Quality of dietary macronutrients is associated with glycemic outcomes in adults with cystic fibrosis.

Objective: Poor diet quality contributes to metabolic dysfunction. This study aimed to gain a greater understanding of the relationship between dietary macronutrient quality and glucose homeostasis in adults with cystic fibrosis (CF). Design: This was a cross-sectional study of N = 27 adults with CF with glucose tolerance ranging from normal (n = 9) to prediabetes (n = 6) to being classified as having cystic fibrosis-related diabetes (CFRD, n = 12). Fasted blood was collected for analysis of glucose, insulin, and C-peptide. Insulin resistance was assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR). Subjects without known CFRD also underwent a 2-h oral glucose tolerance test. Three-day food records were used to assess macronutrient sources. Dietary variables were adjusted for energy intake. Statistical analyses included ANOVA, Spearman correlations, and multiple linear regression. Results: Individuals with CFRD consumed less total fat and monounsaturated fatty acids (MUFA) compared to those with normal glucose tolerance (p < 0.05). In Spearman correlation analyses, dietary glycemic load was inversely associated with C-peptide (rho = -0.28, p = 0.05). Total dietary fat, MUFA, and polyunsaturated fatty acids (PUFA) were positively associated with C-peptide (rho = 0.39-0.41, all p < 0.05). Plant protein intake was inversely related to HOMA2-IR (rho = -0.28, p = 0.048). Associations remained significant after adjustment for age and sex. Discussion: Improvements in diet quality are needed in people with CF. This study suggests that higher unsaturated dietary fat, higher plant protein, and higher carbohydrate quality were associated with better glucose tolerance indicators in adults with CF. Larger, prospective studies in individuals with CF are needed to determine the impact of diet quality on the development of CFRD.

Continuous Glucose Monitoring-Guided Insulin Administration in Hospitalized Patients With Diabetes: A Randomized Clinical Trial.

OBJECTIVE: The efficacy and safety of continuous glucose monitoring (CGM) in adjusting inpatient insulin therapy have not been evaluated. RESEARCH DESIGN AND METHODS: This randomized trial included 185 general medicine and surgery patients with type 1 and type 2 diabetes treated with a basal-bolus insulin regimen. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results, while in the CGM group, insulin adjustment was based on daily CGM profile. Primary end points were differences in time in range (TIR; 70-180 mg/dL) and hypoglycemia (<70 mg/dL and <54 mg/dL). RESULTS: There were no significant differences in TIR (54.51% ± 27.72 vs. 48.64% ± 24.25; P = 0.14), mean daily glucose (183.2 ± 40 vs. 186.8 ± 39 mg/dL; P = 0.36), or percent of patients with CGM values <70 mg/dL (36% vs. 39%; P = 0.68) or <54 mg/dL (14 vs. 24%; P = 0.12) between the CGM-guided and POC groups. Among patients with one or more hypoglycemic events, compared with POC, the CGM group experienced a significant reduction in hypoglycemia reoccurrence (1.80 ± 1.54 vs. 2.94 ± 2.76 events/patient; P = 0.03), lower percentage of time below range <70 mg/dL (1.89% ± 3.27 vs. 5.47% ± 8.49; P = 0.02), and lower incidence rate ratio <70 mg/dL (0.53 [95% CI 0.31-0.92]) and <54 mg/dL (0.37 [95% CI 0.17-0.83]). CONCLUSIONS: The inpatient use of real-time Dexcom G6 CGM is safe and effective in guiding insulin therapy, resulting in a similar improvement in glycemic control and a significant reduction of recurrent hypoglycemic events compared with POC-guided insulin adjustment.

American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

1-h Glucose During Oral Glucose Tolerance Test Predicts Hyperglycemia Relapse-Free Survival in Obese Black Patients With Hyperglycemic Crises.

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.

Kynurenine Metabolism as a Mechanism to Improve Fatigue and Physical Function in Postmenopausal Breast Cancer Survivors Following Resistance Training.

