ABSTRACT
5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a cellular energy sensor, is an essential enzyme that helps cells maintain stable energy levels during metabolic stress. The hypothalamus is pivotal in regulating energy balance within the body. Certain neurons in the hypothalamus are sensitive to fluctuations in food availability and energy stores, triggering adaptive responses to preserve systemic energy equilibrium. AMPK, expressed in these hypothalamic neurons, is instrumental in these regulatory processes. Hypothalamic AMPK activity is modulated by key metabolic hormones. Anorexigenic hormones, including leptin, insulin, and glucagon-like peptide 1, suppress hypothalamic AMPK activity, whereas the hunger hormone ghrelin activates it. These hormonal influences on hypothalamic AMPK activity are central to their roles in controlling food consumption and energy expenditure. Additionally, hypothalamic AMPK activity responds to variations in glucose concentrations. It becomes active during hypoglycemia but is deactivated when glucose is introduced directly into the hypothalamus. These shifts in AMPK activity within hypothalamic neurons are critical for maintaining glucose balance. Considering the vital function of hypothalamic AMPK in the regulation of overall energy and glucose balance, developing chemical agents that target the hypothalamus to modulate AMPK activity presents a promising therapeutic approach for metabolic conditions such as obesity and type 2 diabetes mellitus.
ABSTRACT
Mitochondria function as platforms for bioenergetics, nutrient metabolism, intracellular signaling, innate immunity regulators, and modulators of stem cell activity. Thus, the decline in mitochondrial functions causes or correlates with diabetes mellitus and many aging-related diseases. Upon stress or damage, the mitochondria elicit a series of adaptive responses to overcome stress and restore their structural integrity and functional homeostasis. These adaptive responses to low-level or transient mitochondrial stress promote health and resilience to upcoming stress. Beneficial effects of low-grade mitochondrial stress, termed mitohormesis, have been observed in various organisms, including mammals. Accumulated evidence indicates that treatments boosting mitohormesis have therapeutic potential in various human diseases accompanied by mitochondrial stress. Here, we review multiple cellular signaling pathways and interorgan communication mechanisms through which mitochondrial stress leads to advantageous outcomes. We also discuss the relevance of mitohormesis in obesity, diabetes, metabolic liver disease, aging, and exercise.
ABSTRACT
Since the patient’s airway is shared between an anesthesiologist and a surgeon, airway management during upper airway surgery can be challenging. Beyond the conventional method of general anesthesia, high-flow nasal oxygenation (HFNO) has recently been used as a key technique for tubeless anesthesia. HFNO provides humidified, heated oxygen up to 70 L/min, which promises improved oxygenation and ventilation, allowing for prolonged apneic oxygenation. In previous physiological and clinical studies, HFNO has been demonstrated that tubeless anesthesia safely provide an uninterrupted surgical field during laryngeal surgeries. Although tubeless anesthesia remains uncommon, it can be a good alternative to conventional anesthesia if an anesthesiologist and a surgeon select appropriate patients together with sufficient experience. A safe strategy for tubeless anesthesia, along with appropriate backup plans, including endotracheal intubation and high-frequency jet ventilation, should be considered for upper airway surgery.
ABSTRACT
To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a “Goldilocks” amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones.
ABSTRACT
Hypertrophic osteoarthropathy (HOA) is a rare clinical condition including an abnormal periosteal reaction in the long bones that causes painful swelling and tenderness of the extremities, digital clubbing, arthritis, synovitis, and joint effusions. Most cases are associated with tumorous conditions and most commonly with lung cancer. HOA has been rarely reported in association with other cancers. A patient with a history of recurrent renal cell carcinoma was referred to our clinic with bilateral leg pain, knee joint effusion, and arthritis. Simple radiography and bone scintigraphy confirmed a diagnosis of HOA. Oral non-steroidal anti-inflammatory drugs, joint fluid aspiration, and intra-articular injection of pain medications were found to be effective in the management of HOA pain. HOA prognosis depends on the underlying disease, therefore, cancer treatment is critical. This case demonstrates the need to consider HOA in patients with various malignancies who present with bone or joint pain of the extremities.
ABSTRACT
Purpose@#The number of bariatric surgeries performed at our tertiary hospital has gradually increased since the national health insurance began to cover their expenses in January of 2019. This study examined the early surgical outcomes of laparoscopic sleeve gastrectomy (LSG) performed by experienced gastric cancer surgeons. @*Materials and Methods@#We retrospectively reviewed and analyzed data from 50 patients who underwent LSG between November of 2018 and April of 2020 at the Asan Medical Center by 1 of 5 experienced surgeons each of whom performed approximately 100–300 cases of gastrectomy annually. The age, body mass index (BMI), weight, presence of comorbidities, operation time, hospital stay after surgery, postoperative complications, postoperative excess weight loss (EWL), and resolution of comorbidities were examined. @*Results@#The mean age, BMI, and weight were 37.29±9.77 years, 37.12 kg/m2, and 102.00 kg, respectively. The mean operation time and postoperative length of hospital stay were 109.59±35.88 and 5.06±1.20 days, respectively. Two patients (4.00%) had early postoperative complications and postoperative leakage; bleeding and stenosis were not reported. The EWL after 1 and 6 months of operation was 26.55% and 60.34%, respectively. The resolution of diabetes, hypertension, and dyslipidemia after 6 months of operation was 88.89%, 54.54%, and 50.00%, respectively. @*Conclusion@#LSG is safe and effective when performed by an experienced gastric cancer surgeon; however, a long-term follow-up of patients is required.
ABSTRACT
Background@#Medical nutrition therapy is a fundamental part of diabetes management; however, it is very difficult for patients to maintain the recommended diet programs. We investigated whether providing home-delivered therapeutic meals designed by registered dietitians could be useful in lowering blood glucose levels in patients with type 2 diabetes. @*Methods@#During a 12-day study period, we monitored the blood glucose levels of 19 patients with type 2 diabetes by continuous glucose monitoring. For the first six days, the participants maintained their usual lifestyles and were allowed to eat freely (free meal period). During the last six days, two out of the three main meals per day were replaced with home-delivered therapeutic meals designed for diabetes management (therapeutic meal period), during which snacks and exercise were freely allowed. Blood glucose levels and estimated glycated hemoglobin (eHbA1c) were compared between the two periods. @*Results@#Between the free meal period and the therapeutic meal period, mean blood glucose level and eHbA1c dropped by 11.9 mg/dL (P < 0.001) and 0.4% (P = 0.002), respectively. These results were mainly due to the decrease in postprandial glucose levels rather than preprandial glucose levels. @*Conclusion@#Providing home-delivered therapeutic meals designed for diabetes management was effective in lowering the blood glucose levels in patients with type 2 diabetes.
ABSTRACT
Background@#Medical nutrition therapy is a fundamental part of diabetes management; however, it is very difficult for patients to maintain the recommended diet programs. We investigated whether providing home-delivered therapeutic meals designed by registered dietitians could be useful in lowering blood glucose levels in patients with type 2 diabetes. @*Methods@#During a 12-day study period, we monitored the blood glucose levels of 19 patients with type 2 diabetes by continuous glucose monitoring. For the first six days, the participants maintained their usual lifestyles and were allowed to eat freely (free meal period). During the last six days, two out of the three main meals per day were replaced with home-delivered therapeutic meals designed for diabetes management (therapeutic meal period), during which snacks and exercise were freely allowed. Blood glucose levels and estimated glycated hemoglobin (eHbA1c) were compared between the two periods. @*Results@#Between the free meal period and the therapeutic meal period, mean blood glucose level and eHbA1c dropped by 11.9 mg/dL (P < 0.001) and 0.4% (P = 0.002), respectively. These results were mainly due to the decrease in postprandial glucose levels rather than preprandial glucose levels. @*Conclusion@#Providing home-delivered therapeutic meals designed for diabetes management was effective in lowering the blood glucose levels in patients with type 2 diabetes.
