A Pilot Study on the Efficacy of a Diabetic Diet Containing the Rare Sugar D-Allulose in Patients with Type 2 Diabetes Mellitus: A Prospective, Randomized, Single-Blind, Crossover Study.

High sugar consumption increases the risk of diabetes, obesity, and cardiovascular diseases. Regarding the diet of patients with diabetes, artificial sweeteners are considered a safe alternative to sugar; however, there is also a risk that artificial sweeteners exacerbate glucose metabolism. D-allulose (C-3 isomer of d-fructose), which is a rare sugar, has been reported to have antidiabetic and antiobesity effects. In this study, the efficacy of a diabetic diet containing D-allulose was investigated in patients with type 2 diabetes using an intermittently scanned continuous glucose monitoring system (isCGM). This study was a validated, prospective, single-blind, randomized, crossover comparative study. Comparison of peak postprandial blood glucose (PPG) levels after consumption of a standard diabetic diet and a diabetic diet containing 8.5 g of D-allulose was the primary endpoint. A D-allulose-containing diabetic diet improved PPG levels in type two diabetes patients compared with a strictly energy-controlled diabetic diet. The results also showed a protective effect on endogenous pancreatic insulin secretory capacity owing to reduced insulin requirement. In patients with type two diabetes mellitus, diabetic diets containing 8.5 g D-allulose were effective in improving PPG levels.

Exendin-4 Increases Scavenger Receptor Class BI Expression via Activation of AMPK/FoxO1 in Human Vascular Endothelial Cells.

Glucagon-like peptide-1 receptor agonist (GLP-1RA) has been clinically proven to protect endothelial function. Previously, we demonstrated that endothelial NO synthase (eNOS) was activated by high-density lipoprotein (HDL) via its scavenger receptor of the B class/human homologue of SR-BI, CD36 and LIMPII analogous-1(hSR-BI/CLA-1). Here, we investigated the effect of GLP-1RA and exendin-4 on the expression of hSR-BI/CLA-1 in HUVECs. Our results confirmed that GLP-1R was expressed in HUVECs by PCR and exendin-4 significantly enhanced HDL-induced eNOS activation. Next, exendin-4 increased the expression of hSR-BI/CLA-1 and a blockade of GLP-1R cancelled this effect. Further, the hSR-BI/CLA-1 transcriptional activity was enhanced by exendin-4, which was diminished by the inhibition of AMPK or dominant-negative AMPK-α-subunit. Moreover, AMPK was phosphorylated by the activation of GLP-1R. Next, ChIP assay demonstrated that exendin-4 increased the FoxO1-binding in the hSR-BI/CLA-1 promoter by upregulation of FoxO1. Mutation of FoxO1-binding or silencing of FoxO1 cancelled the effect of exendin-4 on hSR-BI/CLA-1 expression. Exendin-4 reduced FoxO1 phosphorylation and induced its nuclear accumulation, while this effect was altered by the blocking of GLP-1R or inhibition of AMPK pathway. In summary, our results proved that exendin-4 increased hSR-BI/CLA-1 expression via the AMPK/FoxO1 pathway to activate eNOS, providing a basic mechanism underlining the protective effect of GLP-1RA on endothelial function.

Knowledge of diabetes and the practice of diabetes self-management during Ramadan fasting among patients with type 2 diabetes in Malaysia.

BACKGROUND AND AIMS: To assess the level of diabetes knowledge and its association with diabetes self-management practices during Ramadan fasting among patients with type 2 diabetes (T2D). METHODS: A cross-sectional study was conducted involving a sample of Malaysian patients with T2D. Patients aged 18 years and above, and attending an outpatient diabetic unit of a government hospital were recruited between February and April 2021. A self-administered questionnaire was utilized to assess diabetes knowledge and diabetes self-management practices. RESULTS: A total of 306 participants completed the questionnaire. Most of them were females (54.2%) and above 55 years old (75.1%). Resultantly, knowledge of diabetes was considered average among 52% of the participants. Only 9.5% of them avoided the consumption of sweet foods during iftar. Practicing late suhoor (p = 0.012) and self-monitoring of blood glucose (SMBG) (p = 0.026) during Ramadan were significantly associated with a better diabetes knowledge score. Education level (p = 0.000), working status (p = 0.030), and monthly income (p = 0.000) were significantly associated with participants' knowledge level of diabetes. A higher proportion (72.2%) of the participants completed fasting for a month during Ramadan 2020. Meanwhile, hypoglycemia was the main reason (38.8%) for incomplete fasting. CONCLUSIONS: These findings reflect the need to improve patients' knowledge of diabetes and diabetes self-management practices, especially during Ramadan. Such objectives could be achieved by considering the associated factors identified in this study.

