CONTEXT:Glucose tolerance during an oral glucose tolerance test (OGTT) is affected by variations in glucose effectiveness (GE) and glucose absorption and thus affects minimal model calculations of insulin sensitivity (SI). The widely used OGTT SI by Dalla Man et al does not account for variances in GE and glucose absorption. OBJECTIVE:To develop a novel model that concurrently assesses SI, GE, and glucose absorption. METHODS:In this cross-sectional study conducted at an academic medical center, 17 subjects without abnormalities on OGTT (controls) and 88 subjects with diabetes underwent a 75-gram 120-minute 6-timepoint OGTT. The SI from the Dalla Man model was validated with the novel model SI using Bland-Altman limits of agreement methodology. Comparisons of SI, GE, and gastrointestinal glucose half-life (GIGt1/2), a surrogate measure for glucose absorption, were made between subjects with diabetes and controls. RESULTS:In controls and diabetes, the novel model SI was higher than the current OGTT model. The SI from both controls (ƿ=0.90, P < .001) and diabetes (ƿ=0.77, P < .001) has high agreement between models. GE was higher in diabetes (median: 0.021 1/min, interquartile range [IQR]: 0.020-0.022) compared to controls (median: 0.016 1/min, IQR: 0.015-0.017), P = .02. GIGt1/2 was shorter in diabetes (median: 48.404 min, IQR: 54.424-39.426) than in controls (median: 55.086 min, IQR: 61.368-48.502) without statistical difference. CONCLUSION:Our novel model SI has a good correlation with SI from the widely used Dalla Man's model while concurrently calculating GE and GIGt1/2. Thus, besides estimating SI, our novel model can quantify differences in insulin-independent glucose disposal mechanisms important for diabetes pathophysiology.

Objective Approximately 50% of obese Black patients with unprovoked diabetic ketoacidosis (DKA) or severe hyperglycemia (SH) at new-onset diabetes achieve near-normoglycemia remission with intensive insulin treatment. Despite the initial near-normoglycemia remission, most DKA/SH individuals develop hyperglycemia relapse after insulin discontinuation. Traditional biomarkers such as normal glucose tolerance at the time of remission were not predictive of hyperglycemia relapse. We tested whether 1-h plasma glucose (1-h PG) at remission predicts hyperglycemia relapse in Black patients with DKA/SH. Methods Secondary analysis was performed of two prospective randomized controlled trials in 73 patients with DKA/SH at the safety net hospital with a median follow-up of 408 days. Patients with DKA/SH underwent a 5-point, 2-h 75-g oral glucose tolerance test after hyperglycemia remission. Hyperglycemia relapse is defined by fasting blood glucose (FBG) > 130 mg/dl, random blood glucose (BG) >180 mg/dl, or HbA1c > 7%. Results During the median 408 (interquartile range: 110–602) days of follow-up, hyperglycemia relapse occurred in 28 (38.4%) participants. One-hour PG value ≥199 mg/dl discriminates hyperglycemia relapse (sensitivity: 64%; specificity: 71%). Elevated levels of 1-h PG (≥199 mg/dl) were independently associated with hyperglycemia relapse (adjusted hazard ratio: 2.40 [95% CI: 1.04, 5.56]). In a multivariable model with FBG, adding 1-h PG level enhanced the prediction of hyperglycemia relapse, with significant improvements in C-index (Δ: +0.05; p = 0.04), net reclassification improvement (NRI: 48.7%; p = 0.04), and integrated discrimination improvement (IDI: 7.8%; p = 0.02) as compared with the addition of 2-h PG (NRI: 20.2%; p = 0.42; IDI: 1.32%; p = 0.41) or HbA1c (NRI: 35.2%; p = 0.143; IDI: 5.8%; p = 0.04). Conclusion One-hour PG at the time of remission is a better predictor of hyperglycemia relapse than traditional glycemic markers among obese Black patients presenting with DKA/SH. Testing 1-h PG at insulin discontinuation identifies individuals at high risk of developing hyperglycemia relapse.

