NGT Group Research Articles

Plasma C1q/TNF-Related Protein-3 (CTRP-3) and High-Mobility Group Box-1 (HMGB-1) Concentrations in Subjects with Prediabetes and Type 2 Diabetes.

Aims. To detect the association of C1q/TNF-related protein-3 (CTRP-3) and high-mobility group box-1 (HMGB-1) in subjects with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (nT2DM). Methods. 224 eligible participants were included. The 75 g oral glucose tolerance test (OGTT) and several clinical parameters of metabolic disorders and cytokines were measured. All participants were divided into three groups: normal glucose tolerance (NGT, n = 62), pre-DM (n = 111), and nT2DM group (n = 56). Results. Plasma CTRP-3 concentrations were significantly lower in subjects with pre-DM and nT2DM than that of the NGT group, while plasma HMGB-1 levels were higher in pre-DM and nT2DM group compared with the NGT group (P < 0.05). A multiple linear regression analysis showed both plasma CTRP-3 and HMGB-1 concentrations were independently associated with homeostasis model assessment for insulin resistance (HOMA-IR) and interleukin-6 (IL-6) (P < 0.05 for all). Further multiple logistical regression analyses revealed that both plasma CTRP-3 and HMGB-1 levels were significantly associated with pre-DM and nT2DM after adjusting for several confounders (P < 0.001 for all). Conclusions. Circulating CTRP-3 and HMGB-1 concentrations might be promising biomarkers to predict prediabetes and type 2 diabetes.

Relationship of glycemic control markers - 1,5 anhydroglucitol, fructosamine, and glycated hemoglobin among Asian Indians with different degrees of glucose intolerance.

Objective:1,5 anhydroglucitol (1,5 AG) is emerging as a marker of short-term glycemic control. We measured levels of 1,5 AG, fructosamine (FA), and glycated hemoglobin (HbA1c) in Asian Indians with different degrees of glucose intolerance.Materials and Methods:We recruited 210 individuals with normal glucose tolerance (NGT; n = 60), impaired glucose tolerance (IGT; n = 50), and Type 2 diabetes mellitus (T2DM; n = 100) from a large tertiary diabetes center in Chennai in Southern India. Anthropometric measurements were obtained using standardized techniques. Serum 1,5 AG (enzymatic colorimetric assay), FA (NBT/kinetic), and HbA1c (high-performance liquid chromatography) estimations were performed.Results:1,5 AG levels were significantly lower in the T2DM followed by IGT compared with the NGT group (7.9 vs. 18.8 vs. 21.8 µg/ml, P < 0.05). FA and HbA1c were higher in T2DM and IGT compared with NGT individuals (313 vs. 237 vs. 200 µmol/L, P < 0.001) (8.3 vs. 5.8 vs. 5.3%, P < 0.001).1,5 AG showed a significant negative correlation with FA (r = −0.618, P < 0.001) and HbA1c (r = −0.700, P < 0.001). 1,5 AG decreased with increasing quartiles of postprandial glucose (P for trend <0.001). However, even among individuals with HbA1c ≤7%, 27% individuals had decreased 1,5 AG plasma level (<10 µg/ml).Conclusion:Circulatory levels of 1,5 AG correlate negatively with FA and HbA1c, and may provide an additional marker to assess glycemic control in patients with Type 2 diabetes.

Plasma Periostin Levels Are Increased in Chinese Subjects with Obesity and Type 2 Diabetes and Are Positively Correlated with Glucose and Lipid Parameters.

The purpose of this study is to examine the relations among plasma periostin, glucose and lipid metabolism, insulin resistance and inflammation in Chinese patients with obesity (OB), and type 2 diabetes mellitus (T2DM). Plasma periostin levels in the T2DM group were significantly higher than the NGT group (P < 0.01). Patients with both OB and T2DM had the highest periostin levels. Correlation analysis showed that plasma periostin levels were positively correlated with weight, waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), fasting plasma glucose (FPG), 2 h postchallenge plasma glucose (2 h PG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), TNF-α, and IL-6 (P < 0.05 or 0.001) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.001). Multiple linear regression analysis showed that TG, TNF-α, and HOMA-IR were independent related factors in influencing the levels of plasma periostin (P < 0.001). These results suggested that Chinese patients with obesity and T2DM had significantly higher plasma periostin levels. Plasma periostin levels were strongly associated with plasma TG, chronic inflammation, and insulin resistance.

