Preliminary observational study of metabonomics in patients with early and late-onset type 2 diabetes mellitus based on UPLC-Q-TOF/MS.

Non-targeted metabonomic techniques were used to explore changes in metabolic profiles of patients with early onset and late onset T2DM. Newly diagnosed early onset T2DM (EarT2DM) and late onset T2DM (LatT2DM) patients were recruited, and the matched age, sex, and low-risk population of diabetes mellitus were selected as the control group. 117 adults were recruited in the study, including 21 in EarT2DM group with 25 in corresponding control group (heaCG1), and 48 in LatT2DM group with 23 in corresponding control group (heaCG2). There were 15 relatively distinctive metabolic variants in EarT2DM group and 10 distinctive metabolic variants in LatT2DM group. The same changing pathways mainly involved protein, aminoacyl-tRNA biosynthesis, fatty acid biosynthesis, taurine metabolism, arginine biosynthesis, lysosome and mTOR signaling pathway. The independent disturbed pathways in EarT2DM included branched chain amino acids, alanine, aspartate and glutamate metabolism. The independent disturbed pathways in LatT2DM involved linoleic acid metabolism, biosynthesis of unsaturated fatty acids, arginine, proline metabolism and FoxO signaling pathway. T2DM patients at different diagnosed ages may have different metabolite profiles. These metabolic differences need to be further verified.

Application and observation of artificial intelligence in clinical practice of fundus screening for diabetic retinopathy with non-mydriatic fundus photography: a retrospective observational study of T2DM patients in Tianjin, China.

Objective: To observe the consistency of a preliminary report of artificial intelligence (AI) in the clinical practice of fundus screening for diabetic retinopathy (DR) using non-mydriatic fundus photography. Methods: Patients who underwent DR screening in the Metabolic Disease Management Center (MMC) of our hospital were selected as research participants. The degree of coincidence of the AI preliminary report and the ophthalmic diagnosis was compared and analyzed, and the kappa value was calculated. Fundus fluorescein angiography (FFA) was performed in patients referred to the out-of-hospital ophthalmology department, and the consistency between fluorescein angiography and AI diagnosis was evaluated. Results: In total, 6146 patients (12,263 eyes) completed the non-mydriasis fundus examination. The positive DR screening rate was 24.3%. When considering moderate nonproliferative retinopathy as the cut-off point, the kappa coefficient was 0.75 (p < 0.001), the sensitivity was 0.973, and the precision was 0.642, which was shown in the precision-recall curve. Fifty-nine patients referred to receive FFA were compared with non-mydriatic AI diagnoses. The kappa coefficient was 0.53, and the coincidence rate was 66.9%. Conclusion: Non-mydriasis fundus examination combined with AI has a medium-high consistency with ophthalmologists in DR diagnosis, conducive to early DR screening. Combining diagnosis and treatment modes with the Internet can promote the development of telemedicine, alleviate the shortage of ophthalmology resources, and promote the process of blindness prevention and treatment projects.

Association Analysis Between Different Diabetic Family History and Gender with Diagnosed Age of Type 2 Diabetes Mellitus: A Cross-Sectional Study in Tianjin, China.

