New therapeutics for type 2 diabetes using incretin hormone were introduced recently. Incretin-based therapies consist of two types: GLP-1 agonists mainly acting on the GLP-1 receptor and dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors). The former is resistant to DPP-4 and injectable. The latter is oral medications raising endogenous GLP-1 by inhibiting the degrading enzyme DPP-4. The incretin based therapies are promising and more commonly used due to their action and safety profile. Stimulation of insulin secretion by these drugs occurs in a glucose-dependent manner. Incretin based therapies have low risk for hypoglycemia. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and vildagliptin.
Adamantane ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Hypoglycemia ; Incretins ; Insulin ; Nitriles ; Peptides ; Pyrazines ; Pyrrolidines ; Receptors, Glucagon ; Triazoles ; Venoms ; Glucagon-Like Peptide-1 Receptor ; Liraglutide ; Sitagliptin Phosphate

The incretin hormones glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have recently received much attention for their roles in type 2 diabetes therapy. GLP-1 stimulated insulin secretion in a glucose-dependent manner and is secreted by intestinal L cells. It also regulates blood glucose concentration, stomach motility, appetite, and body weight. These actions are mediated through G-protein-coupled receptors highly expressed on pancreatic beta cells and also exert indirect metabolic actions. Activation of GLP-1 receptors also produces nonglycemic effects in various tissues. The pleiotropic effects of GLP-1 have been recently reported. The mechanisms identified in preclinical studies have potential translational relevance for the treatment of disease. Here, the nonglycemic effects of GLP-1, especially those on the liver, central nervous system, and bone, were reviewed.
Appetite ; Blood Glucose ; Body Weight ; Central Nervous System ; Enteroendocrine Cells ; Glucagon ; Glucagon-Like Peptide 1 ; Incretins ; Insulin ; Insulin-Secreting Cells ; Liver ; Receptors, G-Protein-Coupled ; Stomach

BACKGROUND/AIMS: Based on the results of well designed clinical studies, intensive insulin therapy has been established to improve glycemic control in newly diagnosed diabetes. However, discrepancies exist between the findings of clinical trials and experiences in general practice. Furthermore, the efficacy of an early insulin therapy (EIT) - commonly used in general practice - on long-term glycemic control has not been established. Therefore, we evaluated the effects of EIT on pancreatic beta-cell function and glycemic control using insulin-based methods widely employed in general practice. METHODS: We performed a retrospective cohort study that initially involved reviewing patients' medical records. Following a thorough review, 61 patients who received either biphasic or prandial EIT at the time of diagnosis were enrolled. We then evaluated changes in beta-cell function and glycemic control during a 48-month follow-up period. RESULTS: Mean HbA1c decreased significantly as a result of EIT from 10.7 +/- 1.8% to 6.2 +/- 1.1% (p < 0.001). On average, 2.6 months was required to achieve an HbA1c value < 7%. EIT significantly improved the insulinogenic index. Glycemic control was well maintained for 48 months. More than 70% of patients were able to maintain glycemic control following lifestyle modifications or treatment with oral antidiabetic drugs. No significant differences were identified between patients receiving biphasic EIT and prandial EIT in terms of glycemic control or pancreatic beta-cell function. CONCLUSIONS: Our results suggest that regardless of the method of delivery, EIT significantly improves beta-cell function and facilitates long-term glycemic control in patients with newly diagnosed type 2 diabetes mellitus.
Administration, Oral ; Adult ; Blood Glucose/metabolism ; Cohort Studies ; Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/*physiopathology ; Female ; Hemoglobin A, Glycosylated/metabolism ; Humans ; Hypoglycemic Agents/administration & dosage ; Insulin/administration & dosage/*therapeutic use ; Insulin Resistance ; Insulin-Secreting Cells/*drug effects/*physiology ; Male ; Middle Aged ; Retrospective Studies

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.
Appetite ; Asian Continental Ancestry Group ; Body Mass Index ; Compliance ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide 1* ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Hypoglycemia ; Korea ; Obesity ; Overweight ; Postprandial Period ; Prevalence ; Weight Loss ; Glucagon-Like Peptide-1 Receptor

The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (DeltaGH(IO)), and between the OGTT and the OST at the same time point (DeltaGH(OS)) were compared according to the size of the tumor and the response pattern to the OST. DeltaGH(IO) of macroadenomas (n=22) was non-significantly higher than those of microadenomas while DeltaGH(OS) of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. DeltaGH(OS) showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.
Acromegaly/*diagnosis/*pathology ; Adenoma/drug therapy/*pathology ; Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Female ; Glucose Tolerance Test ; Human Growth Hormone/*blood/secretion ; Humans ; Insulin/blood ; Insulin-Like Growth Factor I/analysis ; Male ; Middle Aged ; Octreotide/therapeutic use ; Pituitary Neoplasms/drug therapy/*pathology

