Search

Background and Objective: Psychological insulin resistance (PIR), which refers to the reluctance of diabetic patients to use insulin, is a frequently encountered clinical issue. Needle-free injection (NFI) offers advantages in terms of expediting insulin absorption and mitigating adverse reactions related to injection. To evaluate the effects of subcutaneous injection of insulin aspart 30 with NFI on PIR and insulin dosage in patients with type 2 diabetes mellitus (T2DM)., Methods: Sixty-four patients with T2DM participated in this randomized, prospective, open, crossover study. Insulin aspart 30 was administered subcutaneously to each subject via QS-P NFI and Novo Pen 5 (NP) successively. The effects of NFI on PIR were analyzed. Differences in insulin dosage, glycemic variability, and injection safety were compared at similar levels of glycemic control., Results: After the administration of NFI, the insulin treatment attitude scale score decreased (53.7 ± 7.3 vs. 58.9 ± 10.7, p<0.001), the insulin treatment adherence questionnaire score increased (46.3 ± 4.9 vs. 43.8 ± 7.1, p<0.001), and the insulin treatment satisfaction questionnaire score increased (66.6 ± 10.5 vs. 62.4 ± 16.5, p<0.001). At the same blood glucose level, NFI required a smaller dosage of insulin aspart 30 compared with that of NP (30.42 ± 8.70 vs. 33.66 ± 9.13 U/d, p<0.001). There were no differences in glycemic variability indices (standard deviation, mean amplitude of glycemic excursion or coefficient of variation) between the two injection methods. Compared with NP, NFI did not increase the incidence of hypoglycemia (17.2% vs. 14.1%, p=0.774), and it decreased the incidence of induration (4.7% vs. 23.4%, p=0.002) and leakage (6.3% vs. 20.3%, p=0.022) while decreasing the pain visual analog scale score (2.30 ± 1.58 vs. 3.11 ± 1.40, p<0.001)., Conclusion: NFI can improve PIR in patients with T2DM and be used with a smaller dose of insulin aspart 30 while maintaining the same hypoglycemic effect., Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2400083658., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Men, Wang, Shi, Yin, Li, Zhou and Du.)

Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), which are all complex metabolic disorders. Selenoprotein S (SelS) is an endoplasmic reticulum (ER) resident selenoprotein involved in regulating ER stress and has been found to participate in the occurrence and development of IR and T2DM. However, the potential role and mechanism of SelS in NAFLD remains unclear. Here, we analyzed SelS expression in the liver of high-fat diet (HFD)-fed mice and obese T2DM model (db/db) mice and generated hepatocyte-specific SelS knockout (SelS H-KO ) mice using the Cre-loxP system. We showed that hepatic SelS expression levels were significantly downregulated in HFD-fed mice and db/db mice. Hepatic SelS deficiency markedly increased ER stress markers in the liver and caused hepatic steatosis via increased fatty acid uptake and reduced fatty acid oxidation. Impaired insulin signaling was detected in the liver of SelS H-KO mice with decreased phosphorylation levels of insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/Akt), which ultimately led to disturbed glucose homeostasis. Meanwhile, our results showed hepatic protein kinase Cɛ (PKCɛ) activation participated in the negative regulation of insulin signaling in SelS H-KO mice. Moreover, the inhibitory effect of SelS on hepatic steatosis and IR was confirmed by SelS overexpression in primary hepatocytes in vitro. Thus, we conclude that hepatic SelS plays a key role in regulating hepatic lipid accumulation and insulin action, suggesting that SelS may be a potential intervention target for the prevention and treatment of NAFLD and T2DM., (© 2022. The Author(s).)

Interleukin-8 (IL-8, also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed that metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in db/db mice. The db/m and db/db mice were subcutaneously injected with G31P or equivalent normal saline once a day for 6 wk. The physical and metabolic parameters, glucose tolerance, insulin sensitivity, hepatic lipid accumulation, and inflammation markers were measured. G31P improved hepatic insulin sensitivity by modulating expression of genes related to gluconeogenesis and phosphorylated Akt levels. The expressions of several genes encoding proteins involved in de novo lipogenesis were decreased in G31P-treated db/db mice. Meanwhile, immune cell infiltration and cytokine release were attenuated in db/db mice with G31P treatment. G31P also improved the ratio of proinflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, G31P ameliorates metabolic disturbances via inhibition of CXCR1 and CXCR2 pathways in db/db mice. These data suggest that the selective inhibition of CXC chemokines may have therapeutic effects on symptoms associated with obesity and diabetes.

