A novel mutation in the ABCC8 gene causing maturity-onset diabetes of the young: A case report.

A 34-year-old woman was diagnosed with type 1 diabetes mellitus and treated with insulin for 24 years. The patient has a family history of diabetes in three consecutive generations. Her Whole exon sequencing showed a heterozygous mutation in the ABCC8 gene, and it also found some of her relatives to carry this mutation. She was diagnosed with MODY12 and received glimepiride therapy with the achievement of good glycaemic control.

Magnesium Supplementation Stimulates Autophagy to Reduce Lipid Accumulation in Hepatocytes via the AMPK/mTOR Pathway.

Metabolic-associated fatty liver disease (MAFLD) (previously known as nonalcoholic fatty liver disease (NAFLD)) is a disease with high worldwide prevalence, but with limited available therapeutic interventions. Autophagy is a cell survival mechanism for clearing excess lipids in hepatocytes and affects the occurrence and development of MAFLD. In addition, some studies have shown that magnesium deficiency is common in patients with obesity and metabolic syndrome. Magnesium supplementation can effectively improve metabolism-related diseases such as obesity and fatty liver. Our study successfully constructed a cellular model of MAFLD by 1 mM free fatty acid (FFA) intervention in LO2 cells for 24 h, and there was an increase in lipid accumulation in hepatocytes after FFA intervention. Magnesium supplementation was shown to reduce lipid deposition in hepatocytes induced by FFA, and Western blotting (WB) analysis showed that magnesium supplementation could downregulate the expression of Fasn and SREBP1 and increase the expression of LPL, suggesting that magnesium can reduce lipid accumulation by reducing lipid synthesis and increasing lipid oxidation. Magnesium supplementation could affect cellular lipid metabolism by activating the AMPK/mTOR pathway to stimulate autophagy. Our results identified a relationship between magnesium and lipid accumulation in hepatocytes and showed that magnesium supplementation reduced lipid deposition in hepatocytes by activating autophagy by activating the AMPK-mTOR pathway.

Association between flavonoid and subclasses intake and metabolic associated fatty liver disease in U.S. adults: Results from National Health and Nutrition Examination Survey 2017-2018.

Background: Metabolic associated fatty liver disease (MAFLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Flavonoid is considered a promising candidate for metabolic disease prevention although few studies have explored the relationship between flavonoid intake and MAFLD. Purpose: To assess the relationship between flavonoid intake and MAFLD prevalence in the U.S. adult population. Materials and methods: The data of this cross-sectional study was obtained from National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2017-2018. Flavonoid and subclasses intake was assessed by two 24h recalls. MAFLD was diagnosed according to the consensus definitions. Multivariate logistic regression model was performed to examine the association between flavonoid intake and MAFLD with adjustments for confounders. Results: A total of 4,431 participants were included in this cross-sectional analysis. MAFLD had a weighted prevalence of 41.93% and was not associated with total flavonoid intake. A higher anthocyanin and isoflavone intake, on the other hand, was associated with a lower prevalence of MAFLD. The protective effect of higher anthocyanin intake was significant among male, Non-Hispanic White, and Non-Hispanic Asia participants. Higher isoflavone intake was associated with a lower risk of MAFLD in participants of younger (age < 50), Non-Hispanic Black, Non-Hispanic Asia, and higher HEI-2015 scores compared with the lowest quartile of isoflavone intake. Stratified analysis showed that compared with the lowest quartile of anthocyanin intake, the effect of anthocyanin intake on MAFLD varied by racial groups (P interaction = 0.02). A positive correlation existed between HDL and anthocyanidin intake (P = 0.03), whereas a negative correlation existed between FPG and isoflavone intake (P = 0.02). Conclusion: MAFLD was adversely linked with flavonoid subclasses, anthocyanin and isoflavone. This modifiable lifestyle provides a potential opportunity to prevent MAFLD. These findings promote future research into the links and mechanisms between anthocyanin and isoflavone intake and MAFLD.

Osteocalcin is associated with triglyceride glucose index rather than HOMA-IR in men with type 2 diabetes.

