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Measurement of Acute Tolerance to Alcohol in Human Subjects   总被引:2,自引:0,他引:2  
Acute tolerance can be defined as a decrease in response to alcohol within a single exposure to the drug, which occurs independently of changes in blood alcohol concentrations (BACs). BACs change over time in most human alcohol administration studies, and computational techniques that account for these changes must be used to measure the rate of acute tolerance development. The most widely used acute tolerance measure in human research is often called the Mellanby effect, and involves the comparison of responses at the same BAC on the ascending and descending limbs of the blood alcohol curve. We compared the Mellanby measure with two other measures of acute tolerance: a conceptually similar area under the curve measure, and a slope function approach that used data only from the descending limb of the blood alcohol curve. The measures were intercorrelated and discussed with regard to empirical and conceptual issues. Exploratory comparisons of those with and with-out a family history of alcoholism are reported. Methodological recommendations for the computation of acute tolerance are made. The results suggest new methods for measuring the rate of acquisition of acute tolerance, and suggest areas for future research on tolerance-proneness and risk for alcoholism.  相似文献   

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ABSTRACT Glucose tolerance and reported physical leisure time activity were studied in middle-aged, 47–54 years old, subjects in a health survey. The mean 2-hour blood glucose value after 75 g oral glucose tolerance tests was higher (p<0.001) in 682 subjects with a lower degree of leisure time activity than in 125 subjects who were regularly active at least 2–3 hours per week. The mean 2-hour glucose values in the inactive and active groups, respectively, were 4.61 and 4.09 mmol·1-1 after adjustment for the influence of age, body mass index, smoking and physical job activity by analysis of covariance. The difference between adjusted mean 2-hour glucose values was also significant (p<0.001) in the subgroups of 280 low leisure time activity males (4.53 mmol·1-1) and 91 active males (3.93 mmol·1-1). Thus, a relation between physical leisure time inactivity and raised post load blood glucose values seems to exist in the general population.  相似文献   

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Background:Current mathematical models of postprandial glucose metabolism in people with normal and impaired glucose tolerance rely on insulin measurements and are therefore not applicable in clinical practice. This research aims to develop a model that only requires glucose data for parameter estimation while also providing useful information on insulin sensitivity, insulin dynamics and the meal-related glucose appearance (GA).Methods:The proposed glucose-only model (GOM) is based on the oral minimal model (OMM) of glucose dynamics and substitutes the insulin dynamics with a novel function dependant on glucose levels and GA. A Bayesian method and glucose data from 22 subjects with normal glucose tolerance are utilised for parameter estimation. To validate the results of the GOM, a comparison to the results of the OMM, obtained by using glucose and insulin data from the same subjects is carried out.Results:The proposed GOM describes the glucose dynamics with comparable precision to the OMM with an RMSE of 5.1 ± 2.3 mg/dL and 5.3 ± 2.4 mg/dL, respectively and contains a parameter that is significantly correlated to the insulin sensitivity estimated by the OMM (r = 0.7) Furthermore, the dynamic properties of the time profiles of GA and insulin dynamics inferred by the GOM show high similarity to the corresponding results of the OMM.Conclusions:The proposed GOM can be used to extract useful physiological information on glucose metabolism in subjects with normal glucose tolerance. The model can be further developed for clinical applications to patients with impaired glucose tolerance under the use of continuous glucose monitoring data.  相似文献   

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Loss of the first phase insulin response to intravenous glucose is one of the earliest detectable defects of beta cell dysfunction in Type 2 diabetes mellitus. Impaired glucose tolerance (IGT) is considered a prediabetic condition, therefore loss of first phase insulin secretion in subjects with IGT would suggest beta cell dysfunction as an early lesion in the development of Type 2 diabetes. Three groups of subjects were studied, 7 subjects with persistent IGT (classified as having IGT at two 75 g oral glucose tolerance tests (OGTT) done 6 months apart), 6 subjects with transient IGT (IGT at the first OGTT, but normal glucose tolerance at a repeat OGTT 6 months later), and 7 normal controls. First phase insulin secretion was studied using an intravenous glucose tolerance test with arterialized blood sampling. Fasting, 3, 4 and 5 min samples were assayed for glucose and insulin (specific two-site immunoradiometric assay). The fasting insulin was similar in all three groups, however the 3 min insulin response was significantly lower in those with persistent impaired glucose tolerance (p < 0.02). Thus subjects with persistent impaired glucose tolerance demonstrated loss of the first phase insulin response as an early indicator of beta cell dysfunction while subjects with transient IGT had a normal insulin response to intravenous glucose. During the OGTT, the 30 min glucose was not significantly different (p = 0.1) but the 30 min insulin to glucose ratio was significantly lower in subjects with persistent IGT (p < 0.03). In the whole group the 30 min insulin to glucose ratio during the OGTT showed a significant correlation with the peak insulin response during the IVGTT (r = 0.76, p < 0.001). This study suggests that beta cell dysfunction with impaired early insulin release is present before the development of Type 2 diabetes.  相似文献   

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To assess the relationship between blood pressure (BP) and serum insulin level in nonobese (body mass index (BMI) ≤ 27 kg m?2), middle-aged (40–64 years of age) Japanese subjects with normal glucose tolerance, a three-phase study protocol was designed. First, the responses of plasma glucose and serum insulin to an oral glucose load were compared between 40 patients with untreated essential hypertension and 40 age-, sex- and BMI-matched normotensive control subjects. Second, the glucose and insulin responses to an i.v. glucose load were evaluated in 7 non-obese hypertensive, 7 non-obese normotensive and 7 obese hypertensive subjects. Third, BP and serum lipid profile were compared between 21 hyperinsulinaemic (serum insulin level (while fasting, after glucose loading, or both) > 2 SDs higher than the mean) and 21 age-, sex- and BMI-matched normoinsulinaemic subjects (serum insulin level within 1 SD of the mean). The glucose and insulin responses to the oral glucose load were comparable between the hypertensive and normotensive groups. Similarly, the glucose and insulin responses to the i.v. glucose load were comparable between the non-obese hypertensive and normotensive groups, whereas the mean AUCinsulin in the obese hypertensive group was significantly greater (p < 0.01) than that in either of the non-obese groups. The respective mean values for systolic and diastolic BPs did not differ between the hyperinsulinaemic and normoinsulinaemic groups. The mean serum triglyceride and HDL cholesterol concentrations were significantly higher (p < 0.01) and lower (p < 0.05), respectively, in the hyperinsuslinaemic than in the normoinsulinaemic group. The results suggest no association between serum insulin level and BP in non-obese, middle-aged, Japanese subjects with normal glucose tolerance.  相似文献   

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To evaluate the clinical significance of proinsulin determination, we measured glucose, insulin, C-peptide and proinsulin during 75-g oral glucose loading in 59 patients. In a 2.5-year follow-up study of 37 subjects with impaired glucose tolerance (IGT) at the initial test, 11 patients changed from IGT to a normal state and 5 patients showed worsening to overt Type 2 diabetes with elevation of fasting plasma glucose; 21 patients remained unchanged. Although our data showed that both fasting (IGT: p = 0.4523) and 120-min plasma glucose (IGT: p = 0.8168) values at the initial test were not significantly correlated with increased fasting plasma glucose levels in a 2.5-year follow-up study, subjects with a higher 120-min proinsulin response to glucose during the initial OGTT showed a significant correlation (IGT: p <0.0001) with increased fasting plasma glucose levels after follow-up period and developed Type 2 diabetes. The present findings suggest that the proinsulin response to glucose loading might be a useful indicator for predicting worsening to diabetes in subjects with impaired glucose tolerance.  相似文献   

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The effects of standard oral glucose loading (100 g) on plasma aldosterone and some regulatory factors were assessed in patients with primary hyperaldosteronism and normal subjects. Following overnight fast, mean plasma glucose was identical (10 patients and normal subjects approximately matched per age and sex); plasma insulin, potassium and renin levels were lower and plasma aldosterone higher in the patients. Glucose loading significantly increased plasma glucose and insulin concentrations and decreased plasma potassium and aldosterone levels in both groups; plasma renin activity was significantly increased only in normal subjects. The increases in plasma insulin and the decreases in plasma potassium or aldosterone tended to be blunted in primary hyperaldosteronism.

Relationships among glucose-induced changes in plasma aldosterone and other factors were assessed by multiple regression analysis in these patients and normal subjects as well as an additional group of 21 normal subjects; in the latter, plasma cortisol was also measured and found to decrease significantly after glucose loading. Changes in plasma aldosterone correlated (P< 0.025) more closely with those in plasma potassium in the patients and with variations in plasma renin activity in the normal subjects. These findings suggest that complex metabolic changes occur following glucose ingestion which are capable of modifying aldosterone secretion in normal subjects and primary hyperaldosteronism. The aldosterone-inhibitory effect of glucose tends to be blunted in the latter disorder. This could be related at least in part to an impaired insulin response in primary hyper- aldosteronism.  相似文献   

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In view of recent interest in the role of impaired early development and the pathogenesis of cardiovascular disease and carbohydrate intolerance in adults, this study examines whether reduced skin capillary density contributes to the limited microvascular hyperaemic responses observed in patients with Type 2 diabetes and subjects with impaired glucose tolerance (IGT). Fifteen patients with Type 2 diabetes, 15 subjects with IGT and 15 matched non-diabetic control subjects were studied. Capillary videomicroscopy was used to record images of the skin capillaries on the dorsum of the middle phalanx of the left middle finger before and after 10 min venous occlusion at 35 mmHg. There were no significant differences between the three groups in either basal capillary density (112 (71–144) caps mm−2 Type 2 patients (median and range) vs 107 (76–140) caps mm−2 IGT subjects vs 112(76–138) caps mm−2 control subjects; p = 0.9, Kruskal Wallis), or following venous occlusion (122(87–157) caps mm−2 vs 121 (90–143) caps mm−2 vs 123 (81–147) caps mm−1; p=0.9). In addition there were no differences in blood pressure, BMI or skin temperature. These results do not support the concept of impaired early development of the skin microcirculation in patients with Type 2 diabetes or IGT and suggest that mechanisms other than reduced capillary density are involved in limiting microvascular vasodilation.  相似文献   

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A random sample of the middle-aged population of Malta was studied in a diabetic survey in 1981. Among the 1537 survey responders, in 659 men and 878 women aged 40 years or more the prevalence of diabetes was 16 % in men and 18 % in women, and that of IGT 5 % in both sexes. By the end of 1985, 90 subjects (49 men: 41 women) had died. Mortality/1000 (95 % CI) was among subjects with normal, impaired glucose tolerance and diabetes in the age group 40–59 years 12 (5–19), 25 (23–73), and 61 (17–148), and in the age group of more than 60 years, 102 (68–136), 148 (59–237), and 178 (122–234), respectively. Age standardized mortality/1000 was in men 51, 28, and 100, and in women 34, 33, and 72 in the three categories of glucose tolerance, respectively. Among diabetic subjects aged 40–64 years the risk of death was increased seven-fold as compared with normoglycaemic subjects. Among men there was an inverse association between body mass index and mortality in all categories of glucose tolerance. Among women, no clear trend between body mass index and mortality was found. The relative risk of death for subjects with diabetes adjusting for age, sex, and body mass index was 2.2 (odds ratio: 95 % CI 1.40 to 3.42) as compared with non-diabetic subjects. The age-adjusted survival curves for normoglycaemic subjects were similar for men and women. Among subjects with abnormal glucose tolerance the survival was slightly better in women than in men (p = 0.056). About half of the deaths were from cardiovascular disease and 7 % from diabetes mellitus.  相似文献   

