Correlation between systematic RAS and glucolipid metabolism and β cell function in patients with essential hypertensin
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Objective:The objective of this study was to investigate the relationship between the activity of the renin-angiotensin system (RAS) and glucolipid metabolism and β-cell function in patients with essential hypertension. Method:A sample of 222 patients with essential hypertension was divided into three groups (normal glucose tolerance NGT, impaired glucose tolerance IGT, type 2 diabetes T2DM) according to the WHO (1999) diagnostic criteria of type 2 diabetes after a 75 g glucose tolerance test (OGTT). Insulin resistance and β-cell function were estimated through homeostasis model assessment (HOMA-IR) and HOMAβ respectively. Association between the activity of the renin, Ang Ⅱ, aldosterone, blood sugar, lipids, HOMA-IR, HOMAβ and area under the curve of insulin(AUCI) were compared by ONE-way ANOVA, correlation analysis and multiple linear regression analysis.Result:Plasma AngⅡ, HOMA-IR, TC and LDL-C were significantly elevated in patients with IGT and T2DM, and AngⅡ was positively correlated with Glu 0 min and Glu 120 min(r=0.320, r=0.459,respectively). Similar results were found using multiple linear regression analysis, which showed there was a significant positive correlation between Glu 0 min, Glu 120 min, HOMA-IR and AngⅡ (0.495≤r≤0.671).Conclusion:The activity of the plasma AngⅡwas remarkably increased in essential hypertension patients with glucose metabolic disturbance, which was independent of hypertension. There was a vacious cycle between AngⅡ, hyperglycaemia and insulin resistance. This study witnessed the facts that RAS blockers decreased incidence of type 2 diabetes in high risk group or reversed IGT to NGT.Keywords:
Essential hypertension
Homeostasis
Plasma renin activity
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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.
Key words:
Angiotensin Ⅱ; First-phase of insulin secretion; Second-phase of insulin secretion; Intravenous glucose tolerance test; Adiponectin; Diabetes mellitus, type 2
Impaired fasting glucose
Homeostasis
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Objective
To compare the discursion of endothelial function and metabolism in obese isolated impaired fasting glucose (I-IFG ) and isolated impaired glucose tolerance(I-IGT).
Methods
Sixty cases of I-IFG(group C ) including obesity(group C2;32 cases) and no-obesity (group C1;28cases) and 83 cases of I-IGT(group D ) including obesity(group D2;42 cases) and no-obesity (group D1:41cases) were compared to 142 cases of normal glucose tolerance (group N ) including obesity(group N2;67 cases) and no-obesity (group N1;75 cases). All cases were detected glucose and insulin with oral glucose tolerance test and insulin release test. Fasting venous blood of all samples were obtained to measure the levels of fasting of blood lipids, free fatty acids(FFA), adiponectin (APN), high-sensitivity C-reactive protein (hs-CRP)and serum endothelin-1(SET-1), and urine endothelin-1 (UET-1) and urea-microalbumin(MUA) after collecting urina sanguinis. To be measured waistline, blood pressure, height and weight, and the arteria brachialis diameter was tested at least and after arteria brachialis elevated pressure and glycergl trintrate. To calculate main arterial blood pressure(MAP), area under curve of glucose(glu AUC), area under curve of insulin (INSAUC), second-phase area under curve of insulin(INSAUC two), ratio of the net increment of insulin to plasma glucose at 20 min (△I20/△G20), insulin resistance index(HOMA-IR)and index of pancreatic islets secretion function (HOMA-β).
Results
It is significant difference between groups D and C, and between groups D1 and C1 in hs-CRP, SET, UET(P<0.05 or P<0.01) after adjusting sex and age. It is significant difference between groups D2 and C2 in Hs-CRP(P<0.05 ). Meanwhile between groups D and C in FPG, 2 h PG, glu AUC, HOMA-β, INS120 and △I20/△G20 (P<0.05 or P<0.01), between groups D1 and C1 in FPG, glu AUC, 2 h PG, HOMA-IR, HOMA-β, INS120, INSAUC, INSAUC two and △I20/△G20(P<0.05 or P<0.01), between group D2 and group C2 in MAP, FPG, HOMA-β, 2 h PG and INS120(P<0.05).
Conclusions
To compare to the patients with I-IFG, the endothelial dysfunction which occurs in macrovacular is found and it's more serious which occurs in microvacular in the non-obese of I-IGT, but more serious which occurred in macrovacular in the obese of I-IGT; blood pressure increased in the obese of I-IFG; dysglycemia is more serious but lesser in insulin secretion impairment in I-IGT, and early phase insulin secretion impairment is more serious in the non-obese of I-IGT; insulin resistance is more serious in the obese than in the non-obese of I-IFG and I-IGT, and insulin resistance is more serious in the non-obese of I-IGT who occure hyperinsulinemia in second-phase insulin secretion.
Key words:
Glucose intolerance/CO/PA/ME; Obesity/CO/PA/ME; Endothelins/ME
Impaired fasting glucose
Carbohydrate Metabolism
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Objective: To investigate the correlation between renin -angiotensin system (RAS) and glucose-lipid metabolism,blood pressure and evaluate the mechanism of metabolic syndrome (MS) in obese children. Methods: Plasma renin,angiotensin Ⅱ ,aldosterone,fasting insulin (FINS),blood pressure and fasting plasma glucose (FPG) were measured, and body mass index (BMI),HOMA-β and HOMA-IR were calculated in 26 MS obese children (MS group) and 27 non-MS obese children (control group). Results: In MS group,systolic pressure, diastolic pressure,plasma renin, angiotensin Ⅱ ,FINS and HOMA -β were significantly higher than those in control group (P0.05). RAS levels were positively correlated with systolic pressure (r=0.449), diastolic pressure (r=0.353), BMI (r=0.3) and FPG (r=0.286) in MS group. Conclusion: Hypertension, hyperinsulinemia,RAS activation are characteristic of MS in obese children.RAS is closely correlated with blood pressure and glucose-lipid metabolism.
Hyperinsulinemia
Plasma renin activity
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Objective To investigate the relationship between insulin resistance(IR) and fibrinolysis in patients of hypertension. Methods Plasma plasminogen activator inhibitor type 1(PAI 1), tissue type plasminogen(t PA), plasminogen(PLG) activities were measured. Oral glucose tolerance test(OGTT), insulin release test(IRT) were performed. Insulin resistance was determined by insulin sensitive index(ISIc). Three groups of subjects were categorized as followings: Forty four hypertensive patients with normal glucose tolerance(NGT), 27 with impaired glucose tolerance(IGT) and thirty one healthy subjects as control. Results t PA activities were not different between patients with NGT and IGT, while they are significantly decreased compared to the controls( P 0 05). No differences were found in PAI 1 among the hypertensive patients with IGT, NGT and the healthy control. Plasma PLG was significantly greater in patients with IGT than that in patients of NGT and the controls. ISIc was decreased markedly in both IGT and NGT groups while the most significant changes found in patients of IGT. No correlation was showm between t PA, PAI 1 and ISIc. Conclusion Patients with hypertension had decreased fibrinolysis activities. The most remarkable changes were found in the hypertensive patients with impaired glucose tolerance. No correlation beween insulin sensitive index and activities of t PA and PAI 1 were found.
Plasminogen activator inhibitor-1
Glucose tolerance test
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Aim To compare of pancreatic beta-cell function and insulin resistance in impaired glucose tolerance(IGT)patients and type 2 diabetes patients(T2DM) and investigate the association between insulin secretion and serum glucose levels and the time of maximal insulin value by using oral glucose tolerance test(OGTT).Methods A total of 139 patients were divided into IGT(n=29) and T2DM(n=110) based on 1999 WHO diagnostic criteria for diabetes and OGTT.The correlation of serum glucose levels and insulin secretion,the time of maximal glucose value,homeostasis model assessment of insulin resistance(HOMA-IR) and beta-cell function(HOMA-β) were calculated.Results Correlation test demonstrated that there was a significant inverse correlation between levels of fasting blood glucose and insulin secretion at 2h and peak in subjects with IGT and T2DM(rs=-0.644,P=0.000,rs=-0.529,P=0.003,rs=-0.518,P=0.004).There was a significant inverse correlation between levels of fasting blood glucose and fasting insulin in subjects with T2 DM whose fasting glucose concentration exceeded 12mmol/L.The insulin levels reached peak at 60min and 120min.the level of HOMA-IR in subjects with IFG was significantly lower than HOMA-IR in subjects with T2DM(t=3.238,P=0.002),but level of HOMA-β in the former was significantly higher than that in the latter(t=-3.032,P=0.005).Conclusion The function of beta-cell is impaired and the sensitivity of insulin is reduced in the patients from IGT to T2DM.Therefore,it is particularly important to strengthen the monitoring and intervention of IGT patients.
Impaired fasting glucose
Homeostasis
Glucose tolerance test
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Objective:To investigate the relationship between serum tumour necrosis factor alpha(TNF-α) and insulin resistance in type 2 diabetes mellitus.Methods:The level of TNF-α was measured in 101 type 2 diabetes mellitus (T2DM) patients, 27 subjects with impaired glucose tolerance(IGT) and 18 control subjects(C). Homeostasis model assessment(HOMA) was applied to assess the status of insulin resistance.Results:The results showed the levels of TC, TG, insulin of fasting and after glucose load, TNF-α, HOMA-IR and body fat percentage(BF%) were significantly increased and their HDL-C was remarkably decreased in the subjects of T2DM and IGT compared with control subjects. Stepwise multivariate linear regression analysis showed that FBG, BMI, TNF-α and TG were the main risk factors leading to insulin resistance in type 2 diabetes mellitus (β=0.451, 0.245, 0.218, 0.162, respectively; P=0.000, 0.001, 0.003, 0.030, respectively).In all the subjects, TNF-α level was correlated to DBP, FBG, BG2h, FINS, LDL-C, TC, HOMA-IR and BF(r= 0.218, 0.374, 0.317, 0.293,0.218, 0.215,0.422, 0.200, respectively) and was not associated with BMI and WHR.Conclusions:The level of TNF-α is increased in Type 2 diabetes(T2DM), which probably aggravates insulin resistance.
Homeostasis
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Objective:To investigate the relationship between insulin resistance (IR) and activation of coagulation system in patients with hypertension. Methods:Plasma plasminogen activator inhibitor type-1(PAI-1),fibrinogen (Fg) were measured. Oral glucose tolerance test (OGTT),insulin release test(IRT) were performed. IR was estimated by homeostasis model assessment (HOMA). Three groups of subjects were categorized as followings: Forty-three hypertension patients with normal glucose tolerance (NGT). 26 patients with impaired glucose tolerance (IGT) and 31 healthy subjects as control. Results:Compared with control group the levels of HOMA, PAI-1, Fg were markedly abnormal in both IGT and NGT groups (P0. 05-0. 01);while the most significant changes were found in patients of IGT (P0. 05-0. 01), compared with NGT group. Posetive correlation was shown among HONA and PAL-1, Fg (r=0. 635, 0. 832 respectively). Conclusion: Patient with hypertension has increased insulin resistance and activation of coagulation system. The most remarkable changes are found in hypertension patients with IGT.
Homeostasis
Plasminogen activator inhibitor-1
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Objective To investigate the correlations between insulin resistance level with cortisol,aldosterone and INS-Ab in patients with various glucose tolerance levels. Methods Total 115 patients with increased glucose tolerance were selected as subjects and divided into three groups based on diagnostic criteria for diabetes mellitus( DM),T2 DM group( 39 cases),pre-diabetes( PD) group( 35 cases),and impaired glucose regulation( IGR) group( 41 cases). All the subjects were carried out BMI measurement,75 g OGTT and insulin release test under fasting conditions and HOMA-IR were calculated. The levels of plasma cortisol,aldosterone and INS-Ab under fasting conditions were detected and the results were analyzed. Results There was significantly differences on HOMA-IR between T2 DM,PD and IGR group with that of normal glucose tolerance group( P 0. 01). The plasma cortisol was positive correlated with HOMA-IR( r = 0. 14,P 0. 05),while INS-Ab and plasma aldosterone had no correlation with HOMA-IR. Conclusion Patients with increased glucose tolerance experience insulin resistance. The plasma cortisol may be correlated with insulin resistance in patients with concomitant obesity.
