Effect of intranasally administered insulin on cerebral blood flow and perfusion:a randomized experiment in young and older adults

Pathophysiology, epidemiology and therapy of agein

Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

Abstract The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose was a 2.2% decrease. Administration of water did not affect the hypothalamic BOLD responses. Intranasal insulin did not change circulating glucose and insulin levels. Still, circulating glucose levels showed a significant dampening effect on the BOLD response and insulin levels a significant strengthening effect. Our data provide proof of concept for future experiments testing the potential of intranasal application of insulin to ameliorate defective homeostatic control in patients with type 2 diabetes

Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples

This research was funded by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre. UKCTOCS was core funded by the Medical Research Council, Cancer Research UK, and the Department of Health with additional support from the Eve Appeal, Special Trustees of Bart’s and the London, and Special Trustees of UCLH. OB and JFT also received support from the Eve Appeal Gynaecological Cancer Research Trust and Cancer Research UK PRC Programme Grant A12677

Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar in anorexia nervosa and healthy control subjects

Background. Inconsistent findings about the neurobiology of Anorexia Nervosa (AN) hinder the development of effective treatments for this severe mental disorder. Therefore the need arises for elucidation of neurobiological factors involved in the pathophysiology of AN. The hypothalamus plays a key role in the neurobiological processes that govern food intake and energy homeostasis, processes that are disturbed in anorexia nervosa (AN). The present study will assess the hypothalamic response to energy intake and the hypothalamic structure in patients with AN and healthy controls. Methods. 10 women aged 18-30 years diagnosed with AN and 11 healthy, lean (BMI <23 kg/m2) women in the same age range were recruited. We used functional magnetic resonance imaging (MRI) to determine function of the hypothalamus in response to glucose. Structural MRI was used to determine differences in hypothalamic volume and local grey volume using manual segmentation and voxel-based morphometry.Results. No differences were found in hypothalamic volume and neuronal activity in response to a glucose load between the patients and controls. Whole brain structural analysis showed a significant decrease in grey matter volume in the cingulate cortex in the AN patients, bilaterally.Conclusions. We argue that in spite of various known changes in the hypothalamus the direct hypothalamic response to glucose intake is similar in AN patients and healthy controls

Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy

BACKGROUND AND PURPOSE: Early markers for cerebral amyloid angiopathy (CAA) are largely unknown. We aimed to identify which MRI (performed at 7 tesla and 3 tesla) and cognitive markers are an early sign in (pre-)symptomatic subjects with Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch type (HCHWA-D). METHODS: Twenty-seven DNA-proven Dutch type mutation carriers (15 symptomatic and 12 pre-symptomatic) (mean age of 45.9) and 33 controls (mean age of 45.6) were included. 7T and 3T MRI was performed, CAA and small vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand, and on the other mutation status, adjusted for age, sex and education. RESULTS: In symptomatic patients, all established CAA MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis, microinfarcts, volume of white matter hyperintensities (WMHs) and dilated perivascular spaces in centrum semiovale) were increased compared to controls (p<0.05). In pre-symptomatic subjects, the prevalence of microinfarcts and median volume of WMHs were increased in comparison to controls (p<0.05). Symptomatic patients performed worse on all cognitive domains, whereas pre-symptomatic subjects did not show differences in comparison with controls (p<0.05). CONCLUSIONS: WMHs and microinfarcts are more prevalent among pre-symptomatic subjects and precede cognitive and neuropsychiatric symptoms and intracerebral hemorrhages

Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma : Influence of Gonadal Hormone Exposure

BACKGROUND: Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. METHODS: We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. RESULTS: We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction: .06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. CONCLUSIONS: BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship

Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure

Background Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. Methods We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. Results We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction:.06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. Conclusions BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship