562.