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1.
Diabetes & Metabolism Journal ; : 86-96, 2021.
Article in English | WPRIM | ID: wpr-874531

ABSTRACT

BackgroundNotch signaling pathway plays an important role in regulating pancreatic endocrine and exocrine cell fate during pancreas development. Notch signaling is also expressed in adult pancreas. There are few studies on the effect of Notch on adult pancreas. Here, we investigated the role of Notch in islet mass and glucose homeostasis in adult pancreas using Notch1 antisense transgenic (NAS).MethodsWestern blot analysis was performed for the liver of 8-week-old male NAS mice. We also conducted an intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test in 8-week-old male NAS mice and male C57BL/6 mice (control). Morphologic observation of pancreatic islet and β-cell was conducted in two groups. Insulin secretion capacity in islets was measured by glucose-stimulated insulin secretion (GSIS) and perifusion.ResultsNAS mice showed higher glucose levels and lower insulin secretion in IPGTT than the control mice. There was no significant difference in insulin resistance. Total islet and β-cell masses were decreased in NAS mice. The number of large islets (≥250 µm) decreased while that of small islets (ConclusionOur study provides that Notch1 inhibition decreased insulin secretion and decreased islet and β-cell masses. It is thought that Notch1 inhibition suppresses islet proliferation and induces differentiation of small islets. In conclusion, Notch signaling pathway may play an important role in β-cell mass determination and diabetes.

2.
Diabetes & Metabolism Journal ; : 733-743, 2019.
Article in English | WPRIM | ID: wpr-785717

ABSTRACT

Cancer incidence appears to be increased in both type 1 and type 2 diabetes mellitus (DM). DM represents a risk factor for cancer, particularly hepatocellular, hepatobiliary, pancreas, breast, ovarian, endometrial, and gastrointestinal cancers. In addition, there is evidence showing that DM is associated with increased cancer mortality. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in patients with DM. Although the mechanistic process that may link diabetes to cancer is not completely understood yet, biological mechanisms linking DM and cancer are hyperglycemia, hyperinsulinemia, increased bioactivity of insulin-like growth factor 1, oxidative stress, dysregulations of sex hormones, and chronic inflammation. However, cancer screening rate is significantly lower in people with DM than that in people without diabetes. Evidence from previous studies suggests that some medications used to treat DM are associated with either increased or reduced risk of cancer. However, there is no strong evidence supporting the association between the use of anti-hyperglycemic medication and specific cancer. In conclusion, all patients with DM should be undergo recommended age- and sex appropriate cancer screenings to promote primary prevention and early detection. Furthermore, cancer should be screened in routine diabetes assessment.


Subject(s)
Humans , Breast , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Early Detection of Cancer , Gastrointestinal Neoplasms , Gonadal Steroid Hormones , Hyperglycemia , Hyperinsulinism , Incidence , Inflammation , Mass Screening , Mortality , Obesity , Oxidative Stress , Pancreas , Primary Prevention , Risk Factors , Smoke , Smoking
3.
The Korean Journal of Internal Medicine ; : 62-66, 2017.
Article in English | WPRIM | ID: wpr-225713

ABSTRACT

Since the report of type 1 diabetes reversal in seven consecutive patients by the Edmonton protocol in 2000, pancreatic islet transplantation has been reappraised based on accumulated clinical evidence. Although initially expected to therapeutically target long-term insulin independence, islet transplantation is now indicated for more specific clinical benefits. With the long-awaited report of the first phase 3 clinical trial in 2016, allogeneic islet transplantation is now transitioning from an experimental to a proven therapy for type 1 diabetes with problematic hypoglycemia. Islet autotransplantation has already been therapeutically proven in chronic pancreatitis with severe abdominal pain refractory to conventional treatments, and it holds promise for preventing diabetes after partial pancreatectomy due to benign pancreatic tumors. Based on current evidence, this review focuses on islet transplantation as a realistic approach to treating diabetes.


Subject(s)
Humans , Abdominal Pain , Autografts , Hypoglycemia , Insulin , Islets of Langerhans , Islets of Langerhans Transplantation , Pancreatectomy , Pancreatitis, Chronic , Transplantation, Autologous
4.
Journal of Korean Diabetes ; : 123-133, 2016.
Article in Korean | WPRIM | ID: wpr-726743

ABSTRACT

BACKGROUND: The aim of this study was to assess the psychological well-being and treatment satisfaction in patients with type 2 diabetes mellitus in a general hospital in Korea. METHODS: This study included 440 type 2 diabetes patients above 20 years of age. Well-Being Questionnaire-12 (WBQ-12) and Diabetes Treatment Satisfaction Questionnaire were used to survey well-being and treatment satisfaction, respectively. WBQ-12 consists of 4 categories: negative well-being (NWB), energy (ENE), positive well-being (PWB), and general well-being (GWB). RESULTS: There were significant associations between NWB scores and women, low education, low-income, and number of hospital admissions. Significant associations were also identified between ENE scores and men, higher education, insulin nonusers, high-income, compliance with recommended exercise, number of medications, satisfaction with treatment time, and poor glycemic control. PWB scores were significantly associated with high-income, satisfaction with waiting and treatment times, compliance with recommended diet and exercise, and number of medications. GWB scores were significantly associated with men, higher education, high-income, satisfaction with waiting and treatment times, compliance with recommended exercise, and number of medications. Treatment satisfaction was significantly associated with age, satisfaction with waiting and treatment times, compliance with recommended diet and exercise, and duration of diabetes. CONCLUSION: Diabetes care requires psychosocial support in addition to medical care. Unlike Western studies, our study found that satisfaction with waiting and treatment times had a strong correlation with well-being and treatment satisfaction in diabetes patients.


Subject(s)
Female , Humans , Male , Compliance , Diabetes Mellitus, Type 2 , Diet , Education , Hospitals, General , Insulin , Korea , Morinda , Outpatients
5.
Endocrinology and Metabolism ; : 146-153, 2014.
Article in English | WPRIM | ID: wpr-39634

ABSTRACT

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands). MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above. METHODS: A 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma) 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1. RESULTS: Genomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion. CONCLUSION: There is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma could be suspected.


Subject(s)
Aged , Female , Humans , Brain , Cavernous Sinus , Cranial Nerve Diseases , Diagnosis , Diagnostic Errors , Diplopia , Exons , Genetic Testing , Hemangioma, Cavernous , Islets of Langerhans , Leukocytes , Magnetic Resonance Imaging , Multiple Endocrine Neoplasia Type 1 , Neurologic Manifestations , Paralysis , Pituitary Function Tests , Pituitary Neoplasms , Prevalence
6.
Journal of Korean Diabetes ; : 45-50, 2014.
Article in Korean | WPRIM | ID: wpr-726907

ABSTRACT

Diabetes mellitus is a major risk factor for urinary tract infection (UTI); emphysematous pyelonephritis (EP), a complication of UTIs, often occurs in patients with underlying, poorly controlled diabetes mellitus. We report the case of an 87-year-old woman with EP in type 2 diabetes mellitus who developed pneumatosis cystoides intestinalis (PCI) with portal venous gas. PCI is a radiographic finding, which is found in a linear or cystic form of gas in the submucosa or subserosa of the bowel wall. PCI has two common presentations. Primary PCI is a benign idiopathic condition. Secondary PCI is associated with a wide variety of gastrointestinal and non-gastrointestinal diseases. PCI with portal venous gas in particular is associated with ischemic gastrointestinal disease. Initial pre-enhanced abdominopelvic computed tomography showed EP in the right kidney without PCI. Newly occurring PCI and hepatic portal venous gas were found in the right ascending colon after EP improved. This is a rare case of PCI accompanied by emphysematous pyelonephritis in type 2 diabetes mellitus. The patient's general condition improved with intravenous antibiotics and fluid therapy without a surgical approach. However, she was discharged without further treatment because the family refused any further evaluations and treatments.


Subject(s)
Aged, 80 and over , Female , Humans , Anti-Bacterial Agents , Colon, Ascending , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Fluid Therapy , Gastrointestinal Diseases , Kidney , Pneumatosis Cystoides Intestinalis , Pyelonephritis , Risk Factors , Urinary Tract Infections
7.
Diabetes & Metabolism Journal ; : 449-455, 2014.
Article in English | WPRIM | ID: wpr-183760

ABSTRACT

BACKGROUND: The aim of this study was to investigate whether adjusting diabetic treatment regimens according to the information obtained from a continuous glucose monitoring system (CGMS) might lead to improved glycemic control in patients with type 2 diabetes. METHODS: We reviewed the medical charts of 172 patients who used the CGMS for 1 year starting in December 2008 and the records of 1,500 patients who visited their regular outpatient clinics during December 2008. Of these patients, a total of 65 CGMS patients and 301 regular outpatients (control group) were enrolled in the study after propensity score matching. There were no differences in baseline glycated hemoglobin (HbA1c), age, and duration of diabetes between the CGMS and the control groups after propensity score matching. The changes in the HbA1c levels from baseline to 6 months were calculated. RESULTS: The CGMS group showed a significant improvement in the HbA1c level compared to the control group at 3 months (7.9%+/-1.6% vs. 7.4%+/-1.2%, P=0.001) and at 6 months (7.4%+/-1.2% vs. 7.9%+/-1.6%, P=0.010). There were significant differences in the treatment modality changes between the CGMS group and the control group. CONCLUSION: Using a 3-day CGMS was advantageous for improving glucose control in patients with type 2 diabetes and may help these patients to optimize glycemic control in clinical practice.


Subject(s)
Humans , Ambulatory Care Facilities , Diabetes Mellitus, Type 2 , Glucose , Glycated Hemoglobin , Outpatients , Propensity Score
8.
Endocrinology and Metabolism ; : 450-456, 2014.
Article in English | WPRIM | ID: wpr-126652

ABSTRACT

BACKGROUND: The aim of this study was to assess the clinical differences between acromegalic patients with microadenoma and patients with macroadenoma, and to evaluate the predictive value of growth hormone (GH) levels for early detection of macroadenoma. METHODS: We performed a retrospective analysis of 215 patients diagnosed with a GH-secreting pituitary adenoma. The patients were divided into two groups: the microadenoma group and the macroadenoma group, and the clinical parameters were compared between these two groups. The most sensitive and specific GH values for predicting macroadenoma were selected using receiver operating characteristic (ROC) curves. RESULTS: Compared with the microadenoma group, the macroadenoma group had a significantly younger age, higher body mass index, higher prevalence of hyperprolactinemia and hypogonadism, and a lower proportion of positive suppression to octreotide. However, there were no significant differences in the gender or in the prevalence of diabetes between the two groups. The tumor diameter was positively correlated with all GH values during the oral glucose tolerance test (OGTT). All GH values were significantly higher in the macroadenoma group than the microadenoma group. Cut-off values for GH levels at 0, 30, 60, 90, and 120 minutes for optimal discrimination between macroadenoma and microadenoma were 5.6, 5.7, 6.3, 6.0, and 5.8 ng/mL, respectively. ROC curve analysis revealed that the GH value at 30 minutes had the highest area under the curve. CONCLUSION: The GH level of 5.7 ng/mL or higher at 30 minutes during OGTT could provide sufficient information to detect macroadenoma at the time of diagnosis.


Subject(s)
Humans , Acromegaly , Body Mass Index , Diagnosis , Discrimination, Psychological , Glucose Tolerance Test , Growth Hormone , Growth Hormone-Secreting Pituitary Adenoma , Hyperprolactinemia , Hypogonadism , Octreotide , Prevalence , Retrospective Studies , ROC Curve
9.
Endocrinology and Metabolism ; : 470-478, 2014.
Article in English | WPRIM | ID: wpr-14707

ABSTRACT

BACKGROUND: Primary hypophysitis causes varying degrees of endocrine dysfunction and mass effect. The natural course and best treatment have not been well established. METHODS: Medical records of 22 patients who had been diagnosed with primary hypophysitis between January 2001 and March 2013 were retrospectively reviewed. Based on the anatomical location, we classified the cases as adenohypophysitis (AH), infundibuloneurohypophysitis (INH), and panhypophysitis (PH). Clinical presentation, endocrine function, pathologic findings, magnetic resonance imaging findings, and treatment courses were reviewed. RESULTS: Among 22 patients with primary hypophysitis, 81.8% (18/22) had involvement of the posterior pituitary lobe. Two patients of the AH (2/3, 66.6%) and three patients of the PH (3/10, 30%) groups initially underwent surgical mass reduction. Five patients, including three of the PH (3/10, 33.3%) group and one from each of the AH (1/3, 33.3%) and INH (1/9, 11.1%) groups, initially received high-dose glucocorticoid treatment. Nearly all of the patients treated with surgery or high-dose steroid treatment (9/11, 82%) required continuous hormone replacement during the follow-up period. Twelve patients received no treatment for mass reduction due to the absence of acute symptoms and signs related to a compressive mass effect. Most of them (11/12, 92%) did not show disease progression, and three patients recovered partially from hormone deficiency. CONCLUSION: Deficits of the posterior pituitary were the most common features in our cases of primary hypophysitis. Pituitary endocrine defects responded less favorably to glucocorticoid treatment and surgery. In the absence of symptoms related to mass effect and with the mild defect of endocrine function, it may not require treatment to reduce mass except hormone replacement.


