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Purpose: Diabetes mellitus (DM) is a global health concern linked to various complications, including cardiovascular disease (CVD). However, long-term follow-up studies on the risk of DM and CVD using different blood glucose assessment methods in the general Korean population are lacking. This study aimed to assess the predictive abilities of fasting plasma glucose (FPG), 2-h oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) for new-onset DM and high CVD risk in a middle-aged and older Korean population., Methods: This study used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort. Blood sugar measures (FPG, OGTT, and HbA1c) were examined. The primary endpoint was the development of new-onset DM, and CVD risk was evaluated using the Framingham risk score. The predictive abilities for new-onset DM based on glycemic values were evaluated using Harrell's Concordance index and 95% confidence intervals., Results: Among the 10,030 participants, data of 6813 participants without DM at baseline were analyzed. The study revealed that OGTT outperformed FPG and HbA1c in predicting new-onset DM. The combination of FPG and HbA1c did not significantly enhance predictions for DM compared with OGTT alone. OGTT also outperformed FPG and HbA1c in predicting high CVD risk, and this difference remained significant even after adjusting for additional confounders., Conclusion: OGTT has superior predictive capabilities in identifying new-onset DM and high CVD risk in the Korean population. This suggests that relying solely on individual blood sugar measures may be insufficient for assessing DM and CVD risks., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Glycemic control is crucial in peritoneal dialysis (PD) patients with diabetes. Although fasting blood glucose (FBG) is the most commonly used index to measure blood glucose levels, there is currently no evidence supporting the association between FBG level and mortality risk in PD patients., Methods: A total of 3548 diabetic PD patients between 2002 and 2018 were enrolled from the National Health Insurance Service database of Korea. We investigated the association between FBG levels and the risk of all-cause and cause-specific mortality., Results: Patients with FBG levels 80-99 mg/dL exhibited the highest survival rates, whereas those with FBG levels ≥180 mg/dL had the lowest survival rates. Compared with FBG levels 80-99 mg/dL, the adjusted hazard ratios and 95% confidence interval for all-cause mortality significantly increased as follows: 1.02 (0.87-1.21), 1.41 (1.17-1.70), 1.44 (1.18-2.75), and 2.05 (1.73-2.42) for patients with FBG 100-124 mg/dL, FBG 125-149 mg/dL, FBG 150-179 mg/dL, and FBG ≥180 mg/dL, respectively. The risk for all-cause mortality also showed an increasing pattern in patients with FBG levels <80 mg/L. The risk of cardiovascular death significantly increased as FBG levels exceeded 125 mg/dL. However, the risk of infection-related and malignancy-related deaths did not show a significant increase with increasing FBG levels., Conclusion: There was an increase in the risk of all-cause mortality as FBG levels exceeded 125 mg/dL in PD patients with diabetes, and the risk of cardiovascular death showed a strong correlation with FBG levels compared with other causes of death., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk., Methods: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years., Results: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus)., Conclusions: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner., Plain Language Summary: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful., (© 2024 American Cancer Society.)

Background: Diabetes have been known as a traditional risk factor of developing peripheral artery disease (PAD). However, the study evaluating the impact of long-term glycemic variability on the risk of developing PAD is limited, especially in a general population without diabetes., Methods: We included 152,931 individuals without diabetes from the Korean National Health Insurance Service-Health Screening Cohort. Fasting plasma glucose (FPG) variability was measured using coefficient variance (FPG-CV), standard deviation (FPG-SD), and variability independent of the mean (FPG-VIM)., Results: A total of 16,863 (11.0%) incident cases of PAD were identified during a median follow-up of 8.3 years. Kaplan-Meier curves showed a progressively increasing risk of PAD in the higher quartile group of FPG variability than in the lowest quartile group (log rank P < 0.001). Multivariable Cox proportional hazard analysis showed the hazard ratio for PAD prevalence as 1.11 (95% CI 1.07-1.16, P < 0.001) in the highest FPG-CV quartile than in the lowest FPG-CV quartile after adjusting for confounding variables, including mean FPG. Similar degree of association was shown in the FPG-SD and FPG-VIM. In sensitivity analysis, the association between FPG variability and the risk of developing PAD persisted even after the participants were excluded based on previously diagnosed diseases, including stroke, coronary artery disease, congestive heart failure, chronic kidney disease, or current smokers or drinkers. Subgroup analysis demonstrated that the effects of FPG variability on the risk of PAD were more powerful in subgroups of younger age, regular exercisers, and those with higher income., Conclusions: Increased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes., (© 2022. The Author(s).)

Background: High fasting glucose has been indicated in relation to a higher risk of gastric cancer, but the majority of studies have focused on diabetes (fasting glucose ≥126 mg/dL). Here, we investigated whether fasting glucose levels, including prediabetic and diabetic levels, influence gastric cancer incidence., Methods: A prospective study was conducted with 41,837 participants aged 16 and older who underwent health examinations at the National Cancer Center in South Korea from August 2002 to December 2014. Participants were followed up until December 2017 to identify incident gastric cancer cases. A fasting glucose test was performed based on venous blood samples taken from participants after 8 hours of fasting. We used the Cox proportional hazards regression model to explore the association of fasting glucose levels with gastric cancer incidence., Results: We identified 263 incident gastric cancer cases during the follow-up period. A significant association of high fasting glucose with gastric cancer incidence was found for postmenopausal women [hazard ratio (HR) = 1.88; 95% confidence interval (CI) = 1.11-3.20]. There was also a significant association between high fasting glucose and gastric cancer incidence among all participants who were nonsmokers (HR = 1.89; 95% CI = 1.21-2.95), had a BMI < 25 kg/m 2 (HR = 1.45; 95% CI = 1.00-2.12), and did not have a first-degree family history of gastric cancer (HR = 1.45; 95% CI = 1.06-1.99)., Conclusions: Our findings support that high fasting glucose is a risk factor for gastric cancer development in postmenopausal women., Impact: Our results provide evidence for future planning and management regarding cancer prevention., (©2021 American Association for Cancer Research.)

We investigated the association between oral hygiene indicators of periodontitis, tooth loss, and tooth brushing on the longitudinal fasting glucose level in non-diabetic subjects. Using a nationwide health screening database in Korea, we included non-diabetic individuals who received a health screening program with oral health check in 2009-2010. We constructed a linear mixed model for the longitudinal data of fasting glucose from the baseline to 2015. During the 4.84-year of median follow-up, 91,963 individuals (mean age 56.2 at baseline) underwent 392,780 health examinations with fasting glucose level (mmol/L). The presence of periodontitis was 39.3%. In the multivariate linear mixed analysis, periodontitis was related with increased fasting glucose levels (β = 0.0084, standard error = 0.0035, p = 0.018). Similarly, tooth loss was associated with increased level of fasting glucose (β = 0.0246, standard error = 0.0038, p < 0.001). Compared with tooth brushing ≤2 times/day, tooth brushing ≥3 times/day was associated with decreased fasting glucose levels (β = -0.0207, standard error = 0.0033, p < 0.001). Our data showed that periodontitis and tooth loss were associated with increased fasting glucose levels in non-diabetic individuals. The study findings imply that frequent tooth brushing may reduce fasting glucose levels. Further research is needed to determine the effect of periodontal intervention on glycemic control., Competing Interests: The authors have declared that no competing interests exist.

Aims: Diabetes mellitus (DM) is one of the main risk factors for intracranial cerebral artery stenosis (ICAS), and fasting blood glucose (FBG) might be an effective predictor of ICAS. However, there are a few studies revealing the relationship between FBG and ICAS. We aim to identify the association between FBG and ICAS in Koreans., Methods: This was a secondary study based on a cross-sectional study. A total of 1011 Korean individuals who were asymptomatic but with high cerebrovascular risk underwent an examination in a Korean medical centre from March 2008 to December 2014. The main measure was FBG, while the main outcome was ICAS. Multivariate logistic regression analyses of FBG in the presence of ICAS were performed to examine the potential association. The author used the data provided by the paper "Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease" for secondary analysis., Results: The average age of the participants was 64.2 ± 9.1 years old, and approximately 35% of them were males. There were 24 participants suffering from ICAS in the first FBG tertile (< 5.4 mmol/L), while there were 26 in the second tertile (5.4-7.1 mmol/L) and 50 in the third tertile (≥ 7.1 mmol/L). The non-adjusted relationship between FBG and ICAS was positive. After controlling potential confounders, the association of FPG with ICAS remained positive, as well as in subgroups analysis, such as age, sex, hypertension, diabetes mellitus, hyperlipidaemia and COAD. The association remained unchanged after adjusted sex, age, hypertension, DM, uric acid, hyperlipidaemia, and CAOD (OR = 1.08, 95% CI = 1.02-1.15). The analyses also showed that the positive association was statistically significant (P < 0.05) among individuals without diabetes., Conclusions: This study showed a positive relationship between FBG and ICAS, which suggests that clinicians may need to be simultaneously concerned about FBG and ICAS.

Purpose: High sensitivity C-reactive protein (hs-CRP) has been used as a biomarker to assess the risk of cardiovascular accidents (CVA) and to measure general inflammation in the body. This study investigated the relationship and extent of correlation between serum glucose level markers and hs-CRP as a means to assess CVA risk through hemoglobin A1c (HbA1c) and fasting glucose levels., Methods: This cross-sectional, population-based study used data from the 2017 Korea National Health and Nutrition Examination Survey (KNHANES). From the total sample of 8,127 people, 4,590 subjects were excluded due to age (<19 years) ( n = 1,505), diabetes mellitus (DM) diagnosis or medication ( n = 596), inactivity ( n = 424), pregnancy ( n = 17), hypoglycemia (<70 mg/dL) ( n = 8), smoking history ( n = 1,077), and missing data ( n = 963). In total, 3,537 adults not diagnosed with diabetes were selected. Their hs-CRP levels were compared with the glucose level markers using a complex sample general linear regression analysis., Results: We adjusted for sedentary hours, smoking, binge drinking frequency, age, sex, mean SBP, triglycerides, and waist circumference. Increases in HbA1c correlated with hs-CRP levels ( B  coefficient (95%CI) = 0.185, p = 0.001, and R 2 = 0.087). Changes in the fasting glucose levels were also associated with the hs-CRP levels ( B  coefficient (95%CI) = 0.005, p = 0.006, and R 2 = 0.086)., Conclusion: This study showed a linear association between HbA1c and fasting glucose levels and hs-CRP. It also showed that changes in the hs-CRP level were better correlated with those in the HbA1c levels than in the fasting glucose levels., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Jeong Woo Seo and Sat Byul Park.)

Glucagon-like peptide-1 (GLP-1), an incretin hormone, plays an important role in regulating glucose homeostasis. In this study, the applicability of circulating GLP-1 levels as an early indicator of metabolic syndrome (MetS) risk was examined. Women without diagnosed diseases were grouped according to their number of MetS risk factors (MetS RFs) (no RFs as Super-healthy, n = 61; one or two RFs as MetS risk carriers, n = 60; 3 ≤ RFs as MetS, n = 19). The circulating GLP-1 levels and homeostasis model assessment insulin resistance (HOMA-IR) scores were significantly higher in the MetS group than in the other two groups. The GLP-1 levels correlated positively with adiposity, HOMA-IR, blood pressure, and high sensitivity C-reactive protein (hs-CRP), but not with fasting glucose and lipid profiles, whose significances were maintained after adjustments for age, smoking and drinking habits, menopausal status, and total calorie intake. The GLP-1 levels also increased proportionally with the number of MetS RFs. In the MetS group, the GLP-1 levels were much higher in individuals with obesity (body mass index ≥ 25 kg/m 2 ). In conclusion, the circulating GLP-1 level may be applicable as a potential early indicator of MetS risk in women without diagnosed diseases. Further study with a large population is needed to confirm the conclusion.

The triglyceride-glucose (TyG) index is a simple surrogate marker of insulin resistance. We evaluated the association of the TyG index with low muscle mass using a nationwide population-based representative data. This is a cross-sectional study that included 9477 participants aged ≥ 40 years from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. The TyG index was calculated as ln[triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Dual-energy X-ray absorptiometry was used to measure appendicular lean mass (ALM). Low muscle mass was defined an ALM/weight of 2 standard deviations (SD) below of young participants. The overall prevalence of low muscle mass was 4.7%. The prevalence of low muscle mass increased linearly with the quartiles of the TyG index, 2.5%, 4.2%, 5.6%, and 6.7% in Q1-Q4, respectively. The TyG index was negatively associated with ALM/weight both in men (r = - 0.302) and women (r = - 0.230). The odds ratio (OR) for low muscle mass was 2.08 in the highest quartile compared to the lowest quartile. High TyG index was associated with an increased risk of low muscle mass (OR for 1SD increase: 1.13). Increased TyG index was associated with the risk of low muscle mass independent of confounding factors.

Objective: The importance of continuous monitoring of fasting blood sugar (FBS) levels of diabetic patients has been established., Materials and Methods: An observational prospective study was conducted. Our analysis included 1,700,796 individuals from the nationwide South Korean National Health Insurance System cohort. FBS variability was measured by standard deviation (SD)., Results: Kaplan-Meier curves demonstrated elevated disease probability in the higher FBS fluctuation group compared with the lower FBS fluctuation group. After adjusting for confounding variables, Cox proportional hazards analysis showed that the hazard ratios of 411 individuals in the highest quartile of SD variation of FBS were 1.77 (95% confidence interval 1.37-2.28, p<0.001) compared with the lowest quartile of SD variation of FBS. The impact of FBS fluctuation on the risk of cardiovascular diseases (CVDs), cerebrovascular diseases, CVD mortality and all-cause mortality in the highest quartiles of diabetic and non-diabetic individuals was statistically significant., Conclusions: Visit-to-visit FBS variability has prognostic value for predicting micro- and macrovascular disease, cardiovascular mortality, and all-cause mortality.

This study aimed to evaluate the risk of vascular complications of impaired fasting glucose (IFG). This population-based study included 425,608 participants from the National Health Screening Cohort in Korea in 2003 and 2004 who were followed-up until 2015. The participants were classified into normal, IFG, and diabetes groups based on fasting plasma glucose levels. Incidence rate (per 1000 person-year) was evaluated for the following vascular complications: cardiovascular (ischemic heart disease, cerebrovascular disease, arterial and capillary disease), renal, and retinal diseases. Hazard ratios (HR) of IFG for diabetes were estimated after adjusting for patient characteristics. Among the 88,330 IFG participants, the incidence of cardiovascular, chronic renal and retinal diseases were 11.52, 0.47, and 1.08 per 1000 person-years, respectively. Furthermore, IFG patients with a family history of diabetes, past history of hypertension, and high body mass index had significantly increased risk of vascular complications [adjusted HR, cardiovascular: 1.39 (95% CI 1.33-1.46); renal: 2.17 (95% CI 1.66-2.83); and retinal: 1.14 (95% CI 0.98-1.32)]. IFG patients have a substantial risk of cardiovascular, chronic renal and retinal diseases. Therefore, early preventative interventions are beneficial, especially for those with high-risk factors, in whom should emphasize on maintaining a healthy lifestyle, early screening and continuous follow-up.

