Therapeutic efficacy and factors that affect response of rosiglitazone in insulin-resistant type 2 diabetes / 대한내과학회지

BACKGROUND: Rosiglitazone, an insulin sensitizer of thiazolidinedione class, is known as a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma. This study was performed to evaluate the antidiabetic activity and insulin sensitizing effect of rosiglitazone combination therapy in insulin-resistant type 2 diabetic patients who were poorly controlled with oral agents such as metformin and/or sulfonylurea. The factors affecting response of rosiglitazone were also evaluated on the basis of the degree of glycemic control. METHODS: One hundred twenty insulin-resistant (glucose disposal rate, Kitt < 2.5%/min) type 2 diabetic patients (M:F=42:78, mean age 58.6+/-9.2 years, body mass index 24.2+/-2.8 kg/m2) were enrolled and randomly divided into two groups. For 12 weeks, the treated group daily received 4 mg of rosiglitazone and the control group had diet and exercise therapy in addition to previous medications. The responders were defined as more than 20% decrease of fasting plasma glucose level or more than 1% decrease of HbA1c. As for the indices of insulin resistance and insulin secretory function, Kitt (Kitt=0.693/t1/2 X 100) by insulin tolerance test, HOMA(IR) and HOMA(beta-cell) function by 'HOMA index (Homeostasis model assessment)' were evaluated. RESULTS: In rosiglitazone treated group (60 patients, M:F=19:45), 12 weeks of rosiglitazone treatment decreased fasting plasma glucose (28.2%), postprandial 2-hour glucose (23.2%), and HbA1c (12.2%). Rosiglitazone also significantly decreased HOMA(IR) (41.2%), and increased Kitt (53.3%) and HOMA(beta-cell) function (46.9%). Forty-five patients (75%) satisfied responder. Females and those who had higher body mass index and waist-hip ratio showed better response. The basal fasting plasma glucose, HbA1c, and systolic blood pressure were also higher in responders. The responders showed significantly higher fasting serum insulin level and HOMA(IR), and also higher tendency of fasting serum C-peptide level and HOMA(beta-cell) function than nonresponders. CONCLUSION: From these results, rosiglitazone treatment can improve not only hyperglycemia and insulin resistance but also insulin secretory function in uncontrolled insulin-resistant type 2 diabetes. The factors that affect response of rosiglitazone are female, obesity (especially central obesity), high insulin secretory function, and severe insulin resistance. As a conclusion, the therapeutic efficacy or response of rosiglitazone is likely to depend on the degree of preserved pancreatic beta-cell function and the severity of insulin resistance.

Development of standardized therapeutic model in Korean type 2 diabetic patients / 대한내과학회지

BACKGROUND: There are a few limitations in application of staged diabetes management (SDM) program to Korean type 2 diabetic patients because of their unique characteristics, such as non-obese but centrally obese anthropometry and variable relationships between insulin secretion and insulin resistance compared to western diabetic patients. Therefore, we proposed new therapeutic model which considers ethnic characteristics and assesses patient by insulin secretion and insulin resistance. METHODS: We have previously assessed patient's insulin secretion by serum fasting C-peptide level and insulin resistance by insulin tolerance test (ITT) and proposed new therapeutic model: by cut-off value of 2.5%/min in insulin resistance and 1.1 ng/dL, 1.7 ng/dL in insulin secretion. RESULTS: Total 183 patients were enrolled in this program and 59% of total subjects had to change the treatment modality according to this new therapeutic model. Mean fasting glucose level dropped from 177.0+/-38.6 mg/dL (9.83+/-2.14 mmol/L) to 148.2+/-31.2 mg/dL (8.23+/-1.73 mmol/L) (p<0.001), mean postprandial 2 hour glucose level dropped from 255.6+/-60.1 mg/dL (14.19+/-3.34 mmol/L) to 221.1+/-58.4 mg/dL (12.27+/-3.24 mmol/L) (p<0.001), mean HbA1c level dropped from 8.37+/-1.42% to 7.72+/-1.39% (p<0.001) even though baseline group already received conventional treatment. 51.4% of the post-treatment group achieved a HbA1c valued of less than 7.5% compared to 28.4% of the pre-treatment group. CONCLUSION: The new standardized therapeutic model strongly suggests its valuable clinical application in Korean type 2 diabetic patients.

Metabolic significance of non-alcoholic fatty liver disease in non-obese adults / 대한내과학회지

BACKGROUND: It is well known that non-alcoholic fatty liver disease is associated with metabolic syndrome such as obesity, type II diabetes mellitus, dyslipidemia. Non-alcoholic fatty liver disease is frequently found in non-obese adults, but the meaning of it is unknown. So we studied the association of non-alcoholic fatty liver disease in non-obese adults and metabolic abnormalities. METHODS: We examined 779 Korean adults above 30 years old (274 men, 505 women) participating in medical check-up in Health Promotion Center. Hepatitis B and C serologies were negative, and average weekly alcohol intake was or=25 kg/m2, n=348) group (65.5 vs 32.3%, p<0.05). Compared with obese group, waist circumference, waist hip ratio, body fat, impaired fasting serum glucose, total cholesterol, HDL-cholesterol, total cholesterol to HDL-cholesterol ratio, fasting insulin, proinsulin, HOMA-IR and HOMA-beta were significantly different in non-obese, non-alcoholic fatty liver group. After multiple regression analysis, waist circumference was associated with non-alcoholic fatty liver disease in non-obese individuals. Odd ratios of insulin resistance in non-obese, non-alcoholic fatty liver group were 5.8 (CI: 3.1~10.9). CONCLUSION: The frequency of non-alcoholic fatty liver disease was very high in non-obese adults and well associated with central obesity and insulin resistance.

A Case of Papillary Thyroid Carcinoma Combined with Multiple Endocrine Neoplasia Type 2A / 대한내분비학회지

Multiple endocrine neoplasia (MEN) type 2A is a syndrome of medullary thyroid carcinomas, pheochromocytomas and parathyroid hyperplasia. The simultaneous occurrence of medullary, and papillary, thyroid carcinomas is rare because they are derived from, apparently, different germ layers, the former from the neuroectoderm and the latter from the endoderm. We report a case of a papillary thyroid carcinoma, combined with a medullary thyroid carcinoma, in a patient with MEN type 2A. Molecular genetic studies for screening a RET proto-oncogene mutation revealed a point mutation in codon 631 on chromosome 10, which is reported as highly uncommon in MEN type 2A.

A Case of Metastatic Pulmonary Calcification in Primary Hyperparathyroidism / 대한내분비학회지

Metastatic calcification is the deposition of calcium, in previously normal tissue, as a result of elevated plasma calcium and phosphorus product levels and has been reported in patients with parathyroid adenoma, parathyroid carcinoma, hyperparathyroidism due to chronic renal failure, vitamin D intoxication, and osteolytic bone tumors, such as multiple myelomas. The lungs are the most common site of metastatic calcification. We have experienced metastatic pulmonary calcification in a case of primary hyperparathyroidism. A 55-year old woman was admitted due to general weakness. From the laboratory evaluation, hypercalcemia and excess production of parathyroid hormone (PTH) were noted. technetium-99m-labelled sestamibi scintigraphy indicated an intense uptake in the lower pole area of the left thyroid gland, suggestive of a parathyroid adenoma. A technetium-99m phosphate (99mTc-MDP) bone scan showed increased uptakes in both lungs. A parathyroid lobectomy was performed, and primary hyperparathyroidism, due to a parathyroid adenoma, was finally diagnosed. A follow-up 99mTc-MDP bone scan showed the disappearance of the metastatic pulmonary calcification, with the clinical symptoms and biochemical parameters normalizing after 6 months.