Subject(s)
Humans , Diabetes Insipidus , Disease Progression , Follow-Up Studies , Hydrogen-Ion Concentration , Hypopituitarism , Magnetic Resonance Imaging , Medical Records , Retrospective Studies , Steroids
10.
Endocrinology and Metabolism ; : 65-69, 2013.
Article in English | WPRIM | ID: wpr-146599

ABSTRACT

We report the case of a 36-year-old woman who presented with headache, fever, and amenorrhea. Laboratory analysis revealed hypopituitarism and autoimmune thyroiditis, while a cerebrospinal fluid study suggested concurrent aseptic meningitis. A magnetic resonance image (MRI) scan revealed a 1.0x0.9 cm cystic mass enlarging the sella turcica. Surgical resection via an endoscopic transsphenoidal route was performed. The histological finding of the excised tissue revealed foamy histiocytes with vacuolated cytoplasm, supporting the diagnosis of xanthomatous hypophysitis. Although a residual soft lesion was observed on the MRI image postoperatively, the patient's headache and fever improved. Ten months after surgery, the patient complained of visual impairment and headache, and the residual mass had enlarged into the suprasellar area. High dose (500 mg intravenous) methylprednisolone was administered for 3 days. During the methylprednisolone pulse therapy, the patient's visual acuity and headache improved. A follow-up MRI taken after methylprednisolone therapy showed a marked mass reduction. Our case supports an autoimmune pathophysiology for xanthomatous hypophysitis and suggests that high dose glucocorticoid therapy as a treatment option.


Subject(s)
Female , Humans , Amenorrhea , Cytoplasm , Fever , Follow-Up Studies , Glucocorticoids , Headache , Histiocytes , Hypopituitarism , Magnetic Resonance Spectroscopy , Meningitis, Aseptic , Methylprednisolone , Sella Turcica , Thyroiditis, Autoimmune , Vision Disorders , Visual Acuity
11.
The Korean Journal of Internal Medicine ; : 557-564, 2013.
Article in English | WPRIM | ID: wpr-175094

ABSTRACT

BACKGROUND/AIMS: We investigated the clinical characteristics and follow-up findings of subjects with adrenal incidentalomas in a single, tertiary-care hospital in South Korea. METHODS: The study consisted of a retrospective analysis of 282 adrenal incidentaloma patients who underwent radiographic and endocrinological evaluations at Samsung Medical Center in Seoul, South Korea, between January 2004 and July 2011. RESULTS: Most (86.2%) of the subjects were found to have nonfunctioning tumors. Functioning tumors were seen in 39 patients (13.8%). Among them, 28 (9.9%) had subclinical Cushing syndrome (SCS), six (2.1%) had pheochromocytoma, and five (1.8%) had primary hyperaldosteronism. Malignant adrenal tumors were discovered in three cases: two (0.7%) were primary adrenal cancers, and one (0.4%) was a secondary metastasis from a lung cancer. Significant risk factors for functional tumors were female gender (odds ratio [OR], 3.386; 95% confidence interval [CI], 1.611 to 7.117; p = 0.0013) and a noncontrast attenuation value of > 10 Hounsfield units (OR, 2.806; 95% CI, 1.231 to 6.397; p = 0.0141). During follow-up (mean, 22.5 months) of 72 of the patients, three (4.2%) developed hormonal changes due to functional tumors. One was confirmed as pheochromocytoma by histopathology, and the others were diagnosed with SCS and followed routinely without surgical intervention. No malignant transformation was found in these patients. CONCLUSIONS: Based on these findings, initial hormonal and radiographic evaluations for adrenal incidentalomas appear to be more important than follow-up tests because functional or malignant changes are rare.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adrenal Gland Neoplasms/blood , Cushing Syndrome/blood , Disease Progression , Hormones/blood , Hyperaldosteronism/blood , Logistic Models , Odds Ratio , Pheochromocytoma/blood , Predictive Value of Tests , Prognosis , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Tertiary Care Centers , Time Factors , Tomography, X-Ray Computed , Biomarkers, Tumor/blood
12.
Yonsei Medical Journal ; : 1127-1136, 2013.
Article in English | WPRIM | ID: wpr-198364

