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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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A reduced-fat diet and aerobic exercise in Japanese Americans with impaired glucose tolerance decreases intra-abdominal fat and improves insulin sensitivity but not beta-cell function.
Carr, DB, Utzschneider, KM, Boyko, EJ, Asberry, PJ, Hull, RL, Kodama, K, Callahan, HS, Matthys, CC, Leonetti, DL, Schwartz, RS, et al
Diabetes. 2005;(2):340-7
Abstract
Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, beta-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or beta-cell function and to evaluate these effects over time, we quantified insulin sensitivity and the acute insulin response to glucose (AIRg) in 62 Japanese Americans (age 56.5 +/- 1.3 years; mean +/- SE) with impaired glucose tolerance (IGT) who were randomized to the American Heart Association (AHA) Step 2 diet plus endurance exercise (n = 30) versus the AHA Step 1 diet plus stretching (n = 32) for 24 months. beta-Cell function (disposition index [DI]) was calculated as S(i) x AIRg, where S(i) is the insulin sensitivity index. The incremental area under the curve for glucose (incAUCg) was calculated from a 75-g oral glucose tolerance test. Intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas were measured by computed tomography. At 24 months, the Step 2/endurance group had lower weight (63.1 +/- 2.4 vs. 71.3 +/- 2.9 kg; P = 0.004) and IAF (75.0 +/- 7.9 vs. 112.7 +/- 10.4 cm(2); P = 0.03) and SCF (196.5 +/- 18.0 vs. 227.7 +/- 19.9 cm(2); P < 0.001) areas, greater S(i) (4.7 +/- 0.5 vs. 3.3 +/- 0.3 x 10(-5) min . pmol(-1) . l(-1); P = 0.01), and a trend toward lower AIRg (294.9 +/- 50.0 vs. 305.4 +/- 30.0 pmol/l; P = 0.06) and incAUCg (8,217.3 +/- 350.7 vs. 8,902.0 +/- 367.2 mg . dl(-1) . 2 h(-1); P = 0.08) compared with the Step 1/stretching group after adjusting for baseline values. There was no difference in the DI (P = 0.7) between the groups. S(i) was associated with changes in weight (r = -0.426, P = 0.001) and IAF (r = -0.395, P = 0.003) and SCF (r = -0.341, P = 0.01) areas. Thus, the lifestyle modifications decreased weight and central adiposity and improved insulin sensitivity in Japanese Americans with IGT. However, such changes did not improve beta-cell function, suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term.
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Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males.
Kosaka, K, Noda, M, Kuzuya, T
Diabetes research and clinical practice. 2005;(2):152-62
Abstract
Prevention of type 2 diabetes by intensive lifestyle intervention designed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance (IGT). Male subjects with IGT recruited from health-screening examinees were randomly assigned in a 4:1 ratio to a standard intervention group (control group) and intensive intervention group (intervention group). The final numbers of subjects were 356 and 102, respectively. The subjects in the control group and in the intervention group were advised to maintain body mass index (BMI) of <24.0 kg/m2 and of <22.0 kg/m2, respectively, by diet and exercise. In the intervention group, detailed instructions on lifestyle were repeated every 3-4 months during hospital visits. Diabetes was judged to have developed when two or more consecutive fasting plasma glucose (FPG) values exceeded 140 mg/dl. A 100g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance. The subjects were seen in an ordinary outpatient clinic. The cumulative 4-year incidence of diabetes was 9.3% in the control group, versus 3.0% in the intervention group, and the reduction in risk of diabetes was 67.4% (P < 0.001). Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group (P < 0.001). The control group was subclassified according to increase and decrease in body weight. The incidence of diabetes was positively correlated with the changes in body weight, and the improvement in glucose tolerance was negatively correlated. Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG. Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes, but the differences were not significant. Subjects with a low insulinogenic index (DeltaIRI/DeltaPG 30 min after an oral glucose load) developed diabetes at a significantly higher rate than those with a normal insulinogenic index. Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values, with the exception of the DaQing Study. However, the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI, suggesting that the effect of lifestyle intervention cannot be solely ascribed to the body weight reduction. We conclude that lifestyle intervention aimed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting.