Diabet. Med. 29, 74–79 (2012)AbstractAim To investigate whether the change in glycated albumin 3 weeks after initiating anti‐diabetes treatment (oral hypoglycaemic agent or insulin) could predict the corresponding change in HbA1c 3 months later in Korean patients with Type 2 diabetes.Methods A total of 140 patients were enrolled into two groups: group I (insulin‐based; n = 100) and group II (oral hypoglycaemic agent‐based; n = 40). Both glycated albumin and HbA1c levels were measured as ‘glucose control markers’ during hospitalization. Glycated albumin was measured again at 3 weeks (first visit) after the initial measurement, and HbA1c was measured at 3 months (second visit) after the initial measurement.. The change in glucose control marker was defined as 100 × (follow‐up glucose control marker – hospital glucose control marker)/hospital glucose control marker.Results In both groups, the change in glycated albumin at the first visit and in HbA1c at the second visit showed a moderate linear relationship (r = 0.735; P < 0.01). In group II (r = 0.778; P < 0.01), a slightly stronger linear relationship was demonstrated than in group I (r = 0.738; P < 0.001); however, there was no statistically significant difference between the two groups. A correlation coefficient between the change in glycated albumin and HbA1c was not affected by sex, age, BMI, haemoglobin, serum creatinine or albumin.Conclusion The reduction in glycated albumin 3 weeks after the initiation of treatment corresponded with the reduction in HbA1c 3 months after starting treatment in both the group treated with a oral hypoglycaemic agent and the insulin‐treated group of Korean patients with Type 2 diabetes.

Objective Although glycated haemoglobin (A1c) levels are similar among patients with type 2 diabetes, the glycated albumin (GA)/A1c ratio varies considerably. On the basis of the hypothesis that endogenous insulin secretion might be correlated with the GA/A1c ratio, we investigated whether insulin secretory function or insulin resistance has different effects on the GA/A1c ratio in patients with type 2 diabetes using the standardized liquid meal test. Design A clinical, retrospective study. Patients and measurements A total of 758 patients with type 2 diabetes ingested a standardized liquid meal (i.e. 500 kcal, 17.5 g fat, 68.5 g carbohydrate and 17.5 g protein). The subjects were divided into two groups: those with GA/A1c ratio <2.5 (n = 414) and those with GA/A1c ratio =2.5 (n = 344). We compared the A1c and GA levels, and the GA/A1c ratio and evaluated the relationships between the glycaemic indices and other parameters. Effects of beta-cell function [homeostasis model assessment (HOMA-beta), insulinogenic index (IGI)] and insulin resistance (HOMA-IR) on the GA/A1c ratio were also examined. Results The GA/A1c ratio was significantly correlated with HOMA-beta, IGI and body mass index (BMI) but not with HOMA-IR. Furthermore, after adjusting for age, gender, BMI, haemoglobin and albumin levels, the GA/A1c ratio was still inversely correlated with both HOMA-beta and IGI. Conclusions The GA/A1c ratio is significantly correlated with insulin secretory function but not with insulin resistance.

AIM:We investigated the clinical and metabolic parameters in type 2 diabetic patients who were inadequately controlled on sulfonylurea (SU) before initiating insulin therapy to characterise patients who are likely to achieve target glycaemic control with insulin analogues.METHODS:A total of 120 Korean patients aged ≥ 40 years with insulin-naïve, poorly controlled, SU-treated type 2 diabetes were randomised on the basis of SU dose, and obesity with 1 : 1 ratio of insulin detemir (long-acting analogue; LAA) and 70% insulin aspart protamine and 30% insulin aspart (biphasic insulin analogue; BIA). Patients who failed to reach ≤ 20% glycated albumin (GA) at 3 weeks were switched to therapy with a twice-daily BIA for 16 weeks.RESULTS:Mean HbA(1c) , GA, fasting and stimulated plasma glucose levels were significantly reduced after 16 weeks compared with the baseline in all groups, and 40% of patients reached the target HbA(1c) ( ≤ 7%). Compared with responders, non-responders had significantly longer duration of diabetes and higher dose of glimepiride. However, there was no significant difference in insulin secretory profiles between responders and non-responders. Clinical factors such as diabetes duration, SU dose and BMI were independently associated with inadequate response to insulin analogues in patients with secondary failure.CONCLUSIONS:In type 2 diabetics with secondary SU failure, clinical parameters such as duration of diabetes (< 10 years), SU dose ( ≤ 4 mg) and BMI should be taken into consideration as important factors than laboratory indices related to β-cell function when predicting the response to insulin analogues.

