Pathophysiology of Diabetes Mellitus

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Pathophysiologyof Diabetes Mellitus


The  pathophysiology of diabetes is related to the levels of insulin within the body, and the body’s ability to utilize insulin. There is a total lack of insulin in type 1 diabetes, while in type 2 diabetes, the peripheral tissues resist the effects of insulin. 

Normally, the pancreatic beta cells release insulin due to increased blood glucose concentrations. The brain in order for normal functions to occur continually requires glucose. 

Hypoglycemia, or low plasma glucose levels, is usually caused by drugs used in the treatment of diabetes, including insulin and oral antihyperglycemics.
The pathophysiology of diabetes involves plasm concentrations of glucose signaling the central nervous system to mobilize energy reserves. It is based on cerebral blood flow and tissue integrity, arterial plasma glucose, the speed that plasma glucose concentrations fall, and other available metabolic fuels. 

Low plasma glucose causes a surge in autonomic activity. Diagnosis of hypoglycemia requires verification of low plasma glucose levels. Immediate treatment is the intake of glucose. 

The responses to hypoglycemia include decreased insulin secretion, increased secretion of glucose counter-regulatory hormones such as glucagon and epinephrine, a greater sympathoadrenal response, related symptoms, and finally, cognitive dysfunction, seizures, or coma.
Late hypoglycemia of occult diabetes may develop in some patients with impaired glucose tolerance, or early type 1 or type 2 diabetes. After a high-carbohydrate meal, the patient experiences hypoglycemia.
Pathophysiology of Diabetes Mellitus


The epidemiology and pathophysiology of diabetes have been discussed in previous chapters, as were the major complications of retinopathyneuropathy, and nephropathy.

Similar mechanisms underlie complications stemming from the diabetic foot, including ulcerationgangreneischemia, and, ultimately, amputation. Although glycemic control is imperative in diabetes, it is not sufficient to eliminate complications of the diabetic foot. 

Furthermore, it is important for clinicians to be aware of the etiologic triad leading to diabetic foot complications (i.e., neuropathy, ischemia, and infection) and to recognize that these may occur in isolation but more frequently occur in combination with one another.

Neuropathy

The neuropathy stemming from diabetes mellitus has multiple manifestations within the diabetic foot because it encompasses sensory, motor, and autonomic fibers. Sensory neuropathy affects small-diameter pain and temperature fibers first, and susceptibility to injury is increased because these patients are less sensitive to pressure-related trauma and other minor skin injuriesMotor neuropathy affects the longer fibers that innervate the foot, including intrinsic foot muscles and leg muscles. 

Atrophy, or muscle wasting, in the intrinsic foot muscles allows the strong flexor muscles to draw up the toes in a “clawed” position, and new pressure points emerge at the tips of the toes and the prominent metatarsal heads. Limited joint mobility and rigidity from glycation of scleral proteins exacerbates the situation by further changing the normal weight distribution on the foot. 

Lastly, autonomic neuropathy causes the skin to become dry through loss of sweat and apocrine gland function. The resulting dry, scaly skin has a markedly increased susceptibility to skin breakdown and fissures, thus creating a portal of entry for bacteria. Additionally, diabetic patients can have a blunted neuroinflammatory response and thus are missing a crucial component of the body’s natural first-line defense against pathogens.

Infection

Diabetic patients typically have an altered response to infectious processes owing to defects in their host immune defense system. Moreover, wound healing is delayed in diabetic patients as a result of abnormal cellular and inflammatory pathways involving fibroblastsneutrophils, and advanced glycation end products (AGEs). 

Glycation is a nonenzymatic chemical reaction whereby sulfhydryl protein linkages are replaced by glucose, causing impairment in normal cellular and tissue functions. 

AGEs increase the stiffness of precapillary vessel walls and contribute to the development of diabetic microangiopathy. 

Additionally, the presence of neuropathy and ischemia can potentiate the infectious process. The loss of protective sensation from neuropathy leads to unrecognized injury and secondary infection. 
Ischemia results in poor healing, blunts the inflammatory response, and may lead to inadequate tissue levels of antimicrobial agents.

 
Ischemia

Much progress has been made in identifying the cause of ischemia in the lower extremities of diabetic patients, and results have challenged long-standing misconceptions in the literature and in the medical community at large. 

It is imperative that practitioners continue to reject the “small-vessel disease” theory related to occlusions of the microcirculation, as espoused by a single histologic study in 1959, and instead embrace the notion that ischemia results from both atherosclerotic macrovascular disease and microcirculatory dysfunction. Diabetic patients typically suffer from tibial and peroneal arterial disease with sparing of the foot arteries, especially the dorsalis pedis and its branches 
Research has shown that diabetes causes structural and functional changes within the arteriolar and capillary systems, notably thickening of the basement membrane. In spite of the thickened capillary basement membrane, there is no decrease in capillary luminal diameter. A thickened membrane impairs the migration of leukocytes and hampers the normal hyperemic or vasodilatory response to injury, thus simultaneously increasing the susceptibility to injury while blunting the typical manifestations of such an injury.

Overall, this dysfunction of the microcirculation in diabetic patients creates a functionally ischemic foot despite conditions that would otherwise allow normal blood flow in healthy patients.
Besides causing specific structural changes in the microcirculation, diabetes also causes a compromise in the overall biology of the foot. Diabetes causes an undesirable shift in the natural balance that exists between stress/ulceration and resistance to stress/ulceration. Thus, the diabetic foot is more prone to ulceration from the repetitive low-intensity stress of normal weight bearing. 