This pilot examines whether resistance training (RT) can induce changes in kynurenine (KYN) metabolism, which may contribute to improved physical function in breast cancer survivors (BCSs). Thirty-six BCSs (63.2 ± 1.1 years) underwent assessments of physical function and visual analog scale (100 cm) fatigue and quality of life before and after 12 weeks of RT (N = 22) or non-exercise control (CBCT©: Cognitively Based Compassion Training, N = 10). Blood was collected before and after interventions for assessment of KYN, kynurenic acid (KYNA), and peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α). At baseline, the women were moderately fatigued (mean score: 46 cm) and at risk of poor functional mobility. A group*time interaction was observed for all measures of strength with improvements (~25−35%) following RT (p's < 0.01), but not CBCT. Time effects were observed for fatigue (−36%) and quality of life (5%) (p's < 0.01), where both groups improved in a similar manner. A group*time interaction was observed for KYN (p = 0.02) and PGC-1α (p < 0.05), with KYN decreasing and PGC-1α increasing following RT and the opposite following CBCT. These changes resulted in KYN/KYNA decreasing 34% post-RT, but increasing 21% following CBCT. These data support RT as a therapeutic intervention to counteract the long-term side effect of fatigue and physical dysfunction in BCSs. Additionally, the results suggest that this effect may be mediated through the activation of PGC-1α leading to alterations in KYN metabolism.

Accuracy of Dexcom G6 Continuous Glucose Monitoring in Non-Critically Ill Hospitalized Patients With Diabetes.

OBJECTIVE: Advances in continuous glucose monitoring (CGM) have transformed ambulatory diabetes management. Until recently, inpatient use of CGM has remained investigational, with limited data on its accuracy in the hospital setting. RESEARCH DESIGN AND METHODS: To analyze the accuracy of Dexcom G6, we compared retrospective matched-pair CGM and capillary point-of-care (POC) glucose data from three inpatient CGM studies (two interventional and one observational) in general medicine and surgery patients with diabetes treated with insulin. Analysis of accuracy metrics included mean absolute relative difference (MARD), median absolute relative difference (ARD), and proportion of CGM values within 15, 20, and 30% or 15, 20, and 30 mg/dL of POC reference values for blood glucose >100 mg/dL or ≤100 mg/dL, respectively (% 15/15, % 20/20, % 30/30). Clinical reliability was assessed with Clarke error grid (CEG) analyses. RESULTS: A total of 218 patients were included (96% with type 2 diabetes) with a mean age of 60.6 ± 12 years. The overall MARD (n = 4,067 matched glucose pairs) was 12.8%, and median ARD was 10.1% (interquartile range 4.6, 17.6]. The proportions of readings meeting % 15/15, % 20/20, and % 30/30 criteria were 68.7, 81.7, and 93.8%, respectively. CEG analysis showed 98.7% of all values in zones A and B. MARD and median ARD were higher in the case of hypoglycemia (<70 mg/dL) and severe anemia (hemoglobin <7 g/dL). CONCLUSIONS: Our results indicate that CGM technology is a reliable tool for hospital use and may help improve glucose monitoring in non-critically ill hospitalized patients with diabetes.

Clinical Case Report: Dissociation of Clinical Course of Coexisting Autoimmune Hepatitis and Graves Disease.

