scholarly journals Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ming Shen ◽  
Meng Wang ◽  
Wenqiang He ◽  
Min He ◽  
Nidan Qiao ◽  
...  

Purpose. To evaluate the change in glucose tolerance in treatment-naïve patients with acromegaly after administration of SSA and to identify predictive factors of glucose impairment during SSA therapy. Methods. Oral glucose tolerance testing (OGTT) was performed on 64 newly diagnosed and treatment-naïve patients with acromegaly both at pretreatment and 3 months after initiation of treatment with long-acting SSA. Insulin resistance (IR) was assessed by homeostatic model assessment- (HOMA-) IR and ISOGTT. Insulin secretion was assessed by HOMA-β, INS0/BG0, IGI (insulinogenic index), IGI/IR, ISSI2, and AUCINS/AUCBG. Receiver-operating characteristic (ROC) curves were generated to determine the optimal cutoffs to predict the impact of SSA on glucose metabolism. Results. Pretreatment, 19, 24, and 21 patients were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM), respectively. Posttreatment, IR, represented by ISOGTT, was significantly improved in all 3 groups. Insulin secretion, represented by HOMA-β, declined in the NGT and IGT groups, but was unaltered in the DM group. The glucose tolerance status deteriorated in 18 (28.1%) patients, including 13 patients in the NGT group and 5 patients in the IGT group. Deterioration was associated with lower baseline BG120 (plasma glucose 120 min post-OGTT), less reduction of growth hormone (GH), and greater reduction of insulin secretion after SSA therapy. BG120 greater than 8.1 mmol/l provided the greatest sensitivity and specificity in predicting the stabilization and/or improvement of glucose tolerance status after SSA treatment (PPV 90.7%, NPV 66.7%, p<0.001). Conclusions. The deterioration of glucose metabolism induced by SSA treatment is caused by the less reduction of GH and the more inhibition of insulin secretion, which can be predicted by the baseline BG120 during OGTT.

Author(s):  
Nicole Sheanon ◽  
Deborah Elder ◽  
Jane Khoury ◽  
Lori Casnellie ◽  
Iris Gutmark-Little ◽  
...  

Intro: Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but, it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity and insulin secretion. Methods: Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function. Results: Twenty-one TS girls (35%) met criteria for pre-diabetes. Impaired fasting glucose (IFG) was present in 18% of girls with TS and 2% HC (p-value = 0.0003). Impaired glucose tolerance (IGT) was present in 23% of TS girls and 0% HC (p-value < 0.001). The HbA1c was not different between TS and HC (median 5%, p= 0.42). Youth with TS had significant reductions in insulin sensitivity (SI), β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for BMI z-score (p-values: 0.0006, 0.002, <0.0001 for SI, Φtotal, DI, respectively). Conclusions: β-cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and insulin sensitivity suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.


2015 ◽  
Vol 6 ◽  
pp. JCM.S32743 ◽  
Author(s):  
Hiroko Katayama ◽  
Daisuke Tachibana ◽  
Akihiro Hamuro ◽  
Takuya Misugi ◽  
Koka Motoyama ◽  
...  

Objective The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design. Patients and Methods Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors. Results Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. Conclusions Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixuan Liu ◽  
Tao Yuan ◽  
Shuoning Song ◽  
Shi Chen ◽  
Linjie Wang ◽  
...  

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.


2018 ◽  
Vol 61 (4) ◽  
pp. 153-161 ◽  
Author(s):  
Sufang Chen ◽  
Wei Wei ◽  
Minjie Chen ◽  
Xiaobo Qin ◽  
Lianglin Qiu ◽  
...  

Numerous studies have implicated tumor necrosis factor α (TNFα) in the pathogenesis of type 2 diabetes. However, the role of its primary receptor, TNF receptor 1 (TNFR1), in homeostatic regulation of glucose metabolism is still controversial. In addition to TNFα, lymphotoxin α (LTα) binds to and activates TNFR1. Thus, TNFα and LTα together are known as TNF. To delineate the role of TNF signaling in glucose homeostasis, the present study ascertained how TNF signaling deficiency affects major regulatory components of glucose homeostasis. To this end, normal diet-fed male TNFR1-deficient mice (TNFR1−/−), TNFα/LTα/LTβ triple-deficient mice (TNF/LT∆3) and their littermate controls were subjected to intraperitoneal glucose tolerance test, insulin tolerance test and oral glucose tolerance test. The present results showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had comparable body weight, tolerance to intraperitoneal glucose and sensitivity to insulin. However, their tolerance to oral glucose was significantly increased. Additionally, glucose-induced insulin secretion assessments revealed that TNFR1 or TNF/LT deficiency significantly increased oral but not intraperitoneal glucose-induced insulin secretion. Consistently, qPCR and immunohistochemistry analyses showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had significantly increased ileal expression of glucagon-like peptide-1 (GLP-1), one of the primary incretins. Their oral glucose-induced secretion of GLP-1 was also significantly increased. These data collectively suggest that physiological TNF signaling regulates glucose metabolism primarily through effects on GLP-1 expression and secretion and subsequently insulin secretion.