The presence of neuropathy may necessitate revascularization under conditions of perfusion that would not require revascularization in the absence of neuropathy and is often described as neuroischemia. Because of the compromise caused by this neuroischemia, the diabetic foot requires even more perfusion than usual to resist ulceration or respond appropriately to injury.

Pathophysiology of type 1 diabetes

In this condition the immune system attacks and destroys the insulin producing beta cells of the pancreas. There is beta cell deficiency leading to complete insulin deficiency. Thus is it termed an autoimmune disease where there are anti insulin or anti-islet cell antibodies present in blood. These cause lymphocytic infiltration and destruction of the pancreas islets. The destruction may take time but the onset of the disease is rapid and may occur over a few days to weeks.
There may be other autoimmune conditions associated with type 1 diabetes including vitiligo and hypothyroidism. Type 1 diabetes always requires insulin therapy, and will not respond to insulin-stimulating oral drugs.

 

Pathophysiology of type 2 diabetes

This condition is caused by a relative deficiency of insulin and not an absolute deficiency. This means that the body is unable to produce adequate insulin to meet the needs. There is Beta cell deficiency coupled with peripheral insulin resistance.
Peripheral insulin resistance means that although blood levels of insulin are high there is no hypoglycaemia or low blood sugar. This may be due to changes in the insulin receptors that bring about the actions of the insulin.
Obesity is the main cause of insulin resistance. In most cases over time the patients need to take insulin when oral drugs fail to stimulate adequate insulin release.
Pathophysiology of Diabetes Mellitus
Gestational diabetes is caused when there are excessive counter-insulin hormones of pregnancy. This leads to a state of insulin resistance and high blood sugar in the mother. There may be defective insulin receptors.
Pathophysiology behind symptoms and complications of diabetes
  • Polydipsia or increased thirst is due to high blood glucose that raises the osmolarity of blood and makes it more concentrated.
  • Polyuria or increased frequency of urination is due to excess fluid intake and glucose-induced urination.
  • Weight loss occurs due to loss of calories in urine.
  • Polyphagia or increased hunger due to loss or excess glucose in urine that leads the body to crave for more glucose.
  • Poor wound healing, gum and other infections due to increased blood glucose providing a good source of nutrition to microbes and due to a diminished immunity.
  • Heart disease – this occurs due to changes in the large blood vessels leading to coronary, cerebral, and peripheral artery diseases, atherosclerosis, dyslipidemia etc.
  • Eye damage – this is termed diabetic retinopathy and occurs due to damage of the fine blood vessels of the retina in the eye due to long term exposure to high blood sugar.
  • Kidney damage – similar damage to small and large blood vessels of the kidneys. Initially there is proteinuria or increased outflow of protein and may lead to end stage renal disease (ESRD).
  • Nerve damage – this can affect the arms and legs and is called stocking-glove numbness/tingling. It can also affect autonomic functions leading to impotence, erectile dysfunction, difficulty in digestion or gastroparesis etc.
  • Diabetic foot – this occurs due to peripheral nerve damage as well as blood vessel affliction due to long term diabetes. Little trauma, sores and blisters go unnoticed due to lack of sensation and peripheral vascular disease impairs healing and allows infection.
  • Diabetic Ketoacidosis is caused in type 1 diabetes where there is complete lack of insulin and reliance on fatty acids for energy. This uncontrolled lipid breakdown leads to formation of ketones and causes acidosis and ketonemia. This is a medical emergency.
  • Non-Ketotic Hyperosmolarity – this is caused due to extreme rise of blood sugar. This is seen in type 2 diabetics. There is just enough insulin to suppress ketone synthesis. The high blood sugar leads to excessive concentration or osmolarity of blood which in turn leads to dieresis and collapse of the blood vessels and cardiovascular shock. This is a medical emergency.

Frequently Asked Question


What is the pathophysiology of type 2 diabetes mellitus?
The pathophysiology of type 2 diabetes mellitus is characterized by peripheral insulin resistance, impaired regulation of hepatic glucose production, and diminishing β-cell function, finally causing toβ -cell collapse.
What is the pathophysiology of diabetes mellitus type 1?
Type 1 DM is the culmination of lymphocytic infiltration and degradation of insulin-secreting beta cells of the islets of Langerhans in the pancreas. As beta-cell mass decreases, insulin secretion reduces until the accessible insulin no longer is sufficient to keep normal blood sugar levels.

What is the basic underlying pathology of diabetes mellitus?
Diabetes mellitus is a syndrome with disordered metabolism and Improper hyperglycemia Because of either a Lack of insulin secretion or into Some combination of insulin resistance and Insufficient insulin secretion to compensate

What is a pathophysiology of a disease?
Pathophysiology is the analysis of these changes of mechanical, physiological, and biochemical functions, possibly caused by a disorder or leading to a strange syndrome. By: Haematology Case Studies with Blood Cell Morphology and Pathophysiology,

What is the pathophysiology of hyperglycemia?
Hyperglycemia results in a reduction in the body’s ability to use or store sugar after carbohydrates are consumed and from a rise in the generation of sugar from the liver during the periods between meals.


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