Biological and Psychological Stress Correlates Are Linked to Glucose Metabolism, Obesity, and Gender Roles in Women.

OBJECTIVES: Psychological stress affects central as well as peripheral metabolism and hormone trafficking via the hypothalamic-pituitary-adrenal axis. Stress thereby plays a decisive role in the etiology and progression of overweight and obesity, leading to several chronic diseases, such as diabetes, and mental health disorders. The interplay of biological and psychometric correlates of stress, anthropometric, immunological, and metabolic parameters and psychosocial factors such as gender roles, however, remains poorly understood. METHODS: In this exploratory study, 43 healthy women were assessed for glucose metabolism by an oral glucose tolerance test and computation of functional parameters for insulin secretion, sensitivity, and resistance. Further, the fatty liver index (FLI) and anthropometric parameters body mass index (BMI), waist-to-hip ratio, body fat, and lean mass were assessed. Psychological stress assessment included the "Brief Symptom Inventory" (BSI), the "Burnout Dimensions Inventory" (BODI), and Perceived Stress Scale (PSS). Biological stress response was evaluated with heart rate variability and cortisol levels. Finally, gender role self-identification was assessed with the "Bem Sex-Role Inventory" (BSRI). Generalized linear models were computed for exploratory association with psychometric outcome. Uncorrected p values are reported. RESULTS: Burnout and PSS scores were associated with insulin secretion, sputum cortisol, thyroid-stimulating hormone, anthropometric measures, and gender role. BSI ratings for psychiatric symptom dimensions were associated with insulin resistance, sex hormones, anthropometric measures, and gender role. Female self-identification was associated with higher BMI as well as body fat and a higher FLI. CONCLUSIONS: Considering the increased risk of unfavorable metabolic, cardiovascular, and also mental health outcome in obese women, a higher BMI in women with predominant female gender self-identification may be relevant for clinical risk assessment. The broad range of interacting biological, psychological, and gender-related parameters calls for an integrative management of both mental and endocrinological health. However, the exploratory nature of the study requires replication in larger samples before definite conclusion can be drawn.

Glycemic Dysregulations Are Associated With Worsening Cognitive Function in Older Participants at High Risk of Cardiovascular Disease: Two-Year Follow-up in the PREDIMED-Plus Study.

Introduction: Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease. Methods: We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. Results: Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (ß=-0.11 (95%CI -0.16;-0.06)], as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF [ß=-0.0094 (95%CI -0.0164;-0.0023)], but also between HbA1c levels and changes in GCF [ß=-0.0085 (95%CI -0.0115, -0.0055)], the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF [ß=-0.31 (95%CI -0.44, -0.18)], and other cognitive tests. Conclusions: Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk. Clinical Trial Registration: http://www.isrctn.com/ISRCTN89898870, identifier ISRCTN: 89898870.

The association between insulin resistance, metabolic variables, and depressive symptoms in Mexican-American elderly: A population-based study.

OBJECTIVE: Depressive symptoms are common among older adults with obesity and diabetes. Nonetheless, the mechanisms for this association are not clear but may involve changes in the insulin cascade signaling. We aimed to investigate the association, and potential mediators, between obesity, insulin resistance, and depressive symptoms among older adults from a homogenous cohort of Mexican-Americans. METHODS: We included a total of 500 Mexican-American older adults assessed in the Cameron County Health Study. We evaluated depressive symptoms using the Center for Epidemiologic Survey Depression Scale (CES-D). Central obesity was defined by waist circumference. Insulin resistance was evaluated by the HOMA-IR index. We estimated the association between obesity, insulin resistance, and depressive symptoms by carrying out univariate and multivariate regression analyses. RESULTS: In unadjusted regression analysis, HOMA-IR (unstandardized ß = 0.31 ± 0.12, P = 0.007), waist circumference (unstandardized ß = 0.066 ± 0.0.028, P = 0.017), and Hb1Ac levels (unstandardized ß = 0.52 ± 0.24, P = 0.03) were significantly associated with CES-D scores. The association of HOMA-IR and CES-D remained statistically significant after controlling for socio-demographic and clinical variables in multivariate analysis (unstandardized ß = 0.28 ± 0.11, P = 0.01). CONCLUSION: Our results suggest that depressive symptoms are associated with insulin resistance in older Mexican-American adults. In addition, poorer glucose control and obesity are important mediators of this relationship. Additional studies are needed to evaluate whether interventions that increase insulin sensitivity can also reduce depressive symptoms in this population.

Dysglycemia and Cognitive Dysfunction and Ill Health in People With High CV Risk: Results From the ONTARGET/TRANSCEND Studies.

CONTEXT: Avoidance of death, disability, dementia, and cognitive dysfunction (DDCD) are high priorities for people in aging societies. Evidence is mounting that these conditions are associated with impaired glycemic control. OBJECTIVE: The aim of this study was to assess the strength of relationship between the degree of glucose elevation and the development of the composite elements of DDCD that impede successful/healthy aging in a population at high risk for cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURE: The relationship between baseline fasting plasma glucose values and DDCD was determined among 31 227 participants of the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE intolerant Subjects With Cardiovascular Disease studies followed up for a median of 4.7 years. Several statistical models were used for the entire cohort and for those with and without normal fasting plasma glucose (ie, < 5.6 mmol/L) or a history of diabetes mellitus. RESULTS: After adjusting for age and sex, a diagnosis of diabetes mellitus was associated with an approximately 1.6 greater odds of DDCD; every 1 mmol/L higher baseline fasting plasma glucose value was associated with a 1.09 (95% confidence interval 1.07, 1.10) greater odds. These associations persisted in the multivariate models (a 1.08 95% confidence interval 1.07, 1.1 greater odds after adjustment for age, sex, education, and depression). CONCLUSION: In individuals with high cardiovascular risk, a direct relationship exists between levels of dysglycemia and the risk of DDCD. Further research is needed to understand the mechanisms underlying such an association and whether benefits can be derived from preventative strategies.

Difficulty with learning of exercise instructions associated with 'working memory' dysfunction and frontal glucose hypometabolism in a patient with very mild subcortical vascular dementia with knee osteoarthritis.

We present a patient with no dementia, depression or apathy, who had difficulty in learning self-exercise instructions. The patient was an 80-year-old right-handed woman who was admitted to a rehabilitation unit to receive postoperative rehabilitation after a femoral neck fracture. She was instructed quadriceps isometric exercises to perform 10 repetitions and to hold each stretch for 10 s. She performed the exercise correctly with motivation, but she had difficulty in learning the number of repetitions and the duration of each stretch. She had no history of cerebrovascular accident and the neurological examination was normal. Neuropsychological testing, MRI and (18)F-fluoro- D-glucose-positron emission tomography (FDG-PET) were performed to examine the neural mechanisms associated with this difficulty in learning instructions. Neuropsychological tests revealed dysfunction of working memory while other cognitive domains were relatively preserved. Her neuropsychological tests scores were (1) Mini-Mental State Examination: 24 (mild cognitive impairment), (2) Geriatric Depression Scale-15: 2 (no depression), (3) Apathy Scale: 2 (no apathy), (4) digit span forward: 5 (normal), (5) digit span backward: 2 (impaired), (6) visuospatial span forward: 4 (normal), (7) visuospatial span backward: 2 (impaired), (8) frontal assessment battery: 11 (normal), (9) Weigl test: 0 (impaired), (10) trail making test A: 52 s (normal), (11) train making test B: failed (impaired). T2-weighted and fluid-attenuated inversion recovery MRI showed high signal-intensity lesions in the cerebral deep white matter. FDG-PET revealed hypometabolic areas in the bilateral frontal lobes, particularly in the bilateral dorsolateral frontal area, anterior cingulate cortex and orbitofrontal cortex. One of the possible neural mechanisms underlying the learning difficulties in this patient may have been partial blockage of the cingulofrontal network by deep white matter lesions.

Impaired glucose metabolism and health related quality of life.

AIMS: We aimed at investigating whether different categories of glucose tolerance have any effect on a person's HRQoL. METHODS: Population-based cross-sectional study conducted as a community sample of apparently healthy middle-aged individuals living in Western Finland. The subjects of the study, 1383 individuals, aged 45-70 years, had at least one cardiovascular risk factor but no previous diagnoses of either diabetes or cardiovascular disease. They completed health related quality of life (HRQoL) questionnaire before the oral glucose tolerance test (OGTT) was performed to diagnose the gategories of glucose tolerance. RESULTS: Persons with newly diagnosed type 2 diabetes (NDM) had lower scores for physical functioning, general health and emotional role than subjects with normal glucose tolerance. CONCLUSION: The results of the HRQoL questionnaire demonstrated that NDM is negatively associated with HRQoL, but prediabetes - IFG or IGT - does not.

Exploring temporospatial changes in glucose metabolic disorder, learning, and memory dysfunction in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and contributes significantly to cognitive deficits. The mechanisms underlying these cognitive deficits are often associated with complex metabolic alterations. However, the relationships between temporospatial alterations in cerebral glucose metabolism and the pathophysiology of DAI-related learning and memory dysfunction are not yet completely understood. We used a small animal positron emission tomography (PET) scanner with 2-[F-18]-fluoro-2-deoxy-D-glucose (¹8F-FDG) as a molecular probe to evaluate temporospatial glucose metabolism in vulnerable areas of rats with DAI. The Morris water maze (MWM) was used to evaluate the development and progression of learning and memory dysfunction. Compared to the sham-treated group, PET-MRI fusion images showed that glucose metabolism was reduced in animals with DAI. In addition, the standardized uptake value (SUV) of ¹8F-FDG was significantly decreased in the sensorimotor cortex, hippocampus, corpus callosum, caudate putamen, brain stem, and cerebellum at days 1, 3, and 7 after injury. SUV returned to baseline levels by 30 days after injury. The escape latency of the injured group was significantly increased, and the percentages of distance travelled and time spent in the target quadrant were significantly decreased 1 month after injury. These effects persisted for 3 months. SUVs in the hippocampus at the acute stage were significantly correlated with MWM performance during the recovery stage of DAI. These results demonstrate that microstructural injury-induced hypometabolism in the hippocampus at the acute stage are all significantly correlated with learning and memory dysfunctions during the recovery stage of DAI.

