Diabetes mellitus is a metabolic issue where the body's ability to use glucose, fat and protein is upset because of disability in insulin discharge or potentially insulin opposition prompting persistent hyperglycaemia.
Thusly, having a comprehension of the fundamental pathophysiology and the intense as well as long haul complications of diabetes will empower the improvement of methodologies for enhancing the condition.
People might be delegated having pre-diabetes or diabetes dependent on their fasting blood glucose as well as postprandial blood glucose.
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| How diabetes happens |
On the other hand, disabled glucose resilience (IGT) is in the scope of >7.8
mmol/L to <11.1 mmol/L following a 2 hour oral glucose resistance test and
both IFG and IGT characterize the degree of glucose dysregulation between the
scope of normoglycaemia and type 2 diabetes.
The indicative measures for patients with diabetes
The indicative measures for patients with
diabetes are fasting plasma glucose ≥7.0 mmol/L and oral glucose resistance
Test (OGTT) ≥11.1 mmols/L. adrenaline response.
On the other hand, diabetic
ketoacidosis (DKA) is characterized by hyperglycaemia, ketosis and metabolic
acidosis. It results from absolute or relative insulin deficiency leading to
glucose dysregulation, the release of counter regulatory hormones including
cathecholamines, glucagon and cortisol.
Although lipolysis is a normal
biochemical process, it becomes unregulated in DKA and leads to the formation
of serum free fatty acids, which are used for the production of large
quantities of ketone bodies (acetoacetate, β-hydroxybutyrate (β-OHB), and
acetone), and consequently, metabolic acidosis.
While DKA may become evident within hours of onset, the commencement of Hyperosmolar Hyperglycaemic State (HHS) may present in days and as a result there is increased risk of dehydration and extreme metabolic disturbance.
5 Therefore in patients with HHS, there is usually high
osmolality (often ≥320 mOsmol/Kg); high blood glucose level (usually ≥30
mmol/L) and severe dehydration.
complications of diabetes
The microvascular complications of diabetes often have long-term impact. There is increasing evidence that hyperglycaemia may be responsible for the range of pathological changes that result in diabetic complications following prolonged exposure to high glucose levels.
Firstly, glucose is the primary source of energy production through oxidative phosphorylations and hyperglycaemia has a major impact on metabolic pathways which are related to cellular energy production especially in the mitochondria.
Most cells have the capacity to enhance glucose transport across
the plasma membrane into the cytosol to maintain glucose homeostasis in the
presence of hyperglycaemia.
However, some cells such as capillary endothelial cells in the retina, mesangial cells in renal glomeruli and neuronal cells in the peripheral nerves are not able to adapt and promote glucose transport significantly to prevent intercellular changes in glucose concentration.
3 Therefore, chronic tissue damage may be present in patients with diabetes and this is generally related to the severity and duration of hyperglycaemia. According to Tagulchi and Brownlee, 6 most of the effect of chronic diabetes relates to the microcirculation. With the long standing disease,
there is a progressive narrowing and subsequent blockage of vascular
lumina, resulting in poor perfusion, ischaemia and dysfunction of the tissues
that are affected.
The four possible mechanisms of microvascular complications may be based on hyperglycaemia induced biochemical changes and includes; increased flux of glucose and other sugars through the polyol pathway; formation of advanced glycation end- products (AGEs);
activation of protein kinase C (PKC) isoforms and increased flux through the hexosamine pathway . The polyol pathway is normally inactive, but may become active when intracellular glucose levels rise.
The impact of increased glucose
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The impact of increased glucose flux via the polyol pathway includes the production of powerful glycating sugars (methylglyoxal, acetol and triose phosphates), enhanced oxidative damage and Protein Kinase C (PKC) activation.
In this pathway, aldose reductase reduces glucose to its sugar alcohol, sorbitol. Aldose reductase is found in tissues such as nerves, the retina, the glomeruli and the blood vessel walls where glucose uptake is independent of GLUT 4 and insulin.
In addition, sorbitol is subsequently oxidised to fructose which eventually contributes to the mitochondrial respiratory chain. Sorbitol does not diffuse easily across the cell membranes and damage may occur because of sorbitol induced osmotic stress.
On the other hand, AGEs are formed by the reaction of glucose and other glycating compounds such as methylglyoxal with proteins.
AGEs may cause damage to cells through changing of cellular protein function by cross-linking extracellular matrix molecules such as collagen and laminin, which in the blood vessels increases wall thickness and permeability, and decrease elasticity 3,7 .
The binding of AGEs to its receptors leads to the generation of reactive oxygen species and increased vascular permeability. Protein kinase C (PKC) is an enzyme that phosphorylates a large number of proteins and exists in several isoforms.
It is
activated by diacylglycerol which is stimulated by hyperglycaemia. Excessive
activation of PKC is a further mechanism by which glucose may induce tissue
damage in organs that are prone to complications.
The over production of PKC and Diabetes
The over production of PKC has been implicated in increased vascular permeability, blood flow changes and increased basement membrane synthesis.
With respect to the Hexosamine pathway, this occurs when intracellular glucose is high. Then the normal glucose-6- phosphate metabolic cascade is disrupted and a series of moieties are produced that bind to transcription factors and increase the synthesis of some proteins.
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Despite the challenges of acute and/or
long term complications of diabetes, these can be prevented and their
progression can be delayed through tight control of blood glucose and reduction
of other risk factors of diabetes.
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