Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective

Abstract

Diabetes mellitus is a complex metabolic disorder associated with an increased risk of microvascular and macrovascular disease; its main clinical characteristic is hyperglycaemia. The last century has been characterised by remarkable advances in our understanding of the mechanisms leading to hyperglycaemia. The central role of insulin in glucose metabolism regulation was clearly demonstrated during the early 1920s, when Banting, Best, Collip and Macleod successfully reduced blood glucose levels and glycosuria in a patient treated with a substance purified from bovine pancreata. Later, during the mid-1930s, clinical observations suggested a possible distinction between 'insulin-sensitive' and 'insulin-insensitive' diabetes. Only during the 1950s, when a reliable measure of circulating insulin was available, was it possible to translate these clinical observations into pathophysiological and biochemical differences, and the terms 'insulin-dependent' (indicating undetectable insulin levels) and 'non-insulin-dependent' (normal or high insulin levels) started to emerge. The next 30 years were characterised by pivotal progress in the field of immunology that were instrumental in demonstrating an immune-mediated loss of insulin-secreting β-cells in subjects with 'insulin-dependent' diabetes. At the same time, new experimental techniques allowing measurement of insulin 'impedance' showed a reduced peripheral effect of insulin in subjects with 'non-insulin-dependent' diabetes (insulin resistance). The difference between the two types of diabetes emerging from decades of observations and experiments was further formally recognised in 1979, when the definitions 'type I' and 'type II' diabetes were introduced to replace the former 'insulin-dependent' and 'non-insulin-dependent' terms. In the following years, many studies elucidated the natural history and temporal contribution of insulin resistance and β-cell insulin secretion in 'type II' diabetes. Furthermore, a central role for insulin resistance in the development of a cluster of cardiometabolic alterations (dyslipidaemia, inflammation, high blood pressure) was suggested. Possibly as a consequence of the secular changes in diabetes risk factors, in the last 10 years the limitation of a simple distinction between 'type I' and 'type II' diabetes has been increasingly recognised, with subjects showing the coexistence of insulin resistance and immune activation against β-cells. With the advancement of our cellular and molecular understanding of diabetes, a more pathophysiological classification that overcomes the historical and simple 'glucocentric' view could result in a better patient phenotyping and therapeutic approach.

Plants used to treat diabetes in Sri Lankan Siddha Medicine – An ethnopharmacological review of historical and modern sources

“…DM's symptoms are well known including hyperglycemia with a wide range of complications (Singh et al, 2014) including damage to the nervous system, blood vessels, eyes, gums and teeth, heart, kidneys, or feet and skin (Zaccardi et al, 2015). Three groups are distinguished: (1) Autoimmune T1DM or insulin dependent DM or juvenile DM (2) T2DM or noninsulin dependent DM or Maturity Onset DM and (3) Gestational DM.…”

Nurses' Knowledge of Hypoglycemia and Treatment in the Adult Hospitalized Patiend with Diabetes: A Quality Improvement Project

“…Type 1 diabetes is an autoimmune disorder characterized by the destruction of insulin-producing beta cells in the pancreas (Zaccardi, Webb, Yates, & Davies, 2015). The destruction of beta cells in the pancreas eventually leads to total insulin deficiency.…”

Can Avicenna Help Manage the Diabetes Epidemic in Central Asia?

“…Multiple factors are directly linked both to the onset of diabetes and its progression, and are targets for T2DM treatment and prevention. Recent progress in describing the molecular mechanisms of IR significantly improved our understanding of pathways of T2DM onset and progression [17].…”