Acute Studies on the Glycemic Index After Intake of Different Sorts of Barley in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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In a series of double-blinded randomized cross-over acute studies, the investigators want to study the effects of different types of barley on the glycemic index (GI) in subjects with type 2 diabetes. The most common type of barley in Denmark is with rind and demands processing before use. Processing may remove important nutrients from the barley. Some of the original antiquity barley has a loose rind (nude barley), that falls off during harvesting, and thereby reduces the need for processing. The investigators want to study how this ancient type of barley affects GI. Furthermore, some of the investigators collaborative partners have made it possible to increase the amount of amylose in regular barley by genetic modification. The investigators want to study the effect on GI of this new type of modified barley.

Detailed Description
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Approx. 60 mio. people worldwide live with diabetes and the prevalence is increasing. The increase is primarily due to obesity, unhealthy diet and lack of physical activity. Therefore, it is important to find dietary products that counteracts this development. Intake of food with a low glycemic index (GI) reduces the risk of developing type 2 diabetes (T2D) and helps in the regulation of a preexisting diabetes. Barley has shown some beneficial effects on GI compared with wheat, however, barley is not commonly used in bread making in Denmark. The most common type of barley in Denmark is with rind and demands processing before use. Processing may remove important nutrients from the barley. Some of the original antiquity barley has a loose rind (nude barley), that falls of during harvesting, and thereby reduces the need for processing. However, it is not known how this ancient type of barley affects GI. The composition of the starch in barley is of importance when the grain is degraded after consumption. The starch consists of both amylose (which is slowly degraded) and amylopectin (which is quickly degraded). By genetic modification, it was possible for collaborative researchers at the Universities of Aarhus and Copenhagen to increase the amount of amylose in regular barley. Slowly degraded starch is expected to decrease GI. In a series of acute studies the investigators want to study the effects on the glucose metabolism to intake of bread made with different compositions of wheat, nude barley and gene-modified high-amylose barley in subjects with T2D. It is expected that both nude barley and gene-modified high-amylose barley lowers the postprandial glycemic response more than wheat and hereby positively affect the glycemic regulation for subjects with type 2 diabetes.

Official Title
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HIAMBA-1 - the Effects of Nude Barley and Gene-modified High-amylose Barley on Postprandial Glucose Metabolism in Subjects With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Dietary Supplement: 100% wheat
* Dietary Supplement: 50% nude barley and 50% wheat
* Dietary Supplement: 75% nude barley and 25% wheat
* Dietary Supplement: 50% gene-modified high-amylose barley and 50% wheat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes (T2D) defined by standard Danish guidelines. HbA1c between 48-78 mmol/l. Treatment with drugs for hypertension and high cholesterol is allowed if the treatment dose is stable and does not demand changes during the study period. Participants are encouraged to maintain their present psychical activity level and their smoking and alcohol habits. Exclusion Criteria: Type 1 diabetes Insulin demanding T2D Use of weekly administrated GLP-1 antagonist (e.g. ozempic, trulicity or byetta) Use of acarbose Significant cardiovascular, kidney, liver or endocrine comorbidity Significant psychiatric history Treatment with steroids Alcohol or drug abuse Pregnancy or breastfeeding Legally incompetent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blinded, cross-over, acute, dietary intervention study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 g of 100% wheat bread<br>Intake of 250 ml of tap water and 100 g of bread baked with 100% wheat flour (regular commercial available wheat flour). Consumed over maximum 10 minutes at time 0 min after overnight fasting. At one of four visits. | Dietary Supplement: 100% wheat<br>* 100 g of bread backed with 100% wheat<br>|
| Experimental: Nude barley 50%<br>Intake of 250 ml of tap water and 100 g of bread baked with 50% nude barley flour and 50% wheat flour. Consumed over maximum 10 minutes at time 0 min after overnight fasting. At one of four visits. Ancient nude barley naturally bred in corporation with PlantCarb ApS and researchers at Aarhus and Copenhagen Universities. The wheat flour is standard commercial available flour. | Dietary Supplement: 50% nude barley and 50% wheat<br>* 100 g of bread backed with 50% nude barley and 50% wheat<br>|
| Experimental: Nude barley 75%<br>Intake of 250 ml of tapwater and 100 g of bread baked with 75% nude barley flour and 25% wheat flour. Consumed over maximum 10 minutes at time 0 min after overnight fasting. At one of four visits. Ancient nude barley naturally bred in corporation with PlantCarb ApS and researchers at Aarhus and Copenhagen Universities. The wheat flour is standard commercial available flour. | Dietary Supplement: 75% nude barley and 25% wheat<br>* 100 g of bread backed with 75% of nude barley and 25% wheat<br>|
| Experimental: Gen-modified high-amylose barley<br>Intake of 250 ml of tap water and 100 g of bread baked with 50% gene-modified high-amylose barley and 50% wheat. Consumed over maximum 10 minutes at time 0 min after overnight fasting. At one of four visits. The gene-modified barley is produced by researchers at Aarhus and Copenhagen Universities as published in 'Carciofi M, et al., Concerted suppression of all starch branching enzyme genes in barley produces amylose-only starch granules. BMC Plant Biol. 2012 Nov 21;12:223. doi: 10.1186/1471-2229-12-223' The wheat flour is standard commercial available flour. | Dietary Supplement: 50% gene-modified high-amylose barley and 50% wheat<br>* 100 g of bread backed with 50% gene-modified high-amylose barley and 50% wheat<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glycemic response | Area under the curve for glucose (mmol/L) | Change from -10 minutes to 240 minutes after bread intake (measured at time -10,0,10,20,30,45,60,90,120,150,180,210,240 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial insulin response | Area under the curve for insulin (pmol/L) | Change from -10 minutes to 240 minutes after bread (measured at time -10,0,10,20,30,45,60,90,120,150,180,210,240 minutes) | 
| Postprandial glucagon response | Area under the curve for glucagon (pg/mL) | Change from -10 minutes to 240 minutes after bread (measured at time -10,0,10,20,30,45,60,90,120,150,180,210,240 minutes) | 
| Postprandial triglyceride response | Area under the curve for triglyceride (mmol/L) | Change from -10 minutes to 240 minutes after bread (measured at time -10,0,30,60,120,180,240 minutes) | 
| Postprandial free fatty acid response | Area under the curve for free fatty acids (mmol/L) | Change from -10 minutes to 240 minutes after bread (measured at time -10,0,30,60,120,180,240 minutes) | 
| Postprandial GLP-1 (glucagon-like peptide-1) response | Area under the curve for GLP-1 (pmol/L) | Change from -10 minutes to 240 minutes after bread (measured at time -10,0,30,60,120,180,240 minutes) | 
| Postprandial GIP (Glucose-dependent insulinotropic polypeptide) response | Area under the curve for GIP (pmol/L) | Change from -10 minutes to 240 minutes after bread (measured at time -10,0,30,60,120,180,240 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glycemic index, Postprandial, Barley