Moderate Cardiorespiratory Fitness Is Positively Associated With Resting Metabolic Rate in Young Adults

ObjectiveTo determine whether moderate cardiorespiratory fitness (CRF) or moderate to vigorous physical activity (MVPA) is associated with elevations in resting metabolic rate (RMR) similar to findings previously observed in endurance athletes.Participants and MethodsUsing a cross-sectional design, we measured CRF, RMR, body composition, energy expenditure, and time in MVPA via an arm-based activity monitor in 423 young adults (mean age, 27.6 years). Based on the results of a fitness test, participants were classified into CRF tertiles (low, moderate, or high) by sex.ResultsThere were significant differences among the low-, moderate-, and high-CRF groups for mean ± SD body mass index (calculated as the weight in kilograms divided by the height in meters squared) (28.1±4.1, 25.1±3.4, and 23.6±2.5, respectively; P<.001) and fat mass (28.8±9.7, 20.5±8.2, and 14.8±6.5 kg, respectively; P<.001) but not fat-free mass (53.1±11.5, 53.5±12.4, and 54.7±12.1 kg, respectively; P=.49). There were no differences in mean ± SD unadjusted RMR among the groups (1533.2±266.2, 1519.7±267.6, and 1521.9±253.9 kcal/d, respectively). However, after statistical adjustment for differences in body composition, the moderate- and high-CRF groups had a higher RMR compared with low-CRF individuals by 39.7 and 59.9 kcal/d, respectively (P<.05). After further adjustment for MVPA, RMR was higher in the high-CRF group compared with the low-CRF group by 51.2 kcal/d (P<.05).ConclusionIn this large sample of young adults representing a range of CRF, there was a positive stepwise gradient in RMR across tertiles of CRF independent of body composition. Also, MVPA was independently associated with RMR, although this relationship was modest. These findings underscore the multidimensional role of CRF and MVPA on health.Trial Registrationclinicaltrials.gov Identifier: NCT01746186     

Postchallenge Hyperglycemia Is Positively Associated With Diabetic Polyneuropathy: The KORA F4 study

OBJECTIVE To assess the prevalence of distal sensorimotor polyneuropathy (DSPN) in an older population and to examine its relationship with prediabetes. RESEARCH DESIGN AND METHODS Glucose tolerance status was determined in 61- to 82-year-old participants (n = 1,100) of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 Survey (2006-2008). Clinical DSPN was defined as bilaterally impaired foot-vibration perception and/or foot-pressure sensation. RESULTS Prevalence of clinical DSPN was similar in subjects with known diabetes (22.0%) and subjects with combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (23.9%). Among prediabetic subgroups, IFG-IGT, but not isolated-IFG and -IGT, was associated with a higher risk of clinical DSPN, compared with normal glucose tolerance. A J-shaped association was observed between clinical DSPN and quartiles of 2-h postchallenge glucose, but not with fasting glucose and HbA(1c) levels. CONCLUSIONS Subjects with IFG-IGT and known diabetes had a similar prevalence of clinical DSPN. Elevated 2-h postload glucose levels appeared important for disease risk.     

Increased Trapezius Pain Sensitivity Is Not Associated With Increased Tissue Hardness

Fatiguing exercise can affect muscle pain sensitivity and muscle hardness, as seen with work-related neck and shoulder pain. Objective methods to assess muscle pain sensitivity are important because the reliability of manual assessment is generally poor. The aim of this study was (1) to compare coexistence of tender points identified by manual palpation and pressure algometry or hardness assessments and (2) to examine the influence of exercise on muscle pain sensitivity and hardness. Fourteen sites in the upper trapezius muscle were selected for assessments in 12 healthy subjects. Pressure pain thresholds and muscle hardness were examined by computer-controlled pressure algometry at baseline, immediately after static or dynamic exercise, and 20 minutes after static or dynamic exercise. Before recording of pressure pain thresholds, the trapezius muscle was examined for tender points by manual palpation. Two sites with low pressure pain thresholds were typical locations for tender points, and these were the least hard sites. However, manually detected tender points were often (29%) not colocalized with most sensitive sites according to the pressure algometry. A heterogeneous distribution of pressure pain sensitivity and muscle hardness was found in the upper trapezius. The short duration of exercise until exhaustion did not change muscle sensitivity or muscle hardness in asymptomatic muscles.PerspectiveThis study confirms clinical findings with heterogeniosity in pain sensitivity and hardness across the upper trapezius muscle. Developments of new techniques that objectively can identify tender points are important, but thus far, manual palpation is best clinical practice.     

