Gastrointestinal Symptoms in Type 1 Diabetes: Relationship With Autoimmune and Microvascular Complications.

PURPOSE: To assess reported rates of gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with type 1 diabetes. METHODS: The Gastrointestinal Symptom Scale was used to assess GI symptom type and severity in 2370 patients with type 1 diabetes aged 8 to 45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical, and other diabetes-related factors were evaluated. RESULTS: Overall, 1368 adults (57.7%) aged 19 to 45 years and 1002 (42.3%) pediatric patients aged 8 to 18 years were studied. At least 1 GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P < 0.0001). Common symptoms in children included upper and lower abdominal pain while adults more frequently reported lower GI symptoms. Participants with GI symptoms had higher hemoglobin A1c (HbA1c) levels (68 ±â€…14mmol/mol; 8.35 ±â€…1.37%) than those without symptoms (66 ±â€…15mmol/mol; 8.22 ±â€…1.40%; P = 0.041). Patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) were 1.8 times more likely to report GI symptoms (95% CI: 1.26-2.60; P < 0.01) after adjusting for age and sex. No association was observed between GI symptoms and the presence of autoimmune conditions, including thyroid and biopsy-confirmed CD (odds ratio = 1.1; 95% CI: 0.86-1.42; P = 0.45). MAIN CONCLUSIONS: These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of type 1 diabetes, HbA1c, and microvascular complications but not with autoimmune comorbidities including CD.

Accuracy of Screening Tests for Celiac Disease in Asymptomatic Patients With Type 1 Diabetes.

INTRODUCTION: To evaluate the diagnostic performance of celiac serologic tests in asymptomatic patients with type 1 diabetes (T1D). METHODS: Patients with T1D asymptomatic for celiac disease were prospectively screened with immunoglobulin A anti-tissue transglutaminase. Test characteristics were calculated and optimal cutoffs for a positive screen determined. RESULTS: Two thousand three hundred fifty-three patients were screened and 101 proceeded to biopsy. The positive predictive value of immunoglobulin A anti-tissue transglutaminase at the assay referenced upper limit of normal (30CU) was 85.9%, and the sensitivity and specificity were 100% and 38%, respectively. DISCUSSION: Thresholds extrapolated from the general population for the diagnostic evaluation of celiac disease are not suitable for use in asymptomatic T1D patients. Population-specific screening cutoffs are required.

Impact of a Gluten-Free Diet on Quality of Life and Health Perception in Patients With Type 1 Diabetes and Asymptomatic Celiac Disease.

CONTEXT: Celiac disease (CD) is a common comorbidity seen in patients with type 1 diabetes (T1D) and is frequently asymptomatic. As chronic conditions requiring significant lifestyle changes, there are limited reports assessing changes in health-related quality of life (HRQoL) during transition to a gluten-free diet (GFD) in patients with T1D who are asymptomatic for CD. OBJECTIVE: This work aims to prospectively assess HRQoL and health perception in children and adults with T1D and asymptomatic CD after random assignment to GFD vs usual diet. METHODS: Patients with T1D aged 8 to 45 years without CD symptoms were serologically screened for CD, with positive results confirmed with intestinal biopsy. Participants were randomly assigned in an open-label fashion to a GFD or gluten-containing diet (GCD) for 12 months. Generic and diabetes-specific HRQoL and self-perceived wellness (SPW) were assessed longitudinally. RESULTS: A total of 2387 T1D patients were serologically screened. CD was biopsy-confirmed in 82 patients and 51 participants were randomly assigned to a GFD (N = 27) or GCD (N = 24). Excellent adherence to the assigned diets was observed. Overall, no changes in generic (P = .73) or diabetes-specific HRQoL (P = .30), or SPW (P = .41) were observed between groups over 12 months. Hemoglobin A1c (HbA1c) and gastrointestinal symptoms were consistent predictors of HRQoL and SPW. CONCLUSION: HRQoL and SPW were not significantly affected by the adoption of a GFD over 12 months, but worsened with symptom onset and increased HbA1c. Our findings indicate that transition to a GFD can be made successfully in this population without adversely affecting quality of life.

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Social Determinants of Health Are Associated with Markers of Renal Injury in Adolescents with Type 1 Diabetes.

OBJECTIVE: To examine the relationship between the social determinants of health and markers of early renal injury in adolescent patients with type 1 diabetes (T1D). STUDY DESIGN: Renal outcomes included estimated glomerular filtration rate (eGFR) and albumin-creatinine excretion ratio (ACR). Differences in urinary and serum inflammatory markers also were assessed in relation to social determinants of health. Regression analysis was used to evaluate the association between the Ontario Marginalization Index (ON-Marg) as a measure of the social determinants of health, patient characteristics, ACR, eGFR, and renal filtration status (hyperfiltration vs normofiltration). RESULTS: Participants with T1D (n = 199) with a mean age of 14.4 ± 1.7 years and diabetes duration of 7.2 ± 3.1 years were studied. Mean eGFR was 122.0 ± 19.4 mL/min/1.73 m2. Increasing marginalization was positively associated with eGFR (P < .0001) but not with ACR (P = .605). Greater marginalization was associated with greater median levels of urinary interleukin (IL)-2, IL-12 (p40), macrophage-derived chemokine, monocyte chemoattractant protein-3, and tumor necrosis factor-ß and serum IL-2. ON-Marg was significantly associated with eGFR after we controlled for age, sex, body mass index z score, ethnicity, serum glucose, and hemoglobin A1c in linear regression. A similar association between hyperfiltration and ON-Marg score was observed in multivariable logistic regression. CONCLUSION: Increasing marginalization is significantly associated with both eGFR and hyperfiltration in adolescents with T1D and is associated with significant changes in urinary inflammatory biomarkers. These findings highlight a potentially important interaction between social and biological determinants of health in adolescents with T1D.

Social Determinants of Health Are Associated with Modifiable Risk Factors for Cardiovascular Disease and Vascular Function in Pediatric Type 1 Diabetes.

OBJECTIVE: To evaluate the relationship between social determinants of health (SDH) and cardiovascular disease (CVD) risk factors as well as a measure of arterial stiffness in adolescents with type 1 diabetes (T1D). STUDY DESIGN: SDH were measured with the validated Ontario Marginalization Index, derived from deidentified postal code data and stratified by quintile (first = least deprived; fifth = most deprived). SDH dimensions included material deprivation; ethnic concentration; and measures of dependency and residential instability. Metabolic control (hemoglobin A1c), cardiovascular risk metrics, and pulse wave velocity, as a measure of arterial stiffness, were related to SDH. Data were evaluated from a cohort of Canadian adolescents within the Adolescent Diabetes Cardiorenal Intervention Trial, a T1D clinical trial RESULTS: A total of 704 participants were evaluated, and significant differences in hemoglobin A1c were evident at the extremes of material deprivation (8.4% vs 9.1% for least vs most deprived, P < .01). CVD risk factors were analyzed in 199 participants, with the most deprived reporting significantly less exercise (P = .004) and increased rates of smoking (P = .008). Increased material deprivation was associated with fewer metrics of "ideal" cardiovascular health attained. Arterial stiffness, as measured by pulse wave velocity, was associated positively with age, body mass index z score, and material deprivation. CONCLUSION: Increased material deprivation was associated with poorer glycemic control. Modifiable, lifestyle-related risk factors for CVD and early arterial wall change are associated with SDH and represent a target for clinical intervention to reduce future CVD burden in adolescents with T1D.