Serum and lipoprotein sitostanol and non-cholesterol sterols after an acute dose of plant stanol ester on its long-term consumption.

PURPOSE: Chronic inhibition of cholesterol absorption with large doses of plant stanol esters (staest) alters profoundly cholesterol metabolism, but it is unknown how an acute inhibition with a large staest dose alters the postprandial serum and lipoprotein cholesterol precursor, plant sterol, and sitostanol contents. METHODS: Hypercholesterolemic subjects, randomly and double-blind divided into control (n = 18) and intervention groups (n = 20), consumed experimental diet without and with staest (plant stanols 8.8 g/day) for 10 weeks. Next morning after a fasting blood sample (0 h), the subjects had a breakfast without or with staest (4.5 g of plant stanols). Blood sampling was repeated 4 h later. Lipoproteins were separated with ultracentrifugation, and sterols were measured with gas-liquid chromatography. RESULTS: In 0-h chylomicrons and VLDL, plant sterols were lower in staest than in controls. Postprandially, cholestenol (cholesterol synthesis marker) was reduced in chylomicrons in staest compared with controls (-0.13 ± 0.04 µg/dL vs. 0.01 ± 0.08 µg/dL, P < 0.05). Staest decreased postprandially avenasterol in chylomicrons (P < 0.05 from 0 h). Sitostanol was high at 0 h by chronic staest in serum and VLDL but not in chylomicrons. Postprandial sitostanol was increased by staest in VLDL only. CONCLUSIONS: Chronic cholesterol absorption inhibition with large amount of plant stanol esters decreases plant sterols in triglyceride-rich lipoproteins. Acute plant stanol ester consumption increases sitostanol content in triglyceride-rich lipoproteins but suggests to decrease the risk of plant sterol and plant stanol accumulation into vascular wall by chylomicrons.

Obesity may impair the early outcome of total knee arthroplasty.

BACKGROUND AND AIMS: Obesity has been linked to the development of osteoarthritis of the knee and increases the probability to fall into total knee arthroplasty. In this study we compared short-term outcome of total knee arthroplasty (TKA) in non-obese and obese patients. MATERIAL AND METHODS: A total of 100 patients underwent TKA between October 2006 and March 2007. They were divided into two groups based on the body mass index: 52 of the patients were obese (BMI = 30 kg/m2) and 48 non-obese (BMI < 30 kg/m2). The short-term out-come was studied using clinical, functional and radiological analysis. The mean of the follow-up period was 3 months. RESULTS: There were five complications (2 wound infections, phlebitis, nerve injury and massive edema) in obese patients group compared with no complications in non-obese (p = 0.028). The obese patients had also worse postoperative range of motion (110 degrees vs.118 degrees , p = 0.001) than non-obese and the number of technical errors was 17 in obese and 5 in non-obese group, respectively (p = 0.007). CONCLUSIONS: We suggest that obesity may impair the early outcome of total knee arthroplasty and obese patients should be informed about the increased risk of complications related to TKA. Key words: Total knee arthroplasty; body mass index; obesity; complications; range of motion; mechanical axis.

Alendronate reduces periprosthetic bone loss after uncemented primary total hip arthroplasty - a 5-year follow-up of 16 patients.

BACKGROUND AND AIMS: Periprosthetic bone loss, especially in the proximal part of the femur, is common after cemented and uncemented total hip arthroplasty (THA). Short-term studies suggest that bisphosponates can minimize this bone loss related to stress-shielding phenomenon. The aim of the present randomized study was to investigate whether the positive effect of a 6 months alendronate treatment postoperatively still exists at five-year follow up. MATERIALS AND METHODS: Sixteen uncemented primary THA patients were randomized to receive either 10mg alendronate + 500 mg calcium (n = 7) or 500 mg calcium only (n = 9) daily for 6 months postoperatively. Periprosthetic bone mineral density (BMD) was measured with the dual X-ray absorptiometry (DXA) postoperatively and at 6, 12, 24, 36 and 60 months follow-up. RESULTS: At the 5-year follow up, the calcium group showed mean BMD decreases of 23.1% (SD 14.6) in the proximal part of the femur (prROI) and 9.6% (SD 14.9) in total femoral regions of interest (totROI). In the alendronate group the corresponding BMD decreases were 13.6% (SD 19.0) and 3.9% (SD 7.6) respectively. The positive effect of alendronate was already demonstrated during the first six months postoperatively. Subsequently the bone loss was equal in both groups, and the 5-year BMD changes were not significantly different between the groups. CONCLUSIONS: Alendronate seems to decrease early periprosthetic bone loss after arthroplasty but this pilot study could not provide enough evidence that the positive effect noted in the early postoperative period is still maintained 5 years after the operation.

