The antibacterial activity of a novel NK-lysin homolog and its molecular characterization and expression in the striped catfish, Pangasianodon hypophthalmus.

Aeromonas hydrophila was a common bacterial pathogen in aquaculture resulting in considerable losses to the striped catfish aquaculture industry. As an emergent antimicrobial peptide (AMP), NK-lysin (NKL) had activity against various microorganisms. However, the antibacterial activity of NKL from striped catfish (Pangasianodon hypophthalmus) both in vitro and vivo remains unclear. In this study, the cDNA sequence of P. hypophthalmus NK-lysin gene (PhNK-lysin) was cloned and characterized. The amino acid sequence of PhNK-lysin contains a signal peptide sequence of 17 amino acid (aa) residues and a mature peptide composed of 130 aa. The saposin B domain of mature peptide comprised six conserved cysteines forming three putative disulfide bonds. Phylogenetic analysis revealed that the PhNK-lysin was most closely related to that of the channel catfish (Ictalurus punctatus) NK-lysin. The transcriptional levels of the PhNK-lysin were significantly upregulated in response to A. hydrophila infection in various tissues including heart, liver, spleen, head kidney, trunk kidney and gill. The synthetic PhNK-lysin-derived peptide consisting of 38aa showed antibacterial activity against Vibrio harveii, Aeromonas hydrophila and Escherichia coli. The MIC for V. harveii, A. hydrophila and E. coli were 15.625 µM, 250 µM and 31.25 µM respectively. Besides, the synthetic PhNK-lysin decreased the bacterial load of liver and trunk kidney in vivo as well as increased the survival rate of A. hydrophila infected striped catfish. Hence, these data suggest that PhNK-lysin had antimicrobial effect and protects the host from pathogenic infection.

Diagnosis and genetic analysis of a case with Bardet-Biedl syndrome caused by compound heterozygous mutations in the BBS12 gene.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.

Intergeneric Relationships within the Family Salicaceae s.l. based on Plastid Phylogenomics.

Many Salicaceae s.l. plants are recognized for their important role in the production of products such as wood, oils, and medicines, and as a model organism in life studies. However, the difference in plastid sequence, phylogenetic relationships, and lineage diversification of the family Salicaceae s.l. remain poorly understood. In this study, we compare 24 species representing 18 genera of the family. Simple sequence repeats (SSRs) are considered effective molecular markers for plant species identification and population genetics. Among them, a total of 1798 SSRs were identified, among which mononucleotide repeat was the most common with 1455 accounts representing 80.92% of the total. Most of the SSRs are located in the non-coding region. We also identified five other types of repeats, including 1750 tandems, 434 forward, 407 palindromic, 86 reverse, and 30 complementary repeats. The species in Salicaceae s.l. have a conserved plastid genome. Each plastome presented a typical quadripartite structure and varied in size due to the expansion and contraction of the inverted repeat (IR) boundary, lacking major structural variations, but we identified six divergence hotspot regions. We obtained phylogenetic relationships of 18 genera in Salicaceae s.l. and the 24 species formed a highly supported lineage. Casearia was identified as the basal clade. The divergence time between Salicaceae s.l. and the outgroup was estimated as ~93 Mya; Salix, and Populus diverged around 34 Mya, consistent with the previously reported time. Our research will contribute to a better understanding of the phylogenetic relationships among the members of the Salicaceae s.l.

Looking for agonists of ß2 adrenergic receptor from Fuzi and Chuanwu by virtual screening and dual-luciferase reporter assay.

More and more studies demonstrated that ß2 adrenergic receptor (ß2-AR) plays a crucial role for the treatment of heart failure. Chuanwu and Fuzi have been used over thousands of years in China for the treatment of heart failure. Considering the effects of these herbs are very similar to ß2-AR agonists, we presume whether ß2-AR agonists can be found from Fuzi and Chuanwu. Fuzi and Chuanwu decoction were used to receive the luciferase reporter activity assay to verify the hypothesis, and the result is positive and encouraging. For it is very difficult to get all of the monomer compounds of Fuzi and Chuanwu, virtual screening was used to find potential ß2-AR agonists and a cell-based ß2-AR agonist functional evaluation model, combined with a luciferase reporter assay system, was used to confirm the final result. In this research, 45 compounds were identified as ß2-AR agonists, and four compounds were verified and the rest need further experiment.

Physiological roles of mycothiol in detoxification and tolerance to multiple poisonous chemicals in Corynebacterium glutamicum.

