ABSTRACT
BACKGROUND: The Great East Japan Earthquake and the resulting tsunami and nuclear disaster on March 11, 2011 have had a profound and lasting effect on residents of Japan's Fukushima Prefecture, particularly among evacuees. While there continues to be extensive news coverage and academic study of Fukushima Prefecture's recovery, there has been little exploration of individual narratives. This study aims to illuminate some individual stories of medical students at Fukushima Medical University (FMU) who lived in the Prefecture at the time of the Earthquake. METHODS: A qualitative approach was taken in order to investigate individuals' experiences with the goal of adding a personal dimension to quantitative studies on the subject. 10 open-ended ethnographic interviews were conducted with medical students at FMU in years 1-5 who lived in Fukushima Prefecture at the time of the Great East Japan Earthquake. All interviews were audio recorded and transcribed. Transcriptions were reviewed using inductive thematic analysis under the lens of ethnographic anthropology. RESULTS: Three major themes emerged from these interviews: first, that the events following the Earthquake influenced not only these students' decisions to pursue careers in medicine, but the ways in which they hope to practice medicine in the future. Second, that these students were motivated to share their experiences by a want to change Fukushima Prefecture's public image. And lastly, that the students viewed the opportunity to discuss their experiences through these interviews as healing, both for themselves and for the future. CONCLUSIONS: While multiple factors undoubtably contributed these students' medical education, they cite the Earthquake as essential to their approach to their medical careers. Additionally, opportunities for the participants to discuss their experiences following the Earthquake appear to be rare but valued, as the students view their stories as their "legacies." The enduring, burdening effects of the Earthquake appear to have galvanized the participating students to act on behalf of their communities and their Prefecture. Further qualitative studies in more generalizable populations are needed to improve and deepen our understanding of the societal, cultural, and personal impacts of the Great East Japan Earthquake.
Subject(s)
Disasters , Earthquakes , Fukushima Nuclear Accident , Students, Medical , Humans , JapanABSTRACT
The ongoing COVID-19 pandemic has caused significant psychological impact on medical professionals, including medical students, many who have been caring for patients on the frontlines. Understanding how medical students perceive their stressful life experiences is important as the mental health of these future physicians directly impacts their ability to care for patients. We assessed for post-traumatic growth and resilience in the face of traumatic events among a cohort of medical students that attended a medical school located in an early epicenter of the COVID-19 pandemic. Between October 29, 2020 and December 1, 2020, medical students at the Icahn School of Medicine at Mount Sinai in New York City were surveyed on various stressful life events, including COVID-19. We identified specific resilience behaviors, including establishing a supportive social network, relying on a moral compass, and using cognitive flexibility, that medical students commonly used to cope with traumatic experiences. Compared with students who perceived COVID-19 as their most stressful life event, students who perceived other events, such as family issues or serious illness, as most stressful experienced less COVID-related stress (t = -2.2, p = .03), greater posttraumatic growth (t = 4.3, p < .001), and demonstrated more resilient behaviors including establishing and nurturing a supportive social network (t = 2.2, p = .03), developing brain fitness (t = 2.2, p = .03), and finding meaning and purpose in things (t = 2.9, p = .006). This suggests that stressful experiences prior to or in parallel with COVID-19 encouraged posttraumatic growth and development of resilience behaviors that were protective to COVID-19-related stress.
Subject(s)
COVID-19 , Posttraumatic Growth, Psychological , Resilience, Psychological , Students, Medical , Humans , Pandemics , Students, Medical/psychologyABSTRACT
In March of 2011, a 9.0 magnitude earthquake, tsunami, and nuclear explosion damaged northeastern Japan. While nine years have passed, the memory of this disaster continues to linger. This qualitative study had three main goals. First it aimed to explore the reactions and interpretations of adolescents living in areas affected by the disaster. Second, it sought to examine the behaviors and beliefs that enabled these students to not only recover but thrive. Third, it strived to build a more global and dynamic framework of resilience. A convenience sample of 18 students participated in semi-structured face-to-face interviews. Their narratives were qualitatively analyzed using thematic content analysis. Overall, four themes, each with four codes or sub-themes, emerged as sources of resilience including social support (social networks, role models, and community service), hopeful future orientation (cognitive reappraisal, optimism, and motivation to be physician), active emotions (rational compassion, luck, and suppression) and sense of purpose or duty (sharing of personal story, motivation to educate others, and Fukushima image). These findings reveal the experiences of highly resilient youth facing trauma and the connection between childhood adversity and career choices. They also begin to uncover the unique ways that culture, society, and tradition impact processes of recovery.