Fc receptor endocytosis is controlled by a cytoplasmic domain determinant that actively prevents coated pit localization.

Macrophages and B-lymphocytes express two major isoforms of Fc receptor (FcRII-B2 and FcRII-B1) that exhibit distinct capacities for endocytosis. This difference in function reflects the presence of an in-frame insertion of 47 amino acids in the cytoplasmic domain of the lymphocyte isoform (FcRII-B1) due to alternative mRNA splicing. By expressing wild type and mutant FcRII cDNAs in fibroblasts, we have now examined the mechanism by which the insertion acts to prevent coated pit localization and endocytosis. We first identified the region of the FcRII-B2 cytoplasmic domain that is required for rapid internalization. Using a biochemical assay for endocytosis and an immuno-EM assay to determine coated pit localization directly, we found that the distal half of the cytoplasmic domain, particularly a region including residues 18-31, as needed for coated pit-mediated endocytosis. Elimination of the tyrosine residues at position 26 and 43, separately or together, had little effect on coated pit localization and a partial effect on endocytosis of ligand. Since the FcRII-B1 insertion occurs in the membrane-proximal region of the cytoplasmic domain (residue 6) not required for internalization, it is unlikely to act by physically disrupting the coated pit localization determinant. In fact, the insertion was found to prevent endocytosis irrespective of its position in the cytoplasmic tail and appeared to selectively exclude the receptor from coated regions. Moreover, receptors bearing the insertion exhibited a temperature- and ligand-dependent association with a detergent-insoluble fraction and with actin filaments, perhaps in part explaining the inability of FcRII-B1 to enter coated pits.

Toxoplasma gondii: fusion competence of parasitophorous vacuoles in Fc receptor-transfected fibroblasts.

After actively entering its host cells, the protozoan parasite Toxoplasma gondii resides in an intracellular vacuole that is completely unable to fuse with other endocytic or biosynthetic organelles. The fusion blocking requires entry of viable organisms but is irreversible: fusion competence of the vacuole is not restored if the parasite is killed after entry. The fusion block can be overcome, however, by altering the parasite's route of entry. Thus, phagocytosis of viable antibody-coated T. gondii by Chinese hamster ovary cells transfected with macrophage-lymphocyte Fc receptors results in the formation of vacuoles that are capable of both fusion and acidification. Phagocytosis and fusion appear to involve a domain of the Fc receptor cytoplasmic tail distinct from that required for localization at clathrin-coated pits. These results suggest that the mechanism of fusion inhibition is likely to reflect a modification of the vacuole membrane at the time of its formation, as opposed to the secretion of a soluble inhibitor by the parasite.

Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice.

Mammalian female fertility depends on complex interactions between the ovary and the extraovarian environment (e.g., the hypothalamic-hypophyseal ovarian axis). The role of plasma lipoproteins in fertility was examined using HDL-receptor SR-BI knockout (KO) mice. SR-BI KO females have abnormal HDLs, ovulate dysfunctional oocytes, and are infertile. Fertility was restored when the structure and/or quantity of abnormal HDL was altered by inactivating the apoAI gene or administering the cholesterol-lowering drug probucol. This suggests that abnormal lipoprotein metabolism can cause murine infertility--implying a functional hepatic-ovarian axis--and may contribute to some forms of human female infertility.

Analysis of transport and targeting of syndecan-1: effect of cytoplasmic tail deletions.