Glucose tolerance test
Concomitant
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Background: The relative contribution of insulin secretion and sensitivity in the development of Type 2 diabetes mellitus (T2DM) vary from population to population due to the heterogeneous nature of the disease. The study was undertaken to evaluate insulin secretory capacity and sensitivity in a Bangladeshi Type 2 diabetic population and to explore the association of some of the anthropometric and biochemical factors known to modulate B-cell function and insulin action. Methods: Ninety one T2DM subjects and 32 age-matched controls were studied for their fasting plasma glucose (FPG), lipids, HbA1c (by HPLC), leptin and C-peptide (ELISA). Insulin secretion (HOMA B) and insulin sensitivity (HOMA S) were calculated by homeostasis model assessment (HOMA). Results: Both insulin secretion and sensitivity were significantly reduced in diabetic as compared to control (HOMA B%, geometric mean±SD, 35.65±1.75 vs. 96.29±1.50, p < 0.001; HOMA S%, 68.66±1.71 vs. 104.951.63, p < 0.001). However, B-cell dysfunction was predominant than insulin resistance in predicting T2DM as the discriminate function coefficient for HOMA B (1.098) was greater than that for HOMA S (0.821). In T2DM, HOMA B had positive correlation with BMI (r=0.368, p < 0.001) and HOMA S was inversely correlated to BMI (r=-0.261, p < 0.01), WHR (r=-0.258, p < 0.01) and plasma TG (r=-0.233, p < 0.001). On multiple regression analysis HOMA B and HOMA S were found to be inversely associated to FPG (p < 0.001) and leptin (p < 0.05) in T2DM. Conclusions: Both insulin secretory dysfunction and insulin resistance are present in Bangladeshi T2DM subjects, but B-cell failure seems to be the predominant abnormality. BMI, plasma glucose, insulin and leptin are the major determinants of insulin secretory capacity and generalized as well as central obesity, plasma glucose, triglycerides, insulin and leptin are among the major determinants of insulin sensitivity in this population. Key Words: Leptin, Insulin, Diabetes  doi: 10.3329/jbsp.v3i0.1786 J Bangladesh Soc Physiol. 2008 Dec;(3):1-7.
Homeostasis
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Abstract Objective: We studied plasma adiponectin, insulin sensitivity, and insulin secretion before and after oral glucose challenge in normal glucose tolerant, impaired glucose tolerant, and type 2 diabetic first degree relatives of African‐American patients with type 2 diabetes. Research Methods and Procedures: We studied 19 subjects with normal glucose tolerance (NGT), 8 with impaired glucose tolerance (IGT), and 14 with type 2 diabetes. Serum glucose, insulin, C‐peptide, and plasma adiponectin levels were measured before and 2 hours after oral glucose tolerance test. Homeostasis model assessment‐insulin resistance index (HOMA‐IR) and HOMA‐β cell function were calculated in each subject using HOMA. We empirically defined insulin sensitivity as HOMA‐IR < 2.68 and insulin resistance as HOMA‐IR > 2.68. Results: Subjects with IGT and type 2 diabetes were more insulin resistant (as assessed by HOMA‐IR) when compared with NGT subjects. Mean plasma fasting adiponectin levels were significantly lower in the type 2 diabetes group when compared with NGT and IGT groups. Plasma adiponectin levels were 2‐fold greater (11.09 ± 4.98 vs. 6.42 ± 3.3811 μg/mL) in insulin‐sensitive (HOMA‐IR, 1.74 ± 0.65) than in insulin‐resistant (HOMA‐IR, 5.12 ± 2.14) NGT subjects. Mean plasma adiponectin levels were significantly lower in the glucose tolerant, insulin‐resistant subjects than in the insulin sensitive NGT subjects and were comparable with those of the patients with newly diagnosed type 2 diabetes. We found significant inverse relationships of adiponectin with HOMA‐IR ( r = −0.502, p = 0.046) and with HOMA‐β cell function ( r = −0.498, p = 0.042) but not with the percentage body fat ( r = −0.368, p = 0.063), serum glucose, BMI, age, and glycosylated hemoglobin A1C (%A1C). Discussion: In summary, we found that plasma adiponectin levels were significantly lower in insulin‐resistant, non‐diabetic first degree relatives of African‐American patients with type 2 diabetes and in those with newly diagnosed type 2 diabetes. We conclude that a decreased plasma adiponectin and insulin resistance coexist in a genetically prone subset of first degree African‐American relatives before development of IGT and type 2 diabetes.
Homeostasis
Glucose tolerance test
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