Association between fear of hypoglycemia and physical activity in youth with type 1 diabetes: The SEARCH for diabetes in youth study.

BACKGROUND: Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. OBJECTIVES: To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. METHODS: A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. RESULTS: Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (ß (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA. CONCLUSIONS: In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought.

Product recovery of an enzymatically synthesized (-)-menthol ester in a deep eutectic solvent.

Deep eutectic solvents (DESs) have gained increased attention as alternative reaction media for biocatalysis in recent years. There are many investigations on biotransformations in a variety of DESs, but the purification of bioproducts from DES reaction mixtures has not yet been sufficiently addressed. The present study demonstrates a product recovery strategy from a DES reaction medium composed of (-)-menthol and dodecanoic acid. Since the DES is not formed by equimolar amounts of the substrates, but the eutectic point occurs at a 3:1 molar ratio, product isolation is an important task for effective biocatalytic process development, even if the limiting substrate is converted completely. Both DES compounds acted as substrates and reaction solvent in the lipase-catalyzed esterification to synthesize (-)-menthyl dodecanoate. The product (-)-menthyl dodecanoate ester was separated from the DES reaction mixture by a vacuum distillation step and a second esterification reaction can be performed with the recovered (-)-menthol.

Associations of coffee consumption with markers of liver injury in the insulin resistance atherosclerosis study.

BACKGROUND: Coffee consumption has been associated with reduced risk of developing type 2 diabetes mellitus (T2DM) however, the mechanism for this association has yet to be elucidated. Non-alcoholic fatty liver disease (NAFLD) characterizes and predicts T2DM yet the relationship of coffee with this disorder remains unclear. Our aim was to investigate the associations of coffee with markers of liver injury in 1005 multi-ethnic, non-diabetic adults in the Insulin Resistance Atherosclerosis Study. METHODS: Dietary intake was assessed using a validated 114-item food frequency questionnaire. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and fetuin-A were determined in fasting blood samples and the validated NAFLD liver fat score was calculated. Multivariate linear regression assessed the contribution of coffee to variation in markers of liver injury. RESULTS: Caffeinated coffee showed significant inverse associations with ALT (ß = -0.08, p = 0.0111), AST (ß = -0.05, p = 0.0155) and NAFLD liver fat score (ß = -0.05, p = 0.0293) but not with fetuin-A (ß = 0.04, p = 0.17). When the highest alcohol consumers were excluded, these associations remained (ALT ß = -0.11, p = 0.0037; AST ß = -0.05, p = 0.0330; NAFLD liver fat score ß = -0.06, p = 0.0298). With additional adjustment for insulin sensitivity, the relationship with ALT remained significant (ALT ß = -0.08, p = 0.0400; AST ß = -0.03, p = 0.20; NAFLD liver fat score ß = -0.03, p = 0.27). There were no significant associations of decaffeinated coffee with liver markers. CONCLUSIONS: These analyses indicate a beneficial impact of caffeinated coffee on liver morphology and/or function, and suggest that this relationship may mediate the well-established inverse association of coffee with risk of T2DM.

Incidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: the impact of clinical and therapeutic factors over time.

AIMS: To examine incidence density rate and correlates of incident diabetes mellitus in a cohort of HIV-infected individuals compared with matched non-HIV-infected persons. METHODS: Data were obtained from the South Carolina Medicaid system and the enhanced HIV/AIDS Reporting System surveillance database for persons ≥ 18 years of age who had been attended to during the period 1994 to 2011. Time-dependent proportional hazards analysis and marginal structural models were used to analyse the data. RESULTS: A total of 13 632 individuals (6816, 1:1 matched HIV-infected and non-HIV-infected persons; median age 39 years; 57% male) contributed 88 359 person-years of follow-up. Incidence rate of diabetes was higher in the non-HIV-infected group compared with the HIV-infected group (13.60 vs. 11.35 per 1000 person-years). Multivariable hazards analysis suggested a significantly lower risk of incident diabetes among HIV-infected persons treated with combination antiretroviral therapy compared with the matched non-HIV-infected persons (adjusted hazards ratio 0.55; 95% CI 0.46-0.65). Among HIV-infected persons, marginal structural modelling suggested a significantly higher risk of diabetes with cumulative exposure to protease inhibitors over the observation period (adjusted relative risk 1.35; 95% CI 1.03-1.78), but this association was not significant for exposure to non-nucleoside reverse transcriptase inhibitors. Overall, female gender, older age, non-white race/ethnicity, and pre-existing hypertension, dyslipidaemia, obesity and hepatitis C infection were associated with higher risk of diabetes incidence. CONCLUSIONS: HIV infection may not be independently associated with increased risk of diabetes. Among HIV-infected persons, exposure to protease inhibitor-based regimens may increase the risk of diabetes. Healthcare providers should make every effort to use combination antiretroviral therapy regimens with a better cardiometabolic profile.

Fish consumption, insulin sensitivity and beta-cell function in the Insulin Resistance Atherosclerosis Study (IRAS).

BACKGROUND AND AIMS: Previous research on the association between fish consumption and incident type 2 diabetes has been inconclusive. In addition, few studies have investigated how fish consumption may be related to the metabolic abnormalities underlying diabetes. Therefore, we examined the association of fish consumption with measures of insulin sensitivity and beta-cell function in a multi-ethnic population. METHODS AND RESULTS: We examined the cross-sectional association between fish consumption and measures of insulin sensitivity and secretion in 951 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Fish consumption, categorized as <2 vs. ≥2 portions/week, was measured using a validated food frequency questionnaire. Insulin sensitivity (S(I)) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Higher fish consumption was independently associated with lower S(I)-adjusted AIR (ß = -0.13 [-0.25, -0.016], p = 0.03, comparing ≥2 vs. <2 portions/week). Fish consumption was positively associated with intact and split proinsulin/C-peptide ratios, however, these associations were confounded by ethnicity (multivariable-adjusted ß = 0.073 [-0.014, 0.16] for intact proinsulin/C-peptide ratio, ß = 0.031 [-0.065, 0.13] for split proinsulin/C-peptide ratio). We also observed a significant positive association between fish consumption and fasting blood glucose (multivariable-adjusted ß = 2.27 [0.68, 3.86], p = 0.005). We found no association between fish consumption and S(I) (multivariable-adjusted ß = -0.015 [-0.083, 0.053]) or fasting insulin (multivariable-adjusted ß = 0.016 [-0.066, 0.10]). CONCLUSIONS: Fish consumption was not associated with measures of insulin sensitivity in the multi-ethnic IRAS cohort. However, higher fish consumption may be associated with pancreatic beta-cell dysfunction.

Guard cell anion channel SLAC1 is regulated by CDPK protein kinases with distinct Ca2+ affinities.

In response to drought stress, the phytohormone abscisic acid (ABA) induces stomatal closure. Thereby the stress hormone activates guard cell anion channels in a calcium-dependent, as well as -independent, manner. Open stomata 1 protein kinase (OST1) and ABI1 protein phosphatase (ABA insensitive 1) represent key components of calcium-independent ABA signaling. Recently, the guard cell anion channel SLAC1 was identified. When expressed heterologously SLAC1 remained electrically silent. Upon coexpression with Ca(2+)-independent OST1, however, SLAC1 anion channels appear activated in an ABI1-dependent manner. Mutants lacking distinct calcium-dependent protein kinases (CPKs) appeared impaired in ABA stimulation of guard cell ion channels, too. To study SLAC1 activation via the calcium-dependent ABA pathway, we studied the SLAC1 response to CPKs in the Xenopus laevis oocyte system. Split YFP-based protein-protein interaction assays, using SLAC1 as the bait, identified guard cell expressed CPK21 and 23 as major interacting partners. Upon coexpression of SLAC1 with CPK21 and 23, anion currents document SLAC1 stimulation by these guard cell protein kinases. Ca(2+)-sensitive activation of SLAC1, however, could be assigned to the CPK21 pathway only because CPK23 turned out to be rather Ca(2+)-insensitive. In line with activation by OST1, CPK activation of the guard cell anion channel was suppressed by ABI1. Thus the CPK and OST1 branch of ABA signal transduction in guard cells seem to converge on the level of SLAC1 under the control of the ABI1/ABA-receptor complex.

