Changes in high-density-lipoprotein cholesterol upon statin treatment in type 2 diabetic patients: A meta-analysis

Background and aimTo investigate the diversity of change in high-density-lipoprote in cholesterol (HDL-C) after statin treatment in patients with type 2 diabetes mellitus (T2DM).Methods and resultsA systemic review searched for trials that reported a serum change in HDL-C in patients with T2DM after statin treatment, and extracted data for meta-analysis. Of 6709 articles surveyed, 160 articles were identified as eligible articles. In the analysis of simvastatin, serum HDL-C was increased in Non-Asian and Asian patients with T2DM by 2.17 mg/dl (95% CI 1.43 ∼ 2.90 mg/dl, p < 0.001) and 2.31 mg/dl (95% CI 1.37 ∼ 3.25 mg/dl, p < 0.001), respectively. In the analysis of atorvastatin, although significant, serum HDL-C was subtly increased in Non-Asian patients with T2DM by 1.14 mg/dl (95% CI 0.28 ∼ 2.01 mg/dl, p = 0.010) mg/dl; however, atorvastatin treatment did not significantly change the serum HDL-C by 0.12 mg/dl (95% CI −1.04 ∼ 1.27 mg/dl, p = 0.839) mg/dl in Asian patients with T2DM. According to meta-regression analysis, the baseline HDL-C did not affect the change in serum HDL-C in Asian patients with T2DM after either simvastatin or atorvastatin treatment. However, contrary to simvastatin, the coefficient of regression (r) showed a significant negative association (r = −0.18; 95% CI −0.32 to −0.04; p = 0.01) between baseline HDL-C and the change of HDL-C in non-Asian patients with T2DM after atorvastatin treatment.ConclusionWe have demonstrated for the first time that there may be a discrepancy in the change of serum HDL-C in Asian patients with T2DM after atorvastatin treatment.     

Effects of zinc supplementation on lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

Background and aimFindings on the effects of zinc supplementation on the lipid profile in patients with type 2 diabetes mellitus (T2DM) are conflicting. The current comprehensive systematic review and meta-analysis aimed to summarize available evidence in this regard.Methods and resultsAfter a systematic search in the online databases, we included the randomized controlled trials (RCTs) investigating the effect of zinc supplementation on lipid profile [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)] in patients with T2DM. Altogether, 9 studies with a total sample size of 424 patients with T2DM were included in the analysis. Combining 9 effect sizes from 9 RCTs, we found a significant lowering effect of zinc supplementation on serum levels of TG (weighted mean difference (WMD): −17.08, 95% CI: −30.59, −3.58 mg/dL, P = 0.01) and TC (WMD: −26.16, 95% CI: −49.69, −2.62 mg/dL, P = 0.02). Although the overall effect of zinc supplementation on LDL-C levels was not significant, a beneficial effect was seen in studies that administered <100 mg/d zinc. Based on the non-linear dose–response analysis, a greater reduction in serum levels of TC and LDL-C following zinc supplementation was seen at <12 weeks’ duration of intervention. Unlike the overall effect size, we found a significant increasing effect of zinc supplementation on serum HDL-C concentrations in most subgroups of RCTs according to the subgroup analyses.ConclusionWe found that zinc supplementation may beneficially influence lipid profile in patients with T2DM.     

Clinical and pathological characteristics of DKD patients with early-onset type 2 diabetes

AimsIn diabetic kidney disease (DKD) patients, early-onset T2DM effects on renal disease severity and outcomes remain uncertain. Herein, we aim to investigate the clinicopathological characteristics and renal outcomes in DKD patients with early-onset T2DM.Methods489 patients with T2DM and DKD were retrospectively recruited and classified as having early (age at onset of T2DM < 40 years) and late (age at onset of T2DM ≥ 40 years) T2DM onset, analyzing the clinical and histopathological data. The predictive value of early-onset T2DM to renal outcomes in DKD patients was analyzed by Cox's regression.ResultsAmong 489 DKD patients, 142 and 347 were classified as early and late T2DM onset, respectively. Early-onset T2DM patients exhibited worse glycaemic control (7.36 % ± 1.80 % vs. 6.86 % ± 1.57 %, P = 0.007) and more severe proteinuria (3.69 [1.55 to 7.03] vs. 1.81 [0.50 to 4.33] g/24 h, P < 0.001). Those with early-onset T2DM presented more severe glomerular lesions. In univariable Cox regression, early-onset T2DM showed a significant correlation with renal composite endpoint (HR [95%CI]: 0.56 [0.43 to 0.73], P < 0.001). However, after adjusting for potential confounders, early-onset T2DM was not independently correlated with renal composite endpoint (HR [95%CI]: 0.74 [0.46 to 1.21], P = 0.232).ConclusionsIn DKD patients with early-onset T2DM, renal clinicopathological manifestations were severe. Age at onset in T2DM was significantly correlated with eGFR slope (r = 0.211, P < 0.001).     

