Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION)

Background@#This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. @*Methods@#In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. @*Results@#The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. @*Conclusion@#Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Effect of Sarcopenia and Body Shape on Cardiovascular Disease According to Obesity Phenotypes

BackgroundThis study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes.MethodsWe used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index ResultsThe MHNW participants with sarcopenia had higher risk for CVD than those without sarcopenia (OR, 2.69; 95% confidence interval [CI], 1.56 to 4.64). In the analysis with MHNW participants without sarcopenia as a reference, the participants with sarcopenia showed a higher OR for CVD than those without sarcopenia in both MHO (OR in participants without sarcopenia, 3.31; 95% CI, 1.94 to 5.64) (OR in participants with sarcopenia, 8.59; 95% CI, 2.63 to 28.04) and MUO participants (OR in participants without sarcopenia, 5.11; 95% CI, 3.21 to 8.15) (OR in participants with sarcopenia, 8.12; 95% CI, 4.04 to 16.32). Participants within the second and third tertiles of ABSI had higher ORs for CVDs than the counterpart of obesity phenotypes within the first tertile.ConclusionThese results suggest that clinical approaches that consider muscle and body shape are required.

Effect of Sarcopenia and Body Shape on Cardiovascular Disease According to Obesity Phenotypes

BackgroundThis study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes.MethodsWe used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index ResultsThe MHNW participants with sarcopenia had higher risk for CVD than those without sarcopenia (OR, 2.69; 95% confidence interval [CI], 1.56 to 4.64). In the analysis with MHNW participants without sarcopenia as a reference, the participants with sarcopenia showed a higher OR for CVD than those without sarcopenia in both MHO (OR in participants without sarcopenia, 3.31; 95% CI, 1.94 to 5.64) (OR in participants with sarcopenia, 8.59; 95% CI, 2.63 to 28.04) and MUO participants (OR in participants without sarcopenia, 5.11; 95% CI, 3.21 to 8.15) (OR in participants with sarcopenia, 8.12; 95% CI, 4.04 to 16.32). Participants within the second and third tertiles of ABSI had higher ORs for CVDs than the counterpart of obesity phenotypes within the first tertile.ConclusionThese results suggest that clinical approaches that consider muscle and body shape are required.

Relationships between Thigh and Waist Circumference, Hemoglobin Glycation Index, and Carotid Plaque in Patients with Type 2 Diabetes

Background@#This study investigated the relationships of thigh and waist circumference with the hemoglobin glycation index (HGI) and carotid atherosclerosis in patients with type 2 diabetes. @*Methods@#This observational study included 3,075 Korean patients with type 2 diabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. HGI was defined as the measured hemoglobin A1c (HbA1c) level minus the predicted HbA1c level, which was calculated using the linear relationship between HbA1c and fasting plasma glucose levels. Carotid atherosclerosis was defined as a clearly isolated focal plaque or focal wall thickening >50% of the surrounding intima-media thickness. @*Results@#The frequency of a positive HGI decreased with increasing thigh circumference in men and increased with increasing waist circumference in women after adjusting for potential confounding variables. Thigh and waist circumference had a combined augmentative effect on the likelihood of positive HGI, which was dramatically higher in patients in higher waist-to-thigh ratio quartiles (adjusted odds ratios for the highest compared to the lowest quartile: 1.595 in men and 1.570 in women). Additionally, the larger the thigh circumference, the lower the risk of carotid atherosclerosis, although in women, this relationship lacked significance after adjustment for potential confounders. @*Conclusion@#HGI was associated with thigh circumference in men and waist circumference in women. In addition, the combination of low thigh circumference and high waist circumference was strongly associated with a higher HGI in Korean patients with type 2 diabetes. In particular, thigh circumference was associated with carotid atherosclerosis in men. However, further longitudinal studies are warranted.

Effect of Sarcopenia and Body Shape on Cardiovascular Disease According to Obesity Phenotypes

Background@#This study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes. @*Methods@#We used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index <7 kg/m2 in men and <5.5 kg/m2 in women. A multivariate logistic regression analysis was performed to evaluate the odds ratio (OR) of sarcopenia and ABSI for CVD events according to the obesity phenotype. @*Results@#The MHNW participants with sarcopenia had higher risk for CVD than those without sarcopenia (OR, 2.69; 95% confidence interval [CI], 1.56 to 4.64). In the analysis with MHNW participants without sarcopenia as a reference, the participants with sarcopenia showed a higher OR for CVD than those without sarcopenia in both MHO (OR in participants without sarcopenia, 3.31; 95% CI, 1.94 to 5.64) (OR in participants with sarcopenia, 8.59; 95% CI, 2.63 to 28.04) and MUO participants (OR in participants without sarcopenia, 5.11; 95% CI, 3.21 to 8.15) (OR in participants with sarcopenia, 8.12; 95% CI, 4.04 to 16.32). Participants within the second and third tertiles of ABSI had higher ORs for CVDs than the counterpart of obesity phenotypes within the first tertile. @*Conclusion@#These results suggest that clinical approaches that consider muscle and body shape are required.

Serum Chemerin Levels are Associated with Visceral Adiposity, Independent of Waist Circumference, in Newly Diagnosed Type 2 Diabetic Subjects

PURPOSE: Chemerin has been suggested to be linked to insulin resistance and type 2 diabetes mellitus (T2DM). However, the relationship between visceral adiposity and chemerin levels remains unclear in subjects with T2DM. In this study, we investigated the relationship between serum chemerin levels and visceral adiposity. MATERIALS AND METHODS: This study included 102 subjects newly diagnosed with T2DM. The relationships between serum chemerin levels and clinical and biochemical parameters were examined. Multiple linear regression analysis was performed to determine the predictable factors of serum chemerin levels. RESULTS: Serum chemerin levels showed significant positive correlations with body mass index (BMI), waist circumference (WC), visceral fat thickness (VFT), insulin levels, the homeostasis model assessment of insulin resistance, and levels of triglycerides (log-transformed) and high-sensitivity C-reactive protein, while showing significant negative correlations with high-density lipoprotein cholesterol. After adjusting for BMI and WC, VFT showed a significant relationship with serum chemerin levels (r=0.222, p=0.027). Moreover, VFT was an independent predictive factor of serum chemerin levels (β=0.242, p=0.041). CONCLUSION: We demonstrated that chemerin is linked to metabolic syndrome components. Moreover, serum chemerin levels were associated significantly with obesity, especially visceral adipose tissue, in subjects with T2DM.

A Potential Issue with Screening Prediabetes or Diabetes Using Serum Glucose: A Delay in Diagnosis

The aim of this study was to compare the fasting serum glucose level with the fasting plasma glucose level for diagnosing hyperglycemic states in real-life clinical situations. Additionally, we investigated a usual delay in sample processing and how such delays can impact the diagnosis of hyperglycemic states. Among 1,254 participants who had normoglycemia or impaired fasting glucose (IFG) assessed by the fasting serum glucose level, 20.9% were newly diagnosed with diabetes based on the plasma fasting glucose level. Of the participants with normoglycemia, 62.1% and 14.2% were newly diagnosed with IFG and diabetes, respectively, according to the plasma fasting glucose level. In our clinical laboratory for performing health examinations, the time delay from blood sampling to glycemic testing averaged 78±52 minutes. These findings show that the ordinary time delay for sample processing of the serum glucose for screening hyperglycemic states may be an important reason for these diagnoses to be underestimated in Korea.

Glycosylated Hemoglobin Threshold for Predicting Diabetes and Prediabetes from the Fifth Korea National Health and Nutrition Examination Survey

We aimed to estimate the threshold level of glycosylated hemoglobin (HbA1c) for the fasting plasma glucose of 100 and 126 mg/dL in the Korean adult population, using the 2011 Korea National Health and Nutrition Examination Survey. A total of 4,481 participants over 19 years of age without diabetic medications and conditions to influence the interpretation of HbA1c levels, such as anemia, renal insufficiency, liver cirrhosis, and cancers, were analyzed. A point-wise area under the receiver operating characteristic curve was used to estimate the optimal HbA1c cutoff value. A HbA1c threshold of 6.35% was optimal for predicting diabetes with a sensitivity of 86.9% and a specificity of 99.1%. Furthermore, the threshold of HbA1c was 5.65% for prediabetes, with a sensitivity of 69.3% and a specificity of 71%. Further prospective studies are needed to evaluate the HbA1c cutoff point for diagnosing prediabetes and diabetes in the Korean population.

