Protein intake is not associated with functional biomarkers of physical frailty: A cross-sectional analysis of community-dwelling older adults with type 2 diabetes mellitus

Background and aimFrailty has emerged as a third category of complication in patients with type 2 diabetes mellitus (T2DM). It has been suggested that adequate protein intake is an important dietary strategy for counteracting frailty. Therefore, we explored the association between protein intake and functional biomarkers of frailty in older adults with T2DM.Methods and resultsFrailty was operationalized as the presence of three of the following: exhaustion, low muscle strength, low physical activity, slow gait speed, and weight loss. Functional biomarkers included handgrip strength (HGS), chair stands, the short physical performance battery and gait speed. Eighty-seven older adults (71.2 ± 8.2 years; 66.7% males) were included. A total of n = 6 (~7%) and n = 32 (~37%) participants were identified as frail and pre-frail respectively. No significant difference was observed for protein intake across staging of frailty (pre-frail/frail: 1.3 ± 0.4 g/kg BW; non-frail: 1.4 ± 0.4 g/kg BW; P = 0.320). A significant association was observed for total protein intake and HGS (β = 0.44; 95% CI: 0.23–1.8; P = 0.01). However, this was no longer significant after adjusting for age, gender, physical activity, energy intake and total appendicular lean muscle (β = 0.03; 95% CI: ?0.45–0.60; P = 0.78). Nil other associations were observed between total protein intake and functional biomarkers of frailty.ConclusionAdequate protein intake was not associated with functional biomarkers in older adults with T2DM. Future research should focus on the efficacy of protein on attenuating functional decline in vulnerable older adults with low protein intake.     

Clinical effectiveness of fish oil on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials

AimsThe increase of arterial stiffness is an independent risk factor for cardiovascular diseases (CVD). Fish oil supplementation was shown to reduce the risk of CVD outcomes. However, the effects of fish oil on arterial stiffness remains controversial. This meta-analysis summarized existing randomized clinical trials (RCTs) to determine whether fish oil can affect arterial stiffness in adults.Data synthesisSystematic searches were performed using the PubMed/Medline, EMbase, Cochrane database, Clinical trials, and Web of Science. All RCTs assessed the effect of fish oil intervention on carotid to femoral-Pulse Wave Velocity (cf-PWV), brachial to ankle-PWV (ba-PWV), augmentation index (AIx) and AIx75 were considered. A fixed-effect model was used to calculate the pooled effect.A total of 14 RCTs were included. The pooled data analysis showed that fish oil significantly reduced PWV levels (SMD: ?0.145, 95%CI: ?0.265 to ?0.033, P = 0.012) compared to the control group. In subgroup analyses, a significant decrease in PWV was found in trials that fish oil with low dosages (≤1.8 g/d), short time (<24 weeks), low DHA to EPA ratio (DHA/EPA<1) and among young participant (<50 years old). Besides, the effect of fish oil was more obvious in ba-PWV compared to cf-PWV. In contrast, the effect of fish oil supplementation on AIx (WMD: ?0.588%, 95% CI: ?2.745 to 1.568, P = 0.593) and AIx75 (WMD: 0.542%, 95% CI: ?1.490 to 2.574, P = 0.601) was nonsignificant.ConclusionsThe current study showed that fish oil supplementation had a beneficial effect on pulse wave velocity.     

Neuronal Differentiation 1 gene Ala45Thr polymorphism and type 2 diabetes mellitus: A meta-analysis of 7,940 subjects

Background and aimsPrevious studies have shown that there was a possible relationship between human Neuronal Differentiation 1 (NEUROD1) gene Ala45Thr polymorphism and type 2 diabetes mellitus (T2DM) susceptibility. Nevertheless, no public opinion has been formed because of the conflicting results in the past studies. In order to illuminate the potential association of human NEUROD1 gene Ala45Thr polymorphism and T2DM, the present meta-analysis was conducted.Methods and resultsIn the current meta-analysis, 7940 subjects from 14 individual studies were included. The fixed or random effects models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). The current meta-analysis found a significant association between NEUROD1 gene Ala45Thr polymorphism and T2DM under allelic (OR: 1.21, 95% CI: 1.04–1.41, P = 0.01), dominant (OR: 0.819, 95% CI: 0.734–0.913, P = 3.31 × 10^?4), heterozygous (OR:1.199, 95% CI: 1.068–1.346, P = 0.002), and additive (OR: 1.33, 95% CI: 1.09–1.62, P = 0.004) genetic models.ConclusionsNEUROD1 gene Ala45Thr polymorphism was significantly related to T2DM, especially in the Asian population. More particularly, the Thr45 allele carriers of the NEUROD1 gene may be more susceptible to T2DM.     