Associations between the intake of caffeinated and decaffeinated coffee and measures of insulin sensitivity and beta cell function.

AIMS/HYPOTHESIS: Although protective relationships between coffee consumption and type 2 diabetes mellitus have consistently been observed, few studies have examined the relationships between coffee consumption and underlying pathophysiological defects that characterise diabetes aetiology. The aim of this study was to explore the associations between caffeinated and decaffeinated coffee consumption and measures of insulin sensitivity and secretion. METHODS: The study population included 954 multi-ethnic non-diabetic adults from the Insulin Resistance Atherosclerosis Study (IRAS). Multiple regression analyses were performed to examine the cross-sectional relationships between caffeinated and decaffeinated coffee intake and insulin sensitivity and acute insulin response, measured by a frequently sampled intravenous glucose tolerance test, 2 h postload glucose measured by OGTT, fasting insulin, and proinsulin to C-peptide ratios. RESULTS: Caffeinated coffee intake was positively associated with insulin sensitivity (ß = 0.054; SE = 0.026; p = 0.04) and inversely related to 2 h postload glucose (ß = -0.37; SE = 0.10; p = 0.0003) in fully adjusted models. Caffeinated coffee intake was not associated with acute insulin response or proinsulin ratios. Decaffeinated coffee intake was inversely related to 2 h postload glucose (ß = -0.47; SE = 0.18; p = 0.0096) and positively related to acute insulin response (ß = 0.191; SE = 0.077; p = 0.0132). Decaffeinated coffee intake was inversely related to the ratios of both intact and split proinsulin to C-peptide (ß = -0.150; SE = 0.061; p = 0.0148; ß = -0.254; SE = 0.068; p = 0.0002, respectively). CONCLUSIONS/INTERPRETATION: In this cross-sectional study, caffeinated coffee was positively related to insulin sensitivity and decaffeinated coffee was favourably related to measures of beta cell function. These results provide pathophysiological insight as to how coffee could impact the risk of type 2 diabetes mellitus.

Optimization of solvent-free enzymatic esterification in eutectic substrate reaction mixture.

The Candida rugosa lipase catalyzed esterification of (-)-menthol and lauric acid (LA) was studied in a eutectic mixture formed by both substrates((-)-menthol:LA 3:1, mol/mol). No additional reaction solvent was necessary, since the (-)-menthol:LA deep eutectic solvent (DES) acts as combined reaction medium and substrate pool. Therefore, the esterification is conducted under solvent-free conditions. The thermodynamic water activity (aw) was identified as a key parameter affecting the esterification performance in the (-)-menthol:LA DES. A response surface methodology was applied to optimize the esterification conditions in terms aw, amount of C. rugosa lipase (mCRL) and reaction temperature. Under the optimized reaction conditions (aw = 0.55; mCRL =60 mg; T =45 °C), a conversion of 95 ± 1% LA was achieved (one day), the final (-)-menthyl lauric acid ester concentration reached 1.36 ± 0.04 M (2.25 days). The experimental product formation rate agreed very well with the model prediction.

Summering on the bank: Seasonal distribution and abundance of monkfish on Georges Bank.

