scholarly journals Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease

Diabetologia ◽  
2009 ◽  
Vol 53 (2) ◽  
pp. 277-280 ◽  
Author(s):  
D. Nathanson ◽  
B. Zethelius ◽  
C. Berne ◽  
J. J. Holst ◽  
Å. Sjöholm ◽  
...  
1997 ◽  
pp. 127-131 ◽  
Author(s):  
B Ahren ◽  
H Larsson ◽  
JJ Holst

OBJECTIVE: The gastrointestinal hormones, gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are both released from the gut after oral glucose ingestion and stimulate insulin secretion. This study examined the release of these hormones in subjects with impaired glucose tolerance (IGT), which precedes the development of non-insulin-dependent diabetes. DESIGN AND METHODS: Six postmenopausal women with IGT, aged 59 years, underwent a 75 g oral glucose tolerance test and plasma levels of GIP and GLP-1 were determined regularly during the following 2 h. The results were compared with those in seven age- and weight-matched women with normal glucose tolerance (NGT). RESULTS: Basal plasma levels of GIP and GLP-1 were not different between the groups. In response to the oral glucose ingestion, plasma levels of both GIP and GLP-1 increased in both groups. The plasma GIP increase after glucose ingestion was, however, reduced in women with IGT. Thus, the GIP response as determined as the area under the curve for the 60 min after oral glucose was 34.8 +/- 3.2 pmol/l per min in women with IGT versus 56.4 +/- 7.8 pmol/l per min in those with NGT (P = 0.021). In contrast, the GLP-1 response to oral glucose was not different between the groups. By definition, the glucose response to oral glucose was markedly increased in women with IGT, and the insulin response during the second hour after glucose ingestion was exaggerated. CONCLUSIONS: The GIP response to oral glucose is impaired in postmenopausal women with IGT, whereas the plasma GLP-1 response is not affected.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2436-PUB
Author(s):  
SHISHI XU ◽  
CHARLES A. SCOTT ◽  
RUTH L. COLEMAN ◽  
JAAKKO TUOMILEHTO ◽  
RURY R. HOLMAN

2019 ◽  
Vol 26 (10) ◽  
pp. 1080-1091 ◽  
Author(s):  
Donna Parizadeh ◽  
Neda Rahimian ◽  
Samaneh Akbarpour ◽  
Fereidoun Azizi ◽  
Farzad Hadaegh

Aims To investigate the sex-specific associations of prediabetes with major clinical outcomes including incident type 2 diabetes, chronic kidney disease, hypertension, coronary heart disease, stroke and all-cause mortality. Methods Among 8498 Iranian adults from the Tehran Lipid and Glucose Study, aged ≥30 years and without diagnosed type 2 diabetes, gender-interactions were assessed for each outcome, followed by sex-separated multivariate-adjusted Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals (CIs) of different prediabetes categories, including impaired fasting glucose (IFG), defined by the American Diabetes Association (ADA) and World Health Organization (WHO), as fasting plasma glucose of 5.6–6.9 mmol/L and 6.1–6.9 mmol/L, respectively, and impaired glucose tolerance, defined as 2-h post challenge plasma glucose of 7.8–11 mmol/L. Results Sex-specific associations existed for men between IFG-ADA and chronic kidney disease (hazard ratio: 1.28, 95% CI 0.99–1.65; pinteraction = 0.008) and between IFG-WHO and stroke (hazard ratio: 2.15, 95% CI 1.08–4.27; pinteraction = 0.21); and for women between IFG-ADA and hypertension (hazard ratio: 1.24, 95% CI 1.04–1.48; pinteraction = 0.06) and between impaired glucose tolerance and coronary heart disease (hazard ratio: 1.57, 95% CI 1.14–2.16; pinteraction = 0.05). Among both genders, all prediabetes definitions were associated with type 2 diabetes but none with mortality. Conclusions The hazards of prediabetes definitions may differ between genders depending on the outcome of interest. IFG-WHO among men and impaired glucose tolerance among women are particularly important because of their association with incident stroke and coronary heart disease, respectively. Considering these sex differences could improve personalized management of prediabetes.


Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2136-2144 ◽  
Author(s):  
Jun Ding ◽  
Yan Gao ◽  
Jing Zhao ◽  
Hong Yan ◽  
Shi-ying Guo ◽  
...  

