Table 11: GRADE Quality of Evidence: Effects of GFD on Symptoms and Conditions in Subjects with Asymptomatic Celiac Disease.

Symptom/Condition	Design	Quality	Consistency	Directness	Other Modifying Factors	Summary of Findings	Overall Quality
Type 1 Diabetes Mellitus HbA1c Pediatric	1 prospective case-control study	• Subject selection No serious limitation* • CD diagnosis No limitation • Measure of outcomes No limitation. • Intervention (GFD) No limitation • Losses to f-up No serious limitation • Blinding of outcome measurement No blinding, however, this may not pose a threat to validity since the outcome was objectively measured	Not applicable (1 study)	• Patient population No limitations, however it can only be generalized to the pediatric population • Outcome No limitations	• Sparse data No limitation • Precision No limitation • Publication bias Could not be evaluated	Significantly lower HbA1c in celiac disease patients with type 1 diabetes vs. control before the diagnosis of celiac disease. After the diagnosis, HbA1c levels in subjects with celiac disease and type 1 diabetes rose to a level similar to that of controls.
	Low						Low
Type 1 Diabetes Mellitus (DM1) Hypoglycemia events Pediatric	1 retrospective case-control	• Subject selection Possible selection bias* • CD diagnosis No limitation • Measure of outcomes (-1) Retrospectively identified. There were uncertainties on how the events were ascertained and event severity. • Intervention (GFD) GFD compliance not provided • Losses to f-up No limitation • Blinding of outcome measurement No blinding (not applicable, retrospective study)	Not applicable (1 study)	• Patient population No limitations, however it can only be generalized to the pediatric population • Outcome No limitations	• Sparse data Not considered a serious limitation • Precision Not considered a serious limitation • Publication bias Could not be evaluated	No statistically significant difference between cases and controls from 18 months to 6 months before the celiac disease diagnosis and GFD introduction and > 6 months after the GFD introduction. Cases had a statistically significantly higher number of hypoglycemic episodes vs. controls in the period ranging from 6 months prior to 6 months after the celiac disease diagnosis. The severity of episodes among cases and controls was not reported. GFD compliance was not reported.
	Low	Very Low					Very Low
Type 1 Diabetes Mellitus (DM1) Insulin dosage Pediatric	1 prospective case-control study	• Subject selection No serious limitation* • CD diagnosis No limitation • Measure of outcomes No limitation. • Intervention (GFD) No limitation • Losses to f-up No serious limitation • Blinding of outcome measurement No blinding, however, this may not pose a threat to validity since the outcome was objectively measured	N/A	• Patient population No limitations, however it can only be generalized to pediatric population • Outcome No limitations	• Sparse data No limitation • Precision No limitation • Publication bias Could not be evaluated	No significant difference in insulin dosage between cases and controls either before or after the celiac disease diagnosis. No significant difference in insulin dosage before and after the celiac disease diagnosis among cases.
	Low						Low
Short Stature Growth parameters (growth velocity standard deviation score, height standard deviation score) Pediatric	3 Observational studies (Case Series, before-after comparisons)	• Subject selection Possible selection bias* • CD diagnosis No limitation • Losses to f-up No limitation • Measure of outcomes No limitation • Intervention (GFD) GFD compliance not reported. • Blinding of outcome measurement No blinding, however, this may not pose a threat to validity since outcomes were objectively measured	No limitation	• Patient population No limitation • Outcome No limitations	• Precision Not considered a serious limitation • Sparse data Not considered a serious limitation • Publication bias Could not be evaluated	All studies reported an improvement in growth parameters once a GFD was introduced.
	Low						Low

CD refers to celiac disease; GFD gluten-free diet; HbA1c hemoglobin A1c

^*Participation rate not reported.