Sol Jacobs

Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes Undergoing General Surgery (RABBIT 2 Surgery)

OBJECTIVE The optimal treatment of hyperglycemia in general surgical patients with type 2 diabetes mellitus is not known. RESEARCH DESIGN AND METHODS This randomized multicenter trial compared the safety and efficacy of a basal-bolus insulin regimen with glargine once daily and glulisine before meals (n = 104) to sliding scale regular insulin (SSI) four times daily (n = 107) in patients with type 2 diabetes mellitus undergoing general surgery. Outcomes included differences in daily blood glucose (BG) and a composite of postoperative complications including wound infection, pneumonia, bacteremia, and respiratory and acute renal failure. RESULTS The mean daily glucose concentration after the 1st day of basal-bolus insulin and SSI was 145 ± 32 mg/dL and 172 ± 47 mg/dL, respectively (P < 0.01). Glucose readings <140 mg/dL were recorded in 55% of patients in basal-bolus and 31% in the SSI group (P < 0.001). There were reductions with basal-bolus as compared with SSI in the composite outcome [24.3 and 8.6%; odds ratio 3.39 (95% CI 1.50–7.65); P = 0.003]. Glucose <70 mg/dL was reported in 23.1% of patients in the basal-bolus group and 4.7% in the SSI group (P < 0.001), but there were no significant differences in the frequency of BG <40 mg/dL between groups (P = 0.057). CONCLUSIONS Basal-bolus treatment with glargine once daily plus glulisine before meals improved glycemic control and reduced hospital complications compared with SSI in general surgery patients. Our study indicates that a basal-bolus insulin regimen is preferred over SSI in the hospital management of general surgery patients with type 2 diabetes.

Randomized Study Comparing a Basal Bolus With a Basal Plus Correction Insulin Regimen for the Hospital Management of Medical and Surgical patients With Type 2 Diabetes: Basal Plus Trial

OBJECTIVE Effective and easily implemented insulin regimens are needed to facilitate hospital glycemic control in general medical and surgical patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This multicenter trial randomized 375 patients with T2D treated with diet, oral antidiabetic agents, or low-dose insulin (≤0.4 units/kg/day) to receive a basal-bolus regimen with glargine once daily and glulisine before meals, a basal plus regimen with glargine once daily and supplemental doses of glulisine, and sliding scale regular insulin (SSI). RESULTS Improvement in mean daily blood glucose (BG) after the first day of therapy was similar between basal-bolus and basal plus groups (P = 0.16), and both regimens resulted in a lower mean daily BG than did SSI (P = 0.04). In addition, treatment with basal-bolus and basal plus regimens resulted in less treatment failure (defined as >2 consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL) than did treatment with SSI (0 vs. 2 vs. 19%, respectively; P < 0.001). A BG <70 mg/dL occurred in 16% of patients in the basal-bolus group, 13% in the basal plus group, and 3% in the SSI group (P = 0.02). There was no difference among the groups in the frequency of severe hypoglycemia (<40 mg/dL; P = 0.76). CONCLUSIONS The use of a basal plus regimen with glargine once daily plus corrective doses with glulisine insulin before meals resulted in glycemic control similar to a standard basal-bolus regimen. The basal plus approach is an effective alternative to the use of a basal-bolus regimen in general medical and surgical patients with T2D.

Randomized Controlled Trial of Intensive Versus Conservative Glucose Control in Patients Undergoing Coronary Artery Bypass Graft Surgery: GLUCO-CABG Trial

