某市东部沿海地区糖调节受损人群生化指标变化及危险因素分析

目的 观察分析某市东部沿海地区糖调节受损(IGR)人群血液生化指标和体格特征的变化,探讨影响IGR发生的危险因素.方法 按世界卫生组织糖尿病专家委员会1999年诊断标准,将IGR人群分为I-IFG、I-IGT和IGT/IFG三个类型组,并与正常糖耐量组(NGT)进行比较,然后运用单因素和多因素非条件Logistic回归分析影响IGR发生的危险因素.结果 ① IGR三个类型组与NGT组比较,其年龄、血压、BMI、WHR、FPG、2 hPG、TC、TG、LDL-C、UA、FINS、HOMA-IR水平均较高,HDL-C水平较低,差异具有统计学意义(P<0.05或P<0.01).IFG/IGT组与I-IFG、I-IGT两组比较,其FPG、2 hPG、HbA1c、TC、TG、LDL-C、UA、FINS、HOMA-IR水平均较高,HDL-C水平较低,差异具有统计学意义(P<0.05).②进入多因素非条件Logistic回归模型的因素有年龄、血压、BMI、WHR、TC、TG、LDL-C、低HDL-C、UA及糖尿病家族史(P<0.05或P<0.01).结论 ①IGR人群不同程度存在着血糖、血脂代谢异常和胰岛素抵抗,检测血糖、血脂及胰岛素等生化指标,对于评价IGR有一定的作用.②年龄增长、中心性肥胖、高血压、血脂紊乱、高尿酸血症及糖尿病家族史为IRG的主要危险因素.     

Medical care costs one year after identification of hyperglycemia below the threshold for diabetes

OBJECTIVE: To estimate the resource utilization and medical costs of patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both, in a real-world clinical setting. METHODS: We used fasting and random glucose test results and a previously validated predictive equation to identify glycemic status in 26,111 nondiabetic patients, assigning them to categories of normoglycemia, isolated IFG (I-IFG), isolated IGT (I-IGT), or IFG with possible IGT (IFG/IGT). We then calculated and compared mean annual medical resource utilization and age/sex-adjusted costs over the ensuing 12-month period. RESULTS: I-IGT patients incurred significantly greater age- and sex-adjusted total costs in the observation year compared with normoglycemic and I-IFG patients (both comparisons, P < 0.001). IFG/IGT patients also had significantly greater age- and sex-adjusted total costs in the observation year compared with normoglycemic and I-IFG patients (P < 0.001, both comparisons). In both cases, the differences were driven by significantly greater inpatient costs-20.3% of patients with I-IGT and 17.1% with IFG/IGT were hospitalized during the observation year, whereas approximately 12% of normoglycemic and I-IFG patients had an admission (all comparisons, P < 0.001). CONCLUSIONS: Abnormal glucose tolerance, in particular, IGT, is associated with excess medical care costs relative to normoglycemia. Preventing progression to diabetes, when costs are known to be dramatically greater, would likely provide substantial economic benefit. More research is needed to determine the prevalence of hyperglycemia-related complications at elevated glucose levels below the diabetic threshold and the associated costs of those complications.     

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.     

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.     

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.     

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。     

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.     

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。     

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.     

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.     

Prevalence and risk factors of neuropathic pain in survivors of myocardial infarction with pre‐diabetes and diabetes. The KORA Myocardial Infarction Registry

The lowest glycemic threshold for and the risk factors associated with neuropathic pain have not been established. The aim of this study was to determine the prevalence and risk factors of neuropathic pain in survivors of myocardial infarction with diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), normal glucose tolerance (NGT). Subjects aged 25–74 years with diabetes (n=214) and controls matched for age and sex (n=212) from the population‐based KORA (Cooperative Health Research in the Region of Augsburg) Myocardial Infarction Registry were assessed for neuropathic pain by the Michigan Neuropathy Screening Instrument using its pain‐relevant questions and an examination score cutpoint >2. An oral glucose tolerance test was performed in the controls. Among the controls, 61 (28.8%) had IGT (either isolated or combined with IFG), 70 (33.0%) had isolated IFG, and 81 had NGT. The prevalence of neuropathic pain was 21.0% in the diabetic subjects, 14.8% in those with IGT, 5.7% in those with IFG, and 3.7% in those with NGT (overall p<0.001). In the entire population studied (n=426), age, waist circumference, peripheral arterial disease (PAD), and diabetes were independent factors significantly associated with neuropathic pain, while in the diabetic group it was waist circumference, physical activity, and PAD (all p<0.05). In conclusion, the prevalence of neuropathic pain is relatively high among survivors of myocardial infarction with diabetes and IGT compared to those with isolated IFG and NGT. Associated cardiovascular risk factors including abdominal obesity and low physical activity may constitute targets to prevent neuropathic pain in this population.     

