Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010. / Härtill 3 uppsatser.

The purpose of this research was to evaluate the impact of glycemic measures, and changes in identified risk factors (BMI, waist circumference, lipids, blood pressure) on follow-up glycemia, in Pima children at high risk for type two diabetes (type 2 DM).I computed incidence and cumulative incidence of type 2 DM in Pima children 5-19 years of age between 1983 and 2004. Cox proportional hazards rates for development of type 2 DM were calculated by glycemic measure (HbA1C, 20PG, FPG) controlling for confounding factors (age, sex, BMI, blood pressure, and cholesterol). Diabetes was defined by the presence of at least one of four criteria: 1) 20PG of >200 mg/dl, 2) FPG of >126 mg/dl, 3) HbA1C > 8.0%, or 4) hypoglycemic treatment. Linear regression models were computed to identify the impact of changes in risk factors on changes in HbA1C. Only exams performed in non-diabetic children during childhood were included in the regression models.Among 2658 non-diabetic children, 258 cases of diabetes occurred during mean 9.1 years of follow-up (1.5 - 21.7). The age-sex adjusted incident rate of diabetes was 19.0 cases per 1000 person-years, and cumulative incidence was 54% by age 40. Incidence rates increased with increasing baseline values of 20PG, and FPG, but not for HbA1C. For HbA1C the relationship was u-shaped with the lowest and highest quartiles having the highest DM rates. After adjustment for confounding risk factors using Cox proportional hazards analysis, the risk for diabetes increased 2-fold for every 10 mg/dl increase in FPG. Changes in waist circumference best predicted changes in HbA1C (R2 = 0.48, Ï <0.001). However, the ability of waist circumference to predict change is limited due to the powerful effect of regression to the mean, suggesting that these risk factors contribute very little to changes in HbA1C, at least in childhood.Childhood levels of glycemia predict development of type 2 DM later in life. While changes in waist circumference are associated with only moderate changes in HbA1C, this does not refute the significant contribution of adiposity in childhood to the development of type 2 DM.

Insulin resistance (IR) and type 2 diabetes in Mexican American adolescents living along the United States (US)-Mexico border are linked to genetics, poverty, developmental characteristics, and psychological attributes. Understanding relationships among psychological attributes, health promoting behaviors (HPB) and IR markers addresses gaps in health promotion science that test relationships between lifestyle and biological outcomes.Hendricks' Perceptual Health Promotion Determinants Model provided theoretical underpinnings. The aims were to test the predictive ability of HPB and IR using psychological attributes (self-esteem, self-efficacy, and hope). Biological markers for IR included body mass index (BMI), waist circumference (WC), and Homeostasis Mathematical Assessment Model for Insulin Resistance (HOMA-IR).Forty five Mexican American adolescents (62% female; 16.4 [&plusmn;1.27] mean years) participated. The majority (60%) were obese (BMI &ge; 95th percentile) with 40% overweight (BMI &ge; 85th percentile), 45% with WC &ge; 95th percentile, and 76% with HOMA-IR &ge; 3.16.With self-efficacy for physical activity, 38% (R<super>2<super> = 0.3771; F = 8.27, df = 3; p < 0.002) of variance in HPB was explained by hope. With self-efficacy for nutrition fats/sodium, 44% (R<super>2<super> = 0.4382; F = 10.66; df = 3; p < .0001) of variance in HPB was explained by self-efficacy for nutrition fats/sodium and hope. With self-efficacy for nutrition fruits/vegetables, 49% (R<super>2<super> = 0.4894; F = 13.10; df = 3; p <.0001) of variance in HPB was explained by self-efficacy for nutrition fruits/vegetables and hope.Additionally, with IR reflected as WC, 21% (R<super>2<super> = 0.2129; F = 2.71; df = 4; p = 0.0437) of variance was explained by self-esteem and self-efficacy for physical activity. With IR reflected as HOMA-IR, 22% (R<super>2<super> = 0.2214; F = 2.84; df = 4; p = 0.0364) of variance was explained by self-efficacy for physical activity and 23% (R<super>2<super> = 0.2254; F = 2.91; df = 4; p = 0.0333) of variance was explained by self-efficacy for nutrition fruits/vegetables. Evidence supports using hope and self-efficacy to test interventions to increase HPB and decrease IR in adolescents residing along the US-Mexico border region.

Motivation: The metabolic syndrome is characterized by a group of risk factors for cardiovascular disease (CVD) that includes obesity, dyslipidemia, high blood pressure, insulin resistance, glucose intolerance or non-insulin dependant diabetes mellitus, pro-thrombotic state and pro-inflammatory state. The NHANES I11 study showed the prevalence of this syndrome to be 24.0% in men and 23.4% in women in the USA. These figures translate to more than 47 million US residents having the metabolic syndrome. In the THUSA (acronym for Transition and Health in the Urbanization of South Africans) study in South Africa it was found that 12% and 28.4% of men and women, respectively, of the black population of the North West Province had three or more disturbances characterizing this syndrome. Therefore, it is evident that the metabolic syndrome is a health problem not only for developed countries but also for developing countries. As a result, this syndrome has been identified as a target for dietary therapies to reduce the risk of CVD and type 2 diabetes. Epidemiological studies have consistently demonstrated an inverse association between nut consumption and coronary heart disease (CHD) morbidity and mortality in different population groups. Nut consumption may not only offer protection against heart disease, but also increase longevity. Recently, the benefits of nuts consumption were acknowledged by the U.S. Food and Drug Administration when they approved a qualified health claim that eating nuts (1.5 ounces/day ≈ 42.8 g/day) may reduce the risk of CHD. In this regard, the most comprehensively studied mechanism involved the favourable lipid lowering effects of nuts. There is, however, a lack of data in the literature regarding the effect of nuts on the metabolic syndrome. Objective: The main objective of this study was to examine the effects of a high walnut diet and a high unsalted cashew nut diet on markers of the metabolic syndrome in humans. In order to provide a foundational body of evidence for the aforementioned, a secondary objective included conducting a systematic review that investigates the effects of nuts on the lipid profile. Methods: The main project consisted of a controlled feeding trial with a parallel, randomized controlled study design on participants having the metabolic syndrome. Sixty-four subjects having this syndrome (29 men, 35 women) with a mean (±SD) age of 45±10 y and who met with the selection criteria were all fed a 3-week run-in control diet. After this period, participants were grouped according to gender and age and then randomized into three groups, namely, those that received a controlled feeding diet including walnuts (20% energy (E), 60-100g/day; protein:carbohydrate:fat=18:42:40%E). or unsalted cashew nuts (20%E 66- 1 15g/day; protein:carbohydrate:fat=l9:44:37%E) or no nuts (protein:carbohydrate:fat=20:47:33%E) for 8 weeks. The participants' physical activity and weight were maintained for the duration of the study. For the systematic review. human intervention trials that investigated the independent effects of nuts on lipid concentrations were included. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The main outcome measures for the systematic review, were percentage differences between treatment and control groups for total blood cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDL-C) and triacyglycerols (TG). Results: Regarding the main objective, we found that both the walnut and unsalted cashew nut intervention diets had no significant effect on the lipid profile, serum fructosamine, insulin, insulin sensitivity, insulin resistance, serum high sensitivity C-reactive protein, blood pressure and serum uric acid concentrations when compared to the control dict. All three groups experienced highly significant increases in serum insulin concentrations when comparing the baseline to end (P<0.05). In turn, insulin resistance increased while insulin sensitivity decreased in all three groups. Plasma glucose concentrations increased significantly in the cashew nut group compared to the control group (P<0.05). By contrast, serum fructosamine was unchanged in the cashew nut group while the control group had significantly increased concentrations of this short-term marker of glycaemic control. The literature search for the systematic review yielded 41 5 publications. After screening, 23 nut studies were included in the review with most of these studies including heart-healthy diets. The majority of the studies were short (4-6 weeks) with only one study lasting 6 months. The number of subjects in most of the studies was sufficient to study the effects on TC and LDL-C but not for HDL-C and TG. The results of three almond (50-100g/day), two peanut (35-68g/day), one pecan nut (72g/day) and four walnut (40-84g/day) studies showed convincing evidence for a lipid lowering effect of TC between 2-1 6% and LDL-C between 2- 19%, when compared to their control diets. Currently, there are indications from inadequately designed intervention studies that hazelnuts (lg/day/kg body weight) and pistachios (20%E) may have a lipid lowering effect. At this stage the evidence for macadamia nuts is less convincing. Furthermore, it is apparent that the components in nuts further reduce TC and LDL-C concentrations beyond the effects predicted by equations based solely on dietary fatty acid profiles. Conclusions: In the controlled feeding trial, subjects displayed no improvement in the markers of the metabolic syndrome after following a walnut or unsalted cashew nut diet compared to a control diet while maintaining body weight (8 weeks). Finally, we suspect that the dramatic increase in insulin resistance may have masked the protective effects of the walnut and cashew nut diets in our subjects with the metabolic syndrome Further research is warranted before a consensus can be reached. From the systematic review it was concluded that the consumption of ≈50-100g (≈1.5-3.5 servings) of nuts five or more times/week as part of a heart-healthy diet with total fat content (high in mono- and /or polyunsaturated fatty acids) of ≈ 35% of energy may significantly decrease TC and LDL-C in normo- and hyperlipidemic individuals. Recommendations: A similar nut controlled feeding trial with some form of calorie restriction, should be done on participants having the metabolic syndrome. Future research should use randomized controlled studies with larger sample sizes and longer duration to investigate the effects of nuts on HDL-C and TG concentrations. Also, studies should investigate the effects on the lipid profile of mixed nuts and those individual nuts not yet considered. In addition, the unique nutrient and non-nutrient composition of nuts requires further research in order to elucidate the possible mechanisms responsible for the LDL-C lowering effect / Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2005.