Mycothiol (MSH) plays important roles in maintaining cytosolic redox homeostasis and in adapting to reactive oxygen species in the high-(G + C)-content Gram-positive Actinobacteria. However, its physiological roles are ill defined compared to glutathione, the functional analog of MSH in Gram-negative bacteria and most eukaryotes. In this research, we explored the impact of intracellular MSH on cellular physiology by using MSH-deficient mutants in the model organism Corynebacterium glutamicum. We found that intracellular MSH contributes significantly to resistance to alkylating agents, glyphosate, ethanol, antibiotics, heavy metals and aromatic compounds. In addition, intracellular MSH is beneficial for withstanding oxidative stress induced by various oxidants in C. glutamicum. This study greatly expanded our current knowledge on the physiological functions of mycothiol in C. glutamicum and could be applied to improve the robustness of this scientifically and commercially important species in the future.

Efficacy of adjuvant chemotherapy/maintenance chemotherapy after induction chemotherapy and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Experiences of two centers.

BACKGROUND AND OBJECTIVE: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MATERIAL AND METHODS: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA-NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S-1. Multivariate Cox regression was used to confirm optimal predictors of progression-free survival (PFS), and a nomogram was established to identify patients into low-risk and high-risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. RESULTS: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high-risk cohort had greatly worse 5-year DMFS, LRFS, PFS and OS compared to low-risk cohort (all p < 0.05), and subgroup analysis found that the 5-year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high-risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects. CONCLUSIONS: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high-risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high-risk LA-NPC.

Which Is Safer, Chinese Medicine or Western Medicine? Comparative Analysis Based on Chinese Spontaneous Reporting Database.

OBJECTIVE: To compare the safety differences between Chinese medicine (CM) and Western medicine (WM) based on Chinese Spontaneous Reporting Database (CSRD). METHODS: Reports of adverse events (AEs) caused by CM and WM in the CSRD between 2010 and 2011 were selected. The following assessment indicators were constructed: the proportion of serious AEs (PSE), the average number of AEs (ANA), and the coverage rate of AEs (CRA). Further comparisons were also conducted, including the drugs with the most reported serious AEs, the AEs with the biggest report number, and the 5 serious AEs of interest (including death, anaphylactic shock, coma, dyspnea and abnormal liver function). RESULTS: The PSE, ANA and CRA of WM were 1.09, 8.23 and 2.35 times higher than those of CM, respectively. The top 10 drugs with the most serious AEs were mainly injections for CM and antibiotics for WM. The AEs with the most reports were rash, pruritus, nausea, dizziness and vomiting for both CM and WM. The proportions of CM and WM in anaphylactic shock and coma were similar. For abnormal liver function and death, the proportions of WM were 5.47 and 3.00 times higher than those of CM, respectively. CONCLUSION: Based on CSRD, CM was safer than WM at the average level from the perspective of adverse drug reactions.

Association of the aldosterone synthase gene -344T>C polymorphism with essential hypertension and glucose homeostasis: a case-control study in a Han Chinese population.

1. Aldosterone is a hormone that affects both blood pressure and glucose homeostasis. We studied the association of the aldosterone synthase gene (CYP11B2) polymorphism -344T>C with essential hypertension (EH) and glucose homeostasis in people in China. 2. We investigated the polymorphism -344T>C in CYP11B2 using a case-control study design (1059 cases and 1120 controls). Genotyping was carried out by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using a MassARRAY platform. 3. The aldosterone synthase gene -344T>C polymorphism was found to be associated with EH (odds ratio 1.252; 95% confidence interval 1.067-1.468; P(add) = 0.006). The -344C variant was found to be significantly associated with increased systolic blood pressure (P(add) = 0.003) and diastolic blood pressure (P(add) = 0.024) in controls and increased plasma aldosterone levels (P(add) = 0.0001) in EH cases. The -344C variant was also found to be significantly associated with increased fasting glucose (P(rec) = 0.003) in controls. In the subgroup containing 893 EH cases without a history of diabetes or hypoglycaemia medications, the -344C variant was found to be associated with increased fasting and postprandial plasma glucose levels (P(add) = 0.0001, P(add) = 0.001, respectively) and decreased pancreatic ß-cell function and insulin sensitivity (P(add) = 0.030, P(dom) = 0.019, respectively) by homeostasis model assessments. 4. In this Han Chinese population, the -344T/C polymorphism of the CYP11B2 gene was found to be associated with EH and glucose homeostasis, both of which might be mediated by plasma aldosterone levels, insulin sensitivity and ß-cell function.

[Relationship of epidermal growth factor receptor gene mutations, clinicopathologic features and prognosis in patients with non-small cell lung cancer].

OBJECTIVE: To investigate epidermal growth factor receptor (EGFR) gene mutations in exons 19 and 21 of patients with non-small cell lung cancer (NSCLC) and to analyze the relationship of EGFR mutations with clinicopathological features and prognosis. METHODS: The EGFR gene exons 19 and 21 of paraffin-embedded tumor tissue were amplified by PCR, followed by direct sequencing in 282 surgically-removed specimens of NSCLC. The relationship of EGFR gene mutations in NSCLC with clinicopathological features and prognosis were analyzed. RESULTS: EGFR mutations were detected in 120 of 282 (42.6%) patients with NSCLC. There were 61 cases of the mutations in exon 19 and 66 cases of the mutations in exon 21, including 7 cases of the mutations both in exons 19 and 21. Mutations were more frequently observed in women (55.2%, 53/96) than in men (36.0%, 67/186), in 51 to 60-years-old (51.3%, 39/76) than ≤50-years-old (30.4%, 21/69) and >60-years-old (43.8%, 60/137), in non-smokers (54.3%, 69/127) than smokers (32.9%, 51/155), there was negative correlation of EGFR mutations with smoking status (P=0.000, rs=-0.216). EGFR mutations were more frequently observed in adenocarcinomas (47.8%, 64/134), bronchiolo-alveolar carcinomas (73.0%, 27/37), adenosquamous carcinomas (7/9) than squamous cell carcinomas (23.6%, 17/72) and other types (16.7%, 5/30). The EGFR mutation rate in the well differentiated, the middle differentiated, the poorly differentiated and the undifferentiated was 55.7% (68/122), 50.8% (30/59), 22.7% (17/75), 19.2% (5/26) respectively, the incidences of EGFR mutations decreased with the degrading of differentiation, there was positive correlation of EGFR mutations with differentiation of lung cancer (P=0.000, rs=0.296). The patients with EGFR mutations had better prognosis than those with wild-type EGFR (P=0.027). There was no association of EGFR mutations with clinical TNM stage. CONCLUSIONS: EGFR mutations occur frequently in females, non-smokers and adenocarcinomas, bronchioloalveolar carcinomas, and adenosquamous carcinomas. The patients with EGFR mutations have better prognosis. The results may offer a practical approach to select the patients who may benefit from anti-EGFR target therapy.

Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats.

AIM: To examine whether implantation of islet preparation-derived proliferating islet cells (PIC) could ameliorate diabetes in rats. METHODS: PIC were expanded from rat islet preparation by supplementation of basic fibroblast growth factor (bFGF) and implanted into rats with streptozotocin (STZ)-induced diabetes through the portal vein. Body weight and blood glucose levels were measured. Serum insulin levels were measured by radioimmunoassay. The presence of insulin-positive cells was determined by hematoxylin and immunohistochemical staining. RESULTS: Cultured islet cells (CIC) were demonstrated to dedifferentiate in vitro, and the apoptosis ratios reached more than 50% by the 15th day post-isolation. PIC cells treated with bFGF (20 ng/mL) continued growing within 30 days after isolation, and no apoptotic cells were detected. Implantation of PIC into diabetic rats was capable of ameliorating diabetes, in terms of the restoration of euglycemia, weight gain, improved glucose response and elevated serum insulin levels for up to 130 days. Livers derived from PIC-implanted rats were examined for insulin expression and single insulin-positive cells. In addition, most islets of PIC-implanted STZ-induced diabetic rats were intact at 130 days post-transplantation and comparable to those of normal rats. CONCLUSION: Implantation of bFGF-treated proliferating islet cells is a promising cellular therapeutic approach for diabetes.

[Efficacy and safety of high-dose α-lipoic acid in the treatment of diabetic polyneuropathy].

OBJECTIVE: To evaluate the efficacy and safety of high-dose α-lipoic acid in the treatment of diabetic polyneuropathy with regards to sensory symptoms and nerve conduction velocity. METHODS: A total of 236 diabetics with symptomatic polyneuropathy were enrolled into this 5-center, randomized, double-blind and placebo-controlled study of α-lipoic acid 1800 mg daily (n = 117) or matching placebo (n = 119) for 12 weeks. The primary outcome was total symptom score (TSS). Secondary end points included nerve conduction velocity, individual symptom score, HbA1c and safety parameters. The above parameters were reviewed and recorded at zero point and after treatment for 2, 4, 8, 12 weeks separately. RESULTS: 73.27% patients with symptomatic polyneuropathy improved after treatment with α-lipoic acid for 12 weeks versus 18.27% with placebo. TSS declined by 2.6 ± 2.3 with α-lipoic acid. And it was more than 0.7 ± 1.4 versus placebo (P < 0.05). TSS decreased quickly after treatment with α-lipoic acid for 2 weeks (P < 0.05). And it was better than placebo. Individual symptom scores of pain, extremity numbness, burning sensation or resting abnormal sensations were significantly diminished as compared to those before treatment and placebo group (all P < 0.05). Nerve conduction velocity had no change. HbA1c further decreased at the end of trial after α-lipoic acid treatment (P < 0.05). The incidence rates of adverse effects were 25.4% vs 11.8% in the treatment and control groups. The major manifestation was burning sensation from throat to stomach (12.7%). CONCLUSION: Oral treatment with high-dose α-lipoic acid for 12 weeks may improve symptoms in patients with diabetic polyneuropathy. Dose of 600 mg thrice daily for 2 weeks has marked effects with a reasonable safety.