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.     

糖尿病前期患者血清脂联素和超敏C反应蛋白水平分析

目的探讨血清脂联素、超敏C反应蛋白(hs-CRP)水平变化与糖尿病前期发生的危险因素的关系。方法选取健康对照组(NGT)、糖耐量减低组(IGT)、空腹血糖受损合并糖耐量减低组(IFG/IGT)各100例,测定各受试者血清脂联素、hs-CRP、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。结果 IGT组、IFG/IGT组血清脂联素均显著低于NGT组(P<0.01),IFG/IGT组的脂联素水平低于单纯IGT组(P<0.05)。脂联素水平与空腹血糖、餐后2 h血糖、胰岛素抵抗指数(HOMA-IR)呈负相关(P值均小于0.01)。单纯IGT组、IFG/IGT组血清hs-CRP水平明显高于NGT组(P<0.01),IFG/IGT组血清hs-CRP水平高于单纯IGT组(P<0.05)。血清hs-CRP水平与空腹血糖、餐后2 h血糖、HOMA-IR呈正相关(P值均小于0.01)。结论血清脂联素、hs-CRP可能是加重糖尿病前期胰岛素抵抗的危险因素,糖调节受损期即可能存在慢性低度炎症反应。在糖尿病前期,脂联素、hs-CRP可能参与了糖尿病的发生及发展。     

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)。     

Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes

Abstract

Background/aims. In this present study, we aimed: (i) To clarify if prediabetes is associated with subclinical inflammation independent of underlying obesity, and (ii) to evaluate the effect of postload glucose concentration on subclinical inflammation markers in a group of patients with elevated fasting glucose. Material and methods. In a cohort of 165 patients with newly detected fasting hyperglycemia, according to 75 g oral glucose tolerance test (OGTT), subjects were classified either as newly diagnosed type 2 diabetes (diabetes group, n = 40), impaired fasting glucose (IFG) plus impaired glucose tolerance (IGT) (IFG/IGT group, n = 42) or IFG only (IFG group, n = 83). A control group (n = 47) consisted of age- and body mass index (BMI)-matched healthy subjects with a normal OGTT. Circulating concentrations of lipids, insulin, interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitive C-reactive protein (hsCRP) were measured. HOMA index was calculated. Results. Subclinical inflammation markers were elevated in patients with diabetes and IFG/IGT compared to healthy controls and also IFG patients (diabetes vs. control: p < 0.05 for hsCRP, IL-8, and IL-6; IFG/IGT vs. control: p < 0.05 for hsCRP, and IL-6; diabetes vs. IFG: p < 0.05 for hsCRP, and IL-6; IFG/IGT vs. IFG: p < 0.05 for hsCRP, and IL-6). In multiple regression analysis, postload glucose concentration was independently associated with circulating hsCRP and IL-6 concentrations when the data was controlled for age, gender, BMI and lipid concentrations (p < 0.05 for hsCRP, and IL-6). Conclusion. Our results suggest that patients with prediabetes, independent of underlying obesity, have increased concentrations of subclinical inflammation which is mostly driven by postload glucose concentrations.     

Natural History of Insulin Sensitivity and Insulin Secretion in the Progression From Normal Glucose Tolerance to Impaired Fasting Glycemia and Impaired Glucose Tolerance: The Inter99 Study

