scholarly journals Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly

2001 ◽  
pp. R1-R4 ◽  
Author(s):  
M Peracchi ◽  
S Porretti ◽  
C Gebbia ◽  
C Pagliari ◽  
P Bucciarelli ◽  
...  

OBJECTIVE: Acromegaly is often associated with fasting and postprandial hyperinsulinemia, and the mechanisms involved are only partly understood. Hypersecretion of incretins such as glucose-dependent insulinotropic polypeptide (GIP) could play a role in determining hyperinsulinemia in acromegaly, but the available data are inconsistent. The aim of this study was to characterize the fasting and postprandial pattern of plasma GIP and insulin in a group of acromegalic patients. DESIGN AND METHODS: Eleven non-diabetic patients with newly diagnosed acromegaly and 11 sex- and age-matched healthy subjects were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal for growth hormone (GH), GIP and insulin measurements. RESULTS: Not only insulin, but also fasting and postprandial GIP levels were significantly higher in the patients with acromegaly than the healthy subjects (P<0.01). In the former group fasting GIP levels and the integrated GIP response to the meal correlated significantly with GH basal levels (r=0.83, P<0.01 and r=0.65, P<0.05, respectively). Moreover, multivariate linear regression analysis showed that the presence of acromegalic status was associated with higher fasting and postprandial GIP levels independently of sex, age, fasting and postprandial plasma glucose and insulin levels, and the occurrence of normal or impaired glucose tolerance. CONCLUSION: This study provides evidence that in patients with acromegaly fasting and postprandial GIP levels are abnormally high. GIP hypersecretion in turn might play a role in the pathogenesis of hyperinsulinemia that characterizes acromegaly.

Author(s):  
Elżbieta Kimak ◽  
Andrzej Książek ◽  
Janusz Solski

AbstractStudies were carried out in 183 non-dialyzed, 123 hemodialysis, 81 continuous ambulatory peritoneal dialysis and 35 post-transplant patients and in 103 healthy subjects as a reference group. Lipids and apolipoprotein (apo)AI and apoB were determined using Roche kits. An anti-apoB antibody was used to separate apoB-containing apoCIII and apoE-triglyceride-rich lipoprotein (TRL) in the non-high-density lipoprotein (non-HDL) fraction from apoCIIInonB and apoEnonB in the HDL fraction in four groups of patients with chronic renal failure (CRF) and healthy subjects. Multivariate linear regression analysis was used to investigate the relationship between triglyceride (TG) or HDL-cholesterol (HDL-C) concentrations and lipoproteins. Dyslipidemia varied according to the degree of renal insufficiency, the type of dialysis and therapy regime in CRF patients. Lipoprotein disturbances were manifested by increased TG, non-HDL-C and TRL concentrations, and decreased HDL-C and apoAI concentrations, whereas post-renal transplant patients showed normalization of lipid and lipoprotein profiles, except for TG levels and total apoCIII and apoCIIInonB. The present study indicates that CRF patients have disturbed lipoprotein composition, and that hypertriglyceridemia and low HDL-C concentrations in these patients are multifactorial, being secondary to disturbed lipoproteins. The method using anti-apoB antibodies to separate apoB-containing lipoproteins in the non-HDL fraction from non-apoB-containing lipoproteins in HDL can be used in the diagnosis and treatment of patients with progression of renal failure or atherosclerosis. The variability of TG and HDL-C concentrations depends on the variability of TRL and cholesterol-rich lipoprotein concentrations, but the decreases in TG and increases in HDL-C concentrations are caused by apoAI concentration variability. These relationships, however, need to be confirmed in further studies.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Angelica Rodriguez-Niño ◽  
Sibylle J. Hauske ◽  
Anna Herold ◽  
Jiedong Qiu ◽  
Jacob van den Born ◽  
...  

Background. Carnosinase-1 (CN-1) can be detected in 24 h urine of healthy individuals and patients with type 2 diabetes (T2DM). We aimed to assess whether urinary CN-1 is also reliably measured in spot urine and investigated its association with renal function and the albumin/creatinine ratio (ACR). We also assessed associations between the CNDP1 (CTG)n genotype and CN-1 concentrations in serum and urine. Methods. Patients with T2DM (n=85) and nondiabetic patients with chronic kidney disease (CKD) (n=26) stratified by albuminuria (ACR≤300 mg/g or ACR>300 mg/g) recruited from the nephrology clinic and healthy subjects (n=24) were studied. Results. Urinary CN-1 was more frequently detected and displayed higher concentrations in patients with ACR>300 mg/g as compared to those with ACR≤300 mg/g irrespective of the baseline disease (T2DM: 554 ng/ml [IQR 212-934 ng/ml] vs. 31 ng/ml [IQR 31-63 ng/ml] (p<0.0001) and nondiabetic CKD: 197 ng/ml [IQR 112-739] vs. 31 ng/ml [IQR 31-226 ng/ml] (p=0.015)). A positive correlation between urinary CN-1 and ACR was found (r=0.68, p<0.0001). Multivariate linear regression analysis revealed that ACR and serum CN-1 concentrations but not eGFR or the CNDP1 genotype are independent predictors of urinary CN-1, explaining 47% of variation of urinary CN-1 concentrations (R2=0.47, p<0.0001). Conclusion. These results confirm and extend previous findings on urinary CN-1 concentrations, suggesting that assessment of CN-1 in spot urine is as reliable as in 24 h urine and may indicate that urinary CN-1 in macroalbuminuric patients is primarily serum-derived and not locally produced.


2020 ◽  
Vol 8 (2) ◽  
pp. 99-105
Author(s):  
Sholy K Vareed ◽  
Don Paul Mathew ◽  
P Suresh

Background: Increase in intimal medial thickness (IMT) of the carotid arteries is contemplated as a guide to atherosclerotic vascular disease and subclinical organ damage and foretell cardiovascular disease. The study aimed to analyse IMT in non-diabetic and diabetic subjects. Subjects and Methods: There were 105 diabetic and 95 non-diabetic subjects in this study. Common carotid artery (CCA) IMT was calculated using a linear probe of a high-resolution ultrasound medical system. Results: Diabetic subjects (0.95 mm) showed significantly higher mean intimal medial thickness (IMT) when compared non-diabetic subjects (0.85 mm) (p <0.05). Correlation of IMT was seen with age, total cholesterol, triglycerides, HDL & LDL cholesterol and systolic blood pressure (SBP) in diabetic subjects. Total cholesterol, SBP and diastolic blood pressure (DBP) showed a correlation with IMT in the non-diabetic subjects. Age, total cholesterol, SBP, and diabetes were independent risk factors for intimal medial thickness in multivariate linear regression analysis. Conclusion: Higher intimal medial thickness was seen in diabetic subjects when compared to non-diabetic subjects. We conclude that age, total cholesterol, SBP and duration of diabetes showed a significant correlation with IMT. IMT can be considered as a screening tool in diabetic patients for the early detection of atherosclerosis.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3894-3894
Author(s):  
Caroline Cicin-Sain ◽  
Alice Huang ◽  
Chloe Pasin ◽  
Selina Epp ◽  
Nicolas J Mueller ◽  
...  

