Amyloid in the islets of Langerhans: Thoughts and some historical aspects

Deposition of amyloid, derived from the polypeptide hormone islet amyloid polypeptide (IAPP; ‘amylin’) is the single most typical islet alteration in type 2 diabetes. Islet amyloid was described as hyalinization already in 1901, but not until 1986 was it understood that it is a polymerization product of a novel β-cell regulatory product. The subject of this focused review deals with the pathogenesis and importance of the islet amyloid itself, not with the biological effect of the polypeptide. Similar to the situation in Alzheimer's disease, it has been argued that the amyloid may not be of importance since there is no strict correlation between the degree of islet amyloid infiltration and the disease. However, it is hardly discussable that the amyloid is important in subjects where islets have been destroyed by pronounced islet amyloid deposits. Even when there is less islet amyloid the deposits are widely spread, and β-cells show ultrastructural signs of cell membrane destruction. It is suggested that type 2 diabetes is heterogeneous and that in one major subtype aggregation of IAPP into amyloid fibrils is determining the progressive loss of β-cells. Interestingly, development of islet amyloid may be an important event in the loss of β-cell function after islet transplantation into type 1 diabetic subjects

Thiazolidinediones and blood lipids in type 2 diabetes

We evaluated study population characteristics and treatment effects on blood lipids between studies in which either rosiglitazone (RSG) or pioglitazone (PIO) was investigated in patients with type 2 diabetes. We performed a summary analysis of all published double-blind, placebo-controlled studies with RSG (4 and 8 mg/d) and PIO (15, 30, and 45 mg/d). Data were analyzed by the random-effects model. Nineteen trials met our inclusion criteria, yielding 5304 patients, 3236 in studies with RSG and 2068 in studies with PIO. Subjects treated with PIO were more obese and showed more pronounced hyperglycemia and dyslipidemia (increased triglycerides and decreased HDL cholesterol) at baseline than did subjects treated with RSG. By weighted linear-regression analysis, studies with PIO showed greater beneficial effects on triglycerides, total cholesterol, and LDL cholesterol, after adjustment for the respective lipid levels at baseline. RSG 8 mg/d showed greater increases in total cholesterol and LDL cholesterol than did RSG 4 mg/d. PIO 30 mg/d showed greater reductions in triglycerides than did PIO 15 mg/d. Studies conducted with PIO showed more beneficial effects on blood lipids, but also different study population characteristics in comparison with studies conducted with RSG. Differences in both pharmacologic properties between agents and study population characteristics are likely to have influenced the results

Patient activation in individuals with type 2 diabetes mellitus: associated factors and the role of insulin

Heidi A van Vugt,1,2,* Anne Meike Boels,1,* Inge de Weerdt,2 Eelco JP de Koning,3 Guy EHM Rutten1 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, Utrecht, the Netherlands; 2Dutch Diabetes Federation, Amersfoort 3818 LE, the Netherlands; 3Department of Medicine, Leiden University Medical Center, 2300 RC Leiden, the Netherlands *These authors contributed equally to this work Aim: This study explored the relationship between insulin use and patient activation (a person’s internal readiness and capabilities to undertake health-promoting actions) in individuals with type 2 diabetes mellitus and aimed to identify demographic, clinical and psychosocial factors involved in patient activation.Methods: In this cross-sectional study, baseline data from a Dutch nationwide study were analyzed. Patient activation was assessed with the Patient Activation Measure 13. A linear mixed model was used to take clustering into account.Results: In total, 1,189 persons were included (310 of whom were on insulin), enrolled via 47 general practices and six hospitals. Their mean Patient Activation Measure 13 score was 59±12. We found no association between insulin therapy and patient activation. In the multivariable analysis, individuals with a better health status, very good or very poor social support (vs good social support), individuals who felt they had greater control over their illness and those with a better subjective understanding of their illness showed higher patient activation. Individuals with a lower educational level and those who expected their illness to continue showed a lower activation level.Conclusion: Patient activation does not differ between individuals with type 2 diabetes mellitus on insulin therapy and those on other therapies.Keywords: provider–patient communication, patient participation in health care, social support, patient activation, insulin therapy, psychological aspects, self-managemen

Hypothermic oxygenated machine perfusion of the human donor pancreas

Background Transplantation of beta cells by pancreas or islet transplantation is the treatment of choice for a selected group of patients suffering from type 1 diabetes mellitus. Pancreata are frequently not accepted for transplantation, because of the relatively high vulnerability of these organs to ischemic injury. In this study, we evaluated the effects of hypothermic machine perfusion (HMP) on the quality of human pancreas grafts. Methods Five pancreata derived from donation after circulatory death (DCD) and 5 from donation after brain death (DBD) donors were preserved by oxygenated HMP. Hypothermic machine perfusion was performed for 6 hours at 25 mm Hg by separate perfusion of the mesenteric superior artery and the splenic artery. Results were compared with those of 10 pancreata preserved by static cold storage. Results During HMP, homogeneous perfusion of the pancreas could be achieved. Adenosine 5′-triphosphate concentration increased 6,8-fold in DCD and 2,6-fold in DBD pancreata. No signs of cellular injury, edema or formation of reactive oxygen species were observed. Islets of Langerhans with good viability and in vitro function could be isolated after HMP. Conclusions Oxygenated HMP is a feasible and safe preservation method for the human pancreas that increases tissue viability.</p

The findings of meta-analysis on structural changes by pain-related regions: Gray matter.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094300#pone-0094300-t003" target="_blank">Table 3</a> for the abbreviations of the brain regions. The asterisk denotes that the finding was derived from a ROI-specific analysis. Upward and downward arrows denote positive and negative changes, respectively (without showing the sub-region of the change). a, anterior; m, mid; p, posterior; i, inferior; oribitofrontal; vl, ventrolateral; dl, dorsolateral; PF, connection with the prefrontal cortex; TP, connection with the temporal cortex.</p>1<p>cortical thickness; ²gray matter volume.</p