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.
The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes.
In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics.
Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment.
Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.
Diabetes mellitus; Dipeptidyl peptidase 4; Dipeptidyl peptidase 4 inhibitor; Vildagliptin
While many studies have shown the good efficacy and safety of exenatide in patients with diabetes, limited information is available about exenatide in clinical practice in Korean populations. Therefore, this retrospective cohort study was designed to analyze the effects of exenatide on blood glucose level and body weight in Korean patients with type 2 diabetes mellitus.
We reviewed the records of the patients with diabetes who visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June 2009 to October 2011. After excluding subjects based on their race/ethnicity, medical history, whether or not they changed more than 2 kinds of oral hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they stopped exenatide therapy within 6 months, a total of 52 subjects were included in the final analysis.
The mean glycated hemoglobin (HbA1c) level and weight remarkably decreased from 8.5±1.7% to 6.7±1.0% (P<0.001) and from 82.3±15.8 kg to 78.6±16.3 kg (P<0.001), respectively. The multiple regression analysis indicated that the reduction in HbA1c level was significantly associated with a shorter duration of diabetes, a higher baseline HbA1c level, and greater weight reduction, whereas weight loss had no significant correlation with other factors. No severe adverse events were observed.
These results suggest that a 6-month exenatide injection therapy significantly improved patients' HbA1c levels and body weights without causing serious adverse effects in Korean patients with type 2 diabetes.
Diabetes mellitus, type 2; Exenatide; Glucagon-like peptide 1; Treatment outcome
There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.
Vitamin D; Intact Parathyroid Hormone; Bone Density; Age; Sex
To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC.
genetic association studies; genetic linkage; microsatellite repeats; polymorphism, single nucleotide; quantitative trait, heritable; skin pigmentation
We aimed to determine the characteristics affecting insulin resistance in non-obese middle-aged adults in a rural community.
A total of 1,270 non-diabetic adults aged between 40 and 64 years old with body mass index (BMI) less than 25 kg/m2 were analyzed. Subjects with insulin resistance were defined as those who had the highest quartile value of the homeostasis model assessment of insulin resistance (HOMA-IR) in a non-diabetic population.
A total of 217 subjects (20.6%) had insulin resistance. Prevalence of metabolic syndrome was significantly higher in insulin-resistant subjects in both men (29.3% vs. 10.3%) and women (34.1% vs. 15.6%). Among metabolic syndrome components, elevated waist circumference and elevated triglyceride were higher in insulin-resistant subjects in both genders. After being controlled for socioeconomic status and lifestyle related covariates, the association between insulin resistance and BMI was statistically significant in the category of 23.0-24.9 kg/m2 in men (adjusted OR, 4.63; 95% confidence interval [95% CI], 1.77-12.15) using the category of 18.5-20.9 kg/m2 as a reference. In addition, the association between insulin resistance and abdominal obesity was statistically significant only for men (adjusted OR, 2.57; 95% CI, 1.29-5.11).
Insulin resistance appears to be highly associated with high BMI and abdominal obesity, even in non-obese, non-diabetic middle-aged men.
Abdominal obesity; BMI; Insulin resistance
This study was aimed to investigate the prevalence of diabetic retinopathy and its associated factors in rural Korean patients with type 2 diabetes. A population-based, cross-sectional diabetic retinopathy survey was conducted from 2005 to 2006 in 1,298 eligible participants aged over 40 yr with type 2 diabetes identified in a rural area of Chungju, Korea. Diabetic retinopathy was diagnosed by a practicing ophthalmologist using funduscopy. The overall prevalence of diabetic retinopathy in the population was 18% and proliferative or severe non-proliferative form was found in 5.0% of the study subjects. The prevalence of retinopathy was 6.2% among those with newly diagnosed type 2 diabetes and 2.4% of them had a proliferative or severe non-proliferative diabetic retinopathy. The odds ratio of diabetic retinopathy increased with the duration of diabetes mellitus (5-10 yr: 5.2- fold; > 10 yr: 10-fold), postprandial glucose levels (> 180 mg/dL: 2.5-fold), and HbA1c levels (every 1% elevation: 1.34-fold). The overall prevalence of diabetic retinopathy in rural Korean patients was similar to or less than that of other Asian group studies. However, the number of patients with proliferative or severe non-proliferative diabetic retinopathy was still high and identified more frequently at the time of diagnosis. This emphasizes that regular screening for diabetic retinopathy and more aggressive management of glycemia can reduce the number of people who develop diabetic retinopathy.
Diabetic Retinopathy; Prevalence; Risk Factors
The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD).
A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT).
Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years, P=0.008) and duration of diabetes (16.0±7.5 vs. 5.5±5.7 years, P<0.001). The positive predictive value (PPV) of the ETT was calculated to be 47.8%. The PPV of the ETT increased to 87.5% in elderly patients (≥60 years) with a long duration of diabetes (≥10 years). The latter value is similar to that of patients with T2DM who presented with chest discomfort or exertional dyspnea. The PPV of the ETT in symptomatic patients was 76.9%.
