Metabolic syndrome and prediabetes identify overlapping but not identical populations.

OBJECTIVE: The metabolic syndrome (MetS) is a cluster of risk factors related to cardiovascular disease. Prediabetes, identified by impaired fasting glucose and/or impaired glucose tolerance, may predict future development of diabetes mellitus. However, it is not clear whether MetS and prediabetes represent the same or different clinical entities. This study compares MetS and prediabetes in terms of cardiovascular risk factors and target organ damage. RESEARCH DESIGN AND METHODS: A total of 524 overweight and obese (body mass index, BMI >or= 27 kg/m (2)) adults, mean age 53.6 +/- 10.3 years, 264 men and 260 women, were studied. All participants underwent a thorough clinical and laboratory evaluation, including an oral glucose tolerance test and insulin measurements. Echocardiography, carotid ultrasonography, and pulse wave analysis were also performed for the detection of target organ damage. NCEP-ATP III and ADA criteria were used for the diagnosis of MetS and prediabetes. RESULTS: The prevalence of MetS and prediabetes was 38.7 and 25.4 %, respectively. Overall, 129 individuals (24.6 %) had MetS without prediabetes (group M) and another 59 (11.3 %) prediabetes without MetS (group P). Group P had decreased albumin excretion (p = 0.033) and more thickened common carotid intima-media in comparison to group M (p = 0.032). Furthermore, group M was associated with higher C-reactive protein levels. Multiple logistic regression analysis revealed that advanced age (p < 0.0001, OR 1.11, 95 % CI 1.06 - 1.16), low insulin secretion (p < 0.0001, OR 0.05, 95 % CI 0.02 - 0.18 for insulinogenic index), and increased insulin resistance (p = 0.0003, OR 3.22, 95 % CI 1.71 - 6.07 for HOMA-IR) were associated with group P. CONCLUSIONS: Our data demonstrate that MetS and prediabetes have an overlapping pattern. MetS appears to have a more pronounced effect on early renal dysfunction and increased inflammatory activation, while prediabetes tends to be associated with early carotid structural changes. These findings may be due to a different pathophysiologic substrate of these clinical phenotypes in terms of insulin resistance and secretion, as well as to the varying prevalence of cardiovascular risk factors.     

The predictive value of CRP levels on future severe renal disease in overweight and obese subjects without diabetes mellitus and hypertension

BACKGROUND: Obesity and related disorders have a high prevalence all over the world. Increased C-reactive protein (CRP) value in obese individuals and its potential adverse effects have been reported. Here we have investigated the relationship between CRP levels and renal functions in nondiabetic, nonhypertensive, overweight, and obese individuals. The aim of this study was to evaluate the predictive value of CRP levels on future severe renal disease. METHODS: One hundred sixty individuals were included in the study. They were grouped as normal weight, overweight, and obese. Anthropometric measurements, renal function tests, and serum hsCRP values were obtained. Mean values were compared and correlation analysis was performed. RESULTS: Significant differences were detected between the groups according to body mass index, waist circumference (WC), and body fat percentage. There was a significant difference with respect to creatinine clearance (CC). Difference in the mean urinary albumin excretion (UAE) was significant between normal-weight and overweight subjects. There was a linear increase in serum CRP values in parallel to the increase in body weight; mean values were significant between groups. A positive correlation was detected between CC and body mass index and WC, and there were significant correlations between CRP and anthropometric measurements, CC and UAE. CONCLUSIONS: This study showed that increased CRP levels in nondiabetic, nonhypertensive, overweight, and obese individuals could possibly associated with impaired renal functions that might be originating from endothelial dysfunction. Determination of cutoff levels of CRP, as in cardiovascular diseases, may be useful for early estimation and prevention of renal diseases.     

Metabolic Risks among College Students: Prevalence and Gender Differences

Background: Little is known about the rate of metabolic dysfunction and gender differences in late adolescence or early adulthood. We report here the prevalence of and gender differences in components of the metabolic syndrome (MetS) in a college sample. Methods: Three hundred students (2/3 female) with no prior diagnosis of illness from the University of Kansas, Lawrence, participated in a cross-sectional measurement of weight, height, fasting blood, and 2-hour oral glucose tolerance test. Prevalence of metabolic risks was determined using the Adult Treatment Panel (ATP) III, World Health Organization or International Diabetes Federation criteria. Gender differences in both continuous and dichotomous metabolic variables were tested. Results: The prevalence of MetS was low, but the rate of having at least one abnormal component ranged from 26% to 40%. Different criteria identified different individuals with the MetS. Prevalence was high for low levels of high-density lipoprotein cholesterol (24%), impaired fasting glucose (9%), and hypertriglyceridemia (9%). Fasting insulin was useful in capturing at-risk individuals in addition to ATP-III criteria. Males were more obese, hypertensive, and hypertriglyceridemic than females, but all 9 cases of impaired glucose tolerance were female. Conclusions: The college age and setting are a unique opportunity to monitor and intervene on early risk factors of chronic disease. Undiagnosed metabolic dysfunction is high and problematic in this age group. Unique gender differences in glucose metabolism warrant further research and should be considered in the design of intervention strategies.     

Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening

OBJECTIVE: We sought to study arterial endothelial function and carotid intima-media thickness (IMT), both early markers of atherosclerosis, in overweight compared to normal children. DESIGN: Case-control comparison. SUBJECTS: A total of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25+/-3) aged 9-12 y and 36 age- and gender-matched nonobese healthy children (BMI<21) from a school community. MEASUREMENTS: The key parameters were: BMI, arterial endothelial function (ultrasound-derived endothelium-dependent dilation) and carotid artery IMT. The secondary parameters measured included body fat content, waist-hip ratio (WHR), blood pressures, blood lipids, insulin and glucose. RESULTS: The two groups were well matched for blood pressures, cholesterol and glucose levels, but BMI (P<0.0001), body fat (P=0.001), WHR (P<0.05), fasting blood insulin (P=0.001) and triglyceride levels (P<0.05) were higher in obese children. Overweight was associated with impaired arterial endothelial function (6.6+/-2.3 vs 9.7+/-3.0%, P<0.0001) and increased carotid IMT (0.49+/-0.04 mm vs 0.45+/-0.04 mm, P=0.006). The degree of endothelial dysfunction correlated with BMI (P<0.003) on multivariate analysis. CONCLUSION: Obesity, even of mild-to-moderate degree, is independently associated with abnormal arterial function and structure in otherwise healthy young children.     

Intermediate postchallenge hyperglycemia in overweight and obese subjects: a new marker of impaired glucose regulation?

The objective of this study was to compare subjects with intermediate postchallenge hyperglycemia (INPH) to those with normal glycemic status, impaired fasting glucose (IFG), and/or impaired glucose tolerance (IGT), as well as type 2 diabetes mellitus. Furthermore, the authors evaluated the impact of INPH on target organ damage. In total, 487 overweight and obese adults (BMI > or =27 kg/m(2)), 252 men and 235 women, mean age 52.9 +/-10.2 years, were studied. All participants underwent a clinical and laboratory evaluation, as well as an oral glucose tolerance test (OGTT). They were also investigated by echocardiography, carotid ultrasonography, and pulse wave analysis. Overall, 302 (62%) subjects had normal glycemic status, 64 (13.1%) had IFG and/or IGT, 95 (19.5%) had type 2 diabetes mellitus, and 26 (5.4%) had INPH. Individuals with INPH had an increased index of insulin resistance (higher homeostasis model assessment-insulinogenic index [HOMA-IR], p<0.0001), impaired insulin secretion (lower insulinogenic index, p<0.0001), and higher glycosylated hemoglobin (HbA(1c)) levels (p<0.0001) in comparison with the normoglycemic subjects, but not to those with IFG and/or IGT or diabetes (p = 0.6). No difference was observed concerning the risk factors studied, left ventricular mass and vascular remodeling, among subjects with INPH, IFG and/or IGT, and diabetes. However, individuals with INPH had a higher proportion of echolucent carotid artery plaques in comparison with the normoglycemic subjects (p = 0.04) and those with IFG and/or IGT (p = 0.01). Intermediate postchallenge hyperglycemia seems to represent a new category of glucose metabolism disturbances with increased atherogenic impact. Therefore, evaluating intermediate glucose levels in an OGTT could contribute to better identify overweight individuals at risk of developing diabetes mellitus and cardiovascular events.     

