Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women.

BACKGROUND AND AIMS: Two Amerindian populations--Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. METHODS AND RESULTS: Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. CONCLUSIONS: The high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation.

Plasma markers of inflammation and incidence of hospitalisations for COPD: results from a population-based cohort study.

BACKGROUND: The relationship between plasma markers of inflammation and the incidence of chronic obstructive pulmonary disease (COPD) is still unclear. This population-based study explored whether raised levels of five inflammation-sensitive plasma proteins (ISPs) predicted hospital admissions for COPD during 25 years of follow-up. METHODS: Spirometric tests and measurements of five ISPs (fibrinogen, ceruloplasmin, alpha(1)-antitrypsin, haptoglobin, orosomucoid) were performed in 5247 apparently healthy men from the city of Malmö (mean age 46 years). The incidence of hospitalisations for COPD was studied in relation to the number of ISPs in the fourth quartile. RESULTS: During the follow-up period, 258 men were admitted to hospital with COPD, 211 of whom were smokers at baseline. The incidence of hospital admissions for COPD was significantly associated with the number of raised ISPs. Adjusted for risk factors, the hazards ratio (95% CI) was 1.00 (reference), 1.28 (0.9 to 1.9), 1.29 (0.8 to 2.0) and 2.30 (1.6 to 3.2), respectively, for men with 0, 1, 2 and >or=3 ISPs in the top quartile (p for trend <0.001). This relationship was consistent in men with high and low lung function at baseline. The relationship with the incidence of hospital admissions for COPD was largely the same for all individual ISPs. CONCLUSION: Raised plasma ISP levels are associated with an increased incidence of COPD requiring hospitalisation.

Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study.

Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This population-based longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hypertension. Incidence of hypertension and blood pressure increase over 15.7 (+/-2.2) years follow-up was studied in relation to C3 and C4 at baseline. Among men with initially normal blood pressure (<160/95 mm Hg), incidence of hypertension (>or=160/95 mm Hg or treatment) was 32, 42, 37 and 47%, respectively, for men with C3 in the first, second, third and fourth quartile (trend: P=0.001). This relationship remained significant after adjustment for confounding factors. Among men without blood pressure treatment, systolic BP increase (mean+standard error, adjusted for age, initial blood pressure and follow-up time) was 17.5+0.8, 19.6+0.9, 19.8+0.8 and 20.8+0.8 mm Hg, respectively, in the C3 quartiles (trend: P=0.004). C3 was not associated diastolic blood pressure at follow-up. Although C4 was associated with blood pressure at the baseline examination, there was no relationship between C4 and development of hypertension or future blood pressure increase. It is concluded that C3 in plasma is associated with future blood pressure increase and development of hypertension.

Fatality of acute coronary events in relation to hypertension and low-grade inflammation: a population-based cohort study.

Hypertension has been associated with increased case-fatality rates among individuals who subsequently suffer from acute coronary events. It is unknown whether inflammation modifies this relationship. This population-based study explored the effects of inflammation and hypertension on incidence of coronary event, and on the fatality of the future events. Blood pressure (BP) and five inflammation-sensitive plasma proteins (ISPs, fibrinogen, orosomucoid, alpha 1-antitrypsin, haptoglobin and ceruloplasmin) were determined in 6071 healthy men. During the mean follow-up of 19 years, 679 men had a first coronary event (non-fatal myocardial infarction or death from coronary heart disease). Of them, 197 (29%) were fatal cases (death during the first day). As expected, hypertension was associated with increased incidence of coronary events and increased proportion of fatal cases. At all levels of BP, high ISPs (> or =2 ISPs in top quartile) significantly added to the incidence of events. Men with high ISPs had the highest case-fatality rates. The difference in case-fatality rate between men with and without high ISPs was, however, significant only in men with normal BP (<130/85 mm Hg) (33 vs 19%, P < 0.05), and not in men with moderate or severe hypertension (> or =160/100 mm Hg) (40 vs 35%, P = 0.32). High ISPs add to the incidence of coronary events at all levels of BP. Hypertension and inflammation are both independently associated with increased case-fatality in subjects who later have an acute coronary event. The influence of ISPs on the case-fatality rate seems to be most important in men with normal BP.

Effects of cholesterol and inflammation-sensitive plasma proteins on incidence of myocardial infarction and stroke in men.

BACKGROUND: Although cholesterol is a major cardiovascular risk factor, its association with stroke remains controversial. This study explored whether the cholesterol-related incidence of stroke and myocardial infarction is modified by plasma markers of inflammation in a large, population-based cohort with a long follow-up. METHODS AND RESULTS: Plasma cholesterol and 5 inflammation-sensitive plasma proteins (ISP) (fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid) were determined in 6063 healthy men, 28 to 61 years of age. The incidence of stroke, cardiac events (fatal and nonfatal), and cardiovascular deaths was compared between groups defined by levels of cholesterol and ISP. Mean follow-up was 18.7 years. High ISP level was defined as 2 to 5 ISP in the top quartile. High cholesterol was associated with higher levels of ISP. Hypercholesterolemia (> or =6.5 mmol/L, 251 mg/dL) was associated with an increased incidence of ischemic stroke and cardiac events and with a reduced incidence of intracerebral hemorrhage. The ISP levels modified these associations. After risk factor adjustment, men with hypercholesterolemia and high ISP levels had a significantly higher risk of cardiovascular death (relative risk [RR]=2.4; CI, 1.8 to 3.3), cardiac events (RR=2.3; CI, 1.8 to 3.0), and ischemic stroke (RR=2.1; CI, 1.4 to 3.3) than men with normal cholesterol and low ISP levels. In the absence of high ISP levels, hypercholesterolemia was associated with a moderately higher risk of cardiovascular death (RR=1.4; CI, 1.0 to 2.0) and cardiac events (RR=1.5; CI, 1.2 to 1.9) but not significantly with ischemic stroke (RR=1.25; CI, 0.8 to 2.0). CONCLUSIONS: Hypercholesterolemia is associated with high plasma levels of ISP. These proteins increase the cholesterol-related incidence of cardiovascular diseases. In the absence of elevated ISP levels, no statistically confirmed association was found between hypercholesterolemia and ischemic stroke.

Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins.

BACKGROUND: The inverse relationship between pulmonary function and incidence of cardiovascular disease remains largely unexplained. This prospective study explored the hypothesis of a relationship with inflammation-sensitive plasma proteins. METHODS AND RESULTS: Forced vital capacity (FVC) and plasma levels of fibrinogen, alpha(1)-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 5064 healthy men aged 28 to 61 years. All-cause mortality, cardiovascular mortality, and incidence of myocardial infarction were monitored over a mean follow-up period of 18.4 years. Low FVC (fourth quartile) was associated with higher protein levels and with increased incidences of myocardial infarction and cardiovascular death. Adjustments for protein levels reduced the age-adjusted relative risks (RRs) for myocardial infarction (from 1.99, 95% CI 1.5 to 2.6, to 1.70, 95% CI 1.3 to 2.2) and cardiovascular death (from 2.71, 95% CI 1.9 to 3.9, to 2.28, 95% CI 1.6 to 3.3) among men with low FVC, corresponding to approximately 25% of the excess risk. The risk factor-adjusted RRs were reduced from 1.45 (95% CI 1.1 to 1.9) to 1.38 (95% CI 1.1 to 1.8) and from 1.96 (95% CI 1.4 to 2.8) to 1.85 (95% CI 1.3 to 2.7) for myocardial infarction and cardiovascular death, respectively, corresponding to approximately 10% to 15% of the excess risk. Among men with low FVC, the risk factor-adjusted RR for myocardial infarction was 2.5 (95% CI 1.7 to 3.6) for those with high protein levels (> or =2 proteins in top quartile) and 1.7 (95% CI 1.1 to 2.4) for those with low protein levels (< or =1 protein in top quartile; reference, top quartile of FVC and low protein levels). CONCLUSIONS: FVC is significantly and inversely associated with plasma levels of inflammation-sensitive plasma proteins. This relationship contributes to but cannot fully explain the increased cardiovascular risk among men with low FVC.

Increased skeletal muscle capillary density precedes diabetes development in men with impaired glucose tolerance. A 15-year follow-up.

