BACKGROUND

Alcohol misuse is more common in persons with a family history of alcoholism (FH+) than in those with no such history (FH-). Among FH+, behavioral disinhibition and male sex seem to signal the presence of an increased risk.

METHODS

This study examined cognitive and behavioral characteristics of 175 nonabusing 18- to 30-year-olds, 87 FH+ and 88 FH-, who were further characterized by their degree of behavioral disinhibition using the Sociability scale of the California Personality Inventory. Working memory and decision making were tested using the Stroop Color-Word Test and the Iowa Gambling Task, a simulated card game.

RESULTS

Persons with a family history of alcoholism who were behaviorally disinhibited displayed significantly greater interference on the Stroop task than the other subgroups. On the Iowa Gambling Task, FH+ males, but not the females, were significantly more attentive to financial gains than other subgroups, and they had greater consistency in their choice behaviors.

CONCLUSIONS

Persons with a family history of alcoholism, in combination with behavioral disinhibition, appears to signal working memory deficits and in combination with male sex indicates an attraction to the rewarding aspects of a risk-taking challenge. These findings are not secondary to heavy exposure to alcohol or other drugs, but instead reflect intrinsic risk-related familial and personal characteristics of the subjects.

BACKGROUND

To explore relations between neuroimmune and neuroendocrine systems relative to posttraumatic stress disorder (PTSD) treatment, cortisol and cytokine changes in response to selective serotonin reuptake inhibitor (SSRI) and placebo treatment of chronic PTSD were assessed prospectively.

METHODS

Baseline measures of PTSD, depression, salivary 8 am and 4 pm cortisol, and serum interleukin-1beta (IL-1beta; pro-inflammatory) and soluble interleukin-2 receptors (IL-2R; cell-mediated immunity) were obtained for 58 PTSD and 21 control subjects. The PTSD subjects participated in a 10-week, double-blind treatment with citalopram (n = 19), sertraline (n = 18), or placebo (n = 7).

RESULTS

At baseline, PTSD subjects had significantly greater PTSD, depression, and IL-1beta and lower IL-2R levels than control subjects, with no group differences found for am or pm cortisol levels. Both SSRI groups' IL-1beta correlated negatively with IL-2R; neither cytokine correlated with cortisol levels. Treatment significantly lowered PTSD, depression, and IL-1beta levels and increased IL-2R for all groups to control subject levels. After treatment, both SSRI groups' IL-1beta correlated with an end cortisol measure (one negatively, one positively).

CONCLUSIONS

Our results support a complex relationship between neuroimmune and neuroendocrine systems with PTSD treatment. Implications of normalization of cytokine levels with effective SSRI treatment and placebo are discussed.

Cranberries, high in polyphenols, have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low-energy cranberry juice (Ocean Spray Cranberries, Inc, Lakeville-Middleboro, Mass) will decrease surrogate risk factors of cardiovascular disease, such as lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, participants identified with metabolic syndrome (n = 15-16/group) were assigned to 1 of 2 groups: cranberry juice (480 mL/day) or placebo (480 mL/day) for 8 weeks. Anthropometrics, blood pressure measurements, dietary analyses, and fasting blood draws were conducted at screen and 8 weeks of the study. Cranberry juice significantly increased plasma antioxidant capacity (1.5 ± 0.6 to 2.2 ± 0.4 μmol/L [means ± SD], P < .05) and decreased oxidized low-density lipoprotein and malondialdehyde (120.4 ± 31.0 to 80.4 ± 34.6 U/L and 3.4 ± 1.1 to 1.7 ± 0.7 μmol/L, respectively [means ± SD], P < .05) at 8 weeks vs placebo. However, cranberry juice consumption caused no significant improvements in blood pressure, glucose and lipid profiles, C-reactive protein, and interleukin-6. No changes in these parameters were noted in the placebo group. In conclusion, low-energy cranberry juice (2 cups/day) significantly reduces lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome.

BACKGROUND

Stressful early life experience may have adverse consequences in adulthood and may contribute to behavioral characteristics that increase vulnerability to alcoholism. We examined early life adverse experience in relation to cognitive deficits and impulsive behaviors with a reference to risk factors for alcoholism.

