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Islet amyloid polypeptide response to maximal hyperglycemia and arginine is altered in impaired glucose tolerance and type 2 diabetes mellitus.
Guardado-Mendoza, R, Chávez, AO, Jiménez-Ceja, LM, Hansis-Diarte, A, DeFronzo, RA, Folli, F, Tripathy, D
Acta diabetologica. 2017;(1):53-61
Abstract
AIMS: Pancreatic islet amyloid deposition is a characteristic feature of type 2 diabetes mellitus (T2DM). Islet amyloid polypeptide (IAPP) is co-secreted with insulin, but its secretion profile and relationship to insulin and C-peptide in response to glucose and non-glucose stimuli has not been clearly defined. METHODS Forty subjects (13 NGT, 12 IGT and 15 T2DM) participated in an OGTT and two-step hyperglycemic (225 and 400 mg/dl) clamp (80 min/step) followed by an IV arginine bolus. Acute insulin (AIR), C-peptide (ACPR) and IAPP (AIAR) responses during each hyperglycemic step and following arginine (AIRArg) were assessed. RESULTS AIR and ACPR during both hyperglycemic steps and after arginine progressively decreased from NGT to IGT to T2DM. Fasting IAPP concentrations were higher in T2DM compared to NGT and IGT subjects. The acute IAPP0-10 was markedly decreased only in T2DM, while the acute IAPP80-90 response during the second step (80-160 min) of hyperglycemic clamp and in response to arginine was markedly impaired in both IGT and T2DM. The ratio of IAPP/C-peptide during the first (225 mg/dl) and second step (400 mg/dl), and in response to arginine, was decreased in T2DM versus both NGT and IGT (p < 0.01). The acute IAPP0-10 correlated with ACPR0-10 (r = 0.665, p < 0.001) and AIR0-10 (r = 0.543, p < 0.001). CONCLUSIONS Basal IAPP secretion is higher in T2DM and IGT versus NGT but is reduced in response to hyperglycemia and arginine. The IAPP/C-peptide ratio is reduced with prolonged and more severe hyperglycemia in T2DM individuals. CLINICAL TRIAL REGISTRATION NCT00845182.
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Influence of medical nutrition therapy on borderline glucose intolerance in pregnant Taiwanese women.
Ho, TC, Yan, YH, Lu, MC, Yu, CW, Wang, P
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2016;(7):1181-6
Abstract
OBJECTIVE To investigate the influence of medical nutrition therapy (MNT) on borderline glucose intolerance (BGI) in pregnant Taiwanese women. METHODS A total of 5194 singleton pregnant women were enrolled in this prospective, non-randomized study. The participants were subjected to the 50 g 1-h glucose challenge test (GCT) and 100 g 3-h oral glucose tolerance test (OGTT) to screening gestational diabetes mellitus (GDM). BGI was defined as a positive GCT and normal OGTT results. GDM was defined as a positive GCT and abnormal OGTT results. The women were categorized into the following groups: (1) GCT-negative, n = 3881; (2) BGI with MNT, n = 273; (3) BGI without MNT, n = 712; and (4) GDM, n = 328. Multiple logistic analyses were used to estimate the risks of pregnancy outcomes. RESULTS The odds ratios (95% confidence interval) for total cesareans, third- or fourth-degree perineal lacerations, gestational hypertension or preeclampsia and macrosomia were 1.24 (1.04-1.49), 1.55 (1.06-1.28), 1.78 (1.21-2.61) and 2.50 (1.28-4.91) in the BGI without MNT group compared to the GCT-negative group. There was no difference between BGI with MNT and GCT-negative groups. CONCLUSIONS Women with BGI who did not receive MNT had increased risks of adverse pregnancy outcomes, whereas who received MNT had no different risk with GCT-negative women.
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Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance.
Choudhury, RP, Birks, JS, Mani, V, Biasiolli, L, Robson, MD, L'Allier, PL, Gingras, MA, Alie, N, McLaughlin, MA, Basson, CT, et al
Journal of the American College of Cardiology. 2016;(16):1769-1780
Abstract
BACKGROUND Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression. OBJECTIVES The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. METHODS Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta. RESULTS There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was -3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (-4.30 mg/dl [range: -8.5 to -0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test. CONCLUSIONS There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930).