The relationship between insulin resistance and cardiovascular risk factors in overweight/obese non-diabetic Asian adults: the 1992 Singapore National Health Survey

OBJECTIVE: Insulin resistance (IR) is associated with cardiovascular risk factors including hypertension, dyslipidemia, glucose intolerance and hyperuricemia. The relationship between IR and these cardiovascular risk factors in obese non-diabetic individuals is not well studied. We explore this relationship by comparing the cardiovascular risk factors among insulin-sensitive and insulin-resistant overweight/obese non-diabetic Asian adults in the 1992 National Health Survey of Singapore. DESIGN AND MEASUREMENTS: A total of 3568 subjects were examined in the survey, which involved a combination of disproportionate stratified sampling and systematic sampling. Anthropometric measurements, level of physical activity, blood pressure, insulin, lipid profile, uric acid and standard 75 g oral glucose tolerance test were performed after a 10 h overnight fast. Subjects with diabetes were excluded from the analysis. Homeostasis model assessment (HOMA) was used to assess insulin sensitivity. Relative LDL size was derived from the formula LDL/ApoB. We defined insulin-sensitive individuals as having a HOMA value <1.479 (below median in individuals without diabetes; n=3226) and overweight/obesity as body mass index (BMI) >or=25.0 kg/m(2). RESULTS: There were 156 insulin-sensitive (S) and 679 insulin-resistant (R) overweight/obese individuals, respectively. The groups did not differ in terms of gender and ethnic distribution and level of physical activity. However, subjects in group S were younger than those in group R (mean+/-s.d.; 40.1+/-12.1 vs 42.4+/-12.7 y; P<0.05). Group R individuals were also slightly more obese globally and centrally than group S (BMI=28.2+/-3.2 vs 27.1+/-2.8 kg/m(2); waist circumference (WC)=86.7+/-9.3 vs 82.5+/-8.3 cm; P<0.01). There were more subjects with impaired glucose tolerance (IGT) in group R than in group S (29.7 vs 16.0%; P<0.01). After adjustment for age and indices of global and regional obesity (ie BMI and WC), insulin-resistant individuals showed higher apolipoprotein B, triglyceride, fasting (FPG) and 2 h post-load plasma glucose (2hPG) but lower HDL and LDL size. Further adjustment for FPG, 2hPG and level of physical activity had minimal impact on the results. CONCLUSIONS: Insulin-resistant overweight/obese non-diabetic Asian adults had greater burden of the cardiovascular dysmetabolic syndrome than insulin-sensitive overweight/obese individuals. This could not be fully explained by differences in global and regional obesity, glucose tolerance and level of physical activity.     

A comparison of urinary albumin excretion rate and microalbuminuria in various glucose tolerance subjects.

AIMS: To investigate the difference of urinary albumin excretion rate (UAER) and microalbuminuria (MAU) in various glucose tolerance subjects, especially between isolated-impaired glucose tolerance subjects and isolated-impaired fasting glycaemia subjects. METHODS: A total of 2934 subjects were divided into five groups with various glucose tolerances, based on a 75-g oral glucose tolerance test. Microalbuminuria was defined when urinary albumin excretion rate was between 20 and 200 microg/min. RESULTS: (i) The UAER in the newly diagnosed Type 2 diabetes mellitus group, impaired glucose tolerance/impaired fasting glycaemia group and isolated-impaired glucose tolerance group were all higher than that in the isolated-impaired fasting glycaemia group and normal glucose tolerance group, but it was comparable between isolated-impaired fasting glycemia group and normal glucose tolerance group. The prevalence of MAU and the odds ratio for MAU with adjustment for age and sex in various glucose tolerance groups showed the same trend as the UAER. (ii) After adjusting for age and sex, there is a significant association between logUAER and independent risk factors (partial correlation coefficients: r = 0.26 for 2-h post-challenge blood glucose, r = 0.26 for systolic blood pressure, r = 0.27 for diastolic blood pressure, r = 0.27 for body mass index and r = -0.13 for high density lipoprotein-cholesterol, all P < 0.001). The risks for MAU were 2-h post-challenge blood glucose, body mass index and diastolic blood pressure, while high density lipoprotein-cholesterol was protective. CONCLUSIONS: The urinary albumin excretion rate and prevalence of microalbuminuria were higher in isolated-impaired glucose tolerance subjects than those in isolated-impaired fasting glycaemia subjects. At early abnormal glucose tolerance stage, the increasing post-challenge glycaemia might be a more important risk factor for urinary albumin excretion rate and microalbuminuria than increasing fasting glycaemia.     

Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents

Given the extreme increase in prediabetes, type 2 diabetes, and the potential for metabolic syndrome in obese youth, identifying simplified indexes for assessing stimulated insulin sensitivity is critical. The purpose of this study was validation of two surrogate indexes of insulin sensitivity determined from the oral glucose tolerance test (OGTT): the composite whole body insulin sensitivity index (WBISI) and the insulin sensitivity index (ISI). An obese population (aged 8-18 yr) of normal and impaired glucose tolerance individuals was studied. One group (n = 38) performed both the euglycemic-hyperinsulinemic clamp and OGTT for comparison of insulin sensitivity measurements as well as (1)H-magnetic resonance spectroscopy estimates of intramyocellular lipid content. Another larger (n = 368) cohort participated only in an OGTT. Both the WBISI and ISI represented good estimates (r = 0.78 and 0.74; P < 0.0005) for clamp-derived insulin sensitivity (glucose disposed, M-value), respectively. In the large cohort, the surrogate indexes demonstrated the shift toward poorer function and increased risk profile as a function of insulin resistance. Additionally, the WBISI and ISI correlated with intramyocellular lipid content (r = -0.74 and -0.71; P < 0.0001), a tissue marker for insulin resistance. Insulin sensitivity can be estimated using plasma glucose and insulin responses derived from the OGTT in obese youth with normal and impaired glucose tolerance.     

Metabolic risk factors and markers of cardiovascular and renal damage in overweight subjects

BACKGROUND: The prevalence of overweight and obesity in the United States has dramatically increased. Obesity clusters with a variety of hemodynamic and metabolic disturbances that increase the risk of cardiovascular disease. In this study we evaluated whether overweight subjects with hypertension also manifest hemodynamic and metabolic abnormalities compared with individuals of normal weight. METHODS: In a cohort of 129 patients with essential hypertension we measured the relationship between body mass index (BMI), blood pressure (BP), insulin sensitivity, lipid profile, and markers of organ damage including thickness of the carotid artery (IMT) and urine albumin excretion (UAE). A total of 41 normotensive, age-matched, healthy individuals served as control subjects. RESULTS: Hypertensive individuals showed higher levels of serum triglycerides, insulin area-under-the-curve (AUC), UAE, and greater IMT than normotensive subjects. Overweight hypertensive subjects showed higher levels of serum triglycerides, LDL cholesterol, glucose AUC, insulin AUC, UAE, and IMT than hypertensive subjects with normal body weight (BMI <25). Night-time systolic BP was higher and night-time fall in BP was lower among overweight than among normal-weight hypertensive patients. Simple regression analysis showed that BMI was correlated with age, UAE, BP, insulin and glucose AUC, serum triglycerides, cholesterol, and IMT in hypertensive subjects. However multiple regression analyses showed that BMI significantly correlated only with UAE. CONCLUSIONS: The study results show that increased body weight clusters with a variety of hemodynamic and metabolic abnormalities in hypertensive subjects. However multiple regression analyses showed a significant correlation only between BMI and UAE, a marker and predictor of cardiovascular and renal disease.     

Urinary albumin excretion is independently associated with C-reactive protein levels in overweight and obese nondiabetic premenopausal women

OBJECTIVES: C-reactive protein (CRP) and microalbuminuria are nowadays considered markers of chronic inflammation of the arterial wall and of endothelial dysfunction, respectively. An increase of CRP levels and of urinary albumin excretion (UAE) rate have both been reported to be independently associated with a higher risk of cardiovascular morbidity and mortality in the general population. The aim of the present study was to evaluate the possible correlation between UAE and CRP concentrations in overweight and obese premenopausal women. DESIGN AND SETTING: A cross-sectional study in a primary care setting. SUBJECTS, MAIN OUTCOME MEASURES: CRP levels and UAE rate were measured in 103 overweight and obese premenopausal women, aged 18-45 years. Other measurements included: central fat accumulation, as evaluated by waist circumference, insulin resistance, as calculated by homeostatic model assessment (HOMAIR); fat-free mass (FFM), as measured by bioimpedance analysis; blood pressure; and fasting plasma levels of glucose, insulin, and lipids. RESULTS: Urinary albumin excretion was positively correlated with body mass index (BMI) (P < 0.01), waist circumference (P < 0.001), diastolic blood pressure (P < 0.01), triglycerides (P < 0.01), HOMAIR (P < 0.05), and CRP levels (P < 0.05); and negatively associated with HDL cholesterol (P < 0.001). After multivariate analysis, diastolic blood pressure, HDL cholesterol, and CRP levels maintained their significant correlation with UAE. CONCLUSION: Our study shows a strong relationship between UAE and CRP concentrations, irrespective of age and other anthropometric and metabolic variables. On this basis, it can be argued that inflammation of the arterial wall, as indicated by higher CRP plasma levels, and endothelial dysfunction, as shown by higher UAE rate, might represent simultaneous phenomena in the development of atherosclerosis in overweight and obese premenopausal women.     

