Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus
Neurological disorders and type 2 diabetes mellitus (T2DM) are deeply intertwined. For example, autonomic neuropathy contributes to the development of T2DM and continued unmanaged T2DM causes further progression of nerve damage. Increasing glycemic control has been shown to prevent the onset and pro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2452 |
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| author | Jonathan J. Waataja Anders J. Asp Charles J. Billington |
| author_facet | Jonathan J. Waataja Anders J. Asp Charles J. Billington |
| author_sort | Jonathan J. Waataja |
| collection | DOAJ |
| description | Neurological disorders and type 2 diabetes mellitus (T2DM) are deeply intertwined. For example, autonomic neuropathy contributes to the development of T2DM and continued unmanaged T2DM causes further progression of nerve damage. Increasing glycemic control has been shown to prevent the onset and progression of diabetic autonomic neuropathies. Neuromodulation consisting of combined stimulation of celiac vagal fibers innervating the pancreas with concurrent electrical blockade of neuronal hepatic vagal fibers innervating the liver has been shown to increase glycemic control in animal models of T2DM. The present study demonstrated that the neuromodulation reversed glucose intolerance in alloxan-treated swine in both pre- and overt stages of T2DM. This was demonstrated by improved performance on oral glucose tolerance tests (OGTTs), as assessed by area under the curve (AUC). In prediabetic swine (fasting plasma glucose (FPG) range: 101–119 mg/dL) the median AUC decreased from 31.9 AUs (IQR = 28.6, 35.5) to 15.9 AUs (IQR = 15.1, 18.3) <i>p</i> = 0.004. In diabetic swine (FPG range: 133–207 mg/dL) the median AUC decreased from 54.2 AUs (IQR = 41.5, 56.6) to 16.0 AUs (IQR = 15.4, 21.5) <i>p</i> = 0.003. This neuromodulation technique may offer a new treatment for T2DM and reverse glycemic dysregulation at multiple states of T2DM involved in diabetic neuropathy including at its development and during progression. |
| first_indexed | 2024-03-10T23:00:54Z |
| format | Article |
| id | doaj.art-f07f08486d1f47ff92aeee3df9bbdc60 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:54Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-f07f08486d1f47ff92aeee3df9bbdc602023-11-19T09:41:33ZengMDPI AGBiomedicines2227-90592023-09-01119245210.3390/biomedicines11092452Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes MellitusJonathan J. Waataja0Anders J. Asp1Charles J. Billington2ReShape Lifesciences Inc., Irvine, CA 92618, USADepartment of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55605, USAMinnesota Veterans’ Administration Medical Center, Minneapolis, MN 55417, USANeurological disorders and type 2 diabetes mellitus (T2DM) are deeply intertwined. For example, autonomic neuropathy contributes to the development of T2DM and continued unmanaged T2DM causes further progression of nerve damage. Increasing glycemic control has been shown to prevent the onset and progression of diabetic autonomic neuropathies. Neuromodulation consisting of combined stimulation of celiac vagal fibers innervating the pancreas with concurrent electrical blockade of neuronal hepatic vagal fibers innervating the liver has been shown to increase glycemic control in animal models of T2DM. The present study demonstrated that the neuromodulation reversed glucose intolerance in alloxan-treated swine in both pre- and overt stages of T2DM. This was demonstrated by improved performance on oral glucose tolerance tests (OGTTs), as assessed by area under the curve (AUC). In prediabetic swine (fasting plasma glucose (FPG) range: 101–119 mg/dL) the median AUC decreased from 31.9 AUs (IQR = 28.6, 35.5) to 15.9 AUs (IQR = 15.1, 18.3) <i>p</i> = 0.004. In diabetic swine (FPG range: 133–207 mg/dL) the median AUC decreased from 54.2 AUs (IQR = 41.5, 56.6) to 16.0 AUs (IQR = 15.4, 21.5) <i>p</i> = 0.003. This neuromodulation technique may offer a new treatment for T2DM and reverse glycemic dysregulation at multiple states of T2DM involved in diabetic neuropathy including at its development and during progression.https://www.mdpi.com/2227-9059/11/9/2452type 2 diabetesvagus nervevagus nerve stimulationbioelectronicsneuromodulationneurological disorders |
| spellingShingle | Jonathan J. Waataja Anders J. Asp Charles J. Billington Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus Biomedicines type 2 diabetes vagus nerve vagus nerve stimulation bioelectronics neuromodulation neurological disorders |
| title | Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus |
| title_full | Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus |
| title_fullStr | Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus |
| title_full_unstemmed | Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus |
| title_short | Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus |
| title_sort | combining celiac and hepatic vagus nerve neuromodulation reverses glucose intolerance and improves glycemic control in pre and overt type 2 diabetes mellitus |
| topic | type 2 diabetes vagus nerve vagus nerve stimulation bioelectronics neuromodulation neurological disorders |
| url | https://www.mdpi.com/2227-9059/11/9/2452 |
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