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| Name | Class |
|---|---|
| Danish Diabetes Academy | OTHER |
| Region of Southern Denmark | OTHER |
| Odense Patient Data Explorative Network | OTHER |
| Novo Nordisk A/S |
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Further studies are needed to establish the optimal diet for treating T2D.
The investigators wishes to investigate whether a low carbohydrate diet, high in monounsaturated fats (LCD) will affect cardiovascular function, metabolism and the liver.
135 participants with T2D, will be following either a LCD, or a regular diabetes diet (RDD) for 6 months. Measurements and investigations will be performed at baseline and after 6 months.
Type 2 diabetes (T2D) is an increasing global problem, especially in developing countries. T2D is associated with an increased risk of cardiovascular disease (CVD), where hyperglycemia is especially important for microvascular damage.
Previous studies in T2D on reduced carbohydrate intake has shown beneficial effects on glycemic control, indicated by reduction in HbA1c, fasting insulin and 2h-glucose (OGTT) values. However further studies are needed to establish the optimal diet for treating T2D.
The investigators wishes to investigate whether a low carbohydrate diet, high in monounsaturated fats will:
The study will be conducted through a 6 month randomized controlled trial with 135 participants with type 2 diabetes. 90 participants will be randomized to the intervention group, following a LCD, and 45 participants will be randomized to the control group (regular diet for diabetes, RDD). The below described measurements will be conducted before baseline and after 6 months, and the participants will fill out a QoL questionnaire at 0, 3 and 6 months.
Planned examinations are ultrasound assessment of flow-mediated vasodilation, Dual-energy X-ray absorptiometry (DEXA-scan), retina scan, liver biopsy, liver-scans, blood, urine, hair, saliva and feces. Accelerometers will be applied before, during and after the study to evaluate compliance in unchanged exercise pattern. Compliance with diet will be evaluated by a clinical dietitian and through food diaries.
Baseline histology from the first 50 participants suggest that the current inclusion criteria doesn't cover the full spectrum of NAFLD (NASH and fibrosis) as expected. Further 50 participants who will have had diabetes for more than 10 years and who will not fulfill inclusion criteria number 1 and 2 will be included. On this group of participants we will only perform liver-investigations and DEXA-scan. This group of participants, will not affect the timeschedule of the main study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control-group | No Intervention | The control group will be eating a regular diabetes diet according to the Danish National Recommendations | |
| Intervention-group | Experimental | Intervention-group will be eating a low carbohydrate diet, high in monounsaturated fats |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low carbohydrate diet high in monounsaturated fats | Dietary Supplement | Participants will have to change their diet during 6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glycemic control, dyslipidemia and metabolic markers | Measured by HbA1c, serum cholesterol, blood glucose and metabolic markers | Change from baseline at 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial function | assessed by FMD in the brachial artery as well as microvascular damage assessed by retinal scan, urine albuminuria and minimal forearm vascular resistance (MFVR). | Change from baseline at 6 months |
| Non-Alcoholic Fatty Liver Disease (NAFLD) |
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Inclusion Criteria:
Duration of established T2D for more than six months and less than five years and HbA1c in compliance with T2D (above 48 mmol/mol), but without need for adjustment of antidiabetic treatment*
Serum cholesterol below 4.5 mmol/l and LDL cholesterol below 2.5 mmol/l at inclusion**
Age of 18 or above
Stable diabetic treatment three months prior to inclusion***
Be able to read and understand Danish language
Signed written consent
based on the assumption that metabolic and cardiovascular changes are less likely to be reversible in patients with longstanding T2D. HbA1c and need for adjustment and if the patient is eligible for inclusion will be evaluated individually based on the patients current treatment and current HbA1c by the project responsible. If the patient has duration of diabetes > 5 years but with current treatment ≤ 2 oral antidiabetic drugs and without insulin treatment, the patient will be accepted for enrolment.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Henning Beck-Nielsen, Professor | Odense University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Odense University Hospital | Odense | 5000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41611090 | Derived | Petersen EE, Hansen JK, Torp N, Gram-Kampmann E, Andersen P, Johansen S, Villesen IF, Bech KT, Thorhauge KH, Schnefeld HL, Gjol CMB, Jensen EL, Detlefsen S, Hojlund K, Thiele M, Israelsen M, Krag A, Hansen CD. Health-related quality of life, compliance and sustained adherence on a low-carbohydrate high-fat diet compared with a high-carbohydrate low-fat diet in people with type 2 diabetes. Am J Clin Nutr. 2026 Apr;123(4):101211. doi: 10.1016/j.ajcnut.2026.101211. Epub 2026 Jan 27. | |
| 40677693 |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D050197 | Atherosclerosis |
| D050171 | Dyslipidemias |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001161 | Arteriosclerosis |
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| INDUSTRY |
| University of Southern Denmark | OTHER |
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Assessed by >2 points reduction in NAFLD Activity score with at least 1 point reduction in either lobular inflammation or hepatocellular ballooning, without worsening of fibrosis. |
| Change from baseline at 6 months |
| Quality of life | Assessed by questionaire | Change from baseline at 6 months |
| Gut dysbiosis | Assessed by fecal sample | Change from baseline at 6 months |
| Derived |
| Wernberg CW, Indira Chandran V, Lauridsen MM, Skytthe MK, Hansen CD, Hansen JK, Gronkjaer LL, Jacobsen BG, Di Caterino T, Detlefsen S, Thiele M, Guiliani AM, Villesen IF, Leeming DJ, Karsdal M, Graversen JH, Krag A. Ability of soluble TREM2 and PRO-C3 as biomarkers to predict changes in MASLD activity. JHEP Rep. 2025 Apr 22;7(8):101432. doi: 10.1016/j.jhepr.2025.101432. eCollection 2025 Aug. |
| 37592243 | Derived | Gram-Kampmann EM, Olesen TB, Hansen CD, Hugger MB, Jensen JM, Handberg A, Beck-Nielsen H, Krag A, Olsen MH, Hojlund K. A six-month low-carbohydrate diet high in fat does not adversely affect endothelial function or markers of low-grade inflammation in patients with type 2 diabetes: an open-label randomized controlled trial. Cardiovasc Diabetol. 2023 Aug 17;22(1):212. doi: 10.1186/s12933-023-01956-8. |
| 36508737 | Derived | Hansen CD, Gram-Kampmann EM, Hansen JK, Hugger MB, Madsen BS, Jensen JM, Olesen S, Torp N, Rasmussen DN, Kjaergaard M, Johansen S, Lindvig KP, Andersen P, Thorhauge KH, Brond JC, Hermann P, Beck-Nielsen H, Detlefsen S, Hansen T, Hojlund K, Thiele MS, Israelsen M, Krag A. Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease : A Randomized Controlled Trial. Ann Intern Med. 2023 Jan;176(1):10-21. doi: 10.7326/M22-1787. Epub 2022 Dec 13. |
| D001157 |
| Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |