蚕丝蛋白对糖尿病小鼠空腹血糖和糖耐量的影响

目的:研究蚕丝蛋白对四氧嘧啶糖尿病小鼠的血糖代谢调节作用,为中医药干预糖尿病提供实验依据。方法:于2003-01/06在江苏省疾病预防控制中心毒理室用四氧嘧啶制备糖尿病小鼠模型后,连续用蚕丝蛋白溶液灌胃30d后,观察其对糖尿病模型小鼠以及正常小鼠空腹血糖和糖耐量的影响。结果:蚕丝蛋白在1000和3000mg/kg的剂量下,糖尿病小鼠的空腹血糖值明显低于模型对照组(P<0.05,P<0.01),血糖降低百分率分别达15.50%和17.48%,而模型对照组小鼠的血糖值仅降低了9.95%;1000,3000mg/kg剂量的蚕丝蛋白溶液具有明显增强糖尿病小鼠的糖耐量作用。蚕丝蛋白对正常小鼠的血糖水平无明显影响。结论:蚕丝蛋白对糖尿病小鼠的血糖具有辅助调节作用。     

蚕丝蛋白对糖尿病小鼠空腹血糖和糖耐量的影响

目的：研究蚕丝蛋白对四氧嘧啶糖尿病小鼠的血糖代谢调节作用。为中医药干预糖尿病提供实验依据。方法：于2003—01／06在江苏省疾病预防控制中心毒理室用四氧嘧啶制备糖尿病小鼠模型后，连续用蚕丝蛋白溶液灌胃30d后，观察其对糖尿病模型小鼠以及正常小鼠空腹血糖和糖耐量的影响。结果：蚕丝蛋白在1000和3000mg／ks的剂量下，糖尿病小鼠的空腹血糖值明显低于模型对照组（尸〈0．05，P〈0．01），血糖降低百分率分别达15．50％和17．48％，而模型对照组小鼠的血糖值仅降低了9．95％；1000，3000mg／kg剂量的蚕丝蛋白溶液具有明显增强糖尿病小鼠的糖耐量作用。蚕丝蛋白对正常小鼠的血糖水平无明显影响。结论：蚕丝蛋白对糖尿病小鼠的血糖具有辅助调节作用。     

PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a ubiquitous neuropeptide of the vasoactive intestinal peptide (VIP) family that potentiates glucose-stimulated insulin secretion. Pancreatic beta cells express two PACAP receptor subtypes, a PACAP-preferring (PAC1) and a VIP-shared (VPAC2) receptor. We have applied a gene targeting approach to create a mouse lacking the PAC1 receptor (PAC1(-/-)). These mice were viable and normoglycemic, but exhibited a slight feeding hyperinsulinemia. In vitro, in the isolated perfused pancreas, the insulin secretory response to PACAP was reduced by 50% in PAC1(-/-) mice, whereas the response to VIP was unaffected. In vivo, the insulinotropic action of PACAP was also acutely reduced, and the peptide induced impairment of glucose tolerance after an intravenous glucose injection. This demonstrates that PAC1 receptor is involved in the insulinotropic action of the peptide. Moreover, PAC1(-/-) mice exhibited reduced glucose-stimulated insulin secretion in vitro and in vivo, showing that the PAC1 receptor is required to maintain normal insulin secretory responsiveness to glucose. The defective insulinotropic action of glucose was associated with marked glucose intolerance after both intravenous and gastric glucose administration. Thus, these results are consistent with a physiological role for the PAC1 receptor in glucose homeostasis, notably during food intake.     

重视IFG、IGT的防治

糖耐量低减(impaired glucose tolerance，IGT)和空腹血糖异常(impaired fating glueose,IFG)均为糖尿病自然病程中的中间阶段。目前并未被确认为疾病状态，只认为是正常与疾病之间的一种高危状态，称前糖尿病状态(pre-diabetes)。大规模、前瞻性研究已证实：IGT和(或)IFG人群进展为临床糖尿病的危险显著高于正常糖耐量者(NGT)，年发病率约3％-10％，是临床糖尿病的主要后备人群；IGT和(或)IFG是冠心病、高血压及脑血管意外等疾病的重要危险因素；强化生活方式干预(饮食控制、运动)和一定的药物干预。可有效延缓和减少IGT／IFG人群的糖尿病危险。广东省1998年流行病学调查显示，20-74     

1157例体检者空腹血糖及糖耐量分析

目的 对1 157例体检者空腹血糖及糖耐量分析,掌握该区居民的血糖及其代谢情况.方法 采用人口成比例抽样(PPS)的方法,按经济条件分成3个层次,随机抽取1 157例研究对象采用葡萄糖氧化酶法测定空腹血糖,其中926例口服75 g无水葡萄糖2 h后测量血糖.结果 共计检出高血糖患者198例,检出糖耐量受损者117例,占12.63%,糖尿病患病率则为4.86%.结论 该区糖尿病患者及潜在者形势严峻,该区当前糖尿病防治应以经济较好的市区为重点向开发区辐射直至全区.     

Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose

OBJECTIVE: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.     

Acute effects of nicorandil on glucose tolerance in subjects with borderline fasting blood glucose levels

The acute effect of the anti-ischemic potassium channel opener nicorandil on glucose tolerance and post-challenge insulin levels was investigated in 11 subjects (6 males and 5 females, age 59 +/- 2 years) with borderline fasting blood glucose in a single blinded randomised study. All participants were submitted to two oral glucose tolerance tests in randomised order, once without any premedication and once 30 minutes after oral administration of 20 mg nicorandil. This single dose of nicorandil significantly increased blood glucose levels at 120 minutes (173 +/- 16 vs. 150 +/- 11 mg/dl, p < 0.05 by ANOVA) and 180 minutes (106 +/- 11 vs. 88 +/- 7 mg/dl, p < 0.05 by ANOVA) after ingestion of 75 mg of glucose. Serum insulin levels were not significantly altered. In conclusion we suggest that controlled studies in patients with coronary artery disease should be performed to investigate whether long term treatment with nicorandil increases progression rates from impaired glucose tolerance to type-II diabetes and/or from normal to impaired glucose tolerance with a possibly negative impact on the course of cardiovascular disease in comparison to conventional anti-anginal drugs.     

Evidence for elevated glucose threshold in patients with impaired glucose tolerance and symptoms of hypoglycemia during OGTT

We evaluated the relationship between hypoglycemic symptoms, glucose nadir levels, and hormone changes in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT). The peak counterregulatory hormone response was determined at the glucose nadir identified by continuous glucose monitoring. Eight patients with IGT who had symptoms and signs typical of hypoglycemia at the glucose nadir were compared with completely asymptomatic subjects (5 IGT patients and 13 patients who had normal glucose tolerance [NGT]). The mean glucose nadir of symptomatic IGT patients was 3.50 +/- 0.46 mM, which was not statistically different from the mean of asymptomatic NGT patients (4.10 +/- 0.56 mM) but was significantly lower than that for asymptomatic IGT patients (5.10 +/- 0.81 mM, P less than 0.001). Seven of 8 symptomatic IGT patients had glucose levels that never fell below the range of glucose nadirs for asymptomatic NGT patients. However, the symptomatic IGT group had significantly higher levels of growth hormone, cortisol, epinephrine, and norepinephrine than the asymptomatic groups in response to the nadir. We conclude that patients with IGT are capable of experiencing signs and symptoms of hypoglycemia at physiological glucose levels during OGTT with reflex stimulation of counterregulatory hormone release. This may indicate that symptomatic IGT patients have a higher glucose threshold for eliciting characteristic hypoglycemic symptom episodes than individuals with NGT.     

Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans

OBJECTIVE: To compare the pathophysiology of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a more comprehensive and standardized fashion than has hitherto been done. RESEARCH DESIGN AND METHODS: We studied 21 individuals with isolated IFG (IFG/normal glucose tolerance [NGT]), 61 individuals with isolated IGT (normal fasting glucose [NFG]/IGT), and 240 healthy control subjects (NFG/NGT) by hyperglycemic clamps to determine first- and second-phase insulin release and insulin sensitivity. Homeostasis model assessment (HOMA) indexes of beta-cell function (HOMA-%B) and insulin resistance (HOMA-IR) were calculated from fasting plasma insulin and glucose concentrations. RESULTS: Compared with NFG/NGT, IFG/NGT had similar fasting insulin concentrations despite hyperglycemia; therefore, HOMA-IR was increased approximately 30% (P < 0.05), but clamp-determined insulin sensitivity was normal (P > 0.8). HOMA-%B and first-phase insulin responses were reduced approximately 35% (P < 0.002) and approximately 30% (P < 0.02), respectively, but second-phase insulin responses were normal (P > 0.5). NFG/IGT had normal HOMA-IR but approximately 15% decreased clamp-determined insulin sensitivity (P < 0.03). Furthermore, HOMA-%B was normal but both first-phase (P < 0.0003) and second-phase (P < 0.0001) insulin responses were reduced approximately 30%. IFG/NGT differed from NFG/IGT by having approximately 40% lower HOMA-%B (P < 0.012) and approximately 50% greater second-phase insulin responses (P < 0.005). CONCLUSIONS: Since first-phase insulin responses were similarly reduced in IFG/NGT and NFG/IGT, we conclude that IFG is due to impaired basal insulin secretion and preferential resistance of glucose production to suppression by insulin, as reflected by fasting hyperglycemia despite normal plasma insulin concentrations and increased HOMA-IR, whereas IGT mainly results from reduced second-phase insulin release and peripheral insulin resistance, as reflected by reduced clamp-determined insulin sensitivity.     

Contribution of visceral adiposity to the exaggerated postprandial lipemia of men with impaired glucose tolerance

OBJECTIVE: Impaired glucose tolerance (IGT) has been associated with alterations in numerous coronary heart disease risk factors, including postprandial hyperlipidemia. An excess visceral adipose tissue accumulation is also predictive of IGT and of an exaggerated postprandial lipemia. The objective of the present study was therefore to compare the respective contributions of visceral adipose tissue accumulation versus IGT with the variation in postprandial lipemia. RESEARCH DESIGN AND METHODS: Potential differences in postprandial triglyceride (TG)-rich lipoprotein (TRL) levels following a standardized breakfast with a high fat content were examined among men characterized by normal glucose tolerance (NGT) or IGT. Sixty-seven men were classified according to their glucose tolerance status (<7.8 mmol/l [NGT] or between 7.8 and 11.1 mmol/l [IGT] 2 h after a 75-g oral glucose test). RESULTS: Men with IGT showed the highest TRL-TG concentrations (P < 0.05) at the 4-, 6-, and 8-h time points compared with men with NGT. These higher postprandial TRL-TG levels among men with IGT were also accompanied by a greater postprandial TG total area under the incremental curve in all TRL fractions (large, medium, and small) (P < 0.05). Furthermore, subjects characterized by IGT had also the highest visceral adipose tissue accumulation (P < 0.009). When subgroups of IGT and NGT men were individually matched (n = 11) for similar visceral adipose tissue accumulation, no significant difference was found in postprandial responses of all TRL-TG fractions between the two groups. CONCLUSIONS: These results provide evidence that visceral adipose tissue accumulation is an important factor involved in the deterioration of postprandial lipemia noted among men with IGT.     

空腹血糖正常的原发性高血压患者糖代谢异常状况研究

目的研究原发性高血压伴有糖代谢异常患者的各项指标,为全面干预心血管危险因素提供依据。方法选择既往无糖代谢异常病史,空腹血糖〈5.6 mmol/L的原发性高血压患者398例,测定口服葡萄糖耐量试验（OGTT）后2小时血糖（2 hPG）水平。观察年龄、性别、体质量指数、血压、血脂、尿酸、动脉硬化等参数与OGTT后2hPG的关系。结果 398例患者中检出糖耐量减低99例（24.9%）;2型糖尿病52例（13.1%）。糖代谢异常的患者动脉硬化的比例（71.5%）高于血糖正常组（52.6%）。结论原发性高血压患者合并糖代谢异常的比例高,对于空腹血糖正常的原发性高血压患者,应常规行OGTT测定,以早期发现和干预糖代谢紊乱,减少动脉硬化的发生。     