Abstract 11021: Circulating Cardiac Transforming Growth Factor-β is a Principal Determinant in Inducing Myocardial Hypertrophy in Transgenic Mice Overexpressing Exogenous Hepatic Transforming Growth Factor-β

Introduction: Transforming growth factor (TGF)-β is a potent growth factor that induces myocardial hypertrophy, but an interaction between circulating and myocardial TGF-β has been poorly understood. An extracellular matrix protein, fibulin-2, mediates exogenous TGF-β-induced endogenous TGF-β up-regulation in isolated cardiac fibroblasts. Hypothesis: Systemic TGF-β-induced myocardial hypertrophy is mediated primarily by enhanced myocardial TGF-β via paracrine fashion. Methods: We created double mutant mice with TGF-β1 over-expressing transgenic mice (TG) and fibulin-2 knockout mice (KO). TG developed myocardial hypertrophy due to excessive circulating hepatic TGF-β. We studied TGF-β dynamics between tissues and circulation during hypertrophic changes. Results: TG/WT developed significant myocardial hypertrophy at 8 weeks compared with non-TG (NTG) groups. Hypertrophy in TG/KO was significantly attenuated compared with TG/WT. Myocardial TGF-β mRNA level was significantly up-regulated in TG/WT compared with TG/KO or NGT groups, so was Smad2 activation, but myocardial TGF-β bioactivity was no different among all four groups. Serum carrier-bound TGF-β was significantly higher in TG/WT than in TG/KO or NTG groups, but free unbound TGF-β level was equally elevated in TG groups compared with NTG groups. Thus, hypertrophy in TG/WT may be attributed to increased serum carrier-bound TGF-β levels, not to either myocardial TGF-β activity or serum unbound TGF-β levels. Endogenous TGF-β mRNA level in kidney and liver was equally increased in TG group compared with NTG group, and was comparable in all 4 groups in lung, suggesting fibulin-2 was not involved in TGF-β-induced TGF-β synthesis in kidney, liver, or lung. Conclusions: Hepatic TGF-β-induced-myocardial TGF-β up-regulation was mediated by fibulin-2. In TG/WT, up-regulated myocardial TGF-β was mainly secreted into circulation as a soluble carrier-bound form and did not directly induce hypertrophy via paracrine fashion. It is this circulating endogenous myocardial TGF-β rather than transgene-induced hepatic TGF-β that is responsible for myocardial hypertrophy in TG/WT. Heart is a major endocrine organ in secreting circulating endogenous TGF-β in inducing myocardial hypertrophy.

Impact of glucose load in an oral glucose tolerance test on urinary albumin excretion varies with 2-h glucose levels.

The aim of the present study was to investigate whether an oral glucose load can induce an increase in urinary albumin excretion (UAE). One hundred and thirty subjects without macroalbuminuria or increased fasting serum glucose (≥7.0 mmol/L) were included in the study. At 0600 hours, subjects were asked to empty their bladder and drink 300 mL water. At 0800 hours, venous blood and 2-h urine were collected for fasting examination. Subjects were then asked to drink 300 mL solution containing 75 g glucose and, at 1000 hours, samples were collected again for post-challenge examination. Concentrations of serum glucose, urinary glucose, albumin, N-acetyl-β-D-glucosaminidase and retinol-binding protein were measured. Based on the results of the oral glucose tolerance test, subjects were divided into three groups: (i) normal glucose tolerance (NGT; n = 55); (ii) impaired glucose tolerance (IGT; n = 39); and (iii) newly diagnosed diabetes mellitus (NDM; n = 36). In the NDM group, post-challenge urinary excretion of glucose and albumin was 14- and 1.6-fold greater than fasting values, respectively. In the IGT and NGT groups, although post-challenge urinary glucose excretion was 2.6- and 1.6-fold greater than fasting values, UAE did not increase. There was a positive correlation between post-challenge serum glucose and the UAE rate (UAER; r = 0.24, P < 0.01) and the UAER increment (ΔUAER; r = 0.19, P < 0.05), as well as between the serum glucose increment and post-challenge UAER (r = 0.23, P < 0.01) and ΔUAER (r = 0.18, P < 0.05). Post-challenge serum glucose levels were independently correlated with logarithmically converted post-challenge UAER (β = 0.322, P = 0.008). Oral glucose load can induce a significant increase in UAE in NDM subjects. The main mechanism may be glomerular hyperfiltration.

