Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

BACKGROUND: We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin. METHODS: A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24. RESULTS: The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups. CONCLUSION: In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.

The Anti-inflammatory and Antimicrobial Effects of Selenium-rich Hot Spring Water on a Chronic Bacterial Prostatitis Rat Model / 대한남성과학회지

PURPOSE: The conventional primary therapy for chronic bacterial prostatitis (CBP) is the use of antibiotics. However, the therapy has a low cure rate and long-term use of antibiotics can lead to adverse effects including bacterial resistance. For these reasons, a new therapy for CBP is strongly needed. MATERIALS AND METHODS: To evaluate the anti-inflammatory and antimicrobial effects of selenium-rich hot spring water on CBP, rats were divided into four groups and treatment was administered for four weeks as follows: (1) control (n=8), (2) ciprofloxacin (n=8), (3) selenium-rich hot spring water (n=8), and (4) selenium-rich hot spring water with ciprofloxacin (n=8). Drip infusion of bacterial suspension (E. coli Z17 O2:K1;H-) into Spargue-Dowley rats was then conducted to induce CBP. Four weeks later, the results of prostate tissue and urine culture and histological analysis on the prostate were analyzed in each group. RESULTS: The use of ciprofloxacin, and selenium-rich hot spring water with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in prostatic inflammation compared with the control group (p<0.05). The selenium-rich hot spring water with ciprofloxacin group showed a statistically significantly lower rate of bacterial growth and and greater improvements in prostatic inflammation than the ciprofloxacin group (p<0.05). CONCLUSIONS: These results suggest that spring water may be an effective material in the treatment of CBP. Notably, the combination treatment of selenium-rich hot spring water and ciprofloxacin has synergistic effects. Therefore, we can suggest that the combination of selenium-rich hot spring water and ciprofloxacin may be effective in the treatment of CBP, and with a higher success rate than ciprofloxacin alone.

The Effect of Bone Marrow Transplantation on Bone Mineral Metabolism: 2 - Year Prospective Study / 대한내분비학회지

BACKGROUND: Loss of bone mass is usually detected after bone marrow transplantation (BMT), especially during the early post-transplant period. But little is known about the long-term effects of BMT on bone mineral metabolism. METHODS: We have investigated prospectively 12 patients undergoing BMT (4 autologous, 8 allogeneic) for hematologic diseases (8 leukemia, 3 SAA, 1 MDS). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and bone turnover markers (osteocalcin and ICTP) were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months and 1, 2 years thereafter. Bone mineral density (BMD) was measured with DEXA (Dual Energy X-ray Absorptiometry) before BMT, 1 year and 2 year after BMT. In patients with amenorrbea, hormone replacement therapy was started from around 1 year after BMT RESULTS: 1. The mean bone loss in the lumbar spine, calculated as the percent change from the baseline to the level at 1 year and 2 year was 7.3% and 1.9%, respectively. The mean bone loss in the total proximal femur from the baseline to the level at 1 year and 2 year was 8.0% and 8.3% respectively. 2. The serum ICTP increased progressively until four weeks after BMT. Thereafter, it decreased gradually to reach basal values after one year and thereafter no more change until 2 year. Serum osteocalcin decreased progressively until three weeks after BMT. After that, it increased and reached basal values after 3 months. Osteocalcin increased at 6 month transiently but thereafter, it decreased to the level of slightly above basal value at 2 year. 3. Patients who were treated with TBI or pateints with GVHD had a tendency of lower BMD at l year and 2 year after BMT than those of patients without TBI or GVHD. 4. Eight out of nine women went into a menopausal state immediately after BMT and remained amenorrhea, evidenced by high gonadotropins and low estradiol levels. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. CONCLUSION: The rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in bone loss after BMT. The efficacy of HRT for the correction of hypogonadism and bone loss was evidenced by 2 year BMD which was much more increased compared to 1 year BMD, especially in vertebra.

