Metabolite Profiling of LADA Challenges the View of a Metabolically Distinct Subtype

被引:22
作者
Al-Majdoub, Mahmoud [1 ]
Ali, Arslan [1 ,2 ]
Storm, Petter [3 ]
Rosengren, Anders H. [4 ]
Groop, Leif [1 ,5 ]
Spegel, Peter [1 ,6 ]
机构
[1] Lund Univ, Dept Clin Sci Malmo, Unit Mol Metab, Malmo, Sweden
[2] Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi, Pakistan
[3] Lund Univ, Dept Clin Sci Malmo, Diabet & Endocrinol, Malmo, Sweden
[4] Lund Univ, Dept Clin Sci Malmo, Translat Diabet Res, Malmo, Sweden
[5] Univ Helsinki, FIMM, Helsinki, Finland
[6] Lund Univ, Dept Chem, Ctr Anal & Synth, Lund, Sweden
基金
瑞典研究理事会;
关键词
GLUTAMIC-ACID DECARBOXYLASE; RISK-FACTORS; PLASMA; DISEASE; IDENTIFICATION; ANTIBODIES; CYSTEINE; ADULTS; ONSET;
D O I
10.2337/db16-0779
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Latent autoimmune diabetes in adults (LADA) usually refers to GAD65 autoantibodies (GADAb)-positive diabetes with onset after 35 years of age and no insulin treatment within the first 6 months after diagnosis. However, it is not always easy to distinguish LADA fromtype 1 or type 2 diabetes. In this study, we examined whether metabolite profiling could help to distinguish LADA (n = 50) from type 1 diabetes (n = 50) and type 2 diabetes (n = 50). Of 123 identified metabolites, 99 differed between the diabetes types. However, no unique metabolite profile could be identified for any of the types. Instead, the metabolome varied along a C-peptide-driven continuum from type 1 diabetes via LADA to type 2 diabetes. LADA was more similar to type 2 diabetes than to type 1 diabetes. In a principal component analysis, LADA patients overlapping with type 1 diabetes progressed faster to insulin therapy than those overlapping with type 2 diabetes. In conclusion, we could not find any unique metabolite profile distinguishing LADA from type 1 and type 2 diabetes. Rather, LADA was metabolically an intermediate of type 1 and type 2 diabetes, with those patients closer to the former showing a faster progression to insulin therapy than those closer to the latter.
引用
收藏
页码:806 / 814
页数:9
相关论文
共 23 条
[1]   Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes [J].
Cervin, Camilla ;
Lyssenko, Valeriya ;
Bakhtadze, Ekaterine ;
Lindholm, Eero ;
Nilsson, Peter ;
Tuomi, Tiinamaija ;
Cilio, Corrado M. ;
Groop, Leif .
DIABETES, 2008, 57 (05) :1433-1437
[2]   Predictive Metabolomics Evaluation of Nutrition-Modulated Metabolic Stress Responses in Human Blood Serum During the Early Recovery Phase of Strenuous Physical Exercise [J].
Chorell, Ellin ;
Moritz, Thomas ;
Branth, Stefan ;
Antti, Henrik ;
Svensson, Michael B. .
JOURNAL OF PROTEOME RESEARCH, 2009, 8 (06) :2966-2977
[3]   Development of a gas chromatography/mass spectrometry based metabolomics protocol by means of statistical experimental design [J].
Danielsson, Anders P. H. ;
Moritz, Thomas ;
Mulder, Hindrik ;
Spegel, Peter .
METABOLOMICS, 2012, 8 (01) :50-63
[4]  
El-Khairy L, 1999, AM J CLIN NUTR, V70, P1016
[5]   METABOLIC BASIS FOR DISORDERS OF PURINE NUCLEOTIDE DEGRADATION [J].
FOX, IH .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1981, 30 (06) :616-634
[6]   ISLET CELL ANTIBODIES IDENTIFY LATENT TYPE-I DIABETES IN PATIENTS AGED 35-75 YEARS AT DIAGNOSIS [J].
GROOP, LC ;
BOTTAZZO, GF ;
DONIACH, D .
DIABETES, 1986, 35 (02) :237-241
[7]   Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype Action LADA 7 [J].
Hawa, Mohammed I. ;
Kolb, Hubert ;
Schloot, Nanette ;
Beyan, Huriya ;
Paschou, Stavroula A. ;
Buzzetti, Raffaella ;
Mauricio, Didac ;
De Leiva, Alberto ;
Yderstraede, Knud ;
Beck-Neilsen, Henning ;
Tuomilehto, Jaakko ;
Sarti, Cinzia ;
Thivolet, Charles ;
Hadden, David ;
Hunter, Steven ;
Schernthaner, Guntram ;
Scherbaum, Werner A. ;
Williams, Rhys ;
Brophy, Sinead ;
Pozzilli, Paolo ;
Leslie, Richard David .
DIABETES CARE, 2013, 36 (04) :908-913
[8]   Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS datas -: A potential tool for multi-parametric diagnosis [J].
Jonsson, Par ;
Johansson, Elin Sjovik ;
Wuolikainen, Anna ;
Lindberg, Johan ;
Schuppe-Koistinen, Ina ;
Kusano, Miyako ;
Sjostrom, Michael ;
Trygg, Johan ;
Moritz, Thomas ;
Antti, Henrik .
JOURNAL OF PROTEOME RESEARCH, 2006, 5 (06) :1407-1414
[9]   Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance [J].
Koves, Timothy R. ;
Ussher, John R. ;
Noland, Robert C. ;
Slentz, Dorothy ;
Mosedale, Merrie ;
Ilkayeva, Olga ;
Bain, James ;
Stevens, Robert ;
Dyck, Jason R. B. ;
Newgard, Christopher B. ;
Lopaschuk, Gary D. ;
Muoio, Deborah M. .
CELL METABOLISM, 2008, 7 (01) :45-56
[10]   Increased Levels of Plasma Acylcarnitines in Obesity and Type 2 Diabetes and Identification of a Marker of Glucolipotoxicity [J].
Mihalik, Stephanie J. ;
Goodpaster, Bret H. ;
Kelley, David E. ;
Chace, Donald H. ;
Vockley, Jerry ;
Toledo, Frederico G. S. ;
DeLany, James P. .
OBESITY, 2010, 18 (09) :1695-1700