Intestinal imidazole propioNaTE productioN after histiDinE supplementation in healthy and type 2 Diabetes mellitus subjects: role of the gut microbiota

INTENDED

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON20133

Enrollment

Registered

2020-02-11

Start date

2020-02-11

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 diabetes

Interventions

Histidine supplemenation 4g/day for 7 weeks.

Eligibility

Inclusion criteria

Inclusion criteria: Healthy controls: - 22 healthy controls 40-70 years, BMI <30kg/m2 - 11 controls of Caucasian descent and 11 of Surinamese descent Type 2 Diabetes (T2D) subjects: - 22 T2D patients (11 of Caucasian descent and 11 of Surinamese descent) - 40-70 years - BMI 25-35 - Stable anti diabetic drugs for 3 months (metformin is obligatory) - All on statin - Stable medication uses past 3 months - Able to give informed consent

Exclusion criteria

Exclusion criteria: - Previous major cardiovascular event (e.g. AMI/stroke/TIA) - PPI - GLP1 nor insulin - antibiotic use in the past 3 months - Probiotic or symbiotic usage - Pregnant women, - Chronic illness (including a known history of heart failure, renal failure (eGFR 6 alcohol units per day or >14 alcohol units per week - Active malignancy - HbA1c >9% (75mmol/mol) - The subject is already involved in a clinical trial

Design outcomes

Primary

Measure	Time frame
Evaluate ImP, urocanate, glutamate and histamine plasma level excursions upon 4 grams of histidine supplementation before, during and after a short course of oral antibiotics in T2D and healthy controls of Caucasian and Surinamese ethnicity.	—

Secondary

Measure	Time frame
Imidazole propionate - ImP excursion before ATB challenge in both T2D and healthy controls (evaluation criteria = compare the AUC in both metabolic groups from - ImP excursion immediately after the ATB challenge in both T2D and healthy controls (evaluation criteria = compare the AUC in both metabolic groups between before and after the ATB course) - - Imp excursion during ATB washout in both metabolic groups (evaluation criteria = compare the AUC in both groups). Insulin resistance and glucose metabolism - Evaluate the effect of oral histidine challenge on insulin resistance (evaluation criteria = changes in MMT in both groups and HOMA) in T2D vs healthy controls before short term antibiotics course - Evaluate the effect of oral histidine challenge on insulin resistance (evaluation criteria = changes in HOMA) in T2D vs healthy controls before, during and after short term antibiotics course - - At baseline (V2) and after histidine supplementation (V4), subjects receive a 4-hour mixed meal test with 250cc Nutridrink (Fortimel® Compact 2x125ml, Nutricia) consisting of 96kcal protein, 294kcal carbohydrates and 210kcal fat, total energy content 600 kcal) after an overnight fast. Postprandial plasma samples will be taken at T0min, T30min, T60min and , T 120minvia an intravenous cannula (venflon) and glucose/insulin levels will be determined. Effect of oral histidine challenge on continuous glucose levels (2 weeks Freestyle libre) in T2D vs healthy controls before, during and after short term antibiotics course. Subjects will learn how to implant the Freestyle Libre monitor (http://abbottnextfrontier.com/freestyle-libre) subcutaneously prior to the start of the study Their glucose levels will then be continuously monitored during three-time windows of 2 weeks during the study. Subjects are not required to perform finger pricks in order to calibrate the monitor and can perform all normal activities whilst wearing a monitor Inflammation - Evaluate the effect of oral h	—

Measure

Time frame

Imidazole propionate - ImP excursion before ATB challenge in both T2D and healthy controls (evaluation criteria = compare the AUC in both metabolic groups from - ImP excursion immediately after the ATB challenge in both T2D and healthy controls (evaluation criteria = compare the AUC in both metabolic groups between before and after the ATB course) - - Imp excursion during ATB washout in both metabolic groups (evaluation criteria = compare the AUC in both groups). Insulin resistance and glucose metabolism - Evaluate the effect of oral histidine challenge on insulin resistance (evaluation criteria = changes in MMT in both groups and HOMA) in T2D vs healthy controls before short term antibiotics course - Evaluate the effect of oral histidine challenge on insulin resistance (evaluation criteria = changes in HOMA) in T2D vs healthy controls before, during and after short term antibiotics course - - At baseline (V2) and after histidine supplementation (V4), subjects receive a 4-hour mixed meal test with 250cc Nutridrink (Fortimel® Compact 2x125ml, Nutricia) consisting of 96kcal protein, 294kcal carbohydrates and 210kcal fat, total energy content 600 kcal) after an overnight fast. Postprandial plasma samples will be taken at T0min, T30min, T60min and , T 120minvia an intravenous cannula (venflon) and glucose/insulin levels will be determined. Effect of oral histidine challenge on continuous glucose levels (2 weeks Freestyle libre) in T2D vs healthy controls before, during and after short term antibiotics course. Subjects will learn how to implant the Freestyle Libre monitor (http://abbottnextfrontier.com/freestyle-libre) subcutaneously prior to the start of the study Their glucose levels will then be continuously monitored during three-time windows of 2 weeks during the study. Subjects are not required to perform finger pricks in order to calibrate the monitor and can perform all normal activities whilst wearing a monitor Inflammation - Evaluate the effect of oral h

—

Contacts

Public ContactIlias Attaye

Amsterdam UMC, location AMC

i.attaye@amsterdamumc.nl031650063752

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)