Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Recent Advances in Sodium Glucose Cotransporter-2 Inhibitors / 임상당뇨병

Sodium glucose cotransporter-2 inhibitors (SGLT2i) block SGLT2 in the renal proximal tubule and increase the excretion of glucose into the urine, thereby decreasing serum glucose concentrations. These glucose-lowering effects are independent of insulin action. SGLT2i has been demonstrated to reduce cardiovascular complications and hospitalization for heart failure. SGLT2i has also shown remarkable inhibition effects on the progression of renal complications, decreasing serum creatinine, reducing albuminuria, and decreasing death from renal disease. These cardiorenal protective effects appear to be independent of glycemic control efficacy, and in view of these results, SGLT2i is recommended in type 2 diabetes patients at high risk of cardiovascular or renal disease. This review aims to provide an update on the mechanisms, efficacy, cardiorenal protective effects, and adverse effects of SGLT2i.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Reference Intervals for Bone Turnover Markers in Korean Healthy Women

BACKGROUND: Adequate suppression of bone turnover rate is important to decrease fracture risk without mineralization defect due to oversuppression. This study was performed to determine reference intervals (RIs) for 2 bone turnover markers, serum C-terminal telopeptide of type I collagen (CTX) and osteocalcin, in Korean women.METHODS: A total of 461 Korean women (287 premenopausal and 174 postmenopausal) without any disease or drug history affecting bone metabolism was included. Serum CTX and osteocalcin were measured after overnight fasting. Bone mineral density (BMD) was measured at the 1st to 4th lumbar vertebra using dual energy X-ray absorptiometry. Subjects with normal spinal BMD (T-score ≥−1.0) were included in this study.RESULTS: After stable concentrations were maintained, both CTX and osteocalcin were abruptly increased in 50 to 59 years, and then decreased with increasing age. Median levels and interquartile range of serum CTX and osteocalcin in all subjects were 0.322 (0.212–0.461) ng/mL and 15.68 (11.38–19.91) ng/mL. RIs for serum CTX and osteocalcin in all subjects were 0.115 to 0.861 ng/mL and 6.46 to 36.76 ng/mL. Those were higher in postmenopausal women (CTX, 0.124–1.020 ng/mL, osteocalcin, 5.42–41.57 ng/mL) than in premenopausal women (CTX, 0.101–0.632 ng/mL, osteocalcin, 6.73–24.27 ng/mL). If we use target reference levels as lower half of premenopausal 30 to 45 years in patients with antiresorptive drugs, those were 0.101 to 0.251 ng/mL and 6.40 to 13.36 ng/mL.CONCLUSIONS: We established RIs for serum CTX and osteocalcin in healthy Korean women with normal lumbar spine BMD. Premenopausal RIs for serum CTX and osteocalcin would be useful to monitor patients with low bone mass using osteoporosis drugs.

Changes in the Quality of Life in Patients with Type 2 Diabetes Mellitus According to Physician and Patient Behaviors

BACKGROUND: Diabetes mellitus (DM) is the most common chronic metabolic disorder with an increasing prevalence worldwide. According to a previous study, physicians' treatment patterns or patients' behaviors change when they become aware of the risk for cardiovascular (CV) disease in patients with DM. However, there exist controversial reports from previous studies in the impact of physicians' behaviors on the patients' quality of life (QoL) improvements. So we investigate the changes in QoL according to physicians and patients' behavioral changes after the awareness of CV risks in patients with type 2 DM.METHODS: Data were obtained from a prospective, observational study where 799 patients aged ≥40 years with type 2 DM were recruited at 24 tertiary hospitals in Korea. Changes in physicians' behaviors were defined as changes in the dose/type of antihypertensive, lipid-lowering, and anti-platelet therapies within 6-month after the awareness of CV risks in patients. Changes in patients' behaviors were based on lifestyle modifications. Audit of Diabetes Dependent Quality of Life comprising 19-life-domains was used.RESULTS: The weighted impact score change for local or long-distance journey (P=0.0049), holidays (P=0.0364), and physical health (P=0.0451) domains significantly differed between the two groups; patients whose physician's behaviors changed showed greater improvement than those whose physician's behaviors did not change.CONCLUSION: This study demonstrates that changes in physicians' behaviors, as a result of perceiving CV risks, improve QoL in some domains of life in DM patients. Physicians should recognize the importance of understanding CV risks and implement appropriate management.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

