Effects of Coffee Consumption on Metabolic Markers in Adults With Prediabetes and Obesity

Effects of Three-Month Coffee Consumption on Metabolic Biomarkers in Adults With Prediabetes and Obesity: a Randomized, Double-blind, Placebo-controlled Clinical Trial

Epidemiological studies have shown an inverse association between coffee consumption and risk of type 2 diabetes. However, the randomized controlled trials in prediabetes are limited to evaluate the effects of coffee. The purpose of this study is to investigate the effects of coffee on metabolic factors and inflammation in individuals with prediabetes and obesity. A double-blind, randomized controlled trial is designed to explore the effects of coffee consumption on participants with prediabetes and obesity. A total of 100 eligible participants with prediabetes and obesity will be recruited from the Health Management Center of Nanjing First Hospital. These participants are randomly assigned in a 1:1 ratio to either the coffee capsule group or the control group. The coffee capsule group will be instructed to consume 3.6 g of coffee capsules per day (0.3 g per capsule, 6 capsules per serving, twice a day, once in the morning and once in the middle of the day). The control group will be asked to consume 3.6 g of cornstarch capsules (0.3 g per capsule, 6 capsules per serving, twice a day, once in the morning and once in the middle of the day). 75 g oral glucose tolerance test, 2-week blinded continuous glucose measurement and others will be performed before and after the 3-month intervention. During the three months of intervention, the information on dietary intake, physical activity and sleep of participants will be systematically collected. To comprehensively assess the impact of coffee intake on prediabetes and obesity, we will analyze the effects of coffee capsules on various metabolic and inflammatory markers, including glucose metabolism, lipid profiles, blood pressure, adiponectin, high sensitivity C-reactive protein, interleukin-6, body mass index, body composition, the degree of hepatic steatosis and so on. We will further adjust for potential confounding factors such as lifestyle factors to better understand the underlying biological mechanisms driving this association.

Study Overview

• Status: Recruiting
• Conditions: Prediabetes
• Intervention / Treatment: Dietary supplement: Coffee capsule; Dietary supplement: Corn starch capsule

Detailed Description

Participants with both prediabetes and obesity who undergo physical examinations at the Health Management Center of Nanjing First Hospital will be recruited for this study. The details of this study design are as follows:

1. Inclusion and exclusion criteria for participants. Inclusion criteria are as follows: 1) Age between 18 and 59 years old; 2) Body mass index (BMI) ≥ 28 kg/m2; 3) No consumption of coffee in the past month; 4) Provide written informed consent; 5) Abnormal glucose tolerance, as per the 1999 WHO diagnostic criteria for prediabetes, includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or a combination of both, with blood glucose fluctuations within an abnormal range (fasting blood glucose ≥6.1 mmol/L but <7.0 mmol/L, and/or 2-hour glucose tolerance blood glucose ≥7.8 mmol/L but <11.1 mmol/L). The exclusion criteria for participants include individuals who 1) have been diagnosed with diabetes or are taking anti-diabetic drugs; 2) have a history of diseases such as cancer, liver and kidney dysfunction, existing cardiovascular and cerebrovascular diseases, and other diseases that may affect glucose and lipid metabolism; 3) self-report gastrointestinal reaction or intolerance to coffee and reject coffee consumption; 4) are pregnant or planning to become pregnant in the near future; 5) are deemed unsuitable to participate in this study by researcher believes that they are not to participate in this study.

2. Sample size calculation: Based on the estimation of research purpose, research design, expected effect size, and statistical analysis method, the sample size is determined to be 100 cases, including fifty cases in the intervention group and fifty cases in the control group.

3. Definition of the intervention group and placebo group: the intervention group serves as the coffee capsule group, and will receive 3.6 g of coffee capsules per day (0.3 g/capsule, 6 capsules/time, 2 times/day, once in the morning and once in the middle of the day). The placebo group (control group) is required to consume 3.6 g of cornstarch capsules per day (0.3 g/capsule, 6 capsules/time, 2 times/day, once in the morning and once in the middle of the day).

