Kathleen M. Dungan

Glucose variability and mortality in patients with sepsis

Objective:Treatment and prevention of hyperglycemia has been advocated for subjects with sepsis. Glucose variability, rather than the glucose level, has also been shown to be an important factor associated with in-hospital mortality, in general, critically ill patients. Our objective was to determine the association between glucose variability and hospital mortality in septic patients and the expression of glucose variability that best reflects this risk. Design:Retrospective, single-center cohort study. Setting:Academic, tertiary care hospital. Patients:Adult subjects hospitalized for >1 day, with a diagnosis of sepsis were included. Interventions:None. Measurements:Glucose variability was calculated for all subjects as the average and standard deviation of glucose, the mean amplitude of glycemic excursions, and the glycemic lability index. Hospital mortality was the primary outcome variable. Logistic regression was used to determine the odds of hospital death in relation to measures of glucose variability after adjustment for important covariates. Main results:Of the methods used to measure glucose variability, the glycemic lability index had the best discrimination for mortality (area under the curve = 0.67, p < 0.001). After adjustment for confounders, including the number of organ failures and the occurrence of hypoglycemia, there was a significant interaction between glycemic lability index and average glucose level, and the odds of hospital mortality. Higher glycemic lability index was not independently associated with mortality among subjects with average glucose levels above the median for the cohort. However, subjects with increased glycemic lability index, but lower average glucose values had almost five-fold increased odds of hospital mortality (odds ratio = 4.73, 95% confidence interval = 2.6-8.7) compared with those with lower glycemic lability index. Conclusions:Glucose variability is independently associated with hospital mortality in septic patients. Strategies to reduce glucose variability should be studied to determine whether they improve the outcomes of septic patients.

Racial and Ethnic Differences in Mean Plasma Glucose, Hemoglobin A1c, and 1,5-Anhydroglucitol in Over 2000 Patients with Type 2 Diabetes

CONTENT Recent studies have reported hemoglobin A(1c) (A1c) differences across racial/ethnic groups. Our diverse population allows for further investigation of potential differences in measurements of glycemia. OBJECTIVES Our objectives were to describe and explore baseline racial/ethnic differences in self-monitored plasma glucose profiles, A1c, and 1,5-anhydroglucitol (1,5-AG) in patients with type 2 diabetes enrolled in the Assessing DURAbility of Basal vs. Lispro Mix 75/25 Insulin Efficacy trial. DESIGN, SETTING, PATIENTS The trial enrolled 2094 patients with type 2 diabetes, ages 30-80 yr, from 11 countries. MAIN OUTCOME MEASURES Estimated mean plasma glucose (MPG), A1c, and 1,5-AG were compared among racial/ethnic groups before and after adjusting for factors affecting glycemia: age, sex, duration of diabetes, body mass index, and MPG. RESULTS Baseline estimated MPG +/- sd was 220.0 +/- 82.0 mg/dl, mean A1c was 9.0 +/- 1.3%, and 1,5-AG was 5.0 +/- 4.1microg/ml. Estimated MPG did not differ between Caucasian and non-Caucasian groups. A1c was higher in Hispanics (9.4 +/- 1.4%; P < 0.001), Asians (9.2 +/- 1.4%; P < 0.01), and patients of other racial/ethnic groups (9.7 +/- 1.5%; P < 0.001) compared with Caucasians (8.9 +/- 1.2%). Paradoxically, 1,5-AG was higher for Asian (5.7 +/- 4.6 microg/ml) and African patients (6.2 +/- 5.4 microg/ml) vs. Caucasians (4.9 +/- 3.9 microg/ml) (P < 0.01). After adjusting for factors affecting glycemia, A1c was higher (all P <or= 0.002) in Hispanics, Asians, Africans, and patients of other racial/ethnic groups, and 1,5-AG was higher in Asian and African patients (P < 0.001) vs. Caucasians. CONCLUSIONS There were differences in A1c and 1,5-AG, but not MPG, among racial/ethnic groups. Comparisons of glycemia across racial/ethnic groups using these parameters may be problematic due to inherent biological variability and methodological issues.

1,5-anhydroglucitol (GlycoMark™) as a marker of short-term glycemic control and glycemic excursions

1,5-anhydroglucitol (1,5-AG) is a validated marker of short-term glycemic control. It is a metabolically inert polyol that competes with glucose for reabsorption in the kidneys. Otherwise stable levels of 1,5-AG are rapidly depleted as blood glucose levels exceed the renal threshold for glucosuria. 1,5-AG more accurately predicts rapid changes in glycemia than hemoglobin A1C (A1C) or fructosamine. It is also more tightly associated with glucose fluctuations and postprandial glucose. Thus, 1,5-AG may offer complementary information to A1C. This review will summarize the limitations of current methods of assessing glycemic control, assess the data to support 1,5-AG as a glycemic marker and highlight the scenarios by which 1,5-AG may fill the gap in assessing glycemic control.

