Glucose Intolerance In Group Research Articles

Prevalance of impaired glucose tolerance and its association with adverse perinatal outcomes in non-gestational diabetes pregnancies

Objective: Gestational diabetes mellitus (GDM) is characterized by glucose intolerance with onset during pregnancy and is one of the most common metabolic disorders complicating pregnancy. The aim of this study was to evaluate the risk of maternal and neonatal outcomes in non-gestational diabetes pregnancies with abnormal glucose challenge test (GCT) and abnormal glucose tolerance test (GTT) results.
 
 Methods: In this retrospective cohort study of 2982 singleton pregnancies, all patients underwent a non-fasting 50 g GCT at 24 to 28 weeks of gestation. A GCT cutoff of ≥ 140 mg/dl was selected. Women with an elevated GCT underwent prompt diagnostic testing with a 3-hour GTT. Subjects were divided into four groups according to GCT and GTT results.
 
 Results: There was an impaired glucose tolerance in 19.2 % of patients and 14.7 % of them had mild glucose intolerance and 4.5 % of them had moderate glucose intolerance. As expected, there was statistically significant difference in fetal macrosomia, neonatal hypoglicemia, PE, primary CS, and preterm birth between secreening negative and GDM patients (p < 0.0001). We also observed statistically significant difference in neonatal hypoglicemia (p = 0.0001) and PE (p = 0.0277) between screning negative and mild glucose intolerance group. Moreover, there was a significant difference in fetal macrosomia (p=0.0480) between mild glucose intolerance and moderate glucose intolerance groups.
 
 Conclusion: Compared with screening negative group, mild and moderate glucose intolerance are associated with increased adverse maternal and neonatal outcomes even in the absence of GDM.

66-LB: Poor Sleep Is Correlated with Higher Parenting Stress in Women Who Have Had Gestational Diabetes

Background: Theoretically, women who have had GDM are likely to have increased stress levels following pregnancy related to parental stress exacerbated by concerns about personal health (e.g., development of T2DM). Such stress may negatively impact sleep, however, the relationship between parenting stress and sleep in women who have had GDM has not been well investigated. Therefore, the purpose of the study was to explore the correlations between sleep and parenting stress in people who have had GDM. Methods: Twenty-six woman (ages: 34.22 ± 3.51 years; ethnicity: African American [38.46%], Hispanic [30.77%], Caucasian [19.23%], and Asian [11.54%]; A1C: 5.78 ± .98 %; BMI: 36.28 ± 10.70; age of child from GDM pregnancy: 6.07 ± 3.95 months; number of children: range1-6; months of postpartum: 6.06 ± 3.96) who had GDM on the previous pregnancy completed self-reported questionnaires. These included Parenting Stress Index (PSI-4, SF), PROMIS Global Health-Physical (v.1.2;2a), PROMIS Fatigue (v.1.0;8a), PROMIS Sleep Disturbance (v.1.0;8b), and PROMIS Sleep-Related Impairment (v.1.0;8a). The Spearman’s correlation was used to analyze data using STATA 17.0. Results: The mean total score on the Parenting Stress Index was positively correlated with PROMIS Fatigue (Spearman’s r = 0.61, p < .01); PROMIS Sleep Disturbance (r = 0.61, p < .001); and PROMIS Sleep-Related Impairment (r= 0.57, p < .001). On the other hand, the mean total score on the Parenting Stress Index was negatively correlated with PROMIS Global Health-Physical (r = -0.58, p < .01), and was not correlated with A1C and BMI. Conclusion: In this glucose intolerant group of women with previous GDM, parenting stress was correlated with fatigue alone with sleep disturbances and impairments. In addition, parenting stress was negatively correlated with individuals’ assessment of their health. Finding suggested that it is necessary to explore the associations between parenting stress, sleep, and glucose metabolism in women who have had GDM. Disclosure M. Park: None. Y. Song: None. M. Chu: None. L. T. Quinn: None.

Impact of glucose intolerance on the risk of carotid plaque instability assessed by MRI

