Month: September 2020

It is intriguing that amylin and Ab, especially Ab1-42, were positively associated in plasma, suggesting that naturally occurring amylin may also enhance removal of Ab from the brain. In general, a positive association between two peptides in a compartment in the body can occur by three mechanisms, e.g. 1) co-production/co-secretion, 2) competitive degradation/clearance, or 3) one peptide moving another to the same location. It is logical to anticipate that if two molecules do not encounter each other in the same tissue regions, they generally will not compete for the same protease degradation or bind the same receptor to be cleared or influence each other, and thus will not have a positive association. Although amylin is a peripheral peptide produced and secreted by the pancreas and Ab occurs primarily in the brain, especially the AD brain, amylin does readily cross the BBB and thus amylin and Ab may therefore encounter each other in the brain. insulin is much less likely than amylin to be transported into the brain via the BBB. It is not surprising that in the same plasma samples we did not find any association between insulin and Ab. Note that when using cell cultures, insulin and Ab and a significantly positive relationship between insulin and Ab is observed. Amylin levels were inversely associated with the Ab1-40/Ab1- 42 ratio in plasma. Two large, prospective population studies have shown that a high plasma Ab40/Ab42 ratio, determined by both low Ab42 and high Ab40, increases the risk of AD. While Ab42 is a major component of AD pathology in the brain, Ab40 is a component of cerebral amyloid angiopathy . High levels of plasma Ab40 are associated with cerebral microvascular pathology, white matter hyperintensities and lacunar infarcts. The plasma Ab42 decline seen in the pre-clinical stage of AD, indicating the formation of AD pathology. Thus a high Ab40/ Ab42 ratio in plasma may be a biomarker of cerebral microvascular pathology, which is associated with high plasma Ab40, coexisting AD pathology, which is associated with low plasma Ab42. Since plasma amylin levels were found to be inversely associated with Ab40/Ab42 ratio, it is possible that higher plasma amylin is a protecting factor for the development of AD. ApoE4 is a major risk factor for late-onset AD as well as for cerebrovascular disease. The positive association between amylin and Ab1-40in blood disappeared in the presence of ApoE4. Although the effect of ApoE4 on the relationship between amylin and Ab is unknown, we hypothesized that ApoE4 may attenuate amylin’s activity in removing Ab, especially Ab40, out of the brain via the BBB. Ab40 is the primary peptide that is Y-27632 deposited in the cerebrovasculature of the AD brain under the influence of the ApoE4 allele. BBB dysfunction, decreased cerebral blood flow, and impaired vascular clearance of Ab from brain are all thought to contribute to AD pathogenesis. Amylin has been shown to have a vasorelaxant effect that may result in enhanced removal of Ab from the brain.

The risk for NODM was determined using competing-risks analysis in this study. In this observational cohort study, the incidence of NODM of chronic kidney disease 5 patients receiving PD was 2.4 per 100 patients/year and 3.7 per 100 patients/year in those receiving HD. Compared to PD patients, HD patients had a 41% LY2109761 700874-71-1 increased risk for developing of NODM in 6 months after HD and 2-fold increased risk for developing NODM more than 6 months after HD. The association between HD and risk of NODM was independent of patient’s age, gender, comorbid hypertension, hematocrit, and serum albumin. The elevated NODM risk in HD patients may be explained by HD treatment per se. The bloodmembrane interaction in HD treatment can induce increased cytokines such as C-reactive protein and interleukins-6 in HD patients but not in patients treated with PD. The increased risk for NODM in HD patients may be explained by the chronic subclinical inflammation induced by the HD dialyzer. The decreased risk for NODM among PD patients may be related to their physical activity. Most of the PD patients take more responsibility in their treatment as they need to performed PD exchanges on their own. Thus, PD patients may have better physical activities in daily life than HD patients. Increased physical activities may prevent the development of diabetes. It is of note, that patient’s age was negatively associated with early type NODM and positively associated with late type NODM. The increased risk for late type NODM with age can be explained by an increased insulin resistance in aging process. Patients who developed early type NODM were older and had a higher mortality rate. Patient’s overall mortality was highest in the first 3 to 6 months of dialysis. Therefore, patients without early type NODM may have a better survival. This may explain the association between patient’s age and risk of early type NODM. Although glucose load leads to an elevated FBG glucose loading is not a risk factor of NODM. Nutrition supplements had been considered as a risk factor of NODM. An increased serum albumin and hematocrit was linked to an increase risk of early type NODM. This finding may indirectly support the influence of nutrition supplements on the development of NODM. In addition, chronic inflammation may play an important role in the development of late type NODM. This is also supported by the negative association between hematocrit, albumin and risk of NODM. Glucose is one of the components in dialysate used in HD and PD, the FBG measurement may not be “truly” fasting blood glucose. Thus a FBG to defined diabetes was performed. The incidence of NODM decreased, but patients receiving HD was consistently associated with an increased risk of NODM than those receiving PD. Based on the patient’s age of diabetes diagnosed, most of NODM patients may have type 2 diabetes. As oralhypoglycemic agents was not available in the registry data, it is unknown if insulin is needed in these NODM patients.