Heterozygosity for the Pax6 allele is associated with impaired glucose tolerance in humans. With a Pax6 mutant mouse model, we found many of the metabolic abnormalities were consistent with the effects of down-regulating the expression of glucagon-like peptide 1 (GLP-1). In addition to impaired glucose tolerance, adult heterozygous mutant mice (Pax6m/+) secreted less insulin responding to glucose and arginine administration compared with control mice. Moreover, Pax6m/+ mice showed increased food intake compared with control mice, although they were resistant to diet-induced fat accumulation. Indeed, levels of circulating GLP-1 and intestinal transcription of Gcg/Proglucagon were dramatically reduced in Pax6m/+ mice. Mutated Pax6 also failed to activate the Gcg/Proglucagon promoter by in vitro transfection assay. Finally, administering the GLP-1 receptor agonist exendin-4 to Pax6m/+ mice largely reversed their abnormal food intake, glycemic excursion, and insulin secretion. Our studies suggested that disruption of metabolic homeostasis mainly caused by Pax6 haploinsufficiency was mainly mediated by down-regulation of GLP-1. Administration of exendin-4 may be a useful therapy in humans with a similar mutation.


2020 ◽  
Author(s):  
Hertzel C. Gerstein ◽  
Ruth L. Coleman ◽  
Charles A.B. Scott ◽  
Shishi Xu ◽  
Jaakko Tuomilehto ◽  
...  

OBJECTIVE <p>We examined the impact of acarbose, an alpha-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD).</p> <p>RESEARCH DESIGN AND METHODS</p> <p>Participants were randomly assigned to acarbose or placebo and followed with four-monthly FPGs and annual OGTTs. Incident diabetes was defined as two successive diagnostic FPGs ≥ 7 mmol/L or 2-hr PGs ≥ 11.1 mmol /L while taking study medication, or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-hr PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA<sub>1c</sub>, FPG, 2h-PG, BMI eGFR), for IGT alone and for IGT+IFG, and for use of thiazides, ACE inhibitors/angiotensin receptor blockers, beta blockers, calcium channel blockers or statins). </p> <p>RESULTS</p> <p>Incident diabetes was less frequent with acarbose, compared with placebo, being 3.2 and 3.8 <i>per</i> 100 person-years respectively (rate ratio (RR) 0.82, 95%CI 0.71–0.94, p=0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose, compared with placebo, being 16.3 and 14.1 <i>per</i> 100 person-years respectively (RR 1.16, 95%CI 1.08–1.25, p<0.0001). This effect was greater in participants not taking an ACEi or ARB (RR 1.36, 95%CI 1.21–1.53; P<sub>interaction</sub>=0.0006). The likelihood of remaining in normoglycemic regression did not differ between acarbose and placebo groups (P=0.41).</p> <p>CONCLUSIONS</p> <p>Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD. </p>


2020 ◽  
Author(s):  
Seyyed Saeed Moazzeni ◽  
Hamidreza Ghafelehbashi ◽  
Mitra Hasheminia ◽  
Donna Parizadeh ◽  
Arash Ghanbarian ◽  
...  

Abstract Background: Coronary heart disease (CHD) is one of the main causes of deaths. Alarmingly Iranian populations had a high rank of CHD worldwide. The current study aimed to assess the prevalence of CHD across different glycemic categories. Methods: This study was conducted on 7,718 Tehranian participants (Men=3427) aged ≥ 30 years from 2008 to 2011. They were categorized based on glycemic status. The prevalence of CHD was calculated in each group, separately. CHD was defined as hospital records adjudicated by an outcome committee. The association of different glycemic categories with CHD was calculated using multivariate logistic regression, compared with normal fasting glucose /normal glucose tolerance (NFG/NGT) group as reference. Results: The age-standardized prevalence of isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), both impaired fasting glucose and impaired glucose tolerance (IFG/IGT), newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM) were 14.30% [95% confidence interval (CI): 13.50-15.09], 4.81% [4.32-5.29], 5.19% [4.71-5.67], 5.79% [5.29-6.28] and 7.72% [7.17-8.27], respectively. Among a total of 750 individuals diagnosed as cases of CHD (398 in men), 117 (15.6%), 453 (60.4%), and 317 (42.3%) had history of myocardial infarction (MI), cardiac procedure, and unstable angina, respectively. The age-standardized prevalence of CHD for Tehranian population was 7.71% [7.18-8.24] in total population, 8.62 [7.81-9.44] in men and 7.19 [6.46-7.93] in women. Moreover, among diabetic participants, the age-standardized prevalence of CHD were 13.10 [9.83-16.38] in men 10.67 [8.90-12.44] in women, respectively, which were significantly higher than corresponding values for NFG/NGT and prediabetic groups. Across 6 levels of glycemic status, CHD was associated with IFG/IGT [ odds ratio (OR) and 95% CI: 1.38 (1.01-1.89)], NDM [1.83 (1.40-2.41)], and KDM [2.83 (2.26-3.55)] groups, in the age and sex adjusted model. Furthermore, in the full-adjusted model, only NDM and KDM status remained to be associated with the presence of CHD by ORs of 1.40 (1.06-1.85) for NDM and 1.90 (1.50-2.41) for KDM. Conclusion: The high prevalence of CHD, especially among diabetic populations, necessitates urgent implementation of behavioral interventions among Tehranian population, according to evidence-based guidelines for the clinical management of diabetic patients.


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