OBJECTIVE: Concurrent autoimmune disorders, including autoimmune hepatitis (AIH), with Graves disease have been reported. Glucocorticoids can simultaneously lower thyroid hormone levels and treat AIH. Recurrence of hyperthyroidism is associated with recurrence of hepatitis. We present a case of coexisting AIH and Graves thyrotoxicosis, which improved with prednisone, but the thyrotoxicosis recurred during a prednisone taper while the hepatitis stayed in remission. METHODS: Evaluation included measurements of liver enzyme levels, thyroid function tests, and thyroid-stimulating antibodies as well as abdominal ultrasound, magnetic resonance imaging, and liver biopsy. RESULTS: A 47-year-old woman presented with nausea and jaundice. Workup showed an aspartate aminotransferase level of 1956 (reference, 10-42) U/L and alanine aminotransferase level of 1634 (reference, 14-54) IU/L. The liver biopsy was consistent with AIH. Nine months later, she reported palpitations, heat intolerance, and weight loss and was diagnosed with Graves disease. The patient received prednisone at 60 mg daily, and the liver and thyroid functions normalized after 1 month. Prednisone was tapered to 5 mg daily. Seven months later, she presented with a thyroid-stimulating hormone level of 0.049 (reference, 0.340-5.6) µIU/mL) and free thyroxine level of 3.96 (reference, 0.58-1.64) ng/dL. Liver enzymes remained at normal levels. Prednisone was increased from 5 to 20 mg to treat hyperthyroidism. The patient was referred for thyroidectomy for a diagnosis of Graves disease with thyrotoxicosis. CONCLUSION: This case is an example of coexisting autoimmune diseases, Graves disease and AIH, with different clinical courses. Despite initial resolution with glucocorticoid therapy, Graves disease recurred, while AIH stayed in remission.

Sitagliptin for the prevention and treatment of perioperative hyperglycaemia in patients with type 2 diabetes undergoing cardiac surgery: A randomized controlled trial.

AIM: To assess whether treatment with sitagliptin, starting before surgery and continued during the hospital stay, can prevent and reduce the severity of perioperative hyperglycaemia in patients with type 2 diabetes undergoing coronary artery bypass graft (CABG) surgery. MATERIALS AND METHODS: We conducted a double-blinded, placebo-controlled trial in adults with type 2 diabetes randomly assigned to receive sitagliptin or matching placebo starting 1 day prior to surgery and continued during the hospital stay. The primary outcome was difference in the proportion of patients with postoperative hyperglycaemia (blood glucose [BG] > 10 mmol/L [>180 mg/dL]) in the intensive care unit (ICU). Secondary endpoints included differences in mean daily BG in the ICU and after transition to regular wards, hypoglycaemia, hospital complications, length of stay and need of insulin therapy. RESULTS: We included 182 participants randomized to receive sitagliptin or placebo (91 per group, age 64 ± 9 years, HbA1c 7.6% ± 1.5% and diabetes duration 10 ± 9 years). There were no differences in the number of patients with postoperative BG greater than 10 mmol/L, mean daily BG in the ICU or after transition to regular wards, hypoglycaemia, hospital complications or length of stay. There were no differences in insulin requirements in the ICU; however, sitagliptin therapy was associated with lower mean daily insulin requirements (21.1 ± 18.4 vs. 32.5 ± 26.3 units, P = .007) after transition to a regular ward compared with placebo. CONCLUSION: The administration of sitagliptin prior to surgery and during the hospital stay did not prevent perioperative hyperglycaemia or complications after CABG. Sitagliptin therapy was associated with lower mean daily insulin requirements after transition to regular wards.

Comparison of the FreeStyle Libre Pro Flash Continuous Glucose Monitoring (CGM) System and Point-of-Care Capillary Glucose Testing in Hospitalized Patients With Type 2 Diabetes Treated With Basal-Bolus Insulin Regimen.

