Our Science

Definitions

  • Glucose – A sugar that your body uses as an energy source, and is part of many carbohydrates.
  • Glycemic index (GI) – A scale used to predict how much specific foods increase blood sugar levels. High GI foods would be expected to raise your blood sugar to a higher level.
  • Glycemic load is another measure to attempt to predict glucose response and is calculated as: food item GI and amount of carbohydrate/100.
  • Insulin – a hormone produced by the pancreas which controls the amount of glucose in your blood and helps your body use and store energy. 
  • Leptin – a hormone made by fat cells which generally lowers hunger and fat storage. 
  • Fasting glucose – your blood glucose level after 8 hours without food or drink. Normal fasting glucose is less than 100 mg/dl; 100-125mg/dl may represent pre-diabetes; higher than 126 mg/dl may represent diabetes. 
  • Impaired glucose tolerance – blood glucose increases to higher than expected levels, but not yet to the point of diabetes range, although it is a risk factor for diabetes and cardiovascular disease.
  • Metabolic syndrome – a syndrome defined by a combination of increased blood pressure, high blood sugar, excess abdominal or body fat, and increased cholesterol, which together increase the risk of diabetes, heart disease, stroke, and other medical issues.
  • Continuous Glucose Monitor – a small machine that detects and reports interstitial glucose (sugar level in the fluid around your fat cells).
  • Body Mass Index (BMI) – a number calculated using your height and weight. More than 25 is considered overweight, and more than 30 is considered obese. Some people’s health will not be adequately predicted by their BMI.
  •  

Eating most foods causes a detectable increase in your blood glucose levels.

  • Many foods that you eat cause a detectable increase in your level of blood glucose (sugar). Digestion starts as you chew, continues as food and liquids are broken down in your stomach, and eventually results in your intestines absorbing nutrients (including glucose) into your blood. Holst, Jens Juul, Fiona Gribble, Michael Horowitz, and Chris K. Rayner. “Roles of the Gut in Glucose Homeostasis.” Diabetes Care 39, no. 6 (June 1, 2016): 884–92. https://doi.org/10.2337/dc16-0351
  • Americans are eating more, and more frequently, increasing the number of times a day glucose levels will rise. (Popkin, Barry M, and Kiyah J Duffey. “Does Hunger and Satiety Drive Eating Anymore? Increasing Eating Occasions and Decreasing Time between Eating Occasions in the United States.” The American Journal of Clinical Nutrition 91, no. 5 (May 1, 2010): 1342–47. https://doi.org/10.3945/ajcn.2009.28962)
  •  

Even healthy people can have high and unpredictable glucose spikes, which get larger and more unpredictable as you develop impaired glucose tolerance (often due to weight gain).

  • Even [non-overweight or diabetic] people can have issues with glucose management. In one study, scientists watched glucose levels using a continuous glucose monitor (CGM) for generally healthy participants- the average participant was 41 years old, had a BMI between 25-26, nondiabetic- essentially right on the border of being overweight. They found that “nearly all individuals without diabetes exceeded the IGT [impaired glucose tolerance] threshold of 140mm/dl at some point during the day.” A quarter spent 75 minutes over the normal high limit, and some even spent more than 5 hours out of range! (Borg, R., J. C. Kuenen, B. Carstensen, H. Zheng, D. M. Nathan, R. J. Heine, J. Nerup, K. Borch-Johnsen, and D. R. Witte. “Real-Life Glycaemic Profiles in Non-Diabetic Individuals with Low Fasting Glucose and Normal HbA1c: The A1C-Derived Average)
  • People have unique glucose responses based on their own body and in their own contexts to different foods. Different people have “High variability in response to identical meals, suggesting that universal dietary recommendations may have limited utility.” People eating an assigned diet that had a wide array of reasonable options from experimentally discovered food easily controlled glucose levels. (Zeevi, David, Tal Korem, Niv Zmora, David Israeli, Daphna Rothschild, Adina Weinberger, Orly Ben-Yacov, et al. “Personalized Nutrition by Prediction of Glycemic Responses.” Cell 163, no. 5 (November 2015): 1079–94. https://doi.org/10.1016/j.cell.2015.11.001.)
  • Glucose levels can in part be predicted by the glycemic index when separated into low, moderate, and high categories; however, even for the same food there is variation in response per person. Publicly available food does not generally come with a “glycemic index” value and even if it did, it would not account for meal combinations. (Brand-Miller, Jennie C, Karola Stockmann, Fiona Atkinson, Peter Petocz, and Gareth Denyer. “Glycemic Index, Postprandial Glycemia, and the Shape of the Curve in Healthy Subjects: Analysis of a Database of More than 1000 Foods.” The American Journal of Clinical Nutrition 89, no. 1 (January 1, 2009): 97–105. https://doi.org/10.3945/ajcn.2008.26354.)
  • As people develop metabolic syndrome, they may have larger “mean amplitude glycemic excursions,” indicating increasing inability to regulate glucose levels. Yang, Xubin, Yanhua Zhu, Sihui Luo, Lin Chen, Jinhua Yan, Longyi Zeng, Wen Xu, and Jianping Weng. “[Glucose characteristics in normal glucose tolerance subjects with metabolic syndrome].” Zhonghua Yi Xue Za Zhi 95, no. 14 (April 14, 2015): 1070–73.)