Effects of the Serum Adiponectin to Tumor Necrosis Factor-alpha (TNF-alpha) Ratio on Carotid Intima-Media Thickness in Newly Diagnosed Type 2 Diabetic Patients

OBJECTIVES: Type 2 diabetes, a leading cause of cardiovascular disease, is well known for its association with accelerated atherosclerosis. Adiponectin and tumor necrosis factor - alpha (TNF-alpha), which are produced and secreted in adipose tissue, have been suggested as predictors for cardiovascular disease. However, little is known about the influence of adiponectin and TNF-alpha ratio on the progression of carotid atherosclerosis in newly diagnosed type 2 diabetic patients. This study was conducted to evaluate the influence of serum adiponectin/TNF-alpha levels on the progression of carotid atherosclerosis. METHODS: One hundred eleven newly diagnosed type 2 diabetes patients were enrolled. Anthropometric and biochemical data including serum adiponectin, TNF-alpha were measured for each participant. Also we measured carotid intima-media thickness (CIMT) at baseline and at 1 year follow-up (n=81). We finally examined the relationship among serum adiponectin over TNF-alpha levels (ADPN/TNF-alpha), baseline CIMT, and progression of CIMT at 1 year. RESULTS: ADPN/TNF-alpha negatively correlated with baseline CIMT (r=-0.231, p=0.025). Moreover, progression of CIMT was significant at 1 year (0.011+/-0.138 mm). There was a negative correlation between ADPN/TNF-alpha and progression of CIMT at 1 year (r=-0.172, p=0.038). In multiple regression analysis, age and HbA1c were found to be independent risk factors for baseline CIMT. However, only HbA1c was an independent risk factor for the progression of CIMT. CONCLUSION: ADPN/TNF-alpha was negatively associated with baseline CIMT and the progression of CIMT at 1 year. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

A Case of Hyponatraemic Seizure Following Terlipressin Therapy for a Variceal Hemorrhage in a Patient with Liver Cirrhosis / 대한내과학회지

Terlipressin has splanchnic vasoconstrictive effects, and is generally used for the management of gastroesophageal variceal bleeding secondary to liver cirrhosis. Terlipressin is a synthetic arginine vasopressin (AVP) analog containing a nonapeptide sequence. Terlipressin has increased selectivity for the V1 receptor, compared with AVP; hence, it is considered to be a safe vasoconstrictor. However, side effects such as hyponatremia and seizure, although very rare, have been reported. Hyponatremia related to terlipressin may be caused by the syndrome of inappropriate antidiuresis (SIAD), which is a disorder of sodium and water balance characterized by hypotonic hyponatremia without elevation of the antidiuretic hormone level. Here, we report a case of hyponatremic seizure induced by an infusion of terlipressin in a 52-year-old female who had isolated gastric variceal bleeding secondary to alcoholic liver cirrhosis.

Gender and age differences in obesity among Korean adults

No abstract available.

Diabetes Educator Training Module (DETM) / 임상당뇨병

The Diabetes Educator Training Module (DETM), which was developed in 2011, contained more than 900 slides. The purpose of the DETM is to help Korean diabetes educators develop programs for diabetic patients and health professionals. In this paper, we present information regarding the history, the principles of development, the contents, and the use of the DETM program. We hope that the DETM will be a useful tool for helping diabetic patients to understand their disease and to improve their glycemic control and treatment adherence.

Anti-Obesity Drugs: A Review about Their Effects and Safety

The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

Impact of Serum Adiponectin Concentration on Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

BACKGROUND: Increased cardiovascular events, which is the leading cause of death in type 2 diabetic patients, are mainly caused by accelerated atherosclerosis. Adiponectin has been suggested as a risk factor for cardiovascular diseases in cross-sectional studies. However, little is known about the impact of adiponectin on the progression of carotid atherosclerosis in type 2 diabetic patients. This study was conducted to evaluate the impact of early adiponectin levels on the progression of carotid atherosclerosis. METHODS: From March 2009, 150 patients with type 2 diabetes were consecutively enrolled in our affiliated outpatient clinic. Anthropometric and biochemical data, including adiponectin levels, were measured in each participant. We measured the carotid intima-media thickness (CIMT) at baseline and at 1-year follow-up (n = 111). Then, we prospectively studied the relationship between the serum adiponectin levels and the progression of CIMT for 1 year. RESULTS: Adiponectin levels negatively correlated with CIMT (r = -0.219, P = 0.015). Moreover, mean progression of CIMT was 0.016 +/- 0.040 mm. However, there was no correlation between adiponectin levels and the progression of CIMT within 1-year follow-up period (r = -0.156, P = 0.080). Age (beta = 0.556, P = 0.004), LDL cholesterol (beta = 0.276, P = 0.042), and A1C (beta = 0.309, P = 0.038) were found to be independent risk factors for CIMT. However, A1C (beta = 0.311, P = 0.042) was found to be the only independent risk factor for the progression of CIMT. CONCLUSION: In our study, adiponectin levels were negatively associated with CIMT. However, it did not affect the progression of CIMT at 1-year follow-up. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

