黄斑区形态改变在糖尿病视网膜病变早期诊断中的价值

目的探讨黄斑区形态改变在糖尿病视网膜病变（DR）早期诊断中的价值。方法选取2018年1月~2019年6月在我院治疗的2型DR患者108例，其中非增殖性DR（NPDR组）68例，增殖性DR（PDR组）40例，同时选取单纯2型糖尿病患者50例作为对照，各组均行光学相干断层扫描血流成像（OCTA）检查，比较各组黄斑区血流密度（MVD）、黄斑中心凹无血管区（FAZ）及黄斑视网膜厚度差异。结果NPDR组和PDR组黄斑区MVD分别为（0.48±0.02）%和（0.47±0.03）%，低于对照组（P < 0.05）；NPDR组和PDR组FAZ竖径分别为0.37±0.03 mm和0.38±0.02 mm，高于对照组（P < 0.05）；PDR组FAZ面积为0.49±0.04 mm2，高于对照组和NPDR组（P < 0.05）；对照组、NPDR组和PDR组黄斑区平均视网膜厚度的差异无统计学意义（P>0.05）；黄斑区MVD、FAZ竖径、FAZ面积诊断NPDR和PDR的ROC曲线下面积分别为0.845、0.840和0.922（P < 0.05），截断值分别为0.50%、0.37 mm和0.43 mm2，敏感度分别为80.50%、79.80%和88.50%，特异性分别为78.00%、75.00%和84.00%。结论DR患者黄斑区MVD降低，而FAZ竖径及面积扩大，在诊断中有一定应用价值。      

糖尿病视网膜病变黄斑区血流密度和黄斑中心凹无血管区面积的变化及其意义

【目的】探讨糖尿病视网膜病变(diabetic retinopathy,DR)黄斑区血流密度(macular vascular density,MVD)和黄斑中心凹无血管区(foveal avascular zone,FAZ)面积的变化及其意义。【方法】选取2015年2月至2017年2月在本院就诊的74例糖尿病患者(DM组)及同期40例健康查体者(CON)的临床资料,糖尿病患者根据眼科检查分为无DR组(No-DR组)、非增殖性糖尿病DR组(NPDR组)和增殖性糖尿病DR组(PDR组)。光学相干断层扫描血管成像技术(optical coherence tomography angiography,OCTA)检测各组MVD和FAZ横径、竖径和面积并比较。【结果】DM组共有135只眼,其中No-DR组共71只,NPDR组共53只眼,PDR组共11只眼,正常CON共80只眼。PDR组、NPDR组在表层、内层视网膜及脉络膜毛细血管层的MVD均明显低于CON(均P<0.05)。No-DR组在表层、内层视网膜的MVD均明显低于CON(均P<0.05);PDR组、NPDR组在表层、内层视网膜及脉络膜毛细血管层MVD明显低于No-DR组(均P<0.05)。与CON相比,PDR组FAZ竖径、横径及面积明显较大(均P<0.05);No-DR组、NPDR组FAZ面积明显较大(P=0.000),而FAZ竖径、横径无显著差别(均P>0.05)。【结论】DR患者FAZ面积扩大及MVD降低,对早期诊断DR具有重要临床价值。     

Quantitative assessment and determinants of foveal avascular zone in healthy volunteers

ObjectivesTo evaluate the foveal avascular zone (FAZ) area in healthy volunteers using optical coherence tomography angiography (OCTA) and identify factors that influence the FAZ.MethodsThis single-center cross-sectional study included 526 eyes of 263 healthy volunteers who underwent macular scanning by Zeiss OCTA. A linear mixed model was used to investigate the effects of systemic factors (age, sex, blood pressure, height, and weight) and ocular factors (intraocular pressure, biometric parameters, and central macular thickness) on FAZ.ResultsIn total, 520 eyes of 262 healthy volunteers were included in the analysis. The mean volunteer age was 38.59 ± 22.03 years (range, 5–84 years); 124 volunteers were male (47.33%) and 138 volunteers were female (52.67%). The mean FAZ area was 0.30 ± 0.03 mm² (95% confidence interval [CI], 0.29–0.31 mm²). Univariate analysis showed that FAZ area was associated with age (β = 0.0011), anterior chamber depth (β = −0.0513), and axial length (β = −0.0202). Multivariate analysis showed that FAZ area was negatively correlated with axial length (β = −0.0181).ConclusionsThe mean FAZ area in healthy volunteers, measured using Zeiss OCTA, was 0.30 ± 0.03 mm². Furthermore, FAZ area was negatively associated with axial length; this relationship should be considered in clinical practice.     

Cefoperazone sodium/sulbactam sodium vs piperacillin sodium/tazobactam sodium for treatment of respiratory tract infection in elderly patients

BACKGROUNDRespiratory tract infections in the elderly are difficult to cure and can easily recur, thereby posing a great threat to patient prognosis and quality of life.AIMTo investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection. METHODSSeventy-four elderly patients with respiratory tract infection were randomly allocated to a study (n = 37; treated with cefoperazone sodium/sulbactam sodium) or control (n = 37; treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support) group. Both groups were treated for 7 d. Time to symptom relief (leukocyte recovery; body temperature recovery; cough and sputum disappearance; and rale disappearance time), treatment effect, and laboratory indexes [procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NE)] before and 7 d after treatment and the incidence of adverse reactions were assessed.RESULTSIn the study group, the time to WBC normalization (6.79 ± 2.09 d), time to body temperature normalization (4.15 ± 1.08 d), time to disappearance of cough and sputum (6.19 ± 1.56 d), and time to disappearance of rales (6.68 ± 1.43 d) were shorter than those of the control group (8.89 ± 2.32 d, 5.81 ± 1.33 d, 8.77 ± 2.11 d, and 8.69 ± 2.12 d, respectively; P = 0.000). Total effective rate was higher in the study group (94.59% vs 75.68%, P = 0.022). Serum PCT (12.89 ± 3.96 μg/L), CRP (19.62 ± 6.44 mg/L), WBC (20.61 ± 6.38 × 10⁹/L), and NE (86.14 ± 7.21%) levels of the study group before treatment were similar to those of the control group (14.05 ± 4.11 μg/L, 18.79 ± 5.96 mg/L, 21.21 ± 5.59 × 10⁹/L, and 84.39 ± 6.95%, respectively) with no significant differences (P = 0.220, 0.567, 0.668, and 0.291, respectively). After 7 d of treatment, serum PCT, CRP, WBC, and NE levels in the two groups were lower than those before treatment. Serum PCT (2.01 ± 0.56 μg/L), CRP (3.11 ± 1.02 mg/L), WBC (5.10 ± 1.83 × 10⁹/L), and NE (56.35 ± 7.17%) levels were lower in the study group than in the control group (3.29 ± 0.64 μg/L, 5.67 ± 1.23 mg/L, 8.13 ± 3.01 × 10⁹/L, and 64.22 ± 8.08%, respectively; P = 0.000). There was no significant difference in the incidence of adverse reactions between the groups (7.50% vs 12.50%, P = 0.708).CONCLUSIONPiperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/ sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.     

The expression of oxidative stress genes related to myocardial ischemia reperfusion injury in patients with ST-elevation myocardial infarction

BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10⁹/L vs.6.41±0.72×10⁹/L,P<0.05;N:9.27±4.75×10⁹/L vs.3.89±0.81×10⁹/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.     

Clinical stages of recurrent hepatocellular carcinoma: A retrospective cohort study

BACKGROUNDHepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and has relatively high recurrence rates. Few studies have been published on the clinical stages of recurrent HCC.AIMTo assess the applicability of the Barcelona Clinic Liver Cancer (BCLC) staging for recurrent HCC and the need to establish clinical stage criteria for recurrent HCC.METHODSThe clinicopathological data of 81 patients with recurrent HCC who were admitted to the Hospital of Guangxi Zhuang Autonomous Region from January 2013 to December 2017 were collected. The patients were divided into three groups according to the BCLC staging system as follows: (1) Group A with BCLC stage A, 51 patients; (2) Group B with BCLC stage B, 14 patients; and (3) Group C with BCLC stage C, 16 patients. The median time to tumor recurrence and the median overall survival were compared. RESULTSThe median time to tumor recurrence in groups A, B, and C was 16 ± 1.5 mo, 10 ± 2.8 mo, and 6 ± 0.5 mo, respectively, with a statistically significant difference among them (χ² = 70.144, P < 0.05); no statistically significant difference was noted between group A and group B (χ² = 2.659, P > 0.05), although there were statistically significant differences between group A and group C and between group B and group C (χ² = 62.110, and 19.972, P < 0.05). The median overall survival in groups A, B, and C were 42 ± 5.1 mo, 22 ± 3.1 mo, and 13 ± 1.8 mo, respectively, with a statistically significant difference among them (χ² = 38.949, P < 0.05); there were statistically significant differences between group A and group B, group A and group C, and group B and group C (χ² = 9.577, 37.172, and 7.183, respectively; P < 0.05).CONCLUSIONThere are different prognoses in recurrent HCC patients according to the BCLC staging. Therefore, BCLC staging is applicable to recurrent HCC and it is essential to formulate clinical stage criteria for recurrent HCC.     

Three-year follow-up of Coats disease treated with conbercept and 532-nm laser photocoagulation

BACKGROUNDCoats disease is an idiopathic exudative outer retinopathy caused by abnormal retinal vascular development.AIMTo evaluate the long-term outcomes of intravitreal conbercept injection with laser photocoagulation as a treatment for Coats disease in adults.METHODSThis retrospective case series study included patients diagnosed with Coats disease and treated with intravitreal conbercept injection and 532-nm laser photocoagulation at the Ophthalmology Department of Shenzhen People’s Hospital between January 2016 and January 2017. Best-corrected visual acuity (BCVA) measurements, noncontact tonometry, ophthalmoscopy, fundus photography, fundus fluorescein angiography and optical coherence tomography were performed before treatment and at 1 wk, 1 mo, 3 mo, 6 mo, 9 mo, 12 mo, 24 mo and 36 mo after therapy. Best-corrected visual acuity was measured using the early treatment of diabetic retinopathy study chart.RESULTSThe study included eight eyes of 8 patients (7 men) aged 36.10 ± 6.65 years. The average BCVA of the affected eye before treatment was 51.17 ± 15.15 letters (range, 28–70 letters), and the average central macular thickness was 303.30 ± 107.87 µm (range, 221–673 µm). Four eyes were injected once, three were injected twice, and one was injected three times. Average follow-up duration was 37.33 ± 2.26 mo. Average BCVA of the affected eye was 51.17 ± 15.15 letters before treatment and was increased by 13.50 ± 3.20, 16.25 ± 7.73, 18.25 ± 8.96, 18.03 ± 5.27, 18.63 ± 3.35, 19.75 ± 6.96, 18.05 ± 5.36 and 17.88 ± 3.45 letters at 1 wk, 1 mo, 3 mo, 6 mo, 9 mo, 12 mo, 24 mo and 36 mo after treatment, respectively (P < 0.01). The patients showed varying degrees of subretinal fluid resorption after treatment. None of the patients had serious complications such as increased intraocular pressure, development/progression of cataracts, endophthalmitis or retinal detachment.CONCLUSIONIntravitreal injection of conbercept combined with 532-nm laser photocoagulation may be a feasible treatment for Coats disease in adult patients.     

