Resting energy expenditure in type 2 diabetic patients and the effect of insulin bolus

Aims: Resting energy expenditure (REE) plays a critical role in the regulation of body weight, with important implications in type 2 diabetes (T2D). However, the relationships between REE and T2D have not been extensively evaluated. We compared REE in persons with diabetes and in persons without diabetes. We also investigated the acute effect of insulin on REE and venous lactate, the latter an indirect measure of neoglucogenetic activity.

Methods: REE was measured using indirect calorimetry in 14 newly diagnosed, untreated T2D adults and in 14 non-diabetic age-, gender- and body mass index-matched persons. The REE and lactate venous concentrations were also measured in a subgroup of 5 T2D patients in the hour following an IV insulin bolus.

Results: The REE normalized for fat-free mass (FFM) was significantly higher in T2D patients than in the group without diabetes (mean ± SD: 27.6 ± 1.9 vs. 25.8 ± 1.9 kcal/kg-FFM·24 h; P = 0.02). REE normalized for FFM was correlated with fasting plasma glucose concentration (r = 0.51; P = 0.005). Following the insulin venous bolus REE (0′: 2048 ± 242; 10′: 1804 ± 228; 20′: 1684 ± 230; 30′: 1634 ± 212; 45′: 1594 ± 179; 60′: 1625 ± 197 kcal/24 h; P < 0.001) and both glucose (P < 0.001) and lactate (P < 0.001) concentrations progressively declined in the ensuing hour.

Conclusions: Patients with diabetes have a higher energy expenditure, likely a consequence of higher gluconeogenetic activity. This study may contribute to recognizing the nature of body weight reduction that occurs in concomitance with poorly controlled diabetes, and of body weight gain as commonly observed when hypoglycemic treatment is started.


Alex’s Notes: First line treatment of many metabolic diseases such as type-2 diabetes is simply weight loss. Since most are confounded by excess fat, this makes sense. Is it always the case? No, but 95% of the time it is, and thus it makes sense to look at how these conditions impact metabolic rate.

The study at hand recruited nine males and five females (n=14) with newly diagnosed (within 3 weeks before the intervention) type-2 diabetes and compared them to 14 non-diabetic, gender-, age-, and BMI-matched controls. All participants were between 30-65 years of age (avg. 47-years) and had an average BMI of just over 35 kg/m2. Resting energy expenditure (REE) was calculated with indirect calorimetry.

What was found?

REE was not significantly difference between the diabetic and control groups over 24-hours. However, when expressed as a variable of fat-free mass (FFM), the diabetic REE was significantly higher than the controls, by about 6.6%! Moreover, as would be expected, the diabetics had significantly greater fasting plasma glucose and HbA1c than the controls, and there was a significant association between the REE normalized for FFM and fasting glucose levels. All this suggests that changes in REE may indeed be a consequence of poor glucose control. Especially when we look to part II of the study, where five of the diabetic patients underwent a standard insulin bolus that progressively reduced their REE in the subsequent hour by 20% and lower blood glucose and lactate concentrations as well. The authors speculate that,

“The increased REE observed in participants with diabetes may be a consequence of an increased neoglucogenetic activity. Neoglucogenesis is, in fact, an energy costly metabolic pathway that characterizes individuals with diabetes, and is responsible for the increased FPG because it contributes to the hepatic glucose output in about 40% vs. 25% of individuals without diabetes [25] and [26]. This hypothesis is supported by the observation that REE was reduced significantly when we administered the IV insulin bolus, which has a well-known suppressive effect on neoglucogenesis [27], seeming to suggest a progressive and significant, reduction in lactate concentrations.”

Bottom line

Notwithstanding the limited sample size that prevented proper multivariate analysis to test for confounders such as age and gender, it appears that newly diagnosed type-2 diabetics (and I would extend this to persons who are pre-diabetic as well) are not at any disadvantage to lose weight and prevent the complications that persist. In fact, they may have a slight advantage, and seeing what insulin does to REE, going on insulin therapy is definitely something to be avoided.


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