%0 Journal Article
%T Effects of genetic risk on incident type 2 diabetes and glycemia: the T2D-GENE lifestyle intervention trial.
%A Lankinen MA
%A Nuotio P
%A Kauppinen S
%A Koivu N
%A Tolonen U
%A Malkki-Keinänen K
%A Oravilahti A
%A Kuulasmaa T
%A Uusitupa M
%A Schwab U
%A Laakso M
%J J Clin Endocrinol Metab
%V 0
%N 0
%D 2024 Jun 18
%M 38888187
%F 6.134
%R 10.1210/clinem/dgae422
%X <B>BACKGROUND: </B>Lifestyle intervention prevents or delays type 2 diabetes (T2D) in subjects at a high risk of T2D. However, it is not known whether genetic variants modify the effect on incident T2D during lifestyle intervention.<BR><B>OBJECTIVE: </B>To investigate whether a low or high genetic risk has effects on incident T2D in a group-based lifestyle intervention study.<BR><B>METHODS: </B>The T2D-GENE trial involved 973 men from the Metabolic Syndrome in Men (METSIM) cohort, aged 50-75 years, body mass index ≥25 kg/m2, fasting plasma glucose 5.6-6.9 mmol/l, and HbA1c <48 mmol/mol and either a low or high genetic risk score for T2D. There were two intervention groups, a low (n=315) and high genetic risk for T2D (n=313). They were provided with a 3-year group-based intervention with access to a web portal focused on healthy diet and physical activity. There were also corresponding population-based control groups at low (n=196), and high genetic risk for T2D (n=149) who had two laboratory visits (0 and 3 years) and general health advice as a part of their METSIM cohort protocol. The primary outcome was incident T2D, and a secondary outcome glycemia.<BR><B>RESULTS: </B>The intervention significantly lowered the risk of T2D among the participants with a high genetic risk for T2D (HR 0.30, 95% CI 0.16-0.56, p<0.001) whereas in the low genetic risk group the effect was not significant (HR 0.69, 95% CI 0.36-1.32, p=0.262). The intervention effect was not significantly different between the high and low genetic risk groups (p=0.135). The intervention significantly ameliorated the worsening of glycemia and decreased weight both in the low and high genetic risk groups.<BR><B>CONCLUSIONS: </B>Our results showed that individuals with a high genetic risk for T2D benefited from a low-cost group-based intervention focusing on healthy diet and physical activity. Therefore, all individuals at risk of T2D should be encouraged to make lifestyle changes regardless of genetic risk.