This study determined if insulin resistance (IR), induced by an acute bout of eccentrically-biased contractions that resulted in muscle injury, was attenuated following a repeated bout of contractions. Female subjects (n = 10, age 24.7 ± 3.0 yr, weight 64.9 ± 7.4 kg, height 1.67 ± 0.02 m, body fat 29.1 ± 1.9 %) performed two 30 minute bouts of downhill treadmill running (DTR 1 and DTR 2, -12 % grade, 8.0 mph) separated by 14 days. Oral glucose tolerance tests (OGTT) were administered at baseline and 48 hours following DTR 1 and DTR 2, with IR assessed by calculation of insulin and glucose areas under the curve (AUC). Maximum isometric quadriceps strength (MVC), muscle soreness (SOR), and serum creatine kinase (CK) were assessed pre-, immediately post-, and 48 hours post-DTR 1 and DTR 2 to determine the presence of muscle injury. Compared to baseline OGTT, insulin and glucose AUC (37.6 ± 8.4 and 21.4 ± 4.7 % increase, respectively), and peak insulin (44.1 ± 5.1 vs. 31.6 ± 4.0 uU·mL-1) and glucose (6.5 ± 0.4 vs. 5.5 ± 0.4 mmol·L-1) were elevated following DTR 1. These same insulin and glucose measures showed no increase above baseline 48 hours following DTR 2 (p > 0.05). MVC was reduced to a greater degree immediately following DTR 1 (16.7 ± 2.6 vs. 8.6 ± 1.2 % decline) and, although demonstrating a significant degree of recovery, remained reduced by 9.4 ± 2.7 % 48 hours following exercise. In contrast, MVC made a full recovery back to baseline values 48 hours after DTR 2. SOR was elevated to a greater degree 48 hours following DTR 1 than after DTR 2 (48.08 ± 6.16 vs. 12.70 ± 3.24 mm). There was a tendency for an attenuated serum CK response 48 hours following DTR 2 (812.8 ± 365.1 vs. 162.5 ± 42.5 U·L-1, p = 0.08). In conclusion, a novel bout of eccentrically-biased contractions resulting in a moderate degree of muscle injury confers a protective effect, whereby a subsequent bout of contractions 14 days later results in complete elimination of the IR observed following the initial bout.

