Combined effect of cigarette smoking and prediabetes on structural and functional changes of large arteries

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Ioakeimidis ◽  
I Dima ◽  
D Terentes-Printzios ◽  
C Georgakopoulos ◽  
A Angelis ◽  
...  

Abstract Purpose Smoking is a major risk factor for cardiovascular disease and prediabetes is associated with excess risks for adverse cardiovascular outcomes and death. Aim of this study was to explore whether smoking and prediabetes exert a synergistic unfavourable effect on functional and structural parameters of large arteries. Methods We measured carotid-femoral pulse wave velocity (cfPWV), augmentation index (AIx) and carotid intima media thickness (cIMT) in 407 individuals without known atherosclerotic disease (mean age: 52±8 years) categorized into four age-matched groups according to glucose metabolic and smoking status: Smokers with diabetes (n=68), Smokers with prediabetes (n=87), Non-smokers with prediabetes (n=98) and Non- smokers with normal fasting blood glucose (FBG) (n=154). Prediabetes was defined as impaired fasting glucose (100–125 mg/dL), impaired glucose tolerance (2-hour glucose level of 140–199 mg/dL during an oral glucose tolerance test), or glycosylated hemoglobin (HbA1c) level of 5.7% to 6.4%. High sensitivity C-reactive protein (hsCRP) was measured in all patients. Results Systolic pressure, pulse pressure were increased and hsCRP levels were higher in smokers with diabetes compared to the three other groups (overall P<0.05, P<0.01 and P<0.05, respectively, ANOVA). The cumulative tobacco exposure (measured in pack-years) was similar between smokers with diabetes and smokers with prediabetes (45 pack-years). Figure 1 shows cfPWV, AIx and cIMT of the four groups. Interestingly, smokers with diabetes and smokers with prediabetes have similar mean cfPWV and cIMT and significantly higher values compared to non-smokers with prediabetes and non-smokers with normal FBG. The associations remained statistically significant even after adjusting for systolic pressure and hsCRP level. AIx was not different between the four study groups. Conclusion The combination of prediabetes and smoking is associated with higher cfPWV and cIMT values compared to prediabetes alone. The smokers with impaired glucose regulation have functional and structural alterations of large arteries similar to that of smokers with established diabetes. Considering the risk for developing prediabetes in relation to smoking status and the number of cigarettes smoked daily and the independent predictive value of assessing vascular changes in large arteries, the present findings may have important clinical and prognostic implications. Figure 1. Smoking, prediabetes and vascular changes Funding Acknowledgement Type of funding source: None

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Boyoung Kim ◽  
Yoo Yeon Kim ◽  
Phuong Thi-Thanh Nguyen ◽  
Hajin Nam ◽  
Jun Gyo Suh

Abstract Considering that sex differences in glucose metabolism are observed in mice, researchers unconsciously use male mice to reduce variations by an estrogen cycle in female mice. In this study, we investigated the sex differences in glucose homeostasis in streptozotocin (STZ)-induced diabetes inbred mice (C57BL/6J). The C57BL/6J male and female mice were injected with or without STZ (40 mg/kg) for 5 consecutive days. Levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1C), lipid profiles, oral glucose tolerance, and insulin resistance were measured at 3 and 6 weeks after STZ treatment. The FBG level in the STZ-induced male (M-STZ) group was significantly higher than that in the STZ-induced female (F-STZ) group during the entire experimental period. Furthermore, HbA1C and glucose tolerance levels in the M-STZ group were significantly higher than those in the F-STZ group at 3 and 6 weeks after STZ treatment. The glucagon/insulin ratio in the M-STZ group was significantly higher than that in the F-STZ group. Values of the homeostatic model assessment-insulin resistance, an indicator of β-cell function and insulin resistance, significantly increased in both the M-STZ and F-STZ groups at 3 weeks after STZ treatment. However, insulin resistance was observed in the M-STZ group, but not in the F-STZ group, at 6 weeks after STZ treatment. Taken together, our results indicate that glucose metabolism in the M-STZ group was worse than that in the F-STZ group, indicating that estrogen may have an important role in glucose metabolism by STZ treatment.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249239
Author(s):  
Jason A. West ◽  
Anastasia Tsakmaki ◽  
Soumitra S. Ghosh ◽  
David G. Parkes ◽  
Rikke V. Grønlund ◽  
...  

Combinatorial gut hormone therapy is one of the more promising strategies for identifying improved treatments for metabolic disease. Many approaches combine the established benefits of glucagon-like peptide-1 (GLP-1) agonism with one or more additional molecules with the aim of improving metabolic outcomes. Recent attention has been drawn to the glucose-dependent insulinotropic polypeptide (GIP) system due to compelling pre-clinical evidence describing the metabolic benefits of antagonising the GIP receptor (GIPR). We rationalised that benefit might be accrued from combining GIPR antagonism with GLP-1 agonism. Two GIPR peptide antagonists, GIPA-1 (mouse GIP(3–30)NH2) and GIPA-2 (NαAc-K10[γEγE-C16]-Arg18-hGIP(5–42)), were pharmacologically characterised and both exhibited potent antagonist properties. Acute in vivo administration of GIPA-1 during an oral glucose tolerance test (OGTT) had negligible effects on glucose tolerance and insulin in lean mice. In contrast, GIPA-2 impaired glucose tolerance and attenuated circulating insulin levels. A mouse model of diet-induced obesity (DIO) was used to investigate the potential metabolic benefits of chronic dosing of each antagonist, alone or in combination with liraglutide. Chronic administration studies showed expected effects of liraglutide, lowering food intake, body weight, fasting blood glucose and plasma insulin concentrations while improving glucose sensitivity, whereas delivery of either GIPR antagonist alone had negligible effects on these parameters. Interestingly, chronic dual therapy augmented insulin sensitizing effects and lowered plasma triglycerides and free-fatty acids, with more notable effects observed with GIPA-1 compared to GIPA-2. Thus, the co-administration of both a GIPR antagonist with a GLP1 agonist uncovers interesting beneficial effects on measures of insulin sensitivity, circulating lipids and certain adipose stores that seem influenced by the degree or nature of GIP receptor antagonism.