Cardiometabolic risk in impaired fasting glucose and impaired glucose tolerance: the Atherosclerosis Risk in Communities Study

OBJECTIVE: We compared and contrasted cardiovascular disease (CVD) risk factors, subclinical manifestations of CVD, incident coronary heart disease (CHD), and all-cause mortality by categories of impaired glucose regulation in nondiabetic individuals. RESEARCH DESIGN AND METHODS: The study included 6,888 participants aged 52-75 years who had no history of diabetes or CVD. All-cause mortality and incident CHD were ascertained over a median of 6.3 years of follow-up. RESULTS: Agreement between fasting and postchallenge glucose impairment was poor: 3,048 subjects (44%) had neither impaired fasting glucose (IFG) nor impaired glucose tolerance (IGT), 1,690 (25%) had isolated IFG, 1,000 (14%) had isolated IGT, and 1,149 (17%) had both IFG and IGT. After adjustment for age, sex, race, and center, subjects with isolated IFG were more likely to smoke, consume alcohol, and had higher mean BMI, waist circumference, LDL cholesterol, and fasting insulin and lower HDL cholesterol than those with isolated IGT, while subjects with isolated IGT had higher mean triglycerides, systolic blood pressure, and white cell counts. Measures of subclinical CVD and rates of all-cause mortality and incident CHD were similar in isolated IFG and isolated IGT. CONCLUSIONS: Neither isolated IFG nor isolated IGT was associated with a more adverse CVD risk profile.     

Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy

OBJECTIVE: To characterize a cohort of patients with neuropathy and impaired glucose tolerance (IGT) but no other identifiable cause of neuropathy. Of patients with diabetes, 10% have peripheral neuropathy at the time of their diagnosis, suggesting that axonal injury may occur early in the course of glucose intolerance. The American Diabetes Association (ADA) revised diagnostic criteria to recognize IGT (a serum glucose between 140 and 200 mg/dl in a 2-h oral glucose tolerance test [OGTT]) as a risk factor for cardiovascular disease independent of development of diabetes. RESEARCH DESIGN AND METHODS: Using revised ADA criteria for diabetes and IGT, we prospectively evaluated 107 sequential patients with idiopathic neuropathy. RESULTS: A total of 13 of the 107 patients had diabetes, whereas 36 (34%) had IGT, nearly three times the prevalence in age-matched control subjects (P < 0.01). OGTT was often elevated, whereas both fasting plasma glucose and HbA(1c) were normal. Comparing patients with diabetes, IGT, or normal OGTT, age and BMI were similar. However, painful sensory symptoms were more common in patients with IGT and diabetes, and family history of neuropathy was significantly more common in normoglycemic patients. Electrodiagnostic findings of axonal injury were less severe in patients with IGT and were more likely to be confined to sensory fibers than in patients with diabetes. CONCLUSIONS: Our results suggest that IGT may cause or contribute to small-fiber neuropathy, which is similar in phenotype to the painful sensory neuropathy commonly encountered in diabetes. Two-hour OGTT is more sensitive than other measures of glucose handling in screening these patients.     

Lack of agreement between the revised criteria of impaired fasting glucose and impaired glucose tolerance in children with excess body weight

OBJECTIVE: The aim of this study was to describe the agreement between impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) in children with excess body weight using the original and the revised definitions of IFG. RESEARCH DESIGN AND METHODS: Obese and overweight children aged 4-17 years were included (n = 533). Anthropometric parameters and biochemical tests (fasting and 2-h glucose tests after an oral glucose load [1.75 g/kg]) were performed. Case subjects with a fasting plasma glucose >/=126 mg/dl were excluded. The diagnostic parameters of the original and the revised definitions of IFG for detecting IGT were estimated. The analysis of agreement between these categories was made using the kappa test. RESULTS: The prevalence of IFG increased from 6.2 to 13.3% using the new criteria. The prevalence of IFG became closer to the prevalence of IGT (14.8%). The revised criteria increased the sensitivity from 26.6 to 36.7%. However, the new IFG definition was not useful for identifying IGT cases. Of the 71 case subjects with IFG, only 29 (40.8%) had IGT. In addition, 50 case subjects with IGT (9.4%) and 13 with diabetes (2.4%) had a fasting glycemia <100 mg/dl. A poor agreement was found between the 2003 IFG definition and abnormal 2-h postchallenge plasma glucose (kappa = 0.359). The proportion of false-positive cases increased (36.3-59.1%) under the new definition. CONCLUSIONS: The new definition modestly increases the sensitivity of IFG for detecting IGT in children with excess body weight. Despite this, more than one-half of these cases are not detected. In addition, the false-positive rate was increased by 61%.     

