Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes

Abstract

Since early times, being overweight and obesity have been associated with impaired glucose metabolism and type 2 diabetes (T2D). Similarly, a less frequent adult-onset diabetes in low body mass index (BMI) people has been known for many decades. This form is mainly found in developing countries, whereby the largest increase in diabetes incidence is expected in coming years. The number of non-obese patients with T2D is also on the rise among non-white ethnic minorities living in high-income Western countries due to growing migratory flows. A great deal of energy has been spent on understanding the mechanisms that bind obesity to T2D. Conversely, the pathophysiologic features and factors driving the risk of T2D development in non-obese people are still much debated. To reduce the global burden of diabetes, we need to understand why not all obese people develop T2D and not all those with T2D are obese. Moreover, through both an effective prevention and the implementation of an individualized clinical management in all people with diabetes, it is hoped that this will help to reduce this global burden. The purpose of this review is to take stock of current knowledge about the pathophysiology of diabetes not associated to obesity and to highlight which aspects are worthy of future studies.

Etiologies underlying subtypes of long-standing type 2 diabetes

“…The patients were mostly lean, had early onset disease, mild/moderate β-cell dysfunction, and mild insulin resistance. This subtype of T2D has been previously identified in non-Caucasian ethnic groups in developing countries [ 35 – 37 ]. It is not surprising, therefore, that this cluster was identified among the Emiratis.…”

Insulin resistance and secretion change after 3 years follow-up and the risk for developing diabetes in non-diabetic adults

“…be partly due to age-related decline in β-cell insulin secretion, a high prevalence of latent autoimmune adult diabetes in the Chinese population, and a relatively low degree of insulin resistance in slender Chinese [12][13][14][15]. But, no conclusion might be made whether degeneration of insulin secretion with aging may explain the increased risk of glucose metabolism disorders.…”

The Anti-Diabetic Potential of Baicalin: Evidence from Rodent Studies

“…In this case, patients must be treated with the exogenous hormone [ 18 , 19 , 22 ]. Type 2 diabetes is often associated with low physical activity, excessive energy intake in a diet, and the resulting overweight or obesity [ 18 , 19 , 20 , 24 , 25 , 26 ]. However, in some populations, type 2 diabetes develops despite normal body mass [ 26 ].…”

“…Type 2 diabetes is often associated with low physical activity, excessive energy intake in a diet, and the resulting overweight or obesity [ 18 , 19 , 20 , 24 , 25 , 26 ]. However, in some populations, type 2 diabetes develops despite normal body mass [ 26 ]. Irrespective of body mass, inflammatory processes and accompanying oxidative stress have been largely implicated in the pathogenesis and progression of type 2 diabetes.…”