This thesis is an investigation of the interactions of insulin resistance (IR), metabolic markers, neutrophil function, and reproductive health in peripartum dairy cows, including the evaluation of a hand-held glucometer for diagnosis of IR. The neutrophil functions of interest were oxidative burst and phagocytosis capacity, and reproductive diseases were endometritis and cervicitis. A total of 81 Holstein cows were enrolled 3 wk prior to expected calving date from November 2010 until October 2011, and were followed until 5 wk postpartum. Known markers of IR, neutrophil function, and disease were monitored through this period. The hand-held glucometer was identified as a useful alternative to laboratory measurements of glucose. Markers of IR influenced phagocytosis capacity and reproductive disease. High haptoglobin concentrations were associated with increased risk of reproductive disease and diminished oxidative burst function. Metabolically related inhibition of neutrophil function may be important in development of reproductive disease. / National Sciences and Engineering Research Council of Canada, Ontario Graduate Scholarship Program

In recent years, studies have revealed a central role for the intestine in regulation of lipid homeostasis and development of insulin resistance and type-2 diabetes. The function of intestinal Scavenger Receptor Class-B type-I remains unknown, however it is believed to play a role in dietary lipid uptake. Recently, our laboratory demonstrated a correlation between intestinal SR-BI expression and chylomicron secretion. We hypothesized that intestinal SR-BI is involved in chylomicron secretion and contributes to chylomicron oversecretion in insulin resistance. I first characterized chylomicron production in healthy and insulin resistant Syrian golden hamsters. Inhibition of SR-BI resulted in reduced postprandial chylomicron accumulation in plasma, and resistance to diet-induced hyperlipidemia and weight-gain. Lower postprandial triglyceride levels were also observed in SR-BI-/- mice. In summary, these data demonstrate a key role for intestinal SR-BI in chylomicron secretion and control of lipid homeostasis, implicating intestinal SR-BI in chylomicron overproduction in insulin resistant states.

The primary objective of this research was to explore the impact of glucose ingestion on 2-back task performance (accuracy, discrimination, and reaction times (RT) to target), its relationship to neural activation, using functional magnetic resonance imaging, and potential modulation by insulin resistance (IR) and low density lipoprotein (LDL) in hypertensive but otherwise healthy older adults. While there was no effect of glucose ingestion on task performance or task-relevant neural activation patterns, this study uniquely observed that IR and LDL associated with all 3 measures of 2-back performance and task-relevant neural activation patterns. The left and right precuneus, left cingulate, and left insula were identified as task-associated regions according to our specific target minus nontarget contrast. Of particular importance was the task activation in the right precuneus as it both showed sensitivity to IR and predicted task RTs to targets, suggesting it plays a modulatory role linking IR to task performance.

While the excess accumulation of abdominal subcutaneous and visceral adipose tissue (abdominal SAT and VAT, respectively), is independently associated with increased health risk, the relative amount of lower body SAT is associated with an improved health profile. In contrast to the established metabolic benefit of reducing VAT and abdominal SAT, the first study in this thesis investigated whether loss of lower-body SAT during diet and/or exercise induced weight-reduction resulted in a deterioration of metabolic profile in a sample of obese men (n = 58) and women (n = 49). After control for potential confounders, reductions in VAT, abdominal and lower body SAT were all associated with improvements in certain metabolic risk factors. However, only reductions in VAT and abdominal SAT remained associated with improvement in risk factors independent of changes in other AT depots. Recently, it was suggested that a large breast size among women may predict type-II diabetes risk independent of body mass index (BMI) and waist circumference. While the mechanism is unknown, a large breast size may predict health risk by indicating fat deposition in ectopic depots such as VAT or inter-muscular AT (IMAT). The second study investigated the independent associations between breast volume with metabolic risk and regional fat distribution in 92 overweight or obese premenopausal women. Although breast volume was not significantly associated with metabolic risk, after control for age, BMI and waist circumference level, women with the highest breast volume had approximately 1.1 and 1.3 kg more VAT and IMAT, respectively, by comparison to women with the smallest breast volume. In contrast to the metabolic benefits of weight loss among metabolically-abnormal obese (MAO) individuals, weight loss among metabolically healthy obese (MHO) individuals may be unnecessary or even harmful. In the third study, 63 MHO and 43 MAO men and women participated in an exercise or diet weight-loss intervention. In response to similar weight loss, MHO and MAO men and women showed significant improvements in insulin sensitivity. However, significant improvements in other metabolic variables (triglycerides, fasting glucose, HDL-cholesterol, and total cholesterol) were only observed among MAO, but not MHO subjects. / Thesis (Ph.D, Kinesiology & Health Studies) -- Queen's University, 2010-04-29 20:55:08.67

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