scholarly journals SUN-LB121 Nifedipine Worsens Glucose Tolerance in C57BL/6J Mice Exposed to Intermittent Hypoxia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Stanley M Chen Cardenas ◽  
Larissa A Shimoda ◽  
Naresh M Punjabi

Abstract Background: Intermittent hypoxemia (IH), a pathognomonic component of obstructive sleep apnea (OSA), has been independently associated with development of glucose intolerance, insulin resistance, and type 2 diabetes. L-type calcium channel blockers (CCB) influence glucose homeostasis including insulin sensitivity and secretion. To date, the potential impact of the combined effects of L-type CCB and IH on fasting glycemia and glucose tolerance have not been examined. The objective of this study was to determine whether CCB alters glucose metabolism in a murine model of IH. Methods: Adult male C57BL6/J mice (age 19-week-old) were exposed to IH using an automated system with specially-modified cages that oscillated FiO2from 21% to 5.5% at a target rate of 60 events/h during a 12 h (7am – 7pm) light cycle to simulate severe OSA for 5 days. The L-type CCB, nifedipine, or vehicle (polyethleneglycol-400) were administered at a dose of 20mg/kg/day via subcutaneous osmotic pumps (Alzet model 2001). Mice were exposed to IH or intermittent air (IA) with four resulting groups: IA-vehicle (n=12), IH-vehicle (n=16), IA–nifedipine (n=10), and IH–nifedipine (n=13). Fasting glucose, intraperitoneal glucose tolerance test, and insulin levels were obtained after exposures. Results: In the absence of a L-type CCB, IH increased fasting (105.1 vs. 71.2 mg/dL; p<0.001) and 2-hour glucose levels (104.8 vs. 82.0 mg/dL; p=0.003). The area under the glucose tolerance curve (AUC) was also higher with IH than IA in mice treated with vehicle (17896.3 vs.13965.8 mg-min/dL; p<0.001). Although the effects of IH on fasting glucose levels were comparable with and without L-type CCB treatment, the 2-hour glucose levels and the AUCs were substantially different. A statistically significant interaction was noted for the 2-hr glucose levels between IH and treatment with a L-type CCB (IH-CCB: 193.7; IH-V: 122.6; IA-CCB: 103.5; and IA-V: 82.0 mg/dL; p<0.05 for interaction between IH and CCB). Finally, the AUC for IH-CCB treated mice was significantly higher than the AUC for IH-V treated mice (IH-CCB: 30223.1; IH-V: 17896.3. mg-min/dL; p=0.0001) Conclusions: In a murine model of IH, treatment with an L-type CCB exacerbates the deleterious effects of IH on glucose tolerance. Thus, use of CCB in patients with OSA should take into consideration these unfavorable effects particularly in those who are metabolically compromised.

2020 ◽  
Vol 26 (5) ◽  
pp. 529-534
Author(s):  
Juan Carlos Lizarzaburu-Robles ◽  
Lizardo Torres-Aparcana ◽  
Raúl Mansilla ◽  
José Valera ◽  
Gabriela Vargas ◽  
...  

Objective: The aim of this study was to evaluate the association between the 1-hour oral glucose tolerance test (OGTT) (≥155 mg/dL) and metabolic syndrome (MS) in a sample with previous impaired fasting glucose (IFG). Methods: Three hundred and twenty four Peruvian subjects with a history of IFG ≥100 mg/dL were selected for a cross-sectional study. They underwent a 75 g OGTT and were assigned to different groups according to the result. We evaluated the association between 1-hour OGTT and MS. Results: The mean age was 56.5 ± 12.6 years and 191 (61.5%) were female. During the OGTT, we found 28 (8.6%) subjects with diabetes, 74 (22.8%) with IGT, and 222 (68.5%) with a normal glucose tolerance test with a 2-hour glucose <140 mg/dL (NGT). In the NGT group, 124 (38.3%) had 1-hour glucose levels <155 mg/dL, while 98 (30.2%) had 1-hour glucose levels ≥155 mg/dL. Evaluating the association between the 1-hour value in the OGTT and MS, we found that subjects with a 1-hour glucose ≥155 mg/dL were more than twice as likely to have MS as those with a 1-hour glucose <155 mg/dL (odds ratio = 2.64, 95% confidence interval: 1.52 to 4.57). In addition, body mass index, fasting glycemia, triglycerides, and waist circumferences were significantly higher in subjects with 1-hour glucose levels ≥155 mg/dL compared to those with 1-hour glucose levels <155 mg/dL ( P<.05). Conclusion: Among subjects with IFG, performing an OGTT was helpful to identify subjects with 1-hour glucose levels ≥155 mg/dL and NGT who were significantly more likely to have MS and a worse cardiometabolic risk profile. Abbreviations: AST = aspartate aminotransferase; BMI = body mass index; CI = confidence interval; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; LDL = low-density lipoprotein; MS = metabolic syndrome; NGT = normal glucose tolerance; OGTT = oral glucose tolerance test; OR = odds ratio; T2DM = type 2 diabetes; TG = triglycerides


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yoshihiro Kokubo ◽  
Makoto Watanabe ◽  
Aya Higashiyama ◽  
Yoko M Nakao ◽  
Takashi Kobayashi ◽  
...  

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


2019 ◽  
Vol 147 (7-8) ◽  
pp. 416-421
Author(s):  
Tatjana Novakovic ◽  
Zlatica Mirkovic ◽  
Nenad Milosevic ◽  
Zorica Zivkovic ◽  
Dijana Miric ◽  
...  

