New sagittal abdominal diameter and transverse abdominal diameter based equations to estimate visceral fat area in type 2 diabetes patients.

OBJECTIVE: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) are considered gold standards for measuring visceral fat area (VFA). However, their relatively high prices and potential radiation exposure limit their widespread use in clinical practice and everyday life. Therefore, our study aims to develop a VFA estimated equation based on sagittal abdominal diameter (SAD) and transverse abdominal diameter (TAD) using anthropometric indexes. To the best of our knowledge, there have been limited studies investigating this aspect thus far. METHODS: This study was designed as a cross-sectional, retrospective cohort survey. A total of 288 patients (167 males and 121 females) aged 18-80 with type 2 diabetes (T2D) were consecutively collected from a multicenter hospital, and VFA was measured by CT. Subsequently, variables highly correlated with VFA were screened through general linear correlation analysis. A stepwise regression analysis was then conducted to develop a VFA estimated equation. Discrepancies between the estimated and actual VFA values were assessed using the Bland-Altman method to validate the accuracy of the equation. RESULTS: In the female T2D population, triglyceride (TG), SAD, TAD were found to be independently correlated with VFA; in the male T2D population, BMI, TG, SAD and TAD showed independent correlations with VFA. Among these variables, SAD exhibited the strongest correlation with VFA (r = 0.83 for females, r = 0.88 for males), followed by TAD (r = 0.69 for females, r = 0.79 for males). Based on these findings, a VFA estimated equation was developed for the T2D population: VFA (male) =-364.16 + 15.36*SAD + 0.77*TG + 9.41*TAD - 5.00*BMI (R2 = 0.75, adjusted R2 = 0.74); VFA(female)=-170.87 + 9.72*SAD-24.29*(TG^-1) + 3.93*TAD (R2 = 0.69, adjusted R2 = 0.68). Both models demonstrated a good fit. The Bland-Altman plot indicated a strong agreement between the actual VFA values and the estimated values, the mean differences were close to 0, and the majority of differences fell within the 95% confidence interval. CONCLUSIONS: In the T2D population, a VFA estimated equation is developed by incorporating SAD and TAD along with other measurement indices. This equation demonstrates a favorable estimated performance, suggesting to the development of novel and practical VFA estimation models in the future study.

The prevalence, hospitalization outcomes and risk factors of euthyroid sick syndrome in patients with diabetic ketosis/ketoacidosis.

BACKGROUND: To investigate the prevalence of euthyroid sick syndrome (ESS) and to evaluate the outcomes and risk factors associated with ESS among hospitalized patients with diabetic ketosis (DK) or diabetic ketoacidosis (DKA). METHODS: Laboratory and clinical data of 396 adult hospitalized DK/DKA patients with or without ESS were collected and analyzed. Spearman linear analysis and multivariable logistic regression analyses were used to evaluate correlated factors of thyroid hormones and risk factors of ESS. RESULTS: Most of the individuals were diagnosed with type 2 diabetes (359/396, 90.7%). The prevalence of ESS was 57.8% (229/396). Patients in ESS group were older and had a longer course of diabetes. Levels of thyroid hormones, serum lipids, and parameters reflecting acidosis were significantly decreased in ESS group. The proportion of patients with infection, acute renal injury and DKA was significantly higher in ESS group than in control group, accompanied by longer hospitalization stay and higher hospitalization costs. Free triiodothyronine positively correlates with albumin, eGFR, parameters reflecting acidosis and lipid profiles (All P < 0.001), and negatively correlates with age, onset age, 24-h urine albumin, hsCRP and WBC count (All P < 0.001). Hypoalbuminemia, low level of carbon dioxide combining power, high level of HbA1c and WBC, and co-infection are shown to be risk factors for ESS (OR = 0.866, 0.933, 1.112, 1.146, 1.929, respectively; All P < 0.05). CONCLUSIONS: The prevalence of ESS was high in adult DK/DKA patients. Patients with ESS had inferior clinical and socioeconomic outcomes. Early recognition and management of patients with ESS may be necessary to improve outcome.

Incidence of microcarcinoma and non-microcarcinoma in ultrasound-found thyroid nodules.

BACKGROUNDS: The incidence of thyroid nodules is increasing year by year around the world. However, ultrasound is not recommended as a screening test for the general population or patients with a normal thyroid on palpation by the American Association of Clinical Endocrinologists (AACE). In practice, some individuals with normal thyroid palpation have nodules that can just be found out by ultrasound. No studies have directly described the risk of nodules found by ultrasound or by palpation up to now. More evidence is needed to carry out for helping us balance the over diagnosis and missed diagnosis of malignant lesions. Therefore, we carried out a retrospective study to investigate the incidence of malignant lesions in ultrasound-found nodules in a large cohort. METHODS: We conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between Jan 2013 and Dec 2019. The cytologic examinations were analyzed based on the Bethesda system. For nodules suspected to be follicular neoplasm or other malignant tumors by cytological tests, patients were recommended for surgery and histopathology examinations. RESULTS: Compared with palpation-found nodules, ultrasound-found nodules were presenting less as purely cystic nodules (10.1 % vs. 39.9 %, x2 = 355.69, p = 0.000), smaller size (17.5 ± 9.9 mm vs. 28.0 ± 12.5 mm, t = 23.876 p = 0.000), and higher TI-RADS score (5.5 ± 2.9 vs. 3.4 ± 3.3, t = 18.084, p = 0.000), respectively. More ultrasound-found nodules were diagnosed as carcinoma by histology examinations [136 (11.2 %) nodules found by ultrasound vs. 68 (3.9 %) by palpation, x2 = 59.737, p = 0.000], and 88 (64.7 %) nodules found by ultrasound were non-microcarcinoma. Among the malignant nodules confirmed by histopathology, a higher proportion of microcarcinoma was detected in ultrasound-found nodules [35.3 % (48/136) vs. 16.2 % (11/68), x2 = 8.183, p = 0.004]. CONCLUSIONS: In view of the results observed in our research, malignant nodules were more common in nodules screened out by ultrasound, and nearly two thirds of them were non-microcarcinoma. We suggest the recommendation against screening thyroid nodules by ultrasound needs to be re-evaluated.

A rare combination of MODY5 and duodenal atresia in a patient: a case report.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous group of hereditary diabetes, generally caused by one abnormal gene. MODY5 is caused by mutations of the hepatocyte nuclear factor 1 homeobox ß gene (HNF1ß), always as a part of Chr17q12 deletion, whereas heterozygous mutation in B lymphocyte kinase (BLK) gene is responsible for MODY11. CASE PRESENTATION: We report a patient who developed diabetes with a 1.58-Mb Chr17q12 microdeletion and BLK gene c.211G > A mutation using the cytoscan high-density array and whole-exome sequencing analysis. The patient received the surgery at five days after birth for the duodenal atresia and had normal growth postoperatively. Mild elevated liver enzymes were found along with the normal renal function. Quantitative analysis of ß-cell function markers, including fasting insulin (< 0.2 mIU/L), fasting C-peptide (0.02 µg/L), postprandial-2 h insulin (< 0.2 mIU/L), and postprandial-2 h C-peptide (0.03 µg/L) suggested a severe loss of insulin secreting capacity. Meanwhile, islet autoantibodies (GADA, IA-2, ICA, and IAA) in the patient's blood appeared negative. Neither dysplasia in other tissues nor abnormality in development and behavior was found. CONCLUSION: To date, gastrointestinal malformations were extremely rarely reported in patients with MODY. Our clinical report further expands the clinical presentation and variability of MODY5.

Long-term renal outcomes associated with sodium glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIMS: The long-term impact of sodium glucose cotransporter 2 (SGLT2) inhibitors on renal functions remains undefined. This study was undertaken to investigate the renal outcomes associated with SGLT2 inhibitors in patients with type 2 diabetes (T2DM) in the long term. METHODS: A systematic literature search of PubMed and ClinicalTrials.gov was conducted. Randomized controlled trials which reported renal outcomes at the study endpoint in patients with T2DM receiving treatments of SGLT2 inhibitors were included. Renal adverse events were determined using prespecified lists from the Medical Dictionary for Regulatory Activities or laboratory values. Odds ratio with 95% confidence interval (CI) was used for assessment of dichotomous data. The mean difference or standardized mean difference with 95% CI was used for assessment of continuous data. Random effects models were adopted to measure the pooled outcomes. RESULTS: Thirty-nine studies involving 35 trials were identified. Compared with placebo or other anti-diabetic medications, SGLT2 inhibitors were associated with significant lower incidence of composite renal outcome and acute renal failure or injury in patients with T2DM. The risk of progression of albuminuria also appeared to be decreased. No significant changes of estimated glomerular filtration rate levels or urine albumin-creatinine ratios were found in patients receiving SGLT2 inhibitors. CONCLUSIONS: Overall renal safety and beneficial effects are indicated for SGLT2 inhibitors. Further confirmative data from large trials and real-world studies are needed.

