diabetes

• In 2014, about 422 million people had DM.
• 463 million people had DM in 2019.
• 8.5% of adults ≥18 years had DM in 2019.
• According to Diabetes UK, 4.3 million people had DM in 2023.
• 8% of people with DM had Type 1 DM.
• 90% of people with DM had Type 2 DM.
• 2% of people with DM had other types of DM.
• 2.4 million people were at risk of having DM in 2019.
• 850,000 people were undiagnosed with DM in 2019.
• Blood glucose regulation involves the absorptive and post-absorptive state.
• In the absorptive state, blood glucose levels increase 3-4 hours after a meal due to the uptake of glucose by cells as the primary energy source.
• In the post-absorptive state, blood glucose levels decrease as glycolysis leading to energy production and the storage of excess glucose.
• Diabetes mellitus (DM) is characterised by high blood glucose levels due to insulin deficiency or insulin resistance.
• The two main groups of DM are primary (idiopathic) and secondary types of diabetes mellitus.
• Primary DM includes Type 1 Diabetes mellitus (T1DM), Juvenile-onset DM, and Latent autoimmune diabetes in adults (LADA).
• Secondary DM includes Pancreatic diabetes (type 3c), Abnormal concentrations of antagonistic hormones, and Iatrogenic causes.
• T1DM is characterised by insulin deficiency due to beta cell destruction, initial increase in insulin secretion followed by a decline, and is immune mediated, with onset before 15 years of age and less frequent occurrence of 10% of all diagnosed cases.
• T1DM is also characterised by the presence of at least 25 autoantibodies, with 4 autoantibodies of clinical importance: Insulin antibodies (IAA), Glutamic acid decarboxylase (GAD) antibodies (GADA), IA2(tyrosine phosphatase) antibodies, and Islet cell antibodies (ICA).
• T1DM can be triggered by infections and is characterised by progressive loss of insulin production due to autoimmune destruction of pancreatic beta cells.
• Underlying causes of T1DM include failure to delete autoreactive cells and can be triggered by infections.
• Autoantibodies serve as diagnostic markers but are not pathogenic in T1DM.
• B cells function as Antigen Presenting Cells in the pathogenesis of T1DM.
• Type-2 Diabetes mellitus (T2DM) is characterised by high blood glucose levels due to insulin resistance.
• T2DM is characterised by the presence of two main groups: primary (idiopathic) and secondary types of diabetes mellitus.
• Glucose-dependent insulinotropic peptide secretion is stimulated by glucose in the gut.
• Insulin has effects on metabolism including increased uptake of blood glucose by cells, increased glycogenesis, inhibition of glycogenolysis, inhibition of gluconeogenesis, uptake of blood fatty acids, and inhibition of lipolysis.
• Feedback control of glucagon secretion in the opposite direction to insulin.
• Insulin is a small protein composed of 51 amino acids (5808kDa).
• Insulin has a primary control via a direct negative-feedback loop between blood glucose and the pancreatic b cells.
• GLUT-4 expression on the plasma membrane is insulin-dependent and insulin receptor signals trigger GLUT-4-containing vesicles to fuse with the plasma membrane.
• Laboratory Diagnosis of Diabetes mellitus involves blood glucose levels.
• Glucose conversion into triglycerides occurs if glycogen capacity is reached.
• The liver plays a key role in maintaining blood glucose levels by storing excess glucose as glycogen and releasing glucose into the blood as normal levels drop.
• Incretins increase Ca2+ levels in beta cells resulting in insulin secretion.
• Glucose stimulation of insulin secretion results in rapid phosphorylation, G-6-P oxidation, and exocytosis of secretory granules containing insulin.
• Insulin is composed of A (20aa) and B (31aa) chains.
• The insulin gene (INS) is located on chromosome 11 in humans.
• Insulin mRNA encodes the single chain precursor protein – preproinsulin.
• Parasympathetic nervous stimulation by vagus nerve increases Ca2+ via IP3 signaling pathway.
• A rise in blood glucose levels stimulates secretion of insulin.