A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes
Abstract Background Iatrogenic peripheral hyperinsulinemia, resulting from peripheral insulin administration in type 1 diabetes, may increase insulin resistance and impair endothelial function. We hypothesized that lowering iatrogenic peripheral hyperinsulinemia via a one-week, reduced-carbohydrate...
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BMC
2025-03-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02658-z |
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| author | Justin M. Gregory T. Jordan Smith Sara H. Duffus David Brooks M. Naweed Akbar Margaret-Anne Huntley JoAnn A. Gottlieb Lauren M. LeStourgeon Christopher S. Wilson Joshua A. Beckman Alan D. Cherrington |
| author_facet | Justin M. Gregory T. Jordan Smith Sara H. Duffus David Brooks M. Naweed Akbar Margaret-Anne Huntley JoAnn A. Gottlieb Lauren M. LeStourgeon Christopher S. Wilson Joshua A. Beckman Alan D. Cherrington |
| author_sort | Justin M. Gregory |
| collection | DOAJ |
| description | Abstract Background Iatrogenic peripheral hyperinsulinemia, resulting from peripheral insulin administration in type 1 diabetes, may increase insulin resistance and impair endothelial function. We hypothesized that lowering iatrogenic peripheral hyperinsulinemia via a one-week, reduced-carbohydrate diet (RCD) would improve insulin sensitivity and endothelial function compared with an isocaloric standard carbohydrate diet (SCD). Methods In this randomized, single-blinded, crossover trial, we studied 12 adults with type 1 diabetes. Participants completed both a one-week RCD and a one-week SCD, separated by a three-week washout. After each intervention, we measured insulin sensitivity using a hyperinsulinemic–euglycemic clamp and assessed endothelial function via brachial-artery flow-mediated vasodilation (FMD). Results The RCD reduced total daily insulin doses by 16% compared with the SCD. Despite this reduction, insulin sensitivity did not improve (median glucose infusion rates: RCD 8.1 mg/kg FFM/min [IQR 6.7–10.1] vs. SCD 8.6 mg/kg FFM/min [7.0–11.0], p = 0.47). Similarly, endothelial function did not differ significantly (FMD after RCD 7.50% [3.25–15.5] vs. SCD 9.81% [4.96–14.3], p = 0.91). Although higher insulin doses correlated with lower insulin sensitivity under both conditions, lowering insulin dose through the RCD alone did not yield measurable improvements. Conclusions Although a one-week RCD significantly lowered insulin requirements, it failed to enhance insulin sensitivity or endothelial function in adults with type 1 diabetes. These findings underscore the complex and dynamic relationship between insulin exposure and cardiometabolic health. Similar basal overnight insulin delivery may have masked potential benefits by the time of testing, highlighting the need for further studies to refine strategies aimed at mitigating hyperinsulinemia’s adverse effects. Trial registration ClinicalTrials.gov NCT04118374. Graphical abstract |
| format | Article |
| id | doaj-art-373ee50340df4af99fc725d4ace2de66 |
| institution | OA Journals |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-373ee50340df4af99fc725d4ace2de662025-08-20T01:57:51ZengBMCCardiovascular Diabetology1475-28402025-03-0124111510.1186/s12933-025-02658-zA one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetesJustin M. Gregory0T. Jordan Smith1Sara H. Duffus2David Brooks3M. Naweed Akbar4Margaret-Anne Huntley5JoAnn A. Gottlieb6Lauren M. LeStourgeon7Christopher S. Wilson8Joshua A. Beckman9Alan D. Cherrington10Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of MedicineIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of MedicineIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of MedicineMildred Stahlman Division of Neonatology, Vanderbilt University School of MedicineIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of MedicineIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of MedicineVanderbilt Institute for Clinical and Translational Research, Vanderbilt University School of MedicineDepartment of Internal Medicine, Vanderbilt University School of MedicineIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of MedicineDivision of Vascular Medicine, University of Texas SouthwesternDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of MedicineAbstract Background Iatrogenic peripheral hyperinsulinemia, resulting from peripheral insulin administration in type 1 diabetes, may increase insulin resistance and impair endothelial function. We hypothesized that lowering iatrogenic peripheral hyperinsulinemia via a one-week, reduced-carbohydrate diet (RCD) would improve insulin sensitivity and endothelial function compared with an isocaloric standard carbohydrate diet (SCD). Methods In this randomized, single-blinded, crossover trial, we studied 12 adults with type 1 diabetes. Participants completed both a one-week RCD and a one-week SCD, separated by a three-week washout. After each intervention, we measured insulin sensitivity using a hyperinsulinemic–euglycemic clamp and assessed endothelial function via brachial-artery flow-mediated vasodilation (FMD). Results The RCD reduced total daily insulin doses by 16% compared with the SCD. Despite this reduction, insulin sensitivity did not improve (median glucose infusion rates: RCD 8.1 mg/kg FFM/min [IQR 6.7–10.1] vs. SCD 8.6 mg/kg FFM/min [7.0–11.0], p = 0.47). Similarly, endothelial function did not differ significantly (FMD after RCD 7.50% [3.25–15.5] vs. SCD 9.81% [4.96–14.3], p = 0.91). Although higher insulin doses correlated with lower insulin sensitivity under both conditions, lowering insulin dose through the RCD alone did not yield measurable improvements. Conclusions Although a one-week RCD significantly lowered insulin requirements, it failed to enhance insulin sensitivity or endothelial function in adults with type 1 diabetes. These findings underscore the complex and dynamic relationship between insulin exposure and cardiometabolic health. Similar basal overnight insulin delivery may have masked potential benefits by the time of testing, highlighting the need for further studies to refine strategies aimed at mitigating hyperinsulinemia’s adverse effects. Trial registration ClinicalTrials.gov NCT04118374. Graphical abstracthttps://doi.org/10.1186/s12933-025-02658-zEndothelial dysfunctionEndothelial functionHyperinsulinemiaInsulin resistanceInsulin sensitivityReduced-carbohydrate diet |
| spellingShingle | Justin M. Gregory T. Jordan Smith Sara H. Duffus David Brooks M. Naweed Akbar Margaret-Anne Huntley JoAnn A. Gottlieb Lauren M. LeStourgeon Christopher S. Wilson Joshua A. Beckman Alan D. Cherrington A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes Cardiovascular Diabetology Endothelial dysfunction Endothelial function Hyperinsulinemia Insulin resistance Insulin sensitivity Reduced-carbohydrate diet |
| title | A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes |
| title_full | A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes |
| title_fullStr | A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes |
| title_full_unstemmed | A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes |
| title_short | A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes |
| title_sort | one week reduced carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized crossover trial in patients with type 1 diabetes |
| topic | Endothelial dysfunction Endothelial function Hyperinsulinemia Insulin resistance Insulin sensitivity Reduced-carbohydrate diet |
| url | https://doi.org/10.1186/s12933-025-02658-z |
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