Abstract Background: Vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been approved rapidly. However, pivotal studies have been conducted in healthy volunteers, while recipients of allogeneic hematopoietic cell transplantations (allo-HCT) may have different dynamics and patterns of response to the vaccine and data in this cohort is lacking. Methods: Here, we examined longitudinal antibody (AB) titers to SARS-CoV-2 vaccination with BNT162b (Comirnaty ®) or mRNA-1273 (Moderna Covid-19 Vaccine ®) in allo-HCT recipients who had undergone allo-HCT &gt;3months (m) ago and in healthy controls (hospital employers). Serial AB titers (prior to (T0); 1m after 1 st dose (T1); 1m (T2), 3m (T3), 6m (T4) post 2 nd dose) were measured with an in-house developed multiplex Antibody CORonavirus Assay (ABCORA) that measures SARS-CoV-2 IgG, IgA, and IgM reactivities against RBD (receptor binding domain), S1 (subunit 1 of the spike protein), S2 (subunit 2 of the spike protein) and N (nucleoprotein), thereby allowing to differentiate immunity after vaccination versus immunity after infection. As neutralization activity correlates well with S1 AB binding, the potency of the AB response was defined as the sum of S1 IgG, IgA and IgM reactivities (cumulative S1 (cS1)). Based on computational methods high neutralization potency was predicted above a cS1 threshold of 17. Results: We enrolled 114 allo-HCT patients (median age 57y (range 18y-74y)) between March 9th 2021 and May 31st 2021 at the University Hospital Zurich, Switzerland. Currently, AB responses at T1, T2, and T3 are available for 99, 95 and 89 patients, respectively. Patients were grouped into those (A) 3-6m post-HCT (T1: n=25 at, T2: n=23, T3: n=20); (B) 6-12m post-HCT (T1: n=13, T2: n=13, T3: n=12); and (C) &gt;12m post-HCT (T1: n=61, T2: n=59, T3: n=57). In addition, AB responses are available for healthy controls (median age 35y (range 23y-64y)) (T1: n=75, T2: n=69, T3: n=48). There were 10 patients and 5 healthy subjects with a reported or detected SARS-CoV-2 infection. There was a statistically significant difference of cS1 AB levels between the 4 groups at T1, T2, and T3 (ANOVA p-values (p) &lt;0.001, respectively, Fig 1) with the lowest AB response in group A (cS1 median value 0.957 at T1, 5.22 at T2, 1.90 at T3) and B (cS1 median value 0.973 at T1, 4.76 at T2, 11.9 at T3) compared to group C (cS1 median value 6.21 at T1, 199 at T2, 76.4 at T3) and healthy controls (cS1 median value 54.9 at T1, 228 at T2, 91.1 at T3). Using a multivariate linear regression analysis adjusted on age and gender, we found that patients in groups A and B had significantly lower cS1 levels than groups C and healthy subjects (p&lt;0.001, p&lt;0.001, p=0.034 of healthy versus groups A, B, C respectively at T2, and p&lt;0.001, p=0.004, p=0.12 at T3), and that preinfected patients had higher cS1 levels at T2 and T3 respectively (p=0.003 and 0.006). The dynamics of the AB response were more diverse in allo-HCT recipients. In a multivariate linear regression analysis (Fig 2) assessing factors associated with humoral immune responses in allo-HCT recipients, we found consistently lower cS1 responses in patients early post-HCT (group A+B (p=0.002)) and higher cS1 levels in those who had been preinfected with SARS-CoV-2 (p=0.012). Patients under immunosuppressive treatment (IST) and those who had relapsed disease post-HCT showed significantly lower cS1 immune responses (p=0.028 and 0.005, respectively). The presence of moderate or severe chronic GVHD was not a statistically significant factor influencing AB levels. This may be explained by (i) the heterogeneity of the condition of chronic GVHD and low patient numbers; (ii) the late time point &gt;12m post-HCT with generally higher AB levels. Consistent with other reports age &gt;65y was also associated with lower cS1 responses (p=0.03). Conclusion: Allo-HCT recipients early post-transplant, those of older age, and those given IST displayed insufficient AB titers to the vaccine. Such knowledge is of critical importance to transplant recipients and their physicians to guide treatment decisions regarding re-vaccination, and social behavior during this pandemic. Monitoring AB development in all allo-HCT recipients and vulnerable patients with other immunocompromising conditions may be crucial to determine those at increased risk for infection and for the timing of booster vaccines. Figure 1 Figure 1. Disclosures Manz: CDR-Life Inc: Consultancy, Current holder of stock options in a privately-held company; University of Zurich: Patents & Royalties: CD117xCD3 TEA.