BACKGROUND/AIMS: Due to recent increases in the disease burden of diabetes mellitus, the Health Insurance Review and Assessment Service (HIRA) of Korea implemented a quality assessment of the treatment of diabetes to improve patient care. The present study was conducted to identify any changes after the implementation of the diabetes quality assessment (DQA). METHODS: The present study evaluated eight quality assessment indicators that were proposed by the HIRA in all patients with diabetes who visited a university hospital in Korea between 2009 and 2014. The indicators were statistically compared according to the characteristics of the subjects. RESULTS: There were several significant differences in the indicators among the subjects according to their demographic characteristics. Female patients had a higher continuity of treatment (COT) than that of male patients, and the insulin-treated group had a higher COT than that of the non-treated group, as well as a higher rate of undergoing the diabetes complication tests (DCTs). Patients between 40 and 80 years of age had the highest COT, while patients under 40 years of age had the lowest COT but the highest rate of taking the DCTs. Patients receiving treatment from an endocrinologist exhibited higher numbers of DCTs performed but displayed lower proportions for the prescription indicators. CONCLUSIONS: The present analysis of the DQA findings revealed that endocrinologists combine prevention and management of diabetes complications with measures for glycemic control. Thus, the effective management of diabetes likely entails systematic joint treatment regimens that involve an endocrinologist.
Diabetes Complications ; Diabetes Mellitus ; Endocrinology ; Female ; Humans ; Insurance, Health ; Joints ; Korea* ; Male ; Patient Care ; Prescriptions ; Quality Improvement ; Quality of Health Care

BACKGROUND: Fibrous dysplasia of the bone(FD) is a benign fibrous bone lesion which usually involves the long bones of the extremities. FD may be asymptomatic, but often leads to bone deformity and pathological fracture. The disease is caused by a somatic mutation in the Gsalpha protein, which is responsible for intracellular signal transduction. METHODS: Mutations in the GNAS1 gene, which codes for Gsalpha protein, was investigated in 34 patients with monostotic and polyostotic FD and McCune-Albright syndrome. DNA was extracted from formalin-fixed, paraffin embedded bone tissues, and exons 8 and 9 of the GNAS1 gene amplified using a polymerase chain reaction(PCR). Subsequently, plasmid cloning and DNA sequencing analysis were performed. RESULTS: The PCR was successfully performed in 5 patients with monostotic FD. However, the sequencing analysis failed to identify any significant point mutations in exons 8 or 9 of GNAS1. Nevertheless, 3 point mutations were observed in the intron of the GNAS1 gene in 2 samples. CONCLUSION: In addition to the previously known somatic mutations of the GNAS1 gene, this study suggests that fibrous dysplasia of the bone might be associated with another point mutations of the GNAS1 gene
Bone and Bones ; Clone Cells ; Cloning, Organism ; Congenital Abnormalities ; DNA ; Exons ; Extremities ; Fibrous Dysplasia, Polyostotic ; Fractures, Spontaneous ; GTP-Binding Protein alpha Subunits ; Humans ; Introns ; Paraffin ; Plasmids ; Point Mutation ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Signal Transduction

Thyrotoxic periodic paralysis (TPP) occurs in 2% of the asian patients with hyperthyroidism and is characterized by bilateral flaccid paralysis of the extremity, especially lower limbs. It is well-known that hypokalemia is usually accompanied by TPP. However, hypophosphatemia is usually mild and well neglected. Although paralysis is generally recovered without treatment, in some cases, patients with TPP may die due to cardiopulmonary complications, such as cardiac arrhythmia. Therefore, proper and rapid replacement of potassium is essential. But it should be acknowledged that replacement may cause a rebound. TPP is often unrecognized and over-treated in the emergency room due to its non-specific symptoms. This is why clinicians must be familiar with this disease and its diagnostic clues such as Echocardiography change and clinical features. This is a case report of a 29-year-old male presenting with TPP accompanied by hypokalemia, hypophosphatemia and second degree atrioventricular block, who showed rebound hyperkalemia and hyperphosphatemia after rapid replacement of electrolytes. EKG changed to the normal sinus rhythm in the end after the correction of the electrolytes.
Adult ; Arrhythmias, Cardiac ; Asian Continental Ancestry Group ; Atrioventricular Block ; Echocardiography ; Electrocardiography ; Electrolytes ; Emergencies ; Extremities ; Humans ; Hyperkalemia ; Hyperphosphatemia ; Hyperthyroidism ; Hypokalemia ; Hypophosphatemia ; Lower Extremity ; Male ; Paralysis ; Potassium

BACKGROUND: The Diabcare-Asia study was designed for the purpose of describing diabetes control and management, and late complication status in the diabetic population. METHODS: From the 1st of July 2001 to the 1st of September 2001, data from 1170 diabetic patients were collected in 21 centers (one university hospital and 20 clinics located in Seoul and in Gyeonggi, Korea), and blood samples were collected for centralized HbA1c measurements. RESULTS: Only 16.8% of patients at the clinics reported self-monitoring their blood glucose. The mean HbA1c was 7.3 +/- 1.4% at the hospital and 7.5 +/- 1.5% at the clinics, and the mean fasting plasma glucose (FPG) levels were 7.0 +/- 3.3 mmol/L at the hospital and 7.9 +/- 2.5 mmol/L at the clinics. About 40% of patients had a HbA1c and FPG above the normal upper limits. Screening for microalbuminuria was rarely performed. The available data represents only about 0.9% of the patients at the hospital and 12.3% of the patients at the clinics. Nephropathy (serum creatinine > 2 mg/dL) was found in 0.8% of the patients at the hospital and in 3.4% of the patients at the clinics. Retinopathy and neuropathy were commonly reported diabetic complications. The prevalence of other severe late complications was relatively low. CONCLUSION: The data revealed suboptimal glycemic control in about 40% of patients.
Diabetes Complications/epidemiology/*prevention & control ; Diabetes Mellitus/*epidemiology ; Disease Management ; Female ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Program Evaluation ; Research Support, Non-U.S. Gov't

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor.
Acromegaly* ; Adenoma ; Carcinoid Tumor* ; Colonoscopy ; Female ; Growth Hormone ; Headache ; Humans ; Hyperprolactinemia ; Middle Aged ; Neurologic Manifestations ; Pituitary Neoplasms* ; Polyps ; Prolactin ; Thyrotropin