Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese

The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity, blood pressure, fasting plasma glucose, lipid, insulin, insulin resistance indices, and urinary catecholamine excretion. Using stepwise multiple regression analysis (all P < .001), 34% of the variability of the BMI and 45% of that of the waist circumference were independently related to gender (waist higher in males and BMI higher in females), increased plasma insulin, triglyceride, and urinary norepinephrine excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary epinephrine output. In Chinese subjects with different manifestations of the metabolic syndrome, hyperinsulinemia, insulin resistance, elevated norepinephrine, and reduced epinephrine excretion were closely associated with general and central obesity. Based on these findings, we postulate that complex interactions between the insulin and sympathoadrenal systems may lead to the development of obesity and the metabolic syndrome.     

Microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes in the Korean population

To investigate whether microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes, we studied the association between microalbuminuria and features of insulin resistance syndrome in Korean general population. We selected 1006 subjects by a random cluster sampling among residents aged >40 years living in the Chung-Up district, a rural area of South Korea. Subjects were stratified by oral glucose tolerance status [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus], and by the presence or absence of hypertension. Urinary albumin excretion rate (UAER) was determined using timed overnight urine collection. Various cardiovascular risk factors including anthropometric indices, serum lipid, true insulin and proinsulin concentrations were also measured. The prevalence of microalbuminuria (UAER between 20 and 200 microg/min) increased as the glucose tolerance worsened (6.0% in NGT, 11.8% in IGT, and 21.8% in diabetes; chi(2) trend=25.9, P<0.001). Subjects with microalbuminuria had a higher body mass index (BMI), waist-to-hip circumference ratio (WHR), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose, fasting plasma insulin and proinsulin levels, and lower HDL-cholesterol level than subjects without microalbuminuria. In multiple regression analysis, BMI, diastolic BP, 2 h plasma glucose, and fasting plasma insulin levels were found to be independent factors associated with UAER. Multiple logistic regression analysis showed that not only diabetes mellitus and hypertension, but also fasting hyperinsulinemia and waist-to-hip ratio were independent factors associated with the presence of microalbuminuria. When the normotensive, non-diabetic subjects were analyzed separately, fasting hyperinsulinemia and impaired glucose tolerance remained independent variables associated with the presence of microalbuminuria. These results show that microalbuminuria in the Korean general population is associated with hyperinsulinemia and central obesity, and suggest that microalbuminuria is a feature of the insulin resistance syndrome independent of hypertension or type 2 diabetes.     

The Relationship Between Plasminogen Activator Inhibitor-1 and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Mellitus

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAI-1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin-resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAI-1, 17.6 (11.1–28) vs 8.4 (4.9–14.1) IU ml^?1, p < 0.001. PAI-1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r=0.66, p < 0.001; insulin resistance, r = 0.54, p< 0.005 and urinary albumin excretion, r=0.48, p < 0.01, but not HbA_1c or fasting glucose. PAI-1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAI-1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.     

Microalbuminuria Cardiovascular Risk Factors,and Insulin Resistance in Two Populations with a High Risk of Type 2 Diabetes Mellitus

A total of 359 Wanigelas from Papua New Guinea and 1041 Nauruans had urinary albumin concentrations (UAC), serum insulin, and a number of cardiovascular disease (CVD) risk factors measured during population-based surveys of non-insulin-dependent diabetes mellitus. These data were used to explore the hypothesis that microalbuminuria is closely associated with insulin resistance and the metabolic syndrome. In both Nauruans and Wanigelas, worsening glucose tolerance was associated with increasing prevalence of micro- and macroalbuminuria. Within each category of glucose tolerance, microalbuminuria was associated with general worsening of cardiovascular risk factors including lipid concentrations, blood pressure and obesity, although few of the associations were statistically significant. Correlations between UAC and markers of insulin resistance (fasting insulin, fasting insulin/glucose ratio and HOMAS%, a computer-modelled estimate of insulin sensitivity) were weak and inconsistent irrespective of glucose tolerance status. Relationships between insulin sensitivity and urinary albumin in normoglycaemic Wanigelas and Nauruans, and in diabetic Nauruans, were no longer significant after adjusting for fasting glucose and body mass index. While microalbuminuria in Nauruans and Wanigelas was associated with cardiovascular risk factors irrespective of glucose tolerance, it seems unlikely on the basis of these results that the relationship is mediated through a common association with insulin resistance.     