The Association Of Serum Cortisol Level With Microalbuminuria In Patients With Type 2 Diabetes And Prediabetes.

Whether cortisol secretion is linked with microalbuminuria remains undefined. We aimed to investigate the relationship between serum cortisol levels and the presence of microalbuminuria in patients with type 2 diabetes (T2DM) and prediabetes. A cross-sectional study was conducted with 211 patients with T2DM or prediabetes. Serum cortisol was measured at 8:00 h, 16:00 h, and 0:00 h. The level and circadian rhythm of ACTH were also evaluated. Urine excretion of albumin was measured. Patients were subdivided into microalbuminuria (MAU) group (n= 120) and normoalbuminuria (NAU) group (n = 91) according to the status of microalbuminuria. Levels of serum cortisol (8:00 h: 426.9 ± 155.0 nmol/; 16:00 h: 303.7 ± 144.7 nmol/L) were significantly higher in MAU group than in NAU group (8:00 h: 370.2 ±130.6 nmol/L, P = 0.004; 16:00 h: 234.7 ± 120.2 nmol/L, P = 0.001). After adjustment for multiple factors, the correlation between cortisol levels (both at 8:00 h (P = 0.005) and at 16:00 h (P = 0.001)) and microalbuminuria remained consistent and significant. Higher levels of cortisol (cut-off value: 390.5 nmol/L at 8:00 h, 203.5 nmol/L at 16:00 h) help to detect the development of microalbuminuria. Serum cortisol secretion is associated with the presence of microalbuminuria in patients with T2DM and patients with prediabetes. Higher levels of cortisol, even in the normal range, may be related with the development of microalbuminuria.

Gamma Knife Radiosurgery (GKRS) for Patients with Prolactinomas: Long-Term Results From a Single-Center Experience.

BACKGROUND The aim of this study was to review outcomes of gamma knife radiosurgery (GKRS) for prolactinoma and report our experience with it. MATERIAL AND METHODS We reviewed the patient database in our center and identified 24 patients with prolactinoma who underwent GKRS from 1993 to 2016.  Complete endocrine, clinical, and radiological data were available on these individuals before and after GKRS. RESULTS Data from 5 males and 19 females with a median age of 30.5 years (range, 18.1 to 51.1) were reviewed. The median follow-up was 109.3 months (range, 23.2-269.3). The median margin dose of GKRS was 15 Gy (range, 10.5 to 23.6). In total, prolactin (PRL) normalization after GKRS was achieved in 66.7% of patients. Endocrine remission (normal PRL levels after discontinuation of dopamine agonists) was achieved in 10 patients (41.7%), and endocrine control (normal PRL levels while taking dopamine agonists) was achieved in 6 patients (25.0%). All of the patients showed tumor control. New-onset hypopituitarism post-GKRS occurred in 4 patients (16.7%). No new visual dysfunction or cranial nerve dysfunction were observed after GKRS. CONCLUSIONS For treatment of prolactinomas, GKRS may provide relatively high rates of endocrine remission and tumor control, as well as a low rate of new-onset hypopituitarism. GKRS may be an effective and safe treatment for prolactinomas.

Comparative Study of Liraglutide and Insulin Glargine on Glycemic Control and Pancreatic ß-Cell Function in db/db Mice.

BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic ß-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 µg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 µg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 µg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age. Body weight, pancreatic weight, levels of blood glucose, triacylglycerol, C-peptide, and the intraperitoneal glucose tolerance test (IPGTT) were used. Expression levels of the INS1 gene were measured using reverse transcription polymerase chain reaction (RT-PCR), and pancreatic and duodenal homeobox 1 (Pdx1), paired box 4 (Pax4), and paired box 6 (Pax6) mRNA expression were measured. RESULTS Both insulin glargine and liraglutide improved glycemic control of db/db mice when compared with vehicle. The following were significantly increased in the HLG compared with the GG: the receiver operating characteristic (ROC) area under the curve (AUC) for the IPGTT; C-peptide levels; the pancreas to body weight coefficient; expression levels of the INS1 gene and pancreatic transcription factors Pdx1, Pax4 and Pax6. Liraglutide treatment was without hypoglycemic effects. CONCLUSIONS Liraglutide acted in a dose-dependent manner on glycemic control of db/db mice, and was more effective than insulin glargine, when administered at a high dose.

Arachidonic acid alleviates autoimmune diabetes in NOD mice.

BACKGROUND: Arachidonic acid (AA) is considered to link nutrient metabolism, to inflammation and immunity, suggesting it may have a role in autoimmune diseases. Our previous study suggests that DPP-4 inhibitors (DPP-4i) might regulate AA - relative signaling in type 1 diabetes. AIMS: To examine the effect of AA on autoimmune diabetes and its cross-talk with DPP-4i in The Non-Obese Diabetic (NOD) mice. METHODS: The NOD mice were divided randomly and equally into three groups: AA group, AA plus DPP-4i group and control group. The incidence of diabetes, blood glucose, insulitis and cytokine profiles were monitored. At the end of the experiment, pancreatic tissues were stained by H&E. Serum cytokine profiles were examined using a Mesco Scale Discovery multiplexed-assay kit. RESULTS: Even though AA or AA plus DPP-4i treatment has no effect on incidence of diabetes and weight, AA treatment reduces blood glucose, preserves islet morphology and alleviates inflammatory cell infiltration into pancreatic islets in NOD mice, accompanying with increased serum levels of IL-10, IL-1 ß, IL-6, IL-5, KC/GRO and TNF-α and decreased serum levels of IL-2. CONCLUSION: We observed that AA treatment alleviates autoimmune diabetes in NOD mice by reducing hyperglycemia, alleviating insulitis and improving cytokine profiles. DPP-4i might alleviate the effect of AA by cross-talk. We provide evidence of AA treatment to alleviate type 1 diabetes in NOD mice, which may provide a novel therapeutic option for type 1 diabetes.

Lipidomics based on UHPLC/Q-TOF-MS to characterize lipid metabolic profiling in patients with newly diagnosed type 2 diabetes mellitus with dyslipidemia.

Dyslipidemia often accompanies type 2 diabetes mellitus (T2DM). Elevated blood glucose in patients commonly leads to high levels of lipids. Lipid molecules can play a crucial role in early detection, treatment, and prognosis of T2DM with dyslipidemia. Previous lipid studies on T2DM mainly focused on Western diabetic populations with elevated blood glucose. In this research, we investigate both high blood sugar and high lipid levels to better understand changes in plasma lipid metabolism in newly diagnosed Chinese T2DM patients with dyslipidemia (NDDD). We used a plasma lipid analysis method based on ultra-high performance liquid chromatography coupled with mass spectrometry technology (UHPLC-MS) and statistical analysis to characterize lipid profiles and identify potential biomarkers in NDDD patients compared to healthy control (HC) subjects. Additionally, we examined the differences in lipid profiles between hyperlipidemia (HL) patients and HC subjects. We found significant changes in 15 and 23 lipid molecules, including lysophosphatidylcholine (LysoPC), phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and ceramide (Cer), in the NDDD and HL groups compared to the HC group. These altered lipid molecules are associated with five metabolic pathways, with sphingolipid metabolism and glycerophospholipid metabolism being the most relevant to glucose and lipid metabolism changes. These lipid biomarkers are strongly correlated with traditional markers of glucose and lipid metabolism. Notably, Cer(d18:1/24:0), SM(d18:1/24:0), SM(d18:1/16:1), SM(d18:1/24:1), and SM(d18:2/24:1) were identified as essential potential biomarkers closely linked to clinical parameters through synthetic analysis of receiver operating characteristic curves, random forest analysis, and Pearson matrix correlation. These lipid biomarkers can enhance the risk prediction for the development of T2DM in individuals with dyslipidemia but no clinical signs of high blood sugar. Furthermore, they offer insights into the pathological mechanisms of T2DM with dyslipidemia.

Comparison of Efficacy and Adherence of Patient-Preferred (1 Unit Daily) and ADA/EASD Guideline-Recommended (2 Units Every 3 Days) Basal Insulin Titration Algorithms: Multicenter, Randomized, Clinical Study.

Aim: Insulin titration often faces inertia, hindering glycemic control. A patient-centered approach empowers patients to overcome this inertia. This study aims to compare the effectiveness of patient-preferred and guideline-recommended self-titration algorithms in achieving glycemic targets and improving adherence. Methods: Outpatients with type 2 diabetes (T2D) who did not respond to oral antihyperglycemic drugs (OAD) were assessed. They were randomly assigned to patient-preferred and guideline-recommended groups. In the patient-preferred group, individuals selected an algorithm to self-adjust their insulin glargine dosage by 2 units every 3 days if the mean fasting blood glucose (FBG) over the past 3 consecutive days was ≥7.0 mmol/L, or by 1 unit daily if the FBG on the same day was ≥7.0 mmol/L. In the guideline-recommended group, insulin glargine was titrated by 2 units every 3 days if the mean FBG over the past 3 consecutive days was ≥7.0 mmol/L. The FBG target was set below <7.0 mmol/L. Results: Thirty-nine participants in the patient-preferred group and 42 in the guideline-recommended group completed the study. The cumulative rates of achieving the FBG target in the patient-preferred group compared to the guideline-recommended group were 69.2% vs 54.8% (χ²=1.792, p=0.181) in week 1, 89.7% vs 73.8% (χ²=3.403, p = 0.065) in week 2, 94.9% vs 76.2% (χ²=17.638, p=0.000) in week 3, and 100.0% vs 88.1% (χ²=4.405, p=0.036) in week 4. Adherence rates were significantly higher in the patient-preferred group (97.4%, 37/38) compared to the guideline-recommended group (66.7%, 28/42) (χ²=12.688, p=0.000). Insulin glargine dosage at FBG target achievement was 21.2±4.3 U in the patient-preferred group and 18.8±6.7 U in the guideline-recommended group (t=1.888, p=0.063). Hypoglycemia was reported in 1 patient in the guideline-recommended group, with no instances in the patient-preferred group. Conclusion: The patient-preferred self-titration algorithm demonstrates a higher rate of reaching glucose targets and improved adherence. Trial Registration Number: ChiCTR2100050805.

A maternal low-protein diet impaired glucose metabolism and altered the lncRNA profiles of islets in adult offspring.

A maternal low-protein diet during pregnancy can increase children's susceptibility to diabetes mellitus in adulthood. However, whether long noncoding RNAs (lncRNAs) in islets participate in the development of diabetes in adult offspring following maternal protein restriction is not fully understood. Female mice were fed a low-protein (LP) diet or control diet throughout gestation and lactation. The male offspring were then randomly divided into two groups according to maternal diet: offspring from control diet group dams (Ctrl group) and offspring from LP group dams (LP group). We observed the glucose metabolism of adult offspring. A lncRNA microarray was constructed for the islets from the LP group and Ctrl group to explore the differently expressed lncRNAs. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analyses were subsequently used to predict the functions of the differently expressed lncRNAs. The body weight from birth to 12 weeks of age was significantly lower in the LP offspring. Adult LP offspring exhibited impaired glucose tolerance and decreased insulin secretion, consistent with the reduction in ß-cell proliferation. According to the lncRNA microarray, four lncRNAs, three upregulated lncRNAs, and one downregulated lncRNA were differently expressed in LP offspring islets compared with Ctrl offspring. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed lncRNAs were mostly associated with the hypoxia-inducible factor-1α signaling pathway. Additionally, we validated the expression of these four differentially expressed lncRNAs via quantitative real-time polymerase chain reaction. Our findings demonstrated the expression patterns of lncRNAs in islets from adult offspring of mothers who consumed a maternal low-protein diet.

Cutoffs of different body measurement indexes of central obesity in patients with type 2 diabetes.