Case of Thyroid Hormone Resistance Syndrome with a Mutation in the Thyroid Hormone Receptor Beta Gene / 대한내과학회지

In thyroid hormone resistance syndrome (THR) TSH levels are normal or elevated despite thyroid hormone levels being elevated. THR is distinguished from TSH-producing pituitary adenoma by TRH stimulation and alpha-subunit tests, thyroid hormone receptor (TR) beta gene analysis, and sellar MRI. A 24-year old man with diffuse goiter visited our hospital complaining of fatigue, heat intolerance, palpitation, and weight loss. He had elevated total T3 and free T4 levels, but normal TSH levels. Serum TSH levels during TRH stimulation tests performed before and after T3 suppression showed normal and non-suppressible responses, respectively. The serum basal alpha-subunit test result was normal. A TR beta gene R438H mutation was identified, and a pituitary mass with cystic change was identified by sellar MRI. We report a case of THR with a mutation (R438H) in the TR beta gene, the first case of its kind in Korea.

A Case of Familial Hypocalciuric Hypercalcemia Coexisting with Hypothyroidism / 대한내과학회지

Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder characterized by mild asymptomatic hypercalcemia, hypocalciuria, a decreased urinary calcium-creatinine ratio, and normal or elevated parathyroid hormone levels. FHH is caused by an inactivating heterozygous mutation of the calcium-sensing receptor (CaSR) gene. A 62-year-old woman was referred to our center because of inadequate glucose control. Her son had hypercalcemia. Biochemical and endocrine studies showed hypercalcemia, hypocalciuria, a decreased urinary calcium-creatinine ratio, normal parathyroid hormone levels, normal PTH-related peptide levels, decreased free T4, increased TSH, and thyroid antibody positivity. Direct sequencing analyses revealed a heterozygous mutation of G21R at exon 2 and a single nucleotide polymorphism of R990G at exon 7 of the CaSR gene. Here, we report a case of FHH associated with a heterozygous mutation and a single nucleotide polymorphism of the CaSR gene, which coexisted with autoimmune thyroiditis and hypothyroidism. To our knowledge, this is the first such case reported.

Is A1C Variability an Independent Predictor for the Progression of Atherosclerosis in Type 2 Diabetic Patients? / 당뇨병

BACKGROUND: Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated. RESULTS: With greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (beta = 0.158, P = 0.093). CONCLUSION: Higher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.

A case of hyperglycemia-induced hemiballism-hemichorea associated with diabetic ketoacidosis / 대한내과학회지

Hemiballism-hemichorea (HB-HC) is defined as continuous, non-patterned, and involuntary movement involving one side of the body and is often associated with endocrine diseases such as diabetes mellitus (DM) and hyperthyroidism. In Korea, 16 cases of HB-HC associated with non-ketotic hyperglycemia have been reported. Here, we report the first known case of HB-HC associated with type 2 DM and diabetic ketoacidosis (DKA). A 32-year-old man visited our hospital complaining of hemichoreoballistic movement. The patient had no history of DM. In a neurological examination and laboratory tests, HB-HC associated with type 2 DM and DKA was diagnosed. The patient was immediately treated with intravenous hydration and insulin therapy, and completely recovered. DKA and non-ketotic hyperglycemia should be considered as a possible cause of HB-HC, although these are very rare. In HB-HC associated with DKA, strict blood glucose control is needed.

A case of hyperosmolar nonketotic coma associated with androgen deprivation therapy in prostate cancer / 대한내과학회지

During advanced prostate cancer, androgen deprivation therapy (ADT) using gonadotropin-releasing hormone and antiandrogen is an effective treatment modality. Recently, it has been reported that ADT may result in diabetes mellitus (DM), metabolic syndrome, and cardiovascular disease. Here, we report the first case in the literature of new-onset DM and hyperosmolar nonketotic coma (HNKC) associated with ADT. A 69-year-old man visited our hospital because of altered mentality. The patient had been taking leuprolide and bicalutamide for metastatic prostate cancer for the past 4 months. In laboratory tests, new-onset DM with HNKC was diagnosed. The patient was immediately treated with intravenous hydration and insulin therapy, and recovered without sequela. Because ADT can cause DM, or rarely HNKC, it is necessary to monitor fasting blood glucose and lipid profiles carefully while ADT is performed.