Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With Non-insulin-dependent Diabetes Mellitus (NIDDM)

May 24, 2022 updated by: Paul Hjemdahl, Karolinska Institutet

Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With NIDDM: a Placebo-controlled Dose-response Study With Insulin Aspart (Novorapid®)

The postprandial phase in diabetic patients is characterized by a rapid increase in blood glucose levels, increase in platelet aggregation, LDL oxidation and over production of thrombin.

The aim of the study is to determine whether meal induced platelet activation is related to post-prandial hyperglycemia, and can be attenuated by good postprandial glucose control with rapidly acting insulin in patients with T2DM.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Drug: Insulin aspart (Novorapid®)

Detailed Description

Each patient is admitted in the fasting state, on 3 different occasions . Blood glucose levels are normalized using intravenous infusion of insulin aspart , to a blood glucose level of 6-7 mmol/l. 15 minutes after normalization ,and right before a standardized meal, the patient is given a subcutaneous injection of insulin aspart 0.1 U/kg, 0.2 U/kg or placebo. The order of injections in the cross over study is randomized and blinded to the patient and to the investigators. The patient eats the meal and is followed up for 90 minutes after completion of the meal.

Blood tests for platelet function and other parameters are taken at 3 main points: 1. before glucose normalization.

2. 15 minutes after glucose normalization, and right before the meal. 3. 90 minutes after the meal.

Platelet function is evaluated by flow cytometry in whole blood (P- Selectin expression, Fibrinogen binding,aggregate formation: platelet- leukocyte, platelet-platelet, platelet-monocyte). Agonists that are used for platelet activation in flow cytometry are the thromboxane analogue U46619, ADP, and a collagen peptide that activates GPVI. Platelet adhesion is measured by the IMPACT cone and platelet analyser.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Sweden
- - Stockholm, Sweden, SE 171 76
    - Department of Medicine, Clinical pharmacology Unit, Karolinska University Hospital, Solna.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

Type II Diabetes Mellitus.
Antecubital forearm veins allowing technically good sampling for platelet studies.
HbA1c 6-9 % (Mono-S method).
Below 70 years

Exclusion Criteria:

History of a cardiovascular disease; Ischemic heart disease, Stroke, Peripheral vascular disease.
Acute or chronic renal or liver disease
Contraindication to insulin treatment
Treatment with Glitazones, Sulphonylurea, antiplatelet drugs,
Thrombocytopenia <150 X109/l.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Interventional Model: Crossover Assignment
Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate if platelet activation following a carbohydrate rich meal is related to the post-prandial hyperglycemia, and thus can be attenuated by premeal insulin treatment in patients with T2DM. Time Frame: 90 minutes after the meal	90 minutes after the meal
Co- primary platelet response variables: U46619 stimulated platelet P- selectin activation, platelet-leukocyte aggregation, platelet-platelet aggregates and platelet-monocyte aggregates. Time Frame: After completion of the study in 20 patients	After completion of the study in 20 patients

Secondary Outcome Measures

Outcome Measure	Time Frame
To elucidate if short-term lowering of blood glucose by insulin infusion (pretreatment standardization of blood glucose) reduces platelet activity in patients with T2DM. Time Frame: After completion of the glucose normalization (before the meal)	After completion of the glucose normalization (before the meal)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Investigators

Principal Investigator: Paul Hjemdahl, MD, PhD, Department of Medicine, Clinical Pharmacology Unit, Karolinska institute, Stockhom, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Spectre G, Ostenson CG, Li N, Hjemdahl P. Postprandial platelet activation is related to postprandial plasma insulin rather than glucose in patients with type 2 diabetes. Diabetes. 2012 Sep;61(9):2380-4. doi: 10.2337/db11-1806. Epub 2012 Jun 11.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)