Proinsulin Level And Clinical Significance In First-degree Relatives Of Type 2 Diabetes With High Morbidity Pedigrees

Objective: Exploration of proinsulin secreting pattern and its clinical significance in first-degree relatives (FDR) of type 2 diabetes (T2DM) with high morbidity pedigree in Guangzhou area.Method: 116 cases of T2DM, comprised with probands (n=48) and first-degree relatives of pedigrees (n=113), originally from Guangzhou area, were recruited for the study. According to WHO T2DM diagnostic criteria (1999) and outcomes of oral glucose tolerance test (OGTT), patients are divided into four groups. Normal glucose tolerance (NGT, B group, n=33); impaired glucose tolerance (IGT, C group, n= 22); newly diagnosed T2DM (D group, n= 58) and probands (E group, n=48). Healthy individuals also took part in this study served as controls (A group, n= 16). Total proinsulin (TPI),intact proinsulin(IPI) and true insulin(TI) were measured during an OGTT for all the cases. Fasting total proinsulin ratio [FTPI/(FTPI+FTI)], fasting intact proinsulin ratio [FIPI/(FIPI+FTI)], fasting intact proinsulin to fasting total proinsulin ratio (FIPI/FTPI), HOMA-IR and HBCI (HOMA-β function index) were calculated for all groups. Parameters mentioned above from observed groups were compared with control group.Results: FTPI/(FTPI+FTI) or FIPI/(FIPI+FTI) of all the T2DM groups were higher than control group (P<0. 05) ; D group and E group were also significantly higher than B and C groups (P<0. 01). FIPI/FTPI of all the patient groups were higher than control group (P<0. 05). It was found that there was no significantly difference in FTI levels between groups (P>0. 05), except E group displayed a slightly lower level than D group(P<0.05). Groups of all T2DM pedigree, except B group, had a significantly higher HOMA-IR than control group (P<0. 05). However, mean HBCI of all T2DM pedigree group were significantly lower than control group(P<0.05). When compared between T2DM pedigree groups, HBCI of B and C groups are higher than C and E groups (P<0.01).Conclusion:1. In Guangzhou area, many individuals from T2DM high morbidity pedigree who may already suffer from T2DM are undiagnosed in our data. Systematic scheme, including prevention, early diagnosis and treatment should be called.2. Results from this study show that normal glucose tolerance FDRS have disproportionate hyperproinsulin without high fasting TI and insulin resistance. This imply that a defect of β-cell secreting capacity is exist in this group of our patients. Whether this is due to genetic defect shall be further studied.3. All the groups selected from T2DM families, IPI/TPI ratio was significantly higher than that in control group, with no differences found among B to E groups. This phenomenon presumably reflects an alteration of the process in cleavage of intact proinsulin into proinsulin conversion exist throughout the proceeding of T2DM.4. In FDRS, early from NGT stage to IGT, and finally to T2DM, insulin resistance progressively developed and worsened. Disorder of PI conversion and insulin resistant are not paralleled. PI conversion disorder appeared to have developed early than insulin resistance.