BACKGROUND: Type 2 diabetes mellitus (T2DM) was previously considered a common disease in middle-aged and older people, but the age of diagnosis of T2DM is advancing every year, and the trend toward a younger age is obvious. Early-onset T2DM is a clinical syndrome caused by genetic and environmental factors. This study aimed to investigate the association between diabetic family history and gender with the diagnosed age of T2DM. METHODS: The newly diagnosed T2DM patients admitted to the diabetes identification center of Tianjin 4th Central Hospital (TJ4thch) from October 2017 to June 2020 were registered. According to whether the diagnosis age is over 40 years old, patients were divided into 2 groups (early-onset T2DM group and late-onset T2DM group). In the study, the T2DM family history was divided into 5 types: (a) Father T2DM: father with T2DM, but not the mother; (b) Mother T2DM: mother with T2DM, but not the father; (c) Both parents with T2DM; (d) Another relative(s) (other than the parents) with a history of T2DM; and (e) Without a family history of T2DM. The diagnosed age with different genders and diabetic family history was compared. Multivariate logistic regression analysis was used to investigate the association factors of early-onset T2DM. RESULTS: A total of 3725 patients completed the survey. There were 589 patients (15.8%) with early-onset T2DM, and 2469 patients (66.3%) had a diabetic family history. The T2DM-diagnosed age in males was lower than in females (51.7 ± 11.2 vs 54.0 ± 10.2, P = .000). The result was also reflected in the different T2DM family histories (with Both parents T2DM, 46.7 ± 11.1 vs 48.5 ± 10.3, P = .271; with Father T2DM, 46.8 ± 10.8 vs 49.8 ± 11.3, P = .005; with Mother T2DM, 50.4 ± 10.6 vs 52.3 ± 10.2, P = .019; with Other T2DM family history, 54.0 ± 10.8 vs 55.7 ± 9.5, P = .008; with no T2DM family history, 53.0 ± 11.0 vs 55.9 ± 9.3, P = .000). The order of the T2DM-diagnosed age in the different groups was Both parents T2DM (47.5 ± 11.0) and Father T2DM (47.9 ± 11.1) family history < that with Mother T2DM family history (51.1 ± 10.5) < that with Other T2DM family history (54.7 ± 10.3) and no T2DM family history (54.1 ± 10.5). Logistic regression analysis indicated that gender (OR, 1.733; P = .000), Father T2DM history (OR, 2.738; P = .000), Mother T2DM history (OR, 1.536; P = .001), Both parents T2DM (OR, 2.866; P = .000) and body mass index (OR, 1.108, P = .000) were correlated with early-onset T2DM. CONCLUSION: Patients with early-onset T2DM tend to have a more obvious T2DM family history in China. This survey shows that when a parent has a T2DM family history, especially the father with T2DM, male patients are diagnosed with T2DM earlier. We need more intensive screening for diabetes in children with a family history of diabetes, especially in male children.

Pathological Hyperinsulinemia and Hyperglycemia in the Impaired Glucose Tolerance Stage Mediate Endothelial Dysfunction Through miR-21, PTEN/AKT/eNOS, and MARK/ET-1 Pathways.

Background: Impaired glucose tolerance (IGT) is an important prediabetic stage characterized by elevated concentrations of glucose and insulin in the blood. The pathological hyperglycemia and hyperinsulinemia in IGT may regulate the expression of microRNA-21 (miR-21) and affect the downstream insulin signaling pathways, leading to endothelial cell dysfunction and early renal damage. Methods: The individual and combined effects of insulin and glucose were investigated using human glomerular endothelial cells (HGECs). The expression levels of miR-21, and PTEN/AKT/eNOS and MAPK/ET-1 pathway proteins in the treated cells were measured. The levels of nitric oxide (NO) and endothelin-1 (ET-1) secreted by the cells were also measured. The role of miR-21 in mediating the regulatory effects of insulin and glucose was assessed by overexpression/inhibition of this miRNA using mimics/inhibitor. Results: High (>16.7 mmol/L) concentration of glucose upregulated the expression of miR-21, leading to the activation and inhibition of the PTEN/AKT/eNOS and MAPK/ET-1 pathways, and upregulation of NO and downregulation of ET-1 secretion, respectively. High (>25 ng/mL) concentration of insulin downregulated the expression of miR-21, and lead to the activation of the MAPK/ET-1 and inhibition of the PTEN/AKT/eNOS pathway, thereby upregulating the expression of ET-1 and downregulating the secretion of NO. MiR-21 was observed to play a key role by directly controlling the activation of the insulin signaling pathways when the cells were cotreated with different concentrations of insulin and glucose. The expression of miR-21 was found to be dependent on the relative concentration of insulin and glucose. Under simulated conditions of the IGT stage (8.3 mmol/L glucose + 50 ng/mL insulin), the inhibitory effect of high insulin concentration on miR-21 expression in the cells attenuated the activation by high glucose concentration, resulting in the downregulation of miR-21, upregulation of ET-1 and downregulation of NO secretion. Conclusion: Taken together, these results indicate that high insulin and glucose concentrations regulate the secretory function of glomerular endothelial cells in opposite ways by regulating the expression of miRNA-21. Pathological concentrations of insulin and glucose in the IGT stage may lead to a decrease in miR-21 expression, thereby disordering the secretion of vasoactive factors, resulting in renal tubule ischemia.

