Altered adipokines in obese adolescents: A cross-sectional and longitudinal analysis across the spectrum of glycemia

Author(s):  
Risa M Wolf ◽  
Andrew E Jaffe ◽  
Susana Rodriguez ◽  
Xia Lei ◽  
Dylan C. Sarver ◽  
...  

Obesity and type 2 diabetes is rapidly increasing in the adolescent population. We sought to determine whether adipokines, specifically leptin, C1q/TNF-related proteins 1 (CTRP1) and CTRP9, and the hepatokine fibroblast growth factor 21 (FGF-21), are associated with obesity and insulin resistance in a cohort of lean and obese adolescents, across the spectrum of glycemia. In an observational, longitudinal study of lean and obese adolescents, we measured fasting labs, oral glucose tolerance tests, and adipokines including: Leptin, CTRP1, CTRP9, and FGF-21. Participants completed baseline and 2-year follow-up study visits, and were categorized as lean (n=30), obese normoglycemic (ONG) (n=61), and obese hyperglycemic (OHG) (n=31) adolescents at baseline, and lean (n=8), ONG (n=18), and OHG (n=4) at follow-up. Results showed that at baseline, leptin was higher in all obese groups (p<0.001) compared to LC. FGF-21 was higher in OHG participants compared to LC (p<0.001) and ONG (p<0.001), and positively associated with fasting glucose (p<0.001), fasting insulin (p<0.001), HOMA-IR (p<0.001), and HbA1c (p=0.01). CTRP1 was higher in OHG compared to ONG (p=0.03). CTRP9 was not associated with obesity or hyperglycemia in this pediatric cohort. At 2 years, leptin decreased in ONG (p=0.003) and FGF21 increased in OHG (p=0.02), relative to lean controls. Altered adipokine levels are associated with the inflammatory milieu in obese youth with and without hyperglycemia. In adolescence, the novel adipokine CTRP1 was elevated with hyperglycemia, while CTRP9 was unchanged in this cohort.

2020 ◽  
Vol 183 (3) ◽  
pp. 285-295
Author(s):  
João Pedro Ferreira ◽  
Zohra Lamiral ◽  
Constance Xhaard ◽  
Kévin Duarte ◽  
Emmanuel Bresso ◽  
...  

Objective: Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease. Design: To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort). Methods: A total of 1506 participants attended both the visit 1 and visit 4, separated by ≈20 years. Over 400 proteins, GWAS and genetic associations were studied using models adjusted for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed. Results: People who developed pre-diabetes (n = 555) and/or T2D (n = 73) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable selection, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit 4 (i.e. ≈20 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal analysis, but not in the cross-sectional analysis. The heritability of the circulating PAPP-A was estimated at 44%. In GWAS analysis, the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D. Conclusions: The risk of developing pre-diabetes and T2D increases with age and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic component, was associated with both the development and presence of pre-diabetes and T2D.


2021 ◽  
Vol 10 (4) ◽  
pp. 163-170
Author(s):  
Ayse Didem Esen ◽  
Secil Arica ◽  
Mikail Ozdemir