Identification of two clip domain serine proteases involved in the pea aphid's defense against bacterial and fungal infection.

Phenoloxidases (POs) are required for the pea aphid's defense against bacterial and fungal infection. Prophenoloxidases (PPOs) are proteolytically converted to its active form PO through a clip domain serine protease cascade. In this study, we identified five clip domain serine proteases in the pea aphids. The messenger RNA levels of two of them, Ap_SPLP and Ap_VP, were upregulated by Gram-positive bacterium Staphylococcus aureus and fungus Beauveria bassiana infections. Double-stranded RNA-based expression knockdown of these two genes resulted in reduced PO activity of the aphid hemolymph, higher loads of S. aureus and B. bassiana in the aphids, and lower survival rates of the aphids after infections. Our data suggest that Ap_SPLP and Ap_VP are involved in PPO activation pathway in the pea aphid.

Cytotoxic polyprenylated xanthones from the resin of Garcinia hanburyi.

Twelve new xanthones (1-12), a pair of new natural products (13 and 14), and 18 known related compounds were isolated from the resin of Garcinia hanburyi. The structures of 1-14 were elucidated by detailed spectroscopic analyses. A cytotoxic assay of the isolated compounds revealed that, with the exception of 2, these compounds were active against the HeLa tumor cell line.

Cytotoxic constituents of chinese propolis.

A pair of new flavanol racemates (1a and 1b) and a new flavanol racemic mixture (2) were isolated from crude propolis from Henan Province, People's Republic of China. Also obtained were nine known compounds, including two flavones, four flavonols, two flavanols, and isoferulic acid. Spectroscopic analysis was employed to assign the structures of these new compounds and the absolute configurations of 1a and 1b. Cytotoxicity of the isolated compounds against the HeLa human cervical carcinoma cancer cell line was evaluated, with only compounds 1a, 1b, 2, and rhamnetin (3) being active.

[Prediction of potential distribution of Carpinus cordata in China under climate change.] / 气候变化下千金榆在我国潜在分布区预测.

Climate change seriously affects the geographical distribution of plants. Regional diffe-rences in plant response to climate change will provide important guidance for species introduction and conservation. Based on ArcGIS and MaxEnt model, we used 176 geographic information of Carpinus cordata and 13 climatic variables to reconstruct its current and future niche. The results showed that the model had a high credibility in simulating contemporary potential distribution areas. The AUC values of the test set and the training set of the model were 0.973 and 0.957, respectively. The main core suitable areas were concentrated in Qinling, Changbai Mountain and their adjacent areas, with other sporadic "island" distribution. C. cordata is not distributed in Guizhou, Jiangxi, Yunnan and Fujian, but the model predicted some suitable distribution areas in those provinces. With climate warming in the future, ecologically suitable areas of C. cordata would increase significantly, mainly as "shrinking to high altitude areas", "expanding northward", and "expanding eastward". However, core suitable areas would be slightly reduced, which would be manifested as "shrinking southward", "moderate stability", and "expanding northward". The response of C. cordata distribution to climate warming was obviously regional. Eastern Jiangsu, Anhui, and other places would become ecologically suitable areas for C. cordata because of their unique geographical location and climatic environment. The lower latitudes of the south, the original low-altitude areas might no longer be suitable for survival. The central Qinling region was a transition region from north to south, with strong buffer capacity, and climate warming had little effect on its distribution area. The Changbai Mountain and its adjacent areas at higher latitudes were more suitable for C. cordata.

Ingenane diterpenoids from Euphorbia esula.

An extensive study of metabolites present in Euphorbia esula led to isolation of 16 ingenane diterpenoids 1-16 together with the known ingenane derivative 17 and four known cycloartane triterpenoids. Their structures were elucidated on the basis of spectroscopic studies and comparison with known related compounds. All the compounds were assayed for their inhibitory activity against human HeLa cervical cancer cell line.

