Low-carbohydrate and Ketogenic Diets: Mechanisms for Weight Loss and Diabetes Remission View PDF

A comprehensive examination of current literature underscores the multifaceted mechanisms through which low-carbohydrate and ketogenic diets facilitate weight loss and promote diabetes remission [1- 4]. These dietary approaches, characterized by significant carbohydrate restriction and high fat intake, have garnered attention for their potential to induce profound metabolic changes, improve glycemic control, and alter body composition [5-8].

One of the primary mechanisms attributed to the efficacy of ketogenic diets in weight management and diabetes remission involves metabolic adaptation to ketosis. As outlined by Malinowska and ?endzian-Piotrowska [9], the ketogenic diet induces a shift from glucose-based energy metabolism to fat-based oxidation, leading to increased production of ketone bodies such as beta-hydroxybutyrate. This metabolic switch not only provides an alternative energy substrate but also influences appetite regulation, often resulting in reduced caloric intake and subsequent weight loss. The role of ketone bodies extends beyond energy provision; they may exert signaling functions that modulate inflammation and insulin sensitivity, further contributing to metabolic improvements [9].

The impact of carbohydrate restriction on insulin dynamics is another critical aspect. Long et al. [10] demonstrated that ketogenic diets could induce hepatic insulin resistance and fatty liver disease in animal models, suggesting complex effects on liver metabolism. Conversely, human studies, such as those reviewed by Rafiullah et al. [11], indicate that very-low-carbohydrate ketogenic diets can significantly improve glycemic control in patients with type 2 diabetes. These diets reduce postprandial glucose excursions and decrease insulin demand, which may facilitate remission of type 2 diabetes. Unwin et al. [12] further support this, showing that a primary care-based low-carbohydrate approach achieved drug-free remission in a substantial proportion of patients, emphasizing the diet’s potential to restore normal glucose homeostasis.

The modulation of gut microbiota has emerged as an intriguing mechanism mediating the benefits of ketogenic diets. Defeudis et al. [13] highlighted that very-low-calorie ketogenic diets positively influence gut microbiota composition, which may, in turn, improve metabolic parameters and reduce inflammation. This microbiome-mediated pathway could be pivotal in understanding long-term outcomes, although current evidence remains primarily observational and shortterm. In addition to metabolic shifts, the influence of ketogenic diets on body composition is well-documented. Correa et al. [14] reported significant anthropometric improvements, including weight loss and reduced body fat, which are crucial for managing obesity-related insulin resistance. The rapid weight reduction observed with verylow- calorie ketogenic diets is partly attributed to decreased appetite, increased satiety, and enhanced fat oxidation, as discussed by Laddu et al. [15]. These effects are often achieved through stages of induced ketosis, followed by reintroduction of calories and maintenance strategies, which help sustain weight loss over time.

Furthermore, the role of bile acids in mediating weight loss and metabolic health has been explored. Li et al. [16] found that ketogenic diet consumption elevates serum taurodeoxycholic acid and tauroursodeoxycholic acid, which may reduce calorie absorption and promote weight loss. This mechanism suggests that beyond caloric restriction, ketogenic diets may influence enterohepatic signaling pathways that regulate energy balance. The potential for ketogenic diets to induce diabetes remission is also supported by clinical case reports and retrospective studies. Correa et al. [14] and Moriconi et al. [17] documented cases where significant glycemic improvements led to the discontinuation of antidiabetic medications. Unwin et al. [12] further demonstrated that a low-carbohydrate diet could be a practical, primary care-based intervention for achieving drug-free remission, emphasizing the diet’s therapeutic potential.

However, concerns regarding safety and adverse effects are also present in the literature. Long et al. [10] noted that in animal models, ketogenic diet could induce hepatic insulin resistance, raising questions about long-term safety. Similarly, Buehler et al. [18] discussed safety considerations in managing type 1 diabetes with ketogenic diets, highlighting the need for careful monitoring. Despite these concerns, the overall evidence suggests that, when properly supervised, ketogenic diets are generally safe and well-tolerated, especially in the short term [13].

In summary, the mechanisms underpinning the benefits of lowcarbohydrate and ketogenic diets in weight loss and diabetes remission are multifactorial. They involve metabolic adaptations to ketosis, improved insulin sensitivity, modulation of gut microbiota, alterations in bile acid signaling, and changes in appetite regulation. While the evidence supports their efficacy, especially in the short term, ongoing research is necessary to elucidate long-term safety and sustainability. The current body of literature underscores the potential of these dietary strategies as effective tools in managing obesity and type 2 diabetes, with mechanisms rooted in complex metabolic and microbiome interactions that warrant further exploration