The Association of Hematological Parameters in Early and Middle Pregnancy with the Risk of Gestational Diabetes Mellitus.

Objective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6-12 weeks of gestation) to the second trimester (24-28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM. Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM. Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy. Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.

Relationship between serum uric acid in early pregnancy and gestational diabetes mellitus: a prospective cohort study.

PURPOSE: The association between serum uric acid (UA) and gestational diabetes mellitus (GDM) was still unclear. Serum UA levels in pregnancy differed from that in non-pregnancy. This study aimed to investigate the changes of serum UA in early pregnancy, and to explore the association of serum UA with the risk of GDM. METHODS: A prospective double-center study including 873 singleton pregnant women was conducted in Beijing, China since 2019 (clinical trial number: NCT03246295). Seventy-eight healthy non-pregnant women were selected to compare the changes of biomarkers in pregnancy. Spearman correlation and logistic regression analysis were performed to measure the relationship between serum UA in early pregnancy and GDM. RESULTS: The incidence of GDM in our cohort was 20.27%(177/873). Compared with non-pregnant women, serum UA and creatinine decreased significantly during early pregnancy. Serum UA concentration in early pregnancy was significantly higher in GDM women than that in normal glucose tolerance (NGT) women [217.0(192.9, 272.0) µmol/l vs. 201.9(176.0, 232.0) µmol/l, p < 0.001]. After adjusted for confounding factors, elevated serum UA remained as an independent risk factor for GDM. The risk of GDM increased when serum UA was above 240 µmol/l (adjusted OR 1.964, 95% CI 1.296-2.977, p < 0.001), and stronger relationships between serum UA and GDM were observed in pregnant women aged over 35 years old and preBMI ≥ 24 kg/m2. CONCLUSION: The normal range of serum UA and creatinine in pregnant women were lower than those in non-pregnant women. It is essential to monitor serum UA concentrations since early pregnancy to alert and prevent GDM, especially in older and heavier pregnant women. CLINICAL TRIAL NUMBER: NCT03246295.

A Simplified Screening Model to Predict the Risk of Gestational Diabetes Mellitus in Pregnant Chinese Women.

INTRODUCTION: This study aimed to develop a simplified screening model to identify pregnant Chinese women at risk of gestational diabetes mellitus (GDM) in the first trimester. METHODS: This prospective study included 1289 pregnant women in their first trimester (6-12 weeks of gestation) with clinical parameters and laboratory data. Logistic regression was performed to extract coefficients and select predictors. The performance of the prediction model was assessed in terms of discrimination and calibration. Internal validation was performed through bootstrapping (1000 random samples). RESULTS: The prevalence of GDM in our study cohort was 21.1%. Maternal age, prepregnancy body mass index (BMI), a family history of diabetes, fasting blood glucose levels, the alanine transaminase to aspartate aminotransferase ratio (ALT/AST), and the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were selected for inclusion in the prediction model. The Hosmer-Lemeshow goodness-of-fit test showed good consistency between prediction and actual observation, and bootstrapping indicated good internal performance. The area under the receiver operating characteristic curve (ROC-AUC) of the multivariate logistic regression model and the simplified clinical screening model was 0.825 (95% confidence interval [CI] 0.797-0.853, P < 0.001) and 0.784 (95% CI 0.750-0.818, P < 0.001), respectively. The performance of our prediction model was superior to that of three other published models. CONCLUSION: We developed a simplified clinical screening model for predicting the risk of GDM in pregnant Chinese women. The model provides a feasible and convenient protocol to identify women at high risk of GDM in early pregnancy. Further validations are needed to evaluate the performance of the model in other populations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03246295.

Lean nonalcoholic fatty liver disease and risk of incident type 2 diabetes mellitus: A literature review and meta-analysis.

