Nonobese Japanese Type Research Articles

Close Association of Hypoadiponectinemia and Increased Insulin Resistance in Non-Obese Japanese Type 2 Diabetes with Visceral Adiposity

Objective: Visceral fat accumulation because of obesity plays a central role in metabolic syndrome and causes cardiovascular disease (CVD). Methods: The aims of this study were to investigate associations between visceral fat accumulation and adipokines in non-obese type 2 diabetic patients. Results: In total, 138 type 2 diabetic patients were enrolled, with a mean age of 64 years. Among the participants, 69 were males. We found that serum high-molecular-weight adiponectin level was decreased, C-reactive protein increased, and using homeostatic model assessment of insulin resistance was also increased in non-obese patients with visceral adiposity (body mass index: BMI, <25 kg/m2; visceral fat area: VFA, ≥ 100 cm2) compared with those without visceral adiposity (BMI, <25 kg/m2, VFA, <100 cm2). VFA in non-alcoholic fatty liver disease (NAFLD) was higher than in those with no NAFLD. Conclusion: We demonstrated that visceral fat accumulation is a risk for CVD in non-obese diabetic patients with visceral adiposity.

1229 A phase I study of continuous and intermittent schedules of lapatinib in combination with vinorelbine in solid tumors

The aim of the present study was to investigate the relationship between insulin resistance and tumor necrosis factor α (TNF-α) as well as soluble TNF receptors (sTNF-R), body mass index (BMI), leptin, adiponectin, and serum lipid profile including triglycerides in nonobese Japanese patients with type 2 diabetes.A total of 88 nonobese Japanese type 2 diabetic patients were studied. The duration of diabetes was 11.0 ± 0.8 years. In conjunction with BMI, glycosylated hemoglobin (HbA1c), fasting concentrations of plasma glucose, serum lipids (triglycerides, high-density lipoprotein cholesterol, and total cholesterol), serum leptin, serum adiponectin, serum TNF-α, and soluble TNF receptors (sTNF-R1 and sTNF-R2) were also measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment.Insulin resistance was positively correlated with BMI, triglycerides, leptin, and total cholesterol and negatively correlated with adiponectin and high-density lipoprotein cholesterol. In contrast, insulin resistance was not associated with TNF-α, nor sTNF-R (sTNF-R1 and sTNF-R2) in our diabetic patients. There was no significant relationship between the 3 measures of TNF-α system (TNF-α, sTNF-R1, and sTNF-R2) and BMI, serum triglycerides, leptin, or adiponectin in these patients.From these results, it can be concluded that peripheral levels of TNF-α system activity are not a major factor responsible for insulin resistance in nonobese Japanese type 2 diabetic patients.

Soluble TNF Receptor and Periodontal Disease in Non-obese Japanese Type 2 Diabetic Patients

Soluble TNF Receptor and Periodontal Disease in Non-obese Japanese Type 2 Diabetic Patients

Soluble Tumor Necrosis Factor Receptor 2 Is Independently Associated With Brachial-Ankle Pulse-Wave Velocity in Nonobese Japanese Type 2 Diabetic Patients

Type 2 diabetes is associated with high mortality and morbidity due to atherosclerosis. Biermen (1) estimated that typical risk factors, including blood pressure, cholesterol, and smoking, can account for no more than 30% of excess cardiovascular risk factor in diabetic patients. Thus, other factors seem to play a role in the progression of atherosclerosis in diabetes. Aortic stiffness measured by pulse- wave velocity (PWV) is shown to be highly predictive of cardiovascular mortality in type 2 diabetic patients (2). While age and blood pressure are shown …

Soluble Tumor Necrosis Factor Receptor 1 Is Strongly and Independently Associated With Serum Homocysteine in Nonobese Japanese Type 2 Diabetic Patients

The major clinical consequence of type 2 diabetes is mortality and morbidity from atherosclerotic vascular disease. With regards to the risk factors responsible for the evolution of atherosclerosis, Bierman (1) estimated that typical risk factors, including smoking, cholesterol, and blood pressure, can account for no more than 30% of excess cardiovascular risk factors in diabetic patients. Thus, other factors seem to play a key role in the progression of atherosclerosis in diabetes. One potential factor is homocysteine. Homocysteine has been shown …

Interleukin 6, adiponectin, leptin, and insulin resistance in nonobese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationships between interleukin 6 (IL-6) and insulin resistance, serum leptin, serum adiponectin, or serum lipids including triglycerides in 98 nonobese Japanese type 2 diabetic patients. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Serum IL-6 concentration was negatively correlated to high-density lipoprotein cholesterol ( r = −0.295, P = .004), but was not associated with HOMA-IR ( r = 0.016, P = .871), body mass index (BMI) ( r = 0.090, P = .375), systolic ( r = 0.169, P = .116) and diastolic ( r = −0.061, P = .570) blood pressures, leptin ( r = 0.062, P = .544), and adiponectin ( r = −0.020, P = .841) in these patients. In contrast, serum leptin level was positively correlated to HOMA-IR ( r = 0.291, P = .004), BMI ( r = 0.338, P < .001), and systolic blood pressure ( r = 0.241, P = .025). Serum adiponectin level was negatively correlated to HOMA-IR ( r = −0.288, P = .005), BMI ( r = −0.308, P = .002), diastolic blood pressure ( r = −0.269, P = .012), and triglycerides ( r = −0.338, P < .001), and positively correlated to high-density lipoprotein cholesterol ( r = 0.300, P = .003) in our patients. From these results, it can be suggested that fasting serum IL-6 is not a major factor responsible for the evolution of insulin resistance in nonobese Japanese type 2 diabetic patients.

Soluble TNF Receptors and Albuminuria in Non-obese Japanese Type 2 Diabetic Patients

The aim of this study was to investigate the relationships between albuminuria and tumor necrosis factor (TNF)-alpha or soluble TNF receptors (sTNF-R1, sTNF-R2) in eighty-eight non-obese Japanese type 2 diabetic patients stratified into two groups according to albuminuria status-microalbuminuria or normoalbuminuria. Patients with microalbuminuria were older and had significantly higher concentrations of sTNF-R1 and sTNF-R2 than those with normoalbuminuria. There was, however, no significant difference in sex, diabetes duration, smoking, BMI, systolic and diastolic blood pressure, HbA (1c), serum creatinine, and lipid profile between the two groups. Although serum TNF-alpha was positively correlated to serum sTNF-R1 and sTNF-R2, serum TNF-alpha level did not differ with respect to albuminuria. Univariate regression analysis showed that urinary albumin concentration was positively correlated to age (r=0.380, p<0.001), serum creatinine (r=0.214, p<0.05) and concentrations of sTNF-R1 (r=0.364, p<0.001) and sTNF-R2 (r=0.342, p<0.005). Other variables, including TNF-alpha, were not associated with albuminuria. Multiple regression analyses showed that urinary albumin concentration was independently predicted by the level of sTNF-R1 (F=32.1), which explained 26.3% of the variability of urinary albumin concentration. From these results, it can be concluded that serum soluble TNF receptor is an important independent factor associated with albuminuria in non-obese Japanese type 2 diabetic patients.

Three measures of tumor necrosis factor α activity and insulin resistance in nonobese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationship between insulin resistance and tumor necrosis factor α (TNF- α) as well as soluble TNF receptors (sTNF-R), body mass index (BMI), leptin, adiponectin, and serum lipid profile including triglycerides in nonobese Japanese patients with type 2 diabetes. A total of 88 nonobese Japanese type 2 diabetic patients were studied. The duration of diabetes was 11.0 ± 0.8 years. In conjunction with BMI, glycosylated hemoglobin (HbA1c), fasting concentrations of plasma glucose, serum lipids (triglycerides, high-density lipoprotein cholesterol, and total cholesterol), serum leptin, serum adiponectin, serum TNF- α, and soluble TNF receptors (sTNF-R1 and sTNF-R2) were also measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment. Insulin resistance was positively correlated with BMI, triglycerides, leptin, and total cholesterol and negatively correlated with adiponectin and high-density lipoprotein cholesterol. In contrast, insulin resistance was not associated with TNF- α, nor sTNF-R (sTNF-R1 and sTNF-R2) in our diabetic patients. There was no significant relationship between the 3 measures of TNF- α system (TNF- α, sTNF-R1, and sTNF-R2) and BMI, serum triglycerides, leptin, or adiponectin in these patients. From these results, it can be concluded that peripheral levels of TNF- α system activity are not a major factor responsible for insulin resistance in nonobese Japanese type 2 diabetic patients.

Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationships between insulin resistance and soluble E-selectin, body mass index (BMI), leptin, and serum lipid profile including triglycerides in nonobese Japanese type 2 diabetic patients. A total of 97 nonobese Japanese type 2 diabetic patients aged 43 to 84 years were examined. The duration of diabetes was 11.2 ± 0.8 years. In conjunction with BMI and fasting concentrations of plasma glucose, serum lipids (triglycerides, total cholesterol, and high-density lipoprotein cholesterol) and serum insulin, soluble E-selectin, and leptin were also measured. The low-density lipoprotein (LDL) cholesterol level was calculated using the Friedewald formula. Insulin resistance was estimated by the homeostasis model assessment. The subjects were divided into 2 groups according to the value of insulin resistance estimated by the homeostasis model assessment. Values greater than 2.5 were indicative of the insulin-resistant state, and values less than 2.5 were indicative of the insulin-sensitive state. The insulin-resistant group had significantly higher levels of E-selectin, leptin, triglycerides, total and LDL cholesterol, and diastolic blood pressure as compared with the insulin-sensitive group. There was, however, no significant difference in age, sex, diabetes duration, BMI, systolic blood pressure, HbA1c, and high-density lipoprotein cholesterol between the 2 groups. Univariate regression analysis showed that insulin resistance was positively correlated to E-selectin ( r = 0.305, P = .003), BMI ( r = 0.283, P = .006), leptin ( r = 0.296, P = .004), HbA1c ( r = 0.241, P = .018), serum triglycerides ( r = 0.385, P < .001), serum total ( r = 0.240, P = .019) and LDL cholesterol ( r = 0.254, P = .013) levels, and systolic ( r = 0.247, P = .024) and diastolic ( r = 0.305, P = .006) blood pressure. Multiple regression analyses showed that insulin resistance was independently predicted by serum E-selectin (F = 18.4), serum leptin (F = 14.0) and serum triglycerides (F = 20.0) levels, which explained 45.0% of the variability of insulin resistance. From these results, it can be concluded that in conjunction with serum triglycerides and serum leptin, serum E-selectin is another important independent factor associated with insulin resistance in nonobese Japanese type 2 diabetic patients.

Efficacy of glimepiride in Japanese type 2 diabetic subjects

We investigated the efficacy of glimepiride, a third-generation sulfonylurea (SU), in Japanese type 2 diabetic patients in whom glycemic control had been inadequate with a conventional SU, gliclazide or glibenclamide. A total of 172 Japanese type 2 diabetic patients (HbA1C ≥ 7.0%), maintained on a conventional SU, were randomly assigned to the 3rd SU group (SU treatments switched to glimepiride) or the 2nd SU group (treatments not changed). The conventional SU was switched to the indicated doses of glimepiride (gliclazide 40 mg = glimepiride 1 mg, glibenclamide 2.5 mg = glimepiride 2 mg). After 6 months, glycemic control (HbA1C and fasting plasma glucose) had not changed significantly in either the 2nd or the 3rd SU group. The homeostasis assessment model of insulin resistance (HOMA-IR) in the 3rd SU group was decreased by more than 10% ( p = 0.015), whereas no change was observed in the 2nd SU group. The triglyceride level was decreased by approximately 10% in the 3rd SU group, not a significant change ( p = 0.080). Patients who had been treated with only SU, or treated with SU for a short time (less than 5 years), and who were also obese (BMI ≥ 25) or had a high HOMA-IR (HOMA-IR ≥ 3), showed significantly reduced insulin resistance. According to logistic regression analysis, high BMI (≥25) was the only variable predicting that glimepiride would more effectively improve HbA1C than conventional SU treatment. In conclusion, switching conventional SUs to glimepiride reduced insulin resistance without improving glycemic control. A notable finding of this study is that glimepiride was more beneficial in obese than in non-obese Japanese type 2 diabetic patients.

