Table 1.
Total of 11 studies included
| Title, lead author | Year | Study design | Population: n=sample size, age; mean±SD or median (range), (F/M) | Control group: n=sample size, age; mean±SD or median (range), (F/M) | Results: RHI reported. if RHI not specified, we reported p/r values | Outcomes |
| Adolescents and young adults with type 1 diabetes display a high prevalence of endothelial dysfunction. Scaramuzza et al17 | 2015 | Cohort prospective observational study. Results at baseline and after a 1-year follow-up | n=73 T1D adolescents, diagnosed>1 year, 16.2±3.5 years,(F/M 25/48) | No controls. | 56 (76.7%) had ED, with lower mean RHI scores (1.26±0.22 vs 2.24±0.48, p<0.0001). More with ED had abnormal cardiac autonomic tests (p=0.02) and were more sedentary. After 1-year follow-up in 64/73 patients, 81.8% had ED, despite some improvement in HbA1c. | T1D adolescents had evidence of ED. Good metabolic control (HbA1c ≤7.5%) and regular physical activity might be protective. ED progression despite some improvement to HbA1c. |
| Alpha-lipoic acid and antioxidant diet help to improve endothelial dysfunction in adolescents with type 1 diabetes: a pilot trial. Scaramuzza et al19 | 2015 | Double- blind, randomised controlled trial—snow balling. Results at baseline and after follow-up | n=71 T1D patients, followed for at least 1 year, age 16.3±3.4 years,(F/M 29/42). (a) antioxidant diet 10.000 ORAC+alpha-lipoic acid; (b) antioxidant diet 10.000 ORAC+placebo; | (c)controls | Three double-blind study arms: (a) antioxidant diet 10 000 ORAC+lipoic acid: RHI 1.40±0.68 vs 1.72±0.66 (p<0.05) (baseline vs after 6 months). (b) Antioxidant diet 10 000 ORAC+placebo: RHI 1.39±0.41 vs 1.58±0.40 (p>0.05). (c) Controls: RHI 1.58±0.64 vs 1.54±0.42 (p>0.05). | Improved RHI with alpha-lipoic acid in T1D patients. |
| Effect of metformin on endothelial function in overweight adolescents with type 1 diabetes (T1D). Nadeau et al20 | 2016 | Conference abstract. Endo-PAT scores at baseline and 13 weeks. | Total n=70 overweight T1D patients. n=41 on metformin (up to 2000 mg/day), 12–19 years (mean 15.8) | n=29 placebo group. | Mean baseline RHI 1.8±0.6 in metformin group and 1.7±0.6 placebo group. At 13 weeks, no significant change from baseline RHI (+0.1 in metformin vs −0.0 in placebo, p=0.08). Some improvement in endothelial function in men. | No significant RHI change with metformin overall but some improvement in overweight T1D males. |
| Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus. Babar et al18 | 2019 | Cross-sectional study | T1D adolescents≥12 years. Two groups based on different HbA1c ranges. (a) HbA1c ≥9.5% (n=25) | (b) HbA1c ≤8.5% (n=27). | PAT results were not significantly different between the groups. Pearson correlation showed a significant direct relationship between rising HbA1c and PAT (p=0.03, r=0.31). | Suboptimal glycaemic control (rising HbA1c) causes early atherosclerosis. |
| Improvements in peripheral vascular function with vitamin D treatment in deficient adolescents with type 1 diabetes. Deda et al21 | 2018 | Research article—snow balling. Tested at two different time points. | n=21 T1D patients followed for~2 years. 25-OH-Vit. D levels<37.5 nmol/L. Age 15.7±1.4 years,(F/M 19/12) | Controls: matched age, sex and T1D. | After 4.8±1.3 months of Vit. D supplementation RHI improved: 1.83±0.42 vs 2.02±0.68 (p<0.05). | Vit. D supplementation associated with improvement to endothelial function and reduced urinary inflammatory markers. |
| Non-alcoholic fatty liver disease in hispanic youth with dysglycemia: risk for subclinical atherosclerosis? Bacha et al23 | 2017 | Cross-sectional study | n=23 overweight/ obese with NAFLD, age 15.2±0.5 years. n=12 pre-diabetes, n=11 T2D,(F/M 13/10) |