ABSTRACT
BACKGROUND AND OBJECTIVES@#A relationship between renin-angiotensin system (RAS) components and metabolic syndrome (MetS) has been suggested, but not elucidated clearly. We examined the levels of RAS components in patients with and without MetS and their association with MetS in Korean population.@*METHODS@#This study was approved by the review boards of the participating institutions and endorsed by the Korean Society of Lipid and Atherosclerosis. We screened 892 Koreans aged ≥20 years who underwent evaluation of hypertension, diabetes, or dyslipidemia at 6 tertiary hospitals in 2015–2016. After excluding patients who were taking diuretics, β-blockers, or RAS blockers, or suspected of primary aldosteronism, 829 individuals were enrolled. Anthropometric and biochemical parameters including aldosterone, plasma renin activity (PRA), and aldosterone-to-PRA ratio were evaluated. The homeostasis model assessment for insulin resistance (HOMA-IR) were used for evaluating insulin resistance.@*RESULTS@#The mean age of the participants was 52.8±12.8 years, 56.3% were male, and their mean systolic and diastolic blood pressures were 133.9±20.0 and 81.2±14.6 mmHg, respectively. The levels of serum aldosterone, but not PRA, were significantly higher in subjects with MetS than in those without (20.6±33.6 vs. 15.3±12.2 ng/dL, p < 0.05), and positively correlated with waist circumference, blood pressure, triglycerides, and glycated hemoglobin. The levels of aldosterone were independently associated with the number of MetS components and HOMA-IR after adjusting for conventional risk factors.@*CONCLUSIONS@#Serum aldosterone levels were higher in Korean adults with MetS than in those without. This finding suggests that increased aldosterone level might be closely associated with insulin resistance.
ABSTRACT
BACKGROUND AND OBJECTIVES: A relationship between renin-angiotensin system (RAS) components and metabolic syndrome (MetS) has been suggested, but not elucidated clearly. We examined the levels of RAS components in patients with and without MetS and their association with MetS in Korean population. METHODS: This study was approved by the review boards of the participating institutions and endorsed by the Korean Society of Lipid and Atherosclerosis. We screened 892 Koreans aged ≥20 years who underwent evaluation of hypertension, diabetes, or dyslipidemia at 6 tertiary hospitals in 2015–2016. After excluding patients who were taking diuretics, β-blockers, or RAS blockers, or suspected of primary aldosteronism, 829 individuals were enrolled. Anthropometric and biochemical parameters including aldosterone, plasma renin activity (PRA), and aldosterone-to-PRA ratio were evaluated. The homeostasis model assessment for insulin resistance (HOMA-IR) were used for evaluating insulin resistance. RESULTS: The mean age of the participants was 52.8±12.8 years, 56.3% were male, and their mean systolic and diastolic blood pressures were 133.9±20.0 and 81.2±14.6 mmHg, respectively. The levels of serum aldosterone, but not PRA, were significantly higher in subjects with MetS than in those without (20.6±33.6 vs. 15.3±12.2 ng/dL, p < 0.05), and positively correlated with waist circumference, blood pressure, triglycerides, and glycated hemoglobin. The levels of aldosterone were independently associated with the number of MetS components and HOMA-IR after adjusting for conventional risk factors. CONCLUSIONS: Serum aldosterone levels were higher in Korean adults with MetS than in those without. This finding suggests that increased aldosterone level might be closely associated with insulin resistance.
