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.     

老年人不同糖耐量状态胰岛素抵抗和胰岛β细胞功能的研究

目的观察老年人群中空腹血糖受损(IFG)、糖耐量受损(IGT)和糖调节受损(IFG/IGT)三种不同糖耐量状态下的胰岛素抵抗(IR)和胰岛β细胞功能的变化,了解其发病机制。方法筛选60~75岁的IFG40例,IGT60例,IGT/IFG40例,正常糖耐量(NGT)70例。HOMA-IR评价胰岛素抵抗,HBC I和I30/G30分别评价基础及糖负荷后早期胰岛β细胞功能。结果(1)HOMA-IR:IFG、IFG/IGT和IGT组明显高于NGT组,P<0.01,IFG/IGT组高于IFG和IGT组,P<0.01;(2)HBC I:IFG组和IFG/IGT组明显低于NGT和IGT组,P<0.01;(3)I30/G30:IGT组和IFG/IGT组明显低于NGT组及IFG组,P<0.01。结论老年人群IFG主要表现基础状态下β细胞功能受损伴有胰岛素抵抗,IGT主要表现为早期胰岛素分泌缺陷,IFG/IGT胰岛β细胞早期胰岛素分泌功能受损更明显,胰岛素抵抗更严重。     

Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study.

OBJECTIVE: To determine whether the new category of impaired fasting glucose (IFG) recently proposed by the Expert Committee of the American Diabetes Association is a risk factor for cardiovascular disease. RESEARCH DESIGN AND METHODS: Death certificates and residence transfer documents from the cohort population consisting of participants of the diabetes prevalence study in Funagata, Yamagata prefecture, Japan, 1990-1992, were analyzed up through the end of 1996. First, the cohort population was classified into three groups: normal glucose tolerance (NGT) (n = 2,016), impaired glucose tolerance (IGT) (n = 382), and diabetic (n = 253). Then the same population was reclassified into normal fasting glucose (NFG), IFG, and diabetic. The cumulative survival rates among the groups were compared using the classical life-table method, and age-adjusted analyses, the person-year method, and Cox's proportional hazard model were adopted. RESULTS: At the end of seven observed years, the cumulative survival rates from cardiovascular disease of IGT and diabetes were 0.962 and 0.954, respectively, both significantly lower than that of NGT (0.988). The Cox's proportional hazard model analysis showed that the hazard ratio of IGT to NGT on death from cardiovascular disease was 2.219 (95% CI 1.076-4.577). However, the cumulative survival rate of IFG from cardiovascular disease was 0.977, not significantly lower than that of NFG (0.985). The Cox's hazard ratio of IFG to NFG on death from cardiovascular disease was 1.136 (0.345-3.734), which was not significant either. CONCLUSIONS: IGT was a risk factor for cardiovascular disease, but IFG was not.     

The significance of impaired fasting glucose versus impaired glucose tolerance: importance of insulin secretion and resistance

OBJECTIVE: The American Diabetes Association recommended substituting 2hBS (glycemia at the second hour of an oral glucose tolerance test [OGTT]) for fasting blood glucose (FBS) in screening for glucose intolerance. It is debated whether these tests measure the same abnormality and relate to defective insulin secretion or resistance. This study examines the diagnostic effectiveness of FBS versus 2hBS and their relationship with insulin secretion and resistance. RESEARCH DESIGN AND METHODS: Based on history or physical findings suggesting glucose intolerance, we enrolled 398 unselected subjects admitted to a general Internal Medicine ward. After 5 days of a weight-maintaining diet, FBS, 2hBS, and insulin were measured during OGTT. The homeostatic model assessment was used to assess beta-cell function and insulin resistance. RESULTS: Excluding 19 patients with diabetes (5%), we identified 284 subjects with normal glucose tolerance (NGT), 22 with isolated impaired fasting glucose (IFG), 59 with isolated impaired glucose tolerance (IGT), and 14 with associated IFG/IGT. The sensitivity of FBS in predicting 2hBS was 19%, specificity 93%. Positive and negative predictive values were 39% and 83%, respectively. Insulin resistance was absent in NGT and IFG and markedly elevated in IGT and IFG/IGT, whereas defective insulin release was significant only in isolated IFG. CONCLUSIONS: In unselected patients, elevated FBS depends primarily on defective insulin secretion, and impaired 2hBS on insulin resistance. Because these tests measure different alterations, they are useful in combination.     