Madin-Darby canine kidney (MDCK) cells and Chinese hamster ovary (CHO) cells were transfected with wild-type and cytoplasmic deletion mutants of mouse syndecan-1 to study the requirements for transport and polarized expression of this proteoglycan. Expression in MDCK cells revealed that wild-type syndecan-1 is directed to the basolateral surface via a brefeldin A-insensitive route. A deletion of the last 12 amino acids of the syndecan-1 cytoplasmic tail (CT22) was sufficient to result in the appearance of mutant proteoglycans at both the basolateral and apical cell surfaces. Treatment with brefeldin A was able to prevent apical transport of the mutants. We thus propose that the C-terminal part of the cytoplasmic tail is required for steady-state basolateral distribution of syndecan-1. In CHO cells a deletion of the last 25 or 33 amino acids of the 34-residue cytoplasmic domain (CT9 and CT1, respectively) resulted in partial retention of the mutants in the endoplasmic reticulum (ER). A deletion mutant lacking the last 12 amino acids (CT22) was not retained. Interestingly, the unglycosylated core proteins of the CT9 and CT1 mutants showed a significantly lower apparent molecular weight when analyzed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis than wild-type syndecan-1. However, when CHO transfectants expressing the CT1 mutant were incubated with brefeldin A, causing fusion of the ER and Golgi, CT1 ran with an almost equally high apparent molecular weight as the wild-type molecule. This would suggest that syndecan-1 undergoes extensive posttranslational modifications or forms an SDS-resistant dimer/complex after transit from the ER.

Expression of peripheral-type benzodiazepine receptor and diazepam binding inhibitor in human astrocytomas: relationship to cell proliferation.

The expression of peripheral-type benzodiazepine receptor (PBR) and diazepam binding inhibitor (DBI) were studied in human astrocytic tumors using immunocytochemistry and in situ hybridization. Both PBR and DBI were prominently expressed in neoplastic cells, whereas in normal brain their amount was low or undetectable. Immunocytochemical double staining demonstrated that PBR and DBI were present in the same cells, suggesting that DBI may act in an autocrine manner in these cells. Analysis of 86 cases showed that PBR expression was statistically significantly associated with tumor malignancy grade (P = 0.004) and the proliferative index as determined by immunocytochemistry with the MIB-1 antibody (P = 0.004). Patients having tumors with high levels of PBR-immunoreactive cells had a shorter life expectancy than patients whose tumors showed lower PBR contents (P = 0.024). In conclusion, these results show that PBR expression is higher in neoplastic cells than in normal brain tissue. They also suggest that PBR immunocytochemistry might be useful in evaluating malignancy in brain tumors.

Mid-term Results of Oxford Phase 3 Unicompartmental Knee Arthroplasties at a Small-Volume Center.

BACKGROUND AND AIMS: Unicompartmental knee arthroplasty is considered as an alternative to total knee arthroplasty for patients who have osteoarthritis limited to the medial compartment of the knee. The aim of this retrospective study was to find out clinical and radiological outcomes and related complications using the Oxford phase 3 prosthesis at a small-volume center. MATERIAL AND METHODS: In all, 95 Oxford unicompartmental knee arthroplasties (87 patients) were performed between 2000 and 2010 in North Karelia Central Hospital. Of these, five patients had undergone revision surgery. In all, 52 unicompartmental knee arthroplasties (46 patients) participated in this study. The mean age of patients was 61.4 years, and 78.2% of patients were females. Pain and function levels were evaluated by using the Knee Society score. Radiographic analyses were performed on preoperative and postoperative and follow-up radiographs. RESULTS AND CONCLUSIONS: The mean follow-up time was 6.5 years, and the Kaplan-Meier estimated 9-year implant survival rate was 88.9% (95% confidence interval = 78.7%-99.1%). The median Knee Society score of 77 (range: 18-93) at follow-up was considered good (range: 70-79). In this study, we found out that medial knee pain remains in 10% of unicompartmental knee arthroplasties several years after surgery, although the reason for the pain remained unclear. These mid-term results are promising, and good results can be achieved also at a small-volume center when strict patient selection is followed.

Influences of recovery from wildfire and thinning on soil respiration of a Mediterranean mixed forest.

