Postprandial Blood Glucose Control and Gastric Emptying in Type 1 Diabetes: Pathogenetic Factors and Therapeutic Options

Study Overview
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Brief Summary
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This study evaluates the prevalence of gastric emptying (GE) in type 1 diabetic patients (DM1) free of chronic complications in comparison with a group of healthy control subjects. The investigators will also assess the relationship between GE and glucose control (HbA1c, postprandial glucose variability), gut peptide hormones (GLP-1, GIP, and ghrelin), and gastrointestinal symptoms. In addition, in patients with delayed GE the investigators will investigate the effect of tailored pre-prandial insulin bolus administered by means of insulin pump in reducing postprandial glucose variability, evaluated through continuous glucose monitoring system.

Detailed Description
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Diabetic patients with a delayed GE will be studied in 2 separate occasions in euglycemic condition and under CGM. On both occasions, they will have to take a standard meal poor of lipids (rice 60 g; yellow squash 200 g; extra virgin olive oil 7 g; adult veal lean cuts 90 g; bananas 180 g; ordinary bread 75 g). On the first occasion pre-prandial insulin will be administered as single bolus calculated on the basis of carbohydrate counting and each patient's insulin/glycaemic load. On the second occasion the amount of pre-prandial insulin will be the same as the first one test but fractioned into a double-wave bolus. The tailored insulin bolus will be defined according to the individual pattern of GE, as follows: GE T1/2 121-180 min= 60% as bolus + 40% during following 2 h GE T1/2 >180 min= 40% as bolus + 60% during following 4 h Glycemic variability will be assessed by the means of Continuous Glucose Monitoring System and the following indexes of glucose variability will be calculated: number of hypoglycemic events, number of hyperglycemic events, standard deviation of glycemia, glycemia variation coefficient, mean range of daily glycemia, interquartile range, M value, mean amplitude of glycemic excursions (MAGE), low blood glucose index (LBGI), high blood glucose index (HBGI).

Official Title
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Postprandial Blood Glucose Control and Gastric Emptying in Patients With Type 1 Diabetes: Pathogenetic Factors, Clinical Relevance and Possible Therapeutic Options

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Other: gastric emptying test
* Other: gut hormones determination
* Other: Continuous Glucose Monitoring
* Drug: Insulin single bolus
* Drug: Insulin double-wave bolus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DM1; Use of insulin pump; Disease duration ≥ 3 years. Exclusion Criteria: Presence of chronic complications of DM (including cardiovascular autonomic neuropathy); BMI ≥ 30 kg/m2; Presence of chronic diseases other than DM1; Diseases that interfere with GE; Medications that interfere with blood glucose homeostasis (except insulin) and GE.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cases<br>gastric emptying test gut hormones determination Continuous Glucose Monitoring Insulin single bolus Insulin double-wave bolus | Other: gastric emptying test<br>* gastric emptying rate for solid will be determined using the 13C-OBT. Breath samples will be taken before the meal and then at 15-min intervals for a period of 240 min postprandially. The 13C content will be determined by on-line gas chromatographic purification-isotope ratio mass spectrometry (ABCA; Europe Scientific, Crewe, UK). The 13CO2 excretion curves will be analyzed and the half-emptying time (t½) and lag phase (tlag) calculated.<br>Other: gut hormones determination<br>* blood sampling at 0, 15, 30, 60, 90, 120, 180 min for determination of plasma, glucagon and GI hormones (Ghrelin, GLP-1, GIP)<br>Other: Continuous Glucose Monitoring<br>* 7 days Continuous Glucose Monitoring<br>Drug: Insulin single bolus<br>* pre-prandial insulin administered as single bolus calculated on the basis of carbohydrate counting and each patient's insulin/glycaemic load<br>Drug: Insulin double-wave bolus<br>* pre-prandial insulin fractioned into a double-wave bolus<br>|
| Sham Comparator: Controls<br>gastric emptying test gut hormones determination | Other: gastric emptying test<br>* gastric emptying rate for solid will be determined using the 13C-OBT. Breath samples will be taken before the meal and then at 15-min intervals for a period of 240 min postprandially. The 13C content will be determined by on-line gas chromatographic purification-isotope ratio mass spectrometry (ABCA; Europe Scientific, Crewe, UK). The 13CO2 excretion curves will be analyzed and the half-emptying time (t½) and lag phase (tlag) calculated.<br>Other: gut hormones determination<br>* blood sampling at 0, 15, 30, 60, 90, 120, 180 min for determination of plasma, glucagon and GI hormones (Ghrelin, GLP-1, GIP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gastric emptying measure |  | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut hormones dosage |  | 3 hours | 
| Continuous Glucose Monitoring |  | 7 days | 
| postprandial glucose variability after single insulin bolus |  | 3 hours | 
| postprandial glucose variability after double-wave insulin bolus |  | 3 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes mellitus, Gastric Emptying, Insulin Infusion Pump