Atherosclerotic disease is a complex multifactorial and systemic condition that affects arteries, including carotid arteries. Atherosclerotic plaque instability can predict plaque rupture, the major cause of ischemic strokes. Intraplaque hemorrhage (IPH) is an important contributor of plaque instability caused by the pro-inflammatory and hypoxic environment of the atherosclerotic plaque promoting the development of intraplaque neo-vessels. Metabolic disturbances are known to promote atherosclerotic plaque formation. Ischemic stroke prevalence is increase in patients with obesity and/or type-2 diabetes. The objective of the present study is to evaluate whether glucose intolerance can increase IPH in patients with carotid atherosclerosis. This study involves 57 patients with carotid atherosclerotic plaque with more than 50% stenosis, asymptomatic for more than 6 months, with no surgical indication for endarterectomy and no recent inflammatory disease. IPH was evaluated by magnetic resonance imaging (MRI). A score was defined for IPH (from 0: non hemorrhage to 3: large hemorrhage). Fasting blood glucose level was measured and patients were allocated in glucose tolerant (< 5,6 mM) or glucose intolerant (> 5,6 mM) groups. We showed that the score of IPH quantified by MRI was increased in the glucose intolerant subgroup of patients (0.39 vs. 0.84, P = 0.04). This result was confirmed by a higher prevalence of hemorrhagic plaque in the glucose intolerant group (73 vs. 41%, P < 0.05). Interestingly, the fasting blood glucose level is higher in patients with a hemorrhagic plaque than non-hemorrhagic plaque (5.6 vs. 6.9 mM, P = 0.04). Moreover, neither other known pro-atherogenic markers (LDL, cholesterol, TG) nor obesity seem to increase the degree of IPH. In conclusion, we demonstrated a strong impact of blood glucose level on the risk of plaque instability reflected by IPH. Further experiments are needed to strengthen the relation between type-2 diabetes, blood glucose level and IPH to understand the underlying mechanisms.

Risk of liver fibrosis in patients with prediabetes and diabetes mellitus.

The aim of this study was to assess the risk of liver fibrosis in those with no glucose intolerance, prediabetes, or diabetes. A cross-sectional study was conducted based on a cohort from a health examination program which included a magnetic resonance elastography (MRE). Participants were classified into three groups according to glucose tolerance: no glucose intolerance, prediabetes, and diabetes mellitus. Liver fibrosis was evaluated by liver stiffness measurement (LSM) value using two-dimensional real-time MRE. The risk of significant liver fibrosis was compared among three groups. A total of 2,090 subjects were included: no glucose intolerance (n = 889); prediabetes (n = 985); and diabetes (n = 216). Mean values of LSM in those with no glucose intolerance, prediabetes, and diabetes were 2.37 ± 0.43 kPa, 2.41 ± 0.34 kPa, and 2.65 ± 0.70 kPa, respectively (p<0.001). Proportions of significant fibrosis (LSM ≥2.97 kPa) in no glucose intolerance, prediabetes, and diabetes groups were 3.1%, 4.4%, and 16.7%, respectively (p<0.001). Compared with those with no glucose intolerance, those with diabetes had higher risk of significant fibrosis (adjusted odds ratio [aOR]: 3.02, 95% confidence interval [CI]: 1.57–5.81, p<0.001). However, there was no difference between prediabetes and no glucose intolerance (aOR: 1.05, 95% CI: 0.59–1.86, p = 0.876). A subgroup analysis also showed that prediabetes, unlike diabetes, was not associated with significant fibrosis in subjects with or without liver disease. Diabetes, but not prediabetes, is a risk factor for significant liver fibrosis. This finding is consistent regarldess of the pressence of liver disease.

Gut Microbiota Signature Among Asian Post-gestational Diabetes Women Linked to Macronutrient Intakes and Metabolic Phenotypes

Aberrant gut microbiota dysbiosis in women with a previous history of gestational diabetes mellitus (post-GDM) was comparable to that in adults with type 2 diabetes mellitus (T2DM). Nonetheless, potential relationships between diet, gut microbiota, and metabolic phenotypes in post-GDM women after delivery are yet to be discovered. In this research, we assessed the relationship of the macronutrient intakes, gut microbiota composition, and metabolic phenotypes (i.e., anthropometrics and glycemic control) in post-GDM women with and without postpartum glucose intolerance (GI). About 24 post-GDM women were included in this study, 14 women were grouped in the GI group and 10 women were grouped in the normal glucose tolerance (NGT) group according to oral glucose tolerance test. Macronutrient intake assessment using a 3-day dietary record, anthropometric measurements, biochemical analyses, and fecal sampling were done during 3–6 months postpartum. Gut microbiota profiling was determined using 16S rRNA genes sequencing targeting the V3–V4 regions. The relationships between macronutrient intakes, gut microbiota composition, and metabolic phenotypes were evaluated using Pearson’s correlation coefficient and stepwise regression analyses. In this study, most post-GDM women had significantly poor dietary fiber adherence than the nutritional recommendations. Women from the GI group have significantly higher fasting blood glucose (FBG), HbA1c, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels compared to the NGT group. The group also showed significant elevation of high-sensitivity C-reactive protein (hs-CRP) level when compared to the normal value. Specific gut microbial taxa derived from Proteobacteria and Bacteroidetes such as Parasutterella, Aquicella, Haliscomenobacter, and Prevotellaceae_NK3B31_group were significantly abundant in the GI group compared to the NGT group. Prevotellaceae_NK3B31_group was significantly associated with high FBG, HOMA-IR, and HbA1c levels. Low fiber and monounsaturated fatty acids intakes were associated with Lactobacillus. Meanwhile, Lactobacillus was associated with high body mass index, waist circumference, 2-h postprandial blood glucose, and hs-CRP levels. Our study suggested that macronutrient intake is an important predictor of gut microbiota dysbiosis and is associated with obesity, low-grade inflammation, and poor glycemic control in post-GDM women. Hence, dietary intake modification to remodel gut microbiota composition is a promising T2DM preventive strategy in post-GDM women.

A Mechanism Exploration of Metabolic Syndrome Causing Nodular Thyroid Disease.

Background Metabolic syndrome (MS) and its components have been demonstrated to facilitate the prevalence of thyroid nodules (TNs). The underlying pathogenesis needs to be elucidated. Methods A total of 2722 subjects, who underwent health checkup in our institute from December 2014 to November 2018, were retrospectively and randomly collected. After exclusion, 2068 subjects were chosen, and their anthropic and clinical data were collected. Results After matching age, gender, uric acid (UA), and creatinine (Cr) by propensity score matching (PSM), subjects with MS had higher prevalence of TNs than those without MS, as well as higher thyroid-stimulating hormone (TSH) and inflammatory levels, indicated by the higher white blood cell (WBC), lymphocyte (LY), and monocyte/high-density lipoprotein (Mo/HDL). After matching age, gender, UA, Cr, TSH, free triiodothyronine (FT3), thyroxine (FT4), WBC, NE, LY, Mo, NE/LY, LY/Mo, and Mo/HDL by PSM, no significant difference of the prevalence of TNs was found between MS and non-MS groups. Step logistic regression suggested glucose intolerance (GI), among all the components of MS, was an independent impact factor of TNs and was considered to contribute most to the formation of TNs. The prevalence of TNs was higher in the GI group after matching age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood sugar (FBS), UA, Cr, triglyceride (TG), cholesterol (CHOL), HDL, and low-density lipoprotein (LDL). Conclusions Patients with MS have a higher prevalence of TNs, probably due to the elevated TSH and inflammatory levels in vivo. Among the components of MS, glucose intolerance contributes most to the development of TNs.

Incidence of postpartum glucose intolerance among women with gestational diabetes in Siriraj Hospital

Objectives: To determine the incidence of postpartum glucose intolerance among women with gestational diabetes (GDM) and its associated factors. Methods: A total of 110 GDM women who delivered at Siriraj Hospital were enrolled. A 2-hour 75-gram glucose tolerance test and were offered at 6-12 weeks postpartum to determine incidence of glucose intolerance, which include impaired glucose tolerance (IGT), and type 2 diabetes (T2DM). Demographic data, GDM risks and diagnosis data, and delivery data were collected. Incidence of glucose intolerance was estimated. Comparison was made between glucose intolerance groups to determine possible associated factors. Results: Mean age was 33.7±5.1 years, and 46% were nulliparous. According to pre-pregnancy BMI, 45.5% were overweight/obese, and 24.5% gained weight greater than recommendation. Majority was GDM A1 (85.5%), and 63.6% were diagnosed before 20 weeks of gestation. Mean postpartum follow up time was at 6.2 ± 0.9 weeks. Incidence of postpartum IGT and T2DM were 35.5% and 10% respectively. No difference was found between groups in terms of pre-pregnancy BMI, gestational weight gain, weight retention, and severity of GDM. However, HbA1c level was significantly greater among women with postpartum T2DM than IGT and normal results (6.1±0.5%, 5.6±0.4%, and 5.4±0.3% respectively, p 6% significantly increased the chance of T2DM (33.3% vs. 53.4%, p=0.001). Conclusion: Among GDM pregnant women, incidence of postpartum glucose intolerance was 45.5% (35.5% IGT and 10% T2DM). HbA1c level of >6% significantly increased the chance of postpartum T2DM.

Risk factors for postpartum glucose intolerance in women with gestational diabetes mellitus

Objectives: To determine the risk factors for glucose intolerance (GI) during the postpartum period in women with gestational diabetes mellitus (GDM).Methods: This prospective cohort study included 72 Japanese women with GDM who underwent 75 g oral glucose tolerance tests (OGTT) at 12 weeks after delivery. These women were divided into the GI group and the normal group based on postpartum OGTT. Risk factors for GI, including levels of blood glucose (BG), area under the curve (AUC) of glucose, AUC insulin, HbA1c, homeostasis model assessment-insulin resistance (HOMA-IR), HOMA-β, insulinogenic index (II) and the oral disposition index (DI) in antepartum OGTT, were analyzed by logistic regression analyses.Results: Of the 72 women, 60 (83.3%) were normal and 12 (16.7%) had GI. By univariate logistic regression analyses, fasting BG, AUC glucose, HOMA-β, II and oral DI were selected as risk factors for GI. Multivariate logistic regression analysis revealed that the level of II in antepartum OGTT was a significant factor that predicted GI after delivery (odds ratio, 0.008; 95% CI, 0.0001–0.9; p < 0.05).Conclusions: II measured by OGTT during pregnancy might be a useful predictor of GI within the early postpartum period in women with GDM.

Correlation between inflammatory markers and insulin resistance in pregnancy

Gestational diabetes mellitus (GDM) is associated with an increased risk of postpartum type 2 diabetes mellitus and cardiovascular risk factors, such as obesity, hypertension, dyslipidaemia and systemic inflammation. We aimed to evaluate further lipid profile and inflammatory status assessed by high sensitive C-reactive protein (hsCRP) and TNF-α in GDM. Based on oral glucose tolerance testing, participants were stratified into three groups: normal 50 g glucose challenge test (GCT), normal 100 g glucose tolerance test (NOGTT) (control group) (n = 40); abnormal GCT NOGTT (glucose intolerance) (n = 37); and GDM (n = 39), defined by Carpenter and Coustan. The three groups did not demonstrate significantly different hsCRP levels (p = 0.4180) and lipid profile parameters, such as total cholesterol (p = 0.4210) and LDL-cholesterol (p = 0.4440) levels. Triglycerides (p = 0.0150) and atherogenic index of the plasma levels (p = 0.0280) were slightly higher in the GDM group. But, TNF-α levels increased significantly in the GDM (p < 0.0001) and in glucose intolerance (p = 0.0062) groups as compared with the control group. Among the metabolic syndrome components, insulin resistance was apparently associated with TNF-α, whereas dyslipidaemia was slightly associated with hsCRP because of the effects of maternal age on lipid markers. These findings suggest that TNF-α has a stronger correlation with pregnancy-associated insulin resistance than hsCRP at 24 to 28 weeks’ gestation.

Relationship between serum cholesterol efflux capacity and glucose intolerance in Japanese-Americans.

Serum cholesterol efflux has been suggested to be a key anti-atherogenic function of reverse cholesterol transport. Meanwhile, the quantitative and qualitative alteration of the levels of lipoproteins in the serum has been reported in patients with diabetes, although it remains unclear whether the serum cholesterol efflux capacity is impaired in cases of newly diagnosed glucose intolerance. We thus assessed the relationship between the serum cholesterol efflux capacity and glucose intolerance as detected using oral glucose tolerance tests (OGTTs). We measured the capacity of whole serum to mediate cholesterol efflux from human THP-1 macrophages in a cohort of 439 Japanese-Americans who underwent 75-g OGTTs. A multiple regression analysis was performed to examine the relationship between the serum cholesterol efflux capacity and glucose intolerance. The serum cholesterol efflux capacity was found to be negatively correlated with the area under the curve for the serum glucose concentration during the 75-g OGTTs in all subjects. In addition, the serum cholesterol efflux capacity was found to be modestly but significantly lower in the glucose intolerance group (31.4 ± 6.2%) than in the normal glucose tolerance group (33.2 ± 6.1%). There was also a negative association between the serum cholesterol efflux capacity and glucose intolerance after adjusting for age and sex. Moreover, this association remained significant even after further adjustments for serum total cholesterol, high-density lipoprotein cholesterol, apolipoprotein AI and C-reactive protein. The serum cholesterol efflux capacity is impaired in Japanese-Americans newly diagnosed with glucose intolerance. This impairment may contribute in some manner to increasing the risk of atherosclerotic disease in subjects with glucose intolerance.

Risk interaction of obesity, insulin resistance and hormone-sensitive lipase promoter polymorphisms (LIPE-60 C &gt; G) in the development of fatty liver

BackgroundHormone sensitive lipase (HSL) promoter (LIPE-60 C > G) polymorphism has been found to be involved in hepatic steatosis, obesity, diabetes and dyslipidemia. The precise interactions between these risk factors and genetic susceptibility that may affect non-alcoholic fatty liver disease (NAFLD) are still not fully determined.MethodsA cross-sectional study was conducted in 1056 men. To avoid the confounding effect of plasma glucose, the study population was classified into normal glucose tolerance (NGT, n = 729) and glucose intolerance (GI, n = 299) groups. NAFLD was diagnosed by abdominal ultrasound after ruling out any history of alcohol abuse. A multivariate regression model was used to estimate the impact of these factors on NAFLD.ResultsIn the NGT group, subjects with NAFLD often have complicated metabolic abnormalities. The coexistence of NAFLD and GI has been demonstrated to have a synergistic effect raising BMI, serum insulin and HOMA-insulin resistance (HOMA-IR). BMI and adipose-insulin resistance (Adipo-IR), but not HOMA-IR, significantly contributed to a greater risk of developing NAFLD. Serum triglyceride was significantly up-regulated in men with the (CG + GG) genotype of HSL promoter polymorphism, NAFLD and Adiopo-IR in sequence.ConclusionAdipo-IR, rather than HOMA-IR, appears to be a consistent insulin resistance index in the study of NAFLD. G allele of the HSL promoter polymorphism may contribute the greatest impact raising serum triglyceride in a state of glucose intolerance.

Glucose Intolerance Is Associated With Increased Intimal-Medial Thickness of the Carotid Artery and Increased Pulse-Wave Velocity in Renal Transplant Recipients

BackgroundAlthough new-onset diabetes after transplantation has been demonstrated to have a significant negative impact on allograft and patient survival, the role of glucose intolerance (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT], as asymptomatic hyperglycemia and borderline diabetes, has not been identified in renal transplant recipients. MethodsWe enrolled 32 renal transplant recipients (at least 1year after transplantation) without prior evidence of diabetes at our institution in this study. Transplant recipients were divided into 2 groups (normal glucose tolerance group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose. Glucose intolerance included IFG, IGT, and IFG/IGT. Normal glucose tolerance was detected in 19 patients, and glucose intolerance in 13: had 6 IGT, 2 IFG, and 5 IGT/IFG. Bilateral brachial-ankle pulse-wave velocity (baPWV) and intimal-media thickness (IMT) measured as markers of atherosclerosis were compared between the 2 groups. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic β-cell function evaluated by the homeostasis model assessment of β-cell function and insulinogenic index. ResultsThe patients in the glucose intolerance group showed significantly greater baPWV and IMT than those in the normal glucose tolerance group. HOMA-R in the glucose intolerance patients was significantly higher than in the normal glucose tolerance patients. Linear regression analysis showed the increased IMT in the renal transplant recipients to be significantly correlated with HOMA-R. ConclusionsRenal transplant recipients with glucose intolerance had increased IMT and baPWV, suggesting that glucose intolerance in renal transplant recipients may induce atherosclerosis and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Relation of RAS Gene Polymorphisms with Impaired Glucose Tolerance in Patient with End Stage Renal Failure

Renin angiotensin system (RAS) is a system that is the role of renal hemodynamics, blood pressure and fluid electrolyte balance regulation with progression to end-stage renal disease (ESRD). Angiotensin II (AII),the main mediator of this system, is thought to cause a functional impairment in insulin receptor and post receptor signaling pathways. Our aim; was to show the relation of angiotensin-converting enzyme (ACE), angiotensin II receptor type 1 (AT1 R) and angiotensinogen gene (AGT) polymorphisms, that cause genetic susceptibility to over activation of RAS, to glucose intolerance in patient with end stage renal failure. The study included one hundredth patients. Based on fasting plasma glucose values and oral glucose tolerance test second hours glucose values, patients were grouped as normal patients and patients with glucose intolerance (impaired fasting glycemia (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM)). Insulin resistance was calculated by HOMA-IR method and insulin sensitivity index was calculated by ISI-S method. ACE, AT1 R, AGT polymorphisms were detected by polymerase chain reaction (PCR) method. There was no statistically significant difference between distribution of ACE, AT1R and AGT genotypes and glucose intolerance groups, and insulin resistance. There was a statistically significant difference between MM and TT genotypes and average insulin resistance values (p < 0,04). We have obtained results suggesting a relation between ACE gene D allele and glucose intolerance in patients with end stage renal failure (p=0.06). Moreover, a relation has been shown between AGT gene T allele and insulin resistance (p=0.04).

49 THE ABNORMALITY OF GLUCOSE TOLERANCE TEST IN PHEOCHROMOCYTOMA: ONE OF THE SIGNIFICANT FINDINGS OF POSTOPERATIVE HYPOGLYCEMIA

INTRODUCTION AND OBJECTIVES: The resection of pheochromocytoma inevitably includes several possible life-threatening complications. Although the blood pressure control was investigated, there have been few studies regarding postoperative hypoglycemia. The aim of this study is to analyze the correlation between preoperative variables and postoperative hypoglycemia. METHODS: This study included 14 patients who underwent surgical removal of pheochromocytoma and intraand postoperative closed glucose monitorings. Preoperative variables included age, tumor size, urinary catecholamine levels, HbA1c, 75g oral glucose tolerance test, homeostasis model assessment of insulin resistance, Urinary excretion of C-peptide immunoreactivity and Insulinogenic index. Glucose tolerance was categorized into normal glucose tolerance (NGT), impaired fasting glycemia (IFG), impaired glucose tolerance (IGT) or diabetes mellitus (DM) according to the WHO criteria. We analyzed the relationship of these preoperative parameters and postoperative hypoglycemia. Hypoglycemia was defined as a serum glucose level of 72 mg/dl. RESULTS: Postoperative hypoglycemia was occurred in eight of 14 patients (57.1%). All of them were glucose intolerance group consisting of one IFG, 4 IGT and 3 DM. All 6 patients with normal glucose tolerance did not develop postoperative hypoglycemia. The mean level of lowest glucose was 68.1 20.0 mg/dl in patients with glucose intolerance group. On the other hand, the mean level of lowest glucose was 101.2 16.6 mg/dl in normal glucose tolerance group. Lowest glucose level was significantly lower in the glucose intolerance group (p 0.019). Univariate analysis revealed glucose intolerance had statistically significant (p 0.0003) association with postoperative hypoglycemia. Urinary norepinephrine level (p 0.0028) and age (p 0.02) also had significant association with postoperative hypoglycemia. CONCLUSIONS: Glucose tolerance test abnormality is one of the significant findings of postoperative hypoglycemia. Pheochromocytoma patients with this sign should be monitored closely. Source of Funding: None

Glucose Intolerance Is Associated with Increased Intimal Medial Thickness of the Carotid Artery and Increased Pulse Wave Velocity in Renal Transplant Recipients

Background: New-onset diabetes after transplantation has a significant negative impact on allograft and patient survival, and glucose intolerance (impaired fasting glucose; IFG and/or impaired glucose tolerance; IGT) is asymptomatic hyperglycemia and borderline diabetes. Previous reports have shown that glucose intolerance is a risk factor for diabetes and cardiovascular disease in general populations. However, the clinical significance of glucose intolerance in renal transplant recipients has not been identified. Measurements of the intimal-medial thickness (IMT) of the carotid arteries by B-mode ultrasound and pulse wave velocity (PWV) have been identified as non-invasive methods for assessing atherosclerosis. Our study was designed to determine whether glucose intolerance affects the occurrence of atherosclerosis by the evaluation of IMT and PWV in renal transplant recipients. Patients and methods: A total of 32 renal transplant recipients without prior evidence of diabetes (at least a year after transplantation) at our institution was enrolled in this study. Transplant recipients were divided into two groups (normal glucose tolerance (NGT) group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose (OGTT). NGT was defined as fasting plasma glucose (FPG) < 110 mg/dl and 2h plasma glucose < 140 mg/dl, IFG as 110-126 mg/dl and < 140 mg/dl, IGT as < 110 mg/dl and 140-200 mg/dl, and diabetes mellitus (DM) as >126 mg/dl and >200 mg/dl, respectively. Glucose intolerance included IFG, IGT, IFG/IGT, and DM. Categories of glucose tolerance were defined according to the World Health Organization criteria. NGT was detected in 19 patients as assessed by OGTT, while 13 patients had glucose intolerance; 6 had IGT, 2 had IFG, and 5 had IGT and IFG. No patients had DM. Bilateral brachial-ankle PWV (baPWV) and IMT were measured as markers of atherosclerosis and compared between the subjects with glucose intolerance and those with NGT among the renal transplant recipients. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic β-cell function was evaluated by the homeostasis model assessment of β-cell function (HOMA-β) and insulinogenic index. Results: The patients in the glucose intolerance group showed significantly greater baPWV and IMT than the patients in the NGT group. There was no significant difference in HOMA- β between the two groups, whereas insulinogenic index was significantly lower in the glucose intolerance group than in the NGT group. HOMA-R in the glucose intolerance group was significantly higher than that in the NGT group. Liner regression analysis showed that the rise in IMT in the renal transplant recipients significantly correlated with HOMA-R. Conclusions: This present study demonstrated that renal transplant recipients with glucose intolerance had increased IMT and baPWV. Our results suggested that glucose intolerance in renal transplant recipients may induce atherosclerosis, and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Glucose Intolerance Is Associated with Increased Intimal Medial Thickness of the Carotid Artery and Increased Pulse Wave Velocity in Renal Transplant Recipients