From Pre-Diabetes to Type 2 Diabetes in Obese Youth: Pathophysiological characteristics along the spectrum of glucose dysregulation

OBJECTIVE

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are considered pre-diabetes states. There are limited data in pediatrics in regard to their pathophysiology. We investigated differences in insulin sensitivity and secretion among youth with IFG, IGT, and coexistent IFG/IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 24 obese adolescents with NGT, 13 with IFG, 29 with IGT, 11 with combined IFG/IGT, and 30 with type 2 diabetes underwent evaluation of hepatic glucose production ([6,6-²H₂]glucose), insulin-stimulated glucose disposal (R_d, euglycemic clamp), first- and second-phase insulin secretion (hyperglycemic clamp), body composition (dual-energy X-ray absorptiometry), abdominal adiposity (computed tomography), and substrate oxidation (indirect calorimetry).

RESULTS

Adolescents with NGT, pre-diabetes, and type 2 diabetes had similar body composition and abdominal fat distribution. R_d was lower (P = 0.009) in adolescents with type 2 diabetes than in those with NGT. Compared with adolescents with NGT, first-phase insulin was lower in those with IFG, IGT, and IFG/IGT with further deterioration in those with type 2 diabetes (P < 0.001), and β-cell function relative to insulin sensitivity (glucose disposition index [GDI]) was also lower in those with IFG, IGT, and IFG/IGT (40, 47, and 47%, respectively), with a further decrease (80%) in those with type 2 diabetes (P < 0.001). GDI was the major determinant of fasting and 2-h glucose levels.

CONCLUSIONS

Obese adolescents who show signs of glucose dysregulation, including abnormal fasting glucose, glucose intolerance or both, are more likely to have impaired insulin secretion rather than reduced insulin sensitivity. Given the impairment in insulin secretion, they are at high risk for progression to type 2 diabetes. Further deterioration in insulin sensitivity or secretion may enhance the risk for this progression.Pre-diabetes, defined as the presence of elevated fasting glucose, abnormal glucose tolerance, or both, is associated with an enhanced risk for development of type 2 diabetes in adults (1), but there are limited data to define the significance in children. A recent change in the definition of the abnormal fasting glucose to a lower level (100–125 mg/dl) has increased the prevalence of pre-diabetes in both adults and youth (2–4). It is unclear from the literature what role a defect in insulin secretion or an abnormality of insulin sensitivity might play in the impairment of glucose regulation, leading to glucose intolerance or elevated fasting plasma glucose.Epidemiological studies suggest that subjects with impaired fasting glucose (IFG) have lower insulin sensitivity and higher insulin secretion (5,6) based largely on fasting indexes of insulin sensitivity and an oral glucose tolerance (OGTT)–derived single index of insulin secretion (5). Adult studies reveal similar or lower insulin sensitivity in subjects with impaired glucose tolerance (IGT) compared with those with IFG who have lower insulin secretion (7,8). These studies are contrasted with clamp studies in Pima Indians showing similar insulin sensitivity in subjects with IFG and IGT but lower insulin secretion in those with fasting dysglycemia (9).Pediatric data are limited. In overweight Latino children with a family history of type 2 diabetes (10), children with impaired versus normal fasting glucose had no significant differences in insulin sensitivity or acute insulin response. However, the glucose disposition index (GDI), or insulin secretion relative to insulin sensitivity, was significantly reduced (15% lower) in children with IFG. A more recent study in obese adolescents revealed that subjects with IFG had decreased glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity, whereas those with IGT had more severe degrees of peripheral insulin resistance compared with subjects with normal glucose tolerance (NGT) (11). We recently demonstrated that insulin secretion relative to insulin sensitivity shows a significantly declining pattern: highest in youth with NGT, intermediate in youth with IGT, and lowest in youth with type 2 diabetes (12).In an attempt to clarify the controversy concerning the metabolic derangements in the different categories of the pre-diabetes state, the aims of the present study were to 1) to investigate the metabolic characteristics of insulin sensitivity and secretion in obese youth, with IFG versus IGT, of similar body composition and abdominal adiposity and 2) to compare them not only with those with NGT but also with children with type 2 diabetes.     

Factors responsible for development from normal glucose tolerance to isolated postchallenge hyperglycemia

OBJECTIVE: Isolated postchallenge hyperglycemia (IPH), defined as fasting plasma glucose (FPG) level <7.0 mmol/l and 2-h plasma glucose (PG) level >/=11.1 mmol/l, is a subtype of early-stage diabetes. This study evaluates the metabolic profiles of insulin secretion and insulin sensitivity in IPH to clarify the factors responsible for development of this form of type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted cross-sectional analysis of 231 Japanese men aged 20-70 years. The subjects were classified into the following three groups, based on the results of a 75-g oral glucose tolerance test (OGTT): 1) normal glucose tolerance (NGT), defined as FPG level <6.1 mmol/l and 2-h PG level <7.8 mmol/l (n = 89); 2) impaired glucose tolerance (IGT), defined as FPG level <7.0 mmol/l and 2-h PG level of 7.8-11.1 mmol/l (n = 94); and 3) IPH (n = 48). We compared the three groups for insulin secretion (insulinogenic index) and insulin sensitivity (index of insulin resistance using homeostasis model assessment [HOMA-IR]). RESULTS: The insulinogenic index in IPH was the lowest of the three groups (P < 0.001 versus NGT). The HOMA-IR in the IGT and IPH groups were significantly higher than in the NGT group (P < 0.001), but both were similar. By linear regression analysis, the insulinogenic index rather than fasting insulin or HOMA-IR was the more significant factor in the 2-h PG level in IGT and IPH. CONCLUSIONS: Subjects with IPH exhibited distinctly impaired early-phase insulin secretion and only mild insulin resistance, indicating that reduced insulin secretion is the primary determinant of deterioration from NGT to IGT and IPH in development of type 2 diabetes in these subjects.     

Islet dysfunction in insulin resistance involves impaired insulin secretion and increased glucagon secretion in postmenopausal women with impaired glucose tolerance

OBJECTIVE: To characterize in detail the association between insulin sensitivity and islet function in relation to glucose tolerance in nondiabetic subjects. RESEARCH DESIGN AND METHODS: The study included 108 postmenopausal women, aged 57-59 years, with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) and measured glucose tolerance (World Health Organization, 75 g glucose), insulin sensitivity (euglycemic-hyperinsulinemic clamp), and islet function (the 2-5 min insulin responses [AIR] and glucagon [AGR] responses to 5 g intravenous arginine at fasting, 14 and >25 mmol/l glucose levels). The product of insulin sensitivity and secretion was calculated (disposition index [DI]) and used to study the relationship between the two parameters. RESULTS: Insulin sensitivity and insulin secretion were highly inversely correlated in a hyperbolic manner (r > 0.64, P < 0.001) in women with NGT (n = 71). Women with IGT (n = 37) had reduced insulin sensitivity compared with women with NGT (P = 0.011). The AIRs were not appropriately increased in relation to the reduced insulin sensitivity in the IGT women, demonstrated as reduced DI in IGT compared with NGT (P < 0.001). Further, women with IGT had an increased AGR (P < 0.001) and a reduced glucose inhibition of glucagon secretion (slopeAGR, P = 0.014) compared with women with NGT. In a multivariate regression model including all of the 108 women, 2-h glucose was independently determined by the DI, the AGR, and the slopeAGR (r = 0.63, P < 0.001). CONCLUSIONS: We have shown that both the individual ability to adapt insulin secretion to the ambient insulin sensitivity and the level of glucagon secretion are important parameters for maintenance of NGT. Therefore, islet dysfunction in IGT involves low insulin and high glucagon secretion, which present potential targets for correcting impaired glycemia.     