Interest in high protein diets has recently been increasing for reduction of weight or management of cardiometabolic risks. However, studies on high protein, low carbohydrate diet in Asians are limited. This study aimed to estimate whether the dietary ratio of protein (%) to carbohydrate (%) from total energy intake (p/c ratio) is associated with the risk of metabolic syndrome (MS) and its components in Korean adults using a long-term prospective cohort. A total of 6335 participants from the Korean Genome and Epidemiology Study, aged between 40 and 69 years, with no previous diagnosis of MS, cardiovascular diseases, or cancer at baseline (2001-2002) were followed until 2013. Dietary intake was measured using a validated semiquantitative food-frequency questionnaire. MS components were measured at baseline and every 2 years. During a mean of 7.7 years of follow up, 1198 (36.1%) men and 1169 (38.8%) women developed MS. The multivariate adjusted hazard ratio (HR) of incident MS was 1.43 (95% confidence interval, 1.09-1.89) for the highest compared lowest quintile of p/c ratio in men. When evaluating each component of MS, higher dietary p/c ratio was associated with an increased risk of high triglyceride and fasting glucose in men (HR for fifth vs. first quintile, 1.39 and 1.41 in Model 3, respectively). However, we observed no associations with incident MS and its components and dietary p/c ratio in women. In conclusion, we found that high dietary p/c ratio was associated with an increased risk of MS and its components (i.e., increased triglycerides and fasting glucose) in men. Our study suggested that even if the absolute amount of protein intake is not large, an increased p/c ratio may increase the risk of metabolic diseases.

Introduction: Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM., Methods: We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements., Results: In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18-1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability (P for linear trend <0.001). A 1-SD increase in FPG variability assessed by VIM was significantly associated with a 10.0% increase in gastric cancer risk in the fully adjusted model., Discussion: In a DM-free population, high variability in visit-to-visit FPG levels was independently associated with an increased risk of gastric cancer.

Background: Coronavirus disease 2019 (COVID-19) has become a global pandemic, which prompts a consensus for the necessity to seek risk factors for this critical disease. Risk factors affecting mortality of the disease remain elusive. Diabetes and hyperglycemia are known to negatively affect a host's antiviral immunity. We evaluated the relationship between a history of diabetes, fasting plasma glucose (FPG) levels and mortality among severely ill patients with COVID-19., Methods: This was a retrospective cohort study that assessed 106 adult inpatients (aged ≥18 years) from two tertiary hospitals in Daegu, South Korea. The participants were transferred to tertiary hospitals because their medical condition required immediate intensive care. The demographic and laboratory data were compared between COVID-19 patients who survived and those who did not., Results: Compared with the survivor group, age, and the proportions of diabetes, chronic lung disease and FPG were significantly higher in the deceased group. In the Cox proportional hazards regression model for survival analysis, FPG level and age were identified as significant predictors of mortality (P&lt;0.05). The threshold values for predicting high mortality were age &gt;68 years and FPG of 168 mg/dL, respectively. Among those without diabetes, high FPG remained a significant predictor of mortality (P&lt;0.04)., Conclusion: High FPG levels significantly predicted mortality in COVID-19, regardless of a known history of diabetes. These results suggest intensive monitoring should be provided to COVID-19 patients who have a high FPG level.

Background: Ambient fine particulate matter is a rising concern for global public health. It was recently suggested that exposure to fine particulate matter may contribute to the development of diabetes and dyslipidaemia. This study aims to examine the potential associations of ambient particulate matter exposure with changes in fasting glucose and lipid profiles in Koreans., Method: We used the data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC), a nationwide database representative of the Korean population. A total of 85,869 individuals aged ≥20 years were included. Multiple regression analyses were conducted to assess the associations between exposure to particulate matter and changes in fasting glucose and lipid profiles at 2-year intervals after adjusting for confounders., Results: Significant associations were observed between an increase in interquartile range for particulate matter < 2.5 μm in diameter (PM 2.5 ) and elevated levels of fasting glucose and low-density lipoprotein cholesterol (p for trend = 0.015 and 0.010, respectively), while no association for particulate matter sized 2.5-10 μm in diameter (PM 10-2.5 ) was noted after adjusting for the other covariates. Sub-group analyses showed stronger associations in individuals who were older (≥60 years) or physically inactive., Conclusions: Fine particulate matter exposure affects worsening fasting glucose and low-density lipoprotein cholesterol levels, with no evidence of an association for coarse particulate matter.

Background: Growing evidences shows that fasting glucose target should be different according to their health condition in older adults with diabetes. However, there are limited data regarding the relationship between fasting glucose level and health outcomes in Korean older people with diabetes. We aimed to examine the association of fasting glucose with mortality and cardiovascular events in Korean older adults with type 2 diabetes., Methods: From the Korean National Health Insurance System, 227,938 subjects (aged ≥ 65 years) with type 2 diabetes but no history of cardiovascular events (myocardial infarction or stroke) who underwent ≥ 2 health examinations from 2009 to 2010 and who were followed up until 2017 were identified. The primary exposure variable was the mean fasting glucose level. We estimated the relationship between the baseline fasting glucose level and incidences of all-cause death and cardiovascular events. Comorbidity load was assessed using the Charlson comorbidity index., Results: Fasting glucose levels and all-cause mortality risk showed a J-shaped relationship regardless of sex and number of comorbidities. Fasting glucose levels associated with the lowest mortality and cardiovascular events were 110-124 and 95-124 mg/dL, respectively. Stratified analysis by comorbidity load using the Charlson comorbidity index revealed higher optimal fasting glucose levels for the lowest cardiovascular events in subjects with Charlson comorbidity index ≥ 3 than in those with Charlson comorbidity index ≤ 2 (119 vs. 112 mg/dL, P = 0.04)., Conclusions: J-shaped relationship existed between fasting glucose and all-cause mortality and cardiovascular events in Korean older adults with diabetes. We identified that fasting glucose levels associated with the lowest mortality and cardiovascular events were 110-124 and 95-124 mg/dL respectively. Increased risk of cardiovascular events with low fasting glucose level (< 95 mg/dL) was noted, especially in patients with high comorbidity. These findings suggested that less stringent targets of fasting glucose may be beneficial especially in older adults with multiple comorbidities.

Background: Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited. This longitudinal study evaluated the association of TyG index with CAC progression in asymptomatic adults., Methods: We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations. The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period., Results: During a mean 3.3 years, the overall incidence of CAC progression was 30.6%. The incidence of CAC progression (group I [lowest]: 22.7% versus [vs.] group II: 31.7% vs. group III [highest]: 37.5%, P < 0.001) and annualized Δ√transformed CACS (group I: 0.46 ± 1.44 vs. group II: 0.71 ± 2.02 vs. group III: 0.87 ± 1.75, P < 0.001) were markedly elevated with increasing TyG index tertiles. Multivariate linear regression analysis showed that TyG index was associated with annualized Δ√transformed CACS (β = 0.066, P = 0.036). In multivariate logistic regression analysis, the TyG index was significantly associated with CAC progression in baseline CACS ≤ 100., Conclusion: The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC.

Aims: To investigate the optimal fasting blood glucose (FBG) levels among individuals actively treated or untreated with antidiabetic drugs., Methods: In two population-based cohorts of Korean adults extracted from the National Health Information Database, multivariable-adjusted hazard ratios of outcomes over 10 and 8 years of follow-up were estimated according to achieved FBG levels and antidiabetic drug use. The primary outcomes were major cardiovascular disease (CVD) events and all-cause mortality., Results: In total, 66 533 of 450 537 and 100 556 of 767 382 participants in the respective cohorts received antidiabetic treatment. For untreated FBG, the CVD risk and mortality increased linearly from an FBG threshold of 5.6 mmol/L; however, for FBG treated with antidiabetic drugs there were J-shaped associations with the outcome risks. For treated FBG levels of 4.4 to 5.5 mmol/L, 7.8 to 8.8 mmol/L, 8.9 to 9.9 mmol/L and ≥ 10.0 mmol/L, vs 6.1 to 6.9 mmol/L, the hazard ratios for major CVD events were 1.17 (95% confidence interval [CI] 1.04-1.32), 1.06 (95% CI 0.96-1.18), 1.37 (95% CI 1.22-1.53) and 1.61 (95% CI 1.46-1.78), respectively, and those for all-cause mortality were 1.20 (95% CI 1.11-1.29), 1.05 (95% CI 0.99-1.12), 1.29 (95% CI 1.10-1.50) and 1.69 (95% CI 1.59-1.81), respectively., Conclusions: These findings indicate that pharmacological therapy achieving FBG levels of <7.8 to 8.9 mmol/L and a non-pharmacological approach to maintaining normal glucose levels help reduce the risk of adverse outcomes, while lowering FBG to normal levels through antidiabetic drugs is not beneficial or may even be harmful., (© 2019 John Wiley & Sons Ltd.)

Aims: The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium glucose co-transporter-2 inhibitor, on glycaemic variability in type 2 diabetes patients., Materials and Methods: In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6-day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline., Results: Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was -27.2 ± 4.4 mg/dL and -7.9 ± 4.9 mg/dL, respectively. Between-group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (-19.2 mg/dL; 95% CI, -31.3 to -7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups., Conclusions: Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose-lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve., (© 2019 John Wiley & Sons Ltd.)

Background: The objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older., Methods: This study used 2013 to 2016 data from the Korea National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%., Results: In 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c <6.5%, blood pressure <140/85 mm Hg, and low density lipoprotein cholesterol <100 mg/dL. Only 8.4% of people with diabetes had good control of all three targets., Conclusion: This study confirms that diabetes is as an important public health problem. Efforts should be made to increase awareness, detection, and comprehensive management of diabetes to reduce diabetes-related morbidity and mortality., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

Objective: To investigate the triglyceride-glucose (TyG) index association with coronary artery calcification (CAC) progression in adult Koreans., Research Design and Methods: Various cardiovascular risk factors and anthropometric profiles were assessed in 1,175 subjects who previously had a CAC evaluation at least twice by multidetector computed tomography in a health care center. The TyG index was determined using ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline., Results: CAC progression was seen in 312 subjects (27%) during 4.2 years follow-up. On the basis of the TyG index, subjects were stratified into three groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index tertile. Logistic regression analysis adjusted for various risk factors revealed an odds ratio for CAC progression of 1.82 (95% CI 1.20-2.77; P ≤ 0.01) when the highest and lowest TyG index tertiles were compared., Conclusions: The TyG index is an independent predictor of CAC progression., (© 2019 by the American Diabetes Association.)

Increased glycemic variability (GV) is an independent risk factor for cardiovascular complications in patients with diabetes. We evaluated the risk of future development of cardiovascular disease (CVD) and death according to GV in a general population without diabetes.We used the National Health Insurance Service, providing a population-based, nationwide database of Koreans. We included individuals without diabetes who underwent glucose measurement at least 3 times during 2002 to 2006. GV was calculated as standard deviation (SD) of fasting plasma glucose (FPG) levels. We observed development of CVD or all-cause death from 2007 to 2015, and also evaluated the mortality within 1 year after CVD.Among 3,211,319 people, we found 23,374 incident cases of myocardial infarction (MI), 27,705 cases of stroke, and 63,275 deaths during 8.3 years of follow-up. After multivariate adjustment, GV was found to be a significant predictor of MI, stroke and all-cause death for their highest quartile, with corresponding hazard ratios (HR) of 1.08 (95% confidence interval, CI 1.04-1.11), 1.09 (95% CI 1.06-1.13), and 1.12 (95% CI 1.10-1.15), respectively. The risk of death increased more in those who had both impaired fasting glucose and the highest quartile of GV (HR 1.24 [95% CI 1.21-1.28]). Moreover, early death rate after 1 year of CVD was higher in the highest quartile of GV compared to the lowest quartile (HR 1.21 [95% CI 1.03-1.41]).Long-term FPG variation was independently associated with CVD and mortality in a general population without diabetes.

We investigated associations between breastfeeding duration and number of children breastfed and type 2 diabetes mellitus (T2DM) and glycemic control among parous women. We performed a cross-sectional analysis of data for 9,960 parous women from the Korea National Health and Nutritional Examination Survey (2010 to 2013). Having ever breastfed was inversely associated with prevalent T2DM (adjusted odds ratio [OR], 0.60; 95% confidence interval [CI], 0.42 to 0.87). All ranges of total and average breastfeeding duration showed inverse associations with T2DM. Even short periods of breastfeeding were inversely associated with T2DM (adjusted OR, 0.61; 95% CI, 0.38 to 0.99 for a total breastfeeding duration ≤12 months; adjusted OR, 0.65; 95% CI, 0.42 to 0.99 for an average breastfeeding duration per child ≤6 months). A longer duration of breastfeeding was associated with better glycemic control in parous women with T2DM ( P trend=0.004 for total breastfeeding duration; P trend <0.001 for average breastfeeding duration per child). Breastfeeding may be associated with a lower risk of T2DM and good glycemic control in parous women with T2DM. Breastfeeding may be a feasible method to prevent T2DM and improve glycemic control., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

Objective- We examined the association of cardiovascular health (CVH) metrics with the development and progression of coronary artery calcium (CAC) among apparently healthy adults. Approach and Results- This cohort study included 65 494 men and women 30 years of age and older free of cardiovascular disease at baseline who underwent a comprehensive exam including CAC scoring. CVH metrics were defined according to the American Heart Association Life's Simple 7 metrics based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. CVH scores range from 0 (all metrics considered unhealthy) to 7 (all metrics considered healthy). Participants were followed-up for a maximum of 6.6 years. Compared with participants with ideal CVH scores 0-1, the multivariable-adjusted difference in the change in geometric means of CAC scores over 5 years of follow-up were -0.40 (-0.62 to -0.19), -0.83 (-1.03 to -0.63), -1.06 (-1.25 to -0.86), -1.22 (-1.42 to -1.03), and -1.05 (-1.42 to -0.69) in participants with ideal CVH scores 2, 3, 4, 5, and 6-7, respectively. The inverse association between CVH scores and progression of CAC was observed both in participants with no CAC and in those with CAC detectable at baseline. Conclusions- A higher ideal CVH metrics score was strongly associated with a lower prevalence of CAC and with lower progression of CAC in males and females in a large cohort of healthy adults. Our findings suggest that maintaining a healthy life habits could help reduce the development and progression of subclinical atherosclerosis and ultimately prevent clinically cardiovascular event.

Background: Glycosylated hemoglobin (HbA1c) has been recommended as a diagnostic test for prediabetes and diabetes. Here, we evaluated the level of agreement between diagnoses based on fasting plasma glucose (FPG) versus HbA1c levels and determined optimal HbA1c cutoff values for these diseases in youth and young adults., Methods: The study included 7,332 subjects ( n =4,129, aged 10 to 19 years in youth group; and n =3,203 aged 20 to 29 years in young adult group) from the 2011 to 2016 Korea National Health and Nutrition Examination Survey. Prediabetes and diabetes were defined as 100 to 125 mg/dL (impaired fasting glucose [IFG]) and ≥126 mg/dL for FPG (diabetes mellitus [DM] by FPG [DM FPG ]), and 5.7% to 6.4% and ≥6.5% for HbA1c, respectively., Results: In the youth group, 32.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 72.2% with DM FPG had an HbA1c ≥6.5%. In the young adult group, 27.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 66.6% with DM FPG had an HbA1c ≥6.5%. Kappa coefficients for agreement between the FPG and HbA1c results were 0.12 for the youth group and 0.19 for the young adult group. In receiver operating characteristic curve analysis, the optimal HbA1c cutoff for IFG and DM FPG were 5.6% and 5.9% in youths and 5.5% and 5.8% in young adults, respectively., Conclusion: Usefulness of HbA1c for diagnosis of IFG and DM FPG in Koreans aged <30 years remains to be determined due to discrepancies between the results of glucose- and HbA1c-based tests. Additional testing might be warranted at lower HbA1c levels to detect IFG and DM FPG in this age group., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

Background: This study investigated the association between changes in anthropometric indices and fasting insulin levels among healthy adolescents and whether the association differed by baseline obesity status., Methods: This analysis was based on data collected for the JS High School study; 884 healthy adolescents aged 15 to 16 years followed up for 24 to 30 months were included. Changes in anthropometric indices and fasting insulin levels were computed as the difference between baseline and follow-up values. Multivariate linear regression models were used to determine the association between changes in anthropometric indices and fasting insulin levels. Based on body mass index (BMI)-for-age and waist circumference (WC)-for-age percentiles, participants were classified as normal weight (<85th percentile), overweight (85th percentile to <95th percentile), or obese (≥95th percentile)., Results: Changes in BMI, WC, waist-hip ratio, and waist-height ratio were significantly associated with changes in fasting insulin levels in both sexes ( P <0.05). In analyses stratified by baseline obesity status, the association between change in BMI and change in fasting insulin was significantly stronger in overweight (males: standardized β=1.136; females: standardized β=1.262) and obese (males: standardized β=1.817; females: standardized β=2.290) participants than in those with normal weight (males: standardized β=0.957; females: standardized β=0.976) at baseline. Results were similar for changes in WC., Conclusion: Changes in anthropometric indices were positively associated with fasting insulin level increases. Moreover, those who were overweight or obese at baseline had a higher absolute increase in fasting insulin levels per one standard deviation unit increase in anthropometric indices than adolescents with normal weight., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

Objective: Previous studies have evaluated the link between metabolic syndrome and obesity with impaired lung function, however findings have been controversial. We aimed to compare lung function among subjects with different metabolic health and obesity status., Methods: Total 10,071 participants were evaluated at the Health Promotion Center in Seoul St. Mary's Hospital between January 2012 and December 2014. Being metabolically healthy was defined as having fewer than three of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and abdominal obesity. Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses of pulmonary function were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically health obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO)., Results: Metabolically unhealthy subjects were more prone to decreased lung function compared with their metabolically healthy counterparts, regardless of obesity status. When multinomial logistic regression analysis was performed according to quartiles of forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV1) (% pred), after adjusting for age, sex, and smoking status, odds ratio (OR) for the lowest FVC and FEV1 (% pred) quartiles were significantly higher in MUHO subjects (1.788 [95% CI, 1.531-2.089] and 1.603 [95% CI, 1.367-1.881]) and lower in MHO subjects (0.768 [95% CI, 0.654-0.902] and 0.826 [95% CI, 0.700-0.976]) with MHNO group as the reference, when OR for highest FVC and FEV1 quartiles were considered as 1.0., Conclusion: Metabolic health is more closely associated with impaired lung function than obesity., Competing Interests: The authors have declared that no competing interests exist.

Aim: This study aimed to prospectively examine whether low normal glucose levels and hypoglycaemia are associated with increased mortality due to external causes, especially unintentional accidents., Methods: A total of 345,318 normoglycaemic Korean adults who had undergone health examinations during 2002-2003 were followed-up to 2013. To avoid potential biases related to glucose-lowering medication use, those with known diabetes or hyperglycaemia were excluded., Results: During 3.6 million person-years of follow-up, 1293 participants died because of unintentional accidents. Hazard ratios (HRs) for these accidental deaths were 1.26 (95% CI: 1.11-1.42), 1.60 (1.21-2.11) and 3.07 (1.37-6.85) for fasting serum glucose (FSG) levels of 70-79, 55-69 and <55mg/dL (3.9-4.4, 3.05-3.83 and <3.05mmol/L), respectively, compared with 80-99mg/dL (4.44-5.5mmol/L). FSG levels<80mg/dL were associated with an approximately 30% higher mortality due to accidents: specifically, 40% were non-fall-related injury; 50% were automobile-related; and 80% were motorcycle-related. The associations were weak (approximately 10% higher mortality, with P>0.05 for each cause) for deaths due to traffic accidents (pedestrians, pedal cyclists), falls, intentional self-harm and physical assault. The population attributable risks for FSG levels <80mg/dL were 10% (95% CI: 2-18%) for non-fall-related injury, 11% (6-17%) for car accidents and 17% (6-27%) for motorcycle accidents., Conclusion: FSG levels of 70-79mg/dL (3.9-4.4mmol/L) as well as <70mg/dL are risk factors for accidental death. Appropriate management of the impact of FSG levels <80mg/dL might reduce unintended deaths due to non-fall-related injury, and automobile and motorcycle accidents, by ≥10%., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: Although increasing evidence suggests the association between short-term variability of fasting plasma glucose (FPG) and diabetic complications or mortality, the impact of visit-to-visit variability of FPG on the development of type 2 diabetes (T2D) has not been evaluated., Research Design and Methods: Our analysis included 131,744 Korean men and women without diabetes using the Korean National Health Insurance System cohort with periodic health examination program. FPG variability was calculated using the coefficient of variation (FPG-CV), SD (FPG-SD), and variability independent of the mean (FPG-VIM)., Results: During the median follow-up time of 8.3 years, Kaplan-Meier curves demonstrated lower disease-free probability in the higher FPG variability group compared with the lower FPG variability group. Multivariable Cox proportional hazards analysis exhibited that the hazard ratio for incident T2D was 1.67 (95% CI 1.58-1.77, P < 0.001) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for confounding variables, including mean FPG. The association between FPG variability and the risk of T2D was consistent when modeling using FPG-SD and FPG-VIM in both normal and impaired fasting glucose groups. A 1 SD increase in the FPG-CV was associated with a 24% increased risk of T2D in the fully adjusted model., Conclusions: Increased variability of FPG is associated with the development of T2D independently of diverse risk factors., (© 2018 by the American Diabetes Association.)

Background: It is unclear whether elevated fasting serum glucose level and type 2 diabetes (T2DM) are associated with an increased risk of hepatocellular carcinoma (HCC), irrespective of obesity in patients with chronic hepatitis B., Patients and Methods: Our study population comprised 214,167 Korean men with chronic hepatitis B in the National Health Insurance Service (NHIS) database between January 2002 and December 2006. Data on new events of HCC were obtained by records of the NHIS during the follow-up. We used Cox proportional hazards models adjusted for sociodemographic, lifestyle, health status and clinical conditions to estimate the hazard ratio (HR) and 95% confidence intervals (95% CIs) of HCC associated with different categories of fasting serum glucose level and T2DM, using fasting serum glucose <90 mg/dL as reference., Results: During the 8 years of follow-up, there were 11,241 HCCs in men with chronic hepatitis B. Compared with the reference group, fasting serum glucose level of more than 140 mg/dL (HR = 1.46; 95% CI: 1.36-1.57; p < 0.001) and presence of T2DM (HR = 1.23; 95% CI: 1.15-1.34; p < 0.001) were associated with an increased risk of HCC after controlling for potential confounders. Significant association with fasting serum glucose and HCC was found for both non-obese (<25 kg/m 2 ) and obese (≥25.0 kg/m 2 ) patients (P trend  < 0.001)., Conclusion: In this cohort of men with chronic hepatitis B infection, elevated fasting serum glucose level and T2DM were significantly associated with an increased risk of HCC, regardless of obesity. Glycaemic control in men with chronic hepatitis B patients should be considered in clinical practice to prevent HCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The effect of change in blood glucose levels on the risk of cardiovascular disease among individuals without diabetes is currently unclear. We aimed to examine the association of change in fasting serum glucose with incident cardiovascular disease and all-cause mortality among representative large population., Methods: We analyzed the data from retrospective cohort of Korean National Health Insurance Service. In total, 260,487 Korean adults aged over 40 years, without diabetes mellitus and cardiovascular disease at baseline measured change in fasting serum glucose according to the criteria of impaired and diabetic fasting glucose status: normal fasting glucose (NFG, fasting glucose: < 100 mg/dL), impaired fasting glucose (IFG, fasting glucose: 100.0-125.9 mg/dL), and diabetic fasting glucose (DFG, fasting glucose: ≥ 126.0 mg/dL). Compared to the persistently unchanged group (i.e. NFG to NFG or IFG to IFG), Cox proportional hazards regression analyses were performed in the changed group to obtain the hazards ratio (HR) with 95% confidence interval (CI) for the subsequent median 8-year myocardial infarction, stroke, and all-cause mortality., Results: Compared to individuals with persistent NFG (i.e., NFG to NFG), individuals who shifted from NFG to DFG had an increased risk of stroke (HR [95% CI]: 1.19 [1.02-1.38]) and individuals who shifted from NFG to IFG or DFG had increased risks of all-cause mortality (HR [95% CI]: 1.08 [1.02-1.14] for NFG to IFG and 1.56 [1.39-1.75] for NFG to DFG). Compared to individuals with persistent IFG, individuals who shifted from IFG to DFG had an increased risk of MI and all-cause mortality (HR [95% CI]: 1.65 [1.20-2.27] and 1.16 [1.02-1.33], respectively)., Conclusions: Increasing fasting glucose in non-diabetic population is associated with risks of the MI, stroke, and all-cause mortality, which is more rapid, more severe.

Background: Whether type 2 diabetes is cause or consequence, or both, of pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of fasting blood glucose (FBG), we examined the temporal relationship between hyperglycemia and PaC incidence., Methods: We conducted a nested case-control study of 278 cases and 826 matched-controls from the Korean National Health Insurance Service-Health Screening Cohort. Over 11 years before index date (date of PaC diagnosis for cases), all participants had at least one FBG measurement in each of the three time windows: - 11 to - 8, - 7 to - 4, and - 3 to 0 years. Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and 95% confidence intervals (CIs) for hyperglycemia in the overall period and at each interval; for major long-term patterns of FBG across the three intervals (recent-onset, medium-term, and long-standing hyperglycemia)., Results: Higher FBG over the past 11 years was associated with an increased odds of PaC (p trend  < .0001), with recent FBG more predictive of PaC than distant FBG. By FBG assessed in the - 3 to 0 interval, OR was 1.97 (95% CI 1.32-2.93) for 110-125 mg/dL and 3.17 (95% CI 2.09-4.80) for ≥ 126 mg/dL. By long-term patterns of FBG, compared to consistent normoglycemia, OR was 2.02 (95% CI 1.24-3.31) for long-standing hyperglycemia and 3.38 (95% CI 1.87-6.13) for recent-onset hyperglycemia. These associations were more pronounced among never-smokers than ever-smokers (p interaction  = .06)., Conclusion: Recent-onset hyperglycemia may be an early manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a moderate etiologic factor for PaC.

Background: The changes in insulin resistance and insulin secretion and their association with changes in glucose regulation status in Asians with prediabetes remain uncertain., Materials and Methods: We included Korean adults (aged 20-79 years) with prediabetes who underwent routine medical check-ups at a mean interval of 5 years. Prediabetes was defined as fasting plasma glucose (FPG) 5.6-6.9mmol/l or HbA1c 5.7-6.4% (39-46mmol/mol). Insulin resistance (HOMA-IR) and beta-cell function (HOMA-%B) indices were assessed by homeostasis model assessment. Incident diabetes was defined as FPG ≥ 7.0mmol/l, HbA1c ≥ 6.5% (48mmol/mol), or initiation of antidiabetic medications., Results: Among the 7,208 participants with prediabetes, 4,410 (61.2%) remained as prediabetes (control group), 2,123 (29.5%) reverted to normal glucose regulation (regressors), and 675 (9.4%) progressed to type 2 diabetes (progressors) after 5 years. Compared with the control group, the progressors had higher baseline HOMA-IR (2.48 ± 1.45 versus 2.06 ± 1.20, P < 0.001), but similar baseline HOMA-%B (74.6 ± 47.6 versus 73.1 ± 41.4, P=0.68). By contrast, the regressors had lower baseline HOMA-IR (1.98 ± 1.14 versus 2.06 ± 1.20, P = 0.035) but higher baseline HOMA-%B (77.4 ± 43.1 versus 73.1 ± 41.4, P = 0.001). After 5 years, the progressors showed a 31% increase in HOMA-IR (2.48 ± 1.45 versus 3.24 ± 2.10, P < 0.001) and 15% decrease in HOMA-%B (74.6 ± 47.6 versus 63.8 ± 40.4, P < 0.001), whereas the regressors showed 29% decrease in HOMA-IR (1.98 ± 1.14 versus 1.41 ± 0.78, P < 0.001) and 4% increase in HOMA-%B (77.4 ± 43.1 versus 80.2 ± 47.9, P = 0.010)., Conclusions: Although increase in insulin resistance and decrease in beta-cell function both contributed to the progression to type 2 diabetes from prediabetes, longitudinal change in insulin resistance was the predominant factor in Koreans., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

The prevalence and incidence of type 2 diabetes, impaired fasting glucose, and co-morbidities from 2006 to 2013 in the population aged ≥30 years were estimated using the Korean NHIS database. The prevalence of type 2 diabetes increased 0.2-0.5% annually, from 5.6% in 2006 to 8% in 2013. The prevalence of type 2 diabetes was higher in men than in women and increased with age. The incidence of type 2 diabetes was 0.81% in 2013 and was 1.4 times higher in men than in women and increased with age. An overall decrease in the incidence rate occurred from 2006 to 2013(from 0.95 to 0.81%), which was mirrored in all age groups except the 30-39-year-old group. The prevalence of IFG was 25% in 2013. The prevalence of hypertension(62.5 vs 16.9%) and dyslipidemia(49.5 vs 9.7%) were more prevalent in patients with type 2 diabetes compared to non-diabetic cases. This study shows that type 2 diabetes is both common and increasing and that one-quarter of the Korean adult population has IFG. We also confirmed that the prevalence of hypertension and dyslipidemia are 3.7-fold and 5.1-fold higher, respectively, in diabetic patients than in non-diabetic adults.

Background: Pregabalin binds to the α2δ auxiliary subunit of voltage-gated calcium channels, which are widely distributed throughout the central and peripheral nervous systems and modulate calcium-dependent neurotransmitter release. Pregabalin is indicated for the treatment of peripheral and central neuropathic pain, partial seizures with or without secondary generalization, and treatment of generalized anxiety disorder (GAD)., Objective: The purpose of this study was to assess the bioequivalence of two different formulations of pregabalin 150-mg capsules in healthy Korean male subjects under fasting conditions., Methods: This bioequivalence study was based on an open-label, single-dose, randomized, 2-period, 2-sequence crossover design with a washout period of 7 days. Blood samples for pharmacokinetic (PK) evaluation were collected up to 24 hours postdose. Plasma concentrations of pregabalin were determined using a validated LC-MS/MS method. PK parameters were determined using noncompartmental analysis. Bioequivalence was assumed if the 90% confidence intervals (CIs) for the test/reference ratios of log-transformed C max and AUC last values met the bioequivalence criteria specified by Korean regulatory guidelines (90% CI 0.8 - 1.25)., Results: The extent of exposure in terms of AUC last amounted to 26,018.3 - 3,580.8 µg×h/L for the test formulation and 25,680.2 ± 3,083.6 µg×h/L for the reference formulation. C max reached values of 4,782.7 ± 1,124.2 µg/L and 4,654.0 ± 911.4 µg/L for the test product and reference product, respectively. The geometric mean ratio and 90% CIs of the test product to the reference product were 1.0132 (0.9862 - 1.0351) for AUC last and 1.0153 (0.9351 - 1.1044) for C max , which were well within the range necessary to establish bioequivalence (90% CI 0.8 - 1.25)., Conclusions: The bioequivalence between test and reference formulations under fasting conditions was confirmed both in terms of the rate and extent of absorption.
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Background: The aim of the present study was to compare the association between cardiovascular diseases (CVD) and prediabetes defined by either fasting plasma glucose (FPG), HbA1c, or their combination in a Korean population., Methods: In all, 76 434 South Koreans who voluntarily underwent a general health examination in the Health Screening & Promotion Center (Asan Medical Center) were analyzed after excluding patients with a previous history of CVD. Cardiovascular events and death due to CVD during a median follow-up period of 3.1 years (interquartile range 1.9-4.3 years) were identified from the Nationwide Health Insurance Claims Database and death certificates using ICD-10 codes., Results: Age- and sex-adjusted hazard ratios (HRs) for overall CVD events were significantly greater for subjects with prediabetes defined by FPG only (HR 1.19; 95% confidence interval [CI] 1.08-1.31), HbA1c only (HR 1.28; 95% CI 1.16-1.42), and combined criteria (HR 1.20; 95% CI 1.09-1.32) compared with the normoglycemic group. After adjusting for multiple conventional risk factors (e.g. hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking status, family history of CVD, and BMI), the HRs for overall CVD were significantly increased only for participants with prediabetes defined by HbA1c. Age- and sex-adjusted HRs for major ischemic heart disease events were significantly increased for subjects with prediabetes defined either by HbA1c or combined criteria. Similarly, age- and sex-adjusted HRs for percutaneous coronary intervention were significantly higher for subjects with prediabetes defined by HbA1c only. For diabetes, the multivariate-adjusted HRs for all outcomes were significantly increased by all three criteria., Conclusions: Adding an HbA1c criterion when defining prediabetes in Koreans can help identify individuals with an increased risk of CVD., (© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objectives: Numerous studies have demonstrated that fasting serum glucose (FSG) levels and certain single-nucleotide polymorphisms (SNPs) are related to an increased risk of colorectal cancer (CRC); however, their combined effects are still unclear., Methods: Of a total of 144,527 men and women free of cancer at baseline, 317 developed CRC during 5.3 years of follow-up. A case-cohort study (n=1,691) was used, consisting of participants with a DNA sample available. Three well-known SNPs (rs3802842, rs6983267, rs10795668) were genotyped. Hazard ratios (HR) and 95% confidence intervals (CI) of CRC, colon and rectal cancer were calculated, with the Cox proportional hazard models., Results: The crude incidence rates per 100,000 person-years were 41.1 overall, 48.4 for men, and 29.3 for women. Among participants with dysglycemia, SNPs rs3802842 and rs6983267 were both associated with an increased risk of CRC (HR, 3.2; 95% CI, 1.9 to 5.5 and HR, 1.8; 95% CI, 1.1 to 3.1, respectively) and rectal cancer (HR, 3.4; 95% CI, 1.8 to 6.6 and HR, 3.3; 95% CI, 1.6 to 7.1, respectively). The interaction effect of dysglycemia and SNPs was positive, that is, resulted in an elevated risk of CRC, but was not statistically significant., Conclusions: This study demonstrates that both high FSG and certain SNPs are major risk factors for CRC and rectal cancer but that they did not interact synergistically. The difference in effect size of the SNPs according to CRC subtype (i.e., colon or rectal cancer) and presence of dysglycemia merits further research.

Aim: To investigate the association between liver markers and the risk of type 2 diabetes (T2DM) and impaired fasting glucose (IFG)., Methods: A total of 8863 participants (3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2011). The associations of serum liver markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT, and gamma-glutamyltransferase (GGT) with T2DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers., Results: The prevalence of T2DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the risk of T2DM at 3.21 (95%CI: 1.829-5.622, P < 0.001) in men and 4.60 (95%CI: 3.217-6.582, P < 0.001) in women. Men and women with the highest AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG., Conclusion: Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2DM and IFG.

Background: Insulin resistance has an important role in the pathogenesis of hypertension. We hypothesized that impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) which represents insulin resistance would predict the development of hypertension., Methods: A total of 4,039 subjects without hypertension or diabetes (1,847 men and 2,192 women; age 49.9±8.2 years), from the Ansan-Ansung cohorts within the Korean Genome Epidemiology Study, were enrolled in 2001-2002 and restudied in 2005-2006. The association between the incidence of hypertension and IFG, IGT, or other metabolic factors was studied., Results: During the 4-year follow-up period, 582 of the 4,039 subjects developed hypertension. At baseline, the prevalence of abdominal obesity, dyslipidemia, and IGT was higher in subjects who became hypertensive compared to those that remained normotensive. The prevalence of IFG was not significantly different between the 2 groups. In a multivariate analysis, abdominal obesity and high serum triglyceride were significant risk factors for the development of hypertension. Neither IFG nor IGT were significantly associated with new-onset hypertension. Although the risk of hypertension was higher with the number of metabolic components present at baseline, IFG and IGT were not significant components compared to other metabolic components, especially when abdominal obesity was taken into account., Conclusions: While metabolic syndrome components related to insulin resistance present at baseline are important risk factors of hypertension, we conclude that coexisting metabolic component, mainly abdominal obesity, rather than IFG and IGT have more predictive value for determining the development of hypertension in a Korean population., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To determine whether the TyG index, a product of the levels of triglycerides and glucose, may be a valuable marker for identifying metabolically obese but normal weight (MONW) or metabolically healthy but obese (MHO) individuals., Design and Subjects: A total of 17 029 nondiabetic subjects (7185 men and 9844 women) were selected from the Korea National Health and Nutrition Examination Survey conducted in 2008-2010. Individuals with a normal body mass index (BMI) (≥18·5 and <23 kg/m(2) ) and the highest quartile of the homoeostasis model assessment of insulin resistance (HOMA-IR) were classified as MONW. Individuals with obesity (BMI ≥25 kg/m(2) ) and the lowest quartile of HOMA-IR were classified as MHO., Measurements: The TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]., Results: The levels of the TyG index paralleled with various metabolic risk parameters. The index was significantly higher in the MONW group and lower in the MHO group when compared with the non-MONW group and the non-MHO group, respectively. The odds ratios (ORs) of being categorized into the MONW group were approximately fourfold higher in the highest vs lowest quartiles of the TyG index (3·999: 95% CI, 2·508-6·376 in men; 4·737: 95% CI, 3·418-6·565 in women) among normal weight subjects. Conversely, there was a stepwise decrease in the OR of being categorized into the MHO group across the TyG index quartiles among obese subjects., Conclusions: These data highlight the value of the TyG index in discriminating those subjects with higher risks of metabolic diseases., (© 2014 John Wiley & Sons Ltd.)

Background: We investigated the association between flavonoid intake and type 2 diabetes mellitus (T2DM) risk factors including serum fasting glucose, insulin level, and insulin resistance., Methods: A total of 4186 participants who were involved in the 2007-2009 Korean National Health and Nutrition Examination Survey were examined. The participants were divided into 2 groups by fasting plasma glucose (FPG) as follows: normal fasting glucose (NFG; FPG <100 mg/dl) and impaired fasting glucose (IFG) groups (FPG ≥100 mg/dl)., Results: In the IFG group, body weight, body mass index, and waist circumference were increased. Fasting insulin level and homeostasis model assessment estimate of insulin resistance as markers of insulin resistance were higher in the IFG group. Intakes of energy and nutrients, including protein, fat, carbohydrate, crude fiber, vitamin C, calcium, phosphorus, and iron, did not differ between the 2 groups. For the male subjects, the energy-adjusted flavanone intake was lower in the IFG group than in the NFG group. Insulin and insulin resistance were inversely correlated with intakes of flavones and flavonols among the male subjects., Conclusion: These findings can provide valuable information for further development of appropriate strategies for diabetes prevention in Korea., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Microalbuminuria is significantly associated with long-term prognosis in the general population as well as in diabetic patients. It is well known that insulin resistance (IR) can induce microalbuminuria, but an elevated fasting insulin level, which is an early clinical manifestation of IR, as a risk factor for microalbuminuria has not been clarified, so we investigated the association between fasting insulin level and the development of microalbuminuria in a general population., Methods and Results: A total of 1,192 non-diabetic Korean men without microalbuminuria in 2005 were followed until 2010. They were categorized into 3 groups according to their fasting insulin levels and monitored for the development of microalbuminuria. The incidence of microalbuminuria was compared among groups, and Cox proportional hazards models were used to calculate the hazard ratios for microalbuminuria according to the fasting insulin levels. During 4,013.0 person-years of follow-up, 51 incident cases of microalbuminuria developed between 2006 and 2010. The incidence of microalbuminuria increased in proportion to the fasting insulin levels (tertile 1: 1.8%, tertile 2: 4.5%, tertile 3: 6.5%, P<0.001). Hazard ratios for microalbuminuria also increased in proportion to the fasting insulin levels [tertile 1: reference, tertile 2: 2.44 (1.01-5.89), tertile 3: 3.30 (1.40-7.78), respectively, P for trend 0.013]., Conclusions: Elevated fasting insulin level was associated with the future development of microalbuminuria.

Objective: This study was performed to compare the pharmacokinetic properties and relative bioavailability of two isosorbide-5-mononitrate (5-ISMN) sustained-release drugs in healthy Korean subjects under fasting and fed conditions., Methods: A total of 60 healthy volunteers (30 each in the fasting and fed arms of the study) were enrolled in the study and were randomized to treatment. After the administration of a single dose of one of the investigational products, blood samples were collected at specific time intervals from 0 to 36 hours. The plasma concentrations of 5-ISMN were measured by LC-MS/MS. The pharmacokinetic parameters were calculated, and the 90% confidence intervals (CIs) of the geometric mean ratio (test/reference) of the parameters were obtained by analysis of variance on logarithmically transformed data., Results: The corresponding 90% CIs of AUClast and Cmax for the test/reference geometric mean ratio were 90.75 - 98.44% and 92.28 - 98.33%, respectively, under fasting conditions. In the fed state study, the 90% CIs for the geometric mean ratio of test to reference drugs were 94.79 - 103.33% for AUClast and 99.86 - 108.02% for Cmax., Conclusion: The test product is equivalent to the reference product in subjects under fasting and fed conditions within the Korean regulatory bioequivalence criteria. Both formulations were safe and well tolerated, and there were no noteworthy differences in the safety profiles between the test and reference drugs.

Introduction: The incidence of colorectal cancer (CRC) is steadily increasing worldwide. Numerous studies have demonstrated that diabetes mellitus is related to an increased risk of CRC; however, the association between impaired fasting glucose and CRC is unclear. Therefore, we evaluated the correlation between fasting serum glucose (FSG) levels and the incidence of CRC, which can be used to develop novel methods for preventing CRC., Methods: A total of 175,677 individuals from the Korean Metabolic Syndrome Research Initiative study were enrolled between 2004 and 2011. The incidence of CRC was assessed during a mean follow-up of 4.7 years. Hazard ratios (HR) for CRC according to FSG levels were calculated with the Cox proportional hazard model adjusted for age, sex, body mass index, smoking status, alcohol consumption, and regular exercise., Results: The risk of developing CRC in subjects with high FSG was significant (HR, 1.45; 95% confidence interval [CI], 1.10-1.90), and the risk was higher in men (HR, 1.51; 95% CI, 1.12-2.05). The HR of rectal cancer, but not colon cancer, was significantly higher both in the total population and in men in the high FSG group., Conclusions: The incidence of CRC positively correlated with FSG levels in men. Rectal cancer incidence was especially correlated with high FSG in the site-specific analysis. Therefore, serum glucose levels maybe a potential marker of colorectal cancer. Early detection and intervention for controlling elevated glucose levels may be indicated as a way to prevent carcinogenesis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Vitamin D deficiency is a common condition that is associated with diabetes and insulin resistance. However, the association between vitamin D and insulin resistance has not been fully studied, especially in the general adolescent population. Therefore, we assessed the association between serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance among apparently healthy Korean adolescents., Methods: A total of 260 (135 male and 125 female) adolescents in a rural high school were assessed for serum 25(OH)D, fasting plasma glucose, and insulin. All of the participants were aged 15 to 16 years old, and without known hypertension or diabetes. Serum 25(OH)D was analyzed both as a continuous and categorical variable in association with insulin resistance. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Increased insulin resistance was operationally defined as a HOMA-IR value higher than the sex-specific 75th percentile., Results: In male adolescents, every 10 ng/ml decrease in 25(OH)D level was associated with a 0.25 unit increase in HOMA-IR (p = 0.003) after adjusting for age and BMI. Compared to those in the highest quartile, male adolescents in the lowest 25(OH)D quartile were at significantly higher risk for insulin resistance: unadjusted odds ratio 4.06 (95% CI, 1.26 to 13.07); age and BMI adjusted odds ratio 3.59 (95% CI, 1.03 to 12.57). However, 25(OH)D level, either in continuous or categorical measure, was not significantly associated with insulin resistance among female adolescents., Conclusions: This study suggests that serum 25(OH)D level may be inversely associated with insulin resistance in healthy male adolescents.

Objectives: For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets., Materials and Methods: This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg × 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from predose to 48 hours after dosing. Tolerability assessments were performed throughout the study., Results: Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the Cmax and AUClast were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the Cmax and AUClast were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged tmax for metformin was observed. These results are similar to the effects of food on each component., Conclusion: The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

Background: Studies have investigated clinical association between fasting insulin level and hypertension. However, it is still debatable whether elevated fasting insulin actually increases the risk of hypertension with the passage of time. Thus, this study was aimed at investigating the association between baseline fasting insulin level and the development of hypertension., Methods: 25,062 normotensive, non-diabetic Korean men participating in a medical health check-up program were followed up from 2005 until 2010. They were divided into 4 groups according to baseline fasting insulin levels (first quartile-fourth quartile). The incidence of hypertension was compared among 4 groups, and Cox proportional hazards model was used to determine if hypertension was associated with higher baseline fasting insulin level., Results: The incidence of hypertension increased according to the baseline fasting insulin level (first quartile: 13.3%, second quartile: 15.4%, third quartile: 17.5%, fourth quartile: 23.2%, P<0.001). Even after adjusting for multiple covariates, the HRs (95% CI) for hypertension were higher for the second (1.12; 0.96-1.31), third (1.39; 1.20-1.62) and fourth quartile group (1.75; 1.51-2.03), compared to the first quartile group, respectively (P for trend<0.001)., Conclusion: The risk of hypertension was in proportion to the baseline fasting insulin level. In addition, hyperinsulinemia was an independent risk factor for the future development of hypertension. These findings suggest the value of fasting insulin level as an early predictor of hypertension., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the association between fasting plasma glucose level and pulmonary function., Research Design and Methods: Nutritional information, pulmonary function data, and laboratory test data from 9,223 subjects from the fourth Korea National Health and Nutrition Examination Survey were examined. The participants were divided into five groups according to fasting plasma glucose (FPG) level: normal fasting glucose (NFG)1, FPG <90 mg/dl; NFG2, FPG 90-99 mg/dl; impaired fasting glucose (IFG)1: FPG 100-109 mg/dl; IFG2, FPG 110-125 mg/dl; and diabetes, FPG ≥126 mg/dl and/or current anti-diabetes medications., Results: After adjustment for several variables, the percentage of predicted forced vital capacity(FVC%) decreased with increasing fasting plasma glucose level in both sexes[men: (mean ± SEM) 92.0±0.3 in NFG1; 91.9±0.3 in NFG2; 92.0±0.4 in IFG1; 90.2±0.7 in IFG2; and 89.9±0.5 in diabetes, P = 0.004; women: 93.7±0.3 in NFG1; 93.7±0.3 in NFG2; 93.1±0.5 in IFG1; 91.1±0.9 in IFG2; and 90.7±0.6 in diabetes, P<0.001]. A logistic regression analysis found that IFG2 and diabetes were independently associated with the lowest quintile of predicted FVC% (IFG2: odds ratio [95%CI], 1.50 [1.18-1.89], P = 0.001; diabetes: 1.56 [1.30-1.88], P<0.001) using NFG1 as a control., Conclusions: The current data suggest that forced vital capacity may begin to decrease in the higher range of IFG.

Most recently, 1-h hyperglycemia has been recognized as an additional risk factor for type 2 diabetes. To date, previous genome-wide association studies for glycemic traits have a limited impact on the fasting state and 2-h plasma glucose level in an oral glucose challenge. To identify genetic susceptibility in different stages of glucose tolerance, we performed a meta-analysis for glycemic traits including 1-h plasma glucose (1-hPG) from 14 232 non-diabetic individuals in the Korean population. Newly implicated variants (MYL2, C12orf51 and OAS1) were found to be significantly associated with 1-hPG. We also demonstrated associations with gestational diabetes mellitus. Our results could provide additional insight into the genetic variation in the clinical range of glycemia.