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

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Other: gastric emptying test; Other: gut hormones determination; Other: Continuous Glucose Monitoring; Drug: Insulin single bolus; Drug: Insulin double-wave bolus

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • Recruiting
    • Dept. of "Medicina Clinica e Chirurgia" of Federico II University
    • Contact: Brunella Capaldo, MD; Phone Number: 0817462311; Email: bcapaldo@unina.it
    • Contact: Roberta Lupoli, MD; Phone Number: 0817462427; Email: sereroby@yahoo.it
    • Principal Investigator: Brunella Capaldo, MD
    • Sub-Investigator: Roberta Lupoli, MD
    • Sub-Investigator: Lutgarda Bozzetto, MD
    • Sub-Investigator: Giovanni Annuzzi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cases; gastric emptying test gut hormones determination Continuous Glucose Monitoring Insulin single bolus Insulin double-wave bolus	Other: gastric emptying test; 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.; Other: gut hormones determination; blood sampling at 0, 15, 30, 60, 90, 120, 180 min for determination of plasma, glucagon and GI hormones (Ghrelin, GLP-1, GIP); Other: Continuous Glucose Monitoring; 7 days Continuous Glucose Monitoring; Drug: Insulin single bolus; pre-prandial insulin administered as single bolus calculated on the basis of carbohydrate counting and each patient's insulin/glycaemic load; Drug: Insulin double-wave bolus; pre-prandial insulin fractioned into a double-wave bolus
Sham Comparator: Controls; gastric emptying test gut hormones determination	Other: gastric emptying test; 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.; Other: gut hormones determination; blood sampling at 0, 15, 30, 60, 90, 120, 180 min for determination of plasma, glucagon and GI hormones (Ghrelin, GLP-1, GIP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
gastric emptying measure	4 hours

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): November 1, 2015
• Study Completion (Anticipated): November 1, 2016

Study Registration Dates

• First Submitted: February 4, 2015
• First Submitted That Met QC Criteria: February 18, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Estimate): February 19, 2015
• Last Update Submitted That Met QC Criteria: February 18, 2015
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Gastric Emptying; Type 1 Diabetes mellitus; Insulin Infusion Pump
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Insulin; Insulin, Globin Zinc; Hormones
• Other Study ID Numbers: 248/13