4. Follow-up and data collection: this follow-up period will span three months. Before and after the 3-month intervention the participants will partake in:

1. regular assessments. Demographic characteristics and medical information will be collected, including age, gender, occupation, education level, income, medication history (hormones, contraceptives, etc.), and family history of chronic diseases. Besides, using questionnaires, we also collect lifestyle information such as smoking, drinking, diet intake, physical activity, and sleep of participants. Specifically, the Simplified Food Frequency Questionnaire (FFQ25) and 24-hour Diet Record Questionnaire (DR) are employed to assess the dietary intake of participants in the past six months and the previous 24 hours (one day each in the middle of the week and on the weekend), respectively. International Physical Activity Questionnaire (IPAQ) is utilized to assess various aspects of physical activity, including time, frequency, and intensity. The sleep information (sleep time, sleep quality, etc.) is evaluated by Pittsburgh sleep quality index (PSQI).
2. A 75 g oral glucose tolerance test (75 g-OGTT). Blood samples are taken fasting and 30, 120 minutes after the glucose load. Blood samples are analyzed for glucose, insulin, C-peptide, and glucagon.
3. 2-week continuous glucose measurement using blinded continuous glucose monitor/sensor on upper arm.
4. Fasting blood samples: glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, high sensitivity C-reactive protein (CRP), interleukin 6 (IL-6).
5. Furthermore, blood pressure, transient hepatic elastography for the assessment of fatty liver degree, body composition analysis, and heart rhythm variation analysis are collected using corresponding instrument and equipment inspection. Additionally, blood, urine, and stool samples will be collected for further analysis.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jun Wang, M.D.,phD.; Phone Number: 8613382079966; Email: wangjun868@126.com
• Study Contact Backup: Name: Lin Li, PhD.; Phone Number: 8615380998768; Email: guobaolimu@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Recruiting
      • Nanjing First Hospital
      • Contact: Lin Li, PhD.; Phone Number: 8615380998768; Email: guobaolimu@126.com
      • Contact: Jun Wang, M.D., PhD.; Phone Number: 8613382079966; Email: wangjun868@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age between 18 and 59 years old;
2. Diagnosis of Prediabetes according to the WHO criteria (fasting glucose=6.1-6.9 mmol/L and/or 2-hour post-OGTT glucose=7.8- 11.0 mmol/L);
3. Body mass index ( BMI ) ≥ 28kg/m2;
4. No coffee intake in the past month;
5. Provide written informed consent and be willing to participate.

Exclusion Criteria:

1. Patients with diagnosis of diabetes, or taking anti-diabetic medication;
2. Patients with cardiovascular or cerebrovascular diseases, cancer, renal disease, liver disease, other chronic diseases affecting glucose and lipid metabolism, etc;
3. Participants with known hypersensitivity or intolerance to coffee, or unwilling to accept coffee;
4. Pregnancy, planned pregnancy, or lactation;
5. Investigators, for any reason, consider the participants inappropriate for the study (e.g., uncontrolled bipolar disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Coffee capsule; participants in this arm ingest coffee capsules with 1.8g instant black coffee powder twice daily with breakfast and lunch.	Dietary supplement: Coffee capsule; Take 12 coffee capsules containing 3.6 g instant black coffee powder per day (take 6 coffee capsules twice daily with breakfast and lunch).; Other Names: 0 sugar 0 fat black coffee, instant black coffee. Product standard code: Q/QC 0001S. Food production license number: SC10644190004159.
Placebo Comparator: Placebo; participants in this arm consume cornstarch capsules (without coffee) twice daily with breakfast and lunch.	Dietary supplement: Corn starch capsule; Take 12 placebo capsules containing 3.6 g corn starch per day (take 6 placebo capsules twice daily with breakfast and lunch).; Other Names: Edible corn starch. Product standard code: GB 31637. Food production license number: SC10313102300041.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous glucose monitoring parameters	14 days blinded intermittent-scanned continuous glucose monitoring (CGM): the FreeStyle Libre Pro system is utilized to record glycemic data, with the readout of the device exclusively performed by researchers. During the day, participants will be blinded to their glucose values.	at baseline, after three-month intervention
glucose from a 75 g-oral glucose tolerance test （mmol/L）	Blood samples will be drawn at time points 0 min, 30 min, 120 min for glucose measurements during a 75 g-oral glucose tolerance test (75 g-OGTT). Incremental glucose area under the curve (gAUC) will be calculated using the trapezoidal method.	at baseline, after one-month intervention, after three-month intervention
insulin from a 75 g-oral glucose tolerance test （pmol/L）	Blood samples will be drawn at time points 0 min, 30 min, 120 min for insulin measurements during a 75 g-oral glucose tolerance test (75 g-OGTT). Incremental insulin area under the curve (iAUC) will be calculated using the trapezoidal method.	at baseline, after one-month intervention, after three-month intervention
C-peptide from a 75 g-oral glucose tolerance test (ng/ml)	Blood samples will be drawn at time points 0 min, 30 min, 120 min for C-peptide measurements during a 75 g-oral glucose tolerance test (75 g-OGTT).	at baseline, after one-month intervention, after three-month intervention
glucagon from a 75 g-oral glucose tolerance test（pmol/L）	Blood samples will be drawn at time points 0 min, 30 min, 120 min for glucagon measurements during a 75 g-oral glucose tolerance test (75 g-OGTT).	at baseline, after one-month intervention, after three-month intervention
Glycated hemoglobin (HbA1c) ( % )	Reflect the levels of blood sugar in the past two to three months.	at baseline, after three-month intervention
Fasting total cholesterol (mmol/L)	Serum total cholesterol concentrations under fasting conditions.	at baseline, after one-month intervention, after three-month intervention
Fasting high-density lipoprotein-cholesterol (mmol/L)	Serum high-density lipoprotein-cholesterol (HDL-C) concentrations under fasting conditions.	at baseline, after one-month intervention, after three-month intervention
Fasting low-density lipoprotein-cholesterol (mmol/L)	Serum low-density lipoprotein-cholesterol ( LDL-C) concentrations under fasting conditions.	at baseline, after one-month intervention, after three-month intervention
Fasting triglycerides (mmol/L)	Serum triglycerides concentrations under fasting conditions.	at baseline, after one-month intervention, after three-month intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-reactive protein	Serum levels of inflammatory factors: high-sensitivity C-reactive protein (CRP).	at baseline, after one-month intervention, after three-month intervention
Interleukin-6	Serum levels of inflammatory factors: interleukin-6 (IL-6).	at baseline, after one-month intervention, after three-month intervention
Body mass index ( kg/m^2)	Calculation of body mass index (BMI) using body weight and height.	at baseline, after one-month intervention, after three-month intervention
Fat mass (FM)	Assessed using an InBody bioelectrical impedance analyzer.	at baseline, after one-month intervention, after three-month intervention
body fat percentage (BF)	Assessed using an InBody bioelectrical impedance analyzer.	at baseline, after one-month intervention, after three-month intervention
visceral fat	Assessed using an InBody bioelectrical impedance analyzer.	at baseline, after one-month intervention, after three-month intervention
skeletal muscle mass (SMM)	Assessed using an InBody bioelectrical impedance analyzer.	at baseline, after one-month intervention, after three-month intervention
fat-free mass (FFM)	Assessed using an InBody bioelectrical impedance analyzer.	at baseline, after one-month intervention, after three-month intervention
Adiponectin	high-molecular-weight adiponectin	at baseline, after one-month intervention, after three-month intervention
Systolic blood pressure（mmHg）	After 20 min of rest, blood pressure will be measured between 8:00 and 9:00 in the morning by an experienced nurse and the average of three consecutive measurements will be recorded.	at baseline, after one-month intervention, after three-month intervention
Diastolic blood pressure（mmHg）	After 20 min of rest, blood pressure will be measured between 8:00 and 9:00 in the morning by an experienced nurse and the average of three consecutive measurements will be recorded.	at baseline, after one-month intervention, after three-month intervention
Heart rate （bpm）	After 20 min of rest, heart rate will be measured between 8:00 and 9:00 in the morning by an experienced nurse and the average of three consecutive measurements will be recorded.	at baseline, after one-month intervention, after three-month intervention
Controlled attenuation parameter (CAP)	Controlled attenuation parameter (CAP) by transient hepatic elastography (THE) assesses the degree of hepatic steatosis.	at baseline, after one-month intervention, after three-month intervention
Standard deviation of heart rate variability (SDNN)	Heart Rhythm Variation Analysis.	at baseline, after one-month intervention, after three-month intervention

