Practical guidance for treatment of patients with diabetes using flash glucose monitoring: a pilot study.

BACKGROUND: Flash glucose monitoring (FGM) is a factory-calibrated, blood glucose measuring sensor system for patients with diabetes. We aimed to investigate the correlation between the sensor glucose (SG) value obtained using an FGM device and the traditional self-monitoring of blood glucose (SMBG) value. METHODS: In 30 patients with diabetes under insulin treatment, SG and SMBG values were measured for 2 weeks, and the correlation between the values was analyzed. RESULTS: The mean number of accumulated measurements of SG values was 1223.2 ± 193.0, whereas that of the SMBG values was 49.2 ± 21.3. Although SG and SMBG values showed a favorable correlation (R2 = 0.8413), SG values were lower than SMBG values by an average of 7.9 ± 29.8 mg/dL. The correlation patterns fell into four types: low type (SG values lower than SMBG values; n = 12), high type (SG values higher than SMBG values; n = 3), cross type (the slope of the two regression lines crossed at a certain measurement value; n = 14), and matching type (the values overlapped; n = 1). CONCLUSIONS: Recognition of the characteristic correlation patterns between SG and SMBG values is indispensable for certified diabetes educators to provide appropriate treatment guidance to patients with diabetes.

One-year eGFR decline rate is a good predictor of prognosis of renal failure in patients with type 2 diabetes.

It is difficult to distinguish the onset of renal function decline from the typical variation in estimated glomerular filtration rate (eGFR) measurements in clinical practice. In this study, we used data analysis incorporating smoothing techniques to identify significant trends despite large amounts of noise. We identified the starting points of meaningful eGFR decline based on eGFR trajectories. This was a retrospective observational study of 2533 type 2 diabetes patients. We calculated 1-year eGFR decline rates from the difference between each eGFR value and that of the previous year. We examined the prediction capacity of 1-year eGFR decline rate for renal prognosis. When we performed receiver operating characteristic analysis, the area under the curve of 1-year eGFR decline rate was 0.963 (95% confidence interval: 0.953-0.973). With a cut-off value of more than 7.5% eGFR decline during a 1-year period, the sensitivity was 98.8% and specificity was 82.3%. The predictive accuracy of 1-year eGFR decline rate for renal prognosis was high.

Aß induces oxidative stress in senescence-accelerated (SAMP8) mice.

According to the amyloid hypothesis, amyloid ß accumulates in brains with Alzheimer's disease (AD) and triggers cell death and memory deficit. Previously, we developed a rice Aß vaccine expressing Aß, which reduced brain Aß levels in the Tg2576 mouse model of familial AD. We used senescence-accelerated SAMP8 mice as a model of sporadic AD and investigated the relationship between Aß and oxidative stress. Insoluble Aß and 4-hydroxynonenal (4-HNE) levels tended to be reduced in SAMP8 mice-fed the rice Aß vaccine. We attempted to clarify the relationship between oxidative stress and Aß in vitro. Addition of Aß peptide to the culture medium resulted in an increase in 4-HNE levels in SH-SY5Y cells. Tg2576 mice, which express large amounts of Aß in their brain, also exhibited increased 4-HNE levels; this increase was inhibited by the Aß vaccine. These results indicate that Aß induces oxidative stress in cultured cells and in the mouse brain.

Effect of rice-expressed amyloid ß in the Tg2576 Alzheimer's disease transgenic mouse model.

One of the main hallmarks of Alzheimer's disease (AD) is senile plaques composed of amyloid ß (Aß). We developed a new edible vaccine: rice expressing GFP-Aß42. In a previous report, we described the production of anti-Aß antibodies in B6 mice fed Aß rice mixed with cholera toxin B subunit (CTB). In this report, we investigated whether Aß rice had therapeutic effects in the Tg2576 AD model mice. The anti-Aß antibody titer was increased and levels of intracerebral Aß (soluble and insoluble) and serum Aß decreased. Because the value of IgG1/IgG2a in the Aß feeding group was >1, immunization via Aß rice may induce a non-inflammatory Th2 reaction. We also found that the Aß vaccine improved memory, as assessed in a Y-maze test. The number of arm entries in the Y-maze test was lower in the Aß feeding group than in the control group. These results suggest that the new edible vaccine Aß rice may have therapeutic effects in AD.