Gastrocnemius muscle morphology, metabolic potential, and capillarization were analyzed in 48-year-old men with regard to subsequent development of non-insulin-dependent diabetes mellitus (NIDDM) in 29 subjects with impaired glucose tolerance (IGT) and in 38 control subjects. Over a 15-year period, although participating in an intervention program, 13 of the IGT subjects developed diabetes, but none of the control subjects developed diabetes. In view of their poor aerobic capacity, lack of physical fitness, and reduced glycolytic and oxidative enzymes, these 13 subjects manifested an unexpectedly high number of capillaries around all types of muscle fibers, especially type IIb fibers, as predictors of their progression to diabetes. Moreover, the number of capillaries per muscle fiber and the 2-h insulin value in the oral glucose tolerance test were highly correlated (r = 0.82, P < 0.005), whereas no correlation was found among IGT subjects who remained nondiabetic and in the control group. With body mass index and the 2-h glucose concentration included in a regression model, 68% of the variation in the number of capillaries per muscle fiber was explained (P < 0.05), with the 2-h insulin value independently accounting for 33%. These findings may suggest that the increased circulating insulin concentrations in IGT subjects have a capillary proliferative effect, perhaps to compensate for reduced capillary insulin diffusion and metabolic capacity of the muscle.

Body weight, skeletal muscle morphology, and enzyme activities in relation to fasting serum insulin concentration and glucose tolerance in 48-year-old men.

Tissue samples were taken from the gastrocnemius muscle of 26 randomly selected, glucose-tolerant, 48-yr-old men. Hexokinase, phosphorylase, lactate dehydrogenase (LDH), succinate dehydrogenase, and lipoprotein lipase activity (LPLA), as well as the area per fiber type and capillary density, were determined. Mean fiber area correlated positively with relative body weight (r equals 0.53, P less than 0.01), but capillary density did not. The result is that, in cases of high body weight, each capillary supplies a larger muscle fiber area. Serum insulin concentration in the fasting state correlated positively with body weight (r equals 0.77, P less than 0.001) and with mean fiber area per capillary (r equals 0.87; P less than 0.001). Only during the latter part of an oral glucose tolerance test (OGTT) did blood glucose concentrations correlate with relative body weight and mean fiber area per capillary (r equals 0.42, r equals 0.51, P less than 0.05). A stepwise multiple regression analysis showed that the different muscle morphology measurements could account for 3/4 of the variation in the fasting serum insulin concentration, the fasting insulin/glucose ratio, and the blood glucose concentration at 120 min in the OGTT. Of the intracellular enzymes, only LDH (r equals -0.71, P less than 0.001) correlated with the mean fiber area per capillary. LPLA correlated with capillary density (r equals 0.66, P less than 0.001), and, long with the muscle morphology measurements, could account for 3/4 of the variation in serum triglyceride concentrations. The results show that a large mean muscle fiber area/capillary ratio indicates a morphologic imbalance, which is related to both glucose tolerance and various degrees of insulin sensitivity.

Risk of myocardial infarction and stroke in smokers is related to plasma levels of inflammation-sensitive proteins.

BACKGROUND: The extent to which differences in cardiovascular risk between smokers with similar daily tobacco consumption may be related to plasma levels of inflammation-sensitive proteins (ISP) and whether these proteins are associated with levels of carboxyhemoglobin (COHb%) have not been clarified. METHODS AND RESULTS: In a population-based cohort of 1489 never smokers, 1685 former smokers, and 2901 current smokers, aged 28 to 61 years, plasma levels of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. COHb% levels were available for 2098 of them. Incidence of myocardial infarction, stroke, and death were monitored over 18.7+/-4.7 years. The proportion with high ISP levels (ie, > or =2 ISP in the top quartile) increased progressively with daily tobacco consumption (P<0.01) and COHb% (P<0.01). In all smoking categories, the incidence of stroke, cardiac events, and death was related to ISP. In heavy smokers, high ISP levels were associated with adjusted relative risks of 1.57 (1.05 to 2.35) and 1.50 (1.11 to 2.03) for cardiac events and death, respectively. Corresponding figures for moderate and light smokers were 1.59 (1.13 to 2.24) and 1.14 (0.87 to 1.49), respectively, and 1.32 (0.95 to 1.85) and 1.48 (1.10 to 1.98), respectively. CONCLUSIONS: ISP levels are related to COHb% in smokers. High levels are associated with an increased cardiovascular risk.

