Anthony J. DeSantis

Vitamin D Levels and Bone Turnover in Epilepsy Patients Taking Carbamazepine or Oxcarbazepine

Summary:  Purpose: Evidence suggests that enzyme‐inducing antiepileptic drugs (AEDs) may decrease serum 25‐hydroxyvitamin D (25‐OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC).

CONVERSION OF INTRAVENOUS INSULIN INFUSIONS TO SUBCUTANEOUSLY ADMINISTERED INSULIN GLARGINE IN PATIENTS WITH HYPERGLYCEMIA

OBJECTIVE To determine the optimal dose of insulin glargine needed to maintain glycemic control in patients undergoing conversion from intravenous regular insulin infusions to a subcutaneous insulin regimen. METHODS Seventy-five hospitalized patients receiving continuous insulin infusions were randomized to receive 40%, 60%, or 80% of their total daily insulin requirement, calculated from the rate during the final 6 hours of the infusion, as insulin glargine at the time of conversion to a subcutaneous regimen. Prandial insulin aspart was added to the subcutaneous regimen when patients began oral intake, and the dosage was left to clinical judgment. Capillary blood glucose monitoring (CBGM) was performed before every meal and at bedtime. All CBGM values for the 24-hour period after conversion were collected. RESULTS Three hundred ninety-two CBGM values were recorded and analyzed. The mean for all CBGM values during the 24-hour period after conversion to the subcutaneous insulin regimen was 151.9 +/- 42.5 mg/dL in the 40% group, 164.0 +/- 41.6 mg/dL in the 60% group, and 153.2 +/- 66.2 mg/dL in the 80% group (P = 0.66). The percentage of CBGM values in the predefined study target range (80 to 140 mg/dL) was 43.2%, 34.8%, and 48% in the 40%, 60%, and 80% groups, respectively (P = 0.09). Secondary analysis with use of a glycemic target of 80 to 150 mg/dL and removal of outliers resulted in CBGM values within that range in 58.7%, 44.4%, and 67.6% for the 40%, 60%, and 80% groups, respectively (overall, P = 0.001; 40% group versus the 60% group, P = 0.03; 60% group versus the 80% group, P = 0.0004; and 40% group versus the 80% group, P = 0.18). CONCLUSION Conversion from continuous insulin infusion to subcutaneously administered insulin glargine at a dose equal to 80% of the total daily insulin requirements resulted in the highest percentage of CBGM values in the glycemic target range of 80 to 150 mg/dL within the first 24 hours after regimen conversion in comparison with conversion at 40% and 60%, albeit the difference between the 40% and 80% groups was not statistically significant.

INPATIENT MANAGEMENT OF HYPERGLYCEMIA: THE NORTHWESTERN EXPERIENCE

OBJECTIVE To describe a novel method of safe and effective intensive management of inpatient hyperglycemia with use of cost-effective protocols directed by a glucose management service (GMS). METHODS An intravenous insulin protocol was designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients were transferred from the intravenous protocol to a subcutaneous insulin protocol, which consisted of basal long-acting and prandial and supplemental rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose levels were reviewed by the GMS at least daily for protocol adjustments, when necessary. RESULTS The intravenous insulin protocol was used in 276 patients, and 4,058 capillary blood glucose levels were recorded. Glycemic target levels (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation of insulin drip therapy. The mean capillary blood glucose level during the study interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in 1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only 0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067 capillary glucose levels were documented. The mean blood glucose level was 145.6 +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150 mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL) occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400 mg/dL) occurred in 0.4% of values. CONCLUSION Validated protocols dedicated to the achievement of strict glycemic goals were implemented by a GMS and resulted in substantial improvements in glycemic control on the surgical inpatient services, with a reduced frequency of hypoglycemia. The protocols and the GMS have been well received by the inpatient nursing and surgical staff members, and all of this has been done in a cost-effective manner.

An osteoporosis and fracture intervention program increases the diagnosis and treatment for osteoporosis for patients with minimal trauma fractures.

BACKGROUND As fewer than 25% of patients with an osteoporotic minimal trauma fracture (MTF) are evaluated and treated for osteoporosis, an osteoporosis and fracture intervention program (OFIP) was developed. METHODS Patients hospitalized with MTF were educated about and treated for osteoporosis and were evaluated by the osteoporosis team at 6 and 12 months after discharge. Patients seen in the emergency department were given information about osteoporosis and encouraged to seek medical care at the osteoporosis office. RESULTS While 165 patients hospitalized with an MTF participated in the OFIP, 38 patients received routine osteoporosis education. At the 6-month follow-up, in the OFIP group, 68% of patients with hip fracture and 54% of patients with non-hip fracture were taking antiresorptive medications. There was no change in treatment rate among patients receiving conventional care. CONCLUSIONS The rates of diagnosis of osteoporosis and treatment implementation following an MTF increased when the intervention occurred at the time of hospitalization.