Glucose spikes cause proportional insulin release.

  • Insulin is released in response to elevated blood glucose levels and helps the cells of your body use and store glucose. (Kolb, Hubert, Michael Stumvoll, Werner Kramer, Kerstin Kempf, and Stephan Martin. “Insulin Translates Unfavourable Lifestyle into Obesity.” BMC Medicine 16, no. 1 (13 2018): 232. https://doi.org/10.1186/s12916-018-1225-1.
  • High glycemic load meals cause high blood glucose levels and high insulin levels. “In fact, virtually a straight line relationship between the meal [glucose load] and serum glucose and insulin responses was found.” (Galgani, José, Carolina Aguirre, and Erik Díaz. “Acute Effect of Meal Glycemic Index and Glycemic Load on Blood Glucose and Insulin Responses in Humans.” Nutrition Journal 5, no. 1 (September 5, 2006): 22. https://doi.org/10.1186/1475-2891-5-22.)

Excess insulin leads to weight gain, and this compounds over time.

  • This study concludes: “All known lifestyle-dependent obesity risk factors are associated with, or give rise to, hyperinsulinemia” and, “It seems justified to suggest a lifestyle that avoids high insulin levels for much of the day to limit the period of anabolic fat tissue activity. Appropriate measures include low calorie diets, intermittent fasting, or physical activity.” (Kolb, Hubert, Michael Stumvoll, Werner Kramer, Kerstin Kempf, and Stephan Martin. “Insulin Translates Unfavourable Lifestyle into Obesity.” BMC Medicine 16 (December 13, 2018). https://doi.org/10.1186/s12916-018-1225-1.)
  • This study supports “a causal relationship of genetically determined glucose-stimulated insulin secretion with obesity. Genetic predisposition to higher levels of glucose-stimulated insulin secretion predicted higher adult BMI.” “It appears that a lifetime of high glucose-stimulated insulin secretion, likely in conjunction with typical diets consumed by the individuals in these cohorts, is obesogenic.” (Astley, Christina M., Jennifer N. Todd, Rany M. Salem, Sailaja Vedantam, Cara B. Ebbeling, Paul L. Huang, David S. Ludwig, Joel N. Hirschhorn, and Jose C. Florez. “Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity.” Clinical Chemistry 64, no. 1 (January 2018): 192–200. https://doi.org/10.1373/clinchem.2017.280727.)

Higher glucose, excess insulin and extra weight make it harder to lose weight.

