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Determine whether the twice daily (BID) regimen is superior to the once daily (QD) regimen for managing glycemic variability by comparing the effects of anagliptin 100 mg BID versus sitagliptin 100 mg QD.A double-blinded, randomized, multicenter study was performed in 89 patients with type 2 diabetes treated with metformin alone (6.5%HbA1c 8.5%). Subjects were randomly assigned to anagliptin 100 mg BID or sitagliptin 100 mg QD in a 1:1 ratio for 12 weeks. Continuous glucose monitoring (CGM) was used to measure the mean amplitude of glycemic excursion (MAGE) and postprandial time in range (TIR) before and after DPP-4 inhibitor treatment to compare glycemic variability.The decrease from baseline in MAGE at 12 weeks after DPP-4 inhibitor treatment was significantly greater in the anagliptin BID group than in the sitagliptin QD group (p0.05); -30.4 ± 25.6 mg/dL (p0.001) in the anagliptin group versus -9.5 ± 38.0 mg/dL (p=0.215) in the sitagliptin group. The TIR after dinner increased by 33.0 ± 22.0% (p0.001) in the anagliptin group and by 14.6 ± 28.2% (p=0.014) in the sitagliptin group, with a statistically significant difference (p=0.009). No statistically significant differences were observed between the groups in the changes in HbA1c and fasting plasma glucose (FPG).The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycemic variability, as indicated by MAGE and TIR but equivalent to the QD regimen in terms of HbA1c and FPG. This article is protected by copyright. All rights reserved.

This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients.This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores.A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval -0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (-0.78; Pnoninferiority0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred.The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.

Background: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naive newly-diagnosed type 2 diabetes mellitus. Methods: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was mea sured at week 24. Results: The reduction in the levels of HbA1c was -1.62%±0.07% in the vogmet group and -1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of

We assessed the 24‐week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were −0.94% [least‐squares (LS) mean −1.22, −0.65] and −1.21 mmol/l (−1.72, −0.70), respectively (all p

Objective We evaluated the association of glucose control with changes in arterial stiffness, inflammatory markers, and oxidative stress markers. Methods Sixty-four patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA1c] ≥ 9%) and hypertension were enrolled in this study. The patients were divided into two groups based on their post-treatment HbA1c level: HbA1c ≤ 7% (well-controlled group, n = 28) and HbA1c > 7% (uncontrolled group, n = 36). The pulse wave velocity, augmentation index, and markers of inflammation and oxidative stress were measured and analyzed. Results The patients’ mean baseline HbA1c level was 11.7%. There were no differences in any baseline parameters between the two groups except the duration of diabetes. The mean HbA1c level was significantly lower at 12 weeks in the well-controlled than uncontrolled group (6.1% vs. 9.0%, respectively), but there were no significant differences in the pulse wave velocity (0.33 ± 0.95 vs. 0.36 ± 1.44 m/s), aortic augmentation index (5.1 ± 8.3 vs. 0.7 ± 11.6), or markers of inflammation and oxidative stress. Conclusions Short-term glycemic control did not influence the arterial stiffness in patients with type 2 diabetes mellitus and hypertension.

BACKGROUND The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs). METHODS The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial. RESULTS Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P

BACKGROUND The prevalence of hypoglycemia is increasing due to the growing incidence of diabetes and the latest strict guidelines for glycated hemoglobin (HbA1c) levels under 7%. This study examined the clinical characteristics, causal factors, and medical costs of severely hypoglycemic patients in an emergency room (ER) of Uijeongbu St. Mary's Hospital. METHODS The study consisted of a retrospective analysis of the characteristics, risk factors, and medical costs of 320 severely hypoglycemic patients with diabetes who presented to an ER of Uijeongbu St. Mary's Hospital from January 1, 2006 to December 31, 2009. RESULTS Most hypoglycemic patients (87.5%, 280/320) were over 60 years old with a mean age of 69.5±10.9 years and a mean HbA1c level of 6.95±1.46%. Mean serum glucose as noted in the ER was 37.9±34.5 mg/dL. Renal function was decreased, serum creatinine was 2.0±2.1 mg/dL and estimated glomerular filtration rate (eGFR) was 48.0±33.6 mL/min/1.73 m(2). In addition, hypoglycemic patients typically were taking sulfonylureas or insulin and a variety of other medications, and had a long history of diabetes. CONCLUSION Severe hypoglycemia is frequent in older diabetic patients, subjects with low HbA1c levels, and nephropathic patients. Therefore, personalized attention is warranted, especially in long-term diabetics with multiple comorbidities who may not have been properly educated or may need re-education for hypoglycemia.

Diabet. Med. 29, e121–e125 (2012) Abstract Aims The influence of hyperglycaemia on the performance of glomerular filtration rate (GFR) estimating equations remains to be determined. We compared the performance of creatinine-based GFR with cystatin C-based GFR in patients with Type 2 diabetes according to glycaemic status. Methods In a cross-sectional study of 210 patients with Type 2 diabetes, we staged glycaemic status by HbA1c tertiles [HbA1c≤ 75 mmol/mol (9.0%) (n = 70), HbA1c 76–95 mmol/mol (9.1–10.8%) (n = 70), HbA1c >95 mmol/mol (10.8%) (n = 70)] and measured GFR. Isotopic GFR was measured using renal dynamic imaging with 99mTc-diethylene-triamine-penta-acetic acid. Estimated GFR (eGFR) was measured using creatinine-based formulae (Cockcroft–Gault-eGFR, the Modification of Diet in Renal Disease equation-eGFR and the Chronic Kidney Disease Epidemiology Collaboration formula-eGFR) and a cystatin C-based formula (cystatin C-eGFR). Results The isotopic GFR of all patients was 93.1 ± 34.1 ml min−1 1.73 m−2. All methods for estimating GFR underestimated isotopic GFR [Cockcroft–Gault-eGFR (68.8 ± 38.6 ml min−1 1.73 m−2) (P 95 mmol/mol (10.8%) where there was no difference between cystatin C-eGFR and isotopic GFR. Conclusions Performance of cystatin C-eGFR was superior to creatinine-based GFR in patients with Type 2 diabetes with HbA1c > 95 mmol/mol (10.8%).

Summary Objective Patients with type 2 diabetes mellitus are at greater risk of bone fractures than nondiabetics. However, the risk factors for fractures in patients with diabetes have not been fully evaluated. This study was designed to evaluate the relative frequency of fractures at different sites and the diabetes-associated factors that affect nontraumatic bone fracture in patients with type 2 diabetes. Patients and design This retrospective case–control study recruited 144 patients with type 2 diabetes, who presented with nontraumatic fractures between March 2004 and March 2009 and 150 age-, gender-, body mass index (BMI)- and duration of diabetes-matched control subjects. Nontraumatic fractures were confirmed using patients’ medical records and radiological findings. All subjects were examined for their diabetes status and associated factors for fracture, including bone mineral density (BMD). Results Of 150 reported bone fractures, the hip was the most frequent fracture site (32·7%), followed by the upper extremity (19·3%). Nontraumatic fractures were associated with diabetic retinopathy, diabetic peripheral neuropathy, stroke history, previous fracture and insulin treatment (P

Background: The First Basal Insulin Evaluation (FINE) Asia study is a multinational, prospective, observational study of insulin-naive Type 2 diabetes mellitus (T2DM) patients in Asia, uncontrolled (A1c ≥ 8%) on oral hypoglycemic agents, designed to evaluate the impact of basal insulin initiation. Methods: Basal insulin was initiated with or without concomitant oral therapy and doses were adjusted individually. All treatment choices, including the decision to initiate insulin, were at the physician’s discretion to reflect real-life practice. Results: Patients (n = 2679) from 11 Asian countries were enrolled (mean [±SD] duration of diabetes 9.3 ± 6.5 years; weight 68.1 ± 12.7 kg; A1c 9.8 ± 1.6%). After 6 months of basal insulin (NPH insulin, insulin glargine, or insulin detemir), A1c decreased to 7.7 ± 1.4%; 33.7% patients reached A1c

Background: Hypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. This study analyzed the changes in central aortic waveforms and pulse wave velocity as well as related parameters after treatment with valsartan, an angiotensin II type 1 receptor blocker, in patients with type 2 diabetes and hypertension. Methods: We used pulse wave analysis to measure central aortic waveform in a total of 98 subjects. In 47 of these patients, pulse wave velocity measurements were obtained before and after 12 weeks of treatment with valsartan. Results: In the central aortic waveform analysis, the aortic pulse pressure and augmentation index were significantly decreased after valsartan treatment, as was the aortic pulse wave velocity. Factors contributing to the improvement in pulse wave velocity were the fasting blood glucose and haemoglobin A1c levels. Conclusion: Short-term treatment with valsartan improves arterial stiffness in patients with type 2 diabetes and hypertension, and the glucose status at baseline was associated with this effect.

Bone morphogenetic protein 4 (BMP-4) is involved in the earliest stages of adipocyte differentiation and is recognized as an adipogenic factor for white adipose tissue. The association of serum BMP-4 levels with anthropometric and metabolic parameters has not been previously studied. We aimed to explore the relationship of serum BMP-4 levels with obesity and metabolic syndrome. Serum BMP-4 levels were measured in 104 non-diabetic individuals from the Chungju Metabolic Disease Cohort Study. Anthropometric measurements and components of metabolic syndrome were assessed in all patients. Serum BMP-4 levels were significantly increased in individuals with obesity or metabolic syndrome. After adjusting for age and gender, serum BMP-4 levels were positively correlated with body mass index, waist circumference (WC), waist-to-hip ratio, fasting plasma insulin, homeostasis model assessment index, and triglycerides and were negatively correlated with high-density lipoprotein (HDL) cholesterol. Among these parameters, WC and HDL cholesterol were found to be independent contributing factors for serum BMP-4 levels. Serum BMP-4 levels were also significantly higher in subjects with positive diagnostic criteria for each component of metabolic syndrome. The area under the receiver operating characteristic curve for BMP-4 was 0.661 (P = 0.022, 95% CI = 0.528 to 0.794) and the cut-off value was 2.84 pg/mL. This is the first demonstration that serum BMP-4 levels are associated with adiposity, insulin resistance, and the presence of metabolic syndrome. Whether BMP-4 may be involved in the pathogenesis of obesity and metabolic syndrome deserves further investigation.

A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors.

OBJECTIVE—To investigate the long-term effectiveness of the Internet-based glucose monitoring system (IBGMS) on glucose control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—We conducted a prospective, randomized, controlled trial in 80 patients with type 2 diabetes for 30 months. The intervention group was treated with the IBGMS, while the control group made conventional office visits only. HbA1c (A1C) was performed at 3-month intervals. For measuring of the stability of glucose control, the SD value of A1C levels for each subject was used as the A1C fluctuation index (HFI). RESULTS—The mean A1C and HFI were significantly lower in the intervention group (n = 40) than in the control group (n = 40). (A1C [mean ± SD] 6.9 ± 0.9 vs. 7.5 ± 1.0%, P = 0.009; HFI 0.47 ± 0.23 vs. 0.78 ± 0.51, P = 0.001; intervention versus control groups, respectively). Patients in the intervention group with a basal A1C ≥7% (n = 27) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study (P = 0.022). Control patients with a basal A1C CONCLUSIONS—Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability.

OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS—We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels ≤30 mg/dl (n = 40) and group 2 had Lp(a) levels >30 mg/dl (n = 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value. RESULTS—At baseline and during the follow-up, there was no difference in HbA1c and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 ± 78.0 vs. 108.1 ± 34.9 μmol/l, P = 0.004) and after 2 years (216.9 ± 144.5 vs. 131.3 ± 47.3 μmol/l, P = 0.001), although baseline serum creatinine did not differ significantly between groups. In all, 13 of 14 patients with progression of diabetic nephropathy (progressors) were from group 2. Baseline Lp(a) levels were higher in the progressors than in the nonprogressors (62.9 ± 26.7 vs. 33.5 ± 27.5 mg/dl, P < 0.001). Multiple logistic regression showed that baseline Lp(a) level was a significant and independent predictor of the progression of diabetic nephropathy. CONCLUSIONS—Our study demonstrated that Lp(a) is an independent risk factor for the progression of diabetic nephropathy in type 2 diabetic patients with overt proteinuria.

Pancreatic duct cells are considered to be a major source for beta-cell regeneration or neogenesis. Although epidermal growth factor (EGF) is a well-known important growth factor for pancreas development, the control of pancreatic duct cell growth and differentiation by EGF is poorly understood. In this study, we focused on identifying the genes that were differentially up-regulated in response to EGF stimulation using monolayer cultured porcine neonatal pancreas cells. Cells were obtained from 1 to 3 day old pigs, dispersed and cultured for 8 days. Monolayer cultured porcine pancreas cells were comprised of duct cells and some endocrine and mesenchymal cells (75.2 +/- 15.1, 19.6 +/- 4.9, and 9.5 +/- 3.1%, respectively). After 16 h in serum free media, cells were treated with 100 microg/L EGF for 24 h. Differentially expressed genes were screened by subtractive hybridization. (3)H-thymidine uptake was significantly increased by EGF with time (untreated vs. 24 h treated, untreated vs. 48 h treated: 305.5 +/- 3.5 cpm vs. 380.3 +/- 17.3 cpm (P < 0.05), 309.2 +/- 4.51 vs. 929 +/- 9.19 cpm, (P < 0.005), respectively). Three hundred and fifty cDNA clones were obtained by subtractive hybridization and the inserts were confirmed in 161 colonies and then sequenced. Finally, we found increased mRNA expression of five unknown and five known genes, including cytochrome c oxidase subunit I (COI), cyclooxygenase-2 (COX-2), matrix metalloproteinase-13 (MMP-13), Wiskott-Aldrich syndrome protein interacting protein (WASPIP), and hyaluronan synthase-2 (HAS-2). We confirmed the up-regulation of these genes by Northern blot and semi-quantitative RT-PCR at various time points. The present findings opened new targets for the research on the mechanisms of pancreatic duct cell proliferation by EGF.

There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future.

We thank Byung-Wan Lee for his thoughtful and insightful comments on our study regarding "Efficacy and safety of biphasic insulin aspart 30/70 in type 2 diabetes suboptimally controlled on oral antidiabetic therapy" [1]. To the first point, there have been many guidelines regarding insulin initiation in type 2 diabetic patients. Therefore, various options are available, including the types of insulin to be chosen, the starting dose, and the ratio of prebreakfast to predinner insulin. At the time of the study design and initiation, dividing the premixed insulin dose with the ratio of 2:1 was usual clinical practice in Korea, which was adopted in our study. Regarding the time of single insulin injection in the morning, we wanted to avoid nocturnal hypoglycemia to enhance the adherence to insulin therapy. Second, as we mentioned in our article, oral antidiabetic drug (OAD) treatment should be combined with insulin, even after conversion to insulin treatment, as OAD(s) plays an important role in blood glucose control. Metformin can be used at full dose in concert with insulin, but it is uncertain whether sulfonylurea should be maintained with insulin therapy or decreased. Recent American Diabetes Association/European Association for the Study of Diabetes guideline showed some tips on combination use of insulin and OAD(s). It is recommended that insulin secretagogues be avoided once prandial insulin regimens are employed, and thiazolidinedions be reduced in dose (or stopped) to avoid edema and excessive weight gain [2,3]. Third, the major side effect of insulin therapy is weight gain. The disparity in weight gain between our study and Jang's study may be arise from study population (mean age of 57 years vs. over 65), study design (prospective vs. retrospective) and discontinuation of metformin in our study [1,4]. Finally, insulin therapy in Korean may not be different from other ethnic groups. When we use premixed insulin once or twice and cannot achieve target goals, further actions should be taken to control postlunch blood sugar, such as combining OAD(s) and/or adding prelunch insulin injection.

The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital disorder characterized by aplasia of the uterus and the upper part of the vagina in an XX individual with normal development of secondary sexual characteristics. Individuals with this syndrome may also present with renal and skeletal abnormalities. We report a case of a 16-year-old girl presenting with thyrotoxicosis and primary amenorrhea. After being diagnosed with Graves disease, this patient was placed on antithyroid medication. Although her thyroid function normalized, she did not start to menstruate. Therefore, we assessed her primary amenorrhea and diagnosed the patient with MRKH syndrome through pelvic imaging. To our knowledge, an association between Graves disease and MRKH syndrome has not yet been reported.

Patients with type 2 diabetes mellitus are at greater risk of bone fractures than nondiabetics. However, the risk factors for fractures in patients with diabetes have not been fully evaluated. This study was designed to evaluate the relative frequency of fractures at different sites and the diabetes-associated factors that affect nontraumatic bone fracture in patients with type 2 diabetes.This retrospective case-control study recruited 144 patients with type 2 diabetes, who presented with nontraumatic fractures between March 2004 and March 2009 and 150 age-, gender-, body mass index (BMI)- and duration of diabetes-matched control subjects. Nontraumatic fractures were confirmed using patients' medical records and radiological findings. All subjects were examined for their diabetes status and associated factors for fracture, including bone mineral density (BMD).Of 150 reported bone fractures, the hip was the most frequent fracture site (32·7%), followed by the upper extremity (19·3%). Nontraumatic fractures were associated with diabetic retinopathy, diabetic peripheral neuropathy, stroke history, previous fracture and insulin treatment (P0·05). In multivariate analyses, independently associated factors for bone fracture were diabetic peripheral neuropathy [odds ratio (OR) = 37·3, 95% confidence interval (CI) = 1·46-652·57] and previous fracture (OR = 9·54, 95% CI = 1·18-77·37; P0·05).The hip was the most frequent site of nontraumatic fracture, and diabetic peripheral neuropathy was significantly associated with an increased risk of nontraumatic fractures in patients with type 2 diabetes.

