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Open access

Sakina H Bharmal, Wandia Kimita, Juyeon Ko, and Maxim S Petrov

Objective

Early identification of individuals at high risk for metabolic derangements after an attack of acute pancreatitis (AP) is critical with a view to tertiary preventing of this disease. The aim was to investigate whether fasting pancreatic and gut hormones at baseline were predictive of future risk of new-onset prediabetes after acute pancreatitis (NOPAP) in individuals with non-necrotising AP.

Methods

This was a prospective longitudinal cohort study that included 69 consecutive non-diabetic participants with AP, of whom 55% (n = 38) had normoglycaemia both at baseline and during follow-up, 25% (n = 17) had prediabetes both at baseline and during follow-up, and 20% (n = 14) were normoglycaemic at baseline but developed NOPAP during follow-up. The associations between the study groups and circulating fasting levels of pancreatic and gut hormones (insulin, glucagon, C-peptide, amylin, glucose-dependent insulinotropic peptide, glucagon-like peptide-1, pancreatic polypeptide, and peptide YY) were studied using multinomial regression in both unadjusted and adjusted analyses.

Results

Elevated plasma insulin and glucagon at baseline were significantly associated with NOPAP (adjusted odds ratio 1.99, 95% CI 1.01 to 3.92 and adjusted odds ratio 3.44, 95% CI 1.06 to 11.19, respectively). The same hormones had no significant association with antecedent prediabetes in AP. The other studied hormones were not significantly associated with the study groups.

Conclusions

Normoglycaemic AP individuals with elevated fasting levels of insulin and glucagon at baseline constitute a high-risk group for future NOPAP.

Open access

Xun Gong, Lili You, Feng Li, Qingyu Chen, Chaogang Chen, Xiaoyun Zhang, Xiuwei Zhang, Wenting Xuan, Kan Sun, Guojuan Lao, Chuan Wang, Yan Li, Mingtong Xu, Meng Ren, and Li Yan

Objective

Adiponectin is an adipocyte-derived hormone with an important role in glucose metabolism. The present study explored the effect of adiponectin in diverse population groups on pre-diabetes and newly diagnosed diabetes.

Methods

A total of 3300 individuals were enrolled and their data were collected in the analyses dataset from December 2018 to October 2019. Cluster analysis was conducted based on age, BMI, waistline, body fat, systolic blood pressure, triglycerides, and glycosylated hemoglobin 1c. Cluster analysis divided the participants into four groups: a young-healthy group, an elderly-hypertension group, a high glucose–lipid group, and an obese group. Odds ratio (OR) and 95% CIs were calculated using multivariate logistic regression analysis.

Results

Compared with the first quartile of adiponectin, the risk of pre-diabetes of fourth quartile was decreased 61% (aOR = 0.39, 95% CI (0.20–0.73)) in the young-healthy group; and the risk of diabetes of fourth quartile was decreased 85% (aOR = 0.15, 95% CI (0.02–0.67)) in the obese group. There were no significant correlations between the adiponectin level and diabetes/pre-diabetes in the other two groups. Additionally, receiver operating characteristic curve analysis indicated that adiponectin could significantly improve the diagnosis based on models in the young-healthy group (from 0.640 to 0.675) and the obese group (from 0.714 to 0.761).

Conclusions

Increased adiponectin levels were associated with decreased risk of pre-diabetes in the young-healthy population, and with a decreased the risk of diabetes in the obese population. An increased adiponectin level is an independent protective factor for pre-diabetes and diabetes in a specific population in south China.

Open access

Xiang Hu, Qiao Zhang, Tian-Shu Zeng, Jiao-Yue Zhang, Jie Min, Sheng-Hua Tian, Hantao Huang, Miaomiao Peng, Nan Zhang, Mengjiao Li, Qing Wan, Fei Xiao, Yan Chen, Chaodong Wu, and Lu-Lu Chen

Objective

To explore the influence by not performing an oral glucose tolerance test (OGTT) in Han Chinese over 40 years.

Design

Overall, 6682 participants were included in the prospective cohort study and were followed up for 3 years.

Methods

Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG), FPG and 2h-PG (OGTT), and HbA1c testing using World Health Organization (WHO) or American Diabetes Association (ADA) criteria were employed for strategy analysis.