The Short-term Effects of Bone Marrow Transplantation on Bone Metabolism / 대한내분비학회지

BACKGROUND: The organ transplantation becomes the management of choice for many patients with chronic and life threatening heart, liver, kidney, bone marrow, and pancreatic diseases. A new set of side effects unique to this groups of patients has become recognized. Bone disease is one of these complications. It is well known that there is an interplay between the cells in the bone marrow and the surrounding bone tissue. Marrow stromal cells include the progenitors of the osteoblastic lineage are the sources of effector molecules that support and regulate both hematopoiesis and bone remodeling. But little is known about the effects of myeloablative treatment followed by bone marrow transplantation(BMT) on bone metabolism. METHODS: We have investigated prospectively in 29 patients undergoing BMT(4 autologous, 25 allogenic) for hematologic diseases(19 leukemia, 9 severe aplastic anemia, 1 myelodyspoietic syndrome). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and biochemical markers of bone turnover(osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen(ICTP)] were measured. The samples were collected before BMT and 1, 2, 3, 4, 12 weeks, 6 months and 1 year thereafter. Bone mineral density was measured with DEXA(Dual Energy X-ray Absorptiometry) before and after 1 year of BMT. RESULTS: 1. ICIP was progressively increased until 4 weeks after BMT when peak values were reached. And then decreased thereafter and basal values were regained after 1 year. Osteocalcin was progressively decreased until 3 weeks after BMT when nadir values were reached. And then increased thereafter and basal values were regained after 3 months. No distinct differences were observed in serum biochemical turnover marker between both sexes and between patients who received total body irradiation and those who did not. 2. Lumbar BMD was 2.1% decreased from 1.113 +/- 0.132 g/cm to 1.089 +/- 0.137 g/cm, and femoral BMD was 6.2% decreased fiom 1.078 +/- 0.156 g/cm to 1.011 +/- 0.157 g/cm. 3. 92% of the women (11/12) became menopausal manifested by high gonadotropin and low estradiol levels immediately after BMT. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. CONCLUSION: The rapid impairment of bone formation and also increase in bone resorption, as mirrored by the biochemical markers in this study, might play a role for the post-BMT bone loss. Further studies over many patients with a longer follow up will be needed.

A Case of Partial Hypopituitarism and Central Diabetes Insipidus Developed after Tuberculous Meningitis / 대한내분비학회지

Complications related to tuberculous menngitis (TBM) is frequently encountered in medical field during, just after treatment and long time later. Hypothalamo-pituitary dysfunctions such as diabetes incipidus, dwarfism, hypogonadism, growth failure, and hypopituitarism are one of rare complication secondary to TBM and of which obesity with hypogonadism is most commonly documented. Several pathologic mechanics like a granuloma in hypothalamus, or pituitary stalk, organization and progressive scarring of the purulent exudate in the basal cistern or progressive obliterative endarteritis that supplying the hypothalamo-hypophyseal system is well-defined in hypothalamopituitary dysfunction in neurotuberculosis. We recently experienced a diabetic patient with short stature and sexual infantilism who shows polyuria and polydipsia. Detailed endocrinological evaluation showed partial hypopituitarism and central diabetes incipidus secondary to tuberculous meningitis. Polyuria and polydipsia was improved with dDAVP and height increased 5 cm for 11 month with HGH, libido increased with oxadrolone but his extemal sexual characteristics was not changed until now. We present this case with a review of literature.

A Case of Primary Hyperparathyroidism Associated with Proximal Renal Tubular Acidosis and Postoperative Hungry Bone Syndrome / 대한내분비학회지

Primary hyperparathyroidism is a generalezed disorder of calcium, phosphorus and bone metabolism due to an increased secretion of parathyroid hormone. Single parathyroid adenoma is the most common cause of primary hyperparathyroidism. Because parathyroid hormone has been proposed as an important inhibitor of renal bicarbonate reabsorption of proximal tubule, proximal renal tubular acidosis is not rare in primary hyperparaphyroidism. After parathyroid resection, significant hypocalcemia and hypophosphatemia requiring prolonged medical management may develop, termed hungery bone syndrome. We experienced a case of primary hyperparathyroidism associated with proximal renal tubular acidosis, and severe hungry bone syndrome after resection of the adenoma of parathyroid gland.