Original Data

Rev Diabet Stud, 2016, 13(1):35-58 DOI 10.1900/RDS.2016.13.35

Pancreas Transplantation of US and Non-US Cases from 2005 to 2014 as Reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR)

Angelika C. Gruessner, Rainer W.G. Gruessner

Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA
Address correspondence to: Angelika C. Gruessner, e-mail: gruessna@upstate.edu

Abstract

This report is an update of pancreas and kidney transplant activities in the US and non-US region in two periods, 2005-2009 and 2010-2014. The aim of the report was to analyze transplant progress and success in the US compared to non-US countries, and to compare trends between the two periods. Between 2005-2009 and 2010-2014, the number of US pancreas transplants declined by over 20%, while the overall number of pancreas transplants performed outside the US has increased. The decline in US numbers is predominantly due to the decline in primary and secondary pancreas after kidney transplants (PAK). During the time period studied, the number of PAK transplants dropped by 50%. In contrast, the number of simultaneous pancreas/kidney transplants (SPK) declined by only 10%, and the number of pancreas transplants alone (PTA) by 20%. Over 90% of pancreas transplants worldwide were performed, with a simultaneous kidney transplant and excellent results. Transplant outcomes in SPK improved significantly because of a decrease in the rates of technical and immunologic graft loss. In 2010-2014 vs. 2005-2009, US SPK transplant patient survival at 1 year post-transplant increased from 95.7% to 97.4%, pancreas graft function from 88.3% to 91.3%, and kidney function from 93.6% to 95.5%. A significant improvement was also noted in PAK transplants. One-year patient survival increased from 96.4% to 97.9% and pancreas graft function from 81.0% to 86.0%. PTA 1-year patient survival remained constant at 97%, and pancreas 1-year graft survival improved from 81.0% to 85.7%. With the decline in the number of transplants, a change towards better pancreas donor selection was observed. In solitary transplants, the donors were primarily young trauma victims, and the pancreas preservation time was relatively short. A general tendency towards transplanting older recipients was noted. In 2010-2014 vs. 2005-2009, PTA recipients 50 years of age or older accounted for 32% vs. 22%, PAK for 28% vs. 22%, and SPK for 22% vs. 20%. This may be due to a relatively lower immunologic graft loss rate, especially in solitary transplants, which historically has been high in young recipients. The number of pancreas transplants in patients with type 2 diabetes and end-stage renal disease has increased, and accounted for 9% of all SPK recipients in 2010-2014.

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Rev Diabet Stud, 2016, 13(1):59-65 DOI 10.1900/RDS.2016.13.59

Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes

Kristiina Tertti1, Jorma Toppari2, Helena E. Virtanen2, Sergey Sadov2, Tapani Rönnemaa3

1Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland
2Departments of Physiology and Pediatrics, University of Turku, Turku, Finland
3Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland
Address correspondence to: Kristiina Tertti, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland, e-mail: kristiina.tertti@tyks.fi

Abstract

OBJECTIVES: Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring. Our aim was to determine whether metformin treatment of gestational diabetes mellitus (GDM) affects testicular size in male offspring. METHODS: We compared the testicular size in prepubertal boys born to mothers who participated in a randomized controlled trial (RCT) comparing metformin with insulin in the treatment of GDM. Twenty-five (42.4% of invited) and 27 (52.9% of invited) boys whose mothers had been treated with metformin or insulin, respectively, participated in the study. Testicular size was measured by a ruler, an orchidometer, and by ultrasonography at the age of 33 to 85 months. RESULTS: The mean age of the boys was 60 months at the time of examination, and did not differ between the metformin and insulin group (p = 0.88). There was no difference in testicular size between the boys in the two groups (p always ≥ 0.40), and there were no significant differences in height, weight, BMI, BMI z-score, or waist-to-hip ratio (WHR) between the boys in the groups. CONCLUSIONS: Prepubertal testicular size did not differ between offspring born to metformin-treated mothers and those born to insulin-treated mothers.

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Rev Diabet Stud, 2016, 13(1):66-78 DOI 10.1900/RDS.2016.13.66

Chronic Exposure to Proline Causes Aminoacidotoxicity and Impaired Beta-Cell Function: Studies In Vitro

Zhenping Liu1,2, Per B. Jeppesen1, Søren Gregersen1, Lotte Bach Larsen3, Kjeld Hermansen1

1Department of Medicine and Endocrinology, Aarhus University Hospital, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark
2Department of Endocrinology, PLA 309 Hospital, 17 Heishanhu Road, Haidian District, 100091, Beijing, P. R. China
3Department of Food Science, Faculty of Agricultural Sciences, Aarhus University, DK-8230 Tjele, Denmark
Address correspondence to: Zhenping Liu, e-mail: zhengping.liu@ki.au.dk

Abstract

BACKGROUND: Pancreatic islet-cell dysfunction is a hallmark in the development of diabetes, but the reasons for the primary β-cell defect are still elusive. Elevated circulating proline levels have been found in subjects with insulin resistance, obesity, and type 2 diabetes. Therefore, we assessed β-cell function, gene expressions, and cell death after long-term exposure of pancreatic β-cells to excess proline in vitro. METHODS: Isolated mouse islets and INS-1E cells were incubated with and without excess proline. After 72 h, we examined: (1) β-cell function, including basal insulin secretion (BIS) and glucose-stimulated insulin secretion (GSIS), (2) transcription factors related to insulin gene expression and enzymes involved in the tricarboxylic acid cycle and cholesterol biogenesis, (3) cellular triglycerides (TG) and cholesterol content, (4) the death of INS-1E cells and 3H thymidine incorporation, and (5) protein expression of INS-1E cells in response to proline by proteomics. RESULTS: We found that high doses of proline increased BIS and decreased GSIS in both isolated mouse islets and INS-1E cells. MafA, insulin 1, and the cytochrome c oxidase subunit VIa polypeptide 2 mRNA expressions were all downregulated, indicating that proline impaired insulin gene transcription and mitochondrial oxidative phosphorylation. In contrast, mevalonate decarboxylase gene expression was upregulated, and simultaneously, cholesterol content in INS-1E cells was enhanced. Protein profiling of INS-1E cells revealed that cytosolic non-specific dipeptidase and α enolase were differentially expressed. CONCLUSIONS: Our results indicate that proline-induced insulin transcription and mitochondrial oxidative phosphorylation impairment may contribute to the β-cell dysfunction observed in type 2 diabetes. Caution should be applied in interpreting the pathophysiological role of proline since very high proline concentrations were used in the experiments.

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Rev Diabet Stud, 2016, 13(1):79-90 DOI 10.1900/RDS.2016.13.79

Esophageal and Gastric Dysmotilities are Associated with Altered Glucose Homeostasis and Plasma Levels of Incretins and Leptin

Rebecka Hammersjö1, Bodil Roth1, Peter Höglund2, Bodil Ohlsson1

1Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Malmö, Lund University, Lund, Sweden
2Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Skåne University Hospital, Lund, Lund University, Lund, Sweden
Address correspondence to: Bodil Ohlsson, Department of Clinical Sciences, Skåne University Hospital, Inga Marie Nilsson Street 32, S-205 02 Malmö, Sweden, e-mail: bodil.ohlsson@med.lu.se

Abstract

BACKGROUND: Gastrointestinal complications in diabetes may affect glucose and endocrine homeostasis. Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and leptin regulate glucose homeostasis, food intake, and gastric emptying. AIM: The aim was to investigate associations between diabetes complications and glucose homeostasis and plasma levels of GIP, GLP-1, and leptin. METHODS: Sixteen diabetes patients (seven men) were examined with gastric emptying scintigraphy and 72-h continuous subcutaneous glucose monitoring, 14 with the deep-breathing test, and 12 with esophageal manometry. A fiber-rich breakfast was given during the second day of glucose registration. Blood samples were taken 10 min and right before a fat-rich breakfast, as well as 10, 20, 30, 45, 60, 90, 120, 150, and 180 min afterwards. 20 healthy volunteers acted as controls. Plasma was analyzed regarding GIP, GLP-1, and leptin by Luminex. RESULTS: Gastroparesis lowered maximal concentration (c-max) (p = 0.003) and total area under the curve (tAUC) (p = 0.019) of glucose levels as well as d-min (p = 0.043) of leptin levels. It tended to lower baseline (p = 0.073), c-max (p = 0.066), change from baseline (d-max) (p = 0.073), and tAUC (p = 0.093) of GLP-1 concentrations. Esophageal dysmotility tended to lower tAUC of glucose levels (p = 0.063), and c-min (p = 0.065) and tAUC (p = 0.063) of leptin levels. Diabetes patients had a higher baseline concentration of glucose (p = 0.013), GIP (p = 0.023), and leptin (p = 0.019) compared with healthy subjects. CONCLUSIONS: Gastric and esophageal dysmotility are associated with both lesser increases in postprandial glucose elevations and decreased postprandial changes in GLP-1 and leptin.

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