In addition to today’s post, please review Linking To And Excerpting From “The carbohydrate-insulin model: a physiological perspective on the obesity pandemic”
Posted on May 25, 2025 by Tom Wade MD.
Here is the Online Supplementary Material:
The Carbohydrate-Insulin Model: A Physiological Perspective on the Obesity Pandemic
Ludwig DS, et al.
Online Supplementary Material
This file includes:
Supplementary Table 1: Consideration of Energy Balance in Policy Recommendations, Scientific Statements and Other Influential Writings.
Supplementary Table 2: Predictions Arising from the Carbohydrate-Insulin Model Distinguishing Scientific Models.
Supplementary Figure 1. UK Government’s Obesity System Map, 2007
References
Supplementary Table 1. Consideration of Energy Balance in Policy Recommendations, Scientific Statements and Other Influential Writings. These excerpts highlight the recurring focus on readily available, energy-dense, palatable, processed foods as a main causal driver of increased energy intake; and the central role of energy restriction in the dietary management of obesity.
Organization Role of “energy balance” Factors considered as causally related to increasing obesity prevalence Dietary recommendations USDA (Dietary Guidelines for Americans 2020-2025) (1) • “Losing weight …requires adults to reduce the number of calories they get from foods and beverages and increase the amount expended through physical activity.” • “The causes of childhood obesity are complex and interconnected. Behaviors (e.g., eating habits, level of physical activity, sedentary time) and the community in which a child or adolescent resides can influence risk of obesity. Genetics and the fetal environment also play a role in the development of obesity” • “Estimated calorie needs” according to age and sex provided. • Dietary carbohydrate 45% to 65% per Acceptable Macronutrient Distribution Range
National Heart, Lung and Blood Institute: Balance Food and Activity (2) • “More [energy] IN than OUT over time = weight gain” • “More [energy] OUT than IN over time = weight loss”
– • “[consider] the Estimated Calorie Requirement chart, to get a sense of how many calories (ENERGY IN) you and your family need on a daily basis.” American Diabetes Association (2021) (3) • “Behavioral changes that create an energy deficit, regardless of macronutrient composition, will result in weight loss.” – • “[Interventions should] focus on dietary changes, physical activity, and behavioral strategies to achieve a 500–750 kcal/day energy deficit.” (Evidence Grade A) • In most cases: 1,200–1,500 kcal/day for women and 1,500–1,800 kcal/day for men
Endocrine Society Scientific Statement: The Science of Obesity Management (2018) (4) • “Underlying all … dietary approaches, however, is the fact that to lose weight, energy balance must be negative.” – •Low-calorie diet, 1200-1800 kcal/d •Typical macronutrient composition: <30% fat, 15%–25% protein, carbohydrate 45%–55%
Endocrine Society Scientific Statement: Obesity Pathogenesis (2017) (5) • “Obesity pathogenesis involves two related but distinct processes: (1) sustained positive energy balance (energy intake > energy expenditure) and (2) resetting of the body weight ‘set point’ at an increased value.” • “The long list of potentially relevant environmental factors includes changes of diet composition and lifestyle, environmental toxins, infections, changes in the microbiome, and many others as well.” • “[H]abitual consumption of highly palatable and energy-dense diets predispose to excess weight gain”
– Position of the Academy of Nutrition and Dietetics: Interventions for the Treatment of Overweight and Obesity in Adults (2016) (6) • “…treating obesity requires achieving a state of negative energy balance” • “Many external factors influence consumption, but environmental variables that appear to greatly influence intake are food availability and variety and energy density and portion size of food.” “reduce caloric intake, based on one of the following caloric reduction strategies”: • 1,200 kcal to 1,800 kcal/day;
• energy deficit of approximately 500 kcal/day or 750 kcal/day;
• one of the evidence-based diets that restricts certain food types
European Guidelines for Obesity Management in Adults (2015) (7)
• “At the simplest level, obesity develops as a result of a period of chronic energy imbalance and is maintained by a continued elevated energy intake sufficient to maintain the acquired higher energy needs of the obese state.” • “The rapid increase in the prevalence of obesity over the past 30 years is mainly a result of cultural and environmental influences. High energy density diet, increased portion size, low physical activity and adoption of a sedentary lifestyle as well as eating disorders are considered as important risk factors for the development of obesity.” • “A 15–30% decrease in energy (calorie) intake from habitual intake in a weight-stable individual is sufficient and appropriate” • Decrease/avoid: energy density, portion size, snacking, night eating, binge eating.
Expert Panel Report: Guidelines (2013) for the Management of Overweight and Obesity in Adults (8) • “To achieve weight loss, an energy deficit is required” (Strength of evidence High) • “Foundational to weight loss is the necessity of creating a negative energy balance”
– • “A variety of dietary approaches can produce weight loss in overweight and obese adults.” • “Specification of an energy intake target that is less than that required for energy balance” (usually 1200- 1800 kcal/d)
Textbook of Obesity: Biological, Psychological and Cultural Influences, (2012) (9) • “All diets that result in weight loss do so on one basis and one basis only: they reduce total calorie intake” (p301)
• “the obesogenic environment and a strong defense against too much weight loss make long-term success extremely difficult.” (p295) • “An energy deficit can be achieved by reducing energy intake, increasing energy expenditure through physical activity, or a combination of both” (296) • “The healthiest approach, according to the Centers for Disease Control and Prevention, is to follow the Dietary Guidelines for Americans to increase physical activity and reduce calories by limiting unhealthful foods such as added sugars, saturated fats, and alcohol, all of which provide calories but few or no essential nutrients.” (p297)
American Heart Association Childhood Obesity Research Summit (2009) (10) • “Prevention and treatment of obesity usually require a decrease in energy consumption and an increase in energy expenditure, to improve energy balance.” • “…obesity is usually the result of a complex, interdependent constellation of factors” • “Dietary factors that promote obesity include high-calorie beverages (sugared soft drinks or fruit juice), energy-dense foods, excess refined carbohydrates, excess dietary fat, and large portion sizes.”
– 2006 Canadian Clinical Practice Guidelines on the Management and Prevention of Obesity in Adults and Children (11) • “at the simplest level obesity results from long-term positive energy balance — the interaction of energy intake and energy expenditure.” • “The cause of obesity is complex and multifactorial…. overnutrition and sedentary lifestyle have supplanted physical labour and regular physical activity.” • “a nutritionally balanced diet (designed to reduce energy intake)” • “high-protein or a low-fat diet”
1. Hormonal response to GL – A high-GL meal increases insulin-to-glucagon ratio
– A high-GL meal elicits a GIP-dominant incretin secretion profile
2. Insulin and tissue-specific insulin sensitivity – Insulin administration increases insulin sensitivity in white adipose tissue
– Insulin administration decreases insulin sensitivity in muscle
3. Tissue-specific insulin sensitivity and fat storage. – Insulin resistance in adipose protects against obesity
– Insulin resistance in muscle or brain causes obesity
4. Insulin, glucagon and adiposity – Insulin administration increases energy intake and reduces energy expenditure
– Insulin administration increases adiposity independently of (i.e., without increased) food intake
– Drugs that increase insulin secretion or adipose insulin action cause weight gain
– Tumors secreting insulin or glucagon are associated with weight gain or weight loss, respectively.
– Animal models with increased or reduced insulin secretion are susceptible to vs protected against obesity, respectively
– High insulin secretion describes a unique phenotype, with special susceptibility to weight gain on a high-GL diet
5. GIP-dominant incretin secretion and fat storage – GLP-1 agonists and GIP antagonists cause weight loss
– Genetic GIP receptor ablation protects against obesity
6. GL, metabolic fuels, food preference and energy balance – Metabolic fuels are lower after a high vs low-GL meal in the late postprandial phase
– Cellular energy state in key tissue (muscle, liver) is lower after a high- vs low-GL meal in the late postprandial phase
– Reduced fuel sensing or oxidation in brain, liver or muscle increases hunger and weight gain
– Lower metabolic fuel concentrations occur early in the development of some experimental models of obesity
7. GL, energy balance and obesity – Pure carbohydrate foods are more strongly association with binge eating than pure fat foods
– Low- vs high-GI meals reduce hunger
– Low- vs high-GL diets increase energy expenditure (after physiological adaptation, >3 weeks)
– Low- vs high-GL diets produce greater long-term weight loss (> 6 to 12 months)
– Low- vs isoenergetic high-GL diet decreases adiposity (> 6 to 12 months)
– Drugs or genetic variants that slow the rate of carbohydrate digestion are associated with lower weight
8. Causal direction – In animal models, increased adiposity may occur without (or before) hyperphagia
– Overfeeding leads to a compensatory increase in energy expenditure
– Overfeeding leads to a compensatory decrease in energy intake
– Exercise leads to a partial compensatory decrease in energy expenditure
– Exercise leads to a partial compensatory increase in energy intake
– Weight gain or genetically determined obesity risk predicts reduced physical activity
Supplementary Table 2. Predictions Arising from the Carbohydrate-Insulin Model Distinguishing Scientific Models. See Figure 1 and text for discussion by corresponding number. A range of complementary experimental designs will be needed to test these hypotheses, with the aim of disguising causal mechanisms from potential dietary and non-dietary confounding. Abbreviation: glycemic load, GL.
Supplementary Figure 1: UK Government’s Obesity System Map, 2007 (UK Government Office for Science). “Energy Balance” occupies the central position. Available at https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/296290/obesity-map-full-hi-res.pdf
References
- U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. Available at DietaryGuidelines.gov.
- National Heart, Lung, and Blood Institute. We Can!: Ways to Enhance Children’s Activity & Nutrition. Balance Food and Activity. Available from: https://www.nhlbi.nih.gov/health/educational/wecan/healthy-weight-basics/balance.htm. Accessed 3 August 2021.
- American Diabetes Association. 8. Obesity Management for the Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44(Suppl 1):S100-S10.
- Bray GA, Heisel WE, Afshin A, Jensen MD, Dietz WH, Long M, Kushner RF, Daniels SR, Wadden TA, Tsai AG, et al. The Science of Obesity Management: An Endocrine Society Scientific Statement. Endocr Rev. 2018;39(2):79-132.
- Schwartz MW, Seeley RJ, Zeltser LM, Drewnowski A, Ravussin E, Redman LA, Leibel RL. Obesity Pathogenesis: An Endocrine Society Scientific Statement. Endocrine Reviews. 2017;38(4):267-296.
- Raynor HA, Champagne CM. Position of the Academy of Nutrition and Dietetics: Interventions for the Treatment of Overweight and Obesity in Adults. J Acad Nutr Diet. 2016;116(1):129-47.
- Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, Toplak H, Obesity Management Task Force of the European Association for the Study of Obesity. European Guidelines for Obesity Management in Adults. Obes Facts. 2015;8(6):402-24.
- American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Expert Panel Report: Guidelines (2013) for the management of overweight and obesity in adults. Obesity. 2014;22 Suppl 2:S41-410.
- Nonas CA, Dolins KR. Chapter 17: Dietary interventions approaches to the treatment of obesity. In: Akabas SR, Lederman SA, Moore BJ, editors. Textbook of Obesity: Biological, Psychological and Cultural Influences, 1st Edition: Wiley-Blackwell; 2012. p. 295-309.
- Daniels SR, Jacobson MS, McCrindle BW, Eckel RH, Sanner BM. American Heart Association Childhood Obesity Research Summit: executive summary. Circulation. 2009;119(15):2114-23.
- Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E, Obesity Canada Clinical Practice Guidelines Expert Panel. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. CMAJ. 2007;176(8):S1-13.