Application of non-mydriatic fundus examination and artificial intelligence to promote the screening of diabetic retinopathy in the endocrine clinic: an observational study of T2DM patients in Tianjin, China.

BACKGROUND: We aimed to determine the role of non-mydriatic fundus examination and artificial intelligence (AI) in screening diabetic retinopathy (DR) in patients with diabetes in the Metabolic Disease Management Center (MMC) in Tianjin, China. METHODS: Adult patients with type 2 diabetes mellitus who were first treated by MMC in Tianjin First Central Hospital and Tianjin 4th Center Hospital were divided into two groups according to the time that MMC was equipped with the non-mydriatic ophthalmoscope and AI system and could complete fundus examination independently (the former was the control group, the latter was the observation group). The observation indices were as follows: the incidence of DR, the fundus screening rate of the two groups, and fundus screening of diabetic patients with different course of disease. RESULTS: A total of 5039 patients were enrolled in this study. The incidence rate of DR was 18.6%, 29.8%, and 49.6% in patients with diabetes duration of ⩽1 year, 1-5 years, and >5 years, respectively. The screening rate of fundus in the observation group was significantly higher compared with the control group (81.3% versus 28.4%, χ 2 = 1430.918, p < 0.001). The DR screening rate of the observation group was also significantly higher compared with the control group in patients with diabetes duration of ⩽1 year (77.3% versus 20.6%; χ 2 = 797.534, p < 0.001), 1-5 years (82.5% versus 31.0%; χ 2 = 197.124, p < 0.001) and ⩾5 years (86.9% versus 37.1%; χ2 = 475.609, p < 0.001). CONCLUSIONS: In the case of limited medical resources, MMC can carry out one-stop examination, treatment, and management of DR through non-mydratic fundus examination and AI assistance, thus incorporating the DR screening process into the endocrine clinic, so as to facilitate early diagnosis.

Analysis of factors related to diabetic retinopathy in patients with newly diagnosed type 2 diabetes: a cross-sectional study.

AIM: To investigate the related factors of diabetic retinopathy (DR) and explore the correlation between smoking and DR in patients with newly diagnosed type 2 diabetes mellitus (T2DM). DESIGN: A single-centre cross-sectional study. SETTING: Tianjin 4th Central Hospital. PARTICIPANTS: Patients with newly diagnosed T2DM who visited the outpatient department of the hospital from December 2018 to April 2019. METHODS: A total of 947 patients were enrolled in the study. They were divided into two groups according to whether they were diagnosed with DR (diabetic retinopathy group, DR group; non-diabetic retinopathy group, NDR group). The smoking index (SI) was calculated to assess smoking status. Factors such as sex, age, hypertension, T2DM diagnosed age, family history of diabetes, drinking history, haemoglobin A1c (HbA1c), body mass index (BMI) and smoking status were compared between the two groups. Logistic regression was used to analyse the relationship between DR and the above factors. RESULTS: There was no statistically significant difference between the two groups in sex, age, hypertension, DM diagnosed age, family history of diabetes, drinking history and HbA1c. BMI was significantly higher in DR patients (27.7±4.2 vs 26.7±4.4, p=0.004). Smoking status was also different between the two groups (χ2=6.350, p=0.042). BMI was shown to be a related factor for DR in patients with newly diagnosed diabetes (OR=0.592, p=0.004). When BMI was ≥28 kg/m2, heavy smoking was significantly associated with DR (OR=2.219, p=0.049), and there was a negative correlation between DR and the age of diagnosis of diabetes ≥60 years (OR=0.289, p=0.009). CONCLUSIONS: Heavy smoking was an important related factor for DR in patients with newly diagnosed diabetes mellitus when BMI was ≥28 kg/m2. Delaying the age of diabetes might prevent the occurrence of DR. To elucidate the correlation, long-term cohort studies with large samples are needed.

Effects of dapagliflozin on serum uric acid levels in hospitalized type 2 diabetic patients with inadequate glycemic control: a randomized controlled trial.

BACKGROUND: Raised serum uric acid (SUA) level is commonly observed in patients with type 2 diabetes mellitus (T2DM) and is associated with increased morbidity and mortality. Sodium-glucose cotransporter 2 inhibitor, a novel oral diabetic drug, might exert a potential hypouricemic effect. We evaluated the effects of dapagliflozin on SUA levels in hospitalized T2DM patients with inadequate glycemic control. METHODS: In this randomized controlled trial, 59 T2DM hospitalized patients with inadequate glycemic control were assigned to the dapagliflozin 10 mg group (n=29) or the control group (n=30). The primary outcome was changes in SUA levels from the baseline to good glycemic control. Additional outcomes included correlations between baseline SUA levels, urinary parameters, and the changes in SUA levels. This trial is registered in the Chinese Clinical Trial Registry (number ChiCTR1800015830). RESULTS: Compared to baseline level, SUA levels had significantly decreased in both groups (P<0.001 for the dapagliflozin group and P=0.013 for the control group). Mean changes from baseline in SUA levels for dapagliflozin vs the control group were 68.03 vs 25.90 µmol/L (P=0.0406). Adjusted mean SUA levels were lower in the dapagliflozin group (273.28 vs 307.57 µmol/L; P=0.0089). In T2DM patients treated with dapagliflozin, the decrease in SUA levels was positively correlated with baseline SUA levels (P<0.0001) but not correlated with changes in 24-hour urine volume, 24-hour urine glucose, or 24-hour urinary uric acid. CONCLUSION: Dapagliflozin could improve glycemic control and lower SUA levels in hospitalized patients with uncontrolled T2DM. Longer-time trials are required to further demonstrate the hypouricemic effect of dapagliflozin and explore the potential underlying mechanisms.

[Analyses on the relative factors regarding diabetic nephropathy].

OBJECTIVE: To analyze the related factors regarding diabetic nephropathy (DN). METHODS: A total number of 756 diabetic patients from 2009 to 2011 were analyzed retrospectively. Three groups were formed according to the urinary albumin excretion rates (UAER). Patients with UAER < 20 µg/min was grouped to group A, with UAER from 20 to 200 µg/min as group B, and the others with UAER ≥ 200 µg/min was grouped to group C. General characteristics and laboratory parameters were then compared and related factors of DN analyzed. RESULTS: The constituent ratio of nephropathy was 30.2% (228/756). Patient's age, duration of disease, both diastolic and systolic blood pressure of group A were significantly higher than the non-DN group (A) (P < 0.05). Patient's age, disease duration, both diastolic and systolic blood pressure of group C were (64.08 ± 11.71) years, (14.67 ± 7.34) years, (87.43 ± 14.36) mm Hg, (152.45 ± 18.48) mm Hg, respectively, with statistically significant difference (P < 0.05) between group C and group B. FPG, TG, TC, HDL-C, UA, HbA1c, FINS, FCP of group B were (9.27 ± 3.06) mmol/L, (1.98 ± 0.37) mmol/L, (5.01 ± 1.08) mmol/L, (1.05 ± 0.35) mmol/L, (312.78 ± 39.83) mmol/L, (9.33 ± 1.47)%, (11.45 ± 7.83) µU/ml, (509.73 ± 132.78) pmol/L respectively, with significant difference (P < 0.05) between group B and group A. FPG, TG, HDL-C, UA, FINS, FCP of group C were (9.29 ± 3.12) mmol/L, (2.02 ± 0.36) mmol/L, (1.04 ± 0.27) mmol/L, (389.72 ± 46.32) mmol/L, (11.09 ± 8.29) µU/ml, (575.77 ± 143.29) pmol/L respectively, with significant difference (P < 0.05) between group C and group A. UA, FINS, FCP were found with significant differences (P < 0.05) between group C and group B. Data from multivariate logistic regression showed that DNs were related with disease duration, BMI, systolic blood pressure, HbAlc, FPG, UA. CONCLUSION: DN was closely related to the duration, age, blood sugar, blood lipids, blood pressure, uric acid levels of the disease.