Clinical trial NCT02472951: Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes - Mechanisms of Effective Therapy of Diabetes by Selective Choice of Macronutrients - The Phenotype Study
Official title: Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes - Mechanisms of Effective Therapy of Diabetes by Selective Choice of Macronutrients - The Phenotype Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
First posted: 2015-06-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Scientific evidence for the dietary treatment of type 2 diabetes is insufficient. The investigators hypothesize that a lower carbohydrate content in the diabetic diet than the recommended 55 E% will decrease the postprandial glucose excursion, decrease insulinotropic factors like incretin hormones and decrease their insulinotropic effects due to their glucose dependency. This will reduce postprandial insulin concentration, resulting in an improved insulin sensitivity and glucose metabolism. This clinical study will examine in diabetic, prediabetic and healthy subjects the acute effects of short term highly controlled dietary low carbohydrate intervention on metabolic pathways with respect to insulin action, pancreatic islet function, lipid metabolism, incretin hormones, low grade inflammation in plasma and novel measures of fatty acid metabolism.


Eligibility criteria: Inclusion Criteria:

* Men age 18-70 years
* Postmenopausal women age 55-70 years
* Non-smoker (abstinent at least 6 months)
* HbA1c \< 74 mmol/mol
* Fasting blood glucose \< 11 mmol/L (mean of 3 measurements)
* Negative (\<25 IU/L) plasma glutamate decarboxylase (GAD-65) antibodies (IgG)
* Hemoglobin \> 7.5 mmol/L (men); \> 6.8 mmol/L (women)
* Normal thrombocytes (140-400 x 109/L)
* eGFR \> 45 ml/min per 1.73 m2
* Alkaline phosphatase \< 140 IU/L
* Alanine aminotransferase \< 70 IU/L
* Normal International Normalized Ratio (0.9-1.2)

Exclusion Criteria:

* Critical illness
* Anti-diabetic drugs other than metformin (maximum of 2000 mg / day)
* Steroid treatment e.g. prednisolone
* Reported or journalized severe food allergy or intolerance
* Reported or journalized gut disease e.g. Crohn's disease, Coeliac disease
* Reported or journalized alcohol dependence syndrome

Primary outcomes:
measure: Insulin sensitivity
timeFrame: Measured during meal tests (2 days with each intervention)
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Endocrinological Dept. Bispebjerg University Hospital
state: Zealand
Study officials:
affiliation: Amager og Hvidovre Hospital
name: Steen B Haugaard, MD, DMSc, associate prof.
role: STUDY_DIRECTOR
affiliation: Bispebjerg Hospital
name: Thure Krarup, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Bispebjerg Hospital
name: Amirsalar Samkani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thomsen MN, Skytte MJ, Samkani A, Astrup A, Fenger M, Frystyk J, Hartmann B, Holst JJ, Larsen TM, Madsbad S, Magkos F, Rehfeld JF, Haugaard SB, Krarup T. Weight loss improves beta-cell function independently of dietary carbohydrate restriction in people with type 2 diabetes: A 6-week randomized controlled trial. Front Nutr. 2022 Aug 19;9:933118. doi: 10.3389/fnut.2022.933118. eCollection 2022.
citation: Thomsen MN, Skytte MJ, Astrup A, Deacon CF, Holst JJ, Madsbad S, Krarup T, Haugaard SB, Samkani A. The clinical effects of a carbohydrate-reduced high-protein diet on glycaemic variability in metformin-treated patients with type 2 diabetes mellitus: A randomised controlled study. Clin Nutr ESPEN. 2020 Oct;39:46-52. doi: 10.1016/j.clnesp.2020.07.002. Epub 2020 Aug 1.
citation: Samkani A, Skytte MJ, Anholm C, Astrup A, Deacon CF, Holst JJ, Madsbad S, Boston R, Krarup T, Haugaard SB. The acute effects of dietary carbohydrate reduction on postprandial responses of non-esterified fatty acids and triglycerides: a randomized trial. Lipids Health Dis. 2018 Dec 27;17(1):295. doi: 10.1186/s12944-018-0953-8.
citation: Samkani A, Skytte MJ, Kandel D, Kjaer S, Astrup A, Deacon CF, Holst JJ, Madsbad S, Rehfeld JF, Haugaard SB, Krarup T. A carbohydrate-reduced high-protein diet acutely decreases postprandial and diurnal glucose excursions in type 2 diabetes patients. Br J Nutr. 2018 Apr;119(8):910-917. doi: 10.1017/S0007114518000521.