2013 ◽  
Vol 2 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Taísa A R Vicente ◽  
Ívina E S Rocha ◽  
Roberto Salvatori ◽  
Carla R P Oliveira ◽  
Rossana M C Pereira ◽  
...  

ObjectivesAdult subjects with untreated, lifetime, isolated GH deficiency (IGHD) due to a homozygous GHRH receptor gene mutation (MUT/MUT) residing in Itabaianinha, Brazil, present with lower BMI, higher prevalence of impaired glucose tolerance (IGT), increased insulin sensitivity (IS), and reduced β-cell function (βCF) when compared with non-BMI-matched homozygous normal controls. However, the prevalence of diabetes mellitus (DM) in this cohort is unknown. Comparing their IS and βCF with BMI-matched individuals heterozygous for the same mutation (MUT/N) may be useful to elucidate the role of the GH–IGF1 axis in IS and βCF. The purposes of this work were to verify the prevalence of IGT and DM in adult MUT/MUT subjects from this kindred and to compare IS and βCF in MUT/MUT and MUT/N.DesignCross-sectional study.MethodsWe studied most (51) of the living IGHD adults of this kindred who are GH naive. The oral glucose tolerance test (OGTT) could be performed in 34 subjects, fasting glucose was measured in 15, while two had a previous diagnosis of DM. The OGTT results of 24 MUT/MUT subjects were compared with those of 25 BMI-matched MUT/N subjects. IS was assessed by homeostatic model assessment of insulin resistance (HOMA–IR), quantitative IS check index, and oral glucose IS index for 2 and 3 h. βCF was assayed by HOMA-β, insulinogenic index, and the area under the curve of insulin:glucose ratio.ResultsThe prevalence of DM and IGT in IGHD was 15.68 and 38.23% respectively. IS was increased and βCF was reduced in MUT/MUT in comparison with MUT/N.ConclusionsLifetime, untreated IGHD increases IS, impairs βCF, and does not provide protection from diabetes.


2019 ◽  
Vol 7 (1) ◽  
pp. e000596 ◽  
Author(s):  
Ayaka Tsuboi ◽  
Satomi Minato ◽  
Megumu Yano ◽  
Mika Takeuchi ◽  
Kaori Kitaoka ◽  
...  

ObjectiveTo examine whether serum adiponectin and orosomucoid were associated with postload glucose ≤70 mg/dL during an oral glucose tolerance test (OGTT), termed as postload low glycemia, a possible inverse marker for dysglycemia.Research design and methods75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30–120 min period in 168 normal-weight Japanese women (18–24 years). Insulin resistance (IR) and β-cell function inferred from serum insulin kinetics during OGTT, fat mass and distribution by dual-energy X-ray absorptiometry (DXA), serum adiponectin and inflammatory markers were compared cross-sectionally between 39 women with and 129 women without postload low glycemia.ResultsOf 168 women, 161 had normal glucose tolerance. Women with as compared with those without postload low glycemia had lower fasting and postload glycemia despite similar fasting and postload insulinemia. They had higher insulinogenic index (p=0.03) and lower adipose IR (a product of fasting free fatty acid and insulin, p=0.01), although DXA-derived general and central adiposity, the Matsuda Index and homeostasis model assessment-IR did not differ. In addition, they had higher adiponectin and lower orosomucoid (both p<0.001). Multivariate logistic regression analyses revealed that adiponectin (OR: 1.14, 95% CI 1.03 to 1.26, p=0.009) and orosomucoid (0.96, 0.93 to 0.97, p=0.008) were associated with postload low glycemia independently of adipose IR and insulinogenic index.ConclusionsHigher adiponectin and lower orosomucoid were associated with 70 or lower mg/dL of postload glucose, a possible inverse marker for dysglycemia, in young women independently of DXA-derived fat mass and distribution, insulin secretion and IR.


2011 ◽  
Vol 47 (3) ◽  
pp. 261-271 ◽  
Author(s):  
Inagadapa J N Padmavathi ◽  
Kalashikam Rajender Rao ◽  
Manchala Raghunath

Robust evidence suggests that nutritional insult during fetal development could program the offspring to glucose intolerance, impaired insulin response and insulin resistance (IR). Considering the importance of chromium (Cr) in maintaining carbohydrate metabolism, this study determined the effect of maternal Cr restriction (CrR) on glucose metabolism and plasma insulin in Wistar/NIN (WNIN) rat offspring and the associated biochemical and/or molecular mechanisms. Female, weanling WNIN rats receivedad libitumfor 12 weeks, a control diet or the same with 65% restriction of Cr and mated with control males. Some of the Cr-restricted dams were rehabilitated from conception or parturition and their pups weaned on to control diet. At the time of weaning, half of the Cr restricted offspring were rehabilitated to control diet while others continued on Cr-restricted diet. Maternal CrR increased fasting plasma glucose, fasting insulin, homeostasis model assessment of IR, and area under the curve of glucose and insulin during oral glucose tolerance test in the offspring. Expression and activity of rate-limiting enzymes of glucose metabolism were comparable among different groups and expression of genes involved in insulin secretion was increased albeit in male offspring whereas antioxidant enzyme activities were decreased in offspring of both genders. Rehabilitation, in general, corrected the changes albeit partially. Maternal dietary CrR induced IR, impaired glucose tolerance in WNIN rat offspring and was associated with increased oxidative stress, which may predispose them to type 2 diabetes in their later life.


2013 ◽  
Vol 169 (1) ◽  
pp. 99-108 ◽  
Author(s):  
C Urbani ◽  
C Sardella ◽  
A Calevro ◽  
G Rossi ◽  
I Scattina ◽  
...  

ObjectiveAbnormalities of glucose metabolism are common findings of acromegaly. However, robust evidence on whether therapy with somatostatin analogs (SSAs) or pegvisomant (PEG) differently affects glucose metabolism is lacking. The purpose of this study was to evaluate the effects of therapy with SSAs, PEG, or their combination on glucose metabolism in a large series of acromegalic patients.DesignThis was a historical–prospective study. Among 50 consecutive acromegalic patients under SSA therapy, acromegaly in 19 patients was controlled. PEG used in combination with SSA therapy allowed the control of acromegaly in the remaining 31 patients and was then continued as monotherapy in 18 patients.MethodsThe following parameters were evaluated at the diagnosis of acromegaly and during different treatments: fasting plasma glucose (FPG) and insulin concentrations, insulin sensitivity (QUICK-I), homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Comparison was made using analysis for paired data.ResultsInsulin resistance improved when acromegaly was controlled with therapy with SSAs, PEG, or SSA+PEG. However, FPG concentrations were higher during SSA therapy (alone or combined with PEG) than at the diagnosis of acromegaly, even when corrected for disease activity, whereas they were reduced during PEG therapy. Mean glucose concentrations during the OGTT were higher in patients receiving SSA therapy than in those receiving PEG therapy. In addition, the prevalence of diabetes or impaired glucose tolerance was higher during SSA therapy than at diagnosis or during PEG therapy and was not influenced by disease control.ConclusionsMedical therapies for acromegaly reduce insulin resistance and increase insulin sensitivity; on the contrary, glucose indexes may be differently affected by SSA or PEG therapy.


2021 ◽  
Vol 23 (6) ◽  
pp. 523-531
Author(s):  
O. V. Vasyukova ◽  
P. L. Okorokov ◽  
V. A. Peterkova

BACKGROUND: Incidence of Type 2 Diabetes Mellitus (T2DM) and associated dysglycemic conditions, increasing the risk of diabetes development, continues to rise worldwide, most notably due to ever-growing obesity rate. Early identification of the persons who are exposed to the risk of T2DM development holds much significance for prevention of both this disease and associated cardiometabolic complications.AIM: To study characteristics of insulin secretion and insulin sensitivity among obese children and adolescents versus the glycemic level 60 minutes (GL60) after the standard oral glucose tolerance test (OGTT).METHODS: This open-label comparative cross-sectional study involved 613 children in the age between 6 and 17.9 years old with constitutive-exogenous obesity, divided into 2 groups: 173 patients with GL60 level ≥ 8.6 mmol/L and 440 children with GL60 level < 8.6 mmol/L. They underwent a screening for dyslipidemia, non-alcoholic fatty liver disease, arterial hypertension and impaired glucose tolerance (IGT). Insulin secretion was evaluated on the basis of maximal (IRI max), average level (IRI avg) of insulin in the course of OGTT and insulinogenic index (IGI), insulin resistance (IG) — by Matsuda index.RESULTS: The groups were comparable in the terms of age, sex, sexual maturation stage and obesity level. Children with GL60 level ≥ 8.6 mmol/L were characterized by higher IR (Matsuda 2.8 ± 2.3 vs 3.5 ± 2.2, р < 0.01), hyperinsulinemia (IRI max 190.0 ± 59.5 vs 157.1 ± 63.4 μU/ml, р < 0.001, IRI avg 115.3 ± 59.7 vs 90.2 ± 54.1 μU/ml, p < 0.001) along with low IGI value (1.84 ± 1.62 vs 2.61 ± 1.3, р < 0.01), which is indicative of the first phase insulin secretion impairment. The lowest IGI values were found among the "GL60 level ≥ 8.6 mmol/L" group patients with IGT (1.4 ± 0.9). Besides, the patients with GL60 level ≥ 8.6 mmol/L are characterized by the higher rate of metabolic complications in the form of impaired glucose tolerance, arterial hypertension, fatty hepatosis and steatohepatitis.CONCLUSIONS: GL60 level ≥ 8.6 mmol/L can be used as an additional marker for metabolically complicated obesity among children and adolescents with a high risk of the carbohydrate metabolism disorder development.


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