Background@#Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). @*Methods@#From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. @*Results@#In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. @*Conclusion@#This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Effective Management of Diabetic Ketoacidosis / 임상당뇨병

Diabetic ketoacidosis (DKA) is serious complication of diabetes mellitus that requires prompt recognition, diagnosis and treatment. It is characterized by a triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration. The overall DKA mortality rate recorded among children and adults is < 1%. For patients with DKA, appropriate administration of intravenous fluids and insulin with attention to associated fluid and electrolyte disorders can effectively and rapidly resolve metabolic dysregulation. Following acute management and restoration of physiological glucose levels, DKA requires identification of the precipitating cause to prevent recurrence of potentially life-threatening diabetic complications.

Clinical Characteristics, Causes and Survival in 115 Cancer Patients with Parathyroid Hormone Related Protein-mediated Hypercalcemia

BACKGROUND: The aim of this study is to determine the proportion of cancers presenting with parathyroid hormone (PTH) related protein (PTHrP)-mediated hypercalcemia, examine the clinical and biochemical characteristics, identify predictive factors for survival. And we also compared those characteristics between solid organ and hematologic malignancy groups. METHODS: Cancer patients with PTHrP-mediated hypercalcemia who were treated at Chonnam National University Hospital in Korea from January 2005 to January 2015 were retrospectively reviewed. RESULTS: Of all 115 patients, solid organ malignancies were the most common etiology (98 cases, 85.2%), with squamous cell carcinoma (50 cases, 43.4%), adenocarcinoma (27 cases, 23.4%). Interestingly, hepatocellular carcinoma (HCC; 18 cases, 15.7%) and cholangiocarcinoma (11 cases, 9.6%) were much more common causes than other previous reports. Hematologic malignancy was less common (17 cases, 14.8%), with multiple myeloma (9 cases, 7.8%) and non-Hodgkin's lymphoma (5 cases, 4.3%). Overall median survival was only 37 days. There was significant difference in median survival between two groups (35 days for solid organ malignancy and 72 days for hematologic malignancy; P=0.015). Cox regression analysis identified age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis as independent predictive factors for survival time. CONCLUSIONS: PTHrP-mediated hypercalcemia was most frequently caused by solid organ malignancy. However, HCC and cholangiocarcinoma were important causes of PTHrP-mediated hypercalcemia may be due to geographic differences in cancer incidence in Korean population. Age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis were independent poor predictive factors for survival time.

A Noisy Carbohydrate Addiction / 임상당뇨병

Carbohydrates are a primary source of energy and a major component of the structure of living things-; there are many different kinds. As eating behavior is a part of life, it was usually not described in addiction. However, sometimes it seems aspects of addiction. This eating behavior can also appear with regard to other food. A bio-psycho-social model is required for complex analysis of addiction. When highly addictive agents are excluded, we can usually identify a key factor related to the vulnerability of the individual to addictive behavior. Considering that every source of happiness can potentially lead to addictive behaviors, we need to be cautious about the controlling. Not every carbohydrate can be connected with addictive behavior. Addictive behavior could be associated with a variety of ingredients other than carbohydrates. Until recently, sweet substances were thought to be the primary culprit behind addictive behavior. It is necessary to identify the food component or other factors associated with a specific craving. A multidimensional approach to the psychology of addictive behaviors might be more useful than opposing carbohydrate consumption in general.

Outpatient Testing for Diabetic Complications / 임상당뇨병

Diagnosis and management of chronic complications is very important in diabetes mellitus. In asymptomatic patients, routine screening for chronic diabetic complications is recommended. If not recognized and if preventive care is not implemented, patients are at risk of damage to major organ systems. Tests for diabetic complications vary depending on the type of complications. Some tests require skilled workers and advanced facilities. Many simple screening tests for complications can also be carried out in outpatient clinics. Performing screening tests for complications in outpatient clinics could contribute to timely diagnosis and management of diabetic complications.

A Case of a Coexisting Aldosterone-Producing Adrenal Adenoma and Ipsilateral Renal Artery Stenosis / 대한내과학회지

The simultaneous occurrence of renovascular hypertension and an aldosterone-producing adrenal adenoma is a rare entity. Here, we report the case of a 52-year-old female who had a coexisting aldosterone-producing adrenal adenoma and ipsilateral renal artery stenosis. She was diagnosed with the aldosterone-producing adrenal adenoma and then underwent a laparoscopic left adrenalectomy. Her blood pressure was uncontrolled after the adrenalectomy. Selective renal angiography showed left renal artery stenosis; thus, she underwent balloon angioplasty at the same sitting. Subsequently, her blood pressure returned to normal after administration of a single antihypertensive drug. This case suggests that it is important to recognize the possible coexistence of renal artery stenosis in a patient with an aldosterone-producing adrenal adenoma.

