Why hyperinsulinemia is detrimental to weight loss: insights from type 1 diabetes

Abstract

Background

The global rise in obesity prevalence poses a major health challenge due to its links to hypertension, stroke, type 2 diabetes, cardiovascular disease, depression, and cancer. Effective non-pharmacological strategies are essential to curb this epidemic. Insulin is a major regulator of body weight. It not only mediates glucose uptake but also inhibits hepatic glucose production, lipolysis, and enhances lipogenesis.

Main body

Type 1 diabetes provides insights on insulin’s role in weight regulation. Prior to diagnosis, insulin deficiency commonly produces unintentional weight loss, whereas initiation of exogenous insulin therapy typically restores body mass. Scientific research in non-diabetic populations, including Mendelian randomization studies, has identified elevated insulin secretion as a key contributor to weight gain. Conversely, reductions in insulin secretion have been shown to facilitate weight loss, even in the absence of caloric restriction. One strategy to keep circulating insulin concentrations low is the application of carbohydrate unit tables to estimate expected postprandial glucose excursions in insulin-deficient patients and anticipated insulin responses in non-diabetic individuals. This approach facilitates avoidance of foods that provoke large insulin responses. A complementary approach is postprandial self-monitoring of blood glucose (SMBG). In non-diabetic individuals, this allows for personalized assessment of glycemic and insulin responses to meals. The effectiveness of this approach in promoting weight reduction has been demonstrated across multiple studies. During fasting or adherence to low-carbohydrate diets, circulating insulin concentrations remain low, permitting unrestrained adipose tissue lipolysis and promoting fatty acid oxidation for energy production. Self-monitoring of breath acetone (SMBA) provides a simple, non-invasive biomarker of this metabolic state. Recent findings indicate that a single carbohydrate-rich meal during a ketogenic state suppresses fat mobilization for several days—a phenomenon suggestive of a “memory effect” of insulin on lipolysis inhibition. Although underlying mechanisms remain to be elucidated, awareness of this effect may improve dietary regimens.

Conclusions

Insights from type 1 diabetes offer advice for managing weight development by minimizing episodes of hyperinsulinemia. Effective non-pharmacological measures include the use of carbohydrate unit tables combined with SMBG for avoiding post-meal hyperglycemia and hyperinsulinemia. Additionally, SMBA provides a non-invasive marker of sustained fat mobilization and can help identify and prevent periods of insulin-induced fat accumulation.

Background

Because of the current global rise in obesity prevalence, non-pharmacological strategies aimed at limiting adipose tissue expansion have gained increasing relevance. In this context, it is noteworthy that individuals with type 1 diabetes often experience unintended weight loss during the initial manifestation of the disease [1]. Medical students are likely familiar with the striking visual contrast between archival photographs of a severely emaciated diabetic child and the same child months later, having regained a healthy body weight following the initiation of daily insulin therapy [2]. This landmark moment in endocrine medicine underscores a critical insight: insulin is not only essential for maintaining glucose homeostasis but also plays a pivotal role in the regulation of body weight. Thus, this debate article proposes management strategies—learned from the treatment of type 1 diabetes—that reduce hyperinsulinemia and can therefore be used by people without diabetes to help them effectively manage their body weight. Several components have been evaluated in clinical trials, with encouraging results.

Main text

The role of insulin in body weight development

Insulin is primarily recognized as a mediator of ambient glucose uptake in skeletal muscle and various other cell types. Postprandial elevations in blood glucose levels stimulate pancreatic β-cells to secrete insulin via the portal vein into the bloodstream at rates exceeding basal levels, thereby promoting cellular glucose uptake. While other dietary constituents—such as certain amino acids—can also induce insulin secretion, their impact is comparatively modest [3]. Beyond its role in glucose metabolism, insulin functions as a potent anabolic hormone. Two key hormonal actions underpin insulin’s role in promoting weight gain: the inhibition of lipolysis and the stimulation of lipogenesis. Both processes depend on insulin signaling through its receptor on adipocytes, and notably, the concentration thresholds required to elicit these effects are identical [4]. Although the precise mechanisms governing insulin’s antilipolytic activity remain incompletely understood, current evidence implicates molecular targets within adipocytes and adipose tissue macrophages, as well as interactions with other hormones such as growth hormone [5]. The pathways by which insulin facilitates lipid accumulation—both within adipocytes and at ectopic sites—are even more complex and similarly unresolved [6].

