Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family. Acting in an endocrine fashion, it increases glucose uptake, modulates lipid metabolism, and sensitizes insulin response in metabolically active organs, including the liver and adipose tissue. Emerging evidence shows a strong correlation between circulating FGF21 levels and the incidence and severity of atherosclerosis. Animal studies have demonstrated a beneficial role of FGF21 in protecting against aberrant lipid profile, while recent development in FGF21 mimetics has provided further insight into the lipid-lowering effects of FGF21 signaling. The present review summarizes the physiological roles of FGF21, and discusses major breakthroughs and limitations of FGF21 mimetic-based therapeutic strategies for treating atherosclerosis.
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Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as 68Ga-DOTATATE (68Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace 123I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong.
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Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.
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The proposal that diabetes plays a role in the development of heart failure is supported by the increased risk associated with this disease, even after correcting for all other known risk factors. However, the precise mechanisms contributing to the condition referred to as diabetic cardiomyopathy have remained elusive, as does defining the disease itself. Decades of study have defined numerous potential factors that each contribute to disease susceptibility, progression, and severity. Many recent detailed reviews have been published on mechanisms involving insulin resistance, dysregulation of microRNAs, and increased reactive oxygen species, as well as causes including both modifiable and non-modifiable risk factors. As such, the focus of the current review is to highlight aspects of each of these topics and to provide specific examples of recent advances in each area.
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Glucocorticoids are widely used as potent anti-inflammatory and immunosuppressive drugs to treat a wide range of diseases. However, they are also associated with a number of side effects, including new-onset hyperglycemia in patients without a history of diabetes mellitus (DM) or severely uncontrolled hyperglycemia in patients with known DM. Glucocorticoid-induced diabetes mellitus (GIDM) is a common and potentially harmful problem in clinical practice, affecting almost all medical specialties, but is often difficult to detect in clinical settings. However, scientific evidence is lacking regarding the effects of GIDM, as well as strategies for prevention and treatment. Similarly to nonsteroid-related DM, the principles of early detection and risk factor modification apply. Screening for GIDM should be considered in all patients treated with medium to high doses of glucocorticoids. Challenges in the management of GIDM stem from wide fluctuations in postprandial hyperglycemia and the lack of clearly defined treatment protocols. Together with lifestyle measures, hypoglycemic drugs with insulin-sensitizing effects are indicated. However, insulin therapy is often unavoidable, to the point that insulin can be considered the drug of choice. The treatment of GIDM should take into account the degree and pattern of hyperglycemia, as well as the type, dose, and schedule of glucocorticoid used. Moreover, it is essential to instruct the patient and/or the patient's family about how to perform the necessary adjustments. Prospective studies are needed to answer the remaining questions regarding GIDM.
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Patterns of Glucose Fluctuation are Challenging in Patients Treated for Non-Hodgkin’s Lymphoma
Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring. The next step is a sensor-augmented pump, preferably with a low glucose suspension feature or very frequent contact, and the final step is islet or pancreas transplantation. In Korea, however, none of these treatments are reimbursed by the National Health Insurance, and thus have not been widely implemented. The low prevalence of type 1 diabetes means that Korean physicians are relatively unfamiliar with the new technologies in this field. Therefore, the roles of new technologies and pancreas or islet transplantation in the treatment of problematic hypoglycemia need to be defined in the current clinical setting of Korea.
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Recently, cardiovascular morbidity and mortality have been continuously reduced in people with diabetes through the intensive management of multiple risk factors. However, contrary to this trend, the prevalence and clinical significance of neurodegenerative disorders are steadily increasing. In previous studies, diabetes mellitus has been found to play an important role in increasing the risk of dementia and cognitive dysfunction through various mechanisms. In particular, hypoglycemia is a frequent clinical situation in the strict management of diabetes and is well known as an important factor that directly affects the risk of dementia and cognitive impairment. This article describes the occurrence of hypoglycemia in patients with diabetes, and summarizes the resultant risks of dementia and cognitive dysfunction.
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An adrenal incidentaloma is an adrenal mass found in an imaging study performed for other reasons unrelated to adrenal disease and often accompanied by obesity, diabetes, or hypertension. The prevalence and incidence of adrenal incidentaloma increase with age and are also expected to rise due to the rapid development of imaging technology and frequent imaging studies. The Korean Endocrine Society is promoting an appropriate practice guideline to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues in managing the patients with adrenal incidentaloma. After evaluating core proposition, we propose the most critical 20 recommendations from the initially organized 47 recommendations by Delphi technique.