Introduction: The involvement of osteocalcin in the regulation of glucose tolerance in humans is controversial. We utilized a novel and practical insulin resistance surrogate, the triglyceride-glucose (TyG) index, to investigate the association between serum osteocalcin and insulin resistance in men with type 2 diabetes (T2D). Methods: This was a retrospective cross-sectional study that included 667 male patients suffering from T2D, with measurements of N-terminal mid-fragment of osteocalcin (N-MID), triglycerides (TG), fasting blood glucose (FBG) and C-peptide collected on the same day. We used the TyG index and HOMA-IR as surrogate measures for insulin resistance. Binary logistic regression models that adjust the sociodemographic characteristics and metabolism-related factors were used to assess the associations between osteocalcin and insulin resistance. Restricted cubic spline (RCS) analysis was used to test the potential non-linear relationship between N-MID and the risk of severe insulin resistance. Subgroup analysis evaluated the robustness of the association. Results: N-MID was correlated with the level of insulin resistance when quantified by the TyG index in unadjusted and adjusted binary logistic regression models (all p < 0.05), but the relationship was not observed when assessed by HOMA-IR (all p > 0.05). RCS model further confirmed that the association between N-MID and the severe insulin resistance measured by the TyG index was non-linear (P = 0.047). Subgroup analysis showed that the association was detected only in younger patients with lower BMI and poorer glycemic control, without hypertension or smoking. Conclusions: Osteocalcin was inversely associated with the TyG index in men with T2D.

Association of serum uric acid levels with COVID-19 severity.

AIMS: Hyperuricemia has attracted increasing attention. However, limited concern has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in patients with COVID-19. Therefore, we aim to explore whether patients with COVID-19 had SUA lower than normal and the relationship of SUA and the severity of COVID-19. METHODS: This was a case-control study based on 91 cases with COVID-19 and 273 age- and sex-matched healthy control subjects. We first compared SUA levels and uric acid/creatinine (UA/Cr) ratio between patients with COVID-19 and the healthy controls. Then, we examined the association of SUA levels and UA/Cr ratios with COVID-19 severity in COVID-19 cases only, defined according to the fifth edition of China's Diagnosis and Treatment Guidelines of COVID-19. RESULTS: SUA levels in patients with COVID-19 were 2.59% lower, UA/Cr ratios 6.06% lower at admission compared with healthy controls. In sex stratified analysis, levels of SUA and UA/Cr were lower in male patients with COVID-19 while only level of SUA was lower in female patients with COVID-19. Moreover, SUA and UA/Cr values were 4.27 and 8.23% lower in the severe group than that in the moderate group among male COVID-19 patients. Bivariate and partial correlations analysis showed negative correlations between SUA or UA/Cr ratio and COVID-19 after adjusting for age, sex, BMI and eGFR. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent risk factors associated with lower SUA levels. Male patients with COVID-19 accompanied by low SUA levels had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11, 14.72) at admission. Comparing SUA and UA/Cr ratio at three time points (admission, discharge, and follow-up), we found that male patients experienced severe symptoms had lower SUA and UA/Cr ratio levels comparing to moderate patients, but no significant difference between three time points. On the contrary, female patients had lower SUA and UA/Cr ratio at discharge than those at admission, but no significant difference of SUA and UA/Cr ratio between moderate and severe group. CONCLUSION: Patients with COVID-19 had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher crude risk of developing severe symptoms than those with high SUA levels. During disease aggravation, the level of SUA gradually decreased until discharge. At the follow-up exam, the level of SUA was similar to the levels at admission.

Effects of sevoflurane on NF-кB and TNF-α expression in renal ischemia-reperfusion diabetic rats.

BACKGROUND: Ischemia-reperfusion (I/R) injury is the main reason of acute renal failure. However, inflammatory response and cell apoptosis are important mechanisms implicated in I/R injury. Recent studies indicated that nuclear factor kappa B (NF-кB) and tumor necrosis factor α (TNF-α) are both involved in these mechanisms. Sevoflurane reduces NF-кB and TNF-α expression in rats' heart and decreases their renal I/R injury. However, few studies are available regarding the effect of sevoflurane on kidney of diabetic rats. Therefore, the aim of this study was to evaluate sevoflurane effect on NF-кB and TNF-α expression in diabetic rats to decrease renal I/R injury. METHODS: Male Sprague-Dawley rats were divided into five groups: Group A, non-diabetic rats underwent sham operation; Group B, non-diabetic rats with renal I/R injury; Group C, diabetic rats underwent sham operation; Group D, diabetic rats with renal I/R injury; Group E, diabetic rats with renal I/R injury after sevoflurane pretreatment. Rats of Group E were exposed to 2.5% sevoflurane for 30 min. After 24 h, creatinine (Cr), blood urea nitrogen (BUN), renal cell apoptosis, and NF-кB and TNF-α expression in kidney were assessed. RESULTS: Renal cell apoptosis, NF-кB, and TNF-α expression were significantly higher in diabetic rats with renal I/R injury group compared to diabetic rats that underwent sham operation (P < 0.01). These changes were significantly reduced by sevoflurane (P < 0.01). CONCLUSION: Sevoflurane exerted a protective effect against renal injury by lowering the expression of NF-кB and TNF-α in renal I/R diabetic rats.