Influence of plasma fibrinogen levels on the incidence of myocardial infarction and death is modified by other inflammation-sensitive proteins: a long-term cohort study.

Inflammation may play an important role in atherosclerotic disease. Plasma fibrinogen is an established predictor of cardiovascular events. The aim of this study was to evaluate whether other inflammation-sensitive plasma proteins modify this prediction. We studied the incidence of cardiac events and death in men in relation to fibrinogen levels alone and in combination with other proteins. The study was based on 6075 men, who were, on average, 46 years old at the time of the screening examination, which included the quantitative assessment of plasma levels of fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin. The concentration of each protein was divided into quartiles for each. This classification made it possible to identify 4 groups, ie, men in the first fibrinogen quartile and at the same time either not belonging to the fourth quartile of any of the other proteins (Q1/No group) or also belonging to the fourth quartile of >/=1 of the additional proteins (Q1/Yes group) and corresponding groups in the fourth fibrinogen quartile (Q4/No and Q4/Yes groups). During the follow-up, which occurred at an average of 16 years, 439 (7.2%) men experienced a cardiac event, and 653 (10.7%) died; 278 of these men died of cardiovascular diseases, with 206 deaths attributed to ischemic heart disease. From the lowest to the highest quartile, there was for each protein a stepwise increase in the incidence of cardiac events and mortality. All-cause mortality and cardiovascular mortality were significantly higher in the Q4/Yes group compared with the Q4/No group, but they were similar in the Q4/No and Q1/Yes groups. The incidence of cardiac events was significantly higher in the Q1/Yes and Q4/Yes groups compared with the Q1/No and Q4/No groups, respectively. The increased cardiovascular mortality and cardiac event rates remained after adjustment for several confounders when the Q4/Yes and Q4/No groups were compared. The results suggest that the incidence of cardiac events and death due to cardiovascular diseases in middle-aged men predicted by plasma levels of fibrinogen is modified by other inflammation-sensitive proteins.

Gender, autoantibodies, and obesity in newly diagnosed diabetic patients aged 40-75 years.

OBJECTIVE: To evaluate the frequency of autoimmune markers (islet cell antibodies (ICA] and glutamic acid decarboxylase antibodies [GADA]) and clinical features in newly diagnosed people with diabetes aged 40-75 years. RESEARCH DESIGN AND METHODS: Two hundred fifty-nine consecutive patients (aged 40-75 years) with newly suspected diabetes diagnosed during a 2-year period were studied. The diagnosis of newly discovered diabetes was confirmed in 203 patients. Gender, BMI, HbA1c, fasting C-peptide, ICA, and GADA were evaluated. The frequency of obesity was estimated using two different sets of criteria: 1) National Diabetes Data Group (NDDG) criteria, and 2) criteria based on a Swedish reference population. RESULTS: The annual incidence of diabetes was 106 per 100,000 people. The incidence of diabetes in those patients who were 40-54 years old was significantly higher in men than in women (odds ratio: 2.16; P = 0.001). ICA were detected in 16 of 203 patients (8%), whereas 17 of 203 patients (8%) were GADA+; 10 of 203 (5%) patients were positive for both ICA and GADA. Among the 203 diabetic patients, 19 (9.4%) were classified as having IDDM, giving an IDDM incidence of 10 per 100,000 people aged 40-75 years. The frequency of obesity in NIDDM was high but varied with its definition; the frequency of obesity was highest (P < 0.001) when NDDG criteria, and not Swedish reference values, were used (57 of 75 [76%] vs. 40 of 75 [53%] for women and 66 of 109 [61%] vs. 45 of 109 [41%] for men). CONCLUSIONS: A striking male preponderance was found among incident cases of diabetes in people aged 40-54 years. Autoimmune markers were detected in 10% of incident cases of diabetes in people aged 40-75 years. Using a conservative estimation, as many as 10 of 100,000 middle-aged and elderly subjects developed IDDM. The frequency of obesity in NIDDM was high but this was also the case in the reference population.

Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.

OBJECTIVE: To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Of 165 patients (fasting blood glucose [FBG] > or = 6.7 mmol/l) initially treated with diet alone, 144 (FBG still > or = 6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, with FBG < 6.7 mmol/l as target, using, at most, six dose levels. The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated to high dosage (MGH). Medication was maintained for 6 months after completed dose titration. RESULTS: The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG +/- SE was reduced (P = 0.001) from 9.1 +/- 0.4 to 7.0 +/- 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 +/- 0.8 to 7.8 +/- 0.6 mmol/l. HbA1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 +/- 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups. CONCLUSIONS: Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

Long-term effects of inflammation-sensitive plasma proteins and systolic blood pressure on incidence of stroke.

BACKGROUND AND PURPOSE: The present study investigated the relationships between inflammation-sensitive plasma proteins (ISPs) and systolic blood pressure (SBP), as well as the joint long-term effects of ISP and SBP on incidence of stroke. METHODS: BP and 5 ISPs (fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, orosomucoid) were assessed in 6071 healthy men 28 to 61 years of age. All-cause mortality and incidence of stroke were monitored over a mean follow-up of 18.7 years in men defined by SBP (<120, 120 to 139, >/=140 mm Hg) and ISP (0 to 1 or 2 to 5 ISPs in the top quartile). RESULTS: SBP and diastolic BP were significantly and positively associated with the number of ISPs in the top quartile. As expected, elevated SBP was associated with an increased incidence of stroke. Among men with SBP >/=140 mm Hg, there were, however, significant differences between those with high and low ISP levels. After risk factor adjustment, men with SBP >/=140 mm Hg and high ISP levels had a relative risk of stroke of 4.3 (95% CI, 2.3 to 7.8) compared with men with SBP <120 mm Hg and low ISP levels. In the absence of high ISP levels, the risk associated with SBP >/=140 was 2.5 (95% CI,1.4 to 4.6). Men with high ISP levels had a significantly increased risk of stroke also after exclusion of the events from the first 10 years of follow-up. CONCLUSIONS: High ISP levels are associated with elevated BP. These proteins are associated with an increased risk of stroke among men with high BP and provide information on stroke risk even after many years of follow-up.

Leukocyte activation in atherosclerosis: correlation with risk factors.

Leukocytes have been implicated in the development of atherosclerotic vascular diseases, and numerous abnormalities of leukocytes in conjunction with atherosclerosis have been reported. The aim of this study of middle-aged asymptomatic subjects with early atherosclerosis was to determine whether a relationship exists between the levels of plasma markers of leukocyte activation, i.e. cytokines and proteases and risk factors for atherosclerosis or the degree of atherosclerotic disease. Using ELISAs we measured the plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil protease 4 (NP4) as markers for neutrophil activation, tumor necrosis factor alpha (TNF) and soluble TNF receptor-1 (sTNFR-1) as markers of monocyte/macrophage activation in 156 subjects with asymptomatic carotid artery plaque detected at ultrasound examination. Plasma TNF and sTNFR-1 levels were found to correlate with systolic blood pressure (r = 0.32, P < 0.04 and r = 0.22, P < 0.05, respectively). plasma NGAL level to correlate with diastolic blood pressure (r = 0.22; P < 0.005), the plasma levels of sTNFR-1 and NGAL to correlate with age (r = 0.28, P < 0.001 and r = 0.20, P < 0.05, respectively). As compared with non-smokers (n = 112), smokers (n = 43) had higher plasma levels of TNF (2.9 vs. 1.4 microg/l; P < 0.02) and of NP4 (27.5 vs. 23.4 microg/l; P < 0.05). The plasma NGAL level was higher in hypertensive women (n = 7) than in normotensive women (n = 85) (109 vs. 87 microg/l; P < 0.05). We thus demonstrated that, in subjects with asymptomatic early atherosclerosis, the plasma levels of markers of systemic leukocyte activation were correlated with age and blood pressure, and were higher in smokers and hypertensives. These results support the hypothesized relationship between the level of systemic leukocyte activation and risk factors for atherosclerotic vascular disease.