Few research discuss whether the body measurement indexs of obesity in general populations is applicable to patients with type 2 diabetes. We explore the optimal cutoffs of visceral fat area (VFA) and subcutaneous fat area (SFA) in the diagnosis of central obesity and the cutoffs of corresponding waist circumference (WC) and body mass index (BMI) in patients with Type 2 Diabetes (T2D). Cross-sectional cohort study. 1057 patients with T2D (550 males and 507 females) aged 18 or above that satisfied the criteria were included. The definition and diagnostic criteria of Metabolic syndrome (Mets) were analyzed according to the 2020 Chinese Diabetes Society (CDS) Guideline. The VFA and SFA were measured by bioelectrical impedance analysis (BIA). The optimal VFA and SFA cutoffs and corresponding WC and BMI when two or more nonadipose components of MetS (without central obesity) were met were analyzed by ROC curve. Among all of the T2D patients, the optimal VFA cutoff for identifying two or more nonadipose components of MetS was 73.30 cm2 for females and 69.20 cm2 for males, while the optimal SFA cutoff was 186.70 cm2 for females and 123.30 cm2 for males. The ROC area under curve (AUC) of VFA for identifying two or more nonadipose components of MetS was higher than that of SFA (Female: 0.65 vs. 0.58, P = 0.01). The VFA cutoff of newly diagnosed T2D patients (females = 86.10 cm2, males = 69.00 cm2) was higher than that of non-newly diagnosed T2D patients (females = 73.30 cm2, males = 65.40 cm2). A stratification analysis of gender and whether newly diagnosed with T2D or not showed that the WCs corresponding to VFA were 85.00 cm and BMI was about 24.00 kg/m2. VFA measured by BIA can be a non-invasive method to detect central obesity in patients with T2D, the corresponding WC were 85.00 cm and BMI was 24.00 kg/m2.

Sestrin2 in diabetes and diabetic complications.

Diabetes is a global health problem which is accompanied with multi-systemic complications. It is of great significance to elucidate the pathogenesis and to identify novel therapies of diabetes and diabetic complications. Sestrin2, a stress-inducible protein, is primarily involved in cellular responses to various stresses. It plays critical roles in regulating a series of cellular events, such as oxidative stress, mitochondrial function and endoplasmic reticulum stress. Researches investigating the correlations between Sestrin2, diabetes and diabetic complications are increasing in recent years. This review incorporates recent findings, demonstrates the diverse functions and regulating mechanisms of Sestrin2, and discusses the potential roles of Sestrin2 in the pathogenesis of diabetes and diabetic complications, hoping to highlight a promising therapeutic direction.

Correlation between thyroid function, sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease in euthyroid subjects with newly diagnosed type 2 diabetes.

PURPOSE: To estimate the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and to evaluate the associations between thyroid parameters, MAFLD and liver fibrosis in euthyroid patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: Overall, 776 patients with newly diagnosed T2DM and 120 subjects without diabetes were included. All the participants were euthyroid, and were categorized as non-MAFLD and MAFLD. Demographic information, biochemical parameters, and serum thyroid hormones were collected. The thyroid hormone sensitivity indices were calculated. MAFLD was defined according to abdominal ultrasound and clinical manifestations. Noninvasive fibrosis indices were calculated to identify advanced liver fibrosis. RESULTS: The prevalence of MAFLD was significantly higher in patients with T2DM than in subjects without diabetes. Levels of free triiodothyronine (FT3) and FT3 to free thyroxine (FT4) ratio were significantly higher in subjects with MAFLD. In patients with T2DM, levels of thyroid stimulating hormone (TSH), Thyroid feedback quantile-based index (TFQIFT3) calculated using FT3 and TSH, thyrotroph T3 resistance index (TT3RI) and thyrotroph T4 resistance index (TT4RI) were significantly higher in subjects with MAFLD. The prevalence of MAFLD increased with the rise of FT3, FT3/FT4, TSH, and sensitivity to thyroid hormone indices (TFQIFT3, TT3RI, and TT4RI). But significant correlations were not found between thyroid hormones, sensitivity to thyroid hormones and MAFLD, after adjustment for BMI and HOMA-IR. The incidence of advanced fibrosis tended to increase as the rise of TSH and sensitivity to thyroid hormone indices (TFQIFT3, TT3RI, TT4RI, and TSHI). CONCLUSION: MAFLD was prevalent in euthyroid patients with newly diagnosed T2DM. Higher normal FT3, TSH and impaired sensitivity to thyroid hormones are associated with increased incidence of MAFLD, being dependent on other metabolic factors.

