Background
Multiple barriers and the complex nature of diabetes hinder patients from achieving control of cardio-metabolic risk factors. Empowerment is a key component in improving self-care to attain treatment targets. The discovery of diabetes-associated genetic factors underpins the concept of precision medicine although patient empowerment remains a key factor. Despite accumulating knowledge on genetics of diabetes and its complications, it remains unknown whether genetic testing and counselling would affect self-efficacy and cardio-metabolic control in patients with type 2 diabetes (T2D).
Aim
We conducted this trial to address this knowledge gap.
Method
We conducted a randomized clinical trial whereby T2D patients aged 40-75 with moderate risks of incident endpoints were recruited and randomized into two groups, a genetic counseling group (GC) and a control group. All patients underwent genetic testing for alleles at three risk loci related to diabetic complications, from which an aggregated genetic risk score was calculated. Control group received standardized medical care (including a risk report based on clinical risk factors), whereas GC group received additional genetic counseling, incorporating education on the management of traditional risk factors. The structured personalized risk counseling was based on an established genetic counseling framework for common polygenic genetic disorders, and was designed to convey risk information and helping the individual to understand that risk. Clinical measurements, laboratory tests and questionnaire surveys were collected at baseline and after one-year to assess risk control and disease efficacy using the Diabetes Empowerment Scale (DES-20) and Diabetes Distress Scale (DDS-17). The genetic information was disclosed to the control group at the end of the study period. The primary endpoint was percentage of subjects reaching at least 3 out of 5 of the following treatment targets: i) BP<130/80mmHg, ii) HbA1C<7.0%, iii) LDL-C<2.6mmol/L, iv) TG<2.0mmol/L and v) prescription of ACEI/RAS inhibitors. Secondary outcomes included new-onset CKD or microalbuminuria, patient empowerment, patient behaviour and diabetes-related distress.
Results
We recruited 435 patients into the trial, though 15 had to be excluded subsequently due to pre-existing exclusion criteria. A total of 420 patients were included in the modified intention-to-treat analysis (214 in GC group, mean age 58.5±8.0, mean DM duration 12.7±7.1 years). Among subjects in the GC arm, a total of 186 completed the study and were eligible for the per-protocol analysis, whereas another 28 defaulted the genetic counseling session and had the genetic testing results sent to them. For those who defaulted one-year assessment, we use the method of last-observation brought forward for laboratory results to define outcome.
At the end of the 12-month study period, there was improvement in the percentage of patients from both arms which reach 3 out of 5 of the treatment targets(on-target rate increase: 11.2% for GC vs.13.6% for control). The proportions of patients who did not attained 3 of 5 treatment targets at baseline but attained post-trial was similar in both groups (20.8% for GC vs. 23.8% for control, P>0.05). There was no significant difference in the secondary outcome of microalbuminuria, or new onset CKD. Compared with the control group, subjects in the GC group had lower total DDS score (36.3±12.2 for GC vs. 38.8±13.0 for control), but the difference was not statistically significant. A significant increase in total DES score was observed in GC group (57.7±11.0 for GC vs. 55.1±11.8 for control, P<0.05), especially in scores of three sub-dimensions, achieving diabetes goal (2.98±0.68 for GC vs. 2.82±0.72for control, P<0.05), overcoming barriers score changes (0.15±0.78 for GC vs. (-0.07)±0.73 for control, P<0.05) and determining methods (2.88±0.65 for GC vs. 2.74±0.70 for control, P<0.05). There was some evidence of interaction between underlying genetic risk and response to treatment.
Discussion
Providing individualized genetic counseling on genetic risk of future complications did not impact significantly on risk factor control after 12 months. The lack of benefit associated with genetic testing may be due to the complexity of disease management and the relative short follow-up time (only one year). Genetic counseling significantly improved efficacy in patients with T2D. The impact of genetic testing and counseling as a personalized tool to improve patients’ efficacy over a longer-term warrants further investigations in future studies.

A RCT to compare personalized genetic risk counseling with standard care on patients empowerment and risk factor control