Ji Eun Jun

The association between glycemic variability and diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes

BackgroundIt is presently unclear whether glycemic variability is associated with diabetic cardiovascular autonomic neuropathy (CAN). The aim of this study was to examine whether short- and/or long-term glycemic variability (GV) contribute to CAN.MethodsA total of 110 patients with type 2 diabetes who underwent three-day continuous glucose monitoring (CGM) completed five standardized autonomic neuropathy tests. Short-term GV was measured by the standard deviation (SD), coefficient of variation (CV) of glucose, and the mean amplitude of glycemic excursions (MAGE) in CGM. HbA1c variability was calculated from the intrapersonal SD, adjusted SD, and CV of serial HbA1c over 2-year period. CAN was defined as the presence of at least two abnormal parasympathetic function tests. The severity of CAN was evaluated by total scores of five autonomic function tests.ResultsIn univariate analysis, not only SD and CV in CGM but also all parameters of HbA1c variability were significantly higher in the patients with CAN (nu2009=u200947, 42.7xa0%) than in those without CAN. In multivariate analysis, CV (Odds ratio [OR] 1.07, 95xa0% confidence interval [CI] 1.01–1.13; pu2009=u20090.033), but neither SD nor MAGE in CGM, independently correlated with the presence of CAN. All parameters of HbA1c variability, such as SD of HbA1c (OR 12.10 [95xa0% CI 2.29–63.94], pu2009=u20090.003), adjusted SD of HbA1c (OR 17.02 [95xa0% CI 2.66–108.86], pu2009=u20090.003), and log CV of HbA1c (OR 24.00 [95xa0% CI 3.09–186.48], pu2009=u20090.002), were significantly associated with the presence of CAN. The patients with higher HbA1c variability had an increased risk of advanced CAN.ConclusionCV in CGM and all parameters of HbA1c variability were independently associated with the presence of CAN in patients with inadequately controlled type 2 diabetes requiring CGM.

Association Between Changes in Thyroid Hormones and Incident Type 2 Diabetes: A Seven-Year Longitudinal Study

BACKGROUNDnThyroid hormones are important regulators of glucose homeostasis. However, the association between thyroid hormones within the reference range and type 2 diabetes mellitus (T2DM) remains unclear. The aim of this study was to clarify the incidence of T2DM according to the baseline levels and changes of thyrotropin (TSH) and thyroid hormones (free thyroxine and triiodothyronine) in euthyroid subjects.nnnMETHODSnAmong the participants who consecutively underwent thyroid function tests between 2006 and 2012 through a yearly health checkup program, 6235 euthyroid subjects (3619 men and 2616 women) without T2DM were enrolled in the study. The change in each hormone was calculated by subtracting the baseline value from the level at the end of follow-up or one year before the diagnosis of diabetes.nnnRESULTSnDuring 25,692 person-years of follow-up, there were 229 new cases of T2DM. After full adjustment for potential confounders including HbA1c and fasting glucose in Cox proportional hazards models, the individuals in the highest tertile of TSH change (2.5-4.2u2009μIU/mL) had a greater risk of incident T2DM (hazard ratio [HR]u2009=u20091.44 [confidence interval (CI) 1.04-1.98], pu2009=u20090.027) in comparison with individuals in the lowest tertile (-4.1 to -0.5u2009μIU/mL). Simultaneously, the highest tertile of triiodothyronine change (16.3-104.7u2009ng/dL) and free thyroxine change (0.2-1.6u2009ng/dL) conferred protective effects against diabetes (HRu2009=u20090.60 [CI 0.43-0.85], pu2009=u20090.002, and HRu2009=u20090.34 [CI 0.24-0.48], pu2009<u20090.001, respectively) compared with those in the lowest tertile (-76.5 to -1.8u2009ng/dL and -0.6 to 0.0u2009ng/dL, respectively). These associations remained significant when each of the hormones was analyzed as a continuous variable. However, baseline levels or tertiles of TSH and thyroid hormones were not associated with the risk of diabetes.nnnCONCLUSIONSnIndividual changes in TSH and thyroid hormones, even within the normal reference range, were an additional risk factor of incident T2DM.