Expression of prostaglandin E2 and EP receptors in human papillary thyroid carcinoma.

The objective of the present study is to determine the role of prostaglandin E2 (PGE2) and downstream EP receptors in the development of human papillary thyroid carcinoma (PTC). A total of 90 thyroid specimens excised from patients undergoing total or subtotal thyroidectomy in the Department of General Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, China, from August 2013 to September 2014, were analyzed. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical analyses were employed to examine the messenger RNA (mRNA) and protein expression, respectively. The expressions and significances of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), PGE2, and EP receptors in PTC and nodular goiter were investigated. The COX-2 mRNA and protein expression level significantly increased in the PTC tissues than in the paired noncarcinoma tissues adjacent to the PTC or nodular goiter tissues. The mPGES-1 protein expression was also significantly upregulated in the PTC tissues. All the four subtypes of EP receptors (EP1-4) could express in the thyroid tissues, while only the EP4 mRNA and protein levels significantly increased in the PTC tissues. The local production of PGE2 had a higher-level expression in the PTC tissues than in the noncarcinoma thyroid tissues adjacent to the PTC lesion and the benign nodular goiter tissues. The induction of PGE2 biosynthesis as well as the overexpression of EP4 in PTC suggested that this pathway might play an important role in the carcinogenesis and progression of PTC. These observations raise the possibility that pharmacological inhibition of mPGES-1 and/or EP4 may hold therapeutic promise in this common cancer.

Ketosis onset type 2 diabetes had better islet ß-cell function and more serious insulin resistance.

Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, ß-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal ß-cell function (HOMA-ß) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P = 0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC(0-0.5), AUC0₋1, AUC0₋3 (P < 0.05). Moreover, this group also had higher HOMA-ß and HOMA-IR than nonketotic group (P < 0.05). From these data, we concluded that ketosis onset T2DM had better islet ß-cell function and more serious insulin resistance than nonketotic onset T2DM.

[Insulin sensitivity and beta cell function in female systemic lupus erythematosus patients].

OBJECTIVE: To investigate insulin sensitivity and beta cell function in female systemic lupus erythematosus (SLE) patients with different glucose tolerances. METHODS: Insulin sensitivity and beta cell function were compared between SLE patients and non-SLE subjects in the states of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) respectively. Furthermore, risk factors for insulin sensitivity and beta cell function in SLE patients were analysed by linear regression. RESULTS: In NGT state, insulin sensitivity and beta cell function of newly diagnosed SLE patients without glucocorticoids treatment were not significantly different from those of normal control group (P < 0.05). Compared with newly diagnosed SLE patients without glucocorticoids treatment and normal control group, HOMA insulin resistance index (HOMA-IR), ln (HOMA-ß), ln (early phase insulin secretion index, EISI) and ln (late phase insulin secretion index, LISI) of SLE patients with glucocorticoids treatment were significantly higher (1.91 ± 1.04 vs 0.81 ± 0.75, 0.94 ± 0.27; 5.05 ± 0.65 vs 4.01 ± 0.63, 4.23 ± 0.47; 3.14 ± 0.81 vs 2.42 ± 0.39, 2.50 ± 0.65; 2.30 ± 0.55 vs 1.62 ± 0.57, 1.56 ± 0.43; P < 0.05), while ln (Matsuda index, MI) was significantly lower (4.53 ± 0.54 vs 5.27 ± 0.68, 5.18 ± 0.38; P < 0.05). In IGT and DM state, HOMA-IR (2.84 ± 1.87 vs 1.82 ± 1.22, 3.18 ± 2.29 vs 2.94 ± 2.26) and ln (HOMA-ß) (5.18 ± 0.93 vs 4.06 ± 0.58, 3.99 ± 1.04 vs 3.43 ± 0.83) were significantly higher in SLE patients with glucocorticoids treatment than those of non-SLE subjects (P < 0.05) respectively. BMI and ln (daily glucocorticoids doses) were independent risk factors for insulin sensitivity, and age, the SLE disease activity index (SLEDAI) and ln (daily glucocorticoids doses) were related factors beta cell function. CONCLUSION: In NGT, IGT and DM state, SLE female patients with glucocorticoids treatment have reduced insulin sensitivity and increased beta cell function, these changes are related to the use of glucocorticoids.