n=13 overweight/ obese without NAFLD, age 15.7±0.4 years. n=8 pre-diabetes, n=5 T2D,(F/M 3/10) | NAFLD group had lower RHI (1.4±0.05 vs 1.7±0.09, p=0.002). Hepatic fat is inversely related to RHI (r=−0.49, p=0.002). | Hepatic fat and AST/ALT levels inversely related to RHI. If dysglycemia, NAFLD is associated with worse ED. |
| Endothelial function in youth: A Biomarker modulated by adiposity-related insulin resistance. Tomsa et al22 | 2016 | Cross-sectional study | Total n=60. n=25 obese without DM, n=19 obese with impaired glucose tolerance, n=16 obese T2D but HB1Ac <8%. Age 15.5 (0.2),(F/M 37/23) |
n=21 normal weight, age 15.5 (0.2),(F/M 9/12) | RHI inversely related to % body fat (r = −0.29, p = 0.008), total (r = −0.37, p = 0.004), subcutaneous (r = −0.39, p = 0.003), and visceral abdominal fat (r = −0.26, p = 0.04). | Childhood obesity is associated with ED (lower RHI). RHI lower in obese and T2D. RHI negatively related with percentage body fat, WC, Leptin, TNF-alpha, blood glucose. |
| Circulating fibroblast growth factor-21 (FGF-21): A biomarker of subclinical atherosclerosis in obese youth with non-alcoholic fatty liver disease (NAFLD)? Bacha et al24 | 2017 | Conference abstract | Obese adolescents with NAFLD, 15.4±0.3 years. n=13 normal glucose tolerance, n=19 pre-diabetes, n=16 T2D patients | Control group: no NAFLD. No difference in age/gender between groups. |
Lower RHI in NAFLD group. High FGF-21 concentrations related to RHI (r=−0.33, p=0.03). | Increased FGF-21 in obese adolescents with NAFLD associated with insulin sensitivity and ED. FGF-21 may constitute a biomarker ED. |
| Assessment of Microvascular Function in Children and Adolescents with Diabetes and Obesity. Kochummen et al26 | 2019 | Cross-sectional study | DM group. n=33 T1D with normal weight. n=8 obese T2D, age 12.7 (3.8) years,(F/M 25/16) |
n=17 obese, non-DM children (normal BGL, BP and lipid profile), 12.8 (2.7) years,(F/M 9/8) | For every 1% increase in HbA1C, RHI decreased by 0.097 (p=0.01). RHI of DM group with HbA1C<10% (1.70±0.58) vs those with≥10% (1.21±0.19) (p=0.02). | Poorly-controlled DM (HbA1C ≥10%) had lower RHI. RHI negatively related with HbA1C. RHI similar between obese and normal weight with T1D. Similar between T1D and T2D. |
| Free Vitamin D: Relationship to Insulin Sensitivity and Vascular Health in Youth. Bacha et al27 | 2019 | Cross-sectional study. Comparison across tertiles of free 25(OH)D concentrations | n=79, age 15.4±0.2 years,(F/M 45/34). n=30 overweight. n=31 overweight with pre-diabetes |
n=18 normal weight and normal glucose tolerance. | The lowest tertile group had lower RHI (1.42±0.06, 1.54±0.06, and 1.77±0.09, p=0.002), compared with the second and third tertiles. | Youth with low free 25(OH)D or BioD concentrations have lower insulin sensitivity and worse endothelial function. |
| Urine Albumin-to-Creatinine Ratio (UACR): A Marker of Early Endothelial Dysfunction in Youth. Bartz et al25 | 2015 | Control study. Fasting UACR analysed. | n=25 overweight (OW) with normal glucose tolerance, 15.6±0.2 years,(F/M 17/8). n=20 OW with pre-diabetes,(F/M 11/9). |
n=13 normal weight, 16.3±0.4,(F/M 7/6). | Normal weight group RHI 1.84±0.1. OW with normal glucose tolerance 1.56±0.1. OW with pre-diabetes 1.56±0.1 (p=0.04). UACR was related to RHI (r=−0.33, p=0.01). | UACR is an early marker of endothelial dysfunction in youth, independent of glycaemia. |
Endo-PAT 2000 in paediatric type 1 diabetes mellitus (T1D) patients (five studies), type 2 diabetes and pre-diabetes (six studies).
ED, endothelial dysfunction; NAFLD, non-alcoholic fatty liver disease; ORAC, oxygen radical absorbance capacity units; OW, overweight; RHI, reactive hyperemia index; T1D, type 1 diabetes mellitus; T2D, type 2 diabetes mellitus; UACR, urine albumin-to-creatinine ratio.