OBJECTIVE: There is limited data regarding the risk of incident type 2 diabetes mellitus (T2DM) among lean nonalcoholic fatty liver disease (NAFLD) individuals. We performed a meta-analysis of relevant studies. RESEARCH DESIGN AND METHODS: We collected data using PubMed, Scopus, Cochrane and Web of Science from the databases' inception until December 2022. We included cohort studies in which lean NAFLD was diagnosed through imaging methods or biopsy. Eligible studies were selected according to predefined keywords and clinical outcomes. RESULTS: A total of 16 observational studies with 304,975 adult individuals (7.7% with lean NAFLD) and nearly 1300 cases of incident diabetes followed up over a median period of 5.05 years were included in the final analysis. Patients with lean NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.72, 95% CI 1.56-4.74; I2 = 93.8%). Compared with the lean without NAFLD group, the adjusted HRs (95% CIs) of incident diabetes for participants in the overweight/obese without NAFLD and overweight/obese with NAFLD groups were 1.32 (0.99- 1.77) and 2.98(1.66-5.32). It appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (random-effects HR 3.48, 95% CI 1.92-6.31). Sensitivity analyses and publication bias did not alter these findings. CONCLUSIONS: Lean NAFLD is significantly associated with at least twofold increased risk of incident diabetes in non-overweight subjects. This risk parallels the underlying severity of NAFLD. The presence of NAFLD in non-overweight individuals had a more significant impact on the development of diabetes than being overweight itself.

Diabetes management in patients undergoing total pancreatectomy: A single center cohort study.

Background: Total pancreatectomy (TP) has been increasingly performed in recent years. However, studies on diabetes management after TP during different postoperative periods are still limited. Objectives: This study aimed to evaluate the glycemic control and insulin therapy of patients undergoing TP during the perioperative and long-term follow-up period. Methods: Ninety-three patients undergoing TP for diffuse pancreatic tumors from a single center in China were included. Based on preoperative glycemic status, patients were divided into three groups: nondiabetic group (NDG, n = 41), short-duration diabetic group (SDG, preoperative diabetes duration ≤12 months, n = 22), and long-duration diabetic group (LDG, preoperative diabetes duration >12 months, n = 30). Perioperative and long-term follow-up data, including the survival rate, glycemic control, and insulin regimens, were evaluated. Comparative analysis with complete insulin-deficient type 1 diabetes mellitus (T1DM) was conducted. Results: During hospitalization after TP, glucose values within the target (4.4-10.0 mmol/L) accounted for 43.3% of the total data, and 45.2% of the patients experienced hypoglycemic events. Patients received continuous intravenous insulin infusion during parenteral nutrition at a daily insulin dose of 1.20 ± 0.47 units/kg/day. In the long-term follow-up period, glycosylated hemoglobin A1c levels of 7.43 ± 0.76% in patients following TP, as well as time in range and coefficient of variation assessed by continuous glucose monitoring, were similar to those in patients with T1DM. However, patients after TP had lower daily insulin dose (0.49 ± 0.19 vs 0.65 ± 0.19 units/kg/day, P < 0.001) and basal insulin percentage (39.4 ± 16.5 vs 43.9 ± 9.9%, P = 0.035) than patients with T1DM, so did those using insulin pump therapy. Whether in the perioperative or long-term follow-up period, daily insulin dose was significantly higher in LDG patients than in NDG and SDG patients. Conclusions: Insulin dose in patients undergoing TP varied according to different postoperative periods. During long-term follow-up, glycemic control and variability following TP were comparable to complete insulin-deficient T1DM but with fewer insulin needs. Preoperative glycemic status should be evaluated as it could guide insulin therapy after TP.

Effect of sodium-glucose cotransporter 2 inhibitors on the rate of decline in kidney function: A systematic review and meta-analysis.