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.     

Contribution of common variants of ENPP1, IGF2BP2, KCNJ11, MLXIPL,PPARγ, SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs

BackgroundWhile several type 2 diabetes mellitus (T2DM) susceptibility loci identified through genome-wide association studies (GWAS) have been replicated in many populations, their association in Arabs has not been reported. For this reason, the present study looked at the contribution of ENNP1 (rs1044498), IGF2BP2 (rs1470579), KCNJ11 (rs5219), MLXIPL (rs7800944), PPARγ (rs1801282), SLC30A8 (rs13266634) and TCF7L2 (rs7903146) SNPs to the risk of T2DM in Lebanese and Tunisian Arabs.MethodsStudy subjects (case/controls) were Lebanese (751/918) and Tunisians (1470/838). Genotyping was carried out by the allelic discrimination method.ResultsIn Lebanese and Tunisians, neither ENNP1 nor MLXIPL was associated with T2DM, whereas TCF7L2 was significantly associated with an increased risk of T2DM in both the Lebanese [P < 0.001; OR (95% CI): 1.38 (1.20–1.59)] and Tunisians [P < 0.001; OR (95% CI): 1.36 (1.18–1.56)]. Differential associations of IGF2BP2, KCNJ11, PPARγ and SLC30A8 with T2DM were noted in the two populations. IGF2BP2 [P = 1.3 × 10^?5; OR (95% CI): 1.66 (1.42–1.94)] and PPARγ [P = 0.005; OR (95% CI): 1.41 (1.10–1.80)] were associated with T2DM in the Lebanese, but not Tunisians, while KCNJ11 [P = 8.0 × 10^?4; OR (95% CI): 1.27 (1.09–1.47)] and SLC30A8 [P = 1.6 × 10^?5; OR (95% CI): 1.37 (1.15–1.62)] were associated with T2DM in the Tunisians, but not Lebanese, after adjusting for gender and body mass index.ConclusionT2DM susceptibility loci SNPs identified through GWAS showed differential associations with T2DM in two Arab populations, thus further confirming the ethnic contributions of these variants to T2DM susceptibility.     

Flow-Mediated Dilation Normalization Predicts Outcome in Chronic Heart Failure Patients

BackgroundReduced flow-mediated dilation (FMD) is a known prognostic marker in heart failure (HF), but may be influenced by the brachial artery (BA) diameter. Aiming to adjust for this influence, we normalized FMD (nFMD) by the peak shear rate (PSR) and tested its prognostic power in HF patients.Methods and ResultsBA diameter, FMD, difference in hyperemic versus rest brachial flow velocity (FVD), PSR (FVD/BA), and nFMD (FMD/PSR × 1000) were assessed in 71 HF patients. At follow-up (mean 512 days), 19 HF (27%) reached the combined endpoint (4 heart transplantations [HTs], 1 left ventricle assist device implantation [LVAD], and 14 cardiac deaths [CDs]). With multivariate Cox regression analysis, New York Heart Association functional class ≥III (hazard ratio [HR] 9.36, 95% confidence interval [CI] 2.11–41.4; P = .003), digoxin use (HR 6.36, 95% CI 2.18–18.6; P = .0010), FMD (HR 0.703, 95% CI 0.547–0.904; P = .006), PSR (HR 1.01, 95% CI 1.005–1.022; P = .001), FVD (HR 1.04, 95% CI 1.00–1.06; P = .02), and nFMD (HR 0.535, 95% CI 0.39–0.74; P = .0001) were predictors of unfavorable outcome. Receiver operating characteristic curve for nFMD showed that patients with nFMD >5 seconds had significantly better event-free survival than patients with nFMD ≤5 seconds (log-rank test: P < .0001).ConclusionsnFMD is a strong independent predictor of CD, HT, and LVAD in HF with left ventricular ejection fraction <40%. Patients with nFMD >5 seconds have a better prognosis than those with lower values.     

