ESPE Abstracts

Background: Achondroplasia (ACH) is the most common skeletal dysplasia with an incidence of 1/20,000. Acanthosis nigricans (AN) is commonly seen in conditions associated with reduced insulin sensitivity. AN has been reported in association with skeletal dysplasias due to activating mutations in FGFR3, including ACH.

Objective: Our aim was to evaluate insulin sensitivity and glucose metabolism in patients with ACH carrying c.1138G>A (p.Gly380Arg) variant in FGFR3 gene.

Patients and Methods: The study cohort included 28 patients (15 females) with ACH. Physical examination, anthropometric measurements and puberty examination were carried out. Fasting plasma glucose (FPG), insulin and HbA1c levels were measured and oral glucose tolerance test (OGTT) was performed at a dose of 1.75 g/kg. Homeostatic model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) were calculated. Total insulin level ³ 300 U/mL was accepted as decreased insulin sensitivity.

Results: The mean age of the patients was 12.4±4.5 (ranges 7.9-18) years. The FPG level of all patients was in normal ranges. OGTT was normal in 75% of patients. Approximately 17.9% of patients (n=5) had insulin resistance (IR) and 7.1% of patients (n=2) had impaired glucose tolerance (IGT) at 120 min. All patients with IR or IGT were obese or overweight. HOMA-IR was higher than 2.5 in four of five patients with IR. All of these patients 57.1% was Tanner stage 5, 14.2% was Tanner stage 1 and 28.6% had no information about puberty. Fifty percent of all patients (n=14) had AN. OGTT results of 71.4% patients with AN were normal, 21.4% had IR and 7.1% had IGT. One patient with IGT and another patient with IR did not have AN. The frequency of overweight and obesity were 31.8% and 27.3%, respectively. IR or IGT was detected in 38.5% of overweight and obese patients. There was no significant correlation between IR and age, height SDS or HbA1c level. A significant positive correlation was found between BMI and HOMA-IR (P=0.003).

Conclusion: In our study, the frequency of obesity tendency and IR has been found to be high in ACH. It is important to monitor children with ACH for IR. HOMA-IR is not sufficient to detect IR alone, OGTT is a safe and practical method and can be recommended in patients with ACH to check for glucose metabolism. Prevention of obesity in these cases may prevent the decrease in IR. The frequency of AN was high in ACH patients, however we couldn’t demonstrate a significant relation with IR.