METHODS

We tested 386 healthy young adults (18 to 30 years of age; 224 women; 171 family history positive for alcoholism) using a composite measure of adverse life experience (low socioeconomic status plus personally experienced adverse events including physical and sexual abuse and separation from parents) as a predictor of performance on the Shipley Institute of Living scale, the Stroop color-word task, and a delay discounting task assessing preference for smaller immediate rewards in favor of larger delayed rewards. Body mass index (BMI) was examined as an early indicator of altered health behavior.

RESULTS

Greater levels of adversity predicted higher Stroop interference scores (F = 3.07, p = 0.048), faster discounting of delayed rewards (F = 3.79, p = 0.024), lower Shipley mental age scores (F = 4.01, p = 0.019), and higher BMIs in those with a family history of alcoholism (F = 3.40, p = 0.035). These effects were not explained by age, sex, race, education, or depression.

CONCLUSIONS

The results indicate a long-term impact of stressful life experience on cognitive function, impulsive behaviors, and early health indicators that may contribute to risk in persons with a family history of alcoholism.

OBJECTIVE

This study was conducted to determine the association between the characteristics of calf muscle hemoglobin oxygen saturation (StO(2)) and exercise performance in patients with intermittent claudication.

METHODS

The study comprised 39 patients with peripheral arterial disease limited by intermittent claudication. Patients were characterized on calf muscle StO(2) before, during, and after a graded treadmill test, as well as on demographic and cardiovascular risk factors, ankle-brachial index (ABI), ischemic window, initial claudication distance (ICD), and absolute claudication distance (ACD).

RESULTS

Calf muscle StO(2) decreased 72%, from 55% +/- 18% (mean +/- SD) saturation at rest to the minimum value of 17% +/- 19% saturation attained 459 +/- 380 seconds after the initiation of exercise. After exercise, recovery half-time of calf muscle StO(2) was attained at 129 +/- 98 seconds, whereas full recovery to the resting value was reached at 225 +/- 140 seconds. After adjusting for sex, race, and grouping according to the initial decline constant in calf muscle StO(2) during exercise, the exercise time to minimum calf muscle StO(2) was correlated with the ischemic window (r = -0.493, P = .002), ICD (r = 0.339, P = .043), and ACD (r = 0.680, P < .001). After treadmill exercise, the recovery half-time of calf muscle StO(2) was correlated with the ischemic window (r = 0.531, P < .001), ICD (r = -0.598, P < .001), and ACD (r = -0.491, P = .003).

CONCLUSIONS

In patients limited by intermittent claudication, shorter ICD and ACD values are associated with reaching a minimum value in calf muscle StO(2) sooner during treadmill exercise and with having a delayed recovery in calf muscle StO(2) after exercise.

Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis, is a significant health problem. It manifests in lower extremities as intermittent claudication, limb ischemia, or gangrene and other locations as stroke, renal failure, or mesenteric ischemia. Fontaine and Rutherford classifications are the 2 commonly used classifications to stage the severity of PAD. The diagnostic tools include ankle-brachial index, a valuable tool in diagnosing lower extremity PAD, and a treadmill test. Other useful diagnostic tools include the San Diego Claudication Questionnaire to screen patients for symptoms and imaging modalities such as duplex scan, angiogram, computer tomographic angiogram, and magnetic resonance angiogram. Medical management of PAD involves comprehensive care, including risk factor modification of etiologies predisposing to atherosclerosis. These involve using antiplatelet therapy with aspirin or clopidogrel, controlling hypertension, managing hypercholesterolemia, and using vasodilators such as cilostazol. Exercise rehabilitation is an efficacious approach to improve intermittent claudication and should be recommended to each patient. Revascularization therapy is indicated for those who have critical limb ischemia or severe claudication not improved by medical management. Revascularization consists of endovascular techniques to open up the vessel and traditional bypass surgery to bypass the diseased segment. Recent published guidelines detailing recommendations on different treatment modalities in patients with PAD are described.

BACKGROUND

Pericyte loss is a cardinal feature of early diabetic retinopathy. We previously reported that highly oxidized-glycated low density lipoprotein (HOG-LDL) induces pericyte apoptosis in vitro. In this study, we investigated the role of the mitogen-activated protein kinase (MAPK) signaling pathways in HOG-LDL-induced apoptosis in human pericytes.

METHODS

Human retinal capillary pericytes (HRCP) were exposed to native LDL (N-LDL) and HOG-LDL, and apoptosis was measured using flow cytometry. Time- and dose-dependent responses of extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) following exposure to N-LDL or HOG-LDL were determined using western blotting. U0126 (ERK inhibitor), SB203580 (p38 inhibitor), and SP600125 (JNK inhibitor) were used to determine the role of MAPK signaling in HOG-LDL-induced apoptosis.

