Diabetes and Cancer / 임상당뇨병

Diabetes mellitus and cancer are the most common life-threatening illnesses worldwide. Previous epidemiologic studies have suggested a strong association between increased risk of cancer and diabetes mellitus. Potential biological mechanisms underlying the relationship include obesity, hyperglycemia, hyperinsulinemia, chronic inflammation, and oxidative stress. The most common diabetes-related cancers are pancreatic cancer, hepatocellular cancer, breast cancer, endometrial cancer, and colorectal cancer. Special attention should be paid to diabetic patients using careful cancer screening and providing preventive anti-cancer strategies.

A Case of Xanthelasma Palpebrarum Presenting as “Yellow Eyelines” / 대한피부과학회지

Xanthelasma palpebrarum (XP) is the most common type of xanthoma. It is a benign condition characterized by bright yellowish plaque-like lesions that appear near the inner epicanthus showing symmetrical distribution. It may be accompanied with some familial lipoprotein disorders and systemic hyperlipidemia. A 28-year-old man visited our department with complaints of periorbital hyperpigmentation and linear yellow plaques along the bilateral upper and lower eyelids for 5 years. His father has hyperlipidemia. Laboratory investigations revealed an increase in low density lipoprotein-cholesterol and triglyceride levels. Histopathologic examination showed diffused infiltration of foamy cells and histiocytes in the upper dermis. The patient was diagnosed with XP based on the clinical and histopathological findings. XP usually present as yellow plaques on the upper eyelids. Here, we report a rare case of XP confined to the eyelines.

Association between White Blood Cell Counts within Normal Range and Hemoglobin A1c in a Korean Population

BACKGROUND: We examined whether white blood cell (WBC) count levels within normal range, could be associated with hemoglobin A1c (HbA1c) levels. METHODS: Among the 11,472 people (≥19 years of age) who participated in the 2011 to 2012 Korea National Health and Nutrition Examination, subjects with chronic disease or illness, including 807 patients with diabetes currently taking anti-diabetic medications and/or 1,149 subjects with WBC levels 10,000/µL were excluded. RESULTS: Overall, adjusted HbA1c levels increased across the WBC quartiles (5.55%±0.01%, 5.58%±0.01%, 5.60%±0.01%, and 5.65%±0.01%, P < 0.001) after adjusting for confounding factors, such as age, gender, fasting plasma glucose, college graduation, smoking history, waist circumference, presence of hypertension, serum total cholesterol, serum triglyceride, and presence of anemia. The adjusted proportions (%) of HbA1c levels of ≥5.7%, ≥6.1%, and ≥6.5% showed significant increases across WBC quartiles (P < 0.001, P=0.002, and P=0.022, respectively). Logistic regression analyses of WBC quartiles for the risk of HbA1c levels of ≥5.7%, ≥6.1%, and ≥6.5%, using the variables above as covariates, showed that the odds ratios of the fourth quartile of WBCs were 1.59 (95% confidence interval [CI], 1.35 to 1.89; P < 0.001), 1.78 (95% CI, 1.31 to 2.42; P < 0.001), and 2.03 (95% CI, 1.13 to 3.64; P=0.018), using the first quartile of WBCs as the reference. CONCLUSION: HbA1c levels were positively associated with WBC levels within normal range in a general adult population.

Retrospective Observational Dose-Titration Study of Subjects with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on 15 mg of Pioglitazone / 임상당뇨병

BACKGROUND: The 30 mg pioglitazone tablet was recently introduced in Korea; no study has yet compared its glucose-lowering or weight gain effects to the 15 mg tablet in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: The electronic medical records of 45 patients with T2DM with glycated hemoglobin (HbA1c) levels > 7.0%, despite taking 15 mg/day pioglitazone and a stable dose of other diabetes drugs for 3 months, were retrospectively reviewed. RESULTS: After dose up-titration, HbA1c levels decreased at 3- and 6-month follow-ups compared with baseline (8.5% at baseline vs. 8.2% at 3 months vs. 7.9% at 6 months; baseline vs. 3 months, P = 0.106; baseline vs. 6 months, P = 0.005; 3 months vs. 6 months, P = 0.096). In the subgroup analysis of 36 patients taking pioglitazone, sulfonylurea, and metformin, HbA1c levels also decreased at 3- and 6-month follow-ups compared with baseline (8.5 % vs. 8.2 % vs. 7.9%; baseline vs. 3 months, P = 0.289; baseline vs. 6 months, P = 0.014; 3 months vs. 6 months, P = 0.232). There was no significant body weight change (70.8 kg vs. 70.7 kg vs. 71.0 kg). CONCLUSION: Up-titrating from 15 mg to 30 mg of pioglitazone in patients with inadequate glycemic control (HbA1c > 9%) who were also taking sulfonylurea and metformin showed additive glucose-lowering effects without significant weight gain in Korean patients with T2DM.

Factors Associated with Participation in Diabetes Education: The Korea National Health and Nutrition Examination Survey 2007 to 2009

BACKGROUND: A recent study revealed that the participation rate in diabetes education among diabetic patients was only about 50% in Korea. We investigated the factors associated with participation in diabetes education. METHODS: The study included 1,255 patients (≥19 years old) diagnosed with diabetes drawn from the total Korea National Health and Nutrition Examination Survey 2007 to 2009 population comprising 30,705 individuals. We compared age, sex, and age- and sex-adjusted clinical characteristics in patients who had received diabetes education versus those who had not. RESULTS: Of the 1,255 patients, 19.8% (n=248) had received diabetes education. Patients in the group who received diabetes education were younger, diagnosed at an earlier age, had a longer diabetes duration and were more likely to be using insulin therapy compared with the group who did not receive diabetes education (P<0.001). The group who received diabetes education included fewer manual workers (P<0.001) but more college graduates (P=0.004) compared with the group who did not receive diabetes education. Logistic regression analysis revealed that longer diabetes duration increased the likelihood of receiving diabetes education (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.06; P=0.004). Junior high school (OR, 0.47; 95% CI, 0.24 to 0.91; P=0.026) and elementary school education levels (OR, 0.34; 95% CI, 0.17 to 0.65; P=0.001) versus college graduation were inversely correlated with participation in diabetes self-management education. Non-insulin therapy reduced the likelihood of receiving diabetes education (OR, 0.37; 95% CI, 0.21 to 0.64; P<0.001). CONCLUSION: Longer diabetes duration, insulin therapy, and higher education level were positively associated with the completion of diabetes education.

The Role of Foxo3 in Leydig Cells

PURPOSE: Foxo3 in female reproduction has been reported to regulate proliferation of granulose cells that form follicles. There are no reports so far that discuss on the role of Foxo3 in males. This study was designed to outline the role of Foxo3 in the testes. MATERIALS AND METHODS: Testes from mice at birth to postpartum week (PPW) 5 were isolated and examined for the expression of Foxo3 using immunostaining. To elucidate role of Foxo3 in Leydig cells, R2C cells were treated with luteinizing hormone (LH) and the phosphorylation of Foxo3. Testosterone and steroidogenic acute regulatory (StAR) protein levels were measured after constitutive active [triple mutant (TM)] human FOXO3 adenovirus was transduced and StAR promoter assay was performed. RESULTS: Foxo3 expression in the testicles started from birth and lasted until PPW 3. After PPW 3, most Foxo3 expression occurred in the nuclei of Leydig cells; however, at PPW 5, Foxo3 was expressed in both the nucleus and cytoplasm. When R2C cells were treated with luteinizing hormone, Foxo3 phosphorylation levels by AKT increased. After blocking the PI3K pathway, LH-induced phosphorylated Foxo3 levels decreased, indicating that LH signaling regulates Foxo3 localization. When active FOXO3-TM adenovirus was introduced into a Leydig tumor cell line, the concentrations of testosterone and StAR protein decreased. When FOXO3 and a StAR promoter vector were co-transfected into HEK293 cells for a reporter assay, FOXO3 inhibited the StAR promoter. CONCLUSION: FOXO3 affects testosterone synthesis by inhibiting the formation of StAR protein. LH hormone, meanwhile, influences Foxo3 localization, mediating its function.

Efficacy and Safety of Sustained-Release Recombinant Human Growth Hormone in Korean Adults with Growth Hormone Deficiency

PURPOSE: The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage(TM)) supplement in patients with growth hormone deficiency were evaluated. MATERIALS AND METHODS: This trial is 12-week prospective, single-arm, open-label trial. Men and women aged > or =20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. RESULTS: The IGF-1 level of 108.67+/-74.03 ng/mL was increased to 129.01+/-68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80+/-6.51 to 7.55+/-5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. CONCLUSION: Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.

Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas

BACKGROUND: Cabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline. METHODS: We retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated. RESULTS: Forty patients (90.9%) were treated medically and displayed tumor volume reduction (TVR) of 74.7%, a prolactin normalization (NP) rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery) rate of 70.5%. Most patients (93.1%) with TVR > or =25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR > or =25% without NP and no patients with TVR 25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.

Glycated Hemoglobin Value for Fasting Plasma Glucose of 126 mg/dL in Korean: The 2011 Korea National Health and Nutrition Examination Survey

We aimed to estimate the cutoff value of glycated hemoglobin (HbA1c, A1c) for fasting plasma glucose (FPG) of 126 mg/dL in the Korean adult population, using the 2011 Korea National Health and Nutrition Examination Survey. A total of 5,421 participants without a history of diabetes and over 19 years of age were included in the analysis. A point-wise area under the receiver operating characteristic curve was used to estimate the optimal A1c cutoff value. A1c threshold of 6.1% produced the highest sum of sensitivity (85.2%) and specificity (90.5%) for FPG of 126 mg/dL (area under the curve, 0.941, P or =6.5% might be acceptable in the Korean adult population.

Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy

Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (> or =200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%+/-3.1% vs. 2.3%+/-3.6%, P=0.024; -41.0%+/-24.1% vs. -24.2%+/-31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

A 47,X,+t(X;X)(p22.3;p22.3)del(X)(p11.23q11.2),Y Klinefelter Variant with Morbid Obesity

Klinefelter syndrome is the most common type of genetic cause of hypogonadism. This syndrome is characterized by the presence of 1 or more extra X chromosomes. Phenotype manifestations of this syndrome are small testes, fibrosis of the seminiferous tubules, inability to produce sperm, gynecomastia, tall stature, decrease of serum testosterone and increases of luteinizing hormone and follicle stimulating hormone. Most patients with Klinefelter syndrome are tall, with slender body compositions, and reports of obesity are rare. We report the case of a 35-yr-old man with hypogonadism and morbid obesity and diabetes mellitus. He had gynecomastia, small testes and penis, very sparse body hair and his body mass index was 44.85. He did not report experiencing broken voice and was able to have erections. We conducted a chromosome study. His genotype was 47,X,+t(X;X)(p22.3;p22.3)del(X)(p11.23q11.2). In this case, the patient was diagnosed as Klinefelter syndrome. He showed rare phenotypes like morbid obesity and average height and the phenotype may be caused by the karyotype and the excess number of X chromosome. Further studies of the relationship between chromosomes and phenotype are warranted.

Characteristics of Acromegaly in Korea with a Literature Review

Acromegaly is a slowly progressive disease caused by excessive growth hormone (GH), which is related to a GH secreting pituitary tumor in most cases. Herein, we describe the epidemiology, clinical characteristics, and treatment of acromegaly in Korea with a literature review. The average annual incidence of acromegaly in Korea was 3.9 cases per million people, which was within the range of previous Western studies. The primary treatment for acromegaly was also transsphenoidal adenomectomy, which accounted for 90.4% of patients whose primary therapeutic options were known. The overall surgical remission rates were 89%, 87%, 64%, 70%, and 50% for modified Hardy classification I, II, IIIA, IIIB, and IV, respectively. An updated and larger study regarding the treatment outcome of medical/radiotherapy in Korean acromegalic patients is needed.