Effect of dietary sodium restriction on blood pressure in type 2 diabetes: A meta-analysis of randomized controlled trials

AimsAlthough current guidelines recommend reduction of salt intake in patients with diabetes, the benefits of reducing salt intake in people with type 2 diabetes mellitus (T2DM) lack clear evidence. Therefore, we performed a meta-analysis of available randomized controlled trials (RCTs) of sodium restriction and blood pressure (BP) in patients with T2DM.Data synthesisWe performed a systematic search of the online databases that evaluated the effect of dietary sodium restriction on BP in patients with T2DM. Sodium intake was expressed by 24 h urinary sodium excretion (UNaV). Q statistics and I² were used to explore between-study heterogeneity. A random-effects model was used in the presence of significant heterogeneity; otherwise, a fixed-effects model was applied. Eight RCTs with 10 trials (7 cross-over and 3 parallel designs) were included in the meta-analysis. Compared with ordinary sodium intake, dietary sodium restriction significantly decreased UNaV (weighted mean difference, WMD: ?38.430 mmol/24 h; 95% CI: ?41.665 mmol/24 h to ?35.194 mmol/24 h). Sodium restriction significantly lowered systolic BP (WMD: ?5.574 mm Hg; 95% CI: ?8.314 to ?2.834 mm Hg; I² = 0.0%) and diastolic BP (WMD: ?1.675 mm Hg; 95% CI: ?3.199 to ?0.150 mm Hg; I² = 0.0%) with low heterogeneity among the studies. No publication bias was found from Begg's and Egger's tests.ConclusionsSodium restriction significantly reduces SBP and DBP in patients with T2DM.     

Dietary cholesterol consumption and incidence of type 2 diabetes mellitus: A dose–response meta-analysis of prospective cohort studies

Background and aimThe purpose of this meta-analysis was to evaluate the dose–response relationship between dietary cholesterol (DC) consumption and the incidence of type 2 diabetes mellitus (T2DM).Methods and resultsProspective studies with the endpoint of T2DM were included. The Random-effect model weighted by inverse variance was used. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics. Restricted cubic splines regression models were used to estimate the dose–response relationship. 11 prospective studies comprising of 355 230 subjects were included. Compared to lowest DC consumption, highest DC consumption was associated with an increased risk of T2DM (RR 1.15, 95% CI 1.03 to 1.28, P = 0.012; chi-squared = 31.41, I-squared 58.6%, P _{heterogeneity} = 0.003). Subgroup analyses have shown that this positive association was more evident in western countries than in eastern countries (RR 1.19, 95% CI 1.06 to 1.36 VS 1.34, 95% CI 0.84 to 1.29; P _{subgroup difference} = 0.02). For 100 mg/d increment in DC intake, the pooled RR was 1.05, (95% CI 1.04 to 1.07, P_linearity = 0.000, P_nonlinearity = 0.02), 1.06 (95% CI 1.04 to 1.07, P_linearity=0.000), and 1.01 (95% CI 0.98 to 1.05, P_linearity = 0.525) for the incidence of T2DM, in western and eastern countries, respectively.ConclusionsOur study suggests that there is a positive dose–response association between DC consumption and the incidence of T2DM, especially in western countries.Systematic review registrationPROSPERO CRD42020216318.     

Preliminary study of the interactive effects of coronary heart disease and lacunar infarction on renal function in patients with type 2 diabetes mellitus by gender

