Francisco J. Pasquel

Hyperglycemia during total parenteral nutrition: an important marker of poor outcome and mortality in hospitalized patients.

OBJECTIVE To determine the effect of total parenteral nutrition (TPN)-induced hyperglycemia on hospital outcome. RESEARCH DESIGN AND METHODS The study determined whether blood glucose values before, within 24 h, and during days 2–10 of TPN are predictive of hospital complications and mortality. RESULTS Subjects included a total of 276 patients receiving TPN for a mean duration of 15 ± 24 days (±SD). In multiple regression models adjusted for age, sex, and diabetes status, mortality was independently predicted by pre-TPN blood glucose of 121–150 mg/dl (odds ratio [OR] 2.2, 95% CI 1.1–4.4, P = 0.030), 151–180 mg/dl (3.41, 1.3–8.7, P = 0.01), and >180 mg/dl (2.2, 0.9–5.2, P = 0.077) and by blood glucose within 24 h of >180 mg/dl (2.8, 1.2–6.8, P = 0.020). A blood glucose within 24 h of >180 mg/dl was associated with increased risk of pneumonia (OR 3.1, 95% CI 1.4–7.1) and acute renal failure (2.3, 1.1–5.0). CONCLUSIONS Hyperglycemia is associated with increased hospital complications and mortality in patients receiving TPN.

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.

Hyperosmolar Hyperglycemic State: A Historic Review of the Clinical Presentation, Diagnosis, and Treatment

The hyperosmolar hyperglycemic state (HHS) is the most serious acute hyperglycemic emergency in patients with type 2 diabetes. von Frerichs and Dreschfeld described the first cases of HHS in the 1880s in patients with an “unusual diabetic coma” characterized by severe hyperglycemia and glycosuria in the absence of Kussmaul breathing, with a fruity breath odor or positive acetone test in the urine. Current diagnostic HHS criteria include a plasma glucose level >600 mg/dL and increased effective plasma osmolality >320 mOsm/kg in the absence of ketoacidosis. The incidence of HHS is estimated to be <1% of hospital admissions of patients with diabetes. The reported mortality is between 10 and 20%, which is about 10 times higher than the mortality rate in patients with diabetic ketoacidosis (DKA). Despite the severity of this condition, no prospective, randomized studies have determined best treatment strategies in patients with HHS, and its management has largely been extrapolated from studies of patients with DKA. There are many unresolved questions that need to be addressed in prospective clinical trials regarding the pathogenesis and treatment of pediatric and adult patients with HHS.

Risk factors for inpatient hypoglycemia during subcutaneous insulin therapy in non-critically ill patients with type 2 diabetes.

Objective: We aimed to determine risk factors associated with hypoglycemia during subcutaneous insulin therapy in non-critically ill patients with type 2 diabetes. Methods: We conducted an analysis of three randomized control trials using basal/bolus regimen and regular sliding scale insulin (SSI) in patients with diabetes admitted to medical and surgical settings. Results: We analyzed medical records of 261 general medicine and 211 noncardiac surgery patients treated with basal/ bolus regimen with glargine/glulisine (n = 169), detemir/aspart (n = 67), neutral protamine Hagedorn/regular (n = 63), or with SSI (n = 173). The overall frequency of mild and severe hypoglycemia (<70 and <40 mg/dl) was 19% and 2%, respectively. During treatment, medical patients experienced a higher number of hypoglycemia than surgical patients (23% versus 13%; p = .005), but the rate of severe hypoglycemia was similar between groups (1.9% versus 1.9%; p = not significant). Increasing age, impaired kidney function (glomerular filtration rate < 60 ml/min), total daily insulin dose, and type of insulin regimen (basal/bolus versus SSI) during hospitalization were important contributors for hypoglycemia in both medical and surgical patients. Among these variables, increasing age and type of insulin regimen (basal/bolus versus SSI) were found to be independent predictors of hypoglycemic events. Conclusions: Mild hypoglycemic events are common during subcutaneous insulin therapy in medical and surgical patients with type 2 diabetes. Increasing age, impaired renal function, daily insulin dose, and insulin regimen (basal/bolus versus SSI) are important predictors of hypoglycemia during insulin therapy in patients with type 2 diabetes mellitus.

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.

Glucose Variability is an Independent Predictor of Mortality in Hospitalized Patients Treated with Total Parenteral Nutrition

OBJECTIVE Hyperglycemia is associated with increased mortality in critically ill patients treated with total parenteral nutrition (TPN). The role of glucose variability (GV) in predicting outcomes in these patients is not known. METHODS This retrospective study included medical and surgical patients receiving TPN in a community teaching hospital. GV was calculated by standard deviation (SD) of blood glucose (BG) values and by mean BG daily (Δ) change (daily max - daily minimum). RESULTS A total of 276 medical and surgical patients (mean age: 51 ± 18 years), 19% with a history of diabetes mellitus (DM), and 74% with intensive care unit (ICU) admission were treated with TPN. During TPN, the mean daily BG was 142.9 ± 33 mg/dL; frequencies of hypoglycemia < 70 and < 40 mg/dL were 41% and 3%, respectively; and hospital mortality was 27.2%. The mean GV by SD was 38 ± 21 mg/dL and by mean (D) change 58 ± 34 mg/dL. GV was significantly higher in deceased patients (SD: 48 ± 25 vs. 34 ± 18 mg/dL and Δ change: 75 ± 39 vs. 51 ± 29 mg/dL, both P < .01) than surviving patients. Multivariate analysis adjusted for age, DM status, gender, APACHE (Acute Physiology and Chronic Health Evaluation) score, mean daily glucose, and hypoglycemia revealed that GV was an independent predictor of hospital mortality (P < .05). The association between GV and mortality was limited to patients without a history of DM and was not present in patients with DM. CONCLUSION High GV is associated with increased hospital mortality independent of the presence and severity of hyperglycemia or hypoglycemia during TPN therapy. Prospective randomized trials are needed to determine if reduction in GV with intensive glycemic control improves clinical outcomes in patients treated with TPN.

Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial

BACKGROUND The role of incretin-based drugs in the treatment of patients with type 2 diabetes admitted to hospital has not been extensively assessed. In this study, we compared the safety and efficacy of a dipeptidyl peptidase-4 inhibitor (sitagliptin) plus basal insulin with a basal-bolus insulin regimen for the management of patients with type 2 diabetes in general medicine and surgery in hospitals. METHODS We did a multicentre, prospective, open-label, non-inferiority randomised clinical trial (Sita-Hospital) in five hospitals in the USA, enrolling patients aged 18-80 years with type 2 diabetes and a random blood glucose concentration of 7·8-22·2 mmol/L who were being treated with diet or oral antidiabetic drugs or had a total daily insulin dose of 0·6 units per kg or less, admitted to general medicine and surgery services. We randomly assigned patients (1:1) to receive either sitagliptin plus basal glargine once daily (the sitagliptin-basal group) or a basal-bolus regimen with glargine once daily and rapid-acting insulin lispro or aspart before meals (the basal-bolus group) during the hospital stay. All other antidiabetic drugs were discontinued on admission. The randomisation was achieved by computer-generated tables with block stratification according to randomisation blood glucose concentrations (ie, higher or lower than 11·1 mmol/L). The primary endpoint of the trial was non-inferiority in mean differences between groups in their daily blood glucose concentrations during the first 10 days of therapy (point-of-care measurements; non-inferiority was deemed a difference <1 mmol/L). The safety endpoints included hypoglycaemia and uncontrolled hyperglycaemia leading to treatment failure. All participants who received at least one dose of study drug were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT01845831. FINDINGS Between Aug 23, 2013, and July 27, 2015, we recruited 279 patients, and randomly assigned 277 to treatment; 138 to sitagliptin-basal and 139 to basal-bolus. The length of stay in hospital was similar for both groups (median 4 days [IQR 3-8] vs 4 [3-8] days, p=0·54). The mean daily blood glucose concentration in the sitagliptin-basal group (9·5 mmol/L [SD 2·7]) was not inferior to that in the basal-bolus group 9·4 mmol/L [2·7]) with a mean blood glucose difference of 0·1 mmol/L (95% CI -0·6 to 0·7). No deaths occurred in this trial. Treatment failure occurred in 22 patients (16%) in the sitagliptin-basal group versus 26 (19%) in the basal-bolus group (p=0·54). Hypoglycaemia occurred in 13 patients (9%) in the sitagliptin-basal group and in 17 (12%) in the basal-bolus group (p=0·45). No differences in hospital complications were noted between groups. Seven patients (5%) developed acute kidney injury in the sitagliptin-basal group and six (4%) in the basal-bolus group. One patient (0·7%) developed acute pancreatitis (in the basal-bolus group). INTERPRETATION The trial met the non-inferiority threshold for the primary endpoint, because there was no significant difference between groups in mean daily blood glucose concentrations. Treatment with sitagliptin plus basal insulin is as effective and safe as, and a convenient alternative to, the labour-intensive basal-bolus insulin regimen for the management of hyperglycaemia in patients with type 2 diabetes admitted to general medicine and surgery services in hospital in the non-intensive-care setting. FUNDING Merck.

Metformin-Associated Lactic Acidosis

: Metformin is the most commonly prescribed oral antidiabetic agent. Despite a good safety profile in most patients with diabetes, the risk of metformin-associated lactic acidosis is real if safety guidelines are ignored. Experience with 3 cases of metformin-associated lactic acidosis is reported. Two cases were caused by inappropriate use of metformin in the presence of renal, cardiac and hepatic failure and 1 case followed an intentional overdose. The literature was reviewed on the clinical presentation, prevalence, pathogenesis, prognosis and management of metformin-associated lactic acidosis. This report highlights the importance of proper patient selection, clinical and laboratory monitoring and recommendation on when to stop the drug in ambulatory and hospitalized patients to prevent this unusual but potentially lethal complication.

The impact of hyperglycemia and obesity on hospitalization costs and clinical outcome in general surgery patients

BACKGROUND The impact of obesity on clinical outcomes and hospitalization costs in general surgery patients with and without diabetes (DM) is unknown. MATERIALS AND METHODS We reviewed medical records of 2451 patients who underwent gastrointestinal surgery at two university hospitals. Hyperglycemia was defined as BG ≥140 mg/dl. Overweight was defined by body mass index (BMI) between 25-29.9 kg/m(2) and obesity as a BMI ≥30 kg/m(2). Hospital cost was calculated using cost-charge ratios from Centers for Medicare and Medicaid Services. Hospital complications included a composite of major cardiovascular events, pneumonia, bacteremia, acute kidney injury (AKI), respiratory failure, and death. RESULTS Hyperglycemia was present in 1575 patients (74.8%). Compared to patients with normoglycemia, those with DM and non-DM with hyperglycemia had higher number of complications (8.9% vs. 35.8% vs. 30.0%, p<0.0001), longer hospital stay (5 days vs. 9 days vs. 9 days, p<0.0001), more readmissions within 30 days (9.3% vs. 18.8% vs. 17.2%, p<0.0001), and higher hospitalization costs (