Transgenic rice expressing amyloid ß-peptide for oral immunization.

Various vaccine therapies for Alzheimer's disease (AD) have been investigated. Here we report transgenic rice expressing amyloid ß-peptide (Aß). The Aß42 gene fused with a green fluorescent protein gene was introduced into rice using the Agrobacterium method. When transgenic brown rice expressing Aß was orally administered to mice, serum anti-Aß antibody titers were elevated. The same results were observed when mice were fed boiled, transgenic brown rice. The results indicate that an edible vaccine against AD using rice may be feasible. A vaccine derived from rice would be far cheaper than existing medical vaccines.

Production of anti-amyloid ß antibodies in mice fed rice expressing amyloid ß.

The main signs of Alzheimer's disease (AD) are cognitive impairment and senile plaques composed of amyloid beta (Aß) observed in patients' brains. Therefore, therapy for AD focuses on the removal of Aß. We developed an "edible vaccine" that employs intestinal immunity with little to no side effects. Rice was utilized as an edible vaccine. It expressed GFP-Aß42. Aß rice was administered orally to wild-type (WT) mice causing production of anti-Aß antibodies. Since Aß rice was mixed with the cholera toxin B subunit (CTB), antibody against the rice seed protein was also produced. Then, mice were caused to develop immune tolerance against the rice seed protein by oral administration of Aß rice mixed with CTB. The results indicated that only anti-Aß antibodies were produced.

Reduction of amyloid beta-peptide accumulation in Tg2576 transgenic mice by oral vaccination.

Alzheimer's disease (AD) is pathologically characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid beta-peptide (Abeta) is the main component of senile plaques, and the pathological load of Abeta in the brain has been shown to be a marker of the severity of AD. Abeta is produced from the amyloid precursor protein by membrane proteases and is known to aggregate. Recently, immune-mediated cerebral clearance of Abeta has been studied extensively as potential therapeutic strategy. In previous studies that used a purified Abeta challenge in a mouse model of AD, symptomatic improvement was reported. However, a clinical Alzheimer's vaccine trial in the United States was stopped because of severe side effects. Immunization with the strong adjuvant used in these trials might have activated an inflammatory Th1 response. In this study, to establish a novel, safer, lower-cost therapy for AD, we tested an oral vaccination in a wild-type and a transgenic mouse model of AD administered via green pepper leaves expressing GFP-Abeta. Anti-Abeta antibodies were effectively induced after oral immunization. We examined the immunological effects in detail and identified no inflammatory reactions. Furthermore, we demonstrated a reduction of Abeta in the immunized AD-model mice. These results suggest this edible vehicle for Abeta vaccination has a potential clinical application in the treatment of AD.

Biochemical analysis of oligomerization of expanded polyalanine repeat proteins.

Many human proteins contain amino acid repeats that can form homopolymeric amino acid (HPAA) tracts. HPAA tract proteins that contain polyalanine sequences promote diseases, including oculopharyngeal muscular dystrophy. The pathological properties of these proteins develop when the repeats match or exceed approximately 20 residues. We analyzed the oligomerization of yellow fluorescent protein (YFP) and GST fusion proteins containing >20 alanine repeats by using sucrose density gradient centrifugation. YFP and GST fusion proteins having 23 polyalanine residues sedimented readily in sucrose density gradients, suggesting instability and oligomerization of proteins with an excess of 20 alanine repeats. Moreover, GST fusion proteins were resistant to trypsin digestion after oligomerization. Oligomerized artificial proteins with long polyalanine repeats may be suitable models for studying polyalanine-related diseases.