Subject(s)
Disasters , Earthquakes , Optimism/psychology , Resilience, Psychological , Students, Medical/psychology , Tsunamis , Adolescent , Emotions/physiology , Female , Humans , Interview, Psychological/methods , Japan/epidemiology , Male , Narration , Qualitative Research , Young AdultABSTRACT
On March 11, 2011 ("3/11"), a magnitude 9.0 earthquake in Northeastern Japan triggered a tsunami and nuclear power plant meltdown that killed 16,000 people and displaced more than 470,000 people. Since 2012, a group of volunteer docents from the September 11th Families Association in New York City has traveled throughout Northeastern Japan and held organized meetings where 9/11 and 3/11 survivors share their experiences and stories of trauma as part of an intercultural exchange to promote posttraumatic recovery. We sought to elucidate whether participating 9/11 docents developed a sense of increased resiliency by participating in this international outreach. This study employed photo-taking as well as framing questions, which were developed by 9/11 docents from the August 2016 trip. These questions guided photo-taking and resulting photographs informed discussion in individual and group sharing sessions. This process helped identify codes that guided analysis. Participants acquired a deeper appreciation of their own ability to overcome adversity and experienced a gratifying desire to help 3/11 survivors better cope with their experiences. This narrative photo-taking and group sharing experience demonstrates that a cross-cultural exchange between survivors of different disasters can instill feelings of resilience among participants. It additionally provides early evidence of the efficacy of such an exchange in benefitting disaster survivors in the long term.
Subject(s)
Hope , Photography , Posttraumatic Growth, Psychological , Resilience, Psychological , Survivors/psychology , Cross-Cultural Comparison , Earthquakes , Humans , Japan , Natural Disasters , September 11 Terrorist Attacks , Surveys and Questionnaires , Travel , Tsunamis , United StatesABSTRACT
In March of 2011, an earthquake, tsunami, and nuclear accident struck northern Japan causing profound damage to the surrounding area and lasting effects to all those who lived there. Fukushima Medical University (FMU), the closest hospital that remained open during the disaster, was greatly impacted and its students rallied to help the cause. Many of them were directly affected as their neighborhoods were ruined and family and friends were injured or killed. Our study sought to better understand how this disaster impacted their posttraumatic growth and resilience in the wake of the disaster and today, 8 years later. There were three goals of this study. First, we aimed to replicate previous research that showed positive effects of disaster volunteerism on medical students' posttraumatic growth. Second, we sought to better understand the role of resilience in the wellbeing of these students. Finally, we wanted to explore the advantages to our newly created 10-Factor Resilience Behavioral Scale, which we used alongside the Davidson Trauma Scale (DTS), Posttraumatic Growth Inventory (PTGI-X), and Connor-Davidson Resilience Scale (CD-RISC). Overall, 579 responses were collected (response rate of 71.9%). Volunteers continued to show greater PTG as well as greater overall resilience. Furthermore, there were positive correlations between students' feelings of confusion, anger, sadness, guilt or anxiety and their sense of resilience, both at the time of the disaster and in the most recent month, suggesting that within Japanese culture difficult emotions may promote resilient behaviors and actions.
Subject(s)
Fukushima Nuclear Accident , Posttraumatic Growth, Psychological , Resilience, Psychological , Students, Medical/psychology , Disasters , Earthquakes , Female , Humans , Male , Surveys and Questionnaires , Tsunamis , Volunteers/psychology , Young AdultABSTRACT
Medical students often become involved as post-disaster emergency responders despite incomplete training, and in doing so may suppress their immediate experiences as victims and survivors. This experience, however, may lead them to increase their motivation to help others. We examined how cognitive and emotional reactions to disaster correlated with posttraumatic growth (PTG) in medical students in Fukushima, Japan after the Great East Japan Earthquake of March 11, 2011. To date, Fukushima continues to suffer from radiation concerns following the nuclear power plant meltdown. In a survey three years after the onset of a long-term disaster, with a cross-sectional research design, medical students (N = 494) reported their negative post-disaster reactions, desire to help, and demonstrations of capability, and completed the Posttraumatic Growth Inventory (PTGI). We conducted hierarchical regression analyses and found that the addition of variables pertaining to negative post-disaster reactions (e.g. confusion, anger, and sadness) led to the largest increase in predictive value for PTGI scores; students reporting a past traumatic experience were also more likely to experience PTG. Our results indicate that weathering stressful disaster circumstances created opportunities for positive personal growth and reinforcement at a crucial time in medical students' professional development.
Subject(s)
Disasters , Earthquakes , Emotions/physiology , Posttraumatic Growth, Psychological , Stress Disorders, Post-Traumatic/psychology , Students, Medical/psychology , Adult , Cross-Sectional Studies , Female , Humans , Japan , Male , Young AdultABSTRACT
Six years after the March 2011 Triple Disaster, over 35,000 Japanese individuals remain in temporary housing. Evacuated residents, many of who are elderly, face mental health challenges. This study evaluates the well being of individuals living in temporary housing within Fukushima. Reactions to relocation were explored using Photovoice, a community-based participatory research method, in which a set of research questions are examined qualitatively through photographs and interviews. Seven participants (average age = 69.7) were provided cameras to answer a set of self-generated questions, a process that was repeated three times. An initial analysis found resilience among participants, which was explored using a theoretical framework of resiliency. Residents discussed how relocation has disrupted their lives and coping strategies they employ to ameliorate stressors. They were often optimistic and future-oriented, stating that they wanted to "live strong" after the disaster. These resilient mindsets were personified in action: all engaged in hobbies, critical for their emotional well being. Participants also emphasized the importance of community and familial support. The evidence of resilience in participants is encouraging, suggesting that these vulnerable elderly internally displaced residents are recovering from the disruption of relocation. These themes should be explored in larger temporary housing communities. Considering the number of relocated individuals today, understanding how to foster resilience could be used to inform the development of future temporary housing shelters.
Subject(s)
Adaptation, Psychological/physiology , Community Mental Health Services/methods , Disaster Victims/psychology , Fukushima Nuclear Accident , Mental Health , Resilience, Psychological , Aged , Disaster Victims/rehabilitation , Female , Humans , Japan/epidemiology , MaleABSTRACT
OBJECTIVE: To describe the evolution of thyroid dysfunction in a series of patients with cancer treated with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) monoclonal antibody, nivolumab. METHODS: Cases of thyroid dysfunction after initiation of checkpoint inhibitor treatment were identified from the Division of Endocrinology clinical practice at Mount Sinai Hospital, New York from April 2016 to February 2017. Charts were reviewed to identify patients treated with nivolumab with new onset of thyroid dysfunction. RESULTS: Nine cases of thyroid function in patients who were treated with nivolumab were identified. There were 4 male and 5 female patients, with a mean age of 66 years (range 50-76 years). Seven patients ultimately developed hypothyroidism. Five of the 7 patients developed abnormal thyroid function tests within the first 90 days of starting therapy (range 21-84 days), 3 of whom had transient hyperthyroidism. Transient hyperthyroidism evolved rapidly to hypothyroidism; elevated thyroid-stimulating hormone (TSH) levels were detected within 16 to 32 days of the last documented low TSH. In the 2 patients without a hyperthyroid phase, TSH levels >50 were found 18 to 28 days after the last normal TSH value. CONCLUSION: As the use of immune checkpoint inhibitor therapy increases, the need for prompt diagnosis and treatment of drug-induced thyroid disease will become more important. As illustrated in this case series, in contrast to other causes of auto-immune thyroiditis, hypothyroidism can develop rapidly within 3 months of treatment. Close monitoring is necessary to detect the development of thyroid dysfunction and avoid preventable morbidity. ABBREVIATIONS: Anti-TPO Abs = anti-thyroglobulin antibodies; CT = computed tomography; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; FDA = U.S. Food & Drug Administration; FDG-PET = fluorodeoxyglucose-positron emission tomography; PD-1 = programmed cell death protein-1; PD-L1 = programmed death-ligand 1; T3 = triiodothyronine; T4 = thyroxine; TG = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone.
Subject(s)
Antibodies, Monoclonal/adverse effects , Hypothyroidism/chemically induced , Thyroid Gland/drug effects , Aged , Disease Progression , Drug Monitoring , Female , Humans , Hypothyroidism/pathology , Male , Middle Aged , Neoplasms/drug therapy , Nivolumab , Thyroid Gland/physiopathology , Thyroiditis/chemically induced , Thyroiditis/complications , Time FactorsABSTRACT
The March 2011 "triple disaster" (earthquake, tsunami, and nuclear accident) had a profound effect on northern Japan. Many medical students at Fukushima Medical University volunteered in the relief effort. We aimed to investigate the nature of students' post-disaster involvement and examine the psychological impact of their experiences using a survey containing elements from the Davidson Trauma Scale and Posttraumatic Growth Inventory. We collected 494 surveys (70 % response rate), of which 132 students (26.7 %) had volunteered. Volunteers were more likely to be older, have witnessed the disaster in person, had their hometowns affected, and had a family member or close friend injured. In the month after 3/11, volunteers were more likely to want to help, feel capable of helping, and report an increased desire to become a physician. Both in the month after 3/11 and the most recent month before the survey, there were no significant differences in distressing symptoms, such as confusion, anger, or sadness, between volunteers and non-volunteers. Volunteers reported a significantly higher level of posttraumatic growth than non-volunteers. Participating in a greater variety of volunteer activities was associated with a higher level of posttraumatic growth, particularly in the Personal Strength domain. There may be self-selection in some criteria, since students who were likely to be resistant to confusion/anxiety/sadness may have felt more capable of helping and been predisposed to volunteer. However, participation in post-disaster relief efforts did not appear to have a harmful effect on medical students, an important consideration for mobilizing volunteers after future disasters.
Subject(s)
Disasters , Fukushima Nuclear Accident , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Students, Medical/psychology , Disaster Planning , Earthquakes , Female , Humans , Japan , Male , Students, Medical/statistics & numerical data , Tsunamis , Young AdultABSTRACT
Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.
Subject(s)
Diabetes Insipidus, Neurogenic/epidemiology , Quality of Life , Surveys and Questionnaires , Adult , Aged , Aged, 80 and over , Case-Control Studies , Diabetes Insipidus, Neurogenic/psychology , Female , Humans , Male , Middle AgedABSTRACT
The 2011 Great East Japan Earthquake precipitated a triple disaster of earthquake, tsunami and nuclear radiation disaster. To quantify the prevalence of burnout and psychiatric distress in local healthcare providers (caregivers) more than 2 years after the disaster, this study surveyed caregivers from affected areas through interviews about topics of concerns and two questionnaires: Maslach Burnout Inventory and General Health Questionnaire. Concerns listed by respondents were primarily radiation related: additional stress, concern for children, concern for local food, and sleep difficulties. We found significant number of caregivers to have signs of emotional exhaustion, low personal accomplishment, and psychological distress. Our findings suggest that local caregivers are experiencing substantial mental health burdens, which have unfortunately remained static from the year prior, even 2 years after the fact. Therefore, long term psychological support and improvement in caregiver work conditions are essential to maintain sustainable care in rebuilding disaster stricken areas.
Subject(s)
Burnout, Professional/epidemiology , Caregivers/psychology , Fukushima Nuclear Accident , Adult , Aged , Disasters , Female , Humans , Japan/epidemiology , Male , Middle Aged , Stress, Psychological/epidemiology , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: The triple disaster that struck the Tohoku region on March 11, 2011, has had massive psychiatric, social, and physical effects on the people of Japan. A staggering loss of life and property, as well as an ongoing nuclear disaster, has dramatically affected the ability of the country to recover. OBJECTIVE: In an effort to better understand the current social, health, and mental health needs of the region affected by the disaster and to share lessons from 9/11, a group of 9/11 survivors and doctors from the Icahn School of Medicine at Mount Sinai traveled to sites throughout the Fukushima, Miyagi, and Iwate prefectures. METHODS: A qualitative analysis was performed on transcripts of the cultural and medical exchanges, which occurred on this trip to identify relevant themes about the problems confronting the recovery effort almost 3 years after the disaster. FINDINGS: Significant themes that emerged included a crippling radiation anxiety, a considerable stigma toward addressing mental health care, and a shortage of mental health care throughout the region, as well as ongoing psychiatric symptoms such as insomnia, anxiety, and alcohol misuse. CONCLUSIONS: These issues continue to complicate the recovery effort but suggest avenues for future interventions.
Subject(s)
Earthquakes , Environmental Exposure , Fukushima Nuclear Accident , Mental Health Services/supply & distribution , Mental Health , Tsunamis , Alcohol-Related Disorders/psychology , Anxiety/psychology , Fear/psychology , Female , Health Services Needs and Demand , Humans , International Cooperation , Interprofessional Relations , Japan , Male , Radiation, Ionizing , September 11 Terrorist Attacks/psychology , Sleep Initiation and Maintenance Disorders/psychologyABSTRACT
OBJECTIVE: To report a case of apathetic thyrotoxicosis with an etiology of subacute thyroiditis. METHODS: We describe the patient's clinical findings, laboratory findings, and clinical course. RESULTS: An 85-year-old woman with no history of thyroid disease presented with severe obtundation and altered mental status. Laboratory testing documented elevated free thyroxine and free triiodothyronine concentrations and a suppressed thyrotropin concentration. Thyroid antibodies were absent. A radioactive iodine study revealed severely diminished uptake, suggestive of thyroiditis. After a short course of steroids, the patient's mental status returned to baseline. Follow-up laboratory testing showed normalizing thyroid function. CONCLUSION: Even in the absence of a history of thyroid disease, we recommend considering thyroid dysfunction in the differential diagnosis of patients who present with altered mental status, particularly in the elderly population.
Subject(s)
Thyroiditis, Subacute/complications , Thyroiditis, Subacute/diagnosis , Thyrotoxicosis/diagnosis , Thyrotoxicosis/etiology , Aged, 80 and over , Female , HumansABSTRACT
Bariatric surgery is an effective treatment option for obesity. Commonly utilized procedures are either restrictive, malabsorptive, or both. Substantial weight loss can be achieved. Postoperatively, patients experience nutritional, metabolic, and hormonal changes that have important clinical implications. The postoperative diet should be advanced carefully, according to protocol. Micronutrient deficiencies such as vitamin C, vitamin A, and zinc deficiencies are common, especially following malabsorptive procedures. Bone metabolism is greatly affected, in part due to vitamin D deficiency, decreased calcium absorption, and secondary hyperparathyroidism. Diabetes improves acutely in malabsorptive procedures and in sequence with weight loss in restrictive procedures. Polycystic ovarian syndrome improves in nearly all women with this condition who undergo bariatric surgery. Testosterone levels in men also improve after surgery. Consideration of these nutritional, metabolic, and hormonal changes allows for optimal medical management following bariatric surgery.
Subject(s)
Bariatric Surgery , Metabolic Diseases/prevention & control , Micronutrients/therapeutic use , Nutrition Assessment , Obesity/surgery , Postoperative Care/methods , Vitamins/therapeutic use , Humans , Metabolic Diseases/etiology , Obesity/complicationsABSTRACT
Obesity is a well known risk factor for type 2 diabetes mellitus. Individuals with type 2 diabetes mellitus are at risk for weight gain as a result of multiple influences, including sedentary lifestyle, high-calorie diet, diabetes medications, sociocultural factors, chronic medical and psychiatric illnesses, and a dysregulated enteroendocrine axis. Because both diabetes mellitus and obesity predispose patients to abnormal cardiometabolic profiles and increased cardiovascular disease, management of diabetes mellitus should focus on weight management and optimizing cardiometabolic parameters, concomitant with glycemic control. Lifestyle modification incorporating healthy, calorie-appropriate diets and increased physical activity, in addition to metformin, are central components to diabetes management and weight management. These interventions have been shown to improve body weight, glycemic control, and overall cardiometabolic profile. The weight-neutral and weight-losing diabetes medications include metformin, alpha-glucosidase inhibitors, glucagon-like peptide-1 analogs, dipeptidyl peptidase-4 inhibitors, and amylin analogs. It is essential that providers understand the metabolic and weight effects of diabetes medications in order to develop strategies for managing diabetes mellitus while helping patients maintain or lose weight in order to improve their overall health outcomes.
Subject(s)
Diabetes Mellitus, Type 2/therapy , Weight Loss , Diabetes Mellitus, Type 2/complications , Humans , Life Style , Obesity/complications , Obesity/therapy , Risk FactorsABSTRACT
The consideration of surgery during pregnancy requires weighing the benefit of urgent surgery against the risk to mother and fetus. Surgery during pregnancy involves an increase in both maternal and fetal risks. Thyroid and parathyroid surgery involves physiological risks to both mother and fetus specific to the disease and function of these endocrine glands. Evaluation of a thyroid mass is similar in pregnant patients with ultrasound and fine-needle aspiration biopsy providing the most important information, while the use of radiographic imaging is severely constrained except when specifically required. In general, thyroid surgery can be delayed until after delivery except in cases of airway compromise or aggressive cancer. In contrast, parathyroid surgery is recommended during pregnancy to avoid adverse effects to the neonate.
Subject(s)
Parathyroid Diseases/surgery , Pregnancy Complications/surgery , Thyroid Diseases/surgery , Female , Humans , Infant, Newborn , Parathyroid Diseases/diagnosis , Parathyroid Diseases/etiology , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/etiology , Risk Assessment , Thyroid Diseases/diagnosis , Thyroid Diseases/etiology , Treatment OutcomeABSTRACT
OBJECTIVE: To review the pertinent basic and clinical research describing the complex effects of excess thyroid hormone on carbohydrate metabolism. METHODS: We performed a MEDLINE search of the English-language literature using a combination of words (ie, "thyrotoxicosis and diabetes," "diabetic ketoacidosis and thyroid storm," "carbohydrate metabolism and hyperthyroid," "glucose homeostasis and thyrotoxicosis") to identify key articles addressing various aspects of the thyroid's influence on carbohydrate metabolism. RESULTS: Thyroid hormone affects glucose homeostasis via its actions on a variety of organs including increased hepatic glucose output, increased futile cycling of glucose degradation products between the skeletal muscle and the liver, decreased glycogen stores in the liver and skeletal muscle, altered oxidative and non-oxidative glucose metabolism, decreased active insulin output from the pancreas, and increased renal insulin clearance. Thyroid hormone also affects adipokines and adipose tissue, further predisposing the patient to ketosis. CONCLUSIONS: Thyrotoxicosis can alter carbohydrate metabolism in a type 2 diabetic patient to such an extent that diabetic ketoacidosis develops if untreated. Based on the current understanding of this relationship, all diabetic patients should be screened for thyroid dysfunction because correcting hyperthyroidism can profoundly affect glucose homeostasis. Similarly, patients presenting in diabetic ketoacidosis should undergo a thyroid function assessment.
Subject(s)
Carbohydrate Metabolism/physiology , Diabetes Mellitus, Type 2/complications , Thyrotoxicosis/complications , Thyrotoxicosis/metabolism , Aged , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/etiology , Female , Humans , Models, Biological , Thyroid Hormones/blood , Thyrotoxicosis/bloodABSTRACT
We have previously shown that mice lacking the TSH receptor (TSHR) exhibit osteoporosis due to enhanced osteoclast formation. The fact that this enhancement is not observed in double-null mice of TSHR and TNFalpha suggests that TNFalpha overexpression in osteoclast progenitors (macrophages) may be involved. It is unknown how TNFalpha expression is regulated in osteoclastogenesis. Here, we describe a receptor activator for nuclear factor-kappaB ligand (RANKL)-responsive sequence (CCG AGA CAG AGG TGT AGG GCC), spanning from -157 to -137 bp of the 5'-flanking region of the TNFalpha gene, which functions as a cis-acting regulatory element. We further show how RANKL treatment stimulates the high-mobility group box proteins (HMGB) HMGB1 and HMGB2 to bind the RANKL-responsive sequence and up-regulates TNFalpha transcription. Exogenous HMGB elicits the expression of cytokines, including TNFalpha, as well as osteoclast formation. Conversely, TSH inhibits the expression of HMGB and TNFalpha and the formation of osteoclasts. These results suggest that HMGB play a pivotal role in osteoclastogenesis. We also show a direct correlation between the expression of HMGB and TNFalpha and osteoclast formation in TSHR-null mice and TNFalpha-null mice. Taken together, we conclude that HMGB and TNFalpha play critical roles in the regulation of osteoclastogenesis and the remodeling of bone.
Subject(s)
DNA/genetics , HMGB Proteins/physiology , Osteoclasts/metabolism , Tumor Necrosis Factor-alpha/genetics , Animals , Blotting, Western , Cell Line , Chromatin Immunoprecipitation , DNA/metabolism , Electrophoretic Mobility Shift Assay , Gene Expression Regulation/drug effects , HMGB Proteins/genetics , HMGB Proteins/metabolism , Humans , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Mice , Polymerase Chain Reaction , Promoter Regions, Genetic/genetics , RANK Ligand/pharmacology , Transcription, Genetic/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Many patients with type 2 diabetes also have the metabolic syndrome with its cardinal features of central adiposity, insulin resistance, dyslipidemia, and hypertension. Although there is strong evidence for the importance of tight glycemic control in minimizing the microvascular complications of diabetes, many of the current therapies used for optimizing glycemic control also cause weight gain. With this treatment-induced weight gain, there is a risk of worsening the patient's insulin resistance. Physicians need to be aware of this vicious cycle in their overweight type 2 diabetic patients. This article reviews the strategies currently available to achieve glycemic control while at the same time minimizing weight gain and the associated complications.