Dataset Information

Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study.

ABSTRACT:

Objective

To compare effects of medications and laparoscopic gastric band surgery (LB) on α-cell function in dysglycemic youth and adults in the Restoring Insulin Secretion (RISE) Study protocols.

Research design and methods

Glucagon was measured in three randomized, parallel, clinical studies: 1) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; 2) 267 adults studied at the same time points and treated with MET, G/M, or liraglutide plus metformin (L+M) or given placebo (PLAC); and 3) 88 adults studied at baseline and after 12 and 24 months of LB or MET. Fasting glucagon, glucagon suppression by glucose, and acute glucagon response (AGR) to arginine were assessed during hyperglycemic clamps. Glucagon suppression was also measured during oral glucose tolerance tests (OGTTs).

Results

No change in fasting glucagon, steady-state glucagon, or AGR was seen at 12 months following treatment with MET or G/M (in youth and adults) or PLAC (in adults). In contrast, L+M reduced these measures at 12 months (all P ≤ 0.005), which was maintained 3 months after treatment withdrawal (all P < 0.01). LB in adults also reduced fasting glucagon, steady-state glucagon, and AGR at 12 and 24 months (P < 0.05 for all, except AGR at 12 months [P = 0.098]). Similarly, glucagon suppression during OGTTs was greater with L+M and LB. Linear models demonstrated that treatment effects on glucagon with L+M and LB were largely associated with weight loss.

Conclusions

Glucagon concentrations were reduced by L+M and LB in adults with dysglycemia, an effect principally attributable to weight loss in both interventions.

SUBMITTER: Kahn SE

PROVIDER: S-EPMC8740921 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study.

Kahn Steven E SE Edelstein Sharon L SL Arslanian Silva A SA Barengolts Elena E Caprio Sonia S Ehrmann David A DA Hannon Tamara S TS Marcovina Santica S Mather Kieren J KJ Nadeau Kristen J KJ Utzschneider Kristina M KM Xiang Anny H AH Buchanan Thomas A TA

Diabetes care 20210616 9

<h4>Objective</h4>To compare effects of medications and laparoscopic gastric band surgery (LB) on α-cell function in dysglycemic youth and adults in the Restoring Insulin Secretion (RISE) Study protocols.<h4>Research design and methods</h4>Glucagon was measured in three randomized, parallel, clinical studies: <i>1</i>) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; <i>2</i>) 267 adults studi ...[more]

PMID: 34135015

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Project description:ObjectiveTo determine whether β-cell hyperresponsiveness and insulin resistance in youth versus adults in the Restoring Insulin Secretion (RISE) Study are related to increased glucagon release.Research design and methodsIn 66 youth and 350 adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (drug naive), we performed hyperglycemic clamps and oral glucose tolerance tests (OGTTs). From clamps we quantified insulin sensitivity (M/I), plasma fasting glucagon and C-peptide, steady-state glucagon and C-peptide at glucose of 11.1 mmol/L, and arginine-stimulated glucagon (acute glucagon response [AGR]) and C-peptide (ACPRmax) responses at glucose >25 mmol/L.ResultsMean ± SD fasting glucagon (7.63 ± 3.47 vs. 8.55 ± 4.47 pmol/L; P = 0.063) and steady-state glucagon (2.24 ± 1.46 vs. 2.49 ± 1.96 pmol/L, P = 0.234) were not different in youth and adults, respectively, while AGR was lower in youth (14.1 ± 5.2 vs. 16.8 ± 8.8 pmol/L, P = 0.001). Significant age-group differences in insulin sensitivity, fasting C-peptide, steady-state C-peptide, and ACPRmax were not related to glucagon. Fasting glucose and glucagon were positively correlated in adults (r = 0.133, P = 0.012) and negatively correlated in youth (r = -0.143, P = 0.251). In both age-groups, higher fasting glucagon was associated with higher fasting C-peptide (youth r = 0.209, P = 0.091; adults r = 0.335, P < 0.001) and lower insulin sensitivity (youth r = -0.228, P = 0.066; adults r = -0.324, P < 0.001). With comparable fasting glucagon, youth had greater C-peptide and lower insulin sensitivity. OGTT suppression of glucagon was greater in youth.ConclusionsYouth with IGT or recently diagnosed type 2 diabetes (drug naive) have hyperresponsive β-cells and lower insulin sensitivity, but their glucagon concentrations are not increased compared with those in adults. Thus, α-cell dysfunction does not appear to explain the difference in β-cell function and insulin sensitivity in youth versus adults.