Paricalcitol in hemodialysis patients with secondary hyperparathyroidism and its potential benefits

BACKGROUNDSecondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT can increase bone fragility and calcification of blood vessels and soft tissues, which greatly increases the risk of death.AIMTo discuss the outcome, safety and other potential benefits of paricalcitol injection in hemodialysis patients with SHPT. METHODSWe recruited 40 patients who received hemodialysis at our hospital for chronic renal failure with SHPT between March and December 2019. They received paricalcitol injection for 24 wk (starting dose, 0.06–0.08 μg/kg), three times per week. They were followed up at the baseline (week 0), week 4, week 12 and week 24. The primary outcome indicator was the percentage of patients with a > 30% decrease in intact parathyroid hormone (iPTH) levels at week 24 compared with the baseline. The secondary outcome indicators included percentage decrease in iPTH levels at week 24, standard-reaching rate of iPTH (percentage of patients with iPTH down to 130–585 pg/mL), changes in serum levels of calcium (Ca), phosphate (P), Ca × P product, alkaline phosphatase (ALP), creatinine (Cre), hemoglobin (Hb), and C-reactive protein (CRP), and incidence of adverse events (AEs). RESULTSAfter 24 wk of treatment, iPTH levels decreased significantly (598.88 ± 381.29 pg/mL vs 888.84 ± 376.88 pg/mL, P < 0.05). More than 30% decrease of iPTH was found in 21 of 36 (58.33%) patients. The average decrease in iPTH levels was 32.16 ± 4.33%; the standard-reaching rate of iPTH levels was 66.67% (24/36); and ALP levels decreased significantly compared with the baseline (113.72 ± 41.73 IU/L vs 133.45 ± 56.86 IU/L) (t = 2.798, P < 0.05). There were no significant differences in the serum levels of calcium, Hb, Cre and CRP compared with the baseline (P > 0.05). After 24 wk of treatment, serum P levels decreased compared with the baseline (1.91 ± 0.40 mmol/L vs 2.16 ± 0.66 mmol/L) (t = 2.830, P < 0.05). Ca × P product decreased significantly compared with the baseline (56.38 ± 13.22 mg²/dL² vs 63.97 ± 20.30 mg²/dL²) (t = 2.717, P < 0.05). No serious adverse events occurred.CONCLUSIONParicalcitol was a safe and effective treatment for hemodialysis patients with SHPT. It decreased serum levels of iPTH, ALP and P and maintained stability of serum Ca levels.     

New indicators in evaluation of hemolysis,elevated liver enzymes,and low platelet syndrome: A case-control study

BACKGROUNDIndices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW) are considered new markers of the systemic inflammatory response (SIR), and have been widely implemented for the diagnosis of patients with inflammatory diseases. These new indicators have also been widely investigated in preeclampsia (PE) but less analyzed in hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome.AIMTo compare SIR markers among HELLP patients, PE only patients, and healthy gravidae.METHODSThis retrospective case-control study enrolled 630 cases, including 210 patients with HELLP syndrome (HELLP group), 210 patients with only PE (PE group) and 210 healthy gravidae (control group). The three groups were matched by age, parity, status of assisted reproduction, and multiple pregnancies. Birthweight, gestational age at complete blood count collection, gestational age at delivery, mode of delivery, etc. were recorded. The main indices as NLR, PLR, MPV, PDW, and RDW among the groups were compared, as well as some secondary outcomes including neutrophil, platelets, and hemoglobin.RESULTSThe NLR (6.4 vs 4.3 vs 3.5), MPV (11.9 vs 11.2 vs 10.7), PDW (16.4 vs 13.3 vs 14.2), leukocyte (12.4 × 10⁹/L vs 9.7 × 10⁹/L vs 8.7 × 10⁹/L) and neutrophil count (9.9 × 10⁹/L vs 7.3 × 10⁹/L vs 6.1 × 10⁹/L) were highest in the HELLP group, lower in the PE group, and lowest in the control group. Both the overall comparisons between the three groups (all ^bP < 0.01) and pairwise comparisons between every two groups elicited statistically significant differences (all ^dP < 0.01, except control vs PE: ^cP < 0.05 in PDW). The average lymphocyte counts were 1.4 (1.1, 2.0) × 10⁹/L in the HELLP group, 1.6 (1.3, 2.0) × 10⁹/L in the PE group and 1.7 (1.4, 2.0) × 10⁹/L in the control group. The overall comparison of lymphocyte count within the three groups had statistically significant differences (P = 0.000). The pairwise comparisons between every two groups demonstrated that the HELLP group had a lower lymphocyte count than both the PE (P = 0.019) and control groups (P = 0.000), but the difference between the PE and control groups was not statistically significant (P = 0.432). The overall comparisons on platelet counts and the PLR among these three groups also showed statistically significant differences (both P = 0.000), from low to high being those in the HELLP group (43.4 × 10⁹/L, 64.0), control group (180.5 × 10⁹/L, 103.6) and PE group (181.5 × 10⁹/L, 112.8). Pairwise comparisons of neither index displayed statistically significant differences between the PE and control groups (both P > 0.05), while the differences in the two indices between the HELLP group and the two other groups were still statistically significant (all P = 0.000). RDW values were highest in the HELLP group (14.5% [13.6, 15.3]), lower in the control group (14.1% [13.5, 14.8]) and lowest in the PE group (13.9% [13.4, 14.9]). The difference between the PE and control group did not show statistical significance (P = 1.000), while RDW values in the HELLP group were higher than those in the other two groups (^cP < 0.05 vs control, ^dP < 0.01 vs PE).CONCLUSIONSIR markers such as NLR, RDW, MPV, and PDW were increased and PLR was decreased in HELLP. These SIR markers may become new indicators in the evaluation of HELLP syndrome.     