OBJECTIVE: We compared the performance of the FreeStyle Libre Pro continuous glucose monitoring (CGM) and point-of-care capillary glucose testing (POC) among insulin-treated hospitalized patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a prospective study in adult patients with T2D admitted to general medicine and surgery wards. Patients were monitored with POC before meals and bedtime and with CGM during the hospital stay. Study end points included differences between POC and CGM in mean daily blood glucose (BG), hypoglycemia <70 and <54 mg/dL, and nocturnal hypoglycemia. We also calculated the mean absolute relative difference (MARD), ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL and error grid analysis between matched glucose pairs. RESULTS: Mean daily glucose was significantly higher by POC (188.9 ± 37.3 vs. 176.1 ± 46.9 mg/dL) with an estimated mean difference of 12.8 mg/dL (95% CI 8.3-17.2 mg/dL), and proportions of patients with glucose readings <70 mg/dL (14% vs. 56%) and <54 mg/dL (4.1% vs. 36%) detected by POC BG were significantly lower compared with CGM (all P < 0.001). Nocturnal and prolonged CGM hypoglycemia <54 mg/dL were 26% and 12%, respectively. The overall MARD was 14.8%, ranging between 11.4% and 16.7% for glucose values between 70 and 250 mg/dL and higher for 51-69 mg/dL (MARD 28.0%). The percentages of glucose readings within ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL were 62%, 76%, and 91%, respectively. Error grid analysis showed 98.8% of glucose pairs within zones A and B. CONCLUSIONS: Compared with POC, FreeStyle Libre CGM showed lower mean daily glucose and higher detection of hypoglycemic events, particularly nocturnal and prolonged hypoglycemia in hospitalized patients with T2D. CGM's accuracy was lower in the hypoglycemic range.

A Randomized Controlled Trial Comparing Glargine U300 and Glargine U100 for the Inpatient Management of Medicine and Surgery Patients With Type 2 Diabetes: Glargine U300 Hospital Trial.

OBJECTIVE: The role of U300 glargine insulin for the inpatient management of type 2 diabetes (T2D) has not been determined. We compared the safety and efficacy of glargine U300 versus glargine U100 in noncritically ill patients with T2D. RESEARCH DESIGN AND METHODS: This prospective, open-label, randomized clinical trial included 176 patients with poorly controlled T2D (admission blood glucose [BG] 228 ± 82 mg/dL and HbA1c 9.5 ± 2.2%), treated with oral agents or insulin before admission. Patients were treated with a basal-bolus regimen with glargine U300 (n = 92) or glargine U100 (n = 84) and glulisine before meals. We adjusted insulin daily to a target BG of 70-180 mg/dL. The primary end point was noninferiority in the mean difference in daily BG between groups. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences between glargine U300 and U100 in mean daily BG (186 ± 40 vs. 184 ± 46 mg/dL, P = 0.62), percentage of readings within target BG of 70-180 mg/dL (50 ± 27% vs. 55 ± 29%, P = 0.3), length of stay (median [IQR] 6.0 [4.0, 8.0] vs. 4.0 [3.0, 7.0] days, P = 0.06), hospital complications (6.5% vs. 11%, P = 0.42), or insulin total daily dose (0.43 ± 0.21 vs. 0.42 ± 0.20 units/kg/day, P = 0.74). There were no differences in the proportion of patients with BG <70 mg/dL (8.7% vs. 9.5%, P > 0.99), but glargine U300 resulted in significantly lower rates of clinically significant hypoglycemia (<54 mg/dL) compared with glargine U100 (0% vs. 6.0%, P = 0.023). CONCLUSIONS: Hospital treatment with glargine U300 resulted in similar glycemic control compared with glargine U100 and may be associated with a lower incidence of clinically significant hypoglycemia.

Safety And Efficacy Of Dpp-4 Inhibitors For The Management Of Hospitalized General Medicine And Surgery Patients with Type 2 Diabetes.