To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] and arterial stiffness in patients with type 2 diabetes.Serum 25(OH)D was measured in a cross-sectional sample of 131 men and 174 women aged 30 years and over in Korea. Arterial stiffness was assessed by pulse wave velocity (PWV) obtained with a VP-2000 pulse wave unit. Fasting plasma glucose, insulin, lipid profile, HbA1c, calcium, phosphorous, and HS-CRP were measured.The prevalence of vitamin D deficiency was high (85.9%). Those with lower vitamin D levels had increased PWV. Using multivariate regression analysis, low 25(OH)D concentrations independently predicted PWV (p0.001) in people with type 2 diabetes after adjustment for other risk factors such as age, smoking, hypertension, HS-CRP, diabetes duration, hypertension duration, HbA1c, and BMI.Vitamin D deficiency is common in type 2 diabetes, and a low 25(OH)D level is significantly associated with increased arterial stiffness in these patients. Vitamin D may influence the development of cardiovascular disease. Clinical intervention studies are needed to clarify whether treatment with vitamin D decreases the risk of cardiovascular disease in patients with type 2 diabetes.

A conference was convened by the Korean Diabetes Association and the Korean Endocrine Society on September 7, 2009 to discuss and organize the results of research on intensive glucose control for the prevention of cardiovascular disease in patients with type 2 diabetes. Professor Kyung Soo Park led the conference, and Professors Kwang Won Kim and Ho Young Son acted as chairmen. Professors Doo Man Kim, Tae Sun Park, and Bong Soo Cha reported on intensive glucose control and diabetic complications, including the UK Prospective Diabetes Study (UKPDS), Diabetes Control and Complication Trial (DCCT) research results, the recently published Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) research, as well as meta-analyses. Professor Jeong-Taek Woo reported on the manuscript written by the committee for the Korean Diabetes Association which dealt with the treatment of diabetes mellitus. Professors Kyung Soo Ko, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Dong-Won Byun, and Yoon-Sok Chung participated in the discussion and collected information for the manuscript from all of the participants. The aim of the debate was to determine how to establish target goals for intensive glucose control and how to individualize those goals. The participants concluded that there was no need to modify the recommendation of maintaining an HbA1c under 6.5%, the current blood glucose treatment goal that is recommended by the Korean Diabetes Association. In addition, individual target goals for glucose control were recommended depending on the situation of each patient. We report on the consensus statement from the meeting.

Aims/Introduction: Mitiglinide is the newest drug in the meglitinide family. It increases the early‐phase insulin release through rapid association‐dissociation kinetics in the pancreatic β cells. The efficacy and safety of adding meglitinide to metformin monotherapy in patients with type 2 diabetes are unknown. Materials and Methods: We carried out a prospective, randomized, multicenter trial to assess the efficacy and safety of combined treatment with mitiglinide and metformin for patients with type 2 diabetes who showed inadequate glycemic control with metformin monotherapy. Subjects with glycated hemoglobin (HbA1c) >7.0% after an 8‐week metformin run‐in phase were randomized to a 16‐week trial phase with metformin plus mitiglinide (Met + Mit) or metformin plus placebo (Met + Pcb). Results: Compared with the Met + Pcb group, the Met + Mit group showed a greater reduction in HbA1c (−0.7 ± 0.6%vs−0.4 ± 0.7%, P = 0.002), fasting plasma glucose (−0.77 ± 1.76 mmol/L vs−0.05 ± 1.60 mmol/L, P = 0.015) and 2‐h postprandial glucose (−3.76 ± 3.57 mmol/L vs−0.84 ± 3.07 mmol/L, P

Evaluating increasing circulating adiponectin levels is becoming an important strategy in the prevention of diabetes mellitus and cardiovascular events. This study was designed to investigate the effect of the angiotensin II receptor blocker valsartan on blood adiponectin levels and insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension. A total of 91 Korean patients were treated with 80 mg/day valsartan for 4 weeks followed by 160 mg/day for a further 8 weeks. Blood pressure, adiponectin levels and metabolic parameters were measured before and after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an insulin sensitivity index. Valsartan significantly decreased mean blood pressure and increased circulating adiponectin levels. There were no differences in metabolic parameters, including HOMA-IR, glycosylated haemoglobin and lipid levels before and after treatment. These results indicated that valsartan increases circulating adiponectin levels, but does not change insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension.

