Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus

Objective: To evaluate the relationship between different indexes of weight variability and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study. The clinical data of 2 180 T2DM patients without DKD who underwent case management at Lee's United Clinic in Taiwan, China from 2002 to 2018 were retrospectively analyzed, including 1 103 females and 1 077 males, with an average age of (64.8±12.4) years. Regular follow-up was conducted for patients for at least 2 years, and their metabolic indexes were monitored annually. BMI variability independent of the mean (BMI-VIM), average yearly mean square successive difference (BMI-ASV), coefficient of variation (BMI-CV) and standard deviation (BMI-SD) were calculated,based on the body mass index (BMI) recorded annually by the patients. Patients were divided into four groups (Q1-Q4) based on the quartiles of the four weight variability indexes. DKD group and non-DKN group(NDKD group) were defined based on the occurrence of DKD at the end of the follow-up. Cox proportional hazards regression models were used to analyze the relationship between the four weight variability indicators and the incidence of DKD. Subgroup analysis was performed by categorizing patients into non-obesity (BMI<28 kg/m2) and obesity groups (BMI≥28 kg/m2) to investigate the impact of the four weight variability indicators on the risk of DKD. Results: After a follow-up of (4.55±2.13) years, 904 patients developed DKD. Compared with the NDKD group, patients in the DKD group had a higher proportion of females, older age, longer duration of diabetes, more insulin users, higher waist-to-hip ratio, higher levels of BMI-VIM, BMI-ASV, BMI-CV, BMI-SD, systolic blood pressure, diastolic blood pressure, and urine albumin-creatinine ratio, a lower proportion of hypoglycemic drugs, estimated glomerular filtration rate, and high-density lipoprotein cholesterol level, with statistically significant differences between the two groups(all P<0.05). Cox proportional hazards regression analysis results revealed that the risk of DKD in T2DM patients increased with the increase in BMI-SD, BMI-CV, BMI-VIM, and BMI-ASV after correcting a series of influencing factors. In the BMI-VIM subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.4% [HR=1.224 (95%CI:1.008-1.487), P=0.041]. In the BMI-ASV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 51.1% [HR=1.511 (95%CI:1.240-1.841), P<0.01]. In the BMI-CV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.006-1.485), P=0.044]. In the BMI-SD subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.002-1.490), P=0.048]. Sub-group analysis showed that when the non-obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.551 (95%CI:1.228-1.958), P<0.001];when the obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.703 (95%CI:1.168-2.485), P=0.006]. Conclusion: Increases in BMI-VIM, BMI-ASV, BMI-CV, and BMI-SD are associated with an increased risk of DKD in T2DM patients.

Long non-coding RNAs (lncRNAs) are key regulators of gene expression. Some studies have reported the association of polymorphisms in lncRNA genes with diabetes mellitus (DM) and its chronic complications, including diabetic kidney disease (DKD); however, the results are still inconclusive. Thus, we investigated the association of the rs3200401/MALAT1, rs1894720/MIAT, rs3931283/PVT1, rs11993333/PVT1, rs5749201/TUG1, and rs7158663/MEG3 polymorphisms with DKD in patients with type 2 DM (T2DM). This study comprised 902 patients with T2DM and DKD (cases) and 394 patients with T2DM without DKD (controls). The six polymorphisms of interest were genotyped by real-time PCR using TaqMan probes. Frequency of the rs3931283/PVT1 G/G genotype was 36.2% in cases and 31.9% in controls (P = 0.331). After adjustment for gender, glycated hemoglobin, HDL cholesterol, ethnicity, hypertension, and diabetic retinopathy, the G/G genotype was associated with risk for DKD (OR = 1.625, 95% CI 1.020-2.588; P = 0.041). The rs3931283/PVT1 G/G genotype was also associated with higher urinary albumin excretion levels compared to A allele carriers (P = 0.017). No difference was found in rs7158663/MEG3 genotype frequencies between T2DM controls and DKD patients (OR = 1.087, 95% CI 0.686-1.724; P = 0.722). However, the rs7158663/MEG3 G/G genotype was associated with protection against severe DKD (OR = 0.694, 95% CI 0.488-0.989; P = 0.043, for patients with severe DKD vs. T2DM controls). The rs7158663/MEG3 G/G genotype was also associated with lower creatinine levels (P = 0.007) and higher estimated glomerular filtration rate (P = 0.010) compared to A allele carriers. No association was found between the rs11993333/PVT1, rs3200401/MALAT1, rs1894720/MIAT, and rs5749201/TUG1 polymorphisms and DKD or its laboratory markers. The rs3931283/PVT1 G/G and rs7158663/MEG3 G/G are associated with DKD and markers of renal function in T2DM patients from a Brazilian population.

Background: Prevalence of metabolic syndrome (MetS) amongst people with Type 2 diabetes mellitus (T2DM) is high. Though, diabetic kidney disease (DKD) is an increasingly important cause of morbidity and mortality worldwide, its association with MetS is not profoundly evaluated in Indian population. Objectives: We aim to assess the prevalence of MetS and evaluate the impact of MetS on the occurrence of DKD amongst people with T2DM. Methods: The demographic, anthropometry, blood pressure, lipids, CVD (based on ECG and history of CVD) and DKD (based on e-GFR < 60 ml/min/1.73 m2) data of 1037 T2DM was obtained. MetS was defined by NCEP - ATP - III guidelines. Association of DKD was evaluated with other variables including MetS and its components in terms of unadjusted OR. The Odds Ratios were adjusted by considering covariates like age, gender, duration of diabetes and HbA1c in the logistic regression model. Results: The prevalence of MetS was 86.98% (female-91.3%, male-84.5%), DKD 6.85% and CVD 13.5%. Waist circumference contributed the most to MetS (91.69%) followed by HDL-C (71.73%) and TG (63.08%). Age and duration of diabetes showed significant positive association in occurrence of DKD. OR for people with MetS to develop DKD was high in univariate and multivariate analysis, though statistically insignificant. T2DM with hypertension are at higher risk of DKD with OR 2.1957 [95% CI: 1.1618, 4.1496] versus those without hypertension (p = 0.0154). Conclusion: Indian people with T2DM have high prevalence of MetS, where waist and low HDL-cholesterol are major contributors. MetS insignificantly, while hypertension significantly increases the risk of DKD in people with T2DM having MetS.

The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

The correlation between thyroid hormone (TH) sensitivity and microvascular complications of type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to explore the association between TH sensitivity and the risk of diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic neuropathy (DNP) in euthyroid T2DM patients. This study included a total of 946 hospitalized T2DM patients and calculated their sensitivity to the TH index, and each patient completed screenings for DKD, DR, and DNP. Multivariate logistic regression, generalized additive modeling, and subgroup analysis were used to assess the association between TH index sensitivity and the risks of DKD, DR, and DNP. After adjusting for confounding factors, a significant linear correlation was observed between the sensitivity of the thyroid feedback quartile index 3 (TFQI3) and DKD risk. However, the sensitivities of thyroid-stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI) and partial thyroid feedback quartile index (PTFQI) exhibited nonlinear correlations with the risk of developing DKD. The effect sizes to the left of the inflection point for TSHI, TT4RI and PTFQI were (odd ratio [OR] = 0.53, 95% confidence interval [CI]: 0.288–0.977), (OR = 0.863, 95%Cl: 0.751–0.992) and (OR = 0.007, 95%Cl: 0-0.724), respectively. However, there was no significant correlation between TH index sensitivity and DR/DNP risk. This study provides valuable insights into the relationship between TH sensitivity and the risks of DKD, DR, and DNP, with substantial clinical implications for individual prediction among T2DM patients.

