Groundbreaking Study by AGH Neurosurgical Team Suggests Artery Compressing Base of Brain Is Factor in Type 2 Diabetes Mellitus
7 of 10 Patients in Trial Who Underwent Microvascular Decompression Surgery Experience Significant Improvement in Glucose Control
August 12, 2010
A team of Allegheny General Hospital (AGH) physicians led by neurosurgical pioneer Peter Jannetta, MD, has made an important new discovery linking the central nervous system to the onset and progression of type 2 diabetes mellitus.
Reporting today in the journal Surgical Neurology International, Dr. Jannetta and his colleagues present evidence from a prospective clinical trial that vascular compression of a section of the brain called the medulla oblongata is a factor in some patients with type 2 diabetes and that microvascular decompression surgery (MVD) may be an effective treatment for the condition.
Recognized world-wide as one of the preeminent authorities on diseases associated with vascular compression of the cranial nerves, Dr. Jannetta is credited with developing the MVD technique, which is now generally considered the surgical standard of care for a host of debilitating cranial nerve diseases, including trigeminal neuralgia, hemifacial spasm, vertigo, Meniere's disease and spasmodic torticollis.
Microvascular decompression is a procedure that involves repositioning compressive arteries in the brain and placing a protective pad between the nerve and artery.
Dr. Jannetta, who serves as Vice Chair of Academics in AGH's Department of Neurosurgery, and his team have performed more than 6,000 such operations.
Over the past three decades, research by Dr. Jannetta and others has led to observations about the potential role of vascular compression in metabolic syndromes such as hypertension and diabetes.
A disease of epidemic proportions in the United States, type 2 diabetes mellitus is a chronic condition marked by high levels of sugar (glucose) in the blood. Although obesity is a primary risk factor for the disease, it can also develop in those who are not obese, especially among the elderly. Without medical intervention or aggressive lifestyle changes, type 2 diabetes often leads to serious cardiovascular, vision and renal problems.
In a previous, retrospective study of 15 patients with type 2 diabetes who were operated on by Dr. Jannetta for an unrelated right-sided cranial nerve disease, arterial compression of the right anterolateral medulla oblongata was documented in every single case (Stroke 1999:30:1707-10).
The medulla oblongata is the lowermost portion of the brain, continuous with the spinal cord, that is responsible for respiration, circulation and the body's autonomic reflexes, including function of the pancreas.
"Insulin resistance, or hyperinsulinemia, is central to the development of type 2 diabetes mellitus. We have documented previously that pulsatile arterial compression of the right anterolateral medulla oblongata is associated with autonomic dysfunction that adversely impacts the pancreas and increases insulin resistance. Building upon that knowledge, we hypothesized that decompressing the right cranial nerve X - or the vagus nerve - and the medulla oblongata could result in better glycemic control for patients with this disease," said Dr. Jannetta.
Ten patients with steadily progressive type 2 diabetes mellitus and visible right lateral medullary compression by arterial loops on MRI were enrolled in the team's follow up study. Each patient in the trial underwent right retromastoid craniectomy and microvascular decompression. At intraoperative visual evaluation, the vascular compression was even more severe than seen on MRI scans in 9 of the 10 patients, Dr. Jannetta said.
Patients in the study were followed for 12 months post-operatively, during which time no changes in diet, weight or activity level were permitted. In addition to blood glucose monitoring, studies of glycemic control, pancreatic function and insulin metabolism were performed regularly by the team.
Study participants whose glycemic control either improved or did not worsen during the course of the trial were considered "good" responders, while "failed" responders had no slowing in the natural progression of the disease.
Results of the trial showed that seven of the ten patients who underwent MVD experienced significant improvement in their glucose control, based on measurement of diabetes markers (changes in hemoglobin A1c, fasting blood glucose and serum insulin levels) and decrease of diabetes medication dosages. One patient was able to discontinue his diabetic medications entirely.
Dr. Jannetta said body mass index also appeared to be an important factor in who responded well to surgery. Those in the study who had the best outcome from MVD had BMIs classified as overweight while those who did not respond had BMIs in the obese category.
"Diabetes is a tremendously difficult condition to manage and, for patients, to live with. Though our study involves a relatively small sampling of patients, we believe that it represents a major breakthrough in our understanding about the central nervous system etiology of the disease and the potential of surgical intervention as an alternative therapy for a significant subset of patients. The next step is a much larger prospective clinical investigation to further corroborate what we have found," Dr. Jannetta said.
Commenting on the study in an accompanying editorial, Sunil Patel, MD, Chair of the Department of Neurosciences at the Medical University of South Carolina and Joyce Nicholas, Ph.D., Associate Professor in MUSC's Department of Biostatistics and Epidemiology, concur on the importance of the AGH team's work and the need for continued investigation:
"These observations point the way to further questions that need to be answered to conclude definitively that pulsatile arterial compression of the right anterolateral medulla is an independent risk factor for type 2 diabetes mellitus. Like Dr. Jannetta's earlier observations on essential hypertension, the observations presented [in the current study] are valuable starting points for questions related to the exact location of arterial compression relevant to type 2 diabetes mellitus, the best experimental measure of response, and the subset of patients most likely to benefit from microvascular decompression surgery. We encourage their continued efforts and those of other researchers in addressing the questions raised by this valuable contribution to our understanding of the disease and its treatment."
In addition to Dr. Jannetta, other AGH physicians who participated in the study include neurosurgeon Ray Sekula, MD, endocrinologist Peter Grondzioski, MD, and research coordinator Lynn Fletcher, RN.