The Beneficial Effects of a Multispecies Probiotic Supplement on Glycaemic Control and Metabolic Profile in Adults with Type 1 Diabetes: A Randomised, Double-Blinded, Placebo-Controlled Pilot-Study.

Objective: In this pilot-study, the effects of a multispecies probiotic supplement on glycaemic control and metabolic parameters in adults with type 1 diabetes (T1DM) were explored. Material and Methods: A total of 50 T1DM patients were enrolled and randomly placed into a group receiving capsules containing multi-probiotic strains (Bifidobacterium longum, Lactobacterium bulagricumi, Streptococcus thermophilus) and insulin (probiotics group, n = 27) or a group receiving a placebo and insulin (placebo group, n = 23). All patients underwent continuous glucose monitoring at baseline and 12 weeks after intervention. The primary outcomes were determined by comparing factors such as changes in fasting blood glucose (FBG) and haemoglobin A1c (HbA1c) between the groups. Results: Probiotic supplementation significantly reduced FBG (-1.0 ± 4.7 vs 1.8 ± 4.7 mmol/L, p = 0.048), 30 min postprandial glucose (-0.5 ± 4.6 vs 1.9 ± 3.3 mmol/L, p = 0.0495), and low-density lipoprotein cholesterol (-0.07 ± 0.45 vs 0.32 ± 0.78 mmol/L, p = 0.0413), compared with the placebo. Although not statistically significant, probiotic supplementation also lowered HbA1c levels by 0.49% (-5.33 mmol/mol, p = 0.310). Besides, no significant difference was observed in the continuous glucose monitoring (CGM) parameters between the two groups. Further subgroup analysis revealed a significant reduction in mean sensor glucose (MSG; -0.75 (-2.11, 0.48) mmol/L vs 1.51 (-0.37, 2.74) mmol/L, p = 0.010) and time above range (TAR; -5.47 (-20.1, 3.04)% vs 18.9 (-1.11, 35.6)%, p = 0.006), as well as an greater improvement in the time in range (TIR; 9.32 (-4.84, 16.6)% vs -19.9 (-31.4, 0.69)%, p = 0.005) in male patients than female patients in the probiotics group. Conclusion: Multispecies probiotics exerted beneficial effects on fasting and postprandial glucose and lipid profiles in adult T1DM patients, especially for male patients and those with higher baseline FBG levels.

Adaptive Neural Consensus Tracking Control for Nonlinear Multiagent Systems Using Integral Barrier Lyapunov Functionals.

This article presents the adaptive tracking control scheme of nonlinear multiagent systems under a directed graph and state constraints. In this article, the integral barrier Lyapunov functionals (iBLFs) are introduced to overcome the conservative limitation of the barrier Lyapunov function with error variables, relax the feasibility conditions, and simultaneously solve state constrained and coupling terms of the communication errors between agents. An adaptive distributed controller was designed based on iBLF and backstepping method, and iBLF was differentiated by means of the integral mean value theorem. At the same time, the properties of neural network are used to approximate the unknown terms, and the stability of the systems is proven by the Lyapunov stability theory. This scheme can not only ensure that the output of all the followers meets the output trajectory of the leader but also make the state variables not violate the constraint bounds, and all the closed-loop signals are bounded. Finally, the efficiency of the proposed controller is revealed.

Metformin improves glycemic variability in adults with type 1 diabetes mellitus: an open-label randomized control trial.

INTRODUCTION: Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM. OBJECTIVES: In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored. PATIENTS AND METHODS: A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests, and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000-2000 mg metformin daily add-on insulin (MET group, n = 34) or insulin (non-MET group, n = 31). After, baseline measurements were repeated. RESULTS: The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with non-MET group (-1.58 (-3.35, 0.31) mmol/L vs 1.36 (-1.12, 2.24) mmol/L, P = 0.004). In parallel, the largest amplitude of glycemic excursions (-2.83 (-5.47, -0.06) mmol/L vs 0.45 (-1.29, 4.48) mmol/L, P = 0.004), the s.d. of blood glucose (-0.85 (-1.51, 0.01) mmol/L vs -0.14 (-0.68, 1.21) mmol/L, P = 0.015), and the coefficient of variation (-6.66 (-15.00, 1.50)% vs -1.60 (-6.28, 11.71)%, P = 0.012) all demonstrated improvement in the MET group, compared with the non-MET group. Significant reduction in insulin dose, BMI, and body weight was observed in patients in MET, not those in non-MET group. CONCLUSION: Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as an adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.

Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway.

