Elevated plasma levels of glucagon-like peptide-1 after oral glucose ingestion in patients with pancreatic diabetes

OBJECTIVE: The purpose of the present study was to evaluate plasma glucagon-like peptide-1 (GLP-1) responses after oral glucose ingestion in patients with chronic pancreatitis and to clarify how GLP-1 secretion relates to pancreatic diabetes. METHODS: An oral glucose tolerance test (OGTT) was performed in 17 patients with chronic pancreatitis. Plasma glucose, immunoreactive insulin (IRI), C-peptide, glucagon, and GLP-1 levels at each time point during OGTT were measured. The diagnosis of chronic pancreatitis was made by the findings of endoscopic retrograde pancreatography (ERP): evident dilation of the main pancreatic duct with or without pancreatolithiasis. RESULTS: The patients were divided into three groups according to the World Health Organization classification of diabetes based on plasma glucose levels after OGTT. The groups were: normal (three patients), impaired glucose tolerant (IGT) (six patients), and diabetic (DM) (eight patients). In the DM group, IRI and C-peptide response levels after oral glucose ingestion were significantly reduced as compared with those of the normal and IGT groups. No significant glucagon responses to oral glucose ingestion were found in the three groups. In contrast, plasma GLP-1 levels were significantly elevated after oral glucose ingestion in the DM groups as compared with normal and IGT groups. CONCLUSIONS: The present study affords evidence that plasma GLP-1 levels become elevated with development of pancreatic diabetes, although the precise mechanism of this elevation remains undetermined.     

Enhanced endothelium-dependent microvascular responses in patients with Wegener's granulomatosis

OBJECTIVE: To assess endothelial cell (EC) function of the cutaneous microcirculation in patients with Wegener's granulomatosis (WG) and to relate EC function to EC activation and presence of atherosclerosis. METHODS: We studied 28 WG patients with inactive disease and 28 age and sex matched controls. Common carotid intima-media thickness (IMT), as a measure of atherosclerosis, was determined by ultrasonography. EC function of microcirculation in the fingers was assessed using laser Doppler fluxmetry in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), which are endothelium-dependent and endothelium-independent vasodilators, respectively. In addition to vascular responses, traditional cardiovascular risk factors were recorded, and EC activation was assessed by serological measures. RESULTS: WG patients had increased IMT compared to controls (0.71 mm vs 0.66 mm; p < 0.05). In WG patients IMT correlated positively with age and body mass index (BMI), and negatively with duration of prednisolone use and cumulative prednisolone dose. Levels of von Willebrand factor and C-reactive protein were increased in patients with WG (p < 0.05). ACh-induced but not SNP-induced vasodilatation was enhanced in WG patients compared to controls. When patients and controls with increased IMT were excluded, the difference in relative response to ACh became significant (median 567% vs 334%; p = 0.007). The response to ACh correlated negatively with age. CONCLUSION: We confirmed that WG patients have accelerated atherosclerosis as measured by IMT. EC activation and disturbed microvascular endothelium-dependent vasodilatation were present in the microcirculation of WG patients with inactive disease and without signs of atherosclerosis, indicating and contributing to a proatherogenic state.     

Plasma islet amyloid polypeptide levels in obesity, impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

We examined the response of plasma islet amyloid polypeptide (IAPP) to an oral glucose load in non-obese and obese subjects with normal glucose tolerance or impaired glucose tolerance (IGT), and in non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma IAPP response to intravenous glucagon injection in NIDDM patients was also studied. Plasma IAPP concentration was determined by a sensitive and specific radioimmunoassay. Basal levels of plasma IAPP in non-obese subjects with normal glucose tolerance, IGT and NIDDM were not significantly different from each other. Non-obese subjects with IGT showed delayed and higher plasma IAPP response to oral glucose load compared to normal non-obese subjects. In NIDDM patients, IAPP response to glucose was delayed and lower when compared to normal non-obese subjects. Basal levels of plasma IAPP in normal obese subjects and obese subjects with IGT were significantly higher than those in normal non-obese subjects. Plasma IAPP response to glucose load in these obese subjects was higher than that in normal non-obese subjects. Plasma IAPP response was decreased in diabetic patients treated with diet, oral hypoglycemic agents and insulin in that order. We conclude that the secretion of IAPP is reduced with progression of NIDDM, although it appears to be rather augmented in IGT compared to normal non-obese subjects.     

Vascular responsiveness in the microcirculation of patients with systemic lupus erythematosus is not impaired

As endothelial dysfunction is one of the earliest signs of atherosclerosis, which is accelerated in systemic lupus erythematosus (SLE), we assessed whether vascular responses of the cutaneous microcirculation are disturbed in SLE patients and influenced by Raynaud's phenomenon (RP). Laser Doppler fluxmetry (LDF) was used in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), an endothelium-dependent and endothelium-independent vasodilator respectively. 42 SLE patients with inactive disease, 12 of whom had RP and 19 age- and sex-matched controls were included. Furthermore, traditional and non-traditional risk factors for cardiovascular disease (CVD) were assessed, and markers of inflammation and endothelial activation were measured. Vascular responses of SLE patients without RP did not differ from controls. However, SLE patients with RP exhibited decreased vasodilatation compared with controls. SLE patients with RP also had longer arrival times of ACh and SNP than controls. Markers of inflammation and von Willebrand factor were increased in SLE patients. Smoking, the presence of SLE and RP were negatively associated with vascular responses in univariate analysis. In multivariate analyses, the only independent variable of vascular responses to ACh and SNP was the presence of RP. Despite signs of endothelial activation, SLE patients with inactive disease do not have altered vascular responses in the microcirculation compared with controls. In SLE patients with RP, cutaneous vascular responses to both ACh and SNP are impaired. Therefore, LDF of the microcirculation seems not to be the appropriate method to distinguish those SLE patients with an increased risk to develop CVD.     

Blood pressure increase with impaired glucose tolerance in young adult american blacks

Hypertension and non-insulin-dependent diabetes mellitus are more prevalent in blacks than whites. The convergence of these 2 disorders augments the expression and severity of cardiovascular disease. The purpose of this study was to determine whether alterations in glucose metabolism are related to an increase in blood pressure (BP). This study was conducted on 304 nondiabetic blacks (mean age=32 years). Measurements in all subjects included BP, anthropometric measures, oral glucose tolerance test, insulin clamp to measure insulin sensitivity, and plasma lipids. The sample was stratified according to plasma glucose on oral glucose tolerance test to normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM). A 2-way ANOVA was performed to determine differences between the metabolic groups. With the use of American Diabetic Association criteria, 20.4% of the samples were classified as IGT and 5.9% were diabetic. A significant increase in BP existed from NGT to IGT to DM, which was stronger in women than men (systolic blood pressure in women: NGT=122, IGT=127, and DM=140 mm Hg, P<0.001) with a significant linear trend (P<0.001). With the use of body mass index as a covariate, the group difference in BP remained significant (P=0.006). Measures of insulin sensitivity demonstrated significant metabolic group differences (P<0.001) with a linear trend (P<0.001) of decreasing insulin sensitivity from NGT to DM. These results indicate that early alterations in glucose metabolism effects an upward shift in BP. The higher BP in IGT and DM may be due to vascular endothelial cell resistance to insulin action.     

Oxidized LDL and small LDL particle size are independently predictive of a selective defect in microcirculatory endothelial function in type 2 diabetes

AIM: To explore the associations of LDL (low-density lipoprotein) particle size and oxidized LDL with endothelium-dependent function of the forearm microcirculation in diabetes. METHODS: Endothelium-dependent function was examined in 43 middle-aged men and women with type 2 diabetes and 10 age-matched controls. All received aspirin to inhibit endothelial cyclo-oxygenase. Forearm blood flow (FBF) was measured using venous occlusion plethysmography with separate administration of acetylcholine (ACh) and bradykinin (BK) into the brachial artery. Endothelium-independent function was assessed using sodium nitroprusside (SNP). N(G)-monomethyl-L-arginine (L-NMMA) was co-infused with ACh (ACh + L-NMMA) and BK (BK + L-NMMA) to assess non-NO-mediated contributions to endothelium-dependent function. RESULTS: Subjects with diabetes had impaired endothelium-dependent and endothelium-independent function compared with controls (p < 0.01 for ACh, BK and SNP). In multivariate regression analysis, LDL size (r = 0.41 and p = 0.007), oxidized LDL (r = -0.41 and p = 0.007) and duration of diabetes (r = -0.37 and p = 0.02) predicted FBF response to ACh independently of age, gender and systolic blood pressure. There were no associations between LDL size, oxidized LDL, duration of diabetes and FBF response to BK, SNP, ACh + L-NMMA or BK + L-NMMA. CONCLUSION: In type 2 diabetes, small dense LDL particles, duration of diabetes and oxidized LDL may independently contribute to endothelial dysfunction of the microcirculation. These disturbances may occur via a selective defect, because ACh and BK activate endothelial NO synthase via different G-protein signal transduction pathways.     

Prevalence of abnormal glucose tolerance following a transient ischemic attack or ischemic stroke

BACKGROUND: Despite current preventive therapies, patients with transient ischemic attack (TIA) and ischemic stroke remain at high risk for recurrent brain disease and cardiovascular events. In an effort to develop new therapies, abnormal glucose tolerance has recently been proposed as an interventional target. Among persons not otherwise known to be diabetic, impaired glucose tolerance (IGT) and diabetic glucose tolerance (DGT) are each associated with an increased risk for incident vascular disease, vascular disease mortality, and all-cause mortality. We conducted this study to determine if IGT and DGT are sufficiently common among patients with TIA and ischemic stroke to warrant therapeutic trials of antihyperglycemic agents. METHODS: Men and women older than 45 years were recruited from 3 hospitals in south central Connecticut. Eligibility criteria included a recent TIA or nondisabling ischemic stroke, no history of physician-diagnosed diabetes mellitus, and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). After an overnight fast, subjects were admitted to a clinical research center for a standard 75-g oral glucose tolerance test. Impaired glucose tolerance was defined by a 2-hour plasma glucose value of 140 to 199 mg/dL (7.8-11.0 mmol / L) and DGT by a value of 200 mg/dL or greater (> or =11.1 mmol/L). RESULTS: Between June 2000 and August 2003, we enrolled 98 eligible patients. The average time from TIA or stroke to measurement of glucose tolerance was 105 days (range, 24-180 days) and the median age was 71 years. Twenty-seven subjects (28%) had IGT and 24 (24%) had diabetes. In a forward stepwise logistic regression model, only a fasting plasma glucose level of 110 mg/dL or greater (> or =6.1 mmol / L) and lower waist circumference were associated with an increased risk for IGT or DGT. CONCLUSIONS: Impaired glucose tolerance and DGT are present in most persons with a recent TIA or ischemic stroke who have no history of diabetes and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). Our findings bring new urgency to the initiation of research to examine the effectiveness of antihyperglycemic therapies among patients with cerebrovascular disease and abnormal glucose tolerance.     

Noninvasive Assessment of Endothelial Dysfunction in Essential Hypertension: Comparison of the Forearm Microvascular Reactivity with Flow-mediated Dilatation of the Brachial Artery

Endothelial dysfunction is detectable both in the forearm skin microcirculation by laser Doppler flowmetry and in the brachial artery by Duplex Ultrasound. The aim of the study was to evaluate whether endothelium-dependent vasodilation in the forearm microcirculation is related to endothelium-dependent flow mediated dilation (FMD) of the brachial artery. In 22 treated male essential hypertensive patients (EHT) who had impaired FMD of the brachial artery, and in 11 male normotensive subjects (NT) we measured first the postocclusive reactive hyperemic response (PORH), then the effect of two doses of acetylcholine (ACh) and sodium nitroprusside (SNP) on the forearm skin microcirculation. FMD resulted from forearm reactive hyperemia induced by 5 minutes of ischaemia and the vasodilation induced by sublingual nitroglycerine (GTN) were also measured. Responses were calculated as the maximal percent increase above baseline. PORH and the responses to ACh were significantly (p < 0.05, p <0.01) reduced in EHT (272 ± 180, 177 ± 194, 463 ± 302) as compared to NT (409 ± 123, 470 ± 467, 805 ± 603). Response to SNP was similar. FMD was significantly (p < 0.001) reduced in EHT as compared to NT (3.98 ± 2.2 vs 9.3 ± 2.88), while response to GTN was similar. There was no significant relationship (p = n.s.) either between maximal response to ACh and FMD (r = 0.28), or between PORH and FMD (r = –0.01). Endothelial dysfunction was detectable with both methods in EHT. Our results show that endothelium-dependent vasodilation in forearm microcirculation is not related to FMD of the brachial artery. This can be explained by the differences in vascular beds and mechanism involved in the hyperemic response. The study was supported by a grant of the Hungarian Scientific Council (OTKA T29420).     

High plasma insulin and triglyceride concentrations and blood pressure in offspring of people with impaired glucose tolerance

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non-obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p less than 0.05, Student's t-test) in offspring of parents with IGT (718 +/- 71 pmol l-1 h) than in the subjects whose parents had normal glucose tolerance (524 +/- 47 pmol l-1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17 +/- 0.11 vs 0.92 +/- 0.08 mmol l-1, 0.10 greater than p greater than 0.05), as were both systolic (132 +/- 5 vs 118 +/- 3 mmHg, p less than 0.05) and diastolic (79 +/- 3 vs 70 +/- 2 mmHg, p less than 0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.     

Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

Aims/hypothesis We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. Methods Non-diabetic offspring (n = 874; mean age 40 ± 10.4 years; BMI 26.6 ± 4.9 kg/m²) of type 2 diabetic patients from five different European Centres (Denmark, Finland, Germany, Italy and Sweden) were examined with regard to insulin sensitivity (euglycaemic clamps), insulin release (IVGTT) and glucose tolerance (OGTT). The levels of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) were measured during the OGTT in 278 individuals. Results Normal glucose tolerance was found in 634 participants, while 110 had isolated IFG, 86 had isolated IGT and 44 had both IFG and IGT, i.e. about 28% had a form of reduced glucose tolerance. Participants with isolated IFG had lower glucose-corrected first-phase (0–10 min) and higher second-phase insulin release (10–60 min) during the IVGTT, while insulin sensitivity was reduced in all groups with abnormal glucose tolerance. Similarly, GLP-1 but not GIP levels were reduced in individuals with abnormal glucose tolerance. Conclusions/interpretation The primary mechanism leading to hyperglycaemia in participants with isolated IFG is likely to be impaired basal and first-phase insulin secretion, whereas in isolated IGT the primary mechanism leading to postglucose load hyperglycaemia is insulin resistance. Reduced GLP-1 levels were seen in all groups with abnormal glucose tolerance and were unrelated to the insulin release pattern during an IVGTT.     

Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations.     

激光多普勒—离子电渗透药理系统测定皮肤微血管内皮细胞功能方法学评价

目的 内皮细胞功能障碍与高血压等多种疾病有关，本研究用激光多普勒－离子电渗透技术测定了健康人内皮细胞功能并对其方法学进行评价。方法 12例28－45岁健康志愿者接受测试，将1％硝普钠（生理盐水为稀释液）用离子电渗透法导入前臂皮肤，皮肤血管则产生非内皮细胞依赖的血管舒张。将1％乙酰胆碱（5％磷酸二氢钠为稀释液）用离子电爱法导入前臂皮肤，皮肤血管则产生内皮细胞依赖的血管舒张。结果 乙酰胆碱和硝普钠电渗透后，皮肤血流量在2－5分钟内可增加5－10倍，硝普钠电渗透后的皮肤血流量略高于乙酰胆碱电渗透后的血流量。当放电量小于6mC时，电流介导的非特异性血管扩张对内皮细胞功能检查没有明显影响。结论 激光多普勒－离子电渗透法是一种有临床应用前景的无创性评价皮肤血管内皮细胞功能的方法。     

Pancreatic polypeptide response to oral glucose load in patients with liver cirrhosis--interrelationship between PP and other pancreatic endocrine hormones

The purpose of the present study was to elucidate the interrelationship between pancreatic polypeptide (PP) and other pancreatic endocrine hormones. For this purpose, a radioimmunoassay (RIA) system of plasma PP was established and the changes in plasma PP, plasma immunoreactive insulin (IRI), plasma C-peptide reactivity (CPR) and plasma immunoreactive glucagon (IRG) following oral administration of glucose were examined in ten normal subjects and twenty-five patients with liver cirrhosis. Patients with liver cirrhosis were classified into a normal glucose tolerance group (NGT), an impaired glucose tolerance group (IGT), and a diabetes mellitus group (DM) on the basis of the glucose tolerance curves obtained after the oral administration of glucose. In the IGT and DM groups, fasting plasma PP levels were significantly elevated when compared with those in the control and NGT groups. Also oral administration of 75g glucose elicited an exaggerated rise in plasma PP in the IGT and DM groups when compared with the response in the control and NGT groups. On the other hand, PP response to glucose in the NGT group was similar to that in the control group. Plasma IRI increased markedly before and after oral administration of glucose in the IGT and DM groups when compared with the control groups. In these patients, plasma levels of CPR almost paralleled those of IRI. No significant difference was noted between the NGT group and the control group with regard to plasma IRI and CPR levels before and after oral glucose loading. Accordingly, insufficient insulin action was considered to exist in the IGT and DM groups. This insufficiency in insulin action was expressed in terms of the indices of increase in plasma IRI and CPR, delta IRI/delta BS and delta CPR/delta BS, which corresponded to the elevated blood glucose levels, being significantly lower in the IGT and DM groups than in the control and NGT groups 30 minutes after oral administration of glucose. No significant difference was noticeable between the NGT group and control group with regard to these indices. In the patients with liver cirrhosis, the delta PP value, obtained by subtracting the plasma PP level during fasting from the PP level 30 minutes after oral glucose loading, was inversely correlated with the values of both delta IRI/delta BS and delta CPR/delta BS.(ABSTRACT TRUNCATED AT 400 WORDS)     

Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.