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Quantitative assessment of the effect of cholesterol on blood glucose measurement using near infrared spectroscopy and a method for error reduction.
Jiang, J, Zhang, K, Qin, J, Min, X, Zhang, L, Zou, D, Xu, K
Lasers in surgery and medicine. 2015;(1):88-97
Abstract
BACKGROUND AND OBJECTIVE There is a growing body of evidence suggesting that the accurate measurement of blood glucose concentration can be perturbed by many factors. Current literature is limited in describing the influence of cholesterol on non-invasive blood glucose measurements by near-infrared spectroscopy (NIRS). This study aims to investigate the influence of cholesterol on blood glucose measurement through clinical oral glucose tolerance test (OGTT) and NIRS. Further, a method to reduce the prediction errors induced by cholesterol is proposed, facilitating the clinical application of non-invasive blood glucose sensing by NIRS. STUDY DESIGN/MATERIAL AND METHODS We obtained clinical data of glucose and cholesterol concentrations at specific time points (0, 0.5, 1, 2, and 3 h) during OGTTs from 115 subjects. The subjects were grouped into: Norm for normal control, IGT for Impaired Glucose Tolerance, and Diabetes. In addition, spectral data between 1200 and 1800 nm were collected from 130 phantom samples, which are separated into seven groups depending on glucose and cholesterol levels. Statistical methods including One Sample T-test (OSTT), Pearson Correlation Analysis(PCA), and Unary Linear Regression (ULR) were used to analyze clinical data and spectral data to determine the relationship between glucose and cholesterol concentrations with the time course of OGTT. Reference wavelength-based method (RWM) was introduced to diminish the influence of cholesterol on glucose measurement and further the prediction error induced by cholesterol was reduced when using partial least square (PLS) model. RESULTS Clinical results statistically show that there is a strong negative correlation between the changes of glucose and cholesterol concentrations in the diabetes group. The spectra of cholesterol exhibit similar absorbance peaks to those of glucose within NIR range. PLS modelling results demonstrate that glucose prediction is influenced by cholesterol concentrations in a calibration model. Furthermore, a model expression (ΔCg=0.0356Cc+1.0129 R(2) = 0.993) is fitted to quantitatively describe the glucose prediction increment (ΔCg) due to cholesterol concentration (Cc). The results show that glucose prediction accuracy can be improved up to 38.36% by using RWM when using NIRS. CONCLUSIONS The cholesterol has an effect on blood glucose sensing. RWM is useful to help realize non-invasive blood glucose sensing by NIRS.
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Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged americans.
Hruby, A, Meigs, JB, O'Donnell, CJ, Jacques, PF, McKeown, NM
Diabetes care. 2014;(2):419-27
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Abstract
OBJECTIVE To assess 7-year associations between magnesium intake and incident prediabetes and/or insulin resistance (IR), and progression from these states to type 2 diabetes. RESEARCH DESIGN AND METHODS In 2,582 community-dwelling participants 26-81 years old at baseline, magnesium intake and risk of incident "metabolic impairment," defined as impaired fasting glucose (FG) (≥5.6 to <7.0 mmol/L), impaired glucose tolerance (2-h postload glucose ≥7.8 to <11.1 mmol/L), IR, or hyperinsulinemia (≥90th percentile of homeostasis model assessment of IR or fasting insulin, respectively), was estimated among those with normal baseline status, and risk of incident diabetes was estimated among those with baseline metabolic impairment. In participants without incident diabetes, we examined magnesium intake in relation to 7-year changes in fasting and postload glucose and insulin, IR, and insulin sensitivity. RESULTS After adjusting for age, sex, and energy intake, compared with those with the lowest magnesium intake, those with the highest intake had 37% lower risk of incident metabolic impairment (P trend = 0.02), and in those with baseline metabolic impairment, higher intake was associated with 32% lower risk of incident diabetes (P trend = 0.05). In the combined population, the risk in those with the highest intake was 53% (P trend = 0.0004) of those with the lowest intake. Adjusting for risk factors and dietary fiber attenuated associations in the baseline normal population but did not substantially affect associations in the metabolically impaired. Higher magnesium intake tended to associate with lower follow-up FG and IR, but not fasting insulin, postload values, or insulin sensitivity. CONCLUSIONS Magnesium intake may be particularly beneficial in offsetting risk of developing diabetes among those at high risk. Magnesium's long-term associations with non-steady-state (dynamic) measures deserve further research.
