- Apolipoprotein CIII and diabetes. Is there a link? [Review]
- DMDiabetes Metab Res Rev 2018 Dec 17; :e3118
- Apolipoprotein CIII (ApoCIII), a small protein that resides on the surface of lipoprotein particles, is a key regulator of triglyceride metabolism. The inhibition of lipoprotein lipase (LPL), the inc...
Apolipoprotein CIII (ApoCIII), a small protein that resides on the surface of lipoprotein particles, is a key regulator of triglyceride metabolism. The inhibition of lipoprotein lipase (LPL), the increased assembly and secretion of very low-density lipoproteins (VLDL) and the decreased reuptake of triglyceride-rich lipoproteins (TRLs) by the liver are mechanisms associating elevated serum ApoCIII levels and hypertriglyceridemia. ApoCIII concentration is high in individuals with diabetes mellitus indicating a possible positive correlation with impairment of glucose metabolism. The aim of this review (based on a Pubmed search until August 2018) is to present the possible mechanisms linking ApoCIII and deterioration of carbohydrate homeostasis. ApoCIII enhances pancreatic β-cells apoptosis via an increase of the cytoplasmic Ca2+ levels in the insulin producing cells. In addition, overexpression of ApoCIII enhances non-alcoholic fatty liver disease and exacerbates inflammatory pathways in skeletal muscles, affecting insulin signaling and thereby inducing insulin resistance. Moreover, recent studies reveal a possible mechanism of body weight increase and glucose production through a potential ApoCIII-induced LPL inhibition in the hypothalamus. Also, the presence of ApoCIII on the surface of high-density lipoprotein particles is associated with impairment of their antiglycemic and atheroprotective properties. Modulating ApoCIII may be a potent therapeutic approach to manage hypertriglyceridemia and improve carbohydrate metabolism.
- Adherence to Therapeutic Footwear in Type 2 Diabetes in Malta. [Journal Article]
- ECExp Clin Endocrinol Diabetes 2018 Dec 17
- CONCLUSIONS: This study demonstrated suboptimal adherence to wearing therapeutic footwear among people with type 2 diabetes. Although the literature highlights the importance of adherence to therapeutic footwear in high risk populations for the prevention of diabetic foot complications, this study provides the reasons as to why patients still do not comply in wearing their prescribed therapeutic footwear. In order to improve behavioral changes patients would require on-going care, empowerment and support combined with educational programs to achieve a higher level of adherence. More research is warranted to explore further psychosocial interventions in diabetes care.
- Peripheral Insulin Extraction in Non-Diabetic Subjects and Type 2 Diabetes Mellitus Patients. [Journal Article]
- ECExp Clin Endocrinol Diabetes 2018 Dec 17
- CONCLUSIONS: We propose that in non-diabetic individuals, besides passive diffusion, an active high-affinity pathway with limited capacity around lower physiologic insulin levels exists for insulin transendothelial transport, contributing to glycemic control. In T2D patients, this mechanism of peripheral insulin uptake is diminished or even absent. Modulation of insulin extraction from the circulation may be a novel target to improve glucose metabolism in T2D.
- Assessment of Exercise Capacity in Children with Type 1 Diabetes in the Cooper Running Test. [Journal Article]
- IJInt J Sports Med 2018 Dec 17
- Regular physical activity increases lifespan for those with type 1 diabetes. However, disease-related barriers may deter children from exercise and affect their fitness. This study examined the safet...
Regular physical activity increases lifespan for those with type 1 diabetes. However, disease-related barriers may deter children from exercise and affect their fitness. This study examined the safety of the Cooper test concerning diabetes-related acute complications in children with type 1 diabetes and their fitness. Blood glucose was recorded before and 0, 30, 60 min after the test. The covered distances were transformed to z-scores based on the national charts. Body mass index, body fat percentage and glycated hemoglobin were measured. The run was completed by 80 individuals (45% boys, age 13.6±2.1 years; diabetes duration 6.3±3.5 years). During the follow-up 11 children reached glucose alert values (3-3.9 mmol/L), 3 presented clinically significant hypoglycemia (<3 mmol/L), none experienced severe hypoglycemia. The covered distance was 1914±298 m, not significantly different from the reference population (z-score -0.12±0.71 vs 0, p=0.12). The study participants were more overweight than general pediatric population in terms of body mass index (z-score 0.48±0.94 vs 0, p<0.001) and body fat percentage (z-score: 0.37±0.85 vs 0, p<0.001). In conclusion, the Cooper test can be safely used in children with diabetes to assess their physical capacity. Youth with type 1 diabetes present fitness similar to healthy children but exhibit increased body mass index and adiposity.
- Cubilin Single Nucleotide Polymorphism Variants are Associated with Macroangiopathy While a Matrix Metalloproteinase-9 Single Nucleotide Polymorphism Flip-Flop may Indicate Susceptibility of Diabetic Nephropathy in Type-2 Diabetic Patients. [Journal Article]
- NNephron 2018 Dec 17; :1-10
- CONCLUSIONS: This study highlights that MMP-9 or CUBN-SNPs may exert effects on risk of susceptibility to DN or ESRD. We provide novel evidence on genetic susceptibility for macroangiopathy in patients with a missense variant of CUBN (Ile2984Val) in patients with T2D.