RESULTS

HOG-LDL induced apoptosis in HRCP in a dose-dependent manner at concentrations from 5 to 50 mg/l, with a constant effect from 50 to 200 mg/l. When compared to serum-free medium (SFM), this effect of HOG-LDL was found to be significant at all doses above 10 mg/l. In contrast, N-LDL at 200 mg/l did not induce apoptosis compared with SFM. Exposure to N-LDL versus HOG-LDL induced similar phosphorylation of ERK, p38, and JNK, peaking at 5 min, with similar dose-dependent responses up to 25 mg/l that were constant from 25 to 100 mg/l. Blocking of the ERK, p38, and JNK pathways did not inhibit pericyte apoptosis induced by HOG-LDL.

CONCLUSIONS

Our data suggest that apoptosis induced by HOG-LDL in HRCP is independent of the activation of MAPK signaling pathways.

OBJECTIVE

Matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitor of metalloproteinases (TIMPs), regulate important biological processes including the homeostasis of the extracellular matrix, proteolysis of cell surface proteins, proteinase zymogen activation, angiogenesis and inflammation. Studies have shown that their balance is altered in retinal microvascular tissues in diabetes. Since LDLs modified by oxidation/glycation are implicated in the pathogenesis of diabetic vascular complications, we examined the effects of modified LDL on the gene expression and protein production of MMPs and TIMPs in retinal pericytes.

METHODS

Quiescent human retinal pericytes were exposed to native LDL (N-LDL), glycated LDL (G-LDL) and heavily oxidised and glycated LDL (HOG-LDL) for 24 h. We studied the expression of the genes encoding MMPs and TIMPs mRNAs by analysis of microarray data and quantitative PCR, and protein levels by immunoblotting and ELISA.

RESULTS

Microarray analysis showed that MMP1, MMP2, MMP11, MMP14 and MMP25 and TIMP1, TIMP2, TIMP3 and TIMP4 were expressed in pericytes. Of these, only TIMP3 mRNA showed altered regulation, being expressed at significantly lower levels in response to HOG- vs N-LDL. Quantitative PCR and immunoblotting of cell/matrix proteins confirmed the reduction in TIMP3 mRNA and protein in response to HOG-LDL. In contrast to cellular TIMP3 protein, analysis of secreted TIMP1, TIMP2, MMP1 and collagenase activity indicated no changes in their production in response to modified LDL. Combined treatment with N- and HOG-LDL restored TIMP3 mRNA expression to a level comparable with that after N-LDL alone.

CONCLUSIONS

Among the genes encoding for MMPs and TIMPs expressed in retinal pericytes, TIMP3 is uniquely regulated by HOG-LDL. Reduced TIMP3 expression might contribute to microvascular abnormalities in diabetic retinopathy.

We compared apoptosis, cellular oxidative stress, and inflammation of cultured endothelial cells treated with sera from 130 patients with peripheral artery disease (PAD) and a control group of 36 patients with high burden of comorbid conditions and cardiovascular risk factors. Second, we compared circulating inflammatory, antioxidant capacity, and vascular biomarkers between the groups. The groups were not significantly different (P>> .05) on apoptosis, hydrogen peroxide, hydroxyl radical antioxidant capacity, and nuclear factor κ-light-chain enhancer of activated B cells. Circulating tumor necrosis factor α (TNF-α; P = .016) and interleukin 8 (IL-8; P = .006) were higher in the PAD group, whereas vascular endothelial growth factor A (VEGF-A; P = .023) was lower. The PAD does not impair the endothelium beyond that which already occurs from comorbid conditions and cardiovascular risk factors in patients with claudication. However, patients with PAD have lower circulating VEGF-A than the control group and higher circulating inflammatory parameters of TNF-α and IL-8.