Effects of mindful breathing combined with sleep-inducing exercises in patients with insomnia

BACKGROUNDInsomnia is the most common sleep disorder. It disrupts the patient’s life and work, increases the risk of various health issues, and often requires long-term intervention. The financial burden and inconvenience of treatments discourage patients from complying with them, leading to chronic insomnia.AIMTo investigate the long-term home-practice effects of mindful breathing combined with a sleep-inducing exercise as adjunctive insomnia therapy.METHODSA quasi-experimental design was used in the present work, in which the patients with insomnia were included and grouped based on hospital admission: 40 patients admitted between January and April 2020 were assigned to the control group, and 40 patients admitted between May and August 2020 were assigned to the treatment group. The control group received routine pharmacological and physical therapies, while the treatment group received instruction in mindful breathing and a sleep-inducing exercise in addition to the routine therapies. The Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder 7-item (GAD-7) scale, and Insomnia Severity Index (ISI) were utilized to assess sleep-quality improvement in the patient groups before the intervention and at 1 wk, 1 mo, and 3 mo postintervention.RESULTSThe PSQI, GAD-7, and ISI scores before the intervention and at 1 wk postintervention were not significantly different between the groups. However, compared with the control group, the treatment group exhibited significant improvements in sleep quality, daytime functioning, negative emotions, sleep latency, sleep duration, sleep efficiency, anxiety level, and insomnia severity at 1 and 3 mo postintervention (P < 0.05). The results showed that mindful breathing combined with the sleep-inducing exercise significantly improved the long-term effectiveness of insomnia treatment. At 3 mo, the PSQI scores for the treatment vs the control group were as follows: Sleep quality 0.98 ± 0.48 vs 1.60 ± 0.63, sleep latency 1.98 ± 0.53 vs 2.80 ± 0.41, sleep duration 1.53 ± 0.60 vs 2.70 ± 0.56, sleep efficiency 2.35 ± 0.58 vs 1.63 ± 0.49, sleep disturbance 1.68 ± 0.53 vs 2.35 ± 0.53, hypnotic medication 0.53 ± 0.64 vs 0.93 ± 0.80, and daytime dysfunction 1.43 ± 0.50 vs 2.48 ± 0.51 (all P < 0.05). The GAD-7 scores were 2.75 ± 1.50 vs 7.15 ± 2.28, and the ISI scores were 8.68 ± 2.26 vs 3.38 ± 1.76 for the treatment vs the control group, respectively (all P < 0.05).CONCLUSIONThese simple, cost-effective, and easy-to-implement practices used in clinical or home settings could have profound significance for long-term insomnia treatment and merit wide adoption in clinical practice.     

Risk of Blindness Among Patients With Diabetes and Newly Diagnosed Diabetic Retinopathy

OBJECTIVETo evaluate the association between initial diabetic retinopathy (DR) severity/risk of blindness in patients with newly diagnosed DR/good vision in the U.S.RESEARCH DESIGN AND METHODSThis retrospective cohort study evaluated adult patients with good vision (20/40 or better) and newly diagnosed DR between 1 January 2013 and 31 December 2017 (index date) in the American Academy of Ophthalmology’s Intelligent Research in Sight (IRIS) Registry. The primary exposure of interest was DR severity at index: mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). The main outcome measure was development of sustained blindness (SB), defined as study eyes with Snellen visual acuity readings of 20/200 or worse at two separate visits ≥3 months apart that did not improve beyond 20/100.RESULTSAmong 53,535 eligible eyes (mean follow-up 662.5 days), 678 (1.3%) eyes developed SB. Eyes with PDR at index represented 10.5% (5,629 of 53,535) of the analysis population but made up 26.5% (180 of 678) of eyes that developed SB. Kaplan-Meier analysis revealed that eyes with moderate NPDR, severe NPDR, and PDR at index were 2.6, 3.6, and 4.0 times more likely, respectively, to develop SB after 2 years of DR diagnosis versus eyes with mild DR at index. In a Cox proportional hazards model adjusted for index characteristics/development of ocular conditions during follow-up, eyes with PDR had an increased risk of developing SB versus eyes with mild NPDR at index (hazard ratio 2.26 [95% CI 2.09−2.45]).CONCLUSIONSIn this longitudinal ophthalmologic registry population involving eyes with good vision, more advanced DR at first diagnosis was a significant risk factor for developing SB.     

Changes in Prandial Glucagon Levels After a 2-Year Treatment With Vildagliptin or Glimepiride in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy

OBJECTIVE

To determine if the dipeptidyl peptidase-4 inhibitor vildagliptin more effectively inhibits glucagon levels than the sulfonylurea glimepiride during a meal.

RESEARCH DESIGN AND METHODS

Glucagon responses to a standard meal were measured at baseline and study end point (mean 1.8 years) in a trial evaluating add-on therapy to metformin with 50 mg vildagliptin b.i.d. compared with glimepiride up to 6 mg q.d. in type 2 diabetes (baseline A1C 7.3 ± 0.6%).

RESULTS

A1C and prandial glucose area under the curve (AUC)_{0–2 h} were reduced similarly in both groups, whereas prandial insulin AUC_{0–2 h} increased to a greater extent by glimepiride. Prandial glucagon AUC_{0–2 h} (baseline 66.6 ± 2.3 pmol · h⁻¹ · l⁻¹) decreased by 3.4 ± 1.6 pmol · h⁻¹ · l⁻¹ by vildagliptin (n = 137) and increased by 3.8 ± 1.7 pmol · h⁻¹ · l⁻¹ by glimepiride (n = 121). The between-group difference was 7.3 ± 2.1 pmol · h⁻¹ · l⁻¹ (P < 0.001).