OBJECTIVE The optimal level of glycemic control needed to improve outcomes in cardiac surgery patients remains controversial. RESEARCH DESIGN AND METHODS We randomized patients with diabetes (n = 152) and without diabetes (n = 150) with hyperglycemia to an intensive glucose target of 100–140 mg/dL (n = 151) or to a conservative target of 141–180 mg/dL (n = 151) after coronary artery bypass surgery (CABG) surgery. After the intensive care unit (ICU), patients received a single treatment regimen in the hospital and 90 days postdischarge. Primary outcome was differences in a composite of complications, including mortality, wound infection, pneumonia, bacteremia, respiratory failure, acute kidney injury, and major cardiovascular events. RESULTS Mean glucose in the ICU was 132 ± 14 mg/dL (interquartile range [IQR] 124–139) in the intensive and 154 ± 17 mg/dL (IQR 142–164) in the conservative group (P < 0.001). There were no significant differences in the composite of complications between intensive and conservative groups (42 vs. 52%, P = 0.08). We observed heterogeneity in treatment effect according to diabetes status, with no differences in complications among patients with diabetes treated with intensive or conservative regimens (49 vs. 48%, P = 0.87), but a significant lower rate of complications in patients without diabetes treated with intensive compared with conservative treatment regimen (34 vs. 55%, P = 0.008). CONCLUSIONS Intensive insulin therapy to target glucose of 100 and 140 mg/dL in the ICU did not significantly reduce perioperative complications compared with target glucose of 141 and 180 mg/dL after CABG surgery. Subgroup analysis showed a lower number of complications in patients without diabetes, but not in patients with diabetes treated with the intensive regimen. Large prospective randomized studies are needed to confirm these findings.

Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes: A pilot, randomized, controlled study

OBJECTIVE This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients. RESEARCH DESIGN AND METHODS In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups. RESULTS Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86). CONCLUSIONS Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.

A Comparison Study of Continuous Insulin Infusion Protocols in the Medical Intensive Care Unit: Computer-Guided Vs. Standard Column-Based Algorithms

PURPOSE To compare the safety and efficacy of continuous insulin infusion (CII) via a computer-guided and a standard paper form protocol in a medical intensive care unit (ICU). METHODS Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n = 77) or a standard paper protocol (n = 76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL. RESULTS The Glucommander resulted in a lower mean BG value (103 ± 8.8 mg/dL vs. 117 ± 16.5 mg/dL, P < 0.001) and in a shorter time to reach BG target (4.8 ± 2.8 vs.7.8 hours ± 9.1 hours, P < 0.01), and once at target resulted in a higher percentage of BG readings within target (71.0 ± 17.0% vs. 51.3 ± 19.7%, P < 0.001) than the standard protocol. Mean insulin infusion rate in the Glucommander was similar to the standard protocol (P = 0.12). The percentages of patients with ≥1 episode of BG <40 mg/dL and <60 mg/dL were 3.9% and 42.9% in the Glucommander and 5.6% and 31.9% in the standard, respectively [P = not significant (NS)]. Repeated measures analyses show that the probabilities of BG reading <40 mg/dL or <60 mg/dL were not significantly different between groups (P = 0.969, P = 0.084) after accounting for within-patient correlations with or without adjusting for time effect. There were no differences between groups in the length of hospital stay (P = 0.704), ICU stay (P = 0.145), or inhospital mortality (P = 0.561). CONCLUSION Both treatment algorithms resulted in significant improvement in glycemic control in critically ill patients in the medical ICU. The computer-based algorithm resulted in tighter glycemic control without an increased risk of hypoglycemic events compared to the standard paper protocol.

Hospital Discharge Algorithm Based on Admission HbA1c for the Management of Patients With Type 2 Diabetes