The ecosystem recovery after wildfire and thinning practices are both key processes that have great potential to influence fluxes and storage of carbon within Mediterranean semiarid ecosystems. In this study, started 7years after a wildfire, soil respiration (SR) patterns measured from 2008 to 2010 were compared between an unmanaged-undisturbed mature forest stand (UB site) and a naturally regenerated post-wildfire stand (B site) in a Mediterranean mixed forest in Spain. The disturbed stand included a control zone (unthinned forest, BUT site) and a thinned zone (BT site). Our results indicated that SR was lower at naturally regenerated after fire sites (BUT and BT) than at unburnt one. Soil under the canopy layer of pine and oak trees exhibited higher SR rates than bare or herbaceous layer soils, regardless of the site. The effect of thinning was only manifest, with a significant increase of SR, during the 1st year after thinning practices. SR showed a clear soil temperature-dependent seasonal pattern, which was strongly modulated by soil water content (SWC), especially in summer. Site-specific polynomial regression models were defined to describe SR responses, being mainly controlled by both soil temperature (Ts) and SWC at UB site, or Ts at burnt sites. The sensitivity of SR rate to Ts variations (Q10) ranged between 0.20 and 6.89, with mean annual values varying between 0.92 and 1.35. Q10 values were higher at BT than at UB-BUT sites. The results revealed a significant, non-linear dependence, of Q10 on both Ts and SWC at UB site, and on Ts at both burnt sites. This study contributes to (i) improve the understanding of how natural recovery and management practices affect soil respiration in a Mediterranean forest during their early stages after fire disturbance and (ii) highlight the importance of Q10 values <1 which emphasizes drought stress effect on SR temperature sensitivity.

Erythrocyte membrane skeleton phosphoproteins: identification of two unrelated phosphoproteins in band 4.9.

Human erythrocyte membrane band 4.9 is phosphorylated by several erythrocyte protein kinases. Chromatography of erythrocyte membrane skeleton proteins on DEAE-Sephacel produces two proteins with relative mobilities, on gel electrophoresis, similar to that of band 4.9. The first, with a molecular mass of 49 kDa, is quite basic (pI greater than 8) while the second, 50.5 kDa, is slightly acidic (pI = 6.2). Comparative two-dimensional peptide mapping reveals that both proteins are present in band 4.9 on one-dimensional gels of total erythrocyte membrane proteins and membrane skeleton proteins. The 49 kDa protein, but not the 50.5 kDa protein, binds to actin filaments in a sedimentation assay. In intact erythrocytes metabolically labeled with [32P]orthophosphate, the 49 kDa protein is phosphorylated by protein kinase C, cAMP-dependent protein kinase, and protein kinases which are active in the absence of exogenous kinase activators. In contrast, the 50.5 kDa protein is phosphorylated by protein kinase C but not by the other protein kinases examined. Finally, two-dimensional peptide mapping was employed to compare the 49 kDa protein and a 57 kDa protein which copurifies with, and has many characteristics of, the 49 kDa protein. Significant similarities were found in both 125I-labeled chymotryptic peptide maps and 32P-labeled tryptic peptide maps, suggesting that the 49 kDa and 57 kDa proteins are closely related.

Relationship of socioeconomic status to the incidence and prehospital, 28-day, and 1-year mortality rates of acute coronary events in the FINMONICA myocardial infarction register study.

BACKGROUND: Low socioeconomic status (SES) is associated with increased coronary heart disease mortality rates. There are, however, very little data on the relation of SES to the incidence, recurrence, and prognosis of myocardial infarction (MI) events. METHODS AND RESULTS: The FINMONICA MI Register recorded detailed information on all MI events among men and women aged 35 to 64 years in 3 areas of Finland during the period of 1983 to 1992. We carried out a record linkage of the MI register data with files of Statistics Finland to obtain information on indicators of SES, such as taxable income and education, for each individual who is registered. In the analyses, income was grouped into 3 categories (low, middle, and high), and education was grouped into 2 categories (basic and secondary or higher). Among men with their first MI event (n=6485), the adjusted incidence rate ratios were 1.67 (95% CI 1.57 to 1.78) and 1.84 (95% CI 1.73 to 1.95) in the low- and middle-income categories compared with the high-income category. For 28-day mortality rates, the corresponding rate ratios were 3.18 (95% CI 2.82 to 3.58) and 2.33 (95% CI 2.03 to 2.68). Significant differentials were observed for prehospital mortality rates, and they remained similar up to 1 year after the MI. Findings among the women were consistent with those among the men. CONCLUSIONS: The excess coronary heart disease mortality and morbidity rates among persons with low SES are considerable in Finland. To bring the mortality rates of low- and middle-SES groups down to the level of that of the high-SES group constitutes a major public health challenge.