The American monkfish is an important commercial species that is widely distributed across a range of depths and temperatures from North Carolina to southern Nova Scotia, including on Georges Bank. We examined changes in the seasonal distribution and relative abundance of monkfish in the scallop access areas in Closed Area I and Closed Area II on Georges Bank using catch data from a three-year seasonal scallop dredge survey. Over the course of the survey, more than 6,000 monkfish were caught and measured, and clear seasonal changes in monkfish abundance were documented. Monkfish catch peaked in the summer and early fall when they were caught across the entire survey area, while they were caught only in deeper waters at the edges of the bank in the winter. Monkfish relative abundance was modeled using a generalized linear mixed model with a Tweedie distribution, and the final model, with month, depth, and bottom temperature as fixed effects, effectively explained the seasonal shifts in the location and relative abundance of monkfish observed during this study. The results suggest that monkfish movements are driven by seasonal changes in bottom temperature. Management measures for monkfish are determined primarily based on data collected during the Northeast Fisheries Science Center bottom trawl surveys, yet this survey catches few monkfish, adding uncertainty to stock assessments. Our research indicates that increasing the use of dredge surveys to collect data on monkfish would be a positive step toward improving monkfish assessments. If monkfish movements are impacted by changes in thermal habitat, their distributions may shift in response to climate change, increasing the need for improved monkfish assessment strategies to effectively manage the species in the future.

Changeable camouflage: how well can flounder resemble the colour and spatial scale of substrates in their natural habitats?

Flounder change colour and pattern for camouflage. We used a spectrometer to measure reflectance spectra and a digital camera to capture body patterns of two flounder species camouflaged on four natural backgrounds of different spatial scale (sand, small gravel, large gravel and rocks). We quantified the degree of spectral match between flounder and background relative to the situation of perfect camouflage in which flounder and background were assumed to have identical spectral distribution. Computations were carried out for three biologically relevant observers: monochromatic squid, dichromatic crab and trichromatic guitarfish. Our computations present a new approach to analysing datasets with multiple spectra that have large variance. Furthermore, to investigate the spatial match between flounder and background, images of flounder patterns were analysed using a custom program originally developed to study cuttlefish camouflage. Our results show that all flounder and background spectra fall within the same colour gamut and that, in terms of different observer visual systems, flounder matched most substrates in luminance and colour contrast. Flounder matched the spatial scales of all substrates except for rocks. We discuss findings in terms of flounder biology; furthermore, we discuss our methodology in light of hyperspectral technologies that combine high-resolution spectral and spatial imaging.

Longitudinal changes in the dietary inflammatory index: an assessment of the inflammatory potential of diet over time in postmenopausal women.

BACKGROUND/OBJECTIVES: The dietary inflammatory index (DII) measured at one time point is associated with risk of several chronic diseases, but disease risk may change with longitudinal changes in DII scores. Data are lacking regarding changes in DII scores over time; therefore, we assessed changes in the DII in the Women's Health Initiative (WHI). SUBJECTS/METHODS: DII scores were calculated using data from repeated food frequency questionnaires in the WHI Observational Study (OS; n=76 671) at baseline and year 3, and the WHI Dietary Modification trial (DM; n=48482) at three time points. Lower DII scores represent more anti-inflammatory diets. We used generalized estimating equations to compare mean changes in DII over time, adjusting for multiple comparisons, and multivariable-adjusted linear regression analyses to determine predictors of DII change. RESULTS: In the OS, mean DII decreased modestly from -1.14 at baseline to -1.50 at year 3. In the DM, DII was -1.32 in year 1, -1.60 in year 3 and -1.48 in year 6 in the intervention arm and was -0.65 in year 1, -0.94 in year 3 and -0.96 in year 6 in the control arm. These changes were modified by body mass index, education and race/ethnicity. A prediction model explained 22% of the variance in the change in DII scores in the OS. CONCLUSIONS: In this prospective investigation of postmenopausal women, reported dietary inflammatory potential decreased modestly over time. Largest reductions were observed in normal-weight, highly educated women. Future research is warranted to examine whether reductions in DII are associated with decreased chronic disease risk.

Association of adherence to a Mediterranean diet with glycemic control and cardiovascular risk factors in youth with type I diabetes: the SEARCH Nutrition Ancillary Study.