OBJECTIVE Effective treatment algorithms are needed to guide diabetes care at hospital discharge in general medicine and surgery patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This was a prospective, multicenter open-label study aimed to determine the safety and efficacy of a hospital discharge algorithm based on admission HbA1c. Patients with HbA1c <7% (53.0 mmol/mol) were discharged on their preadmission diabetes therapy, HbA1c between 7 and 9% (53.0–74.9 mmol/mol) were discharged on a preadmission regimen plus glargine at 50% of hospital daily dose, and HbA1c >9% were discharged on oral antidiabetes agents (OADs) plus glargine or basal bolus regimen at 80% of inpatient dose. The primary outcome was HbA1c concentration at 12 weeks after hospital discharge. RESULTS A total of 224 patients were discharged on OAD (36%), combination of OAD and glargine (27%), basal bolus (24%), glargine alone (9%), and diet (4%). The admission HbA1c was 8.7 ± 2.5% (71.6 mmol/mol) and decreased to 7.3 ± 1.5% (56 mmol/mol) at 12 weeks of follow-up (P < 0.001). The change of HbA1c from baseline at 12 weeks after discharge was −0.1 ± 0.6, −0.8 ± 1.0, and −3.2 ± 2.4 in patients with HbA1c <7%, 7–9%, and >9%, respectively (P < 0.001). Hypoglycemia (<70 mg/dL) was reported in 22% of patients discharged on OAD only, 30% on OAD plus glargine, 44% on basal bolus, and 25% on glargine alone and was similar in patients with admission HbA1c ≤7% (26%) compared with those with HbA1c >7% (31%, P = 0.54). CONCLUSIONS Measurement of HbA1c on admission is beneficial in tailoring treatment regimens at discharge in general medicine and surgery patients with type 2 diabetes.

The Use of Functional Imaging in a Patient with Head and Neck Paragangliomas

A 21-yr-old male presented to the National Institutes of Health with five head and neck paragangliomas, found after treatment for chronic ear infections. Symptoms experienced by the patient included constant right ear pain, mild yellowish discharge from the right ear, decreased hearing, and a constant vibration sound on the right side but no symptoms related to catecholamine excess. On evaluation five paragangliomas were found on anatomical imaging (computed tomography and magnetic resonance imaging) as follows: 2.7- × 1.6-cm right carotid body tumor; 3.1- × 2.6-cm left carotid body tumor; 3.6- × 2.4-cm left glomus vagale tumor; 1.0- × 1.0-cm tumor in the left jugular fossa; and a 2.1- × 1.8-cm tumor in the right jugular fossa, which had caused extensive bone destruction involving the bony walls of the jugular fossa, the external auditory canal, the condylar fossa of the temporal mandibular joint, and the hypotympanic cavity of the right middle ear. Biochemistry (plasma fractionated catecholamines and metanephrines; 24 h fractionated urinary catecholamines and metanephrines) was unremarkable except for elevation of plasma dopamine to 437 pg/ml (reference range 3–46 pg/ml) and urinary dopamine to 431 μg per 24 h (reference range 65–400 μg per 24 h). Genetic testing revealed a mutation (p.Pro81Leu) in the succinate dehydrogenase subunit D gene. Head and neck paragangliomas are often biochemically silent (normal catecholamine and metanephrine values), making imaging a very important diagnostic tool (1,2). Here we present a patient whose head and neck paragangliomas were localized on computed tomography (CT) (Fig. 1​1)) and show avid uptake with four functional imaging techniques: 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET) (Fig. 2A​2A);); 18F-fluorodopamine (18F-FDA) PET/CT (Fig. 2B​2B);); 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT (Fig. 2C​2C);); and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy (Fig. 2D​2D).). Two of these modalities, 18F-FDA PET/CT and 123I-MIBG scintigraphy, are paraganglioma specific, targeting the norepinephrine transporters expressed in these tumors (3,4). Although 18F-FDG and 18F-FDOPA PET are not paraganglioma-specific imaging modalities, their efficacy for the localization of these tumors is represented here. 18F-FDOPA PET, in particular, showed avid uptake in all five tumors and should be considered a good imaging technique for head and neck paragangliomas, as previously reported (5). As demonstrated here, multiple imaging modalities, both anatomical and functional, can be used for the accurate localization of head and neck paragangliomas. However, because CT imaging is nonspecific for paragangliomas, functional imaging modalities are a good tool for confirming in the diagnosis of head and neck paragangliomas. Figure 1 Coronal reconstructed CT of the neck. There are five tumors identified: right (1) and left (2) glomus jugulare tumors; a left glomus vagale tumor (3); and left (4) and right (5) carotid body tumors. All five tumors demonstrate homogeneous enhancement. ... Figure 2 A, 18F-FDOPA PET. B, 18F-FDA PET/CT. C, 18F-FDG PET/CT. D, 123I-MIBG scintigraphy. Four functional imaging modalities were used to localize five head and neck paragangliomas: right (1) and left (2) glomus jugulare tumors; a left glomus vagale tumor ( ...