Is salt, vitamin, or endocrinopathy causing this encephalopathy? A review of endocrine and metabolic causes of altered level of consciousness.

Altered level of consciousness describes the reason for 3% of critical emergency department (ED) visits. Approximately 85% will be found to have a metabolic or systemic cause. Early laboratory studies such as a bedside glucose test, serum electrolytes, or a urine dipstick test often direct the ED provider toward endocrine or metabolic causes. This article examines common endocrine and metabolic causes of altered mentation in the ED via sections dedicated to endocrine-, electrolyte-, metabolic acidosis-, and metabolism-related causes.

Disturbed glucose disposal in patients with major depression; application of the glucose clamp technique.

OBJECTIVE: To assess the whole-body glucose disposal in patients with both typical and atypical depression and to characterize the neuroendocrine responses during a hyper-, eu-, hypoglycemic stepwise clamp experiment in patients with both subtypes of major depression. Depressive disorders and alterations in glucose metabolism are closely associated. The glucose clamp technique is considered to be the "gold standard" for the assessment of whole-body glucose disposal. METHODS: We studied 19 patients with typical major depressive disorder (MDD), 7 patients with atypical major depression, and 30 men and women of a healthy comparator group using a stepwise glucose clamp procedure. Glucose disposal rates were assessed and concentrations of hormones involved in glucose allocation were measured. RESULTS: Glucose disposal rates were lower by 19% in patients with typical MDD and 30% in patients with atypical MDD than in the group of healthy controls (3.2 +/- 0.8 and 2.8 +/- 0.7 versus 4.0 +/- 1.0 mmol h(-1) kg(-1)). C-peptide concentrations were 26% higher in patients with atypical MDD and similar in patients with typical MDD and healthy controls. Vascular endothelial growth factor concentrations were 30% higher in typical MDD and similar in atypical MDD and the control group. CONCLUSIONS: Whole-body glucose disposal is reduced in patients with typical and atypical depression. The observed neuroendocrine responses suggest a hyperactive allocation system in typical depression and a hypoactive allocation system in atypical depression.

Adverse effects of atypical antipsychotic agents and their effects on quality of life.

STUDY OBJECTIVES: To determine how axis III metabolic disturbances associated with atypical antipsychotic agents (weight gain, diabetes mellitus, and hyperlipidemia) affect patients' quality of life by comparing perceived quality of life of patients taking these agents who developed the disorders with those who did not develop them. A secondary objective was to compare patients' assessments of their quality of life with assessments made of the same patients by their treating psychiatrists. DESIGN: Analysis of questionnaire results. PATIENTS: Thirty three patients hospitalized at a Missouri Department of Mental Health long-term care psychiatric facility after January 1, 1990. MEASUREMENTS AND MAIN RESULTS: Participating patients independently completed the "long" form of the Quality of Life Enjoyment and Satisfaction Questionnaire. The psychiatrists who treated these patients completed the Physical Health-Activities section of the same questionnaire, based on their assessments of their patients' quality of life. Fifteen patients had a diagnosed axis III metabolic disturbance. For the group with these comorbid illnesses, the mean score on overall life satisfaction and contentment was 3.6 (fair to good). The corresponding value for the group without these comorbid diseases was 4.538 (good to very good). Psychiatrists' assessments of their patients' quality of life were less positive than the patients' own assessments, regardless of the existence of comorbid disease. CONCLUSION: Patients receiving atypical antipsychotic drugs had a perceived high quality of life and were satisfied with a variety of aspects of their lives. However, metabolic disturbances had a significant, detrimental effect on patients' perceived quality of life.

Glucose metabolic dysfunction in subjects with a clinical dementia rating of 0.5.

OBJECTIVE: To investigate the cerebral glucose metabolism of subjects who had a Clinical Dementia Rating (CDR) of 0.5, we studied 40 subjects whose CDR was 0.5 and 40 age-matched healthy subjects. METHODS: Cerebral glucose image of each subject was obtained by [18F]-2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET). The anatomically standardized images were produced with NEUROSTAT. Then, the two groups were compared with the Statistical Parametric Mappings (SPM) 99. RESULTS: A comparison with the SPM 99 revealed that relative cerebral glucose metabolism was lower in the posterior cingulate gyri and parietal lobules in the CDR 0.5 group than in the healthy subjects group. CONCLUSION: These findings are very similar to those in patients with probable Alzheimer's disease (AD) and suggest that the majority of subjects with CDR 0.5 are suffering from very mild AD or at least a prodromal state of AD.