Relationship between serum secreted Frizzled-related protein 4 and the pancreatic β cell function

Objective To investigate the relationship between serum secreted frizzled-related protein 4(SFRP4) and the first-phase of glucose-stimulated insulin secretion from pancreatic β cell under different glucose tolerance statuses. Methods Fifty-six patients with newly diagnosed type 2 diabetes mellitus(T2DM group), 52 patients with impaired glucose tolerance(IGT group), and 42 subjects with normal glucose tolerance(NGT group)underwent intravenous glucose tolerance test. Fasting serum SFRP4 and interleukin(IL)-1β were assayed by ELISA. Acute insulin response(AIR), the area under the curve of the first-phase(0-10 min)insulin secretion(AUC), glucose disposition index(GDI), homeostasis model assessment for β cell function index(HOMA-β), and insulin resistance index(HOMA-IR)were calculated. Results (1)The levels of SFRP4 and IL-1β in T2DM group and IGT group were significantly higher than that in NGT group[(184.38±61.34 or 141.64±40.46 or 95.46±20.13)ng/ml, P<0.01]. AIR, AUC, and GDI in T2DM group and IGT group were significantly lower than those in NGT group(P<0.01), and these results were more significantly reduced in T2DM group compared with those in IGT group.(2)SFRP4 was negatively correlated with AIR, AUC, GDI, HOMA-β(P<0.01), and positively correlated with fasting plasma glucose, 2 h plasma glucose after glucose loading, HbA1C, IL-1β, and high sensitive C-reactive protein(P<0.01). (3)Multiple stepwise regression analysis showed that AUC, HOMA-IR, and serum IL-1β level were independently associated with SFRP4. Conclusion The concentration of serum SFRP4 is closely correlated with the glycolipid metabolic disorder, the first-phase of glucose-stimulated insulin secretion, and chronic low-grade inflammation. SFRP4 may be involved in the mechanism of β cell dysfunction in type 2 diabetes mellitus. Key words: Secreted frizzled-related protein 4; β-cell function; Intravenous glucose tolerance test; Interleukin-1β; Diabetes mellitus, type 2

Abstract 63: Absence of Fibulin-2 Attenuates Cardiac Hypertrophy and Fibrosis in Transgenic Mice Over-expressing Circulating Transforming Growth Factor-beta

Background: TGF-β is a potent growth factor that induces myocardial hypertrophy and fibrosis. However, the interaction between circulating TGF-β and local myocardial TGF-β in inducing cardiac hypertrophy is not well understood. Fibulin-2 is an ECM protein that mediates TGF-β activation during cardiac hypertrophy in response to chronic angiotensin (Ang) II infusion. We tested the hypothesis that fibulin-2 mediates systemic TGF-β-induced cardiac hypertrophy. Materials &amp; Methods and Results: We created double mutant mice by crossing TGF-β over-expressing transgenic mice (TG) and fibulin-2 knockout mice (KO). TG are known to produce excessive mature porcine TGF-β from the liver. TG/WT developed significant myocardial hypertrophy at 8 weeks compared with non-TG (NTG) groups. Hypertrophy in KO/TG was significantly attenuated compared with TG/WT. Myocardial TGF-β mRNA up-regulation was significantly higher in TG/WT than in TG/KO or NGT groups, so was Smad2 activation, but myocardial TGF-β bioactivity measured by PAI-1 promoter/luciferase bioassay was comparable among all four groups. Serum carrier-bound TGF-β (total TGF-β) in WT/TG was significantly higher than that in KO/TG and NTG groups, but free TGF-β level was equally elevated in TG groups compared with NTG groups. The difference in hypertrophy between WT/TG and KO/TG may be attributed to increased myocardial TGF-β[[Unable to Display Character: &amp;#61472;]]mRNA and elevated serum total TGF-β in WT/TG, not directly to bioactive myocardial TGF-β[[Unable to Display Character: &amp;#61472;]]or serum free TGF-β. Endogenous TGF-β mRNA levels in kidney and liver were equally increased in TG groups compared with NTG groups, and were same in all 4 groups in lung, suggesting fibulin-2 was not involved in TGF-β-induced TGF-β synthesis in these organs. Conclusion: Systemic TGF-β-induced-endogenous TGF-β up-regulation was mediated by fibulin-2 in the myocardium. After secretion, endogenous myocardial TGF-β may be either sequestrated into insoluble ECM or directly released into circulation as a soluble carrier-bound form. It is circulating endogenous TGF-β secreted from the heart that is primarily responsible for myocardial hypertrophy. Heart is a major source of circulating endogenous TGF-β in the TG/WT, which assumes an endocrine role in inducing myocardial hypertrophy.

