Genetic Testing and Counseling to Reduce Diabetic Complications
Condition: Diabetic Complication
MeSH terms: Diabetes Complications
Study type: Interventional

Summary: 
      The risk of diabetic kidney complications includes non-modifiable risk factors such as
      genetic predictors, as well as modifiable risk factors such as hyperglycaemia, hypertension,
      hyperlipidaemia and proteinuria. Genetic testing for personalized medicine is increasing in
      popularity, though evidence that genetic testing can empower patients to modify behaviour and
      reduce clinical risk remains lacking. In this project, the investigators aim to utilize a
      personalized risk counseling with genetic testing to evaluate its impact on risk factor
      control in diabetic patients. The investigators hypothesize that knowledge of genetic +/-
      clinical risk will empower patients and lead to improvement in the number of treatment
      targets achieved. The investigators will recruit 400 patients with diabetes. All subjects
      will undergo a comprehensive assessment of the risk of diabetic complications based on
      clinical risk factors. Half of the patients will be randomized to receive additional genetic
      testing of a panel of genetic markers proven to predict renal complications in our
      population: ACE I/D, aldose reductase (CA)n and PRKCB1 gene polymorphisms. The results of
      personalized risk assessment will be communicated by a health counsellor in the intervention
      arm. The impact of testing and patient knowledge of the result of genetic testing on
      achievement of treatment targets (A1c, BP, LDL-cholesterol, TG, use of ACEI/ARB) and patient
      behavior will be evaluated after 12 months. The other arm will receive results of the genetic
      testing at the completion of the study period. The study will help towards developing a
      strategy to empower patients through structured and personalized risk assessment will provide
      a novel approach to identify high-risk subjects for early intensive management, and may lead
      to reduction in long-term complications.
    

Detailed description: 
      Asia is in the midst of an epidemic of diabetes. Approximately 1 in 10 people in China has
      diabetes [1]. Asian patients with diabetes are characterized by early age of onset and
      increased risk of kidney complications. Young age of onset and long disease duration will
      place Chinese diabetic patients at high risk for complications. In the Hong Kong Diabetes
      Registry, which includes more than 7000 patients with type 2 diabetes, we have reported a
      high risk of diabetic complications, with 30% having died or sustained a major clinical event
      within 10years after diagnosis, including 10% developing cardiovascular complications, and
      10% developing end-stage renal disease [2] [3]. The medical costs for the diabetic patient
      with complication is 2.2-3.8 fold that of patients without complications, and patients with
      cardiorenal complications are the most costly to manage [4]. Using our registry, we have
      identified clinical risk predictors for developing renal complications as glycaemic control,
      elevated blood pressure, hyperlipidaemia, and albuminuria [2] [3, 5], and have derived
      clinical risk prediction algorithms and incorporated them into a patient management portal,
      which can generate a standardized report for risk counseling based on clinical risk factors
      [6, 7]. Furthermore, in a multi-centre study utilizing a multidisciplinary team, we found
      that intensive management aiming to achieve targets of A1c, lipids, BP can significantly
      reduce the risk of developing kidney complication [8]. Therefore, the ability to identify
      subjects at risk of complications, and to target and motivate them to optimize modifiable
      risk factors for diabetic complications will be of clinical benefit and potentially
      cost-saving.

      There has been much recent interest in the use of genetic testing for personalized medicine
      [9]. Diabetic kidney complications has high heritability of around 40% and several genetic
      factors have been found to be associated with diabetic renal complications. Using
      candidate-gene approach, our group has identified several genetic markers for diabetic kidney
      complications [10, 11] [12]. These include the angiotensin converting enzyme deletion/
      insertion (ACE D/I) polymorphism and the aldose reductase (ALR2) 5'-(CA) n microsatellite
      polymorphism, each being associated with 2-3 fold increased risk of diabetic cardio-renal
      complications in Chinese [10, 13]. More recently, we have found that carriers of risk alleles
      at the protein kinase C-β1 (PRKCB1) locus can have up to 6-fold increased risk of developing
      end-stage renal disease during follow-up, after adjusting for the effect of clinical risk
      predictors [12].

      The recent increase in consumer-initiated genetic testing has been driven by
      direct-to-consumer genetic testing, which assumes that personal genetic information can
      motivate positive behavioural change in patients [14]. Interestingly, a recent survey of
      patients without type 2 diabetes suggests that genetic testing may be able to motivate
      patients, with 71% of respondents reporting that they would be "much more motivated" to make
      behavioural changes if they were informed to be of high genetic risk for diabetes [15].
      Although evidence that genetic testing can lead to behavioural changes is still lacking,
      several randomized clinical trials are currently underway to examine the impact of genetic
      testing on behaviour to reduce risk of diabetes. Given the disabling consequences of diabetic
      complications, and the ability to predict those at risk of developing complications, we plan
      to examine the role of personalized risk counseling incorporating genetic markers, and to
      examine its role in patient empowerment and risk factor control, which may help to reduce the
      risk of developing complications.
    

Intervention name(s): Personalized Risk Counselling; Normal usual care
Intervention type(s): Behavioral; Other
Intervention description(s): Motivational message- towards lifestyle change, improved compliance and risk factors control Review overall control of clinical risk factors based on lab test results; General education on diabetes and diabetic complications
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Primary purpose: Health Services Research