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Objective:The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism.Methods:Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables.Results:Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P<0.01] and LCN2 levels decreased [(34.15±9.95 vs 57.50±29.75)ng/ml, P<0.01] in patients with acromegaly. Homeostasis model assessment for insulin resistance (HOMA-IR) was also elevated ( P<0.01), but homeostasis model assessment for β cell function (HOMA-β) and area under curve of insulin during 0-120 min of the oral glucose tolerance test (AUC INS) changed non-significantly in acromegaly compared to normal controls ( P>0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 ( β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin ( β=0.512, P<0.01). In the multivariate models, low LCN2 ( β=-0.398, P=0.017) and elevated serum osteocalcin ( β=0.553, P=0.001) were predictors for AUC INS, osteocalcin was a positive predictor of HOMA- β ( β=0.519, P=0.004). GH ( β=0.294, P=0.029) and IGF-1( β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions:Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly.
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Objective To investigate the frequencies of the impaired glucose tolerance and diabetes mellitus in a large cohort of active acromegaly and to identify risk factors associated with the presence of diabetes at diagnosis in these patients.Methods This study included 88 patients with newly diagnosed acromegaly.Patients were further divided into normal glucose tolerance (NGT),impaired glucose regulation (IGR),and diabetes (DM) groups according to oral glucose tolerance test or previous history.Insulin sensitivity and β cell function were also evaluated by homeostasis model assessment (HOMA).Logistic regression analysis was used to explore the independent risk factors for diabetes in patients with acromegaly.Results Impaired glucose regulation was found in 25 (28.4％),and DM in 37(42.0％) acromegaly patients.Compared to NGT and IGR patients,higher proportion of DM patients had family history of diabetes (P＜0.05).Compared to NGT group,higher post-OGTT growth hormone (GH) levels were detected in IGR and DM groups.Insulin-like growth factor 1 (IGF-1) levels were higher in IGR group while lower in DM group (P＜0.01).Homeostasis model assessment for β cell function (HOMA-β) was slightly higher in IGR group,but significantly lower in DM group (P ＜ 0.01).Homeostasis model assessment for insulin resistance (HOMA-IR) was slightly higher in IGR and DM groups but without significant difference among 3 groups.In multivariate analyses,family history of diabetes(OR=12.710,95％ CI 1.176-137.30,P=0.036),age(OR=1.106,95％ CI 1.018-1.202,P=0.017),and GH levels(OR=1.075,95％ CI 1.007-1.147,P=0.030) were independent risk factors of diabetes in acromegaly patients.Conclusion Impaired glucose metabolism is present in nearly 70％ of patients at diagnosis of acromegaly,and is associated with age,family history of diabetes,and higher GH levels,but not with IGF-1 levels.
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Objective To investigate the pancreas size and echo characteristics of patients with glucose metabolism disorders including type 2 diabetes,and to study its related factors.Methods One hundred and fifty-seven patients from Nanjing Drum Tower Hospital with normal glucose metabolism,impaired glucose regulation,newly diagnosed type 2 diabetes and established type 2 diabetes were collected.The average gray scale intensity of the liver,kidney,pancreas region of interest was measured by using the histogram method.Then the liver and kidney echo ratio,liver attenuation coefficient was calculated,and the fat content of liver was determined by using formula.The size of pancreas head,body and tail was detected by ultrasound,and the sum of three values was used as the pancreas size indicator.Univariate and multivariate logistic regression analysis was performed on the size of pancreas and intensity of echo.Results The size of pancreas ranged from 2.39 ～ 6.09 cm with a mean size of (4.43 ± 0.59) cm,and the size was ≤ 5 cm in 130patients,＞5 cmin 27 patients.The intensity of echo ranged from 41.0 ～ 190.6 with a mean number of 120.0 ±31.1,and the intensity of echo was ≤120 in 83 patients,＞ 120 in 74 patients.The content of liver fat ranged from-1.11％ ～ 62.50％ with a mean number of (15.67± 11.97)％.Univariate logistic regression analysis suggested the size of pancreas was related to age and obesity,and pancreas echo was related to obesity degree,types of participants,the level of blood glucose,and grade of fatty liver (all P ＜ 0.05).Multivariate logistic regression analysis indicated obesity degree is the most important factor for prediction of pancreas size and echo (P ＜ 0.05).Conclusions Quantitative ultrasound measurement of pancreas size and echo can reflect the degree of fat infiltration of pancreas,and it has some clinical value.
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Objective To study the relationship between u rinary,serum laminin (LN) and urinary albumin (Alb) in type 2 diabetes mellitus.Methods Urinary,serum LN and urinary creatinine (Cr) were measure d in 116 patients with type 2 diabeties mellitus and 31 normal controls .Results ①Urinary LN/Cr in DM microalbumi nuria (DMMA) group was higher than control group (group C) (P
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Urinary excretions of transforming grow th factor-? 1 (TGF-? 1), laminin (LN) and type Ⅳ collagen were determined i n 182 type 2 diabetic patients. Urinary excretions of TGF-? 1, LN and type Ⅳ collagen were increased in type 2 diabetic patients, and these findings were fa irly well correlated with severity of diabetic nephropathy (DN). Urinary TGF-? 1 seems to be the early index of DN, urinary LN and type Ⅳ collagen appear to be the indices of DN severity.