Aims: We investigated the effect of mosapride, 5HT-4 (5-hydroxytryptamine) agonist, on blood glucose level and insulin sensitivity in subjects with impaired glucose tolerance (IGT) and conducted an in vitro study to evaluate the action mechanism.Methods: Thirty IGT patients were randomly assigned to receive either mosapride or placebo for 2 weeks. Biochemical profiles and insulin sensitivity index from euglycemic hyperinsulinemic clamp test were assessed before and after treatment. In cultured myotubes from human skeletal muscle cells, insulin- and mosapride-induced GLUT4 translocation and tyrosine phosphorylation of IRS-1 were determined.Results: After 2 weeks of treatment with mosapride, glucose disposal rates were significantly increased up to those of control (mosapride 5.47 +/- 1.72 vs 7.06 +/- 2.13, P = 0.004, placebo 5.42 +/- 1.85 vs 5.23 +/- 1.53 mg kg(-1) min(-1)). Fasting plasma glucose (FPG) and insulin levels were decreased. Mosapride increased the contents of GLUT4 in plasma membrane representing the increased recruitment of glucose transporters from intracellular pool. While insulin treatment on human skeletal muscle cell resulted in an increased tyrosine phosphorylation of IRS-1, mosapride did not have any effect.Conclusions: Mosapride is effective in decreasing FPG without stimulating insulin secretion in IGT subjects, possibly by inducing GLUT4 translocation in skeletal muscles. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Aims We examined the effect of rosiglitazone on insulin sensitivity, abdominal fat and mid-thigh intramuscular fat distribution, and plasma concentrations of adipocytokines in patients with Type 2 diabetes.Methods Rosiglitazone was administered at a daily dose of 4 mg to 42 Type 2 diabetes patients [age 32-70 years, body mass index (BMI) 17.5-32.6 kg/m(2), 15 women, 27 men] for 12 weeks. Various anthropometric and metabolic profiles, plasma adiponectin, leptin, and resistin levels were measured, and insulin resistance was calculated from the short insulin tolerance test. Body fat composition was assessed by computed tomography.Results Twelve weeks' rosiglitazone treatment resulted in improved insulin resistance despite increases in body weight and BMI. There was a significant decrease in abdominal visceral adipose tissue area (145 +/- 65.6 vs. 129 +/- 73.1 cm(2), P = 0.049). Mid-thigh low-density muscle area (TLDMA) increased from 23 +/- 9.6 to 26 +/- 8.2 cm(2) (P = 0.009). There were significant changes in plasma adipocytokines, but they were not significantly correlated with changes in insulin resistance.Conclusions Rosiglitazone treatment resulted in an improvement of insulin responsiveness in Type 2 diabetic subjects, which was associated with the redistribution of visceral and subcutaneous adipose tissue, an increase in TLDMA, and changes in serum adipocytokine levels. Further studies are needed to elucidate the insulin sensitizing mechanism of rosiglitazone on peripheral skeletal muscles.