Decline in out-of-hospital coronary heart disease deaths has contributed the main part to the overall decline in coronary heart disease mortality rates among persons 35 to 64 years of age in Finland: the FINAMI study.

BACKGROUND: Out-of-hospital deaths constitute the majority of all coronary heart disease (CHD) deaths and are therefore of considerable public health significance. METHODS AND RESULTS: We used population-based myocardial infarction register data to examine trends in out-of-hospital CHD deaths in Finland during 1983 to 1997. We included in out-of-hospital deaths also deaths in the emergency room and all deaths within 1 hour after the onset of symptoms. Altogether, 3494 such events were included in the analyses. The proportion of out-of-hospital deaths of all CHD deaths depended on age and gender. In the age group 35 to 64 years, it was 73% among men and 60% among women. These proportions did not change during the study. The annual average decline in the age-standardized out-of-hospital CHD death rate was 6.1% (95% CI, -7.3, -5.0%) among men and 7.0% (-10.0, -4.0%) among women. These declines contributed among men 70% and among women 58% to the overall decline in CHD mortality rate. In all, 58% of the male and 52% of the female victims of out-of-hospital CHD death had a history of symptomatic CHD. Among men with a prior history of myocardial infarction, the annual average decline in out-of-hospital CHD deaths was 5.3% (-7.2, -3.2%), and among men without such history the decline was 2.9% (-4.4, -1.5%). Among women, the corresponding changes were -7.8% (-14.2, -1.5%) and -4.5% (-8.0, -1.0%). CONCLUSIONS: The decline in out-of-hospital CHD deaths has contributed the main part to the overall decline in CHD mortality rates among persons 35 to 64 years of age in Finland.

Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans.

The relative importance of insulin resistance and abnormal insulin secretion as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM) is still controversial. Few data are available on insulin secretion as a risk factor for the development of NIDDM, especially in subjects with normal glucose tolerance. We examined the relation of fasting insulin (as a marker of insulin resistance) and the ratio of change in insulin to change in glucose during the first 30 min after glucose ingestion (delta I30/delta G30) (as a marker of insulin secretion) as predictors of the 7-year development of NIDDM in 714 initially nondiabetic Mexican-Americans. NIDDM developed in 99 subjects. The relative risk of NIDDM increased with higher quartiles of fasting insulin (quartile 1 [low], 1.0; quartile 2, 1.5; quartile 3, 2.0; and quartile 4 [high], 3.7; P < 0.0001) and lower delta I30/delta G30 (quartile 1 [low], 6.9; quartile 2, 1.9; quartile 3, 1.1; quartile 4 [high], 1.0; P < 0.001). Subjects with both increased fasting insulin and decreased delta I30/delta G30 had independent increases in NIDDM incidence (P < 0.001). Further, when we stratified subjects by baseline glucose tolerance, both increased fasting insulin and decreased delta I30/delta G30 significantly predicted NIDDM in subjects with both impaired and normal glucose tolerance at baseline. We conclude that both decreased insulin secretion (as assessed by low delta I30/delta G30) and increased insulin resistance (as assessed by fasting insulin) predict the development of NIDDM in Mexican-Americans, a group previously characterized as having hyperinsulinemia and insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Leptin concentrations in diabetic and nondiabetic Mexican-Americans.

