Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension

Background@#This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. @*Methods@#In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). @*Results@#Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. @*Conclusion@#Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

A Case of Graves' Disease Occurring after Subacute Thyroiditis / 대한내과학회지

Graves' disease following subacute thyroiditis is uncommon. Some patients in these cases showed positive for thyroid antibody only transiently in the resolving phase. However, Graves' disease can rarely be caused by the presence of antibodies after subacute thyroiditis, although the pathophysiology of this is unclear. A 40-year-old woman presented with anterior neck pain and swallowing difficulty. Thyroid function testing showed reduced thyroid-stimulating hormone (TSH) and elevated free thyroxine levels. A thyroid scan revealed decreased uptake in the bilateral thyroid gland. The patient was initially diagnosed with subacute thyroiditis and treated with steroids. Five months later, thyroid function testing showed recurrent hyperthyroidism with positive conversion of TSH receptor antibody, indicating Graves' disease. Since then, she needed the long-term methimazole treatment. In summary, we herein report a case of Graves' disease occurring after subacute thyroiditis.

Correlations between Glucagon Stimulated C-peptide Levels and Microvascular Complications in Type 2 Diabetes Patients

BACKGROUND: This study aimed to investigate whether stimulated C-peptide is associated with microvascular complications in type 2 diabetes mellitus (DM). METHODS: A cross-sectional study was conducted in 192 type 2 diabetic patients. Plasma basal C-peptide and stimulated C-peptide were measured before and 6 minutes after intravenous injection of 1 mg glucagon. The relationship between C-peptide and microvascular complications was statistically analyzed. RESULTS: In patients with retinopathy, basal C-peptide was 1.9+/-1.2 ng/mL, and stimulated C-peptide was 2.7+/-1.6 ng/mL; values were significantly lower compared with patients without retinopathy (P=0.031 and P=0.002, respectively). In patients with nephropathy, basal C-peptide was 1.6+/-0.9 ng/mL, and stimulated C-peptide was 2.8+/-1.6 ng/mL; values were significantly lower than those recorded in patients without nephropathy (P=0.020 and P=0.026, respectively). Stimulated C-peptide level was associated with increased prevalence of microvascular complications. Age-, DM duration-, and hemoglobin A1c-adjusted odds ratios for retinopathy in stimulated C-peptide value were 4.18 (95% confidence interval [CI], 1.40 to 12.51) and 3.35 (95% CI, 1.09 to 10.25), respectively. The multiple regression analysis between nephropathy and C-peptide showed that stimulated C-peptide was statistically correlated with nephropathy (P=0.03). CONCLUSION: In patients with type 2 diabetes, the glucagon stimulation test was a relatively simple method of short duration for stimulating C-peptide response. Stimulated C-peptide values were associated with microvascular complications to a greater extent than basal C-peptides.

Serial Measurements of Off-Thyroxine Serum TSH and Thyroglobulin Levels to Predict Local and/or Systemic Metastasis of Papillary Thyroid Cancer after Total Thyroidectomy / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Off-thyroxine serum thyroglobulin (Tg) level is important to predict metastatic disease (MD) in papillary thyroid cancer (PTC); however, it is unclear whether a single off-thyroxine Tg level is sufficient for predicting MD. In this study, we determined whether serial measurement of off-thyroxine serum Tg level can predict metastasis in PTC patients after total thyroidectomy. MATERIALS AND METHODS: We enrolled 140 PTC patients in whom serum thyroid-stimulating hormone (TSH) and Tg levels were measured 7 days before radio-iodine (RAI) treatment (TSHA and TgA) and on the day of RAI treatment (TSHB and TgB) with withholding L-thyroxine for 4 weeks before RAI treatment. The values of TSHinc (TSHB-TSHA) and Tginc (TgB-TgA), Tgratio (TgB/TgA), Tginc/TSHinc and Tgratio/TSHinc were calculated. Tginc/TSHinc and Tgratio/TSHinc were tested if those parameters can predict MD in patients with TSHA>30 microIU/mL and TgA30 microIU/mL and TgA<10 ng/mL (MD, 9; non-MD, 34), both Tginc/TSHinc (100%) and Tgratio/TSHinc (89%) had higher sensitivities for predicting MD than TgB (78%). CONCLUSION: With the increment in serum Tg corrected for the increment in serum TSH, serial measurements of off-thyroxine serum TSH and Tg levels can help predict PTC metastasis.