  • People with higher baseline insulin levels had decreased weight loss during an energy restriction diet, and were more prone to regaining the weight. (Kong, Ling Chun, Pierre-Henri Wuillemin, Jean-Philippe Bastard, Nataliya Sokolovska, Sophie Gougis, Soraya Fellahi, Froogh Darakhshan, et al. “Insulin Resistance and Inflammation Predict Kinetic Body Weight Changes in Response to Dietary Weight Loss and Maintenance in Overweight and Obese Subjects by Using a Bayesian Network Approach.” The American Journal of Clinical Nutrition 98, no. 6 (December 2013): 1385–94. https://doi.org/10.3945/ajcn.113.058099.)
  • As you eat, hormones produced by your intestine help prevent absorption of some amount of glucose from a large meal. As you become obese or diabetic, you start to lose this ability, and you absorb more glucose from each meal. (Holst, Jens Juul, Fiona Gribble, Michael Horowitz, and Chris K. Rayner. “Roles of the Gut in Glucose Homeostasis.” Diabetes Care 39, no. 6 (June 1, 2016): 884–92.https://doi.org/10.2337/dc16-0351.) (Bagger, Jonatan I., Filip K. Knop, Asger Lund, Henrik Vestergaard, Jens J. Holst, and Tina Vilsbøll. “Impaired Regulation of the Incretin Effect in Patients with Type 2 Diabetes.” The Journal of Clinical Endocrinology and Metabolism 96, no. 3 (March 2011): 737–45. https://doi.org/10.1210/jc.2010-2435.)
  • Usually, elevated glucose levels make you feel full. As people gain weight and become obese, the higher amount of glucose circulating you have no longer prevents you from becoming hungry, meaning that you might continue to eat even if you don’t need to. Keeping your glucose in a normal range decreased interest in food. (Page, Kathleen A., Dongju Seo, Renata Belfort-DeAguiar, Cheryl Lacadie, James Dzuira, Sarita Naik, Suma Amarnath, R. Todd Constable, Robert S. Sherwin, and Rajita Sinha. “Circulating Glucose Levels Modulate Neural Control of Desire for High-Calorie Foods in Humans.” The Journal of Clinical Investigation 121, no. 10 (October 2011): 4161–69. https://doi.org/10.1172/JCI57873.)
  • High glycemic index meals cause higher insulin responses, and thus contribute to weight gain. High glycemic meals may also suppress leptin, preventing you from feeling full. (Barkoukis, Hope, Christine M. Marchetti, Brian Nolan, Sakita N. Sistrun, Raj K. Krishnan, and John P. Kirwan. “A High Glycemic Meal Suppresses the Postprandial Leptin Response in Normal Healthy Adults.” Annals of Nutrition and Metabolism 51, no. 6 (2007): 512–18. https://doi.org/10.1159/000112309.)
  • High glucose response to meals can lead to a “crash” effect, where your glucose drops quickly, causing increased hunger as well as stimulating reward behavior in your brain, increasing your chance of another unhealthy meal. (Lennerz, Belinda S., David C. Alsop, Laura M. Holsen, Emily Stern, Rafael Rojas, Cara B. Ebbeling, Jill M. Goldstein, and David S. Ludwig. “Effects of Dietary Glycemic Index on Brain Regions Related to Reward and Craving in Men.” The American Journal of Clinical Nutrition 98, no. 3 (September 1, 2013): 641–47. https://doi.org/10.3945/ajcn.113.064113.)
  •  

Controlling glucose and insulin leads to weight loss (in part, because controlling glucose requires modifying harmful diet habits and increasing activity, which influences insulin secretion and resistance).

