ABSTRACT
Maturity-onset diabetes of the young (MODY) is an inherited monogenic type of diabetes. Genetic mutations in MODY often cause nonsynonymous changes that directly lead to the functional distortion of proteins and the pathological consequences. Herein, we proposed that the inherited mutations found in a MODY family could cause a disturbance of protein abundance, specifically in serum. The serum samples were collected from a Uyghur MODY family through three generations, and the serum proteins after depletion treatment were examined by quantitative proteomics to characterize the MODY-related serum proteins followed by verification using target quantification of proteomics. A total of 32 serum proteins were preliminarily identified as the MODY-related. Further verification test toward the individual samples demonstrated the 12 candidates with the significantly different abundance in the MODY patients. A comparison of the 12 proteins among the sera of type 1 diabetes, type 2 diabetes, MODY, and healthy subjects was conducted and revealed a protein signature related with MODY composed of the serum proteins such as SERPINA7, APOC4, LPA, C6, and F5.
Subject(s)
Blood Proteins/analysis , Diabetes Mellitus, Type 2/genetics , Proteomics , Family , Female , Humans , Male , Mutation , PedigreeABSTRACT
To study the status of diet and nutrition in Uyghur families with maturity onset diabetes of young (MODY).Four MODY families were composed of four generations of Uyghur with 50 members collected from Kashgar,Shanshan,and Ili regions of Xinjiang Uyghur Autonomous Region.A dietary survey with a semi-quantitative food frequency questionnaire was conducted.According to the sex and different intensities of physical activity,the nutrient intake was calculated by nutrition calculator software,and the results were compared with recommended nutrients intake(RNI).Cereals,livestock,and poultry meat,being the main food stuff in Uyghur MODY families,accounted for 54.11％ and 13.87％ of total energy respectively,while fruit,fish,and shrimps were seldom taken,and accounted for 0.41％ and 0.26％ of total energy respectively.Carbohydrate,protein,and fat accounted for 55.0％,16.7％,and 28.4％ of total energy intake respectively,within the scope of the RNI for diabetes suggested by both Chinese Diabetes Society and the American Diabetes Association.The total energy and all three major nutrients were excessively taken by subjects of different genders and different intensities physical activity from Uyghur MODY families in Xinjiang.Uyghur diets lead to excessive calorie intake in the Uyghur MODY family members.The Health education of Uyghur language and text should be strengthened,so as to improve the scientific dietary knowledge.
ABSTRACT
ObjectiveTo study the characteristics of serum metabolites in two Uyghur families with maturityonset diabetes of the young(MODY).MethodsTwo MODY families were composed of four generations of Uyghur with 52 members collected from Kashgar region,Xinjiang Uyghur Autonomous Region.The general information,blood glucose and lipid levels,and blood pressure were analyzed.Using 1H nuclear magnetic resonance (1H NMR )spectroscopy,serum metabolites were measured for each subject.After having conducted data pretreatment on the spectrogram,orthogonal partial least squares discriminant analysis ( OPLS-DA ) was used to interpret data.The subjects were divided into two groups according to blood glucose ( diabetes and non-diabetes ),blood pressure,body mass index ( BMI ) for comparing differences in the metabolites.The differences of serum metabolic components between two groups were determined using pearson correlation coefficients with significant difference detection and two-dimensional spectrum technology.Results lsoleucine and tyrosine levels in diabetes group were decreased significantly,while α-glucose and β-glucose levels were increased significantly compared with non-diabetes group( all P＜0.05 ).Citrate,phaseomannite,1 -methyl histidine,and tyrosine levels in hypertension group were all decreased significantly compared with normal blood pressure group( all P＜0.05 ).No significant metabonomic differences were observed between normal BMI group and high BMI group.ConclusionsMetabonomic changes in diabetic patients from MODY families indicate that diabetic patients suffer from disordered tricarboxylic acid cycle ( TCA cycle )metabolism,with reduced glycolysis of glycogen in liver and muscle.There exist the metabolic disorder in TCA cycle and obstruction of fat metabolism in patients with hypertension from the MODY families.
