Modulation of coronary heart disease risk by insulin resistance in subjects with normal glucose tolerance or prediabetes
2014; 51 (6): 1033-1039
Effect of liraglutide administration and a calorie-restricted diet on lipoprotein profile in overweight/obese persons with prediabetes.
Nutrition, metabolism, and cardiovascular diseases : NMCD
2014; 24 (12): 1317-1322
Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study.
2014; 37 (7): 1944-1950
To evaluate the effects of 14 weeks of liraglutide plus modest caloric restriction on lipid/lipoprotein metabolism in overweight/obese persons with prediabetes.Volunteers with prediabetes followed a calorie-restricted diet (-500 Kcal/day) plus liraglutide (n = 23) or placebo (n = 27) for 14 weeks. The groups were similar in age (58 ± 7 vs. 58 ± 8 years) and body mass index (31.9 ± 2.8 vs. 31.9 ± 3.5 kg/m(2)). A comprehensive lipid/lipoprotein profile was obtained before and after intervention using vertical auto profile (VAP). Weight loss was greater in the liraglutide group than in the placebo group (6.9 vs. 3.3 kg, p < 0.001), as was the fall in fasting plasma glucose concentration (9.9 mg/dL vs. 0.3 mg/dL, p < 0.001). VAP analysis revealed multiple improvements in lipid/lipoprotein metabolism in liraglutide-treated compared with placebo-treated volunteers, including decreases in concentrations of total cholesterol, low-density lipoprotein cholesterol and several of its subclasses, triglyceride, and non-high-density cholesterol. The liraglutide-treated group also had a significant shift away from small, dense low-density lipoprotein-particles, as well as decreases in apolipoprotein B concentration and ratio of apolipoprotein B/apolipoprotein A-1. There were no significant changes in the lipoprotein profile in the placebo-treated group.Treatment with liraglutide plus modest calorie restriction led to enhanced weight loss, a decrease in fasting plasma glucose concentration, and improvement in multiple aspects of lipid/lipoprotein metabolism associated with increased cardiovascular disease (CVD) risk. The significant clinical benefit associated with liraglutide-assisted weight loss in a group at high risk for CVD - obese/overweight individuals with prediabetes - as seen in our pilot study, suggests that this approach deserves further study.
View details for DOI 10.1016/j.numecd.2014.06.010
View details for PubMedID 25280957
Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study
2014; 57 (3): 455-462
Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance.This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment.Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change -7% [95% CI -10 to -14] vs. 1% [-3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (-25% [-34 to -15] vs. -6% [-26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (-23% [-30 to -16] vs. 3% [-10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms.Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion.
View details for DOI 10.2337/dc13-2977
View details for PubMedID 24963111
CLINICAL CHARACTERISTICS AND PITUITARY DYSFUNCTION IN PATIENTS WITH METASTATIC CANCER TO THE SELLA
2013; 19 (6): 914-919
Liraglutide can modulate insulin secretion by directly stimulating beta cells or indirectly through weight loss and enhanced insulin sensitivity. Recently, we showed that liraglutide treatment in overweight individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) led to greater weight loss (-7.7% vs -3.9%) and improvement in insulin resistance compared with placebo. The current study evaluates the effects on beta cell function of weight loss augmented by liraglutide compared with weight loss alone.This was a parallel, randomised study conducted in a single academic centre. Both participants and study administrators were blinded to treatment assignment. Individuals who were 40-70 years old, overweight (BMI 27-40 kg/m(2)) and with prediabetes were randomised (via a computerised system) to receive liraglutide (n = 35) or matching placebo (n = 33), and 49 participants were analysed. All were instructed to follow an energy-restricted diet. Primary outcome was insulin secretory function, which was evaluated in response to graded infusions of glucose and day-long mixed meals.Liraglutide treatment (n = 24) significantly (p ≤ 0.03) increased the insulin secretion rate (% mean change [95% CI]; 21% [12, 31] vs -4% [-11, 3]) and pancreatic beta cell sensitivity to intravenous glucose (229% [161, 276] vs -0.5% (-15, 14]), and decreased insulin clearance rate (-3.5% [-11, 4] vs 8.2 [0.2, 16]) as compared with placebo (n = 25). The liraglutide-treated group also had significantly (p ≤ 0.03) lower day-long glucose (-8.2% [-11, -6] vs -0.1 [-3, 2]) and NEFA concentrations (-14 [-20, -8] vs -2.1 [-10, 6]) following mixed meals, whereas day-long insulin concentrations did not significantly differ as compared with placebo. In a multivariate regression analysis, weight loss was associated with a decrease in insulin secretion rate and day-long glucose and insulin concentrations in the placebo group (p ≤ 0.05), but there was no association with weight loss in the liraglutide group. The most common side effect of liraglutide was nausea.A direct stimulatory effect on beta cell function was the predominant change in liraglutide-augmented weight loss. These changes appear to be independent of weight loss.ClinicalTrials.gov NCT01784965 FUNDING: The study was funded by the ADA.