OBJECTIVES: The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus. BACKGROUND: Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS: The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS: Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.     

空腹血糖异常、糖耐量减低患者血清胰岛素水平的变化及其意义

目的 观察空腹血糖异常(IFG)、糖耐量减低(IGT)患者血清胰岛素水平的变化。方法 对50例空腹血糖和糖耐量正常者(NGT)、40例IFC和80例IGT患者行口服葡萄糖耐量试验(0GTT)，用氧化酶法检测血糖，用放免法测定血清空腹及餐后2小时胰岛素。结果 IFG、IGT组空腹血糖、空腹胰岛素水平及胰岛素敏感指数较NGT组明显升高(P＜0.05或P＜0．01)，IFG组胰岛素敏感指数与IGT组比较无显著性差异(P＞0．05)。结论 在IFG、IGT状态下已经存在胰岛素抵抗，而且在程度上两者间并没有显著性差异，应早期干预治疗。     

beta-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis

The nature of the progressive beta-cell failure occurring as normal glucose tolerant (NGT) individuals progress to type 2 diabetes (T2DM) is incompletely understood. We measured insulin sensitivity (by a euglycemic insulin clamp) and insulin secretion rate (by deconvolution of plasma C-peptide levels during an oral glucose tolerance test) in 188 subjects [19 lean NGT (body mass index [BMI] 相似文献   

Additive effect of coexistent type 2 diabetes and arterial hypertension on endothelial dysfunction in resistance arteries of human forearm vasculature

Population studies suggest that vascular complications accumulate when arterial hypertension supervenes on diabetes mellitus. Although it has been demonstrated that endothelial function is impaired in patients with either diabetes mellitus or arterial hypertension it is unknown whether or not both diseases exert additive effects on endothelial dysfunction. The authors therefore investigated endothelium-dependent and endothelium-independent vasodilation in the forearm vasculature of 44 individuals: in 10 type 2 diabetic patients (DM), in 12 patients with arterial hypertension (HT), in 10 patients with both DM and HT (DM+HT), and in 12 healthy control subjects (C). Forearm blood flow (FBF) was measured by venous occlusion plethysmography at rest and following intraarterial infusion of acetylcholine (ACh) and the NO-donor sodium nitroprusside (SNP) at increasing doses. FBF at rest was significantly lower in diabetic patients: 2.2 +/- 0.1 (DM) and 2.6 +/- 0.2 (DM+HT) versus 3.1 +/- 0.1 (HT) and 3.4 +/- 0.2 (C) mL/min per 100 mL of tissue. ACh and SNP both increased FBF dose-dependently in each group. The maximum response to ACh was progressively decreased in DM and HT: 13.7 (C) > 8.1 (DM) > 7.6 (HT) > and 5.7 (DM+HT) mL/min per 100 mL of tissue. Reduction of the endothelium-dependent flow reserve assessed as percent increase in maximum FBF was also impaired following the same rank order: 349 (C) > 268 (DM) > 160 (HT) > 126 (DM+HT)%. The flow response to the NO-donor SNP amounted to: 327 (C), 306 (DM), 200 (HT), and 194% (DM+HT). In DM+HT the reduction of endothelium-dependent flow response was more pronounced compared with the endothelium-independent flow response. The present data provide evidence that type 2 diabetes and arterial hypertension impair endothelium-dependent dilation of resistance arteries in an additive manner suggesting that this progressive endothelial dysfunction might contribute to the increased incidence of cardiovascular complications when both diseases are coexistent.     