2018 ◽  
Vol 37 (3) ◽  
pp. 373-378 ◽  
Author(s):  
Suleyman Baldane ◽  
Ismail Can Kendir ◽  
Cem Onur Kirac ◽  
Suleyman Ipekci ◽  
Gulsum Tekin ◽  
...  

Summary Fractalkine (FKN) is an inflammatory cytokine that has been shown with increased serum levels in diabetic patients and is considered to contribute to the adipose tissue inflammation by supporting monocyte adhesion to adipocytes which has an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our aim was to evaluate the effects of glucose ingestion on the serum fractal - kine levels in healthy subjects with normal glucose tolerance (NGT) and newly diagnosed T2DM patients. A total of 67 patients were included in this study, and they were divided into NGT (n=34) and T2DM (n=33) groups according to their oral glucose tolerance test (OGTT) results. The serum FKN and C-reactive protein (CRP) levels were measured at 0 and 120 minutes during an OGTT following overnight fasting. The 0-minute (basal) and 120-minute OGTT FKN levels were found to be significantly higher in the T2DM group when compared to the NGT group (p=0.012 and p=0.001, respectively). However, no significant differences were observed in terms of the changes in the basal and 120-minute OGTT FKN levels in the T2DM and NGT groups (p=0.433 and p=0.06, respectively). A significant positive correlation was observed between the 120-minute OGTT FKN and glucose levels in the study group consisting of all of the patients (r=0.331, p=0.006). Conclusions: In this study, basal and post-glycemic load FKN levels were found to be higher in newly diagnosed T2DM patients than those with NGT; however, there was no additional change in FKN levels by glycemic load.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Nakamura ◽  
Y K Kataoka ◽  
H H Hosoda ◽  
T N Nakashima ◽  
S H Honda ◽  
...  

Abstract Background Type 2 diabetic patients with coronary artery disease (CAD) is a high-risk subjects who require intensive secondary preventive management. The current guideline recommends lowering LDL-C with a statin as a first-line therapy in diabetic patients with CAD. However, its anti-atherosclerotic efficacy is diminished compared to non-diabetic subjects. These suggest the need to further identify additional therapeutic target associated with diabetic atherosclerosis. Lipoprotein (a) [Lp (a)] is a plasma lipoprotein which consists of an LDL-like particle with apolipoprotein (a). While Lp (a) has been shown to associate with ASCVD, whether this lipoprotein promotes diabetic coronary atherosclerosis under LDL-C control with a statin remains to be fully elucidated. Purpose To investigate the relationship between Lp (a) and coronary lipidic atheroma by near-infrared spectroscopy (NIRS), which quantitatively measures lipidic burden in vivo. Methods Culprit lesions in 127 type 2 diabetic patients with CAD who already received a statin were evaluated by NIRS imaging. Maximum 4-mm lipid core burden index at culprit lesion (MaxLCBI4mm) was measured. Results High-intensity statin and ezetimibe were used in 13 and 14% of study subjects, respectively. Their on-treatment LDL-C level and Lp (a) were 2.0±0.7 mmol/l and 22.1±26.7 mg/dl. Despite these lipid lowering therapy, average MaxLCBI4mm was 419.6±248.2 and MaxLCBI4mm≥400 was observed in 49% of study subjects. Multivariate linear regression analysis demonstrated LDL-C and Lp (a) as independent determinants associated with MaxLCBI4mm (Table). Of note, in subjects who achieved LDL-C<1.8 mmol/l, an elevated Lp (a) level but not LDL-C predicts MaxLCBI4mmat culprit lesions (Table). Multivariate linear regression analysis t p-value Entire subjects (n=127)   LDL-C 2.04 0.04   Lp (a) 2.88 <0.01 LDL-C <1.8 mmol/l (n=47)   LDL-C 0.45 0.66   Lp (a) 2.74 0.01 Conclusions The association of Lp (a) with coronary lipid-rich atheroma even under guideline-recommended LDL-C control indictaes Lp (a) as an additional therapeutic target to further stabilize diabetic atherosclerosis.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Xubin Yang ◽  
Qiongyan Lin ◽  
Xiaoshan Li ◽  
Lin Wu ◽  
Wen Xu ◽  
...  