Electrolyte Imbalance in Patients with Sheehan's Syndrome

BACKGROUND: We investigated the prevalence of electrolyte imbalance and the relationship between serum electrolyte and anterior pituitary hormone levels in patients with Sheehan's syndrome. METHODS: In a retrospective study, we investigated 78 patients with Sheehan's syndrome. We also included 95 normal control subjects who underwent a combined anterior pituitary hormone stimulation test and showed normal hormonal responses. RESULTS: In patients with Sheehan's syndrome, the serum levels of sodium, potassium, ionized calcium, magnesium, and inorganic phosphate were significantly lower than those in control subjects. The prevalence of hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia, and hypophosphatemia in patients with Sheehan's syndrome was 59.0% (n=46), 26.9% (n=21), 35.9% (n=28), 47.4% (n=37), and 23.1% (n=18), respectively. Levels of sodium and ionized calcium in serum were positively correlated with levels of all anterior pituitary hormones (all P<0.05). Levels of potassium in serum were positively correlated with adrenocorticotrophic hormone (ACTH) and growth hormone (GH) levels (all P<0.05). Levels of inorganic phosphate in serum were positively correlated with levels of thyroid-stimulating hormone, prolactin, and GH (all P<0.05), and levels of magnesium in serum were positively correlated with delta ACTH (P<0.01). CONCLUSION: Electrolyte imbalance was common in patients with Sheehan's syndrome. Furthermore, the degree of anterior pituitary hormone deficiency relates to the degree of electrolyte disturbance in patients with this disease.

Inflammatory Myofibroblastic Tumor of the Thyroid Gland: A Brief Case Report

No abstract available.

Intermittent Fasting in Diabetic Patients / 임상당뇨병

Obesity is becoming increasingly prevalent worldwide. It is linked to health problems including cardiovascular disease, diabetes, cancer, musculoskeletal problems and even psychiatric problems. Intermittent fasting is an interventional strategy wherein individuals are subjected to varying periods of fasting. Intermittent fasting has recently attracted attention because experimental studies have highlighted its potential for correcting metabolic abnormalities. Preliminary findings indicate that intermittent fasting may be associated with increased lifespan, decreased mortality from cancers and cardiovascular diseases, improved insulin sensitivity, and reduced oxidative stress and inflammation. However, some of the data still remain controversial. No human studies have examined the effects of intermittent fasting in diabetics. Studies examining intermittent fasting in diabetic patients have encountered problems with compliance, malnutrition, and hypoglycemia rather than seeing benefits of weight loss. Regular meals (at least three meals each day) and a balanced diet are crucial in the management of blood sugar levels in diabetic patients.

Associations among Body Mass Index, Insulin Resistance, and Pancreatic beta-Cell Function in Korean Patients with New-Onset Type 2 Diabetes

BACKGROUND/AIMS: We investigated the associations among body mass index (BMI), insulin resistance, and beta-cell function in Korean patients newly presenting with type 2 diabetes. METHODS: In total, 132 patients with new-onset type 2 diabetes mellitus were investigated. A standard 75-g oral glucose tolerance test was performed, and the indices of insulin secretion and insulin resistance were calculated. RESULTS: A higher BMI was associated with higher homeostasis model assessment values for insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function (HOMA-beta), and insulinogenic index as well as lower levels of insulin sensitivity index composite (ISIcomp) and disposition index (DI). In multiple regression models, BMI had independent positive associations with HOMA-IR, ISIcomp, and HOMA-beta and inverse associations with the DI. CONCLUSIONS: Our results showed that BMI had independent positive associations with indices of insulin resistance and an inverse association with beta-cell function adjusted for insulin resistance in Korean patients newly presenting with type 2 diabetes.

