Anitra D M Koopman1, Joline W Beulens2, Ellis Voerman3, Simone P Rauh3, Amber A van der Heijden4, Timothy J McDonald5, Marlous Langendoen-Gort4, Femke Rutters3. 1. Amsterdam UMC, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands. Electronic address: ad.koopman@vumc.nl. 2. Amsterdam UMC, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, the Netherlands. 3. Amsterdam UMC, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands. 4. Amsterdam UMC, Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands. 5. Academic Department of Clinical Biochemistry, University of Exeter Medical School and Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Abstract
CONTEXT: Antibodies to the 65 kD isoform of glutamic acid decarboxylase (GAD65) have been associated with incident Type 2 Diabetes Mellitus, however results are inconsistent. OBJECTIVE: To assess the association between GAD65 antibody positivity and incident Type 2 Diabetes Mellitus in a non-diabetic adult (≥18 years) population, in a systematic review and meta-analysis. DATA SOURCES: A systematic literature search was conducted in Pubmed (MEDLINE) and Embase until January 14th, 2019. STUDY SELECTION: Included studies were 1) prospective studies on the association between GAD65 antibodies and incident Type 2 Diabetes Mellitus; 2) in a non-diabetic adult (≥18 years) population. To strengthen the review, unpublished data from 1302 Hoorn Study participants were included. DATA EXTRACTION: Data extraction and quality assessment were performed independently by two observers. Ten studies were rated for methodological quality and seven were pooled using a random-effects meta-analysis, of which 2 strong, 2 moderate and 3 of low methodological quality. DATA SYNTHESIS: The pooled risk estimate of incident Type 2 Diabetes Mellitus for GAD65 antibody positivity, compared to GAD65 antibody negativity was 3.36 (95% CI: 1.9-5.9). This result was robust to sensitivity analyses. Heterogeneity between studies was significant with I2 statistic of 79% (p < 0.0001). However, excluding one study showed a decrease of I2 to 19% (p < 0.0001), explaining a large part of the heterogeneity. CONCLUSION: GAD65 antibody positivity was associated with an increased risk of future Type 2 Diabetes Mellitus in adults.
CONTEXT: Antibodies to the 65 kD isoform of glutamic acid decarboxylase (GAD65) have been associated with incident Type 2 Diabetes Mellitus, however results are inconsistent. OBJECTIVE: To assess the association between GAD65 antibody positivity and incident Type 2 Diabetes Mellitus in a non-diabetic adult (≥18 years) population, in a systematic review and meta-analysis. DATA SOURCES: A systematic literature search was conducted in Pubmed (MEDLINE) and Embase until January 14th, 2019. STUDY SELECTION: Included studies were 1) prospective studies on the association between GAD65 antibodies and incident Type 2 Diabetes Mellitus; 2) in a non-diabetic adult (≥18 years) population. To strengthen the review, unpublished data from 1302 Hoorn Study participants were included. DATA EXTRACTION: Data extraction and quality assessment were performed independently by two observers. Ten studies were rated for methodological quality and seven were pooled using a random-effects meta-analysis, of which 2 strong, 2 moderate and 3 of low methodological quality. DATA SYNTHESIS: The pooled risk estimate of incident Type 2 Diabetes Mellitus for GAD65 antibody positivity, compared to GAD65 antibody negativity was 3.36 (95% CI: 1.9-5.9). This result was robust to sensitivity analyses. Heterogeneity between studies was significant with I2 statistic of 79% (p < 0.0001). However, excluding one study showed a decrease of I2 to 19% (p < 0.0001), explaining a large part of the heterogeneity. CONCLUSION:GAD65 antibody positivity was associated with an increased risk of future Type 2 Diabetes Mellitus in adults.
Authors: Sine Knorr; Magnus C Lydolph; Birgitte Bytoft; Zuzana Lohse; Tine D Clausen; Rikke Beck Jensen; Peter Damm; Kurt Højlund; Dorte M Jensen; Claus H Gravholt Journal: Endocrinol Diabetes Metab Date: 2021-11-19
Authors: Olov Rolandsson; Christiane S Hampe; Stephen J Sharp; Eva Ardanaz; Heiner Boeing; Guy Fagherazzi; Francesca Romana Mancini; Peter M Nilsson; Kim Overvad; Maria-Dolores Chirlaque; Miren Dorronsoro; Marc J Gunter; Rudolf Kaaks; Timothy J Key; Kay-Tee Khaw; Vittorio Krogh; Tilman Kühn; Domenico Palli; Salvatore Panico; Carlotta Sacerdote; Maria-José Sánchez; Gianluca Severi; Annemieke M W Spijkerman; Rosario Tumino; Yvonne T van der Schouw; Elio Riboli; Nita G Forouhi; Claudia Langenberg; Nicholas J Wareham Journal: Diabetologia Date: 2019-11-11 Impact factor: 10.122