The purpose of this study was to compare calf muscle hemoglobin oxygen saturation response during exercise between smokers and non-smokers with peripheral arterial disease. Patients limited by intermittent claudication who were smokers (n = 12) were compared with those who had not smoked (n = 28) for at least 1 year prior to investigation. Ankle/brachial index (ABI) measurements were obtained with Doppler ultrasound, and maximal calf blood flow was measured by venous occlusion plethysmography. Hemoglobin oxygen saturation (StO2) of the calf muscle, initial claudication distance (ICD), and absolute claudication distance (ACD) were obtained during a graded treadmill test. Smokers refrained from smoking on the morning of the test. Smokers had similar ABI values compared with non-smokers (0.70 +/- 0.26 vs 0.73 +/- 0.23 [mean +/- SD]; p = 0.808), whereas the smokers had lower values for maximal calf blood flow (8.71 +/- 5.76 %/min vs 11.48 +/- 4.46 %/min; p = 0.038), ICD (122 +/- 123 m vs 243 +/- 177 m; p = 0.023), and ACD (284 +/- 170 m vs 452 +/- 263 m; p = 0.023). Additionally, smokers had lower calf muscle StO2 values at the end of 1 minute (16 +/- 15% vs 37 +/- 19%; p = 0.002) and 2 minutes of exercise (16 +/- 16% vs 35 +/- 25%; p = 0.008), and at the occurrence of ICD (17 +/- 17% vs 32 +/- 23%; p = 0.033) and ACD (16 +/- 16% vs 32 +/- 24%; p = 0.024). After adjusting for blood flow, calf muscle StO2 values remained lower in the smokers (p < 0.05). Finally, calf muscle StO2 at the end of the first minute of exercise was related to ICD (r = 0.611, p < 0.001) and ACD (r = 0.443, p < 0.01). In conclusion, smokers limited by intermittent claudication have lower calf muscle StO2 during exercise than nonsmokers, and lower StO2 during exercise is associated with shorter ICD and ACD.

The use of hormonal contraception (HC) may affect salivary cortisol levels at rest and in response to a pharmacological or stress challenge. Therefore, the current study used a secondary data analysis to investigate the effect of HC on salivary cortisol levels in response to the mu-opioid receptor antagonist naltrexone and a psychosocial stressor, and also across the diurnal curve. Two hundred and nine women (n=72 using hormonal contraception; HC+) completed a two-session stress response study that consisted of a stress day, in which they were exposed to public speaking and mental arithmetic, and a rest day, in which unstimulated cortisol levels were measured to assess the diurnal rhythm. A subset of seventy women (n=24 HC+) also completed a second study in which they were administered oral naltrexone (50mg) or placebo in a randomized, placebo-controlled, double blind fashion. Women who were HC+ had a significantly reduced salivary cortisol response to both the psychosocial stressor (p<0.001) and naltrexone (p<0.05) compared to HC- women. Additionally, HC+ women had a significantly altered morning diurnal cortisol rhythm (p<0.01), with a delayed peak and higher overall levels. The results of the current study confirm that HC attenuates salivary cortisol response to a psychosocial stressor and mu-opioid receptor antagonism, and also alters the morning diurnal cortisol curve.

Blood pressure (BP) and cardiovascular hemodynamics were assessed at baseline and after caffeine administration in a 4-week, placebo-controlled, double-blind, randomized, crossover trial of caffeine tolerance formation. Half of the subjects developed tolerance to the pressor effect of caffeine, whereas the other half continued to show increases in BP after caffeine ingestion (F = 16.7, p <0.0001). In the subjects who did not develop tolerance, peripheral resistance increased incrementally as the daily dose of caffeine increased (F = 2.8, p = 0.05).

The study goals were to (1) establish the variability in postprandial glucose control in healthy young people consuming a mixed meal and, then (2) determine the acute and residual impact of a single exercise bout on postprandial glucose control. In study 1, 18 people completed two similar mixed meal trials and an intravenous glucose tolerance test (IVGTT). There were strong test-retest correlations for the post-meal area under the curve (AUC) for glucose, insulin, and Cpeptide (r = 0.73-0.83) and the Matsuda insulin sensitivity index (ISI, r = 0.76), and between meal and IVGTT-derived ISI (r = 0.83). In study 2, 11 untrained young adults completed 3 trials. One trial (No Ex) was completed after refraining from vigorous activity for ≥3 days. On the other 2 trials, a 45-min aerobic exercise bout was performed either 17-hours (Prior Day Ex) or 1-hour (Same Day Ex) before consuming the test meal. Compared to No Ex and Prior Day Ex, which did not differ from one another, there were lower AUCs on the Same Day Ex trial for glucose (6%), insulin (20%) and C-peptide (14%). Thus, a single moderate intensity exercise session can acutely improve glycemic control but the effect is modest and short-lived.