Response: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:41-9)

No abstract available.

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. METHODS: Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. RESULTS: ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean+/-standard error, 23.1+/-0.6 U/L vs. 18.6+/-0.8 U/L; P9%) showed significantly increased ADA activity (21.1+/-0.8 U/L vs. 25.4+/-1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9+/-1.0 U/L vs. 28.1+/-2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy. CONCLUSION: Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients

BACKGROUND: Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. METHODS: Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed. RESULTS: A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226). CONCLUSION: Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.

The Biochemical Markers of Coronary Heart Disease Correlates Better to Metabolic Syndrome Defined by WHO than by NCEP-ATP III or IDF in Korean Type 2 Diabetic Patients / 당뇨병

BACKGROUND: Metabolic syndrome (MetS) is constellation of cardiovascular risk factors. There are three typically used definitions of MetS proposed by WHO, IDF and NCEP-ATP III. We conducted this study to compare the associations of MetS by WHO, IDF and NCEP-ATP III definition to various metabolic markers of coronary heart diseases in Korean type 2 diabetes patients. METHODS: We enrolled 151 Korean type 2 diabetes patients in one hospital. Anthropometric and biochemical parameters, including high-sensitivity C-reactive protein (hsCRP), homocysteine, uric acid were measured. And then, we divided MetS group from non-MetS group according to three other definitions. RESULTS: Serum hsCRP level was higher in those with MetS group than non-MetS group by WHO definition (0.33 +/- 0.36 mg/dL vs 0.18 +/- 0.26 mg/dL, P < 0.001). But, there are no difference in MetS group and non-MetS group by IDF and NCEP-ATPIII definition. (By IDF, 0.28 +/- 0.31 mg/dL vs 0.25 +/- 0.34 mg/dL, P = 0.64; By NCEP-ATP III, 0.28 +/- 0.33 mg/dL vs 0.22 +/- 0.32 mg/dL, P = 0.41). Uric acid and homocysteine levels were higher in those with MetS by WHO definition (P < 0.05). Similarly, analyses according to IDF and NCEP ATP III definition showed no significant difference. CONCLUSION: In conclusion, WHO definition of MetS has a stronger relationship with the biochemical markers of coronary heart disease in Korean type 2 diabetes patients.

A Case of 45,X Turner's Syndrome with Iron Deficiency Anemia due to Menometrorrhagia and Spontaneous Sexual Development / 대한내분비학회지

Short stature and gonadal dysgenesis are two characteristic clinical features of Turners syndrome. Very rarely, patients with Turners syndrome may menstruate and even be fertile. We experienced a case of Turners syndrome with spontaneous sexual development and menstruation. A 16-year-old girl was referred for severe anemia and menometrorrahgia. She had nearly normal features, with the exception of a short stature and a single right kidney. Also, she had spontaneous development of secondary sexual characteristics. We performed and anemia study and evaluated her short stature. In chromosomal study of her bone marrow and peripheral blood lymphocytes, she was revealed to have monosomy 45,X. Herein, this case is reported, with a brief review of literature

A Case of Fuctioning Extraadrenal Paraganglioma Mimicking Acute Coronary Syndrome / 대한내분비학회지

A functioning paraganglioma is a rare catecholamine-producing tumor that arises from the extra-adrenal chromaffin tissue. Recently we experienced a case in which a 42 year-old male patient with a functioning extra-adrenal paraganglioma mimicked an acute coronary syndrome. A functioning extra-adrenal paraganglioma was diagnosed by means of a biochemical study and a radiological imaging study. After stabilizing his blood pressure, using alpha adrenergic blocker, we successfully removed a 6?cm sized paraganglioma from between the aorta and the IVC in the retroperitoneal space.