Long-term effects of lowering postprandial glucose level on cardiovascular outcomes in early-stage diabetic patients with coronary artery disease: 10-year post-trial follow-up analysis of the DIANA study

AimsTo elucidate the long-term cardiovascular benefit of lowering postprandial hyperglycemia (PPG) in early-stage T2DM patients.MethodsThis 10-year post-trial follow-up study included 243 patients from the DIANA (DIAbetes and diffuse coronary Narrowing) study, a multi-center randomized controlled trial which compared the efficacy of one-year life-style and pharmacological (voglibose/nateglinide) intervention lowering PPG on coronary atherosclerosis in 302 early-stage T2DM subjects [impaired glucose tolerance (IGT) or newly-diagnosed T2DM] (UMIN-CTRID#0000107). MACE (all-cause death, non-fatal MI or unplanned coronary revascularization) were compared in (1) three assigned therapies (life-style intervention/vogliose/nateglinide) and (2) patients with and without improvement of PPG (reversion from IGT to NGT or from DM to IGT/NGT on 75 g oral glucose tolerance test).ResultsDuring the 10-year post-trial observational period, voglibose (HR = 1.07, 95%CI: 0.69–1.66, p = 0.74) or nateglinide (HR = 0.99, 95%CI: 0.64–1.55, p = 0.99) did not reduce MACE. Similarly, achieving the improvement of PPG was not associated with a reduction of MACE (HR = 0.78, 95%CI: 0.51–1.18, p = 0.25). However, in IGT subjects (n = 143), this glycemic management significantly reduced the occurrence of MACE (HR = 0.44, 95%CI: 0.23–0.86, p = 0.01), especially unplanned coronary revascularization (HR = 0.46, 95%CI: 0.22–0.94, p = 0.03).ConclusionsThe early improvement of PPG significantly reduced MACE and unplanned coronary revascularization in IGT subjects during the post-trial 10-year period.     

Presence of retinopathy and incident kidney and cardiovascular events in type 2 diabetes with normoalbuminuria – A post-hoc analysis of the PRIORITY randomized clinical trial

AimsBaseline diabetic retinopathy (DR) and risk of development of microalbuminuria, kidney function decline, and cardiovascular events (CVEs) in type 2 diabetes.MethodsPost-hoc analysis of the PRIORITY study including 1758 persons with type 2 diabetes and normoalbuminuria followed for a median of 2.5 (IQR: 2.0–3.0) years. DR diagnosis included non-proliferative and proliferative abnormalities, macular oedema, or prior laser treatment. Cox models were fitted to investigate baseline DR presence with development of persistent microalbuminuria (urinary albumin-creatinine ratio > 30 mg/g); chronic kidney disease (CKD) G3 (eGFR <60 ml/min/1.73m²); and CVE. Models were adjusted for relevant risk factors.ResultsAt baseline, 304 (17.3 %) had DR. Compared to persons without DR, they were older (mean ± SD: 62.7 ± 7.7 vs 61.4 ± 8.3 years, p = 0.019), had longer diabetes duration (17.9 ± 8.4 vs. 10.6 ± 7.0 years, p < 0.001), and higher HbA_1c (62 ± 13 vs. 56 ± 12 mmol/mol, p < 0.001). The adjusted hazard ratios of DR at baseline for development of microalbuminuria (n = 197), CKD (n = 166), and CVE (n = 64) were: 1.50 (95%CI: 1.07, 2.11), 0.87 (95%CI: 0.56, 1.34), and 2.61 (95%CI: 1.44, 4.72), compared to without DR.ConclusionsPresence of DR in normoalbuminuric type 2 diabetes was associated with an increased risk of developing microalbuminuria and CVE, but not with kidney function decline.     