To investigate the effect of two common ATP-binding cassette transporter 1 (ABCA1) polymorphisms (rs4149263 and rs2020927) on atherogenic dyslipidaemia in Korean Type 2 diabetic patients who were treated with rosiglitazone.Two hundred and fifty-six patients with Type 2 diabetes who had never previously received peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists or lipid-lowering treatment were treated with 4 mg of rosiglitazone daily for 12 weeks without any adjustment to their glucose-lowering regimen. The primary outcome was the change in atherogenic index of plasma (AIP), calculated as log [triglyceride (mmol/l)/high-density lipoprotein cholesterol (mmol/l)], before and after rosiglitazone treatment. The effect of rosiglitazone on the change in AIP was compared across the ABCA1 single nucleotide polymorphisms (SNPs) rs41429263 and rs2020927.Before adjustment, the change in AIP at 12 weeks was significantly different across the rs4149263 genotypes [median (interquartile range): -0.05 (-0.21, 0.09) for TT; 0.02 (-0.09, 0.17) for TC; and 0.11 (0.03, 0.25) for CC; P = 0.003], but not across the rs2020927 [-0.04 (-0.18, 0.10) for TT; 0.03 (-0.17, 0.15) for TC; and -0.03 (-0.13, 0.10) for CC; P = 0.401]. After controlling for age, gender and duration of diabetes, the presence of the C-allele was significantly associated with an increase in AIP by 0.13 [95% confidence interval (CI), 0.04-0.21; P = 0.003]. This association did not change significantly when body mass index and pretreatment metabolic parameters were additionally controlled for (the change in AIP: 0.14; 95% CI, 0.04-0.24; P = 0.007).The ABCA1 SNP rs4149263 may be associated with the change in atherogenic lipid profile in Type 2 diabetes treated with rosiglitazone.

Objective: Our objective was to investigate whether determination of the quantity of visceral fat has an additional benefit in assessing atherosclerotic burden in men with type 2 diabetes compared with the traditional measurement of waist circumference (WC) alone. Methods: This was an observational study performed in 368 men with type 2 diabetes, consecutively enrolled in Diabetes Clinics. Common carotid artery far-wall intima-media thickness (IMT), WC and visceral fat thickness (VFT), as measured by ultrasonography, were measured for each subject. Abdominal and visceral obesity were defined as a WC >90 cm and a VFT ⩾47.6 mm, respectively. Results: Among subjects with abdominal obesity ( n =174), 35 subjects did not have visceral obesity. In contrast, among the subjects without abdominal obesity ( n =194), 88 patients had visceral obesity. Despite no differences in age, glucose control, lipid profile and treatment modalities, there was a significant difference in carotid IMT based on VFT strata, but not WC strata. The subjects without abdominal obesity, but who had visceral obesity, had a higher carotid IMT compared with subjects with abdominal obesity, but without visceral obesity (maximal, 0.94±0.35 vs 0.78±0.17 mm; and average, 0.74±0.19 vs 0.64±0.14 mm, respectively, P <0.001). Conclusions: Subjects having visceral obesity, regardless of a normal WC, showed a higher carotid IMT compared with those with increased WC, but less visceral fat. In addition to WC, a direct estimation for visceral fat may provide an additional role in assessing atherosclerotic burden in men with type 2 diabetes.

Although the HLA class II alleles and immunological abnormalities are associated with type 1 diabetes mellitus (T1DM) in all racial groups, there are considerable variations in the genotypes and the prevalence of autoantibodies. In order to investigate the characteristics of the immunogenetic patterns and to use these as an early diagnostic tool and guideline for a therapeutic plan, we examined the clinical characteristics and the patterns of anti-GAD antibody (GADA), IA-2 antibody (IA-2A), HLA-DR and HLA-DQ in Korean adult-onset T1DM patients. Adult-onset patients had higher serum C-peptide levels than child-onset patients. In adult-onset patients, the prevalence of GADA and IA-2A were 59.5% and 15.3% respectively, and increased frequencies of HLADR4 and-DR9 were found. The frequencies of HLADQA1,-DQB1 and-DQ heterodimers were similar to those of the control, but child-onset patients had high frequencies of the HLA-DR3,-DR4,-DR9, DQA1*0301, DQA1*0501 and DQB1*0201 genotypes. In conclusion, Korean adult-onset T1DM patients had a lower prevalence of GADA, which was comparable to that found in Caucasian patients. The detection of GADA might help to predict the insulin dependency of adult-onset diabetes. Difference in the frequencies of diabetes associated with HLA type suggests that there might be a heterogeneity in the pathogenesis of diabetes according to the age of onset.

