Table 2.
Summary of main studies addressing insulin-sensitivity in CAH patients.
| Study | Patients and CAH form | Age range (years) | Mean HC dose (mg/m2/day) | Mean FC dose(μg/m2/day) | Methods | Outcomes |
|---|---|---|---|---|---|---|
| Finkielstain et al. (8) |
-139 Classic (97 SW, 42 SV) -31 Non-classic |
0.6–17 | 15 | n.a. | n.a. | ↑ Prevalence of obesity (35%) vs. normal pediatric population (17%), with no difference between Classic and NC CAH and between males and females↑ HOMA-IR↑ BP (about 40% Classic and 20% NC CAH) |
| Marra et al. (30) |
-20 Classic (15 SW, 5 SV) -20 Controls |
11.1–16.1 | 15 | 54.8 | HOMA | ↑ BMI and ↑ fat mass and waist/height ratio vs. controls; ↑ HOMA-IR vs. controls; No difference between males and females Comparable lipids and BP between CAH and controls ↓ exercise capacity vs. controls LV diastolic dysfunction in CAH male patients |
| Kim et al. (33) |
-28 Classic (20 SW, 8 SV) -28 Controls |
12.4–18.8 | 19.5 | 210 μg/day | HOMA | 60.7% of patients obese or overweight; ↑ VAT, SAT and VAT/SAT vs. controls; No difference between males and females Elevated HOMA in 18% of CAH |
| Charmandari et al. (36) |
-16 Classic (12 SW, 4 SV) -28 Controls |
2–12 | 14.8 | 114 μg/day | HOMA | BMI comparable to controls ↑ HOMA-IR vs. controls ↑ Leptin in patients vs. controls; No difference between males and females |
| Harrington et al. (37) |
-14 Classic (11 SW, 3 SV) 53 Controls |
11.6–18 | 13.3 | 108.3 μg/day | HOMA | BMI comparable to controls, ↑ WHtR vs. controls ↑ HOMA-IR vs. controls ↑ SBP vs. controls ↓ FMD and smooth muscle function vs. controls IMT, CRP, lipids comparable between CAH and controls |
| Mooij et al. (23) |
-26 Classic (24 SW, 2 SV) |
8–16 | 11.2 | 98.5 | HOMA | ↑ BMI vs. reference population (25.9% obese and 14.8% overweight) 44.4% of patients HOMA-IR > 75th and 29.6% HOMA-IR >90th percentile ↑ SBP in 18.5%, lower than reference population 48.1% ↓ nocturnal dip |
| Amr et al. (24) |
-32 Classic (24 SW, 8 SV) -32 Controls |
3–17 | 15 | 50–100 | HOMA OGTT |
↑ BMI in patients (22% obese) vs. controls ↑ HOMA-IR, CIMT, SBP vs. controls ↑ Stimulated glucose levels vs. controls Comparable lipids, stimulated insulin vs. controls |
| Zimmermann et al. (38) |
-27 Classic (12 SW, 15 SV) -27 Controls |
4–31 | 21.5 (SW) 16.2 (SV) |
50–100 μg/day | HOMA IRI ISI OGTT |
BMI comparable to controls ↓ HOMA-IS and ↑ HOMA-IR, HOMA-B, IRI, stimulated glucose and insulin levels vs. controls ↑ Small dense LDL subfractions and HDL vs. controls Comparable LDL, T-COL, triglycerides between CAH and controls |
| Ariyawatkul et al. (31) |
-21 Classic (10 SW, 11 SV) -21 Controls |
9–28 | 21.4 | 50–150 μg/day | HOMA | BMI, fat and lean mass comparable between CAH and controls ↑ Waist/hip and waist/height ratio vs. controls Comparable HOMA, BP, lipids, leptin between CAH and controls |
| Subbarayan et al. (25) |
-107 Classic (79 SW, 28 SV) | 0.4–20.5 | 13.3 | 102 | HOMA | ↑ Prevalence of obesity (23.6%) vs. normal population (14.8–17.1%) ↑ SBP vs. normal population 9.5% high plasma triglycerides No difference between males and females ↓ HOMA-IR vs. controls |
| Williams et al. (28) |
-25 Classic -12 Non-classic -41 Controls |
0.5–15.8 | 13.9 8.2 |
82 μg/day 18 μg/day |
HOMA OGTT |
↑ Fat mass in classic CAH vs. controls ↑ Lean mass in NC CAH vs. controls Comparable HOMA-IS between CAH (classic and NC) and controls ↑ Stimulated glucose and insulin in NC CAH vs. controls Comparable BP and lipids between classic CAH and controls ↑ SBP in NC CAH vs. controls |
| Saygili et al. (39) |
-18 Non-classic -26 Controls |
25.7 ± 8.9 (mean ± SD) | Untreated | Untreated | HOMA | BMI comparable to controls ↑ HOMA-IR vs. controls |
| Bayraktar et al. (40) |
-50 Non-classic -25 Controls |
22.1 ± 2.91 (mean ± SD) | Untreated | Untreated | HOMA | BMI comparable to controls Comparable HOMA-IR and lipids between CAH and controls |
| Speiser et al. (41) |
-6 Non-classic -12 Controls |
16–45 | Untreated | Untreated | i.v. GTT | BMI comparable to controls ↓ Insulin sensitivity vs. controls |
| Wasniewska et al. (42) |
-9 Classic SW -9 Non-classic -16 Controls |
13.3–20.4 | 17.1 | 100 μg/day | HOMA | BMI comparable to controls ↑ HOMA-IR in Classic CAH vs. controls Comparable HOMA-IR between NC CAH and controls ↑ SBP in classic CAH vs. controls ↑ DBP in classic CAH and NC CAH vs. controls Comparable lipids between CAH and controls ↑ IMT in classic CAH and NC CAH vs. controls |
CAH, Congenital Adrenal Hyperplasia; HC, hydrocortisone; FC, fludrocortisones; SW, salt wasting; SV, simple virilizing; HOMA, homeostatic model assessment; BMI, body mass index; HOMA-IR, HOMA insulin resistance; BP, blood pressure; LV, left ventricle; VAT, visceral adipose tissue; SAT, subcutaneous adipose tissue; WHtR, waist-to-height ratio; SBP, systolic blood pressure; FMD, flow-mediated dilatation; IMT, intima media thickness; CRP, C reactive protein; OGTT, oral glucose tolerance test; IRI, insulin resistance index; ISI, insulin sensitivity index; LDL, low density lipoproteins; HDL, high density lipoproteins; NC, non-classic; T-COL, total cholesterol; i.v. GTT, intravenous glucose tolerance test; DBP, diastolic blood pressure. ↑ increased; ↓ decreased.