The skeletal muscle Na:K ratio is not increased in hypertension: evidence for the importance of obesity and glucose intolerance.

Several previous studies have suggested that hypertension is associated with altered sodium transport across the cell membrane. The aim of the present study was to study the skeletal muscle Na:K ratio in relation to blood pressure and glucose tolerance in obese and non-obese men. Muscle biopsies were taken from the femoral vastus lateralis muscle in men aged 52 +/- 5 years and the electrolytes were analyzed. Ten obese men with impaired glucose tolerance and hypertension, 10 obese normotensive controls, 10 lean men with hypertension and 10 lean normotensive controls participated in the study. Higher insulin levels were found in both hypertensive groups compared with the respective normotensive groups. Increased muscle Na:K ratio was found in obesity (P less than 0.01) and this was further enhanced when combined with hypertension and impaired glucose tolerance (P less than 0.001). However, hypertension in lean individuals was not associated with an increased muscle Na:K ratio. These data suggest that the increased muscle Na:K ratio in obese subjects and those with impaired glucose tolerance is not solely due to insulin resistance and hyperinsulinemia. Furthermore, the data clearly suggest that there is no important general perturbation of the Na-K pump in hypertension per se.

Insulin resistance is coupled to low physical fitness in normotensive men with a family history of hypertension.

OBJECTIVE: To investigate insulin sensitivity and the influence of level of physical fitness in men with a family history of hypertension and in control subjects. DESIGN: Insulin sensitivity was determined and physical fitness estimated in 39 normotensive, glucose-tolerant men with a family history of hypertension (Relatives group) and in 29 age- and body mass index-matched normotensive men with no such family history (Controls group). METHODS: The euglycaemic hyperinsulinaemic clamp technique (steady-state insulin concentration approximately 100 mU/l) was used to determine insulin sensitivity. Physical fitness, measured as maximal oxygen uptake, was estimated from the heart rate response to a submaximal exercise test. RESULTS: Insulin sensitivity index and estimated maximal oxygen uptake were lower in the Relatives than in the Controls. There was a positive correlation between insulin sensitivity and maximal oxygen uptake in both groups. In the Controls there was a negative correlation between insulin sensitivity and waist:hip ratio, but this relationship was not found in the Relatives. CONCLUSIONS: The present findings indicate that reduction of insulin sensitivity precedes the development of high blood pressure and may be coupled to low physical fitness. As abdominal fat distribution seems not to be related to insulin sensitivity in subjects with a family history of hypertension, changes in muscle fibre composition or muscle glucose metabolism, or both, might explain the lower insulin sensitivity and physical fitness in the Relatives.

The epidemiology of thyroid disorders in a seaport community in southern Sweden.

The prevalence of thyroid disorders was studied in two birth cohorts (1928 and 1941) of men and women living in Malmö, a non-iodine deficient area. In the 1928 cohort, the prevalence of thyroid disorders was 11.5% overall (mean 2.4% , women 20.3%), and higher among immigrant women (20.7%) than among women of the native population, e.g. women born in and still living in Malmö (14.7%). In the 1941 cohort, the overall prevalence of thyroid disorders was 7.9% (men 1.5%, women 14.1%); and the prevalence of goiter was lower among immigrant women (9.5%) than among women of the native population (15.0%). Among the native population, the prevalence of goiter did not differ significantly between the two cohorts, whereas among immigrant women it was significantly greater in the 1928 cohort. The findings suggest that, although iodine deficiency is the most probable cause of goiter among immigrants of the 1928 cohort, where the native population is concerned (both men and women), some other goitrogenic factor(s) must be involved.

The Malmö Food Study: validity of two dietary assessment methods for measuring nutrient intake.