Differences across fields and experience levels are frequently considered in discussions of ethical decision-making and ethical behavior. In the present study, doctoral students in the health, biological, and social sciences completed measures of ethical decision-making. The effects of field and level of experience with respect to ethical decision-making, metacognitive reasoning strategies, social-behavioral responses, and exposure to unethical events were examined. Social and biological scientists performed better than health scientists with respect to ethical decision-making. Furthermore, the ethical decision-making of health science students decreased as experience increased. Moreover, these effects appeared to be linked to the specific strategies underlying participants' ethical decision-making. The implications of these findings for ethical decision-making are discussed.

Despite the fact that numerous major public health problems have plagued American Indian communities for generations, American Indian participation in health research traditionally has been sporadic in many parts of the United States. In 2002, the University of Oklahoma Health Sciences Center (Oklahoma City, Oklahoma) and 5 Oklahoma American Indian research review boards (Oklahoma City Area Indian Health Service, Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, and Choctaw Nation) agreed to participate collectively in a national research trial, the Treatment Options for Type 2 Diabetes in Adolescence and Youth (TODAY) Study. During that process, numerous lessons were learned and processes developed that strengthened the partnerships and facilitated the research. Formal Memoranda of Agreement addressed issues related to community collaboration, venue, tribal authority, preferential hiring of American Indians, and indemnification. The agreements aided in uniting sovereign nations, the Indian Health Service, academics, and public health officials to conduct responsible and ethical research. For more than 10 years, this unique partnership has functioned effectively in recruiting and retaining American Indian participants, respecting cultural differences, and maintaining tribal autonomy through prereview of all study publications and local institutional review board review of all processes. The lessons learned may be of value to investigators conducting future research with American Indian communities.

We compared plasma apolipoprotein profiles in subjects with peripheral artery disease (PAD) treated with statin medications (n = 21), subjects with PAD who are untreated with statins (n = 18), and control subjects (n = 70). Subjects were assessed on plasma apolipoproteins, medical history, physical examination, ankle-brachial index, and exercise performance using a treadmill test. The percentage of subjects with an abnormal value of apolipoprotein B (ApoB) (≥ 95 mg/dL) was 53% in the PAD group untreated with statins, 29% in the treated PAD group, and 13% in the controls (p < 0.001). The PAD group untreated with statins had higher values for ApoB (p < 0.001), triglycerides (p < 0.01), low-density lipoprotein (LDL)-cholesterol / high-density lipoprotein (HDL)-cholesterol ratio (p < 0.05), and glucose (p < 0.01) than the control group. In contrast, when the statin-treated PAD group was compared with controls, none of the variables were different except that the treated PAD group had lower LDL-cholesterol (p < 0.01) and higher glucose (p < 0.01). Furthermore, the PAD group treated with statins had lower ApoB (p < 0.01), triglycerides (p < 0.001), LDL-cholesterol (p < 0.05), LDL-cholesterol / HDL-cholesterol ratio (p < 0.05), and non-HDL-cholesterol (p < 0.05) than the untreated PAD group. In conclusion, subjects with PAD who are untreated with statin medications have higher levels of ApoB than controls, whereas subjects treated with statins have a more favorable risk profile, characterized by lower ApoB, LDL-C, LDL-C / HDL-C ratio, and non-HDL-C concentrations. Statin therapy may be efficacious for improving apolipoprotein profiles in subjects with PAD and intermittent claudication.

We compared the prevalence and management of metabolic syndrome (MetS) and its components in men and women with peripheral artery disease (PAD). A total of 70 men and 70 women with PAD were evaluated for presence of MetS. There was no significant gender difference in presence of MetS (P = .399) and the number of MetS components (P = .411). Among PAD patients with each MetS component, there was no significant gender difference in the use (P = .617) and number (P = .716) of blood pressure medications, the use (P = .593) and number (P = .591) of lipid-lowering medications, and the number (P = .155) of diabetic medications. Significantly more women were treated with diabetic medications compared with men (85 vs 57%, P = .026). The prevalence and management of MetS and its components was similar between men and women with PAD, except that more women were treated for diabetes. Patients with PAD having MetS did not receive optimal medical management.

BACKGROUND

Studies suggest that moderate drinking may benefit cognition and the effect may favor women. This study investigated effects of moderate drinking on visuospatial functioning in postmenopausal women. Visuospatial processes are sensitive to alcohol abuse and are thought to be sensitive to hormonal fluctuations. Three questions were posed in order to: explore visuospatial processes in moderate-drinking and abstaining postmenopausal women, assess visuospatial differences in women using no estrogen replacement therapy (No-ERT), ERT alone (ERT-only), and ERT with progestin (ERT+Pro), and identify alcohol/ERT interactions associated with visuospatial performance.