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Slow-release insulin in cystic fibrosis patients with glucose intolerance: a randomized clinical trial.
Minicucci, L, Haupt, M, Casciaro, R, De Alessandri, A, Bagnasco, F, Lucidi, V, Notarnicola, S, Lorini, R, Bertasi, S, Raia, V, et al
Pediatric diabetes. 2012;(2):197-202
Abstract
BACKGROUND Early stages of glucose metabolism impairment are a period at risk in the long-term prognosis of cystic fibrosis (CF). Slow-release synthetic insulin glargine can be a therapeutic tool in this metabolic condition. METHODS In this phase 3 multicenter, controlled, two-arm, randomized clinical study, glargine was administered up to a dosage of 0.15 U/kg/die for a period of 18 months. Primary endpoint was the improvement of nutritional status [body mass index (BMI) Z score], while glucose tolerance [hemoglobin A1c (HbA1C) and respiratory function (FEV1 predicted] improvement were the secondary endpoints. RESULTS Thirty-four subjects (18 in the glargine arm and 16 in the control arm) were evaluated. Adherence to insulin treatment was excellent. No significant adverse events were reported. There were no significant differences in BMI, HbA1C and FEV1 values between the two groups nor within groups, except for HbA1C improvement in the glargine arm at month +18 (p = 0.04). CONCLUSIONS Glargine treatment was well accepted and tolerated. No real efficacy in improving clinical and glycometabolic conditions was demonstrated. Further studies are necessary to test glargine at higher dosage and for a longer follow-up period.
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Effect of insulin resistance improvement due to lifestyle intervention on overweight perimenopausal Japanese women: a preliminary study.
Chihara, H, Kawase, R, Otsubo, Y, Hiraizumi, Y, Takeshita, T
Journal of Nippon Medical School = Nippon Ika Daigaku zasshi. 2008;(1):15-22
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OBJECTIVE We hypothesized that body composition and biomarkers of menopausal obesity would be affected by administration of a nutrition and exercise regimen. To test this hypothesis, an interventional study was performed in which perimenopausal subjects increased their daily level of physical activity and decreased their daily caloric intake for a period of 12 weeks. METHOD Nine patients with a chief complaint of obesity and menopausal disorders were enrolled in this study. We prescribed that the subjects engage in the daily physical activity of walking more than 10,000 steps, which is equivalent to 150 to 400 kcal per day, and reduce their daily nutritional intake by 200 kcal. Daily physical activity was measured with a computerized accelerometer, and nutrition intake was measured using food frequency questionnaires. Body composition was measured via biophysical impedance analysis. Biochemical examinations were performed before and after the study. As an assessment of glucose tolerance, homeostasis model assessment-insulin resistance (HOMA-IR) values were measured. RESULTS There were no significant changes in weight, body mass index, or body composition after 12 weeks. However, daily physical activity related to energy consumption was slightly but not significantly increased. Six of the nine subjects (66.7%) had abnormal baseline HOMA-IR values (mean 7.0 +/- 2.6; normal upper limit = 1.5) and demonstrated decreases in HOMA-IR values, with an average of 5.2 +/- 2.3 (P <0.05), after 12 weeks of study. CONCLUSION Our mild intervention on daily physical activity and nutrition changed HOMA-IR values, an assessment of impaired glucose tolerance. These results suggest that longitudinal mild intervention on daily physical activity and nutrition could change insulin sensitivity even without weight reduction.
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Factors responsible for deteriorating glucose tolerance in newly diagnosed type 2 diabetes in Japanese men.
