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

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

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.     

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.     

Coronary artery calcification in type 2 diabetes and insulin resistance: the framingham offspring study

OBJECTIVE: To assess risk for subclinical coronary atherosclerosis using electron beam- computed tomography in subjects with or without insulin resistance and with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT/impaired fasting glucose [IFG]) or type 2 diabetes. RESEARCH DESIGN AND METHODS: We categorized glucose tolerance by type 2 diabetes therapy (diagnosed diabetes) or with an oral glucose tolerance test (OGTT) (IFG, IGT, and OGTT-detected diabetes) and insulin resistance as an elevated fasting insulin level, in subjects attending the fifth examination (1991-1995) of the Framingham Offspring Study. A representative subset of subjects without clinical atherosclerosis was selected for electron beam computed tomography in 1998-1999 from age- and sex-stratified quintiles of the Framingham risk score. The presence of subclinical atherosclerosis was defined as the upper quartile of the Agatston score distribution (score > 170). We assessed risk for subclinical atherosclerosis using multivariable logistic regression. RESULTS: Of 325 subjects aged 31-73 years, 51% were men, 11.2% had IFG/IGT, and 9.9% had diabetes (2.8% with diagnosed diabetes); 14.5% had insulin resistance. Compared with NGT, subjects with IFG/IGT tended to be more likely (adjusted odds ratio 1.5, 95% CI 0.7-3.4) and those with diabetes were significantly more likely (2.7, 1.2-6.1) to have subclinical coronary atherosclerosis. In age- and sex-adjusted models, subjects with insulin resistance were more likely to have subclinical atherosclerosis than those without insulin resistance (2.1, 1.01-4.2), but further risk factor adjustment weakened this association. In adjusted models including insulin resistance, diabetes remained associated with risk for subclinical atherosclerosis (2.8, 1.2-6.7); diagnosed diabetes (6.0, 1.4-25.2) had a larger effect than OGTT-detected diabetes (2.1, 0.8-5.5). CONCLUSIONS: Individuals with diabetes have an elevated burden of subclinical coronary atherosclerosis. Aggressive clinical atherosclerosis prevention is warranted, especially in diagnosed diabetes.     

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.     

综合干预对老年人糖代谢异常进程的影响

目的分析在综合干预状态下,老年糖耐量正常者(NGT)进展为糖调节异常者(IGR),以及IGR进展为糖尿病(DM)的情况。方法于2002年对军队老年离退休干部心血管疾病危险因素进行了4年综合干预,对其中549例NGT、110例IGR定期随访4年。结果综合干预结束时,研究人群的血压、血脂、体质量指数(BMI)均有显著性下降(P<0.01)。NGT进展为IGR的比率为30.97%,其中6.74%进展为空腹血糖受损(IFG),16.39%进展为糖耐量异常(IGT),7.83%进展为空腹血糖受损合并糖耐量异常(IFG/IGT),由NGT进展为IGT的比率明显高于IFG(P<0.01);IFG检出率增加了1.11倍,进展为IFG1的比率(4.55%)明显高于IFG2(2.19%)(P<0.05)。110例IGR人群中,19.61%的IGT进展为DM,16.28%的IFG进展为DM,IGT与IFG进展为糖尿病的比例差异无统计学意义(P>0.05)。8.70%的IFG1进展为DM,25.00%的IFG2进展为DM(P>0.05);43.75%的IFG/IGT进展为DM,进展率明显高于IFG、IGT(P<0.05)。基线时IGR累计进展为DM的比率是21.82%。结论老年人进展为IGT的比率明显高于IFG,IFG/IGT进展为DM的比率明显高于单独的IFG或IGT。     

The rising prevalence of diabetes and impaired glucose tolerance: the Australian Diabetes, Obesity and Lifestyle Study

OBJECTIVE: To determine the population-based prevalence of diabetes and other categories of glucose intolerance (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) in Australia and to compare the prevalence with previous Australian data. RESEARCH DESIGN AND METHODS: A national sample involving 11,247 participants aged > or =25 years living in 42 randomly selected areas from the six states and the Northern Territory were examined in a cross-sectional survey using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma glucose concentrations. The World Health Organization diagnostic criteria were used to determine the prevalence of abnormal glucose tolerance. RESULTS: The prevalence of diabetes in Australia was 8.0% in men and 6.8% in women, and an additional 17.4% of men and 15.4% of women had IGT or IFG. Even in the youngest age group (25-34 years), 5.7% of subjects had abnormal glucose tolerance. The overall diabetes prevalence in Australia was 7.4%, and an additional 16.4% had IGT or IFG. Diabetes prevalence has more than doubled since 1981, and this is only partially explained by changes in age profile and obesity. CONCLUSIONS: Australia has a rapidly rising prevalence of diabetes and other categories of abnormal glucose tolerance. The prevalence of abnormal glucose tolerance in Australia is one of the highest yet reported from a developed nation with a predominantly Europid background.     

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 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.     