Glycated albumin and its variability as an indicator of cardiovascular autonomic neuropathy development in type 2 diabetic patients

BackgroundWe investigated whether glycated albumin (GA) and its variability are associated with cardiovascular autonomic neuropathy (CAN) and further compared their associations with glycated hemoglobin (HbA1c).MethodsThis retrospective longitudinal study included 498 type 2 diabetic patients without CAN. CAN was defined as at least two abnormal results in parasympathetic tests or presence of orthostatic hypotension. The mean, standard deviation (SD), and coefficient of variance (CV) were calculated from consecutively measured GA (median 7 times) and HbA1c levels (median 8 times) over 2xa0years. Logistic regression analysis was used to compare the associations between CAN and GA- or HbA1c-related parameters. Receiver operating characteristic (ROC) curve analysis was used to compare the predictive power for CAN between GA- and HbA1c-related parameters.ResultsA total of 53 subjects (10.6%) developed CAN over 2xa0years. The mean, SD, and CV of GA or HbA1c were significantly higher in subjects with CAN. Higher mean GA and GA variability were associated with the risk of developing CAN, independent of conventional risk factors and HbA1c. In ROC curve analysis, the SD and CV of GA showed higher predictive value for CAN compared to the SD and CV of HbA1c, whereas the predictive value of mean GA did not differ from that of mean HbA1c. The mean, SD, and CV of GA showed additive predictive power to detect CAN development along with mean HbA1c.ConclusionsHigher serum GA and its variability are significantly associated with the risk of developing CAN. Serum GA might be a useful indicator for diabetic complications and can enhance HbA1c’s modest clinical prediction for CAN.

Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome

Aim Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults. Methods We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS. Results During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094–2.785) in men and 2.156 (95% CI 1.738–2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229–1.326) in men and 1.366 (95% CI 1.288–1.447) in women. Conclusions Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development of MetS.

Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome

Aim Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Methods Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. Results A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Conclusions Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

Relationship Between Relative Skeletal Muscle Mass and Nonalcoholic Fatty Liver Disease: A 7‐Year Longitudinal Study

Nonalcoholic fatty liver disease (NAFLD) has been associated with relative skeletal muscle mass in several cross‐sectional studies. We explored the effects of relative skeletal muscle mass and changes in relative muscle mass over time on the development of incident NAFLD or the resolution of baseline NAFLD in a large, longitudinal, population‐based 7‐year cohort study. We included 12,624 subjects without baseline NAFLD and 2943 subjects with baseline NAFLD who underwent health check‐up examinations. A total of 10,534 subjects without baseline NAFLD and 2631 subjects with baseline NAFLD were included in analysis of changes in relative skeletal muscle mass over a year. Subjects were defined as having NAFLD by the hepatic steatosis index, a previously validated NAFLD prediction model. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight–adjusted appendicular skeletal muscle mass, which was estimated by bioelectrical impedance analysis. Of the 12,624 subjects without baseline NAFLD, 1864 (14.8%) developed NAFLD during the 7‐year follow‐up period. Using Cox proportional hazard analysis, compared with the lowest sex‐specific SMI tertile at baseline, the highest tertile was inversely associated with incident NAFLD (adjusted hazard ratio [AHR] = 0.44, 95% confidence interval [CI] = 0.38‐0.51) and positively associated with the resolution of baseline NAFLD (AHR = 2.09, 95% CI = 1.02‐4.28). Furthermore, compared with the lowest tertile of change in SMI over a year, the highest tertile exhibited a significant beneficial association with incident NAFLD (AHR = 0.69, 95% CI = 0.59‐0.82) and resolution of baseline NAFLD (AHR = 4.17, 95% CI = 1.90‐6.17) even after adjustment for baseline SMI. Conclusion: Increases in relative skeletal muscle mass over time may lead to benefits either in the development of NAFLD or the resolution of existing NAFLD.

The effect of TSH change per year on the risk of incident chronic kidney disease in euthyroid subjects

The objective of this study is to evaluate the predictive values of baseline thyroid-stimulating hormone and the rate of thyroid-stimulating hormone change within the euthyroid state on the development of chronic kidney disease. We conducted a longitudinal study in 17,067 Korean adults with normal thyroid function and no history of thyroid disease. Incident chronic kidney disease was defined as an estimated glomerular filtration rate <60u2009ml/min/1.73u2009m2. The rate of thyroid-stimulating hormone change was determined by subtracting the baseline thyroid-stimulating hormone level from the thyroid-stimulating hormone level measured at the last visit prior to the diagnosis of chronic kidney disease or at the final visit in subjects without chronic kidney disease, divided by the observation period (years). Subjects were stratified into quintiles according to rates of thyroid-stimulating hormone change. During 86,583 person-years of follow-up (median follow-up 5.2 years), there were 561 incident cases of chronic kidney disease. The risk of incident chronic kidney disease was significantly higher in subjects with rapid increases (quintile 5) or decreases (quintile 1) in thyroid-stimulating hormone levels compared to the reference group (quintile 3). In fully adjusted models, the hazard ratios of quintiles 1 and 5 were 3.15 (95u2009% confidence interval 2.34 to 4.24; pu2009<u20090.001) and 3.37 (95u2009% confidence interval 2.52 to 4.51; pu2009<u20090.001), respectively. However, there was no significant association between baseline thyroid-stimulating hormone and risk of incident chronic kidney disease. The development of chronic kidney disease is associated with the rate of changes in thyroid-stimulating hormone level rather than with baseline thyroid-stimulating hormone levels.

TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects.

PurposeThyroid function is known to influence glucose metabolism, and thyroid-stimulating hormone is the most useful parameter in screening for thyroid dysfunction.Therefore, the aim of this study was to investigate the incidence of type 2 diabetes according to baseline thyroid-stimulating hormone level and thyroid-stimulating hormone change in euthyroid subjects.MethodsWe identified and enrolled 17,061 euthyroid subjects without diabetes among participants who had undergone consecutive thyroid function tests between 2006 and 2012 as a part of yearly health check-up program. Thyroid-stimulating hormone changes were determined by subtracting baseline thyroid-stimulating hormone level from thyroid-stimulating hormone level at 1 year before diagnosis of diabetes or at the end of follow-up in subjects who did not develope diabetes.ResultsDuring 84,595 person-years of follow-up, there were 956 new cases of type 2 diabetes. Cox proportional hazards models showed the risk of incident type 2 diabetes was significantly increased with each 1u2009μIU/mL increment in TSH after adjustment for multiple confounding factors (hazard ratiou2009=u20091.13, 95% confidence interval: 1.07–1.20, Pu2009<u20090.001). Compared with individuals in the lowest tertile (−4.08 to 0.34u2009μIU/mL), those in the highest thyroid-stimulating hormone change tertile (0.41–10.84u2009μIU/mL) were at greater risk for incident type 2 diabetes (hazard ratiou2009=u20091.25, 95% confidence interval: 1.05–1.48, P for trendu2009=u20090.011). However, baseline thyroid-stimulating hormone level and tertile were not associated with the risk for diabetes.ConclusionsProminent increase in thyroid-stimulating hormone concentration can be an additional risk factor for the development of type 2 diabetes in euthyroid subjects.

ApoB/ApoA-I ratio is independently associated with carotid atherosclerosis in type 2 diabetes mellitus with well-controlled LDL cholesterol levels.

Background/Aims This study aimed to investigate whether the apolipoprotein (Apo) B/ApoA-I ratio is associated with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM) subjects with low density lipoprotein cholesterol (LDL-C) levels less than 100 mg/dL. Methods This cross-sectional study included 845 subjects aged with T2DM 40 to 75 years who had visited Huh’s Diabetes Center in Seoul, Republic of Korea for CIMT measurement. Traditional fasting lipid profiles, ApoB and ApoA-I levels were examined. CIMT was measured at three points on the far wall of 1 cm long section of the common carotid artery in the proximity of the carotid bulb. The mean value of six measurements from right and left carotid arteries were used as the mean CIMT. In this study, carotid atherosclerosis was defined as having a focal plaque or diffuse thickening of the carotid wall (mean CIMT ≥ 1.0 mm) Results The prevalence of carotid atherosclerosis increased with ApoB/ApoA-I ratio. The ApoB/ApoA-I ratio, expressed as both quartiles (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21 to 3.79; p for trend = 0.014) and continuous values (OR, 10.05; 95% CI, 3.26 to 30.97; p < 0.001), was significantly associated with a higher risk for carotid atherosclerosis, regardless of conventional cardiovascular disease risk factors. The optimal ApoB/ApoA-I ratio cutoff value for detecting carotid atherosclerosis was 0.57, based on receiver operating characteristic curve analysis with a sensitivity of 58.0% and a specificity of 55.1%. Conclusions A high ApoB/ApoA-I ratio was significantly associated with carotid atherosclerosis in T2DM patients with LDL-C levels less than 100 mg/dL.

Baseline level and change in serum albumin concentration and the risk of incident type 2 diabetes

AIMSnWe aimed to determine whether baseline level and change in serum albumin concentration are predictive of future development of type 2 diabetes (T2D).nnnMETHODSnA total of 15,428 subjects (8764 men and 6664 women) without diabetes at baseline, aged 21-88years (mean age of 51.0years), were enrolled from a health screening program.nnnRESULTSnDuring the 5-year follow-up period, a total of 599 incident cases (3.9%) of T2D developed. Higher baseline serum albumin concentration was associated with increased T2D risk, independent of age, sex, or body mass index; however, this association was confounded and was not significant after further adjustment for other T2D risk factors. Compared with subjects in the lowest tertile of change in serum albumin concentration, subjects in the highest tertile showed a lower risk for T2D development, independent of risk factors for T2D and baseline serum albumin concentration [OR (95% CI), 0.30 (0.21-0.43), p for trend <0.001].nnnCONCLUSIONnHigher baseline serum albumin concentration was not an independent risk factor of future T2D, whereas an increase in serum albumin concentration was independently associated with a lower diabetes risk.