Relationship of betatrophin with youth onset type 2 diabetes among Asian Indians

Background and AimsBetatrophin is emerging as a marker for compensatory beta cell proliferation. While betatrophin has been mainly investigated in adults, there is a lack of data on betatrophin levels in youth-onset type 2 diabetes mellitus (T2DM-Y). The aim of this study was to determine levels of betatrophin and its association with T2DM-Y in Asian Indian participants. MethodsWe recruited 100 individuals with normal glucose tolerance (NGT; n=50) and newly-diagnosed cases (within 18 months of first diagnosis) of T2DM-Y (n=50) with onset between 12 and 24 years of age from a large tertiary diabetes center in Chennai in southern India. Insulin resistance was measured by homeostatic model (HOMA-IR) and insulin secretion by oral disposition index (DIO). Betatrophin levels were measured by enzyme-linked immunosorbent assay. ResultsBetatrophin levels were significantly lower in the T2DM-Y group compared with the NGT group (803 vs 1104pg/ml, p<0.001). Betatrophin showed a significant inverse correlation with waist circumference (p=0.035), HOMA-IR (p<0.001), fasting and 2h postprandial glucose (p<0.01), glycated hemoglobin (p=0.019) and a positive correlation with fasting C-peptide (p<0.001) and DIO (p=0.012). In regression analysis, betatrophin was independently associated with T2DM-Y even after adjustment for age, gender, and waist circumference (OR per standard deviation: 0.562, 95% CI: 0.342–0.899, p=0.019). However, the association was lost when HOMA-IR was included in the model (OR: 1.141, 95% CI: 0.574–2.249; p=0.646). ConclusionBetatrophin levels are lower in T2DM-Y and this association is likely mediated through insulin resistance.

Abstract P337: Association of Glucose Intolerance and Insulin Resistance with Incident Cardiovascular Disease in a Japanese Urban Cohort: The Suita Study

Introduction: Glucose intolerance and insulin resistance are known risk factors for cardiovascular disease (CVD). However, few prospective studies were reported the association between combinations of these two factors and incident CVD. We assessed the hypothesis that insulin resistance increased the association between glucose intolerance and CVD in Japanese general population. Methods: We studied 4,638 Japanese individuals (mean age 56.1 years, without CVD) who completed a baseline medical examination and a 75g oral glucose tolerance test in the Suita Study. Glucose categories were defined as follows: diabetes mellitus (DM; fasting plasma glucose levels [FPG] ≥126 mg/dL, 2 hours post-loaded glucose levels [2h-PG] ≥ 200 mg/dL, and/or DM medication); impaired glucose tolerance (IGT; FPG &lt;126 mg/dL and 2h-PG =140-199 mg/dL); impaired fasting glucose (IFG; FPG =100-125 mg/dL and 2h-PG &lt;140 mg/dL); and normal glucose tolerance [NGT]. Insulin resistance was the following formula: HOMA-IR = [FPG] x [fasting insulin] / 405. Insulin resistance was defined as HOMA-IR ≥2.5. Multivariable-adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated after adjusting for age, sex, body mass index, blood pressure category, hyperlipidemia, smoking, and drinking at the baseline. Results: During the 11.7-year follow-up, we documented 127 cerebral infarctions, 63 hemorrhagic stroke, 12 unclassified strokes, and 143 coronary heart disease events. The adjusted HRs (95% CIs) of subjects with FPG =100-125 mg/dL and ≥126 mg/dL were 1.38 (1.01-1.89) and 2.00 (1.12-3.58) for stroke and 1.47 (0.99-2.19) and 2.73 (1.43-5.22) for cerebral infarction, respectively, compared with the fasting NGT group. On the basis of the subjects with 2h-PG &lt;140 mg/dL group, the adjusted HRs (95% CIs) of subjects with 2h-PG ≥200 mg/dL were 1.71 (1.07-2.72) for stroke and 2.06 (1.20-3.54) for cerebral infarction. Compared to the NGT group, the adjusted HRs (95% CIs) of the subjects with IFG, IGT, and DM were 1.59 (1.10-2.30), 1.34 (0.89-2.00), and 1.86 (1.16-3.00) for stroke and 1.82 (1.13-2.90), 1.55 (0.93-2.56), and 2.43 (1.39-4.26) for cerebral infarction, respectively. Compared to the subjects with HOMA-IR &lt;1.5, the adjusted HRs (95% CIs) of CVD and stroke with HOMA-IR ≥2.5 were 1.45 (1.07-1.96) and 1.61 (1.07-2.42), respectively. Compared to the NGT group without insulin resistance, the IFG and DM groups with insulin resistance were observed the increased risks of stroke (HRs [95% CIs]; 2.05 [1.17-3.57] and 2.11 [1.17-3.83]) and cerebral infarction (HRs [95% CIs]; 2.45 [1.20-5.00] and 3.56 [1.84-6.88]), respectively. Conclusions: Fasting glucose intolerance and insulin resistance are predictive factors for the incidence of stroke and cerebral infarction. Insulin resistance increased the risks of incident stroke and cerebral infarction in general inhabitants with IFG and DM.