Aim: The most valuable approach to prevent the spread of the novel COVID-19, which is a pandemic today, is to detect, isolate, and treat patients. The majority of patients are mild or asymptomatic cases. These cases are followed up and isolated at home in many countries. With a governmental decision issued in Turkey, it has been deemed appropriate to follow up the suspected, contact or definitive diagnosis patients who do not indicate inpatient treatment, have a mild clinical course, or do not have a risk factor that may lead to a severe course of COVID-19, at home by the family practice units. In this study, we aimed to investigate the characteristics of the patients with COVID-19 who were being monitored at home. Methods: The study was designed as a retrospective cross-sectional observational study. In this study, 321 people who were registered at the Education and Family Health Centers of our hospital and followed up as COVID-19 suspects, contacts, or definitive cases were identified. Home follow-up data of these patients between April 1-30 were obtained retrospectively from the records of family health centers. Data, such as the presence and course of symptoms of people followed at home, their isolation status, medicine usage status, and test results were recorded electronically for further analysis. Results: In this study, 321 patients, 163 (50.28%) males, and 158 (49.22%) females were included. Among 321 patients, 287 (89.41%) were contact patients, 54 (16.82%) were suspected patients, and 28 (8.72%) had a definitive diagnosis. The mean age of the patients was 40.00±20.68. Among the patients included in this study, 27 (8.41%) were hospitalized, symptoms worsened in 8 (2.49%), 5 (1.56%) were re-applied to the hospital, 5 (1.56%) were re-hospitalized, and 28 people (8.72%) were administered medication. Conclusion: The mean age of patients who complied with the measures of isolation was higher than patients who did not. The mean age of hospitalized patients was higher than in non-hospitalized patients. The frequency of observed symptoms was consistent with the previous studies in the literature. Keywords: cough, fever, pandemics, quarantine, SARS-CoV-2


1983 ◽  
Vol 102 (4) ◽  
pp. 549-556 ◽  
Author(s):  
K. Berntorp ◽  
E. Trell ◽  
J. Thorell ◽  
B. Hood

Abstract. In a material of 3596 oral glucose tolerance tests (OGTT) performed in a population investigation of middle-aged males in Malmö, fasting and 120 min values of blood glucose and plasma insulin immunoreactivity (IRI) were studied while taking factors like body weight, smoking, alcohol, gastric resection and selfreported diabetes heredity into account. The fasting as well as the 120 min levels of both glucose and IRI were markedly influenced by body weight and smoking habits but not by the hereditary background. At 120 min, but not in the fasting state, there was a linear correlation between the IRI and glucose levels. The increase of IRI on glucose was significantly steeper in most of the hereditary subjects in comparison with their non-hereditary controls.


2020 ◽  
Vol 9 (10) ◽  
pp. 3367
Author(s):  
Małgorzata Jacewicz-Święcka ◽  
Irina Kowalska

Data concerning metabolic consequences in women with polycystic ovary syndrome (PCOS) are delivered mainly by cross-sectional studies. In this research, we re-examined 31 Caucasian PCOS women after a median period of 120.9 months to evaluate the changes in metabolic syndrome components. Clinical examination, oral glucose tolerance test with estimations of glucose and insulin, lipids, sex hormone-binding globulin (SHBG) and sex hormones assessments were performed on two occasions. Additionally, the euglycaemic hyperinsulinaemic clamp technique was used at the baseline to assess insulin sensitivity (M-clamp value). In the end, the median age of participants was 35. We observed an increase in glucose concentrations, a decrease in insulin concentrations and no changes in insulin resistance markers. Final mean glucose, mean insulin, Matsuda index and body mass index (BMI) were correlated with baseline M-clamp value and SHBG (p < 0.01). During the follow-up, no one in the sample developed diabetes. The annualised incidence rate for conversion from normoglycaemia to prediabetes totalled 4.5%. Baseline BMI, free androgen index, fasting glucose and M-clamp value were identified as prediabetes predictors in young PCOS women (respectively, OR = 1.17, OR = 1.42, OR = 1.2, OR = 0.73, p < 0.05). Prediabetes appeared in 76.47% of the women with a final BMI of ≥ 25 kg/m2 and in 7.14% of the normal-weight women (p = 0.0001). In conclusion, we report a high rate of adverse change in glucose metabolism in overweight and obese participants, a deterioration in β-cell function and strong correlations between metabolic parameters assessed in the third and the fourth decade in PCOS women, emphasising the role of early intervention to prevent cardiometabolic diseases.


2019 ◽  
Vol 104 (12) ◽  
pp. 6201-6206 ◽  
Author(s):  
Hung Pham ◽  
Chinmay S Marathe ◽  
Liza K Phillips ◽  
Laurence G Trahair ◽  
Seva Hatzinikolas ◽  
...  

