The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals
We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance te...
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| Published in | ENDOCRINE JOURNAL Vol. 62; no. 6; pp. 485 - 492 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Japan
The Japan Endocrine Society
2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0918-8959 1348-4540 |
| DOI | 10.1507/endocrj.EJ14-0611 |
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| Abstract | We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA-β and the oral disposition index (DIO). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA-β and DIO. Odds ratios (95% CI) of PC1/3, HOMA-β, and DIO were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3(≤1.7) combined with decreased HOMA-β (≤30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA-β or DIO. A combined decrease in estimated fasting PC1/3 activity and HOMA-β measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied. |
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| AbstractList | We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA-β and the oral disposition index (DI(O)). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA-β and DI(O). Odds ratios (95% CI) of PC1/3, HOMA-β, and DI(O) were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3(≤1.7) combined with decreased HOMA-β (≤30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA-β or DI(O). A combined decrease in estimated fasting PC1/3 activity and HOMA-β measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied. We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA-β and the oral disposition index (DIO). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA-β and DIO. Odds ratios (95% CI) of PC1/3, HOMA-β, and DIO were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3(≤1.7) combined with decreased HOMA-β (≤30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA-β or DIO. A combined decrease in estimated fasting PC1/3 activity and HOMA-β measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied. [Abstract] We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA-β and the oral disposition index (DIO). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA-β and DIO. Odds ratios (95%CI) of PC1/3, HOMA-β, and DIO were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3(<1.7) combined with decreased HOMA-β (<30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA-β or DIO. A combined decrease in estimated fasting PC1/3 activity and HOMA-β measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied. We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA- beta and the oral disposition index (DI sub(O)). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA- beta and DI sub(O). Odds ratios (95% CI) of PC1/3, HOMA- beta , and DI sub(O) were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3( less than or equal to 1.7) combined with decreased HOMA- beta ( less than or equal to 30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA- beta or DI sub(O). A combined decrease in estimated fasting PC1/3 activity and HOMA- beta measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied. |
| Author | Kondo, Takuma Tanaka, Toshiaki Ozawa, Sachihiko Inukai, Kouichi Katsuta, Hidenori Sumitani, Yoshikazu Takahashi, Kazuto Ishida, Hitoshi Nishida, Susumu Suzuki, Kiyoshi Hosaka, Toshio |
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| CitedBy_id | crossref_primary_10_1371_journal_pone_0162603 crossref_primary_10_7554_eLife_18134 crossref_primary_10_1016_j_jddst_2019_05_002 crossref_primary_10_1507_endocrj_EJ20_0795 crossref_primary_10_1021_acschembio_6b00602 |
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| Snippet | We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese... [Abstract] We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese... |
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| SubjectTerms | Adult Aged Algorithms Biomarkers - blood Cohort Studies Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - diagnosis Diabetes Mellitus, Type 2 - ethnology Diabetes Mellitus, Type 2 - metabolism Female HOMA-β Humans Insulin - blood Insulin Resistance - ethnology Isoenzymes - metabolism Japan Male Middle Aged Non-obese Prohormone convertase Proinsulin - blood Proinsulin - metabolism Proinsulin processing Proprotein Convertases - metabolism Protein Processing, Post-Translational Proteolysis Sensitivity and Specificity Type 2 diabetes |
| Title | The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals |
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