This study aimed to explore the association of globulin and albumin-to-globulin ratio (AGR) with diabetic kidney disease (DKD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). This study used data from the China National Diabetic Chronic Complications Study in Shaanxi Province. From April to May 2019, T2DM patients at disease surveillance sites in Shaanxi Province were investigated using a stratified multi-stage sampling method. The participants completed questionnaire surveys, anthropometric and blood pressure measurements, laboratory tests, and fundus photograph examinations. Multivariate Logistic regression and restricted cubic spline model were used to analyze the association of globulin and AGR with DKD and DR, and subgroup analysis was performed according to age, sex, and diabetes duration to test the stability of the results. A total of 1494 T2DM patients were enrolled in this study, including 495 patients with DKD (33.1%) and 341 patients with DR (22.8%). After adjusting for all covariates, globulin and AGR were linearly associated with DKD. For every 1g/L increase in globulin level, the risk of DKD increased by 7% (OR=1.07, 95% CI=1.04, 1.10). For every 1 unit increase in AGR, the risk of DKD was reduced by 55% (OR=0.45, 95% CI=0.28, 0.72). Subgroup analysis showed that the association between globulin and DKD was consistent across all subgroups, and the association between AGR and DKD was consistent across subgroups of age and diabetes duration; however, only in males, higher AGR was associated with a reduced risk of DKD. No association was found between globulin and AGR with DR. Globulin is an independent risk factor and AGR is an independent protective factor for DKD. Screening for DKD should be performed in T2DM patients with high globulin and low AGR levels, especially in men.

AimThe study aimed to explore the associations of the remnant cholesterol (RC) levels with the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).MethodsThe study collected data from 23324 patients with T2DM from the UK Biobank (UKB) cohort and 3059 patients with T2DM from the Chongqing Diabetes Registry (CDR) cohort. UKB and CDR cohort were followed for incident DKD until October 2020 and March 2023, respectively. Cox proportional hazards regression was performed to explore the relationship between RC levels and incident DKD.ResultsParticipants from the UKB and CDR were followed for a mean period of 13.72 years and 1.92 years, respectively. The incidences of DKD are 12.9% and 24.5%. Participants were divided into 4 groups: 0.41 mmol/L or less, 0.41 to 0.56 mmol/L, 0.56 to 0.73 mmol/L, and greater than 0.73 mmol/L according to RC levels. Lower RC levels (≤0.41 mmol/L) were used as a reference, multi-adjusted model showing that patients with higher RC levels (>0.73 mmol/L) in the UKB were associated with increased risk of incident DKD [hazard ratio [HR], 1.27; 95% CI, 1.10–1.46; P = 0.001]. These results were consistent in the CDR [HR (95% CI): 1.39 (1.03, 1.89); P = 0.034]. In the stratified analyses, we observed an increase in the risk of incident DKD with RC in the elderly patients, while not in the middle-aged patients in both UKB cohort [HR (95% CI): 1.33 (1.13, 1.57) vs 1.16 (0.89, 1.50), P for interaction = 0.043] and CDR cohort [HR (95% CI): 1.53 (1.02, 2.30) vs 1.23 (0.76, 2.00), P for interaction = 0.009].ConclusionHigh RC might be an independent risk factor for new-onset DKD in T2DM population after adjusting for traditional risk factors, especially in elderly T2DM patients.

Objectives: This study aims to assess the association between the estimated glucose disposal rate (eGDR) and the risk of diabetic microvascular complications in patients with T1DM.Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted up to August 2024, including studies that examined the relationship between eGDR and diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN) in patients with T1DM. A meta-analysis was performed to compare the eGDR values in patients with and without microvascular complications and assess the risk of these complications.Results: 22 studies were included. Lower eGDR values were significantly associated with a higher risk of microvascular complications. Specifically, a one-unit increase in eGDR was associated with a 18% reduction in the risk of DKD (ES: 0.82, 95% CI: 0.74-0.92), a 21% reduction in the risk of DR (OR: 0.79, 95% CI: 0.73-0.85). Patients with DKD, DR, and DN had eGDR values significantly lower by 1.29, 0.75, and 0.64 units, respectively, compared to those without complications.Conclusion: This meta-analysis highlights the potential role of eGDR as a non-invasive marker for the early detection of microvascular complications, highlighting the importance of regular eGDR monitoring to facilitate timely interventions.