AIM: To investigate the influence of sodium/glucose cotransporter-2 inhibitors (SGLT-2i) on renal function during the course of its administration, particularly in the initial weeks. MATERIALS AND METHODS: Randomized controlled trials (RCTs) related to SGLT-2i were searched in databases (MEDLINE, EMBASE, and Cochrane Central Register) from the database's inception to August 31, 2021. All RCTs reported the kidney outcomes of SGLT2i versus active or placebo control were included, regardless of the presence of diabetes in the patients and the baseline estimated glomerular filtration rate (eGFR). The Cochrane Collaboration risk of bias tool was used to assess the quality of the included studies. All outcome comparisons were performed using the RevMan 5.4 software. RESULTS: Eleven RCTs with 58 534 participants reporting prespecified renal outcomes were identified. There was no heterogeneity in the baseline eGFR and urine albumin-to-creatinine ratio in the included studies. In the initial 2-4 weeks, there was an acute decline of eGFR in the SGLT-2i group compared with placebo group (weighted mean difference [WMD] -3.35 ml/min/1.73 m2 ; 95% CI, -3.81 to -2.90; I2  = 35%, p = .15); When compared to baseline eGFR in the SGLT-2i group, the WMD was -4.02 ml/min/1.73 m2 (95% confidence interval [CI], -3.61 to -4.44; I2  = 0%, p = .45). The renoprotective effect gradually appeared, and the decline rate of eGFR in the SGLT-2i group was sustained slower than placebo. However, the statistically significant benefit of SGLT-2i did not appear until the 104th week (the second year) (WMD 0.35 ml/min/1.73 m2 , 95% CI, 0.04 to 0.66; I2  = 45%, p = .08). Subgroup analysis showed SGLT-2i had a similar benefit on renal function regardless of baseline eGFR values. CONCLUSION: SGLT-2i consistently slowed the deterioration of eGFR since the early stage of administration, even in patients with chronic kidney disease. However, there was an acute decline in eGFR in the initial 2-4 weeks; afterwards the renoprotective effect of SGLT-2i gradually appeared and remained stable in the next few years.

ALT/AST as an Independent Risk Factor of Gestational Diabetes Mellitus Compared with TG/HDL-C.

OBJECTIVE: This study aimed to find the association between alanine transaminase-to-aspartate aminotransferase ratio (ALT/AST) and the incidence of gestational diabetes mellitus (GDM). METHODS: A total of 1128 pregnant women were included in this prospective, double-center, observational cohort study. ALT, AST and total bilirubin (TBil) were tested during 6-12 weeks of gestation and 75-g oral glucose tolerance test (OGTT) was conducted during 24-28 weeks of gestation to screen GDM. The association between ALT/AST and glucose concentration during OGTT was analyzed by linear regression model. The OR with 95% CI for incidence of GDM associated with ALT/AST was estimated by binary logistic regression. The discriminatory values of ALT/AST and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) for GDM were calculated by the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: The incidence of GDM was 22.07% (249/1128). ALT/AST was higher in GDM group than in NGT group (0.92 [0.75, 1.18] vs 0.80[0.65, 1.02], P <0.001). ALT/AST had positive correlations with fasting blood glucose, 1-hour and 2-hour blood glucose concentration during OGTT (0.089 [95% CI: 0.034, 0.163], 0.176 [95% CI: 0.052, 0.104], and 0.115 [95% CI: 0.199, 0.609], respectively). The OR of ALT/AST for incidence of GDM was 1.603 (95% CI:1.097, 2.344). The ROC-AUC of ALT/AST and TG/HDL-C reached 0.615 (95% CI: 0.575, 0.655) and 0.619 (95% CI: 0.580, 0.659), respectively. CONCLUSION: ALT/AST in early pregnancy was an independent risk factor of GDM. The predictive ability of ALT/AST was similar to TG/HDL-C for GDM.

HOMA-IR as a risk factor of gestational diabetes mellitus and a novel simple surrogate index in early pregnancy.