Prevalence of periodontal bacterial infection in non-obese Japanese type 2 diabetic patients: relationship with C-reactive protein and albuminuria.

The aim of the present study was to investigate the relationship between periodontal bacteria infection ( Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedius) and C-reactive protein (CRP) and albuminuria in non-obese Japanese type 2 diabetic patients. One hundred and thirty-four non-obese Japanese type 2 diabetic patients without evidence of current acute illness including clinically significant acute infectious disease were enrolled into the study. The degree of periodontal bacterial infection was evaluated using IgG titer against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, or Prevotella intermedius. The bacterial sonic extracts were used as antigens. High-sensitivity CRP (hCRP), glucose, glycosylated hemoglobin (HbA (1c)), and lipids were also measured after an overnight fast. Urinary albumin excretion rate as a ratio of urinary albumin and urinary creatinine was assessed in a morning spot urine sample using a commercial enzymatic immunoassay. The prevalence of Porphyromonas gingivalis infection was 52.2 % and that of Actinobacillus actinomycetemcomitans and Prevotella intermedius was 7.5 and 14.2 %, respectively. IgG titer against Porphyromonas gingivalis significantly correlated with CRP (r = 0.225, p < 0.001) and albuminuria (r = 0.185, p < 0.05), while IgG titer against Actinobacillus actinomycetemcomitans or Prevotella intermedius was not associated with either parameter. These results suggest that among periodontal bacteria, Porphyromonas gingivalis infection is associated with atherosclerosis in non-obese Japanese type 2 diabetic patients.

Platelet count is independently associated with insulin resistance in non-obese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationship between platelet count and insulin resistance in non-obese Japanese type 2 diabetic patients. A total of 163 non-obese Japanese type 2 diabetic patients (112 men and 51 women, aged 36 to 84 years, body mass index [BMI] 16.2 to 26.9 kg/m 2) were studied. In conjunction with BMI, glycosylated hemoglobin (HbA 1c), fasting concentrations of plasma glucose and serum lipids (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol), and hematological parameters (platelets, white blood cell count, red blood cell count, hematocrit, hemoglobin) were measured. LDL cholesterol was calculated using the Friedewald formula. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Univariate regression analysis showed that HOMA-IR was positively correlated to BMI ( r = 0.465, P < .0001), HbA 1c ( r = 0.423, P < .0001), platelet count ( r = 0.310, P < .0001), triglycerides ( r = 0.277, P < .0005), white blood cell count ( r = .222, P = .005), red blood cell count ( r = 0.210, P = .008), hematocrit ( r = 0.156, P = .047), total cholesterol ( r = 0.178, P = .023), and systolic ( r = 0.216, P = .011) and diastolic ( r = 0.263, P = .002) blood pressure, and inversely correlated to HDL cholesterol ( r = −0.312, P < .0001) level in our diabetic patients. Multiple regression analysis showed that HOMA-IR was independently predicted by BMI ( P < .0001, F = 22.45), HbA 1c ( P < .0001, F = 16.15), platelet count ( P < .0001, F = 10.75), and serum triglycerides ( P < .0001, F = 10.47) levels, which explained 34% of the variability of HOMA-IR in non-obese Japanese type 2 diabetic patients. These results indicate that not only BMI, HbA 1c, and triglycerides levels but also platelet counts are independent predictor of insulin resistance in non-obese Japanese type 2 diabetic patients.