老年2型糖尿病患者尿白蛋白排泄率与胰岛素抵抗的相关性研究

目的探讨老年2型糖尿病患者不同尿白蛋白分期与胰岛素抵抗的关系,为糖尿病肾病的预防与控制提供有益的参考。方法将152例老年2型糖尿病患者根据24小时尿微量白蛋白,分为正常白蛋白尿、微量白蛋白尿和大量白蛋白尿3组,分别测定体质指数、血压、空腹血糖、空腹胰岛素、糖化血红蛋白、血脂、血尿酸、24小时尿白蛋白定量等,并计算胰岛素抵抗指数(HOMA-IR)及估算的肾小球滤过率(eGFR)。结果与正常白蛋白尿组比较,微量白蛋白尿组患者的年龄、高血压合并率、HOMA-IR均明显升高,而eGFR明显下降(P<0.05);大量白蛋白尿组患者的高血压合并率、血压、空腹血糖、空腹胰岛素、总胆固醇、HOMA-IR亦均明显升高,而eGFR明显下降(P<0.05)。与微量白蛋白尿组比较,大量白蛋白尿组患者舒张压、空腹血糖、空腹胰岛素、总胆固醇均明显增高(P<0.05)。多因素逐步回归分析显示HOMA-IR是影响老年2型糖尿病患者尿白蛋白排泄率的独立危险因素。结论老年2型糖尿病患者尿白蛋白增多与胰岛素抵抗有关。     

Urinary albumin excretion in lean, overweight and obese glucose tolerant individuals: its relationship with dyslipidaemia, hyperinsulinaemia and blood pressure.

The presence of microalbuminuria has become an important tool for therapeutic intervention. In this study we investigated whether the dysmetabolic syndrome of obesity was associated with or could occur in the absence of microalbuminuria. The study was conducted in 71 clinically healthy, glucose tolerant Hispanics (age: 43 +/- 1.4 years, body mass index (BMI): 28.7 +/- 0.6 kg/m(2), systolic blood pressure (SBP): 117 +/- 2 mm Hg, diastolic blood pressure (DBP): 77 +/- 1.3 mm Hg, urinary albumin excretion: 10.2 +/- 0.6 mg/24 h). Subjects were classified as lean (BMI <25), overweight (BMI >25 <30) and obese (BMI >30 kg/m(2)). Greater BMI was associated with higher body weight, waist-to-hip ratio (WHR), BP, fasting insulin, triglyceride, post glucose load insulin and glucose, and lower high-density lipoprotein (HDL) cholesterol levels. However, no significant differences in the urinary albumin excretion (mg/24 h) were found between lean (9.0 +/- 0.9; median: 9.1), overweight (11.3 +/- 1.2; median: 10.5) and obese (11.1 +/- 1.2; median: 9.7) subjects. In addition, microalbuminuria (urinary albumin excretion >30 mg/24 h) was not found in any of the study subjects. For all subjects combined, as well as for each of the groups separately, the urinary albumin excretion was unrelated to the BMI, WHR, body weight, triglyceride, cholesterol (total, LDL or HDL), fasting or post-load glucose and insulin plasma concentrations. Neither in females nor in males, abdominal fat accumulation was associated with an increase in the urinary albumin excretion. However, in the obese groups, urinary albumin excretion was strongly related to the level of SBP (r(2): 0.67; P < 0.0001) and DBP (r(2): 0.55; P < 0.0001). In summary, obesity, hyperinsulinaemia and dyslipidaemia per se are not determinants of increased albumin excretion. However, in the obese subjects, the BP, particularly the SBP, was a strong determinant of the level of albumin in the urine. Microalbuminuria may occur later in the course of the dysmetabolic syndrome, due to worsening of hypertension and development of hyperglycaemia.     