Abstract Context It is not known whether glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels correlate within individuals, nor whether levels change with age. Previous studies have all been cross-sectional in design. Objective To evaluate longitudinal changes in fasting and glucose-stimulated incretin hormone concentrations in healthy older subjects. Patients and Design Forty-one healthy older subjects had measurements of plasma GLP-1 and GIP while fasting and after a 75-g oral glucose load on two occasions separated by 5.9 ± 0.1 years [mean age at the initial study: 71.2 ± 3.8 (SD) years]. Breath samples were collected to calculate the gastric 50% emptying time (T50). Results For GLP-1, both fasting concentrations (P < 0.001) and area under the curve 0 to 120 minutes (P = 0.001) were decreased at followup. Fasting GIP was also lower (P = 0.03) at follow up, but there was no change in the area under the curve 0 to 120 minutes (P = 0.26). The gastric emptying T50 was slower at followup (P = 0.008). Neither the change in T50 nor the body mass index at the initial study was a determinant of the change in incretin responses. Between the two study days, fasting GIP (r = 0.72, P < 0.001) correlated well, but not fasting GLP-1 (r = 0.23, P = 0.18). However, both glucose-stimulated GLP-1 (r = 0.50, P = 0.002) and GIP (r = 0.60, P < 0.001) showed correlations between the initial and follow-up studies. Conclusions Fasting GIP and glucose-stimulated GLP-1 and GIP concentrations correlate within individuals over a follow-up period of ∼5.9 years. Aging is associated with reductions in fasting GLP-1 and GIP, and glucose-stimulated GLP-1, which may predispose to the development of glucose intolerance and type 2 diabetes.


2013 ◽  
Vol 98 (7) ◽  
pp. 2993-3000 ◽  
Author(s):  
Cosimo Giannini ◽  
Ariel E. Feldstein ◽  
Nicola Santoro ◽  
Grace Kim ◽  
Romy Kursawe ◽  
...  

Objective: Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF% &lt;5.5% and HFF% ≥5.5%, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis, and insulin sensitivity. Methods: A total of 217 lean and obese adolescents with both low and high HFF% (lean = 31; obese low HFF% = 107; and obese high HFF% = 79) underwent an oral glucose tolerance test, a fast gradient magnetic resonance imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels were measured as a biomarker of liver apoptosis. A subset of adolescents underwent a 2-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N = 14), to assess insulin sensitivity and steatohepatitis, respectively. Results: Compared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (P &lt; .001). FGF-21 significantly correlated with adiposity indexes (P &lt; .001), visceral fat (r2 = 0.240, P &lt; .001), hepatic fat content (r2 = 0.278, P &lt; .001), cytokeratin 18 (r2 = 0.217, P &lt; .001), and alanine aminotransferase (r2 = .164, P &lt; .001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the nonalcoholic fatty liver disease activity score (r2 = 0.27, P = .04). Stepwise regression analysis indicated that these relationships are independent of body mass index, visceral fat, and insulin sensitivity. An inverse correlation was documented with insulin, hepatic resistance indexes, and adipose resistance indexes, which disappeared after adjusting for hepatic fat content. Conclusions: Plasma FGF-21 levels are increased in obese adolescents, particularly in those with fatty liver. FGF-21 concentrations significantly and independently correlate with hepatic fat content and markers of hepatic apoptosis in obese youths.


2020 ◽  
Vol 33 (5) ◽  
pp. 377-385
Author(s):  
Alexander Sirakov ◽  
Pervinder Bhogal ◽  
Markus Möhlenbruch ◽  
Stanimir Sirakov

