Erica Hall

Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients

Recent animal studies have shown that d-glucose is a potential biodegradable magnetic resonance imaging (MRI) contrast agent for imaging glucose uptake in tumors. We show herein the first translation of that use of d-glucose to human studies. Chemical exchange saturation transfer (CEST) MRI at a single frequency offset optimized for detecting hydroxyl protons in d-glucose was used to image dynamic signal changes in the human brain at 7 T during and after d-glucose infusion. Dynamic glucose enhanced (DGE) image data from 4 normal volunteers and 3 glioma patients showed a strong signal enhancement in blood vessels, while a spatially varying enhancement was found in tumors. Areas of enhancement differed spatially between DGE and conventional gadolinium-enhanced imaging, suggesting complementary image information content for these 2 types of agents. In addition, different tumor areas enhanced with d-glucose at different times after infusion, suggesting a sensitivity to perfusion-related properties such as substrate delivery and blood-brain barrier (BBB) permeability. These preliminary results suggest that DGE MRI is feasible for studying glucose uptake in humans, providing a time-dependent set of data that contains information regarding arterial input function, tissue perfusion, glucose transport across the BBB and cell membrane, and glucose metabolism.

Glycemic Predictors of Insulin Independence after Total Pancreatectomy with Islet Auto Transplantation

Context Total pancreatectomy with islet auto transplantation (TPIAT) is a treatment for medically refractory chronic pancreatitis that can prevent postsurgical diabetes in some patients. Predictors of insulin independence are needed for appropriate patient selection and counseling. Objective To explore glycemic predictors of insulin independence after TPIAT. Design A prospective cohort of patients. Methods We investigated 34 patients undergoing TPIAT from 2011-2016 at Johns Hopkins Hospital, all had a 75-g oral glucose tolerance test (OGTT) administered prior to their TPIAT. The primary outcome was insulin independence 1 year after TPIAT. Results Ten of 34 (29%) patients were insulin independent 1 year after TPIAT. All patients with impaired fasting glucose and/or impaired glucose tolerance preoperatively were insulin dependent at 1 year. In age-adjusted regression analyses, fasting glucose ≤ 90 mg/dL [odds ratio (OR) = 6.56; 1.11 to 38.91; P = 0.04], 1-hour OGTT glucose ≤ 143 mg/dL (OR = 6.65; 1.11 to 39.91; P = 0.04), and 2-hour OGTT glucose ≤ 106 mg/dL (OR = 11.74; 1.46 to 94.14; P = 0.02) were significant predictors of insulin independence. In receiver operating characteristic analyses, homeostatic model assessment of β-cell function (HOMA-β) was the most robust predictor of insulin independence [area under the curve (AUC) = 0.88; 0.73 to 1.00]. Conclusions Normal preoperative glucose status and lower fasting and postchallenge OGTT glucose values are significant predictors of insulin independence after TPIAT. Higher islet function (HOMA-β) was the strongest predictor. OGTT testing may be a useful tool to aid in patient counseling prior to TPIAT and should be further investigated.

Diabetes and pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States with a 5-year survival rate of less than 5%. There are substantial evidences that smoking, male gender, alcohol use, African American race, type 2 diabetes, family history, obesity, and pancreatitis increase the risk of pancreatic cancer. The prevalence of diabetes in individuals with pancreatic cancer is reported to range between 5% and 20%. Pancreatic cancer and diabetes have a bidirectional and complex relationship. Although preexisting diabetes may be an etiological factor in the development of pancreatic cancer, it has also been proposed that, as pancreatic cancer destroys pancreatic parenchyma, it can lead to diabetes, though a relatively large degree of pancreatic tissue needs to be destroyed for this to occur. Pancreatic cancer typically progresses without early detection because of a lack of overt symptoms. Cohort and case-control studies indicate that 25%-50% of patients with pancreatic cancer develop diabetes mellitus within the 3 years before the cancer diagnosis, and given the close temporal association, it was speculated this new-onset diabetes may be directly linked to the malignancy. However, studies have failed to identify reliable imaging protocols as a means to detect early pancreatic cancer in patients with new-onset diabetes mellitus. Moreover, the partial pancreatectomy (ie, Whipple) classically performed to treat early pancreatic cancer commonly leads to the development of diabetes postoperatively. Total pancreatectomy results in total insulin deficiency and near-absent glucagon production. All of these patients develop diabetes and require treatment with insulin. In this review, we focus on 3 areas: (1) type 2 diabetes, obesity, and the risk of developing pancreatic cancer; (2) association of metformin, insulin use, and the risk of pancreatic cancer; and (3) glycemic management in patients who have undergone partial or total pancreatectomy.

Foreign Body with Gas Gangrene in an Elderly Patient with Diabetes.

A 76-year-old African-American man who lived alone, with an 11year history of poorly controlled diabetes and symptomatic peripheral neuropathy, presented to the Emergency Department with right foot pain and swelling. His initial evaluation included a lower extremity Doppler that ruled out a deep venous thrombosis and the patient was discharged. The patient returned to the Emergency Department after one week for worsening right foot pain and swelling. He was afebrile and hemodynamically stable. The physical exam revealed new unroofed blisters on the dorsal aspect of the right foot. Foot x-ray (Panel 1) showed a 3 cm linear metallic foreign body, which appeared to be a broken sewing needle in the soft tissues between distal first and second metatarsals. Computed Tomography (CT) scan (Panel 2) showed moderate air suggesting deep tissue infection, with multiple tiny gas bubbles within the proximal phalanx of the second digit, concerning for gas gangrene. He received broad-spectrum intravenous antibiotics and underwent a two-stage operation on his right leg. The first stage was a guillotine amputation. The patient remained afebrile and hemodynamically stable. Antibiotics were stopped since now, after removal of the gangrenous tissue, there was adequate source control of the infection. A few days later, he underwent a definitive, below-theknee amputation. The differential diagnoses for gas gangrene includes inflammation