Impaired fasting glucose and impaired glucose tolerance in women with prior gestational diabetes are associated with a different cardiovascular profile

OBJECTIVE: The purpose of this study was to investigate the association of cardiovascular risk factors to impaired glucose tolerance (IGT) and to impaired fasting glucose (IFG) in women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We studied 838 women with prior GDM. Postpartum glucose tolerance status was classified as normal, IFG, IGT, IFG plus IGT, and diabetes according to the World Health Organization criteria. Postpartum BMI, waist circumference, blood pressure, triglyceride, cholesterol, and HDL cholesterol were assessed. RESULTS: BMI and blood pressure were significantly higher in women with IFG than in women with normal glucose status. BMI and waist circumference were significantly higher in women with IFG plus IGT than in women with normal glucose status. No differences were observed between women with IGT and normal glucose status. The prevalence of hypertension and obesity was significantly increased in IFG compared with normal glucose status. The prevalence of obesity and abnormal lipids was significantly increased in IFG plus IGT compared with normal glucose status. IGT showed no increased prevalence of cardiovascular risk factors. CONCLUSIONS: Traditional cardiovascular risk factors have a stronger association with isolated IFG than with isolated IGT in women with prior GDM.     

空腹血糖受损与糖耐量受损者胰岛β细胞功能及胰岛素抵抗的比较

目的：比较空腹血糖受损与糖耐量受损者胰岛β细胞功能及胰岛素抵抗的不同。方法：选择正常糖耐量者40例，空腹血糖受损者32例，糖耐量受损者38例。测体重指数、血压、血脂、空腹及糖负荷后的血糖、血胰岛素。用稳态模式胰岛素抵抗指数HOMA—IR抵抗作为胰岛素抵抗指标，稳态模式HOMA—β作为基础胰岛素分泌指标，糖负荷30min净增胰岛素／净增葡萄糖作为早期胰岛素分泌指数。结果：空腹血糖受损组HOMA-IR较耐量受损组增高，差异有显著性（P〈0．05）。空腹血糖受损组HOMA—β较糖耐量受损组降低，差异有显著性（P〈0.05）。糖耐量受损组净增胰岛素／净增葡萄糖与空腹血糖受损组比较有下降，但差异无统计学意义。结论：空腹血糖受损人群较糖耐量受损人群有着更严重的胰岛素抵抗，空腹血糖受损人群基础状态下胰岛β细胞功能受损，而糖耐量受损人群的早期胰岛素分泌反应减弱。     

Impact of differences in fasting glucose and glucose tolerance on the hyperbolic relationship between insulin sensitivity and insulin responses

OBJECTIVE: To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance. RESEARCH DESIGN AND METHODS: We studied 219 healthy subjects (88 male and 131 female subjects, aged 26-75 years) with fasting plasma glucose (FPG) <6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the latter a measure of intravenous glucose tolerance. RESULTS: Si and AIRg were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG <5.56 mmol/l vs. IFG, FPG 5.56-6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was left shifted in the IFG compared with NFG group (P < 0.001) and was progressively more left shifted with decreasing Kg (P < 0.001), consistent with decreasing beta-cell function. These changes were not observed for the curves relating Si and fasting insulin, suggesting that in the fasting state beta-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (Si x AIRg) was calculated as a measure of beta-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG. CONCLUSIONS: The inverse relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a hyperbolic relationship, a decrease in beta-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.