Alkaline Diet for Insulin Sensitivity

Type 2 Diabetes Mellitus Clinical Trial

— ADIS  

Official title:

Alkaline Diet for Insulin Sensitivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02501343
• Other study ID #: ADIS (SVH 14/157)
• Status: Completed
• Phase: N/A
• First received: July 13, 2015
• Last updated: March 5, 2017
• Start date: March 2015
• Est. completion date: December 2016

Study information

• Verified date: March 2017
• Source: Garvan Institute of Medical Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the effect of increasing the body pH acutely with an alkaline medication (sodium bicarbonate, NaHCO3, sodibic) on glucose metabolism post meal in non diabetic subjects with normal renal function.

The investigators aim to determine whether there is an acute reduction in venous blood pH following a typical Western-style (high acid load) breakfast in healthy men and women, and whether this effect is attenuated by the concurrent administration of an alkaline medication. The effect on glucose metabolism, hunger/satiety and arterial stiffness post meal will be assessed.

Description:

The aim of the study is to test the effect of increasing the body pH acutely with an alkali (NaHCO3) prior to a high acid load meal on glucose metabolism in non-diabetic men and women.

This is a double-blind placebo-controlled randomised study with a crossover design.

Study Procedures:

Two (2) meal studies will be performed 1 to 2 weeks apart. Studies will include collecting fasting blood to assess circulating glucose, insulin, C-peptide, free fatty acids, glucagon-like peptide-1, acid/base markers, including electrolytes (EUC) and venous blood pH. Participants will then be either administered sodibic (1680 mg) or matching placebo and a standardised Western style/high acid load meal. Investigators and participants will be blinded to the intervention. Blood will be drawn every 15 min in the first hour and then every 30 min for 3 hours in total. Arterial stiffness and appetite score will be evaluated at ½ h intervals.

Sample size: 30

sample size calculation: To detect a difference in area under the curve (AUC) of venous blood pH with a paired crossover design, 32 individuals will be required with statistical power 1-β>0.8 (allowing for drop-out).

statistical considerations: Differences between AUC of outcome measures post sodium bicarbonate vs. placebo will be tested using paired t-tests. Two-way repeated measure ANOVA tests will be conducted to assess differences in the response to the meal with sodium bicarbonate vs. placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 22 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age range: 22-65

• Disease status: Healthy.

• Laboratory parameters: Fasting plasma glucose <7 mmol/L, HbA1c <6.5% (48 mmol/mol).

• Willingness to give written informed consent and willingness to participate and comply with the study.

Exclusion Criteria:

• Individuals with a personal history of diabetes, hypertension, cardiovascular disease, kidney disease, respiratory disease or inflammatory disease.

• Individuals treated with medications known to affect insulin sensitivity.

• Individuals with fasting plasma glucose =7 mmol/L, HbA1c =6.5% (48 mmol/mol).

• Individuals with an unstable body weight in the past 3 months (+/- 2 kg or more).

• Individuals with a history of a psychological illness or condition that may interfere with the participant's ability to understand the requirements of the study.

• Individuals who smoke.

• Individuals who consume more than 40 g of alcohol daily.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Dysglycemia
• Insulin Resistance
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sodium Bicarbonate Oral Capsule
Sodium bicarbonate 1680 mg will be administered prior to the meal
• Placebo
Sodibic-matching placebo (Stenlake Compounding Chemist, NSW, Australia) will be administered prior to the meal on a different day 1 to 2 weeks apart

Locations

Country	Name	City	State
Australia	Garvan Institute of Medical Research	Darlinghurst	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Garvan Institute of Medical Research

Country where clinical trial is conducted

Australia, 

References & Publications (15)

Adeva MM, Souto G. Diet-induced metabolic acidosis. Clin Nutr. 2011 Aug;30(4):416-21. doi: 10.1016/j.clnu.2011.03.008. Review. — View Citation

Akter S, Eguchi M, Kurotani K, Kochi T, Pham NM, Ito R, Kuwahara K, Tsuruoka H, Mizoue T, Kabe I, Nanri A. High dietary acid load is associated with increased prevalence of hypertension: the Furukawa Nutrition and Health Study. Nutrition. 2015 Feb;31(2):298-303. doi: 10.1016/j.nut.2014.07.007. — View Citation

Crawford SO, Hoogeveen RC, Brancati FL, Astor BC, Ballantyne CM, Schmidt MI, Young JH. Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study. Int J Epidemiol. 2010 Dec;39(6):1647-55. doi: 10.1093/ije/dyq126. — View Citation

DeFronzo RA, Beckles AD. Glucose intolerance following chronic metabolic acidosis in man. Am J Physiol. 1979 Apr;236(4):E328-34. — View Citation

Fagherazzi G, Vilier A, Bonnet F, Lajous M, Balkau B, Boutron-Rualt MC, Clavel-Chapelon F. Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study. Diabetologia. 2014 Feb;57(2):313-20. — View Citation

Farwell WR, Taylor EN. Serum bicarbonate, anion gap and insulin resistance in the National Health and Nutrition Examination Survey. Diabet Med. 2008 Jul;25(7):798-804. doi: 10.1111/j.1464-5491.2008.02471.x. — View Citation

Hayata H, Miyazaki H, Niisato N, Yokoyama N, Marunaka Y. Lowered extracellular pH is involved in the pathogenesis of skeletal muscle insulin resistance. Biochem Biophys Res Commun. 2014 Feb 28;445(1):170-4. doi: 10.1016/j.bbrc.2014.01.162. — View Citation

Heilbronn LK, Gan SK, Turner N, Campbell LV, Chisholm DJ. Markers of mitochondrial biogenesis and metabolism are lower in overweight and obese insulin-resistant subjects. J Clin Endocrinol Metab. 2007 Apr;92(4):1467-73. — View Citation

Juraschek SP, Selvin E, Miller ER, Brancati FL, Young JH. Plasma lactate and diabetes risk in 8045 participants of the atherosclerosis risk in communities study. Ann Epidemiol. 2013 Dec;23(12):791-796.e4. doi: 10.1016/j.annepidem.2013.09.005. — View Citation

Lovejoy J, Newby FD, Gebhart SS, DiGirolamo M. Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin. Metabolism. 1992 Jan;41(1):22-7. — View Citation

Maalouf NM, Cameron MA, Moe OW, Adams-Huet B, Sakhaee K. Low urine pH: a novel feature of the metabolic syndrome. Clin J Am Soc Nephrol. 2007 Sep;2(5):883-8. — View Citation

Mandel EI, Curhan GC, Hu FB, Taylor EN. Plasma bicarbonate and risk of type 2 diabetes mellitus. CMAJ. 2012 Sep 18;184(13):E719-25. doi: 10.1503/cmaj.120438. — View Citation

Reaich D, Graham KA, Channon SM, Hetherington C, Scrimgeour CM, Wilkinson R, Goodship TH. Insulin-mediated changes in PD and glucose uptake after correction of acidosis in humans with CRF. Am J Physiol. 1995 Jan;268(1 Pt 1):E121-6. — View Citation

Samocha-Bonet D, Campbell LV, Mori TA, Croft KD, Greenfield JR, Turner N, Heilbronn LK. Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans. PLoS One. 2012;7(5):e36320. doi: 10.1371/journal.pone.0036320. — View Citation

Souto G, Donapetry C, Calviño J, Adeva MM. Metabolic acidosis-induced insulin resistance and cardiovascular risk. Metab Syndr Relat Disord. 2011 Aug;9(4):247-53. doi: 10.1089/met.2010.0108. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in venous blood pH	The investigators aim is to determine whether venous blood pH decreases after a high acid load meal, and whether this effect is attenuated by administration of sodium bicarbonate prior to a mixed meal study	Baseline (fasting) and 3 hours post meal
Secondary	Changes in glycemic response to the meal	Postprandial glucose excursion will be compared between sodium bicarbonate and placebo	Baseline (fasting) and 3 hours post meal
Secondary	Changes in insulin response to the meal	Postprandial insulin excursion will be compared between sodium bicarbonate and placebo	Baseline (fasting) and 3 hours post meal
Secondary	Changes in arterial stiffness	Postprandial arterial stiffness (measured by the augmentation index derived from Sphygmocore, Atcor Medical, Australia) will be compared between sodium bicarbonate and placebo	Baseline (fasting) and 3 hours post meal
Secondary	Changes in hunger and satiety scores	Postprandial hunger and satiety will be compared between sodium bicarbonate and placebo	Baseline (fasting) and 3 hours post meal