Insulin as a mediator of drug-based weight management

Reduced insulin levels in the absence of dietary restriction can likewise be induced pharmacologically, such as by treatment with diazoxide or the somatostatin analog octreotide [7–9]. In these trials, significant weight loss was observed. Pharmaceuticals such as glucagon-like peptide 1 receptor agonists (GLP-1-RA) mimic the incretin effect by enhancing glucose-dependent insulin secretion, slowing gastric emptying, and increasing satiety. Long-term treatment is associated with substantial weight loss in combination with reduced 24-h insulin levels. The magnitude of weight reduction correlated with the lowering of insulin levels [10, 11]. A direct comparison between the GLP-1-RA semaglutide and the dual glucose-dependent insulinotropic polypeptides (GIP)/GLP-1-RA tirzepatide demonstrated for the latter a more pronounced long-term decrease in insulin secretion [12]. Sodium-glucose cotransporter (SGLT)−2 inhibitors have been shown to reduce insulin levels, which may partly explain their influence on body weight regulation [11]. Nutritional approaches also support this paradigm: supplementation with myo-inositol, known for its beneficial effects on metabolic health, has been found to lower fasting insulin levels and promote favorable changes in body composition [13].

The role of genetically determined insulin levels in obesity

Complementing these findings, Mendelian randomization studies have revealed that genetically determined elevations in post-challenge insulin secretion are positively correlated with body mass index (BMI), reinforcing the causal role of insulin in promoting adiposity [14]. Similarly, genetic approaches in animal models have demonstrated that reduced insulin gene expression leads to decreased adiposity, including reductions in visceral fat despite normal access to food [15]. Moreover, selective disruption of the insulin receptor gene in adipocytes resulted in an approximately 90% reduction in insulin-stimulated glucose uptake and conferred protection against age-related obesity, again without limiting food supply [16].

Insulin-mediated inhibition of lipolysis

To appreciate insulin’s predominant role in body weight regulation, it is essential to recognize that its physiological effects are highly concentration-dependent—as studies reported toward the end of the twentieth century (reviewed by [17]). In non-obese adults, the mean plasma insulin concentration required to achieve a 50% maximal effect (EC₅₀) on glucose uptake ranged from 348 to 720 pmol/L across five studies. In contrast, the EC₅₀ for inhibiting lipolysis was significantly lower, ranging from 42 to 120 pmol/L in seven studies—approximately fivefold lower on average. In a large non-obese control cohort from a similar geographic region and study period, the geometric mean fasting insulin concentration was approximately 46 pmol/L. These data suggest that individuals with fasting insulin levels exceeding this mean may already exhibit partial suppression of lipolysis and stimulation of lipogenesis, thereby placing them at increased risk for adipose tissue expansion and eventual obesity.

Exogenous insulin therapy and hyperinsulinemia promote weight gain

Overtreatment of type 1 diabetes with insulin can lead to unintended weight gain and, over time, to obesity. This phenomenon has been substantiated by findings from the multicenter Diabetes Control and Complications Trial and its long-term follow-up studies, which documented significant weight gain among patients receiving higher insulin doses [18]. Additional evidence supports the broader role of insulin in promoting somatic growth and adiposity. In diabetes therapy, exogenous insulin is injected into the subcutaneous adipose tissue. There, it forms a small depot from which it becomes absorbed into the bloodstream. However, it first acts locally in the adipose tissue, where high insulin concentrations provoke localized fat accumulation [19]. Thus, insulin therapy in individuals with type 2 diabetes has similarly been associated with weight gain [20, 21]. These observations suggest that the anabolic actions of insulin are not dependent on the initial pass through the liver, as is the case for insulin released from pancreatic islets, but are directly associated with systemic hyperinsulinemia [22].

Per definition, insulin resistance increases the amount of insulin needed to mediate glucose uptake into the cells [23]. Physiologically, in case of lifestyle and/or nutrition-mediated hyperinsulinemia, insulin resistance can be seen as a preventive measure of the body to protect itself from metabolic stress caused by glucose overload in the cells [24–27]. In a longitudinal study of Pima Indian children, elevated fasting insulin concentrations were predictive of greater annual weight gain [28]. Likewise, in adult offspring of parents with type 2 diabetes, higher insulin secretion in response to intravenous glucose at baseline was associated with increased annual weight gain over a mean follow-up period of 16.7 years [29]. Further support comes from pediatric cohorts: obese children and adolescents exhibiting insulin hypersecretion demonstrated significantly greater adipogenesis and ectopic fat deposition at 2-year follow-up compared to their normosecreting counterparts [30].