View details for DOI 10.1007/s00125-013-3134-3
View details for Web of Science ID 000331558400003
Benefits of Liraglutide Treatment in Overweight and Obese Older Individuals With Prediabetes
2013; 36 (10): 3276-3282
Objective: Metastatic disease to the sella is uncommon and there are limited available data regarding the clinical aspects of this disease. We sought to characterize the clinical demographics of sellar metastases.Methods: Retrospective chart review of adults at Stanford University Medical Center from 1980 to 2011 with metastatic disease to the sella.Results: 13 subjects were identified (9 F). The mean age at diagnosis was 55 years (range: 25-73 y). 6 (46%) had breast carcinoma, 3 (23%) had renal cell carcinoma, 2 (15%) had squamous cell carcinoma of the head and neck, 1 had bronchoalveolar carcinoma of the lung, and 1 had nodular sclerosing Hodgkin's lymphoma. The most common presenting signs and symptoms were headache (58%), followed by fatigue (50%), polyuria (50%), visual field defects (42%), and ophthalmoplegia (42%). 75% presented with at least one pituitary hormone insufficiency, including 6 (50%) with diabetes insipidus (DI). 8 (67%) subjects had secondary hypothyroidism, and 5 (45%) had secondary adrenal insufficiency. Of the patients with stalk involvement, 86% had DI. All patients had a prior diagnosis of malignancy for a mean duration of 95 months.Conclusion: In this retrospective review, the most common neoplastic sources to the sella were breast and renal cell carcinoma. Secondary hypothyroidism was the most common endocrine abnormality, followed by DI, and adrenal insufficiency. New onset central hypothyroidism and diabetes insipidus along with known malignancy in a patient with a sellar lesion should raise the suspicion of a metastatic source.
View details for DOI 10.4158/EP12407.OR
View details for Web of Science ID 000327645900010
View details for PubMedID 23757610
Relations between obesity, insulin resistance, and 25-hydroxyvitamin D
AMERICAN JOURNAL OF CLINICAL NUTRITION
2012; 95 (5): 1055-1059
OBJECTIVEThe aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance, cardiovascular disease (CVD) risk factors, and inflammation in a high-risk population for type 2 diabetes (T2DM) and CVD.RESEARCH DESIGN AND METHODSWe randomized 68 older individuals (mean age, 58 ± 8 years) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks. All subjects were advised to decrease calorie intake by 500 kcal/day. Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Traditional CVD risk factors and inflammatory markers also were assessed.RESULTSEleven out of 35 individuals (31%) assigned to liraglutide discontinued the study compared with 6 out of 33 (18%) assigned to placebo (P = 0.26). Subjects who continued to use liraglutide (n = 24) lost twice as much weight as those using placebo (n = 27; 6.8 vs. 3.3 kg; P < 0.001). Liraglutide-treated subjects also had a significant improvement in SSPG concentration (-3.2 vs. 0.2 mmol/L; P < 0.001) and significantly (P ≤ 0.04) greater lowering of systolic blood pressure (-8.1 vs. -2.6 mmHg), fasting glucose (-0.5 vs. 0 mmol/L), and triglyceride (-0.4 vs. -0.1 mmol/L) concentration. Inflammatory markers did not differ between the two groups, but pulse increased after liraglutide treatment (6.4 vs. -0.9 bpm; P = 0.001).CONCLUSIONSThe addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance, systolic blood pressure, glucose, and triglyceride concentration in this population at high risk for development of T2DM and CVD.