Background. Cardiovascular autonomic dysfunction is closely related to increased mortality in patients with diabetes. Previous studies have proved that cystatin C (CysC) is an important predictor of both peripheral neuropathy and cardiovascular events. However, whether CysC is also associated with cardiovascular autonomic dysfunction remains unclear. Therefore, the aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. Methods. A total of 161 type 2 diabetic patients with normal serum creatinine (less than 133 μmol/l) and estimated glomerular filtration rate (eGFR) higher than 60 ml/min per 1.73 m2 were recruited in our study. Cardiovascular autonomic dysfunction was determined by heart rate variability (HRV) measured by a 24-hour Holter monitor. Serum CysC was tested by particle-enhanced turbidimetric immunoassay, and subjects were divided into three groups based on the tertiles of CysC. Pearson correlation analysis was used to evaluate the association between different indexes, and the association of CysC with HRV indexes was assessed by multivariate linear regression analysis. Results. The HRV parameters were lower in the group with the highest CysC concentration than in the groups with lower levels of CysC (P<0.05). Pearson correlation analysis showed a negative relationship between CysC and the HRV parameters, including SDNN (r=−0.31, P<0.001), SDANN (r=−0.25, P=0.002), and logLF (r=−0.18, P=0.023). Furthermore, multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (β=−24.11, P=0.015) and SDANN (β=−19.88, P=0.047) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. Conclusions. Serum CysC levels are associated with cardiovascular autonomic dysfunction; furthermore, CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Camila Lima ◽  
Etienne Macedo

Abstract Background and Aims In the last decades, clinical research biomarker (BM) to improve assessment of kidney function have been intensive, and proenkephalin (PENK) has been identified as a new BM of filtration. We hypothesized whether PENK would have a better accuracy for the diagnosis of severe AKI than serum cystatin (CYS) and the serum creatinine (Scr). We evaluate patient in the peri op of liver transplant (LT). Method Blood samples were collected during the pre and post (until 48 hours) operative (op.) period of LT in 57 eligible patients. Where was analyzed PENK (Sphingotest®), CYS (Milipex) and Scr (Quimioluminence). AKI diagnosis was based on the Kidney Disease International Global Outcomes (KDIGO) criteria using Scr. KDIGO 1 was subclassified according to the International Club of Ascites (ICA). Results Of the 57 patients undergoing LT, 50 (88%) developed AKI according to the KDIGO criteria in the first week after LT. Twenty-one patients without AKI and with KDIGO 1-A (37%) were summarized as the no AKI/mild AKI group, whereas 36 patients with KDIGO 1-B, 2 and 3 (63%) were summarized as the severe AKI group. Before the intra - operative insult only PENK was significantly higher in patients that developed severe AKI, median 55 [P25-75(44,25 – 94,55)] in no AKI/mild AKI versus 90,16 [P25-75(64,70 – 135,76)] pmol/l in severe AKI p 0,021, an AUC 0,685 (CI 0,536 – 0,833), with a cutoff 55 pmol/l, sensibility of 0,86 and specificity 0,52, accuracy 0,75 to severe AKI. Scr levels in pre-op. were non- significantly higher in severe AKI; p=0,088. The CYS in the pre-op was similar within the groups. Pos-operative 48 hours after LT, PENK was significantly higher in severe AKI, median 81 [P25-75(61,25 – 101,50)] versus 161,45 [P25-75(122,85 – 294,03)] in severe AKI - p &lt;0,0001 an AUC 0,83 (CI 0,72 - 0,94) with a cutoff 119,05 pmol/l, sensibility of 0,80 and specificity 0,90, accuracy 0,84 to severe AKI. Scr levels in post-op achieve an AUC 0,77 (CI 0,63 - 0,92) with a cutoff 1,49mg/dl, sensibility of 0,94, specificity 0,67 and accuracy 0,82. In a multivariate linear regression analysis adjusted for age, anestesia time, urine output and fluid balance, the PENK only was independently associated of severe AKI in pre-op. with OR 4,40 (CI 1,40 – 13,88) – p0,001 and the post-op. with OR 44,64 (CI 5,40 – 368,5) – p&lt;0,0001. Conclusion PENK is a promisor filtration biomarker and showed a better acuracy to severe AKI in pre-operative than standard AKI diagnostic by Scr. Prediction of severe AKI in pre-operative period by PENK can help the management of these patients in the future.