A Case of Latent Autoimmune Diabetes in Adults Developed after Surgical Cure of Growth Hormone Secreting Pituitary Tumor

Acromegaly is generally caused by a benign growth hormone (GH)-secreting pituitary adenoma. It is characterized by a wide range of complications; cardiovascular, respiratory, bone and joint, and metabolic complications. Among them, impaired glucose tolerance and diabetes mellitus, due to GH-induced insulin resistance, has been reported in approximately 16-46% and 19-56%. They are usually improved following the treatment of acromegaly, surgical or medical therapy. We report a first case of 36-year-old man who was paradoxically diagnosed with GAD antibody positive latent autoimmune diabetes in adults (LADA) after the surgical cure of acromegaly.

Update in Prolactinomas / 한양의대학술지

Prolactinomas are frequent causes of gonadal dysfunction and infertility. Dopamine agonists are the main treatment of prolactinoma and the excellent efficacy of the dopamine agonist is well known. Current challenges related to the treatment of prolactinomas include the relationship of long term use of cabergoline and cardiac valvulopathy, the remission after discontinuation of dopamine agonists, the management of pregnant women with prolactinoma, and the role for surgery on long-term management of prolactioma. Herein, these current issues and questions in the management of prolactinomas, including safety of cabergoline, recurrence after discontinuance of dopamine agonist, pregnancy, and role of surgical resection are addressed.

Recurrent Coccidioidomycosis Manifesting as Osteomyelitis in Korea

Coccidioidomycosis is a fungal infection that results from inhaling the airborne arthroconidia of the Coccidioides species. It is an endemic disease in the southwest part of North America and rarely diagnosed in Korea. As tourism to endemic areas and the number of immunocompromised patients have been increasing, the incidence of this infection has increased in non-endemic areas. Treatment is usually successful with antifungal agents; however, recurrence is common. It is difficult to decide when to discontinue the antifungal treatment especially in non-endemic areas where doctors are not familiar with the disease. We report a case of recurrent coccidioidomycosis manifesting as osteomyelitis after the treatment of the patient for disseminated coccidioidal infection. The complement fixation test was a useful tool for the assessment of patient response and to evaluate suspected recurrence.

Recurrent Coccidioidomycosis Manifesting as Osteomyelitis in Korea

Coccidioidomycosis is a fungal infection that results from inhaling the airborne arthroconidia of the Coccidioides species. It is an endemic disease in the southwest part of North America and rarely diagnosed in Korea. As tourism to endemic areas and the number of immunocompromised patients have been increasing, the incidence of this infection has increased in non-endemic areas. Treatment is usually successful with antifungal agents; however, recurrence is common. It is difficult to decide when to discontinue the antifungal treatment especially in non-endemic areas where doctors are not familiar with the disease. We report a case of recurrent coccidioidomycosis manifesting as osteomyelitis after the treatment of the patient for disseminated coccidioidal infection. The complement fixation test was a useful tool for the assessment of patient response and to evaluate suspected recurrence.

Black Esophagus Associated with Alcohol Abuse

Black esophagus is a rare condition of the esophagus that manifests as endoscopic findings of black-colored esophageal mucosa, which is usually caused by acute esophageal necrosis. We report a case of alcoholic patient who developed black esophagus. The 85-year-old man was admitted to Severance Hospital due to copious hematemesis over 2 days. Upper gastrointestinal endoscopy showed black-colored mucosa in the distal esophagus. Endoscopic biopsies of the esophagus revealed necrotic tissue, without any viable cells. Follow-up upper gastrointestinal endoscopy performed after supportive care with a proton-pump inhibitor, sucralfate, and total parenteral nutrition resulted in the remarkable healing of the esophageal wall with no complications.