Serum Cathepsin S Is Associated With Decreased Insulin Sensitivity and the Development of Type 2 Diabetes in a Community-Based Cohort of Elderly Men

OBJECTIVE

To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

RESEARCH DESIGN AND METHODS

Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

RESULTS

After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase −0.09 [95% CI −0.14 to −0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08–2.01], P = 0.01).

CONCLUSIONS

Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.Adipokines, inflammatory cytokines secreted from adiopose tissue, have been suggested to play a key role in the development of insulin resistance and diabetes (1). Cathepsin S is a potent cysteine protease that is highly expressed and secreted in adipose tissue of obese individuals (2) and has been suggested to be an important regulator of inflammatory activity (3). We thus hypothesized that cathepsin S levels would be involved in the early dysregulation of glucose and insulin metabolism before development of diabetes. Accordingly, we investigated the association between serum cathepsin S and the two major underlying causes of diabetes—impaired insulin sensitivity and impaired insulin secretion—in a community-based sample of elderly men without diabetes. In secondary analyses, we also investigated the longitudinal association between serum cathepsin S and the incidence of diabetes.     

Hormonal and Metabolic Factors Associated With Variations in Insulin Sensitivity in Human Pregnancy

OBJECTIVE

The objective of this study was to determine maternal hormonal and metabolic factors associated with insulin sensitivity in human pregnancy.

RESEARCH DESIGN AND METHODS

This was a prospective observational cross-sectional study of 180 normal pregnant women, using samples collected at the time of a blinded oral glucose tolerance test (OGTT) between 24 and 32 weeks'' gestation as an ancillary to the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The study was conducted at two public university teaching hospitals, Cleveland, Ohio, and Brisbane, Australia. Fasting maternal serum cholesterol, triglycerides, free fatty acids, insulin, leptin, tumor necrosis factor-α, placental growth hormone (PGH), insulin-like growth factors (IGFs) 1 and 2, and insulin-like growth factor binding proteins (IGFBPs) 1 and 3 were assayed. Correlation and multiple regression analyses were used to determine factors associated with maternal insulin sensitivity (IS) estimated using both OGTT-derived (IS_OGTT) and fasting (using the homeostasis model assessment [HOMA]; IS_HOMA) insulin and glucose concentrations.

RESULTS

Insulin sensitivity correlated (r = x and y for IS_OGTT and IS_HOMA, respectively) with fasting maternal serum leptin (−0.44 and −0.52), IGFBP1 (0.42 and 0.39), and triglycerides (−0.31 and −0.27). These factors were significantly associated with insulin sensitivity in multiple regression analyses (adjusted R² 0.44 for IS_OGTT and IS_HOMA). These variables explained more than 40% of the variance in estimates of insulin sensitivity.

CONCLUSIONS

Maternal hormonal and metabolic factors related to the placenta, adipose tissue, and the growth hormone axis are associated with the variation in insulin sensitivity seen during normal human pregnancy.The development of insulin resistance in pregnancy has been recognized for many years, but the causal mechanisms remain unclear. Ryan et al. (1) first demonstrated a 40% decrease in insulin sensitivity in women with gestational diabetes as compared with a control group at term. Later, Catalano at al. (2) confirmed these results describing longitudinal changes in insulin sensitivity and insulin response in women with normal glucose tolerance and gestational diabetes before and during pregnancy. Despite a general tendency to attribute whole-body insulin resistance in pregnancy to placental hormones (3), the precise contribution of various hormonal factors remains poorly defined. Human placental lactogen was an early candidate, although findings have been variable (4). Kirwan et al. (5) have suggested an important role for tumor necrosis factor (TNF)-α, whereas placental growth hormone (PGH) has been shown to induce insulin resistance in a mouse model (6) and to correlate with maternal glycemia in patients with diabetes (7). Our study was designed to further explore the maternal metabolic and hormonal correlates of insulin resistance in a healthy pregnant population. We hypothesized that factors in addition to placental hormones were associated with insulin resistance during normal pregnancy.     

