Isolated and Combined Effect of a Low Carbohydrate Diet and Exercise in Hypoxia in Patients With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Isolated and Combined Effect of a Low Carbohydrate Diet and Chronic Exercise Exposure to Hypoxia on Glycaemic Control and Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05094505
• Other study ID #: BD2020.06520
• Status: Completed
• Phase: N/A
• Start date: October 1, 2021
• Est. completion date: July 18, 2023

Study information

• Verified date: July 2023
• Source: Universidade do Porto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the effects of isolated chronic exercise in hypoxia and combined exercise in hypoxia with a low carbohydrate diet on hypoxia-induced transcription factor (HIF1-α); glycaemic control and cardiovascular risk factors in patients with type 2 diabetes.

Description:

At baseline, diet plans will be individualized and energy-content prescriptions will be constant throughout the study to maintain the isocaloric control between diets. The planned macronutrient compositions will be, 30% of energy from carbohydrates, 20% from protein and 50% from fat for low carbohydrate diet (LCD) and 30% of energy from fat, 20% from protein and 50% from carbohydrates for the low-fat diet (control diet), during the 8 weeks. Both diets emphasis on low-glycemic index foods and limited saturated fat to 10% of energy, and calculated with appropriate software.

Exercise in hypoxia (at 3000m altitude, 3 sessions/week) will occur during a 8-week period intervention and all testing sessions carried out in a hypoxic chamber at Exercise Medical Center, Porto - Portugal. This chamber allows control of O2 (11-20.97%), temperature (until 50ºC), humidity (until 80%) and altitude (until 8000m). Exercise in hypoxia sessions will consist in 60 min on an ergometer (Excalibur, Lode, Netherlands) of continuous moderate and high intensity interval training, these latter considered as an efficient strategy to improve cardiorespiratory and metabolic health in patients with type 2 diabetes. Loads will be quantified according to pre-intervention testing assessments and controlled throughout each training session. All exercise testing and training sessions will be carried out at the same time of day (± 2 hours) and visits will be separated by at least 48h of recovery.

Height will be measured with use of a stadiometer (SECA), waist circumference was measured by using a tape measure positioned 3 cm above the iliac crest. Body mass index (BMI), weight, fat mass (FM) and fat-free mass (FFM) were determined by using whole-body dual-energy X-ray absorptiometry (Lunar Prodigy; General Electric Corp.). Blood pressure will be measured by using an automated sphygmomanometer (Dinamap Pro; Medical Systems,Tampa, FL) and haematological adaptations will be measured by collecting a venous blood sample from a vein in the arm using a needle. A total of 3 blood samples (pre, 1h post first intervention testing and 48h post the last intervention testing) will be taken.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 18, 2023
• Est. primary completion date: July 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosis of type 2 diabetes for at least one year

• Glycosylated haemoglobin less than 10%

• Pharmacological regimen stabilized for at least three months

• Main complications of diabetes tracked and controlled (diabetic retinopathy, diabetic nephropathy, diabetic foot and main factors of cardiovascular risk)

• Previous participation in supervised exercise programs in the last 3 months

• Smoking absence in the last 6 months.

Exclusion Criteria:

• Diagnosis of type 2 diabetes for less than a year

• Glycosylated haemoglobin above 10%

• Pharmacological regimen less than three months

• Main complications of diabetes (diabetic retinopathy, diabetic nephropathy, diabetic foot and main factors of cardiovascular risk)

• Sedentary participants

• Smoking participants

Related Conditions & MeSH terms

• Carbohydrate
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Exercise
• Hypoxia

