Diabetes in Cystic Fibrosis: Multicenter Screening Results Based on Current Guidelines

Abstract

BackgroundPublished estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations. Therefore, we evaluated age-dependent occurrence of glucose abnormalities and associated risk factors in CF patients who participated in a multicenter screening program using oral glucose tolerance tests (OGTT).MethodsBetween 2001 and 2010, 43 specialized CF centers from Germany and Austria serially performed 5,179 standardized OGTTs in 1,658 clinically stable, non-pregnant CF patients with no prior steroid medication or lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD) diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards models were created to elucidate the influence of sex or underweight.ResultsAt baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI 1.23–10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22–3.98] times higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11–1.71]) and IFG+IGT (1.43 [1.11–1.83]), and in males also for DGT (1.49 [1.09–2.04]).Conclusions/SignificanceIf confirmation of diabetes by a second test is required, as recommended in current guidelines, age at CFRD diagnosis was higher compared to most previous studies. However, known risk factors for glucose abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test is important for a consistent diagnosis of CFRD.

ISPAD Clinical Practice Consensus Guidelines 2018: Management of cystic fibrosis-related diabetes in children and adolescents

“…Early diabetes is characterized by normal fasting glucose levels, but over time fasting hyperglycemia develops. Isolated‐impaired fasting glucose (IFG) is sometimes present in persons with CF but the significance is unclear …”

Diabetes mellitus in pediatric solid organ recipients without and with cystic fibrosis: An analysis from the German-Austrian diabetes database (Diabetes Patienten Verlaufsdokumentation)

“…PTDM patients with CF had the lowest weight and BMI z‐scores. From our data on CF patients needing SOT, however, it is difficult to determine whether increased disease severity affected weight development or low weight was a risk factor for SOT …”

“…PTDM and CFRD share some common aspects like reduced first‐phase insulin secretion, elements of insulin resistance, and the absence of antibodies . Underweight is a significant risk factor for the development of diabetes in CF . The incidence of thinness is greatly increased in CF after SOT and might further aggravate the risk of diabetes development …”

“…9 Underweight is a significant risk factor for the development of diabetes in CF. 11,12 The incidence of thinness is greatly increased in CF after SOT and might further aggravate the risk of diabetes development. 13 The diagnosis of diabetes in SOT patients may be delayed or the onset of diabetes may remain unrecognized.…”

Diagnosing cystic fibrosis-related diabetes: current methods and challenges

“…However, this recommendation is not always achieved and may delay the diagnosis [88]. At the time of OGTT patients are required to have consumed high energy, high carbohydrate diet prior to a prolonged period of fasting.…”