Nonalcoholic fatty liver disease and the heart in children and adolescents

Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease (NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome (MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.     

Coronary flow velocity reserve reduction is comparable in patients with erectile dysfunction and in patients with impaired fasting glucose or well-regulated diabetes mellitus.

BACKGROUND: There is growing evidence that erectile dysfunction is a sentinel for future coronary artery disease. Recently published studies have shown signs of impaired coronary endothelial function in patients with erectile dysfunction, without clinical cardiovascular disease and diabetes. We evaluated the magnitude of coronary vasodilatory dysfunction in men with erectile dysfunction, as compared with men with impaired glucose metabolism (impaired fasting glucose or diabetes) and healthy controls. METHODS: We investigated men aged 68-73 years with erectile dysfunction (n=12), age-matched men with impaired glucose metabolism, who all proved to have erectile dysfunction (n=15), and age-matched male controls (n=12). Erectile dysfunction was evaluated using the International Index of Erectile Function (IIEF)-5 questionnaire. Coronary flow velocity reserve in the left anterior descending artery was examined using Doppler ultrasound and intravenous adenosine provocation. RESULTS: Coronary flow velocities at rest did not differ between the three groups, but maximum coronary flow velocity was significantly lower in the erectile dysfunction group (P=0.004) and in the impaired glucose metabolism group (P=0.019), as compared with controls. There was no difference between the erectile dysfunction and impaired glucose metabolism groups. Coronary flow velocity reserve was reduced in the erectile dysfunction group (P=0.026) compared to controls, but was similar compared to the impaired glucose metabolism group. In multivariate analysis including all groups, erectile dysfunction score was the only independent predictor of reduced coronary flow velocity reserve (P=0.020). CONCLUSIONS: The magnitude of early coronary endothelial and smooth muscle cell dysfunction in otherwise healthy men with erectile dysfunction was comparable to that of patients with impaired glucose metabolism: a well known risk factor for coronary artery disease.     

Metabolic syndrome in hypertensive patients:An unholy alliance

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.     

Non-invasive evaluation of endothelial dysfunction in uncomplicated obesity: relationship with insulin resistance

Obesity is associated with increased cardiovascular morbidity and amortality. Endothelial dysfunction, involved in the pathogenesis of cardiovascular events, has been demonstrated in obese patients with invasive techniques requiring artery catheterization. The aim of our investigation was to evaluate, with a non-invasive method readily employable on clinical grounds, impaired vasodilatation and its relationship with insulin resistance in uncomplicated obesity. 15 uncomplicated obese subjects (BMI = 36.6 +/- 3.2) and 10 lean controls (BMI = 22.9 +/- 1.25) were enrolled in this study. All subjects underwent measurement of endothelium-dependent (FBFr) vasodilatation by forearm venous occlusion pletysmography after increasing times of ischemia, and measurement of insulin sensitivity by the euglycemic hyperinsulinemic clamp technique (M index), by fasting glucose and insulin (HOMA-IR) and by oral glucose tolerance test (ISI index). Endothelium-independent (N-FBFr) vasodilatation was assessed as well. The FBFr was markedly blunted in obese patients versus lean controls (30 s: 2.12 +/- 0.34 vs. 3.63 +/- 0.22, P < 0.01; 60 s: 2.34 +/- 0.42 vs. 3.82 +/- 0.53, P < 0.01; 180 s: 3.20 +/- 0.45 vs. 7.15 +/- 0.35, P < 0.01; 300 s: 4.08 +/- 0.94 vs. 14.1 +/- 0.82, P < 0.001). The N-FBFr was not different in the two groups. High correlation was found between M index and FBFr at all ischemia times. HOMA-IR and ISI were not related with FBFr. The non-invasive evaluation of endothelial dysfunction by a simple and reliable method based on venous occlusive plethysmography shows high correlation between impaired endothelium-dependent vasodilatation and insulin resistance in uncomplicated obesity. This non-invasive test of endothelial function may be routinely performed in the assessment of cardiovascular risk in uncomplicated obesity.     

Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to < 126 mg/dL; (2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/dL and < 200 mg/dL; or (3) hemoglobin A1c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index (BMI)-SD score, and VAT. In multiple regression analysis with WBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI (standardized coefficient B, -0.398; P = 0.001) as well as HOMA-IR (0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes (OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.     

Is metabolic syndrome a condition independent of prediabetes and type 2 diabetes mellitus? A report from Turkey

It has been suggested that metabolic syndrome (MetS) overlaps prediabetes and type 2 diabetes and that it is not necessary to consider it as a separate clinical entity. In the present study, patients with normoglycemia and dysglycemia were compared in terms of MetS frequency and MetS criteria characteristics, in order to test the appropriateness of considering MetS as a condition independent of prediabetes and type 2 diabetes. A total of 1222 (801 females, 401 males, mean age: 51.50 11.73 y) consecutive patients attending Internal Medicine outpatient clinics were included. Cases were assigned into two groups: patients with normoglycemia (fasting plasma glucose <100 mg/dl, n = 555) or dysglycemia (fasting plasma glucose >/=100 mg/dl and/or receiving antidiabetic treatment, n = 667). Groups were compared in terms of MetS frequency and MetS criteria characteristics. A 2-hour oral glucose tolerance test was administered to the normoglycemia group. In addition, patients with MetS were assigned into two groups: patients with normoglycemia and dysglycemia. These two groups were also compared in terms of MetS criteria characteristics. Adult Treatment Panel III criteria were used for the diagnosis of MetS. The overall frequency of MetS was 52.2%. MetS was found in 72.7% of patients with dysglycemia and 27.6% of patients with normoglycemia (p = 0.001). Mean systolic and diastolic blood pressure, waist circumference and triglyceride levels were similar between normoglycemic and dysglycemic MetS patients (p>0.05). Impaired glucose tolerance was higher among normoglycemic MetS patients compared to normoglycemic patients without MetS (13.7% vs. 6.5%, p = 0.006). In conclusion, although MetS is a well known risk factor for type 2 diabetes, our results support that it is a separate entity independent of prediabetes and type 2 diabetes mellitus.     

良性肥胖对2型糖尿病、心血管事件和死亡的影响——大庆糖尿病预防23年随访研究

目的探讨良性肥胖对2型糖尿病、心血管事件和死亡等长期临床结局的影响。方法1986年纳入大庆市经口服葡萄糖耐量试验诊断的糖耐量正常者519名和新诊断2型糖尿病者630例,之后评估23年随访的长期临床结局。良性肥胖即超重肥胖而无代谢异常(定义为无糖尿病、高血压和高脂血症)。最终纳入682例受试者(糖耐量正常者350名和新诊断2型糖尿病者332例),根据基线状态分为正常体重无代谢异常组(211例)、超重肥胖无代谢异常组(58例)、超重肥胖伴高血压组(81例)、超重肥胖伴2型糖尿病组(109例)、超重肥胖伴高血压和2型糖尿病组(223例)。比较各组2型糖尿病、心血管事件和死亡发病率。结果23年后随访,超重肥胖无代谢异常组心血管事件和死亡发病风险与正常体重无代谢异常组相比无差异,但是其2型糖尿病发病率为正常体重无代谢异常组的2倍(24.1%、12.5/1000人年对10.9%、5.2/1000人年,P=0.01)。多因素回归分析调整了年龄、性别、吸烟史的影响后,这种差别依然存在[风险比(HR)=2.42,95%CI 1.24~4.74,P=0.01]。超重肥胖伴高血压组、超重肥胖伴2型糖尿病组及超重肥胖伴高血压和2型糖尿病组的全因死亡、心血管事件和死亡的发病风险均高于正常体重无代谢异常组,并依次递增(P<0.05)。结论良性肥胖人群长期心血管病风险和死亡与正常组无差异,但其2型糖尿病发病率显著增加。肥胖合并其他代谢紊乱人群的2型糖尿病、心血管事件和死亡的发病风险增加更甚。     