2012 ◽  
Vol 19 (04) ◽  
pp. 462-468
Author(s):  
M. IKRAM ◽  
SYED HAIDER HASAN ALAM ◽  
SHAFQAT MUKHTAR ◽  
M. Saeed

Introduction: Gestational diabetes mellitus is common disorder in pregnancy. It is associated with adverse pregnancy outcome. There is no consensus regarding the optimal approach to screening of gestational diabetes mellitus. The present study has tried toobserve the value of fasting blood glucose in screening of gestational diabetes. Objective: To determine the frequency of patients in whomfasting blood glucose and 100gm glucose tolerance show agreement for screening of gestational diabetes mellitus at 24 -28 wks. Studydesign: Comparative cross sectional study. Settings: The study was conducted at Gynecology and Obstetrics department Shaikh ZayedFederal Post Graduate Institute Lahore. Duration of study with dates: 6 months from 12Nov 2010 to 11 May 2011. Material and method: Thestudy included 135 booked patients with positive family history of diabetes mellitus. All patients underwent fasting blood glucose at 24-28 weeksof gestation, regardless of results of fasting blood glucose on next visit they underwent 100g oral glucose tolerance test (OGTT). The agreementbetween fasting blood glucose and 100g oral glucose tolerance test was calculated in frequency and percentages. Results: The mean age ofwomen in studied population was 27.15±3.70.Out of 135 patients 86.7 %( 117) showed agreement between results of fasting blood glucose and100g OGTT while 13.31 %( 18) showed no agreement between both of the tests. Conclusions: Fasting blood glucose is a good screeningoption for gestational diabetes mellitus along with positive history. It provides a simple, cheap and more practical test for screening of gestationaldiabetes mellitus. However diagnostic confirmation with 100g OGTT should be done.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yanan Shi ◽  
Dan Liu ◽  
Jihong Yuan ◽  
Lihui Yan ◽  
Zhenfeng Zhan ◽  
...  

Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mani Mokou ◽  
Shan Yang ◽  
Bin Zhan ◽  
Shan Geng ◽  
Kejia Li ◽  
...  

Background. Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR). Methods. The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA. Results. Serum Fetuin-B and TNF-α levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2 h blood glucose after glucose overload, fasting insulin, 2 h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-α, while negatively associated with M value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR. Conclusion. Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tara Ahanian ◽  
Philip Curman ◽  
Ivone U. S. Leong ◽  
Kerstin Brismar ◽  
Etty Bachar-Wikstrom ◽  
...  

Abstract Background Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. We hypothesize that DD patients have a diabetes-like metabolic phenotype and the objective of this study was to examine the association between DD with impaired glucose tolerance and diabetes. Methods Cross-sectional clinical study on 25 DD patients and 25 matched controls. Metabolic status was assessed primarily by fasting blood glucose, oral glucose tolerance test, HOMA2-%S (insulin resistence) and HOMA2-%B (beta cell function). Results DD subjects showed normal oral glucose tolerance test and HOMA2-%S, while fasting blood glucose was lower and c-peptide as well as HOMA2-%B was higher. Conclusion Increased HOMA2-%B values are indicative of increased basal insulin secretion which is a type of beta cell dysfunction associated to diabetes development. These results supports a role of ER stress in diabetes pathophysiology and contribute to the understanding of DD as a multi-organ syndrome.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Eko Farida ◽  
Lilis Nuraida ◽  
Puspo E. Giriwono ◽  
Betty S. L. Jenie

Some lactic acid bacteria (LAB) are observed to be potential probiotics with functional properties such as lowering fasting blood glucose (FBG), as a promising hyperglycemia management. This study investigated the ability and mechanism of Lactobacillus rhamnosus BSL and Lactobacillus rhamnosus R23 on lowering FBG in diabetic rats induced by streptozotocin (STZ). The rats were orally administered with L. rhamnosus BSL and L. rhamnosus R23 by giving 1 mL cell suspension (109 CFU/mL) daily for 30 days. The body weight (BW) was recorded once in three days, and FBG was recorded once in six days. An oral glucose tolerance test (OGTT) was measured 1 week after injection with STZ and before sacrifice. Fecal samples were collected on days 0, 15, and 30 for LAB population and identification, performed by PCR detecting 16S rRNA. Oral administration of L. rhamnosus BSL and L. rhamnosus R23 decreased FBG and improved glucose tolerance via downregulation of glucose-6-phosphatase (G6pc) expression by 0.57- and 0.60-fold change, respectively (P<0.05). The lipid profiles, BUN, creatinine, SGOT, and SGPT were significantly (P<0.05) different between normal and diabetic rats, but they were not significantly (P>0.05) different among diabetic rats. Both strains were effective in increasing fecal LAB population. Molecular identification of the isolated LAB from fecal sample indicated that they were able to survive and pass through the digestive tract. These results suggested that both strains have the ability to manage blood glucose level and become a promising agent to manage hyperglycemia and diabetes.


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