Intervention

Other:
• Exercise in normoxia
Exercise at sea level, 3 sessions per week, during a 8-week period intervention and will consist in 60 min on an ergometer, of continuous moderate and high intensity interval training. . All exercise testing and training sessions will be carried out at the same time of day (± 2 hours) and visits will be separated by at least 48h of recovery.
• Control diet
Control diet: diet plans will be individualized and energy-content prescriptions will be constant throughout the study to maintain the isocaloric control between diets. The planned macronutrient compositions will be 20% of energy from fat, 20% from protein and 60% from carbohydrates for the low-fat diet during the 8 weeks. Diets emphasis on low-glycemic index foods and limited saturated fat to 10% of energy. Participants will meet individually with a dietitian two times for 8 weeks and should start the dietary intervention along with the intervention with exercise.
• Exercise in hypoxia
Exercise at 3000m altitude, 3 sessions per week, during a 8-week period intervention and will consist in 60 min on an ergometer, of continuous moderate and high intensity interval training. . All exercise testing and training sessions will be carried out at the same time of day (± 2 hours) and visits will be separated by at least 48h of recovery.
• Low carbohydrate diet
Low carbohydrate diet: diet plans will be individualized and energy-content prescriptions will be constant throughout the study to maintain the isocaloric control between diets. The planned macronutrient compositions will be 40% of energy from fat, 20% from protein and 40% from carbohydrates for the low-fat diet during the 8 weeks. Diets emphasis on low-glycemic index foods and limited saturated fat to 10% of energy. Participants will meet individually with a dietitian two times for 8 weeks and should start the dietary intervention along with the intervention with exercise.

Locations

Country	Name	City	State
Portugal	University of Maia	Porto
Portugal	University of Porto	Porto

Sponsors (3)

Lead Sponsor	Collaborator
Universidade do Porto	Fundação para a Ciência e a Tecnologia, University Institute of Maia

Country where clinical trial is conducted

Portugal, 

References & Publications (13)

Burtscher M, Pachinger O, Ehrenbourg I, Mitterbauer G, Faulhaber M, Puhringer R, Tkatchouk E. Intermittent hypoxia increases exercise tolerance in elderly men with and without coronary artery disease. Int J Cardiol. 2004 Aug;96(2):247-54. doi: 10.1016/j.ijcard.2003.07.021. — View Citation

Davis NJ, Tomuta N, Schechter C, Isasi CR, Segal-Isaacson CJ, Stein D, Zonszein J, Wylie-Rosett J. Comparative study of the effects of a 1-year dietary intervention of a low-carbohydrate diet versus a low-fat diet on weight and glycemic control in type 2 diabetes. Diabetes Care. 2009 Jul;32(7):1147-52. doi: 10.2337/dc08-2108. Epub 2009 Apr 14. — View Citation

Elhayany A, Lustman A, Abel R, Attal-Singer J, Vinker S. A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study. Diabetes Obes Metab. 2010 Mar;12(3):204-9. doi: 10.1111/j.1463-1326.2009.01151.x. — View Citation

Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, Neumiller JJ, Nwankwo R, Verdi CL, Urbanski P, Yancy WS Jr. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2014 Jan;37 Suppl 1:S120-43. doi: 10.2337/dc14-S120. No abstract available. — View Citation

Faramoushi M, Amir Sasan R, Sari Sarraf V, Karimi P. Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude. J Cardiovasc Thorac Res. 2016;8(1):26-33. doi: 10.15171/jcvtr.2016.05. Epub 2016 Mar 14. — View Citation

Haider T, Casucci G, Linser T, Faulhaber M, Gatterer H, Ott G, Linser A, Ehrenbourg I, Tkatchouk E, Burtscher M, Bernardi L. Interval hypoxic training improves autonomic cardiovascular and respiratory control in patients with mild chronic obstructive pulmonary disease. J Hypertens. 2009 Aug;27(8):1648-54. doi: 10.1097/HJH.0b013e32832c0018. — View Citation

Kirk JK, Graves DE, Craven TE, Lipkin EW, Austin M, Margolis KL. Restricted-carbohydrate diets in patients with type 2 diabetes: a meta-analysis. J Am Diet Assoc. 2008 Jan;108(1):91-100. doi: 10.1016/j.jada.2007.10.003. — View Citation

Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, Jung ME, Gibala MJ. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J Appl Physiol (1985). 2011 Dec;111(6):1554-60. doi: 10.1152/japplphysiol.00921.2011. Epub 2011 Aug 25. — View Citation

Millet GP, Debevec T, Brocherie F, Malatesta D, Girard O. Therapeutic Use of Exercising in Hypoxia: Promises and Limitations. Front Physiol. 2016 Jun 10;7:224. doi: 10.3389/fphys.2016.00224. eCollection 2016. No abstract available. — View Citation

Miyashita Y, Koide N, Ohtsuka M, Ozaki H, Itoh Y, Oyama T, Uetake T, Ariga K, Shirai K. Beneficial effect of low carbohydrate in low calorie diets on visceral fat reduction in type 2 diabetic patients with obesity. Diabetes Res Clin Pract. 2004 Sep;65(3):235-41. doi: 10.1016/j.diabres.2004.01.008. — View Citation

Sousa A, Figueiredo P, Zamparo P, Pyne DB, Vilas-Boas JP, Fernandes RJ. Exercise Modality Effect on Bioenergetical Performance at V O2max Intensity. Med Sci Sports Exerc. 2015 Aug;47(8):1705-13. doi: 10.1249/MSS.0000000000000580. — View Citation

Urdampilleta A, Gonzalez-Muniesa P, Portillo MP, Martinez JA. Usefulness of combining intermittent hypoxia and physical exercise in the treatment of obesity. J Physiol Biochem. 2012 Jun;68(2):289-304. doi: 10.1007/s13105-011-0115-1. Epub 2011 Nov 3. — View Citation

Wolever TM. Carbohydrate and the regulation of blood glucose and metabolism. Nutr Rev. 2003 May;61(5 Pt 2):S40-8. doi: 10.1301/nr.2003.may.S40-S48. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes from pre- to pos intervention on cardiovascular risk factor	A venous blood sample from the arm will be collected and C-Reactive Protein will be measured and expressed in mg/L.	Baseline and week 8
Other	Changes from pre- to pos intervention respiratory and pulmonary gas-exchange variables	Minute ventilation, oxygen uptake, carbon dioxide production and oxygen saturation, in mL/min, will be measured using the new telemetric portable gas analyser K5 (Rome, Italy), which will be connected to the participants through a traditional facemask and will be calibrated according to manufacturing setting.	Baseline and week 8
Other	Changes from pre- to pos intervention on body composition	Fat mass (FM) and fat-free mass (FFM) were determined by using whole-body dual-energy X-ray absorptiometry (Lunar Prodigy; General Electric Corp.).	Baseline and week 8
Other	Changes from pre- to pos intervention on body mass index (BMI)	Height (in meters) will be measured with use of a stadiometer (SECA) and weight (in kilograms) will be measured by using whole-body dual-energy X-ray absorptiometry (Lunar Prodigy; General Electric Corp.), which will determine the BMI, in kg/m^2.	Baseline and week 8
Other	Changes from pre- to pos intervention on waist circumference	Waist circumference will be measured by using a tape measure (centimeters) positioned 3 centimeters above the iliac crest.	Baseline and week 8
Other	Changes from pre- to pos intervention on blood pressure	Systolic, diastolic, and mean blood pressure will be measured using an automated sphygmomanometer (Dinamap Pro; Medical Systems, Tampa, FL).	Baseline and week 8
Other	Changes from pre- to pos intervention on lipid profile	A venous blood sample from the arm will be collected and total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides will be measured and expressed mg/dL.	Baseline and week 8
Primary	Changes from pre- to pos intervention on glycated haemoglobin	A venous blood sample from the arm will be collected and glycated hemoglobin will be measured and expressed in mmol/mol and as a percentage (%).	Baseline and week 8
Secondary	Changes from pre- to post intervention in insulin resistance index and ß-cell capacity	A venous blood sample from the arm will be collected and fasting blood glucose (mg/dL) and fasting blood insulin (micro international unit/dL) will be measured, which will determine the homeostasis model assessment (mmol/dL) and homeostasis model assessment 2 for ß-cell function (%).	Baseline and week 8
Secondary	Changes from pre- to pos intervention in angiogenesis	A venous blood sample from the arm will be collected and, serum Hypoxia Inducible Factor 1 alpha (HIF1-a) will be measured using specific ELISA kit instructions.	Baseline and week 8