Differences in cardiovascular risk factors, insulin resistance, and insulin secretion in individuals with normal glucose tolerance and in subjects with impaired glucose regulation: the Telde Study

OBJECTIVE: To assess the cardiovascular risk profile, the degree of insulin resistance, and beta-cell secretion in a cohort of subjects with different categories of impaired glucose regulation (IGR): impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT. RESEARCH DESIGN AND METHODS: We studied 902 nondiabetic subjects between 30 and 80 years of age, recruited from a cross-sectional population-based study in Telde, Gran Canaria Island, Spain. Categories of glucose tolerance were defined according to 2003 modified American Diabetes Association criteria. Risk factors for cardiovascular disease, the presence of the metabolic syndrome, and indirect measures of both insulin resistance and beta-cell function were analyzed. RESULTS: A total of 132 (14.6%) participants had isolated IFG, 59 (6.5%) isolated IGT, and 48 (5.3%) combined IFG/IGT. Groups with normal glucose tolerance (NGT) and combined IFG/IGT had, respectively, the most favorable and unfavorable levels of cardiovascular risk factors, metabolic syndrome rates, and measures of insulin resistance. Subjects with IFG and IGT showed an intermediate profile between NGT and IFG/IGT categories. We found no significant differences between IFG and IGT in cardiovascular risk factors, metabolic syndrome prevalence, or insulin resistance. The IFG group exhibited a more impaired insulin secretion than those with IGT or IFG/IGT. CONCLUSIONS: Individuals with IGR, especially those with IFG/IGT, have increased values of cardiovascular risk factors and higher indexes of insulin resistance. Groups with isolated IFG and isolated IGT present similar cardiovascular risk profiles. Subjects with IFG are characterized by more defective beta-cell function than other forms of IGR.     

Decreased beta-cell function in overweight Latino children with impaired fasting glucose

OBJECTIVE: To determine whether overweight Latino children with impaired fasting glucose (IFG) (> or = 100 mg/dl) have increased insulin resistance or decreased beta-cell function compared with those with normal fasting glucose (NFG). RESEARCH DESIGN AND METHODS: We studied 207 healthy overweight Latino children, aged 8-13 years, with a family history of type 2 diabetes. Fasting and 2-h glucose and insulin were assessed by oral glucose tolerance test. Insulin sensitivity (S(i)), the acute insulin response to glucose (AIRg), and the disposition index (DI; an index of beta-cell function) were determined using the insulin-modified intravenous glucose tolerance test and minimal modeling. Body composition was determined by dual-energy X-ray absorptiometry. RESULTS: There were no differences in body composition between NFG (n = 182) and IFG (n = 25) children. Compared with children with NFG, children with IFG had higher fasting and 2-h glucose values and higher fasting insulin. After adjusting for covariates, children with IFG had no difference in S(i) but 15% lower DI than NFG children (2,224 +/- 210 vs. 2,613 +/- 76, P < 0.05). Multivariate linear regression showed that AIRg and DI, but not S(i), were significant predictors of fasting blood glucose. CONCLUSIONS: In overweight Latino adolescents with a family history of type 2 diabetes, IFG is associated with impaired beta-cell function and therefore may identify children likely to be at risk for progression to type 2 diabetes. The actual risk of progression of IFG to type 2 diabetes remains to be determined by prospective longitudinal studies.     

Contribution of insulin-stimulated glucose uptake and basal hepatic insulin sensitivity to surrogate measures of insulin sensitivity

