OBJECTIVE To evaluate the direct impact of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the functions and viability of pancreatic β-cells. RESEARCH DESIGN AND METHODS We developed an mfat-1 transgenic mouse model in which endogenous production of n-3 PUFAs was achieved through overexpressing a C. elegans n-3 fatty acid desaturase gene, mfat-1. The islets and INS-1 cells expressing mfat-1 were analyzed for insulin secretion and viability in response to cytokine treatment. RESULTS The transgenic islets contained much higher levels of n-3 PUFAs and lower levels of n-6 PUFAs than the wild type. Insulin secretion stimulated by glucose, amino acids, and glucagon-like peptide-1 (GLP-1) was significantly elevated in the transgenic islets. When challenged with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and γ-interferon (IFN-γ), the transgenic islets completely resisted cytokine-induced cell death. Adenoviral transduction of mfat-1 gene in wild-type islets and in INS-1 cells led to acute changes in the cellular levels of n-3- and n-6 PUFAs and recapitulated the results in the transgenic islets. The expression of mfat-1 led to decreased production of prostaglandin E₂ (PGE₂), which in turn contributed to the elevation of insulin secretion. We further found that cytokine-induced activation of NF-κB and extracellular signal–related kinase 1/2 (ERK_1/2) was significantly attenuated and that the expression of pancreatic duodenal hemeobox-1 (PDX-1), glucokinase, and insulin-1 was increased as a result of n-3 PUFA production. CONCLUSIONS Stable cellular production of n-3 PUFAs via mfat-1 can enhance insulin secretion and confers strong resistance to cytokine-induced β-cell destruction. The utility of mfat-1 gene in deterring type 1 diabetes should be further explored in vivo.

Aim. To examine whether the baseline 25-hydroxyvitamin D [25(OH)D] level was predictive of the onset of prediabetes or type 2 diabetes (T2DM) in the Chinese population. Methods. This was a 4-year follow-up study that was conducted in the Chengdu region of China as part of the China National Diabetes and Metabolic Disorders Study. The study included 490 participants that were free of prediabetes and type 2 diabetes mellitus (T2DM) at baseline and had complete data by follow-up examinations. Glucose, insulin, and 25(OH)D levels were measured at baseline and at 4 years later. Prediabetes and T2DM were defined by results obtained from an oral glucose tolerance test. Results. Over a 4-year follow-up, 95 (48.5‰) developed prediabetes and 31 (15.8‰) individuals developed diabetes. Low 25(OH)D status was significantly associated with the risk of developing prediabetes [OR 3.01 (95% CI: 1.50–6.06), P=0.002] and T2DM [OR 5.61 (95% CI: 1.73–18.27), P=0.004] after adjustment for multiple potential confounders. In a multiple linear regression analysis, low baseline levels of 25(OH)D were an independent predictor of increased insulin resistance over a 4-year period (P<0.05). Conclusions. The current prospective study suggests that low 25(OH)D levels might have contributed to the incidence of prediabetes or T2DM in Chinese individuals. This trial is registered with TR-CCH-ChiCTR-OCS-09000361.

The aim of this study was to evaluate the association between gamma-glutamyltransferase (GGT) and mortality through a comprehensive analysis of existing evidence. PubMed, Embase, Chinese Biomedical Literature, and Science Citation Index databases were electronically searched. Studies were included if the study design was prospective and included reference and at-risk levels of GGT at baseline and mortality as a separate outcome. The quality of the studies included was assessed on the basis of Newcastle-Ottawa scale. Data from selected qualified studies were systematically reviewed, pooled, and analyzed according to the MOOSE guidelines and PRISMA statement. The results included the following: 1. 35 studies including 571,511 participants and 72,196 cases of mortality; 2. GGT, even at physiologic levels, was associated with increased all-cause mortality and cardiovascular mortality, and might also be associated with cancer-related mortality in the general population; and 3. GGT was very likely to be associated with all-cause mortality and cardiovascular mortality in patients with coronary artery disease and type 2 diabetes mellitus. Many of the studies included did not specifically exclude subjects with hepatic diseases or alcohol abuse, which may have obscured the results. Moderate heterogeneity was observed in the meta-analysis of GGT and all-cause mortality. Different compositions of cause-specific mortality might be the reason. However, subgroup analysis could only be performed on cardiovascular death because of insufficient information. GGT, even at physiologic high levels, predicted mortality, especially cardiovascular mortality and cancer mortality. The underlining mechanism and potential effects of GGT-targeted intervention on health warrant further investigation.

Background and Objective: Primary adrenal lymphoma is a rare, progressive, easily misdiagnosed adrenal tumor with a poor prognosis. There are limited data on its clinical characteristics, and these have been derived from small sample studies. This study aimed to identify the clinical characteristics and prognosis of primary adrenal lymphoma. Methods: This single-center study retrospectively analyzed data of 50 primary adrenal lymphoma patients treated between January 2008 and January 2018. Demographic information, biochemical indexes, computed tomography images, pathological findings, treatment regimens, and prognostic factors were analyzed. Results: The median age of onset was 60.3 years, and 30 (60.0%) of 50 patients were male. Abdominal pain was the most common symptom, followed by incidentaloma and B symptoms. On average, patients presented with elevated lactate dehydrogenase (348 IU/L, normal range 110–220 IU/L) and hydroxybutyrate dehydrogenase levels (287 IU/L, normal range 72–182 IU/L) and decreased high-density lipoprotein cholesterol levels (0.88 mmol/L, normal range > 0.9 mmol/L). Bilateral lesions in the adrenal glands were observed in 30 (60.0%) patients. Computed tomography showed that 42 (84%) patients had signs of infiltration. Diffuse large B-cell lymphoma was present in 44 (88%) patients. Immunohistochemistry revealed that 70.6% (12/17), 89.5% (17/19), 92.0% (23/25), and 68.8% (11/16) of patients were positive for MYC, p53, BCL2, and both MYC and BCL2, respectively. Combined chemotherapy was associated with a good prognosis. Conclusions: Early diagnosis of primary adrenal lymphoma depends on a combination of biochemical examination, imaging studies, and pathological biopsy, and combined chemotherapy may lead to a better prognosis.

Background: Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis. Methods: Pubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient. Results: A final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (MD=21.50 pg/ml, 95% CI (15.63, 27.37), P<0.00001) and slightly increased urinary calcium levels (MD = 1.65 mmol/24 h, 95% CI (1.24, 2.06), P < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery. Conclusions: PA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.