Reduced attenuation of bone resorption after oral glucose in type 2 diabetes

Objective  To investigate the effect of oral glucose on bone resorption and osteoprotegerin (OPG) in subjects with varying degrees of glucose tolerance.
Design and Patients  In a cross-sectional study, 163 postmenopausal women aged 50–88 years without previous history of diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were recruited. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and were then classified as having normal glucose tolerance (NGT), IFG, IGT or diabetes according to American Diabetes Association (ADA) criteria.
Measurements  Plasma glucose, serum insulin, C-terminal telopeptide of type I collagen (CTX-I) and OPG were measured.
Results  Fasting insulin levels increased progressively from subjects with NGT, IFG/IGT to diabetes. After adjusted for age and body mass index (BMI), there was no significant difference in fasting CTX-I and OPG levels across the various degrees of glucose tolerance. After oral glucose, there was a significant decrease in serum CTX-I and OPG ( P <  0·001) except for serum OPG in diabetic subjects. In addition, the percentages of change from baseline for both serum CTX-I and OPG were significantly less in diabetic subjects when compared to those in NGT subjects (–40·9% and 0·6% for diabetes and –50·2% and –10·6% for NGT, respectively).
Conclusions  Oral glucose intake causes suppression of serum CTX-I and OPG in postmenopausal women. The effect is attenuated in women with type 2 diabetes.     

Involvement of low adiponectin levels in impaired glucose tolerance

To investigate the association between serum adiponectin levels and 2-hour post-75-g oral glucose load glycemia, we conducted 75-g oral glucose tolerance tests in 50 subjects who had been diagnosed as having impaired glucose tolerance (IGT) within the prior 3 years. When adjusted for age, body mass index, and sex, serum adiponectin levels in the IGT and diabetes mellitus groups were significantly lower than those in the normal glucose tolerance and impaired fasting glucose groups (P < .0001). To determine which variables had significant impacts on 2-hour post-oral glucose glycemia, we performed multiple regression analyses. In stepwise analysis, serum adiponectin levels showed the highest F value (F = 6.43), suggesting the adiponectin level to be an independent predictor of 2-hour post-oral glucose glycemia. Thus, our clinical data suggest the involvement of low adiponectin levels in IGT and diabetes mellitus. To further assess this possibility, we prepared mice fed a high-fat diet for 2 months as an IGT model. Afterward, we compared the 2-hour postglucose glycemia in the IGT mice overexpressing recombinant adiponectin with that in control IGT mice. Mice overexpressing adiponectin showed significantly blunted 2-hour postglucose glycemia (5.66 ± 0.39 mmol/L) as compared with control mice (8.52 ± 0.67 mmol/L), whereas fasting glycemia was not significantly altered by adiponectin overexpression. Taken together, our results reveal the plasma glucose level in response to a glucose load to be negatively associated with serum adiponectin levels, suggesting low adiponectin levels to be one of the predictors of abnormal glucose homeostasis in IGT.     

Early insulin secretion failure leads to diabetes in Chinese subjects with impaired glucose regulation

Background Both beta‐cell dysfunction and decreased insulin sensitivity are involved in the pathogenesis of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), while their relative contribution in the progression to type 2 diabetes still remains controversial. The aim of the present study is to clarify this process in Chinese subjects by using cross‐sectional method. Methods 2975 Chinese subjects were classified into: normal glucose tolerance (NGT), impaired glucose regulations (IGR), and diabetes mellitus (DM) based on oral glucose tolerance test (OGTT). The IGR group was sub‐classified as isolated IFG, isolated IGT and combined glucose intolerance (CGI). The DM group was sub‐classified as normal fasting plasma glucose and 2‐hour hyperglycemia (N0D2), fasting hyperglycemia and normal 2‐hour plasma glucose (D0N2), and both fasting and 2‐hour hyperglycemia (D0D2). Results As far as insulinogenic index (IGI) was concerned, there was no difference between IFG and IGT in either gender, however, HOMA2‐B% (homeostasis model assessment for beta‐cell function) of IGT was higher than that of IFG and CGI in both male and female (P < 0.05). In the diabetic sub‐groups, IGI of N0D2 was higher than that of D0N2, and both deteriorated compared with those of IGT and IFG, respectively. HOMA2‐B% of N0D2 was still higher than that of D0N2 and D0D2. No significant difference was detected in OGIS and HOMA2‐S% (homeostasis model assessment for insulin sensitivity) between IFG and IGT, and this was the case between N0D2 and D0N2. OGIS and HOMA‐IR of IGR sub‐groups were not different from those of their diabetic counterparts. Conclusion Failure of beta‐cell function might be the main reason for both IGT and IFG developing into diabetes instead of aggravated insulin resistance. Copyright © 2008 John Wiley & Sons, Ltd.