Background: New-onset diabetes after transplantation has a significant negative impact on allograft and patient survival, and glucose intolerance (impaired fasting glucose; IFG and/or impaired glucose tolerance; IGT) is asymptomatic hyperglycemia and borderline diabetes. Previous reports have shown that glucose intolerance is a risk factor for diabetes and cardiovascular disease in general populations. However, the clinical significance of glucose intolerance in renal transplant recipients has not been identified. Measurements of the intimal-medial thickness (IMT) of the carotid arteries by B-mode ultrasound and pulse wave velocity (PWV) have been identified as non-invasive methods for assessing atherosclerosis. Our study was designed to determine whether glucose intolerance affects the occurrence of atherosclerosis by the evaluation of IMT and PWV in renal transplant recipients. Patients and methods: A total of 32 renal transplant recipients without prior evidence of diabetes (at least a year after transplantation) at our institution was enrolled in this study. Transplant recipients were divided into two groups (normal glucose tolerance (NGT) group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose (OGTT). NGT was defined as fasting plasma glucose (FPG) < 110 mg/dl and 2h plasma glucose < 140 mg/dl, IFG as 110-126 mg/dl and < 140 mg/dl, IGT as < 110 mg/dl and 140-200 mg/dl, and diabetes mellitus (DM) as >126 mg/dl and >200 mg/dl, respectively. Glucose intolerance included IFG, IGT, IFG/IGT, and DM. Categories of glucose tolerance were defined according to the World Health Organization criteria. NGT was detected in 19 patients as assessed by OGTT, while 13 patients had glucose intolerance; 6 had IGT, 2 had IFG, and 5 had IGT and IFG. No patients had DM. Bilateral brachial-ankle PWV (baPWV) and IMT were measured as markers of atherosclerosis and compared between the subjects with glucose intolerance and those with NGT among the renal transplant recipients. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic β-cell function was evaluated by the homeostasis model assessment of β-cell function (HOMA-β) and insulinogenic index. Results: The patients in the glucose intolerance group showed significantly greater baPWV and IMT than the patients in the NGT group. There was no significant difference in HOMA- β between the two groups, whereas insulinogenic index was significantly lower in the glucose intolerance group than in the NGT group. HOMA-R in the glucose intolerance group was significantly higher than that in the NGT group. Liner regression analysis showed that the rise in IMT in the renal transplant recipients significantly correlated with HOMA-R. Conclusions: This present study demonstrated that renal transplant recipients with glucose intolerance had increased IMT and baPWV. Our results suggested that glucose intolerance in renal transplant recipients may induce atherosclerosis, and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

The Clinical Significance of HbA1c as a Predictive Factor for Abnormal Postprandial Glucose Metabolism in NAFLD Patients with an Elevated Liver Chemistry

NAFLD patients often show normal fasting glucose levels despite having abnormal postprandial glucose levels. This study is aimed at examining the possibility of utilizing HbA1c as a surrogate marker for abnormal glucose tolerance in NAFLD. This study was conducted on ninety-one NAFLD patients exhibiting elevated liver enzyme. Oral glucose tolerance tests (OGTT) (75g) were performed. Insulin concentrations were measured in a fasting state, and again at 120 minutes. Sixteen subjects (44.7%) showed abnormal postprandial glucose levels among subjects with normal fasting glucose level (<100mg/dL). Among subjects whose fasting glucose levels were within the 100-125mg/dL range, 30 patients (68.2%) showed abnormal OGTT findings and 13 patients (29.5%) were diagnosed as diabetics. In univariate analysis, the predictive factors for abnormal glucose tolerance were found to be HbA1c, age, fasting glucose and 120-minute insulin. However, in multivariate analysis, only HbA1c was found to be a significant predictive factor ((β)=0.43, p=0.017). The mean values for HbA1c were higher in the diabetes (6.2%) and glucose intolerance groups (5.8%) than in the normal group (5.5%). Using HbA1c 5.8% as the cut-off level in AUROC, sensitivity and specificity for predicting abnormal OGTT were 71.0% and 89.9%. Of NAFLD patients who showed HbA1c concentrations of 5.8% or higher, 90.9% showed abnormal OGTT. In NAFLD patients, an HbA1c concentration of 5.8% or higher can be used as an index for predicting abnormal postprandial glucose tolerance.

Impaired glucose tolerance, but not impaired fasting glucose, is a risk factor for early‐stage atherosclerosis

The study aimed to investigate early-stage atherosclerosis in patients with impaired fasting glucose compared with patients with impaired glucose tolerance. Body mass index, systolic blood pressure, fasting plasma glucose, lipid variables, ankle-brachial pressure index and brachial-ankle pulse wave velocity were measured in 2842 subjects from Takasaki city located approximately 100 km north of Tokyo in Japan. The subjects were divided into the following five groups based on a 75-g oral glucose tolerance test: (i) normal fasting plasma glucose/normal glucose tolerance group, (ii) impaired fasting glucose group, (iii) impaired glucose tolerance group, (iv) combined glucose intolerance group and (v) diabetic glucose intolerance group. In comparison with fasting plasma glucose levels (r = 0.269, P < 0.0001), 2-h post-challenge glucose levels were more closely correlated with pulse wave velocity values (r = 0.300, P < 0.0001). The groups with impaired glucose tolerance, combined glucose intolerance and diabetic glucose intolerance had significantly higher pulse wave velocity values compared with the groups with normal glucose tolerance and impaired fasting glucose. Multiple regression analyses showed an independent association of age, systolic blood pressures, total cholesterol, fasting and 2h plasma glucose with pulsewave velocityvalues. Furthermore, pulse wave velocity was not significantly correlated with fasting plasma glucose, but was correlated with increased 2h plasma glucose. Groups with impaired glucose tolerance and combined glucose intolerance had significantly higher brachio-ankle pulse wave velocity values compared with the group with normal glucose tolerance. Although the group with impaired fasting glucose showed a marginal increase in pulse wave velocity values compared with the group with normal glucose tolerance, the difference was not significant. Thus impaired glucose tolerance, but not impaired fasting glucose, is a risk factor for early-stage atherosclerosis.

The flavonoid-rich fraction of Coreopsis tinctoria promotes glucose tolerance regain through pancreatic function recovery in streptozotocin-induced glucose-intolerant rats

Infusions of Coreopsis tinctoria Nutt. flowering tops have been used traditionally in Portugal to control hyperglycaemia and a previous study revealed that daily administration of the infusion during a 3-week period promoted the recovery of glucose tolerance by a mechanism different from inhibition of glucose absorption and direct promotion of insulin secretion. We know report the study of the ethyl acetate fraction of Coreopsis tinctoria flowers infusion aiming to confirm flavonoids as bioactive metabolites. To give one step forward into the antihyperglycaemic mechanism of action of this traditionally used plant we also studied the activity of Coreopsis tinctoria flavonoids on the pancreatic function of glucose-intolerant rats. A standard antioxidant, Trolox, was also studied for comparative purposes as the antioxidant mechanism has been frequently purposed as one of the mechanisms mediating antihyperglycaemic effects of flavonoid-rich extracts. Thirteen compounds, mainly of flavanone and chalcone flavonoidal type, have been identified in this fraction by HPLC-DAD-ESI-MS/MS, and the major one (marein) quantified by HPLC-UV. The fraction (125 mg containing 20 mg of marein/kg b.w.) and Trolox (50 mg/kg b.w.) were administered daily by oral gavage to normal and STZ (40 mg/kg b.w.)-induced glucose-intolerant Wistar rats for 3 weeks. Blood glucose levels were measured weekly by Oral Glucose Tolerance Test. Pancreatic function was evaluated by plasma lipase of treated and non-treated glucose-tolerant and- intolerant rats after the 3-week treatment period. After 2 weeks oral treatment with Coreopsis tinctoria AcOEt fraction the animals were no longer glucose-intolerant, an effect maintained over the remaining experimental period. Additionally, plasma lipase values of glucose-intolerant animals treated with the AcOEt fraction (13.5 ± 0.84 U/L) showed a clear reduction when compared with the glucose-intolerant group (34.60 ± 1.76 U/L; P<0.001) and normoglycaemic control (8.35 ± 0.69 U/L) demonstrating recovery of pancreatic function. On the other hand, treatment with standard antioxidant Trolox had no effect on glucose homeostasis of glucose-intolerant rats. The oral treatment with Coreopsis tinctoria fraction caused no hepatotoxicity, as determined by blood alanine and aspartate transaminases, and had also no effect on glucose homeostasis and pancreatic function of normal rats. AcOEt fraction, containing the same amount of marein as the infusion, promoted glucose tolerance regain in the rats more quickly, which means that the bioactivity is probably due to the several flavonoids present in Coreopsis tinctoria extracts and not to marein alone. The results also strongly suggest that these compounds act by promoting pancreatic cell function recovery from STZ-induced injury, possibly through a mechanism of action other than merely antioxidant mediated.

The Consequences for Live Kidney Donors With Preexisting Glucose Intolerance Without Diabetic Complication: Analysis at a Single Japanese Center

Because of lack of deceased donors in Japan, there has been a need to expand the eligibility criteria for live kidney donation. To assess the indications for live kidney donation in glucose intolerance (GI), we analyzed perioperative complications associated with donor nephrectomies performed at our institution and followed up the long-term consequences. The 444 live kidney donors were divided into two groups based on the results of the 75-g oral glucose tolerance test: a GI group (n=71) who showed a diabetic (n=27) or impaired glucose tolerance (n=44) pattern, and a non-GI group (n=373) who showed a normal oral glucose tolerance test pattern. Perioperative complications, longterm survival rate, and frequencies of hypertension, diabetes, hyperlipidemia, and renal dysfunction in long term were compared in each group. The incidence of perioperative complications was not higher in the GI group than in the non-GI group (4.3% vs. 5.4%, respectively; NS). Survival rates in the GI group at 5, 10, and 20 years were 98.3%, 95.1%, and 89.2%, respectively, whereas those in the non-GI group were 98.0%, 96.1%, and 91.5%, thus showing equivalent mortality. None of the patients in the diabetes mellitus group had developed severe diabetic complications or end-stage renal disease at a mean follow-up point of 88+/-71 (range, 14-225) months. Our results suggest that individuals who have GI without diabetic complication may be able to donate their kidney safely with little surgical complication and little major morbidity if strict evaluation is performed before transplant.