This article is more than 5 years old. Information may no longer be current.
Appetite increases with decreased energy intake in type 2 diabetes
Click Here to Manage Email Alerts
Feedback control of energy intake plays a larger role than energy expenditure in weight loss and regain, according to an analysis of data from a placebo-controlled trial published in Obesity.
“Several experiments in humans have quantified how energy expenditure adapts in response to alterations of energy intake and body weight. In contrast, energy intake adaptations have yet to be accurately quantified in humans despite the widespread belief that feedback control of energy intake is critical for body weight regulation and acts as part of a complex neurobiological system to determine overall human food intake behavior,” David Polidori, PhD, of Janssen Research and Development, San Diego, and colleagues wrote. “Unfortunately, free-living subjects are notorious for being unable to provide accurate estimates of energy intake using self-report methods, and the expense and difficulty of employing objective biomarker methods severely limit their applicability.”
Researchers studied 153 patients with type 2 diabetes who participated in a previously published yearlong study of canagliflozin. Polidori and colleagues reviewed data on participants’ body weight and used a validated mathematical model to determine changes in energy intake throughout the study.
The canagliflozin group’s mean body weight declined, and patients “reached a new equilibrium several kilograms lower” than the placebo group, Polidori and colleagues wrote. However, as the treatment group’s mean weight decreased, appetites increased. Polidori and colleagues calculated that the patients’ energy intake increased by approximately 350 kcal/day. The overall increase was roughly 100 kcal/day above baseline for each kilogram of weight lost. In the placebo group, the researchers reported, energy intake briefly fell by roughly 100 kcal/day before it returned to baseline levels.
“In the absence of ongoing efforts to restrain food intake following weight loss, feedback control of energy intake will result in eating above baseline levels with an accompanying acceleration of weight regain,” Polidori and colleagues wrote. “The few individuals who successfully maintain weight loss over the long term do so by heroic and vigilant efforts to maintain behavior changes in the face of increased appetite along with persistent suppression of energy expenditure in an omnipresent obesogenic environment. Permanently subverting or countering this feedback control system poses a major challenge for the development of effective obesity therapies.” – by Andy Polhamus
Disclosure: Polidori is a full-time employee of Janssen Research & Development. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.
Perspective
Back to Top
Samuel Klein
This is an important study using a robust calculation to estimate energy intake that is not subject to the inaccuracy of traditional diet records. Although the data themselves are pristine, the clinical and physiologic implications of the results are open to interpretation. In this study, weight loss induced by increasing urinary glucose in people with type 2 diabetes caused an increase in appetite (defined as energy intake not hunger). The increase in energy intake reduced the magnitude of weight lost expected by the loss of calories (glucose) in urine. Therefore, these data clearly show that “something” made the study participants eat more calories than they usually consume, which blunted the weight loss effect of the glycosuria. The mechanism responsible for increased energy intake cannot be determined from this study. The authors posit that their results demonstrate that weight loss stimulates a feedback control system that increases energy intake and attenuates weight loss. This might indeed be the case, and data from other studies have shown that plasma hormones involved in regulating food intake are affected by weight loss. But are there other possible explanations? Other diabetes medications that improve glycemic control, such as insulin, sulfonylurea drugs and thiazolidinediones, increase food intake and cause weight gain. Is it possible that lowering blood glucose stimulates appetite and that the effect of canagliflozin therapy on energy intake is not simply related to weight loss? Is it possible that renal SGLT-2 inhibition affects appetite? This carefully done study identifies a unique experimental model that can be used in future studies to explore the complex interaction between weight loss and energy intake in people.
Disclosure: Klein reports being a shareholder at Aspire Bariatrics and has served on the scientific advisory boards for Novo Nordisk, Takeda and Janssen Pharmaceuticals.
Click Here to Manage Email Alerts