Associations of apolipoproteinA1, high density lipoprotein cholesterol with hemoglobin glycation index and triglyceride-glucose index in Chinese adults with coronary artery disease

AimsScarce data explored the associations of apolipoproteins with hemoglobin glycation index (HGI) and triglyceride-glucose (TyG) index. This study determined associations of serum apolipoproteinA1 (ApoA1) and high density lipoprotein cholesterol (HDL-C) with HGI and TyG index in coronary artery disease (CAD) patients.MethodsA total of 10,803 CAD patients were included in this cross-sectional pilot study. Serum concentrations of ApoA1 and HDL-C were measured. Analyses of covariance were used to compare the mean differences in glucose metabolism indices (e.g., HGI, TyG index, hemoglobin glycation [HbA1c], fasting blood glucose [FBG]) among the quartiles of ApoA1, HDL-C and HDL-C/ApoA1 ratio.ResultsIn multivariate analysis, higher ApoA1, HDL-C and HDL-C/ApoA1 ratio were associated with significantly lower HGI (Quartile [Q]4 vs. Q1: −0.032 % vs. 0.017 % for ApoA1; −0.072 % vs. 0.079 % for HDL-C; −0.083 % vs. 0.085 % for HDL-C/ApoA1 ratio). Intermediate ApoA1 level was inversely associated with TyG index (Q2 vs. Q1: 296.278 vs. 306.794). The mean TyG index were significantly decreased with increased HDL-C and HDL-C/ApoA1 ratio (Q4 vs. Q1: 298.584 vs. 309.221 for HDL-C; 300.405 vs. 315.218 for HDL-C/ApoA1 ratio). Moreover, the inverse associations of ApoA1, HDL-C and HDL-C/ApoA1 ratio with HbA1c and FBG also were observed. In path analysis, the associations of HDL-C and HDL-C/ApoA1 ratio with TyG index were mediated by obesity.ConclusionThis study provided further support for the hypoglycemic effects of ApoA1 and HDL-C in patients with CAD. Replication of these findings is warranted in further longitudinal studies in different populations.     

Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: A systematic review and meta-analysis

BackgroundThe efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains unclear.AimTo conduct a meta-analysis to evaluate the efficacy of 3 novel glucose-lowering drug classes, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors on hepatic parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Bilirubin, and FIB-4 (Fibrosis).MethodsMEDLINE was searched from inception through October 2021 for randomized placebo or active glucose-lowering drug-controlled trials. A random-effects model was used to pool the results. A p-value of less than or equal to 0.05 was considered significant. Results were presented as weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs).ResultsOur pooled analysis consisted of 40 studies. A significant reduction was seen in AST with SGLT2 inhibitors (WMD = -2.31 IU/L, 95%CI: -3.16 to -1.47 IU/L, P < 0.00001) and GLP-1RA (WMD = -3.29 IU/L, 95%CI: -5.98 to -0.61 IU/L, P = 0.02). Similarly, significant reduction was seen in ALT with SGLT2 inhibitors (WMD = -5.93 IU/L, 95%CI: -7.70 to -4.16 IU/L, P < 0.00001) and GLP-1RAs (WMD = -9.92 IU/L, 95%CI: -19.89 to 0.05 IU/L, P = 0.05). In contrast, DPP-4 inhibitors showed no significant reduction in AST (WMD = -3.20 IU/L, 95%CI: -11.13 to 4.73 IU/L, P = 0.43) or ALT (WMD = -4.81 IU/L, 95%CI: -15.83 to 6.21 IU/L, P = 0.39). A significant reduction in GGT was seen with SGLT2 inhibitors (WMD = -6.49 IU/L, 95%CI: -11.09 to -1.89 IU/L, P = 0.006) and GLP-1RAs (WMD = -12.38 IU/L, 95%CI: -15.69 to -9.07 IU/L, P < 0.00001). However, significant results were not observed with DPP-4 inhibitors (WMD = -0.92 IU/L, 95%CI: -5.80 to 3.96 IU/L, P = 0.71). There was a statistically significant reduction in FIB-4 index with SGLT2 inhibitors (WMD = -0.21, 95%CI: -0.40 to -0.03, P = 0.02) and GLP-1 RA (WMD = -0.15, 95%CI: -0.29 to 0.00, P = 0.05). Lastly, SGLT2 inhibitors led to a significant change in bilirubin levels (WMD = 2.03, 95%CI: 0.76 to 3.30, P = 0.002) while the change in bilirubin was not significant with GLP-1 agonists (WMD = -0.21, 95%CI: -1.09 to 0.66, P = 0.63) and DPP-4 inhibitors (WMD = 0.14, 95%CI: -1.55 to 1.83, P = 0.87).ConclusionSGLT2 inhibitors and GLP-1 agonists have a beneficial effect on hepatic parameters in patients with NAFLD. However, further research is needed to evaluate the effect of DPP-4 inhibitors on hepatic function properly.     