Recovery of the incretin effect in type 2 diabetic patients after biliopancreatic diversion.

Bariatric surgery often results in remission of the diabetic state in obese patients. Increased incretin effect seems to play an important role in the glycemic improvements after Roux-en-Y gastric bypass, but the impact of biliopancreatic diversion (BPD) remains unexplored. The objective was to elucidate the effect of BPD on the incretin effect and its interplay with beta-cell function and insulin sensitivity (IS) in obese subjects with type 2 diabetes (T2DM). Twenty-three women were studied: a control group of 13 lean, normal glucose-tolerant women (lean NGT) studied once and 10 obese patients with T2DM studied before, 1 and 12 months after BPD. The ObeseT2DM group underwent BPD. The main outcome measure was the change in incretin effect as measured by the isoglycemic intravenous glucose infusion test. Secondary outcomes encompassed IS and beta-cell function. At baseline, the incretin effect was lower in obese T2DM compared to lean NGT (P < .05). One month after BPD, the incretin effect was not changed, but at 12 months it reached the level of the lean NGT group (P > .05). IS improved (P < .05) 1 month after BPD and at 12 months it resembled the levels of the lean NGT group. Insulin secretory rate and beta-cell glucose sensitivity increased after BPD and achieved levels similar to lean NGT group 1 month after BPD and even higher levels at 12 months (P < .05). BPD has no acute impact on the reduced incretin effect, but 12 months after surgery the incretin effect normalizes alongside normalization of glucose control, IS and beta-cell function.

Correlation of the plasma levels of soluble RAGE and endogenous secretory RAGE with oxidative stress in pre-diabetic patients

BackgroundSoluble RAGE (sRAGE), endogenous secretory RAGE (esRAGE) and oxidative stress played important roles in the pathogenesis of diabetes and its complications. The changes in sRAGE and esRAGE during pre-diabetes were indefinite. MethodsPatients were divided into NGT, pre-diabetes (pre-DM), and newly diagnosed diabetes mellitus (DM) groups according to blood glucose levels. The levels of sRAGE, esRAGE, 8-isoprostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD) activity, total antioxidant capacity (TAOC), malondialdehyde (MDA), and other related indicators were then assessed. ResultssRAGE and esRAGE in the pre-DM and DM groups were significantly lower than in the NGT group (p<0.05). In the pre-DM group, sRAGE was positively correlated with esRAGE (r=0.382, P=0.007), and negatively correlated with homeostasis model assessment-estimated insulin resistance (HOMA-IR), MDA, and 8-iso-PGF2α (r=−0.314, −0.313, and −0.34, P=0.028, 0.028, and 0.016, respectively). The concentration of esRAGE was positively correlated with sRAGE and TAOC (r=0.382 and 0.598, and P=0.007, <0.001), and negatively correlated with MDA (r=−0.397, P=0.005). ConclusionsChanges in sRAGE, esRAGE, and oxidative stress occurred in pre-diabetic patients. sRAGE and esRAGE might play an essential role in the balance between oxidative stress and antioxidant defense. The significant findings of the studyChanges in sRAGE, esRAGE, and oxidative stress occurred in pre-diabetic patients. This study addssRAGE, esRAGE, and oxidative stress are altered early during pre-diabetes. sRAGE and esRAGE may have played different roles in the balance between oxidative stress and the antioxidant defense.

Serum IL-9, IL-17, and TGF-β levels in subjects with diabetic kidney disease (CURES-134)

The role of inflammation in both diabetes and diabetic kidney disease (DKD) is becoming more widely accepted. However, the role of recently characterized T cell cytokines interleukin (IL)-9 and IL-17 in diabetes and especially DKD is less well studied. Transforming growth factor beta (TGF-β) controls the secretion of both of these cytokines. In this study, we estimated the levels of IL-9, IL-17, and TGF-β in the serum of subjects with normal glucose tolerance (NGT=88) and subjects with type 2 diabetes without (diabetes mellitus (DM)=65) and with DKD (DKD=97) using enzyme-linked immunosorbent assay (ELISA), and we correlated these levels with the clinical risk factors of diabetes and DKD. IL-17 levels showed a serial decline and TGF-β levels showed a serial increase from NGT to DM to DKD (p<0.001). However, the IL-9 levels were significantly reduced in the DM group compared to the NGT and DKD group (p<0.001). While TGF-β and IL-17 showed a positive and negative correlation, respectively, with fasting and postprandial glucose levels and glycated hemoglobin (HbA1c), IL-9 showed positive correlation with urea and microalbuminuria. Apart from pro-inflammatory cytokines, T helper (Th) cytokines might play an important role in insulin resistance and DKD.

Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes.

Dioxin or dioxin-like compounds are ligands of the aryl hydrocarbon receptor (AhR), which is a ligand-activated nuclear transcription factor. There are limited studies about the association of serum AhR ligand activities and T2DM. Our objective was to investigate the association of serum AhR ligand activities with T2DM and its related metabolic parameters. This case-control study involved 83 subjects with T2DM as well as age-, sex-, and body mass index (BMI)-matched subjects with impaired glucose tolerance (IGT, n=130) and normal glucose tolerance (NGT, n=83). Serum AhR ligand activities were measured using a cell-based AhR ligand assay and standardized as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDDeq, pmol/l). The T2DM group had the highest AhR ligand activities compared to the IGT and NGT groups [median (interquartile range), 68.1 (53.1, 81.5), 60.2 (45.8, 75.1), and 53.3 (46.1, 63.7)pmol/l, respectively; P=0.003]. In the multivariate analysis, the log2-transformed TCDDeq levels were significantly associated with the risk of T2DM after adjusting for age, sex, and BMI (odds ratio 2.26, 95% confidence interval 1.34-3.82; P=0.002). In nondiabetic subjects, serum AhR ligand activities showed a positive correlation with fasting glucose and insulin concentrations and the homeostasis model assessment of insulin resistance, but showed a negative correlation with adiponectin concentrations. Serum AhR ligand activities were higher in the T2DM group and were correlated with the parameters of insulin resistance. Further investigation is required to elucidate the causal relationship between AhR ligand activity and T2DM.

Correlation of the incretin effect with first- and second-phase insulin secretions in Koreans with various glucose tolerance statuses.

To examine the relationship between beta-cell function and the incretin effect. We performed a 180-min hyperglycaemic clamp study with oral glucose administration at 60 min in Korean subjects with normal glucose tolerance (NGT, n = 9), impaired fasting glucose (IFG, n = 6) and type 2 diabetes mellitus (T2DM, n = 6). First- and second-phase insulin secretions were measured during the first 60 min. The insulin response to intravenous glucose during the 60- to 120-min interval (Insiv) was calculated using a prediction method. The insulin response to oral glucose (Ins(oral)) was calculated by subtracting the Insiv from the overall insulin response during the 60- to 120-min interval (Ins(overall)). The incretin effect under the hyperglycaemic clamp condition (IE(clamp)) was calculated by the equation: 100 × [(Ins(overall) - Insiv)/Ins(overall)]. The IE(clamp) was comparable among the three groups (46.3 ± 6.4%, 35.7 ± 8.8% and 51.4 ± 7.4% for the NGT, IFG and T2DM group, respectively, P = 0.327) and was not correlated with the first- and second-phase insulin secretions. However, the Ins(oral) (mU/l 60 min) was significantly different between the NGT, IFG and T2DM groups (5199 ± 1185, 2164 ± 956 and 1034 ± 355, respectively; P = 0.010) and was well correlated with the first- and second-phase insulin secretions. The incretin effect measured by the hyperglycaemic clamp with oral glucose loading was neither correlated with beta-cell function nor different between NGT, IFG and T2DM groups in Koreans.

MR quantification of total liver fat in patients with impaired glucose tolerance and healthy subjects.

ObjectiveTo explore the correlations between liver fat content and clinical index in patients with impaired glucose tolerance (IGT) and healthy subjects.Materials and Methods56 subjects were enrolled and each of them underwent upper-abdominal MRI examination that involved a T1 VIBE Dixon sequence. 14 was clinically diagnosed with IGT (collectively as IGT group ) while 42 showed normal glucose tolerance,(collectively as NGT group). NGT group was further divided into NGTFat (BMI≥25, 18 subjects) and NGTLean (BMI<25, 24 subjects). The total liver fat contents was measured and compared with clinical findings and laboratory results in order to determine statistical correlations between these parameters. Differences among IGT, NGTFat and NGTLean groups were evaluated.ResultsFor all the subjects, fat volume fractions (FVFs) ranged from 4.2% to 24.2%, positive correlations was observed with BMI, waist hip ratio(WHR), low density lipoprotein(LDL), fasting plasma insulin(FPI), homeostasis model assessment insulin resistance (HOMA-IR) and homeostasis model assessment β(HOMAβ). FVFs of IGT group (p = 0.004) and NGTFat group (p = 0.006) were significantly higher than those of NGTLean group.ConclusionsPeople with higher BMI, WHR and LDL levels tend to have higher liver fat content. Patients with BMI≥25 are more likely to develop IGT. Patients with higher FVF showed higher resistance to insulin, thus obtained a higher risk of developing type 2 diabetes mellitus.

Association between fetuin-A levels with insulin resistance and carotid intima-media thickness in patients with new-onset type 2 diabetes mellitus.

Fetuin-A, which is known to inhibit insulin signaling and pathological calcification, has emerged as a diabetes risk biomarker. In the present study, the association between the fetuin-A levels with insulin resistance (IR) and carotid intima-media thickness (CIMT) was investigated in patients with new-onset type 2 diabetes mellitus (nT2DM). A total of 100 patients with nT2DM (nT2DM group) and 100 normal glucose tolerance (NGT group) controls were evaluated. The serum fetuin-A level was measured by a commercial solid-phase ELISA kit. The estimate of IR was calculated by homeostasis model assessment (HOMA-IR). CIMT was measured by B-mode ultrasound. The association between the serum fetuin-A levels and the metabolic parameters was also analyzed. The serum fetuin-A levels were increased significantly in the nT2DM group compared to the NGT group (368.5±15.6 mg/ml vs. 152.7±7.1 mg/ml, P<0.01). Fetuin-A was positively correlated with HOMA-IR, CIMT, glycated hemoglobin, triglyceride, low-density lipoprotein cholesterol, body mass index, systolic blood pressure, fasting blood glucose and 2 h post-glucose load blood glucose (P<0.05 and P<0.01), but negatively correlated with fasting plasma insulin, 2 h plasma insulin after glucose overload, high-density lipoprotein cholesterol and HOMA-β-cell insulin secretion index (P<0.05 and P<0.01). To the best of our knowledge, the study demonstrated for the first time that there is a significant association between the serum fetuin-A levels with IR and CIMT in nT2DM. These results indicate that serum fetuin-A levels can be used as independent markers in the diagnosis of macroangiopathies in nT2DM.

Role of visfatin in the pathogenesis of gestational diabetes mellitus and its relationship with insulin resistance

To investigate the role of visfatin in the pathogenesis of gestational diabetes mellitus (GDM) and its correlation with insulin resistance. The study recruited 58 pregnant women of 24 to 28 gestational weeks in People's Hospital of Hebei Province from January to June 2013. Among them, 30 were patients with GDM (GDM group), 28 had normal oral glucose tolerance test and was referred as healthy pregnancy group (NGT group). Fourteen age-matched female who were first-degree relatives (FDR1) of type 2 diabetes mellitus patients, and 27 healthy nonpregnant women with normal oral glucose tolerance test were referred as high-risk group and normal controls (NC), respectively. The fasting plasma glucose (FPG), 1 hour and 2 hours postprandial glucose levels were measured by glucose oxidase method. The fasting insulin (FIN) levels were measured by radioimmunoassay and the homeostatic model assessment-insulin resistance index (HOMA- IR) was calculated. The levels of total cholesterol (TC), triglycerdes (TG), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) were determined. The visfatin levels were measured by ELISA. (1)The levels of FPG were significantly higher in GDM, FDR1 and NC group [(5.5 ± 0.7), (5.1 ±0.6), (5.2 ± 0.4)mmol/L] than that in NGT group [(4.5 ± 0.3) mmol/L], respectively (P < 0.05). (2) The levels of INS [(14 ± 6)mU/L], HOMA- IR (4.0 ± 2.0), 1 hour [(10.9 ± 1.8) mmol/L] and 2 hours [(8.6 ± 1.8) mmol/L] postprandial glucose levels of GDM group were significantly higher than those in NGT group [(12 ± 4) mU/L, 2.0 ± 1.0, (7. 4 ± 1.3) and (6.2 ± 0.9) mmol/L], respectively (P < 0.05). (3) The levels of TC, TG, HDL and LDL levels in GDM group were (5.5 ± 0.9), (2.8 ± 0.8), (1.8 ± 0.4) and (3.3 ± 0.8) mmol/L, and were(5.9 ± 0.8), (2.5 ± 0.7), (1.9 ± 0.4) and (3.4 ± 0.6) mmol/L in NGT group. The levels of lipid in the two groups were significantly higher than those in FDR1 or NC group, respectively(P < 0.05).(4)The levels of visfatin in GDM group and NGT group [(43 ± 10), (45 ± 12) µg/L] were significantly higher than that in FDR1 or NC group [(29 ± 9), (36 ± 7) µg/L], respectively (P < 0.05), but the visfatin levels in FDR1 group were significantly lower than that in NC group (P < 0.05). The visfatin levels in GDM group were slightly lower than that in NGT group, but the difference was not statistically significant (P > 0.05). (5)The visfatin levels in NGT group were negatively correlated to the levels of FPG, HOMA-IR and TC (r = -0.38, -0.44, -0.47, respectively, P < 0.05). But the visfatin levels in GDM group were not correlated with the levels of FPG, HOMA-IR, TC (r = -0.16, -0.01, 0.33, respectively, P > 0.05). While in NC group, the levels of visfatin were negatively correlated with FPG and 2 hours postprandial glucose(r = -0.48, -0.42, respectively, P < 0.05). Visfatin may be an important adipokine that involved in the carbohydrate and lipid metabolism in GDM, and is related to the pathogensis of GDM and insulin resistance.