Subject(s)
Adult , Humans , Male , Aldosterone , Atherosclerosis , Blood Pressure , Diuretics , Dyslipidemias , Glycated Hemoglobin , Homeostasis , Hyperaldosteronism , Hypertension , Insulin Resistance , Insulin , Metabolic Syndrome , Plasma , Renin , Renin-Angiotensin System , Risk Factors , Tertiary Care Centers , Triglycerides , Waist CircumferenceABSTRACT
In the original article, the legend of Fig. 1 was incorrect. The solid line was noninsulinoma, and the dotted line was insulinoma.
ABSTRACT
No abstract available.
Subject(s)
Aphasia, Broca , Diabetes Mellitus, Type 2 , Hyperglycemic Hyperosmolar Nonketotic ComaABSTRACT
BACKGROUND: The aim of this study is to evaluate the influence of immunosuppressants on in-hospital mortality from sepsis. METHODS: Using data of the Health Insurance Review & Assessment Service, we collected data from patients who were admitted to the hospital due to sepsis from 2009 to 2013. Based on drugs commonly used for immunosuppression caused by various diseases, patients were divided into three groups; immunosuppressant group, steroid-only group, and control group. Patients with no history of immunosuppressants or steroids were assigned to the control group. To identify risk factors of in-hospital mortality in sepsis, we compared differences in patient characteristics, comorbidities, intensive care unit (ICU) care requirements, and immunodeficiency profiles. Subgroup analysis according to age was also performed. RESULTS: Of the 185,671 included patients, 13,935 (7.5%) were in the steroid-only group and 2,771 patients (1.5%) were in the immunosuppressant group. The overall in-hospital mortality was 38.9% and showed an increasing trend with age. The steroid-only group showed the lowest in-hospital mortality among the three groups except the patients younger than 30 years. The steroid-only group and immunosuppressant group received ICU treatment more frequently (p < 0.001), stayed longer in the hospital (p < 0.001), and showed higher medical expenditure (p < 0.001) compared to the normal group. Univariate and multivariate analyses revealed that age, male gender, comorbidities (especially malignancy), and ICU treatment had a significant effect on in-hospital mortality. CONCLUSIONS: Despite longer hospital length of stay and more frequent need for ICU care, the in-hospital mortality was lower in patients taking immunosuppressive drugs than in patients not taking immunosuppressive drugs.
Subject(s)
Humans , Male , Comorbidity , Health Expenditures , Hospital Mortality , Immunosuppression Therapy , Immunosuppressive Agents , Insurance , Insurance, Health , Intensive Care Units , Korea , Length of Stay , Mortality , Multivariate Analysis , Risk Factors , Sepsis , SteroidsABSTRACT
BACKGROUND: The aim of this study is to evaluate the influence of immunosuppressants on in-hospital mortality from sepsis. METHODS: Using data of the Health Insurance Review & Assessment Service, we collected data from patients who were admitted to the hospital due to sepsis from 2009 to 2013. Based on drugs commonly used for immunosuppression caused by various diseases, patients were divided into three groups; immunosuppressant group, steroid-only group, and control group. Patients with no history of immunosuppressants or steroids were assigned to the control group. To identify risk factors of in-hospital mortality in sepsis, we compared differences in patient characteristics, comorbidities, intensive care unit (ICU) care requirements, and immunodeficiency profiles. Subgroup analysis according to age was also performed. RESULTS: Of the 185,671 included patients, 13,935 (7.5%) were in the steroid-only group and 2,771 patients (1.5%) were in the immunosuppressant group. The overall in-hospital mortality was 38.9% and showed an increasing trend with age. The steroid-only group showed the lowest in-hospital mortality among the three groups except the patients younger than 30 years. The steroid-only group and immunosuppressant group received ICU treatment more frequently (p < 0.001), stayed longer in the hospital (p < 0.001), and showed higher medical expenditure (p < 0.001) compared to the normal group. Univariate and multivariate analyses revealed that age, male gender, comorbidities (especially malignancy), and ICU treatment had a significant effect on in-hospital mortality. CONCLUSIONS: Despite longer hospital length of stay and more frequent need for ICU care, the in-hospital mortality was lower in patients taking immunosuppressive drugs than in patients not taking immunosuppressive drugs.