OBJECTIVE—The aim of this study was to describe the natural history of insulin secretion and insulin sensitivity in the development of isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT.RESEARCH DESIGN AND METHODS—Baseline and 5-year follow-up data from the Inter99 study were used. Individuals with normal glucose tolerance (NGT) at baseline and i-IFG, i-IGT, combined IFG/IGT, or NGT at the 5-year follow-up were examined with an oral glucose tolerance test (n = 3,145). Insulin sensitivity index (ISI), homeostasis model assessment of insulin sensitivity (HOMA-IS), early-phase insulin release (EPIR), and insulin secretion relative to insulin action (disposition index) were estimated.RESULTS—Five years before the pre-diabetes diagnoses (i-IFG, i-IGT, and IFG/IGT), ISI, HOMA-IS, EPIR, and disposition index were lower than in individuals who maintained NGT. During the 5-year follow-up, individuals developing i-IFG experienced a significant decline only in HOMA-IS, whereas individuals developing i-IGT experienced significant declines in ISI, EPIR, and disposition index. Individuals with IFG/IGT exhibited pronounced declines in ISI, HOMA-IS, EPIR, and disposition index during the 5-year follow-up.CONCLUSIONS—A stationary reduced insulin secretion followed by a decline in primarily hepatic insulin sensitivity characterizes the transition from NGT to i-IFG. In contrast, low whole-body insulin sensitivity with a secondary lack of β-cell compensation is associated with the development of i-IGT. Thereby, i-IFG and i-IGT appear to result from different underlying mechanisms, which may have implications for the prevention and treatment of the diabetes that succeeds them.During the past few years, it has been established that the pre-diabetic conditions of isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined fasting and postchallenge hyperglycemia (IFG/IGT) represent distinct pathways to diabetes. These pre-diabetic states are characterized by different degrees of insulin sensitivity, insulin secretion, and hepatic glucose output as well as secretion of glucagon and incretin hormones (1–8). Nevertheless, the primary abnormalities inherent in the different pre-diabetic conditions are still unknown.Randomized trials have shown beneficial effects of lifestyle intervention on diabetes risk in individuals with i-IGT and IFG/IGT (9,10), but whether lifestyle interventions have the same preventive effects in individuals with i-IFG is not known. Indeed, a more profound insight into the pathogenesis of the disease is needed to optimize prevention and treatment of type 2 diabetes. In particular, focus on the initial defects responsible for hyperglycemia in the fasting and postprandial states is essential for interrupting the progression from normal to abnormal glucose metabolism.Most previous studies have examined the pathophysiology of pre-diabetes in cross-sectional settings without knowing the time of onset of glycemic abnormalities. However, the observed abnormalities in pre-diabetes may be related to traits already apparent in the normoglycemic state. Prospective studies are therefore needed to clarify whether this is the case or whether the metabolic abnormalities associated with i-IFG, i-IGT, and IFG/IGT develop simultaneously with the increases in fasting and/or postchallenge plasma glucose levels.The aim of this study was to describe the natural history of insulin sensitivity and insulin secretion during the progression from normal glucose tolerance (NGT) to the pre-diabetic states of i-IFG, i-IGT, and combined IFG/IGT.     

不同糖耐量人群胰岛素抵抗和胰岛β细胞功能的比较研究

目的观察不同糖耐量人群胰岛素抵抗(Insulin Resistance,IR)和胰岛β细胞功能改变的特点,为临床正确选择干预病变的靶点和治疗措施提供依据。方法对9922例初诊或疑诊为2型糖尿病(T2DM)患者的口服75 g葡萄糖耐量试验(Oral Glucose Tolerance Test,OGTT)及胰岛素释放结果进行分析。根据空腹血糖(FBG)6.1 mmol/L和7.0 mmol/L及餐后2 h血糖(2 hPG)7.8 mmol/L和11.1 mmol/L四个切点将人群分为正常糖耐量组1362例(NGT组)、单纯空腹血糖受损组982例(I-IFG组)、单纯糖耐量减低组778例(I-IGT组)、联合糖耐量减低组1300例(C-IGT组)、空腹正常型糖尿病组250例(NFD组)、空腹受损型糖尿病组1186例(IFD组)、餐后正常型糖尿病组14例(NPD组)、餐后受损型糖尿病组332例(IPD组)、空腹合并餐后型糖尿病组3708例(CFPD组)。结果①稳态模型胰岛素抵抗指数(HOMA-IR)由小到大依次为NGT组、I-IGT组、NFD组、I-IFG组、C-IGT组、IFD组、IPD组、CFPD组,组间比较差异有统计学意义(P<0.05);NPD组与NGT组、I-IGT组、C-IGT组比较差异有统计学意义(P<0.05),与其他组差异无统计学意义。②胰岛素分泌指数(ΔI30/ΔG30)由小到大依次为CFPD组、IFD组、NFD组、IPD组、C-IGT组、NPD组、I-IGT组、I-IFG组、NGT组,各组间比较差异有统计学意义(P<0.05)。③校正IR影响后,胰岛β细胞分泌功能由弱到强依次为CFPD组、IPD组、IFD组、NPD组、NFD组、C-IGT组、I-IFG组、I-IGT组、NGT组,各组间比较差异有统计学意义(P<0.05)。结论不同糖耐量人群IR和胰岛β细胞功能具有FBG越高基础胰岛素抵抗越严重,单纯以餐后增高为特征的糖尿病患者并未表现出基础胰岛素抵抗,主要是早晚相胰岛素分泌缺陷,空腹相当时餐后血糖越高胰岛分泌功能越弱,即随着空腹、餐后糖代谢紊乱的不断进展,IR逐渐加重,胰岛β细胞分泌功能进行性减退。针对此特点进行个体化干预及治疗尤为重要。     

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.     

Cardiovascular Characteristics in Subjects With Increasing Levels of Abnormal Glucose Regulation: The Strong Heart Study

OBJECTIVE

To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function.