Albuminuria in Australian Aboriginal people: prevalence and associations with components of the metabolic syndrome

Aims/hypothesis. To examine the prevalence and associations with the metabolic syndrome of albuminuria among Australian Aboriginal people.¶Methods. Early-morning urine specimens were collected as part of community-based risk factor surveys assessing the prevalence of diabetes and cardiovascular disease in eight remote communities, with a sample size of 1,075 people. Microalbuminuria was defined as urinary albumin : creatinine ratio 3.4–33.9 mg/mmol, macroalbuminuria as albumin : creatinine ratio equal to or greater than 34 mg/mmol.¶Results. There were high prevalences of microalbuminuria (men 22.2 %, women 26.9 %) and of macroalbuminuria (men 10.4 %, women 13.5 %). There were highly statistically significant linear associations of microalbuminuria and macroalbuminuria with increasing number of coexisting components of the metabolic syndrome (hypertension, glucose intolerance, dyslipidaemia, insulin resistance, abdominal obesity): among people with zero, one, two and three to five of these conditions, respectively, prevalence of microalbuminuria was 16 %, 20 %, 36 % and 32 % (p < 0.001); prevalence of macroalbuminuria was 2 %, 6 %, 12 % and 32 % (p < 0.001). There were independent associations of microalbuminuria with hypertension (odds ratio, 95 % confidence interval = 2.36, 1.63–3.42) and diabetes (2.10, 1.28–3.45): macroalbuminuria was independently associated with hypertension (6.39, 3.93–10.4), diabetes (3.49, 1.93–6.28) and abdominal obesity (4.56, 2.40–8.64) and had a weaker association with insulin resistance (1.99, 1.12–3.54). Dyslipidaemia and impaired glucose tolerance were neither independently associated with microalbuminuria or macroalbuminuria, nor was insulin resistance or abdominal obesity independently associated with microalbuminuria.¶Conclusion/interpretation. There was a strong clustering of albuminuria with components of the metabolic syndrome. Diabetes, hypertension and abdominal obesity are major contributors to high rates of albuminuria among Australian Aboriginal people. [Diabetologia (2000) 43: 1397–1403]     

Relationship between smoking habits and the features of the metabolic syndrome in a non-diabetic population

INTRODUCTION: Cigarette smoking is a risk factor for type 2 diabetes mellitus. The effect of smoking on the pathogenic factors for the development of diabetes is little explored. We evaluate the relation of smoking with the features of the insulin resistance syndrome, insulin resistance, and insulin secretion. METHODS: 2412 non-diabetic men, aged 35-65 years, were studied. Smoking habit was investigated by questionnaire. Anthropometry, blood pressure, forced expiratory volume (FEV1), fasting glucose, triglycerides, total and HDL cholesterol, plasma free fatty acids (FFA), insulin and fibrinogen were measured. HOMA-IR and HOMA beta cell were calculated. The metabolic syndrome was defined according to ATP III criteria. RESULTS: The metabolic syndrome was more prevalent in smokers than non-smokers (OR: 1.34; 95% CI 1.01-1.77). This was mainly due to a higher prevalence of dyslipidemia - high triglycerides (46.1% vs 29.9%, p<0.001), or low HDL cholesterol (42.2% vs 30.4%, p<0.001), in smokers. In smokers, other features of insulin resistance - i.e. obesity, hypertension, and hyperglycemia were significantly less frequent and FFA were lower (p<0.001). Plasma insulin and HOMA beta cell were similar in the two groups (8.3 vs 8.0microU/ml and 80.7% vs 82.9%, respectively), but HOMA-IR was significantly lower in smokers (p<0.001) due to the lower glucose values observed in these people. CONCLUSIONS: Among the features of the metabolic syndrome, only dyslipidemia is associated with chronic smoking. Smoking in not associated with enhanced insulin resistance, or with impaired insulin secretion. Alternative hypotheses should be explored for the increased risk of diabetes in smokers.     