Leptin, the product of the OB gene, is increased in obese individuals, suggesting resistance to its effect. We questioned whether subjects with NIDDM have an altered regulation of serum leptin levels. We used a radioimmunoassay to measure serum leptin levels in three groups from the San Antonio Heart Study: 1) 50 Mexican-Americans with NIDDM; 2) 50 nondiabetic Mexican-Americans matched by age and sex to the diabetic Mexican-Americans; and 3) 50 nondiabetic Mexican-Americans matched by age, sex, and BMI to the diabetic Mexican-Americans. Leptin concentrations did not differ significantly by diabetic status. Leptin concentrations were significantly correlated with BMI in all groups (NIDDM women: r = 0.637; nondiabetic women: r = 0.772; NIDDM men: r = 0.849; and nondiabetic men: r = 0.686; all P < 0.001). Leptin levels were higher in women than in men regardless of diabetic status. We concluded that the leptin concentrations were not different in diabetic and nondiabetic subjects and that the association of leptin with obesity was similar in diabetic and nondiabetic subjects.

Higher proinsulin and specific insulin are both associated with a parental history of diabetes in nondiabetic Mexican-American subjects.

Both insulin resistance and decreased insulin secretion have been hypothesized to be precursors of non-insulin-dependent diabetes. An elevated proinsulin concentration reflects abnormal proinsulin processing and could indicate abnormal insulin secretion. We examined fasting insulin (measured by a radioimmunoassay that does not cross-react with proinsulin), as a marker of insulin resistance, and proinsulin and the fasting proinsulin-to-insulin ratio, as markers of impaired proinsulin processing, in 597 nondiabetic Mexican-Americans from the San Antonio Heart Study. Fasting insulin, proinsulin, and the fasting proinsulin-to-insulin ratio were higher in subjects with a parental history of diabetes than in subjects without such a history. These differences remained statistically significant after adjustment for obesity, body fat distribution, and glucose tolerance. A parental history of diabetes in nondiabetic Mexican-Americans is associated with an increase in fasting specific insulin and a disproportionate increase in proinsulin relative to insulin. These data suggest that both increased insulin resistance and abnormal processing of proinsulin are present in offspring of parents with diabetes.

Metabolic precursors of hypertension. The San Antonio Heart Study.

BACKGROUND: The relation of possible metabolic precursors (especially insulin resistance) to hypertension has been controversial. In addition, these associations may differ by level of obesity or ethnicity. METHODS: We followed up 1039 initially nondiabetic, nonhypertensive subjects from the San Antonio Heart Study for 7 years. RESULTS: Hypertension developed in 93 subjects. Age, body mass index, waist-to-hip ratio, and fasting insulin and triglyceride levels predicted the development of hypertension in univariate analyses. After adjustment for age, body mass index, waist-to-hip ratio, gender, ethnicity, and fasting glucose levels, higher levels of triglyceride and fasting insulin predicted the development of hypertension. Body mass index and fasting insulin and triglyceride levels predicted the development of hypertension in Mexican Americans and non-Hispanic whites. In addition, fasting insulin levels predicted the development of hypertension in lean and obese subjects. Increased insulin secretion (as judged by the 30-minute insulin increment) on an oral glucose tolerance test also predicted the development of hypertension. CONCLUSIONS: A cluster of atherogenic changes may precede the development of hypertension, and increased fasting insulin concentration predicts hypertension in important subgroups of subjects.

Nondiabetic Mexican-Americans do not have reduced insulin responses relative to nondiabetic non-Hispanic whites.

OBJECTIVE: To study why Mexican-Americans have a threefold increase in NIDDM relative to non-Hispanic whites. The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion proposed as precursors of NIDDM. RESEARCH DESIGN AND METHODS: We examined possible ethnic differences in fasting insulin (as a marker of insulin resistance) and change in insulin-to-change in glucose ratio (delta I30:delta G30) during the first 30 min after oral glucose ingestion (as a marker of abnormal whites from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Fasting insulin and delta I30:delta G30 were evaluated as continuous variables. RESULTS: Mexican-Americans had increased insulin concentrations at fasting and 30, 60, and 120 min after an oral glucose load as well as an increased 0- to 30-min increment in insulin and delta I30:delta G30 relative to non-Hispanic whites. These results remained unchanged after adjustment for age, sex, obesity, body fat distribution, and glucose tolerance. CONCLUSIONS: These results suggest that increased insulin resistance rather than decreased insulin secretion is characteristic of nondiabetic Mexican-Americans, a high-risk population for NIDDM.

Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality: the 22-year follow-up results of the Helsinki Policemen Study.

OBJECTIVE: To investigate the association of plasma insulin with all-cause, cardiovascular, and noncardiovascular mortality. RESEARCH DESIGN AND METHODS: We studied 22-year mortality data from the Helsinki Policemen Study The study population comprised 970 men, 34-64 years of age, who were free of coronary heart disease, other cardiovascular disease, and diabetes. Area under the insulin response curve (AUC insulin) during an oral glucose tolerance test was used to reflect plasma insulin levels. RESULTS: During the follow-up period, 276 men died: 130 from cardiovascular and 146 from noncardiovascular causes. The hazard ratio (HR) for hyperinsulinemia (highest AUC insulin quintile vs. combined lower quintiles) with regard to all-cause mortality adjusting for age, was 1.94 (95% CI 1.20-3.13) during the first 10 years of the follow-up period and 1.51 (1.15-1.97) during the entire 22 years; adjusting for other risk factors, the HR was 1.88 (1.08-3.30) and 1.37 (1.00-1.87) during 10 and 22 years, respectively The corresponding HRs for cardiovascular mortality during 10 and 22 years were 2.67 (1.35-5.29) and 1.73 (1.19-2.53), respectively, for age-adjusted and 2.30 (1.03-5.12) and 1.39 (0.90-2.15), respectively, for multiple-adjusted HRs. A U-shaped association was observed between insulin and noncardiovascular mortality, multiple-adjusted HRs for lowest and highest versus middle AUC insulin quintiles were 1.85 (1.20-2.86) and 1.43 (0.91-2.24), respectively CONCLUSIONS: Hyperinsulinemia was associated with increased all-cause and cardiovascular mortality in Helsinki policemen independent of other risk factors, although these associations weakened with the lengthening of the follow-up period. The association of insulin with noncardiovascular mortality was U-shaped.

The homeostasis model in the San Antonio Heart Study.

OBJECTIVE: Both insulin resistance and decreased insulin secretion have been shown to predict the development of NIDDM. However, methods to assess insulin sensitivity and secretion are complicated and expensive to apply in epidemiological studies. The homeostasis model assessment (HOMA) has been suggested as a method to assess insulin resistance and secretion from the fasting glucose and insulin concentrations. However, this method has not been extensively evaluated, particularly in different ethnic groups. RESEARCH DESIGN AND METHODS: We applied the HOMA model to cross-sectional analyses of the San Antonio Heart Study (n = 2,465). RESULTS: HOMA insulin resistance (IR) was very strongly correlated with fasting insulin (r = 0.98) and HOMA beta-cell function (beta-cell) was moderately correlated with the 30-min increment in insulin concentration over the 30-min increment in glucose concentration (delta I30/delta G30) in an oral glucose tolerance test (OGTT) (r = 0.44). NIDDM was characterized by both high HOMA IR and low HOMA beta-cell function. In Mexican-Americans, HOMA IR in NIDDM subjects was 9.5 compared with 2.7 in normal glucose tolerance (NGT) subjects. In contrast, HOMA beta-cell function showed only small differences in Mexican-Americans (176 NIDDM; 257 NGT). However, the delta I30/delta G30 (pmol/mmol) showed much larger differences (75 NIDDM; 268 NGT). When modeled separately, impaired glucose tolerance (IGT) was characterized by high HOMA IR and high HOMA beta-cell function. However, when analyzed in the same regression model, high HOMA IR and low HOMA beta-cell function characterized subjects with IGT. These results were similar in both ethnic groups. Mexican-Americans had increased insulin resistance (as judged by both HOMA IR and fasting insulin) and insulin secretion (by HOMA beta-cell and delta I30/delta G30) relative to non-Hispanic whites. CONCLUSIONS: We conclude that HOMA provides a useful model to assess insulin resistance and beta-cell function in epidemiological studies in which only fasting samples are available and that, further, it is critical to take into account the degree of insulin resistance in assessing insulin secretion by the HOMA model.