Mitsui, R, Fukushima, M, Nishi, Y, Ueda, N, Suzuki, H, Taniguchi, A, Nakai, Y, Kawakita, T, Kurose, T, Yamada, Y, et al
Metabolism: clinical and experimental. 2006;(1):53-8
Abstract
Hyperglycemia frequently continues to worsen even after the diagnosis of overt diabetes. The aim of this study is to evaluate the factors contributing to increasing glucose intolerance after onset of type 2 diabetes in Japanese subjects. Five hundred fifty newly diagnosed type 2 diabetic patients were classified into 3 degrees of hyperglycemia based on plasma glucose levels estimated by 75-g oral glucose tolerance test: diabetes mellitus with isolated fasting hyperglycemia (DM/IFH), DM with isolated postchallenge hyperglycemia (DM/IPH), and DM with fasting and postchallenge hyperglycemia (DM/FPH). In addition, the DM/IFH and DM/IPH groups were subdivided to clarify the determinants of fasting and postchallenge hyperglycemia. Insulin secretion was evaluated by insulinogenic index, and insulin sensitivity was evaluated by composite index of insulin sensitivity (ISI composite). The insulinogenic index in DM/IFH was highest of the 3 groups (P < .0001). The insulinogenic index in DM/IPH was higher than in DM/FPH (P < .0001). The international sensitivity index composite in DM/IPH was highest of the 3 groups (P < .05). Although impaired early-phase insulin secretion plays the crucial role in deterioration from DM/IFH to DM/FPH in Japanese subjects, impaired early-phase insulin secretion and decreased insulin sensitivity both are factors in deterioration from DM/IPH to DM/FPH. In addition, comparison of subgroups of DM/IFH and DM/IPH shows that although decreased early-phase insulin secretion plays the more significant role in postchallenge hyperglycemia in Japanese subjects, insulin sensitivity is the more important factor in fasting hyperglycemia.
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Postprandial interleukin-6 release from skeletal muscle in men with impaired glucose tolerance can be reduced by weight loss.
Corpeleijn, E, Saris, WH, Jansen, EH, Roekaerts, PM, Feskens, EJ, Blaak, EE
The Journal of clinical endocrinology and metabolism. 2005;(10):5819-24
Abstract
CONTEXT Obesity and type 2 diabetes mellitus are associated with increased levels of IL-6, a marker of inflammation. OBJECTIVE This study addressed the question of whether IL-6 was released from skeletal muscle after a high-fat meal in men with impaired glucose tolerance (IGT), a prediabetic state, and whether IL-6 release could be reduced by weight loss. DESIGN Skeletal muscle metabolism was studied in men with IGT (n = 11) and compared with men with normal glucose tolerance (NGT, n = 9), matched for body mass index and age. IL-6 flux over skeletal muscle was measured with the forearm model. Eight IGT men were willing to participate in a 12-wk weight loss program and were tested again. RESULTS IL-6, but not C-reactive protein or TNF-alpha receptor 1 and 2, was released by skeletal muscle. Muscle IL-6 release was higher in IGT than in NGT during fasting (IGT = 2.26 +/- 1.89 vs. NGT = 0.87 +/- 0.48 fmol x 100 ml tissue(-1) x min(-1), P = 0.04) and after a meal (mean area under the curve per minute: IGT = 3.48 +/- 2.63 vs. NGT = 1.37 +/- 0.75 fmol x 100 ml tissue(-1) x min(-1); P = 0.03). In the IGT men, body weight loss resulted in a decrease of postprandial IL-6 release from skeletal muscle (-52%; P = 0.04), reaching levels of the obese, NGT controls. CONCLUSION The present data suggest that a high-fat meal can evoke IL-6 release from muscle and that the IL-6 release is a consequence rather than a cause of the obese, insulin-resistant, and/or IGT state.
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Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile: a randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance.
Gunton, JE, Cheung, NW, Hitchman, R, Hams, G, O'Sullivan, C, Foster-Powell, K, McElduff, A
Diabetes care. 2005;(3):712-3