The influence of the insulin-degrading enzyme on the duration of insulin action

Circulating insulin levels are governed not only by the rate of insulin secretion but also by the rate of plasma clearance. Insulin clearance is primarily performed by the liver and the kidneys, with ~ 50–80% of secreted insulin being removed from the blood during first liver pass. Within the liver, insulin binds to receptors on hepatocytes, becomes internalized via endocytosis, and is intracellularly degraded by the insulin-degrading enzyme (IDE). Under normal physiological conditions increasing glucose uptake leads to increasing insulin secretion but reduced hepatic extraction [31]. Genetic polymorphisms within the IDE gene region have been associated with variations in fasting insulin concentrations [32]. Individuals exhibiting IDE-dependent elevations in insulin levels have demonstrated an increased risk of developing type 2 diabetes and, consequently, central obesity [33]. IDE activity has been shown to be modulated by estradiol and progesterone, which increase insulin binding and degradation; thus, the decline in estrogen levels characteristic of menopause leads to reduced IDE activity and a subsequent rise in circulating insulin concentrations [34]. This mechanism provides a plausible explanation for menopause-associated weight gain, even in the absence of significant changes in dietary intake [35]. Therapeutic interventions targeting this pathway have shown promising results. Estrogen-containing hormone replacement therapy has been found to mitigate menopause-related hyperinsulinemia and reduce weight gain [36]. Additionally, the progesterone and glucocorticoid receptor antagonist mifepristone has been shown to enhance insulin degradation via IDE activation, thereby improving hyperinsulinemia and promoting weight loss [37]. The degradation of insulin by IDE is subject to modulation by various exogenous factors. In individuals with obesity, insulin clearance by the liver and kidneys is diminished, contributing to elevated circulating insulin levels [38]. Dietary composition also plays a role: high-carbohydrate intake has been shown to reduce hepatic insulin clearance [39], while a low-carbohydrate diet enhances clearance of insulin [40]. Physical activity and exercise are common strategies to reduce insulin resistance and to increase insulin sensitivity. Both also enhance insulin degradation. This improvement is thought to be mediated by interleukin 6, a cytokine released during muscle contraction that activates IDE [41, 42]. Finally, reducing hyperinsulinemia is also expected to reduce the risk of cardiovascular complications [22].

Collectively, insights from type 1 diabetes—characterized by weight loss in the context of insulin deficiency despite unrestricted food intake—are corroborated by pharmacological and genetic studies (Fig. 1).

Fig. 1.

Relationship between insulin secretion and body weight development. Insulin secretion plays a pivotal role in determining body weight trajectories through its dual actions: promoting lipogenesis and suppressing lipolysis. Elevated insulin levels facilitate adipose tissue expansion by enhancing lipid storage and inhibiting fat breakdown. Such increases in circulating insulin are observed following exogenous insulin administration in type 1 diabetes, consumption of digestible carbohydrates, intake of insulinogenic food additives such as artificial sweeteners, or due to genetic predispositions favoring heightened insulin secretion. Conversely, low insulin levels—as seen in untreated type 1 diabetes—permit ongoing lipolysis and do not support lipogenesis, resulting in weight loss. Insulin concentrations remain low under carbohydrate-restricted dietary conditions and following interventions with pharmaceuticals such as diazoxide, octreotide, semaglutide, tirzepatide, sodium-glucose cotransporter (SGLT)−2 inhibitors, or myo-inositol. Genetic factors may also contribute to a naturally lower insulin profile, thereby favoring fat oxidation over storage. Importantly, sustained elevations in insulin levels have been shown to induce insulin resistance, a metabolic state that further exacerbates adiposity and promotes the development of obesity, and vice versa. This underscores the complex interplay between insulin dynamics and long-term body weight regulation. CHO, carbohydrate; T1D, type 1 diabetes

Strategies learned from type 1 diabetes

Controlling insulin secretion by use of carbohydrate unit tables

For weight management, the absolute amount of calorie intake does not seem to be important except in case of a hypocaloric diet. Excess calorie intake will only result in adipogenesis if lipogenesis dominates over lipolysis, which is the case if postprandial insulin levels are high and/or the duration of insulin action is extended, as summarized in Fig. 1. An example mentioned above is the hyperinsulinemia in menopause and concomitant weight gain in the absence of dietary modifications [35]. During a high-calorie, high-fat, but low-carbohydrate Atkins diet, postprandial insulin levels remain low and weight loss is observed. Finally, in type 1 diabetes, unwanted weight loss occurs regardless of calorie intake if no exogenous insulin is administered. Thus, for weight management, circulating insulin levels appear of primary importance.

