Study of Oral Anthocyanins on Insulin Resistance

Dietary strategies for alleviating the metabolic complications such as diabetes associated with obesity are actively being pursued as alternatives to pharmaceutical interventions The genus Vaccinium (e.g. blueberry, blaeberry, cranberry) has been used traditionally as a source of folk remedies for established diabetic symptoms, primarily as leaf or stem infusions or decoctions. Berries from this family such as blaeberry (BL) and blueberry (BB) are enriched in anthocyanins, polyphenolics recognized for their ability to provide and activate cellular antioxidant protection, inhibit inflammatory gene expression, and consequently protect against oxidant-induced and inflammatory cell damage and cytotoxicity. The association of obesity with adipose tissue stress, macrophage recruitment, and inflammatory gene expression suggests that eating edible berries from this genus might provide an effective alternative or supplementary intervention to attenuate obesity- associated inflammation and the associated insulin resistance.

The aim of this study is to determine the effects of anthocyanin supplementation in the form of a concentrated blaeberry extract on insulin resistance and inflammation particularly in the adipose tissue following a three week supplementation period.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Dietary supplement: Mirtoselect

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom, AB21 9SB
    • University of Aberdeen Rowett Institute of Nutrition and Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Obese male subjects (BMI > 30)
• Aged > 40 and < 70 years of age
• Type 2 diabetes; subjects controlling their diabetes by diet alone or with impaired glucose tolerance
• All the obese subjects will have a waist circumference over 40 inches
• All subjects must live the Aberdeenshire area of Scotland

Exclusion Criteria:

Medical exclusion criteria:

• Chronic illness, including:

  • thromboembolic or coagulation disease,
  • unregulated thyroid disease,
  • kidney disease,
  • hepatic disease,
  • severe gastrointestinal disorders,
  • pulmonary disease (e.g. chronic bronchitis, COPD),
• Alcohol or any other substance abuse,
• Eating disorders,
• Psychiatric disorders (including severe depression, lithium treatment, schizophrenia, severe behavioural disorders),
• Skin conditions on the abdomen,
• Allergy to skin dressings,

Medication exclusion criteria:

• Oral steroids,
• Tricyclic antidepressants, neuroleptics,
• Anticoagulants,
• Digoxin and antiarrhythmics,
• Chronic use of antiinflammatories (e.g. high doses of aspirin, ibuprofen),
• Insulin, Sulphonylureas, Thiazolidinediones (glitazones), metformin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Blaeberry concentrated caspule; 30 obese male subjects (BMI > 30) with type 2 diabetes controlling their diabetes by diet alone or impaired glucose tolerance. Volunteers will be given a total daily dose of 1.4 grams of mirtoselect (a concentrated blaeberry extract) a day formulated in hard gelatin capsules (0.47 gram per capsule) administered thrice a day for 21 days. Mirtoselect provided by Indena S.p.A. (http://www.mirtoselect.info/)	Dietary supplement: Mirtoselect; Male subjects (BMI > 30) with type 2 diabetes controlling their diabetes by diet alone or impaired glucose tolerance. Volunteers will be given either a total daily dose of 1.4 grams of concentrated blaeberry extract (mirtoselect provided by Indena S.p.A. (http://www.mirtoselect.info/) in a hard gelatin capsules or control capsules containing lactose administered thrice a day for 21 days.
Placebo Comparator: Placebo capsules containing lactose; 30 obese male subjects (BMI > 30) with type 2 diabetes controlling their diabetes by diet alone or impaired glucose tolerance. Volunteers will be given a placebo consisting of lactose formulated in hard gelatin capsules administered thrice a day for 21 days.	Dietary supplement: Mirtoselect; Male subjects (BMI > 30) with type 2 diabetes controlling their diabetes by diet alone or impaired glucose tolerance. Volunteers will be given either a total daily dose of 1.4 grams of concentrated blaeberry extract (mirtoselect provided by Indena S.p.A. (http://www.mirtoselect.info/) in a hard gelatin capsules or control capsules containing lactose administered thrice a day for 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Glucose Tolerance Test	Change in Oral Glucose Tolerance following intervention	Day 0 and 21 days post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose/insulin	Change in fasting blood glucose/insulin in response to intervention	Day 0, 7, 14, and 21 days post intervention

Collaborators and Investigators

• Sponsor: University of Aberdeen
• Investigators: Principal Investigator: Nigel Hoggard, PhD, University of Aberdeen Rowett Institute of Nutrition and Health

Publications and helpful links

General Publications

• DeFuria J, Bennett G, Strissel KJ, Perfield JW 2nd, Milbury PE, Greenberg AS, Obin MS. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. J Nutr. 2009 Aug;139(8):1510-6. doi: 10.3945/jn.109.105155. Epub 2009 Jun 10.
• Martineau LC, Couture A, Spoor D, Benhaddou-Andaloussi A, Harris C, Meddah B, Leduc C, Burt A, Vuong T, Mai Le P, Prentki M, Bennett SA, Arnason JT, Haddad PS. Anti-diabetic properties of the Canadian lowbush blueberry Vaccinium angustifolium Ait. Phytomedicine. 2006 Nov;13(9-10):612-23. doi: 10.1016/j.phymed.2006.08.005. Epub 2006 Sep 18.
• Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D. Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res. 2007 Jun;51(6):675-83. doi: 10.1002/mnfr.200700002.
• Lau FC, Bielinski DF, Joseph JA. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J Neurosci Res. 2007 Apr;85(5):1010-7. doi: 10.1002/jnr.21205.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 11, 2010
• First Posted (Estimate): August 12, 2010

Study Record Updates

• Last Update Posted (Actual): August 2, 2019
• Last Update Submitted That Met QC Criteria: August 1, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: blueberries; type 2 diabetes; inflammation; insulin resistance; Adipose tissue; anthocyanin; blaeberries; bilberries; mirtoselect
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: REC 10/S0802/27; Rowett 901 (Other Identifier: Rowett institute study code)