OBJECTIVE: DPP-4 inhibitors (DPP-4i) have been shown to be effective for the management of inpatient diabetes. We report pooled data from 3 prospective studies using DPP-4i in general medicine and surgery patients with type 2 diabetes (T2D). METHODS: We combined data from 3 randomized studies comparing DPP-4i alone or in combination with basal insulin or a basal-bolus insulin regimen. Medicine (n = 266) and surgery (n = 319) patients admitted with a blood glucose (BG) between 140 and 400 mg/dL, treated with diet, oral agents, or low-dose insulin therapy were included. Patients received DPP-4i alone (n = 144), DPP-4i plus basal insulin (n = 158) or basal-bolus regimen (n = 283). All groups received correctional doses with rapid-acting insulin for BG >140 mg/dL. The primary endpoint was differences in mean daily BG between groups. Secondary endpoints included differences in hypoglycemia and hospital complications. RESULTS: There were no differences in mean hospital daily BG among patients treated with DPP-4i alone (170 ± 37 mg/dL), DPP-4i plus basal (172 ± 42 mg/dL), or basalbolus (172 ± 43 mg/dL), P = .94; or in the percentage of BG readings within target of 70 to 180 mg/dL (63 ± 32%, 60 ± 31%, and 64 ± 28%, respectively; P = .42). There were no differences in length of stay or complications, but hypoglycemia was less common with DPP-4i alone (2%) compared to DPP-4i plus basal (9%) and basal-bolus (10%); P = .004. CONCLUSION: Treatment with DPP-4i alone or in combination with basal insulin is effective and results in a lower incidence of hypoglycemia compared to a basal-bolus insulin regimen in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; BMI = body mass index; CI = confidence interval; DPP-4i = dipeptidyl peptidase-4 inhibitors; HbA1c = hemoglobin A1c; OR = odds ratio; T2D = type 2 diabetes.

Sitagliptin for the prevention of stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery.

Aims: To determine if treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor, can prevent stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery. Methods: We conducted a pilot, double-blinded, placebo-controlled randomized trial in adults (18-80 years) without history of diabetes. Participants received sitagliptin or placebo once daily, starting the day prior to surgery and continued for up to 10 days. Primary outcome was differences in the frequency of stress hyperglycemia (blood glucose (BG) >180 mg/dL) after surgery among groups. Results: We randomized 32 participants to receive sitagliptin and 28 to placebo (mean age 64±10 years and HbA1c: 5.6%±0.5%). Treatment with sitagliptin resulted in lower BG levels prior to surgery (101±mg/dL vs 107±13 mg/dL, p=0.01); however, there were no differences in the mean BG concentration, proportion of patients who developed stress hyperglycemia (21% vs 22%, p>0.99), length of hospital stay, rate of perioperative complications and need for insulin therapy in the intensive care unit or during the hospital stay. Conclusion: The use of sitagliptin during the perioperative period did not prevent the development of stress hyperglycemia or need for insulin therapy in patients without diabetes undergoing CABG surgery.

A Randomized Controlled Trial on the Safety and Efficacy of Exenatide Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes.

OBJECTIVE: This multicenter, open-label, randomized trial examined the safety and efficacy of exenatide alone or in combination with basal insulin in non-critically ill patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 150 patients with blood glucose (BG) between 140 and 400 mg/dL, treated at home with diet, oral agents, or insulin at a total daily dose <0.5 units/kg, were randomized to exenatide alone (5 µg twice daily), exenatide plus basal insulin, or a basal-bolus insulin regimen. The primary end point was difference in mean daily BG concentration among groups. RESULTS: Mean daily BG was similar between patients treated with exenatide plus basal and a basal-bolus regimen (154 ± 39 vs. 166 ± 40 mg/dL, P = 0.31), and exenatide plus basal resulted in lower daily BG than did exenatide alone (177 ± 41 mg/dL, P = 0.02). Exenatide plus basal resulted in a higher proportion of BG levels in target range between 70 and 180 mg/dL compared with exenatide and basal-bolus (78% vs. 62% vs. 63%, respectively, P = 0.023). More patients in the exenatide and exenatide plus basal groups experienced nausea or vomiting than in the basal-bolus group (10% vs. 11% vs. 2%, P = 0.17), with three patients (6%) discontinued exenatide owing to adverse events. There were no differences in hypoglycemia <54 mg/dL (2% vs. 0% vs. 4%, P = 0.77) or length of stay (5 vs. 4 vs. 4 days, P = 0.23) among basal plus exenatide, exenatide, and basal-bolus groups. CONCLUSIONS: The results of this pilot study indicate that exenatide alone or in combination with basal insulin is safe and effective for the management of hospitalized general medical and surgical patients with T2D.

Glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in patients with type 2 diabetes undergoing non-cardiac surgery: A multicentre randomized clinical trial.

AIMS: The use of incretin-based therapy, rather than or complementary to, insulin therapy is an active area of research in hospitalized patients with type 2 diabetes (T2D). We determined the glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in hospitalized surgical patients with T2D. MATERIALS AND METHODS: This prospective open-label multicentre study randomized T2D patients undergoing non-cardiac surgery with admission blood glucose (BG) of 7.8 to 22.2 mmol/L who were under treatment with diet, oral agents or total insulin dose (TDD) ≤ 0.5 units/kg/day to either linagliptin (n = 128) daily or basal-bolus (n = 122) with glargine once daily and rapid-acting insulin before meals. Both groups received supplemental insulin for BG > 7.8 mmol/L. The primary endpoint was difference in mean daily BG between groups. RESULTS: Mean daily BG was higher in the linagliptin group compared to the basal-bolus group (9.5 ± 2.6 vs 8.8 ± 2.3 mmol/L/dL, P = 0.03) with a mean daily BG difference of 0.6 mmol/L (95% confidence interval 0.04, 1.2). In patients with randomization BG < 11.1 mmol/L (63% of cohort), mean daily BG was similar in the linagliptin and basal-bolus groups (8.9 ± 2.3 vs 8.7 ± 2.3 mmol/L, P = 0.43); however, patients with BG ≥ 11.1 mmol/L who were treated with linagliptin had higher BG compared to the basal-bolus group (10.9 ± 2.6 vs 9.2 ± 2.2 mmol/L, P < 0.001). Linagliptin resulted in fewer hypoglycaemic events (1.6% vs 11%, P = 0.001; 86% relative risk reduction), with similar supplemental insulin and fewer daily insulin injections (2.0 ± 3.3 vs 3.1 ± 3.3, P < 0.001) compared to the basal-bolus group. CONCLUSIONS: For patients with T2D undergoing non-cardiac surgery who presented with mild to moderate hyperglycaemia (BG < 11.1 mmol/L), daily linagliptin is a safe and effective alternative to multi-dose insulin therapy, resulting in similar glucose control with lower hypoglycaemia.

Sitagliptin for prevention of stress hyperglycemia in patients without diabetes undergoing general surgery: A pilot randomized study.

AIM: We investigated if a dipeptidyl peptidase-4 inhibitor, sitagliptin, can prevent perioperative stress hyperglycemia in patients without prior history of diabetes mellitus undergoing general surgery. METHODS: This double-blind pilot trial randomized general surgery patients to receive sitagliptin (n = 44) or placebo (n = 36) once daily, starting one day prior to surgery and continued during the hospital stay. The primary outcome was occurrence of stress hyperglycemia, defined by blood glucose (BG) >140 mg/dL and >180 mg/dL after surgery. Secondary outcomes included: length-of-stay, ICU transfers, hypoglycemia, and hospital complications. RESULTS: BG >140 mg/dL was present in 44 (55%) of subjects following surgery. There were no differences in hyperglycemia between placebo and sitagliptin (56% vs. 55%, p = 0.93). BG >180 mg/dL was observed in 19% and 11% of patients treated with placebo and sitagliptin, respectively, p = 0.36. Both treatment groups had resulted in similar postoperative BG (148.9 ±â€¯29.4 mg/dL vs. 146.9 ±â€¯35.2 mg/dL, p = 0.73). There were no differences in length-of-stay (4 vs. 3 days, p = 0.84), ICU transfer (3% vs. 5%, p = 1.00), hypoglycemia <70 mg/dL (6% vs. 11%, p = 0.45), and complications (14% vs. 18%, p = 0.76). CONCLUSION: Preoperative treatment with sitagliptin did not prevent stress hyperglycemia or complications in individuals without diabetes undergoing surgery.

Diabetes mellitus and insulin resistance in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE(S): To analyze whether first-degree relatives (FDR) of patients with polysystic ovary syndrome (PCOS) have an increased risk of insulin resistance and glucose intolerance. DESIGN: Systematic review and meta-analysis. SETTING: None. PATIENT(S): Parents and siblings of women with and without PCOS. INTERVENTION(S): Search of PubMed database from 1960 to September 2017 with cross-checking of references of relevant articles in English. MAIN OUTCOME MEASURE(S): Prevalence of type 2 diabetes mellitus (T2DM) and impaired glucose tolerance, and levels of fasting insulin, 2-hour insulin levels, and homeostatic model assessment insulin resistance (HOMA IR). RESULT(S): Our search retrieved 4,796 articles of which 19 were included. The prevalence of T2DM was significantly increased in mothers and fathers of PCOS probands (rate ratio [RR] 2.43; 95% confidence interval [CI], 1.58-3.75, and RR 2.27; 95% CI, 1.25-4.12). Moreover, the fasting insulin (in mothers, fathers, and sisters) and HOMA IR (in mothers, fathers, and sisters) levels were statistically significantly higher in parents and siblings of PCOS patients. The sisters (RR 1.34; 95% CI, 0.59-3.03) and brothers (RR 1.51; 95% CI, 0.63-3.62) had a higher prevalence of T2DM than the control subjects, but the difference was not statistically significant. CONCLUSION(S): Our meta-analysis provides quantitative evidence demonstrating clustering of T2DM and insulin resistance in the parents and siblings of PCOS probands. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2016 CRD42016048551.

THE EFFICACY AND SAFETY OF CO-ADMINISTRATION OF SITAGLIPTIN WITH METFORMIN IN PATIENTS WITH TYPE 2 DIABETES AT HOSPITAL DISCHARGE.

OBJECTIVE: Few randomized controlled trials have focused on the optimal management of patients with type 2 diabetes (T2D) during the transition from the inpatient to outpatient setting. This multicenter open-label study explored a discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in general medicine and surgery patients with T2D. METHODS: Patients with HbA1c ≤7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53-75 mmol/mol) and those >9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge. RESULTS: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 ± 2.3% and decreased to 7.30 ± 1.5% and 7.30 ± 1.7% at 3 and 6 months ( P<.001). Patients with HbA1c <7% went from 6.3 ± 0.5% to 6.3 ± 0.80% and 6.2 ± 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction from 8.0 ± 0.6% to 7.3 ± 1.1% and 7.3 ± 1.3%, and those with HbA1c >9% from 11.3 ± 1.7% to 8.0 ± 1.8% and 8.0 ± 2.0% at 3 and 6 months after discharge (both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in 4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose <40 mg/dL was reported in <1% in all groups. CONCLUSION: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes.

Metabolic syndrome, hypertension, and hyperlipidemia in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To provide an evidence-based assessment of metabolic syndrome, hypertension, and hyperlipidemia in first-degree relatives of women with polycystic ovary syndrome (PCOS). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Mothers, fathers, sisters, and brothers of women with and without PCOS. INTERVENTION(S): An electronic-based search with the use of PubMed from 1960 to June 2015 and cross-checked references of relevant articles. MAIN OUTCOME MEASURE(S): Metabolic syndrome, hypertension and dyslipidemia, and surrogate markers, including systolic blood pressure (BP), diastolic BP, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. RESULT(S): Fourteen of 3,346 studies were included in the meta-analysis. Prevalence of the following was significantly increased in relatives of women with PCOS: metabolic syndrome (risk ratio [RR] 1.78 [95% confidence interval 1.37, 2.30] in mothers, 1.43 [1.12, 1.81] in fathers, and 1.50 [1.12, 2.00] in sisters), hypertension (RR 1.93 [1.58, 2.35] in fathers, 2.92 [1.92, 4.45] in sisters), and dyslipidemia (RR 3.86 [2.54, 5.85] in brothers and 1.29 [1.11, 1.50] in fathers). Moreover, systolic BP (mothers, sisters, and brothers), total cholesterol (mothers and sisters), low-density lipoprotein cholesterol (sisters), and triglycerides (mothers and sisters) were significantly higher in first-degree relatives of PCOS probands than in controls. CONCLUSION(S): Our results show evidence of clustering for metabolic syndrome, hypertension, and dyslipidemia in mothers, fathers, sisters, and brothers of women with PCOS. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2016 CRD42016048557.

Stress hyperglycemia in general surgery: Why should we care?

AIMS: To determine the frequency of increasing levels of stress hyperglycemia and its associated complications in surgery patients without a history of diabetes. METHODS: We reviewed hospital outcomes in 1971 general surgery patients with documented preoperative normoglycemia [blood glucose (BG) <140mg/dL] who developed stress hyperglycemia (BG >140mg/dL or >180mg/dL) within 48h after surgery between 1/1/2010 and 10/31/2015. RESULTS: A total of 415 patients (21%) had ≥1 episode of BG between 140 and 180mg/dL and 206 patients (10.5%) had BG>180mg/dL. The median length of hospital stay (LOS) was 9days [interquartile range (IQR) 5,15] for BG between 140 and 180mg/dL and 12days (IQR 6,18) for BG>180mg/dL compared to normoglycemia at 6days (IQR 4,11), both p<0.001. Patients with BG 140-180mg/dL had higher rates of complications with an odds ratio (OR) of 1.68 [95% confidence interval (95% CI) 1.15-2.44], and those with BG>180mg/dL had more complications [OR 3.46 (95% CI 2.24-5.36)] and higher mortality [OR 6.56 (95% CI 2.12-20.27)] compared to normoglycemia. CONCLUSION: Increasing levels of stress hyperglycemia are associated with higher rates of perioperative complications and hospital mortality in surgical patients without diabetes.

Clinical characteristics and outcomes of symptomatic and asymptomatic hypoglycemia in hospitalized patients with diabetes.

IMPORTANCE: The frequency and impact of asymptomatic hypoglycemia in hospitalized patients with diabetes is not known. OBJECTIVE: We determined the clinical characteristics and hospital outcomes of general medicine and surgery patients with symptomatic and asymptomatic hypoglycemia. RESEARCH DESIGN AND METHODS: Prospective observational study in adult patients with diabetes and blood glucose (BG) <70 mg/dL. Participants were interviewed about signs and symptoms of hypoglycemia using a standardized questionnaire. Precipitating causes, demographics, insulin regimen, and complications data during admission was collected. RESULTS: Among 250 patients with hypoglycemia, 112 (44.8%) patients were asymptomatic and 138 (55.2%) had symptomatic hypoglycemia. Patients with asymptomatic hypoglycemia were older (59±11 years vs 54.8±13 years, p=0.003), predominantly males (63% vs 48%, p=0.014), and had lower admission glycosylated hemoglobin (8.2%±2.6 % vs 9.1±2.9%, p=0.006) compared with symptomatic patients. Compared with symptomatic patients, those with asymptomatic hypoglycemia had higher mean BG during the episode (60.0±8 mg/dL vs 53.8±11 mg/dL, p<0.001). In multivariate analysis, male gender (OR 2.08, 95% CI 1.13 to 3.83, p=0.02) and age >65 years (OR 4.01, 95% CI 1.62 to 9.92, p=0.02) were independent predictors of asymptomatic hypoglycemia. There were no differences in clinical outcome, composite of hospital complications (27% vs 22%, p=0.41) or in-hospital length of stay (8 days (IQR 4-14) vs 7 days (IQR 5-15), p=0.92)) between groups. CONCLUSIONS: Asymptomatic hypoglycemia was common among insulin-treated patients with diabetes but was not associated with worse clinical outcome compared with patients with symptomatic hypoglycemia. Older age and male gender were independent risk factors for asymptomatic hypoglycemia.