Effects of Dietary Carbohydrate Content on Circulating Metabolic Fuel Availability in the Postprandial State

Kim J Shimy; Henry A. Feldman; Gloria L Klein; Lisa Bielak; Cara B Ebbeling; David S Ludwig


J Endo Soc. 2020;4(7) 

In This Article

Abstract and Introduction


Context: According to the carbohydrate-insulin model of obesity, an elevated insulin-to-glucagon ratio in response to a high-carbohydrate diet directs metabolic fuels toward storage, resulting in lower circulating energy.

Objective: To determine differences in total circulating energy post-meal related to dietary carbohydrate.

Design: Ancillary study within the Framingham State Food Study.

Setting: University community.

Participants: 29 adults (aged 20 to 65 years) with overweight or obesity (body mass index ≥25 kg/m2)

Intervention: After achieving 10% to 14% weight loss on a run-in diet, participants were randomized to weight-loss-maintenance test diets varying in carbohydrate content (high-carbohydrate, 60% of total energy, n = 11; moderate-carbohydrate, 40%, n = 8; low-carbohydrate, 20%, n = 10) and controlled for protein (20%). During 24-hour metabolic ward admissions between 10 and 15 weeks on the test diets, metabolic fuels and hormones were measured.

Main Outcome Measure: Energy availability (EA) based on energy content of blood glucose, beta-hydroxybutyrate, and free fatty acids, in the late postprandial period (180 to 300 minutes). Insulin at 30 minutes into the test meal (Meal Insulin-30) was measured as an effect modifier.

Results: Insulin-to-glucagon ratio was 7-fold higher in participants on the high- vs low-carbohydrate diet (2.5 and 0.36, respectively). Late postprandial EA was 0.58 kcal/L lower on the high- vs low-carbohydrate diet (P < 0.0001), primarily related to suppression of free fatty acids. Early postprandial EA (30 to 180 minutes) declined fastest in the high-carbohydrate group, and Meal Insulin-30 modified this diet effect.

Conclusions: During weight-loss maintenance on a high-carbohydrate diet, late postprandial EA is reduced, consistent with the carbohydrate-insulin model.


Many people with excess weight have difficulty maintaining long-term weight loss.[1] Physiological adaptations to weight loss, such as a decline in energy expenditure and increase in hunger,[2,3] may be among the factors driving weight regain. Although the conventional approach to weight loss has focused on energy restriction, an alternative strategy aims to reduce total or high–glycemic index carbohydrate intake, based on the carbohydrate-insulin model of obesity.[4,5]

Insulin secretion in response to dietary carbohydrate is known to promote storage of circulating glucose and fatty acids into tissues (liver, muscle, and adipose), and to suppress ketone formation. By lowering the insulin-to-glucagon ratio, a diet low in glycemic load (the arithmetic product of glycemic index and carbohydrate amount) may improve metabolic fuel availability in the late postprandial phase, thereby attenuating hunger[6,7] and increasing energy expenditure.[8–10] Conversely, a high glycemic load may increase hunger and stimulate brain centers controlling reward and craving 4 hours after a meal.[11] In a preliminary study of 1-month duration, total energy from circulating metabolic fuels was observed to be tightly controlled, in the range of 4 to 6 kcal/L, and lower in the late postprandial period following a high- vs low-carbohydrate meal.[12] However, the longer-term effects of glycemic load on metabolic fuel availability during weight loss maintenance, controlled from dietary protein, have not been studied.

The primary aim of this study was to evaluate the effect of 3 diets varying widely in carbohydrate content on postprandial energy availability (EA), defined as circulating fuel level multiplied by relative energy content for glucose, beta-hydroxybutyrate (BOHB), and free fatty acids (FFA) in a large-scale, relatively long-term feeding trial. Specifically, we hypothesized that during weight-loss-maintenance, total EA (EAGlucose + EABOHB + EAFFA) during the late postprandial period (180–300 minutes) would be lowest on a high-carbohydrate diet compared to a moderate- or low-carbohydrate diet. The carbohydrate-insulin model has focused on the late postprandial period as critical to understanding the control of energy intake at the subsequent meal, and possibly also energy expenditure.[6,7,9,11,12]