METHODS

Two hundred fourteen postmenopausal women participated (75 No-ERT; 63 ERT-only; 76 ERT+Pro. All were moderate drinkers or teetotalers and all received the Block Design test from the Wechsler Adult Intelligence Scale-Revised. A raw score was calculated and progress at 30-sec intervals was assessed.

RESULTS

ANOVA revealed an alcohol main effect [F(3,202) = 4.74; p < 0.004] on 60- to 120-sec change scores. Teetotalers had significantly smaller change scores (less improvement) compared with all levels of drinkers. ANOVA on design 9 (the most difficult trial) revealed an ERT main effect [F(3,202) = 4.37; p < 0.02]. ERT nonusers scored significantly lower than ERT-only and ERT+Pro groups. A design 9 trend toward an alcohol x ERT interaction was noted [F(6,202) = 1.93; p < 0.08], and a design 9 time x alcohol interaction was revealed [F(6,404) = 2.65; p < 0.02].

CONCLUSIONS

These data suggest that moderate drinking may be positively associated with visuospatial processes in postmenopausal women. They also suggest that ERT, alone and with progestin, is positively associated with visuospatial processes, but only when the task is difficult. These findings support Kaplan's assertion that subtle performance deficits may not be detectible with traditional endpoint measures. A provocative alcohol x ERT trend suggests that alcohol consumption should be considered in studies of ERT effects on cognitive ability.

We compared arterial elasticity in American Indian and Caucasian children, adolescents, and young adults, and we assessed whether demographic, body composition, and ambulatory activity measures were predictive of arterial elasticity within each group. Fifty-one American Indians and 66 Caucasians between the ages of 8 and 30 years were assessed on large artery elasticity index, small artery elasticity index, body fat percentage, and daily ambulatory activity during 7 consecutive days. American Indians had a higher percentage of body fat than Caucasians (p = 0.002), whereas daily ambulatory activity measures were similar (p>> 0.05). American Indians had a 16% lower large artery elasticity index (p = 0.007) and a 19% lower small artery elasticity index (p < 0.001) than Caucasians. The regression model for large artery elasticity index included average cadence (p = 0.001), fat-free mass (p < 0.001), age component (Caucasian only) (p < 0.001), and sex (p = 0.025). The regression model for small artery elasticity index included fat-free mass (p < 0.001), maximum cadence for 30 continuous minutes (p = 0.009), race (p = 0.005), and average cadence (p = 0.049). Between 8 and 30 years of age, elasticity means for the large and small arteries is lower in American Indians than in Caucasians. A smaller difference was observed in children, with a trend to a much larger difference in young adults. Furthermore, greater fat-free mass and higher daily ambulatory cadence are associated with higher arterial elasticity in both American Indians and Caucasians.

BACKGROUND

In nondiabetic pregnancy, cross-sectional studies have shown associations between maternal dyslipidemia and preeclampsia (PE). In type 1 diabetes mellitus (T1DM), the prevalence of PE is increased 4-fold, but prospective associations with plasma lipoproteins are unknown.

OBJECTIVE

The aim of this study was to define lipoprotein-related markers and potential mechanisms for PE in T1DM.

METHODS

We conducted a multicenter prospective study in T1DM pregnancy.

METHODS

We studied 118 T1DM women (26 developed PE, 92 remained normotensive). Subjects were studied at three visits before PE onset [12.2 ± 1.9, 21.6 ± 1.5, and 31.5 ± 1.7 wk gestation (means ± SD)] and at term (37.6 ± 2.0 wk). Nondiabetic normotensive pregnant women (n = 21) were included for reference.

METHODS

Conventional lipid profiles, lipoprotein subclasses [defined by size (nuclear magnetic resonance) and by apolipoprotein content], serum apolipoproteins (ApoAI, ApoB, and ApoCIII), and lipolysis (ApoCIII ratio) were measured in T1DM women with and without subsequent PE.