BackgroundCoronary heart disease (CHD) and lacunar infarction (LI) are the most common cardio- cerebrovascular complications of type 2 diabetes mellitus (T2DM) and a recognized risk factor for renal injury. Although a unidirectional association of CHD or LI with T2DM or the kidney has been demonstrated, however, it remains unknown whether there is an interactive effect of the coexistence of CHD and LI on renal function in T2DM patients. The aim of our study was to investigate the interaction between CHD and LI on renal function in gender-specific patients with T2DM and the association between cardio-cerebrovascular disease-related conventional serum markers and the estimated glomerular filtration rate (eGFR).MethodsWe conducted a cross-sectional study in Beijing and Tianjin from April 2019 to August 2021. Participants with T2DM aged ≥18 years were asked to complete a one-to-one questionnaire and physical examination.ResultsIn this study, 389 eligible patients with T2DM were included, with a mean age of 63.04 ± 9.41 years, of whom 200 (51.41 %) were male. The proportions of patients with CHD, LI, and both CHD and LI were 28.53 %, 24.42 %, and 11.05 %, respectively. Compared to T2DM patients without either CHD or LI, those with both CHD and LI were found to have a significantly greater risk of reduced eGFR (OR: 12.82, 95 % CI 5.06–32.52, P < 0.001) than those with CHD alone (OR: 2.42, 95 % CI 1.37–3.00, P = 0.004) or LI alone (OR: 1.15, 95 % CI 0.61–2.18, P = 0.664). The combined presence of CHD and LI is associated with a significantly greater risk of decreased eGFR in female T2DM patients compared to their male counterparts. We found both multiplicative and additive effects in all T2DM patients; however, when stratified by sex, only multiplicative effects were observed. After controlling for interference from CHD, LI, and age, we found that total cholesterol (TC) was negatively correlated with eGFR in females (r = −0.156, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) was negatively correlated with eGFR in males (r = −0.229, P = 0.001).ConclusionThis study provides novel evidence that the synergistic effect of CHD and LI on renal injury in patients with T2DM is significantly greater than their individual effects. Women with T2DM who have both CHD and LI are at a 4.85-fold higher risk of decreased eGFR than men. Therefore, increased clinical attention should be given to preventing and treating vascular complications in T2DM patients, as well as aggressively reducing lipid levels, particularly TC and LDL-C, to delay or prevent renal dysfunction in T2DM patients.     

All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based,open cohort study

AimThe glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting.MethodsWe conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n = 8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n = 16,541).ResultsPatients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56–0.74, P-value < 0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53–0.76, P -value = 0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83–1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories.ConclusionsGLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.     

Dietary inflammatory index and cardiorenal function in women with diabetes and prediabetes

Background and aimsPrevious studies had shed a new light on the importance of multiple inflammatory mechanisms in the pathogenesis of arterial stiffness. The dietary inflammatory index (DII®) is a new tool for estimating the overall inflammatory potential of the diet. The aim of this study is to assess the association of the inflammatory potential of diet with peripheral arterial stiffness and renal function in women with diabetes and prediabetes.Methods and resultsThis is an observational cross-sectional study. A total of 2644 females aged 45–75 years were included for the study. Dietary intake in the past 12 months was assessed by a validated China National Nutrition and Health Survey 2002 (CNHS2002) food-frequency questionnaire. Energy-adjusted DII (E-DII) scores were calculated from daily dietary information. In a multivariable linear regression analysis adjusted for potential confounders, E-DII was positively associated with brachial ankle pulse wave velocity (baPWV) in participants with diabetes (β = 12.820; 95% CI = 2.565, 23.076; P = 0.014) and prediabetes (β = 29.025; 95% CI = 1.110, 56.940; P = 0.042), but not in females with normal glucose homeostasis. In addition, per unit increase of E-DII was significantly associated with lower eGFR (β = -1.363; 95% CI = -2.335, ?0.392; P = 0.006) in patients with diabetes.ConclusionWe identi?ed a direct association between E-DII and arterial stiffness, decreasedeGFR in middle-aged and elderly women with diabetes or prediabetes. Future studies are needed to verify and clarify the role of E-DII as an intervention target for cardiorenal complications of chronic hyperglycemia.     

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.     

Postprandial glucose is correlated with an increasing risk of liver fibrosis in Chinese patients with nonalcoholic fatty liver disease

AimType 2 diabetes (T2DM) is closely related to nonalcoholic fatty liver disease (NAFLD) and is an important risk factor for the progression of liver fibrosis, but the role of 2-h postprandial blood glucose (PPG) as a biomarker in this process remains unclear. This study was designed to investigate the relationship between PPG and liver fibrosis in Chinese NAFLD populations with or without T2DM.MethodsThis study included three independent NAFLD populations: 1) 618 inpatients with T2DM or pre-diabetes, 2) 255 patients with T2DM or pre-diabetes who underwent liver biopsy, and 3) a prospective community-based cohort without diabetes who completed a median of 4.22 years follow-up. The degree of liver fibrosis was assessed by liver fibrosis stage in subjects with a liver biopsy, and by NAFLD fibrosis score (NFS) in subjects without liver biopsy.ResultsIn the first population, PPG {OR 0.02, [95% CI (0.01–0.03)], P< 0.001} was positively correlated with NFS. In the second population, an increasing PPG was associated with increase in the proportion of advanced liver fibrosis (P = 0.012). Multivariate line regression revealed that PPG {OR 0.03 [95% CI (0.00–0.06)], P = 0.049}was positively associated with liver fibrosis stages. In the third population, PPG {OR 0.103, [95% CI (0.011–0.194) P = 0.028} at baseline was positively associated with NFS at follow-up. Furthermore, changes in PPG were significantly associated with NFS change after follow-up. We did not find a similar association between fasting glucose or HbA1c and liver fibrosis.ConclusionsPPG was independently associated with the severity of liver fibrosis in the Chinese NAFLD population.     