Introduction Many African-Americans (AA) with obesity with newly diagnosed diabetes presenting with diabetic ketoacidosis (DKA) or severe hyperglycemia (SH) discontinue insulin therapy and achieve near-normoglycemia remission (hemoglobin A1c (HbA1c) <7%, fasting blood glucose (FBG) <130 mg/dL) and able to be managed on oral antidiabetic agents (OAD) during follow-up. Using combined data from two randomized controlled trials, we assessed long-term carbohydrate tolerance and changes in insulin sensitivity and insulin secretion. Research design and methods Seventy-five participants with DKA (n=33) and SH (n=42) underwent 2-hour 75 g oral glucose tolerance test (OGTT) after insulin discontinuation and every 6 months until hyperglycemia relapse (FBG ≥130 mg/dL, HbA1c >7% or two random BG ≥180 mg/dL) while treated with OAD (metformin, sitagliptin or pioglitazone) or placebo. Glucose tolerance status was defined as per the American Diabetes Association. Sensitivity index (Si) was calculated by oral minimal model, insulin secretion as the incremental area under the curve of insulin (IncreAUCi) and disposition index (DI) as Si×IncreAUCi. Results During remission, OGTT showed normal glucose tolerance (NGT) (n=9 (12%)), prediabetes (n=34 (45%)) and diabetes (n=32 (43%)). DI and Si were higher in patients with NGT versus prediabetes versus diabetes (p<0.001), while IncreAUCi was not significantly different among NGT, prediabetes and diabetes (p=0.14). Achieving NGT status did not prolong near-normoglycemia remission. OAD treatment significantly prolonged hyperglycemia relapse-free survival (log-rank p=0.0012) compared with placebo and was associated with lower hyperglycemia relapse (HR: 0.45, 95% CI: (0.21 to 0.96), p=0.04). Conclusions In AA patients with obesity with history of DKA and SH, near-normoglycemia remission is associated with improved insulin secretion and action with half of patients achieving NGT or prediabetes, and only half having diabetes on OGTT. NGT and prediabetes on OGTT were not associated with prolonged hyperglycemia relapse-free survival. Trial registration number NCT01099618, NCT00426413.

The identification of cost-effective glycaemic management strategies is critical to hospitals. Treatment with a basal-bolus insulin (BBI) regimen has been shown to result in better glycaemic control and fewer complications than sliding scale regular insulin (SSI) in general surgery patients with type 2 diabetes mellitus (T2DM), but the effect on costs is unknown.

CONTEXT:A higher prevalence of diabetes-related complications is reported in minority populations; however, it is not known if there are racial disparities in diabetes care and outcomes in hospitalized patients.OBJECTIVE:Our objective was to determine the association between hyperglycemia, in patients with and without diabetes mellitus (non-DM), and complications among different racial groups.DESIGN:This observational study compared the frequency of hyperglycemia (blood glucose ≥ 180 mg/dL; 10 mmol/L) and DM and hospital complications between Black and White patients hospitalized patients between January 2012 and December 2013.SETTING AND PARTICIPANTS:Adults admitted to medical and surgery services in two academic hospitals were included in this study.RESULTS:Among 35 866 patients, there were 14 387 Black (40.1%) and 21 479 White patients (59.9%). Blacks had a higher prevalence of hyperglycemia (42.3% vs 36.7%, P < .0001) and DM (34.5% vs 22.8%, P < .0001) and a higher admission rate and mean daily blood glucose (P < .001). Blacks also had higher rates of complications (22.2% vs 19.2%, P < .0001), both in patients with DM (24.7 vs 22.9%, P = .0413) and non-DM with hyperglycemia (41.2% vs 37.2%, P = .0019). Using sequential modelling adjusted for age, gender, body mass index, comorbidities, and insurance coverage, non-DM Blacks with normoglycemia (odds ratio, 1.22; 95% confidence interval, 1.10-1.35) and non-DM Blacks with hyperglycemia (odds ratio, 1.18; 95% confidence interval, 1.04-1.33) had higher number of complications compared to Whites.CONCLUSIONS:Black patients have higher rates of hyperglycemia and diabetes, worse inpatient glycemic control, and greater frequency of hospital complications compared to Whites. Non-DM Blacks with hyperglycemia are a particularly vulnerable group. Further investigation is needed to better understand factors contributing the racial disparities in the hospital.