In the interest of cost-effectiveness, screening for asymptomatic CAD could be limited to elderly patients with a duration of diabetes ≥10 years.
Diabetes mellitus; Duration of diabetes; Exercise treadmill test; Silent myocardial ischemia
Currently, there is no consensus on the necessity of repeated radioiodine therapy (RAI) in patients who show iodine uptake in the thyroid bed on a diagnostic whole-body scan (DxWBS) despite undetectable thyroglobulin (Tg) levels after remnant ablation. The present study investigated the clinical outcomes of scan-positive, Tg-negative patients (WBS+Tg-) who did or did not receive additional RAI.
We retrospectively reviewed 389 differentiated thyroid carcinoma patients who underwent a total thyroidectomy and received high-dose RAI from January 2003 through December 2005. The patients were classified according to surveillance DxWBS findings and TSH-stimulated Tg levels 6 to 12 months after the initial RAI.
Forty-four of the 389 patients (11.3%) showed thyroid bed uptake on a DxWBS despite negative Tg levels (WBS+Tg-). There was no difference in clinical and pathological parameters between WBS+Tg- and WBS-Tg- patients, except for an increased frequency of thyroiditis in the WBS+Tg- group. Among the 44 WBS+Tg- patients, 27 subjects were treated with additional RAI; 25 subjects showed no uptake in subsequent DxWBS. Two patients were evaluated only by ultrasonography (US) and displayed no persistent/recurrent disease. The other 17 patients received no further RAI; Eight patients and two patients showed no uptake and persistent uptake, respectively, on subsequent DxWBS. Six patients presented negative subsequent US findings, and one was lost to follow-up. Over the course of 53.2 ± 10.1 months, recurrence/persistence was suspicious in two patients in the treatment group.
There were no remarkable differences in clinical outcomes between observation and treatment groups of WBS+Tg- patients. Observation without repeated RAI may be an alternative management option for WBS+Tg- patients.
Iodine radioisotopes; Thyroglobulin; Thyroid neoplasms; Whole body scan
We aimed at determining the cutoff value of waist circumference with respect to its ability to reflect insulin resistance in a Korean population.
Materials and Methods
A total of 8,817 subjects aged 40 years and over were analyzed. Insulin resistant individuals were defined as those who had the highest quartile value of the homeostasis model assessment of insulin resistance (HOMA-IR) in a non-diabetic population. Receiver operating characteristic (ROC) curve analysis and multiple logistic regression analysis were applied.
The cutoff value of waist circumference reflecting insulin resistance from the ROC analysis was 84.4 cm for men and 80.6 cm for women. Sensitivity and specificity were 70.0% and 54.2% in men and 71.1% and 59.3% in women, respectively. After being controlled for other covariates, the odds ratio for the risk of insulin resistance using < 70 cm of waist circumference as a reference increased significantly in the category of 85.0-89.9 cm for men and 80.0-84.9 cm for women. In addition, statistically significant associations were consistently observed over the category of 85.0-89.9 cm for men and 80.0-84.9 cm for women.
The optimal cutoff value for waist circumference reflecting insulin resistance is considered to be 85 cm for men and 80 cm for women, suggesting that the Asian criterion of abdominal obesity (90 cm for men and 80 cm for women) as a component of metabolic syndrome (MetS) might not be applicable for middle-aged to older men in Korea.
Metabolic syndrome; waist circumference; insulin resistance
Gastrointestinal (GI) symptoms are common among patients with non-insulin dependent diabetes mellitus (NIDDM). Our aim was to investigate the frequency of chronic GI symptoms in Korean patients with NIDDM.
A cross-sectional survey, using a reliable and valid questionnaire, was performed in diabetes clinics from seven hospitals of the Catholic University of Korea.
A total of 608 patients (249 males and 359 females, mean age 53.7±10.9 years) were investigated. The frequencies of weekly heartburn and acid regurgitation (esophageal symptoms) were 7.1% (95% confidence interval [CI], 5.0 to 9.2) and 4.4% (95% CI, 2.8 to 6.1), respectively. The frequency of dyspepsia was 13.2% (95% CI, 10.5 to 15.8). The frequencies of constipation and diarrhea were 15.0% (95% CI, 12.2 to 18.0) and 5.3% (95% CI, 3.5 to 7.1), respectively. Nausea and the use of manual maneuvers to facilitate defecation were more prevalent in women than in men. Constipation and fecal incontinence were more common in diabetes patients with long duration (>10 years). Fecal incontinence and using laxatives were more frequent in the complicated diabetes group. Using laxatives was more frequent in the uncontrolled diabetes group.
Two-thirds of diabetic patients experienced GI symptoms. The prevalence of GI symptoms was more common in patients who had diabetic complications and a long duration of diabetes.