Association between KCNJ11 E23K polymorphism and the risk of type 2 diabetes mellitus: A global meta-analysis

BackgroundPotassium inwardly rectifying channel, subfamily J member 11(KCNJ11) is considered to be a potential susceptible gene of type 2 diabetes mellitus (T2DM), and the association between KCNJ11 E23K polymorphism and T2DM risk is still controversial worldwide. This meta-analysis was performed to assess the association more accurately between KCNJ11 E23K polymorphism and T2DM risk.MethodsThe up-to-data meta-analysis was conducted based on studies selected from eight databases (PubMed, Web of Science, Medline, Scopus, Embase, CNKI, WanFang, and Vip). Five gene models were included in our study: allele model (K-allele vs. E-allele), heterozygous model (EK vs. EE), homozygous model (KK vs. EE), dominant genetic model (EK + KK vs. EE), and recessive genetic model (EK + EE vs. KK). Association strength was evaluated by odds ratio (OR) and 95% confidence interval (CI), publication bias was evaluated by Begg's funnel plot and Egger's test, sensitivity analysis and trial sequential analysis (TSA) were used to evaluate the stability of the results.ResultsAccording to the inclusion and exclusion criteria, 31 eligible articles were finally selected in our meta-analysis, including 8754 T2DM cases and 7587 controls. We found that allelic model (OR = 1.25, 95%CI: 1.15–1.35, P < 0.01), heterozygous model (OR = 1.31, 95% CI: 1.18–1.44, P < 0.01), homozygous model (OR = 1.48, 95% CI: 1.24–1.76, P < 0.01), and dominant genetic model (OR = 1.35, 95% CI: 1.22–1.50, P < 0.01) were significantly associated with increased risk of T2DM, but recessive genetic model (OR = 0.78, 95% CI: 0.67–0.91, P < 0.01) was considered as a protective factor for T2DM. No significant evidence of publication bias was found.ConclusionOur meta-analysis confirms the association between KCNJ11 E23K polymorphism and the risk of T2DM, highlighting that gene-gene interaction and gene-environment interaction should be investigated in future.     

Effect of urinary albumin creatinine ratio on type 2 diabetic retinopathy and is cut-off value for early diabetic retinopathy diagnosis

ObjectiveTo evaluate the effect of Urinary albumin creatinine ratio (UACR) on diabetic retinopathy (DR) in People with Type 2 diabetes (T2D) and the cut-off value of UACR for predicting DR using receiver operating characteristic curve (ROC).MethodsA prospective cohort study of 2490 people with T2D was conducted with follow-up ranging from 3 to 10 years, with a mean follow-up of 7 years. Dilated fundus examination and urine examination were performed annually. Medical history and clinical data were collected and analyzed. Linear mixed effect models with unstructured variance-covariance were carried out to longitudinally assess the influence of UACR and other factors on DR, and ROC curve was drawn to evaluate the value of UACR in early diagnosis of DR.ResultsLinear Mixed-effect models revealed that UACR was positively correlated with the development of DR (β = 0.001, 95 %CI: 1.023–1.241, P < 0.001). The area under the ROC curve for UACR was 0.634 (95 %CI: 0.605–0.664, P < 0.001), cut-off value for early diagnosis of DR was 27.81 mg/g, the sensitivity was 0.586, and the specificity was 0.632.ConclusionUACR can predict the occurrence of DR in people with T2D, so it can be considered as a preliminary indicator of DR.     

Serum uric acid levels and diabetic kidney disease in patients with type 2 diabetes mellitus: A dose-response meta-analysis

ObjectiveOur study aimed to assess the existing evidence on whether serum uric acid (SUA) levels are associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).MethodsWe conducted a systematic search of articles up to October 2021 in Medline, Embase, The Cochrane Library and Web of Science that estimated DKD by SUA levels in patients with T2DM. Pooled relative risks with 95% CI were calculated using random effects modelsResultsA total of eight cohort studies involving 25,741 T2DM patients were included. Meta-analysis showed that compared the highest with the lowest category of SUA level, the summary risk ratios were 2.04 (95%CI 1.43–2.92, P < 0.001). The linear dose-response analysis revealed that the risk of DKD increased by 24% for each 1 mg/dl increase of SUA. The non-linear dose-response analysis also showed a significant relevance between SUA and the risk of DKD in patients with type 2 diabetes mellitus (P < 0.001).ConclusionsSerum uric acid is associated with an increased risk of diabetic kidney disease in patients with type 2 diabetes mellitus. Serum uric acid level could be a good indicator for predicting diabetic kidney disease in patients with type 2 diabetes mellitus.     

Serum Isthmin-1 is negatively correlated with HDL-C in type 2 diabetes mellitus

BackgroundIsthmin-1 (Ism-1) is a newly identified insulin-like adipokine that increases glucose uptake by adipocytes and inhibits hepatic lipid synthesis. Recent studies have shown that Ism-1 can improve the metabolic disorders associated with type 2 diabetes mellitus (T2DM) and improve lipid metabolism. The classic function of high-density lipoprotein cholesterol (HDL-C) is to transport cholesterol from extra-hepatic tissues to the liver for metabolism. In contrast, disorders of lipid metabolism and inflammation are the leading causes of atherosclerosis (As). Atherosclerosis often manifests as loss of elasticity, lipid accumulation, fibrous tissue proliferation and calcium deposits in the affected arteries, eventually forming plaques.AimTo illustrate the correlation between HDL-C and Ism-1 in T2DM, and the relationship between lipoprotein cholesterol and carotid plaque.MethodsA total of 128 patients with T2DM were enrolled in the study and basic information was collected. HDL-C levels were measured chemically. Serum Ism-1 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Linear regression analysis was used to assess the correlation between serum Ism-1 levels and HDL-C in patients with T2DM. Basic information was again collected from 226 patients with T2DM. Independent sample t-tests were performed to explore the relationship between carotid plaque formation and lipids.ResultsHDL-C was divided into four groups according to quartiles and there was a between-group difference in Ism-1 (p = 0.040). Multivariable linear regression showed a negative association between Ism-1 and HDL-C in T2DM (β = −0.235, p < 0.001), even after adjusting for related factors (β = −0.165, p = 0.009). Low-density lipoprotein cholesterol (LDL-C) and HDL-C showed significant differences between the carotid plaque group and the non-carotid plaque group (p_LDL-C = 0.007, p_HDL-C = 0.003).ConclusionSerum Ism-1 and HDL-C are negatively correlated in T2DM. LDL-C is significantly higher in carotid plaque group than non-carotid plaque group, while HDL-C is significantly lower than in the non-carotid plaque group.     

Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan—A 3-year prospective study

AimsTo explore the role of serum uric acid (SUA) concentration in diabetic retinopathy (DR) for patients with type 2 diabetes mellitus (T2DM).MethodsA 3-year prospective study in 749 patients with T2DM and without proliferative diabetic retinopathy (PDR) was conducted at a medical center. Baseline SUA concentration and parameters of glycemic control, blood pressure, kidney disease, and lipid profiles were analyzed to determine their contribution to DR.ResultsFundus examination showed that 184 patients (24.6%) had non-proliferative retinopathy and 565 (75.4%) without DR at baseline. After 3 years, increase in the severity of DR was recognized in 103 patients (13.8%), including 81 patients with newly developed DR. Patients with increase in severity of DR positively associated with duration of DM (11.9 vs. 9.4 years, p = 0.001), HbA1c (7.6 vs. 7.2%, p = 0.001), albuminuria (45.5 vs. 31.0%, p = 0.006), and SUA (6.47 vs. 5.87 mg/dl, p < 0.001) than did those without change in DR stage. Cox regression showed that patients with SUA in the 3rd (5.9–6.9 mg/dl) and 4th (≥7.0 mg/dl) quartiles had hazard ratios for DR worsening of 2.57 and 3.66 (95% C.I. 1.30–5.08 and 1.92–7.00) when compared with patients with SUA in the 1st quartile (<4.9 mg/dl).ConclusionsSUA concentration is associated with the increase in severity of DR over a 3-year period in patients with T2DM. Further study is required to define the exact role of SUA in DR.     

Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study

Background and aimsType 2 diabetes mellitus (T2DM) is a condition defined by hyperglycaemia, but also often presents with dyslipidaemia and suppressed HDL cholesterol. Mendelian randomization studies have suggested a causal link between low HDL cholesterol and T2DM. However, influences of gender, polymorphisms and lifestyle, all known to influence HDL cholesterol, have not been fully explored in a prospective cohort.Methods and resultsIn 2001–2002, a random sample of 1514 males (18–87 years old) and 1528 females (18–89 years old) were recruited in the ATTICA study. The 10-year follow-up (2011–2012) included 1485 participants. Lipids and lipoproteins levels, glucose and insulin levels were measured together with apolipoprotein A1 (apoA1) 75 G/A genotype, which is known to influence HDL-cholesterol. In total, 12.9% of the study sample developed T2DM within the 10-year follow-up period. In multivariable models, for each mg/dL increase in apoA1 levels in males, 10-year T2DM risk decreased 1.02%; while every unit increase in apoB/LDL-cholesterol ratio increased risk 4-fold. Finally, for every unit increase in triglycerides/apoA1 ratio, the risk increased 85%. HOMA-IR independently predicted T2DM 10-year incidence only for carriers of GG polymorphism (all, p < 0.05), but not in carriers of the GA polymorphism (all, p > 0.05).ConclusionApoA1 was associated with decreased T2DM risk and TG/ApoA1 and apoB/LDL were associated with increased risk of T2DM, only in males. ApoA1 polymorphism, which is associated with lower HDL cholesterol, influenced the predictive effects of HOMA-IR on T2DM incidence, which appeared to be moderated by physical activity, suggesting potential scope for more targeted preventative strategies.     

Use of DPP4i reduced odds of clinical deterioration and hyperinflammatory syndrome in COVID-19 patients with type 2 diabetes: Propensity score analysis of a territory-wide cohort in Hong Kong

Background and objectivesType 2 diabetes mellitus (T2DM) patients with Coronavirus Disease 2019 (COVID-19) have poorer prognosis. Inconclusive evidence suggested dipeptidyl peptidase-4 inhibitors (DPP4i) might reduce inflammation and prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry, hence further evaluation on DPP4i is needed.Methods1214 Patients with T2DM were admitted with COVID-19 between 21st January 2020 and 31st January 2021 in Hong Kong. Exposure was DPP4i use within the 90 days prior to admission for COVID-19. Assessed outcomes included clinical deterioration, clinical improvement, low viral load, positive Immunoglobulin G (IgG) antibody, hyperinflammatory syndrome, proportion of IgG antibody, clinical status and length of hospitalization. Multivariable logistic and linear regression models were performed to estimate odds ratios (OR) and their 95% confidence intervals (CI) of event outcomes and continuous outcomes, respectively.ResultsDPP4i users (N = 107) was associated with lower odds of clinical deterioration (OR=0.71, 95%CI 0.54 to 0.93, P = 0.013), hyperinflammatory syndrome (OR=0.56, 95%CI 0.45 to 0.69, P < 0.001), invasive mechanical ventilation (OR=0.30, 95%CI 0.21 to 0.42, P < 0.001), reduced length of hospitalization (-4.82 days, 95%CI –6.80 to –2.84, P < 0.001), proportion of positive IgG antibody on day-3 (13% vs 8%, p = 0.007) and day-7 (41% vs 26%, P < 0.001), despite lack of association between DPP4i use and in-hospital mortality.ConclusionDPP4i use was associated with reduced odds of clinical deterioration and hyperinflammatory syndrome. Prospective studies are warranted to elucidate the role of DPP4i in T2DM and COVID-19.     