Objective Obesity is associated with increased risk of diabetes, hypertension and cardiovascular mortality. Several studies have reported increased length of hospital stay and complications; however, there are also reports of obesity having a protective effect on health, a phenomenon coined the ‘obesity paradox’. We aimed to investigate the impact of overweight and obesity on complications and mortality in hospitalized patients with hyperglycemia and diabetes. Research design and methods This retrospective analysis was conducted on 29 623 patients admitted to two academic hospitals in Atlanta, Georgia, between January 2012 and December 2013. Patients were subdivided by body mass index into underweight (body mass index <18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (>30 kg/m2). Hyperglycemia was defined as a blood glucose >10 mmol/L during hospitalization. Hospital complications included a composite of pneumonia, acute myocardial infarction, respiratory failure, acute kidney injury, bacteremia and death. Results A total of 4.2% were underweight, 29.6% had normal weight, 30.2% were overweight, and 36% were obese. 27.2% of patients had diabetes and 72.8% did not have diabetes (of which 75% had hyperglycemia and 25% had normoglycemia during hospitalization). A J-shaped curve with higher rates of complications was observed in underweight patients in all glycemic groups; however, there was no significant difference in the rate of complications among normal weight, overweight, or obese patients, with and without diabetes or hyperglycemia. Conclusions Underweight is an independent predictor for hospital complications. In contrast, increasing body mass index was not associated with higher morbidity or mortality, regardless of glycemic status. There was no evidence of an obesity paradox among inpatients with diabetes and hyperglycemia.

OBJECTIVE After intensive insulin treatment, many obese African American patients with new-onset diabetic ketoacidosis (DKA) and severe hyperglycemia are able to achieve near-normoglycemia remission. The optimal treatment to prevent hyperglycemic relapses after remission is not known. RESEARCH DESIGN AND METHODS This prospective, 4-year, placebo-controlled study randomly assigned 48 African American subjects with DKA and severe hyperglycemia to metformin 1,000 mg daily (n = 17), sitagliptin 100 mg daily (n = 16), or placebo (n = 15) after normoglycemia remission. Hyperglycemic relapse was defined as fasting glucose >130 mg/dL (7.2 mmol/L) and HbA1c >7.0% (53 mmol/mol). Oral glucose tolerance tests were conducted at randomization and at 3 months and then every 6 months for a median of 331 days. Oral minimal model and incremental area under the curve for insulin (AUCi) were used to calculate insulin sensitivity (Si) and β-cell function, respectively. Disposition index (DI) was calculated as a product of Si and incremental AUCi. RESULTS Relapse-free survival was higher in sitagliptin and metformin (P = 0.015) compared with placebo, and mean time to relapse was significantly prolonged in the metformin and sitagliptin groups compared with the placebo group (480 vs. 305 days, P = 0.004). The probability of relapse was significantly lower for metformin (hazard ratio 0.28 [95% CI 0.10–0.81]) and sitagliptin (0.31 [0.10–0.98]) than for placebo. Subjects who remained in remission had a higher DI (P = 0.02) and incremental AUCi (P < 0.001) than those with hyperglycemia relapse without significant changes in Si. CONCLUSIONS This study shows that near-normoglycemia remission was similarly prolonged by treatment with sitagliptin and metformin. The prolongation of remission was due to improvement in β-cell function.

OBJECTIVE Clinical guidelines recommend point-of-care glucose testing and the use of supplemental doses of rapid-acting insulin before meals and at bedtime for correction of hyperglycemia. The efficacy and safety of this recommendation, however, have not been tested in the hospital setting. RESEARCH DESIGN AND METHODS In this open-label, randomized controlled trial, 206 general medicine and surgery patients with type 2 diabetes treated with a basal-bolus regimen were randomized to receive either supplemental insulin (n = 106) at bedtime for blood glucose (BG) >7.8 mmol/L or no supplemental insulin (n = 100) except for BG >19.4 mmol/L. Point-of-care testing was performed before meals, at bedtime, and at 3:00 a.m. The primary outcome was the difference in fasting BG. In addition to the intention-to-treat analysis, an as-treated analysis was performed where the primary outcome was analyzed for only the bedtime BG levels between 7.8 and 19.4 mmol/L. RESULTS There were no differences in mean fasting BG for the intention-to-treat (8.8 ± 2.4 vs. 8.6 ± 2.2 mmol/L, P = 0.76) and as-treated (8.9 ± 2.4 vs. 8.8 ± 2.4 mmol/L, P = 0.92) analyses. Only 66% of patients in the supplement and 8% in the no supplement groups received bedtime supplemental insulin. Hypoglycemia (BG <3.9 mmol/L) did not differ between groups for either the intention-to-treat (30% vs. 26%, P = 0.50) or the as-treated (4% vs. 8%, P = 0.37) analysis. CONCLUSIONS The use of insulin supplements for correction of bedtime hyperglycemia was not associated with an improvement in glycemic control. We conclude that routine use of bedtime insulin supplementation is not indicated for management of inpatients with type 2 diabetes.

Summary Body mass index ( BMI ) and mortality in old adults from the general population have been related in a U ‐shaped or J ‐shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic P ub M ed/ EMBASE / CINAHL / SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m 2 ), the most adjusted hazard ratios ( HRs ) according to a pre‐defined list of covariates were obtained from authors and pooled by random‐effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow‐up were meta‐analysed. Compared with normal weight, all‐cause mortality HRs were 1.41 (95% CI = 1.26–1.58) for underweight, 0.85 (95% CI = 0.73–0.99) for overweight and 0.74 (95% CI = 0.57–0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections ( HR = 1.65 [95% CI = 1.13–2.40]). RR results corroborated primary HR results, with additionally lower infection‐related mortality in overweight and obese than in normal‐weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.

Background Managing hyperglycemia and diabetes is challenging in geriatric patients admitted to long-term care (LTC) facilities. Methods This randomized control trial enrolled patients with type 2 diabetes (T2D) with blood glucose (BG) >180 mg/dL or glycated hemoglobin >7.5% to receive low-dose basal insulin (glargine, starting dose 0.1 U/kg/day) or oral antidiabetic drug (OAD) therapy as per primary care provider discretion for 26 weeks. Both groups received supplemental rapid-acting insulin before meals for BG >200 mg/dL. Primary end point was difference in glycemic control as measured by fasting and mean daily glucose concentration between groups. Results A total of 150 patients (age: 79±8 years, body mass index: 30.1±6.5 kg/m2, duration of diabetes mellitus: 8.2±5.1 years, randomization BG: 194±97 mg/dL) were randomized to basal insulin (n=75) and OAD therapy (n=75). There were no differences in the mean fasting BG (131±27 mg/dL vs 123±23 mg/dL, p=0.06) between insulin and OAD groups, but patients treated with insulin had greater mean daily BG (163±39 mg/dL vs 138±27 mg/dL, p<0.001) compared to those treated with OADs. There were no differences in the rate of hypoglycemia (<70 mg/dL) between insulin (27%) and OAD (31%) groups, p=0.58. In addition, there were no differences in the number of hospital complications, emergency room visits, and mortality between treatment groups. Conclusions The results of this randomized study indicate that elderly patients with T2D in LTC facilities exhibited similar glycemic control, hypoglycemic events and complications when treated with either basal insulin or with oral antidiabetic drugs. Trial registration number ClinicalTrials.gov Identifier: NCT01131052.

OBJECTIVE:To evaluate the impact of different subcutaneous basal insulin regimens on glycemic variability (GV) and hospital complications in non-intensive care unit (ICU) patients with type 2 diabetes (T2D). METHODS:This study is a post hoc analysis of 279 general medicine and surgery patients treated with either a "Basal Bolus" insulin regimen using glargine once daily and glulisine before meals or a "Basal Plus" regimen using glargine once daily plus correction doses of glulisine before meals for glucose >140 mg/dL. GV was calculated as mean delta (Δ) daily glucose, mean SD, and mean amplitude of glycemic excursions (MAGE). RESULTS:Treatment with Basal Bolus and Basal Plus regimens resulted in similar mean daily glucose, hypoglycemia, length of stay (LOS), and hospital complications (all P>.05). There were no differences in GV between treatment groups by Δ change (72.5 ± 36 vs. 69.3 ± 34 mg/dL), SD (38.5 ± 18 vs. 37.1 ± 16 mg/dL) and MAGE (67.5 ± 34 vs. 66.1 ± 39 mg/dL) (all P>.05). Surgery patients treated with Basal Bolus had higher GV compared to those treated with Basal Plus (Δ daily glucose and SD: P = .02, MAGE: P = .009), but no difference in GV was found between treatment groups for the general medicine patients (P>.05). Patients with hypoglycemia events had higher GV compared to subjects without hypoglycemia (P<.05), but no association was found between GV and hospital complications (P>.05). CONCLUSION:Treating hospitalized, non-ICU, diabetic patients with Basal Plus insulin regimen resulted in similar glucose control and GV compared to the standard Basal Bolus insulin regimen. Higher GV was not associated with hospital complications.