The relationship between endothelial dysfunction and oxidative stress in diabetes and prediabetes

Objective: Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). The aim of the present study was to determine whether increased OS and impaired endothelial function, are present in early states of diabetes, such as impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Methods: Brachial artery flow‐mediated dilatation (FMD) and nitrate‐induced dilatation were measured in 133 subjects with carbohydrate abnormalities (45 IGT, 44 IFG and 44 Type 2 diabetes mellitus) and in 46 subjects with normal glucose tolerance (NGT). Waist circumference, body mass index, blood pressure and fasting lipid profiles were obtained, and glucose and insulin values in response to a 75‐g oral glucose load were also measured. Plasma malondialdehyde (MDA) and superoxide dismutase (SOD) activity were determined. Results: Patients with diabetes and prediabetes had a higher plasma MDA concentration, but a lower plasma SOD activity than the NGT group (p = 0.006) and SOD activity was positively associated with FMD (p = 0.039). FMD were significantly reduced in the groups of subjects with abnormal carbohydrate metabolism compared with the NGT group (p = 0.035). Among the subjects with diabetes and prediabetes, FMD showed a negative correlation with fasting glucose and/or plasma glucose level at 120 min after oral glucose tolerance test (p = 0.028). Conclusions: The results showed that endothelial dysfunction and increased OS were present in subjects with IGT and IFG, indicating endothelial damage in these stages.     

Epidemiology of diabetes among Arab Americans

OBJECTIVE: To examine the prevalence of diabetes and glucose intolerance by age and sex in the Arab-American community of Dearborn, Michigan. RESEARCH DESIGN AND METHODS: Participants were randomly selected adult Arab Americans, 20-75 years of age, from randomly selected households in Dearborn, Michigan. Demographic and anthropometric data were recorded. Glucose tolerance was assessed with 2-h 75-g oral glucose tolerance tests and classified according to 1997 American Diabetes Association and 1998 World Health Organization criteria. RESULTS: A total of 626 eligible adults were selected, and 542 participated (87% response rate). Because prevalence increases with age and the overall response rate for women (328/352; 93%) was higher than that for men (214/274; 78%), prevalence rates were adjusted for age and sex. The overall prevalence of diabetes was 15.5% (95% CI 12.2-18.7%) in women and 20.1% (15.0-25.2%) in men (P = 0.13). The prevalence of previously diagnosed diabetes was similar to that of undiagnosed diabetes. Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) were present in 16.8% (12.8-20.8%) of women and 29.7% (23.4-35.9%) of men (P = 0.0007). The combined rates of glucose intolerance (diabetes, IGT, and IFG) were 32.3% (27.8-36.7%) for women and 49.8% (43.1-56.4%) for men (P < 0.0001). Among younger adults, the prevalence in men was higher than that in women. As expected, subjects with diabetes or IGT/IFG were older and had greater BMI and waist-to-hip ratios than subjects with normal glucose tolerance. CONCLUSIONS: The prevalence of diabetes and glucose intolerance is extremely high among adult Arab Americans in Michigan and represents a major clinical and public health problem. Community-based intervention programs to prevent and treat diabetes are urgently needed.     

Cardiovascular morbidity and mortality associated with the metabolic syndrome

OBJECTIVE: To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization RESEARCH DESIGN AND METHODS: A total of 4,483 subjects aged 35-70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome. In subjects who had type 2 diabetes (n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798) or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years. RESULTS: In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes. The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome (P < 0.001). Cardiovascular mortality was markedly increased in subjects with the metabolic syndrome (12.0 vs. 2.2%, P < 0.001). Of the individual components of the metabolic syndrome, microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P = 0.002). CONCLUSIONS: The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from diferent studies.     

The Singapore impaired glucose tolerance follow-up study: does the ticking clock go backward as well as forward?

OBJECTIVE: To 1). document the change in glucose tolerance for subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) over time, 2). identify baseline factors associated with worsening of glucose tolerance, and 3). determine whether cardiovascular disease (CVD) risk factors associated with IGT improved in tandem with glucose tolerance. RESEARCH DESIGN: Subjects with IGT and NGT (matched for age, sex, and ethnic group) were identified from a cross-sectional survey conducted in 1992. Subjects with IGT (297) and NGT (298) (65.0%) were reexamined in 2000. Glucose tolerance (assessed by 75-g oral glucose tolerance test), anthropometric data, serum lipids, blood pressure, and insulin resistance were determined at baseline and at the follow-up examination. RESULTS: For NGT subjects, 14.0% progressed to IGT and 4.3% to diabetes over 8 years. For IGT subjects, 41.4% reverted to NGT, 23.0% remained impaired glucose tolerant, and 35.1% developed diabetes. Obesity, hypertriglyceridemia, higher blood pressure, increased insulin resistance, and lower HDL cholesterol at baseline were associated with worsening of glucose tolerance in both IGT and NGT subjects. Those with IGT who reverted to NGT remained more obese and had higher blood pressure than those with NGT in both 1992 and 2000. However, serum triglyceride, HDL cholesterol, and insulin resistance values in 2000 became indistinguishable from those of subjects who maintained NGT throughout the study period. CONCLUSIONS: Some, but not all, CVD risk factors associated with IGT and with the risk of future diabetes normalize when glucose tolerance normalizes. Continued surveillance and treatment in subjects with IGT, even after they revert to NGT, may be important in the prevention of CVD.     

