Elena Succurro

Universita' degli Studi "Magna Græcia" di Catanzaro, Catanzaro, Calabria, Italy

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Publications (54)221.32 Total impact


  • No preview · Article · Feb 2016 · The Journal of Clinical Endocrinology and Metabolism

  • No preview · Article · Feb 2016
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    ABSTRACT: To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic eating habits.
    Full-text · Article · Dec 2015 · Medicine
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    ABSTRACT: Subjects with normal glucose tolerance but 1-h post-load glucose ≥155 mg/dl (NGT-1h-high) exhibit an intermediate cardio-metabolic risk profile between individuals with NGT and impaired glucose tolerance (IGT). To evaluate whether NGT-1h-high subjects have different cardio-metabolic characteristics and an increased risk of type 2 diabetes as compared to individuals with isolated impaired fasting glucose (IFG). A cross-sectional analysis was performed on 595 non-diabetic subjects who underwent an oral glucose tolerance test and an euglycemic hyperinsulinemic clamp. In addition, a longitudinal analysis was performed on 392 individuals, who were reexamined after a follow-up of 5.2±0.9 years. Ambulatory care. Insulin sensitivity, beta-cell function, risk of developing diabetes. Subjects with NGT-1h-high have a significant reduction of peripheral insulin sensitivity and beta-cell function, assessed by the disposition index, as compared to either NGT-1h-low or IFG individuals, but not as compared to IGT. Among the 392 subjects studied in the longitudinal analysis the incidence rate of type 2 diabetes over the follow-up period was 2.9, 16.7, 12.5, and 31.4% for subjects with NGT-1h-low, NGT-1h-high, IFG, and IGT, respectively. In a Cox proportional hazard regression analysis the risk of developing diabetes for NGT 1h-high subjects was 4.02 (95%CI 1.06-15.26); an even higher risk (6.67 [95%CI 2.09-21.24]) was observed in subjects with IGT, but not in the isolated IFG group (1.91 [95%CI 0.44-8.29]). NGT-1h-high subjects exhibit a higher risk of developing diabetes than those with IFG or NGT-1h-low, likely due to decreased insulin sensitivity and beta-cell function.
    No preview · Article · Aug 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: IntroductionInsulin glargine is a human insulin analog produced with recombinant DNA technology, administered once daily as a basal source of insulin in patients with type 1 or type 2 diabetes mellitus. The addition of two basic amino acids (arginine) to the B-chain and the switching of asparagine with glycine in position A21 in the insulin molecule determines a shift of the isoelectric point from a pH of 5.4 to 6.7. Therefore, insulin glargine precipitates at physiological pH in subcutaneous tissue after injection, delaying the absorption. Moreover, the addition of zinc to stabilize interhexamer contacts prolongs the activity of this analog. Studies in healthy volunteers have indicated that insulin glargine has a smooth peak less profile of action that is required from a basal insulin injected once daily [1].Several side effects have been reported during the treatment with insulin glargine, such as hypoglycemia and irritation at the injection site. These effects are common and the irr ...
    No preview · Article · Jan 2015 · Acta Diabetologica
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    ABSTRACT: Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm, (OR 3.95, 95% CI 1.12-13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22-10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors.
    Full-text · Article · Aug 2014 · PLoS ONE
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    ABSTRACT: Glucose tolerant subjects with 1-h post-load glucose ≥155 mg/dl (NGT-1 h-high) are at increased risk for type 2 diabetes (T2DM). Prospective studies showed that chronic subclinical inflammation is a predictor of T2DM. In this study, we aimed to evaluate the inflammatory profile in NGT-1 h-high subjects as compared with individuals with 1-h post-load glucose <155 mg/dl (NGT-1 h-low). To this end, an oral glucose tolerance tests (OGTT) were performed in 1,099 nondiabetic whites. Cardio-metabolic risk factors including high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen, and complement C3 (C3) were determined. Of the 1,099 subjects examined, 497 had NGT-1 h-low, 154 had NGT-1 h-high, 158 had isolated impaired fasting glucose (IFG), and 290 had impaired glucose tolerance (IGT). As compared with NGT-1 h-low, NGT-1 h-high and IGT subjects exhibited significantly higher hsCRP, ESR, fibrinogen, and C3 levels. Notably, hsCRP, ESR, and C3 were also significantly higher as compared with IFG individuals. In a logistic regression analysis adjusted for age and gender, NGT-1 h-high and IGT subjects had a 1.8-fold increased risk of having the highest value of the Inflammatory Score. These data suggest that a value of a 1-h OGTT glucose ≥155 mg/dl may be helpful to identify a subset of normal glucose tolerance individuals at risk for chronic subclinical inflammation, a predictor of T2DM, and cardiovascular diseases.
    No preview · Article · Mar 2014 · Acta Diabetologica
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    ABSTRACT: Since the skin represents a common site of adverse drug reactions, few data are reported at this time regarding the development of skin rash during the treatment with antidiabetic drugs. We report a 29-year old woman that developed a facial skin rash during the treatment with metformin. Clinical and laboratory findings excluded the presence of systemic diseases, but several diagnosis and many drugs were administered without clinical improvement. The self-dismission of metformin induced an improvement of symptoms, while the re-challenge documented an impairments of skin rash. The Naranjo probability scale suggested a probable association between metformin and skin rash and metformin was definitively dismissed. We report for the first time a non vasculitis facial skin manifestation related to metformin in a young woman. However, this case may emphasizes the need to consider the ADRs as a differential diagnosis in order to reduce medical errors and the related medical costs.
    Full-text · Article · Feb 2014 · BMC pharmacology & toxicology
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    Nadia Innaro · Elena Succurro · Giuseppe Tomaino · Franco Arturi
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    ABSTRACT: Thyroid angiosarcoma is an uncommon thyroid carcinoma and its incidence is the highest in the European Alpine regions. Thyroid angiosarcoma is also a very aggressive tumor that can rapidly spread to the cervical lymph nodes, lungs, and brain or can metastasize to the duodenum, small boewl, and large bowel. Although it is histologically well defined, clear-cut separation between the angiosarcoma and anaplastic thyroid carcinoma is difficult. A 49-year-old Caucasian female patient, born and resident in Southern Italy (Calabria), in an iodine-sufficient area, was admitted to the Surgery Department because she presented with a painless mass in the anterior region of neck enlarged rapidly in the last three months. After total thyroidectomy and right cervical lymphadenectomy, postoperative histological examination revealed the presence of a thyroid angiosarcoma with positive staining for CD31 and for both Factor VIII-related antigen and Vimentin and only partially positive for staining pancytokeratin and presence of metastasis in cervical, supraclavicular, mediastinal and paratracheal lymph nodes. The patient started adjuvant chemotherapy and she was treated for 6 cycles with Doxorubicin, Dacarbazine, Ifosfamide, and Mesna (MAID). After 22 months from surgery, the patient is still alive without both local and systemic recurrence of the disease.
    Full-text · Article · Nov 2013 · Case Reports in Oncological Medicine
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    ABSTRACT: Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥8.6 mmol/l (155 mg/dl) at 1 h during an oral glucose tolerance test (OGTT) can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high). The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low). To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001) and insulin clearance (P = 0.006) after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02) in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.
    Full-text · Article · Oct 2013 · PLoS ONE
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    ABSTRACT: Metabolically healthy obese (MHO) are relatively insulin sensitive and have a favorable cardio-metabolic risk profile compared with metabolically abnormal obese (MAO). To evaluate whether MAO individuals have a decreased insulin clearance compared with MHO individuals, 49 MHO, 147 MAO, and 172 non-obese individuals were analyzed in this cross-sectional study. Insulin clearance and insulin sensitivity were assessed through euglycemic hyperinsulinemic clamp. MHO subjects exhibited significant lower triglycerides, total cholesterol, 2-h post-challenge glucose, fasting and 2-h post-challenge insulin, steady-state plasma insulin, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase as compared with MAO individuals. Disposition index was higher in MHO subjects as compared with MAO individuals after adjusting for gender and age (P = 0.04). Insulin clearance was significantly lower in MAO individuals as compared with MHO and non-obese individuals. The difference between the two obese subgroups remained significant after adjusting for gender, age, waist circumference, fat mass, and insulin-stimulated glucose disposal (P = 0.03). The hepatic insulin extraction (C-peptide/insulin) in the fasting state was significantly higher in MHO subjects as compared with MAO individuals (P < 0.0001). In univariate analysis adjusted for gender and age, insulin clearance was correlated with hepatic insulin extraction (P = 0.01). In conclusion, insulin clearance differs among obese subjects with different metabolic phenotypes. Impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia observed in MAO individuals.
    Full-text · Article · Aug 2013 · Acta Diabetologica
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    ABSTRACT: The aim of this study was to investigate whether insulin clearance is independently associated with carotid artery intima-media thickness (IMT), a well-recognized index of vascular damage. 361 Non-diabetic Caucasian subjects were subjected to euglycemic hyperinsulinemic clamp to assess insulin sensitivity, and insulin clearance. IMT of the common carotid was measured by ultrasonography. Among the study group, 270 subjects had normal glucose tolerance, 33 had impaired fasting glucose, and 58 had impaired glucose tolerance. Univariate correlations showed that age, BMI, waist, blood pressure, triglycerides, fasting and 2-h post-load glucose and insulin levels were positively correlated with carotid IMT whereas HDL, insulin clearance, and insulin-stimulated glucose disposal were negatively correlated with IMT. A multivariate regression analysis in a model including, in addition to insulin clearance, age, gender, BMI, waist, blood pressure, triglycerides, HDL, fasting and 2-h post-load glucose, insulin-stimulated glucose disposal, fasting and 2-h post-load insulin showed that the traits independently associated with carotid IMT were BMI (β = 0.42, P < 0.0001), insulin clearance (β = -0.29, P < 0.0001), age (β = 0.19, P < 0.0001), waist (β = 0.18, P = 0.01), diastolic blood pressure (β = 0.17, P = 0.01), and 2-h post-load glucose (β = 0.12, P = 0.03). These factors explained 26% of the variance in carotid IMT. Subjects in the lowest tertile of insulin clearance had a 4.06-fold higher odds of having vascular damage (IMT > 0.9 mm) as compared with those in the highest tertile (OR 4.06, 95%CI 1.15-13.24). Insulin clearance is independently associated with carotid IMT in adult non-diabetic subjects. Individuals with lower levels of insulin clearance have a higher odds of vascular damage.
    Full-text · Article · Aug 2013 · Atherosclerosis
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    ABSTRACT: Carotid Intima-Media Thickness (C-IMT) is a reliable predictor of cardiovascular events. We examined if increased C-IMT was associated with defects in glucose metabolism in non-diabetic subjects independently of age. In 366 Caucasian non-diabetic subjects of the CARAMERIS study, we measured glucose response during a 75 g-Oral Glucose Tolerance Test (OGTT), insulin sensitivity index (ISI, by Matsuda Index), Liver Insulin Resistance Index (Liver-IR), insulin secretion by ΔAUC Ins0-120/Glu0-120 (ΔI/ΔG) and beta cell function (Disposition Index, DI). Subjects were divided in two groups according to the median age (AGE1 ≤ 45 y; AGE2 > 45 y). Only 5 subjects in AGE1 and 32 in AGE2 had C-IMT > 0.9 mm. Compared to AGE1, AGE2 had a worse cardio-metabolic profile, increased cholesterol, glucose and insulin concentrations, blood pressure and C-IMT. Both ΔI/ΔG ratio and DI were significantly reduced in AGE2. By considering tertiles of C-IMT in each AGE group (G1-G3, where G3 comprised the highest C-IMT), we found that G3 showed increased OGTT glucose profiles and Liver IR, decreased ISI and DI, compared to G1 in each AGE group. Increased C-IMT, but within normal ranges, is associated independently of age with altered postprandial glucose profile, increased peripheral and hepatic insulin resistance, decreased b-cell function. C-IMT measurement should become a routine analysis even in younger subjects to predict the risk of cardio-metabolic disease.
    No preview · Article · Aug 2013 · Atherosclerosis
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    ABSTRACT: Background and aims: The A1C diagnostic criterion for identifying individuals at increased risk for diabetes, introduced by the American Diabetes Association in 2010, was not defined on the basis of the principal pathophysiological abnormalities responsible for the development and progression of type 2 diabetes; we therefore wished to gain a deeper insight into the metabolic abnormalities characterizing the group of at risk individuals with an A1C value of 5.7-6.4%. Methods and results: As many as 338 non-diabetic offspring of type 2 diabetic patients were consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT), and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. As compared with subjects with A1C <5.7%, individuals with A1C of 5.7-6.4% exhibited lower insulin sensitivity after adjusting for age, gender and body mass index (BMI). Insulin secretion estimated from the OGTT, did not differ between the two groups. By contrast, as compared with subjects with A1C <5.7%, the acute insulin response (AIR) during an IVGTT and both IVGTT-derived and OGTT-derived disposition indexes were reduced in individuals with A1C of 5.7-6.4% after adjusting for age, gender and BMI. As A1C increased to ≥ 5.7%, a sharp decrease in insulin sensitivity and β-cell function, measured as disposition index, was observed. Conclusions: Caucasian individuals with A1C ≥ 5.7% exhibit both core pathophysiological defects of type 2 diabetes i.e. insulin resistance and β-cell dysfunction.
    Full-text · Article · Apr 2013 · Nutrition, metabolism, and cardiovascular diseases: NMCD
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    ABSTRACT: Background and Aims Normoglucosetolerants (NGT) are considered at low risk, even if a 1-hour post-load glucose (PLG) value ≥155mg/dl identifies NGT at high-risk for type-2 diabetes (T2) and subclinical organ damage. Specific dietary factors may affect insulin sensitivity and the risk of T2D. However, it’s unknown whether dietary components affect 1-h PLG in NGT hypertensives. Methods and Results We selected 188 subjects (94 NGT<155 and 94 NGT>155), well matched for age, gender and BMI. Insulin sensitivity was evaluated using Matsuda index. Dietary intake was quantified by a semiquantitative food frequency questionnaire validated in the EPIC study. NGT>155 had significantly reduced insulin sensitivity (40.3+19.8 vs 73.3+28.8; P<0.0001). With the exclusion of total calories, lipids, alcohol and fiber consumption we observed a significant difference, between groups, in starch (214.1+52.4 vs 268.8+71.8 g; P<0.0001), saturated (27.4+8.7 vs 24.1+8.5 g; P=0.009), monounsaturated (45.5+8.9 vs 48.8+10.7 g; P=0.023) and polyunsaturated fatty acids (FA) (14.5+4.0 vs 16.8+4.7 g; P<0.0001), fructose (14.5+5.3 vs 11.2+4.8 g; P<0.0001), and oligosaccharides (103.2+26.6g vs 89.9+29.2g; P=0.001) consumption. In the whole population, starch was the major predictor of 1-h PLG, explaining 23.2% of variation (P<0.0001). In NGT<155, fructose was the strongest predictor, accounting for 15.4% of variation; BMI, gender and polyunsaturated FA, added another 6.6%, 3.6% and 3.2%, respectively. In NGT>155, saturated and polyunsaturated FA were retained as the major predictors of 1-h PLG, explaining 18.2% and 11.4% of variation. Conclusions Present data demonstrate that dietary patterns affect 1-h PLG, remarking the importance of both quantitative and qualitative composition of diet.
    No preview · Article · Jan 2013 · Nutrition, metabolism, and cardiovascular diseases: NMCD
  • A Grembiale · C Cloro · F Iorio · S Cufone · E Succurro · F Arturi
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    ABSTRACT: Hyperglycaemia in patients with Acute Coronary Syndrome (ACS)is common, and is an independent predictor of mortality and morbidity in patients both with and without diabetes mellitus. Hyperglycaemia may be a marker of pre-existing diabetes or glucose intolerance or may also represent a transient stress response mediated through the autonomic nervous system with release of adrenal corticosteroids and catecholamines. Several evidences suggest that an intensive control of hyperglycaemia results in a significant improvement of the adverse outcomes in the short and long term. In fact, an intensive metabolic treatment can counteract the negative effects of hyperglycaemia. However, the main difficulty to intensive glucose control in patients with ACS remains hypoglycaemia that is associated with an increased risk of mortality and myocardial re-infarction. No definitive data are available about the beneficial effects of insulin intensive treatment. Therefore, randomized multicenter clinical trials will be needed to definitively establish whether intensive glucose control will reduce the associated increased mortality rate and higher rates of complications in hospitalized ACS patients with hyperglycaemia. Clin Ter 2012; 163(5):403-409.
    No preview · Article · Sep 2012 · La Clinica terapeutica
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    ABSTRACT: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, which was associated with insulin resistance. Dimethylarginine dimethylaminohydrolase (DDAH) is the major determinant of plasma ADMA. Examining data from the DIAGRAM+ (Diabetes Genetics Replication And Meta-analysis), we identified a variant (rs9267551) in the DDAH2 gene nominally associated with type 2 diabetes (P = 3 × 10(-5)). initially, we assessed the functional impact of rs9267551 in human endothelial cells (HUVECs), observing that the G allele had a lower transcriptional activity resulting in reduced expression of DDAH2 and decreased NO production in primary HUVECs naturally carrying it. We then proceeded to investigate whether this variant is associated with insulin sensitivity in vivo. To this end, two cohorts of nondiabetic subjects of European ancestry were studied. In sample 1 (n = 958) insulin sensitivity was determined by the insulin sensitivity index (ISI), while in sample 2 (n = 527) it was measured with a euglycemic-hyperinsulinemic clamp. In sample 1, carriers of the GG genotype had lower ISI than carriers of the C allele (67 ± 33 vs.79 ± 44; P = 0.003 after adjusting for age, gender, and BMI). ADMA levels were higher in subjects carrying the GG genotype than in carriers of the C allele (0.68 ± 0.14 vs. 0.57 ± 0.14 µmol/l; P = 0.04). In sample 2, glucose disposal was lower in GG carriers as compared with C carriers (9.3 ± 4.1 vs. 11.0 ± 4.2 mg × Kg(-1) free fat mass × min(-1); P = 0.009). A functional polymorphism of the DDAH2 gene may confer increased risk for type 2 diabetes by affecting insulin sensitivity throughout increased ADMA levels.
    Full-text · Article · Apr 2012 · PLoS ONE
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    ABSTRACT: We evaluated whether cardiometabolic risk profiles differ for subjects identified as having prediabetes by A1C, fasting glucose (FPG), or 2-h postchallenge glucose (2-PG) criteria. Atherosclerosis risk factors, oral glucose tolerance test, and ultrasound measurement of carotid intima-media thickness (IMT) were analyzed in 780 nondiabetic individuals. Poor agreement existed for A1C and FPG criteria for identification of subjects with prediabetes (κ coefficient = 0.332). No differences in cardiometabolic risk profiles were observed among the three groups of individuals with prediabetes by A1C only, FPG only, and both A1C and FPG. Poor agreement also existed for A1C and 2-PG criteria for identification of individuals with prediabetes (κ coefficient = 0.299). No significant differences in cardiometabolic risk factors were observed between IGT-only and individuals with prediabetes by A1C and 2-PG. Compared with subjects with prediabetes identified by A1C only, IGT-only individuals exhibited a worse cardiometabolic risk profile, with significantly higher systolic blood pressure, pulse pressure, 2-h postchallenge insulin, triglycerides, high-sensitivity C-reactive protein, and carotid IMT, and lower HDL cholesterol levels and insulin sensitivity. These results suggest that considerable discordance between A1C, FPG, and 2-PG exists for the identification of individuals with prediabetes and that the cardiometabolic risk profile of these individuals varies by metabolic parameter, with 2-PG showing the stronger association with cardiometabolic risk factors and subclinical atherosclerosis than FPG or A1C.
    Full-text · Article · Mar 2012 · Diabetes care
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    ABSTRACT: Individuals with normal glucose tolerance (NGT), whose 1-h postload plasma glucose is ≥155 mg/dL (NGT 1h-high), have an increased risk of type 2 diabetes. The purpose of this study was to characterize their metabolic phenotype. A total of 305 nondiabetic offspring of type 2 diabetic patients was consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Compared with individuals with a 1-h postload plasma glucose <155 mg/dL (NGT 1h-low), NGT 1h-high individuals exhibited lower insulin sensitivity after adjustment for age, sex, and BMI. Insulin secretion estimated from the OGTT did not differ between the two groups of individuals. By contrast, compared with NGT 1h-low individuals, the acute insulin response during an IVGTT and the disposition index were significantly reduced in NGT 1h-high individuals after adjustment for age, sex, and BMI. Incretin effect, estimated as the ratio between total insulin responses during OGTT and IVGTT, was higher in NGT 1h-high individuals compared with NGT 1h-low individuals. NGT 1h-high individuals may represent an intermediate state of glucose intolerance between NGT and type 2 diabetes characterized by insulin resistance and reduced β-cell function, the two main pathophysiological defects responsible for the development of type 2 diabetes. Postload hyperglycemia is the result of an intrinsic β-cell defect rather than impaired incretin effect.
    Full-text · Article · Feb 2012 · Diabetes care
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    ABSTRACT: Metabolically healthy but obese (MHO) subjects have a favourable cardio-metabolic risk profile, but whether they are also at lower risk for kidney dysfunction is still questionable. A total of 106 MHO, 122 normal-weight and 212 insulin-resistant obese (IRO) subjects were stratified on the basis of their insulin sensitivity and body mass index (BMI). The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR) and ISI index was used to estimate insulin sensitivity. eGFR was significantly lower in IRO as compared to MHO subjects after adjusting for age, gender and BMI (P = 0.008). In a logistic regression model adjusted for age, gender and BMI, IRO subjects showed an increased risk of having eGFR in the lowest quartile (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.01-3.58; P = 0.04) as compared with MHO subjects. This association was maintained when waist, lean body mass, blood pressure, HDL cholesterol, triglyceride, fasting glucose and insulin levels were additionally included into the model (OR 2.49, 95%CI 1.17-5.27; P = 0.01), but its independence was not retained with further inclusion of insulin-like growth factor-1 (IGF-1) levels (OR 2.16, 95%CI 0.93-5.04; P = 0.07) No differences in eGFR were observed between non-obese and MHO individuals. These results indicate that heterogeneity in obese phenotypes may account for conflicting evidence regarding the significance of obesity as a risk factor for chronic kidney disease. Our findings suggest that obesity is associated with lower kidney function only when insulin sensitivity is reduced, and that plasma IGF-1 is likely to be an important mechanism linking the IRO phenotype with reduced eGFR.
    No preview · Article · Dec 2011 · Nutrition, metabolism, and cardiovascular diseases: NMCD