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The aim of this study was to assess the utility of the visceral adiposity index (VAI) and the hypertriglyceridemic waist (HTGW) phenotype as possible hypertension (HTN) predictors in a high-risk population without diabetes and HTN.
Incident HTN over a 7-year follow-up was assessed among 1,375 first-degree non-diabetic and non-hypertensive relatives of consecutive patients with type 2 diabetes who were 30 to 70 years of age. HTN was defined as a blood pressure reading ≥140/90 mm Hg or the use of antihypertensive medications. We examined the incidence of HTN across VAI quintiles and four groups defined according to baseline fasting serum triglyceride (TG) levels and waist circumference (WC).
The VAI and the HTGW phenotype at baseline were related to an increased risk for HTN. In comparison with the lowest VAI quintile, the highest VAI quintile showed a significant associated with HTN in an age- and gender-adjusted model (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07 to 2.55). Those with HTGW were 2.3 times (OR, 2.27; 95% CI, 1.54 to 3.35) more likely to develop HTN than those with a normal WC and normal TG levels.
Greater VAI values weakly predicted HTN, whereas the HTGW phenotype was a stronger predictor of incident HTN in an Iranian high-risk population.
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Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM.
Patients with T2DM (
Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM.
The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM.
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Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes.
In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily,
Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment. Vildagliptin also significantly reduced the MAGE (from 93.8±38.0 to 70.8±19.2 mg/dL,
In this 16-week treatment trial, vildagliptin, but not pioglitazone, reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy, although a reduction of oxidative stress markers was not observed.
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Menstrual irregularity is an indicator of endocrine disorders and reproductive health status. It is associated with various diseases and medical conditions, including obesity and underweight. We aimed to assess the association between body weight changes and menstrual irregularity in Korean women.
A total of 4,621 women 19 to 54 years of age who participated in the 2010 to 2012 Korea National Health and Nutrition Examination Survey were included in this study. Self-reported questionnaires were used to collect medical information assessing menstrual health status and body weight changes. Odds ratios (ORs) and 95% confidence interval (CI) were calculated to evaluate the association between body weight changes and menstrual irregularity.
Significantly higher ORs (95% CI) were observed in the association between menstrual irregularity and both weight loss (OR, 1.74; 95% CI, 1.22 to 2.48) and weight gain (OR, 1.45; 95% CI, 1.13 to 1.86) after adjusting for age, body mass index, current smoking, heavy alcohol drinking, regular exercise, calorie intake, education, income, metabolic syndrome, age of menarche, parity, and stress perception. Of note, significant associations were only observed in subjects with obesity and abdominal obesity, but not in non-obese or non-abdominally obese subjects. U-shaped patterns were demonstrated in both obese and abdominally obese subjects, indicating that greater changes in body weight are associated with higher odds of menstrual irregularity.
We found a U-shaped pattern of association between body weight changes and menstrual irregularity among obese women in the general Korean population. This result indicates that not only proper weight management but also changes in body weight may influence the regulation of the menstrual cycle.
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Insulin resistance is associated with the higher content of intermuscular adipose tissue (IMAT) and the saturation of intramyocellular lipid (IMCL), but a paucity of data exist in humans. This study examined associations among IMAT content, IMCL saturation, and fasting glucose concentration in middle-aged and older adults with overweight or obesity.
Seventy-five subjects (26 males, 49 females) were recruited and thigh muscle and IMAT were assessed using magnetic resonance imaging.
The characteristics of the 75 subjects were as follows: age 59±11 years, body mass index 30±5 kg/m2, fasting glucose concentration 5.2±0.5 mmol/L, fasting insulin concentration 12.2±7.3 µU/mL, fasting homeostatic model assessment of insulin resistance (HOMA-IR) 2.9±2.0 (mean±SD). IMAT to muscle tissue (MT) volume ratio was positively associated with the saturated fatty acid to unsaturated fatty acid ratio in IMCL. IMAT:MT was positively associated with fasting glucose concentration and HOMA-IR. IMCL saturation was positively associated with fasting glucose concentration while muscle cell area, IMCL area, and % IMCL in muscle cell were not associated with fasting glucose concentration.
These results indicate that higher intermuscular fat content and IMCL saturation may impact fasting glucose concentration in middle-aged and older adults with overweight or obesity. The centralization of adipose tissue in the appendicular region of the body may promote insulin resistance.
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Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan.
In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [
No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B.
The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.
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