The growing range of complications of diabetes mellitus Trends in Endocrinology & Metabolism

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Highlights

The prevalence of 'emerging complications' of type 2 diabetes mellitus (T2DM), such as liver disease, dementia, cancer, sarcopenia, and frailty, is rising.

A common pathophysiological characteristic in T2DM is the presence of insulin resistance and chronic low-grade inflammation which can damage the liver, brain, and muscles, and increase the risk of some cancers.

Recently, new drug treatments have targeted the prevention and management of liver disease in T2DM with very promising results. Specific treatments for the other emerging complications of T2DM are not yet available, but drugs that address inflammation and insulin resistance are currently being studied in this context.

Abstract

REVIEW ∙ Online now, January 03, 2025

The growing range of complications of diabetes mellitus

Peter S. Hamblin  ∙ Anthony W. Russell ∙ Stella Talic ∙ Sophia Zoungas Affiliations & Notes^ Article Info^

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With the rising prevalence of type 2 diabetes mellitus (T2DM) and obesity, several previously under-recognised complications associated with T2DM are becoming more evident. The most common of these emerging complications are metabolic dysfunction-associated steatotic liver disease (MASLD), cancer, dementia, sarcopenia, and frailty, as well as other conditions involving the lung, heart, and intestinal tract. Likely causative factors are chronic inflammation and insulin resistance, whereas blood glucose levels appear to play a lesser role. We discuss these

complications and the new approaches being developed to prevent and manage them, especially incretin-based therapies. We argue that these new interventions may work in a complementary way to other proven cardiorenal protective therapies to reduce the burden of T2DM

complications.

Keywords

diabetes ∙ liver ∙ dementia ∙ sarcopenia ∙ frailty ∙ cancer

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Glossary

Advanced glycation end-products

chemically diverse products resulting from non-enzymatic reactions between reducing sugars and proteins, lipids, and nucleic acids. Accumulation of these products promotes oxidative stress and inflammation.

Amyloid

proteins misfolded into a cross-β-sheet structure which can bind dyes such as Congo red.

Synaptic function may be impaired by amyloid accumulation and chronic neurodegeneration, leading to cognitive impairment and dementia. Amyloid is seen in Alzheimer's disease, but may occur in other pathological conditions; amyloid may also be a feature of normal ageing.

Fibrosis 4 (FIB-4) score

a non-invasive scoring system using four parameters: age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet count to provide an estimate of the likelihood of liver fibrosis.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)

GLP-1 is an incretin hormone which potentiates glucose-stimulated insulin secretion. GLP-1 RAs were initially developed as glucose-lowering drugs and are now also used for weight loss.

Glucose-dependent insulinotropic polypeptide (GIP)

an incretin hormone which potentiates glucose-stimulated insulin secretion.

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Haemoglobin A1c (HbA1c)

also known as glycated haemoglobin, HbA1c generally reflects the average blood glucose concentration over the preceding 3 months. It is a measure of diabetes control and can also be used to diagnose new diabetes.

Hepatic steatosis

excessive triglyceride concentration in hepatocytes.

Hepatokines

proteins secreted by the liver that act in an endocrine or paracrine manner.

Incretins

hormones secreted by intestinal cells in response to glucose and fat which stimulate pancreatic insulin secretion in a glucose-dependent manner. Several drugs based on the chemical structure of incretins have been developed and are very effective in lowering blood glucose levels in type 2 diabetes (T2DM) and in promoting weight loss for people with and without T2DM.

Metabolic dysfunction-associated steatotic liver disease (MASLD)

previously known as non-alcoholic fatty liver disease (NAFLD), MASLD ranges from excessive triglyceride accumulation in hepatocytes to fibrosis, cirrhosis, and liver failure.

Tau proteins

proteins which have a primary role in maintaining the stability of axonal microtubules. When hyperphosphorylated, insoluble aggregates may form (called neurofibrillary tangles). These are seen in Alzheimer's disease.

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The growing range of complications of diabetes mellitus Trends in Endocrinology & Metabolism

Highlights

Abstract

The growing range of complications of diabetes mellitus

Get Access 





Keywords

Get full text access

Get Access

References

Glossary

Advanced glycation end-products

Amyloid

Fibrosis 4 (FIB-4) score

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)

Glucose-dependent insulinotropic polypeptide (GIP)

Haemoglobin A1c (HbA1c)

Hepatic steatosis

Hepatokines

Incretins

Metabolic dysfunction-associated steatotic liver disease (MASLD)

Tau proteins

Article metrics

3

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