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University
• Investigators: Principal Investigator: Jun Wang, M.D.,phD., Health Management Center of Nanjing First Hospital

Publications and helpful links

General Publications

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• Ding M, Bhupathiraju SN, Chen M, van Dam RM, Hu FB. Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Diabetes Care. 2014 Feb;37(2):569-86. doi: 10.2337/dc13-1203.
• Scheen AJ, Letiexhe MR, Ernest P. [Prevention of type 2 diabetes: lifestyle changes or pharmacological interventions?]. Rev Med Liege. 2003 Apr;58(4):206-10. French.
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• Bae JM. Coffee consumption and risk of type 2 diabetes mellitus in Asians: A meta-epidemiological study of population-based cohort studies. World J Diabetes. 2021 Jun 15;12(6):908-915. doi: 10.4239/wjd.v12.i6.908.
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• Osama H, Abdelrahman MA, Madney YM, Harb HS, Saeed H, Abdelrahim MEA. Coffee and type 2 diabetes risk: Is the association mediated by adiponectin, leptin, c-reactive protein or Interleukin-6? A systematic review and meta-analysis. Int J Clin Pract. 2021 Jun;75(6):e13983. doi: 10.1111/ijcp.13983. Epub 2021 Jan 21.
• Shahinfar H, Jayedi A, Khan TA, Shab-Bidar S. Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of cohort studies. Nutr Metab Cardiovasc Dis. 2021 Aug 26;31(9):2526-2538. doi: 10.1016/j.numecd.2021.05.014. Epub 2021 May 24.
• Carlstrom M, Larsson SC. Coffee consumption and reduced risk of developing type 2 diabetes: a systematic review with meta-analysis. Nutr Rev. 2018 Jun 1;76(6):395-417. doi: 10.1093/nutrit/nuy014.
• Bhupathiraju SN, Pan A, Manson JE, Willett WC, van Dam RM, Hu FB. Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women. Diabetologia. 2014 Jul;57(7):1346-54. doi: 10.1007/s00125-014-3235-7. Epub 2014 Apr 26.
• van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus. Lancet. 2002 Nov 9;360(9344):1477-8. doi: 10.1016/S0140-6736(02)11436-X.
• Bidel S, Silventoinen K, Hu G, Lee DH, Kaprio J, Tuomilehto J. Coffee consumption, serum gamma-glutamyltransferase and risk of type II diabetes. Eur J Clin Nutr. 2008 Feb;62(2):178-85. doi: 10.1038/sj.ejcn.1602712. Epub 2007 Mar 7.
• Greenberg JA, Boozer CN, Geliebter A. Coffee, diabetes, and weight control. Am J Clin Nutr. 2006 Oct;84(4):682-93. doi: 10.1093/ajcn/84.4.682.
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Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Obesity; Prediabetes; Lipid metabolism; Glucose metabolism; Coffee
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperglycemia; Obesity; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: KY20231109-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No