Haptoglobin 1-1 Genotype Modulates the Association of Glycemic Control With Hippocampal Volume in Elderly Individuals With Type 2 Diabetes

Livny, Abigail; Ravona‐Springer, Ramit; Heymann, Anthony; Priess, Rachel; Kushnir, Tamar; Tsarfaty, Galia; Rabinov, Leeron; Moran, Reut; Tik, Niv; Moshier, Erin; Cooper, Itzik; Greenbaum, Lior; Silverman, Jeremy M.; Levy, Andrew P.; Sano, Mary; Bendlin, Barbara B.; Buchman, Aron S.; Schnaider‐Beeri, Michal

doi:10.2337/db16-0987

Cited by 14 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results together with those of others 8,9 with poor glycemic control in the IDCD study 26 . There is preliminary data that Hp-1 allele has poorer regeneration after endothelial injury 27,28 , suggesting a different mechanism of haptoglobin in the coronary arteries and the brain.…”

Section: Patient Characteristicssupporting

confidence: 90%

Haptoglobin 1-1 is Associated with Larger Carotid Plaque Volume Among Elderly with Type 2 Diabetes: The IDCD Study.

Botvin¹,

Haratz²,

Ravona‐Springer³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background and aims: The haptoglobin (Hp) genotype (Hp 1-1, 1-2, or 2-2) is associated with type 2 diabetes complications. The Hp2-2 genotype has been linked to elevated CHD risk while the 1-1 genotype has been recently related to cerebral small vessel disease. This study investigated whether Hp phenotype is associated with carotid atherosclerotic structure and function among type 2 diabetes elderly patients participating in the Israel Diabetes and Cognitive Decline (IDCD) study. Methods: IDCD participants (n=472) underwent a battery of carotid atherosclerosis ultrasound assessments with measurements of carotid intima media thickness (cIMT), distensibility, elastography, and carotid plaque volume. Ordinal regression models adjusting for demographic and cardiovascular risk factors assessed the associations of categorical measures of carotid plaque volume with Hp phenotype . Logistic regression models were used to assess the association of Hp phenotype with impaired cIMT, carotid distensibility and elastography. Results: Participants averaged 76.4±4.4 years old, 42% were female, mean HbA1c was 6.7±0.7% (50±7.7 mmol/mol). Hp phenotype distribution was 46 (10.4%) Hp 1-1, 186 (40.7%) Hp 2-1 and 209 (45.7%) Hp 2-2 carriers. Carotid plaque volume was categorized into 4 groups: including no plaque (n=128) and tertiles of plaque volume: small plaque (volume ≤122 mm3, n=110), medium plaque (volume 122-273 mm3, n=106) and large plaque (volume≥274 mm3, n=104). The prevalence of Hp 1-1 phenotype increased with greater carotid plaque volume (6.5%, 10.6%, 8.8% and 16.5% in the no, small, medium, and large plaque groups respectively; p=0.027). Compared to Hp-1 carriers, non-carriers (i.e. Hp 2-1 and Hp 2-2) had approximately 30% lower risk for large carotid plaque volume, as estimated using ordinal regression (OR: 0.713 [0.496, 1.03], 0.694 [0.484, 0.997] for Hp 2-1, Hp 2-2 respectively). No associations were found between Hp phenotype and level of carotid stenosis, cIMT, carotid distensibility and carotid elastography.Conclusion: Our findings suggest that among non-demented elderly patients with type 2 diabetes, the Haptoglobin 1-1 phenotype is associated with greater carotid atherosclerosis. These findings add evidence for the involvement of the Hp 1-1 phenotype in the pathophysiology of cerebrovascular disease.

show abstract

Section: Patient Characteristicssupporting

confidence: 90%

Haptoglobin 1-1 is Associated with Larger Carotid Plaque Volume Among Elderly with Type 2 Diabetes: The IDCD Study.

Botvin¹,

Haratz²,

Ravona‐Springer³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Series of studies have shown that Hp 1-1 genotype also confer risk of cerebrovascular disease in both type 1 [15, 48] and type 2 diabetes [49] and may be dependent on hypertension status at baseline. In our study, the prevalence of hypertension did not differ according to the Hp phenotype.…”

Section: Discussionmentioning

confidence: 99%

Association of haptoglobin phenotype with incident acute myocardial infarction in Chinese patients with type 2 diabetes

Gurung

Yiamunaa

Liu

et al. 2019

Cardiovasc Diabetol

View full text Add to dashboard Cite

Background Haptoglobin (Hp) is an abundant plasma protein with anti-oxidant properties. Hp polymorphism is associated with cardio-metabolic dysfunction but the allele conferring risk of developing acute myocardial infarction (AMI) in type 2 diabetes (T2D) patients is unclear. This study aimed to investigate the association of Hp phenotype (Hp 1-1, 2-1 and 2-2) with incident AMI in Chinese T2D patients. Methods This prospective study included Chinese T2D participants from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) and Diabetic Nephropathy (DN) cohorts. Information on incidence of non-fatal AMI was collected by data linkage with the Singapore Myocardial Infarction Registry. Hp phenotype was determined using enzyme-linked immunosorbent assay. Cox proportional hazards regression models were used to evaluate the association of Hp phenotype with incident AMI, adjusted for traditional risk factors separately in two cohorts, then meta-analysed. Results In total, 2324 Chinese participants (SMART2D; N = 1034, mean age [SD] of 59 [11]) and (DN: N = 1290, mean age [SD] of 58 [12]) were included in this study. There were total of 30 (56 events per 10,000 patient-years) and 99 (128 events per 10,000 patient-years) AMI events in SMART2D and DN cohorts respectively. In meta-analysis, presence of Hp 1 allele conferred 43% (hazard ratio [HR] = 1.43 [95% CI 1.10–1.87], P = 0.008, P het = 0.413) increased risk of incident AMI, independent of age, sex, smoking, body mass index, HbA1c, diabetes duration, lipids, hypertension, renal function and usage of insulin and RAS antagonist. In adjusted model, compared to Hp 2-2 groups, individuals with Hp 1-1 (HR = 2.18 [95% CI 1.19–3.76], P = 0.010, P het = 0.193) and Hp 2-1 (HR = 1.45 [95% CI 0.98–2.14], P = 0.065, P het = 0.576) were at a higher risk of incident AMI. Moreover, compared to Hp 2-2 groups, non-Hp 2-2 groups (Hp 1-1 and Hp 2-1) were at 55% increased risk of incident AMI (HR = 1.55 [95% CI 1.07–2.24], P = 0.021, P het = 0.940). Conclusions Hp 1-1 phenotype was associated with increased risk of incident AMI, independent of traditional risk factors, in Chinese patients with T2D. Hp phenotyping may allow for identification of T2D individuals at higher risk for onset of AMI. However, further studies are needed to understand the underlying mechanism between Hp alleles and risk for AMI. Electronic supplementary material The online version of this article (10.1186/s12933-019-0867-4) contains supplementary material, which is available to authorized users.

show abstract

“…It has recently been shown in older persons of white race/ethnicity with type 2 diabetes that poor glycemic control was strongly associated with hippocampal volume among those with the Hp 1-1 genotype but not among other genotypes. 35 This outcome suggests that individuals with the Hp 1-1 genotype may be more vulnerable to the deleterious influences of poor glycemic control.…”

Section: Discussionmentioning

confidence: 99%

Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes

et al. 2018

Self Cite

View full text Add to dashboard Cite

Key Points Question Is the haptoglobin genotype associated with cognition in African American adults with type 2 diabetes? Findings In this cohort study of 466 African American adults with type 2 diabetes, haptoglobin 1-1 carriers had the poorest cognitive function, while haptoglobin 2-1m carriers had the highest cognitive function. Older haptoglobin 1-1 carriers had greater cognitive decline over time compared with the other genotypes. Meaning The haptoglobin gene polymorphism may contribute to cognitive impairment in African American adults who have type 2 diabetes.

show abstract

Haptoglobin 1-1 Genotype Modulates the Association of Glycemic Control With Hippocampal Volume in Elderly Individuals With Type 2 Diabetes

Cited by 14 publications

References 35 publications

Haptoglobin 1-1 is Associated with Larger Carotid Plaque Volume Among Elderly with Type 2 Diabetes: The IDCD Study.

Haptoglobin 1-1 is Associated with Larger Carotid Plaque Volume Among Elderly with Type 2 Diabetes: The IDCD Study.

Association of haptoglobin phenotype with incident acute myocardial infarction in Chinese patients with type 2 diabetes

Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes

Contact Info

Product

Resources

About