Structure elucidation and NMR spectral assignments of three new lignan glycosides from Akebia trifoliata.

Three new lignan glycosides (1-3) were isolated from the stems of Akebia trifoliata. Their structures were elucidated as (7R,8R,7'R,8'R)3,3',5,5'tetramethoxy-4,4'dihydroxy-7,9':7',9-diepoxylignan-4-O-beta-D-glucopyranoside (1), (7S,8S,8'R)-4,4',9-trihydroxy-3,3',5,5'-tetramethoxy-7,9'-epoxylignan-7'-one 9-O-beta-D-glucopyranoside (2), (7R,8R,8'S)-4,4',9-trihydroxy3,3',5,5'-tetramethoxy-7,9'-epoxylignan-7'-one 9-O-beta-D-glucopyranoside (3) by spectral analyses, primarily NMR, MS and CD. The NMR assignments for the compounds were carried out using 1H, 13C, DEPT, COSY, HSQC, HMBC and ROESY NMR experiments.

NMR spectral assignments of isoprenylated flavanones from Sophora tonkinensis.

The phytochemical investigation of extracts from the roots of Sophora tonkinensis yielded three new isoprenylated flavanones, the tonkinochromanes F (2), G (3), and H (5), along with four known compounds. Structural elucidation of the compounds were established on the basis of spectral data, particularly by the use of 1D NMR and several 2D shift-correlated NMR pulse sequences ((1)H-(1)H COSY, HSQC, HMBC, and ROESY).

Endocrinal description of two Chinese Kennedy's disease pedigrees.

Kennedy's disease (KD), also known as X-linked spinal and bulbar muscular atrophy (SBMA), is caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the first exon of the androgen receptor (AR) gene. KD is a late-onset neural-endocrinal disease that is characterized by the degeneration of motor neurons in the brainstem and spinal cord. In addition, partial androgen insensitivity is an important manifestation of KD. Here, we report two Chinese KD pedigrees that reveal the clinical and genetic manifestations and fully elaborate the endocrinal characteristics of KD patients. The proband in pedigree 1 was referred to an endocrinologist for gynaecomastia and sexual dysfunction. A gene analysis of this patient revealed that there were 53 CAG repeats in the AR gene. A family survey identified an additional two KD patients in pedigree 1. The proband in pedigree 2 was diagnosed by a neurologist and did not have gynaecomastia or sexual dysfunction. A family survey identified an additional subclinical patient, and both patients exhibited partial androgen insensitivity at a hormonal level. We therefore suggest that a family survey and hormone tests should be routinely performed in KD patients and that physicians should increase their understanding of the different symptoms of KD to achieve correct diagnoses in affected patients.

Association of body mass index and age with incident diabetes in Chinese adults: a population-based cohort study.

OBJECTIVE: Type 2 diabetes mellitus is increasing in young adults, and greater adiposity is considered a major risk factor. However, whether there is an association between obesity and diabetes and how this might be impacted by age is not clear. Therefore, we investigated the association between body mass index (BMI) and diabetes across a wide range of age groups (20-30, 30-40, 40-50, 50-60, 60-70 and ≥70 years old). DESIGN: We performed a retrospective cohort study using healthy screening programme data. SETTING: A total of 211 833 adult Chinese persons >20 years old across 32 sites and 11 cities in China (Shanghai, Beijing, Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, Nantong) were selected for the study; these persons were free of diabetes at baseline. PRIMARY AND SECONDARY OUTCOME MEASURES: Fasting plasma glucose levels were measured and information regarding the history of diabetes was collected at each visit. Diabetes was diagnosed as fasting plasma glucose ≥7.00 mmol/L and/or self-reported diabetes. Patients were censored at the date of diagnosis or the final visit, whichever came first. RESULTS: With a median follow-up of 3.1 years, 4174 of the 211 833 participants developed diabetes, with an age-adjusted incidence rate of 7.35 per 1000 persons. The risk of incident diabetes increased proportionally with increasing baseline BMI values, with a 23% increased risk of incident diabetes with each kg/m2 increase in BMI (95% CI 1.22 to 1.24). Across all age groups, there was a linear association between BMI and the risk of incident diabetes, although there was a stronger association between BMI and incident diabetes in the younger age groups (age×BMI interaction, p<0.0001). CONCLUSIONS: An increased BMI is also independently associated with a higher risk of developing diabetes in young adults and the effects of BMI on incident diabetes were accentuated in younger adults.