BACKGROUND/OBJECTIVES: This study aimed to determine the association between a Mediterranean diet and glycemic control and other cardiovascular risk factors among youth with type I diabetes (TID). SUBJECTS/METHODS: Incident TID cases aged <20 years at diagnosis between 2002 and 2005 were included. Participants were seen at baseline (N=793), 1-year (N=512) and 5-year follow-up visits (N=501). Mediterranean diet score was assessed using a modified KIDMED index (mKIDMED). Multivariate linear regression and longitudinal mixed model were applied to determine the association between mKIDMED score and log-HbA1c, lipids, blood pressure (BP) and obesity. RESULTS: In cross-sectional analyses using baseline data, for individuals with the hemoglobin A1c (HbA1c) of 7.5%, a two-point higher mKIDMED score (1 s.d.) was associated with 0.15% lower HbA1c (P=0.02). A two-point higher mKIDMED score was associated with 4.0 mg/dl lower total cholesterol (TC) (P=0.006), 3.4 mg/dl lower low-density lipoprotein cholesterol (LDL-C) (P=0.004), 3.9 mg/dl lower non-high-density lipoprotein cholesterol (non-HDL-C) (P=0.004) and 0.07 lower LDL-C/HDL-C ratio (P=0.02). Using longitudinal data, a two-point increase in mKIDMED score was associated with 0.01% lower log-HbA1c (P=0.07), 1.8 mg/dl lower TC (P=0.05), 1.6 mg/dl lower LDL-C (P=0.03) and 1.8 mg/dl lower non-HDL-C (P=0.03) than would otherwise have been expected. HbA1c mediated ∼20% of the association for lipids in both cross-sectional and longitudinal models. An unexpected positive association between mKIDMED score and systolic BP was found among non-Hispanic white youth in cross-sectional analyses (P=0.009). Mediterranean diet was not associated with obesity. CONCLUSIONS: Mediterranean diet may improve glycemic control and cardiovascular health in TID youth.

Associations of short-term weight changes and weight cycling with incidence of essential hypertension in the EPIC-Potsdam Study.

The aim of this study was to examine the relationships of short-term weight gain, weight loss, and weight cycling on the odds of developing hypertension. Normotensive middle-aged German men and women (n=12,362) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study were assigned to categories of 2-year short-term weight changes that were self-reported to have occurred prior to recruitment into the study (gain only, loss only, weight cycling, stable). After 2 years of follow-up after recruitment, 180 cases of incident essential hypertension were identified. In logistic regression models, odds ratios were estimated for the associations between short-term weight changes and risk of developing hypertension. Obesity status (BMI>or=30 or BMI<30 kg/m2) modified the associations between short-term weight change and incidence of diagnosed hypertension. Among obese individuals, short-term weight gain occurring during the 2 years prior to recruitment (OR=2.79, 95% CI 1.19-6.56), weight loss (OR=6.74, 95% CI 2.58-17.6) and weight cycling (OR=4.29, 95% CI 1.55-11.9) were strongly positively associated with incident hypertension, adjusted for age and gender, compared to obese individuals with short-term stable weight. No significant associations between short-term weight changes and risk of diagnosed hypertension were detected among non-obese individuals. Short-term weight changes appeared to present strong risk factors for developing hypertension among obese individuals. The effect seen for weight cycling supports the hypothesis that weight cycling increases the risk of hypertension. The finding for short-term weight loss may be explained by subsequent weight regain and needs further investigation.

Production of fine chemicals using biocatalysis.

Presently, a large number of biotransformations are carried out on an industrial scale and are discussed in a fast increasing number of reviews. Besides this, a significant number of biotransformations have been investigated over the past year, from degrading to transforming and synthetic reactions. The development of more specific and stable biocatalysts, either isolated enzymes or whole cells, generated by the new methods of genetic engineering and improved by reaction engineering have led to new industrial biotransformations.

Augmented TNF-alpha and IL-10 production by primed human monocytes following interaction with oxidatively modified autologous erythrocytes.