Persistent Smoking After a Diagnosis of Lung Cancer Is Associated With Higher Reported Pain Levels

The purpose of this study was to evaluate the impact of smoking status after a diagnosis of lung cancer on reported pain levels. We conducted a telephone survey of patients with lung cancer identified from 4 participating sites between September 2004 and July 2006. Patients were asked to rate their usual pain level over the past week on a 0 to 10 rating scale on which 0 was “no pain” and 10 “pain as bad as you can imagine.” We operationally defined persistent smokers as patients who reported continuing to smoke after their lung cancer diagnosis. A logistic regression analysis was used to test the hypothesis that persistent smokers report higher usual pain levels than nonsmokers. Overall, 893 patients completed the survey. The majority (76%) was found to have advanced cancer (stages IIIb and IV). The mean age was 63 years (SD = 10). Seventeen percent of the patients studied were categorized as persistent smokers. The mean pain score for the study sample was 3.1 (SD = 2.7) and 41% reported moderate (4 to 6) or severe pain (7 to 10). A greater proportion of persistent smokers reported moderate or severe pain than nonsmokers or former smokers (P < .001). Logistic regression analysis revealed that smoking status was associated with the usual pain even after adjusting for age, perceived health status, and other lung cancer symptoms such as dyspnea, fatigue, and trouble eating. In conclusion, patients who continue to smoke after a diagnosis of lung cancer report higher levels of usual pain than nonsmokers or former smokers. More research is needed to understand the mechanisms that relate nicotine intake to pain and disease progression in late-stage lung cancer.PerspectiveThis article examines the relationship between pain and persistent smoking in patients with lung cancer. Although more research is needed to understand the mechanisms that relate nicotine intake to pain and disease progression, physicians can promote smoking cessation in patients with lung cancer to improve health and quality of life.     

Relationship of Insulin Sensitivity,Insulin Secretion,and Adiposity With Insulin Clearance in a Multiethnic Population: The Insulin Resistance Atherosclerosis Study

OBJECTIVE

We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance.

RESEARCH DESIGN AND METHODS

We measured insulin sensitivity index (S_I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study.

RESULTS

MCRI was positively related to S_I and negatively to AIR and adiposity across sex, race/ethnicity populations, and varying states of glucose tolerance, adiposity, and family history of diabetes. Differences in MCRI by race/ethnicity (lower in African Americans and Hispanics compared with non-Hispanic whites) and glucose tolerance were largely explained by differences in adiposity, S_I, and AIR.

CONCLUSIONS

Insulin sensitivity, insulin secretion, and adiposity are correlates of insulin clearance and appear to explain differences in insulin clearance by race/ethnicity and glucose tolerance status.Reduced insulin clearance has been demonstrated in experimental models of insulin resistance (1) and conditions associated with insulin resistance (2–5). Insulin clearance partially explains the variability of fasting insulin independently of the effect of insulin resistance, insulin secretion, adiposity, and plasma glucose (6). In response to their higher insulin resistance, minority populations have lower insulin clearance than non-Hispanic whites (4,5,7). In these studies, however, results were not adjusted for insulin resistance. Therefore, we aimed to examine insulin clearance across sex, race/ethnicity populations, and varying states of glucose tolerance in the Insulin Resistance Atherosclerosis Study (IRAS) (8).     

Copeptin,a Surrogate Marker for Arginine Vasopressin,Is Associated With Cardiovascular and All-Cause Mortality in Patients With Type 2 Diabetes (ZODIAC-31)

OBJECTIVE

Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim was to investigate whether copeptin is associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care.

RESEARCH DESIGN AND METHODS

Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationship of baseline copeptin with CV and all-cause mortality.

RESULTS

We included 1,195 patients (age 67 ± 12 years, 44% male). Median baseline copeptin concentration was 5.4 (interquartile range [IQR] 3.1–9.6) pmol/L. After a median follow-up of 5.9 (IQR 3.2–10.1) years, 345 patients died (29%), with 148 CV deaths (12%). Log₂ copeptin was associated with CV (hazard ratio 1.17 [95% CI 0.99–1.39]; P = 0.068) and all-cause mortality (1.22 [1.09–1.36]; P = 0.001) after adjustment for age, sex, BMI, smoking, systolic blood pressure, total cholesterol to HDL ratio, duration of diabetes, HbA_1c, treatment with ACE inhibitors and angiotensin receptor blockers, history of CV diseases, log serum creatinine, and log albumin to creatinine ratio; however, copeptin did not substantially improve risk prediction for CV (integrated discrimination improvement 0.14% [IQR −0.27 to 0.55%]) and all-cause mortality (0.77% [0.17–1.37%]) beyond currently used clinical markers.

