Bone mineral density in adults growth hormone deficiency with different ages of onset: a real-world retrospective study.

PURPOSE: Bone mineral density (BMD) impairment is one of the critical factors for long-term quality of life in adults growth hormone deficiency (AGHD). This study aims to investigate the annual changes in BMD in AGHD patients with different ages of onset and to identify predicting factors that influence BMD. METHODS: AGHD patients (n = 160) with available data for 4 years follow-up from a major tertiary medical center in China were retrospectively included (110 [68.8%] childhood-onset, 119 [74.4%] male). BMD of the axial bone (including total hip, neck of femur, and L1-4) derived from dual X-ray absorptiometry and final height were investigated at the first visit, 12 months, 24 months, 36 months, and 48 months thereafter. Low BMD was defined as Z-score ≤ -2. RESULTS: The prevalence of low BMD was 30.0% at baseline and 12.5% at 4 years of follow-up. The CO AGHD group presented a significantly lower BMD than the AO AGHD group at the baseline (P = 0.009). In contrast, the CO AGHD group had significantly greater median annual BMD change than the AO AGHD group (0.044 vs. -0.0003 g/cm2/year in L1-4, P < 0.001), indicating a significant difference in the overall BMD trend between CO and AO groups. Childhood-onset (odds ratio [OR] 0.326, P = 0.012), low serum testosterone (OR 0.847; P = 0.004) and FT4 (OR 0.595; P = 0.039) level were independent risk factors for BMD loss. CONCLUSION: The annual changes of BMD show a different pattern in AGHD patients with varying ages of onset. Patients with CO AGHD have a lower bone mass, and in general, appropriate replacement therapy is necessary for long-term bone health in AGHD patients.

Geriatric nutritional risk index is correlated with islet function but not insulin resistance in elderly patients with type 2 diabetes: A retrospective study.

The geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that can predict poor prognosis in elderly subjects. The aim of this study was to evaluate the association between GNRI and both islet function and insulin sensitivity in patients with type 2 diabetes mellitus. This research carries significant implications for the integrated treatment and nutritional management of this patient population. A total of 173 patients with type 2 diabetes mellitus, aged 60 years or older, who were hospitalized in the Endocrinology Department at Hebei General Hospital from February 2018 to June 2021, were selected as the research subjects. These subjects were divided into 4 groups according to the quartile of their GNRI values: T1 (GNRI < 99.4, n = 43), T2 (99.4 ≤ GNRI < 103, n = 43), T3 (103 ≤ GNRI < 106.3, n = 43), and T4 (GNRI ≥ 106.3, n = 44). Glucose, insulin, and C-peptide concentrations were tested at 0, 30, 60, 120, and 180 minutes during a 75 g oral glucose tolerance test. The homeostasis model assessment for insulin resistance and the homeostasis model assessment for ß cell function index were calculated. As the GNRI value increased, the levels of total protein, albumin, hemoglobin, alanine transaminase, aspartate aminotransferase, and 25-hydroxyvitamin D increased significantly. The area under the curve for blood glucose decreased significantly across the 4 groups, while the AUCs for insulin and C-peptide showed an overall increasing trend. ß Cell function index increased significantly with the increase of GNRI; meanwhile, both the early-phase insulin secretion index and the late-phase insulin secretion index increased significantly. Although there was an increasing trend, homeostasis model assessment for insulin resistance did not change significantly among the 4 groups. This study indicates that elderly type 2 diabetes patients with higher nutritional risk have worse islet function, while insulin sensitivity is not associated with nutritional risk.

SIRT3 rs11246020 Polymorphism Associated Postprandial Triglyceride Dysmetabolism.

Purpose: Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism. Patients and Methods: 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism. Results: In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219-0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032). Conclusion: The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.

Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer.

Introduction: Emerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgently needed. Methods: The high-throughput natural compounds screen was performed to screen the important compounds. A rat HFHF model was constructed, the regulatory function of Oxymatrine in HFHF-induced obesity was further explored. Results: We identified Oxymatrine, a natural compound extracted from Sophora flavescens, showed a potential compacity in high-fat diet-induced fatty liver disease. We found that oxymatrine significantly inhibited HFHF-induced obesity using a rat HFHF model. Additionally, we found that oxymatrine altered the enhancer landscape of subcutaneous adipose tissues by ChIP-seq analysis using antibodies against the H3K27ac histone modification. Motif enrichment analysis showed the Smad motif was significantly enriched in enhancers altered post-oxymatrine treatment. Further chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis and luciferase reporter assays showed oxymatrine alters the binding of Smad3 on the enhancer regions of B-cell lymphoma 2 (Bcl2) and the enhancer activity of Bcl2. Discussion: Together, our study highlighted oxymatrine could suppress high-fructose and high-fat diet-induced obesity by inhibiting the suppressor of mothers against decapentaplegic 3 (Smad3) binding on obesity-related enhancers.

