Relationship of left ventricular mass to insulin sensitivity and body mass index in healthy individuals

OBJECTIVE: The objective of this study was to investigate the contribution of insulin resistance, hyperinsulinaemia and obesity, independently of other major factors, to changes in left ventricular mass a cardiovascular risk indicator, in a healthy population without co-morbid states such as diabetes or hypertension. METHODS AND RESULTS: This cross-sectional relational study was perfomed in 153 healthy subjects, comprising 76 men and 77 women with ages ranging from 23 to 67 years. All of them were normotensive and had a normal oral glucose tolerance test, none had cardiovascular disease and none were taking any medication. Weight, height and waist circumference were measured and BMI was calculated. A blood sample was drawn in the fasting state: plasma glucose, insulin, serum total and high density lipoprotein (HDL), low density lipoprotein cholesterol and triglycerides were measured. Insulin resistance was determined by the 'Homeostasis Assessment Model' (HOMA-IR). Subjects were studied by echocardiography. The left ventricular mass was calculated by using the anatomically validated formula of Devereux et al. RESULTS: Left ventricular mass significantly and positively correlated with BMI, age, systolic and diastolic blood pressure and fasting blood glucose. The correlation of left ventricular mass with fasting blood glucose was not maintained after controlling for BMI. BMI, fasting blood glucose, HOMA-IR, systolic and diastolic blood pressure showed significant differences with higher values for people with left ventricular hypertrophy. The logistic regression analysis showed a strong association between left ventricular hypertrophy and BMI (p < 0.05). CONCLUSION: Insulin resistance and fasting insulin is not associated with left ventricular hypertrophy in healthy people, independent of obesity. Obesity appears to be an independent risk factor for left ventricular hypertrophy.     

Associations between plasma insulin and high blood pressure]

We studied the relationship between plasma insulin level and hypertension in 510 cases with normal glucose tolerance and impaired glucose tolerance. In nonobese group (BMI < 25kg/m2), plasma insulin was higher in those with hypertension than those with normal blood pressure (P < 0.0001). There was no correlation between diastole blood pressure and plasma insulin; multiple regression analysis showed that fasting plasma insulin was significantly associated with systolic blood pressure after controlling age, BMI and plasma glucose level (beta = 0.27, P = 0.0078). The result suggested that age, BMI and plasma insulin level were independent risk factors of hypertension. In obese group (BMI > 25kg/m2), blood pressure was significantly associated with age and BMI, there was no association between blood pressure and plasma insulin level.     

Are risk factors for conversion to NIDDM similar in high and low risk populations?

Summary Mexican Americans have an increased risk of non-insulin-dependent diabetes mellitus (NIDDM) relative to non-Hispanic whites which is only partially explained by their excess overall obesity and unfavourable body fat distribution. Non-diabetic Mexican Americans have hyperinsulinaemia and insulin resistance relative to non-Hispanic whites. We therefore hypothesized that the insulin resistance might be a more important predictor of NIDDM in high-risk populations characterized by obesity and insulin resistance, while compromised insulin secretion might be a more important risk factor for NIDDM in low-risk populations. We assessed the ability of ethnicity (Mexican American vs non-Hispanic white), age, overall adiposity (body mass index [BMI]), unfavourable body fat distribution (as assessed by waist-to-hip ratio [WHR]), glucose tolerance (impaired glucose tolerance vs normal glucose tolerance), fasting insulin and compromised insulin secretion (as assessed by increment in insulin to the increment in glucose over the first 30 min of an oral glucose tolerance test (ΔI₃₀/ΔG₃₀)) to predict future NIDDM. In the 8-year follow-up of the San Antonio Heart Study, NIDDM developed in 11.7 % (107/914) of Mexican Americans and in 5.0 % (18/362) of non-Hispanic whites (p < 0.001). Multivariate predictors of NIDDM by multiple logistic regression analysis included increased age, BMI, WHR, fasting insulin and impaired glucose tolerance and decreased insulin secretion. The strongest independent predictors of NIDDM were high fasting insulin and decreased insulin secretion. These risk factors predicted NIDDM equally well in high and low-risk populations. [Diabetologia (1997) 40: 62–66] Received: 16 July 1995 and in revised form: 17 September 1996     

Impaired Glucose Tolerance at Five-year Follow-up of Young Men with Borderline Hypertension

Wall U, Bergbrant A, Jern S. Impaired glucose tolerance at five-year, follow-up of young men with borderline. hypertension. Blood Pressure 1996; 5: 139-147.