Carbohydrates may promote lipogenesis also independent of the stimulation of insulin secretion by direct conversion into fatty acids [43]. However, the substantial weight loss seen during insulin deficiency indicates that lipogenesis from carbohydrates cannot fully substitute for the lipogenic actions of insulin. It is not easy to differentiate between carbohydrate and insulin-induced lipogenesis. At the transcriptional level, two independent pathways, the sterol regulatory element binding protein 1c (SREBP1c) and the carbohydrate response element binding protein (ChREBP) pathway convey lipogenesis. Both are activated by increased glucose concentrations and increased insulin signaling, respectively [44].

In type 1 diabetes, intensive insulin therapy typically involves a combination of basal and meal-associated insulin dosing. This regimen acknowledges that postprandial elevations in blood glucose are the primary stimulus for insulin secretion by pancreatic β-cells. Accordingly, patients are trained to calculate the appropriate insulin dose based on the carbohydrate content of the meal, using standardized tables that quantify digestible carbohydrates in terms of carbohydrate portions or units—a significant advancement in patient empowerment and self-management [45]. Meta-analyses conclude that carbohydrate counting improves glycemic control in type 1 diabetes [46, 47].

Carbohydrate counting does not necessarily enhance diet quality in individuals treated with insulin, as it enables the consumption of sweet or ultra-processed foods while maintaining glycemic control through adjusted meal-time insulin dosing [47]. This principle does not extend to non-diabetic individuals. By estimating the insulinogenic potential of various foods, one can avoid meals that elicit excessive insulin secretion, thereby attenuating insulin’s anabolic effects. The resulting dietary pattern resembles a low-carbohydrate diet without caloric restriction. Numerous clinical trials have demonstrated that limiting digestible carbohydrates—while not restricting total caloric intake—reduces hyperinsulinemia, induces moderate weight loss, and improves cardiovascular risk markers [48–50].

A simplified approach to a low-carbohydrate diet involves eliminating a major source of digestible carbohydrates which in the traditional German diet is bread. In a double-blind design, participants were instructed to replace their usual bread with one of two types matching for texture but differing in digestible carbohydrate content and insulin response. Importantly, there were no restrictions on the quantity of food consumed. After 3 months, participants consuming the low-insulin-response bread exhibited significant weight loss, whereas no change was observed in the control group. These findings suggest that attenuating the insulin response to meals—without altering caloric intake—is a feasible approach to induce weight reduction [51].

Self-monitoring of post-meal blood glucose

Carbohydrate unit tables exhibited limited accuracy in predicting postprandial glucose and insulin responses. For instance, carbohydrate counting does not consider the insulinogenic potential of other food components. There is an impact of artificial food additives on postprandial insulin secretion and their potential contribution to weight gain. Notably, consumption of the non-nutritive sweetener sucralose prior to an oral glucose tolerance test has been shown to elicit significantly higher insulin secretion compared to water [52]. More strikingly, the combination of sucralose and maltodextrin induced such a pronounced insulin response in adolescents that the study was prematurely terminated by the Yale University Ethics Committee due to ethical concerns [53]. Aspartame has also been reported to stimulate endogenous insulin secretion [54], and long-term exposure to aspartame and saccharin has been associated with increased deposition of visceral, intermuscular, and adipose tissue [55]. Beyond non-nutritive sweeteners, several other food additives have been implicated in modulating insulin dynamics. Emulsifiers such as monoglycerides—commonly found in highly processed foods—have demonstrated insulin-stimulatory effects [56, 57]. Additionally, environmental toxins including bisphenol A [58] and substances such as nicotine [59] appear to enhance insulin secretion, further complicating the metabolic landscape.

Moreover, carbohydrate unit tables do not account for elevated insulin secretion during infections or psychological stress, nor for reduced secretion following strenuous physical activity. Additionally, postprandial glycemic responses to identical types and quantities of carbohydrates exhibit substantial interindividual variability, influenced by insulin resistance, gut microbiome composition, meal context and macronutrient profile, lifestyle and circadian factors, as well as genetic and epigenetic determinants [60]. Individuals with type 1 diabetes accommodate this variability through self-monitoring of blood glucose (SMBG), now commonly performed via continuous glucose monitoring systems. These technologies enable patients to assess postprandial glycemic excursions and refine insulin dosing protocols accordingly. Excessive insulin administration may result in hyperinsulinemia and promote adipose tissue growth, whereas insufficient dosing can reduce time in range for blood glucose and elevate the risk of diabetes-related complications [61].