Results

The prevalence of diabetes is 12.4% (95% CI: 11.6–13.3), while the prevalence of prediabetes is 34.1% (95% CI: 32.9–35.3) and 56.5% (95% CI: 55.2–57.8) using WHO and ADA criteria, respectively. 2h-PG determined more diabetes individuals than FPG and HbA1c. The testing cost per true positive case of OGTT is close to FPG and less than 2h-PG or HbA1c. FPG, 2h-PG and HbA1c strategies would increase costs from complications for false-positive (FP) or false-negative (FN) results compared with OGTT. Moreover, the least individuals identified as normal by OGTT at baseline developed (pre)diabetes, and the most prediabetes individuals identified by HbA1c or FPG using ADA criteria developed diabetes.

Conclusions

The prevalence of isolated impaired glucose tolerance and isolated 2-h post-load diabetes were high, and the majority of individuals with (pre)diabetes were undetected in Chinese Han population. Not performing an OGTT results in underdiagnosis, inadequate developing risk assessment and probable cost increases of (pre)diabetes in Han Chinese over 40 years and great consideration should be given to OGTT in detecting (pre)diabetes in this population. Further population-based prospective cohort study of longer-term effects is necessary to investigate the risk assessment and cost of (pre)diabetes.

Open access

Mai Morsi, Torben Schulze, Eike Früh, Dennis Brüning, Uwe Panten, and Ingo Rustenbeck

Observing different kinetics of nutrient-induced insulin secretion in fresh and cultured islets under the same condition we compared parameters of stimulus secretion coupling in freshly isolated and 22-h-cultured NMRI mouse islets. Stimulation of fresh islets with 30 mM glucose after perifusion without nutrient gave a continuously ascending secretion rate. In 22-h-cultured islets the same protocol produced a brisk first phase followed by a moderately elevated plateau, a pattern regarded to be typical for mouse islets. This was also the response of cultured islets to the nutrient secretagogue alpha-ketoisocaproic acid, whereas the secretion of fresh islets increased similarly fast but remained strongly elevated. The responses of fresh and cultured islets to purely depolarizing stimuli (tolbutamide or KCl), however, were closely similar. Signs of apoptosis and necrosis were rare in both preparations. In cultured islets, the glucose-induced rise of the cytosolic Ca2+ concentration started from a lower value and was larger as was the increase of the ATP/ADP ratio. The prestimulatory level of mitochondrial reducing equivalents, expressed as the NAD(P)H/FAD fluorescence ratio, was lower in cultured islets, but increased more strongly than in fresh islets. When culture conditions were modified by replacing RPMI with Krebs–Ringer medium and FCS with BSA, the amount of released insulin varied widely, but the kinetics always showed a predominant first phase. In conclusion, the secretion kinetics of fresh mouse islets is more responsive to variations of nutrient stimulation than cultured islets. The more uniform kinetics of the latter may be caused by a different use of endogenous metabolites.

Open access

Mojca Jensterle, Nika Aleksandra Kravos, Simona Ferjan, Katja Goricar, Vita Dolzan, and Andrej Janez

Objective

Long-term efficacy of metformin in polycystic ovarian syndrome (PCOS) apart from in those with impaired glucose tolerance or diabetes remains unproven. We aimed to evaluate the impact of metformin in overweight-obese patients with PCOS and normal baseline glycemic homeostasis.

Methods

A 10-year longitudinal follow-up of a retrospective cohort comprising 159 patients with PCOS defined by Rotterdam criteria, BMI ≥25 kg/m2 and normal initial glucose homeostasis (age 28.4 ± 6.4 years, BMI 34.9 ± 6.6 kg/m2) that had been receiving metformin 1000 mg BID. Collection data contained 6085 time-points including anthropometric, hormonal and metabolic parameters.