Background: Recent studies suggest that patients with essential hypertension have impaired glucose tolerance and are hyperinsulinemic compared with normotensive subjects. The aims of the study were (I) to follow blood pressures of 56 young men with borderline hypertension for 5 years, (2) to investigate glucose tolerance in these subjects, and (3) to determine the relation of insulin/glucose metabolism to structural vascular changes and hemodynamic patterns in borderline hypertension. Methods: Thirty-nine young (age 22-34 years) male subjects with borderline hypertension (SBP 140-160 and/or DBP 85-95 mmHg initially) and 17 normotensive control subjects (SBP 110-130 and DBP 60-80mmHg) participated in the study. Blood pressure was measured, a standard oral glucose tolerance test (OGTT) was performed, and glucose, insulin and C-peptide were determined before and 30, 60, 90 and 120 minutes after a standard 75-g glucose load. Post-ischemic forearm vasodilatory responses were examined by plethysmography. Results: At follow-up, the borderline hypertensives had maintained significantly higher blood pressures than control subjects. Borderline hypertensives also had significantly impaired glucose tolerance compared to control subjects. The insulin response had a somewhat more sluggish descent, but did not differ significantly from the response of normotensives. The C-peptide response pattern resembled that of insulin, but C-peptide was significantly elevated after 120 min. On the whole group level, there were only weak relations of insulin to blood pressure. By contrast, fasting insulin and post-load insulin levels were strongly correlated with body mass index, the waist-hip circumference ratio, triglyceride, and both total and LDL cholesterol. Across the whole group, there were significant correlations between forearm minimal vascular resistance and fasting insulin (r = + 0.37 p = 0.007) and insulin area-under-the-curve (r = + 0.28 p = 0.044). However, R_min was even more strongly correlated with body mass index, suggesting that this relationship was related to degree of obesity. Conclusion: Borderline hypertension in young men is a persistent condition which is associated with impaired glucose tolerance without hyperinsulinemia. This finding suggests that impaired glucose tolerance might be a more primary phenomenon in early hypertension devoid of lipid metabolic aberrations.     

Metabolic and adipose risk factors for NIDDM and coronary disease in third- generation Japanese-American men and women with impaired glucose tolerance

Summary Since second-generation (Nisei) Japanese Americans are prone to develop the insulin resistance syndrome, younger third-generation (Sansei) Japanese Americans from a cross-sectional 10 % volunteer sample of Sansei men (n=115) and women (n=115) 34 years or older in King County, Washington with normal glucose tolerance or IGT were examined for metabolic and adipose risk factors associated with this syndrome. After an overnight 10-h fast, blood samples were taken for measurement of glucose, insulin, C-peptide, lipids, and lipoproteins, followed by a 3-h 75-g oral glucose tolerance test with blood samples taken for glucose, insulin, and C-peptide measurement. BMI (kg/m²), skinfolds, and body fat areas (by computed tomography) were measured. IGT was diagnosed in 19 % of the men and 31 % of the women. Men with IGT had more adiposity, both overall and in thoracic and visceral sites, had higher fasting plasma insulin and C-peptide, and tended to have higher fasting triglyceride and lower HDL cholesterol than men with normal glucose tolerance. Women with IGT had more thoracic subcutaneous fat and intra-abdominal fat and lower fasting HDL cholesterol than women with normal glucose tolerance, and tended to have higher fasting triglyceride and LDL cholesterol. Women with IGT also had higher fasting plasma insulin than women with normal glucose tolerance but tended to be less hyperinsulinaemic than men. Differences in fasting insulin, C-peptide, and lipids were best predicted by intra-abdominal fat. Thus metabolic (higher fasting insulin and a tendency to higher triglyceride and lower HDL cholesterol) and adipose (visceral adiposity) risk factors associated with the insulin resistance syndrome are identifiable among Sansei men and women with IGT, who may therefore be at increased risk of future development of NIDDM and CHD. [Diabetologia (1994) 37: 524–532] Received: 9 July 1993 and in revised form: 14 December 1993     

Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis study

The association between insulin resistance and insulinemia and hypertension is controversial. We examined the relation between insulin resistance and hypertension in 564 non-Hispanic whites (NHW), 505 Hispanics (H), and 413 African Americans (AA) who participated in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity was measured with a frequently sampled intravenous glucose tolerance test with minimal model analysis. The prevalence of hypertension was 32.5%, 49.4%, and 32.3% in NHW, AA, and H, respectively (P<0.001). When subjects without diabetes in all ethnic groups were combined, age, male sex, race (AA), body mass index (BMI), and insulin resistance, but not fasting insulin, were significantly associated with hypertension. When each ethnic group was analyzed separately, insulin resistance was significantly associated with hypertension in NHW and H, but not AA. After excluding subjects taking antihypertensive medications, male sex, BMI, fasting glucose, and insulin resistance, but not fasting insulin, were significant determinants of blood pressure. When the 3 ethnic groups were analyzed separately, insulin resistance was significantly associated with blood pressure in H, but not NHW, or AA. Neither insulin resistance nor fasting insulin was significantly associated with hypertension or blood pressure in subjects with diabetes of the 3 ethnic groups after adjusting for age, sex, BMI, and waist. In conclusion, insulin resistance, but not insulinemia, was related to hypertension and blood pressure in subjects without diabetes, but ethnic differences in these relations appear to exist. Neither insulin resistance nor insulinemia was related to hypertension or blood pressure in patients with type 2 diabetes in the 3 ethnic groups.     

The role of insulin in clustering of serum lipids and blood pressure in children and adolescents

Summary In adults hyperinsulinaemia is associated with an atherogenic risk profile including obesity, low levels of HDL-cholesterol, high levels of triglycerides and elevated blood pressure. To examine these associations in the young we studied the cross-sectional relationships of insulin with obesity indices (body mass index, subscapular skinfold thickness), serum lipids and blood pressure in 1,865 children, adolescents and young adults aged 6–24 years. We also used longitudinal data to study the value of a single insulin measurement to predict high risk factor levels and clustering of multiple risk factors after a 6-year follow-up. In cross-sectional analyses the levels of triglycerides, HDL-cholesterol, systolic blood pressure and obesity indices were usually significantly different across the quartiles of fasting insulin in both sexes among children, adolescents and young adults. In general, no associations were seen with total cholesterol or LDL-cholesterol. In prospective analysis elevated baseline insulin was related to the incidence of hypertriglyceridaemia (95th percentile) at the follow-up. This relationship persisted even after adjustments for baseline obesity or 6-year change in obesity status. Moreover, baseline insulin concentration was higher in subjects who subsequently showed clustering of high triglycerides, low HDL-cholesterol and high systolic blood pressure levels at the follow-up. We conclude that high fasting insulin levels measured in children and adolescents predict the development of hypertriglyceridaemia years later. In addition, high insulin levels seem to precede the development of a potentially atherogenic risk factor profile including low HDL-cholesterol, high triglycerides and high systolic blood pressure.Abbreviations SBP Systolic blood pressure - DBP diastolic blood pressure - BMI body mass index     

The association of the insulin resistance syndrome with impaired glucose tolerance and NIDDM in the Japanese general population: the Hisayama study

Summary To elucidate the risk factors for initiating glucose intolerance, the relevant factors were explored in a cross-sectional survey conducted in a sample population aged 40–79 years old selected from a Japanese community, Hisayama, Japan in 1988. A 75-g oral glucose tolerance test was used to classify 1,073 men (72.5% of the entire population in the same age range) and 1,407 women (80.5%) into normal, impaired glucose tolerance and diabetes mellitus groups. In all age and sex groups with normal glucose tolerance, the sum of fasting and 2-h post-load insulin values varied widely and demonstrated significant positive correlations with triglycerides, body mass index, waist-hip ratio, systolic and diastolic blood pressure, while it negatively correlated to HDL cholesterol (p<0.05). Insulin resistance was presumed to develop in normal glucose tolerance subjects with hyperinsulinaemia. The sum of the insulin concentrations, triglycerides, body mass index, waist-hip ratio and blood pressure levels was significantly associated with impaired glucose tolerance in all age and sex groups after adjustment for age (p<0.05) and was also related to diabetes in either all or some age and sex groups, respectively (p<0.05). It was shown that glucose intolerance in the general population was associated with the factors related to insulin resistance. These cross-sectional data, therefore, support the hypothesis that insulin resistance is the primary defect in the development of glucose intolerance in the Japanese general population. However, a further prospective study is still needed in order to confirm this hypothesis.Abbreviations OGTT Oral glucose tolerance test - NIDDM non-insulin-dependent diabetes mellitus     

Life style changes improve insulin resistance in hyperinsulinaemic subjects: a one-year intervention study of hypertensives and normotensives in Dalby.