Plasma level of ATPase inhibitory factor 1 (IF1) is associated with type 2 diabetes risk in humans: A prospective cohort study

AimMitochondrial dysfunction is associated with the development of type 2 diabetes mellitus (T2DM). It is thus of clinical relevance to identify plasma biomarkers of mitochondrial dysfunction associated with the risk of T2DM.ATPase inhibitory factor 1 (IF1) endogenously inhibits mitochondrial ATP synthase activity. Here, we analyzed association of the plasma IF1 level with markers of glucose homeostasis and with the conversion to new-onset diabetes (NOD) in individuals with prediabetes.MethodsIn the IT-DIAB prospective study, the baseline plasma level of IF1 was measured in 307 participants with prediabetes. The primary outcome was the incidence of NOD within five years of follow-up. Cross-sectional analysis of the IF1 level was also done in two independent interventional studies. Correlations between plasma IF1 and metabolic parameters at baseline were assessed by Spearman's correlation coefficients, and the association with the risk of NOD was determined using Cox proportional‐hazards models.ResultsIn IT-DIAB, the mean IF1 plasma level was lower in participants who developed NOD than in those who did not (537 ± 248 versus 621 ± 313 ng/mL, P   = 0.01). The plasma IF1 level negatively correlated with clinical variables associated with obesity and insulin resistance, including the body mass index (r = ?0.20, P  = 0.0005) and homeostasis model assessment of insulin resistance (HOMA-IR). (r = ?0.37, P < 0.0001). Conversely, IF1 was positively associated with plasma markers of cardiometabolic health, such as HDL-C (r = 0.63, P  <  0.0001) and apoA-I (r = 0.33, P  <  0.0001). These correlations were confirmed in cross-sectional analyses. In IT-DIAB, the IF1 level was significantly associated with a lower risk of T2DM after adjustment for age, sex, and fasting plasma glucose (HR [95% CI] per 1 SD = 0.76 [0.62; 0.94], P   = 0.012).ConclusionWe identified for the first time the mitochondrial-related biomarker IF1 as being associated with the risk of T2DM.     

Serum fibroblast growth factor 21 concentrations in type 2 diabetic retinopathy patients

Aims/purposeFibroblast growth factor 21 (FGF21) is a major metabolic regulator in the body that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome. However, little is known regarding the circulating levels of FGF21 in type 2 diabetic retinopathy (T2DR) and its association with the severity of the condition.MethodsIn a cross-sectional setting, 142 individuals, consisting of (1) T2DM patients without T2DR, (2) T2DM patients with T2DR, and (3) healthy control subjects were recruited for this study. Various clinical and biochemical parameters were assessed and entered for analysis.ResultsSerum FGF21 levels were significantly elevated in T2DM subjects without retinopathy (103.50 [75.75] pg/mL) compared with healthy controls (99.00 [126.75] pg/mL). Circulating FGF21 levels were comparable across different stages of T2DR (233.00 [109.00] for nonproliferative type 2 diabetic retinopathy [NPT2DR] vs. 215.00 [122.00] for proliferative type 2 diabetic retinopathy [PT2DR] groups, P = 361). FGF21, triglycerides, and duration of diabetes mellitus were significantly associated with T2DM in baseline models. However, after adjustment for potential confounders, in the final multivariate model, FGF21 emerged as the only significant factor associated with T2DM (OR = 13.772, 95% CI = 3.062–61.948, P = 001).ConclusionsSerum FGF21 concentrations are markedly elevated in patients with T2RN. The association between FGF21 and T2DR appears to be independent of the effects of potential confounding variables. These findings may suggest FGF21 as a novel surrogate diagnostic biomarker in initial stages of T2DR (particularly with FGF21 values above 135.5 pg/mL).     

Association of uncoupling protein-2 -866G/A and Ala55Val polymorphisms with susceptibility to type 2 diabetes mellitus: A meta-analysis of case-control studies

Background:Recently, the relationships between uncoupling protein-2 (UCP2) -866G/A (rs659366) and Ala55Val (rs660339) polymorphisms and the risk of type 2 diabetes mellitus (T2DM) have been explored considerably, but the results are greatly inconsistent. This meta-analysis was performed to further identify the association of UCP2 rs659366 and rs660339 with the risk of T2DM.Methods:Eligible studies were searched from PubMed, Embase, Cochrane Library, VIP database, Chinese National Knowledge Infrastructure, and Chinese WanFang database until March 8, 2020. The odds ratios with corresponding 95% confidence intervals (CIs), and P-values were used to assess the strength of the association.Results:A total of 26 studies were included in this study. UCP2 rs659366 was associated with the risk of T2DM in allele model (OR: 1.112, 95%CI: 1.009-1.224, P = 0.032), dominant model (OR: 1.189, 95%CI: 1.035–1.366, P = 0.014), and heterozygous model (OR: 1.177, 95%CI: 1.032–1.342, P = .015). A significantly increased risk of T2DM was detected in Asians by UCP2 rs659366 allele (OR: 1.132, 95%CI: 1.016–1.262, P = .025), dominant (OR: 1.218, 95%CI: 1.046–1.418, P = .011), homozygous (OR: 1.254, 95%CI: 1.022–1.540, P = .031) or heterozygous (OR: 1.198, 95%CI: 1.047–1.371, P = .009) models. There was no significant correlation between UCP2 rs660339 and the risk of T2DM (P>.05).Conclusions:The UCP2 rs65366 is significantly associated with the risk of T2DM, especially in Asian population, while no evidence is found between the UCP2 rs660339 and the susceptibility to T2DM.     

Metformin treatment is associated with an increase in bone mineral density in type 2 diabetes mellitus patients in China: A retrospective single center study

AimsTo investigate the association between metformin and bone mineral density (BMD) in a large cohort of Chinese patients with type 2 diabetes mellitus (T2DM).MethodsA total of 11,458 T2DM patients aged ≥40 years were included. Information on demographic, anthropometric and clinical characteristics was collected from medical records. BMD at lumbar spine (LS), femoral neck (FN), and total hip(TH) was assessed by dual-energy X-ray absorptiometry.ResultsOverall prevalence of osteopenia and osteoporosis was 37.4% and 10.3%, and was lower in patients on metformin (34.6% vs 38.3% and 7.1% vs 11.3%, both p < 0.001). Patients who had a lower BMI, older age, and lower estimated glomerular filtration rate (eGFR), had more osteoporosis, lower BMD (osteoporosis or osteopenia), and a lower T-score at LS, FN and TH. Metformin use and male sex was associated with a higher BMD. Metformin treatment was also independently associated with higher T-score at LS, FN and TH (β values of 0.120, 0.082 and 0.108; all p <0.001), and lower odds ratio of osteoporosis (OR = 0.779, 95%CI: 0.648–0.937, p = 0.008) or low BMD (OR = 0.834, 95%CI: 0.752 - 0.925, p = 0.001). However, when analyzed by sex, this association of a lower odds ratio for osteoporosis with metformin was only significant in women (OR= 0.775, 95% CI: 0.633–0.948; p = 0.013).ConclusionsMetformin treatment was associated with a higher T-score and a lower odds ratio of osteopenia and osteoporosis, especially in the female population, independent of age, BMI, and eGFR.     

Adiponectin predicts the antioxidant capacity and size of high-density lipoprotein (HDL) in individuals with diabetes mellitus

AimsThe relationship between adiponectin and type 2 diabetes mellitus (T2DM) is established; however the evidence on its role in high-density lipoprotein (HDL) functionality is still scant. The aim of this study was to assess the association of adiponectin with HDL functionality especially on the antioxidant capacity and HDL subfractions in individuals with T2DM.MethodsThis case-control study enrolled 356 individuals who were divided into two groups: diabetics [T2DM (n = 188)] and non-diabetic [nT2DM (n = 168)]. The association of adiponectin level on HDL functionality parameters was done in function of the cut-off point for adiponectin [percentile p < 75 = 12.9 μg/mL versus p ≥ 75 = 12.9 μg/mL] and multiple adjustments applied in the logistic regression models.ResultsBody mass index (BMI), waist circumference (WC) and body fat mass (FM) were higher in T2DM. The larger HDL particles (HDL_LARGE) were lower in T2DM group in comparison with nT2DM (28.20% versus 30.40%; p = 0.016). Individuals with T2DM and simultaneous highest adiponectin (p ≥ 75) had 2.25 OR (95% CI = 1.03–4.91) and 5.14 OR (95% CI = 2.37–11.15) to present higher HDL-C and HDL_LARGE concentrations. After adjustment for multiple confounders, high level of adiponectin was independently related with improvement of the HDL antioxidant capacity (OR = 2.78; 95% CI = 1.16–6.67).ConclusionsHigh adiponectin level associates with a lesser negative impact of T2DM on HDL functionality by increase in APO AI, particles size, and cholesterol content. On the same token, higher adiponectin was associated with greater odds to have high antioxidant capacity.