OBJECTIVE: The goal of this study was to evaluate the performance of surrogate measures of insulin sensitivity and insulin secretion. RESEARCH DESIGN AND METHODS: The homeostasis model assessment (HOMA) of insulin resistance (IR) and the insulin sensitivity index (S(i)) from oral glucose tolerance test (OGTT) were compared with the M value from a hyperinsulinemic-euglycemic clamp in 467 subjects with various degrees of glucose tolerance. Endogenous glucose production (EGP) and hepatic insulin sensitivity were determined in a subset (n = 143). Insulin secretion was estimated as the HOMA beta-cell index and as the insulinogenic index from the first 30 min of the OGTT (I/G30) and compared with the first-phase insulin response (FPIR) to an intravenous glucose tolerance test (n = 218). RESULTS: The M value correlated with the HOMA-IR (r = -0.591, P < 0.0001) and the S(i) (r = 0.533, P < 0.0001) indexes in the total study group. HOMA-IR correlated with basal EGP in the total study group (r = 0.378, P < 0.0005) and in subjects with diabetes (r = 0.330, P = 0.01). However, neither HOMA-IR nor S(i) correlated significantly with the M value in subjects with impaired fasting glucose (IFG) (r = -0.108, P = 0.5; r = 0.01, P = 0.9) or IFG/impaired glucose tolerance (IGT) (r = -0.167, P = 0.4; r = 0.09, P = 0.6). The HOMA-IR correlated with hepatic insulin sensitivity in the whole study group (r = -0.395, P < 0.005) as well as in the IFG/IGT subgroup (r = -0.634, P = 0.002) and in the diabetic subgroup (r = -0.348, P = 0.008). In subjects with IFG/IGT, hepatic insulin sensitivity was the most important determinant of HOMA-IR, explaining 40% of its variation. The HOMA beta-cell index showed a weak correlation with FPIR in the whole study group (r = 0.294, P = 0.001) but not in the subgroups. In contrast, the I/G30 correlated with FPIR in the whole study group (r = 0.472, P < 0.0005) and in the IFG/IGT subgroup (r = 0.493, P < 0.005). CONCLUSIONS: HOMA-IR is dependent upon both peripheral and hepatic insulin sensitivity, the contribution of which differs between subjects with normal and elevated fasting glucose concentrations. These discrepancies develop as a consequence of a nonparallel deterioration of the variables included in the equations with worsening of glucose tolerance.     

Impaired insulin sensitivity, insulin secretion, and glucose effectiveness predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention

OBJECTIVE: We examined the determinants of impaired glucose tolerance (IGT) and type 2 diabetes in first-degree relatives of African-American type 2 diabetic patients over 5-8 years (median 6). RESEARCH DESIGN AND METHODS: A total of 81 healthy subjects (age 41.5 +/- 4.8 years; BMI 31.3 +/- 3.6 kg/m(2)) participated in the study. Each subject underwent an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test at baseline. Insulin sensitivity index (S(i)) and glucose effectiveness index (S(g)) were determined by the minimal model method. Homeostasis model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR) and beta-cell function (HOMA-%B). A total of 18 subjects progressed to either IGT or type 2 diabetes (progressors), whereas 19 subjects maintained normal glucose tolerance (nonprogressors). RESULTS: Comparing the progressors and nonprogressors, mean fasting serum glucose levels (95 +/- 8 vs. 80 +/- 14 mg/dl, P < 0.01) and 2-h serum glucose levels (149 +/- 27 vs. 100 +/- 60 mg/dl, P < 0.01) as well as 2-h serum insulin levels (117 +/- 81 vs. 72 +/- 87 microU/ml, P < 0.01) during OGTT were higher at baseline. Mean acute first-phase insulin secretion (205 +/- 217 vs. 305 +/- 230 microU/ml), HOMA-%B (148 +/- 60 vs. 346 +/- 372, P < 01), S(i) (1.61 +/- 1.13 vs. 2.48 +/- 1.25 x 10(-4). min(-1) [microU/ml](-1)), and S(g) (1.48 +/- 0.61 vs. 2.30 +/- 0.97 x 10(-2). min(-1)) were lower in the progressors than in the nonprogressors at baseline. Mean HOMA-IR (3.31 +/- 1.64 vs. 2.36 +/- 1.64) was significantly greater in the progressors than the nonprogressors. At the time of diagnosis of glucose intolerance (IGT + diabetes), HOMA-%B (101 +/- 48 vs. 148 +/- 60, P < 0.001) and HOMA-IR (5.44 +/- 2.55 vs. 3.31 +/- 1.64, P < 0.003) deteriorated in the progressors versus baseline. CONCLUSIONS: We conclude that nondiabetic, first-degree relatives of African-American type 2 diabetic patients who progressed to IGT and type 2 diabetes manifest triple defects (decreased insulin secretion, insulin action, and glucose effectiveness) that antecede the disease.     