CONCLUSIONS

We found copeptin to be associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. Intervention studies should show whether the high CV risk in type 2 diabetes can be reduced by suppression of vasopressin, for example by reducing salt intake.The prevalence of type 2 diabetes and its complications are increasing worldwide (1). One of the major complications in type 2 diabetes is cardiovascular disease (CVD), and CVD is the main cause of morbidity and mortality in this patient group (2).Arginine vasopressin (AVP), or antidiuretic hormone, is a hormone that exerts cardiovascular (CV) and renal effects (3). Several studies have reported that AVP levels are elevated in animals and patients with diabetes (4–7). Increased levels of AVP may have long-term deleterious effects. AVP acts through three different vasopressin receptors, the V_1a, V₂, and V₃ (or V_1b) receptors, which mediate vasoconstriction, stimulate water retention, and facilitate secretion of ACTH, respectively (3). High concentrations of plasma AVP are known to stimulate V_1a receptors preferentially (8), which may contribute to the CV complications in type 2 diabetes.Despite the pivotal role of AVP in CVD, technical difficulties related to AVP’s small size, short plasma half-life, and association with platelets in the circulation have hindered the large-scale clinical use of AVP as a biomarker (3,9,10). Vasopressin is synthesized from a polypeptide precursor that contains AVP, neurophysin II, and copeptin (3). Copeptin, or COOH-terminal proarginine vasopressin, is released in equimolar amounts to AVP during precursor processing and has been found to be a stable and sensitive surrogate marker for AVP (11,12).A recent study of Fenske et al. (8) showed copeptin levels to be strongly associated with CV events and mortality in patients with type 2 diabetes and end-stage renal disease. Copeptin was also found to be associated with CV events in patients with acute myocardial infarction and type 2 diabetes (13). To our knowledge, however, these associations have not been demonstrated for stable, ambulatory patients with type 2 diabetes. This is of particular interest, because it could point to a new modifiable system for treatment and prevention of CV events and mortality in type 2 diabetes (8,14). Our primary objective was to assess the association of baseline plasma copeptin level with CV and all-cause mortality in a population of patients with type 2 diabetes treated in primary care. Our secondary aim was to investigate the additional predictive value of copeptin for risk prediction of CV and all-cause mortality in patients with type 2 diabetes.     

Insulin Sensitivity Is an Important Determinant of Renal Health in Adolescents With Type 2 Diabetes

OBJECTIVE

Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease and is a major cause of mortality in type 2 diabetes. Insulin sensitivity is an important determinant of renal health in adults with type 2 diabetes, but limited data exist in adolescents. We hypothesized that measured insulin sensitivity (glucose infusion rate [GIR]) would be associated with early markers of DN reflected by estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in adolescents with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Type 2 diabetic (n = 46), obese (n = 29), and lean (n = 19) adolescents (15.1 ± 2.2 years) had GIR measured by hyperinsulinemic-euglycemic clamps. ACR was measured and GFR was estimated by the Bouvet equation (combined creatinine and cystatin C).

RESULTS

Adolescents with type 2 diabetes had significantly lower GIR, and higher eGFR and ACR than obese or lean adolescents. Moreover, 34% of type 2 diabetic adolescents had albuminuria (ACR ≥30 mg/g), and 24% had hyperfiltration (≥135 mL/min/1.73 m²). Stratifying ACR and eGFR into tertiles, adolescents with type 2 diabetes in the highest tertiles of ACR and eGFR had respectively lower GIR than those in the mid and low tertiles, after adjusting for age, sex, Tanner stage, BMI, and HbA_1c (P = 0.02 and P = 0.04). GIR, but not HbA_1c, LDL, or systolic blood pressure, was also associated with eGFR after adjusting for sex and Tanner stage (β ± SE: −2.23 ± 0.87; P = 0.02).

CONCLUSIONS

A significant proportion of adolescents with type 2 diabetes showed evidence of early DN, and insulin sensitivity, rather than HbA_1c, blood pressure, or lipid control, was the strongest determinant of renal health.     

Short Leg Length,a Marker of Early Childhood Deprivation,Is Associated With Metabolic Disorders Underlying Type 2 Diabetes: The PROMISE cohort study

OBJECTIVE

Short leg length, a marker of early childhood deprivation, has been used in studies of the association of early life conditions with adult chronic disease risk. The objective of this study was to determine the cross-sectional associations of leg length with measures of insulin sensitivity and β-cell function.