This study was designed to investigate the relationship between adipokines in metabolic syndrome and insulin resistance. Sixty male and female subjects with or without metabolic syndrome and type 2 diabetes were included. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Compared with lean control subjects, patients with metabolic syndrome and type 2 diabetes had lower circulating levels of total adiponectin and high molecular weight (HMW) adiponectin, and higher levels of leptin and interleukin-6 (IL-6). Total and HMW adiponectin and the adiponectin/leptin (A/L) ratio were negatively correlated with HOMA-IR. After adjusting for age and sex, leptin, IL-6 and tumour necrosis factor-α (TNF-α) were positively correlated with HOMA-IR. After also adjusting for body mass index, HOMA-IR was found to be independently associated with leptin, A/L ratio and TNF-α levels. In conclusion, decreased total adiponectin and HMW adiponectin and increased leptin and IL-6 levels are characteristic of patients with metabolic syndrome and type 2 diabetes.

A 73-year-old woman presented at our institution with a 1-day history of drowsy mental status and a 2-month history of headache and general weakness. She had not taken any medications. Laboratory investigations showed severe hyponatremia (Na, 114 mEq/L) and a potassium level of 3.2 mEq/L. A computed tomography (CT) angiogram showed an intrasellar 3.0-cm aneurysm arising from the left internal carotid artery (Fig. 1A and 1B). Basal pituitary hormone profiles showed morning cortisol, 1.43 µg/dL; adrenocorticotrophic hormone, 21.86 pg/mL; thyroid stimulating hormone, 1.36 mIU/L; free thyroxine, 0.6 ng/dL; follicle stimulating hormone, 2.46 IU/L; luteinizing hormone, 0.23 IU/L; and prolactin, 45.72 ng/mL, suggesting panhypopituitarism. A T1-weighted magnetic resonance image (MRI) revealed an aneurysm compressing the pituitary gland that was enhanced heterogeneously after injecting gadolinium (Fig. 1C).

To investigate the long-term effectiveness of the Internet-based glucose monitoring system (IBGMS) on glucose control in patients with type 2 diabetes.We conducted a prospective, randomized, controlled trial in 80 patients with type 2 diabetes for 30 months. The intervention group was treated with the IBGMS, while the control group made conventional office visits only. HbA1c (A1C) was performed at 3-month intervals. For measuring of the stability of glucose control, the SD value of A1C levels for each subject was used as the A1C fluctuation index (HFI).The mean A1C and HFI were significantly lower in the intervention group (n = 40) than in the control group (n = 40). (A1C [mean +/- SD] 6.9 +/- 0.9 vs. 7.5 +/- 1.0%, P = 0.009; HFI 0.47 +/- 0.23 vs. 0.78 +/- 0.51, P = 0.001; intervention versus control groups, respectively). Patients in the intervention group with a basal A1Cor=7% (n = 27) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study (P = 0.022). Control patients with a basal A1C7% (n = 15) showed the characteristic bimodal distribution of A1C levels, whereas the A1C levels in the intervention group remained stable throughout the study with low HFI.Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability.

The aim of the study was to determine if rosiglitazone increases serum levels of lipoprotein(a) [Lp(a)] in Korean patients with type 2 diabetes mellitus. A total of 118 patients were divided into 2 groups: those with rosiglitazone (rosiglitazone group, n = 49) and those without rosiglitazone (control group, n = 69). The rosiglitazone group was given rosiglitazone (4 mg/d) with previous treatment, insulin, or sulfonylurea, for 12 weeks, whereas the control group continued previous treatment with some dose modification for glycemic control. The patients had their blood glucose, lipid levels, as well as Lp(a) levels assessed to obtain a baseline, which were remeasured 12 weeks later. The fasting blood glucose and glycosylated hemoglobin (HbA(1c)) levels decreased significantly in both groups as compared with the baseline. The fasting glucose and HbA(1c) levels in both groups were similar at 12 weeks. The total cholesterol levels increased significantly in the rosiglitazone group (190.6 +/- 32.4 to 212.2 +/- 47.2 mg/dL, P =.002), while they were unchanged in the control group (185.4 +/- 36.8 to 188.0 +/- 35.8 mg/dL, P =.615). The triglyceride levels did not change in either group. Significant increases in high-density lipoprotein (HDL) cholesterol levels were observed in the rosiglitazone group as compared with the baseline (41.7 +/- 10.6 to 45.9 +/- 11.4 mg/dL, P =.004). The low-density lipoprotein (LDL) cholesterol levels increased significantly in the rosiglitazone group (120.5 +/- 29.9 to 136.3 +/- 40.0 mg/dL, P =.012), while they did not change in the control group (113.0 +/- 29.1 to 118.3 +/- 31.7 mg/dL, P =.234). Significant increases in Lp(a) levels were observed in the rosiglitazone group as compared with the baseline (22.4 +/- 17.4 to 25.7 +/- 20.5 mg/dL, P =.015), approximately a 15% increase in average values. In contrast, there was no change in Lp(a) levels in the control group. There was no correlation between the changes in Lp(a) and changes in fasting blood glucose or HbA(1c) levels in all study subjects. In summary, rosiglitazone increased serum total cholesterol, LDL cholesterol, as well as Lp(a) levels in patients with type 2 diabetes mellitus. Considering that patients with type 2 diabetes mellitus have increased risks for cardiovascular disease, caution should be taken when prescribing rosiglitazone to patients who already have other risk factors, such as hypertension and smoking.

