Type 2 diabetes subtypes, aetiology and pathophysiology
Type 2 Diabetes Mellitus (T2DM) is a heterogeneous metabolic disorder characterized by chronic hyperglycemia resulting from a combination of progressive pancreatic beta-cell dysfunction and peripheral insulin resistance. Aetiology & Risk Factors The disease arises from a complex interaction between genetic susceptibility and environmental triggers, including physical inactivity, visceral obesity, poor diet, and aging. Pathophysiology Insulin resistance in muscle, liver, and adipose tissue impairs glucose uptake and suppresses hepatic glucose production. To compensate, pancreatic beta-cells overproduce insulin until progressive beta-cell exhaustion leads to severe insulin deficiency and sustained hyperglycemia. Subtypes (Novel Precision Clusters) Modern classification identifies distinct biological subtypes: Severe Insulin-Deficient Diabetes (SIDD): Marked by early beta-cell failure and high HbA1c. Severe Insulin-Resistant Diabetes (SIRD): Linked to high BMI, severe tissue insulin resistance, and elevated kidney disease risk. Mild Obesity-Related Diabetes (MOD): Associated with early-onset obesity. Mild Age-Related Diabetes (MARD): Occurs in older populations with a milder disease progression. Type 2 Diabetes Mellitus (T2DM) is a heterogeneous metabolic disorder characterized by chronic hyperglycemia resulting from a combination of progressive pancreatic beta-cell dysfunction and peripheral insulin resistance. Aetiology & Risk Factors The disease arises from a complex interaction between genetic susceptibility and environmental triggers, including physical inactivity, visceral obesity, poor diet, and aging. Pathophysiology Insulin resistance in muscle, liver, and adipose tissue impairs glucose uptake and suppresses hepatic glucose production. To compensate, pancreatic beta-cells overproduce insulin until progressive beta-cell exhaustion leads to severe insulin deficiency and sustained hyperglycemia. Subtypes (Novel Precision Clusters) Modern classification identifies distinct biological subtypes: Severe Insulin-Deficient Diabetes (SIDD): Marked by early beta-cell failure and high HbA1c. Severe Insulin-Resistant Diabetes (SIRD): Linked to high BMI, severe tissue insulin resistance, and elevated kidney disease risk. Mild Obesity-Related Diabetes (MOD): Associated with early-onset obesity. Mild Age-Related Diabetes (MARD): Occurs in older populations with a milder disease progression.
Weiterlesen → BeitragVisceral fat endocannabinoid overproduction is associated with insulin resistance and tissue dysfunction in mice and humans
Visceral fat endocannabinoid overproduction is associated with insulin resistance and tissue dysfunction in mice and humans Insulin resistance and severe metabolic dysregulation of adipocytes—rather than total fat mass alone—drive depot-specific endocannabinoid overproduction. Visceral adipose tissue acts as a primary source for elevated systemic endocannabinoid levels in type 2 diabetes, presenting a target for tissue-specific cannabinoid receptor type 1 ($\text{CB}_1$) signaling therapies to alleviate downstream metabolic complications. Insulin resistance and severe metabolic dysregulation of adipocytes—rather than total fat mass alone—drive depot-specific endocannabinoid overproduction. Visceral adipose tissue acts as a primary source for elevated systemic endocannabinoid levels in type 2 diabetes, presenting a target for tissue-specific cannabinoid receptor type 1 ($\text{CB}_1$) signaling therapies to alleviate downstream metabolic complications. Insulin resistance and severe metabolic dysregulation of adipocytes—rather than total fat mass alone—drive depot-specific endocannabinoid overproduction. Visceral adipose tissue acts as a primary source for elevated systemic endocannabinoid levels in type 2 diabetes, presenting a target for tissue-specific cannabinoid receptor type 1 ($\text{CB}_1$) signaling therapies to alleviate downstream metabolic complications. Insulin resistance and severe metabolic dysregulation of adipocytes—rather than total fat mass alone—drive depot-specific endocannabinoid overproduction. Visceral adipose tissue acts as a primary source for elevated systemic endocannabinoid levels in type 2 diabetes, presenting a target for tissue-specific cannabinoid receptor type 1 ($\text{CB}_1$) signaling therapies to alleviate downstream metabolic complications. Insulin resistance and severe metabolic dysregulation of adipocytes—rather than total fat mass alone—drive depot-specific endocannabinoid overproduction. Visceral adipose tissue acts as a primary source for elevated systemic endocannabinoid levels in type 2 diabetes, presenting a target for tissue-specific cannabinoid receptor type 1 ($\text{CB}_1$) signaling therapies to alleviate downstream metabolic complications. Insulin resistance and severe metabolic dysregulation of adipocytes—rather than total fat mass alone—drive depot-specific endocannabinoid overproduction. Visceral adipose tissue acts as a primary source for elevated systemic endocannabinoid levels in type 2 diabetes, presenting a target for tissue-specific cannabinoid receptor type 1 ($\text{CB}_1$) signaling therapies to alleviate downstream metabolic complications.
Weiterlesen → BeitragDeuterium metabolic imaging reveals greater liver fat contribution from lipogenesis in South Asian men than European men: a potential mechanism underlying elevated type 2 diabetes risk
Aims/hypothesis South Asian individuals are up to six times more likely to develop type 2 diabetes than individuals from other ethnic groups, often at a younger age and lower BMI. It has been shown that liver fat accumulates more readily in South Asian individuals, and this is thought to be a key driving factor contributing to the insulin resistance and diabetes in this population. However, the mechanisms underlying this phenomenon remain unclear. Understanding the role of de novo lipogenesis (DNL) in liver fat accumulation has been hampered by a lack of non-invasive techniques to quantify DNL-derived liver fat. We developed a method to quantify DNL-derived liver fat and used it in a proof-of-concept case–control study, hypothesising that there would be greater liver fat contribution from DNL in South Asian individuals than in European individuals. Methods A total of seven South Asian and six European participants, matched for age and BMI, underwent deuterium magnetic resonance scans at baseline and after 5 days of 2H water enrichment, from which the fractional and absolute amounts of liver fat from DNL (DNLMR) were calculated. Proton magnetic resonance spectroscopy (1H-MRS) and MRI were used to determine lipid quantity and composition.
Weiterlesen →Kein Beitrag passt zur gewählten Kategorie oder Suche.