Ah Reum Khang

Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study

Aim: Individuals requiring insulin therapy for type 2 diabetes often require escalation of their regimen to achieve glycaemic control. Optimal management strategies for uncontrolled type 2 diabetes would improve glycaemic control without hypoglycaemia and weight gain. This study compared the efficacy and tolerability of adding sitagliptin, an oral dipeptidyl peptidase‐4 inhibitor, and an up to 20% increase in insulin dose in patients with uncontrolled type 2 diabetes on insulin therapy.

Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study

Objective  We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug‐naïve type 2 diabetic patients.

Subclinical atherosclerosis in a community-based elderly cohort: The Korean Longitudinal Study on Health and Aging

BACKGROUND Early detection of atherosclerosis in elderly people is important because of high cardiovascular mortality. However, only few studies have evaluated the prevalence of subclinical atherosclerosis in Asian elderly people. We evaluated subclinical atherosclerosis using various methods in a population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA). METHODS Subjects aged over 65 years without symptomatic chest pain were recruited for the KLoSHA in 2006 by random stratified sampling (439 men and 561 women). Anthropometrics, biochemical parameters, body composition, and abdominal fat by computed tomography (CT) were measured. Multidetector-row cardiac CT for coronary artery calcium score (CACS) and severity of stenosis, and carotid sonography for intima-media thickness (IMT) were used to detect subclinical atherosclerosis. Pulse wave velocity (PWV) and ankle-brachial index (ABI) were also measured. RESULTS The prevalence of subclinical atherosclerosis defined by coronary stenosis >50%, CACS >100, PWV >9m/s, carotid-IMT >0.8mm, or ABI <0.9 was 17.6%, 28.1%, 37.9%, 39.2%, and 29.6%, respectively. There were significant, but modest correlations among parameters. Although male sex, diabetes mellitus, hypertension, abnormal BMI, and higher insulin resistance were associated with subclinical atherosclerosis, older age was found to be the most robust predictor after controlling for multiple factors. CONCLUSION Our results suggest that proactive screening with multiple measurements in elderly subjects, particularly in men and those with diabetes mellitus or hypertension, may help to identify asymptomatic patient with atherosclerosis. Further studies exploring the predictive value of diagnostic tools can determine the most appropriate measurement for predicting future cardiovascular events.

Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody

Background Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes. Methods We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics. Results The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups. Conclusion The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

Counterintuitive relationship between visceral fat and all-cause mortality in an elderly Asian population.

Abdominal obesity is considered to be a risk factor for mortality. However, recent studies indicate that overweight may be negatively associated with mortality (“obesity paradox”). The relationships between mortality and various obesity markers in an elderly Asian cohort were evaluated.

The risk of second primary malignancy is increased in differentiated thyroid cancer patients with a cumulative 131I dose over 37 GBq

The aim of this study was to investigate the risk factors for second primary malignancy (SPM) diagnosed after differentiated thyroid cancer (DTC).

Effect of carnitine-orotate complex on glucose metabolism and fatty liver: A double-blind, placebo-controlled study

Effective medicines have not been introduced for insulin resistance‐related fatty liver. The efficacy and safety of treatment between a combination of metformin and carnitine‐orotate complex and metformin alone in a 12‐week, double‐blind, randomized, placebo‐controlled study on drug‐naïve patients with impaired glucose metabolism and fatty liver were compared.

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

AIMS The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes. METHODS We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated. RESULTS Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects. CONCLUSIONS In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.

An insulinoma with an aberrant feeder from the splenic artery detected by super-selective arterial calcium stimulation with venous sampling