2013 ◽  
Vol 33 (2) ◽  
pp. 175-181 ◽  
Author(s):  
Tohru Mizumasa ◽  
Hideki Hirakata ◽  
Yusuke Kuroki ◽  
Ritsuko Katafuchi ◽  
Hideki Yotsueda ◽  
...  

BackgroundThe peritoneum begins to undergo morphologic changes before the start of peritoneal dialysis (PD), particularly in diabetic patients. The present study was conducted to investigate the effects of diabetes on the peritoneum.MethodsThis study involved 17 patients who began receiving PD and had diabetes as an underlying disease (DM group), and 30 patients without diabetes who served as a control group (nonDM group). At the start of PD, the parietal peritoneum was sampled to assess submesothelial connective tissue thickness, number of capillaries and postcapillary venules, and indications of vasculopathy (grades 0 – 3).ResultsSubmesothelial connective tissue thickness was significantly greater in the DM group than in the nonDM group ( p < 0.01). The number of capillaries was significantly greater in the DM group ( p < 0.01). Based on multivariate linear regression analysis, diabetes was identified as a significant independent variable of both submesothelial connective tissue thickness and number of capillaries ( p < 0.01).ConclusionsIn diabetic patients, morphologic changes of the peritoneum are marked at the start of PD.


2004 ◽  
pp. 27-32 ◽  
Author(s):  
M Arosio ◽  
CL Ronchi ◽  
C Gebbia ◽  
S Pizzinelli ◽  
D Conte ◽  
...  

OBJECTIVE: Ghrelin, a gut-brain peptide involved in the control of energy homeostasis, affects antero-pituitary and gastro-entero-pancreatic (GEP) hormone secretion in healthy subjects. We aimed to verify whether such hormonal responses are retained in acromegaly, a disease characterized by high GH, subnormal ghrelin and abnormal GEP hormone levels. DESIGN AND METHODS: The effect of ghrelin (3.3 microg/kg given after overnight fasting as an i.v. bolus) on GH, prolactin (PRL), adrenocorticotropin (ACTH), cortisol, insulin, glucose, total somatostatin (SS) and pancreatic polypeptide (PP) circulating levels were evaluated in seven non-diabetic patients with newly diagnosed acromegaly and in nine healthy controls. RESULTS: Ghrelin elicited a prompt, marked increase of serum GH and PRL levels in all normal (from 1.6+/-0.6 to 52.9+/-7.8 and from 9.7+/-0.8 to 24.2+/-4.8 microg/l (means+/-S.E.M.), respectively) and acromegalic subjects (from 11.2+/-4.9 to 91.6+/-21.0 and from 42.9+/-26.1 to 113.8+/-79.0 microg/l, respectively). Both plasma ACTH and serum cortisol levels rose significantly in the controls, whereas the cortisol response was blunted in the acromegalic patients. Glucose levels rose earlier and insulin levels fell later in all subjects, with a significantly greater net insulin decrease in acromegalic than in healthy subjects (-80+/-21 vs -17+/-4 pmol/l, P<0.01). A prompt PP rise and a biphasic SS response occurred in all controls, whereas in the acromegalic group the PP response (from 26.1+/-5.0 to 92.2+/-39.0 pmol/l) and the SS response (from 11.9+/-3.0 to 19.7+/-4.0 ng/l) were quite variable. CONCLUSIONS: Ghrelin affects both pituitary and GEP hormones in acromegalic patients as in normal subjects. These findings suggest that ghrelin actions on the energy balance are mediated by complex interactive endocrine loops that involve also the gut and pancreas.


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