Blood Sugar Control in Alcohol-Consuming Diabetics / 임상당뇨병

Alcohol influences glucose metabolism in both diabetic and non-diabetic individuals. Moderate alcohol consumption significantly decreases fasting glucose levels, but does not affect postprandial glucose levels. However, acute alcohol intake without food may provoke hypoglycemia. Moderate alcohol consumption may inhibit gluconeogenesis and enhance insulin sensitivity, but excessive alcohol intake (three or more drinks per day) may contribute to hyperglycemia. Daily alcohol intake in diabetics should be limited to a moderate amount (one drink per day or less for women and two drinks per day or less for men). Moderate alcohol intake may have cardiovascular benefits for patients with diabetes, but the trade-off between the cardiovascular benefits versus the potential risk of lower adherence associated with self-care behaviors should be considered.

Response: Increased Carotid Intima-Media Thickness Is Associated with Progression of Diabetic Nephropathy in Patients with Type 2 Diabetes

No abstract available.

Associations between Hemoglobin Concentrations and the Clinical Characteristics of Patients with Type 2 Diabetes

BACKGROUND/AIMS: Many studies have demonstrated an association between hemoglobin levels and cardiovascular disease in diabetic patients. The aim of this study was to determine whether there is an association between hemoglobin concentrations and various clinical parameters, including metabolic factors, plasma C-peptide response after a meal tolerance test, and microvascular complications, in Korean patients with type 2 diabetes. METHODS: In total, 337 male patients with type 2 diabetes were recruited. All subjects were subjected to a meal tolerance test and underwent assessment of hemoglobin levels, fasting and postprandial beta-cell responsiveness, and microvascular complications. RESULTS: Patients with lower hemoglobin concentrations had a longer duration of diabetes, a lower body mass index, and lower concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. They also had lower levels of postprandial C-peptide, Delta C-peptide, and postprandial beta-cell responsiveness. They had a higher prevalence of retinopathy and nephropathy. In multivariate analyses, there was a significant association between nephropathy and hemoglobin concentration. Also, hemoglobin concentrations were independently associated with Delta C-peptide levels and postprandial beta-cell responsiveness. CONCLUSIONS: Hemoglobin concentrations are associated with postprandial C-peptide responses and diabetic nephropathy in patients with type 2 diabetes.

Association between Diabetic Polyneuropathy and Cardiovascular Complications in Type 2 Diabetic Patients

BACKGROUND: Diabetes mellitus is a major independent risk factor for cardiovascular disease (CVD), but high cardiovascular risk in diabetes mellitus patients is not completely explained by clustering traditional risk factors. Recently, associations between diabetic polyneuropathy (DPN) and macrovasculopathy have been suggested. We aimed to assess associations between DPN and cardiovascular complications in type 2 diabetic patients. METHODS: Microvascular and cardiovascular complications were evaluated in 1,041 type 2 diabetic patients. RESULTS: In patients with DPN, the age, prevalence of hypertension, diabetes duration, systolic blood pressure, pulse pressure, and hemoglobin glycation (HbA1c) levels were significantly higher, while the high density lipoprotein cholesterol (HDL-C) levels were lower than in those without DPN. The prevalence of CVD was higher in patients with DPN. In multivariate analysis, DPN was independently associated with CVD (odds ratio, 1.801; 95% confidence interval, 1.009 to 3.214). CONCLUSION: Our results showed that DPN was associated with a high prevalence of cardiovascular disease in type 2 diabetic patients, but further studies are needed to investigate the causative nature of associations between DPN and CVD.

The Association between Albuminuria and Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus / 대한내과학회지

BACKGROUND/AIMS: Albuminuria is an early indicator of renal damage in type 2 diabetes mellitus, and has been recognized as a risk factor for peripheral arterial disease (PAD). The aim of this study was to assess the association between albuminuria and PAD in Korean type 2 diabetes patients. METHODS: Our retrospective study included 390 consecutive patients with type 2 diabetes mellitus. The ankle-brachial index (ABI) and toe-brachial index (TBI) were used to assess PAD. The urinary albumin-creatinine excretion ratio (UAE) was evaluated by determining the albumin/creatinine ratio (ACR) in the first voided morning urine sample. RESULTS: Duration of diabetes, serum creatinine levels, and UAE were significantly higher in patients with low ABI scores ( or = 0.9). Age, duration of diabetes, and UAE were significantly higher in patients with low TBI scores ( or = 0.6). Albuminuria was independently associated with low ABI (OR = 1.980, 95% CI = 1.001-3.918). It was also independently associated with low TBI and normal ABI (OR = 3.149, 95% CI = 1.260-7.871). CONCLUSIONS: The results of this study suggest that albuminuria may be associated with PAD, including in arteries distal to the ankle joint.