OBJECTIVE: Insulin resistance and hyperinsulinaemia are, in some prospective studies, linked to an increased cardiovascular risk, at least in men. We tested the hypothesis that hyperinsulinaemia may be reduced by non-pharmacological methods independently of other cardiovascular risk factors. DESIGN: In a non-pharmacological intervention study for 1 year three groups of subjects (hypertensives as well as normotensives) were selected after stratification for insulin level at baseline. Half of the hyperinsulinaemic subjects were randomly assigned to active intervention with physical exercise and dietary regulation (HI-A group), the other half were followed passively during the study period (HI-P group). Normo-insulinaemics and hypo(low)-insulinaemics also underwent active intervention (NI-A and LI-A groups, respectively). SETTING: Primary health care in Sweden. RESULTS: During the 1-year follow-up subjects in the HI-A group reduced their weight, waist:hip ratio and systolic and diastolic blood pressure, as well as their low:high-density lipoprotein (LDL:HDL)-cholesterol ratio. Glucose levels before and during an oral glucose tolerance test did not change. However, plasma insulin and plasma-C-peptide decreased both in the fasting state and after 1 and 2 h of oral glucose tolerance testing. This decrease was independent of the previously mentioned reduction in weight, waist:hip ratio, blood pressure and LDL:HDL-cholesterol ratio. No reduction in insulin levels was seen in the HI-P, NI-A or LI-A groups, but in the HI-P group there was a slight decrease in fasting plasma-C-peptide levels. In the HI-A group dietary improvements were observed during the study period, with a reduction in energy intake, fat consumption and cholesterol intake. Fibre intake was increased. No major changes were seen in the HI-P group. CONCLUSIONS: We conclude that in hypertensive and normotensive subjects with hyperinsulinaemia insulin levels can be reduced by active non-pharmacological treatment for 1 year without altering glucose tolerance. This shows that insulin resistance may be lowered by non-pharmacological treatment, which may be of considerable importance, and not only for hypertensives.     

The impact of 3-year changes in lifestyle habits on metabolic syndrome parameters: the D.E.S.I.R study.

BACKGROUND: The effect of lifestyle changes in cohorts of free-living populations has been surprisingly little evaluated. DESIGN: A longitudinal study. METHODS: In the French Data from an Epidemiological Study on the Insulin Resistance (D.E.S.I.R) study of 1958 men and 2028 women, aged 30-65 years, the impact of 3-year changes in lifestyle habits (sporting activity, physical activity at home and at work, alcohol drinking, smoking) on metabolic syndrome parameters [insulin, glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic blood pressure, waist circumference] and on body mass index (BMI) were investigated. RESULTS: In men, 3-year increases in sporting activity were associated with a lowering of insulin, glucose, systolic blood pressure and waist circumference (all P < 0.05). For women, the only effect was on lowering waist circumference (P < 0.03). Increases in physical activity at home were beneficially associated with HDL-cholesterol, triglycerides, waist circumference and BMI changes (all P < 0.05) in men, but had no apparent effect in women. Decreases in alcohol intake only had an effect in men, with decreases in HDL-cholesterol and systolic blood pressure (P < 0.05), whereas decreasing cigarette smoking in men was associated with significant increases in insulin, glucose, triglycerides, waist and BMI (P < 0.001), and in women HDL-cholesterol, waist circumference and BMI increased (P < 0.02). These results were mainly caused by those who had stopped smoking. CONCLUSIONS: Increases in physical activity over the 3-year period were associated with beneficial effects on syndrome parameters, particularly in men. Smoking cessation and alcohol moderation produced mixed effects on these parameters.     