To investigate the predictors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients and establish a nomogram model for predicting the risk of DKD. The clinical data of T2DM patients, admitted to the Endocrinology Department of Chengde Central Hospital from October 2019 to September 2020 and divided into a case group or a control group based on whether they had DKD, were collected. The predictive factors of DKD were screened by univariate and multivariate analysis, and a nomogram prediction model was constructed for the risk of DKD in T2DM. Bootstrapping was used for model validation, receiver operating characteristic (ROC) curve and GiViTI calibration curve were used for evaluating the discrimination and calibration of prediction model, and decision analysis curve (DCA) was used for evaluating the practicality of model. Predictors for DKD are diabetic retinopathy (DR), hypertension, history of gout, smoking history, using insulin, elevation of body mass index (BMI), triglyceride (TG), cystatin C (Cys-C), and reduction of 25 (OH) D. The nomogram prediction model based on the above nine predictors had good representativeness (Bootstrap method: precision: 0.866, Kappa: 0.334), differentiation [the area under curve (AUC) value: 0.868], and accuracy (GiViTI-corrected curved bands, P = 0.836); the DAC curve analysis showed that the prediction model, whose threshold probability was in the range of 0.10 to 0.70, had clinical practical value. The risk of DKD in T2DM could be predicted accurately by DR, hypertension, history of gout, smoking history, using insulin, elevation of BMI, TG, Cys-C, and reduction of 25 (OH) D.

Prevalence and clinical profile of metabolic syndrome among type 1 diabetes mellitus patients in southern India

Previous studies have linked famine exposure to the incidence of type 2 diabetes (T2D), yet its impact on diabetic microvascular complications (DMC) remains uncertain. This study aims to investigate the longitudinal association between early-life famine exposure and the risk of DMC in adult-hood among individuals with T2D. A retrospective cohort study was conducted among inpatients with T2D at Tianjin Medical University Chu Hsien-I Memorial Hospital from June 2014 to June 2022. The 2409 participants were divided into five famine exposure groups based on birth years: no exposure group (1962-1965), fetal period exposure group (1959-1961), early-childhood exposure group (1956-1958), mid-childhood exposure group (1953-1955), and late-childhood exposure group (1949-1952). Compared with those nonexposed, early-life famine exposure was associated with higher risks of incident overall DMC (HRtrend 1.134, 95% CI 1.052-1.223), diabetic retinopathy (DR) (HRtrend 1.193, 95% CI 1.100-1.293), and diabetic kidney disease (DKD) (HRtrend 1.262, 95% CI 1.117-1.425), but was not associated with diabetic neuropathy (p > 0.05). Notably, significant interactions were found between famine exposure and hypertension regarding the risk of DR, and between famine exposure and both and obesity patterns on the risk of DKD (all p for interaction < 0.05). Exposure to famine in early life was associated with increased risks of overall DMC, DR and DKD among patients with T2D. Specially, the association of DR was more pronounced in individuals with hypertension, while the association with DKD was stronger among those with hypertension or both general and abdominal obesity.

Markers of and Risk Factors for the Development and Progression of Diabetic Kidney Disease