Subject(s)
Humans , Male , Comorbidity , Health Expenditures , Hospital Mortality , Immunosuppression Therapy , Immunosuppressive Agents , Insurance , Insurance, Health , Intensive Care Units , Korea , Length of Stay , Mortality , Multivariate Analysis , Risk Factors , Sepsis , SteroidsABSTRACT
BACKGROUND: Even though several oral anti-diabetic drugs (OAD) with various modes of action are replacing sulfonylurea (SU), some patients seem to be dependent on SU for adequate glycemic control. Therefore, we evaluated the clinical characteristics of such patients. METHODS: We selected the patients with type 2 diabetes who met following criteria from 2009 to 2014 at Seoul National University Hospital: glycated hemoglobin (HbA1c) was maintained below 7.5% for at least 6 months under small dose of SU (glimepiride or =1.2% within 3 months or > or =1.5% within 6 months; and after resuming SU, HbA1c reduction was > or =0.8% or reduction of fasting plasma glucose was > or =40 mg/dL within 3 months. Patients with impaired hepatic or renal function, and steroid users were excluded. RESULTS: Nineteen subjects were enrolled: after averaged 4.8+/-1.5 months of SU-free period, HbA1c increased from 6.7%+/-0.4% to 8.8%+/-0.8% even though adding other OAD such as gliptins. However, HbA1c decreased to 7.4%+/-0.7% after resuming SU within 2.4+/-0.8 months. There was no sexual predominance. Despite their old age (67+/-11 years) and long duration of diabetes (18+/-10 years), fasting C-peptide was relatively well-reserved (3.9+/-2.6 ng/mL), and nephropathy was not observed (albumin-creatinine ratio 21.2+/-16.6 mg/g and estimated glomerular filtration rate 75.8+/-18.0 mL/min/1.73 m2). Strong family history was also noted (73.7%). CONCLUSION: Despite hypoglycemia risk of SU, it seemed indispensable for a subset of patients with regard to insulin secretion. Genetic influences would be evaluated.
Subject(s)
Humans , Blood Glucose , C-Peptide , Diabetes Mellitus , Dipeptidyl-Peptidase IV Inhibitors , Fasting , Glomerular Filtration Rate , Glycated Hemoglobin , Hypoglycemia , Insulin , SeoulABSTRACT
Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from enteroendocrine L-cells upon nutrient absorption; it stimulates glucose-dependent insulin secretion from pancreatic betacells. GLP-1 has pleiotropic effects including deceleration of gastric emptying, decreased appetite, and increased satiety. Treatment with GLP-1 receptor agonists (GLP-1RAs) improves glycemic control in patients with type 2 diabetes without increasing the risk of hypoglycemia or weight gain. Current GLP-1RAs can be classified by their structure (exendin-4-based or human GLP-1-based), duration of action, and molecular size. Different GLP-1RAs exhibit different pharmacokinetics and pharmacodynamics. Herein we review the characteristics of available GLP-1RAs and discuss current issues such as insulin combination therapy and anti-obesity effects.
Subject(s)
Humans , Absorption , Appetite , Deceleration , Diabetes Mellitus, Type 2 , Gastric Emptying , Glucagon-Like Peptide 1 , Hypoglycemia , Incretins , Insulin , Obesity , Pharmacokinetics , Weight Gain , Glucagon-Like Peptide-1 ReceptorABSTRACT
Therapeutic plasma exchange (TPE) is one possible treatment for patients resistant to conventional antithyroid drugs or requiring urgent attention for thyrotoxicosis. We report a 35-yr-old man with thyrotoxicosis, ultimately attributed to Graves' disease in whom antithyroid drug used initially was soon discontinued, due to abnormal liver function, and replaced by Lugol's solution. Three weeks later, an escape phenomenon (to Lugol's solution) was apparent, so we performed TPE to control the thyrotoxicosis. Two courses of TPE by a centrifugal type machine resulted in diminished levels of thyroid hormone levels, which then rebounded after another two courses of membrane filtration type TPE. However, the patient could be treated with radioactive iodine therapy without any complications at present.