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男性高血压患者发生糖代谢异常的危险因素   总被引:4,自引:0,他引:4  
目的探讨正常葡萄糖耐量的男性高血压患者发生糖代谢异常的危险因素。方法对口服葡萄糖耐量试验(OGTT)正常的106例男性原发性高血压患者进行随访研究,随访前后测定OGTT、同步胰岛素释放试验(InRT)、血脂、血压、体重指数(BMI)及腰围,用HOMA-IR、胰岛素敏感性指数(ISI)及胰岛素代谢清除率(MCRi)计算胰岛素敏感性,用HOMA-β及胰岛素1相和2相分泌计算β细胞功能。结果(1)106例正常葡萄糖耐量(NGT)的男性原发性高血压患者,平均随访3年后,新发糖尿病6例(5.7%),进展为IGT的39例(36.8%),保持NGT的61例(57.5%);(2)随访后进展为IGT的患者与仍为NGT的患者相比较,前者随访前的腰围、BMI、空腹血糖、OGTT2h和3h血糖、OGTT2h胰岛素水平均显著增高(P<0.01),ISI及MCRi显著减低(P<0.01);(3)调整年龄、血压、血脂等因素后,多因素Lo-gistic回归显示腹型肥胖和OGTT2h血糖是男性EHT从NGT转为IGT的独立危险因素(OR值分别为6.81和2.13);(4)随访前有腹型肥胖的NGT高血压患者进展为IGT的比率明显高于无腹型肥胖者(60%vs19%,P<0.01)。比较随访前指标发现,腹型肥胖组的ISI和MCRi显著降低、糖负荷后胰岛β细胞分泌显著增强(P<0.01),随访前后比较,腹型肥胖组HOMA-IR和HOMA-β明显增高(P<0.01)。结论腹型肥胖和OGTT2h血糖是无糖代谢异常的男性原发性高血压患者发展为糖耐量异常的风险预测指标。胰岛素敏感性降低及胰岛β细胞功能增强与腹型肥胖的男性NGT高血压患者发生IGT有关。  相似文献   

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男性高血压患者发生糖代谢异常的危险因素   总被引:1,自引:0,他引:1  
目的探讨正常葡萄糖耐量的男性高血压患者发生糖代谢异常的危险因素.方法对口服葡萄糖耐量试验(OGTT)正常的106例男性原发性高血压患者进行随访研究,随访前后测定OGTT、同步胰岛素释放试验(InRT)、血脂、血压、体重指数(BMI)及腰围,用HOMA-IR、胰岛素敏感性指数(ISI)及胰岛素代谢清除率(MCRi)计算胰岛素敏感性,用HOMA-β及胰岛素1相和2相分泌计算β细胞功能.结果 (1)106例正常葡萄糖耐量(NGT)的男性原发性高血压患者,平均随访3年后,新发糖尿病6例(5.7%),进展为IGT的39例(36.8%),保持NGT的61例(57.5%);(2)随访后进展为IGT的患者与仍为NGT的患者相比较,前者随访前的腰围、BMI、空腹血糖、OGTT 2 h和3 h血糖、OGTT 2 h胰岛素水平均显著增高(P<0.01),ISI及MCRi显著减低(P<0.01);(3)调整年龄、血压、血脂等因素后,多因素Logistic回归显示腹型肥胖和OGTT 2 h血糖是男性EHT从NGT转为IGT的独立危险因素(OR值分别为6.81和2.13);(4)随访前有腹型肥胖的NGT高血压患者进展为IGT的比率明显高于无腹型肥胖者(60% vs 19%,P<0.01).比较随访前指标发现,腹型肥胖组的ISI和MCRi显著降低、糖负荷后胰岛β细胞分泌显著增强(P<0.01),随访前后比较,腹型肥胖组HOMA-IR和HOMA-β明显增高(P<0.01).结论腹型肥胖和OGTT 2 h血糖是无糖代谢异常的男性原发性高血压患者发展为糖耐量异常的风险预测指标.胰岛素敏感性降低及胰岛β细胞功能增强与腹型肥胖的男性NGT高血压患者发生IGT有关.  相似文献   

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In a double-blind, randomized, cross-over study, the metabolic effects of a short treatment with metformin (2 times 850 mg day?1 for 2 days and 850 mg 1 h before evaluation) were compared to those of placebo in 15 obese subjects (BMI: 33.2 ± 0.9 kg m?2), with abdominal distribution of adipose tissue and impaired glucose tolerance. An intravenous glucose tolerance test (0.3 g glucose kg?1) was performed after each period of treatment. Areas under the curve (AUC0–180 min) were calculated for plasma glucose, insulin, and C-peptide levels. Glucose tolerance was estimated by the coefficient of glucose assimilation (KG). Insulin sensitivity (SI) and glucose effectiveness (SG) indices were calculated using Bergman's minimal model. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide levels and insulin metabolic clearance rate (MCR) was estimated by dividing AUC ISR by AUC insulin. Fasting plasma insulin levels were reduced after metformin (89.3 ± 15.9 vs 112.4 ± 24.3 pmol I?1; p = 0.04). AUC glucose, KG and SG were similar in both tests. However, AUC insulin was reduced (39.7 ± 6.5 vs 51.8 ± 10.4 nmol min I?1; p = 0.02), while SI (6.98 ± 1.14 vs 4.61 ± 0.42 10?5 min?1 pmol?1 I; p = 0.03) and insulin MCR (715 ± 116 vs 617 ± 94 ml min?1 m?2; p = 0.03) were increased after metformin. The demonstration that metformin rapidly improves insulin sensitivity should encourage further research to evaluate the long-term effects of metformin in android obese subjects with impaired oral glucose tolerance.  相似文献   

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Thirty-one subjects with impaired glucose tolerance were randomly allocated to a group receiving advice to improve their diet and physical activity levels over 6 months (n = 23) or to a control group (n = 8). At 6 months, 18 of the 23 subjects receiving 'healthy living' advice were re-examined (five subjects had withdrawn). Fourteen of the 18 subjects showed an alteration in diet or an increase in exercise. The 18 subjects re-evaluated showed a reduction in systolic blood pressure (118 +/- 15 vs 124 +/- 15 mmHg, p less than 0.05) and decrease in total plasma cholesterol (4.5 +/- 1 vs 5.2 +/- 1 mmol l-1, p less than 0.01) and LDL-cholesterol levels (2.8 +/- 0.9 vs 3.2 +/- 0.9 mmol l-1, p less than 0.05). Plasma glucose levels were unchanged. One subject withdrew from the control group. At 6 months, the seven control subjects examined showed no significant change in metabolic parameters, with little measurable change in diet or exercise. At 2 years, 17 of the 23 'healthy living' subjects were reassessed. Nine of the subjects had continued to exercise or maintained a decreased weight compared to baseline. Fasting plasma glucose levels had increased (6.0 +/- 1.2 vs 5.5 +/- 0.6 mmol l-1, p less than 0.05), with the only continued improvement being a reduced LDL level (2.8 +/- 0.7 vs 3.1 +/- 0.9 mmol l-1, p less than 0.05). At 2 years, a similar proportion of the control group were taking regular exercise compared with the 'healthy living' group.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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为了探讨糖尿病脂蛋白异常血症的发生机理,研究了53例糖耐量异常者(糖耐量异常组)和27例糖耐量正常者(对照组)的血脂和血浆载脂蛋白水平,以及进行了葡萄糖耐量试验和胰岛素释放试验。结果发现,糖耐量异常组空腹及口服葡萄糖后60min血糖和血浆胰岛素水平与对照组无显著差异(P>0.05),而口服葡萄糖后120min血糖(P<0.05)、血浆胰岛素水平(P<0.01)和口服葡萄糖后180min血糖(P<0.01)、血浆胰岛素水平(P<0.05)均比对照组显著升高。糖耐量异常组血浆甘油三酯和总胆固醇显著升高(P<0.01和P<0.05),同时伴有一定程度的低密度脂蛋白胆固醇升高和高密度脂蛋白胆固醇降低,以及载脂蛋白CⅡ、CⅢ及E显著增高(P<0.01、P<0.001和P<0.005),这些血脂改变与糖尿病脂蛋白异常血症类似。此结果表明,胰岛素抵抗、高胰岛素血症在糖尿病脂蛋白异常血症的发生中起着重要的作用。同时也提示对一些空腹血糖正常,糖耐量异常,但还没有临床诊断为糖尿病患者,应进行常规血脂检查,筛选出脂蛋白异常者,并采取相应的措施予以纠正。  相似文献   