A prospective study of glycemia, body size, insulin resistance and the risk of hypertension in Mauritius

OBJECTIVE: To estimate the associations between new-onset hypertension and glycemia, insulin resistance, and overall and regional adiposity in a prospective study conducted in Mauritius. RESEARCH DESIGN AND METHODS: Three thousand five hundred and eighty-one adults without hypertension, pregnancy, or known diabetes at baseline (1987) were followed for incident hypertension in 1992 and 1998, (systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg or antihypertensive medication treatment). Other measurements included fasting plasma glucose and 2-h plasma glucose after a 75-g oral glucose load, fasting insulin, BMI, waist circumference, smoking, alcohol use, exercise, and demographic information. Insulin sensitivity was estimated by the computerized homeostasis model assessment (HOMA2) program. RESULTS: In multivariable logistic models that included age, gender, ethnicity, alcohol use, exercise, education, systolic blood pressure, diastolic blood pressure, homeostasis model assessment, fasting plasma glucose, 2-h plasma glucose, BMI, and waist circumference, the independent predictors of incident hypertension by time of follow-up were (odds ratio for a 1 SD increase; 95% confidence interval): 1992 - age (1.73; 1.47-2.03), Creole ethnicity (1.42; 1.04-1.94), 2-h plasma glucose (1.26; 1.04-1.51); 1998 - age (1.60; 1.40-1.83) and BMI (1.33; 1.05-1.69). Also, systolic blood pressure and diastolic blood pressure significantly predicted hypertension at both time points. CONCLUSION: Risk factor patterns depended on duration of follow-up. Over 5 years, hypertension was related to 2-h plasma glucose but not to measures of body size or homeostasis model assessment, while over 11 years, incident hypertension was related to BMI but not waist circumference, 2-h plasma glucose, or homeostasis model assessment. These findings support a more important role for 2-h plasma glucose and overall adiposity than waist circumference, fasting plasma glucose, or insulin resistance in the development of hypertension in Mauritius.     

Increased waist/hip ratio, metabolic disturbances, and family history of hypertension.

To test whether nonhypertensive subjects with a two-generation positive family history of hypertension (PFH) are characterized by disturbed glucose metabolism, 16 men (38 +/- 6 years old) with PFH and 25 subjects matched for age and with negative family histories of hypertension (NFH) were recruited. Blood pressure; serum lipids; erythrocyte transmembrane sodium transport; and the glucose, plasma insulin, and C-peptide responses to an oral glucose tolerance test were investigated. Subjects with PFH had higher blood pressure, body weight, body mass index (BMI), waist/hip ratio (WHR), and abdominal sagittal diameter than subjects with NFH. Baseline blood glucose, plasma insulin, serum lipids, and transmembrane sodium transport did not differ between the two groups. Blood glucose levels at 90 and 120 minutes after oral glucose were significantly higher in subjects with PFH than in controls. Blood glucose adjusted for BMI and WHR at 90 minutes was significantly related to a PFH. Plasma insulin level at 90 minutes during the glucose load was significantly higher in subjects with PFH. In multivariate analysis, WHR was significantly related to baseline blood pressure, insulin, and cholesterol, whereas BMI was significantly associated with the insulin response to the oral glucose tolerance test. Transmembrane sodium transport was significantly related to blood pressure only. In conclusion, subjects with PFH are characterized by increased body weight and BMI, increased visceral fat accumulation, and an altered blood glucose response to an oral glucose load. It was also shown that WHR was related to blood pressure and that BMI was more related to cholesterol and response to glucose loading than a PFH was.     

Risk factors for the development of hypertension: a 10-year longitudinal study in middle-aged men.

A group of middle-aged men (n = 2322) were examined at a health screening which included an intravenous glucose tolerance test (IVGTT) with insulin determinations, and were then re-examined approximately 10 years later. At the first survey, 19.6% of the participants had hypertension, defined as diastolic blood pressure greater than or equal to 95 mmHg or were receiving drug treatment for hypertension. At follow-up survey, the corresponding figure was 34.7%. Baseline blood pressures were the strongest predictors of future development of hypertension. In the absence of baseline blood pressures, fasting and late insulin levels at IVGTT, difference in body mass index between the surveys and heredity for hypertension were significant risk factors for hypertension. When a difference in diastolic blood pressure was used as an independent variable, the only significant risk factor was the difference in body mass index. Thus, insulin resistance (as reflected by fasting, late insulin levels and body mass index) seems to be related to the development of hypertension.     

Impaired glucose tolerance and fasting hyperglycaemia have different characteristics.