Subject(s)
Adult , Humans , Male , Antithyroid Agents/adverse effects , Cetirizine/adverse effects , Graves Disease/radiotherapy , Hepatitis B, Chronic/complications , Iodides/therapeutic use , Iodine Radioisotopes/therapeutic use , Methimazole/adverse effects , Plasmapheresis/methods , Thyroid Gland/pathology , Thyrotoxicosis/therapyABSTRACT
BACKGROUND: Subjects with normal glucose tolerance (NGT) who have a high 1-hour postload plasma glucose level (> or =155 mg/dL; NGT 1 hour-high) have been shown to be at higher risk for type 2 diabetes than subjects with NGT 1 hour-low postload plasma glucose level (<155 mg/dL). We compared beta-cell function in subjects with NGT 1 hour-high, NGT 1 hour-low, and impaired glucose tolerance (IGT). METHODS: We classified subjects into NGT 1 hour-low (n=149), NGT 1 hour-high (n=43), and IGT (n=52). The beta-cell function was assessed based on insulinogenic index (IGI), oral disposition index (DI), and insulin secretion-sensitivity index-2 (ISSI-2). RESULTS: Insulin sensitivity was comparable between the subjects with NGT 1 hour-high and NGT 1 hour-low. The beta-cell function with/without adjusting insulin sensitivity was significantly different among the three groups. The IGI (pmol/mmol) was 116.8+/-107.3 vs. 64.8+/-47.8 vs. 65.8+/-80.6 (P=0.141), oral DI was 3.5+/-4.2 vs. 1.8+/-1.4 vs. 1.8+/-3.1 (P<0.001), and ISSI-2 was 301.2+/-113.7 vs. 213.2+/-67.3 vs. 172.5+/-87.5 (P<0.001) in NGT 1 hour-low, NGT 1 hour-high, and IGT, respectively. Post hoc analyses revealed that oral DI and ISSI-2 were significantly different between NGT 1 hour-low and NGT 1 hour-high but comparable between NGT 1 hour-high and IGT. CONCLUSION: Among Korean subjects with NGT, those who have a higher 1-hour postload glucose level have a compromised insulin-sensitivity adjusted beta-cell function to a similar degree as IGT subjects.
Subject(s)
Blood Glucose , Glucose Tolerance Test , Glucose , Insulin , Insulin ResistanceABSTRACT
BACKGROUND: Among the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas. METHODS: We reviewed the medical records of patients who underwent evaluation for hypoglycemia from 2000 to 2013. Fourteen patients with histopathologically confirmed insulinoma and 18 patients without clinical evidence of insulinoma were included. The results of a prolonged fast test were analyzed according to the abovementioned criteria. RESULTS: Fulfilling all three Endocrine Society criteria-plasma levels of glucose ( or =8 pmol/L), and C-peptide (> or =0.2 nmol/L)-exhibited 100% sensitivity and 89% specificity. Fulfilling the glucose and C-peptide criteria showed 100% sensitivity and 83% specificity, while fulfilling the glucose and insulin criteria showed 100% sensitivity and 72% specificity. Among the ratio criteria, the insulin-glucose ratio [>24.0 (pmol/L)/(mmol/L)] gave the highest area under the receiver operating characteristic curve, with 93% sensitivity and 94% specificity. CONCLUSION: Fulfilling the glucose, insulin, and C-peptide criteria of the Endocrine Society guidelines exhibited the best diagnostic performance for insulinoma. Nonetheless, the insulin-glucose ratio may still have a role in the biochemical diagnosis of insulinoma.