OBJECTIVE: To assess the association between insulin resistance and gestational diabetes mellitus (GDM) in early pregnancy and find a simple surrogate index of the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: A total of 700 pregnant women were included in this prospective, double-center, observational cohort study. The glucose and lipid metabolic characterization was performed at 6-12 weeks of pregnancy. All participants underwent a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. Linear regression analysis was applied to find a novel surrogate index of HOMA-IR. Binary logistic analysis was applied to estimate possible associations of different indices with GDM and insulin resistance. RESULTS: GDM was diagnosed in 145 of 700 women with singleton pregnancies (20.7%). HOMA-IR was higher in the GDM group than in the normal glucose tolerance (NGT) group and was an individual risk factor for GDM (adjusted risk ratio RR 1.371, 95% confidence interval [CI] 1.129-1.665, P < 0.001). TyHGB index as the surrogate index of HOMA-IR was represented as TG/HDL-C + 0.7*FBG (mmol/L) +0.1*preBMI (kg/m2 )(where TG/HDL-C is triglyceride/high-density lipoprotein cholesterol; FBG is fasting blood glucose, and preBMI is the pre-pregnancy body mass index [calculated as weight in kilograms divided by the square of height in meters]). The cut-off point of the TyHGB index was 6.0 (area under the curve 0.827, 95% CI 0.794-0.861, P < 0.001) for mild insulin resistance. CONCLUSION: Increased HOMA-IR in early pregnancy was a risk factor of GDM. TyHGB index could be a surrogate index of HOMA-IR and had a predictive value for GDM.

Medium- and Long-Term Effects of Dapagliflozin on Serum Uric Acid Level in Patients with Type 2 Diabetes: A Real-World Study.

We aimed to explore the medium- and long-term (≥12 weeks) effects of dapagliflozin on serum uric acid (SUA) level in patients with type 2 diabetes mellitus (T2DM) in the real world study and to explore the influencing factors of dapagliflozin on reducing SUA level. This observational, prospective cohort study was based on the real world. There were 77 patients included in this study. They were divided into two groups. Patients in treatment group (n = 38) were treated as dapagliflozin 10 mg/d combined with therapy of routine glucose-lowering drugs (GLDs), and patients in the control group (n = 39) were treated with their routine GLDs. All measurements of physical examinations, blood, and urine samples, including age, sex, weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and SUA, were collected at baseline for all patients in these two groups and repeated after 12, 24, and 48 weeks of therapy. We compared the changes of metabolic indicators including SUA in these two groups to evaluate the effects of dapagliflozin and analyzed its influencing factors. In the dapagliflozin group, mean SUA levels significantly decreased from 334.2 ± 99.1 µmol/L at baseline to 301.9 ± 73.2 µmol/L after 12 weeks therapy (t = 2.378, p = 0.023). There was no significant statistical difference of SUA levels after 24 weeks treatment of dapagliflozin compared with 12-week and 48-week treatment with dapagliflozin (p > 0.05). We found that baseline SUA had a significant impact on the effect of dapagliflozin on reducing SUA (OR 1.014, 95%CI 1.003−1.025, p = 0.014) by logistic regression analysis. Receiver operating characteristic (ROC) curve showed that T2DM patients with SUA level ≥ 314.5 µmol/L had relative accuracy in recognizing the good effects of dapagliflozin on reducing SUA (sensitivity 76.9%, specificity 76.2%). Combination therapy of dapagliflozin with routine blood-glucose-lowering drugs in T2DM patients showed the significant and sustained stable effect of lowering SUA level in this real-world study.

Predictability of HOMA-IR for Gestational Diabetes Mellitus in Early Pregnancy Based on Different First Trimester BMI Values.

Objective: To investigate the ability of homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy for predicting gestational diabetes mellitus (GDM) in Chinese women with different first-trimester body mass index (FT-BMI) values. Methods: Baseline characteristics and laboratory tests were collected at the first prenatal visit (6−12 weeks of gestation). GDM was diagnosed by a 75 g oral glucose tolerance test (OGTT) at 24−28 weeks of gestation. Partial correlation analysis and binary logistic regression were applied to identify the association between HOMA-IR and GDM. The cutoff points for predicting GDM were estimated using receiver operating characteristic (ROC) curve analysis. Results: Of the total of 1343 women, 300 (22.34%) were diagnosed with GDM in the 24−28 weeks of gestation. Partial correlation analysis and binary logistic regression verified HOMA-IR as a significant risk factor for GDM in the normal weight subgroup (FT-BMI < 24 kg/m2) (adjusted OR 2.941 [95% CI 2.153, 4.016], P < 0.001), overweight subgroup (24.0 kg/m2 ≤ FT-BMI < 28.0 kg/m2) (adjusted OR 3.188 [95% CI 2.011, 5.055], P < 0.001), and obese subgroup (FT-BMI ≥ 28.0 kg/m2) (adjusted OR 9.415 [95% CI 1.712, 51.770], p = 0.01). The cutoff values of HOMA-IR were 1.52 (area under the curve (AUC) 0.733, 95% CI 0.701−0.765, p < 0.001) for all participants, 1.43 (AUC 0.691, 95% CI 0.651−0.730, p < 0.001) for normal weight women, 2.27 (AUC 0.760, 95% CI 0.703−0.818, p < 0.001) for overweight women, and 2.31 (AUC 0.801, 95% CI 0.696−0.907, p < 0.001) for obese women. Conclusions: Increased HOMA-IR in early pregnancy is a risk factor for GDM, and HOMA-IR can be affected by body weight. The cutoff value of HOMA-IR to predict GDM should be distinguished by different FT-BMI values.

Patterns of Insulin Secretion During First-Phase Insulin Secretion in Normal Chinese Adults.

Background: The increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse. Aims: This study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM). Methods: A total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity. Results: Age, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 (p for linear trend <0.05), and the differences between G1 and G2 were also statistically significant (p < 0.05). Glucose peak of most participants in G1 converged at 5 min, and the curves shape of insulin and C-peptide in G2 were the sharpest among three groups. There was no significant difference in all IVGTT-based indices between G1 and G2, but AUCIns, AUCIns/AUCGlu, and △Ins3/△Glu3 in G2 were the highest, and the p-value for linear trend of those indices among three groups were statistically significant (p < 0.05). Conclusions: Two patterns of FPIS were in subjects with NGT, while subjects with later time to glucose peak during FPIS might be less likely to develop T2DM in the future.

The Predictive Ability of Hepatic Steatosis Index for Gestational Diabetes Mellitus and Large for Gestational Age Infant Compared with Other Noninvasive Indices Among Chinese Pregnancies: A Preliminary Double-center Cohort Study.

OBJECTIVE: To evaluate the association of hepatic steatosis index (HSI) in the first trimester and the risk of gestational diabetes mellitus (GDM) as well as large for gestational age (LGA) infant in Chinese women. METHODS: A total of 1082 pregnant women were included in this study. Maternal basic laboratory data, including ALT, AST, FBG, insulin, TG, and HDL-C, were tested during 6-12 weeks of gestation and anthropometric characteristics were monitored during gestation. A 75-g oral glucose tolerance test (OGTT) was conducted at 24-28 weeks of gestation. HSI, nonalcoholic fatty liver disease (NAFLD) liver fat score, triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) and triglyceride-glucose (TyG) index were calculated. Odds ratio with 95% confidence interval for subsequent risk of GDM and LGA by HSI quartiles were assessed by binary logistic regression model. The predictive ability of HSI for GDM and LGA was evaluated by the receiver operating characteristic (ROC) curve analysis and was compared with other indices. RESULTS: The incidence of GDM and LGA were 22.09% (239/1082) and 10.53% (87/826). HSI was higher in GDM group than in NGT group (median, interquartile range: 30.67, 27.20-35.10 vs 27.98, 25.70-30.82, P<0.001). Incidence of GDM was gradually increased with increasing HSI values. Women in the highest HSI quartile had significantly higher risk of LGA delivery than those in the lowest HSI quartile (P<0.05). The area under the ROC curves of HSI for GDM and LGA were higher than other indices, reaching 0.646 (95%CI: 0.605-0.686) and 0.600 (95%CI: 0.541-0.660), respectively. CONCLUSION: Higher HSI was independently associated with higher risk of GDM and LGA in Chinese women. HSI in the first trimester can predict the risk of GDM and LGA.