Relationship of regional adiposity to serum leptin level in nonobese Japanese type 2 diabetic male patients

The aim of the present study was to investigate the relationships between serum leptin levels and regional adipose fat area, BMI, and the measures of variables including serum insulin in nonobese Japanese type 2 diabetic patients. A total of 121 nonobese Japanese type 2 diabetic patients [aged 35 to 83 years, body mass index (BMI) (15.4 to 26.8 kg/m(2))] were studied. They all were male patients. In conjunction with serum leptin level, BMI, glycosylated hemoglobin (HbA(1c)), and fasting concentrations of plasma glucose and serum insulin and lipids (triglycerides, total and HDL cholesterol) were measured. Univariate regression analysis showed that serum leptin levels were positively correlated to subcutaneous (r=0.566, P<0.0001) and visceral (r=0.481, P<0.001) fat area in our diabetic patients. Furthermore, serum leptin levels were positively correlated to serum insulin (r=0.517, P<0.0001), BMI (r=0.428, P<0.0001), serum triglycerides (r=0.279, P<0.005), and age (r=0.225, P<0.05). There was, however, no relationship between serum leptin levels and measures of other variables including total and HDL cholesterol. Multiple regression analyses showed that serum leptin levels were predicted by subcutaneous fat area (F=5.92, P<0.0001) and serum insulin level (F=5.60, P<0.0001), which explained 29.0% of the variability of serum leptin concentrations in our nonobese Japanese type 2 diabetic male patients. Visceral fat area, BMI, serum triglycerides, and age, however, were not independently associated with serum leptin levels in our patients. These results indicate that serum leptin levels are reflective of subcutaneous fat area in nonobese Japanese type 2 diabetic male patients.

Porphyromonas gingivalis infection is associated with carotid atherosclerosis in non-obese Japanese type 2 diabetic patients

The aim of the present study was to investigate whether non-obese Japanese type 2 diabetic patients with porphyromonas gingivalis infection have atherosclerotic vascular diseases. A total of 134 non-obese Japanese type 2 diabetic patients (96 men and 38 women, aged 36 to 84 years, body mass index [BMI] 20.1 to 26.9 kg/m2) were studied. In conjunction with BMI, glycosylated hemoglobin (HbA1c), fasting glucose, and serum lipids (triglycerides, total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol) were measured. LDL cholesterol was calculated using the Friedewald formula. Using high-resolution B-mode ultrasound scan, we measured intimal medial thickness (IMT) in plaque-free segments of bilateral common carotid arteries, and the mean of IMT in 2 vessels was used for the analysis. Furthermore, we calculated the degree of stenosis in plaque segments of bilateral common carotid arteries. The degree of carotid atherosclerosis was expressed as a percentage ratio between the area of plaque and that of the lumen using the formula (Lumen Area Residual − Lumen Area)/Lumem Area × 100. Both the areas were automatically measured by the system on a frozen transverse scanning plane at the site of maximal narrowing. When 2 or more plaques were present in the vessel, only that causing the greatest degree of stenosis was considered for analysis. Values represent mean±SEM unless otherwise stated. Immunoglobulin G (IgG) titer against porphyromonas gingivalis was 245 ± 65 (mean ± 2 SD) in nondiabetic healthy subjects. In contrast, there was a wide variation in IgG titer against porphyromonas gingivalis in type 2 diabetic patients studied (range, 16 to 26,800). Thus, we classified our type 2 diabetic patients into 2 subpopulations according to the value of mean ± 2 SD (= 310) of nondiabetic healthy subjects: one with high IgG titer against porphyromonas gingivalis (>310) (1,422 ± 408) and the other with normal IgG titer against porphyromonas gingivalis (<310) (152 ± 10, P =.002). The populations did not differ with respect to age, sex, BMI, fasting glucose, HbA1c, serum triglycerides, total, HDL, and LDL cholesterol levels. Although the mean IMT in plaque-free segments was not different between the 2 groups (0.73 ±0.03 v 0.68 ± 0.02 mm, P =.098), the degree of stenosis in plaque segments was significantly higher in the high IgG titer group (12.0% ± 2.2%) than in normal one (5.5% ± 1.4%, P =.009). From these results, it can be concluded that porphyromonas gingivalis infection, although still a subclinical infection, is associated with atherosclerotic vascular disease in non-obese Japanese type 2 diabetic patients. Copyright 2003, Elsevier Science (USA). All rights reserved.