We appreciate the interest and comments on our study, "The effect of an angiotensin receptor blocker on arterial stiffness in type 2 diabetes mellitus patients with hypertension," which was published in Diabetes & Metabolism Journal 2011;35:236-242. Hypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. In type 2 diabetes, hypertension often initiates and accelerates the progression of macrovascular events by increasing arterial stiffness [1,2]. Increased arterial stiffness was recently reported to be a powerful and independent risk factor for early mortality and had more clinical prognostic value than previously identified cardiovascular disease risk factors such as age, gender, smoking and dyslipidemia [3]. Previous studies have reported that angiotensin II type 1 receptor blockers reduce arterial stiffness [4-6]. In our study we assessed changes in central aortic waveforms and pulse wave velocity (PWV) as well as related parameters after treatment with valsartan in patients with type 2 diabetes and hypertension. We excluded patients concomitantly using insulin, thiazolidinedion or metformin as insulin resistance is associated with arterial stiffness and premature vascular sclerosis [7,8]. Our group of study subjects was homogeneous in terms of diabetes treatment, which had a minimal effect on insulin resistance. As Dr. Kim noted, our study has some limitations. There was no control group treated with other anti-hypertensive agents and confounding factors, such as lipid-lowering drugs, antiplatelet agents, and smoking, were not considered in the analysis. We were unable to measure PWV in all participants and the potential selection bias and diminished statistical power due to the small number of subjects was another limitation of this study. Although data was not shown in the article, there was no difference in baseline PWV values between the 'PWV decrease' and 'no PWV decrease' groups (11.0±1.8 vs. 10.5±2.0, P=0.297), and baseline PWV values were not associated with fasting blood glucose or HbA1c (P=0.462, P=0.641). We thought that if the number of subjects were larger, there might be association between them. Because there have been reported that fasting glucose and HbA1c were associated with PWV in type 2 diabetes patients with hypertension [9]. In our results, the baseline glucose level was significantly higher in 'no PWV decrease group.' Therefore, we concluded that the change in PWV was associated with baseline glycemic control status. Also, there were no differences between the two groups in terms of systolic or diastolic blood pressure at 12 weeks (P=0.183, P=0.396) or drug compliance, which was verified at every patient visit. Thus a difference in blood pressure control was excluded as a factor influencing the difference in PWV between the two groups. The results of our study suggested that the angiotensin receptor blocker, valsartan, had a modest beneficial effect in reducing arterial stiffness measured as PWV and the augmentation index in patients with type 2 diabetes and hypertension. Fasting glucose and HbA1c levels are likely to be independently associated with PWV improvement as a result of valsartan treatment. In future, further trials are needed to validate the effect observed in our study, to examine its stability over longer periods of follow-up, and to compare it with that obtained with other antihypertensive agents commonly used in clinical practice, and evaluate the pathogenic mechanism.

BACKGROUND Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance. METHODS After treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol. RESULTS After treatment of 10(-7)M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P

Cardiovascular disease (CVD) is the major cause of mortality in type 2 diabetes mellitus. CVD is a clinical manifestation of atherosclerosis, a chronic and progressive inflammatory disease characterized by a long asymptomatic phase. Progression of atherosclerosis can lead to the occurrence of acute cardiovascular events. Atherosclerosis can be identified during the subclinical phase by several methods, including using biomarkers, pulse wave velocity, augmentation index, flow-mediated dilation, carotid ultrasound, and calcium score. The appropriate criteria for identifying asymptomatic patients with type 2 diabetes who should undergo CVD screening and therapeutic intervention remain controversial. Non-invasive methods, such as markers of subclinical atherosclerosis, may aid in risk stratification and the design of tailored therapies for patients with type 2 diabetes mellitus.

Background: The frequency of lower extremity amputation due to diabetic foot has been increasing in type 2 diabetic patients. The aim of this study was to observe the incidence, clinical aspects and associated risk factors for diabetic foot. Methods: We evaluated the incidence of diabetic foot through a five-year observation of type 2 diabetic patients who presented to St. vincent's Hospital between Januar y and December 2003. To identify the risk factors for diabetic foot, we evaluated mean glycosylated hemoglobin A1c (HbA1c) every six months and assessed renal function based on the existence of proteinuria and estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation. Patients were also evaluated for retinopathy, peripheral neuropathy and autonomic neuropathy usi ng Ewing's method. Results: From an initial pool of 613 patients, the observational study o f 508 patients (82.9%) was completed. The mean age, duration of diabetes and HbA1c were 50.3 ± 10.6 yrs, 7.2 ± 6.5 yrs and 8.8 ± 2.1%, respectively. Diabetic foot occurred in 32 patients (6.3%). The incidence of diabetic foot increased when diabetic retinopathy (OR = 6.707, 2.314~19.439), peripheral neuropathy (OR = 2.949, 1.075~8.090), and autonomic neuropathy (OR = 3.967, 1.476~10.660) were present and when the MDRD GFR (OR = 5.089, 1.712~15.130) decreased. Mean HbA1c (OR = 12.013, 1.470~98.179) was found to be an independent risk factor for diabetic foot. Conclusion: The present study confirmed the importance of intensive glycemic control and the role of autonomic dysfunction in the development of diabetic foot. In addition, diabetic retinopathy and impaired renal function proved to be factors associated with the occurrence of diabetic foot. Therefore, intensive glycemic control, as well as periodic examination of renal function, are essential for the prevention of diabetic foot. (Korean Diabetes J 33:315-323, 2009)

Background: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus performed a nationwide survey about the current status of glycemic control and diabetic complications in 2006. Methods: The current study included 5,652 diabetic patients recruited from the rosters of endocrinology clinics of 13 tertiary hospitals in Korea. Age, gender, height, weight, waist circumference and blood pressure were investigated by standard method. Fasting and postprandial 2 hour glucose, glycosylated hemoglobin (HbA1c), lipid profiles, fasting insulin and c-peptide levels were measured. Microvascular (microalbuminuria, retinopathy and neuropathy) and macrovascular (coronary artery disease [CAD], cerebrovascular disease [CVD] and peripheral artery disease [PAD]) complications were reviewed in their medical records. Results: Mean age of total subjects was 58.7 ( 11.6) years and duration of diabetes was 8.8 (050) years. Mean fasting and postprandial 2 hour glucose levels were 145.9 55.0 and 208.0 84.4 mg/dL, respectively. Their mean HbA1c was 7.9 1.9%: the percentage of patients within target goal of glycemic control (

Background: Measuring urine albumin in diabetic patients is an important screening test to identify those individuals at high risk for cardiovascular disease and the progression of kidney disease. Recently, spot urine albumin-to-creatinine ratio (ACR) has replaced 24 hour-collected urine albumin excretion rate (AER) as a screening test for microalbuminuria given its comparative simplicity. The purpose of the current study was to evaluate the degree of correla tion between AER and ACR in the normal, microalbuminuric and macroalbuminuric ranges, and to identify the lower limits of ACR for both genders. Methods: A total of 310 type 2 diabetics admitted to one center were enrolled in the present study. Following the collection of a spot urine sample, urine was coll ected for 24 hours and albumin content was measured in both specimens. Results: Mean patient age was 60.2 years. A total of 25.4% had microalbuminuria and 15.8% had macroalbuminuria. The data revealed a strongly positive correlation between AER and ACR across all ranges of albuminuria (R = 0.8). The cut-off value of ACR for 30 mg/day of AER by the regression equation was 24 μ g/mg for men, 42 μ g/mg for women and 31.2 μ g/mg for all patients. The diagnostic performance expressed as the area under the curve (AUC) was 0.938 (95% CI, 0.911-0.965) for ACR. ACR revealed a sensitivity of 84% and specificity of 84%, when a cut-off value of 31.2 μ g/mg was employed. Conclusion: ACR was highly correlated with AER, particularly in the range of microalbuminuria. The gender combined cut-off value of ACR in type 2 diabetic patients was determined to be 31.2 μg/mg However, additional studies of large outpatient populations, as opposed to the inpatient population used in the present study, are required to confirm the utility of this value. (Korean Diabetes J 33:299-305, 2009)