CONCLUSIONS

Vildagliptin therapy but not glimepiride improves postprandial α-cell function, which persists for at least 2 years.Glucagon levels are increased in type 2 diabetes because of impaired glucose-mediated suppression of glucagon secretion resulting in increased hepatic glucose output with subsequent hyperglycemia (1). Improved glycemia by the dipeptidyl peptidase-4 inhibitor, vildagliptin (2), is mediated primarily by improved β- and α-cell sensitivity to glucose (3). As an add-on to metformin, vildagliptin displays equal efficacy as glimepiride, with the added benefits of a much lower risk of hypoglycemia and no weight gain (4). Here we report prandial assessments of glucagon levels and insulin secretion rates after up to ∼2 years of therapy with the two drugs.     

Diabetic Retinopathy –Incidence And Risk Factors In A Community Setting- A Longitudinal Study

Aim: To evaluate the natural history of diabetic retinopathy (DR) in diabetic patients and to assess long term risk for other chronic diseases associated with DR.

Methods: Retrospective, community-based study. Diabetics who underwent their first fundoscopic examination during 2000–2002, and had at least one follow- up examination by the end of 2007 were included. The primary outcome was the development of DR (proliferative diabetic retinopathy (PDR), non PDR (NPDR) or macular edema.

Patients were followed for another 9 years for documentation of new diagnosis of related diseases.

Results: 516 patients' (1,032 eyes) records were included and were followed first for an average of 4.15?±?1.27 years. During follow-up, 28 (2.7%) of the total 1,032 eyes examined were diagnosed with PDR. An additional 194 (18.8%) eyes were diagnosed with new NPDR. The cumulative incidence of NPDR was 310/1,032 (30.0%). All the patients who developed PDR had prior NDPR. By the end of the 9 years extended follow up, patients with NPDR had a greater risk for developing chronic renal failure HR?=?1.71 (1.14–2.56), ischemic heart disease HR?=?1.57 (1.17–2.09), and had an increased mortality rate HR?=?1.26 (1.02–1.57)

Conclusion: DR is associated with a higher rate of diabetes complications. Patients with DR should be followed more closely.

• Key points

• During a mean follow-up of 4.5 years, the cumulative incidence of diabetic retinopathy in a community cohort was 18.8%.

• NDPR (non-proliferative diabetic retinopathy) is a predictor of PDR (proliferative diabetic retinopathy).

• In a real life setting NPDR is a marker of a poorer prognosis.

• Patients with NDPR should be monitored more closely.

     

Clinical effect of peripheral capsule preservation in eyes with silicone oil tamponade

BACKGROUNDAt present, silicone oil has been widely used in vitrectomy to deal with complex fundus diseases. Usually, cataract extraction is combined with vitrectomy. However, reducing the complications of silicone oil tamponade and facilitating the secondary implantation of intraocular lens (IOL) are still an urgent problem.AIMTo evaluate the clinical effect of vitrectomy combined with peripheral capsule preservation (PCP) in eyes with silicone oil tamponade.METHODSThis single-center retrospective analysis included 70 patients (73 eyes) who underwent vitrectomy and silicone oil tamponade combined with cataract surgery (stage I) between January 2015 and July 2019. All patients underwent selective reoperation for silicone oil extraction and IOL implantation (stage II) more than 3 mo after stage I. These patients were divided into three groups according to the different lens capsule preservation methods: 28 patients (31 eyes) in a whole capsule preserved (WCP) group, 17 (17 eyes) in a capsule absent (CA) group, and 25 (25 eyes) in a peripheral capsule preserved (PCP) group. Intraocular pressure (IOP), best-corrected visual acuity, surgery time, and other complications were recorded at each time point (1 d, 1 wk, and 1 mo after stages I and II).RESULTSThe IOP values were 14.9 ± 8.2 mmHg in the WCP group, 20.3 ± 13.0 mmHg in the CA group, and 14.2 ± 9.7 mmHg in the PCP group (P < 0.05) at 1 mo after stage I operation. Five eyes had IOP higher than 30 mmHg, and one eye in the WCP group appeared to have silicone oil entering the anterior chamber. There was no significant difference in IOP among the three groups at any other time point (P > 0.05). With IOL implantation, visual acuity improved significantly compared to stage I. The incidence rate of posterior capsule opacity was higher in the WCP group than in the other groups (P < 0.001). In the CA group, IOL deviation due to suture relaxation occurred in one case. There was no significant difference in the surgery time among the three groups in stage I (P = 0.618). In stage II, the surgery time of the PCP group and WCP group was significantly shorter than that of the AC group (P = 0.031).CONCLUSIONPreservation of the peripheral capsule in vitrectomy combined with lens removal is a better option. This method has significant advantages in reducing intraoperative and postoperative complications.     

Comparison of ocular axis and corneal diameter between entropion and non-entropion eyes in children with congenital glaucoma

BACKGROUNDChildren with congenital glaucoma are often accompanied by acquired epiblepharon in the lower eyelid, which causes entropion of the lower eyelid and damages the cornea.AIMTo infer the possible causes of lower eyelid entropion by comparing the difference of ocular axis and corneal diameter between inverted and non-inverted ciliary eyes in children with congenital glaucoma.METHODSA total of 15 patients (11 males and 4 females) diagnosed with congenital glaucoma between July 2016 and January 2019 at Tongren Hospital were included. Five patients had bilateral glaucoma, and ten had unilateral glaucoma. Each patient had only one eye with lower eyelid entropion which is associated with congenital glaucoma. All the patients had no entropion in another eye. The clinical data were collected. Main outcome measures were the ocular axis and corneal diameter.RESULTSThe average age of the 15 patients was 1.85 ± 0.49 years. Paired t-test showed that the average ocular axis of congenital glaucoma eyes with lower eyelid entropion (24.86 ± 3.44 mm) was significantly longer than that of congenital glaucoma eyes without lower eyelid entropion (20.79 ± 1.34 mm; P < 0.001). The average corneal diameter of congenital glaucoma eyes with lower eyelid entropion (13.61 ± 0.88 mm) was also significantly greater than that of congenital glaucoma eyes without lower eyelid entropion (11.63 ± 0.48; P < 0.001).CONCLUSIONThe rapid growth of the ocular axis and corneal diameter may be the main cause of congenital glaucoma with acquired lower eyelid entropion. Therefore, children with poor control of intraocular pressure and excessive growth of ocular axis and corneal diameter must be observed for the existence of acquired epiblepharon.     

