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

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

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

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: 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

Primary aldosteronism is due to either a unilateral adrenal adenoma or bilateral hyperplasia of the adrenal cortex in most cases. A unilateral adrenalectomy in hypertensive and hypokalemic patients, with a well-documented adrenal adenoma, is usually followed by the correction of hypokalemia in all subjects, with the cure of hypertension in 60 to 87% of patients. Here, a unique case, in which a unilateral adrenalectomy for the removal of an adrenal adenoma was followed by severe hyperkalemia, low levels of plasma renin activity and serum aldosterone, suggestive of chronic suppression of the renin-aldosterone axis, is reported. In a follow-up Lasix stimulation test on the 70th day after surgery, the suppression of the renin-aldosterone axis was resolved, indicating the suppression was transient. Patients undergoing a unilateral adrenalectomy for an aldosterone-producing adenoma should be closely followed up to avoid severe hyperkalemia.
Adenoma* ; Adrenal Cortex ; Adrenalectomy ; Aldosterone ; Axis, Cervical Vertebra ; Follow-Up Studies ; Furosemide ; Humans ; Hyperaldosteronism ; Hyperkalemia ; Hyperplasia ; Hypertension ; Hypoaldosteronism* ; Hypokalemia ; Plasma ; Renin

Celiac disease is an intestinal autoimmune disorder, triggered by ingestion of a gluten-containing diet in genetically susceptible individuals. The genetic predisposition is related to human leukocyte antigen (HLA) class II genes, especially HLA-DQ2-positive patients. The prevalence of celiac disease has been estimated to be ~1% in Europe and the USA, but it is rarer and/or underdiagnosed in Asia. We report a case of celiac disease in a predisposed patient, with a HLA-DQ2 heterodimer, and Graves' disease that was treated successfully with a gluten-free diet. A 47-year-old woman complained of persistent chronic diarrhea and weight loss over a 9 month period. Results of all serological tests and stool exams were negative. However, the patient was found to carry the HLA DQ2 heterodimer. Symptoms improved after a gluten-free diet was initiated. The patient has been followed and has suffered no recurrence of symptoms while on the gluten-free diet. An overall diagnosis of celiac disease was made in a genetically predisposed patient (HLA-DQ2 heterodimer) with Graves' disease.
Asia ; Celiac Disease* ; Diagnosis ; Diarrhea ; Diet ; Diet, Gluten-Free ; Eating ; Europe ; Female ; Genes, MHC Class II ; Genetic Predisposition to Disease ; Graves Disease* ; Humans ; Leukocytes ; Middle Aged ; Prevalence ; Recurrence ; Serologic Tests ; Weight Loss

BACKGROUND: Recently, a hemoglobin A1c (HbA1c) level of 6.5% has been determined to be a criterion for diabetes mellitus (DM), and it is a widely used marker for the diagnosis of DM. However, HbA1c may be influenced by a number of factors. Anemia is one of the most prevalent diseases with an influence on HbA1c; however, its effect on HbA1c varies based on the variable pathophysiology of anemia. The aim of this study was to determine the effect of anemia on HbA1c levels. METHODS: Anemic subjects (n=112) and age- and sex-matched controls (n=217) who were drug naive and suspected of having DM were enrolled. The subjects underwent an oral glucose tolerance test and HbA1c simultaneously. We compared mean HbA1c and its sensitivity and specificity for diagnosing DM between each subgroup. RESULTS: Clinical characteristics were found to be similar between each subgroup. Also, when glucose levels were within the normal range, the difference in mean HbA1c was not significant (P=0.580). However, when plasma glucose levels were above the diagnostic cutoff for prediabetes and DM, the mean HbA1c of the anemic subgroup was modestly higher than in the nonanemic group. The specificity of HbA1c for diagnosis of DM was significantly lower in the anemic subgroup (P<0.05). CONCLUSION: These results suggest that the diagnostic significance of HbA1c might be limited in anemic patients.
Anemia ; Blood Glucose ; Diabetes Mellitus* ; Glucose Tolerance Test ; Hemoglobin A, Glycosylated* ; Humans ; Prediabetic State ; Reference Values ; Sensitivity and Specificity