ABSTRACT

PURPOSE: Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake. MATERIALS AND METHODS: After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group). RESULTS: Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p<0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups. CONCLUSION: Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.


Subject(s)
Animals , Male , Rats , Adiponectin/metabolism , Adiposity/drug effects , Cell Proliferation/drug effects , Diabetes Mellitus, Type 2/diet therapy , Eating/drug effects , Glucose Intolerance/diet therapy , Insulin Resistance , Insulin-Secreting Cells/drug effects , Piperidines/adverse effects , Pyrazoles/adverse effects , Rats, Inbred OLETF , Receptor, Cannabinoid, CB1/physiology , Thiazolidinediones/therapeutic use
13.
Journal of Korean Medical Science ; : 177-183, 2012.
Article in English | WPRIM | ID: wpr-156437

ABSTRACT

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and beta-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naive acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and beta-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and beta-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI0,120) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI0,120 and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and beta-cell function are improved by tumor resection in acromegalic patients.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Acromegaly/diagnosis , Asian People , Blood Glucose/analysis , C-Peptide/analysis , Diabetes Mellitus/epidemiology , Glucose Tolerance Test , Human Growth Hormone/metabolism , Insulin/blood , Insulin Resistance , Insulin-Secreting Cells/cytology , Prediabetic State/epidemiology , Republic of Korea
14.
Diabetes & Metabolism Journal ; : 452-459, 2012.
Article in English | WPRIM | ID: wpr-184809

ABSTRACT

BACKGROUND: Diabetes self-management education has an important role in diabetes management. The efficacy of education has been proven in several randomized trials. However, the status of diabetes education programs in real Korean clinical practice has not yet been evaluated in terms of patient compliance with the education prescription. METHODS: We retrospectively analyzed clinical and laboratory data from all patients who were ordered to undergo diabetes education during 2009 at Samsung Medical Center, Seoul, Korea (n=2,291). After excluding ineligible subjects, 588 patients were included in the analysis. RESULTS: Among the 588 patients, 433 received education. The overall compliance rate was 73.6%, which was significantly higher in the subjects with a short duration or living in a rural area compared to those with a long duration (85.0% vs. 65.1%, respectively; P<0.001) or living in an urban area (78.2% vs. 70.4%, respectively; P=0.037). The hemoglobin A1c decreased greater in the compliant group (from 7.84+/-1.54 at baseline to 6.79+/-1.06 at 3 months and 6.97+/-1.20 at 12 months after prescription in the compliant group vs. from 7.74+/-1.25 to 7.14+/-1.02 and 7.24+/-1.24 in the non-compliant group; P=0.001). The decrease in hemoglobin A1c was greater in the subjects with a short duration (P=0.032). CONCLUSION: In our study a large percent of patients refuse to get education despite having a prescription from their physician. This refusal rate was higher in the patients with long-standing diabetes or in urban residence. Furthermore, education was more effective in patients with a short duration of diabetes in clinical practice.


Subject(s)
Humans , Compliance , Diabetes Mellitus, Type 2 , Disulfiram , Hemoglobins , Korea , Patient Compliance , Prescriptions , Retrospective Studies , Self Care
15.
Immune Network ; : 113-117, 2012.
Article in English | WPRIM | ID: wpr-216355

ABSTRACT

FasL, perforin, TNFalpha, IL-1 and NO have been considered as effector molecule(s) leading to beta-cell death in autoimmune diabetes. However, the real culprit(s) of beta-cell destruction have long been elusive despite intense investigation. Previously we have suggested IFNgamma/TNFalpha synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFNgamma and TNFalpha but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. IFNgamma treatment conferred susceptibility to TNFalpha-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that IFNgamma/TNFalpha synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by IFNgamma treatment in human islet cells. Taken together, we suggest that IFNgamma/TNFalpha synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.