Purpose: To analyze the impact of dynamic changes in inflammation on atherosclerosis in short-duration type 2 diabetes after multifactorial intervention., Methods: In this randomized controlled study, a total of 150 type 2 diabetes patients who had a mean age of 49.8±7.3years, 51% male, with disease duration <1year and without evidence of atherosclerosis were randomized into an intensive intervention group (IG), in which patients received multiple risk factors intervention by the special project team and tried to reach the pre-determined intervention goals, and a conventional group (CG), in which patients received standard diabetes care by the clinic doctor. All patients recieved intervention study for 7 years, then underwent a 3-year observational follow-up study. The primary endpoints were occurrence of subclinical atherosclerosis, defined as the intima-media thickness of the common carotid artery (CC-IMT)≥1.0mm or formation of atherosclerosis plaques, and the occurrence of cardiovascular events., Results: 68 patients in IG and 65 patients in CG completed the 10-year study. The cumulative incidence of subclinical atherosclerosis was 30.7% vs 57.3% (IG vs CG, HR 0.36, 95% CI 0.22-0.60, P<0.0001) and that of cardiovascular events was 12.0% vs 22.7% (IG vs CG, HR 0.46, 95% CI 0.21-0.98, P=0.0516). High sensitivity C-reactive protein (hs-CRP) reduction from baseline to the 10-year follow-up was -1.54mg/L (IG) and -0.67mg/L (CG) with difference (IG minus CG) of -0.87mg/L(95% CI -0.72 to -1.02, P=0.008) and the natural logarithm of serum amyloid A (SAA) reduction was -4.04 (IG) and -1.44 (CG) with difference (IG minus CG) of -2.60 (95% CI -2.30 to -2.90, P=0.002). The decrease in general score of inflammatory markers (combination of hs-CRP and SAA) was independently associated with subclinical atherosclerosis (OR=0.65, P=0.045) and cardiovascular events (OR=0.60, P=0.042)., Conclusions: Dynamic changes in inflammation act as an important factor that affects the occurrence of atherosclerosis in type 2 diabetes patients. Multifactorial intensive intervention can reduce systemic low-grade inflammation and delay the occurrence of atherosclerosis in short-duration type 2 diabetes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective To investigate the relationship between serum selenoprotein S (SelS) and obesity in patients with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine T2DM patients who were managed by the National Metabolic Management Center (MMC) of the First Affiliated Hospital of Dalian Medical University from November 2017 to November 2019 and 55 healthy people as controls in the health examination center of our hospital were enrolled in the retrospective cross-sectional study. The general condition, biochemical indexes and obesity evaluation parameters were recorded. According to the serum SelS quartile, T2DM patients were divided into Q1 group: ≤95.10 ng/dl (53 cases), Q2 group: 95.12 to 111.62 ng/dl (52 cases), Q3 group: 112.46 to 130.97 ng/dl (52 cases), Q4 group: ≥131.33 ng/dl (52 cases). Analysis of variances, rank sum test and Chi-square test were used for comparison between groups. Multiple stepwise regression was used to analyze the influencing factors of obesity evaluation index. Results There was statistically significant difference in visceral fat index (VAI) among T2DM abdominal obesity group, non-abdominal obesity group and healthy control group (H=36.679, P<0.01), but there was no statistically significant difference in serum SelS. There was statistically significant difference in serum amyloid A (SAA) level among the SelS quartile groups (H=3.560, P<0.01), but there was no statistically significant difference in visceral fat area (VFA), subcutaneous fat area (SFA), visceral fat area to subcutaneous fat area ratio (VSR) and VAI. Serum SelS was positively correlated with VFA, VSR, VAI and SAA (r=0.158 to 0.448, all P<0.05). Serum SelS was an independent risk factor for VFA (β= 0.172, P=0.003), VSR (β=0.001, P=0.01) and VAI (β=0.009, P=0.038). Conclusion Serum SelS level in T2DM patients is positively correlated with VFA, VSR and VAI, which is an independent risk factor for abdominal obesity. [ABSTRACT FROM AUTHOR]