AIMS: Use of the oral glucose tolerance test (OGTT) to define glucose intolerance in the general population may bias towards selection of those with insulin resistance. Beta cell function and insulin resistance markers were analysed in four groups: controls (n = 101); fasting hyperglycaemia (FH, n 45); impaired glucose tolerance; (IGT, n = 16) and those with features of both FH and IGT ('Both', n = 30). METHODS: Subjects underwent an OGTT. Plasma glucose, fasting lipid profiles, fasting, 30 and 120 min insulin were measured and beta cell function (% B) and insulin sensitivity (% S) assessed by homeostatic model assessment (HOMA) RESULTS: The FH group compared to controls had a significantly lower % B. The IGT group compared to controls had features of insulin resistance (higher body mass index (BMI), systolic blood pressure and 2 h insulin concentration). Subjects with 'both' IGT and FH had features of insulin resistance (higher BMI, systolic and diastolic blood pressure and triglyceride concentration) as well as beta cell dysfunction with a lower % B and 30 min insulin-glucose ratio compared to controls. There was a preponderance of males in this group. In all, 192 subjects' 30-min insulin concentration and incremental insulin response showed only a significantly negative correlation with fasting glucose concentration. In a linear regression analysis, a low 30-min insulin-glucose ratio was only a significant factor in the fasting glucose model. Thus, higher fasting glucose concentrations appear to be associated with beta cell dysfunction. However, HbA1 only showed a significant correlation with 120-min glucose, not fasting glucose concentration. CONCLUSIONS: In those with milder degrees of glucose intolerance, FH is associated with beta cell dysfunction and those with IGT and a relatively 'normal' fasting glucose have features of the insulin resistance syndrome.     

Insulin: in search of a syndrome.

The insulin resistance syndrome has been defined as the clustering of hypertension, dyslipidaemia and impaired glucose tolerance in subjects with high fasting plasma insulin concentrations. The latter are usually taken as a surrogate measure of insulin resistance of whole-body glucose disposal. Although hyperinsulinaemia and insulin resistance are reciprocally related to one another, the association is not very strong. In the data-pooling project of the European Group for the study of Insulin Resistance (EGIR), clamp-derived insulin sensitivity (as the M value) and fasting plasma insulin concentrations were available in 1308 non-diabetic subjects with a wide range of age and body mass index. In this cohort, hyperinsulinaemia (as the upper quartile of fasting plasma insulin distribution in the non-obese segment of the population) and insulin resistance (as the bottom quartile of M value in the same subgroup) were each present in approximately 40% of the whole population, but identified only partially overlapping (60%) subsets of individuals. When the subjects with insulin resistance but without hyperinsulinaemia (n = 198) were compared with the subjects with hyperinsulinaemia but without insulin resistance (n = 267), significant differences emerged in the respective clinical phenotypes. Thus, subjects with 'pure' insulin resistance had a more central fat distribution and presented evidence of excessive lipolysis and endogenous glucose production. In contrast, subjects with 'pure' hyperinsulinaemia had suppressed lipolysis, endogenous glucose production and insulin clearance, higher values of systolic blood pressure and lower values of serum HDL-cholesterol concentrations. The only abnormality common to both phenotypes was the presence of raised serum triglycerides concentrations. This analysis indicates that hyperinsulinaemia and insulin resistance identify partially different subgroups of individuals in a non-diabetic population, and suggests that hyperinsulinaemia and insulin resistance carry distinct pathogenic potential in terms of the components of the insulin resistance syndrome.     

A common intron 2 polymorphism of the glucocorticoid receptor gene is associated with insulin resistance in men