Overweight and risk of type 2 diabetes: A prospective Chinese twin study

Objectives: This study aimed to estimate the association between overweight and type 2 diabetes mellitus (T2DM) in twins, and further to explore whether genetic and early-life environmental factors account for this association.Methods: This study included 31,197 twin individuals from the Chinese National Twin Registry (CNTR). Generalized estimating equation (GEE) models were applied for unmatched case-control analysis. Conditional logistic regressions were used in co-twin matched case-control analysis. Logistic regressions were fitted to examine the differences in odds ratios (ORs) from the GEE models and conditional logistic regressions. Bivariate genetic model was used to explore the genetic and environmental correlation between body mass index (BMI) and T2DM.Results: In the GEE model, overweight was associated with a higher T2DM risk (OR=2.71, 95% confidence interval (CI): 1.96～3.73), compared with participants with normal BMI. In the multi-adjusted conditional logistic regression, the association was still significant (OR=2.60, 95% CI: 1.15～5.87). The ORs from the unmatched and matched analyses were different (P = 0.042). Particularly, overweight could increase T2DM risk in monozygotic (MZ) twins, and the difference in ORs between the unmatched and matched designs was significant (P = 0.014). After controlling for age and sex, the positive BMI-T2DM association was partly due to a significant genetic correlation (rA= 0.31, 95% CI: 0.20～0.41).Conclusions: Our findings suggest that genetics and early-life environments might account for the observed overweight-T2DM association. Genetic correlation between BMI and T2DM further provides evidence for the influence of overlap genes on their association.     

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).     

Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis

BackgroundTo evaluate the impact of familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) on arterial properties and the effects of statins.MethodsWe meta-analyzed 51 studies providing data for 4,057 FH patients and 732 FCH patients with random-effects models, meta-regression analysis and publication bias analysis. The main outcomes of interest were (1) brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT), and (3) change of IMT and FMD after treatment with statins.ResultsCompared to normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): ?5.31%, 95% CI ?7.09 to ?3.53%, P < 0.001] and higher carotid IMT (pooled MD: 0.12 mm, 95% CI 0.09–0.15 mm, P < 0.001) and femoral IMT (pooled MD: 0.35 mm, 95% CI 0.18–0.51 mm, P < 0.001). FCH patients had lower FMD and increased IMT (pooled MD: ?3.60%, 95% CI ?6.69 to ?0.50%, P = 0.023; and 0.06 mm, 95% CI 0.04–0.08 mm, P < 0.001, respectively). Total and LDL-cholesterol was a significant determinant of FMD and carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86–7.92%, P < 0.001) and decreased carotid IMT (pooled MD of change: ?0.025 mm, 95% CI ?0.042 to ?0.009 mm, P = 0.003). Changes of both FMD and IMT with statins correlated with the duration × treatment intensity product in FH patients (both P < 0.01). Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%, 95% CI 0.43–3.69%, P = 0.013). No significant publication bias was detected.ConclusionArterial properties are impaired in subjects with FH or FCH. Statins improve arterial function and structure in FH patients in a treatment intensity-related manner.     

Variants within the calpain-10 gene and relationships with type 2 diabetes (T2DM) and T2DM-related traits among Tunisian Arabs