Insulin secretion and sensitivity in non-obese and obese Japanese patients with coronary artery disease

In a cross-sectional study of 240 patients with angiographically documented coronary artery disease (CAD), we investigated whether obese and non-obese subjects differed as to the influence of insulin deficiency and insulin resistance on glucose intolerance and cardiovascular risk. Patients were classified according to a 75-g oral glucose tolerance test as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus (DM). We defined obesity as a body mass index (BMI) exceeding 25 kg/m(2). Early phase insulin secretion (insulinogenic index) declined with worsening glucose intolerance in non-obese (tau = -.216, P <.001; Kendall's correlation coefficient) and obese subjects (tau = -.392, P <.001). Total insulin secretion was higher in obese subjects with NGT or IGT than in controls and decreased in association with worsening glucose intolerance in obese subjects (tau = -.239, P <.001). Insulin sensitivity was calculated by 3 proposed indices. The first of these decreased in association with worsening in glucose tolerance in non-obese subjects (tau = -.137, P <.01). The second showed such a pattern in both groups (non-obese, tau = -.407, P <.001; obese, tau = -.311, P <.001), as did the third (non-obese, tau = -.512, P <.001; obese, tau = -.488, P < 0.001). Because even prediabetic Japanese subjects with CAD showed a latent insulin secretion defect in response to a glucose load, as well as impaired insulin sensitivity, compensatory hyperinsulinemia is not a sensitive indicator of coronary risk.     

Cardiovascular Risk Stratification and Management in Pre-Diabetes

Prediabetes, covering individuals with impaired fasting glycemia, impaired glucose tolerance, or high-risk HbA_1c levels, is associated with a ～20 % increased risk of developing cardiovascular disease (CVD) compared with normoglycemic individuals. It is well-known that lifestyle or pharmacologic interventions can prevent diabetes in prediabetic people; however, the evidence is less clear regarding prevention of CVD. Most diabetes prevention trials have failed to show beneficial effects on CVD morbidity and mortality despite significant improvements of CVD risk factors in individuals with prediabetes. Another challenge is how to estimate CVD risk in prediabetic people. In general, prediction models for CVD do not take glucose levels or prediabetes status into account, thereby underestimating CVD risk in these high-risk individuals. More evidence within risk stratification and management of CVD risk in prediabetes is needed in order to recommend useful and effective strategies for early prevention of CVD.     

Fasting hyperglycaemia blunts the reversal of impaired glucose tolerance after exercise training in obese older adults

Aim: Lifestyle modification, consisting of exercise and weight loss, delays the progression from prediabetes to type 2 diabetes (T2D). However, no study has determined the efficacy of exercise training on glucose metabolism in the different prediabetes subtypes. Methods: Seventy‐six older (65.1 ± 0.6 years) obese adults with impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 9) and combined glucose intolerance (IFG + IGT = CGI; n = 22) were compared with normal glucose tolerant (NGT; n = 15) and T2D (n = 18) groups after 12 weeks of exercise training (60 min/day for 5 days/week at ～85% HR_max). An oral glucose tolerance test was used to assess glucose levels. Insulin sensitivity (IS; euglycaemic hyperinsulinaemic clamp at 40 mU/m²/min), β‐cell function (glucose‐stimulated insulin secretion corrected for IS), body composition (hydrostatic weighing/computed tomography scan) and cardiovascular fitness (treadmill VO₂max) were also assessed. Results: Exercise training reduced weight and increased cardiovascular fitness (p < 0.05). Exercise training lowered fasting glucose levels in IFG, CGI and T2D (p < 0.05) and 2‐h glucose levels in IGT, CGI and T2D (p < 0.05). However, 2‐h glucose levels were not normalized in adults with CGI compared with IGT (p < 0.05). β‐Cell function improved similarly across groups (p < 0.05). Although not statistically significant, IS increased approximately 40% in IFG and IGT, but only 17% in CGI. Conclusion: The magnitude of improvement in glucose metabolism after 12 weeks of exercise training is not uniform across the prediabetes subtypes. Given the high risk of progressing to T2D, adults with CGI may require more aggressive therapies to prevent diabetes.