From diabetes care to metabolic care
Year: 2023
Type: article
Abstract: The management of excess blood glucose and its markers (e.g., glycated hemoglobin) has defined the specialty of diabetology. While hyperglycemia and its attendant consequences are clearly important targets, advances in our understanding of the underlying biological processes make it clear that this is a rather narrow view of a vast field. Glucose excess is only one of the phenotypic expressions of a plethora of linked metabolic perturbations that result from the interaction of genetic predisposition (and epigenetic imprinting) with environmental factors determined by modern lifestyle in urban and now rural settings as well. The major environmental influences include (a) departure from traditional food practices, including quantity, timeliness, preparations, and process, (b) reduction in activity and exercise, sedentary lifestyle, enhanced screen times, (c) change in exposure times to light and dark, and (d) reduction, lengthening, or alteration in sleep patterns. These changes result in caloric excess leading to excess adipose tissue, alteration in fuel partitioning resulting in loss of metabolic flexibility, mitochondrial dysfunction, and changes in the gut and other microbiomes.[1] Excessive fat storage in the adipose tissue leads to local insulin resistance and consequent attraction of helper T cells from the bone marrow, which undergoes a phenotypic switch into killer cells and to the formation of adipokines and chemokines. The fat cell undergoes inflammation and later, apoptosis;[2] fat consequently becomes ectopic to the liver, muscle, heart, and pancreas, among others. This is accompanied by systemic inflammation and insulin resistance. Beta-cell dysfunction and diabetes are one of the ways that this metabolic dissonance is expressed; others include chronic kidney disease, atherosclerotic heart disease, and metabolic dysfunction associated with steatotic liver disease (MASLD). The expression of one or other disease entity may be determined by genetic predisposition and/or other comorbid conditions. The degree of obesity (and amount and type of fat) is an important but not exclusive determinant of the expression and outcome of conditions. Obesity, for instance, is associated with increased progression of microvascular outcomes. Conversely, treatment of obesity through metabolic surgery is associated with improved microvascular[3] and cardiovascular outcomes.[4] In the DiRect study, 10 kg weight loss at 2 years was associated with 64% remission of diabetes.[5] The presence of one metabolic comorbidity/complication appears to influence the expression and outcome of others. Worsening estimated glomerular filtration rate and its rate of decline are associated with both an increase in major adverse cardiovascular event, as well as heart failure.[6] The presence of type 2 diabetes (T2DM) is associated with greater progression to cirrhosis as well as hepatocellular cancer in those with MASLD.[7] The management of one of these metabolic conditions is influenced by the coexistence of others. Not surprisingly, therefore, improvement in one condition through medical or surgical management is reflected by improvement in other conditions as well. The approach to metabolic management will encompass prevention at a primordial and primary level to reduce the impact of environmental influences—improving quality and regulating the quantity of food intake, along with improved activity, microbiota, exercise, and sleep. Therapies aimed at reducing weight and fat content are an important common denominator and find increasing resonance with various society recommendations.[8] Available technology with artificial intelligence, big data and machine learning have made digital therapeutics possible. Technology allows quantification of risk, lifestyle support and choice, and monitoring of multiple therapeutic targets. Many of the currently available and pipeline molecules that reduce hyperglycemia have additional salutary effects in reducing weight, improving cardiovascular, renal and liver outcomes (e.g., Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists). In addition, they address different facets of the pathology of metabolic dysfunction. The choice of therapy for one condition will require the consideration of their effects on the outcome of other metabolic conditions present. For example the presence of increased risk for heart failure in T2DM warrants consideration of an SGLT2 inhibitor which in addition improves renal outcomes and reduces weight.[9] A holistic approach to the care of these conditions is required. The prevention and care of the initial expression of these conditions are thus best done at a primary care level with additional training and upskilling; progression and further expression being managed by subspecialists. Training programs directed at producing a new generation of metabolic medicine specialists are probably not a long time away—existing postgraduate curricula must factor in the need for holistic metabolic care. Societies and educators must consider expanding the scope of interest and continuing education to transition from diabetes care to metabolic care. And the sooner this is done, the better for the overall health of our patients with various metabolic disorders, of which hyperglycemia is perhaps just the proverbial tip of the iceberg! Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Journal of Diabetology
Authors: Krishna G Seshadri, Viswanathan Mohan
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4385818062