Roma Y. Gianchandani

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.

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.

Micromachined bulk PZT tissue contrast sensor for fine needle aspiration biopsy

This paper describes a micromachined piezoelectric sensor, integrated into a cavity at the tip of a biopsy needle, and preliminary experiments to determine if such a device can be used for real-time tissue differentiation, which is needed for needle positioning guidance during fine needle aspiration (FNA) biopsy. The sensor is fabricated from bulk lead zirconate titanate (PZT), using a customized process in which micro electro-discharge machining is used to form a steel tool that is subsequently used for batch-mode ultrasonic micromachining of bulk PZT ceramic. The resulting sensor is 50 microm thick and 200 microm in diameter. It is placed in the biopsy needle cavity, against a steel diaphragm which is 300 microm diameter and has an average thickness of 23 microm. Devices were tested in materials that mimic the ultrasound characteristics of human tissue, used in the training of physicians, and with porcine fat and muscle tissue. In both schemes, the magnitude and frequency of an electrical impedance resonance peak showed tissue-specific characteristics as the needle was inserted. For example, in the porcine tissue, the impedance peak frequency changed approximately 13 MHz from the initial 163 MHz, and the magnitude changed approximately 1600 Omega from the initial 2100 Omega, as the needle moved from fat to muscle. Samples including oils and saline solution were tested for calibration, and an empirical tissue contrast model shows an approximately proportional relationship between measured frequency shift and sample acoustic impedance. These results suggest that the device can complement existing methods for guidance during biopsies.

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.

PRIDE Statement on the Need for a Moratorium on the CMS Plan to Cite Hospitals for Performing Point-of-Care Capillary Blood Glucose Monitoring on Critically Ill Patients

OBJECTIVE A writing committee of the Planning Research in Inpatient Diabetes (PRIDE) group has written this consensus article on behalf of the group in response to a specific request for input from the Centers for Medicare and Medicaid Services (CMS). The purpose of this article is to respond to the March 13, 2015 statement from that agency regarding plans to enforce prohibition of the off-label use of point of care (POC) capillary blood glucose monitor (BGM) testing in most critically ill patients. The article discusses: 1) how POC BGM testing is currently regulated; 2) how POC BGM testing is currently used in the United States; and 3) how POC BGM testing can be safely and effectively regulated in the future through cooperation between the clinician, laboratory, regulatory, industry, and patient communities. PARTICIPANTS Nine members of PRIDE volunteered to write the statement on behalf of the entire group. EVIDENCE Descriptions of current medical practice for critically ill patients were derived from the experience of the authors. Descriptions of the performance of various methods for measuring glucose levels for intensive insulin therapy came from a literature review. CONSENSUS PROCESS Eleven questions were developed by the PRIDE writing group. After extensive electronic and telephone discussion, the article was written and reviewed by all nine authors and then reviewed by two outside experts in the care of critically ill patients. All suggestions by the authors and the outside experts were incorporated. CONCLUSIONS Although the CMS is attempting to protect patients with abnormal glycemic control from harm due to inaccurate POC fingerstick capillary BGM testing, their plan will result in more harm than good. A moratorium on enforcement of the prohibition of off-label use of POC capillary BGM testing is needed.

Compact, power-efficient architectures using microvalves and microsensors, for intrathecal, insulin, and other drug delivery systems☆

This paper describes a valve-regulated architecture, for intrathecal, insulin and other drug delivery systems, that offers high performance and volume efficiency through the use of micromachined components. Multi-drug protocols can be accommodated by using a valve manifold to modulate and mix drug flows from individual reservoirs. A piezoelectrically-actuated silicon microvalve with embedded pressure sensors is used to regulate dosing by throttling flow from a mechanically-pressurized reservoir. A preliminary prototype system is demonstrated with two reservoirs, pressure sensors, and a control circuit board within a 130cm(3) metal casing. Different control modes of the programmable system have been evaluated to mimic clinical applications. Bolus and continuous flow deliveries have been demonstrated. A wide range of delivery rates can be achieved by adjusting the parameters of the manifold valves or reservoir springs. The capability to compensate for changes in delivery pressure has been experimentally verified. The pressure profiles can also be used to detect catheter occlusions and disconnects. The benefits of this architecture compared with alternative options are reviewed.

