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Review
. 2025;25(1):8-36.
doi: 10.2174/0118715303282327240507184902.

Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes

Marco Chianelli  1 , Marina Armellini  2 , Maria Carpentieri  2 , Carmela Coccaro  3 , Carla Micaela Cuttica  4 , Alessandra Fusco  5 , Simonetta Marucci  6 , Anna Nelva  7 , Maurizio Nizzoli  8 , Maria Chantal Ponziani  9 , Marcello Sciaraffia  10 , Francesco Tassone  11 , Luca Busetto  12
Affiliations
Review

Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes

Marco Chianelli et al. Endocr Metab Immune Disord Drug Targets. 2025.

Abstract

Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.

Keywords: Obesity; diabetes prevention; fatty liver disease; lifestyle; nutrition; obesity comorbidities.; pharmacological therapy; prediabetes.

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Conflict of interest statement

The authors declare no conflict of interest, financial or otherwise.

Figures

Fig. (1)
Fig. (1)
Simplified scheme of progression towards diabetes in genetically predisposed subjects. Increased glucose availability consequent to reduced muscular uptake induces compensatory increase in insulin production and promote reduction of liver and beta cell insulin sensitivity; this further increases glucose levels and cause development of obesity, inflammation and post-prandial hyperglycaemia; excess insulin production, increased levels of glucose and of fatty acid determine, in predisposed individuals, oxidative stress of beta cells with loss of function and onset of diabetes.
Fig. (2)
Fig. (2)
Correlations between sleep quality and development of obesity/type 2 diabetes mellitus.
Fig. (3)
Fig. (3)
Ketogenic diet targets pathological mechanisms linking obesity and diabetes mellitus.
Fig. (4)
Fig. (4)
Spectrum of possible evolution of NAFLD.
See this image and copyright information in PMC

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