Results

After the first year body mass (BM) decreased for 3.9 ± 6.8 kg (P < 0.001) and remained stable during the following 3 years. Menstrual frequency (MF) increased to 3.0 ± 3.9 bleeds/year (P < 0.001) after first year to over 11 bleeds/year in the following years. The total testosterone and androstenedione decreased to 15.4 ± 47.9% and 11.3 ± 46.4% within first year, with further decrease in total testosterone and androstenedione to 37.8 ± 61.8 and 24.8 ± 40.5% at the fifth year of the follow-up. The total conversion rate to prediabetes and diabetes was extremely low throughout observation period. Less than 25% of patients continued with metformin for more than 5 years with further dropout to only 6% on metformin therapy at the tenth year of follow-up.

Conclusions

Long-term metformin treatment of overweight-obese women with PCOS and normal baseline glycemic homeostasis resulted in reduction and stabilization of BM, improvements of MF and androgen profile and low conversion rate to diabetes.

Open access

Xiaoli Liu, Lanxiang Liu, Rui Wang, Xiaojiao Jia, Binbin Liu, Ning Ma, and Qiang Lu

Background

We aimed to investigate early arteriosclerosis and its risk factors in populations with prediabetes and new-onset diabetes.

Materials and methods

A total of 148 participants who did not have diabetes mellitus were assigned to three groups through an oral glucose tolerance test: the normal glucose tolerance (NGT) group; the impaired glucose regulation, also known as prediabetes group and the new-onset type 2 diabetes mellitus group. The insulin resistance index was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR). An ELISA was used to determine the level of fibroblast growth factor 21 (FGF21). An arteriosclerosis detector was used to measure the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). The baPWV, ABI, and FGF21 were used to assess early arteriosclerosis.

Results

Significant differences in age, systolic blood pressure (SBP), fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), 2-h insulin (2hINS), and HOMA-IR were found between the NGT group and the prediabetes and new-onset diabetes groups. All of the above, except 2hINS, showed an increasing trend. Moreover, the FGF21 was higher in the new-onset diabetes group than in the NGT group. The baPWV was higher in the new-onset diabetes group than in the other two groups, but no significant difference was noted in the ABI. Age, SBP, diastolic blood pressure, FPG, 2hPG, and FGF21 were positively correlated with the baPWV. In addition, FPG, SBP, FGF21, and HOMA-IR were independent risk factors for the baPWV.

Conclusions

Patients with prediabetes and new-onset diabetes may have more significant early arteriosclerosis. The blood glucose level and insulin resistance index may be independent risk factors for early arteriosclerosis.

Open access

Xiangyu Gao, Wanwan Sun, Yi Wang, Yawen Zhang, Rumei Li, Jinya Huang, and Yehong Yang

Background

Islet autoantibodies occur in type 2 diabetes. Our study aimed to investigate the prevalence of positive islet autoimmunity in community patients with type 2 diabetes.

Methods

A total of 495 community patients with type 2 diabetes were recruited using the method of cluster sampling in this cross-sectional study. Three islet autoantibodies including glutamic acid decarboxylase antibody (GADA), insulin autoantibody (IAA) and islet cell antibody (ICA) were measured, and clinical characteristics involved in those individuals were evaluated.

Results

The positive rate of islet autoantibodies was 28.5% in total, while combinations of different autoantibodies were rarely seen. Compared with GADA-negative group, positive counterparts significantly tended to have lower levels of body mass index (BMI), waist-hip ratio (WHR), and urinary microalbumin (mALB) (P < 0.05). Adjusted for confounding factors, WHR, triglycerides (TG), and mALB seemed to be negative independent predictors of GADA (OR < 1, P < 0.05). Patients with positive IAA tended to receive insulin treatment (P < 0.0001). Besides, fasting blood glucose (FBG), serum levels of high-density lipoprotein cholesterol (HDL-CH), aspartate transaminase (AST), and γ-glutamyltransferase (GGT) were more likely to be higher in IAA positive subgroup in comparison with the negative counterparts. While after AST was adjusted by unconditional logistic regression analysis, history of insulin treatment, FBG, HDL-CH, and GGT were confirmed as positive predictors of IAA. Furthermore, in patients who were IAA positive, those treated with exogenous insulin tended to have longer duration of diabetes than non-insulin treatment counterparts (P < 0.0001). With regard to ICA, however, there were no significant differences between the two subgroups, except that serum level of AST/ALT seemed to be slightly different (P = 0.064).

Conclusion

These data suggested that type 2 diabetic community patients with positive GADA tended to be lean and were able to maintain normal lipid metabolism, while patients with positivity of IAA were frequently accompanied with insulin treatment and more closely associated with diabetic liver damage.

Open access

Tingting Shu, Zhigang Lv, Yuchun Xie, Junming Tang, and Xuhua Mao

It has been well established that glucotoxicity induces pancreatic β-cells dysfunction; however, the precise mechanism remains unclear. Our previous studies demonstrated that high glucose concentrations are associated with decreased hepcidin expression, which inhibits insulin synthesis. In this study, we focused on the role of low hepcidin level-induced increased iron deposition in β-cells and the relationship between abnormal iron metabolism and β-cell dysfunction. Decreased hepcidin expression increased iron absorption by upregulating transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) expression, resulting in iron accumulation within cells. Prussia blue stain and calcein-AM assays revealed greater iron accumulation in the cytoplasm of pancreatic tissue isolated from db/db mice, cultured islets and Min6 cells in response to high glucose stimulation. Increased cytosolic iron deposition was associated with greater Fe2+ influx into the mitochondria, which depolarized the mitochondria membrane potential, inhibited ATP synthesis, generated excessive ROS and induced oxidative stress. The toxic effect of excessive iron on mitochondrial function eventually resulted in impaired insulin secretion. The restricted iron content in db/db mice via reduced iron intake or accelerated iron clearance improved blood glucose levels with decreased fasting blood glucose (FBG), fasting blood insulin (FIns), HbA1c level, as well as improved intraperitoneal glucose tolerance test (IPGTT) results. Thus, our study may reveal the mechanism involved in the role of hepcidin in the glucotoxcity impaired pancreatic β cell function pathway.

Open access

Sara Ullsten, Sara Bohman, Marie E Oskarsson, K Peter R Nilsson, Gunilla T Westermark, and Per-Ola Carlsson

Islet amyloid and beta cell death in type 2 diabetes are heterogeneous events, where some islets are affected early in the disease process, whereas others remain visibly unaffected. This study investigated the possibility that inter-islet functional and vascular differences may explain the propensity for amyloid accumulation in certain islets. Highly blood-perfused islets were identified by microspheres in human islet amyloid polypeptide expressing mice fed a high-fat diet for three or 10 months. These highly blood-perfused islets had better glucose-stimulated insulin secretion capacity than other islets and developed more amyloid deposits after 10 months of high-fat diet. Similarly, human islets with a superior release capacity formed more amyloid in high glucose culture than islets with a lower release capacity. The amyloid formation in mouse islets was associated with a higher amount of prohormone convertase 1/3 and with a decreased expression of its inhibitor proSAAS when compared to islets with less amyloid. In contrast, levels of prohormone convertase 2 and expression of its inhibitor neuroendocrine protein 7B2 were unaltered. A misbalance in prohormone convertase levels may interrupt the normal processing of islet amyloid polypeptide and induce amyloid formation. Preferential amyloid load in the most blood-perfused and functional islets may accelerate the progression of type 2 diabetes.

Open access

Darling M Rojas-Canales, Michaela Waibel, Aurelien Forget, Daniella Penko, Jodie Nitschke, Fran J Harding, Bahman Delalat, Anton Blencowe, Thomas Loudovaris, Shane T Grey, Helen E Thomas, Thomas W H Kay, Chris J Drogemuller, Nicolas H Voelcker, and Patrick T Coates

Islet transplantation is currently the only minimally invasive therapy available for patients with type 1 diabetes that can lead to insulin independence; however, it is limited to only a small number of patients. Although clinical procedures have improved in the isolation and culture of islets, a large number of islets are still lost in the pre-transplant period, limiting the success of this treatment. Moreover, current practice includes islets being prepared at specialized centers, which are sometimes remote to the transplant location. Thus, a critical point of intervention to maintain the quality and quantity of isolated islets is during transportation between isolation centers and the transplanting hospitals, during which 20–40% of functional islets can be lost. The current study investigated the use of an oxygen-permeable PDMS microwell device for long-distance transportation of isolated islets. We demonstrate that the microwell device protected islets from aggregation during transport, maintaining viability and average islet size during shipping.