PCOS: Hyperandrogenism Associated With Changes in Gut Microbiome

MedicalResearch.com Interview with:

Varykina Thackray, Ph.D. Associate Professor of Reproductive Medicine University of California, San Diego

Dr. Thackray

Varykina Thackray, Ph.D.
Associate Professor of Reproductive Medicine
University of California, San Diego

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies have shown that changes in the composition of intestinal microbes (gut microbiome) are associated with metabolic diseases. Since many women with polycystic ovary syndrome (PCOS) have metabolic dysregulation that increases the risk of developing type 2 diabetes and cardiovascular disease, we wondered whether PCOS was associated with changes in the gut microbiome and if these changes were linked to any clinical features of PCOS.

We collaborated with Beata Banaszewska and her colleagues at the Poznan University of Medical Sciences in Poznan, Poland to obtain clinical data and fecal samples from 163 premenopausal women recruited for the study. In collaboration with Scott Kelley at San Diego State University, we used 16S ribosomal RNA gene sequencing and bioinformatics analyses to show that the diversity of the gut microbiome was reduced in Polish women with PCOS compared to healthy women and women with polycystic ovaries but no other symptoms of PCOS.

The study confirmed findings reported in two other recent studies with smaller cohorts of Caucasian and Han Chinese women. Since many factors could affect the gut microbiome in women with PCOS, regression analysis was used to identify clinical hallmarks that correlated with changes in the gut microbiome. In contrast to body mass index or insulin resistance, hyperandrogenism was associated with changes in the gut microbiome in this cohort of women, suggesting that elevated testosterone may be an important factor in shaping the gut microbiome in women.

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Post-Menopausal Hormones Mitigates Effects of Stress on Cortisol and Working Memory

MedicalResearch.com Interview with:

Alexandra Ycaza Herrera, Ph.D. Postdoctoral Scholar Leonard Davis School of Gerontology Department of Psychology University of Southern California Los Angeles, Ca 90089

Dr. Herrera

Alexandra Ycaza Herrera, Ph.D.
Postdoctoral Scholar
Leonard Davis School of Gerontology
Department of Psychology
University of Southern California
Los Angeles, Ca 90089 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ​Previous research has shown that estradiol treatment after menopause can reduce the stress response when exposed to a stressor, including the cortisol response to stress. Other work has shown that stress can impair certain types of memory​. We wanted to test whether post-menopause estradiol treatment would not only attenuate the cortisol response to stress, but if it could also reduce the negative effects of stress on memory. In particular, we tested the effects on a type of memory called working memory. Working memory allows us to maintain and update information we need to readily access in short-term memory. For example, imagine you stop at the grocery store after work and only have a mental list of the items you need to make dinner. Working memory is the memory type engaged in helping you maintain and update your mental list of items as you grab items off the shelves and check them off your list.

We recruited women through the Early versus Late Intervention Trial with Estradiol, a randomized, double-blinded, placebo-controlled clinical trial. Women who participated in our study had received nearly 5 years of either estradiol or placebo.

We found that women receiving estradiol showed significantly smaller cortisol responses to stress and less of an effect of stress on working memory than women that had been receiving placebo.

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Maternal Blood Pressure Rise During Pregnancy Linked To Increased Risk Of Childhood Obesity

MedicalResearch.com Interview with:

Duo Li, PhD Chief professor of Nutrition Institute of Nutrition and Health Qingdao University, China. 

Dr. Duo Li

Duo Li, PhD
Chief professor of Nutrition
Institute of Nutrition and Health
Qingdao University, China. 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Childhood obesity is becoming an emerging public health issue worldwide, owing to its association with a variety of health problems at younger ages in adulthood, including obesity, type 2 diabetes and cardiovascular diseases. Identification of prenatal and early life risk factors is key for curbing the epidemic of the childhood obesity.

Main finding of the present study is that among pregnant women, elevated blood pressure is associated with a greater risk of overweight and obesity for their children.

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Risk of Type 2 Diabetes Elevated in Women With PCOS – Polycystic Ovary Syndrome

MedicalResearch.com Interview with:

Dorte Glintborg Overlæge, ph.d, dr.med Endokrinologisk Afdeling M Odense Universitetshospital

Dr. Glintborg

Dorte Glintborg
Overlæge, ph.d, dr.med
Endokrinologisk Afdeling M
Odense Universitetshospital

MedicalResearch.com: What is the background for this study?

Response: Polycystic ovary syndrome (PCOS) is a common endocrine disorder. PCOS is most often defined according to the Rotterdam criteria, which include irregular ovulation, biochemical/clinical hyperandrogenism, and/or polycystic ovaries when other etiologies are excluded. PCOS is associated with insulin resistance and obesity, but data regarding development and risk factors for type 2 diabetes (T2D) in PCOS are limited.

We performed a National Register-based study on Danish women with PCOS and included data regarding T2D events according to diagnosis codes and filled medicine prescriptions (N=18,477). Three age-matched controls were included per patient (N=54,680).

MedicalResearch.com: What are the main findings?

Response: We found that the risk for development of type 2 diabetes was 4 times increased in women with PCOS compared to controls. The median age at diagnosis of  type 2 diabetes was 31 years in women with PCOS compared with 35 years in controls suggesting that T2D was diagnosed 4 years earlier in PCOS. Increasing body mass index was associated with increased risk of development of T2D, whereas higher number of births was negatively associated with development of type 2 diabetes.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Further studies are needed regarding predictors of  type 2 diabetes in PCOS. Our data support a considerable increased risk for type 2 diabetes in obese women with PCOS. 

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Development and risk factors of type 2 diabetes in a nationwide population of women with polycystic ovary syndrome

Katrine Hass Rubin Dorte Glintborg Mads Nybo Bo AbrahamsenMarianne Andersen

The Journal of Clinical Endocrinology & Metabolism, jc.2017-01354,https://doi.org/10.1210/jc.2017-01354

Published29 August 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

Risks of Surgery For Thyroid Cancer Higher Than Expected

MedicalResearch.com Interview with:

Megan Rist Haymart MD Assistant Professor University of Michigan

Dr. Haymart

Megan Rist Haymart MD
Assistant Professor
University of Michigan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Thyroid cancer is typically treated with thyroid surgery. It is common practice for physicians to inform patients that the risk of vocal cord paralysis or hypoparathyroidism with thyroid surgery is 1-3%.

However, most of these estimates are based on single institution studies with high volume surgeons. In our study we evaluated surgical risks in a population-based cohort. Using the Surveillance, Epidemiology, and End Results-Medicare database, we found that 6.5% of thyroid cancer patients developed general post-operative complications (fever, infection, hematoma, cardiopulmonary and thromboembolic events) and 12.3% developed thyroid surgery specific complications (hypoparathyroidism/hypocalcemia, vocal cord/fold paralysis).

Older patient age, presence of comorbidities, and advanced stage disease were associated with the greatest risks of surgical complications.

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Bisphenol A May Promote Obesity By Interfering with Leptin Early in Life

MedicalResearch.com Interview with:
Alfonso Abizaid PhD

Department of Neuroscience
Carleton University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Bisphenol A (BPA) is a compound considered to be a potential environmental hazard and an endocrine disruptor. We have found an association between exposure to BPA at levels that are considered safe by Health Canada and the EPA early in life, and the development of obesity. In addition, we found that this propensity to develop obesity is due to under development of the hypothalamic projection field of POMC neurons, a set of neurons that regulate satiety and stimulate metabolic rate.

In this paper we replicate those findings and also show that this abnormal development is due to BPA altering the secretion of the hormone leptin at critical times where this hormone is important for the post-natal development of these POMC neurons.

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Gut Inflammation & Bacterial Changes Linked to Type 1 Diabetes

MedicalResearch.com Interview with:

Prof Lorenzo Piemonti, MD Professor of Endocrinology Deputy Director, Diabetes Research Institute (SR-DRI) Head, Beta Cell Biology Unit Vita-Salute San Raffaele University, San Raffaele Scientific Institute Milano Italy

Prof Lorenzo Piemonti

Prof Lorenzo Piemonti, MD
Professor of Endocrinology
Deputy Director, Diabetes Research Institute (SR-DRI)
Head, Beta Cell Biology Unit
Vita-Salute San Raffaele University,
San Raffaele Scientific Institute
Milano Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The potential role of gut inflammation and microbiome is becoming a hot topic in the field of diabetes. Several very recent publications report the presence of intestinal abnormalities associated with autoimmune diabetes in both experimental rodent models and patients. We have previously published that, compared to healthy subjects, patients with type 1 diabetes or at high risk of developing type 1 diabetes shows increased intestinal permeability.

Among the factors that may modify the intestinal barrier and impact on its immune activation, the gut microbiota is at present the main suspect. Our study is the first in literature that had the opportunity to analyze the inflammatory profile, the microbiome and their correlation on duodenum biopsies of patients with type 1 diabetes, in comparison with patients with celiac disease and healthy controls. Previous papers pointed out a significant difference in the composition of the stool microflora in subjects with autoimmune diabetes.

A major advancement of our work comes from the direct analysis of small intestine, instead of studies on stool samples. In fact, because of their close functional and spatial relationships, as well as a shared blood supply, it is logical to consider the duodenum and the pancreas correlated. We found big differences among the groups: gut mucosa in diabetes shows a peculiar signature of inflammation, a specific microbiome composition and we also discovered a strong association between some analysed inflammatory markers and specific bacteria genera. We think that our data add an important piece to disentangle the complex pathogenesis of type 1 diabetes and more generally of autoimmune diseases.

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Clinicians Found To Have Inadequate Training in Transgender Health

MedicalResearch.com Interview with:
Caroline J. Davidge-Pitts, M.B., Ch.B

Mayo Clinic
Rochester, Minn.

MedicalResearch.com: What is the background for this study?

Response
: The awareness of transgender healthcare issues has increased, leading to improved coverage of both hormonal and non-hormonal therapies. In endocrinology practices, there is an increased demand for providers who are competent in these areas. We wanted to assess the current status of knowledge and practice in transgender health amongst our current and future endocrinologists.

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Menopausal Hormone Therapy Benefits Bone Health For Several Years After Discontinuation

MedicalResearch.com Interview with:

Dr Georgios Papadakis FMH, Médecin InternenMédecin assistant Service d'endocrinologie, diabétologie et métabolisme Lausanne

Dr Georgios Papadakis

Dr Georgios Papadakis
FMH, Médecin InternenMédecin assistant
Service d’endocrinologie, diabétologie et métabolisme
Lausanne

MedicalResearch.com: What is the background for this study?

Response: This study was mainly motivated by the absence of available data on the effect of menopausal hormone therapy (MHT) on bone microarchitecture, as well as contradictory results of previous trials regarding the persistence of a residual effect after MHT withdrawal.

We performed a cross-sectional analysis of 1279 postmenopausal women aged 50-80 years participating in OsteoLaus cohort of Lausanne University Hospital. Participants had bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) at lumbar spine, femoral neck and total hip, as well as assessment of trabecular bone score (TBS), a textural index that evaluates pixel grey-level variations in the lumbar spine DXA image, providing an indirect index of trabecular microarchitecture.

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Hypoglycemia Linked To Increased Mortality in Hospitalized Patients

MedicalResearch.com Interview with:
Amit Akirov, MD
Institute of Endocrinology
Rabin Medical Center- Beilinson Hospital
Petach Tikva, Israel

MedicalResearch.com: What is the background for this study?

Response: As hypoglycemia is common among hospitalized patients with and without diabetes mellitus, we aimed to investigate the association between spontaneous and insulin-related hypoglycemia including severe hypoglycemia and all-cause mortality among a large cohort of hospitalized patients.

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Hormone Combination Effective For Male Contraception But With Many Side Effects

MedicalResearch.com Interview with:
Mario Philip Reyes Festin, MD

World Health Organization
Geneva, Switzerland. 

MedicalResearch.com: What is the background for this study?

Response: Researchers are trying to identify a hormonal male contraceptive that is effective, reversible, safe, acceptable, affordable, and available. Most of the research has been done either by groups of university researchers. However, in the 1990s, WHO undertook two multi-center, multinational studies.

The studies were unable to provide evidence to support the development of a commercially viable, and user-acceptable product.

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Even With Normal TSH, Some Patients Still Feel Hypothyroid

MedicalResearch.com Interview with:

Antonio C. Bianco, MD, PhD Rush University Medical Center

Dr. Antonio C. Bianco

Antonio C. Bianco, MD, PhD
Rush University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The standard of care for patients with hypothyroidism is treatment with levothyroxine. The dosage of levothyroxine is adjusted for each patient with the goal of normalizing blood levels of TSH. About 15% of the patients treated this way exhibit variable degrees of residual symptoms, despite having a normal TSH level. These symptoms include difficulty losing weight, low energy and depression. However, given the subjective nature of these complains and that the blood levels of TSH are normal, many times such symptoms are dismissed by physicians as non-thyroid related.

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Urinary Citrate Excretion May Be Indirect Biomarker of Bone Health

MedicalResearch.com Interview with:
Jonas Esche

Dipl.-Mol. Biomed
University of Bonn
Institute of Nutritional and Food Sciences
DONALD Study

MedicalResearch.com: What is the background for this study?

Response: Modern western diets increase diet-dependent acid load and net acid excretion which are suggested to have adverse long-term effects on bone. Urinary potential renal acid load (uPRAL) is an established parameter to assess nutritional acid load. Urinary citrate, on the other hand, integrates nutritional and also systemic influences on acid-base homeostasis with high citrate indicating prevailing alkalization.
Against this background urinary citrate excretion was used as a new index of acid-base status and its relationship with bone strength and long-term fracture risk was examined.

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Nighttime Hot Flashes With Sleep Disruption Linked To Depressive Symptoms During Menopause

MedicalResearch.com Interview with:

Hadine Joffe, MD, MSc Associate Professor of Psychiatry, Harvard Medical School Vice Chair for Psychiatry Research Director of Division of Women's Mental Health / Dept of Psychiatry / Brigham and Women’s Hospital Director of Psycho-Oncology Research / Dept of Psychosocial Oncology and Palliative Care /Dana Farber Cancer Institute www.brighamwharp.org

Dr. Hadine Joffe

Hadine Joffe, MD, MSc
Associate Professor of Psychiatry, Harvard Medical School
Vice Chair for Psychiatry Research
Director of Division of Women’s Mental Health / Dept of Psychiatry / Brigham and Women’s Hospital
Director of Psycho-Oncology Research / Dept of Psychosocial Oncology and Palliative Care /Dana Farber Cancer Institute
www.brighamwharp.org

MedicalResearch.com: What is the background for this study?

Response: We conducted this study to advance our understanding about causes of mood disturbance in the menopause transition that are specifically related to menopause. We used an experimental model to dissect out the contributions of hot flashes and sleep disturbance from contribution of changing levels of estrogen because hot flashes, sleep problems, and estrogen fluctuations co-occur and are difficult to distinguish from one another. Understanding whether hot flashes and/or sleep disturbance are causally related to mood disturbance will help us identify who is at risk for mood changes during the menopause transition. This is incredibly important now that we are finding effective non-hormonal treatments for hot flashes and sleep disruption.

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Intestinal Microbiome Linked to Obesity and Fat Storage in Children

MedicalResearch.com Interview with:

Nicola Santoro, MD, PhD Associate Research Scientist in Pediatrics (Endocrinology) Yale University

Dr. Nicola Santoro

Nicola Santoro, MD, PhD
Associate Research Scientist in Pediatrics (Endocrinology)
Yale University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study start from previous observations showing an association between the gut microbiota and obesity.

Similarly to what previously described in adults and in children, we found an association between the gut microbiota and obesity. We took a step further and also observed that the gut flora is associated to body fat partitioning (amount of fat in the abdomen). Moreover, we observed that the effect of microbiota could be mediated by the short chain fatty acids a product of gut flora.

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Vitamin D Levels Fall When Estrogen-Containing Birth Control Pills Stopped

MedicalResearch.com Interview with:

Quaker Harmon M.D., Ph.D. Epidemiology Branch National Institute of Environmental Health Sciences Research Triangle Park, NC 27709

Dr. Quaker Harmon

Quaker Harmon M.D., Ph.D.
Epidemiology Branch
National Institute of Environmental Health Sciences
Research Triangle Park, NC 27709

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vitamin D is important for bone health. In the United States many women are vitamin D deficient. Vitamin D does not naturally occur in many foods, however some foods are fortified with vitamin D. Supplements and sunshine are the most reliable sources of vitamin D.
Previous studies suggested that women using birth control pills containing estrogen had higher levels of vitamin D. These studies were generally small and were not always able to examine important factors such as time spent outside. We were interested in examining the association between hormonal contraception and vitamin D levels in a larger group of women.

We found that women who use estrogen-containing contraception had a 20% increase in their vitamin D levels. This increase was not due to time spent outside or behaviors related to choice of contraception. The magnitude of increase for hormonal contraception was smaller than for regular use of a supplement containing vitamin D.

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Sleep Duration Affects Diabetes Risk Differently in Men and Women

MedicalResearch.com Interview with:

Dr. Femke Rutters Department of Epidemiology and Biostatistics Vrije Universiteit Medical Centre Amsterdam, The Netherlands; EMGO+ Institute for Care Research

Dr. Femke Rutters

Dr. Femke Rutters
Department of Epidemiology and Biostatistics
Vrije Universiteit Medical Centre
Amsterdam, The Netherlands;
EMGO+ Institute for Care Research

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In the past 10 years the interest in sleep as a possible cause for obesity/diabetes has risen. But data up until now used mainly self-reported sleep and simple measures of diabetes (related parameters), such as fasting glucose. A study on well-measured insulin sensitivity and beta-cell function was lacking. Such a study could provide more information on the pathophysiology.

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Malignant Thyroid Nodules Less Common But More Aggressive With Age

Erik K. Alexander, MD FACP Chief, Thyroid Section, Division of Endocrinology Brigham & Women's Hospital Associate Professor of Medicine, Harvard Medical School

Dr. Erik Alexander

MedicalResearch.com Interview with:
Dr. Erik K. Alexander, MD FACP
Chief, Thyroid Section, Division of Endocrinology
Brigham & Women’s Hospital
Associate Professor of Medicine, Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Dr. Alexander: Thyroid nodular disease has become an increasingly common medical illness, with prevalence reported to range between 26-67% in the adult.  Though advancing age is known to influence the formation of thyroid nodules, their precise relationship remains unclear.  Furthermore, it is uncertain whether age influences the risk that any thyroid nodule may prove cancerous.  Thus we conducted a study to determine the impact of patient age on nodule formation, the number of thyroid nodules, and risk of thyroid malignancy.

Medical Research:  What are the main findings?

Dr. Alexander: Our study is a prospective cohort analysis of consecutive adults who presented for evaluation of nodular disease from 1995-2011 at Brigham and Women’s Hospital, Boston, MA.  6,391 patients underwent thyroid ultrasound and fine needle aspiration that resulted in 12,115 thyroid nodules ≥1 cm.  Patients were stratified into six age groups and compared using sonographic, cytologic, and histologic endpoints.
We found that the prevalence of thyroid nodular disease increases with advancing age.  The mean number of nodules at presentation increased from 1.5 in the youngest cohort (ages 20–30) to 2.2 in the oldest cohort (>70 years).  In contrast, the risk for malignancy in a newly identified nodule declined with advancing age.  Thyroid cancer incidence per patient was 22.9% in the youngest cohort, but 12.6% in the oldest cohort.  Despite a lower likelihood of malignancy, identified cancers in older patients demonstrated a more aggressive cancer subtype.  While nearly all malignancies in younger patients were well-differentiated, older patients were more likely to have higher risk papillary thyroid cancer variants, poorly differentiated cancer, or anaplastic carcinoma.

