Parental history of type 2 diabetes, TCF7L2 variant and lower insulin secretion are associated with incident hypertension. Data from the DESIR and RISC cohorts.
OBJECTIVE
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
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.
Service Endocrinologie-Diabétologie, CHU Rennes, Université Rennes 1, Inserm UMR 991, Rennes, France, fabrice.bonnet@chu-rennes.fr.
Fabrice
F
Bonnet
Ronan
R
Roussel
Andrea
A
Natali
Stéphane
S
Cauchi
John
J
Petrie
Martine
M
Laville
Loïc
L
Yengo
Philippe
P
Froguel
Céline
C
Lange
Olivier
O
Lantieri
Michel
M
Marre
Beverley
B
Balkau
Ele
E
Ferrannini
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
D007328:Insulin; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein