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Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes
  1. Rogelio U Almario1,
  2. Wendy M Buchan2,
  3. David M Rocke3,4,
  4. Sidika E Karakas1,5
  1. 1Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The University Of California at Davis, Sacramento, California, USA
  2. 2Department of Family and Consumer Sciences, University of Sacramento, Sacramento, California, USA
  3. 3Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, California, USA
  4. 4Department of Biomedical Engineering, University of California, Davis, California, USA
  5. 5Department of Veterans Affairs Northern California Health Care System, Sacramento, California, USA
  1. Correspondence to Dr Sidika E Karakas, 4150 V. Street,Sacramento, CA 95817; sekarakas{at}


Objective Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding.

Research design and methods This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized.

Results During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10−5) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels.

Conclusions Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.

  • whey protein
  • type 2 diabetes
  • continuous glucose monitoring

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  • Contributors RUA conducted clinical studies, organized data. WMB designed the controlled feeding menus. DMR planned and carried out the statistical analysis of the data and contributed to the writing and editing of the manuscript. SEK designed the study, supervised the clinical studies and laboratory assays, facilitated collaborations and contributed to data analysis. SEK prepared the manuscript with contributions from all the coauthors. All authors have read and approved the final version of the manuscript. SEK has the primary responsibility for the final content of the article.

  • Funding The study was supported by a grant from the California Dairy Research Foundation to the University of California, Davis, for SEK. The clinical studies were also partly supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through grant #UL1 TR000002. Whey protein and placebo were produced and donated by Glanbia Nutritionals, Twin Falls, Idaho, USA.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Insitutional Review Board (IRB) of the University of California Davis which complies with the Helsinki Declaration as revised in 1983.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement This manuscript includes all the data available.

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