Study on correlation of glucagons, type 2 diabetes and impaired glucose regulation

To analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes. Study objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC). Obvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS). Glucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA-IR and negatively correlated with INS, HOMA-beta and ISI. The increase in glucagons of T2DM and IGT patients indicated inappropriate secretion of pancreatic alphabeta cells among patients with type 2 diabetes.

Gestational diabetes outcome in a single center study: higher BMI in children after six months.

The aim of the study was to examine obstetric outcomes and metabolic disorders in patients with gestational diabetes mellitus (GDM) and their offspring compared to mothers without GDM and their offspring. We performed a retrospective single center cohort study of mothers with GDM using a questionnaire with items concerning the maternal medical history, neonatal complications, and child development. Mothers with gestational diabetes (GDM; n=130) and those with normal glucose tolerance (NGT; n=77) were recruited. GDM mothers were older (37.58 years vs. 34.32 years, p<0.0001) and had a greater body mass index (25.18 kg/m² vs. 23.37 kg/m², p<0.01). There were no significant differences regarding the mean birth weight, the frequency of Cesarean sections, and the prevalence of macrosomia (> 4 000 g). At follow-up (pediatric U5 screening visit after 6 months of birth) children of mothers with GDM had significantly higher BMI than the children of the NGT group (17.07 kg/m² vs. 16.59 kg/m², p=0.042). GDM women in need of insulin therapy during pregnancy had higher BMI than dieting GDM mothers and experienced more frequently an operative vaginal delivery (17.95% vs. 6.17%, OR 3.23, p=0.04). We found less significant differences between GDM mothers with treatment of impaired glucose tolerance and NGT mothers concerning the neonatal outcome than expected. Despite higher BMI of the GDM group's offspring at follow-up U5 visit, the children did not show any other development disorder. In conclusion treatment of GDM could minimize the frequency of obstetric and neonatal complications in this risk group.

On the status of β-cell dysfunction and insulin resistance of breast cancer patient without history of diabetes after systemic treatment.

To estimate the status of β-cell dysfunction and insulin resistance of breast cancer (BC) patient without history of diabetes mellitus (DM) after systemic treatment through an oral glucose tolerance test (OGTT) and insulin releasing test (IRT). All the 128 BC patients without history of DM after systemic treatment underwent OGTT and IRT test. Fasting and 2-h glucose levels were measured to confirm undiagnosed DM and prediabetes. Insulin sensitivity was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index and disposition index (IGI/HOMA-IR). Insulin secretion was estimated by the insulinogenic index (IGI) [Δ insulin/Δ glucose (30-0 min)]. Insulin concentrations during the OGTT and IRT at baseline were used to derive the patterns of insulin secretion curve (pattern 1, pattern 2, pattern 3, pattern 4 and pattern 5), which were used to estimate the risk of developing DM. Of 128 BC patients without history of DM after systemic treatment, there were 46 cases (35.9%) of NGT, 60 cases (46.9%) of prediabetes and 22 cases (17.2%) of DM. The BMI of prediabetes and DM were higher than NGT groups with statistical significance. After adjusted for BMI, IGI was significantly lower in DM group but not significantly different between NGT group and prediabetes group. HOMA-IR, Matsuda index and disposition index were significantly different in DM group compared with NGT group and prediabetes and also significantly different between NGT and prediabetes groups. The total rates of patterns 4 and 5 in NGT and prediabetes groups were 15.3% (10.9 and 4.4%) and 48.3% (31.6 and 16.7%), respectively. β-Cell dysfunction and insulin resistance may appear in BC patients after systemic treatment. BC patients have high risk in development of DM even in NGT and prediabetes groups confirmed by OGTT.