Retinal Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM. Results: Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001). Conclusion: Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.

The effect of statins on bone turnover biomarkers: a systematic review and meta-analysis of randomized controlled trials.

Few studies have considered the effect of statins on bone turnover biomarker levels and the results of these studies are inconsistent. Here we performed a meta-analysis of the effect of statins on bone turnover biomarker levels. We used keywords, free words, and related words that included the terms "hydroxymethylglutaryl-CoA reductase inhibitors," "statin," and "bone turnover biomarkers" to search PubMed, Cochrane Library, and Embase. The Cochrane Risk Bias Evaluation Tool was used to evaluate the risk of bias, and Review Manager 5.3 and Stata 13.0 were used for statistical analyses. Six randomized controlled trials involving a total of 382 subjects were included in the meta-analysis. The results showed that statins increased the osteocalcin (OC) [mean difference (MD) = 0.73 ng/mL, 95% CI: 0.12, 1.35, I2 = 23% and p = 0.26], and decreased cross-linked N-telopeptide (NTX) (MD = -1.14 nM BCE, 95% CI: -2.21, -0.07, I2 = 0%, p = 0.53) and C-terminal peptide of type I collagen (CTX) (MD = -0.03 ng/mL, 95% CI: -0.05, -0.01, I2 = 0% and p = 0.56). There was no effect on bone-specific alkaline phosphatase (MD = -1.37 U/L, 95% CI: -3.09, 0.34, I2 = 0% and p = 0.94) and intact parathyroid hormone (MD = -1.73 pg/mL, 95% CI: -4.35, 0.89, I2 = 0% and p = 0.77). Statins increase bone formation biomarker OC and decrease bone resorption biomarker NTX and CTX levels.

Association between hemoglobin glycation index and non-alcoholic fatty liver disease.

Objective: The hemoglobin glycation index (HGI) reflects biological variability in hemoglobin A1c. Even so, studies on the relationship between HGI and non-alcoholic fatty liver disease (NAFLD) are limited. Therefore, this study aimed to explore the relationship between HGI and NAFLD. In addition, the study also aimed to provide new methods to identify patients with a high risk for the development of NAFLD. Methods: This was a retrospective study based on physical examination data from Japan. Patients were divided into quartiles (Q1-Q4) according to their HGI level; the lowest quartile (Q1) was used as the reference group. Patents were also classified into two subgroups based on the presence or absence of NAFLD. Baseline characteristics between the groups were compared. Multivariate logistic regression analysis was used to investigate the association between the HGI and NAFLD. A mediation analysis examined the mediation relationship between HGI and NAFLD. Subgroup analyses were performed to the reliability of the results. Results: A total of 14280 patients were eligible for inclusion in this study; 2515 had NAFLD. Patients in the NAFLD group had higher levels of HGI than patients in the non-NAFLD group. Increases in HGI correlated with an increased risk of NAFLD. After adjusting for confounding factors, the multivariate logistic regression analysis revealed that HGI was positively related to the prevalence of NAFLD. In addition, mediation analysis showed that body mass index (BMI) partly mediated the indirect impact of HGI on NAFLD preference. Subgroup analyses were performed according to age, sex, smoking status, and waist circumference. Our results indicated that HGI significantly correlated with NAFLD in patients with one of the following factors: age ≤60 years, BMI >28 kg/m2, female sex, a history of smoking, and abdominal obesity. Conclusions: HGI was an independent risk factor for NAFLD, and BMI partly mediated the association between HGI and NAFLD.

Association Between Serum Vitamin D Levels and Ketosis Episodes in Hospitalized Patients with Newly Diagnosed Ketosis-Prone Type 2 Diabetes.