RESEARCH DESIGN AND METHODS

Subjects (n = 462) at risk for type 2 diabetes were recruited into the PROspective Metabolism and ISlet cell Evaluation (PROMISE) longitudinal cohort. Leg length was calculated from sitting and standing height at the 3-year clinical examination. Glucose tolerance status was determined using an oral glucose tolerance test. Insulin sensitivity was assessed using homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda insulin sensitivity index (ISI), while the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion sensitivity index 2 (ISSI-2) determined β-cell function. Multiple linear regression analysis was conducted, adjusting for covariates including age, sex, ethnicity, family history of diabetes, waist, and weight.

RESULTS

Leg length and leg-to-height ratio were significantly associated with HOMA-IR (β = −0.037, β = −10.49, respectively; P < 0.0001), ISI (β = 0.035, β = 8.83, respectively; P < 0.0001), IGI/IR (β = 0.021, P < 0.05; β = 7.60, P < 0.01, respectively), and ISSI-2 (β = 0.01, P < 0.03; β = 3.34, P < 0.01, respectively) after adjustment for covariates. The association of shorter leg length with lower insulin sensitivity was most evident for those with high waist circumferences.

CONCLUSIONS

Shorter legs were independently associated with lower insulin sensitivity and β-cell function, suggesting that early childhood deprivation may increase the risk of developing diabetes.Over 285 million individuals worldwide are afflicted with type 2 diabetes (1). The increasing prevalence of this condition and its associated comorbidities represent a significant public health concern. Type 2 diabetes is a complex, multifactorial disease characterized by a decrease in both β-cell function and insulin sensitivity, the underlying causes of which have not been fully elucidated. An emerging hypothesis in the study of the natural history of type 2 diabetes focuses on the role of early life deprivation (2); this hypothesis posits that environmental conditions such as poor nutrition, stress, and infection during early life compromise later adult health and increase the risk for chronic diseases.The period between 0 and 4 years of age is considered a nutritionally dependent phase of growth (3). During this period, growth occurs predominately in the head and the legs (4,5). Nutritional deprivation or stressful circumstances during this time period can interrupt growth, permanently affecting the development of the legs and other organs. Low socioeconomic status (SES) during childhood (6,7), low parental education (8,9), displacement during infancy because of war (10), not being breast-fed or having a lower energy intake during childhood (7) have been shown to be associated with shorter adult leg length, independent of birth weight (11). Thus, leg length may be a useful marker of early childhood conditions when studying the impact of early life deprivation on adult disease risk.A number of previous articles have reported inverse associations of leg length with type 2 diabetes prevalence and incidence (12–17), though there have been some inconsistencies in the literature (18,19). In addition, a limited number of investigations have evaluated the association of leg length with metabolic disorders underlying type 2 diabetes; while some studies found inverse relationships of leg length with insulin resistance (12,13,20,21), the findings have not been entirely consistent (19). Of note, these studies have used simpler, fasting-based measures of insulin resistance (i.e., homeostasis model assessment of insulin resistance [HOMA-IR]), with none using more detailed measures of insulin sensitivity or assessing β-cell function. The lack of information regarding associations with β-cell function, defined as the compensatory relationship between insulin secretion and sensitivity, is a particularly important limitation given the central role of this disorder in the pathogenesis of type 2 diabetes. In addition, there may be potential interactions between stature components and other risk factors, such as waist circumference (which reflects current adult metabolic status), that may highlight the match-mismatch between early and late life (2,22), although to our knowledge this has not been investigated in the literature. Therefore, the objectives of this study were to determine the associations of leg length with insulin sensitivity and β-cell function in adults at risk for type 2 diabetes and to test for potential interactions with other risk factors for type 2 diabetes (including waist circumference). We hypothesized that shorter leg length would be associated with poorer insulin sensitivity and β-cell function and that shorter legs and larger waist circumferences would display the poorest insulin sensitivity and β-cell function in this at-risk population.     

Abdominal Adiposity Is Associated With Elevated C-Reactive Protein Independent of BMI in Healthy Nonobese People

OBJECTIVE

There is debate over the most appropriate adiposity markers of obesity-associated health risks. We evaluated the relationship between fat distribution and high-sensitivity C-reactive protein (hs-CRP), independent of total adiposity.

