Variety and quantity of dietary protein intake from different sources and risk of new-onset diabetes: a Nationwide Cohort Study in China

Background The relation of the variety and quantity of different sources of dietary proteins intake and diabetes remains uncertain. We aimed to investigate the associations between the variety and quantity of proteins intake from eight major food sources and new-onset diabetes, using data from the China Health and Nutrition Survey (CHNS). Methods 16,260 participants without diabetes at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of protein sources consumed at the appropriate level, accounting for both types and quantity of proteins. New-onset diabetes was defined as self-reported physician-diagnosed diabetes or fasting glucose ≥7.0mmol/L or glycated hemoglobin ≥6.5% during the follow-up. Results During a median follow-up of 9.0 years, 1100 (6.8%) subjects developed diabetes. Overall, there were U-shaped associations of percentages energy from total protein, whole grain-derived and poultry-derived proteins with new-onset diabetes; J-shaped associations of unprocessed or processed red meat-derived proteins with new-onset diabetes; a reverse J-shaped association of the fish-derived protein with new-onset diabetes; L-shaped associations of egg-derived and legume-derived proteins with new-onset diabetes; and a reverse L-shaped association of the refined grain-derived protein with new-onset diabetes (all P values for nonlinearity<0.001). Moreover, a significantly lower risk of new-onset diabetes was found in those with a higher variety score of protein sources (per score increment; HR, 0.69; 95%CI, 0.65–0.72). Conclusions There was an inverse association between the variety of proteins with appropriate quantity from different food sources and new-onset diabetes.

Validation of a Pancreatic Cancer Detection Test in New-Onset Diabetes Using Cell-Free DNA 5-Hydroxymethylation Signatures

BACKGROUND Pancreatic cancer (PaC) has poor (10%) 5–year overall survival, largely due to predominant late-stage diagnosis. Patients with new-onset diabetes (NOD) are at a six– to eightfold increased risk for PaC. We developed a pancreatic cancer detection test for the use in a clinical setting that employs a logistic regression model based on 5–hydroxymethylcytosine (5hmC) profiling of cell-free DNA (cfDNA). METHODS: cfDNA was isolated from plasma from 89 subjects with PaC and 596 case–control non–cancer subjects, and 5hmC libraries were generated and sequenced. These data coupled with machine–learning, were used to generate a predictive model for PaC detection, which was independently validated on 79 subjects with PaC, 163 non–cancer subjects, and 506 patients with non–PaC cancers. RESULTS: The area under the receiver operating characteristic curve for PaC classification was 0.93 across the training data. Training sensitivity was 58.4% (95% confidence interval [CI]: 47.5–68.6) after setting a classification probability threshold that resulted in 98% (95% CI: 96.5–99) specificity. The independent validation dataset sensitivity and specificity were 51.9% (95% CI: 40.4–63.3) and 100.0% (95% CI: 97.8–100.0), respectively. Early–stage (stage I and II) PaC detection was 47.6% (95% CI: 23%–58%) and 39.4% (95% CI: 32%–64%) in the training and independent validation datasets, respectively. Sensitivity and specificity in NOD patients were 55.2% [95% CI: 35.7–73.6] and 98.4% [95% CI: 91.3–100.0], respectively. The PaC signal was identified in intraductal papillary mucinous neoplasm (64%), pancreatitis (56%), and non-PaC cancers (17%). CONCLUSIONS: The pancreatic cancer detection assay showed robust performance in the tested cohorts and carries the promise of becoming an essential clinical tool to enable early detection in high–risk NOD patients.

Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young

BackgroundWe aimed to analyze a novel ABCC8 variant of a Chinese patient with suspected maturity-onset diabetes of the young (MODY) and to provide evidence for precise diagnosis and appropriate treatment.MethodA Chinese family with suspected MODY was recruited in this study, which included a 15-year-old female patient with diabetes. Clinical data and blood samples were collected from the proband and other family members. All of the living relatives were given an oral glucose tolerance test. Next-generation sequencing was performed to identify the mutated genes in the proband. Sanger sequencing was utilized to confirm the location of the pathogenic variant in all subjects. Further treatment was referred to targeted family members according to genetic testing.ResultsThe proband was found to have a random blood glucose level of 244.8 mg/dl and an HbA1c level of 9.2%. Before this investigation, her grandparents had been diagnosed with diabetes. The second uncle, two aunts, mother, and cousin of the proband were diagnosed with diabetes by abnormal HbA1C (6.5–12.1%) and fasting blood glucose (FBG, 91.4–189.7 mg/dl). The second aunt of the proband had impaired glucose homeostasis (HbA1C = 6.4% and FBG = 88.0 mg/dl). One novel missense variant c.1432G&gt;A (p.A478T) in exon 9 of the ABCC8 gene was detected in the proband with suspected MODY. The variant was also found in six family members with diabetes or impaired glucose homeostasis, including her second uncle, two aunts, mother, and cousin. After the treatment was switched to glimepiride, the fasting blood glucose was adjusted to 99.54 mg/dl, the 2-h postprandial blood glucose was 153.54 mg/dl, serum fructosamine was 259 μmol/l, and HbA1c was 5.8%. The glycemic control remained optimal, and no hypoglycemic episodes were observed in the living relatives.ConclusionThis study revealed one novel missense variant of the ABCC8 gene in Chinese families. The present findings indicated that the members of this family responded to treatment with sulfonylureas as previously seen in ABCC8 MODY.

Etiology and Epidemiology of Maturity-onset Diabetes of the Young

Evidence indicates that Maturity-onset diabetes of the young (MODY) exhibits an autosomal dominant inheritance and is the most common type of monogenic diabetes. However, it should be noted that misdiagnosis of the condition is very common, as patients are usually mistaken for both types I and type II diabetes mellitus. In the present study, we have discussed the etiology, pathogenesis, and epidemiology of MODY based on an extensive literature review. Genetic mutations are mainly attributed to the development of the disease, which usually manifests throughout the second to fifth decades of life. Pancreatic islet cell destruction, impaired insulin secretion, defects regarding threshold to serum glucose levels, and other pathological events are usually observed in these patients. Data regarding the epidemiology of the condition is not adequately reported in the literature, especially among non-European populations, indicating the need to conduct future investigations. Ethnic and age variations are potentially epidemiological characteristics of the disease. However, not enough data are present in the literature to support such conclusions.