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Impaired glucose tolerance is associated with an increased risk of Type 2 diabetes. This prospective cohort study has examined the variables associated with hyperglycaemic progression in order to elucidate the aetiology of this deterioration. The 5 mg glucose-kg ideal body weight-min?1 continuous infusion of glucose with model assessment (CIGMA) test was used to quantitate glucose tolerance, beta cell function, and insulin sensitivity. Twenty-two Caucasian subjects who had impaired glucose tolerance identified on two separate tests underwent repeat testing after a median period of 24 months. At follow-up, 2 of the 22 subjects (9%) had Type 2 diabetes, 18 (82%) had impaired glucose tolerance, and 2 (9%) were normoglycaemic. The fasting and achieved (60-min) glucose levels were significantly higher at follow-up (mean ± SD) (5.7 ± 0.8 vs 5.5 ± 0.5 mmol l?1, p = 0.029 and 10.0 ± 0.9 vs 9.6 ± 0.6 mmol l?1, p = 0.021, respectively), and beta cell function was significantly lower (median and interquartile range): 75% (50–93%) vs 90% (70–135%), p = 0.009. The changes in fasting plasma glucose were found to correlate with change in body mass index (rs = 0.46, p = 0.03). We conclude that impaired glucose tolerance is associated with decline in beta cell function, and denotes substantial risk of hyperglycaemic progression. Randomized controlled trials are warranted to determine whether exercise programmes, dietary advice, and attentive follow-up and effective preventive strategies for subjects with impaired glucose tolerance.  相似文献   

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INTRODUCTION: Excessive postprandial (pp) glucose excursion in people with IGT and type 2 diabetes is associated with a cascade of proatherogenic events. Acarbose, a potent competitive inhibitor of alpha-glucosidases of the small intestine specifically reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in Cochrane metaanalysis. This is associated with pleiotropic effects on a broad spectrum of cardiovascular (CV) risk factors: reduction of overweight, lowering of blood pressure, triglycerides, hsCRP, fibrinogen and other biomarkers of low grade inflammation. RESULTS AND DISCUSSION: Flow mediated vasodilation was improved and progression of intima media thickness was reduced by acarbose. In the STOP-NIDDM trial in people with IGT acarbose decreased the incidence of diabetes by 36%. The STOP-NIDDM trial with CV events as secondary objective is the only intervention trial in people with IGT so far with a significant benefit for CV disease inclusive hypertension. In a metaanalysis of controlled studies (MeRIA) in patients with type 2 diabetes, treatment with acarbose was associated with a 64% lower rate of myocardial infarction and 35% less CV events. CONCLUSION: Thus results so far available prove that acarbose is an effective and safe drug to treat abnormal glucose tolerance. They suggest that acarbose can help to control a broad spectrum of CV risk factors and may prevent CV disease.  相似文献   

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The purpose of this study was to determine whether an approach of multisensor technology with integrated data analysis in an armband system (SenseWear® Pro Armband, SWA) can provide estimates of plasma glucose concentration in diabetes. In all, 41 subjects with diabetes participated. On day 1 subjects underwent an oral glucose tolerance test (OGTT) and on day 2 a 60-minute treadmill test (TT). SWA plasma glucose estimates were compared against reference peripheral venous glucose concentrations. A continuous glucose monitoring device (CGM) was also placed on each subject to serve as a reference for clinical comparison. Pearson coefficient, Clarke error grid (CEG), and mean absolute relative difference (MARD) analyses were used to compare the performance of plasma glucose estimation. There were significant correlations between plasma glucose concentrations estimated by the SWA and the reference plasma glucose concentration during the OGTT (r = .65, P < .05) and the TT (r = .91, P < .05). CEG analysis revealed that during the OGTT, 93% of plasma glucose concentration readings were in the clinically acceptable zone A+B for the SWA and 95% for the CGM. During the TT, the SWA had 96% of readings in zone A+B, compared to 97% for the CGM. During OGTTs, MARDs for the SWA and CGM were 26% and 18%, respectively. During TTs, MARDs were 16% and 12%, respectively. Plasma glucose concentration estimation by the SWA’s noninvasive multisensor approach appears to be feasible and its performance in estimating glucose approaches that of a CGM. The success of this pilot study suggests that multisensor technology holds promising potential for the development of a wearable, noninvasive, painless glucose monitor.  相似文献   

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