Higher concentration of 25-hydroxycholesterol in treatment-naïve patients with type 2 diabetes compared to healthy individuals.

BACKGROUND: Oxysterols are cholesterol oxidation derivatives with diverse biological activities. However, little is known about the oxysterol levels in treatment-naïve patients with type 2 diabetes. OBJECTIVE: We utilized gas chromatography-mass spectrometry to investigate the potential association between oxysterol concentrations and type 2 diabetes and atherosclerosis in treatment-naïve patients diagnosed with type 2 diabetes. METHODS: This case-control study enrolled 53 eligible patients with type 2 diabetes and 50 healthy volunteers. We compared serum oxysterol concentrations between the two groups; we examined the correlation between the oxysterol concentrations and the carotid plaque score in the type 2 diabetes group. RESULTS: Univariate analysis revealed significant differences in the concentrations of oxysterols (i.e., cholesterol-5α, 6α-epoxide; cholesterol-5ß, 6ß-epoxide; 7ß-hydroxycholesterol; and 25-hydroxycholesterol [25-HC]) and other cardiovascular risk factors between the two groups. The 25-HC concentration was almost twofold greater in the type 2 diabetes group than in the healthy volunteers (median [interquartile range]: 8.52 [6.37-11.26] vs. 4.58 [3.45-5.44] ng/mL). After adjusting for multiple covariates, such as age, body mass index, mean arterial pressure, and triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels, only the concentration of 25-HC showed a significant association with type 2 diabetes. However, the univariate analysis failed to demonstrate any significant correlation between oxysterol concentrations and the carotid plaque score among individuals with type 2 diabetes. CONCLUSIONS: The levels of various oxysterols differ between treatment-naïve patients with type 2 diabetes and healthy individuals; the 25-HC level differs the most prominently.

Lipoprotein lipase concentration in umbilical cord blood reflects neonatal birth weight.

BACKGROUND: Insulin resistance (IR) is exacerbated during pregnancy via increases in insulin counterregulatory hormones. Maternal lipids are strong determinants of neonatal growth, although triglyceride-rich lipoproteins (TGRLs) cannot be transferred directly to the fetus through the placenta. The catabolism of TGRLs under physiological IR and the reduced synthesis of lipoprotein lipase (LPL) are poorly understood. We examined the association of maternal and umbilical cord blood (UCB)-LPL concentrations with maternal metabolic parameters and fetal development. METHODS: Changes in anthropometric measures and lipid-, glucose-, and insulin-related parameters, including maternal and UCB-LPL concentrations, were examined in 69 women during pregnancy. The relationship between those parameters and neonatal birth weight was assessed. RESULTS: Parameters reflecting glucose metabolism did not change during pregnancy, whereas those associated with lipid metabolism and IR changed markedly, particularly in the second and third trimesters. In the third trimester, the maternal LPL concentration gradually decreased, by 54%, whereas the UCB-LPL concentration was âˆ¼2-fold higher than the maternal LPL concentration. Univariate and multivariate analyses showed that the UCB-LPL concentration was a significant determinant of neonatal birth weight, together with placental birth weight. CONCLUSION: The LPL concentration in UCB reflects neonatal development under a decreased LPL concentration in maternal serum.

Changes in prescription patterns and doses of oral antidiabetic drugs in Japanese patients with type 2 diabetes (JDDM70).

We assessed the prescription patterns of oral antidiabetic drugs in Japanese patients with type 2 diabetes between 2002 and 2020 using data from the Computerized Diabetes Care database. Among 172,960 patients treated with oral antidiabetic drugs, both the sulfonylurea prescription rate and dose decreased from 2002 to 2020. Prescriptions of biguanides, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors increased; their dose and dose frequency remained relatively stable. Trends in oral antidiabetic drug prescriptions changed over time, reflecting guideline recommendations and existing evidence.

Treatment Patterns and Lipid Profile in Patients with Familial Hypercholesterolemia in Japan.

AIM: To evaluate the epidemiology and real-world treatment patterns associated with lipid-modifying therapies (LMTs) among groups of Japanese patients with familial hypercholesterolemia (FH). METHODS: A retrospective observational study was conducted using an electronic hospital-based administrative claims database and electronic medical records. Patients with existing diagnosis of FH (FH-D) and patients with suspected FH (FH-S) defined by low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL were included, and medical records of hospitals across Japan were analyzed to assess the diagnostic status, management of LDL-C levels, and treatment patterns. RESULTS: Among the 3,495 patients who met the inclusion criteria, 193 patients were FH-D and 3,339 patients were FH-S. Among them, 83.5% had not achieved the LDL-C of ＜100 mg/dL recommended for patients with FH at the index date. Mean LDL-C levels for all patients and for FH-D and FH-S patients were 145.8 mg/dL, 119.2 mg/dL, and 147.6 mg/dL, respectively. 44.5% of the patients were not currently treated with LMTs. High-intensity statins were used only in 19.2% and 2.3% of the FH-D and FH-S patients, respectively. Furthermore, among the FH-D and FH-S statin-treated patients, 61 (69.3%) and 1,059 (89.7%) remained on monotherapy even when their LDL-C was ≥100 mg/dL. CONCLUSIONS: Treatment and management of LDL-C in Japanese FH patients remain suboptimal. The results suggest that FH is underdiagnosed in real-world, routine clinical practice in Japan. There is an urgent need to improve the diagnostic rate of FH and to provide the appropriate therapy to achieve the recommended LDL-C levels of ＜100 mg/dL or a more than 50% reduction for patients with FH in Japan.

Global analysis of the expression patterns of transcriptional regulatory factors in formation of embryoid bodies using sensitive oligonucleotide microarray systems.

We manufactured a highly sensitive oligonucleotide microarray system comprised entirely of transcription regulatory factors (a TF oligo microarray) in order to comprehensively analyze the expression profiles of transcription factors in mice. We compared the expression profiles of transcription regulatory factors in mouse embryonic stem (ES) cells and ES-differentiated cells by using this TF oligo microarray, a cDNA microarray, a GeneChip system, and quantitative RT-PCR. The TF oligo microarray was able to comprehensively analyze the expression profile of transcription regulatory factors. In addition, we used the manufactured TF oligo microarray to analyze the expression patterns of transcriptional regulatory factors during the formation of embryoid bodies. The TF array was able to reveal the chronologic expression profile of transcription regulatory factors involved in embryogenesis or the maintenance of pluripotency in ES cells.

Global analysis of the regulatory network structure of gene expression in Saccharomyces cerevisiae.

Gene expression in eukaryotic cells is controlled by the concerted action of various transcription factors. To help clarify these complex mechanisms, we attempted to develop a method for extracting maximal information regarding the transcriptional control pathways. To this end, we first analyzed the expression profiles of numerous transcription factors in yeast cells, under the assumption that the expression levels of these factors would be elevated under conditions in which the factors were active in the cells. Based on the results, we successfully categorized about 400 transcription factors into three groups based on their expression profiles. We then analyzed the effect of the loss of function of various induced transcription factors on the global expression profile to investigate the above-mentioned assumption of a correlation between transcription elevation and functional activity. By comparing the expression profiles of wild-type with those of disruption mutants using microarrays, we were able to detect a substantial number of relations between transcription factors and the genes they regulate. The results of these experiments suggested that our approach is useful for understanding the global transcriptional networks of eukaryotic cells, in which most genes are regulated in a temporal and conditional manner.