Effects of an Educational Program and a Standardized Insulin Order Form on Glycemic Outcomes in Non-Critically Ill Hospitalized Patients

BACKGROUND The optimal approach to managing hyperglycemia in noncritically ill hospital patients is unclear. OBJECTIVE To investigate the effects of targeted quality improvement interventions on insulin prescribing and glycemic control. DESIGN A cohort study comparing an intervention group (IG) to a concurrent control group (CCG) and an historic control group (HCG). SETTING University of Michigan Hospital. PATIENTS Hyperglycemic, noncritically ill hospital patients treated with insulin. INTERVENTION Physician and nurse education and a standardized insulin order form based on the principles of physiologic insulin use. MEASUREMENTS Glycemic control and insulin prescribing patterns. RESULTS Patients in the IG were more likely to be treated with a combination of scheduled basal and nutritional insulin than in the other groups. In the final adjusted regression model, patients in the IG were more likely to be in the target glucose range (odds ratio [OR], 1.72; P = 0.01) and less likely to be severely hyperglycemic (OR, 0.65; P < 0.01) when compared to those in the CCG. Patients in the IG were also less likely to experience hypoglycemia than those in the CCG (P = 0.06) or the HCG (P = 0.01). Over 80% of all patient-days for all groups contained glucose readings outside of the target range. CONCLUSIONS Standardized interventions encouraging the physiologic use of subcutaneous insulin can lead to significant improvements in glycemic control and patient safety in hospitalized patients. However, the observed improvements are modest, and poor metabolic control remains common, despite these interventions. Additional research is needed to determine the best strategy for safely achieving metabolic control in these patients.

Stress Hyperglycemia During Surgery and Anesthesia: Pathogenesis and Clinical Implications

Numerous studies have demonstrated an association between hyperglycemia in the perioperative period and adverse clinical outcomes. Many patients who experience hyperglycemia while hospitalized do not have a known history of diabetes and experience a transient phenomenon often described as “stress hyperglycemia” (SH). We discuss the epidemiology and pathogenesis of SH as well as evidence to date regarding predisposing factors and outcomes. Further research is needed to identify the long-term sequelae of SH as well as perioperative measures that may modulate glucose elevations and optimal treatment strategies.

Prevalence and Determinants of Glycemic Abnormalities in Cardiac Surgery Patients without a History of Diabetes: A Prospective Study.

Objective To evaluate the prevalence and persistence of postoperative glycemic abnormalities in patients without a history of diabetes, undergoing cardiac surgery (CS). Methods Ninety-two patients without diabetes with planned elective CS procedures at a tertiary institution were evaluated preoperatively and 3 months postoperatively for measures of glucose control including hemoglobin A1c, fasting plasma glucose, 2-h post oral glucose load, and insulin levels. Data from the hospital course were recorded. Results Valid data were available from 61 participants at 3 months; 59% had prediabetes and 10% had diabetes preoperatively by one or more diagnostic criteria and continued to be dysglycemic at 3 months. Preoperative A1C was an independent predictor of postoperative hyperglycemia (p = 0.02). Insulin resistance and BMI rather than glycemic abnormalities before surgery were associated with a longer duration of the postoperative insulin infusion (p = 0.004, p = 0.048). Conclusion Seventy percent of CS patients without known diabetes met criteria for diabetes or prediabetes preoperatively, and these abnormalities persisted after surgery.

Diabetes and Stress Hyperglycemia in the Intensive Care Unit: Outcomes After Cardiac Surgery

Abstract Background: Hyperglycemia is common in the post–cardiac surgery population and has been associated with increased mortality rates, surgical length of stay, and infection rates. Although hospitalized patients with diabetes are known to have more complications, recent studies in various hospital settings have reported worse outcomes in patients with stress hyperglycemia than in those with diabetes. Aim: The primary objective of this study was to analyze 30- and 90-day mortality rates in post–cardiac surgery patients with stress hyperglycemia and diabetes who were managed to achieve similar moderate blood glucose goals using the University of Michigan Hospital (Ann Arbor, MI) insulin protocol between 2005 and 2008. The secondary outcomes were rates of postoperative complications, including hypoglycemia. Methods: A standardized glucose management program was followed to treat all patients in the cardiac intensive care unit, with a blood glucose goal of 100 to 140 mg/dL. Data from 1973 patients with either diabetes or stress hyperglycemia were analyzed to identify associations between mean postoperative blood glucose levels and mortality, incidence of hypoglycemia, and complication rates. Results: Mortality rates did not differ between patients with diabetes and stress hyperglycemia (3.4 and 2.3%; P = 0.2). Rates of severe hypoglycemia were low (1%) for both groups and were not associated with an increase in mortality (P = 0.95). Other complication rates were similar between patients with diabetes and stress hyperglycemia. Conclusion: Maintaining a blood glucose range between 100 to 140 mg/dL in post–cardiac surgery patients was associated with a low mortality rate, low risk of hypoglycemia, and with complications rates that were similar in patients with diabetes and stress hyperglycemia.