[show abstract][hide abstract] ABSTRACT: Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients.
Among type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated.
With greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (beta = 0.158, P = 0.093).
Higher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.
[show abstract][hide abstract] ABSTRACT: In diabetic nephropathy, transforming growth factor beta1 (TGFbeta1) is related to p38 mitogen-activated protein kinase (MAPK) that induces production of fibronectin in mesangial cells. We investigated the effects of alpha-lipoic acid (ALA), a potent antioxidant, on proteinuria and TGFbeta1-p38 MAPK-fibronectin pathway in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After ALA treatment for 5 weeks in OLETF rats at 30 weeks of age, plasma malondialdehyde, urinary protein excretion, renal cortical TGFbeta1, and fibronectin protein levels were decreased; and urinary protein excretion was positively correlated with renal cortical TGFbeta1 and fibronectin protein levels. Phospho-form but not total-form levels as well as fold activations of each protein consisting of p38 MAPK pathway were also attenuated. These results suggest that ALA ameliorates proteinuria by attenuating expressions of TGFbeta1 and fibronectin proteins, and these favorable effects are related to inhibition of phosphorylating activation of p38 MAPK pathway in renal cortex of OLETF rats.
Metabolism: clinical and experimental 06/2009; 58(5):616-23. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study aimed to investigate thyroid hormone (TH) status and its relationship with myocardial function as well as clinical and biochemical parameters in stress cardiomyopathy (CMP).
Forty-five patients with stress CMP (the patient group), 31 patients without stress CMP (the control II group), and 58 healthy subjects (the control I group) were included. Sick euthyroid syndrome (SES) was defined as low total triiodothyronine (T(3)) with normal TSH levels.
In the patient group at admission, prevalence of SES was 62.2%. Compared with the control I group, the patient group had a decrease in left ventricular ejection fraction (LVEF) and systolic blood pressure (BP) and an increase in troponin-I, CK-MB, and B-type natriuretic peptide (BNP) levels. Total T(3) levels were reduced, and anti-thyroid peroxidase antibody (anti-TPO Ab) positivity, C-reactive protein (CRP) and cortisol levels were elevated. Total T(3) levels were associated with acute physiology and chronic health evaluation II (APACHE II) score, LVEF, systolic BP, and cortisol levels in multivariate analysis. In the control II group, total T(3) levels were not associated with any variables. In the SES (n=28) and myocardial dysfunction (MDys, n=27) subgroups, increased APACHE II score and BNP levels as well as decreased LVEF and systolic BP were significant. Total T(3) levels were reduced, and CRP, cortisol and catecholamines levels were elevated. In the MDys subgroup, anti-TPO Ab positivity and titer were increased.
These results suggest that total T(3) levels may be associated with myocardial contractility, clinical severity, and cortisol levels. Thyroid autoimmunity may influence myocardial contractility in stress CMP.
European Journal of Endocrinology 03/2009; 160(5):799-806. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: The use of a real time continuous glucose monitoring system (RT-CGM) was studied as a behavior modification tool and the effectiveness of a RT-CGM in glucose control for patients with type 2 diabetes was determined.
We conducted a prospective, open-label, randomized, controlled clinical trial in 65 patients with poorly controlled type 2 diabetes (8.0</=HbA1c</=10%) over a 3-month period. The intervention group was monitored monthly with a RT-CGM (three days at a time for 3 months) and the control group continued self-monitoring blood glucose (SMBG) at least four times a week for 3 months.
The HbA1c of the RT-CGM group was significantly reduced after 12 weeks compared with the SMBG group (9.1+/-1.0% to 8.0+/-1.2% vs. 8.7+/-0.7% to 8.3+/-1.1%, respectively; P=0.004). In the RT-CGM group, there was a significant reduction in total daily calorie intake, weight, body mass index (BMI), and postprandial glucose level, and a significant increase in total exercise time per week after 3 months.
We demonstrated that the RT-CGM was useful in modifying a patient's diet and exercise habits and could induce better glycemic control than SMBG for patients with type 2 diabetes.
Diabetes research and clinical practice 09/2008; 82(1):73-9. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults.
One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography.
Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62.8 +/- 16.0 mg/l vs. 51.7 +/- 14.6 mg/l, P < 0.0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0.0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0.3097, P = 0.0002).
Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.
[show abstract][hide abstract] ABSTRACT: Even though visfatin has been suggested as a proinflammatory adipokine, there are few studies of the relationship between plasma visfatin concentrations and proinflammatory markers in the nondiabetic population. We showed that plasma visfatin concentrations were positively associated with circulating interleukin-6 levels and diastolic blood pressure independent of obesity in nondiabetic healthy Korean women. These results suggest that circulating visfatin may be related with some proinflammatory condition even in a nondiabetic state.
Diabetes research and clinical practice 02/2008; 79(1):108-11. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined the association between interleukin-10 (IL-10), adiponectin levels and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP). Furthermore, the association of these anti-/pro-inflammatory cytokine levels with the metabolic syndrome was investigated. The study subjects were composed of 312 Korean individuals without diabetes. Serum adiponectin level was associated with hsCRP (r=-0.21, P<0.001), IL-6 (r=-0.13, P<0.05) and IL-10 (r=-0.22, P<0.001) levels. Subjects without the metabolic syndrome showed higher adiponectin (17.03 microg/ml versus 13.85 microg/ml, P<0.001) and IL-10 (4.74 pg/ml versus 4.34 pg/ml, P=0.014) levels, and lower serum hsCRP (0.38 microg/ml versus 0.66 microg/ml, P=0.001) and IL-6 (0.94 pg/ml versus 1.32 pg/ml, P=0.009) levels compared to those with the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome was associated with sex, age, waist circumference, systolic blood pressure, HDL cholesterol, triglyceride, fasting blood glucose and interleukin-10. Furthermore, serum adiponectin levels are associated with serum hsCRP, IL-6 and IL-10 levels. These results suggest that adiponectin might be associated with the metabolic syndrome through regulation of pro-/anti-inflammatory cytokines.
Diabetes Research and Clinical Practice 02/2007; 75(2):235-40. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been recently reported that activation of PPAR-δ, by specific agonists or genetic manipulation, alleviates dyslipidemia, hyperglycemia, and insulin resistance in animal models of obesity and type 2 diabetes. The purpose of the present study was to determine whether the PPAR-δ agonist has a direct effect on adipokines in visceral adipose tissue of rats and in cultured adipocytes. We examined the expression of visfatin, adiponectin, and resistin mRNA in visceral adipose tissue of Wistar rats fed a high-fat diet and 3T3-L1 adipocytes treated with PPAR-δ agonist (L-165041). Body weight and biochemical measurements were performed.Rats fed a high-fat diet showed a greater increase in body weight than those fed a standard diet (P
Biochemical and Biophysical Research Communications 01/2007; 357(1):62-67. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Thiazolidinediones have favorable influences on surrogate markers of atherosclerosis such as adiponectin, and arterial stiffness in diabetic patients. However, it is not well known whether these beneficial effects occur in subjects without diabetes, such as prediabetes or the non-diabetic metabolic syndrome (MetS). The present study was therefore designed to evaluate the effectiveness of the insulin-sensitizing agent rosiglitazone on circulating adipocytokine levels and brachial-ankle pulse wave velocity (baPWV) in non-diabetics.
Ninety-nine subjects with prediabetes or non-diabetic MetS were randomly assigned to either rosiglitazone or an untreated control group (50 and 49 subjects respectively). The rosiglitazone group was treated daily for 12 weeks with 4 mg rosiglitazone. All subjects received a 75 g oral glucose test (OGTT) before and after treatment. In addition, baPWV, together with the levels of adiponectin, resistin, and high sensitivity C-reactive protein (hsCRP) were determined.
Rosiglitazone treatment significantly increased circulating adiponectin levels (P < 0.001) relative to the control group (P = 0.21). Plasma resistin levels were unchanged in both the rosiglitazone-treated and -untreated groups, but baPWV and hsCRP were significantly decreased (P < 0.001 and P = 0.003 respectively) in the rosiglitazone group only. Multiple linear regression analysis showed that changes in plasma adiponectin and baPWV were significantly affected by rosiglitazone treatment.
These data suggest that rosiglitazone may have an anti-atherogenic effect in subjects with prediabetes or non-diabetic MetS.