Dipeptidyl peptidase-4 inhibition by vildagliptin and the effect on insulin secretion and action in response to meal ingestion in type 2 diabetes

OBJECTIVE—The purpose of this study was to determine the mechanism by which dipeptidyl peptidase-4 inhibitors lower postprandial glucose concentrations.RESEARCH DESIGN AND METHODS—We measured insulin secretion and action as well as glucose effectiveness in 14 subjects with type 2 diabetes who received vildagliptin (50 mg b.i.d.) or placebo for 10 days in random order separated by a 3-week washout. On day 9 of each period, subjects ate a mixed meal. Insulin sensitivity (S_I), glucose effectiveness, and β-cell responsivity indexes were estimated using the oral glucose and C-peptide minimal models. At 300 min 0.02 unit/kg insulin was administered intravenously.RESULTS—Vildagliptin reduced postprandial glucose concentrations (905 ± 94 vs. 1,008 ± 104 mmol/6 h, P = 0.02). Vildagliptin did not alter net S_I (7.71 ± 1.28 vs. 6.41 ± 0.84 10⁻⁴ dl · kg⁻¹ · min⁻¹ · μU⁻¹ · ml⁻¹, P = 0.13) or glucose effectiveness (0.019 ± 0.002 vs. 0.018 ± 0.002 dl · kg⁻¹ · min⁻¹, P = 0.65). However, the net β-cell responsivity index was increased (35.7 ± 5.2 vs. 28.9 ± 5.2 10⁻⁹ min⁻¹, P = 0.03) as was total disposition index (381 ± 48 vs. 261 ± 35 10⁻¹⁴ dl · kg⁻¹ · min⁻² · pmol⁻¹ · l⁻¹, P = 0.006). Vildagliptin lowered postprandial glucagon concentrations (27.0 ± 1.1 vs. 29.7 ± 1.5 μg · l⁻¹ · 6 h⁻¹, P = 0.03), especially after administration of exogenous insulin (81.5 ± 6.4 vs. 99.3 ± 5.6 ng/l, P = 0.02).CONCLUSIONS—Vildagliptin lowers postprandial glucose concentrations by stimulating insulin secretion and suppressing glucagon secretion but not by altered insulin action or glucose effectiveness. A novel observation is that vildagliptin alters α-cell responsiveness to insulin administration, but the significance of this action is as yet unclear.Glucagon-like peptide-1 (GLP-1) is a peptide hormone produced by the enteroendocrine L cells of the intestinal mucosa and is released in response to caloric intake. The major form of secreted GLP-1, GLP-1-(7,36)-amide, is a powerful insulin secretagogue that also suppresses glucagon secretion in a glucose-dependent fashion and may increase insulin action (1). These characteristics would theoretically make the hormone ideal therapy for use in type 2 diabetes, a disorder characterized by defective insulin secretion and action.However, GLP-1 is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), a widely distributed enzyme, which converts the intact peptide to the metabolite GLP-1-(9,36)-amide. GLP-1–based therapy for type 2 diabetes has required the development of GLP-1 receptor agonists such as exenatide, which are resistant to the action of DPP-4, or, alternatively, compounds that inhibit DPP-4 and thereby raise endogenous concentrations of active GLP-1 (2). GLP-1 (3), GLP-1 receptor agonists (4), and DPP-4 inhibitors (2) all lower postprandial glucose concentrations.GLP-1 and its analogs delay gastric emptying (5), whereas DPP-4 inhibitors do not (6), indicating that the effects of the latter on postprandial glucose concentrations must occur via other mechanisms. It is uncertain whether the lack of gastrointestinal effects of DPP-4 inhibitors occurs because the resulting rise in peripheral active GLP-1 concentrations is not elevated or sustained, in marked contrast with concentrations observed during peripheral GLP-1 infusion. Another potential explanation is that DPP-4 inhibition may alter concentrations of other gut hormones with effects on appetite or motility (such as peptide YY), which neutralize the effect of GLP-1 (7). DPP-4 inhibitors, GLP-1, and its analogues decrease postprandial glucagon concentrations (2). In contrast with GLP-1 and GLP-1 receptor agonists, the effect of DPP-4 inhibition on insulin secretion has been more uncertain: placebo-controlled studies have demonstrated similar insulin concentrations in the presence or absence of DPP-4 inhibition, despite lower glucose concentrations (6). This result implies that such compounds also increase insulin secretion for a given glucose concentration, as has been demonstrated previously using model-based parameters of β-cell function (8).It is possible, however, that these agents lower postprandial glucose concentrations through changes in insulin action and glucose effectiveness. The direct effects of GLP-1 on the ability of glucose per se to stimulate its own uptake and suppress its own release (glucose effectiveness) are less clear (9). Some (10,11) but not all (12) studies have suggested that, when given in pharmacological doses, GLP-1 increases the ability of insulin and glucose to stimulate glucose uptake and to suppress glucose production. Similar controversy exists with regard to the effects of GLP-1 on insulin action (9). Given the known differences in DPP-4 inhibitors, in comparison with other GLP-1–based therapy, it is possible that these compounds also differ with regard to their direct effects on glucose metabolism.To gain greater insight into the mechanism(s) by which DPP-4 inhibitors lower postprandial glucose concentrations, we used a randomized, double-blind, placebo-controlled crossover design in which subjects received vildagliptin, a DPP-4 inhibitor, or placebo over a 10-day period. The disposition index, a measure of insulin secretion for the prevailing insulin action, was measured using the oral glucose (13) and oral C-peptide minimal models (14). Glucose effectiveness was also measured simultaneously. We report that whereas vildagliptin stimulated insulin secretion and enhanced suppression of glucagon, it had no effect on either insulin action or glucose effectiveness. Taken together with previous studies in the same subjects indicating that vildagliptin does not alter gastric emptying (6), these data indicate that DPP-4 inhibitors lower postprandial glucose concentrations solely by alterations of islet cell function.     