  • Meta-analysis of low glycemic index diets showed that compared to other diets, a low glycemic index diet lowered body mass, BMI, and cholesterol. (Thomas, D. E., E. J. Elliott, and L. Baur. “Low Glycaemic Index or Low Glycaemic Load Diets for Overweight and Obesity.” The Cochrane Database of Systematic Reviews, no. 3 (July 18, 2007): CD005105.https://doi.org/10.1002/14651858.CD005105.pub2.); Juanola-Falgarona, Martí, Jordi Salas-Salvadó, Núria Ibarrola-Jurado, Antoni Rabassa-Soler, Andrés Díaz-López, Marta Guasch-Ferré, Pablo Hernández-Alonso, Rafael Balanza, and Mònica Bulló. “Effect of the Glycemic Index of the Diet on Weight Loss, Modulation of Satiety, Inflammation, and Other Metabolic Risk Factors: A Randomized Controlled Trial.” The American Journal of Clinical Nutrition 100, no. 1 (July 2014): 27–35. https://doi.org/10.3945/ajcn.113.081216.
  • “In this sample of overweight but otherwise healthy adults, A moderately [high carbohydrate/low fat] breakfast meal [when compared to low carb/high fat] resulted in higher postprandial insulin, a more rapid acute rise and fall in peak glucose concentration, lower glucose concentrations hours following the meal, and more hunger at 3 and 4 hours after meal consumption. Importantly, the earlier rise and fall in circulating glucose, rather than the concentration of glucose per se, explained the earlier return of hunger following the high carbohydrate/low fat meal. This pattern describes a potential mechanism to explain why increases in meal frequency have occurred in the US concomitantly with increased carbohydrate and reduced fat contents of diets.” Chandler-Laney, Paula C., Shannon A. Morrison, Laura Lee T. Goree, Amy C. Ellis, Krista Casazza, Renee Desmond, and Barbara A. Gower. “Return of Hunger Following a Relatively High Carbohydrate Breakfast Is Associated with Earlier Recorded Glucose Peak and Nadir.” Appetite 80 (September 1, 2014): 236–41. https://doi.org/10.1016/j.appet.2014.04.031.
  • The “GEM” paradigm (glycemic load, exercise, monitoring glucose) for patients with relatively newly diagnosed DM2 was an effective method of weight loss. GEM focuses on reducing postprandial glucose elevations by avoidance of high glycemic load foods and eating foods that don’t cause large elevations in blood glucose, rather than a specific diet, recommends physical activity, and relies heavily on systematic glucose monitoring to educate, activate, and motivate individuals. In this study, they were using fingerstick (self-monitored blood glucose) checks. While weight loss was not a focus, enrolled patients had a 4% body weight loss over 6 months. They saw significant reductions in HgA1C (a measure of circulating blood sugar over a 3 month period). Addressing high sugars led to weight loss. (Cox, Daniel J., Ann G. Taylor, Harsimran Singh, Matthew Moncrief, Anne Diamond, William S. Yancy, Shefali Hegde, and Anthony L. McCall. “Glycemic Load, Exercise, and Monitoring Blood Glucose (GEM): A Paradigm Shift in the Treatment of Type 2 Diabetes Mellitus.” Diabetes Research and Clinical Practice 111 (January 2016): 28–35. https://doi.org/10.1016/j.diabres.2015.10.021.)
  • The “GEM” paradigm was again studied in a preliminary study the same year where the subjects used CGMs instead of self monitored blood glucose checks – and they had an average of 16 lb (7%) weight loss over 3 months; also had significant decreases in BMI, HgA1C, blood pressure, and other health markers. (Cox, Daniel J., Ann G. Taylor, Matthew Moncrief, Anne Diamond, William S. Yancy, Shefali Hegde, and Anthony L. McCall. “Continuous Glucose Monitoring in the Self-Management of Type 2 Diabetes: A Paradigm Shift.” Diabetes Care 39, no. 5 (May 1, 2016): e71–73. https://doi.org/10.2337/dc15-2836.)
  • In experimental conditions, direct suppression of insulin secretion with octreotide infusions over 24 weeks induced marked weight loss for some and significant weight loss for more. Interestingly, when insulin was suppressed, subjects also had decreases in total caloric intake and carbohydrate cravings. (Velasquez-Mieyer, PA, PA Cowan, KL Arheart, CK Buffington, KA Spencer, BE Connelly, GW Cowan, and RH Lustig. “Suppression of Insulin Secretion Is Associated with Weight Loss and Altered Macronutrient Intake and Preference in a Subset of Obese Adults.” International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity 27, no. 2 (February 2003): 219–26. https://doi.org/10.1038/sj.ijo.802227.)
  •  

Controlling glucose improves mood, helps regulate sleep, and using CGMs inspires behavioral change.

  • This study showed that a “high-glycemic load diet was associated with higher depression symptoms, total mood distrubance, and fatigue compared to a low-glycemic load diet especially in overweight/obese, but otherwise healthy, adults.” (Breymeyer, Kara L., Johanna W. Lampe, Bonnie A. McGregor, and Marian L. Neuhouser. “Subjective Mood and Energy Levels of Healthy Weight and Overweight/Obese Healthy Adults on High-and Low-Glycemic Load Experimental Diets.” Appetite 107 (December 1, 2016): 253–59. https://doi.org/10.1016/j.appet.2016.08.008.)
  • “Greater glycemic variability may be associated with lower quality of life and negative moods” in a study of 23 women with Type 2 diabetes who wore a continuous glucose monitor. (Penckofer, Sue, Lauretta Quinn, Mary Byrn, Carol Ferrans, Michael Miller, and Poul Strange. “Does Glycemic Variability Impact Mood and Quality of Life?” Diabetes Technology & Therapeutics 14, no. 4 (April 2012): 303–10. https://doi.org/10.1089/dia.2011.0191.)
  • Yoo et al in 2008 evaluated use of CGMs in 65 patients with poorly controlled DM2. The intervention group used the CGM for three days a month over 3 month in addition to doing finger sticks, whereas the control group only did fingerstick glucose checks. In 3 months the CGM group lost 2.2 kgs and the control group lost 1.4 kgs (they were looking primarily at markers of diabetes, such as HgA1C, which all significantly improved as well). And that was with only 9 days of CGM use in 3 months! Patients that used the CGM also statistically significantly decreased their daily calorie intake and increased (nearly doubled) weekly exercise time. So, even intermittent use of CGMs showed significant potential to change lifestyle factors and contributed to weight loss. (Yoo, H. J., H. G. An, S. Y. Park, O. H. Ryu, H. Y. Kim, J. A. Seo, E. G. Hong, et al. “Use of a Real Time Continuous Glucose Monitoring System as a Motivational Device for Poorly Controlled Type 2 Diabetes.” Diabetes Research and Clinical Practice 82, no. 1 (October 1, 2008): 73–79. https://doi.org/10.1016/j.diabres.2008.06.015.)
  • Allen et al in 2009 looked at using CGMs in patients with DM2 as part of a physical activity program. Half the patients were provided with training and an activity monitor, the other half also received a CGM and the subsequent education on how physical activity affected their CGM curves. They only had the CGM on for 3 days at the start of the experiment (a very small intervention window). Over 8 weeks, the patients that had the CGM initially had significant increases in physical activity and decreases in BMI. (Allen, Nancy A., James A. Fain, Barry Braun, and Stuart R. Chipkin. “Continuous Glucose Monitoring Counseling Improves Physical Activity Behaviors of Individuals with Type 2 Diabetes: A Randomized Clinical Trial.” Diabetes Research and Clinical Practice 80, no. 3 (June 1, 2008): 371–79. https://doi.org/10.1016/j.diabres.2008.01.006.)
  • Bailey et al 2016 ran a pilot study showing that using a CGM improved adherence to an exercise plan in individuals with impaired glucose tolerance (both DM and pre-DM). Bailey, Kaitlyn J., Jonathan P. Little, and Mary E. Jung. “Self-Monitoring Using Continuous Glucose Monitors with Real-Time Feedback Improves Exercise Adherence in Individuals with Impaired Blood Glucose: A Pilot Study.” Diabetes Technology & Therapeutics 18, no. 3 (February 17, 2016): 185–93. https://doi.org/10.1089/dia.2015.0285.
  • This review article by Erhrhardt published in 2019 laments the use of CGMs as a reactionary tool only for treatment of DM1 and DM2, and emphasizes its potential role as an adjunct to lifestyle changes and weight reduction for patients with DM 1,2 and pre-DM. “Behavior Modification in Prediabetes and Diabetes: Potential Use of Real-Time Continuous Glucose Monitoring – Nicole Ehrhardt, Enas Al Zaghal, 2019.” Accessed January 14, 2021. https://journals.sagepub.com/doi/10.1177/1932296818790994.)
  • “Sleep loss can lead to impairments in glucose metabolism and increases in insulin levels… partial sleep deprivation is also associated with changes in the appetite regulating hormones, leptin and ghrelin, and these changes would indicate an increase in appetite, which may lead to increased food intake and weight gain.” (Knutson, Kristen L. “Impact of Sleep and Sleep Loss on Glucose Homeostasis and Appetite Regulation.” Sleep Medicine Clinics 2, no. 2 (June 2007): 187–97. https://doi.org/10.1016/j.jsmc.2007.03.004.)
  • Another study linking poor sleep, insulin resistance, and weight gain: Eckel, Robert H., Christopher M. Depner, Leigh Perreault, Rachel R. Markwald, Mark R. Smith, Andrew W. McHill, Janine Higgins, Edward L. Melanson, and Kenneth P. Wright. “Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity.” Current Biology 25, no. 22 (November 16, 2015): 3004–10. https://doi.org/10.1016/j.cub.2015.10.011.)
  •