Diabetic nephropathy (DN), a kind of microvascular complication, is a primary cause of end-stage renal disease worldwide. However, therapeutic drugs for DN treatment are still in lack. The glomerular endothelium is essential to maintain selective permeability of glomerular filtration barrier and glomerular vasculature function. Growing evidences show that endothelial dysfunction or injury is the initial stage of vascular damage in DN, which can be induced by hyperglycemia, lipotoxicity, and inflammation. Therefore, to improve the function of vascular endothelium in kidney is a key point for treatment of DN. As a plant isoflavone, tectorigenin (TEC) has attracted considerable attention due to its anti-proliferative and anti-inflammatory functions. However, whether TEC could inhibit the DN development remains unknown. In this study, we examined the effects of TEC on DN development in db/db mice, a type of genetic defect diabetic mice that can spontaneously develop into severe renal dysfunction. Intriguingly, TEC treatment restored diabetes-induced glucose and lipid metabolic disorder; and improved the deterioration of renal function, particularly the renal endothelium function in db/db mice. Additionally, TEC inhibited the renal inflammation via reducing macrophages infiltration and M1 polarization. Moreover, TEC inhibited lipopolysaccharide (LPS)-induced endothelial injury and M1 polarization in vitro. Mechanistically, TEC partially restored the reduction in expression of adiponectin receptor 1/2 (AdipoR1/2), pi-LKB1, pi-AMPKα, and PPARα in vitro and in vivo. Noteworthy, these beneficial pharmacological activities mediated by TEC were significantly attenuated after AdipoR1/2 knockdown by siRNA, indicating that AdipoR1/2 plays a critical role in protection against DN. Collectively, these results suggested that TEC have a potently effect for retarding type 2 diabetes-associated DN.

Tanshinone IIA improves diabetes mellitus via the NF-κB-induced AMPK signal pathway.

Diabetes mellitus (DM) is a systemic metabolic disease. Tanshinone IIA (Tan-IIA) presents potential benefits for DM. The purpose of this study was to investigate the efficacy of Tan-IIA in type 2 DM rats and explore its potential mechanism in renal cells. A type 2 DM rat model was established and administered with Tan-IIA or PBS. It was demonstrated that Tan-IIA treatment significantly reduced levels of total cholesterol, non-esterified fatty acids, total triglyceride and low-density lipoprotein cholesterol in experimental DM rats compared with the control group. The results indicated that Tan-IIA treatment significantly decreased levels of interleukin (IL)-8, tumor necrosis factor-α, C-reactive protein and IL-6. It was identified that Tan-IIA treatment significantly decreased nuclear factor-κB levels and significantly elevated 5' adenosine monophosphate-activated protein kinase levels. Western blot analysis indicated that Tan-IIA elevated immunocyte precipitation in renal cells. Furthermore, Tan-IIA treatment improved lipid metabolism, glucose metabolism, insulin resistance and body weight of type 2 DM rats. In conclusion, Tan-IIA administration may inhibit inflammatory cytokines and alleviate type 2 DM symptoms in experimental rats.

Cushing's syndrome during pregnancy caused by adrenal cortical adenoma: a case report and literature review.

Cushing's syndrome (CS) during pregnancy is a rare condition with significant maternal and fetal complications. A case of CS during the third trimester of pregnancy secondary to adrenocortical adenoma was reported. Literature review revealed the disadvantages of different treatments in this period. Besides the conservative treatment, surgery is recommended for CS during the third trimester of pregnancy secondary to adrenal adenoma, if an experienced surgeon is available.

Prognostic value of ultra-sensitive pregnancy associated plasma protein-A in patients with acute coronary syndrome.

OBJECTIVE: To investigate the prognostic value of ultra-sensitive pregnancy associated plasma protein-A (PAPP-A) level in the early phase of acute coronary syndrome (ACS) attack. METHODS: Patients diagnosed as ACS were enrolled and the level of circulatory PAPP-A was measured within 12 hours after ACS attack. The patients were followed at the time of 1st, 6th, and 12th months post-ACS attack in order to observe the incidence of the cardiovascular adverse events. According to the highest quintile, the patients were divided into 2 groups: high level (≥26.08 µg/L) group and low level (<26.08 µg/L) group, to evaluate the association between the level of PAPP-A and the incidence of the cardiovascular events. RESULTS: Compared with the low level group, the incidence of the composite outcome is significantly increased in the high level group, and the values of OR are 4.76, 4.38, 3.75 for 1st, 6th, 12th months respectively (P=0.000). For myocardial infarction (MI) + cardiac death (CD) the values of OR were 9.81, 6.08, 4.12 (P<0.01). Multivariate logistic regression analysis demonstrates that PAPP-A was an independent risk factor for the cardiovascular adverse events in the early, median, and late phase of ACS (P<0.05). CONCLUSION: In the early phase of ACS attack, the elevation of PAPP-A is an independent risk factor for the occurrence of cardiovascular adverse events.