Multitissue insulin resistance despite near-normoglycemic remission in Africans with ketosis-prone diabetes

OBJECTIVE—To characterize insulin action in Africans with ketosis-prone diabetes (KPD) during remission.RESEARCH DESIGN AND METHODS—At Saint-Louis Hospital, Paris, France, 15 African patients with KPD with an average 10.5-month insulin-free near-normoglycemic remission period (mean A1C 6.2%) were compared with 17 control subjects matched for age, sex, BMI, and geographical origin. Insulin stimulation of glucose disposal, and insulin suppression of endogenous glucose production (EGP) and nonesterified fatty acids (NEFAs), was studied using a 200-min two-step (10 mU · m⁻² body surface · min⁻¹ and 80 mU · m⁻² · min ⁻¹ insulin infusion rates) euglycemic clamp with [6,6-²H₂]glucose as the tracer. Early-phase insulin secretion was determined during an oral glucose tolerance test.RESULTS—The total glucose disposal was reduced in patients compared with control subjects (7.5 ± 0.8 [mean ± SE] vs. 10.5 ± 0.9 mg · kg⁻¹ · min⁻¹; P = 0.018). EGP rate was higher in patients than control subjects at baseline (4.0 ± 0.3 vs. 3.0 ± 0.1 mg · kg⁻¹ · min⁻¹; P = 0.001) and after 200-min insulin infusion (10 mU · m⁻² · min⁻¹: 1.6 ± 0.2 vs. 0.6 ± 0.1, P = 0.004; 80 mU · m⁻² · min⁻¹: 0.3 ± 0.1 vs. 0 mg · kg⁻¹ · min⁻¹, P = 0.007). Basal plasma NEFA concentrations were also higher in patients (1,936.7 ± 161.4 vs. 1,230.0 ± 174.1 μmol/l; P = 0.002) and remained higher after 100-min 10 mU · m⁻² · min⁻¹ insulin infusion (706.6 ± 96.5 vs. 381.6 ± 55.9 μmol/l; P = 0.015).CONCLUSIONS—The triad hepatic, adipose tissue, and skeletal muscle insulin resistance is observed in patients with KPD during near-normoglycemic remission, suggesting that KPD is a form of type 2 diabetes.Impairment of insulin sensitivity is considered the background defect that interplays with the add-on progressive β-cell dysfunction to underlie the development of type 2 diabetes (1,2). An atypical form of diabetes, ketosis-prone diabetes (KPD), has been described over the past 2 decades and may represent a significant proportion of diabetes cases in people of sub-Saharan African origin (3,4). Patients with KPD present at onset with acute hyperglycemia, usually >30 mmol/l, and ketosis or ketoacidosis as type 1 diabetes but do not have autoimmune markers against the islet β-cell (3,5–7). The correction of those insulin-requiring acute-phase disorders is followed in >50% of cases by an insulin-free near-normoglycemic remission weeks to months later (8–10), thus resembling the course of type 2 diabetes. The pathogenesis and, consequently, the classification of KPD are still debated. It was classified under idiopathic type 1 diabetes or type 1B diabetes (11). However, growing evidence based on clinical and metabolic studies suggests its high phenotypical likeness to type 2 diabetes, and “ketosis-prone type 2 diabetes” has been proposed as a provisional name and is being used elsewhere (4,8,12). Metabolic studies have evidenced insulin secretion deficiency as the major determinant of the ketotic onset (8–10). This deficit is marked by a loss of acute-phase insulin secretion in response to intravenous glucose (10) or a decrease in C-peptide response to glucagon (9,10). The subsequent remission process is due to a restoration, at least partial, of the β-cell insulin secretory capacity after achievement of good metabolic control (8,10). Insulin action was assessed in three reports, but only toward glucose metabolism, and was found to be normal or decreased while patients were in good metabolic control (6,8,10). Moreover, most studies on KPD have been reported in African-Americans who are more overweight than native Africans and may be metabolically different from them, as suggested earlier (13).In this study, we aimed at characterizing all aspects of insulin action in Africans with KPD when in the near-normoglycemic state without insulin treatment compared with control subjects of the same geographic origin.     

