Glucose tolerance in cystic fibrosis.

Abstract

Glucose tolerance was evaluated in 356 living and dead patients with cystic fibrosis who were recorded at the Danish Cystic Fibrosis Centre. Twenty two patients (6%) were treated elsewhere, 25 (7%) were unable, unwilling or too young (age <2 years) to participate; 309 patients (87%) were therefore eligible for the study of whom 99 (32%) were dead and 210 (68%) were alive. Of the dead patients, 13 also had diabetes mellitus (13%). Of the living patients (median age 14 years, range 2-40), nine (4%) were known to have diabetes and all were being treated with insulin. In the remaining 201 patients an oral glucose tolerance test (1-75 g/kg body weight, maximum 75 g) was carried out. A total of 155 patients (74%) had normal glucose tolerance, 31 (15%) had impaired glucose tolerance, and 15 (7%) had diabetes mellitus according to the WHO criteria. The percentage of glycated haemoglobin (HbA1j) (reference range 4.1-6-4%) increased significantly as glucose tolerance decreased: when glucose tolerance was normal the median was 5-2%; when it was impaired the figure was 5-5%; in patients whose diabetes was diagnosed by the oral glucose tolerance test it was 5-9%; and in patients already known to have diabetes mellitus it was 8-6%. The incidence and prevalence of impaired glucose tolerance and diabetes mellitus increased with age. From the age of 15 to 30 years the decrease in the prevalence of normal glucose tolerance was almost linear. Within this age span the proportion of patients with cystic fibrosis with normal glucose tolerance was reduced by roughly 5%/ year. Only 35% (95% confidence interval (CI) 22 to 48%) of the patients with cystic fibrosis who were alive at the age of 25 years had normal glucose tolerance; 32% (95% CI 14 to 49%) were diabetic.The prevalence of glucose intolerance in cystic fibrosis is rapidly increasing with age; its potentially harmful effect on the prognosis of cystic fibrosis is of increasing importance as the length of survival of these patients increases.Cystic fibrosis is an autosomal recessive disorder that affects many organs including the pancreas. In addition to insufficiency of pancreatic exocrine function, there is a high incidence of pancreatic endocrine dysfunction. October 1989, 99 patients (50 men) had died, and 22 (12 men) had been treated elsewhere. From the records of the dead patients, information was obtained about sex, age at death, family history of diabetes, presence or absence of diabetes mellitus (diagnosed by raised blood glucose concentration or glycosuria, or both), and, if they were diabetic, the age at the time of diagnosis of the diabetes.Of the 235 patients (119 men) currently attending the clinic regularly, 210 (89%) patients (104 men) were willing to participate in the study. Reasons given for not taking part were: unwillingness (n=9), inability because of mental disease (n= 3), and age less than 2 years (n= 13), which was the minimal age for inclusion. The median age of the 210 patients was 14 years (range 2-40), median height 152 cm (range 81-190), and...

Glucose Homeostasis and Genotype-Phenotype Interplay in Cystic Fibrosis Patients With CFTR Gene ΔF508 Mutation

“…It is, however, interesting to note that the Bϫ S product in cystic fibrosis patients with AGH was not as altered as that observed in our type 2 diabetic cohort nor as that in diabetic subjects with chronic pancreatitis; yet, 80% of AGH patients had a formal diagnosis of diabetes. This difference in secretory function adjusted for individual insulin sensitivity could account for the relative mild clinical expression of AGH in cystic fibrosis (13). In keeping with this, only five subjects had diabetes-related clinical symptoms at diabetes diagnosis.…”

“…Such improvement underlies the subsequent rise in the prevalence of abnormal glucose homeostasis (AGH) in later life, including a secondary form of diabetes, which is becoming a major comorbidity associated with cystic fibrosis (2,7,8). For some investigators, diabetes in cystic fibrosis is related to pancreatic exocrine-endocrine insufficiency, which itself correlates with CFTR mutations (9 -12), but this link has not been confirmed by others (13)(14)(15). On the other hand, impaired insulin sensitivity has also been reported as an additional factor for developing diabetes (16).…”

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

“…Alterations in glucose tolerance are characterized by marked glycemic peaks often followed by rapid normalization (11)(12)(13). Fasting glycemia is generally lower than in other forms of diabetes and fasting hypoglycemia has been reported (14).…”

Natural history of glucose tolerance, beta-cell function and peripheral insulin sensitivity in cystic fibrosis patients with fasting euglycemia

“…The prevalence of glucose intolerance in CF is actually growing, probably due to these patients' increasing life expectancy. Impaired glucose tolerance (IGT) affects up to 40% of patients with CF and 10% to 15% of CF adults develop overt diabetes mellitus (DM) with fasting hyperglycemia (2).…”