Comparing Data-Independent Acquisition and Parallel Reaction Monitoring in Their Abilities To Differentiate High-Density Lipoprotein Subclasses.

High-density lipoprotein (HDL) is a diverse group of particles with multiple cardioprotective functions. HDL proteome follows HDL particle complexity. Many proteins were described in HDL, but consistent quantification of HDL protein cargo is still a challenge. To address this issue, the aim of this work was to compare data-independent acquisition (DIA) and parallel reaction monitoring (PRM) methodologies in their abilities to differentiate HDL subclasses through their proteomes. To this end, we first evaluated the analytical performances of DIA and PRM using labeled peptides in pooled digested HDL as a biological matrix. Next, we compared the quantification capabilities of the two methodologies for 24 proteins found in HDL2 and HDL3 from 19 apparently healthy subjects. DIA and PRM exhibited comparable linearity, accuracy, and precision. Moreover, both methodologies worked equally well, differentiating HDL subclasses' proteomes with high precision. Our findings may help to understand HDL functional diversity.

A Prospective Randomized Controlled Trial of the Metabolic Effects of Sleeve Gastrectomy with Transit Bipartition.

PURPOSE: To compare the effects of the sleeve gastrectomy with transit bipartition (SG + TB) procedure with standard medical therapy (SMT) in mildly obese patients with type II diabetes (T2D). METHODS: This is a prospective, randomized, controlled trial. Twenty male adults, ≤ 65 years old, with T2D, body mass index (BMI) > 28 kg/m2 and < 35 kg/m2, and HbA1c level > 8% were randomized to SG + TB or to SMT. Outcomes were the remission in the metabolic and cardiovascular risk variables up to 24 months. RESULTS: At 24 months, SG + TB group showed a significant decrease in HbaA1c values (9.3 ± 2.1 versus 5.5 ± 1.1%, P = < 0.05) whereas SMT group maintained similar levels from baseline (8.0 ± 1.5 versus 8.3 ± 1.1%, P = NS). BMI values were lower in the SG + TB group (25.3 ± 2.8 kg/m2 versus 30.9 ± 2.5 kg/m2; P = < 0.001). At 24 months, none patient in SG + TB group needed medications for hyperlipidemia/hypertension. HDL-cholesterol levels increased in the SG + TB group (33 ± 8 to 45 ± 15 mg/dL, P < 0.001). After 24 months, the area under the curve (AUC) of GLP1 increased and in the SG + TB group and the AUC of the GIP concentrations was lower in the SG + TB group than in the SMT. At 3 months, SG + TB group showed a marked increase in FGF19 levels (74.1 ± 45.8 to 237.3 ± 234 pg/mL; P = 0.001). CONCLUSIONS: SG + TB is superior to SMT and was associated with a better metabolic and cardiovascular profile.

A randomized controlled trial comparing treatment with oral agents and basal insulin in elderly patients with type 2 diabetes in long-term care facilities.

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/m(2), 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.

Randomized study comparing a Basal-bolus with a basal plus correction insulin regimen for the hospital management of medical and surgical patients with type 2 diabetes: basal plus trial.

OBJECTIVE: Effective and easily implemented insulin regimens are needed to facilitate hospital glycemic control in general medical and surgical patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This multicenter trial randomized 375 patients with T2D treated with diet, oral antidiabetic agents, or low-dose insulin (≤ 0.4 units/kg/day) to receive a basal-bolus regimen with glargine once daily and glulisine before meals, a basal plus regimen with glargine once daily and supplemental doses of glulisine, and sliding scale regular insulin (SSI). RESULTS: Improvement in mean daily blood glucose (BG) after the first day of therapy was similar between basal-bolus and basal plus groups (P = 0.16), and both regimens resulted in a lower mean daily BG than did SSI (P = 0.04). In addition, treatment with basal-bolus and basal plus regimens resulted in less treatment failure (defined as >2 consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL) than did treatment with SSI (0 vs. 2 vs. 19%, respectively; P < 0.001). A BG <70 mg/dL occurred in 16% of patients in the basal-bolus group, 13% in the basal plus group, and 3% in the SSI group (P = 0.02). There was no difference among the groups in the frequency of severe hypoglycemia (<40 mg/dL; P = 0.76). CONCLUSIONS: The use of a basal plus regimen with glargine once daily plus corrective doses with glulisine insulin before meals resulted in glycemic control similar to a standard basal-bolus regimen. The basal plus approach is an effective alternative to the use of a basal-bolus regimen in general medical and surgical patients with T2D.

Exon 3-deleted genotype of growth hormone receptor (GHRd3) positively influences IGF-1 increase at generation test in children with idiopathic short stature.

CONTEXT: A GHR-exon 3 polymorphism has been reported to influence the growth response to hGH therapy in short stature children. None of these studies provided data on IGF-1 generation test. OBJECTIVE: To evaluate the influence of the GHR-exon 3 polymorphism on the generation test in children with idiopathic short stature (ISS). DESIGN AND PATIENTS: A total of 45 prepubertal ISS children were submitted to IGF-1 and IGFBP-3 generation test (4 days of hGH 33 microg/kg/day). Children were genotyped for GHR-exon 3: full-length (fl) and exon 3-deleted (d3) alleles. MEASUREMENTS: IGF-1 and IGFBP-3 increment as absolute values and standard deviation scores (SDS). RESULTS: Basal clinical and laboratory data were similar among patients with different genotypes (fl/fl vs. fl/d3 or d3/d3). All patients presented IGF-1 increase >or= 15 microg/l at generation test. Children with GHRd3 allele, as a group, presented a statistically significant higher IGF-1 SDS increase at generation test than children homozygous for GHRfl allele (1.0 ranging from 0.1 to 3.7 for fl/fl vs. 1.2 ranging from 0.3 to 4.4 for fl/d3 and d3/d3; P = 0.037). Multiple linear regression found a positive association between increase in IGF-1 SDS with chronological age (P = 0.007) and GHR genotype (P = 0.027), which together explain 24% of the variability of IGF-1 SDS increment at generation test. There was no difference in IGFBP-3 generation test between the two genotype groups. CONCLUSION: This study demonstrates that ISS children carrying the GHRd3 allele, as a group, present a slightly higher GH sensitivity regarding short-term IGF-1 generation during hGH stimulus than children homozygous for GHRfl allele.