A 3-Week Ketogenic Diet Increases Skeletal Muscle Insulin Sensitivity in Individuals With Obesity: A Randomized Controlled Crossover Trial.

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• In the short-term, the KD may kickstart blood-sugar control and weight loss in individuals with obesity through reduced circulating insulin levels and improved muscle insulin sensitivity.

• However, effects are unclear in the long-term.

Introduction

• The ketogenic diet (KD) has been shown in previous research to improve glycaemic control and decrease the reliance on glucose-lowering drugs in individuals with type 2 diabetes (T2D). However,mechanisms behind this are unclear.

• This study aimed to determine whether improved glycaemic control associated with KD was because of improved insulin sensitivity in skeletal muscle, liver and adipose tissue in individuals with obesity and insulin resistance (IR).

Methods

• This was a randomised control crossover trial of 11 individuals who were given a 3-week ketogenic diet and a 3-week standard diet, separated by a 1-week washout period.

• The KD was isocaloric with 5% energy from carbohydrates, 20% energy from protein, and 75% energy from fat.

• Participants were responsible for cooking meals and adhering to the diet at home.

• To ensure adherence, the ketone beta-hydroxybutyrate was measured and individuals were excluded if they did not reach ketosis.

• Body chemistry and composition were measured.

• Insulin sensitivity was assessed using a hyperinsulinaemic-euglycaemic clamp.

Results

• When individuals were eating a  KD, their weight, body mass index, fat mass, lean mass, and triglycerides were all significantly reduced compared to standard diet (P=<0.05 for all).

• Blood glucose levels were also significantly reduced with KD compared to standard diet (P= <0.001).

• Compared to the standard diet, there was an increase in the rate of glucose uptake by skeletal muscle after the KD (ΔR_d 2.0 [1.7–3.4] vs. 1.6 [0.9–2.9] mg/kg/min; P= < 0.05).

• No improvements in hepatic insulin sensitivity were seen with the KD. (ΔEGP% 71 ± 31% vs. 78 ± 15%; P = 0.53).

• There was a reduction in lipolysis during KD, which indicated that adipose tissue insulin sensitivity was reduced (62 ± 16 vs.76±8%; P= < 0.05).

Conclusion

• A 3-week KD improved glycaemic control, however in this small study, there were conflicting effects on insulin sensitivity in various organ systems.

• A positive association was observed between muscle insulin sensitivity and  KD, however no improvements were found in hepatic insulin sensitivity and a worsening of adipose tissue insulin sensitivity.

• In the short-term, a KD may reduce blood glucose levels in obese individuals and induce weight loss.This may be due to decreased circulating insulin levels and associated increased muscle insulin sensitivity.

• However, given that liver insulin sensitivity remained unchanged and adipose tissue became less sensitive to insulin, the long-term effects of the KD on blood glucose management is unclear.

• Clinicians should closely monitor blood glucose in individuals with obesity who undertake a KD.

• Future research should focus on the long-term effects of KD on blood glucose management.

• Other mechanisms of action could also be investigated such as whether KD affects insulin-mediated hepatic glucose production.