Purpose: This study aimed to investigate the relationship between 25-hydroxyvitamin D (25OHD) and the onset of ketosis in newly diagnosed patients with ketosis-prone type 2 diabetes (KPT2D). Patients and Methods: A total of 162 patients with non-autoimmune newly diagnosed diabetes mellitus were included in this cross-sectional study. Patients were classified into KPT2D (n = 71) or non-ketotic type 2 diabetes (NKT2D, n = 91). Anthropometric parameters, islet functions, biochemical parameters, and body composition were determined in both KPT2D and NKT2D groups. Correlation analysis was performed to determine the associations between 25OHD and plasma ketones. The risk factors associated with ketosis episodes in patients with new-onset KPT2D were evaluated using binary logistic regression analysis. Results: Vitamin D deficiency was observed in both patients with KPT2D and NKT2D. Compared with the NKT2D group, serum 25OHD values were lower in the participants of the KPT2D group [14.20 (10.68, 19.52) vs 16.98 (13.54,2.96) ng/mL, P = 0.011]. Serum 25OHD was associated with plasma ketones (R = -0.387). Serum 25OHD is an independent protective factor for ketosis or ketoacidosis episodes in patients with new onset of KPT2D (P = 0.037, OR = 0.921). Conclusion: Vitamin D levels are associated with ketosis episodes in patients with KPT2D. Serum 25OHD is an independent protective factor for ketosis episodes in patients with KPT2D.

Circulating Bone Morphogenetic Protein-9 is Decreased in Patients with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease.

Objective: We aimed to examine the association between bone morphogenetic protein-9 (BMP-9) and type 2 diabetes mellitus (T2DM) in conjunction with non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) and to identify evidence supporting the potential role of BMP-9 in the clinical prevention and treatment of T2DM in conjunction with NAFLD. Methods: One hundred and twenty subjects were included in this study. We sorted all of the subjects into four groups of equal size (n=30 each). A trained expert assessed the height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the subjects and computed the body mass index (BMI). All subjects had their fasting blood glucose (FBG), fasting insulin (FINS), serum BMP-9, and biochemical indices assessed. Results: Significant variations were observed in BMI, SBP, DBP, ALT, TC, TG, HDL-C, LDL-C, ApoB, FBG, FINS, HOMA-IR, and serum BMP-9 among the four groups (P<0.05). The level of serum BMP-9 was positively correlated with HDL-C, while the level of serum BMP-9 was negatively correlated with BMI, SBP, DBP, ALT, TC, TG, LDL-C, FBG, FINS, and HOMA-IR. Multiple stepwise regression analyses revealed that FINS, LDL-C, HDL-C, and BMI were independent factors impacting serum BMP-9 levels (P<0.05). Logistic regression analyses revealed that BMP-9 was a protective factor for T2DM paired with NAFLD, while HOMA-IR was a risk factor. Conclusion: Serum BMP-9 levels are significantly lower in the T2DM+NAFLD group when compared to other groups, and BMP-9 is an independent risk factor for T2DM paired with NAFLD.

The Relationships Between Glycated Hemoglobin and Bone Turnover Markers in Patients with Type 2 Diabetes but No Diabetic Nephropathy.

Purpose: To investigate the relationships between glycated hemoglobin (HbA1c) level and bone turnover markers (BTMs) in patients with type 2 diabetes mellitus (T2DM) but no diabetic nephropathy. Patients and Methods: Patients with T2DM were recruited at Hebei General Hospital in China. The participants were allocated to three groups: an HbA1c <7% group, an HbA1c 7%-9% group, and an HbA1c ≥9% group. Their general characteristics, biochemical indices, and BTM concentrations were recorded. Results: The ages of the HbA1c <7% group and the HbA1c 7%-9% group were significantly higher than that of the HbA1c ≥9% group (P<0.05). The prevalence of a history of hypertension in the HbA1c 7%-9% group was significantly higher than that in the HbA1c ≥9% group. The circulating low-density lipoprotein-cholesterol concentration in the HbA1c ≥9% group and the apolipoprotein B concentration in the HbA1c 7%-9% group were significantly higher than those in the HbA1c <7% group (P<0.05). Compared with that in the HbA1c <7% group, the circulating 25-hydroxyvitamin D (25OHD) concentration was significantly lower in the HbA1c ≥9% group (P<0.05). Additionally, the circulating 25OHD and osteocalcin (OC) concentrations negatively correlated with HbA1c (P<0.05). Conclusion: An increase in HbA1c is associated with gradual decreases in the circulating concentrations of 25OHD and OC.

Quantitative proteomics analysis based on tandem mass tag labeling coupled with labeling coupled with liquid chromatography-tandem mass spectrometry discovers the effect of silibinin on non-alcoholic fatty liver disease in mice.

In recent years, the beneficial effects of silibinin (SIL) on nonalcoholic fatty liver disease (NAFLD) have attracted widespread attention. We tried to study the intervention effect of SIL on NAFLD, and explore the potential mechanisms and targets of SIL on NAFLD improvement. Thirty-three male C57BL6/J mice were divided into three groups, and, respectively, fed a normal diet (ND), a high-fat diet (HFD) or a HFD given SIL treatment (HFD+SIL). Biochemical indexes and histopathological changes of mice in each group were detected. In addition, quantitative proteomics analysis based on tandem mass tag (TMT) labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis was performed on protein changes in the livers. SIL could reduce the weight of mice, reduce liver lipid deposition, and improve glucose metabolism. Through comparison among the three experimental groups, a total of 30 overlapping proteins were found. These identified proteins were closely linked to liver lipid metabolism and energy homeostasis. Moreover, some drug targets were found, namely perilipin-2, phosphatidate phosphatase LPIN1, farnesyl pyrophosphate synthase, and glutathione S-transferase A1. In conclusions, high-fat diet increases the expressions of proteins implicated in lipid synthesis and transport in the liver, which can result in disorders of liver lipid metabolism. SIL can decrease liver lipid deposition and increase insulin sensitivity by regulating the expressions of these proteins. It not only improves the disorder of lipid metabolism in vivo, but also improves the disorder of glucose metabolism.

Thymic Carcinoid as the First Manifestation of Multiple Endocrine Neoplasia Type 1 Syndrome: A Case Report and Review of the Literature.

The present study reported a rare case with thymic carcinoid as the first manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome, which presented with gene mutations of the MEN1 and glucokinase regulatory protein (GCKR). In this report, a 40-year-old male was diagnosed as MEN1 syndrome with thymic carcinoid, pancreatic cancer, hyperparathyroidism, and insulinoma with intrahepatic metastasis. Genetic testing showed the mutations of the MEN1 (c.378 G>A, p. Trp126*) in the patient, his children and two sisters, and GCKR (c.151C>T, p. Arg51*) gene in the patient and his children. The pathological examination showed that neuroendocrine tumor (NET) of the pancreas was characterized as 6 mitoses per 10 high-power fields (HPF), infiltration of adipose tissue, no intravascular tumor thrombus and nerve infiltration. In addition, NET of the liver was characterized as 4 mitoses per 10 HPF, no intravascular tumor thrombus and nerve infiltration. Immunohistochemical staining showed Ckpan (+), Syn (+), CgA (+), CD 56 (+), PGP 9.5 (+), and Ki67-positive cells (8-10%) in NET. Therefore, we suggested that genetic testing in family members of MEN1 patient, which may be helpful for early diagnosis.

The Relationship Between Vitamin D Deficiency and Glycated Hemoglobin Levels in Patients with Type 2 Diabetes Mellitus.

PURPOSE: The aims of this study were to determine the relationship between 25-hydroxyvitamin D [25(OH) D] and glycated hemoglobin (HbA1c) levels in male and female patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: The participants were adults diagnosed with T2DM recruited from Hebei General Hospital. Patient information and information regarding blood indicators were collected. The subjects were divided into no vitamin D deficiency group [25(OH) D >20 ng/mL] and vitamin D deficiency group [25(OH) D <20 ng/mL], and these groups were then further subdivided into male-only or female-only subgroups. And then, the subjects were divided into male group and female group in different 25(OH) D levels. RESULTS: HbA1c levels in the vitamin D deficiency group were significantly higher than those in the no vitamin D deficiency group for all subjects. The same was true for female patients but not for male patients. There was no difference in HbA1c levels between male and female patients with T2DM, regardless of 25(OH) D deficiency. A negative correlation existed between 25(OH) D and HbA1c in all subjects, as well as in the male-only and female-only subgroups. Vitamin D deficiency was associated with high HbA1c levels before and after adjusting for confounding factors in all participants and in the female-only subgroup, but not in the male-only subgroup. CONCLUSION: This study confirmed that vitamin D deficiency was related with high HbA1c levels in patients with T2DM, and this relationship differs between female and male patients.