- Short-Term Steroid Regimen for Adult Steroid-Sensitive Minimal Change Disease. [Journal Article]
- AJAm J Nephrol 2018 Dec 17; 49(1):54-63
- CONCLUSIONS: The short-term steroid regimen may represent an effective treatment option that ensures lower steroid exposure when treating adult steroid-sensitive MCD patients.
- Dipeptidyl peptidase-4 inhibition protects the liver of insulin-resistant female rats against triglyceride accumulation by suppressing uric acid. [Journal Article]
- BPBiomed Pharmacother 2018 Dec 14; 110:869-877
- Dipeptidyl peptidase-4 (DPP-4) inhibition has been shown to exert beneficial effects against insulin resistance (IR) and type 2 diabetes. Combined oral contraceptive (COC) treatment is associated wit...
Dipeptidyl peptidase-4 (DPP-4) inhibition has been shown to exert beneficial effects against insulin resistance (IR) and type 2 diabetes. Combined oral contraceptive (COC) treatment is associated with impaired glucose and lipid metabolism but the mechanisms are elusive. We therefore, hypothesized that DPP-4 inhibition ameliorates COC-induced glucose dysregulation and hepatic triglyceride (TG) accumulation through adenosine deaminase (ADA) /xanthine oxidase (XO) /uric acid-dependent pathway. Female Wistar rats received (po) vehicle and COC (1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel; po) with or without DPP-4 inhibitor (sitagliptin; 100 mg/kg; po) for 8 weeks (n = 6/group). Glucose dysmetabolism was assessed by elevated fasting blood glucose, impaired oral glucose tolerance test and homeostatic model assessment of IR. Treatment with COC led to increased plasma fasting glucose, triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, IR and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic TG, TG/HDL-cholesterol ratio, malondialdehyde, uric acid (plasma; 25.2 ± 0.6 mg/dl; hepatic 128.9 ± 8.0 mg/100 mg tissue), lactate dehydrogenase, DPP-4, ADA and XO (plasma;10.5 ± 1.1 U/L; hepatic 21.2 ± 1.4 U/g protein) activities. Likewise, COC led to reduction in nitric oxide level. However, DPP-4 inhibition significantly ameliorated these alterations induced by COC treatment through suppression of uric acid (plasma; 15.1 ± 1.0 mg/dl, hepatic; 75.6 ± 5.0 mg/100 mg tissue), XO (plasma; 4.1 ± 0.9 U/L, hepatic; 8.7 ± 0.4 U/g protein), ADA and DPP-4 activities suggesting their involvement in glucose dysregulation and hepatic TG accumulation induced by COC treatment. Therefore, DPP-4 inhibition would impact positively on cardiometabolic disorders, at least in part, through XO, ADA and uric acid suppression.
- Identification of novel PPARα/γ dual agonists by pharmacophore screening, docking analysis, ADMET prediction and molecular dynamics simulations. [Journal Article]
- CBComput Biol Chem 2018 Nov 27; 78:178-189
- PPARα and PPARγ play an important role in regulating glucose and lipid metabolism. The single and selective PPARα or PPARγ agonists have caused several side effects such as edema, weight gain and car...
PPARα and PPARγ play an important role in regulating glucose and lipid metabolism. The single and selective PPARα or PPARγ agonists have caused several side effects such as edema, weight gain and cardiac failure. In the recent years, the dual PPARs agonist development has become a hot topic in the antidiabetic medicinal chemistry field. In this paper, the compound CHEMBL230490 were gained from CHEMBL database, by means of complex-based pharmacophore (CBP) virtual screening, molecular docking, ADMET prediction and molecular dynamics (MD) simulations. The compound CHEMBL230490 not only displayed higher binding scores and better binding modes with the active site of PPARα a/γ, but also had more favorable the pharmacokinetic properties and toxicity evaluated by ADMET prediction. The representative compound CHEMBL230490 was performed to MDs for studying a stable binding conformation. The results indicated that the CHEMBL230490 might be a potential antidiabetic lead compound. The research provided a valuable approach in developing novel PPARα/γ dual agonists for the treatment of type 2 diabetes mellitus (T2DM).
- Validation of Diagnostic and Performance Characteristics of the Wireless Motility Capsule in Patients With Suspected Gastroparesis. [Journal Article]
- CGClin Gastroenterol Hepatol 2018 Dec 14
- CONCLUSIONS: Although there is agreement in analysis of gastric emptying by GES vs WMC, WMC provides higher diagnostic yield than GES. WMC detects delayed gastric emptying more frequently than GES and identifies extra-gastric transit abnormalities. Diabetic vs non-diabetic subjects have different results from GES vs WMC. These findings could affect management of patients with suspected gastroparesis. ClinicalTrials.gov no: NCT02022826.
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- Association between ambient particulate matter air pollution and ST-elevation myocardial infarction: A case-crossover study in a Chinese city. [Journal Article]
- CChemosphere 2018 Dec 12; 219:724-729
- CONCLUSIONS: This is the first study in China that suggested acute exposure to elevated PM concentrations may trigger STEMI. Patients with cardiometabolic comorbidities were slightly more susceptible to air pollution.