Endothelial Dysfunction: Associations with Exposure to Ambient Fine Particles in Diabetic Individuals

Background Exposure to fine airborne particulate matter [≤2.5 μm in aerodynamic diameter (PM2.5)] has been associated with cardiovascular and hematologic effects, especially in older people with cardiovascular disease. Some epidemiologic studies suggest that adults with diabetes also may be a particularly susceptible population. Objectives The purpose of this study was to analyze the short-term effects of ambient PM2.5 on markers of endothelial function in diabetic volunteers. Methods We conducted a prospective panel study in 22 people with type 2 diabetes mellitus in Chapel Hill, North Carolina (USA), from November 2004 to December 2005. We acquired daily measurements of PM2.5 and meteorologic data at central monitoring sites. On 4 consecutive days, we measured endothelial function by brachial artery ultrasound in all participants and by pulsewave measurements in a subgroup. Data were analyzed using additive mixed models with a random participant effect and adjusted for season, day of the week, and meteorology. Results Flow-mediated dilatation decreased in association with PM2.5 during the first 24 hr, whereas small-artery elasticity index decreased with a delay of 1 and 3 days. These PM2.5-associated decrements in endothelial function were greater among participants with a high body mass index, high glycosylated hemoglobin A1c, low adiponectin, or the null polymorphism of glutathione S-transferase M1. However, high levels of myeloperoxidase on the examination day led to strongest effects on endothelial dysfunction. Conclusions These data demonstrate that PM2.5 exposure may cause immediate endothelial dysfunction. Clinical characteristics associated with insulin resistance were associated with enhanced effects of PM on endothelial function. In addition, participants with greater oxidative potential seem to be more susceptible.

Inpatient Diabetes Education Is Associated With Less Frequent Hospital Readmission Among Patients With Poor Glycemic Control

OBJECTIVE To explore the relationship between inpatient diabetes education (IDE) and hospital readmissions in patients with poorly controlled diabetes. RESEARCH DESIGN AND METHODS Patients with a discharge diagnosis of diabetes (ICD-9 code 250.x) and HbA1c >9% who were hospitalized between 2008 and 2010 were retrospectively identified. All-cause first readmissions were determined within 30 days and 180 days after discharge. IDE was conducted by a certified diabetes educator or trainee. Relationships between IDE and hospital readmission were analyzed with stepwise backward logistic regression models. RESULTS In all, 2,265 patients were included in the 30-day analysis and 2,069 patients were included in the 180-day analysis. Patients who received IDE had a lower frequency of readmission within 30 days than did those who did not (11 vs. 16%; P = 0.0001). This relationship persisted after adjustment for sociodemographic and illness-related factors (odds ratio 0.66 [95% CI 0.51–0.85]; P = 0.001). Medicaid insurance and longer stay were also independent predictors in this model. IDE was also associated with reduced readmissions within 180 days, although the relationship was attenuated. In the final 180-day model, no IDE, African American race, Medicaid or Medicare insurance, longer stay, and lower HbA1c were independently associated with increased hospital readmission. Further analysis determined that higher HbA1c was associated with lower frequency of readmission only among patients who received a diabetes education consult. CONCLUSIONS Formal IDE was independently associated with a lower frequency of all-cause hospital readmission within 30 days; this relationship was attenuated by 180 days. Prospective studies are needed to confirm this association.

Effects of therapy in type 1 and type 2 diabetes mellitus with a peptide derived from islet neogenesis associated protein (INGAP)

Islet neogenesis associated protein (INGAP) has beta cell regenerating effects in experimental models.

The effect of glycaemic control and glycaemic variability on mortality in patients hospitalized with congestive heart failure

Diabetes and CHF are common comorbidities in hospitalized patients but the relationship between glycaemic control, glycaemic variability, and mortality in patients with both conditions is unclear.

The Effect of Diabetes on Hospital Readmissions

Hospital readmission is an important contributor to total medical expenditures and is an emerging indicator of quality of care. Diabetes, similar to other chronic medical conditions, is associated with increased risk of hospital readmission. Risk factors include previous hospitalization, extremes in age, and socioeconomic barriers. Preliminary studies suggest that acute and/or chronic glycemic control may be of importance when diabetes is the primary diagnosis or when it is a comorbidity. Very limited evidence from prospective randomized controlled trials aimed at improving glycemic control is available. However, whether one concludes that inpatient or outpatient glycemic control is partly responsible for reduced hospitalizations, attention to glycemic control in the hospital may facilitate sustained glycemic control post-discharge. Limited prospective and retrospective evidence suggest that the involvement of a diabetes specialist team may improve readmission rates, but attention to more generalized comprehensive approaches may also be worthwhile. Prospective interventional studies targeting interventions for improving glycemic control are needed to determine whether glycemic control impacts readmission rates.

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.

Relationship between glycemic control and readmission rates in patients hospitalized with congestive heart failure during implementation of hospital-wide initiatives.

OBJECTIVE To determine the relationship between inpatient glycemic control and hospital readmission in patients with congestive heart failure (CHF). METHODS We used an electronic data collection tool to identify patients with a discharge diagnosis of CHF who underwent point-of-care glucose assessments. Timeweighted mean glucose (TWMG), hemoglobin A1c, and glycemic lability index (GLI) served as glycemic indicators, and readmission for CHF was determined at 30 days and between 30 and 90 days. RESULTS The analysis included 748 patients. After adjustment for significant covariates, log-transformed increasing TWMG (odds ratio 3.3; P = .03) and log-transformed hemoglobin A1c (odds ratio 5.5; P = .04) were independently associated with higher readmission for CHF between 30 and 90 days, but not by 30 days. Renal disease, African American race, and year of hospital admission were also significantly associated with readmission, but GLI was not. There was no significant difference in TWMG when analyzed on the basis of race or renal status. We noted a decrease in TWMG (P = .004) and a trend for reduction in readmission rates between 30 and 90 days (P = .06) after hospital-wide interventions were implemented to improve glycemic control, but no significant difference was detected in GLI or hypoglycemia. CONCLUSION Increasing glucose exposure, but not glycemic variability, was associated with higher risk of readmission between 30 and 90 days in patients with CHF. Prospective studies are needed to confirm or refute these results.