Management of Intractable Hypoglycemia With Yttirum-90 Radioembolization in a Patient With Malignant Insulinoma

Metastatic insulinomas may present with recurrent life-threatening hypoglycemia. Treatment of hypoglycemia in such patients is difficult and frequently fails to respond to numerous therapeutic agents, requiring continuous dextrose infusion. The authors present our experience with Yttirum-90 radioembolization in a patient with metastatic malignant insulinoma who failed to respond to distal pancreatectomy, systemic chemotherapy with capecitabine and everolimus and medical treatment with somatostatin analogues, diazoxide and corticosteroids. Treatment with repeated Y-90 radioembolization resulted in rapid resolution of hypoglycemic events, allowing discontinuation of dextrose infusion and hospital discharge. However, the effect of Y-90 administration seems to be transient and without evidence of tumor shrinkage in imaging studies.

Differences in inpatient glycemic control and response to subcutaneous insulin therapy between medicine and surgery patients with type 2 diabetes

OBJECTIVE To determine differences in inpatient glycemic control and response to two different glargine-based insulin regimens in general medicine and surgery patients with type 2 diabetes (T2D). METHODS This is a post-hoc analysis of a prospective, multicenter, randomized trial of 298 non-ICU medicine and surgery patients with T2D treated with Basal Bolus regimen with glargine once daily and glulisine before meals and with Basal Plus regimen with glargine once daily and supplemental doses of glulisine before meals for blood glucose (BG)>140mg/dl. Major study outcomes included differences in mean daily BG, frequency of treatment failures (defined as >2 consecutive BG>240mg/dl or a mean daily BG>240mg/dl), and hypoglycemia between the medicine and surgery cohorts. RESULTS Patients treated with Basal Bolus or with Basal Plus experienced similar improvement in mean daily BG after 1st day of therapy (p=0.16), number of treatment failures (p=0.11) and hypoglycemic events (p=0.50). Compared to surgery patients (n=130), medicine patients (n=168) had higher admission BG (p=0.01) and HbA1c levels (p<0.01); however, they had similar response to either treatment regimen without differences in mean daily BG after 1st day of therapy (p=0.18), number of treatment failures (p=0.58), daily insulin requirements (p=0.36), or in the frequency of hypoglycemia (p=0.79). CONCLUSION The Basal Plus regimen with glargine once daily and correction doses with glulisine before meals resulted in similar glycemic control to basal bolus regimen. We observed no differences in response to either basal insulin regimen between medicine and surgery patients with type 2 diabetes.

Hospitalization costs and clinical outcomes in CABG patients treated with intensive insulin therapy

BACKGROUND The financial impact of intensive (blood glucose [BG] 100-140mg/dl [5.5-7.8mM] vs. conservative (141-180mg/dl (7.9-10.0mM) glucose control in the ICU in patients, with and without diabetes, undergoing coronary artery bypass graft (CABG) surgery is not known. METHODS This post-hoc cost analysis determined differences in hospitalization costs, resource utilization and perioperative complications in 288 CABG patients with diabetes (n=143) and without diabetes (n=145), randomized to intensive (n=143) and conservative (n=145) glucose control. RESULTS Intensive glucose control resulted in lower BG (131.4±14mg/dl-(7.2±0.8mM) vs. 151.6±17mg/dl (8.4±0.8mM, p<0.001), a nonsignificant reduction in the median length of stay (LOS, 7.9 vs. 8.5days, p=0.17) and in a composite of perioperative complications including wound infection, bacteremia, acute renal and respiratory failure, major cardiovascular events (42% vs 52%, p=0.10) compared to conservative control. Median hospitalization costs were lower in the intensive group (