Comparison of glucose time in range and area under curve in range in relation to risk of diabetic retinopathy in type 2 diabetes patients

Aims/introductionWe proposed a novel continuous glucose monitoring (CGM)‐based metric, area under the curve in range (AucIR), for integrating both the amplitude and duration of dysglycemia, and further compared AucIR with the emerging key CGM‐derived metric, time in range (TIR).Materials and methodsA total of 2,030 adult patients with type 2 diabetes were enrolled during May 2020 to October 2021. AucIR and TIR were measured with 7‐day CGM data. Logistic regression analysis and the C‐statistic was carried out to assess the association of AucIR and TIR with diabetic retinopathy (DR).ResultsBoth AucIR (r = −0.89) and TIR (r = −0.95) were strongly correlated with mean glucose levels. Compared with TIR, AucIR showed a tighter relationship with parameters of glycemic variability, including the coefficient of variation (r = −0.56), standard deviation (r = −0.89) and mean amplitude of glycemic excursions (r = −0.70). For each absolute 10% decrease in AucIR, the risk of DR was increased by 7% (95% confidence interval 1.02–1.13) after adjustment for confounders. With respect to TIR, each absolute 10% decrease was associated with an 8% (95% confidence interval 1.03–1.14) increased risk of DR. The model discrimination for DR, as measured by C‐statistic, did not differ significantly between the two metrics (P > 0.05).ConclusionsAucIR did not provide added benefit over TIR in the assessment of DR risk among patients with type 2 diabetes. The potential value of AucIR needs to be explored in future studies.     

The interaction of carbaryl with the metabolism of isolated hepatocytes: II. Effect on gluconeogenesis

1. The effects of 1-naphthyl-N-methylcarbamate (carbaryl) upon glucose production from several precursors (lactate, glycerol, alanine, fructose and pyruvate) and on activities of gluconeogenic enzymes (glucose-6-phosphatase, lactate dehydrogenase and aspartate aminotransferase) in isolated rat hepatocytes was studied.2. The results show that carbaryl inhibits lactate-gluconeogenesis at all concentrations of substrate studied. Gluconeogenesis from 10 mM fructose or 10 mM pyruvate or 10 mM alanine is also inhibited by carbaryl 1 mM. However, glycerol-gluconeogenesis is unaffected.3. Concentrations of carbaryl at 0.01 and 0.1 mM did not significantly modify lactic dehydrogenase activity, but at 1.0 mM this activity was reduced by 38% in relation to the dimethylsulphoxide-treated group.4. The synthetic activity of glucose-6-phosphatase is enhanced by carbaryl, but the increase is only significant for 1 mM carbaryl. In the study of aspartate aminotransferase activities two fractions, cytoplasmic and mitochondrial, are differentiated; and, it is observed that both fractions are inhibited by 0.1 and 1.0 mM carbaryl.5. The results indicate that carbaryl produces major decreases of the glucose production by hepatic cells, and suggest that the carbaryl-induced hyperglycemia in the fasted animal would be due to deficiencies in the peripheral utilization of the glucose.     

糖化血清白蛋白在2型糖尿病患者中的临床应用

目的分析2型糖尿病患者糖化血清白蛋白(GA)与各常用血糖参数的相关性及GA的影响因素,评价GA与糖尿病微血管并发症的相关性。方法 2007年5月—2009年10月我院2型糖尿病住院患者1 597例。患者入院初测定空腹静脉血糖(FPG)、餐后2 h血糖(2hPG)、GA、糖化血红蛋白(HbA_(lc))、24 h尿白蛋白定量,并行连续血糖监测(CGMS),全部患者均由眼科医生眼底摄片。结果 2型糖尿病患者入院时GA值为(25.8±7.8)%,HbA_(lc)为(9.0±2.3)%。GA与HbA_(lc)、FPG、2hPG、CGMS血糖均值均正相关(r=0.788、0.396、0.406、0.470,均P<0.01)。体重指数、2hPG、CGMS血糖均值是影响GA的主要因素。GA>17%组患者糖尿病视网膜病变的检出率高于GA≤17%组(P<0.01),GA>17%组患者糖尿病肾病的检出率与GA≤17%组间无显著差异(P>0.05)。结论 GA是一个可准确反映短期内平均血糖水平及变化的优良且检测方便的指标,GA与糖尿病视网膜病变的发生相关。     

Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations

PurposeCongenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising the two.MethodsWe identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence- and structure-based predictions and/or functional assays.ResultsWe identified eight probands with CHH with (n = 3; Kallmann syndrome) or without anosmia (n = 5) and SHFM, seven of whom (88%) harbor FGFR1 mutations. Of these seven, one individual is homozygous for p.V429E and six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, or p.L712P. All mutations were predicted by in silico analysis to cause loss of function. Probands with FGFR1 mutations have severe gonadotropin-releasing hormone deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was observed only in the patient with the homozygous p.V429E mutation; V429 maps to the fibroblast growth factor receptor substrate 2α binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of fibroblast growth factor receptor substrate 2α to FGFR1, thereby resulting in reduced mitogen-activated protein kinase signaling.ConclusionFGFR1 should be prioritized for genetic testing in patients with CHH and SHFM because the likelihood of a mutation increases from 10% in the general CHH population to 88% in these patients.Genet Med17 8, 651–659.     

Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1⁺), myeloid-committed progenitors (CD11b⁺, Gr-1⁺), and lymphoid-committed progenitors (CD45⁺, CD3e⁺). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1⁺ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b⁺ and Gr-1⁺ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45⁺ and CD3e⁺ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.     

Impact of serum uric acid on subclinical myocardial injury in general population

Background and aimsHyperuricemia is widely thought as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the relation of serum uric acid (sUA) and subclinical myocardial injury (SCeMI) remains unclear. We hypothesize that sUA is associated with subclinical myocardial injury.Methods and resultsA total of 5880 adult individuals (57.9 ± 13.0 years, 54.23% women) without known cardiovascular disease from National Health and Nutrition Examination Survey (NHANES) III were included. Determined by Cardiac Infarction Injury Score (CIIS) from 12-lead electrocardiogram, SCeMI was defined by CIIS ≥10 units. The relationship between sUA and SCeMI was analyzed by using logistic regression models and the smooth curve fitting. Subgroup analyses were conducted. After adjusting for potential confounding variables, the smooth curve fitting revealed a non-linear relationship between sUA level and SCeMI. When sUA was above the inflection point 266.5 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 15%. In women group, when sUA>340.3 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 71%, but no significant correlation was observed in men group.ConclusionsOur findings confirm that sUA is an independent risk factor for subclinical myocardial injury after adjusting for potential confounding variables, and existence of such an association in women only, which require more random control trials to confirm the strategy of cardiovascular disease prevention based on sUA reduction in female.     

Impact of Omega-3 supplementation on homocysteine levels in humans: A systematic review and meta-regression analysis of randomized controlled trials

AimsAlthough some evidence suggests that omega-3 polyunsaturated fatty acids (PUFAs) supplementation influences enzymes involved in forming homocysteine (Hcy) and improving hyperhomocysteinemia, these findings are still contradictory in humans. The aim of this systematic and meta-analysis study was to investigate the effects of omega-3 supplementation on Hcy using existing randomized controlled trials (RCTs).Data synthesisAvailable databases, including PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library, and Embase, were searched to find relevant RCTs up to June 2021. The effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI).ConclusionA total of 20 RCT studies with 2676 participants were included in this article. Our analyses have shown that omega-3 supplementation significantly reduced plasma Hcy levels (WMD: 1.34 μmol/L; 95% CI: 1.97 to ?0.72; P < 0.001) compared to the control group. The results of subgroup analysis showed that omega-3 supplementation during the intervention <12 weeks and with a dose ≥3 gr per day causes a more significant decrease in Hcy levels than the intervention ≥12 weeks and at a dose <3 gr. In addition, omega-3 supplements appear to have more beneficial effects in individuals with high levels of normal Hcy. This meta-analysis showed that omega-3 supplementation significantly improved Hcy. However, further studies are needed to confirm the findings.