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 of diabetes and impaired glucose tolerance in 64-year-old Swedish women: experiences of using repeated oral glucose tolerance tests

OBJECTIVE: The purpose of this study was to describe the prevalence of diabetes and impaired glucose tolerance (IGT) in middle-aged women and to examine the variability and practical use of the oral glucose tolerance test (OGTT) in the screening for IGT and diabetes. RESEARCH DESIGN AND METHODS: All 64-year-old women living in G?teborg, Sweden, were invited to take part in a screening examination (n = 4,856). Of these, 82% (n = 3,998) responded and 53% (n = 2,595) participated and underwent anthropometric measurements and a 75-g standardized OGTT that was repeated within 2 weeks in those not showing normal glucose tolerance (NGT). RESULTS: The prevalences of known and new diabetes, IGT at both OGTTs, and impaired fasting glucose were 4.7, 4.8, 14.4, and 6.4%, respectively. Half of the women with diabetes were previously undiagnosed, and 37% of the diagnoses were based on OGTT and diabetes 2-h values at both or one of the two examinations. Women with IGT at both OGTTs, in comparison with those with one impaired and one normal OGTT, had higher BMI, waist girth, and blood pressure. More than 40% of the women showed impaired glucose metabolism. CONCLUSIONS: Among these women, the prevalence of undetected diabetes was high and repeated OGTTs were needed to identify and not misclassify a considerable proportion of patients. The degree of glucose tolerance impairment and the number of abnormal OGTTs were directly associated with occurrence of components of the metabolic syndrome.     

The prevalence of diabetes and impaired glucose tolerance in Sivas, Central Anatolia, Turkey

OBJECTIVE: The aim of this study was to determine type 2 diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) prevalence in Sivas, Turkey. RESEARCH DESIGN AND METHODS: This cross-sectional study was conducted in the city center of Sivas. The study population of 771 subjects was selected by the cluster sampling method from 115,998 individuals aged > or =30 years. Participants with fasting venous plasma glucose concentrations <100 mg/dl were classified as "normal." Diabetes was diagnosed in participants if they had fasting blood glucose levels > or =126 mg/dl. An oral glucose tolerance test (OGTT) was performed in subjects with fasting blood glucose levels > or =100 mg/dl and <126 mg/dl. RESULTS: According to the fasting blood glucose levels of the 771 subjects, 44 (5.7%) had diabetes. OGTTs were performed in 80 (10.4%) subjects. According to OGTT results, there were 5 subjects with diabetes, 20 subjects with IGT (2.6%), and 55 subjects with IFG (7.1%). The combined prevalence of IFG and IGT was 9.7%. After OGTT, the total number of diabetic subjects was determined to be 49 (6.4%). Twenty-four (3.1%) of the subjects had a previous diagnosis of diabetes. Multivariate analyses showed that age, sex, hypertension, cigarette smoking, obesity, and family history of diabetes were risk factors for type 2 diabetes (P < 0.05). CONCLUSIONS: Diabetes incidence increases with changes in dietary habits and lifestyle. Education is particularly important for public health, as the community may then have required knowledge about the disease and its risk factors.     

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.     

Insulin and C-peptide levels, pancreatic beta cell function, and insulin resistance across glucose tolerance status in Thais

Impaired pancreatic beta cell function and insulin sensitivity are fundamental factors in the pathogenesis of type 2 diabetes; however, the predominant defect appears differ among ethnic groups. We conducted a cross-sectional study to evaluate the contribution of impaired beta cell function and insulin sensitivity at different stages of the deterioration of glucose tolerance in Thais. The study involved 420 urban Thais of both sexes, 43-84 years old. A 75-g oral glucose tolerance test was performed on all of the subjects. Indices of insulin resistance and beta cell function were calculated with the use of a homeostasis model assessment. The subjects were classified as having normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG and IGT, or type 2 diabetes mellitus according to the American Diabetes Association (ADA) criteria. There were no differences between groups with regard to gender and age. The percentage of obesity was significantly greatest in the diabetic group. Fasting serum insulin and C-peptide levels progressively increased from the NGT to the diabetic subjects. Serum C-peptide was more strongly associated with newly diagnosed diabetes than insulin, and was an independent factor associated with newly diagnosed diabetic subjects. The insulin resistance index progressively increased when the glucose tolerance stage changed from NGT through diabetic subjects. Beta cell function did not change significantly in any other group compared to the NGT group. An increase in fasting serum C-peptide may be a risk factor for type 2 diabetes. Obesity and insulin resistance are the predominant features in the deterioration of glucose tolerance in Thais.