European Journal of Endocrinology 04/2006; 154(3):433-40. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hypopituitarism is not a common cause of delayed puberty. A 22 year old man was referred to our clinic because of the absence of the development of secondary sexual characteristics. The patient had no complaints of physical discomfort. Random serum testosterone and luteinizing hormone level were obtained and found to be low. The combined pituitary function stimulation test revealed a partial hypopituitarism. A pituitary magnetic resonance imaging (MRI) was obtained and showed decreased pituitary stalk enhancement and ectopic neurohypophysis. Therefore, we conclude that the delayed puberty was a result of hypopituitarism due to pituitary stalk dysgenesis and ectopic neurohypophysis. The patient was started on hormone replacement therapy and gradually developed secondary sexual characteristics.
The Korean Journal of Internal Medicine 04/2006; 21(1):68-72.
[show abstract][hide abstract] ABSTRACT: In this study, we examined the effects of green tea on inflammation and arterial stiffness in type 2 diabetes patients. As results, inflammatory markers, such as hsCRP and IL-6, were unchanged after green tea consumption, and neither were blood glucose, lipid profiles, insulin resistance, or serum adiponectin levels. Furthermore, tea consumption did not improve baPWV. These results suggest that the above-described mechanisms are unlikely to explain the cardiovascular risk reduction by tea consumption observed in epidemiological studies.
Diabetes Research and Clinical Practice 04/2006; 71(3):356-8. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined the association between serum osteoprotegerin (OPG) levels, systemic inflammation and arterial stiffness in normal and diabetic patients.
The study subjects comprised 49 newly diagnosed diabetic patients and 72 age- and sex-matched normal glucose controls. Anthropometric parameters, blood pressure, fasting blood glucose (FBG), lipid profiles, serum OPG, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and brachial-ankle pulse wave velocity (baPWV) were measured.
Serum OPG levels (6.1 +/- 1.4 vs. 5.4 +/- 1.3 pmol/l, P = 0.011) and baPWV (1562 +/- 354 vs. 1399 +/- 257 cm/s, P = 0.004) were significantly higher in the diabetic group than in the normal glucose group. Serum OPG levels in normal and diabetic patients correlated significantly with systolic blood pressure (r = 0.20, P = 0.035), FBG (r = 0.30, P = 0.002), right baPWV (r = 0.22, P = 0.021), left baPWV (r = 0.26, P = 0.006), homeostasis model assessment insulin resistance (HOMA-IR) (r = 0.19, P = 0.045), IL-6 (r = 0.32, P = 0.001) and hsCRP (r = 0.21, P = 0.027) after adjusting for age and sex. Multiple regression analysis showed that serum OPG level was significantly associated with age, FBG, IL-6, systolic blood pressure, triglyceride and hsCRP (R(2) = 0.299).
In summary, serum OPG and baPWV levels are elevated in diabetic patients and serum OPG levels are significantly associated with inflammation and arterial stiffness.
[show abstract][hide abstract] ABSTRACT: A variety of adipocytokines and peptides secreted from adipocytes have been considered to play a crucial role in obesity, insulin resistance, and type 2 diabetes. Recently, visfatin, a new adipocytokine, known as a pre-B cell colony-enhancing factor, has been isolated from visceral fat deposits. It has been shown to activate insulin receptors in a manner different from insulin. To understand the role of adipocytokines in improving insulin sensitivity via activation of the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and -gamma (PPAR-gamma), we examined the expression of visfatin, adiponectin, and TNF-alpha in visceral fat depots of Otsuka Long-Evans Tokushima fatty (OLETF) rats from early to advanced diabetic stage (from 28 to 40 weeks of age). Serum glucose and insulin concentrations significantly (P<0.05) decreased in rosiglitazone or fenofibrate-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone significantly increased serum adiponectin concentration from 20 to 40 weeks of age (P<0.05), whereas fenofibrate reduced TNF-alpha concentration. The expression of visfatin and adiponectin mRNA in visceral fat deposits was elevated by rosiglitazone or fenofibrate treatments when compared to untreated OLETF rats (P<0.05), whereas, TNF-alpha mRNA was down-regulated by these drugs (P<0.05). These results suggest that rosiglitazone and fenofibrate may prevent type 2 diabetes by regulating adipocytokines including visfatin, adiponectin, and TNF-alpha.
Biochemical and Biophysical Research Communications 11/2005; 336(3):747-53. · 2.41 Impact Factor