The presence of dysfunctional/damaged red blood cells (RBCs) has been associated with adverse clinical effects during the inflammatory response. The aim of this study was to elucidate whether oxidatively modified, autologous RBCs modulate monocyte cytokine responses in humans. Monocyte tumor necrosis factor alpha (TNF-alpha) and IL-10 production was measured in whole blood from healthy volunteers using ELISA and flow cytometry. Oxidatively modified RBCs (15 mM phenylhydrazine, 1 h, OX-RBC) or vehicle-treated RBCs (VT-RBC) opsonized by autologous serum were administered alone or in combination with one of three priming agents: E. coli lipopolysaccharide (LPS, 0.2 ng/ml), zymosan A (1 mg/ml), or phorbol 12-myristate 13-acetate (PMA, 50 ng/ml). OX-RBC or VT-RBC alone did not result in the release of TNF-alpha or IL-10. LPS, zymosan, and PMA caused marked and dose-dependent increases in TNF-alpha and IL-10 production. Addition of OX-RBC augmented the LPS-, zymosan-, and PMA-induced TNF-alpha release by approximately 100%. OX-RBC augmented LPS- and zymosan-induced IL-10 release by 400-600%. Flow cytometry analyses showed that monocytes were responsible for TNF-alpha and IL-10 production in whole blood. The presence of OX-RBC alone increased the complexity of CD14+ monocytes but caused no cytokine production. LPS alone induced cytokine production without altering cell complexity. After the combined (OX-RBC+LPS) treatment, monocytes of high complexity were responsible for TNF-alpha production. The presence of mannose or galactose (at 10-50 mM) did not alter the observed augmentation of cytokine production by OX-RBC, suggesting that lectin receptors are not involved in the response. These studies indicate that the interaction between damaged autologous erythrocytes and monocytes has a major impact on the cytokine responses in humans. An augmented cytokine production by the mononuclear phagocyte system may adversely affect the clinical course of injury and infections especially in genetic or acquired RBC diseases or after transfusions.

Multiple metabolic syndrome is associated with lower heart rate variability. The Atherosclerosis Risk in Communities Study.

OBJECTIVE: To test at the population level whether people with multiple metabolic syndrome (MMS) disorders have reduced cardiac autonomic activity (CAA). RESEARCH DESIGN AND METHODS: We examined the association between the level of CAA and MMS disorders, at the degree of clustering and the segregate combination levels, using a random sample of 2,359 men and women aged 45-64 years from the biracial, population-based Atherosclerosis Risk in Communities (ARIC) Study. Supine resting 2-min beat-to-beat heart rate data were collected. High-frequency (HF) (0.15-0.35 Hz) and low-frequency (LF) (0.025-0.15 Hz) spectral powers, the ratio of LF to HF, and the SD of all normal R-R intervals (SDNN) were used as the conventional indices of heart rate variability (HRV) to measure CAA. The MMS disorders included hypertension, type 2 diabetes, and dyslipidemia. RESULTS: HRV indices were significantly lower in individuals with MMS disorders. The multivariable adjusted mean HF was 0.85 (beat/min)2 in subjects with all three MMS disorders, in contrast to 1.31 (beat/min)2 in subjects without any MMS disorder. At the segregated combination level, the multivariable adjusted means +/- SEM of HF were 1.34 +/- 0.05, 1.16 +/- 0.05, 1.01 +/- 0.17, and 1.34 +/- 0.05 (beat/min)2, respectively, for subjects without any MMS disorder, with hypertension only, with diabetes only, and with dyslipidemia only, and the means +/- SEM of HF were 0.93 +/- 0.04, 0.70 +/- 0.15, and 1.20 +/- 0.05 (beat/min)2, respectively, for subjects with diabetes and hypertension, diabetes and dyslipidemia, and hypertension and dyslipidemia. An increase in fasting insulin of 1 SD was associated with 88% higher odds of having a lower HF. The pattern of associations was similar for LF and SDNN. CONCLUSIONS: These findings suggest that MMS disorders adversely affect cardiac autonomic control and a reduced cardiac autonomic control may contribute to the increased risk of subsequent cardiovascular events in individuals who exhibit MMS disorders.

Elevated fasting insulin predicts incident hypertension: the ARIC study. Atherosclerosis Risk in Communities Study Investigators.

