Amisha Wallia

Insulin Therapy for Type 2 Diabetes Mellitus

IMPORTANCE The incidence and prevalence of type 2 diabetes mellitus are increasing. OBJECTIVE To review currently available insulin therapy, as well as evidence on the use, application, initiation, and intensification of insulin in the outpatient setting. EVIDENCE REVIEW Data sources included PubMed for trials and investigations in type 2 diabetes examining insulin use from January 1998 to April 2014. FINDINGS The hemoglobin A1c target for most patients with type 2 diabetes is 7% but needs to be modified when there is increased risk of hypoglycemia, reduced life expectancy, extensive comorbidities, or reduced resources. Insulin therapy may be considered early or late in the disease course; adverse effects include weight gain and hypoglycemia. Basal insulin can be added to oral hypoglycemic agents (generally stopping sulfonylureas) initially, and later, prandial insulin can be added in a stepwise fashion. Insulin treatment must be individualized, and there are a number of challenges to insulin initiation and intensification. CONCLUSIONS AND RELEVANCE Insulin can help achieve ideal hemoglobin A1c goals for patients with type 2 diabetes. Barriers such as adherence, patient preferences, clinician preferences, and resource allocation must be addressed.

Posttransplant Hyperglycemia is Associated With Increased Risk of Liver Allograft Rejection

Background. Intensive glycemic control has been shown to positively impact outcomes in an intensive care setting. Whether this practice is beneficial after liver transplantation (LT) is not known. Methods. A retrospective review of patients undergoing LT from February 2002 to July 2007 was conducted to analyze the association between perioperative hyperglycemia and outcomes after LT. Covariates included preexisting diabetes, mean glucose 3 months pre-LT, need for insulin drip post-LT, mean total glucose during the post-LT hospitalization, age, sex, type of transplant, and model for end-stage liver disease score. Outcomes within 1 year of LT included rejection, infection, rehospitalization, prolonged ventilation, and patient/graft survival. Results. One hundred thirteen LT and 31 liver-kidney recipients were included. By multivariate logistic regression adjusting for covariates, the rejection rate was significantly lower for patients with postoperative glucose levels less than 200 mg/dL (n=114) vs. more than 200 mg/dL (n=30) (odds ratio: 0.055; 95% confidence interval: 0.0154–0.200; P<0.001). The need for prolonged ventilation was more common in patients with glucose less than 200 vs. more than 200 mg/dL (odds ratio: 4.30; 95% confidence interval: 1.284–14.388; P=0.018). Although other outcomes, infection, rehospitalization, patient/graft survival, were not different among the glucose control groups, rejection was associated with increased rehospitalizations and infections. Conclusion. Our data demonstrate an association between the immediate posttransplant glycemic control and the development of subsequent rejection. Prospective trials investigating the effects of perioperative glycemic control on outcomes and morbidity after LT are warranted.

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.

Association between urinary cadmium levels and prediabetes in the NHANES 2005–2010 population

Evidence suggests an association between exposure to cadmium and dysglycemia. To investigate this matter, we examined the relationship between urinary cadmium and prediabetes in the cross sectional National Health and Nutrition Examination Survey (NHANES). NHANES participants for the years 2005 through 2010 aged ≥ 40 years were included in the analysis. Participants with nephropathy, overt diabetes, or missing required data were excluded. To assess the non-linear relationship between cadmium and Prediabetes, non-parametric logistic regression with B spline expansion of urinary cadmium/creatinine ratio was performed. This analysis revealed a complex non-linear association between higher cadmium levels and prediabetes. This relationship persisted, though with varying magnitudes across smoking groups (never smokers, moderate smokers, heavy smokers). In a conventional logistic regression analysis, this relationship was less evident with significantly increased OR for prediabetes was found in the highest quintile of urine cadmium compared to the lowest quintile in the overall population and in moderate smokers. In an age stratified analysis, a significant linear association was found only in the age groups 60-69 and ≥ 70. We conclude that there is a significant non-linear, complex relationship between urinary Cd levels, age, smoking habits and odds of prediabetes.

Acute diabetes insipidus mediated by vasopressinase after placental abruption.

CONTEXT Postpartum, diabetes insipidus (DI) can be part of Sheehans syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual. CASE PRESENTATION This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks. OBJECTIVE The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream. METHODS AND RESULTS Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patients serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patients postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP. CONCLUSIONS Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

Round Table Discussion on Inpatient Use of Continuous Glucose Monitoring at the International Hospital Diabetes Meeting

In May 2015 the Diabetes Technology Society convened a panel of 27 experts in hospital medicine and endocrinology to discuss the current and potential future roles of continuous glucose monitoring (CGM) in delivering optimum health care to hospitalized patients in the United States. The panel focused on 3 potential settings for CGM in the hospital, including (1) the intensive care unit (ICU), (2) non-ICU, and (3) continuation of use of home CGM in the hospital. The group reviewed barriers to use and solutions to overcome the barriers. They concluded that CGM has the potential to improve the quality of patient care and can provide useful information to help health care providers learn more about glucose management. Widespread adoption of CGM by hospitals, however, has been limited by added costs and insufficient outcome data.In May 2015 the Diabetes Technology Society convened a panel of 27 experts in hospital medicine and endocrinology to discuss the current and potential future roles of continuous glucose monitoring (CGM) in delivering optimum health care to hospitalized patients in the United States. The panel focused on 3 potential settings for CGM in the hospital, including (1) the intensive care unit (ICU), (2) non-ICU, and (3) continuation of use of home CGM in the hospital. The group reviewed barriers to use and solutions to overcome the barriers. They concluded that CGM has the potential to improve the quality of patient care and can provide useful information to help health care providers learn more about glucose management. Widespread adoption of CGM by hospitals, however, has been limited by added costs and insufficient outcome data.

Intensive glycemic control after heart transplantation is safe and effective for diabetic and non-diabetic patients.

Some studies have shown increased mortality, infection, and rejection rates among diabetic (DM) compared to non‐diabetic (non‐DM) patients undergoing heart transplant (HT). This is a retrospective chart review of adult patients (DM, n = 26; non‐DM, n = 66) undergoing HT between June 1, 2005, and July 31, 2009. Glycemic control used intravenous (IV) and subcutaneous (SQ) insulin protocols with a glucose target of 80–110 mg/dL. There were no significant differences between DM and non‐DM patients in mean glucose levels on the IV and SQ insulin protocols. Severe hypoglycemia (glucose <40 mg/dL) did not occur on the IV protocol and was experienced by only 3 non‐DM patients on the SQ protocol. Moderate hypoglycemia (glucose >40 and <60 mg/dL) occurred in 17 (19%) patients on the IV protocol and 24 (27%) on the SQ protocol. There were no significant differences between DM and non‐DM patients within 30 d of surgery in all‐cause mortality, treated HT rejection episodes, reoperation, prolonged ventilation, 30‐d readmissions, ICU readmission, number of ICU hours, hospitalization days after HT, or infections. This study demonstrates that DM and non‐DM patients can achieve excellent glycemic control post‐HT with IV and SQ insulin protocols with similar surgical outcomes and low hypoglycemia rates.

Improvement in insulin sensitivity during mifepristone treatment of cushing syndrome: Early and late effects

Increased adiposity and direct effects of glucocorticoid excess on muscle, liver, and β-cells are responsible for the high prevalence of impaired glucose tolerance (IGT) and type 2 diabetes in patients with Cushing syndrome (CS) (1,2). In the SEISMIC study, the glucocorticoid receptor antagonist mifepristone improved glucose tolerance and produced weight loss over 24 weeks in CS patients (3). Using oral glucose tolerance test data from SEISMIC, our goal was to assess whole-body insulin sensitivity (Matsuda index), β-cell function (insulinogenic index, homeostasis model assessment-β [HOMA-β]), disposition index (4,5), weight (WT), and waist circumference (WC) over time. Complete data in patients not receiving insulin were available in 19 patients, 8 with diabetes and/or IGT (C-DM) and 11 with hypertension only (C-HT). Within-group comparisons for change over time were analyzed with a mixed-effects repeated measures two-way ANOVA with cohort (C-DM and C-HT), time, and cohort by time interaction as fixed effects; unpaired Student t tests were used to assess differences between groups …

Comparison of Glycemic and Surgical Outcomes After Change in Glycemic Targets in Cardiac Surgery Patients

OBJECTIVE To compare perioperative glycemic and long-term surgical outcomes in patients undergoing cardiac surgery before and after the recommended 2009 changes in inpatient glycemic targets. RESEARCH DESIGN AND METHODS We performed a retrospective review of patients who underwent cardiac surgery between 4 September 2007 and 30 April 2011. Comparison was made of blood glucose (BG) outcomes 3 days after surgery, and 30-day cardiac outcomes before and after a change in insulin protocol that took place on 1 September 2009, which consisted of raising the glycemic targets during intravenous insulin infusions from 80–110 mg/dL (80–110 group) to 110–140 mg/dL (110–140 group). RESULTS When compared with the 80–110 group (n = 667), the 110–140 group (n = 658) had higher mean postoperative BG levels during the intravenous insulin infusion (141 ± 15 vs. 121 ± 15 mg/dL, P < 0.001) and the subcutaneous insulin period (134 ± 24 vs. 130 ± 23 mg/dL, P < 0.001), and for 3 days postoperatively (141 ± 17 vs. 127 ± 15 mg/dL, P < 0.001). Fewer patients in the 110–140 mg/dL group experienced moderate hypoglycemia (BG <70 mg/dL) (177 vs. 73, P = 0.04). Severe hypoglycemia (BG <40 mg/dL) occurred in only one patient in the 80–110 group and three patients in the 110–140 group. There were no significant differences in mortality or surgical complication rates (with the exception of reintubation) between the groups. CONCLUSIONS The higher glycemic target of 110–140 mg/dL resulted in similar mean glucose values, with significantly less hypoglycemia and no significant differences in mortality/morbidity compared with the more strict target of 80–110 mg/dL.

Consensus Statement on Inpatient Use of Continuous Glucose Monitoring

In June 2016, Diabetes Technology Society convened a panel of US experts in inpatient diabetes management to discuss the current and potential role of continuous glucose monitoring (CGM) in the hospital. This discussion combined with a literature review was a follow-up to a meeting, which took place in May 2015. The panel reviewed evidence on use of CGM in 3 potential inpatient scenarios: (1) the intensive care unit (ICU), (2) non-ICU, and (3) transitioning outpatient CGM use into the hospital setting. Panel members agreed that data from limited studies and theoretical considerations suggested that use of CGM in the hospital had the potential to improve patient clinical outcomes, and in particular reduction of hypoglycemia. Panel members discussed barriers to widespread adoption of CGM, which patients would benefit most from use of this technology, and what type of outcome studies are needed to guide use of CGM in the inpatient setting.