Background and purpose Low-profile self-expandable stents have increased the number of intracranial aneurysms treated by endovascular means. The new low-profile visible intraluminal support device LVIS EVO (Microvention), the successor of LVIS Jr, is a self-expandable and retrievable microstent system, designed for implantation into intracranial arteries with a diameter up to 2.0 mm. In this retrospective study we aimed to elucidate the technical feasibility and clinical safety of the novel LVIS EVO stent for stent-assisted coil embolisation of intracranial aneurysms. Materials and methods A single centre technical report of the first six consecutive cases of stent-assisted coil embolisation with the novel LVIS EVO stent for the treatment of unruptured or recanalised intracranial aneurysms. Records were made of basic demographics, aneurysmal characteristics, device properties and related technical details, adverse events, clinical outcomes and occlusion rates on available radiological follow-up. Results Six LVIS EVO devices were successfully implanted in all subjects to treat a total number of six intracranial aneurysms. No device-related intraprocedural complications were seen. At early clinical follow-up six out of six (100%) patients had a modified Ranking score of 0–1. Early angiographic and cross-sectional radiological follow-up, available in five out of six (83.3%) of the patients confirmed unchanged aneurysmal occlusion rates. A minor, transitory neurological deficit was recorded in one of the six (16.6%) patients. Mortality was 0%. Conclusions Preliminary experience in this subset of our patients confirms a notably improved technical behaviour of the novel LVIS EVO stent system when compared to its ancestor LVIS Jr. The enhanced visibility of the stent and the refined delivery/retrieval capabilities of the stent further increase the safety margins of the devices profile, especially in cases of tortuous anatomy.


2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Kevin J Scully ◽  
Gregory Sawicki ◽  
Jessica Kremen ◽  
Melissa S Putman

Abstract Cystic fibrosis–related diabetes (CFRD) is associated with worsening pulmonary function, lower body mass index, increased infection frequency, and earlier mortality. While the incidence of CFRD is rising, its development in patients under the age of 10 years is uncommon. We present a 9-year-old girl with cystic fibrosis (CF) who presented with a 5-year history of nonprogressive hyperglycemia, demonstrated by abnormal oral glucose tolerance tests, glycated hemoglobin A1c (HbA1c) levels consistently &gt;6.5%, and negative pancreatic autoantibodies. Subsequent genetic testing revealed a pathogenic heterozygous recessive mutation in the GCK gene at c.667G&gt;A (p.Gly223Ser), consistent with a diagnosis of GCK-MODY. Significant dysglycemia in young children with CF should raise suspicion for alternative etiologies of diabetes and warrants further investigation. The clinical impact of underlying monogenic diabetes in patients with CF is unclear, and close follow-up is warranted. This case also offers unique insight on the impact of hyperglycemia in the absence of insulin deficiency on CF-specific outcomes.


VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 6-26 ◽  
Author(s):  
Fabian Rengier ◽  
Philipp Geisbüsch ◽  
Paul Schoenhagen ◽  
Matthias Müller-Eschner ◽  
Rolf Vosshenrich ◽  
...  

Transcatheter aortic valve replacement (TAVR) as well as thoracic and abdominal endovascular aortic repair (TEVAR and EVAR) rely on accurate pre- and postprocedural imaging. This review article discusses the application of imaging, including preprocedural assessment and measurements as well as postprocedural imaging of complications. Furthermore, the exciting perspective of computational fluid dynamics (CFD) based on cross-sectional imaging is presented. TAVR is a minimally invasive alternative for treatment of aortic valve stenosis in patients with high age and multiple comorbidities who cannot undergo traditional open surgical repair. Given the lack of direct visualization during the procedure, pre- and peri-procedural imaging forms an essential part of the intervention. Computed tomography angiography (CTA) is the imaging modality of choice for preprocedural planning. Routine postprocedural follow-up is performed by echocardiography to confirm treatment success and detect complications. EVAR and TEVAR are minimally invasive alternatives to open surgical repair of aortic pathologies. CTA constitutes the preferred imaging modality for both preoperative planning and postoperative follow-up including detection of endoleaks. Magnetic resonance imaging is an excellent alternative to CT for postoperative follow-up, and is especially beneficial for younger patients given the lack of radiation. Ultrasound is applied in screening and postoperative follow-up of abdominal aortic aneurysms, but cross-sectional imaging is required once abnormalities are detected. Contrast-enhanced ultrasound may be as sensitive as CTA in detecting endoleaks.


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