RESEARCH DESIGN AND METHODS

We studied 350 people with abdominal adiposity (waist-to-hip ratio [WHR] ≥0.9 in male and ≥0.85 in female subjects) and 199 control subjects (WHR <0.9 in male and <0.85 in female subjects) matched for BMI and age. We measured hs-CRP and major cardiovascular risk factors.

RESULTS

Participants with abdominal adiposity had BMI similar to that in control subjects (24.8 ± 2.5 vs. 24.7 ± 2.2 kg/m², respectively), but significantly higher waist circumference (96.4 ± 6.0 vs. 83.3 ± 6.7 cm; P < 0.01) and WHR (1.07 ± 0.08 vs. 0.85 ± 0.05; P < 0.001). Compared with the control subjects, participants with abdominal adiposity had an adverse cardiovascular risk factor profile, significantly higher hs-CRP (1.96 ± 2.60 vs. 1.53 ± 1.74 mg/dl; P < 0.01), and a twofold prevalence of elevated CRP values (>3 mg/dl).

CONCLUSIONS

In nonobese people, moderate abdominal adiposity is associated with markers of subclinical inflammation independent of BMI.There is debate over the most appropriate adiposity markers of obesity-associated health risks. Large studies have shown that measures of abdominal adiposity, such as waist circumference and waist-to-hip ratio (WHR), are more closely associated with the risk of diabetes, cardiovascular disease, and death than BMI, which is a measure of general adiposity (1,2). The excess cardiometabolic risk associated with abdominal adiposity is only partly explained by established risk factors; additional less extensively explored mechanisms may include systemic low-grade inflammation (3). Indeed, high-sensitivity C-reactive protein (hs-CRP) is a powerful marker of cardiovascular risk despite normal cholesterol levels, thus expanding the indication for use of statins beyond hyperlipidemia, because these drugs lower both cholesterol and CRP levels (4). To assess the impact of abdominal adiposity on low-grade inflammation independent of BMI, we compared hs-CRP in people with or without abdominal adiposity but with the same BMI.     

Mechanisms of Impaired Endothelial Function Associated With Insulin Resistance

BACKGROUND: The insulin-resistant (IR) syndrome is causally related to hypertension and cardiovascular events; however, the underlying mechanism remains elusive. The current study was designed to determine (1) whether the IR syndrome causes vascular dysfunction and (2) whether insulin resistance alters the activity of the individual endothelium-derived relaxing factors. METHODS AND RESULTS: Insulin resistance was induced in Sprague-Dawley rats by a 4-week fructose-rich diet. Subsequently, mesenteric arteries ( approximately 250 μM) were removed from control and IR rats, and intraluminal diameter was used to assess vascular response to pharmacological probes. Studies with sodium nitroprusside showed that vascular relaxation did not differ between IR and control groups. In contrast, maximal vascular relaxation to acetylcholine (10(-9) to 10(-4) mol/L) in phenylephrine preconstricted arteries was decreased in the IR group (44 +/- 4%) versus control (89 +/- 5%) (P <.01). N-nitro-L-arginine (LNNA) pretreatment further impaired acetylcholine-induced maximal relaxation in the IR group from 44 +/- 4% to 12 +/- 3%; P <.01. In control rats, maximal relaxation was only slightly impaired by the addition of LNNA (89 +/- 5% to 68 +/- 6%; P <.05). The addition of indomethacin to acetylcholine did not affect maximal relaxation in either group. When potassium chloride (KCl) was used fro preconstriction, relaxation to acetylcholine in the IR group was similar to that found with phenylephrine preconstriction (41 +/- 4% v 44 +/- 4%, respectively); however, KCl preconstriction significantly decreased acetyolcholine-induced relaxation in control rats (89 +/- 5% to 43 +/- 5%; P >.01). CONCLUSION: Insulin resistance impairs endothelium-dependent relaxation in small mesenteric arteries. It appears that insulin resistance transforms the primary relaxant factor from endothelial-derived hyperpolarizing factor to nitric oxide. These findings suggest that hypertension and atherosclerosis associated with the IR syndrome are caused, at least in part, by endothelial dysfunction.     