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Growth Hormone Reduced Fractures in Osteoporosis Patients

MedicalResearch.com Interview with:
Emily Krantz (né Amundson) MD
Södra Älvsborgs Hospital
Borås, Sweden

Medical Research: What is the background for this study? What are the main findings?

Response: This study is a 10-year follow up of a double-blind placebo controlled trial in which women with post menopausal osteoporosis received Growth Hormone (GH) for 3 years (Landin-Wilhelmsen JBMR 2003;18:393-404). Positive effects of the treatment on the patients bone mineral density and bone mineral content were seen after another 7 years. Furthermore and most interestingly, fracture incidence decreased dramatically from 56% to 28% (p=.0003) in the osteoporosis patients while fractures increased significantly in the control group, from 8% to 32% (p=.0008). Health Related Quality of Life was also measured throughout the study’s duration and it did not change nor did it differ from the control group.

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Overnight Sleep Loss Can Have Long Term Metabolic Consequences

Jonathan Cedernaes M.D., Ph.D. Department of Neuroscience Uppsala University SwedenMedicalResearch.com Interview with:
Jonathan Cedernaes M.D., Ph.D.
Department of Neuroscience
Uppsala University Sweden

Medical Research: What is the background for this study? What are the main findings?

Dr. Cedernaes: Previous studies have demonstrated that experimental sleep loss and simulated shift work (i.e. misalignment of circadian rhythms) reduces energy expenditure and insulin sensitivity, providing links to why sleep loss may increase the risk of e.g. type-2 diabetes and obesity. Such phenotypes have also been observed in animals in which clock genes are ablated. Clock genes regulate the circadian rhythms of all cells and variants in these have also been associated with increased risk of obesity, insulin resistance and type-2 diabetes in humans. Almost no study has however investigated whether overnight wakefulness – mimicking a situation which recurrently occurs in shift work – can affect the expression of such clock genes in metabolically important tissues, i.e. adipose tissue and skeletal muscle, in humans. Such gene expression changes may both acutely and more long-term be regulated by changes in methylation, i.e. an epigenetic change, which have been found in blood of e.g. shift workers and in e.g. adipose tissue of type-2 diabetic subjects. However, whether sleep loss can lead to epigenetic changes has been unknown, and therefore also whether this could affect genes important for metabolism, such as the core clock genes which are essential for orchestrating and synchronizing downstream metabolic processes according to our circadian rhythms.

With this background in mind, I and associate professor Christian Benedict set out to conduct a study to investigate how one night of sleep loss altered gene transcription and methylation of core clock genes in adipose tissue and skeletal muscle, and whether this would be reflected at the systemic level by an impaired glucose tolerance test in healthy young individuals.

For the study, we had 15 participants undergo two almost 2-day long sessions in our lab, with the first night of each session serving as a baseline or habituation night, with a normal sleep period. On the second night, in random order, participants slept a full night (8.5 hours) in one session, and were kept awake the entire night while being bed-restricted in the other of two sessions. After each of these conditions, we took biopsies in the fasting condition from the subcutaneous adipose tissue and the skeletal muscle.

In collaboration with researchers from the Karolinska Institute, Gothenburg University and the German Institute of Human Nutrition, we were able to observe transcriptional repression of clock genes in the muscle, but not in the adipose tissue following sleep loss compared with normal sleep. Instead, we found methylation of regulatory elements of clock genes to be increased in the adipose tissue but not the skeletal muscle following sleep loss compared with normal sleep. Finally, we observed that participants had an impaired glucose tolerance test when they had been kept awake as compared with their response after sleep. Continue reading