Project description:BackgroundObesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults.Subjects and methodsWe evaluated 66 pubertal youth (mean ± SD: age 14.2 ± 2.0 years, body mass index [BMI] 36.6 ± 6.0 kg/m2 , hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4 years, BMI 35.1 ± 5.1 kg/m2 , HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults.ResultsObese pubertal youth were more insulin resistant than comparably obese adults (P < .001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P = NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low-density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high-density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ≤ .05 for group differences).ConclusionsEffects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol.Clinical trial registrationThe RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov.

Project description:ObjectiveCatheter-based intervention (CBI) has become an increasingly popular option for treating pulmonary embolism (PE); however, the real benefits are unknown. The purpose of the present study was to compare the outcomes of patients treated with CBI with the outcomes of those treated with medical or surgical approaches.MethodsWe performed a retrospective analysis of patients admitted from October 2015 to December 2017 with a diagnosis of acute PE. We compared patients aged ≥18 years with a diagnosis of acute PE treated with CBI against a control group identified by propensity score matching. The control group was divided into those who had undergone surgical pulmonary embolectomy (SPE) as the surgical group and those who had not undergone SPE as the medical group. The primary outcome was mortality (in-hospital and overall mortality). The secondary outcomes were major bleeding, length of hospital stay, thrombus resolution, right ventricle improvement in systolic function and dilatation, and recurrent PE.ResultsOf the 108 patients, 30 were in the CBI group and 78 were in the control group (62 in the medical group and 16 in the surgical group). The patient characteristics on admission were similar, except for the body mass index, which was greater in the CBI group (P = .03). No difference was found in clinical severity, clot burden, right ventricle function, or biomarkers. Recurrent PE was less frequent in the CBI group than in the medical group (0% vs 6.4%). Otherwise, no significant differences were found in the outcomes between the CBI and medical groups. When CBI was compared with the surgical group, SPE was associated with improved mortality (0% vs 16.6%) but a longer median length of hospital stay (median, 7 days; interquartile range, 3-12 days; vs median, 8 days; interquartile range, 6.5-17 days).ConclusionsThe use of CBI reduced the number of recurrent PE events compared with the medically treated patients; however, the mortality was higher than that in the surgical group.

Project description:BackgroundDigital health interventions might extend service provisions for youth with chronic medical conditions (CC) and comorbid mental health symptoms. We aimed to comprehensively evaluate the efficacy of Internet- and mobile-based interventions (IMIs) for different psychological and disease-related outcomes in children and adolescents with CC.MethodStudies were identified by systematic searches in CENTRAL, Embase, MEDLINE/PubMed and PsycINFO, complemented by searches in reference lists of eligible studies and other reviews. We included studies, when they were randomized controlled trials (RCTs) comparing the efficacy of an IMI to control conditions in improving psychological and disease-related outcomes in youth (mean age ≤ 18 years) with CC. Study selection, data extraction and risk of bias assessment were conducted independently by two reviewers. Meta-analyses were performed within a random-effects model, and Hedges' g (with 95% confidence intervals) was calculated as effect size measure. Primary outcomes were comorbid mental health symptoms (i.e., depression, anxiety and stress), as well as quality of life and self-efficacy.ResultsA total of 19 randomized controlled trials (2410 patients) were included in this meta-analysis. IMIs were associated with improvements in self-efficacy (g = 0.38; 95% CI, 0.15 to 0.61; I 2 = 0) and combined disease-related outcomes (g = -0.13; 95% CI, -0.25 to -0.01; I 2 = 21). Meta-analyses on other outcomes were non-significant, and some pre-planned analyses were not feasible because of a shortage of studies.ConclusionThe available evidence on IMIs for improving mental and health-related outcomes in youth with CC is limited. Our findings point to a rather small benefit and limited efficacy. Future research is needed, to comprehensively assess the potential of IMIs to extend collaborative care, and to identify factors contributing to improved user-centered interventions with better treatment outcomes.

Dataset Information

Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study.

Objective

Research design and methods

Results

Conclusions

Publications

Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study.

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