BackgroundCommon variations in the calpain 10 (CAPN10) gene variants UCSNP-43, UCSNP-19 and UCSNP-63, and the 112/121 diplotype, are associated with an increased risk of type 2 diabetes (T2DM) and T2DM-related traits.MethodsThe association of UCSNP-43, -19 and -63 CAPN10 SNPs with T2DM was assessed in 917 Tunisian T2DM patients and 748 ethnically matched non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP.ResultsSignificant differences in UCSNP-19 MAF, but not UCSNP-43 or -63, and genotype distribution were seen between patients and controls. Heterogeneity in UCSNP-19, but not UCSNP-43 and -63, genotype distribution was noted according to geographical origin. Obesity was associated with UCSNP-19, while raised fasting glucose was associated with UCSNP-63, and increased HDL was associated with UCSNP-43. Enrichment of homozygous UCSNP-19 2/2 was seen in overweight and obese compared with lean patients; logistic-regression analyses demonstrated a positive association of the 2/2 genotype with overweight [P = 0.003; OR (95% CI) = 2.07 (1.28–3.33)] and obese [P = 0.021; OR (95% CI) = 1.83 (1.10–3.07)] patients. Of the six CAPN10 haplotypes identified, significant enrichment of only haplotype 111 was seen in T2DM patients [Pc = 0.034; OR (95% CI) = 1.22 (1.06–1.41)], while the frequency of all identified CAPN10 diplotypes, including the high-risk 112/121, was comparable between patients and controls.ConclusionWhile CAPN10 UCSNP-19 SNP and haplotype 111 contribute to the risk of T2DM in Tunisian subjects, no significant association between CAPN10 diplotypes and T2DM was demonstrated.     

Increased cardio-ankle vascular index is independently associated with chronic kidney disease: A cross-sectional study in Chinese patients with type 2 diabetes mellitus

AimsThis cross-sectional study aimed to investigate the association between arterial stiffness and chronic kidney disease (CKD) in Chinese patients with type 2 diabetes mellitus (T2DM).MethodsThis study included 1025 patients with T2DM (796 men, 229 women). The cardio-ankle vascular index (CAVI) served as an index to evaluate arterial stiffness. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m² and/or urinary albumin-creatine ratio ≥ 30 mg/g. Increased CAVI was defined as a value ≥9.ResultsThe mean CAVI was 8.4 ± 1.2. Among the patients, 314 (40%) had increased CAVI and 229 (22.3%) had CKD. Blood pressure, HbA1c levels, total cholesterol, low-density lipoprotein cholesterol, uric acid and CAVI were higher among patients with CKD than among those without CKD. Patients with increased CAVI were at a 1.82-fold (95% CI, 1.20–2.75; P < 0.001) higher prevalence of CKD after adjusting for other variables. The odds ratio for CKD was 2.69 (95% CI, 1.12–6.47; P = 0.027) in women and 1.62 (95% CI, 1.01–2.61; P = 0.045) in men.ConclusionIncreased CAVI was independently associated with CKD in patients with T2DM. Further longitudinal studies with large sample sizes are warranted to investigate the effect of CAVI on CKD in patients with T2DM.     

Relationship between achieved personalized glycaemic targets and monitoring of clinical events in elderly diabetic patients

AimRecent guidelines for the management of type 2 diabetes (T2DM) in the elderly recommend adjusting the therapeutic target (HbA_1c) according to the patient's health. Our study aimed to explore the association between achieving the recommended personalized HbA_1c target and the occurrence of major clinical events under real-life conditions.MethodsThe T2DM S.AGES cohort was a prospective multicentre study into which 213 general practitioners recruited 983 non-institutionalized T2DM patients aged > 65 years. The recommended personalized HbA_1c targets were < 7%, < 8% and < 9% for healthy, ill and very ill patients, respectively. Major clinical events (death from any cause, major vascular events and/or hospitalization) were recorded during the 3-year follow-up. Mixed-effects logistic regression models were used for the analyses.ResultsOf the 747 patients analyzed at baseline, 551 (76.8%) were at their recommended personalized HbA_1c target. During follow-up, 391 patients (52.3%) experienced a major clinical event. Of the patients who did not achieve their personalized HbA_1c target (compared with those who did), the risk (OR) of a major clinical event was 0.95 (95% CI: 0.69–1.31; P = 0.76). The risk of death, major vascular event and hospitalization were 0.88 (95% CI: 0.40–1.94; P = 0.75), 1.14 (95% CI: 0.7–1.83; P = 0.59) and 0.84 (95% CI: 0.60–1.18; P = 0.32), respectively.ConclusionOver a 3-year follow-up period, our results showed no difference in risk of a major clinical event among patients, regardless of whether or not they achieved their personalized recommended HbA_1c target. These results need to be confirmed before implementing a more permissive strategy for treating T2DM in elderly patients.     

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis

Background and aimsThe association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region).Material and methodsOur data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression.ResultsOf 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33–2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27–3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54–3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78–6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07–2.88; p = 0.024).ConclusionOur result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.