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.     

Relationship between urinary bisphenol A levels and prediabetes among subjects free of diabetes

Bisphenol A (BPA) is a high volume production chemical used in the manufacture of polycarbonate plastics and epoxy resins. Recent experimental studies have suggested that BPA affects glucose metabolism through diverse mechanisms including insulin resistance, pancreatic β-cell dysfunction, adipogenesis, inflammation and oxidative stress. Prediabetes is a stage earlier in the hyperglycemia continuum associated with increased future risk of developing diabetes. Therefore, we examined the association between BPA exposure and prediabetes among subjects free of diabetes. We examined the association between urinary BPA levels and prediabetes in 3,516 subjects from the National Health and Nutritional Examination Survey 2003–2008. Urinary BPA levels were examined in tertiles. Prediabetes was defined as fasting glucose concentration 100–125 mg/dL or 2-h glucose concentration of 140–199 mg/dL or an A1C value of 5.7–6.4 %. Overall, we observed a positive association between higher levels of urinary BPA and prediabetes, independent of potential confounders including body mass index, alcohol intake, blood pressure and serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95 % confidence interval) of prediabetes associated with tertile 3 of BPA was 1.34 (1.03–1.73), p-trend = 0.02. In subgroup analysis, this association was stronger among women and obese subjects. Higher urinary BPA levels are found to be associated with prediabetes independent of traditional diabetes risk factors. Future prospective studies are needed to confirm or disprove this finding.     

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.     

Correlations of urinary albumin excretion and atherosclerosis in Japanese type 2 diabetic patients

Microalbuminuria and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 36 Japanese patients with type 2 diabetes and microalbuminuria (age: 56+/-9 years, mean+/-S.D.) and a control group of 44 age-matched patients with normoalbuminuria (56+/-7 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. BaPWV was used as an index of atherosclerosis. The BaPWV was higher in the microalbuminuria group than in the normoalbuminuria group (p<0.005). Fasting plasma glucose (p<0.05) and insulin concentrations (p<0.005), and the homeostasis model assessment (HOMA) index (p<0.0005), were higher in the microalbuminuria group than in the normoalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by BaPWV and HOMA index. Our results indicate that the presence of microalbuminuria in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV, HOMA index are independent predictors of urine albumin excretion.     

Microalbuminuria, cardiovascular autonomic dysfunction, and insulin resistance in patients with type 2 diabetes mellitus

Urinary albumin excretion/microalbuminuria and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria would correlate with cardiovascular autonomic dysfunction and insulin resistance in type 2 diabetic patients. The study group consisted of 15 Japanese patients with type 2 diabetes and microalbuminuria (age: 56 +/- 10 years, mean +/- SD). The control group consisted of 19 age-matched patients with normalbuminuria (56 +/- 7 years). Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma norepinephrine concentration, and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy. BRS was lower in the microalbuminuria group than in the normalbuminuria group (P < .05). Early and delayed 123I-MIBG myocardial uptake values were lower (P < .05 and P < .005, respectively) and the percent washout rate of 123I-MIBG was higher (P < .0005) in the microalbuminuria group than in the normalbuminuria group. Fasting plasma glucose (P < .05) and insulin concentrations (P < .05), and the homeostasis model assessment (HOMA) index (P < .01) were higher in the microalbuminuria group than in the normalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by the myocardial uptake of 123I-MIBG at delayed phase, fasting plasma insulin concentration, and the HOMA index. Our results indicate that the presence of microalbuminuria in our Japanese patients with type 2 diabetes is characterized by depressed cardiovascular autonomic function and insulin resistance, and that the myocardial uptake of 123I-MIBG at delayed phase, fasting plasma insulin, and HOMA index are independent predictors of urinary albumin excretion.     