RESULTS

In women with vs. without subsequent PE, at the first and/or second study visits: low-density lipoprotein (LDL)-cholesterol, particle concentrations of total LDL and large (but not small) LDL, serum ApoB, and ApoB:ApoAI ratio were all increased (P < 0.05); peripheral lipoprotein lipolysis was decreased (P < 0.01). These early differences remained significant in covariate analysis (glycated hemoglobin, actual prandial status, gravidity, body mass index, and diabetes duration) but were not present at the third study visit. High-density lipoprotein and very low-density lipoprotein subclasses did not differ between groups before PE onset.

CONCLUSIONS

Early in pregnancy, increased cholesterol-rich lipoproteins and an index suggesting decreased peripheral lipolysis were associated with subsequent PE in T1DM women. Background maternal lipoprotein characteristics, perhaps masked by effects of late pregnancy, may influence PE risk.

Type 1 diabetes (T1D) is a risk factor for cardiovascular disease. However, it is unclear whether increased body weight amplifies that risk in T1D patients. This is a cross-sectional study examining the presence of cardiovascular risk factors in normal and overweight children, both with and without T1D. Sixty-six children (aged 16±2.2 years) were included in one of the following groups: (T1D and normal weight, T1D and overweight, healthy and normal weight, and healthy and overweight). A fasting blood sample was analyzed for lipid profile (triglyceride, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), apolipoprotein B (apoB), and apolipoprotein C-III (apoC-III) levels. Body composition was determined by dual energy x-ray absorptiometry and vascular elasticity by HDI/Pulsewave CR-2000 (Hypertension Diagnostics, Eagan, MN). Statistical analyses examined the effect of T1D and body weight status and their interactions on cardiovascular risk parameters. In this study, the authors were unable to demonstrate an additive effect of body weight status and T1D on cardiovascular risk profile. However, subgroup analysis of patients with T1D revealed higher apoC-III levels in overweight patients with T1D (P=.0453) compared with normal-weight diabetic children. Most notably, there was a direct relationship of small artery elasticity to body weight status. This seemingly paradoxical observation supports recent data and warrants further investigation.

OBJECTIVE

This study examined parental factors associated with outcomes of youth in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial.

METHODS

Of 699 youth with type 2 diabetes in the TODAY cohort, 623 (89.1%) had a parent participate and provide data at baseline, including weight, HbA1c, blood pressure, symptoms of depression, binge eating (BE), and medical history. Youth were followed 2-6.5 years. Data were analyzed using regression models and survival curve methods.

RESULTS

Parental diabetes (43.6% of parents) was associated with higher baseline HbA1c (P < 0.0001) and failure of youths to maintain glycemic control on study treatment (53.6% vs. 38.2% failure rate among those without a diabetic parent, P = 0.0002). Parental hypertension (40.6% of parents) was associated with hypertension in youth during TODAY (40.4% vs. 27.4% of youth with and without parental hypertension had hypertension, P = 0.0008) and with higher youth baseline BMI z scores (P = 0.0038). Parents had a mean baseline BMI of 33.6 kg/m(2). Parental obesity (BMI >30 kg/m(2)) was associated with higher baseline BMI z scores in the youth (P < 0.0001). Depressive symptoms in parents (20.6% of parents) were related to youth depressive symptoms at baseline only (P = 0.0430); subclinical BE in parents was related to the presence of subclinical BE (P = 0.0354) and depressive symptoms (P = 0.0326) in youth throughout the study period.

CONCLUSIONS

Parental diabetes and hypertension were associated with lack of glycemic control, hypertension, and higher BMI z scores in youth. Further research is needed to better understand and address parental biological and behavioral factors to improve youth health outcomes.

Peripheral artery disease (PAD) is associated with exercise impairment and greater thrombotic risk. We investigated whether clot formation and platelet aggregation assessed by thromboelastography and light-transmission aggregometry correlate with the severity of symptomatic PAD assessed by ambulatory function measures. We studied 40 symptomatic patients with PAD in whom severity of disease was assessed using ankle-brachial index, peak walking time (PWT), claudication onset time, peak oxygen uptake, daily ambulatory activity, and walking impairment questionnaire (WIQ) scores. Clot strength correlated negatively with peak oxygen uptake, PWT, WIQ distance, and stair-climbing scores. Time to clot formation did not correlate with exercise parameters. Platelet aggregation was negatively correlated with WIQ distance score and was positively correlated with PWT and peak oxygen uptake. In conclusion, clot strength and platelet aggregation correlated with objective and self-perceived ambulatory measures. Patients with PAD having more severe walking impairment may be likely to form stronger clots.