Salivary Cortisol Release and Hypothalamic Pituitary Adrenal Axis Feedback Sensitivity in Fibromyalgia Is Associated With Depression But Not With Pain

Results on hypothalamicpituitary-adrenal (HPA) axis function in fibromyalgia are heterogeneous and studies that integrate psychological and biological mechanisms in the search for pathways to fibromyalgia are rare. The goal of the study was to evaluate cortisol release and HPA axis feedback regulation in fibromyalgia and its association with psychopathology and pain. Beneath assessment of pain thresholds and self-report of pain, salivary free cortisol release over the day before and after intake of 0.5 mg of dexamethasone was measured in 21 female patients with fibromyalgia and 26 control women. Depression was assessed by questionnaires and clinical interview. We found reduced feedback sensitivity and slightly enhanced cortisol release in patients with fibromyalgia compared with healthy control subjects. Post hoc analyses showed that these effects are exclusively found in those patients, who also had major depressive disorder. Patients with fibromyalgia had lower pain pressure threshold, whereas heat pain thresholds were comparable with control subjects. Pain pressure and heat pain thresholds were not associated with cortisol release. On the other hand measurements of affective pain experience and depression were positively correlated with salivary cortisol over the day. Our results support the hypotheses that HPA axis related alterations are associated with affective disturbances, for example, depression, in patients with fibromyalgia.     

Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort

OBJECTIVEWhereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of study participants across a wide range of age and insulin sensitivity.RESEARCH DESIGN AND METHODS[¹⁸F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 participants scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acid levels, C-reactive protein levels, HbA_1c, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling.RESULTSInsulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin-resistant participants BGU was enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with additional increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein and free fatty acid levels, sex, and HbA_1c were not associated with BGU.CONCLUSIONSIn this large cohort of participants of either sex across a wide range of age and insulin sensitivity, insulin sensitivity was the best predictor of BGU.     

Hypnotizability Is Associated With a Protective but Not Acquisitive Self-Presentation Style

Self-presentation refers to the behavioral strategies a person adopts to convey desired social images of oneself to other people. The Concern for Appropriateness Scale (CAS) measures a defensive and fearful social approach aimed at avoiding social threats whereas the Revised Self-Monitoring Scale (RSMS) measures an active and flexible social approach aimed at gaining power and status. In this study, a significant correlation was found between hypnotizability, as measured by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) scores and CAS (r = .43, p = .002) but not between hypnotizability and RSMS (r = .070, p = .631). These results suggest that a protective self-presentation style may incline certain individuals to cooperate with hypnotic suggestions.     

Adherence to the DASH Diet Is Inversely Associated With Incidence of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study

OBJECTIVE

The Dietary Approaches to Stop Hypertension (DASH) diet has been widely promoted; however, little is known about its impact on type 2 diabetes.

RESEARCH DESIGN AND METHODS

We evaluated the association of the DASH diet with incidence of type 2 diabetes among 862 participants of the Insulin Resistance Atherosclerosis Study (IRAS) who completed a 1-year food frequency questionnaire at baseline. Type 2 diabetes odds ratios (ORs) were estimated at tertiles of the DASH score.

RESULTS

An inverse association was observed in whites (tertile 2 vs. tertile 1, OR 0.66 [95% CI 0.29–1.48]) that became significant for the most extreme contrast (tertile 3 vs. tertile 1, 0.31 [0.13–0.75]), with adjustment for covariates. No association was observed in blacks or Hispanics (tertile 2 vs. tertile 1, 1.16 [0.61–2.18 ]; tertile 3 vs. tertile 1, 1.34 [0.70–2.58 ]).

CONCLUSIONS

Adherence to the DASH dietary pattern, which is rich in vegetables, fruit, and low-fat dairy products, may have the potential to prevent type 2 diabetes.The effectiveness of dietary and lifestyle modification approaches in the prevention of type 2 diabetes is well recognized. The American Diabetes Association Nutritional Recommendations emphasize moderate weight loss via modification of energy and fat intake and physical activity for primary prevention among high-risk individuals but do not provide specific information regarding a dietary pattern (1). The Dietary Approaches to Stop Hypertension (DASH) trial demonstrated that a dietary pattern rich in vegetables, fruit, and low-fat dairy products can reduce blood pressure (2) and has been widely promoted (3,4). To the best of our knowledge, the DASH dietary pattern has not been evaluated with respect to potential influence on diabetes development. Thus, the aim of our study was to evaluate the impact of adherence to the DASH diet on risk of type 2 diabetes in the multiethnic Insulin Resistance Atherosclerosis Study (IRAS).