SummaryObjective Low birthweight is associated with insulin resistance later in life, and adiponectin is known to play an important role in insulin resistance. We have investigated whether birthweight has a relationship with adiponectin levels in adolescence.Patients An at‐home questionnaire survey was completed by 660 middle‐school students (aged 12–15 years) in Seoul, Korea, and 152 participants were selected randomly based on their birthweight.Measurements Subjects were separated into three groups according to birthweight. We recorded the birthweight and measured anthropometric factors including blood pressure, lipid profile, homeostasis model assessment of insulin resistance (HOMA‐IR) and β‐cell function (HOMA‐β), and adiponectin levels of the subjects. These parameters were compared among the groups. The relationship between birthweight and physiological characteristics in adolescence was examined.Results Systolic blood pressure, lipid profiles and fasting plasma glucose were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C‐peptide and HOMA‐IR were higher in the low birthweight tertile. After adjustment for confounding factors, birthweight was inversely related to diastolic blood pressure, insulin, C‐peptide and HOMA‐IR. Adiponectin level had a significant relationship with current body mass index (BMI) (r = –0·291; P < 0·001) but not with birthweight (r = 0·117; P = 0·166).Conclusions Although birthweight is closely related to insulin resistance during adolescence, adiponectin levels during adolescence had no significant relationship with birthweight. This result implies that low birthweight may not permanently affect adiponectin levels, but current body size is more closely associated with a decreased adiponectin level. However, the limited importance of birthweight as a determining factor on the adiponectin level later in life needs to be further evaluated.

The aim of this study was to investigate whether low-density lipoprotein (LDL) particle size is associated with insulin resistance and to explore the association between LDL particle size and preclinical atherosclerosis in nondiabetic Korean population. We measured the carotid intima-media thickness (IMT), LDL particle size, and insulin resistance in 136 nondiabetic subjects. Low-density lipoprotein particle size was significantly correlated with insulin resistance, but the independent risk factors of LDL particle size determined by the multiple regression analysis were age, triglyceride, and high-density lipoprotein cholesterol (HDL-C). Carotid IMT was associated with traditional risk factors of atherosclerosis, which are age, HDL-C, LDL cholesterol, systolic and diastolic blood pressure, but LDL particle size was not correlated with carotid IMT. We conclude that LDL particle size was associated with insulin resistance, but age, triglyceride, and HDL-C contributed independently to the variability in LDL particle size, and LDL particle size was not a predictor of preclinical atherosclerosis in nondiabetic Koreans.

Background: Atherosclerosis is one of the major causes of morbidity and mortality in patients with type 2 diabetes and pioglitazone has been reported to have antiatherogenic effect.The aim of this study was to investigate whether pioglitazone affects carotid intima-media thickness (IMT) and pulsatility index (PI) in type 2 diabetic patients.Methods: A total of 40 type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (pioglitazone 15 mg/day with gliclazide 80～320 mg/day for 12 weeks) (n = 20) and control group (gliclazide 80～320 mg/day for 12 weeks) (n = 20).The changes in lipid profile, insulin resistance, IMT, and PI were monitored to determine that pioglitazone improves cerebrovascular blood flow.Results: The pioglitazone treatment significantly increased HDL-C, reduced triglyceride, insulin resistance and PI.IMT tended to decrease but the change was not significant.This study revealed that treatment with pioglitazone was associated with the improvement of cerebrovascular blood flow.Conclusions: Pioglitazone appears to be effective for the improvement of cerebrovascular blood flow in type 2 diabetic patients (J Kor Diabetes Assoc 30:96～103, 2006).

Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-beta, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-beta were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight.