Eun-Hee Jang

Diabetic retinopathy is associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus

AIMS We aimed to evaluate the association between diabetic microangiopathy and subclinical atherosclerosis as a marker of cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes. METHODS A total of 142 newly diagnosed type 2 diabetics who were free from CVD underwent evaluation of diabetic microangiopathy. Subclinical atherosclerosis was assessed by measuring carotid intima-media thickness (IMT), and the 10-year absolute risk of CVD was estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine. RESULTS Subclinical atherosclerosis was found in 27 subjects (19.0%). The rates of hypertension and diabetic retinopathy were significantly higher among patients with subclinical atherosclerosis. The UKPDS 10-year risk for CVD was significantly increased in subjects with subclinical atherosclerosis. Old age, hypertension and the presence of diabetic retinopathy showed a significant association to subclinical atherosclerosis after further adjustments for gender, body mass index, smoking status, HbA1c, HDL cholesterol, LDL cholesterol and the presence of diabetic nephropathy. CONCLUSIONS This study shows that diabetic retinopathy is an independent risk marker for subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. We suggest that a diagnosis of diabetic retinopathy may warrant a more careful cardiovascular assessment even in the early stages of diabetes.

Serum BMP-4 levels in relation to arterial stiffness and carotid atherosclerosis in patients with Type 2 diabetes

AIM The aim of this study was to evaluate the association between the circulating BMP-4 levels and atherosclerosis in patients with Type 2 diabetes. MATERIAL & METHODS Serum BMP-4 levels were measured in 174 diabetic patients, and the degree of atherosclerosis was assessed by measuring the carotid intima-media thickness and the cardio-ankle vascular index. RESULTS Serum BMP-4 levels were inversely correlated with systolic blood pressure, triglycerides, free fatty acids, cardio-ankle vascular index and carotid intima-media thickness. Lower BMP-4 levels were shown to be an independent predictor of the increased cardio-ankle vascular index and carotid intima-media thickness after adjusting for conventional cardiovascular risk factors in patients with Type 2 diabetes. CONCLUSION Serum BMP-4 levels are inversely associated with surrogate markers of arterial stiffness and carotid atherosclerosis in patients with Type 2 diabetes.

Higher levels of small dense low-density lipoprotein (LDL) are associated with cardiac autonomic neuropathy in patients with Type 2 diabetes

To investigate the relationship between small dense LDL cholesterol and cardiac autonomic neuropathy among patients with Type 2 diabetes.

Changes in serum levels of bone morphogenic protein 4 and inflammatory cytokines after bariatric surgery in severely obese korean patients with type 2 diabetes.

Serum bone morphogenic protein- (BMP-) 4 levels are associated with human adiposity. The aim of this study was to investigate changes in serum levels of BMP-4 and inflammatory cytokines after Roux-en-Y gastric bypass (RYGB). Fifty-seven patients with type 2 diabetes underwent RYGB. Serum levels of BMP-4 and various inflammatory markers, including high-sensitivity C-reactive protein (hsCRP), free fatty acids (FFAs), and plasminogen activator inhibitor- (PAI-) 1, were measured before and 12 months after RYGB. Remission was defined as glycated hemoglobin <6.5% for at least 1 year in the absence of medications. Levels of PAI-1, hsCRP, and FFAs were significantly decreased at 1 year after RYGB. BMP-4 levels were also significantly lower at 1 year after RYGB than at baseline (P = 0.024). Of the 57 patients, 40 (70%) had diabetes remission at 1 year after surgery (remission group). Compared with patients in the nonremission group, patients in the remission group had lower PAI-1 levels and smaller visceral fat areas at baseline. There was a difference in the change in the BMP-4 level according to remission status. Our data demonstrate a significant beneficial effect of bariatric surgery on established cardiovascular risk factors and a reduction in chronic nonspecific inflammation after surgery.