RESEARCH DESIGN AND METHODS

We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m² (age 46–65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT).

RESULTS

BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m^2.7 in men) was 3.5 in IFG participants (95% CI 0.68–17.76; P = NS) and 9.76 (2.03–46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders.

CONCLUSIONS

Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).Diabetes increases the risk of cardiovascular (CV) disease and mortality (1), an association that is independent of other CV risk factors (2). Evidence has also emerged of an increased CV risk in individuals with abnormal glucose regulation (3,4). Both states of abnormal glucose regulation (i.e., impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]) are reported to be associated with excess body weight and increased levels of CV risk factors, morbidity, and mortality (5–7), although these associations are not universally recognized (8,9).Whether increased plasma glucose above the normal range but below that of clinical diabetes has an impact on cardiac geometry and function is little explored. Cohort studies in communities have shown increased left ventricular (LV) mass and remodeling in individuals with prediabetes (10–12), which appear to be mediated by insulin resistance and body fat distribution (11). However, there are limited clinical or population studies examining CV phenotype in individuals with IGT (13,14), and they included participants with hypertension and/or CV disease, making it difficult to evaluate the role of abnormal glucose levels.Glucose dysregulation is a continuum from elevation of either fasting or postprandial glucose concentration to impairment of both and, eventually, to type 2 diabetes. This progression is associated with worsening CV risk profile, and individuals with both IFG and IGT have more severe metabolic abnormalities and a greater risk of conversion to type 2 diabetes than those with isolated IFG or IGT (5). Thus, it is plausible that CV phenotype also may worsen in parallel with more severe glucose impairment. Accordingly, in the population of the Strong Heart Study (SHS), we compared the metabolic and echocardiographic features of nondiabetic participants who had either IFG or IFG and IGT combined from the second exam; we hypothesized that the combination of IFG and IGT is associated with more severe abnormalities of cardiac geometry and function than isolated IFG.     

Impaired fasting glucose in cystic fibrosis

OBJECTIVE

While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.

RESEARCH DESIGN AND METHODS

Data were retrieved from the University of Minnesota CF database on oral glucose tolerance tests (OGTTs) performed in 1996–2005. Subjects were identified as normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CF–related diabetes without fasting hyperglycemia (CFRD FH−). Patients with fasting hyperglycemia were excluded. The presence of IFG was assessed within each category. In a separate case-control cohort study, subjects with IFG were matched to CF control subjects by age, sex, and OGTT class to explore outcomes.

RESULTS

For the total population (n = 310), the prevalence of IFG was 22%, and by OGTT class was NGT 14%, IGT 31%, CFRD FH− 53%. Within the cohort study, mortality was significantly reduced in IFG (two vs. nine deaths, odds ratio [OR] = 0.2 [95% CI 0.04–0.9]). IFG did not confer increased risk of progression to diabetes (OR 0.66 [0.29–1.48]). Lung function was better in pediatric IFG subjects with IGT and not significantly worse in adults with IGT or adults and children with NGT and CFRD FH−. BMI was not significantly different in IFG subjects versus control subjects.

CONCLUSIONS

Contrary to expectations in patients with CF, IFG appeared to be associated with improved survival and was not associated with worse nutritional or pulmonary status or increased progression to fasting hyperglycemia.Oral glucose tolerance test (OGTT) categories were defined decades ago by the World Health Organization (WHO). In 1997, the American Diabetes Association (ADA) lowered the fasting glucose level used to define diabetes from 140 mg/dl (7.8 mmol/l) to 126 mg/dl (7.0 mmol/l) to better reflect risk of microvascular complications. The ADA also introduced the concept of impaired fasting glucose (IFG) because fasting glucose elevation in the range of 110–125 mg/dl (6.1–6.9 mmol/l) was shown to be a risk factor for the development of diabetes. In 2003, the ADA further lowered this prediabetes threshold to 100 mg/dl (5.6), again based on the future risk of developing diabetes. Using these newer criteria, the prevalence of IFG in the general population may be as high as 30% among U.S. adults (1) and 11% among adolescents (2).Oral glucose tolerance abnormalities are found in the majority of patients with cystic fibrosis (CF) (3), but IFG has been infrequently reported (4,5). No studies have reported current or future clinical outcomes in CF patients with IFG. Because impaired glucose tolerance (IGT) is associated with pulmonary function deterioration in CF (6) and risk of progression to diabetes (7), we hypothesized that IFG would also be associated with worse clinical status and the development of diabetes. Our aim was to determine the prevalence of IFG in the University of Minnesota (UM) CF population and the consequences of that diagnosis over a period of at least 3.5 years'' follow-up.