BACKGROUND: Nutritional epidemiology relies largely on dietary assessment methods for the estimation of the "exposure' variables which may be related to disease risk. METHODS: This paper describes a methodological study conducted in Malmö, Sweden, to compare nutrient intake--estimated by two alternative dietary assessment methods--with a reference method consisting of 18 days of weighed food records. The two candidate methods were an extensive food frequency questionnaire with portion size to be estimated from a booklet of 120 sets of photos (method A) and a method involving the combination of a shorter questionnaire and a two-week food record (method B). RESULTS: In absolute values, both methods overestimated nutrient intake by 20-40%, with method B closer to the reference for most nutrients. Both crude and energy-adjusted correlations between A-reference and B-reference were of the order of 0.50-0.60 for energy, energy-providing nutrients and most vitamins and minerals. Correlations were in the same range for most of the 14 fatty acids considered in the analyses. Protein intake, estimated from the analyses of urinary nitrogen on 6-8 repeated 24-hour urine collections per subject, was almost identical to the reference method values. Correlation between nitrogen-derived values and dietary measurement was 0.75. CONCLUSIONS: Overall, the study indicated that both methods A and B had good ranking validity compared to the reference and that in most cases the combined method (B) performed slightly better than the extensive food frequency method (A).

Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency.

Homocysteine is an amino acid considered to cause vascular injury, arteriosclerosis, and thromboembolism. Total plasma homocysteine (free and protein-bound) was found to be twice as high in asymptomatic vitamin B12-deficient subjects (23.8 +/- 3.8 mumol/L, means +/- SEM, n = 20) as in controls (11.5 +/- 0.9 mumol/L, P less than .0001, n = 21), and higher than in heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency (13.8 +/- 1.6 mumol/L, P less than .01, n = 14), who were recently shown to be much more common among patients with premature vascular disease than expected. Eight (40%) vitamin B12-deficient and two (14%) heterozygote subjects had significant homocysteinemia (greater than mean +2 SD for controls). After administration of hydroxycobalamin to vitamin B12-deficient subjects, homocysteine levels decreased to normal (-49%, 12.2 +/- 1.5 mumol/L, P less than .0001, n = 20). Thus, if homocysteine does cause vascular injury, theoretically vitamin B12-deficiency might be associated with an increased frequency of vascular disease.

Overweight is associated with lower serum leptin in Peruvian Indian than in Caucasian women: A dissociation contributing to low blood pressure?

We tested whether plasma levels of leptin and insulin are associated with the lower blood pressure in women of Peruvian Indian heritage compared with Caucasian women. A total of 181 women from Peru and 85 from Sweden, aged 20 to 60 years, with normal plasma glucose levels participated in the study. Measurements of anthropometry, blood pressure, and blood tests were performed after overnight fasting. Compared with women from Umeå in Sweden, women from Lima, Peru had higher body mass index (BMI) (26.2 +/- 4.9 v 24.4 +/- 3.8 kg/m(2)), waist circumference (85 +/- 11 v 79 +/- 10 cm), lower systolic blood pressure (99 +/- 15 v 114 +/- 14 mm; P <.001) and diastolic blood pressure (67 +/- 7 v 74 +/- 10 mm; P <.001). In addition, they had a reduction of the ratio of plasma leptin to BMI (0.52 +/- 0.22 v 0.61 +/- 0.36; P <.001), greater plasma insulin (80 +/- 42 v 41 +/- 21 pmol/L), but lower plasma glucose (4.2 +/- 0.5 v 5.1 +/- 0.5 mmol/L; P <.001). Furthermore, the 181 women from Lima had higher plasma triglyceride levels (1.5 +/- 0.8 v 1.3 +/- 0.7; P =.039), but lower plasma high-density lipoprotein (HDL)-cholesterol (1.0 +/- 0.2 v 1.5 +/- 0.4 mmol/L; P <.001) and total plasma cholesterol (5.0 +/- 1.1 v 5.9 +/- 1.3 mmol/L; P <.001) levels. Plasma leptin correlated with blood pressure and BMI in both populations (P <.001). In multiple regression analysis, BMI, but not log leptin, emerged as the determinant for systolic blood pressure. We concluded that women living in Lima have significant lower blood pressure levels in association with elevated plasma insulin concentrations, but lower plasma leptin values adjusted for BMI in comparison with women from northern Sweden. This may suggest that the concept of metabolic syndrome is different among women with Peruvian Indian heritage in comparison to a Caucasian population.