Effect of Short-Term Low-Intensity Exercise on Insulin Sensitivity, Insulin Secretion, and Glucose and Lipid Metabolism in Non-Obese Japanese Type 2 Diabetic Patients

The aim of the present study was to investigate the effects of short-term physical exercise that did not change body mass on insulin sensitivity, insulin secretion, and glucose and lipid metabolism in 39 non-obese Japanese type 2 diabetic patients. Insulin sensitivity and insulin secretion were estimated with homeostasis model assessment insulin resistance (HOMA-IR) and HOMA-B-cell function proposed by Matthews et al., respectively. All patients were hospitalized and were engaged in low-intensity exercise that consisted of walking and dumbbell exercise for successive 7 days. There were no changes in hospital diet and the dose of any medications used throughout the study. Fasting glucose, insulin, and lipids were measured before and after exercise. After exercise, serum triglyceride levels significantly decreased, but no significant changes were observed in total and HDL cholesterol concentrations. Fasting glucose, insulin, and HOMA-IR levels significantly decreased after exercise, but HOMA-B-cell function did not change during the study. There was no significant difference between BMI levels before and after exercise. From these results, it can be concluded that short-term (7 days) low-intensity physical exercise combined with hospital diet reduces serum triglycerides, insulin resistance, and fasting glucose levels without affecting BMI in non-obese Japanese type 2 diabetic patients.

Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.

The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state. The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients. These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients.

Assessment of insulin sensitivity and insulin secretion from the oral glucose tolerance test in nonobese Japanese type 2 diabetic patients: comparison with minimal-model approach.

Assessment of insulin sensitivity and insulin secretion from the oral glucose tolerance test in nonobese Japanese type 2 diabetic patients: comparison with minimal-model approach.

Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach.

Insulin sensitivity, glucose effectiveness, and endogenous glucose production (EGP) during stable-labeled, frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) were evaluated by a single-and two-compartment minimal model combined with nonparametric deconvolution in eleven nonobese Japanese type 2 diabetic patients. Four patients were treated with sulfonylureas, and the remaining seven with diet therapy alone. None had diabetic retinopathy and microalbuminuria. Their fasting glucose level was 117+/-7 mg/dl (mean +/- SE), and HbA1c was 6.6+/-0.3%. Age-, sex-, and BMI-matched subjects with normal glucose tolerance served as control subjects. Plasma insulin response to the stimuli and insulin sensitivity indexes (S(I), S(I)*, and S(I)2* were derived from a minimal model and single- and two-compartment-labeled minimal models) were impaired in the type 2 diabetic patients. The combined ability of glucose, per se, to increase its own uptake and suppress EGP (glucose effectiveness [SG]), which was derived from kinetic analysis of plasma glucose by a minimal model, was significantly lower in the type 2 diabetic patients (0.0132+/-0.0015 vs. 0.0203+/-0.0022; P<0.05). However, the ability of glucose, per se, to stimulate glucose uptake, assessed as S(G)* and S(G)2* from the kinetic analysis of labeled glucose by single- and two-compartment minimal model, was not impaired in those patients. EGP of the type 2 diabetic patients as a whole was suppressed to the level similar to that of the control subjects despite a higher plasma glucose level throughout FSIGT. When EGP in the diabetic subjects was analyzed, considering their recent glycemic control, the initial suppression was blunted in the patients with higher HbA1c levels. In conclusion, glucose mass action to stimulate glucose uptake remains near-normal in the lean Japanese type 2 diabetic patients of this study, whereas ability of glucose to suppress EGP is impaired in the patients with recent hyperglycemia. This blunted suppression of EGP might be one of the conspirators for decreased S(G) in subjects with type 2 diabetes.