Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes

Guerrero‐Berroa, Elizabeth; Ravona‐Springer, Ramit; Heymann, Anthony; Schmeidler, James; Levy, Andrew P.; LeRoith, Derek; Beeri, Michal Schnaider

doi:10.1007/s00125-014-3487-2

Cited by 16 publications

(14 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that Hp 2 carriers have a 30% lower risk for larger carotid plaque volume compared to Hp 1-1 carriers. These results are consistent with recent literature of associations of Hp 1-1 with cerebrovascular disease 8,25 . In contrast, we did not nd signi cant associations between Hp phenotype and cIMT, carotid distensibility and elastography measures.…”

Section: Patient Characteristicssupporting

confidence: 93%

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: 93%

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

“…Carotid atherosclerosis was reported to be associated with an increased risk of stroke and poorer cognitive performance in the elderly [ 44 ]. In addition, patients with the Hp 1-1 genotype were identified to have an increased risk of stroke in a longitudinal study of type 1 diabetes and poorer cognitive function in elderly individuals with type 2 diabetes [ 45 , 46 ]. The influence of Hp genotypes on stroke might be partly attributed to their association with carotid atherosclerosis, which appears to have a different aetiology than that of coronary artery disease.…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients

Wang

Zhang

et al. 2018

Cardiovasc Diabetol

View full text Add to dashboard Cite

BackgroundHaptoglobin (Hp) functions as an antioxidant by binding with haemoglobin. We investigated whether serum Hp has a causal effect on macroangiopathy via Mendelian randomization (MR) analysis with common variants of the Hp gene in Chinese patients with type 2 diabetes.MethodsA total of 5687 type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical features and vascular imaging tests were applied to diagnose macroangiopathy. The association between common Hp genotypes and macroangiopathy was analyzed in the whole population. Serum Hp levels were measured by enzyme-linked immunosorbent assay in a subset of 935 patients. We individually analyzed the correlations among Hp levels, Hp genotypes and macroangiopathy. Further, 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative marker of DNA damage, was examined to evaluate the levels of oxidative stress.ResultsCommon Hp genotypes were correlated with macroangiopathy (OR = 1.140 [95% CI 1.005–1.293], P = 0.0410 for the Hp 1 allele). Serum Hp levels were associated with both common Hp genotypes (P = 3.55 × 10−31) and macroangiopathy (OR = 2.123 [95% CI 1.098–4.102], P = 0.0252) in the subset of 935 patients. In the MR analysis, the directional trends of the observed and predicted relationships between common Hp genotypes and macroangiopathy were the same (OR 1.357 and 1.130, respectively). Furthermore, common Hp genotypes and Hp levels were associated with serum 8-OHdG levels (P = 0.0001 and 0.0084, respectively).ConclusionsOur study provides evidence for a causal relationship between serum Hp levels and macroangiopathy in Chinese type 2 diabetes patients by MR analysis.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0662-7) contains supplementary material, which is available to authorized users.

show abstract

“…Serum was extracted from blood samples, and Hp genotypes were determined by polyacrylamide gel electrophoresis from 10 μL of plasma using established methods ( 14 ) and dichotomized as Hp 1-1 carriers versus Hp 2-1 or Hp 2-2 carriers. We chose to use the dichotomy of Hp 1-1 carriers versus others because we found no difference between the Hp 1-2 and Hp 2-2 carriers in our prior studies assessing the association of Hp with cognition ( 11 , 12 ). Demographic details and T2D-related characteristics including longitudinal glycemic control based on repeated HbA 1c levels, systolic and diastolic blood pressure, LDL, HDL, total cholesterol, and creatinine were available for all participants.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, the association of glycemic control with cognitive function was primarily observed for individuals with Hp 1-1 but not for Hp 1-2 and Hp 2-2 carriers. These findings suggest that individuals with the Hp 1-1 genotype may be more susceptible to the deleterious effects of poor glycemic control ( 12 ). We examined the interrelationship of Hp genotype, HbA 1c levels, and regional volume of the hippocampus obtained from MRI of the brain in older individuals with T2D.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

Recent evidence suggests that glycemic control is associated with cognitive function in older patients with type 2 diabetes who are carriers of the haptoglobin (Hp) 1-1 genotype compared with noncarriers. We assessed whether poor glycemic control in Hp 1-1 carriers is more strongly associated with smaller hippocampal volume than in noncarriers. Hippocampal volume was generated from high-resolution structural T1 MRI obtained for 224 participants (28 Hp 1-1 carriers [12.5%] and 196 noncarriers [87.5%]) from the Israel Diabetes and Cognitive Decline (IDCD) study, who had a mean (SD) number of years in the Maccabi Healthcare Services (MHS) registry of 8.35 (2.63) and a mean (SD) HbA1c level of 6.66 (0.73)% [49 mmol/mol]. A stronger negative association between right hippocampal volume and HbA1c was found in patients with the Hp 1-1 genotype, with a 0.032-mL decrease in right hippocampal volume per 14% increase in HbA1c (P = 0.0007) versus a 0.009-mL decrease in Hp 1-1 noncarriers (P = 0.047), after adjusting for total intracranial volume, age, sex, follow-up years in the registry, and cardiovascular factor (interaction, P = 0.025). This indicates that 29.66% of the total variance in right hippocampal volume is explained by HbA1c levels among Hp 1-1 carriers and that 3.22% is explained by HbA1c levels among Hp 1-1 noncarriers. Our results suggest that the hippocampus of Hp 1-1 carriers may be more vulnerable to the insults of poor glycemic control.

show abstract

Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes

Cited by 16 publications

References 50 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.

Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients

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

Contact Info

Product

Resources

About