To the Editor, A pancreatic insulinoma is a rare endocrine neoplasm with an estimated incidence of four cases per million person-years. Because the typical size of an insulinoma is < 2 cm, computed tomography (CT) or magnetic resonance imaging (MRI) may not detect the location of the tumor. The sensitivity of detecting an insulinoma is 70% to 80% for CT, 85% for MRI, and 85% to 90% for endoscopic ultrasound (EUS) [1]. Selective arterial calcium stimulation with hepatic venous sampling (ASVS) is a good complementary tool that increases the sensitivity to 84% to 100% [2]. However, ASVS does not always locate the insulinoma, and equivocal findings are reported frequently. We hereby report a case of an insulinoma in the pancreatic head with an aberrant feeder artery arising from the splenic artery, which was detected by angiography and super-selective ASVS. A 50-year-old woman, who had never been diagnosed with diabetes mellitus, was admitted to a local emergency department for loss of consciousness. Her capillary blood glucose level was 41 mg/dL, and she recovered consciousness immediately after intravenous glucose administration. An abdominal CT scan did not indicate any definite pancreatic mass (Fig. 1A). Therefore, she was referred to our hospital for further evaluation. Figure 1 (A) Abdominal computed tomography image. (B) No definite mass was found. Celiac arteriography shows the tumor (arrow) and the feeding artery (arrowheads) originating from the proximal splenic artery. Her medical history was unremarkable, and she had no family history of endocrine disease. She had suffered from fatigue and dizziness for the last 6 months. No specific findings were revealed on a physical examination. Laboratory results, including a complete blood cell count and basic chemistry tests, were within normal ranges. A 72-hour fasting test was performed but was terminated after 2 hour due to symptomatic hypoglycemia. Her serum glucose level was 51 mg/dL, and she felt severe fatigue. Serum insulin (9.9 mIU/mL) and C-peptide (2.2 ng/mL) levels were elevated sufficiently to diagnose inappropriate endogenous hyperinsulinemia. Because we thought that the size of the potential insulinoma was very small, no further imaging studies, including EUS, were performed. ASVS was performed to identify and localize the insulin-secreting tumor. First, celiac and superior mesenteric arteriography was performed. A small hypervascular tumor in the pancreatic head and a feeding artery originating from the proximal portion of the splenic artery were observed (Fig. 1B). Blood samples were obtained from the hepatic vein 0, 30, 60, and 120 seconds after injecting 5 mL calcium gluconate diluted in normal saline (0.025 mEq/kg) via the superior mesenteric artery, gastroduodenal artery, splenic artery, and the feeder artery originating from the splenic artery. Serum insulin and C-peptide levels are shown in Fig. 2. Figure 2 Insulin (A) and C-peptide (B) levels in hepatic venous blood samples after selective arterial calcium stimulation of three major pancreatic arteries and the feeder artery. Insets depict insulin and C-peptide levels after calcium stimulation of three major ... Insulin and C-peptide levels in the splenic artery during conventional ASVS were higher than those in the superior mesenteric or gastroduodenal arteries. We took a step further using super-selective ASVS on the aberrant feeder artery from the splenic artery. The results showed remarkable increases in insulin and C-peptide secretion (Fig. 2), indicating that the tumor stained in the pancreatic head was an insulinoma. A pylorus-preserving pancreaticoduodenectomy was performed without complications. The pathology was consistent with a well-differentiated benign endocrine tumor based on the 2000 World Health Organization Classification for Pancreatic Endocrine Neoplasms. The tumor was 1.4 × 0.7 × 0.5 cm3 in size, the mitotic count was < 1/10 at a high power field, and Ki-67 was positive in 0.27% (15/5,524) of the tumor cells. Immunohistochemical studies revealed that most of the tumor cells were positive for chromogranin, synaptophysin, insulin, and CD56, but negative for glucagon, somatostatin, carcinoembryonic antigen, and mucin-1 (Fig. 3). The premeal capillary blood glucose level recovered after surgery and was maintained within 100 to 150 mg/dL. Her fasting plasma glucose level was 89 mg/dL at the 3-month follow-up. Serum insulin and C-peptide levels decreased to 1.4 mIU/mL and 1.2 ng/mL, respectively. She did not experience hypoglycemic symptoms. Figure 3 (A-F) Immunohistochemical staining of the insulinoma (×200). Hematoxylin and eosin staining of the insulinoma is consistent with a neuroendocrine tumor (A). The proportion of Ki-67-positive cells (arrowheads) was 0.27% (15/5,524) of tumor cells ... This was a case of a pancreatic head insulinoma supplied by an aberrant artery from the splenic artery. Conventional ASVS assumes two distinctive portions of the pancreas: the pancreatic head portion supplied by the superior mesenteric or gastroduodenal artery and the pancreatic body to tail portion supplied by the splenic artery. However, many variations in pancreatic vascular anatomy have been reported, particularly in the head portion. Okahara et al. [3] found that 36% of inferior pancreaticoduodenal arteries arose from branches other than the superior mesenteric artery, and that 2% of the superior pancreaticoduodenal arteries arose from branches other than the gastroduodenal artery. An insulinoma with an aberrant feeder artery, as in our case, has not yet been reported. Two studies on super-selective ASVS have been published [4,5]. However, these studies performed intra-arterial calcium stimulation through the splenic artery divided into proximal, middle, and distal portions, whereas we selected the tumor feeding artery specifically. Notably, the results of conventional ASVS indicated that the insulinoma could be in the pancreatic body or the tail portion, because higher insulin and C-peptide levels were obtained via the splenic artery compared with the superior mesenteric or gastroduodenal arteries. However, peak insulin levels 60 seconds after the calcium injection via the feeder artery was in hundreds of basal insulin levels of the three major arteries supplying the pancreas. We could have resected the pancreatic body and tail if we had not found tumor staining in the pancreatic head and its feeder artery. As such, super-selective ASVS was necessary to localize and functionally diagnose the insulinoma accurately. Interestingly, baseline insulin and C-peptide levels were highly elevated compared with those of the three major arteries supplying the pancreas during super-selective ASVS for the feeder artery. One study reported elevated insulin levels in tumor-supplying arteries before calcium stimulation, as in our case [4]. This finding can be explained by delayed calcium perfusion into the insulinoma from prior stimulation tests or by the radiocontrast media used during angiography. A 15-minute interval between stimulations has been suggested to avoid this delayed effect [4]. In conclusion, this case report emphasizes the importance of careful angiography and super-selective ASVS to diagnose suspicious insulinomas that are difficult to locate using conventional imaging methods.