Population insulin sensitivity from sparsely sampled oral glucose tolerance tests.

OBJECTIVE: This work aimed to estimate population-level insulin sensitivity (SI) from 2-hour oral glucose tolerance tests (OGTT) with less than 7 samples. RESEARCH DESIGN AND METHODS: The current methodology combines the OGTT mathematical model developed by Dalla Man et al., with nonlinear multilevel (NLML) statistical model to estimate population-level insulin sensitivity (SI) from sparsely sampled datasets (3 or 4 samples per subject obtained in 120 min). To validate our novel methodology of population SI estimation, we simulated 50 virtual subjects. We simulated 10 observations per subject over 240 minutes. After estimating their SI using the OGTT model, the virtual subjects were split into two groups, subjects with SI above the average and ones with below average. Subsequently, the simulated data were analyzed using statistical software and employing a t-test. The mean estimates of population SI for the two groups of virtual subjects and their respective 95% CI were compared to the estimates obtained with our novel NLML group SI estimates obtained using the 3 and 4 time points per subject. To further validate the performance of the novel NLML model, a set of 34 prediabetic and 30 diabetic subjects with T2D was used. As outlined above for the in-silico subjects, differences between the prediabetic and T2D subjects in regard to SI was assessed using the classical two-stage approach (individual SI estimation followed by statistical comparison of the two groups). The average estimates obtained with the classical two-stage approach were compared to the group estimated obtained with the NLML approach using 3 (0, 60, and 120 minutes) points per subject obtained in 120 minutes. RESULTS: Unique and identifiable individual estimates of SI were obtained for all virtual subjects. In comparison to the subjects with above average SI (n=25), the subjects with simulated below average SI (n=25) exhibited significantly lower insulin sensitivity (P<0.001). Our novel NLML population model confirmed these findings (4-point OGTT: P<0.001; 3-point OGTT: P<0.001). In a similar fashion to the one outlined for the virtual subjects, the median insulin sensitivities estimated with the classical two-stage approach were different between the prediabetic (n=34) and T2D subjects (n=32, P=0.004). Using 3 points per subject, our novel NLML model confirmed these findings (P<0.001). CONCLUSIONS: The population estimates of SI from OGTT data is an effective tool to assess population insulin sensitivity and assess differences that may not be possible when calculating individual SI or when less than 7 samples are available.

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 ($20,273 vs. $79,545 vs. $72,675, p<0.0001). In contrast, compared to normal-weight subjects, overweight and obesity were not associated with increased hospitalization costs ($58,313 vs. $58,173 vs. $66,633, p=0.74) or risk of complications, except for AKI (11.9% vs. 14.8% vs. 20.5%, p<0.0001). Multivariate analysis revealed that DM (OR=4.4, 95% CI=2.8,7.0) or perioperative hyperglycemia (OR=4.1, 95% CI=2.7-6.2) were independently associated with increased risk of complications. CONCLUSION: Hyperglycemia but not increasing BMI, in patients with and without diabetes undergoing gastrointestinal surgery was associated with a higher number of complications and hospitalization costs.

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.