Precision medicine for diabetes: potential, pitfalls and dangers, not ready to enter the golden age!

Type 2 diabetes is a multifactorial, heterogeneous, polygenic metabolic disorder with flaws
in the "one-size-fits-all" approach to diagnosis and treatment.
In this article, the researchers highlight the limitations of some of the current research evidence and the challenges that need to be overcome before implementing precision medicine in the
prevention and management of type 2 diabetes.

Academics have long advocated stratification and developed diabetes risk scores, the derivatives of which are used in many diabetes prevention and early detection programs
.
Recently, researchers have investigated the potential for more nuanced screening protocols based on simple phenotypic and/or genetic information to minimize harm and maximize benefits
by changing screening intervals and age at which screening begins.
However, there are substantial differences between the rough stratification of the population and the so-called precision medicine approach that advises individuals on disease prevention or treatment, and there is still a lack of evidence of effectiveness, let alone cost-effectiveness
.

The ADA-EASD consensus report defines precision diabetes medicine as shown in the figure below, and the main difference from standard medical methods is the use of complex data to describe an individual's health status, disease susceptibility, prognosis, and treatment response
.

There are many successful precision medicine approaches for single-gene disorders, such as specific diets for phenylketonuria, and sulfonylurea therapy for certain types of MODY (see examples).

However, most chronic diseases are polygenetic.

Research strategies for single-gene diseases are unlikely to bring similar changes
to the practice of polygenic traits.

Example: Previous studies have found that sulfonylurea therapy is safe in the short term and may be more effective
than insulin therapy in patients with diabetes caused by KCNJ11 mutations.
This pharmacogenetic response to sulfonylurea may be due to the closure of mutant KATP channels, which increase insulin secretion in response to incretin and glucose metabolism
.

Personalized medicine vs precision medicine

Most people with diabetes have other comorbidities and therefore require other treatments
at the same time.
This needs to be taken into account regarding diabetes treatment options
.
The personalized medicine approach involves education, consultation, and shared decision-making with the patient, followed by monitoring the patient's acceptability, side effects, adherence, quality of life, and HbA1c
for the next 10 weeks.
The new policy needs to prove superior to this strategy
before it can be implemented.

Currently, there are limitations in the design and analysis of precision medicine studies, many of which are based on case-control studies or sampling
from extreme characteristics of exposure distribution and outcomes.
Because the differential measures (sensitivity, specificity, and area under the receiver operating profile curve) are not independent of prevalence, the predictive utility of precision medicine features is likely to be exaggerated
.
In addition, although precision medicine research often focuses on predictions, such as drug reactions or adverse reactions, results are often expressed
in odds ratios rather than differentiating measures such as sensitivity, specificity, predictive value, likelihood ratio, or area under the ROC curve.

The main determinant of health

Simply put, precision medicine is an exciting field of scientific research that has the potential to revolutionize clinical practice
.
Unfortunately, successful implementation in the field of type 2 diabetes is limited
by the heterogeneous and polygenic nature of the disease.
Many precision medicine methods are too precise, too complex, and too narrowly focused on blood sugar levels and individuals rather than their backgrounds
.
The evidence to date is insufficient to demonstrate the widespread application of precision medicine methods to routine clinical practice
.

Hypoglycemic drug selection strategies based on routinely available phenotypic data show promise, but require more trial evaluation and should consider drug adherence
.
Our focus should continue to be on improving the application of personalized medicines, treatments, and policies that are often helpful to patients and cost-effective
.
When developing and evaluating precision medicine, it is important to consider the new approach as complementary
to more traditional personalized medicine.

More trials are needed to increase understanding of this area, and such trials should expand the assessment to include non-glycaemic outcomes such as other cardiovascular risk factors and quality of life
.

References: 1.
Griffin S.
Diabetes precision medicine: plenty of potential, pitfalls and perils but not yet ready for prime time.
Diabetologia.
2022 Nov; 65(11):1913-1921.
doi: 10.
1007/s00125-022-05782-7.
Epub 2022 Aug 24.
PMID: 35999379;

2.
Pearson ER, Flechtner I, Njolstad PR, et al.
Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.
2 mutations.
N Engl J Med.
2006; 355(5):467–477.
doi: 10.
1056/NEJMoa061759.