Subject(s)
Animals , Humans , Mice , Apoptosis , Autoimmunity , Cytokines , Diabetes Mellitus, Type 1 , Insulinoma , Interleukin-1 , Islets of Langerhans , Mice, Inbred NOD , Perforin , Tumor Necrosis Factor-alpha
16.
Journal of Korean Medical Science ; : 1439-1443, 2012.
Article in English | WPRIM | ID: wpr-111758

ABSTRACT

Congenital adrenal hyperplasia (CAH) is characterized by decreased adrenal hormone production due to enzymatic defects and subsequent rise of adrenocorticotrophic hormone that stimulates the adrenal cortex to become hyperplastic, and sometimes tumorous. As the pathophysiology is basically a defect in the biosynthesis of cortisol, one may not consider CAH in patients with hypercortisolism. We report a case of a 41-yr-old man with a 4 cm-sized left adrenal tumorous lesion mimicking Cushing's syndrome who was diagnosed with CAH. He had central obesity and acanthosis nigricans involving the axillae together with elevated 24-hr urine cortisol level, supporting the diagnosis of Cushing's syndrome. However, the 24-hr urine cortisol was suppressed by 95% with the low dose dexamethasone suppression test. CAH was suspected based on the history of precocious puberty, short stature and a profound suppression of cortisol production by dexamethasone. CAH was confirmed by a remarkably increased level of serum 17-hydroxyprogesterone level. Gene mutation analysis revealed a compound heterozygote mutation of CYP21A2 (I173N and R357W).


Subject(s)
Adult , Humans , Male , 17-alpha-Hydroxyprogesterone/blood , Acanthosis Nigricans/complications , Adrenal Hyperplasia, Congenital/complications , Cushing Syndrome/diagnosis , DNA Mutational Analysis , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Heterozygote , Hydrocortisone/urine , Mutation , Obesity/complications , Steroid 21-Hydroxylase/genetics , Tomography, X-Ray Computed
17.
Journal of Korean Medical Science ; : 1196-1200, 2011.
Article in English | WPRIM | ID: wpr-28039

ABSTRACT

We tested the correlation between diabetes and aggressiveness of colorectal polyps in diabetic patients and matched non-diabetic controls. We retrospectively studied 3,505 type 2 diabetes (T2DM) patients without gastrointestinal symptoms who underwent colonoscopy for colorectal cancer at Samsung Medical Center, Seoul, Korea from August 1995 to August 2009. We matched 495 non-diabetic subjects with colon polyps to the diabetic patients in whom polyps were detected by year of colonoscopy, age, sex and body mass index (BMI). Among the 3,505 T2DM patients screened, 509 were found to have 1,136 colon polyps. Those with diabetes had a greater proportion of adenomatous polyps (62.8% vs 53.6%) compared to the control. Multivariate logistic regression analysis identified DM, male gender, age and BMI as independent risk factors for multiple polyps (more than three polyps). Polyp multiplicity in diabetic patients was significantly associated with male gender (OR 2.360, P = 0.005), age (OR 1.033, P = 0.005) and BMI (OR 1.077, P = 0.028). Neither aspirin nor metformin use affected either size or number of polyps in diabetic patients. Male patients older than 65 yr with T2DM and BMI greater than 25 have increased risk for multiple adenomatous polyps and should be screened with colonoscopy to prevent colorectal cancer.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenomatous Polyps/complications , Age Factors , Body Mass Index , Colonic Polyps/diagnosis , Colonoscopy , Colorectal Neoplasms/complications , Diabetes Mellitus, Type 2/complications , Logistic Models , Odds Ratio , Republic of Korea , Retrospective Studies , Risk Factors , Sex Factors
18.
Diabetes & Metabolism Journal ; : 193-198, 2011.
Article in English | WPRIM | ID: wpr-42491

ABSTRACT

Diabetes mellitus is a serious and growing health problem worldwide and is associated with severe acute and chronic complications. Moreover, epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. Several studies indicate an association between diabetes and the risk of liver, pancreas, endometrium, colon/rectum, breast, and bladder cancer. Mortality is also moderately increased in subjects with diabetes. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in diabetic patients. Hyperinsulinemia most likely favors cancer in diabetic patients as insulin is a growth factor with pre-eminent metabolic as well as mitogenic effects, and its action in malignant cells is favored by mechanisms acting at both the receptor and post-receptor level. The effect of diabetes treatment drugs, aside from metformin, on cancer is not conclusive. In order to fight the perfect storm of diabetes and cancer, strategies to promote primary prevention and early detection of these conditions are urgently needed.


