Effects of coffee drinking on glucose metabolism, cytokines and gastrointestinal hormone secretion

ISRCTN	ISRCTN12547806
DOI	https://doi.org/10.1186/ISRCTN12547806
Secondary identifying numbers	N/A

Submission date: 28/04/2009
Registration date: 03/07/2009
Last edited: 04/06/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Jaakko Tuomilehto
Scientific

Department of Public Health
Faculty of Medicine
P.O. Box 41 (Mannerheimintie 172)
FIN-00014
University of Helsinki
Helsinki
00300
Finland

Phone	+358 20 6108316
Email	jaakko.tuomilehto@helsinki.fi

Study information

Study design	Randomised single-blind three-stage three-arm trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Other
Scientific title	Effects of coffee drinking on glucose metabolism, cytokines and gastrointestinal hormone secretion: a single-blind randomised controlled trial
Study acronym	COGMI
Study objectives	All biomarkers determined in this study have been associated with type 2 diabetes and glucose metabolism in some way. First, glucose and insulin levels are the principal and very well known markers of diabetes. We hypothesise that coffee compounds may affect oral glucose tolerance test (OGTT) curve profile of glucose or insulin or both. Second, many inflammation markers are associated with development of type 2 diabetes. For example, interleukin-6 (IL-6) concentration is strongly related to fat mass in subjects with type 2 diabetes. Low-grade inflammation and increased C-reactive protein (CRP) have also been implicated in the development of type 2 diabetes. We hypothesise that some coffee compounds may act as protective factors of inflammation and furthermore prevent the progression of type 2 diabetes. The inflammation state is defined with measuring different plasma inflammation markers such as RANTES/CCL5, inter-cellular adhesion molecule 1 (ICAM-1), macrophage migration inhibiting factor (MIF), macrophage inflammatory protein-1 alpha (MIP-1a), IL-6 and CRP. The antioxidant properties of coffee may result in a reduction in inflammation markers. We will also determine the plasma levels of the gastric hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are critical in the regulation of glucose and insulin metabolism. In a previous acute-dose study they were found to be modified by coffee drinking. Obesity is an important factor in the aetiology of type 2 diabetes. Circulating leptin concentrations, on the other hand, increase when energy stores are high. We will clarify the possible connection between leptin concentration and components of coffee since this has not been studied before. We hypothesise that coffee may decrease appetite through leptin and furthermore decrease obesity and type 2 diabetes. Ghrelin is a neurotransmitter, which increases food intake. We assume that some compounds of coffee could affect ghrelin concentrations and keep the food intake in balance. Adiponectin participates in the long-term control of energy balance and has been suggested to affect on progression of insulin resistance, which is a very important factor in the etiology of type 2 diabetes. We hypothesise that coffee may reduce insulin resistance by affecting adiponectin levels. We are not trying to prevent the development of manifest type 2 diabetes with coffee in this trial since the trial period is too short. Instead, we focus on the possible mechanisms of coffee-derived compounds which may be responsible for the favourable effects on glucose and insulin levels. The main hypothesis is that coffee consumption has favorable effects on glucose metabolism, and chlorogenic acid and caffeic acid, or their metabolites, are responsible for these effects, and that there is a dose-response. By correlating the serum concentrations of biomarkers reflecting effects with serum concentrations of bioavailability and metabolism, we will investigate whether specific coffee-derived compounds or their metabolites, are responsible for them. In addition, we will be able to determine the mode of action of these compounds in this trial design. Aims: 1. To evaluate the effects of coffee drinking on glucose metabolism, glucose tolerance and the secretion of gastrointestinal hormones 2. To examine the effects of coffee drinking on the biomarkers of oxidative stress, protein expression, and cellular activation 3. To investigate the bioavailability, metabolism and pharmacokinetics of coffee derived compounds. Emphasis will be on chlorogenic acid and caffeic acid.
Ethics approval(s)	Joint Authority for the Hospital District of Helsinki and Uusimaa Ethics Committee, Department of Medicine, approved on the 14th December 2005 (ref: 302/E5/05)
Health condition(s) or problem(s) studied	Glucose metabolism; type 2 diabetes
Intervention	This is a randomised, single blind, national, three stage and three group (men, women, and women with gestational diabetes history) clinical trial, which lasts for three months. Trial plan: The trial plan indicates the number and timing of the planned visits. Eight clinic visits are planned. Subjects are asked to fast overnight before each visit. Visit 1 will occur before the trial to explain the points of the trial for the subjects and for fasting glucose, insulin level, GIP, GLP-1, leptin, ghrelin, adiponectin, RANTES, ICAM-1, MIF, MIP-1a, IL-6, CRP and SAA assessment at baseline. At visit 1 the subjects will get advice for exercise and nutrition to find out other sources of chlorogenic acid and caffeine. After two weeks of each stage a fasting sample will be taken and glucose, insulin level, GIP, GLP-1, leptin, ghrelin, adiponectin, RANTES, ICAM-1, MIF, MIP-1a, IL-6, CRP and SAA will be obtained. This includes visits 1, 2, 4, 6 and 8. At the end of each stage (after four weeks coffee consumption) subjects pass the OGTT and blood samples for glucose, insulin level, GIP, GLP-1, leptin, ghrelin, adiponectin, RANTES, ICAM-1, MIF, MIP-1a, IL-6, CRP and SAA will be obtained. On arrival at the clinic, an intravenous cannula is inserted into a forearm (antecubital) vein, and a baseline blood sample is taken. Then subjects will consume 75 g glucose dissolved in water. Blood samples are taken at intervals for the following 2 hours. 0-, 10-, 30-, 60-, 90- and 120-samples are taken. This includes visits 3, 5 and 7. Biomarkers of bioavailability of coffee-derived compounds will be analysed from serum samples obtained at the beginning of the study and at the end of each stage. The primary interest lies in serum concentrations of chlorogenic acid, caffeic acid and its metabolites. Caffeine and some of its metabolites will also be analysed in serum. Trial coffee consumption: 1. Type of the coffee and presentation: the trial coffee will be supplied by the Paulig Group. All trial coffee will be in form of roasted, brewed Juhla Mokka coffee. During the fixed period of trial 1, the subjects will be given 0, 3 or 5 packages of trial coffee. One package is 500 g. 2. Storage: all trial coffee packages will be stored at or below 10°C and protected from light and moisture. 3. Dosage: coffee will be prepared with coffee maker and will be drunk daily. Subjects will cook their daily amount of coffee in the morning and they maintain it in a thermos if it's impossible to prepare the coffee before drinking. 4. Subject restriction: subjects should refrain from coffee consumption on the morning of clinic visits. Also, the subjects are advised to maintain their normal physical activities and diet during the trial. Details of Joint Sponsors: Institute for Scientific Information on Coffee (ISIC) Roel Vaessen (ISIC Secretariat) Sir Winstonchurchilllaan 366 (19th floor) P.O. Box 161 AD Rijswijk NL-2280 Netherlands Tel: +31 (0)70 336 5166 Fax: +31 (0)70 336 5167 Email: isic@isic-coffee.org (c/o Jessica van Kalkeren) Gustav Paulig Ltd c/o Karla Koullias Gustav Pauligin katu 5 Helsinki 00990 Finland Tel: +358 (0)40 5030 845 Email: Karla.koullias@paulig.fi
Intervention type	Other
Primary outcome measure	The following will be assessed as described in the Interventions field: 1. Incretins 2. Serum cytokines and other inflammatory markers 3. Serum concentrations of polyphenols (caffeic acid and six metabolites of chlorogenic acid and caffeic acid, including their methylated and hydrated forms), caffeine, and the caffeine metabolite paraxanthine
Secondary outcome measures	1. Dietary assessment: at the end of each stage subjects fill three-day food diary to assess the normal intake of chlorogenic acid 2. Physical examination: a detailed medical history, including family history of diabetes, alcohol intake, use of any medications, as well as coronary heart disease (CHD) will be recorded
Overall study start date	01/06/2006
Completion date	31/08/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	75
Total final enrolment	49
Key inclusion criteria	For inclusion in this trial subjects must fulfill all of the following criteria: 1. Written informed consent to participate in this trial 2. All drugs which may interfere with glucose metabolism must be discontinued. These include all medication for diabetes, asthma, heart diseases and stomach. Regular non-steroidal anti-inflammatory drug (NSAID) use must also be discontinued. 3. Men and women aged less than 65 years (no lower age limit) 4. Normal fasting insulin level 5. 13 points as a result in the diabetes risk score 6. 7.0 - 12.0 mmol/l as 2-hour blood glucose value in the OGTT
Key exclusion criteria	Any of the following is regarded as a criterion for exclusion from the trial: 1. Deterioration any of base examination which reveal diabetic state 2. Persons with previous diagnosis of diabetes mellitus 3. Use of drugs, which interfere with glucose metabolism or receiving treatment to lower blood glucose 4. Pregnant women and women who are breast feeding 5. History of malignancy, which needs any therapeutic intervention 6. History of any chronic diseases or other medical characteristics likely to interfere with participation in the study 7. Subjects with imbalanced clinical conditions, such as thyroid and liver diseases, which could interfere with glucose metabolism 8. History of alcohol or drug abuse, or both
Date of first enrolment	01/06/2006
Date of final enrolment	31/08/2006

Locations

Countries of recruitment

Finland

Study participating centre

Department of Public Health

Helsinki
00300
Finland

Sponsor information

Physiologic Effects of Coffee Committee (PEC) (Netherlands)
Research organisation

Secretariat: Alice Mathijssen
P.O. Box 161
AD Rijswijk
NL-2280
Netherlands

Phone	+31 38 466 27 17
Email	pec@pec-coffee.org

Funders

Funder type

Research organisation

Institute for Scientific Information on Coffee (ISIC) (Switzerland)

No information available

Physiologic Effects of Coffee Committee (PEC) (Netherlands)

No information available

Paulig Oy (Finland) (ref: 21/05/BD/EL)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2019	04/06/2019	Yes	No

Editorial Notes

The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.