To investigate the association of diabetic self-management with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. Cross-sectional study. Recruited patients with type 2 diabetes mellitus in the Desheng community of urban Beijing between November 2009 and May 2011. All patients were surveyed using a standardized questionnaire and underwent detailed ophthalmic examination. Patients were classified into DR group or diabetic without retinopathy (DWR) group according to the grading of fundus color photographs using the Early Treatment of Diabetic Retinopathy Study (ETDRS) standard grading protocol. In the DR group, proliferative diabetic retinopathy (PDR) was further defined. The overall levels of diabetes self-management in the study population were assessed and compared for the differences between DR and DWR, PDR and NPDR groups. One thousand one hundred patients with type 2 diabetes mellitus were recruited. The prevalence of DR was 32.1% (353/1100) in the study population. Sixty-three percent (652/1035) of patients had glycated hemoglobin (HbA1c) level less than 7.0%. The majority of patients (85.4%, 916/1072) conducted a diet control, 77.3% (827/1070) exercised, 56.0% (609/1088) monitored blood glucose regularly, 56.8% (416/733) detected HbA1c more than once every six months, 71.7% (762/1062) had ophthalmologic examination after the diagnosis of diabetes mellitus, and 47.9% (525/1097) had mydriatic check-up. Increased risk of DR was associated with longer duration of diabetes (more than 10 years) (OR = 3.90, 95% CI:2.97-5.51, P < 0.05), higher HbA1c level of ≥ 7.0% (OR = 3.23, 95% CI:2.44-4.28, P < 0.05), insulin therapy (OR = 4.82, 95% CI:3.55-6.57, P < 0.05), male gender (OR = 1.41, 95% CI:1.08-1.84, P < 0.05), lower level of education (OR = 1.90, 95% CI:1.39-2.62, P < 0.05), lower monthly income (OR = 1.46, 95% CI:1.12-1.91, P < 0.05), lower obedience to diet control (OR = 1.72, 95% CI:1.22-2.43, P < 0.05), no exercise (OR = 1.42, 95% CI:1.04-1.94, P < 0.05), change of therapeutic protocol during the last five years (OR = 1.78, 95% CI:1.32-2.41, P < 0.05), and family history of diabetes (OR = 1.35, 95% CI:1.01-1.78, P < 0.05). Increased risk of PDR was associated with the diagnosis age of diabetes (OR = 0.92, 95% CI:0.89-0.95, P < 0.05), longer duration of diabetes (more than 10 years) (OR = 4.54, 95% CI:1.95-12.32, P < 0.05), and insulin therapy (OR = 4.85, 95% CI:2.34-10.90, P < 0.05). In the multifactor logistic regression model, male gender (OR = 2.21, 95% CI:1.57-3.11, P < 0.05), lower level of education (OR = 1.98, 95% CI:1.33-2.94, P < 0.05), lower monthly income (OR = 1.66, 95% CI:1.15-2.39, P < 0.05) ,longer duration of diabetes (more than 10 years) (OR = 2.46, 95% CI:1.77-3.41, P < 0.05) ,HbA1c ≥ 7.0% (OR = 2.24, 95% CI:1.64-3.07, P < 0.05) and insulin therapy (OR = 3.38, 95% CI:2.38-4.8, P < 0.05) were associated with higher risk of DR. The diagnosis age of diabetes (OR = 0.94, 95% CI:0.91-0.98, P < 0.05) and insulin therapy (OR = 3.49, 95% CI:1.47-8.27, P < 0.05) were associated with PDR. Higher risk of DR is associated with longer duration of diabetes,insulin therapy, higher HbA1c level, male gender, and lower level of education, whereas higher risk of DR is also associated with lower obedience to diet control and less exercise, which suggest that lower level of diabetic self-management increased the risk of DR.

ObjectiveTo analyze the associations between serum albumin (sALB) level and diabetic microvascular complications, including diabetic retinopathy (DR) and diabetic kidney disease (DKD), in patients with type 2 diabetes mellitus (T2DM).MethodsThis retrospective study included 951 hospitalized patients with T2DM who had completed screening for DR and DKD during hospitalization. Patients were divided into three groups according to sALB tertiles. Multivariate logistic regression analysis was used to assess the association of sALB with microvascular complications.ResultsThe prevalence of DR, DKD and macroalbuminuria increased with decreasing sALB levels. Multivariate logistic regression analysis showed that lower levels of sALB (Q1) were associated with higher risk of DR (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.12–2.26), DKD (OR: 3.00, 95% CI: 2.04–4.41) and macroalbuminuria (OR: 9.76, 95% CI: 4.62–20.63) compared with higher levels of sALB (Q3) after adjustment for other risk factors. After stratification by sex and age, the effect of lower levels of sALB (Q1) on DR incidence was more obvious in patients with male (OR: 1.60, 95% CI: 1.00–2.56), and aged<65 years (OR: 1.74, 95% CI: 1.14–2.65) (P < 0.05 for all); the effect of lower levels of sALB (Q1) on the incidence of DKD was significant in both males (OR: 3.78, 95% CI: 2.26–6.32) and females (OR: 2.35, 95% CI: 1.26–4.35) (P < 0.05 for all), while only the age <65 years (OR: 3.46, 95% CI: 2.16–5.53) was significant in the age subgroup (P < 0.001).ConclusionDecreased sALB levels may be an independent risk indicator of DR and DKD in patients with T2DM, and significantly associated with DKD progression. For DR screening, special attention should be paid to men aged <65 years, while screening for DKD should pay attention to people <65 years old.

Screening for Diabetic Retinopathy in Youth-Onset Diabetes