Impaired glucose tolerance and impaired fasting glucose share similar underlying pathophysiologies

Both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states. IGT was defined as having normal fasting plasma glucose (< 6.1 mmol/l) and abnormal 2-hr post-challenge plasma glucose. IFG was defined as having abnormal fasting plasma and normal 2-hr post-challenge plasma glucose (< 7.8 mmol/l). To explore whether these two abnormalities share similar underlying pathophysiologies, we evaluated risk factors of IGT and IFT using the models of factor analysis. The present study included 107 subjects with IGT and 52 with IFG. An oral glucose tolerance test and insulin suppression test, which could quantify insulin resistance, were performed on separate days. The risk factors include waist-to-hip ratio (WHR), triglycerides, high-density lipoprotein (HDL)-cholesterol, blood pressure, and fasting plasma glucose, which are associated with metabolic syndrome and insulin resistance. Factor analysis is a commonly used statistical method that could reduce a large number of risk factors into smaller numbers of groups, also called dimension. Accordingly, the complicated data could be interpreted more easily, since the related risk factors are grouped in one dimension. The results showed that the risk factors of IGT and IFG have similar grouping patterns. Triglyceride, insulin resistance, and HDL-cholesterol were grouped in one dimension (the lipid dimension), while WHR, mean blood pressure and fasting plasma glucose were grouped in another dimension (the metabolic dimension). In conclusion, except for WHR, the grouping patterns of the components in both IGT and IFG were nearly identical. These results suggest that IGT and IFG may share similar pathophysiologies.     

糖调节受损患者血清超敏C反应蛋白和细胞间黏附分子-1水平的变化

目的检测空腹血糖调节受损(IFG)及糖耐量减低(IGT)人群空腹血清超敏C反应蛋白(hs-CRP)、细胞间黏附分子-1(ICAM-1)水平,探讨血清hs-CRP、ICAM-1与胰岛素抵抗(IR)之间的关系。方法选取健康对照组30例,IFG组30例,IGT组30例,IFG并IGT组30例,新发2型糖尿病组(T2DM)30例。对所有受试者空腹测血清hs-CRP、ICAM-1、血糖、甘油三酯、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹胰岛素等(FINS)项目,应用稳态模型评估法评价胰岛素抵抗指数(HOMA-IR)。结果各试验组的FINS、空腹血糖(FBG)、HOMA-IR均高于正常对照组,差异有显著性(P<0.05);IGT组、IFG并IGT组、T2DM组的CRP、ICAM-1高于正常对照组,差异有显著性(P<0.05);CRP、ICAM-1在IFG组与正常组之间无显著性差异(P>0.05)。T2DM组的FINS、FBG、HOMA-IR、CRP、ICAM-1高于IGT组,差异有显著性(P<0.05),IFG并IGT组与IGT组比较,上述指标均无显著性差异(P>0.05)。逐步多元回归分析显示,BMI、hs-CRP、ICAM-1是影响HOMA-IR的重要危险因素。结论 (1)T2DM组、糖调节受损人群(包括IFG、IGT、IFG并IGT)存在明显的胰岛素抵抗,CRP、ICAM-1、BMI是胰岛素抵抗的危险因素;(2)随着糖耐量受损的加重,血清hs-CRP、ICAM-1水平逐渐升高;(3)糖调节受损时期即可能存在内皮功能损伤,并出现大血管病变的一些病理生理改变(如急性时相蛋白CRP,ICAM-1)。     