Risk variables of insulin resistance syndrome in African-American and Caucasian young adults with microalbuminuria: the Bogalusa heart study

Microalbuminuria is a strong predictor of cardiovascular disease. Previous studies are inconsistent regarding the relationship between microalbuminuria and insulin resistance syndrome. Therefore, we examined this relationship in 1031 young adults (61% Caucasian, 39% African-American) aged 19 to 32 years. Individuals with either urinary albumin to creatinine ratio at or above the 90th percentile (age, race, and gender specific) or urinary albumin level at or above 30 mg/L were considered as having slightly elevated albumin excretion (microalbuminuria). The multiple risk variables of insulin resistant syndrome measured include body mass index, waist circumference, blood pressure (BP), triglycerides, high-density lipoprotein (HDL) cholesterol, glucose, insulin, insulin resistance index (calculated from a homeostasis model assessment equation), and uric acid. After controlling for age and gender, African-Americans with microalbuminuria by either measure had higher mean systolic (P < .001) and diastolic (P < .05) BP, prevalence of hypertension (P < .05), and, contrary to expectations, HDL cholesterol (P < .05) than those without this condition. On the other hand, Caucasians showed no such associations. In African-Americans, the above differences in BP levels persisted when hypertensive subjects were excluded. None of the other risk variables displayed any relation to microalbuminuria in both races. These results suggest that microalbuminuria is not necessarily an intrinsic component of the insulin resistance syndrome, at least in the young adult age. Furthermore, the observed association between hypertension and microalbuminuria among young African-Americans may reflect early evidence of renal dysfunction due to the burden of elevated BP in this group.     

Hyperinsulinaemia is associated with increased long-term mortality following acute myocardial infarction in non-diabetic patients.

AIMS: To study the impact of disturbances in glucose metabolism on total mortality in non-diabetic patients with acute myocardial infarction. METHODS AND RESULTS: Four hundred and ninety four patients with a verified myocardial infarction and no history of diabetes were studied. The study population comprised a subgroup of patients screened for participation in the Trandolapril Cardiac Evaluation (TRACE) study. At baseline, fasting insulin, fasting glucose, glycosylated haemoglobin (HbA1c), and urinary albumin excretion were measured. Survival status was determined after 6-8 years. Patients with hyperinsulinaemia were more obese and more frequently suffered from hypertension, previous myocardial infarction and congestive heart failure. In a univariate regression analysis, values in the upper quartile of insulin, glucose, HbA1c, and urinary albumin were associated with an excess mortality risk (RR=1.8 (1.2-2.7), p=0.002; RR=1.6 (1.2-2.1), p=0.001; RR= 1.9 (1.3-2.9), p=0.001; RR=1.6 (1.2-2.1), p=0.02 respectively). However, only a high insulin level remained significant in a multivariable analysis (RR=1.54 (1.03-2.31), p=0.04) including baseline variables, left ventricular systolic function and in-hospital complications. CONCLUSIONS: High fasting plasma insulin is an independent risk factor of all-cause mortality in non-diabetic patients with acute myocardial infarction. This justifies future intervention studies aiming at reducing insulin resistance and using fasting insulin as the target variable.     

The metabolic syndrome and changing relationship between blood pressure and insulin with age, as observed in Aboriginal and Torres Strait Islander peoples.

AIMS: To determine the prevalence of the metabolic syndrome (MS) among Aboriginal and Torres Strait Islander peoples. A further objective was to investigate the relationships between fasting insulin and blood pressure (BP) within these groups with increasing age. METHODS: A cross-sectional population-based study included 369 Torres Strait Islanders (residing in Torres Strait and Far North Queensland), and 675 Aborigines from central Australia. Data necessary for classification of MS was collected, including fasting and 2-h glucose and insulin, urinary albumin and creatinine, anthropometric measurements, BP, serum lipids. RESULTS: The ATPIII criteria classified 43% of Torres Strait Islanders and 44% of Aborigines with MS, whereas 32 and 28%, respectively, had the MS according to WHO criteria. Agreement between the two criteria was only modest (kappa coefficient from 0.28 to 0.57). Factor analyses indicated no cluster including both insulin and BP in either population. Significant correlations (P < 0.05) [adjusted for gender, body mass index (BMI) and waist circumference] were observed between BP and fasting insulin: a positive correlation for Torres Strait Islanders aged 15-29 years, and an inverse correlation for Aborigines aged 40 years and older. CONCLUSION: Torres Strait Islanders and Aborigines had very high prevalences of the MS. Specific population characteristics (high prevalences of central obesity, dyslipidaemia, renal disease) may make the WHO definition preferable to the ATPIII definition in these population groups. The poor agreement between criteria suggests a more precise definition of the metabolic syndrome that is applicable across populations is required. This study showed an inverse relationship with age for the correlation of BP and fasting insulin.     

Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome

Summary In a population-based survey of 2,930 subjects, prevalence rates for obesity, Type 2 (non-insulin-dependent) diabetes mellitus, impaired glucose tolerance, hypertension, hypertriglyceridaemia, and hypercholesterolaemia were 54.3, 9.3, 11.1, 9.8, 10.3 and 9.2%, respectively. The prevalence, however, of each of these conditions in its isolated form (free of the other five) was 29.0% for obesity, 1.3% for Type 2 diabetes, 1.8% for impaired glucose tolerance, 1.5% for hypertension, 1.0% for hypertriglyceridaemia, and 1.7% for hypercholesterolaemia. Two-by-two associations were even rarer. The large differences in prevalence between isolated and mixed forms indicate a major overlap among the six disorders in multiple combinations. In the isolated form, each condition was characterized by hyperinsulinaemia (both fasting and 2 h after oral glucose), suggesting the presence of insulin resistance. In addition, in any isolated condition most of the variables categorising other members of the sextet were still significantly altered in comparison with 1,049 normal subjects. In the whole of the subjects who presented with one or another disorder (1,881 of 2,930 or 64%), marked fasting and post-glucose hyperinsulinaemia was associated with higher body mass index, waist:hip ratio, fasting and post-glucose glycaemia, systolic and diastolic blood pressure, serum triglycerides and total cholesterol levels, and with lower HDL-cholesterol concentrations (all p <0.001). We conclude that (1) insulin sensitivity, glucose tolerance, blood pressure, body fat mass and distribution, and serum lipids are a network of mutually interrelated functions; and (2) an insulin resistance syndrome underlies each and all of the six disorders carrying an increased risk of coronary artery disease.     

Prediabetes in rural and urban children in 3 states in Mexico

The authors studied the frequency, distribution, and factors associated with prediabetes (fasting glucose, 100-125 mg/dL) in rural and urban children from San Luis Potosí, León, and Querétaro in central Mexico. Family history, somatometry, and levels of fasting insulin, glucose, and lipids were collected in 1238 children 6 to 13 years of age. The authors found no cases of type 2 diabetes and a 5.7% frequency of prediabetes. The group with prediabetes had higher homeostasis model assessment of insulin resistance scores and total cholesterol and high-density lipoprotein cholesterol levels. Prediabetes was more frequent in León, with similar distribution in rural and urban children. The frequency of insulin resistance was 24.1%, with higher figures in urban groups and in San Luis Potosí. In multivariate analysis, prediabetes was associated with insulin resistance and residence in León. The authors concluded that in central Mexico the frequency of prediabetes is significant, and it is associated with insulin resistance and a geographic location, but not with obesity or urban vs rural dwelling.     

Albumin Excretion Rate in Normal Adolescents: Relation to Insulin Resistance and Cardiovascular Risk Factors and Comparisons to Type 1 Diabetes Mellitus Patients

Background and objectives: Although albumin excretion rates have been related to cardiovascular morbidity and mortality in both diabetic and nondiabetic adults, little is known about the relation between albuminuria and either cardiovascular risk factors or the insulin resistance syndrome in adolescents. A normal range for albumin excretion in adolescents was established, correlations between albumin excretion and cardiovascular risk factors were evaluated, and albumin excretion in normal adolescents was compared with that in type 1 diabetes mellitus adolescents.Design, setting, participants, & measurements: Albumin excretion rate was measured in 368 normal and 175 diabetic adolescents. Multiple regression analysis was used to predict the relation of age, sex, Tanner stage, body mass index, and systolic blood pressure to albumin excretion in both cohorts. In addition, correlations between albumin excretion and age, blood pressure, body mass index, lipids, and measurements of insulin resistance were performed in the normal adolescents.Results: Mean albumin excretion was significantly lower in normal adolescents (4.0 μg/min) than in type 1 diabetic adolescents (5.0 μg/min). Albumin excretion increased with age in diabetics. Albumin excretion did not significantly correlate with any measure of cardiovascular risk or insulin resistance but did significantly correlate with fasting insulin.Conclusions: Albumin excretion rate is not related to insulin resistance or traditional cardiovascular risk factors in adolescence but is related to fasting insulin. Diabetic adolescents have increased albumin excretion compared with normal adolescents.Microalbuminuria (MA) is a significant predictor of both future kidney disease (1–3) and mortality (4) in patients with diabetes, and elevated levels of urinary albumin excretion have been shown to predict cardiovascular disease and all-cause mortality in adult nondiabetic hypertensive patients (5) and in the general adult population (6–8). However, the role of elevated albumin excretion rate (AER) as an early marker of cardiovascular risk in children has not been as well studied. Recent studies have found that 10% of obese children have elevated albumin/creatinine ratios (ACR) (9), obese children with elevated ACR have impaired glucose tolerance compared with obese children without elevated ACR (9), and 37% of obese children with the metabolic syndrome have elevated ACR, compared with 20% of obese children without the metabolic syndrome (10). A Hungarian study has shown that obese children have significantly higher ACR in association with fasting hyperinsulinemia, impaired glucose tolerance, and hypercholesterolemia than nonobese children (11).Studying the factors associated with cardiovascular risk is becoming increasingly relevant in children. The relation among childhood obesity, lipids, blood pressure (BP), and fasting insulin (12) and their tracking into adulthood (13) are well known. Recent epidemiologic studies in children have shown a high prevalence of the metabolic syndrome in childhood (14), and the presence of target organ vascular disease in the form of arterial plaques and fatty streaks (15) and increased carotid intima media thickness (16) has been established in children and young adults. Thus, it seems reasonable to suggest that early changes in AER might be detectable in children in association with obesity or other cardiovascular risk factors known to be related to development of adult disease.The present study was conducted in a cohort of healthy 11- to 17-yr-old children participating in a longitudinal study of obesity and insulin resistance and compares them to a cohort of adolescents of the same age with type 1 diabetes mellitus (T1DM). In addition to determining the relation of AER to cardiovascular risk factors in the normal cohort of children, this report presents normal reference data for AER in a North American population.     

Microalbuminuria in insulin-dependent diabetes: Prevalence and practical consequences

Urinary albumin excretion in a representative sample of 679 patients with Type I (insulin-dependent) diabetes, 18 to 50 years of age, was investigated. Patients on antihypertensive therapy were excluded. Urinary albumin excretion was examined in one 24 hour urine sample using an ELISA technique. Twenty-three per cent of the patients had microalbuminuria, i.e., 30–300 mg albumin/24 h. The prevalence of microalbuminuria was independent of sex, age, insulin dose and diabetes duration. In the majority of those cases in which microalbuminuria was found during the first 10 years of diabetes, the concentrations were in the lower range, i.e., 30–50 mg/24 h. The prevalence of incipient nephropathy (urinary albumin excretion in a single urine sample of 51–300 mg/24 h) increased with diabetes duration. In patients with inciplent nephropathy hemoglobin A_1c tended to be, and blood pressure was, elevated compared with age, sex, and duration matched patients with normal urinary albumin excretion rates (p=0.08 and p<0.001, respectively). Urinary albumin excretion and blood pressure were significantly correlated in the total group (n=401, r=0.2, p<0.001). On the basis of these findings practical guidelines for the handling of patients with microalbuminuria are proposed.