Subject(s)
Female , Humans , Breast , Diabetes Mellitus , Endometrium , Hyperinsulinism , Insulin , Liver , Metformin , Obesity , Pancreas , Primary Prevention , Risk Factors , Smoke , Smoking , Urinary Bladder Neoplasms
19.
Korean Journal of Orthodontics ; : 174-183, 2011.
Article in Korean | WPRIM | ID: wpr-651027

ABSTRACT

OBJECTIVE: Orthodontically induced root resorption (OIRR) involves partial loss of cementum and dentin of teeth caused by routine orthodontic treatment. It decreases root length and influences the function of affected teeth. In this study, the treatment and patient factors causing apical root resorption in Koreans were determined. The observed factors were extraction, gender, age, displacement of root apex, total treatment period, total teeth length, and shape of the root. METHODS: The records of 137 patients treated with full, fixed edgewise appliances were obtained from the Department of Orthodontics, Dankook University Dental Hospital, from November 2007 to December 2008. Periapical radiographs of the maxillary central incisors and cephalometric radiographs of each patient were used to assess apical root resorption and type of tooth movement. RESULTS: The mean amount of resorption was 1.62 +/- 1.58 mm. The amount of resorption in the extraction and non-extraction groups was 2.10 +/- 1.64 mm and 1.18 +/- 1.39 mm, respectively. The amount of root resorption increased with the total tooth length. Severe root resorption (> 4 mm) was related to abnormal root shape (blunt, pointed, or eroded). CONCLUSIONS: The variables significantly related to OIRR were extraction, initial tooth length, and root shape.


Subject(s)
Humans , Dental Cementum , Dentin , Displacement, Psychological , Incisor , Orthodontics , Root Resorption , Tooth
20.
Diabetes & Metabolism Journal ; : 536-542, 2011.
Article in English | WPRIM | ID: wpr-22249

ABSTRACT

BACKGROUND: Small dense low density lipoprotein (sdLDL) has recently emerged as an important risk factor of coronary heart disease. METHODS: The mean LDL particle size was measured in 203 patients with type 2 diabetes mellitus (T2DM) and 212 matched subjects without diabetes using polyacrylamide tube gel electrophoresis. Major vascular complications were defined as stroke, angiographically-documented coronary artery disease or a myocardial infarction. Peripheral vascular stenosis, carotid artery stenosis (> or =50% in diameter) or carotid artery plaque were considered minor vascular complications. Overall vascular complications included both major and minor vascular complications. RESULTS: Diabetic patients had significantly smaller mean-LDL particle size (26.32 nm vs. 26.49 nm) and a higher percentage of sdLDL to total LDL compared to those of subjects without diabetes (21.39% vs. 6.34%). The independent predictors of sdLDL in this study were serum triglyceride level and body mass index (odds ratio [OR], 1.020 with P<0.001 and OR 1.152 with P<0.027, respectively). However, no significant correlations were found between sdLDL and major vascular complications (P=0.342), minor vascular complications (P=0.573) or overall vascular complications (P=0.262) in diabetic subjects. CONCLUSION: Diabetic patients had a smaller mean-LDL particle size and higher proportion of sdLDL compared to those of subjects without diabetes. Obese diabetic patients with hypertriglyceridemia have an increased risk for atherogenic small dense LDL. However, we could not verify an association between LDL particle size and vascular complications in this study.


Subject(s)
Humans , Acrylic Resins , Body Mass Index , Carotid Stenosis , Constriction, Pathologic , Coronary Artery Disease , Coronary Disease , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Electrophoresis , Heart , Hypertriglyceridemia , Lipoproteins , Myocardial Infarction , Particle Size , Risk Factors , Stroke
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