A pilot study on the effect of D-allulose on postprandial glucose levels in patients with type 2 diabetes mellitus during Ramadan fasting.

BACKGROUND: During Ramadan fasting, postprandial hyperglycemia is commonly observed after iftar (break of fast at sunset) meal. D-allulose is a rare sugar and is reported to have several health benefits, including the suppression of increase in postprandial glucose levels. This study investigates whether D-allulose (a C-3 epimer of D-fructose) improves the postprandial glucose in patients with type 2 diabetes mellitus (T2DM) during Ramadan. METHODS: This was a pilot, prospective single-arm study design that was conducted for 10 consecutive days; 5 days of control and 5 days of consumption. The primary outcome was postprandial peak glucose levels. During the consumption period, 8.5 g of D-allulose was consumed by the participants before iftar meal. Postprandial glucose was measured using a continuous glucose monitoring system. RESULTS: A total of 12 participants completed the study. Significant lower (p < 0.01) postprandial glucose values and the glucose incremental area under the curve (iAUC) were observed from 0 to 180 min during the consumption period compared to the control period. The consumption period demonstrated significantly higher percentages of time in which glucose values were found in the target range (p = 0.0032), and when the glucose levels above the target range were reduced (p = 0.0015). CONCLUSIONS: The supplementation with D-allulose has the potential to improve postprandial hyperglycemia in patients with T2DM after iftar during Ramadan. Further studies are needed to confirm these findings. Trial registration ClinicalTrials.gov NCT05071950. Retrospectively registered, 8 October 2021.

Effects of 2-Methoxyestradiol, a Main Metabolite of Estradiol on Hepatic ABCA1 Expression in HepG2 Cells.

ATP-binding cassette transporter A1 (ABCA1) is a key regulator of lipid efflux, and the absence of ABCA1 induces hepatic lipid accumulation, which is one of the major causes of fatty liver. 2-Methoxyestradiol (2-ME2) has been demonstrated to protect against fatty liver. In this study, we investigated the effects of 2-ME2 on the hepatic lipid content and ABCA1 expression. We found that 2-ME2 dose-dependently increased ABCA1 expression, and therefore, the lipid content was significantly decreased in HepG2 cells. 2-ME2 enhanced the ABCA1 promoter activity; however, this effect was reduced after the inhibition of the PI3K pathway. The overexpression of Akt or p110 induced ABCA1 promoter activity, while dominant-negative Akt diminished the ability of 2-ME2 on ABCA1 promoter activity. Further, 2-ME2 stimulated the rapid phosphorylation of Akt and FoxO1 and reduced the nuclear accumulation of FoxO1. Chromatin immunoprecipitation confirmed that FoxO1 bonded to the ABCA1 promoter region. The binding was reduced by 2-ME2, which facilitated ABCA1 gene transcription. Furthermore, mutating FoxO1-binding sites in the ABCA1 promoter region or treatment with FoxO1-specific siRNA disrupted the effect of 2-ME2 on ABCA1 expression. All of our results demonstrated that 2-ME2 might upregulate ABCA1 expression via the PI3K/Akt/FoxO1 pathway, which thus reduces the lipid content in hepatocytes.

Oxidized LDL Downregulates ABCA1 Expression via MEK/ERK/LXR Pathway in INS-1 Cells.

Impaired insulin secretion is one of the main causes of type 2 diabetes. Cholesterol accumulation-induced lipotoxicity contributes to impaired insulin secretion in pancreatic beta cells. However, the detailed mechanism in this process remains unclear. In this study, we proved that oxidized low-density lipoprotein (OxLDL) reduced insulin content, decreased PDX-1 expression, and impaired glucose-stimulated insulin secretion (GSIS) in INS-1 cells, which were rescued by addition of high-density lipoprotein (HDL). OxLDL receptors and cholesterol content were increased by OxLDL. Consistently, OxLDL suppressed cholesterol transporter ABCA1 expression and transcription in a dose-dependent and time-dependent manner. Inhibition of MEK by its specific inhibitor, PD98059, altered the effect of OxLDL on ABCA1 transcription and activation of ERK. Next, chromatin immunoprecipitation assay demonstrated that liver X receptor (LXR) could directly bind to ABCA1 promoter and this binding was inhibited by OxLDL. Furthermore, OxLDL decreased the nuclear LXR expression, which was prevented by HDL. LXR-enhanced ABCA1 transcription was suppressed by OxLDL, and the effect was cancelled by mutation of the LXR-binding sites. In summary, our study shows that OxLDL down-regulates ABCA1 expression by MEK/ERK/LXR pathway, leading to cholesterol accumulation in INS-1 cells, which may result in impaired insulin synthesis and GSIS.