Janna C. Castro

Relationship between Inpatient Hyperglycemia and Insulin Treatment after Kidney Transplantation and Future New Onset Diabetes Mellitus

BACKGROUND AND OBJECTIVES Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose > or = 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C > or = 6.5%, fasting venous serum glucose > or = 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. RESULTS The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). CONCLUSION Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT.

Hyperglycemia during the Immediate Period after Kidney Transplantation

BACKGROUND AND OBJECTIVES Hyperglycemia and new-onset diabetes occurs frequently after kidney transplantation. The stress of surgery and exposure to immunosuppression medications have metabolic effects and can cause or worsen preexisting hyperglycemia. To our knowledge, hyperglycemia in the immediate posttransplantation period has not been studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective, observational study to characterize the prevalence and assess the pharmacologic management of hyperglycemia in kidney transplant recipients who underwent transplantation at our center between June 1999 and December 2006. Data were abstracted from electronic and pharmacy databases. RESULTS The study cohort included 424 patients (mean age 51 yr; 58% men; 25% with pretransplantation diabetes). All patients with and 87% without pretransplantation diabetes had evidence of hyperglycemia (bedside glucose >or=200 mg/dl or physician-instituted insulin therapy), whereas the prevalence of hypoglycemia was low (4.5%). Hyperglycemia was sustained throughout hospitalization. All patients with and 66% without pretransplantation diabetes required insulin at hospital discharge. Patients with pretransplantation diabetes were treated primarily with short-acting insulin during the first 24 h after transplantation but were transitioned to long-acting insulin as the hospital stay progressed. CONCLUSIONS Investigators have historically attempted to identify hyperglycemia after hospital discharge. Our data indicate that a substantial number of patients without pretransplantation diabetes develop hyperglycemia and require insulin during the hospital phase of their care immediately after kidney transplantation. Prospective studies are needed to delineate factors that contribute to development of new-onset diabetes after transplantation among patients with transient hyperglycemia.

Continuous subcutaneous insulin infusion (insulin pump) therapy can be safely used in the hospital in select patients.

OBJECTIVE To analyze data on inpatient insulin pump use and examine staff compliance with hospital procedures, glycemic control, and safety. METHODS We conducted a retrospective review of charts and bedside glucose data for patients who had been receiving outpatient insulin pump therapy and were admitted to our teaching hospital between November 1, 2005, and February 8, 2008. RESULTS During the study period, there were 50 hospitalizations involving 35 patients who had been receiving outpatient insulin pump therapy. The mean age and duration of diabetes of the 35 patients was 55 years and 32 years, respectively. Sixty-six percent were women, and 91% had type 1 diabetes. Patients in 31 of the hospitalizations (62%) were deemed candidates for continued insulin pump therapy during their stay. Of the 31 hospitalizations, 80% had the presence of the pump documented at admission; 100% had an admission glucose value; 77% had documentation of signed patient consent; 81% had evidence of completed preprinted insulin pump orders; 77% received an endocrine consultation; and 68% had a completed bedside flow sheet. Patients continuing insulin pump therapy had mean bedside glucose levels similar to those whose pump therapy was discontinued (P = .11); however, the proportion of hypoglycemic events was lower among insulin pump users (P<.01) than among nonusers. CONCLUSIONS Insulin pump therapy is safe for select inpatients. Overall, staff compliance with procedures was high, although we identified areas for improvement. Continued study is needed on the effectiveness of insulin pump therapy in controlling inpatient hyperglycemia.

Transitioning Insulin Pump Therapy from the Outpatient to the Inpatient Setting: A Review of 6 Years' Experience with 253 Cases

Background: We reviewed the care of a large cohort of patients with diabetes mellitus on insulin pump therapy who required an inpatient stay. Methods: Records were reviewed of patients hospitalized between January 1, 2006, and December 31, 2011. Results: A total of 136 patients using insulin pumps had 253 hospitalizations. Mean (standard deviation) patient age was 55 (16) years, diabetes duration was 29 (15) years, and pump duration was 6 (5) years. Insulin pump therapy was continued in 164 (65%) hospitalizations. Adherence to core process measures improved over time: by 2011, 100% of cases had an endocrinology consultation, 100% had the required insulin pump order set completed, and 94% had documentation of the signed agreement specifying patient responsibilities for continued use of the technology while hospitalized. Documentation of the insulin pump flow sheet also increased but could still be located in only 64% of cases by the end of 2011. Mean glucose was not significantly different among patients who remained on insulin pump therapy compared to those for whom it was discontinued (p > .1), but episodes of severe hyperglycemia (>300 mg/dl) and hypoglycemia (<40 mg/dl) were significantly less common among pump users. No pump site infections, mechanical pump failures, or episodes of diabetic ketoacidosis were observed among patients remaining on therapy. Conclusions: With appropriate patient selection and usage guidelines, most patients using insulin pumps can safely have their therapy transitioned to the inpatient setting. Further study is needed to determine whether this approach can be translated to other hospital settings.

Use of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Hospital: A Review of One Institution's Experience

Background: This article reviews the performance of our hospitals inpatient insulin pump policy. Methods: Twenty-five hospital admissions of 21 unique patients receiving outpatient insulin pump therapy were reviewed. Results: Between November 1, 2005, and November 30, 2006, there were 25 hospital admissions involving 21 patients receiving outpatient insulin pump therapy. The average age and duration of diabetes among these 21 patients was 50 and 29 years, respectively; 67% were women, 90% had type 1 diabetes, and all were white. The mean length of hospital stay was 4 days, and the average reported length of insulin pump therapy was 4 years. Patients in 16 of the admissions were identified as candidates for continued use of the insulin pump during the hospital stay. Over 90% of patients remaining on the insulin pump had documentation by nursing of the presence of the pump at the time of admission; 100% of the patients had an admission glucose recorded; 88% had a record of signed patient consent; 81% had evidence of completed preprinted insulin pump orders; 75% received a required endocrine consultation; and 75% of cases had documentation of completed bedside flow sheet. A high frequency of both hypoglycemic and hyperglycemic events occurred in the patients; however, no adverse events were related directly to the insulin pump. Conclusions: Insulin pump therapy can be safely continued in the hospital setting. While staff compliance with required procedures was high, there was still room for improvement. More data are needed, however, on whether this method of insulin delivery is effective for controlling hyperglycemia in hospitalized patients.

Outpatient-to-Inpatient Transition of Insulin Pump Therapy: Successes and Continuing Challenges

Background: Insulin pump therapy is a complex technology prone to errors when employed in the hospital setting. When patients on insulin pump therapy require hospitalization, practitioners caring for them must decide whether to allow continued pump use. We provide the largest review regarding transitioning insulin pump therapy from the outpatient to inpatient setting. Method: Records of inpatient insulin pump users were retrospectively analyzed at a metropolitan Phoenix hospital between January 2006 and December 2009. Adherence to institutional procedures on insulin pump use was assessed, glycemic control was determined, and adverse events were examined. Results: We examined records on 65 patients with insulin pumps, totaling 125 hospitalizations. Mean (standard deviation) patient age was 55 (17) years, diabetes duration was 27 (14) years, pump duration was 6 (5) years, length of hospital stay was 4.7 (6.3) days, hemoglobin A1c was 7.3 (1.3)%, 85% had type 1 diabetes mellitus, 57% were women, and 97% were white. Admissions involving insulin pumps increased (23 in 2006, 17 in 2007, 40 in 2008, and 45 in 2009). Insulin pump therapy was continued in 83 (66%) hospitalizations. Among these hospitalizations, endocrinology consultations were obtained in 89%, consent agreements were found in 83%, insulin pump order sets were completed in 89%, admission glucose was checked in 100%, and nursing assessments of pump insertion sites were documented in 89%, but bedside insulin pump flow sheets were found in only 55%. Mean glucose of 175 (57) mg/dl was not significantly different than that in hospitalizations where insulin pumps were discontinued [175 (42) mg/dl] or used intermittently [177 (7) mg/dl]. There was one instance of a pump catheter kinking; however, no other adverse events (pump site infections, mechanical pump failure, diabetic ketoacidosis) were observed, and there were no use-related fatalities. Conclusions: Most patients using insulin pumps can safely have their therapy transitioned when hospitalized. A policy on inpatient continuous subcutaneous insulin infusion use can be successfully implemented. Compliance with required procedures can be achieved, although there was room to improve adherence with some process measures. Further study is needed to determine how to optimize glycemic control when pumps are allowed during hospitalization.

Overcoming clinical inertia in the management of postoperative patients with diabetes

OBJECTIVE To assess the impact of an intervention designed to increase basal-bolus insulin therapy administration in postoperative patients with diabetes mellitus. METHODS Educational sessions and direct support for surgical services were provided by a nurse practitioner (NP). Outcome data from the intervention were compared to data from a historical (control) period. Changes in basal-bolus insulin use were assessed according to hyperglycemia severity as defined by the percentage of glucose measurements >180 mg/dL. RESULTS Patient characteristics were comparable for the control and intervention periods (all P≥.15). Overall, administration of basal-bolus insulin occurred in 9% (8/93) of control and in 32% (94/293) of intervention cases (P<.01). During the control period, administration of basal-bolus insulin did not increase with more frequent hyperglycemia (P = .22). During the intervention period, administration increased from 8% (8/96) in patients with the fewest number of hyperglycemic measurements to 60% (57/95) in those with the highest frequency of hyperglycemia (P<.01). The mean glucose level was lower during the intervention period compared to the control period (149 mg/dL vs. 163 mg/dL, P<.01). The proportion of glucose values >180 mg/dL was lower during the intervention period than in the control period (21% vs. 31% of measurements, respectively, P<.01), whereas the hypoglycemia (glucose >70 mg/dL) frequencies were comparable (P = .21). CONCLUSION An intervention to overcome clinical inertia in the management of postoperative patients with diabetes led to greater utilization of basal-bolus insulin therapy and improved glucose control without increasing hypoglycemia. These efforts are ongoing to ensure the delivery of effective inpatient diabetes care by all surgical services.

Clinical inertia during postoperative management of diabetes mellitus: relationship between hyperglycemia and insulin therapy intensification.

Objective: Our objective was to assess the application of insulin regimens in surgical postoperative patients with diabetes. Methods: A chart review was conducted of patients with diabetes who were hospitalized postoperatively between January 1 and April 30, 2011. Analysis was restricted to patients hospitalized for ≥3 days and excluded cases with an endocrinology consult. Insulin regimens were categorized as “basal plus short acting,” “short acting only,” or “none,” and the pattern of use was evaluated by hyperglycemia severity according to tertiles of both mean glucose and the number of glucose measurements >180 mg/dl. Results: Among cases selected for analysis (n = 119), examination of changes in insulin use based on tertiles of mean glucose showed that use of basal plus short-acting insulin increased from 10% in the lowest tertile (mean glucose, 120 mg/dl) to 18% in the highest tertile (mean glucose, 198 mg/dl; p < .01); however, 70% of patients in the highest tertile continued to receive short-acting insulin only, with 12% receiving no insulin. Intensification of insulin to a basal plus short-acting regimen was also seen when changes were evaluated by the number of measurements >180 mg/dl (p < .01), but 70% and 12% of patients in the highest tertile still remained only on short-acting insulin or received no insulin, respectively. Conclusions: Use of basal plus short-acting insulin therapy increased with worsening hyperglycemia, but many cases did not have therapy intensified to the recommended insulin regimen—evidence of clinical inertia. Strategies should be devised to overcome inpatient clinical inertia in the treatment of postoperative patients with diabetes.

Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia

Importance Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon. Objective To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm. Design, Setting, and Participants This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio. Main Outcomes and Measures Odds ratio (OR) assessment for AID-directed therapies. Results Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P < .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug’s category was observed. Conclusions and Relevance In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti–tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

Care directed by a specialty-trained nurse practioner or physician assistant can overcome clinical inertia in management of inpatient diabetes

OBJECTIVE The studys objective was to determine the impact of care directed by a specialty-trained nurse practitioner (NP) or physician assistant (PA) on use of basal-bolus insulin therapy and glycemic control in a population of noncritically ill patients with diabetes. METHODS A retrospective review of diabetes patients evaluated between July 1, 2011 and December 31, 2011 was conducted. Patients cotreated by a specialty-trained NP/PA were compared with patients who did not receive such care. RESULTS In total, 171 patients with 222 hospitalizations were cotreated by an NP/PA and 543 patients with 665 hospitalizations were not. Patients with NP/PA involvement were younger, and had more frequent hyperglycemia, and had greater corticosteroid use than patients without NP/PA involvement (P<.01 for all). Basal-bolus insulin therapy was administered to 80% of patients with NP/PA involvement and 34% of patients without it (P<.01). After adjustment for age, sex, hyperglycemia measures, and corticosteroid use, the odds of basal-bolus insulin therapy being administered were increased significantly through NP/PA care (odds ratio, 3.66; 95% confidence interval, 2.36-5.67; P<.01). After adjustment for these variables and insulin regimen, NP/PA care was significantly correlated with lower mean point-of-care glucose levels at 24 hours before discharge (P = .042). CONCLUSION Diabetes care assisted by an NP/PA trained in inpatient diabetes management results in greater use of recommended basal-bolus insulin therapy and is correlated with lower mean glucose levels before discharge. Adapting this model for use outside an endocrinology consult service needs to be explored so that the expertise can be brought to a broader inpatient population with diabetes.