Does β-Cell Autoimmunity Play a Role in Cystic Fibrosis–Related Diabetes? Analysis Based on the German/Austrian Diabetes Patienten Verlaufsdokumentation Registry

Abstract

OBJECTIVEResearch on b-cell autoimmunity in cystic fibrosis (CF)-related diabetes (CFRD) is still rare. We aimed to analyze the frequency of b-cell autoimmunity and the influence on age at diabetes onset, insulin requirement, type of insulin therapy, and hypoglycemic or ketoacidotic events in patients with CFRD compared with antibody-negative patients with CFRD in the Diabetes Patienten Verlaufsdokumentation (DPV) registry. RESEARCH DESIGN AND METHODSWe analyzed data of 837 patients with CFRD in the German/Austrian DPV database by multivariable mixed-regression modeling. RESULTSIn our cohort, 8.5% of patients with CFRD (n = 72) were found to be b-cell antibody positive. There was a female preponderance in this patient group: 65.3 vs. 57.6%. Diabetes onset (median [interquartile range]) was earlier (14.00 [10.15-15.90] vs. 16.10 [13.50-21.20] years; P < 0.005), and insulin dose/kg body weight was higher (0.95 [0.61-1.15] vs. 0.67 [0.33-1.04] IU/kg; P < 0.05). There were also differences in the type of insulin treatment. Insulin pump therapy was used significantly more often in patients with CFRD with b-cell autoimmunity (18.2 vs. 6.4%; P < 0.05). The differences for multiple daily injections (ICT) and conventional therapy (CT) were not significant (ICT: 67.7 vs. 79.0%; CT: 15.2 vs. 14.6). Oral antidiabetic agents were rarely used in both groups. Rate of severe hypoglycemia with coma and rate of ketoacidosis were higher in antibody-positive patients (hypoglycemia with coma: 8.0 vs. 1.4, P < 0.05; ketoacidosis: 9.3 vs. 0.9, P < 0.05). CONCLUSIONSPresence of b-cell autoantibodies in our cohort of patients with CFRD (8.5%) appeared to be greater than in the general population and was associated with female sex, earlier onset of diabetes, and higher insulin requirement. Insulin pump therapy was used significantly more often in patients with b-cell antibodies. Severe hypoglycemia and ketoacidosis were significantly more frequent in CFRD with b-cell autoimmunity compared with b-cell antibody-negative patients with CFRD.

Patient and Disease Characteristics Associated With the Presence of Diabetes Mellitus in Adults With Chronic Pancreatitis in the United States

“…We also did not assess whether beta cell autoimmunity (type 1 diabetes) was a contributor to diabetes development in this cohort; however, interestingly, 1 in every 106 study participants was diagnosed with DM at age <21 years, fourfold higher than the expected rate of childhood onset diabetes of 1 in every 418 children in the United States in 2009 (23), even though most were not yet diagnosed with CP at time of childhood onset DM. Future studies—including those emerging from the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) research consortium—will be necessary to better define diagnostic protocols to accurately classify type 3c vs. type 2 DM, and to explore whether markers of β-cell autoimmunity are more prevalent in those with CP, as has been reported recently for cystic fibrosis-related diabetes (24), and whether markers such as pancreatic polypeptide can adequately distinguish true type 3c vs. classic type 2 DM in those with CP.…”

Islet Interleukin-1β Immunoreactivity Is an Early Feature of Cystic Fibrosis That May Contribute to β-Cell Failure

“…susceptibility alleles are not observed with greater frequency, although studies differ with respect to the prevalence of islet autoantibodies (6,7). Physiologically, CFRD appears to have more in common with type 2 diabetes.…”

Characteristics of cystic fibrosis‐related diabetes: Data from two different sources the European cystic fibrosis society patient registry and German/Austrian diabetes prospective follow‐up registry

“…In detail, 95 198 patients with type 1 diabetes, 271 798 with type 2 diabetes, and 10 392 with other types of diabetes, including 757 patients with CFRD. Previously, the DPV group published several reports dealing with various aspects of CFRD . Contrary to the definition of CFRD in the ECFSPR, in DPV all patients with CFRD had a clinical diagnosis according to the World Health Organization (WHO)/American Diabetes Association (ADA) classification.…”