Farnesoid X receptor agonist decreases lipid accumulation by promoting hepatic fatty acid oxidation in db/db mice.

The development of type­2 diabetes and its complications is associated with lipid metabolism disorder. Farnesoid X receptor (FXR) has an important role in regulating lipid and glucose metabolism. However, the underlying mechanism of this remains unclear. The present study investigated the role of fexaramine (Fex), an FXR agonist, on lipid metabolism. For this purpose, 6­week­old db/db mice were treated with Fex for 8 weeks via oral gavage and db/db mice treated with corn oil were used as controls. Body weight and food intake were monitored daily and bi­weekly, respectively. A glucose tolerance test was performed during the final week of feeding. Blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, and liver tissues were analyzed by histology and molecular examination. The results indicated that serum and liver triglyceride levels were decreased in db/db mice administered with Fex. Fewer small lipid droplets were observed in the liver. Small heterodimer partner (SHP), a downstream gene of FXR, was upregulated following Fex treatment. The mRNA and protein expression of genes associated with fatty acid oxidation [acetyl coenzyme A carboxylase (ACC), carnitine palmitoyl transferase 1α (CPT1­α) and peroxisome proliferator­activated receptor­coactivator­1α] was also increased. Additionally, the expression of AMP­activated protein kinase (AMPK) was also increased. However, the expression of sterol­regulatory element binding protein­1c and fatty acid synthase, which are associated with fatty acid synthesis, was not significantly different. Taken together, the results of the present study suggested that activation of FXR and its downstream gene SHP may induce the AMPK­ACC­CPT1­α signaling pathway, which promotes fatty acids oxidation, ultimately achieving its lipid­lowering effect.

The association between birth weight and the risk of type 2 diabetes mellitus: a systematic review and meta-analysis.

Previous studies have shown a relationship between type 2 diabetes mellitus and birth weight. We performed this meta-analysis to resolve the problem of inconsistent results. We conducted a literature search of PubMed, Embase and the Cochrane Library using "Diabetes Mellitus, Type 2," "Birth Weight," and some related free words. Twenty-one studies were included in accordance with inclusion and exclusion criteria, involving a total of 313,165 participants and 22,341 type 2 diabetes mellitus cases. A modified version of the Newcastle-Ottawa Scale was used to evaluate the methodological quality of studies included. We used Review Manager 5.3 for data merging and statistical analysis. Results were expressed as odds ratio (OR) and 95% confidence interval (95% CI). The risk of diabetes with low birth weight (<2,500 g) was higher than that with birth weight ≥2,500 g, (OR = 1.51, 95% CI: 1.43, 1.58). Compared with normal birth weight (2,500-4,000 g), low birth weight, but not high birth weight, increased the risk of diabetes (OR = 1.41, 95% CI: 1.26, 1.58). There is a negative association between birth weight and the future risk of type 2 diabetes mellitus.

MicroRNA-802 regulates hepatic insulin sensitivity and glucose metabolism.

The expression level of microRNA-802 (miR-802) is increased in livers of high-fat diet (HFD)-fed mice and obese human subjects; however, the function of miR-802 in the development of obesity-associated insulin resistance remains incompletely understood. Here we studied the potential role of miR-802 in regulating hepatic glucose metabolism and insulin sensitivity. Mice were fed either a standard chow diet or HFD for 12 weeks, and then the HFD mice were infected by injection with an adeno-associated virus expressing miR-802 or miR-802-SP. Six weeks after the injection, we measured blood glucose, plasma insulin, and insulin sensitivity in the mice. In addition, hepatic glucose levels and PI3K-Akt pathway gene expression were analyzed. Adeno-associated viral-mediated overexpression of miR-802 in the livers of HFD mice caused impaired glucose homeostasis and insulin sensitivity, thus giving rise to decreased protein level of pAkts473 and pPI3K, and increased protein levels of pPTEN, G6PC, and GluT2. In contrast, loss of miR-802 function in the liver of HFD mice led to increased pAkts473 and pPI3K, and decreased levels of pPTEN, G6PC, and GluT2, thereby improving glucose metabolism and insulin resistance. Our findings confirmed MiR-802 as a regulator of liver glucose metabolism and insulin signaling.