Objective  Clinical similarities between the metabolic syndrome and Cushing's syndrome have led to speculation of genetic association between them. The Bcl1 polymorphism in intron 2 of the glucocorticoid receptor (GR) gene has been associated with insulin resistance/hyperinsulinaemia. Our objective was to test the association of rs2918419, a T→C single nucleotide change in intron 2 downstream of the Bcl1 locus, with components of the metabolic syndrome and its interaction with the Bcl1 locus.
Design and methods  We genotyped a subsample of 325 White subjects (116 men) in the Newcastle Heart Project (NHP), a population-based study in north-east England. Gender-specific statistical analysis by stepwise backward multiple regression was performed to test the association of allele status with adiposity, glucose and insulin responses to oral glucose tolerance test (OGTT), fasting lipids and blood pressure.
Results  Minor allele frequency was 0·14 for rs2918419 and 0·39 for the Bcl1 polymorphism. rs2918419 was associated with higher fasting insulin concentration and insulin resistance in men but not in women. Contrary to earlier studies, the Bcl1 polymorphism on its own was not associated with insulin resistance/hyperinsulinaemia in either gender. Subjects carrying variant rs2918419 alleles also had variant alleles at the Bcl1 locus. In men, but not women, Bcl1 variant alleles on a background of rs2918419 wild-type alleles associated with lower fasting insulin compared to wild-type alleles at both loci or variant alleles at both loci.
Conclusions  We report that rs2918419 was linked with hyperinsulinaemia and insulin resistance in men. Carrying Bcl1 variant alleles without rs2918419 was not associated with hyperinsulinaemia/insulin resistance. Previous reports of the association of Bcl1 polymorphism with obesity-related characteristics may reflect linkage disequilibrium with rs2918419.     

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.     

Factors related to the development of diabetes during a 20-year follow-up. A prospective study in a homogeneous group of middle-aged men

BACKGROUND AND AIMS: To investigate factors associated with the development of type 2 diabetes mellitus (DM) during a 20-year follow-up in a homogeneous group of initially healthy middle-aged men with similar socioeconomic status. METHODS AND RESULTS: We studied 1802 executives and businessmen, born 1919-34, without type 2 DM at baseline and with coronary heart disease (CHD) risk factor measurements in 1974-75. Diagnosis of type 2 DM during the follow-up was based on entitlement to re-imbursement for type 2 DM medication during 1975-1995, retrieved from national registers, self-report of type 2 DM or fasting blood glucose (> or = 6.7 mmol/L) in 1985-1986 (72% of the initial cohort re-evaluated). During the follow-up (up to 1995) type 2 DM was diagnosed using the above criteria in 94 men (5.2%). At baseline, men who later developed type 2 DM smoked more (p = 0.01), and had significantly higher body mass index (BMI), systolic and diastolic blood pressure, pulse pressure, serum triglycerides, and fasting and one-hour blood glucose. In a subset of high-risk men, those who developed type 2 DM also showed signs of white-coat effect on blood pressure (p = 0.008). Already at baseline, the CHD risk score was 23% higher in future type 2 DM subjects (p = 0.008). Re-evaluation in 1985-1986 showed essentially similar results for risk factors, but in addition, LDL cholesterol without lipid lowering drugs was significantly lower (p = 0.0018) in type 2 DM subjects. During the follow-up, 23.4% of the men with type 2 DM developed CHD as compared to 13.4% of those without (p = 0.008). CONCLUSIONS: During a 20-year follow-up, several cardiovascular risk factors, including smoking, pulse pressure and the white-coat effect, predicted the development of type 2 DM in initially healthy middle-aged men. However, despite the higher incidence of CHD, development of type 2 DM was associated with lowered LDL cholesterol.     

高血压病合并脂肪肝发病的危险因素分析

目的探讨高血压病合并脂肪肝发病的危险因素。方法选择进行了肝脏B超检查的住院高血压病患者,根据超声影像的诊断结果分为高血压合并脂肪肝组(98例)和高血压未合并脂肪肝组(102例),分析体重指数(BMI)、收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)、胰岛素抵抗指数(HO-MA-IR)、糖耐量试验各时段的血糖水平、胰岛素释放试验的胰岛素水平与脂肪肝之间的关系。结果(1)Logistic回归分析的结果表明空腹血糖升高、肥胖、糖负荷后3小时胰岛素水平升高、高甘油三酯血症是高血压患者脂肪肝形成的独立危险因素;(2)高血压合并脂肪肝组的HOMA-IR、TG、空腹和糖负荷后2、3小时的血糖和胰岛素水平高于对照组(均P<0.05)。校正两组BMI后,上述差异仍然存在。结论(1)高血压病患者脂肪肝发病的独立危险因素是空腹血糖升高、肥胖、糖负荷后3小时胰岛素水平升高、高甘油三酯血症,随着这些危险因素的聚集,脂肪肝的检出率增加。(2)脂肪肝是高血压病患者胰岛素抵抗的“重要标志”,脂肪肝是代谢综合征的一种表现。     

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.