A similar approach appears appropriate for non-diabetic individuals aiming to minimize postprandial hyperinsulinemia and associated lipogenesis. Continuous glucose monitoring with real-time feedback on glycemic responses enables individuals to identify the impact of specific foods on blood glucose levels, thereby promoting reduced consumption of high-glycemic carbohydrates and facilitating improved dietary choices. Indeed, studies have shown that self-monitoring of postprandial glucose in non-diabetic obese individuals leads to weight reduction, likely driven by autonomous dietary and lifestyle modifications [62, 63]. Carbohydrate unit tables can support the identification of foods with low insulinogenic potential and may allow SMBG to be limited to an initial training phase and periods of lifestyle or dietary change.

Recognition of low insulin activity by self-monitoring of breath acetone

In individuals with type 1 diabetes, self-monitoring of breath acetone (SMBA) is employed to detect ongoing strong lipolysis resulting from severely diminished insulin levels. Excessive production of ketone bodies under these conditions poses a risk of metabolic acidosis, with breath acetone concentrations reaching 50 ppm or higher during episodes of diabetic ketoacidosis [64]. This risk is substantially mitigated by the administration of long-acting basal insulin preparations, which help maintain minimal insulin activity and suppress excessive ketogenesis [65].

In contrast, basal circadian insulin secretion is intact in non-diabetic individuals. While the absolute insulin concentration in the fasting state seems to be relatively constant, meals and physical activity mainly account for the diurnal insulin patterns [66, 67]. However, insulin sensitivity seems to be daytime-dependent with higher secretion rates in response to a standard meal in the morning compared to the evening [68]. The higher insulin sensitivity in the afternoon is associated with increased insulin-dependent lipolysis inhibition [69]. The circadian dampening of lipolysis does not represent full suppression of lipolysis [17]. Consequently, dietary interventions such as low-carbohydrate or low-insulin diets, as well as fasting, may elevate breath acetone levels to a range of 5–20 ppm—well below the threshold associated with acidosis [70–72]. These moderate elevations reflect a physiological shift toward fat oxidation in the absence of sufficient glucose availability. Importantly, breath acetone—or alternatively, circulating ketone bodies—serves as a direct and non-invasive biomarker of lipolytic activity and fatty acid metabolism and can be used to control for active lipolysis during weight management. Unlike measures influenced by individual variability in postprandial glucose excursions, insulin secretion, IDE activity, or insulin resistance, ketone levels provide a robust indicator of insulin’s ultimate effect on lipid catabolism.

Elevated levels of non-esterified fatty acid (NEFA) are known to disrupt insulin’s effects on muscle glucose uptake and on endogenous liver glucose production. However, these impairments have been observed particularly in individuals with elevated NEFA levels. Although during dietary intervention plasma NEFA concentrations increased in the short term (1–4 weeks) in patients with type 2 diabetes, in the long term a normalization of beta cell function and significant improvements in insulin sensitivity can be observed [72]. Thus, NEFA-mediated effects are dose-dependent and have no deteriorating effect during lipolysis on metabolic health in the long term.

During the assessment of breath acetone concentrations as a marker of fat oxidation in response to a very-low-carbohydrate diet, we observed a striking phenomenon suggestive of a “memory effect” of insulin on the inhibition of lipolysis. According to the study protocol, participants performed an oral glucose tolerance test (OGTT) and then adhered to a strict low-carbohydrate diet for 1 week, successfully reaching a state of nutritional ketosis, defined by fasting breath acetone concentrations exceeding 7.0 ppm. Subsequently, each participant consumed a single meal consisting of two white bread rolls (72 g digestible carbohydrates), after which the original low-carbohydrate diet was resumed. As anticipated, fasting acetone levels declined sharply—by more than 50%—indicating a suppression of lipolysis triggered by postprandial insulin secretion. However, the return to stable ketosis was delayed, requiring an average of 5 days. Notably, participants in the highest tertile of baseline fasting insulin levels failed to re-establish stable ketosis within the 7-day observation period following the carbohydrate-rich meal [73]. These findings suggest that even a single meal or snack eliciting a moderate-to-high insulin response can impair fat oxidation for several days, despite resumption of a ketogenic dietary pattern (Fig. 2). These results extend earlier findings that after the induction of ketosis a single dose of carbohydrates completely alleviated ketosis for more than the observation period of 36 h [74]. A possible mechanism is suggested by the observation while insulin’s glucose-lowering effect is transient, its influence on lipid metabolism may persist for several days [75]. The prolonged suppression of lipolysis after a single carbohydrate snack remains to be confirmed in further studies. Since individuals with higher basal insulin levels (and usually a higher BMI) experience a longer inhibition of lipolysis after a carbohydrate-rich meal, the resulting recommendation would be to continuously and strongly restrict carbohydrate intake in the initial phase of lifestyle intervention to avoid periods of lipolysis inhibition. When a certain amount of weight loss has occurred metabolic flexibility has been restored [76].

Fig. 2.

Long-term suppression of fat breakdown following a single carbohydrate-rich meal. A notable observation was the prolonged suppression of fat oxidation following a single carbohydrate-rich meal. Participants performed an oral glucose tolerance test (OGTT) and then adhered to a very-low-carbohydrate diet for eight consecutive days, resulting in a substantial rise in fasting breath acetone concentrations—an established marker of fatty acid breakdown for energy production. Stable lipolysis was defined as fasting breath acetone levels ≥ 7 ppm. On day eight, participants consumed a breakfast consisting of two white bread rolls, providing a total of 72 g digestible carbohydrates. This single meal led to a pronounced decline in breath acetone levels, indicating an acute suppression of lipolysis in response to postprandial insulin secretion. Remarkably, the return to pre-intervention acetone levels required an average of 5 days, despite resumption of the original low-carbohydrate diet (modified after [73])

Conclusions

This debate article highlights key observations from type 1 diabetes for the management of body weight regulation. Specifically, β-cell dysfunction leads to unintended weight loss due to insufficient endogenous insulin secretion, while exogenous insulin administration effectively restores body weight. As discussed, elevated insulin secretion promotes weight gain across various clinical and genetic contexts, including Mendelian randomization studies. Conversely, protocols aimed at reducing insulin levels as described here—whether pharmacological, dietary, or behavioral—consistently result in weight loss among overweight and obese individuals, even in the absence of caloric restriction.

Drawing from the effective self-management strategies practiced by individuals with type 1 diabetes, the use of carbohydrate unit tables offers a valuable method for estimating the insulinogenic potential of various foods. In the context of obesity, this approach enables individuals to identify dietary components that disproportionately stimulate insulin secretion, thereby contributing to adipose tissue growth. Complementing this strategy, continuous glucose monitoring provides a practical tool for detecting postprandial hyperglycemia, which serves as an indirect marker of elevated insulin levels. Combining carbohydrate unit tables for the preselection of likely appropriate food components may permit restriction of continuous blood glucose self-monitoring to initial training and time-limited periods thereafter.

A lifestyle focused on minimizing glycemic excursions throughout the day facilitates fat oxidation, as evidenced by increased circulating ketone bodies and elevated breath acetone concentrations. However, our findings indicate that even a single carbohydrate-rich meal or snack can suppress lipolysis for several days, likely due to a persistent effect of transient hyperinsulinemia. The underlying mechanism of this “memory effect” remains to be elucidated and currently cannot be circumvented. Nonetheless, systematic evaluation of dietary patterns and lifestyle behaviors for periods of hyperglycemia—and their targeted modification—can help minimize prolonged elevations in blood glucose and insulin. This approach enables individuals to harness fat breakdown under conditions of low insulin availability, offering a promising strategy for sustainable weight management.

Abbreviations

BMI

Body mass index

CHO

Carbohydrate

ChREBP

Carbohydrate response element binding protein

EC₅₀

Mean insulin concentration for 50% effect

GIP

Glucose-dependent insulinotropic polypeptide

GLP-1-RA

Glucagon-like peptide 1 receptor agonist

IDE

Insulin-degrading enzyme

NEFA

Non-esterified fatty acid

OGTT

Oral glucose tolerance test

SGLT2

Sodium-glucose cotransporter 2

SMBA

Self-monitoring of breath acetone

SMBG

Self-monitoring of blood glucose

SREBP1c

Sterol regulatory element binding protein 1c

T1D

Type 1 diabetes

Authors' contributions

SM, HK and KK wrote the manuscript. All authors read and approved the final manuscript.

Funding

We thank the Freunde und Förderer der Heinrich-Heine-Universität Düsseldorf for financial support of publication costs.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.