Efficacy and safety of basal-bolus insulin at 1:1.5 ratio compared to 1:1 ratio using a weight-based initiation and titration (WIT2) algorithm in hospitalized patients with type 2 Diabetes: a multicenter, randomized, clinical study.

BACKGROUND: Most studies initiated basal-bolus insulin in a ratio of 1:1 and titrated based on glucose. This study aimed to investigate the effectiveness and safety of a weight-based and ratio of 1:1.5 basal-bolus insulin using an algorithm for both initiation and titration in hospitalized patients with type 2 diabetes (T2D). METHODS: Hospitalized patients with T2D were randomly assigned to two groups in equal numbers to receive 1:1.5 and 1:1 ratios of basal-bolus insulin using a weight-based algorithm for both initiation and titration. The primary outcome was the time taken to reach the fasting blood glucose (FBG) target and 2-h postprandial blood glucose (2hBG) targets after three meals. The secondary outcome included insulin dosage to achieve glycemic control and the incidence of hypoglycemia during hospitalization. RESULTS: 250 patients were screened between October 2021 and June 2022, 220 were randomly grouped, and 182 completed the trial (89 in the 1:1.5 and 93 in the 1:1 groups). The time taken to reach FBG targets was comparable between the two groups (3.4 ± 1.7 vs. 3.0 ± 1.3 days, p = 0.137) within about 3 days. The 2hBG after three meals was shorter in the 1:1.5 group than in the 1:1group (2.9 ± 1.5 vs. 3.4 ± 1.4 days, p = 0.015 for breakfast, 3.0 ± 1.6 vs. 3.6 ± 1.4 days, p = 0.005 for lunch, and 3.1 ± 2.1 vs. 4.0 ± 1.5 days, p = 0.002 for dinner). No significant difference in insulin dosages was found between the two groups at the end of the study. The incidence of hypoglycemia was similar in both groups. CONCLUSIONS: We demonstrated that fixed dose-ratio basal-bolus insulin at 1:1.5 calculated using a weight-based initiation and titration algorithm was simple, as effective, and safe as ratio at 1:1 in managing T2D in hospitalized patients. Trial Registration ChiCTR 2,100,050,963. Date of registration: September 8, 2021.

The impact of tumor characteristics on cardiovascular disease death in breast cancer patients with CT or RT: a population-based study.

Background: Previous studies focused on the impact of cardiovascular diseases (CVD) risk factors in breast cancer patients with chemotherapy (CT) or radiotherapy (RT). This study aimed to identify the impact of tumor characteristics on CVD death in these patients. Methods: Data of female breast cancer patients with CT or RT between 2004 and 2016 were included. The risk factors of CVD death were identified using Cox regression analyses. A nomogram was constructed to evaluate the predicted value of tumor characteristics, and then validated by the concordance indexes (C-index) and calibration curves. Result: A total of 28,539 patients were included with an average follow-up of 6.1 years. Tumor size > 45 mm (adjusted HR = 1.431, 95% CI = 1.116-1.836, P = 0.005), regional (adjusted HR = 1.278, 95% CI = 1.048-1.560, P = 0.015) and distant stage (adjusted HR = 2.240, 95% CI = 1.444-3.474, P < 0.001) were risk factors of CVD death for breast cancer patients with CT or RT. The prediction nomogram of tumor characteristics (tumor size and stage) on CVD survival was established. The C-index of internal and external validation were 0.780 (95% Cl = 0.751-0.809), and 0.809 (95% Cl = 0.768-0.850), respectively. The calibration curves showed consistency between the actual observation and nomogram. The risk stratification was also significant distinction (P < 0.05). Conclusion: Tumor size and stage were related to the risk of CVD death for breast cancer patients with CT or RT. The management of CVD death risk in breast cancer patients with CT or RT should focus not only on CVD risk factors but also on tumor size and stage.

Inhibition of Sestrin2 overexpression in diabetic cardiomyopathy ameliorates cardiac injury via restoration of mitochondrial function.

Mitochondrial dysfunction-induced apoptosis plays a crucial role in the progression of diabetic cardiomyopathy (DCM). Sestrin2 is an important oxidative stress response protein and is involved in the maintenance of mitochondrial function, especially under stress. The aim of the present study was to investigate the role of Sestrin2 in DCM and to explore the underlying mechanisms. H9c2 cardiomyocytes were induced with high glucose (HG) medium (33 mmol/l glucose) for an in vitro DCM model. C57BL/6 mice were induced for the in vivo DCM model by intraperitoneal streptozotocin injection. H9c2 cardiomyocytes were exposed to HG and infected with lentiviruses to express Sestrin2 short hairpin RNA (shRNA). The study found that cell viability and mitochondrial function were impaired while cell apoptosis and oxidative stress were increased in DCM. Sestrin2 was significantly upregulated in myocardial tissues of DCM mice and H9c2 cardiomyocytes in HG conditions. Downregulation of Sestrin2 increased cell viability, decreased cell apoptosis, and attenuated oxidative stress in H9c2 cells exposed to HG. Moreover, HG-induced mitochondrial injury was alleviated by Sestrin2 silencing. In conclusion, our finding indicated that the inhibition of enhanced Sestrin2 expression ameliorates cardiac injury in DCM, which might be largely attributed to the restoration of mitochondrial function.

RHOA G17V induces T follicular helper cell specification and involves angioimmunoblastic T-cell lymphoma via upregulating the expression of PON2 through an NF-κB-dependent mechanism.

Angioimmunoblastic T-cell lymphoma (AITL) is a malignant hematologic tumor arising from T follicular helper (Tfh) cells. High-throughput genomic sequencing studies have shown that AITL is characterized by a novel highly recurring somatic mutation in RHOA, encoding p.Gly17Val (RHOA G17V). However, the specific role of RHOA G17V in AITL remains unknown. Here, we demonstrated that expression of Rhoa G17V in CD4+ T cells increased cell proliferation and induces Tfh cell specification associated with Pon2 upregulation through an NF-κB-dependent mechanism. Further, loss of Pon2 attenuated oncogenic function induced by genetic lesions in Rhoa. In addition, an abnormality of RHOA G17V mutation and PON2 expression is also detected in patients with AITL. Our findings suggest that PON2 associated with RHOA G17V mutation might control the direction of the molecular agents-based AITL and provide a new therapeutic target in AITL.

Evaluation of the Thyroid Characteristics and Correlated Factors in Hospitalized Patients with Newly Diagnosed Type 2 Diabetes.

Background: Diabetes mellitus (DM) and thyroid dysfunction (TD) are two closely associated disorders. The objective of the present study was to investigate the thyroid status and the relationships between thyroid hormones, diabetic complications and metabolic parameters in hospitalized patients with newly diagnosed type 2 DM (T2DM). Methods: This was an observational cross-sectional study, conducting on 340 patients with newly diagnosed T2DM who were admitted to ward of endocrinology department and 120 matched individuals without diabetes. Anthropometric, clinical and biochemical data were collected. Spearman correlation coefficients were calculated to evaluate the correlations between thyroid hormones and other variables. Factors associated with diabetic nephropathy (DN) was analyzed with multivariate logistic regression. Results: Levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were significantly lower in patients with T2DM as compared to control group without diabetes. The prevalence of TD was 21.2% in patients with diabetes, higher than that in controls (4.2%). The low T3 syndrome was the most frequent TD, shown in 14.7% of patients. The presence of diabetic complications DN, diabetic ketosis or ketoacidosis), metabolic and demographic factors, including age, glycemic control and insulin resistance were factors significantly associated with levels of thyroid hormones. FT3 level was inversely correlated with the level of urinary total protein (mg/24h) and the presence of DN. Multivariate analysis indicated low FT3 level as a strong independent risk factor (OR = 0.364, P = 0.001) for DN. Conclusion: TD is not rarely seen in hospitalized patients with newly diagnosed T2DM. Diabetic complications and diabetes-related metabolic and demographic factors are related to thyroid hormone levels. Decreased FT3 is strongly correlated with the presence of DN.