Safety And Efficacy Of Dpp-4 Inhibitors For The Management Of Hospitalized General Medicine And Surgery Patients with Type 2 Diabetes.

OBJECTIVE: DPP-4 inhibitors (DPP-4i) have been shown to be effective for the management of inpatient diabetes. We report pooled data from 3 prospective studies using DPP-4i in general medicine and surgery patients with type 2 diabetes (T2D). METHODS: We combined data from 3 randomized studies comparing DPP-4i alone or in combination with basal insulin or a basal-bolus insulin regimen. Medicine (n = 266) and surgery (n = 319) patients admitted with a blood glucose (BG) between 140 and 400 mg/dL, treated with diet, oral agents, or low-dose insulin therapy were included. Patients received DPP-4i alone (n = 144), DPP-4i plus basal insulin (n = 158) or basal-bolus regimen (n = 283). All groups received correctional doses with rapid-acting insulin for BG >140 mg/dL. The primary endpoint was differences in mean daily BG between groups. Secondary endpoints included differences in hypoglycemia and hospital complications. RESULTS: There were no differences in mean hospital daily BG among patients treated with DPP-4i alone (170 ± 37 mg/dL), DPP-4i plus basal (172 ± 42 mg/dL), or basalbolus (172 ± 43 mg/dL), P = .94; or in the percentage of BG readings within target of 70 to 180 mg/dL (63 ± 32%, 60 ± 31%, and 64 ± 28%, respectively; P = .42). There were no differences in length of stay or complications, but hypoglycemia was less common with DPP-4i alone (2%) compared to DPP-4i plus basal (9%) and basal-bolus (10%); P = .004. CONCLUSION: Treatment with DPP-4i alone or in combination with basal insulin is effective and results in a lower incidence of hypoglycemia compared to a basal-bolus insulin regimen in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; BMI = body mass index; CI = confidence interval; DPP-4i = dipeptidyl peptidase-4 inhibitors; HbA1c = hemoglobin A1c; OR = odds ratio; T2D = type 2 diabetes.

Sitagliptin for prevention of stress hyperglycemia in patients without diabetes undergoing general surgery: A pilot randomized study.

AIM: We investigated if a dipeptidyl peptidase-4 inhibitor, sitagliptin, can prevent perioperative stress hyperglycemia in patients without prior history of diabetes mellitus undergoing general surgery. METHODS: This double-blind pilot trial randomized general surgery patients to receive sitagliptin (n = 44) or placebo (n = 36) once daily, starting one day prior to surgery and continued during the hospital stay. The primary outcome was occurrence of stress hyperglycemia, defined by blood glucose (BG) >140 mg/dL and >180 mg/dL after surgery. Secondary outcomes included: length-of-stay, ICU transfers, hypoglycemia, and hospital complications. RESULTS: BG >140 mg/dL was present in 44 (55%) of subjects following surgery. There were no differences in hyperglycemia between placebo and sitagliptin (56% vs. 55%, p = 0.93). BG >180 mg/dL was observed in 19% and 11% of patients treated with placebo and sitagliptin, respectively, p = 0.36. Both treatment groups had resulted in similar postoperative BG (148.9 ±â€¯29.4 mg/dL vs. 146.9 ±â€¯35.2 mg/dL, p = 0.73). There were no differences in length-of-stay (4 vs. 3 days, p = 0.84), ICU transfer (3% vs. 5%, p = 1.00), hypoglycemia <70 mg/dL (6% vs. 11%, p = 0.45), and complications (14% vs. 18%, p = 0.76). CONCLUSION: Preoperative treatment with sitagliptin did not prevent stress hyperglycemia or complications in individuals without diabetes undergoing surgery.

Comparison of Computer-Guided Versus Standard Insulin Infusion Regimens in Patients With Diabetic Ketoacidosis.

BACKGROUND: This study was performed to investigate the efficacy of Glucommander (GM) (Glytec®), a computer-based algorithm versus standard (paper form-based) continuous insulin infusion (CII) in the treatment of patients with diabetic ketoacidosis (DKA). METHODS: This was a retrospective multicenter study involving 2665 patients with DKA treated with either GM (n = 1750) or standard protocols (n = 915) across 34 institutions in the United States. GM estimates the rate of CII using an insulin sensitivity factor referred to as a "multiplier" that ranges between 0.01 and 0.03. Outcomes of interest were differences in time to resolve DKA (blood glucose [BG] <200 mg/dL and bicarbonate < 18 mmol/L) and number of hypoglycemic events defined as a BG <70 mg/dl. RESULTS: Treatment with GM was associated with lower rates of hypoglycemia during the time of the insulin drip (12.9% vs 35%, P = .001), faster time to normalization of blood glucose (9.7 ± 8.9 vs 10.97 ± 10.2 hours, P = .0001) and resolution of metabolic acidosis (13.6 ± 11.8 vs 17.3 ± 19.6 hours, P = .0001), and shorter hospital length of stay (3.2 ± 2.9 vs 4.5 ± 4.8 days, P = .01) compared to standard care. Best treatment outcomes were achieved with an initial multiplier of 0.01 and a glucose target range between 120 and 180 mg/dl. CONCLUSION: The GM algorithm in DKA treatment resulted in lower rates of hypoglycemia and faster DKA resolution over standard paper-based algorithms. Prospective randomized clinical trials comparing the efficacy and cost of computer-based algorithms versus standard CII regimens are warranted.

Stress hyperglycemia in general surgery: Why should we care?

AIMS: To determine the frequency of increasing levels of stress hyperglycemia and its associated complications in surgery patients without a history of diabetes. METHODS: We reviewed hospital outcomes in 1971 general surgery patients with documented preoperative normoglycemia [blood glucose (BG) <140mg/dL] who developed stress hyperglycemia (BG >140mg/dL or >180mg/dL) within 48h after surgery between 1/1/2010 and 10/31/2015. RESULTS: A total of 415 patients (21%) had ≥1 episode of BG between 140 and 180mg/dL and 206 patients (10.5%) had BG>180mg/dL. The median length of hospital stay (LOS) was 9days [interquartile range (IQR) 5,15] for BG between 140 and 180mg/dL and 12days (IQR 6,18) for BG>180mg/dL compared to normoglycemia at 6days (IQR 4,11), both p<0.001. Patients with BG 140-180mg/dL had higher rates of complications with an odds ratio (OR) of 1.68 [95% confidence interval (95% CI) 1.15-2.44], and those with BG>180mg/dL had more complications [OR 3.46 (95% CI 2.24-5.36)] and higher mortality [OR 6.56 (95% CI 2.12-20.27)] compared to normoglycemia. CONCLUSION: Increasing levels of stress hyperglycemia are associated with higher rates of perioperative complications and hospital mortality in surgical patients without diabetes.

COMPARISON OF EFFICACY AND SAFETY OF GLARGINE AND DETEMIR INSULIN IN THE MANAGEMENT OF INPATIENT HYPERGLYCEMIA AND DIABETES.

OBJECTIVE: Glargine and detemir insulin are the two most commonly prescribed basal insulin analogues for the ambulatory and inpatient management of diabetes. The efficacy and safety of basal insulin analogues in the hospital setting has not been established. METHODS: This observational study compared differences in glycemic control and outcomes in non-intensive care unit patients with blood glucose (BG) >140 mg/dL who were treated with glargine or detemir, between January 1, 2012, and September 30, 2015, in two academic centers. RESULTS: Among 6,245 medical and surgical patients with hyperglycemia, 5,749 received one or more doses of glargine, and 496 patients received detemir during the hospital stay. There were no differences in the mean daily BG (glargine, 182 ± 46 mg/dL vs. detemir, 180 ± 44 mg/dL; P = .70). There were no differences in mortality, hospital complications, or re-admissions between groups (all, P>.05). After adjusting for potential confounders, there was no statistically significant difference in hypoglycemia rates between treatment groups. Patients treated with detemir required higher total daily basal insulin doses (0.27 ± 0.16 units/kg/day vs. 0.22 ± 0.15 units/kg/day; P<.001). Glargine-treated patients had statistically longer length of stay; however, this difference may not be clinically relevant (6.8 ± 7.4 days vs. 6.0 ± 6.3 days; P<.001). CONCLUSION: Our study indicates that treatment with glargine and detemir results in similar inpatient glycemic control in general medicine and surgery patients. Detemir treatment was associated with higher daily basal insulin dose and number of injections. A prospective randomized study is needed to confirm these findings. ABBREVIATIONS: BG = blood glucose BMI = body mass index CI = confidence interval eGFR = estimated glomerular filtration rate HbA1c = glycated hemoglobin ICD-9 = International Classification of Diseases, ninth revision ICU = intensive care unit IQR = interquartile range LOS = length-of-stay OR = odd ratio.

Inflammation and Oxidative Stress in Cardiac Surgery Patients Treated to Intensive Versus Conservative Glucose Targets.

Objective: We aimed to determine (a) longitudinal changes of inflammatory and oxidative stress markers and (b) the association between markers of inflammation and perioperative complications in coronary artery bypass surgery (CABG) patients treated with intensive vs conservative blood glucose (BG) control. Methods: Patients with diabetes (n = 152) and without diabetes with hyperglycemia (n = 150) were randomized to intensive (n = 151; BG: 100-140 mg/dL) or to conservative (n = 151; BG: 141-180 mg/dL) glycemic targets. Plasma cortisol, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α, interleukin-6 (IL-6), thiobarbituric acid-reactive substances, and 2'-7'-dichlorofluorescein were measured prior to and at days 3, 5, and 30 after surgery. Results: Intensive glycemic control resulted in lower mean BG (132 ± 14 mg/dL vs 154 ± 17 mg/dL, P < 0.001) in the intensive care unit. Plasma cortisol and inflammatory markers increased significantly from baseline after the third and fifth day of surgery (P < 0.001), and returned to baseline levels at 1 month of follow-up. Patients with perioperative complications had higher levels of cortisol, hsCRP, IL-6, and oxidative stress markers compared with those without complications. There were no significant differences in inflammatory and oxidative stress markers between patients, with or without diabetes or complications, treated with intensive or conventional glucose targets. Conclusion: We report no significant differences in circulating markers of acute inflammatory and oxidative stress response in cardiac surgery patients, with or without diabetes, treated with intensive (100-140 mg/dL) or conservative (141-180 mg/dL) insulin regimens.