Ultrasonographic assessment of cardiac function and disease severity in coronary heart disease

BACKGROUNDCoronary heart disease (CHD) causes many adverse cardiovascular events and poses a threat to the patient’s health and quality of life. AIMTo evaluate ultrasonography for evaluation of cardiac function and lesion degree in patients with CHD.METHODSA total of 106 patients with CHD (study group) and 106 healthy individuals (control group) in our hospital from March 2019 to September 2020 were selected for this study. All subjects were examined by ultrasound, and the mitral orifice’s early-to-late diastolic blood flow velocity ratio (E/A), left ventricular end-diastolic volume (LVDd), and left atrial diameter (LAD) were measured. Values were compared between the study group and healthy group, and the correlation between the ultrasonic parameters of patients with different cardiac function grades and the degree of CHD were assessed. In addition, the ultrasonic parameters of patients with different prognoses were compared after a follow-up for 6 mo.RESULTSE/A (1.46 ± 0.34) of the study group was smaller than that of the control group (1.88 ± 0.44), while LVDd (58.24 ± 5.05 mm) and LAD (43.31 ± 4.38 mm) were larger (48.15 ± 3.93 and 34.94 ± 2.81, respectively; P < 0.05). E/A for patients with grade III disease (1.41 ± 0.43) was smaller and their LVDd (60.04 ± 4.21 mm) and LA (44.16 ± 2.79 mm) were larger than those in patients with grade II disease (1.71 ± 0.48, 52.18 ± 3.67 mm, and 39.68 ± 2.37, respectively; P < 0.05). Patients with grade IV disease had smaller E/A (1.08 ± 0.39) and larger LVDd (66.81 ± 5.39 mm) and LAD (48.81 ± 3.95 mm) than patients with grade II and III disease (P < 0.05). In patients with moderate disease, E/A (1.44 ± 0.41) was smaller and LVDd (59.95 ± 4.14 mm) and LAD (45.15 ± 2.97 mm) were larger than in patients with mild disease (1.69 ± 0.50, 51.97 ± 3.88 and 38.81 ± 2.56 mm, respectively; P < 0.05). In patients with severe disease, E/A (1.13 ± 0.36) was smaller and LVDd (67.70 ± 6.11 mm) and LAD (49.09 ± 4.05 mm) were larger than in patients with moderate disease (P < 0.05). E/A was negatively correlated with cardiac function classification and disease severity, while LVDd and LAD were positively correlated with cardiac function classification and disease severity (P < 0.05). E/A (1.83 ± 0.51) for patients with good prognosis was higher than that for those with poor prognosis (1.39 ± 0.32), while LVDd (49.60 ± 4.39 mm) and LAD (36.13 ± 3.05 mm) were lower (P < 0.05).CONCLUSIONThe ultrasonic parameters of patients with CHD are abnormal, and differ significantly in patients with different cardiac function grades, lesion degree, and prognosis.     

Is a Priming Dose of Insulin Necessary in a Low-Dose Insulin Protocol for the Treatment of Diabetic Ketoacidosis?

OBJECTIVE—The purpose of this study was to assess the efficacy of an insulin priming dose with a continuous insulin infusion versus two continuous infusions without a priming dose.RESEARCH DESIGN AND METHODS—This prospective randomized protocol used three insulin therapy methods: 1) load group using a priming dose of 0.07 units of regular insulin per kg body weight followed by a dose of 0.07 unit · kg⁻¹ · h⁻¹ i.v. in 12 patients with diabetic ketoacidosis (DKA); 2) no load group using an infusion of regular insulin of 0.07 unit · kg body weight⁻¹ · h⁻¹ without a loading dose in 12 patients with DKA, and 3) twice no load group using an infusion of regular insulin of 0.14 · kg⁻¹ · h⁻¹ without a loading dose in 13 patients with DKA. Outcome was based on the effects of insulin therapy on biochemical and hormonal changes during treatment and recovery of DKA.RESULTS—The load group reached a peak in free insulin value (460 μU/ml) within 5 min and plateaued at 88 μU/ml in 60 min. The twice no load group reached a peak (200 μU/ml) at 45 min. The no load group reached a peak (60 μU/ml) in 60–120 min. Five patients in the no load group required supplemental insulin doses to decrease initial glucose levels by 10%; patients in the twice no load and load groups did not. Except for these differences, times to reach glucose ≤250 mg/dl, pH ≥7.3, and HCO₃⁻ ≥15 mEq/l did not differ significantly among the three groups.CONCLUSIONS—A priming dose in low-dose insulin therapy in patients with DKA is unnecessary if an adequate dose of regular insulin of 0.14 unit · kg body weight⁻¹ · h⁻¹ (about 10 units/h in a 70-kg patient) is given.Although positive therapeutic responses to low-dose insulin therapy have been established in adult patients with diabetic ketoacidosis (DKA) (1–8), none of these studies and guidelines for the treatment of DKA, including the American Diabetes Association (ADA) Consensus and Position Statements, has ever assessed or addressed the use of a continuous insulin infusion without a loading dose of insulin (9). In the current study, we used a dose of 0.14 unit · kg⁻¹ · h⁻¹ without a loading dose instead of the recommended 0.1 unit · kg⁻¹ · h⁻¹ with a loading dose. This insulin regimen was chosen because one study in a pediatric population used a dosing regimen of 0.1 unit · kg⁻¹ · h⁻¹ without a loading dose that resulted in a total plasma insulin level of 50–60 μU/ml (10). This level proved to be too low for optimal suppression of hepatic glucose output and optimal glucose uptake (11). In addition, bolus doses of insulin may result in hypokalemia as well as other undesirable effects (12), especially when used in a routine hospital setting.The efficacy of low-dose insulin without a priming dose has not been established in a prospective randomized study (13). Thus, the following questions have remained unanswered in the treatment of DKA: 1) Is an insulin bolus needed before a continuous insulin infusion? 2) What is the optimal insulin infusion rate if a bolus dose is not used? and 3) What is the dose response of continuous insulin infusion used alone in regard to decremental changes in glucose, metabolic parameters, cortisol, and free fatty acids (FFAs)? Therefore, we evaluated responses to three low-dose insulin regimens in 37 consecutive patients with DKA in a prospective randomized fashion to address these issues. Changes in plasma free insulin, serum potassium levels, and outcome recovery measures were assessed using a higher infusion dose (0.14 unit · kg⁻¹ · h⁻¹ without a bolus dose) compared with a lower infusion dose (0.07 unit · kg⁻¹ · h⁻¹) with and without a loading dose (0.07 unit/kg) of insulin.