OBJECTIVE: The prospective association of insulin and hypertension has been under debate in the context of the development of the insulin resistance or multiple metabolic syndrome. We examined the predictive associations of fasting serum insulin with incident hypertension occurring alone or as part of the multiple metabolic syndrome. DESIGN: Analyses were restricted to 5221 middle-aged participants of the Atherosclerosis Risk in Communities Study cohort who were free of component disorders of the multiple metabolic syndrome (hypertension; diabetes; high triglycerides and/or low HDL cholesterol (dyslipidaemias)) at baseline. OUTCOME: A total of 1018 individuals developed hypertension, 801 in the absence of components of the metabolic syndrome and 217 in combination with diabetes or dyslipidaemias, between 1987 and 1993. RESULTS: Elevated fasting insulin (top quartile versus lowest quartile) was associated with overall incident hypertension in European Americans [hazard rate ratio (HRR) 2.0, 95% confidence interval (CI) 1.7-2.4] but the results were inconclusive in African Americans (HRR 1.3, 95% CI 0.9-1.8) after adjustment for age, gender and study centre. Among European Americans, body mass index and abdominal girth only partly explained the observed association. Elevated fasting insulin was more strongly predictive of hypertension occurring as a component of the multiple metabolic syndrome (HRR 2.4, 95% CI 1.5-3.9) than of hypertension occurring alone (HRR 1.3, 95% CI 1.0-1.7) adjusting statistically for age, gender, study centre, body mass index and abdominal girth. CONCLUSIONS: The results are consistent with the concept of an aetiological heterogeneity for hypertension and may explain previously reported inconsistent findings on the association of insulin with incident hypertension.

Development of the multiple metabolic syndrome in the ARIC cohort: joint contribution of insulin, BMI, and WHR. Atherosclerosis risk in communities.

PURPOSE: The natural history of the multiple metabolic syndrome (MMS) and its predictors has rarely been addressed in population samples. This study evaluated the predictive role of fasting serum insulin, body mass index (BMI), and waist-to-hip ratio (WHR) on the development of incident MMS components (diabetes, hypertension, and dyslipidemias) over the course of three years. METHODS: The study population comprised the cohort of middle-aged African American and European American men and women of the Atherosclerosis Risk in Communities Study (1987-1992). RESULTS: Among 6113 individuals free of MMS components at baseline, high insulin (> 14 microU/ ml) was independently predictive of the development of one or more MMS components (OR:1.5, 95% CI:1.2-1.8), as was a BMI > or = 30 (OR:1.7, 95% CI:1.4-2.0), and a high WHR (> 0.98) (OR:1.5, 95% CI:1.3-1.8) adjusting statistically for age, gender, and ethnicity/center. These associations were markedly stronger for combinations of MMS components (two or more) than for isolated components. CONCLUSIONS: The findings confirm earlier reports on the predictive role of insulin, BMI, and WHR, and suggest that these antecedent factors may be integral to the development of combinations of disorders, i.e., the particular clustering identified as the MMS.

Alcohol, blood pressure and hypertension.

In the last 30 years a large number of cross-sectional studies, a smaller number of prospective cohort studies and several intervention studies have addressed the alcohol-blood pressure relationship. Although a number of questions--such as the validity of measurement of alcohol intake, shape of the alcohol-blood pressure relationship, threshold dose for hypertension, and plausible pathophysiological mechanisms--have not yet been answered satisfactorily, it is clear that a causal association exists between chronic intake of > or = 30-60 g alcohol per day and blood pressure elevation in men and women. To call the alcohol-blood pressure relationship causal is justified because chance and, to a large degree, bias and confounding, have been ruled out as plausible explanations in most observational studies. More importantly, the intervention studies support the observational studies and show a remarkable consistency in demonstrating a potentially valuable decrease in blood pressure when heavy drinkers abstain or restrict their alcohol intake. From the different studies a rule of thumb can be derived: above 30 g of alcohol intake per day an increment of 10 g of alcohol per day increases on average systolic blood pressure by 1-2 mmHg and diastolic blood pressure by 1 mmHg.