Introduction/Objective. The aim of the study was to determine the profile of cardiovascular risk factors in patients with impaired glucose tolerance (IGT) in comparison to patients with impaired fasting glucose (IFG). Methods. The study consisted of 222 adult participants with established fasting blood glucose values within the 5.6?6.9 mmol/L range. IGT was defined as blood glucose of 7.8?11.1 mmol/L in the second hour after the administration of 75 g during oral glucose tolerance test. IFG is the metabolic state between normal and impaired glucose tolerance, where fasting glucose levels are 5.6?6.9 mmol/L, and normal oral glucose tolerance test values. IGT was confirmed in 142 of these individuals (107 females and 35 males; aged 54 ? 13 years). The remaining 80 participants (56 females and 24 males, p = 0.329; aged 53 ? 13 years, p = 0.76) were considered the IFG group. The following parameters were analyzed in both groups: body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin levels, HOMA-IR (homeostasis model assessment ? insulin resistance), C-reactive protein, fibrinogen concentrations and lipid profile. Results. Participants in the IGT group were more obese than those in the IFG group (body mass index 30.8 ? 5.5 kg/m2 vs. 26.7 ? 3.8 kg/m2, p < 0.001), and with greater waist circumference (111 ? 12 cm vs. 101 ? 6 cm; p < 0.001). Glucose levels (6.02 ? 0.75 mmol/L vs. 5.80 ? 0.62 mmol/L; p < 0.001), and blood insulin levels (21.61 ? 3.46 vs. 6.00 ? 2.8 mIU/L; p < 0.001), as well as HOMA-IR (5.78 ? 2.68 mIU/L vs. 1.54 ? 1.46 mIU/L; p < 0.001) were also higher in the IGT group. Median levels of HbA1c in IGT subjects were higher compared with those in the IFG group, but the difference was not statistically significant (6.21 ? 0.75% vs. 5.92 ? 0.43%; p = 0.105). Median hs-CRP levels in the IGT subjects (6.7 ? 4.88 mg/L) were higher than in the IFG subjects (5.83 ? 6.47 mg/L), but without statistical significance (p = 0.76). Conclusion. Our study indicates the presence of a large number of cardiovascular risk factors in both groups. Still, obesity, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, higher diastolic blood pressure, as well as sedentary lifestyle, were statistically significantly more prevalent in patients with IGT.


1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
Author(s):  
W. N. Spellacy ◽  
W. C. Buhi ◽  
S. A. Birk

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.


2015 ◽  
Vol 10 (2) ◽  
pp. 326 ◽  
Author(s):  
Emordi Jonathan Emeka ◽  
Agbaje Esther Oluwatoyin ◽  
Oreagba Ibrahim Adekunle ◽  
Iribhogbe Osede Ignis

<p>The purpose of this study is to evaluate the hypoglycaemic properties and preliminary phytochemical screening of <em>Uveria chamae</em>. The hypoglycaemic properties of <em>Uveria chamae</em> was assessed on normoglycaemic rat that received single dose of the extract at 250 and 500 mg/kg body weight and blood glucose levels estimated at 2, 4, and 6 hours (single dose study). The hypoglycaemic property of the extract was also evaluated in normoglycemic rats by oral glucose tolerance test. Phytochemical screening of the extract for the presence of secondary metabolites was performed with standard methods. The extract showed a significant (p&lt;0.05) reduction in blood glucose levels at 2h and 6h compared to control.  The oral glucose tolerance test  result also showed a significant decrease (p&lt;0.05) in blood glucose levels . The study showed that the extract, <em>Uveria chamae</em> has hypoglycaemic properties which may be accounted for by the presence of the phytochemicals.</p><p> </p>


2006 ◽  
Vol 155 (4) ◽  
pp. 623-632 ◽  
Author(s):  
G Neil Thomas ◽  
C Mary Schooling ◽  
Sarah M McGhee ◽  
Sai-Yin Ho ◽  
Bernard M Y Cheung ◽  
...  

Background: The use of fasting and post-prandial glucose levels in the classification of hyperglycaemic states often identifies distinct subjects, but the factors determining these intermediate-isolated glucose intolerant states are yet to be clearly elucidated in Chinese subjects. Methods: Representative subjects (n = 2769) were randomly recruited from the Hong Kong Chinese population and glycaemic status was determined using both fasting and 2h 75 g oral glucose tolerance test glucose levels. The relationship between the groups with isolated glucose intolerance and vascular risk factors was investigated using ANOVA and logistic regression analyses. Results: Using either criterion, diabetes was identified in 265 (9.6%) subjects and glucose intolerance in 568 (20.5%) subjects. Of those 568, isolated impaired glucose tolerance (IGT) using the post-load criterion was identified in 49.5% and isolated impaired fasting glucose (IFG) in 30.5%. Ageing and hyperinsulinaemia were common determinants of IGT and IFG; with small hip circumference a marker of poorer early life development and being born in China rather than Hong Kong, a possible low birth weight marker was also associated with IFG. Hypertension, hypertriglyceridaemia and poor education were also associated with IGT. When we looked for factors differentially associated with these glucose intolerant states, female sex, greater hip circumference, high triglyceride levels, low fasting insulin levels, and not being born in China were independently associated with isolated IGT compared with isolated IFG. Conclusion: Despite common antecedents to the glucose intolerant states, isolated IFG appeared to be particularly associated with early life development, and isolated IGT was more strongly associated with obesity-related determinants such as hypertriglyceridaemia.


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