View details for DOI 10.2337/dc13-0354
View details for Web of Science ID 000324749500073
The role and regulation of microRNAs in asthma
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY
2012; 12 (1): 49-52
Although low circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance and obesity, the relations between these 3 variables have not been completely resolved.The objective was to compare circulating 25(OH)D concentrations in apparently healthy individuals who were matched for degree of obesity or insulin sensitivity.This was a case-control study in which 78 apparently healthy individuals were classified as being normal weight (NW) or obese (OB) on the basis of their BMI and as being insulin sensitive (IS) or insulin resistant (IR) on the basis of their steady state plasma glucose (SSPG) concentration during the insulin suppression test.Groups did not differ in terms of age, sex distribution, race, or mean (± SD) plasma 25(OH)D concentration. Values for 25(OH)D were 32 ± 10, 30 ± 10, and 28 ± 8 ng/mL in NW-IS, OB-IS, and OB-IR groups, respectively. These concentrations were essentially identical when comparing IR with IS subjects matched for BMI or when comparing OB with NW subjects matched for SSPG. Concentrations of 25(OH)D ? 30 ng/mL were somewhat more common in OB subjects than in NW subjects (54% compared with 35%), but SSPG concentrations were not different within either the IR or IS groups when subgroups with 25(OH)D concentrations ? 30 or > 30 ng/mL were compared.In 78 individuals, 47% of whom were vitamin D deficient or insufficient (? 30 ng/mL), 25(OH)D concentrations did not vary with differences in insulin sensitivity (SSPG concentration) when matched for BMI (OB-IR compared with OB-IS). Similarly, when matched for SSPG concentrations, plasma 25(OH)D concentrations were not different in NW or OB individuals (NW-IS compared with OB-IS).
View details for DOI 10.3945/ajcn.111.032060
View details for Web of Science ID 000303140700010
View details for PubMedID 22440850
Simulation-based training is superior to problem-based learning for the acquisition of critical assessment and management skills
CRITICAL CARE MEDICINE
2006; 34 (1): 151-157
Asthma is a common chronic inflammatory airway disorder that is characterized by variable and recurring airflow obstruction, chronic airway inflammation and bronchial hyper-responsiveness. The etiopathogenesis of asthma remains a complex issue. The intricacy in developing a more effective therapeutic strategy may be due to a large diversity in causative agents and a lack of understanding of the precise molecular mechanism involved in asthma. However, recent identification of microRNAs (miRs) has enhanced technological abilities to understand the disease process.miRs regulate gene expression by controlling the translation of a specific type of messenger RNA. miRs have been recently identified as key regulatory RNAs with immense significance in numerous biological processes including asthma. miRs have been implicated to have a fundamental role in acute and chronic asthma and in airway remodeling by the regulation of multiple signal transduction pathways that are involved in the pathogenesis of asthma. It is possible that miRs may bring a fundamental change to our understanding of the pathophysiology of asthma. This may then lead to the development of novel efficacious therapeutic strategies in asthma.In this review, we highlight the current understanding of the role and regulation of miRs in asthma.
View details for DOI 10.1097/ACI.0b013e32834ecb7f
View details for Web of Science ID 000299110000009
View details for PubMedID 22157155
To determine whether full-scale simulation (SIM) is superior to interactive problem-based learning (PBL) for teaching medical students acute care assessment and management skills.Randomized controlled trial.Simulation center at a U.S. medical school.Thirty-one fourth-year medical students in a week-long acute care course.After institutional review board approval and informed consent, eligible students were randomized to either the SIM or PBL group. On day 1, all subjects underwent a simulator-based initial assessment designed to evaluate their critical care skills. Two blinded investigators assessed each student using a standardized checklist. Subsequently, the PBL group learned about dyspnea in a standard PBL format. The SIM group learned about dyspnea using the simulator. To equalize simulator education time, the PBL group learned about acute abdominal pain on the simulator, whereas the SIM group used the PBL format. On day 5, each student was tested on a unique dyspnea scenario.Mean initial assessment and final assessment checklist scores and their change for the SIM and PBL groups were compared using the Student's t-test. A p < .05 was considered significant. The SIM and PBL groups had similar mean (PBL 0.44, SIM 0.47, p = .64) initial assessment scores (earned score divided by maximum score) and were deemed equivalent. The SIM group performed better than the PBL group on the final assessment (mean, PBL 0.53, SIM 0.72, p < .0001). When each student's change in score (percent correct on final assessment minus percent correct on the initial assessment) was compared, SIM group students performed better (mean improvement, SIM 25 percentage points vs. PBL 8 percentage points, p < .04)For fourth-year medical students, simulation-based learning was superior to problem-based learning for the acquisition of critical assessment and management skills.
View details for DOI 10.1097/01.CCM.0000190619.42013.94
View details for Web of Science ID 000234381900020
View details for PubMedID 16374169