Aims/hypothesis:
The relationship between insulin secretion and the incidence of hypertension has not been well characterised. We hypothesised that both a parental history of diabetes and TCF7L2 rs7903146 polymorphism, which increases susceptibility to diabetes because of impaired beta cell function, are associated with incident hypertension. In a separate cohort, we assessed whether low insulin secretion is related to incident hypertension.
Methods:
Nine year incident hypertension was studied in 2,391 normotensive participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. The relationship between insulin secretion and 3 year incident hypertension was investigated in 1,047 non-diabetic, normotensive individuals from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort. Insulin secretion during OGTT was expressed in relation to the degree of insulin resistance, as assessed by a hyperinsulinaemic-euglycaemic clamp.
Results:
In the DESIR cohort, a parental history of diabetes and the TCF7L2 at-risk variant were both associated with hypertension incidence at year 9, independently of waist circumference, BP, fasting glucose, insulin levels and HOMA-IR at inclusion (p = 0.02 for parental history, p = 0.006 for TCF7L2). In the RISC cohort, a lower insulin secretion rate during the OGTT at baseline was associated with both higher BP and a greater risk of hypertension at year 3. This inverse correlation between the insulin secretion rate and incident hypertension persisted after controlling for baseline insulin resistance, glycaemia and BP (p = 0.007).
Conclusions/interpretation:
Parental history of diabetes, TCF7L2 rs7903146 polymorphism and a reduced insulin secretion rate were consistently associated with incident hypertension. A low insulin secretion rate might be a new risk factor for incident hypertension, beyond insulin resistance.
Citing Articles
Degree of Blood Glucose Control and Risk of Hypertension in Chinese Adults with T2DM: A Cross-Sectional Study.
Zhang J, Yao X, Chen Y, Feng Q, Zhang Y, Jiang T
Diabetes Metab Syndr Obes. 2024; 17:3227-3238.
PMID: 39224112
PMC: 11368100.
DOI: 10.2147/DMSO.S462748.
Prediction of Drug Targets for Specific Diseases Leveraging Gene Perturbation Data: A Machine Learning Approach.
Zhao K, Shi Y, So H
Pharmaceutics. 2022; 14(2).
PMID: 35213968
PMC: 8878225.
DOI: 10.3390/pharmaceutics14020234.
Association of family history of type 2 diabetes with blood pressure and resting heart rate in young normal weight Japanese women.
Honda M, Tsuboi A, Minato-Inokawa S, Kitaoka K, Takeuchi M, Yano M
Diabetol Int. 2022; 13(1):220-225.
PMID: 35059258
PMC: 8733113.
DOI: 10.1007/s13340-021-00525-2.
Association of Combined TCF7L2 and KCNQ1 Gene Polymorphisms with Diabetic Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus.
Rattanatham R, Settasatian N, Komanasin N, Kukongviriyapan U, Sawanyawisuth K, Intharaphet P
Diabetes Metab J. 2021; 45(4):578-593.
PMID: 33752320
PMC: 8369220.
DOI: 10.4093/dmj.2020.0101.
Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes.
Porcu E, Gilardi F, Darrous L, Yengo L, Bararpour N, Gasser M
Sci Rep. 2021; 11(1):6197.
PMID: 33737653
PMC: 7973501.
DOI: 10.1038/s41598-021-85684-7.
Integrated analysis of the transcriptome-wide m6A methylome in preeclampsia and healthy control placentas.
Wang J, Gao F, Zhao X, Cai Y, Jin H
PeerJ. 2020; 8:e9880.
PMID: 32983644
PMC: 7500358.
DOI: 10.7717/peerj.9880.
Risk of hypertension in middle-aged and elderly participants with newly diagnosed type 2 diabetes and prediabetes.
Sasaki N, Ozono R, Maeda R, Higashi Y
BMJ Open Diabetes Res Care. 2020; 8(1).
PMID: 32933951
PMC: 7493116.
DOI: 10.1136/bmjdrc-2020-001500.
Association of Established Blood Pressure Loci With 10-Year Change in Blood Pressure and Their Ability to Predict Incident Hypertension.
Poveda A, Atabaki-Pasdar N, Ahmad S, Hallmans G, Renstrom F, Franks P
J Am Heart Assoc. 2020; 9(16):e014513.
PMID: 32805198
PMC: 7660819.
DOI: 10.1161/JAHA.119.014513.
Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases.
Wang Z, Luo J, Xu L, Zhou H, Zhang W
Pharmacogenomics J. 2017; 18(3):351-358.
PMID: 28696417
DOI: 10.1038/tpj.2017.28.
Impact of statistical models on the prediction of type 2 diabetes using non-targeted metabolomics profiling.
Yengo L, Arredouani A, Marre M, Roussel R, Vaxillaire M, Falchi M
Mol Metab. 2016; 5(10):918-925.
PMID: 27689004
PMC: 5034686.
DOI: 10.1016/j.molmet.2016.08.011.
The Association of Type 2 Diabetes Loci Identified in Genome-Wide Association Studies with Metabolic Syndrome and Its Components in a Chinese Population with Type 2 Diabetes.
Kong X, Zhang X, Xing X, Zhang B, Hong J, Yang W
PLoS One. 2015; 10(11):e0143607.
PMID: 26599349
PMC: 4657988.
DOI: 10.1371/journal.pone.0143607.
Glucose and the risk of hypertension in first-degree relatives of patients with type 2 diabetes.
Janghorbani M, Bonnet F, Amini M
Hypertens Res. 2015; 38(5):349-54.
PMID: 25693857
DOI: 10.1038/hr.2015.10.
rs7903146 polymorphism at transcription factor 7 like 2 gene is associated with total cholesterol and lipoprotein profile in HIV/hepatitis C virus-coinfected patients.
Pineda-Tenor D, Berenguer J, Jimenez-Sousa M, Carrero A, Garcia-Alvarez M, Aldamiz-Echevarria T
AIDS Res Hum Retroviruses. 2014; 31(3):326-34.
PMID: 25353718
PMC: 4348080.
DOI: 10.1089/aid.2014.0195.
Low fasting plasma insulin is associated atrial fibrillation in men from a cohort study--the Malmö preventive project.
Johnson L, Juhlin T, Engstrom G, Nilsson P
BMC Cardiovasc Disord. 2014; 14:107.
PMID: 25150967
PMC: 4236524.
DOI: 10.1186/1471-2261-14-107.
