Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians, with a worldwide prevalence of 1 in 2500 live births [
1]. Patients with CF may develop numerous disease-related comorbidities, the most common is diabetes mellitus which manifests after a progressive reduction in glucose tolerance [
2]. The pathophysiology of CF-related diabetes (CFRD) is extremely complex. As in type 1 diabetes mellitus (T1DM), progressive loss of pancreatic islet cells occurs in CFRD; however, unlike T1DM, beta cell autoimmunity markers are negative and the onset of diabetic ketoacidosis (DKA) is extremely rare since there is a minimal insulin production. As in type 2 diabetes mellitus (T2DM), insulin resistance occurs, linked to frequent infective pulmonary exacerbations or use of glucocorticoid agents. Glucose homeostasis is further disrupted by the requirement for high caloric intake, gut abnormalities and liver disease resulting in progressive insulin deficiency [
3]. Since CFRD is often clinically silent, and glycosylated haemoglobin (HbA1c) is not considered a diagnostic tool, due to its small reliability with the glucose impairment, routine screening by oral glucose tolerance test (OGTT) is recommended. The OGTT is the only accepted screening test, starting from ten years of life and performed in stable baseline health conditions. Some authors suggested to extend OGTT test as screening of early glucose derangements under 10 years of age also [
4,
5]. According to the American Diabetes Association (ADA) [
6] and the ISPAD guidelines [
7], diagnosis of diabetes can be made, during acute illnesses, when fasting plasma glucose (FPG) levels ≥126 mg/dL (≥ 7.0 mmol/L) or plasma glucose ≥200 mg/dL (≥ 11.1 mmol/L) persist for more than 48 h. During a period of stable baseline health, if FPG level is ≥126 mg/dL (≥7.0 mmol/L) or ≥ 200 mg/dL (≥11.1 mmol/L) at time (T) 120 of the OGTT; or if random blood glucose is
> 200 mg / dL (
> 11.1 mmol / L) on 2 or more occasions with symptoms, diagnosis of CFRD-fasting hyperglycemia plus (CFRD-FH+) and less (CFRD-FH-) can be respectively performed. Normal glucose tolerance (NGT) is defined by fasting blood glucose < 100 mg/dL (< 5.5 mmol/ L) or < 140 mg/dL (< 7.7 mmol/ L) at T120 of OGTT. The OGTT may reveal other prediabetic glucose alterations: impaired glucose tolerance (IGT), if blood glucose
> 140 mg/dL (
> 7.7 mmol/l) and < 200 mg/dL (< 11.1 mmol/l) at T120 and Indeterminate Glucose Tolerance (INDET) in NGT patients with one or more glucose values ≥200 mg/dL (≥11.1 mmol/L) at T30, T60 and/or T90 during OGTT [
7]. Children with IGT or INDET compared to those with NGT show increased risk to develop CFRD [
8,
9]. CFRD can also occur early in childhood [
10] with increased prevalence as patients get older [
2]. An insidious decline in clinical status of patients with CF showing early glucose alterations has been described in the years before the diagnosis of CFRD [
11‐
14]. In children the decline in pulmonary function and nutritional parameters, correlated with insulin insufficiency, appear long before glucose levels are high enough to diagnose CFRD [
15,
16] as in adults where prediabetes has a negative impact on the number of respiratory exacerbations, on the lung function and on the nutritional status even 2–4 years before CFRD diagnosis [
17‐
19]. In IGT patients the drop in forced expiratory rate in the first second (FEV1) after four years of follow-up is higher as compared to NGT [
11]. Insulin secretion in IGT is significantly lower than that of NGT patients, and the FEV1 positively correlates with beta cell function, as assessed by insulin resistance index HOMA% B [
20]. The condition of insulin-deficiency determines an increase in protein catabolism [
21]. Moreover, a more active inflammatory state (higher fibrinogen level) has been demonstrated in patients with IGT [
20], therefore this may contribute to augment the pulmonary exacerbations. According to ISPAD guidelines [
7] insulin therapy is the only recommended medical treatment for CFRD and evidence that insulin treatment may have an advantage on clinical outcomes of CF children showing early glucose derangements is scarce. In our previous report we showed that insulin treatment could represent an important strategy to improve lung function and BMI z-score, and to reduce pulmonary exacerbations in patients with CF showing prediabetic glucose alterations [
14,
22]. We present a case of an adolescent with CFRD onset during the COVID-19 pandemic lockdown, but already treated with glargine basal insulin due to a prediabetic condition diagnosed four years earlier.