Usefulness of Albuminuria as Predictor for Coronary Artery Stenosis, Regardless of Estimated Glomerular Filtration Rate, in Patients With Type 2 Diabetes Mellitus

The aim of the present study was to evaluate the independent predictors of coronary artery stenosis in patients with type 2 diabetes mellitus (DM) and subclinical atherosclerosis. A total of 232 patients with type 2 DM and subclinical atherosclerosis underwent multislice computed tomography coronary angiography. Subclinical atherosclerosis was determined by the carotid intima-media thickness (IMT) or carotid plaque. Multislice computed tomography coronary angiography revealed significant coronary stenosis (>50% in diameter) in 71 subjects (31%). The subjects who had significant coronary stenosis were much older and had had a longer duration of DM. In particular, the log-transformed albumin/creatinine ratio (ACR) was greater in the subjects with significant coronary stenosis compared to the subjects without significant coronary stenosis. The age- and gender-adjusted odds ratio for significant coronary stenosis increased in proportion to albuminuria with a given estimated glomerular filtration rate. The ACR as a continuous variable (odds ratio 4.167, 95% confidence interval 1.497 to 11.599) or categorical variable (ACR >30 μg/mg, odds ratio 4.619, 95% confidence interval 1.562 to 13.659) was associated with an increased risk of significant coronary stenosis, independent of conventional cardiovascular risk factors. In receiver operating characteristic analysis, the ACR had an additive effect with carotid IMT for predicting significant coronary stenosis (area under the curve 0.625 with carotid IMT; area under the curve 0.710 with carotid IMT plus ACR, p = 0.0144). In conclusion, the presence of albuminuria is an independent predictor for significant coronary stenosis in patients with type 2 DM and subclinical atherosclerosis.

β-Cell dysfunction and insulin resistance in gestational glucose intolerance

See Article on Page 306-313 Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy. Therefore, one cannot exclude the possibility that undiagnosed glucose intolerance antedated or began concomitantly with the pregnancy. Recently, the International Association of Diabetes and Pregnancy Study Groups recommended that high-risk women found to have diabetes based on standard criteria at their initial prenatal visit should be considered to have overt, not gestational, diabetes mellitus [1]. Moreover, they recommended new criteria for diagnosing GDM using a 75-g oral glucose tolerance test (OGTT). The new criteria require only one abnormal value to make the diagnosis of GDM compared with the two abnormal values required in the criteria using a 100-g OGTT. In 2011, the American College of Obstetricians and Gynecologists announced that they continue to recommend use of the old diagnostic criteria for GDM. Although several countries and international organizations have adopted the new criteria, the World Health Organization has not released its report on this topic. The United States National Institutes of Health plan to hold a conference in 2013 to develop consensus on this topic. The Korean Diabetes Association suggested both old and new criteria for the diagnosis of GDM, depending on the decision of clinicians. GDM is associated with increased risks of maternal, fetal, and neonatal adverse outcomes, depending on the degree of hyperglycemia. Furthermore, GDM has long-term sequelae for both the mother and offspring after delivery. Several studies have reported postpartum type 2 diabetes mellitus (T2DM) rates ranging from 3% to 38% within 1 year after delivery, depending on ethnicity and the proportion of participants with severe hyperglycemia during pregnancy. Cho et al. [2] found that the incidence of T2DM was approximately 41% in Korean women with previous GDM. Like prediabetes, gestational impaired glucose tolerance (GIGT) can be diagnosed when only one abnormal glucose value is seen on the 100-g OGTT. GIGT was thought to be an intermediate phenotype between normal glucose tolerance (NGT) and GDM. However, recent studies showed that the maternal and fetal outcomes are poorer if GIGT is not treated [3,4]. In this issue of The Korean Journal of Internal Medicine, Yang et al. [5] analyzed various indices of insulin resistance and insulin secretion in 1,163 pregnant Korean women undergoing 100-g OGTT. Based on the OGTT results, the study subjects were subdivided into three groups: NGT, GIGT (only one abnormal value based on the criteria of Carpenter and Coustan), and GDM. The subjects with GDM were older than the subjects with NGT and had a higher prepregnancy body mass index (BMI). In addition, the GDM group had higher insulin resistance indexes and lower insulin secretion indexes, as compared to the NGT group. These findings are similar to those of previous reports. It was thought that GDM develops when β-cells fail to adapt to the increasing demand for insulin release during the second half of pregnancy, when insulin resistance is greatest. Buchanan et al. [6] showed that insulin secretion during pregnancy increases in parallel in women with and without GDM, but from a lower starting point in women with GDM. This means that the β-cell defect in GDM is somewhat chronic, rather than acquired during pregnancy. Consequently, the β-cell dysfunction in GDM may worsen over time, which results in overt diabetes mellitus postpartum. Yang et al. [5] found that the insulin resistance indices were significantly worse in the GDM group than in the GIGT group, as expected. However, the insulin levels at each time point in the 100-g OGTT and the area under the curve for insulin were significantly higher in the GIGT group than in the GDM group. This suggests that compensation for insulin secretion occurs in the GIGT group. Insulin secretion indices were significantly lower in subjects with GDM compared with the other two groups. Among the subjects with GIGT, the 1-hour abnormal group had a significantly greater weight gain during pregnancy, and the values from the 50-g OGTT were higher than in the other two groups. Although the insulin resistance indices among the three groups were not different, HOMA-β as an index of insulin secretion capacity was lowest in the 1-hour abnormal group, which means that an insulin secretion defect is prominent in that group. This finding is similar to that of Retnakaran et al. [7]. However, recent studies suggest that women with a single abnormal glucose value at 1 hour on the OGTT had a metabolic phenotype similar to GDM, whereas GIGT at 2 or 3 hours on the OGTT is similar to NGT. Retnakaran et al. [7] reported that the caesarian section rate was higher in women with an abnormal glucose value at 1 hour on the OGTT, and this was associated with postpartum glycemia, insulin resistance, and β-cell dysfunction. Compared with Caucasians, Asians have a smaller β-cell mass with a lower insulin secretion capacity, whereas visceral adiposity with greater insulin resistance is common in Asians, even with a lower BMI. These pathophysiological differences between Caucasians and Asians could explain the recent abrupt increase in the prevalence of type 2 diabetes in Asian countries. In a study that assessed the changes in insulin resistance and β-cell function in a multiethnic population-based cohort of pregnant women [8], the increase in insulin resistance was similar across the ethnic groups. However, the increase in β-cell function was significantly lower for East and South Asians compared with Western Europeans. This suggests that there are similar pathophysiological differences between Asians and Caucasians in pregnancy. Gestational diabetes is a very interesting disease entity because it has a natural course similar to that of type 2 diabetes, which is characterized by two main pathogenic factors: insulin resistance and an insulin secretion defect. Furthermore, most GDM disappears after delivery, which provides a clue to the mechanisms for reversing type 2 diabetes to NGT. Recently, Kwak et al. [9] reported that obesity was a risk factor for both early (2 months postpartum) and late (more than 1 year after delivery) type 2 diabetes converters in women with a history of GDM. In addition, early converters had more pronounced defects in β-cell function. If there is a genetic component of the insulin secretory defect in Asian women, a reduction in insulin resistance after delivery might be the only way to prevent future type 2 diabetes in women with previous GDM.

Influence of Visceral Adiposity on Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus

Background The aim of this study was to investigate the influences of visceral adiposity on cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus. Methods Two hundred eleven patients with type 2 diabetes participated in this study. Anthropometric and metabolic parameters were measured, and the visceral fat area was assessed using computed tomography. CAN was diagnosed using a cardiovascular reflex test. We analyzed the correlation between the visceral fat area and each parameter in this test. Results The mean age, body mass index (BMI), and duration of diabetes of the study population were 60±14 years (mean±standard deviation), 25.1±4.2 kg/m2, and 12.3±8.9 years, respectively. The visceral fat area showed positive correlations with age, BMI, waist circumference, and subcutaneous fat area. There was no statistically significant difference in the cardiovascular reflex test outcome between genders. Univariate linear regression analysis showed that an increased visceral fat area diminished good heart rate response to a Valsalva maneuver (R2=4.9%, P=0.013 in an unadjusted model), but only in women. This statistical association was preserved after adjusting for age and BMI (R2=9.8%, P=0.0072). Conclusion The results of this study suggest that visceral adiposity contributes to an autonomic imbalance to some degree, as demonstrated by the impaired cardiovascular reflex test among women with type 2 diabetes.