yperinsulinemic-Euglycemic Clamp Strengthens the Insulin Resistance in Nonclassical Congenital Adrenal Hyperplasi

Author(s)

Delai, Ariane ^[1] ; Gomes, Patricia M. ^[1] ; Foss-Freitas, Maria Cristina ^{[1, 2, 3]} ; Elias Jr, Jorge ; Antonini, Sonir R. ^[4] ; Castro, Margaret ^[1] ; Moreira, Ayrton C. ^[1] ; Mermejo, Livia M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Michigan, Caswell Diabet Inst, Ann Arbor, MI 48109 - USA

^[3] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 107, n. 3, p. E1106-E1116, FEB 17 2022.
• Web of Science Citations: 0

Abstract

Objective Insulin sensitivity evaluation by hyperinsulinemic-euglycemic clamp in nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxilase deficiency. Design and Setting Cross-sectional study at university hospital outpatient clinics. Patients and Methods NC-CAH patients (25 females, 6 males; 24 +/- 10 years) subdivided into C/NC (compound heterozygous for 1 classical and 1 nonclassical allele) and NC/NC (2 nonclassical alleles) genotypes were compared to controls. Results At diagnosis, C/NC patients presented higher basal and adrenocorticotropin-stimulated 17-hydroxyprogesterone and androstenedione levels than NC/NC genotype. Patients and controls presented similar weight, body mass index, abdominal circumference, and total fat body mass. NC-CAH patients showed higher waist-to-hip ratio, lower adiponectin and lower high-density lipoprotein cholesterol levels with no changes in fasting plasma glucose, glycated hemoglobin, homeostatic model assessment for insulin resistance, leptin, interleukin 6, tumor necrosis factor alpha, C-reactive protein, and carotid-intima-media thickness. All patients had used glucocorticoid (mean time of 73 months). Among the 22 patients with successful clamp, 13 were still receiving glucocorticoid-3 patients using cortisone acetate, 9 dexamethasone, and 1 prednisone (hydrocortisone equivalent dose of 5.5mg/m(2)/day), while 9 patients were off glucocorticoid but had previously used (hydrocortisone equivalent dose of 5.9mg/m(2)/day). The NC-CAH patients presented lower M-ffm than controls (31 +/- 20 vs 55 +/- 23 mu mol/min(-1)/kg(-1), P = 0.002). The M-ffm values were inversely correlated with the duration of glucocorticoid treatment (r = -0.44, P = 0.04). There was association of insulin resistance and glucocorticoid type but not with androgen levels. Conclusion Using the gold standard method, the hyperinsulinemic-euglycemic clamp, insulin resistance was present in NC-CAH patients and related to prolonged use and long-acting glucocorticoid treatment. Glucocorticoid replacement and cardiometabolic risks should be monitored regularly in NC-CAH. (AU)

• FAPESP's process: 18/10789-4 - Cardio-metabolic risk factors in patients with non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency
• Grantee: Lívia Mara Mermejo
• Support Opportunities: Regular Research Grants