血糖调节异常者血脂代谢的初步研究

目的初步评价血糖调节受损患者血脂代谢异常情况。方法检测糖耐量正常(NGT)、单纯空腹血糖异常(IFG)、单纯糖耐量异常(IGT)、空腹血糖异常合并糖耐量异常(IFG IGT)和糖尿病(DM)患者空腹血糖和餐后2 h血糖及空腹血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A-I(apo A-I)和载脂蛋白B(apo B)水平,计算非高密度脂蛋白胆固醇(non-HDL-C)和血浆致动脉硬化指数(AIP),比较各组间血清脂质成分的差异。结果IFG组血清TC、LDL-C、non-HDL-C和apo B水平较NGT组明显升高(P<0.01),而TG、HDL-C、AIP差异无统计学意义(P>0.05)。IGT组血清TC、TG、LDL-C、non-HDL-C、apo A-I、apo B和AIP水平较NGT组显著升高(P<0.01),前6项指标与IFG IGT组差异无统计学意义(P>0.05)。IFG IGT组与NGT组比较,各指标差异均有统计学意义(P<0.01);HDL-C、non-HDL-C和AIP水平与IFG组比较差异有统计学意义(P<0.01)。DM组表现出典型的DM性脂代谢紊乱伴AIP水平显著异常。non-HDL-C和apo B间存在良好的相关性(P<0.01)。结论血糖调节受损者不同程度的存在血脂代谢异常,主要表现为TC、TG、LDL-C、non-HDL-C和apo B水平的升高和HDL-C、apo A-I的降低,伴不同程度AIP水平的改变。     

Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose

Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are intermediate states in glucose metabolism that exist between normal glucose tolerance and overt diabetes. Epidemiological studies demonstrate that the two categories describe distinct populations with only partial overlap, suggesting that different metabolic abnormalities characterize IGT and IFG. Insulin resistance and impaired beta-cell function, the primary defects observed in type 2 diabetes, both can be detected in subjects with IGT and IFG. However, clinical studies suggest that the site of insulin resistance varies between the two disorders. While subjects with IGT have marked muscle insulin resistance with only mild hepatic insulin resistance, subjects with IFG have severe hepatic insulin resistance with normal or near-normal muscle insulin sensitivity. Both IFG and IGT are characterized by a reduction in early-phase insulin secretion, while subjects with IGT also have impaired late-phase insulin secretion. The distinct metabolic features present in subjects with IFG and IGT may require different therapeutic interventions to prevent their progression to type 2 diabetes.     

Assessing progression to impaired glucose tolerance and type 2 diabetes mellitus

BACKGROUND: A prospective evaluation of the relationship between insulin secretion and insulin sensitivity, derived from the fasting state, is needed in clinical practice in order to identify the worsening of glucose metabolism. In this study the authors examine whether the product of insulin sensitivity and insulin secretion, assessed from the fasting state, predicts progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) and from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A cohort of 300 subjects with NGT and 75 subjects with IGT were followed up over a 5-year period. Insulin sensitivity was calculated using the Belfiore index (B) and insulin secretion by the homeostasis model analysis beta-cell (HOMA-beta cell) index: the product of B-beta is expressed as: (40 x Ins(0) pmol L(-1))/Glu(0) mmol L(-1){[(Glu(0) mmol L(-1)x Ins(0) pmol L(-1)) + 1] - 3.5[(Glu(0) mmol L(-1) x Ins(0) pmol L(-1)) - 1]}, where Glu(0) is fasting glucose and Ins(0) is fasting insulin. RESULTS: From baseline at the end of the follow-up period, the product B-beta decreased 10.7% and 52.2% in progressors to IGT and T2DM, respectively. The product B-beta predicts the progression from NGT to IGT [relative risk (RR) 2.7, CI(95%) 1.2-9.1] and from IGT to T2DM (RR 5.3, CI(95%) 1.3-8.55). The cut-off point for the product B-beta that better predicts progression from NGT to IGT is 0.25 (sensitivity 88%, specificity 92%) and from IGT to T2DM 0.15 (sensitivity 92%, specificity 95%). CONCLUSIONS: Adaptation of insulin secretion to compensate for decreased insulin sensitivity during transition to IGT and T2DM can be successfully assessed with simple measures derived from the fasting state. The product B-beta predicts the development to IGT and T2DM.     

糖耐量减低者体内氧化应激水平升高

目的 探讨糖耐量减低患者体内氧化应激状况.方法 选取糖耐量减低（IGT）组45例和糖耐量正常（NGT）组51例,测定其血清超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH）、活性氧（ROS）和丙二醛（MDA）水平.比较IGT组与NGT组的氧化应激状况,并对氧化应激指标进行相关性分析.结果 与NGT组相比,IGT组血清SOD和GSH水平明显下降,而血清ROS和MDA水平明显升高（P＜0.05）;而且经校正性别和年龄后,两组问的差异仍具有统计学意义（P＜0.05）.Spearman相关分析显示,GSH与年龄、BMI、FBG以及TG呈负相关;SOD与年龄、FBG、HOMA-IR以及TC呈负相关;ROS与年龄、BMI、FBG、HOMA-IR以及TG呈正相关;MDA与HOMA-IR和TG呈正相关.结论 此研究结果提示,糖耐量减低者体内存在着高水平的氧化应激状态,但仍有待于更大样本的进一步研究来证实.     