Glycemic Control by a Glucose Management Service and Infection Rates After Liver Transplantation

OBJECTIVE To present an analysis of glycemic control before and after introduction of a dedicated glucose management service (GMS) and outcomes within 1 year after liver transplantation (LT). METHODS We conducted a retrospective review of patients undergoing LT, who were treated with insulin infusions after LT, before and after introduction of a GMS. Outcome measures within 1 year after LT included graft rejection, infection, prolonged ventilation (>48 hours on a ventilator), and graft survival. A multiple logistic regression was used to examine the relationship between GMS use and outcomes. RESULTS This study consisted of 73 (35 GMS and 38 non-GMS) organ transplant recipients. The mean perioperative blood glucose level in the GMS group was lower than in the non-GMS group: unadjusted, by 31.1 mg/dL (P = .001); adjusted for pre-insulin drip glucose, age, sex, Model for End-Stage Liver Disease (MELD) score, and type of transplant, by 23.4 mg/dL (P = .020). There were 27 rejection episodes, 48 infections, 26 episodes of prolonged ventilation, and 64 patients with graft survival at 1 year. The infection rate was lower in the GMS group than in the non-GMS group: the unadjusted odds ratio was 0.28 (P = .015); when adjustments were made for pre-insulin drip glucose, pretransplant glucose, age, sex, MELD score, type of transplant, and diabetes status before transplantation, the odds ratio was 0.24 (95% confidence interval, 0.06 to 0.97; P = .045). No significant associations were noted between GMS group and rejection rates, prolonged ventilation, or graft survival. CONCLUSION In this study of LT patients, a GMS was associated with improved glycemic control and reduced postoperative infections. Further studies investigating effects of strict glycemic control after LT are warranted.

Current and emerging therapies in osteoporosis

Osteoporosis is a systemic skeletal disorder leading to decreased bone mineralisation and a propensity for fracture. The disease affects millions of people and is a source of significant morbidity and mortality. Fracture-related costs have skyrocketed in recent years and projections suggest an increase as the population ages. Recent advances in the understanding of bone biology have improved the therapeutic options for osteoporosis. This is a review of the osteoporotic therapies that have recently become available and a discussion of emerging options. An overview on current practice guidelines is provided.

Insulin resistance following cardiothoracic surgery in patients with and without a preoperative diagnosis of type 2 diabetes during treatment with intravenous insulin therapy for postoperative hyperglycemia

OBJECTIVE To assess insulin resistance postoperatively in patients with (DM) and without (nonDM) a prior diagnosis of diabetes. RESEARCH DESIGN AND METHODS Following cardiac surgery, 122 nonDM and 33 DM were treated with insulin infusions to obtain glucose levels <110 mg dl(-1). Glucose levels, insulin infusion rates, and insulin infusion rate/glucose ratios were calculated to assess insulin resistance. RESULTS The average blood glucose at insulin drip initiation (209 vs. 173 mg dl(-1); P<.001) and during the first 12 h (146 vs. 135 mg dl(-1); P<.05) was higher in DM, but during Hours 12-24 glucose levels were not different. The peak (5.7 vs. 4.1 U h(-1); P<.001) and average insulin drip rates (3.7 vs. 2.9 U h(-1); P<.01) were higher in DM. Insulin resistance (insulin drip rate/glucose ratio) was higher in DM during Hours 1-12 (0.029 vs. 0.022 U h(-1) mg(-1) dl(-1); P<.001), but not during Hours 12-24 (P=.57). To eliminate glucotoxicity as a cause of the insulin resistance, 23 DM patients were pair matched with 23 nonDM patients based first on glucose levels at drip initiation then by body mass index (BMI) and then catecholamine use to maintain blood pressure. The average blood glucose levels, insulin drip rates, and insulin resistance ratios were not significantly different between the pair-matched groups at all time points. CONCLUSIONS When matched for initial glucose levels, insulin resistance is not different between DM and nonDM following cardiac surgery, likely due to the overwhelming stress response. Insulin drip protocols used postoperatively do not have to be modified for those with a prior diagnosis of diabetes.

Two patients with primary sellar leiomyomas, a rare entity

Leiomyomas are benign smooth muscle tumors commonly found in the genitourinary or gastrointestinal tracts. Rarely, they present as primary intracranial extra-axial brain tumors. Most of these lesions have been described in immunocompromised patients, but have been found very rarely in the immunocompetent patient. We present two patients with sporadic sellar leiomyomas. The first patient is a 25-year-old woman who presented with a 2-year history of amenorrhea and a heterogeneous lesion. The second is a 53-year-old man who presented with headaches and progressive panhypopituitarism, and a large cystic lesion expanding the sella. In both patients, transnasal transphenoidal surgery was performed for resection of the tumor. We review the intraoperative findings, neuropathology and immunohistochemistry and the clinical follow-up. A literature search, which revealed only two prior reported cases of sporadic sellar leiomyomas, and subsequent review led us to conclude that the natural history of sellar leiomyomas relates to the immune status of the patient and that these tumors may cause pituitary dysfunction through infiltration of the gland, mass effect and compression, or even potentially as a byproduct of prolactin secretion intrinsic to the tumor itself. Complete surgical resection of these infiltrating tumors may not be advisable when pituitary function is intact. Long-term endocrine follow-up in these patients is advised.

Recent results of exenatide use as adjunctive therapy in the treatment of patients with type 2 diabetes

Exenatide is a GLP-1 receptor agonist approved for use in type 2 diabetes mellitus. In clinical trials, significant reductions in serum glucose and weight were demonstrated for exenatide with primary glycemic effects of the twice daily formulation on prandial glucose control. In this paper, we review recent research with exenatide as adjunctive therapy in type 2 diabetes mellitus. In particular, studies demonstrate ongoing benefit on glycemic control and weight reduction with continued therapy up to 82 weeks duration and efficacy as adjunctive therapy for patients taking metformin, thiazolidinediones, and/or a sulfonylurea and as compared to sitagliptin and various insulin formulations. Compared to insulin, exenatide likely has greatest benefit for those patients who are overweight or who need improved prandial glucose control. The new long-acting release formulation of exenatide has demonstrated slightly improved efficacy compared to the twice daily formulation as well as a reduction in gastrointestinal side effects. Emerging research is further exploring novel benefits of exenatide as adjunctive DM therapy, effects on prandial glycemic control, markers of hepatic inflammation, alternative dosage forms including intra-nasal administration, and effects on beta cell function.