Diabetes mellitus, type 2; Prevalence; Signs and symptoms, digestive; Diabetes complications
OBJECTIVE—We investigated whether cardiovascular autonomic dysfunction was associated with glycemic control status over time in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—From 1999 to 2000, cardiovascular autonomic nerve function testing (AFT) was performed on patients with type 2 diabetes (n = 1,021) and was followed-up in 2006 and February 2008. Tests for cardiovascular autonomic functions measured heart rate variability parameters (expiration-to-inspiration [E/I] ratio, responses to the Valsalva maneuver, and standing). AFT scores were determined from the results of the each test as follows: 0 for normal and 1 for abnormal. We began with those who had a score of 0 and assessed the changes in total score along with biannual A1C levels.
RESULTS—At follow-up, the development of cardiovascular autonomic dysfunction was 34.5% (E/I ratio 21.9%, Valsalva maneuver 77.8%, and posture 58.9%; n = 783). The development of cardiovascular autonomic dysfunction was higher in older patients (P < 0.001); in those with longer duration of diabetes (P < 0.001); of hypertension (P = 0.005), and of diabetic retinopathy (P < 0.001); and in those who had higher levels of microalbuminuria (P = 0.002). Logistic regression analysis revealed that the development of cardiovascular autonomic dysfunction was strongly associated with the mean A1C level during the follow-up period (mean A1C >9.0% vs. ≤7.0%, odds ratio 2.984, 95% CI 1.177–7.561; P = 0.021).
CONCLUSIONS—The development of cardiovascular autonomic dysfunction was independently associated with microvascular complications and glycemic control status during this 7.5-year follow-up in patients with type 2 diabetes.
Statins have been postulated to affect the bone metabolism. Recent experimental and epidemiologic studies have suggested that statins may also have bone protective effects. This study assessed the effects of simvastatin on the proliferation and differentiation of human bone marrow stromal cells (BMSCs) in an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear cells were isolated and cultured to osteoblastic lineage. In the primary culture, 10-6 M simvastatin diminished the mean size of the colony forming units-fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of each group were measured by the time course of the secondary culture. Simvastatin increased the ALP activity in a dose dependent manner, and this stimulatory effect was more evident during the early period of culture. A 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed during the secondary culture in order to estimate the effect of simvastatin on the proliferation of human BMSCs. When compared to the control group, simvastatin significantly decreased the proliferation of cells of each culture well. 10-6 M of simvastatin also significantly enhanced the osteocalcin mRNA expression level. This study shows that simvastatin has a stimulatory effect on bone formation through osteoblastic differentiation, and has an inhibitory effect on the proliferative potential of human BMSCs
Simvastatin; Osteoblasts; Cell Proliferation; Cell Differentiation; Bone Marrow Cells; Stromal Cells
This study was conducted to investigate the association of diabetic peripheral neuropathy (DPN) with both arterial stiffness and intima–media thickness (IMT).
RESEARCH DESIGN AND METHODS
We conducted a cross-sectional analysis of 731 subjects with type 2 diabetes. DPN was diagnosed on the basis of neuropathic symptoms, insensitivity to a 10-g monofilament, abnormal pin-prick sensation, and abnormal current perception threshold. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), and IMT was assessed by B-mode ultrasonography.
Patients with DPN had higher CAVI than those without DPN in multivariate-adjusted models, whereas no differences in IMT were observed between patients with and without DPN after adjustment for age and sex. In the multivariate analysis, CAVI was a significant determinant of DPN (odds ratio 1.36 [95% CI 1.13–1.65], P = 0.001).
DPN is significantly associated with arterial stiffness without carotid intimal changes in patients with type 2 diabetes.
Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.
We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.
HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.
The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.
Diabetes mellitus, type 2; Glimepiride; Metformin; Rosiglitazone
We introduced a new information technology-based diabetes management system, called the Internet-based glucose monitoring system (IBGMS), and demonstrated its short-term and long-term favorable effects. However, there has been no report on clinical effects of such a new diabetes management system on the development of diabetic complications so far. This study was used to simulate the complication reducing effect of the IBGMS, given in addition to existing treatments in patients with type 2 diabetes.
Research Design and Methods
The CORE Diabetes Model, a peer-reviewed, published, validated computer simulation model, was used to project long-term clinical outcomes in type 2 diabetes patients receiving the IBGMS in addition to their existing treatment. The model combined standard Markov submodels to simulate the incidence and progression of diabetes-related complications.
The addition of IBGMS was associated with improvements in reducing diabetic complications, mainly microangiopathic complications, including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and diabetic foot ulcer. The IBGMS also delayed the development of all diabetic complications for more than 1 year.
This study demonstrated that the simulated IBGMS, compared to existing treatment, was associated with a reduction of diabetic complications. As a result, it provides valuable evidence for practical application to the public in the world.
diabetic complications; health economics; Internet; simulation