Metabolic characteristics in individuals with impaired glucose homeostasis

We sought to clarify whether impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both (IFG/IGT) represent the most severe impairment in insulin resistance (IR) and insulin secretion. Among the 159 Chinese subjects, 21 were diagnosed as having IFG, 103 as having IGT and 35 as having both. IR and beta-cell function were assessed using homeostatic model assessment (HOMA) and an insulin-suppression test (IST). No differences were evident between the groups in blood pressure, body mass index, plasma insulin fasting levels and lipid profiles. However, plasma 2-h insulin levels were higher in the IGT and IFG/IGT groups. Beta-cell functions were not different between these groups. But, the result of glucose tolerance was different, in which the IFG/IGT and IFG groups displayed higher insulin sensitivity than IGT via HOMA instead of no difference via IST in the three patient groups.     

探讨糖尿病前期患者血浆IL-18、PAI-1水平变化与胰岛素抵抗的相关性

目的探讨血浆白细胞介素-18(IL-18)、纤溶酶原激活物抑制物-1(PAI-1)水平变化与Ⅱ型糖尿病发病危险因素的关系.方法 设立健康人对照(NGT)组、糖耐量减低( IGT )组、空腹血糖受损合并糖耐量减低(IFG/IGT)组,每组各100例.测定各受试者血浆 IL-18、PAI-1、血清空腹胰岛素、空腹血糖、餐后2 h血糖,应用稳态模型评估法评价胰岛素抵抗(HOMA-IR).结果 IGT组、IFG/IGT组血浆 IL-18、PAI-1 水平均高于NGT组(P<0.01).IFG/IGT组血浆 IL-18、PAI-1 水平均高于IGT组(P<0.05).相关分析显示IL-18、PAI-1 水平与空腹血糖、餐后2 h血糖、HOMA-IR呈正相关(P<0.01).结论血浆 IL-18、PAI-1 水平升高可能是加重糖尿病前期患者胰岛素抵抗的危险因素;在糖尿病前期,IL-18、PAI-1可能参与了Ⅱ型糖尿病的发生、发展.     

Immunoglobulin E and mast cell proteases are potential risk factors of impaired fasting glucose and impaired glucose tolerance in humans

Aim. Mast cells are important in experimental diabetes. Plasma levels of immunoglobulin E (IgE), tryptases, and chymases are inflammatory markers of human diabetes. Whether they also correlate with the risk of pre-diabetes, however, remains unknown.

Methods and results. A total of 260 subjects 55–75 years of age were grouped as normal glucose tolerance (NGT), isolated impaired fasting glucose (I-IFG), isolated impaired glucose tolerance (I-IGT), and mixed IFG/IGT. There were significant differences in plasma levels of high-sensitivity C-reactive protein (hsCRP) (P < 0.001) and IgE (P = 0.003) among all subgroups of pre-diabetes, and chymase in I-IGT (P = 0.043) and mixed IFG/IGT (P = 0.037) subgroups compared with NGT group. High-sensitivity CRP was a risk factor in all subgroups of pre-diabetes; IgE was a risk factor of mixed IFG/IGT; and chymase was a risk factor of I-IGT and mixed IFG/IGT. Interactions between hsCRP and high waist circumference (WC), waist-to-hip ratio (WHR), or HOMA-β index, and interactions between IgE and high WC or tryptase levels all increased further the risk of developing I-IFG, I-IGT, or mixed IFG/IGT.

Conclusion. Plasma hsCRP, IgE, and chymase levels associate with pre-diabetes status. While hsCRP, IgE, and chymase are individual risk factors of pre-diabetes, interactions with metabolic parameters increased further the risk of pre-diabetes.