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Objective To investigate the relationship between serum secreted frizzled-related protein 4 (SFRP4) and the first-phase of glucose-stimulated insulin secretion from pancreatic β cell under different glucose tolerance statuses. Methods Fifty-six patients with newly diagnosed type 2 diabetes mellitus ( T2DM group), 52 patients with impaired glucose tolerance (IGT group), and 42 subjects with normal glucose tolerance (NGT group) underwent intravenous glucose tolerance test. Fasting serum SFRP4 and interleukin ( IL)-1β were assayed by ELISA. Acute insulin response ( AIR), the area under the curve of the first-phase (0-10 min) insulin secretion (AUC), glucose disposition index(GDI), homeostasis model assessment for β cell function index(HOMA-β), and insulin resistance index(HOMA-IR) were calculated. Results (1) The levels of SFRP4 and IL-1β in T2DM group and IGT group were significantly higher than that in NGT group [(184. 38 ± 61. 34 or 141. 64 ± 40. 46 or 95. 46 ± 20. 13)ng/ ml, P<0. 01]. AIR, AUC, and GDI in T2DM group and IGT group were significantly lower than those in NGT group(P<0. 01), and these results were more significantly reduced in T2DM group compared with those in IGT group. (2) SFRP4 was negatively correlated with AIR, AUC, GDI, HOMA-β (P<0. 01), and positively correlated with fasting plasma glucose, 2 h plasma glucose after glucose loading, HbA1C , IL-1β, and high sensitive C-reactive protein(P<0. 01). (3) Multiple stepwise regression analysis showed that AUC, HOMA-IR, and serum IL-1β level were independently associated with SFRP4. Conclusion The concentration of serum SFRP4 is closely correlated with the glycolipid metabolic disorder, the first-phase of glucose-stimulated insulin secretion, and chronic low-grade inflammation. SFRP4 may be involved in the mechanism of β cell dysfunction in type 2 diabetes mellitus.
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ObjectiveTo compare the sensitivity and specificity of a new index of insulin resistance (IR) derived from plasma triglyceride and glucose with homeostasis model assessment for insulin resistance index ( HOMA-IR) and insulin sensitivity index from frequent sampling intravenous glucose tolerance test (FSIGT-ISI).Methods A total of 1024 subjects (240 normal control,335 with obesity,312 impaired glucose regulation,and 137 type 2 diabetes mellitus) were included in the present study.Standard oral glucose tolerance test,insulin release test,lipid profiles,and other biochemical markers were measured. Among them 540 subjects were selected to undertake FSIGT.TyG index is derived from plasma triglyceride and fasting glucose.TyG2 index is derived from plasma triglyceride and postprandial 2 plasma glucose.ResultsPearson correlation coefficient between TyG and HOMA-IR or FSIGT-ISI was 0.427 ( P＜0.01 ) and -0.100 ( P=0.024 ),respectively,and that between TyG2 and HOMA-IR or FSIGT-ISI was 0.455 ( P＜0.01 ) and - 0.162 ( P＜0.01 ),respectively.The sensitivity and specificity of TyG index for diagnosis of IR was 68.5％ and 63.5％ compared with HOMA-IR,and 68.5％ and49.5％ compared with FSIGT-ISI.For TyG2 index,the slightly higher sensitivity ( 81.7％ with HOMA-IR,75.7％ with FSIGT-ISI),but lower specificity (51.5％ with HOMA-IR,48.2％ with FSIGT-ISI) were found.ConclusionsBothTyGandTyG2 indices could be used as a surrogate for assessing IR in Chinese subjects.However,considering its moderately high sensitivity but low specificity,these two indices are limited in the use of large-scale epidemiological screening.
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The relationship between oxidative stress and the first-phase of pancreatic β cell insulin secretion in subjects with different statuses of glucose tolerance was explored. Fasting adiponectin, 8-hydroxydeoxyguanosin ( 8-OHdG), malondialdehyde ( MDA ), superoxide dismutase ( SOD ), insulin area under the curve ( AUC ) from 0 to 10 min, and AIR3-5 were measured. The levels of oxidative stress-related markers were elevated, the activities of superoxide dismutase,adiponectin, and first-phase of insulin secretion were reduced with the disease progression. MDA and 8-OHdG were negatively correlated with adiponectin, homeostasis model assessment β cell function index ( HOMA-β ),AUC ,and AIR3-5. SOD was positively correlated with adiponectin, HOMA-β, AUC, AIR3-5. The plasma 8-OHdG and SOD were independently associated with AIR3-5. Oxidative stress exerts a significant effect on the first phase of pancreatic β cell insulin secretion, which may contribute to the pathogenesis of type 2 diabetes.
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Objective To investigate the relationship between angiotensin Ⅱ and pancreatic islet β cell secretion function under different glucose tolerance statuses. Method Forty-two patients with newly diagnosed type 2diabetes mellitus ( DM group), 38 subjects with impaired fasting glucose/impaired glucose tolerance ( IFG/IGTgroup) ,and 40 normal control subjects (NGT group) underwent intravenous glucose tolerance test. Fasting plasma angiotensin Ⅱ ( Ang Ⅱ ) and adiponectin were assayed by ELISA. Acute insulin response from 3 to 10 min( AIR3-10 ),the area under the curve( AUCⅠ ) and the peak concentration of the first-phase ( 0-10 min) insulin secretion, the area under the curve of the second-phase( 10-120 min) insulin secretion( AUCⅡ), homeostasis model assessment for β cell function index(HOMA-β) and homeostasis model assessment for insulin resistance index(HOMA-IR) were calculated to explore the relationship with Ang Ⅱ. Result ( 1 ) The levels of Ang Ⅱ in DM group and IFG/IGT group were significantly higher than that in NGT group( P＜0.05 ). The AIR3-10, AUCⅠ and peak concentration, AUCⅡ ,adiponectin in DM group and IFG/IGT group were significantly lower than those in the NGT group ( P＜0. 05), and these results were more significantly reduced in DM group compared with those in IFG/IGT group. (2) Ang Ⅱ was negatively correlated with AIR3-10, AUCⅠ and the peak concentration, AUCⅡ, adiponectin, HOMA-β ( P＜0. 01 ), and positively correlated with fasting blood glucose,2 h blood glucose after glucose loading, fasting insulin, HOMA-IR (P＜0. 05 ). (3)Multiple stepwise regression analysis showed that Ang Ⅱ was independently associated with AUCⅠ and AUCⅡ.Conclusion Ang Ⅱ was an independent factor that affected the insulin secretion function of pancreatic islet βcells. Ruling out the effect of blood pressure, body position, drugs, and other factors, high levels of Ang Ⅱ could predict the dysfunction of pancreatic islet β cell as well as insulin resistance in patients with type 2 diabetes.
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Objective To investigate the relationship between adiponectin and the first-phase of pancreatic P-cell insulin secretion in subjects with different statuses of glucose tolerance. Methods Thirty-seven patients with newly diagnosed type 2 diabetes mellitus (DM) , 30 patients with abnormal glucose tolerance (IGR) , and 40 normal control subjects (NGT) underwent intravenous glucose tolerance test (IVGTT). Fasting adiponectin and proinsulin (PI) was assayed by EL1SA. Fasting free fatty acid ( FFA) was measured by colorimetry. Insulin area under the curve ( AUC ) , incremental AUC (iAUC) from 0 min to 10 min, AIR3-5, homeostasis model assessment for insnlin resistance (HOMA-IR) , and for β cell function ( HOMA-p) were calculated. The relationship between adiponectin and AUC, iAUC, AIR3-5, proinsulin, FFA, and HOMA-IR was explored. Results (1) The levels of AUC, iAUC, AIR3-5, and adiponectin in DM group and IGR group were significantly lower than those in NGT group (P<0.05), reduced in DM group than those in IGR group(P<0.05). (2) The levels of PI in DM group and IGR group were significantly higher than that in NGT (P<0.05). (3) Adiponectin was positively correlated with HOMA-p,AUC,iAUC,AIR3-5, and HDL-C,while negatively correlated with proinsulin, HOMA-IR, and LDL-C. (4) Proinsulin was positively correlated with HOMA-IR. (5 ) Multiple regression stepwise analysis showed that adiponectin was independently associated with AUC. Conclusions Adiponectin was an independent factor affecting the first phase of pancreatic p-cell insulin secretion. Low adiponectin level could predict the dysfunction of the first phase pancreatic p-cell secretion as well as insulin resistance in patients with type 2 diabetes.
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Objective To investigate the factors which may affect the secretions of human leptin and free fatty acids (FFA) by measuring plasma glucose, serum insulin, leptin and FFA levels during reduced sample number intravenous glucose tolerance tests (IVGTT) in the subjects with different status of insulin resistance and ? cell function. Methods According to oral glucose tolerance test, 7 normal, 10 overweight/obese individuals, 12 subjects with impaired glucose tolerance (IGT) and 11 with type 2 diabetes mellitus (DM) were recruited. During IVGTT, serum insulin, leptin and FFA levels at 12 time points were simultaneously measured. Results Compared to the stable secretion of leptin, during 180 min in the IVGTT, the FFA secretion showed a "U" shape profile. The correlation analysis showed that the average serum leptin and FFA levels in 3 h were independent to fasting plasma glucose concentration. The partial correlation coefficient of leptin and insulin decreased after being adjusted for FFA (before r=0.77, P0.05). Conclusion The changes of serum FFA levels in IVGTT are more significant than those of leptin after glucose loading. Fasting plasma glucose levels do not significantly affect the average serum levels of leptin and FFA. On the contrary, insulin manifests such action but does not affect the secretion profile of these parameters.
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0.05.Conclusion:The prior glucose bolus does not affect the following euglycemic clamp.The Botnia clamp is a useful method for simultaneous independent assessment of insulin secretion and insulin sensitivity.