Pancreatic Pathology Online

Pathology of Diabetes Mellitus

A chronic disorder of carbohydrate, fat and protein metabolism.

Dr Sampurna Roy MD                              July 2016

 

Ancient History of Diabetes Mellitus - 12 interesting facts which we should all remember about 'Honey or Sugar Urine'

Diabetes Mellitus is growing worldwide mainly due to the aging population, obesity and sendentary lifestyle.

Types of diabetes:

Type-I (Juvenile diabetes)-10 to 20%

Type-II (Adult onset)- 80 to 90%

Physiology of Insulin:

Insulin is synthesized & stored in the beta-cells of pancreatic islets.  Rise of blood glucose stimulates beta-cells for immediate release of insulin and also initiate synthesis of insulin.

Insulin is a major anabolic hormone, necessary for:

i) Trans-membrane transport of glucose and amino acids.

ii) Glycogen formation in the liver and skeletal muscles.

iii) Conversion of glucose to triglycerides.

iv) Nucleic acid synthesis and protein synthesis.

Main metabolic function of insulin is to increase the rate of glucose transport into the striated muscles, myocardial cells, fibroblasts and fat cells.

These tissues constitute two-thirds of the entire body weight.

Action of insulin is regulated by the  "receptors of insulin " (Tyrosine kinase), which is present in the tissue cells.

Initially "Glucose transport units" is translocated from Golgi apparatus to plasma membrane and facilitate cellular uptake of glucose.

Only feature of diabetes mellitus is the impaired glucose tolerance.

Glucose tolerance test:

In a normal person, ingestion of 75 Gms. of glucose after overnight fasting will raise the blood glucose, returning to normal within one hour. (maximum 140mg.%).

In a diabetic/potential diabetic, rise of blood glucose will be very high (more than 200 mg.%), and remain at that high level for several hours (2 hrs. or more).

This is due to the lack of insulin secretion by beta cells or lack of utilization of receptors in the target cells or both.

Pathogenesis:

 

Type-I :

This is due to severe or absolute lack of insulin caused by the reduction of beta-cell mass.

It develops in childhood and becomes severe at puberty.

Patient survives on the supply of insulin. Without insulin supply they develop keto-acidosis and coma.

Genetic factor, autoimmunity and immune mediated injury are implicated as the cause of beta-cell loss.

Type-II :

Two basic metabolic defects:

i) Primary factor is the impaired insulin release by beta-cells

ii) Debatable factor is the inability of the peripheral tissues to respond to insulin.

In addition to genetic factor following points are also considered in the pathogenesis of Type-II diabetes.

I. Obesity- 80 % of Type II diabetes are obese.  Weight loss and physical exercise reverse impaired glucose tolerence.

II. The protein 'Amylon' is co-secreted with insulin by the beta-cells, in response to ingestion of food. Amylon accumulates in the pancreatic sinusoids around beta-cells in close contact with cell membrane, and ultimately forms amyloid. Amyloid may contribute to beta-cells non-responsive to glucose.

 

                                                                                                                                      

Pathological changes in the Islets in two types of Diabetes:

Normal Islets of Langerhans

Type I Diabetes:

Leukocytic infiltration into the islet occurs at the time of onset of type 1 diabetes.

This lymphocytic insulitis does not affect all the islets at the same time, since a normal islet can be observed close to one involved with insulitis.

The lymphocytic infiltrate is limited to islets and is apparently induced by the autoimmune process.

This inflammatory response produces specific destruction of the B-cells either by the direct action of cytotoxic T- lymphocytes or by lymphokines released by this immune reaction or by a combination of these mechanisms. 

Interleukin-1 inhibits insulin release from isolated islets and with tumour necrosis factor and interferon-gamma.

The combined action of these lymphokines can result in destruction of B-cells.

Over a period of months and years there is a gradual complete elimination of the B-cells leaving A, D, F, and G cells within the islets.

In the era before insulin therapy,the persistent hyperglycemia in these patients caused degranulation of the unaffected B-cells early in the course of diabetes and subsequently the deposition of massive quantities of glycogen in these cells.

Initially this lesion was called 'hydropic degeneration of B-cells' since the cells appeared vacuolated and it was assumed that the vacuoles contained water.

The use of special stains demonstrated that the vacuoles actually contained glycogen.

The lesion rarely occurs now, since relatively few patients die in diabetic acidosis and severe hyperglycemia.

Type II Diabetes:

In type II diabetes the B-cell mass and the degree of B-cell granulation may be normal or moderately reduced. 

The lesion that is found in the islets of some of the type II diabetes is amylodosis of the islets.

By light microscopy, amyloid appears as an eosinophilic, amorphous material material deposited around the capillaries of the islets, compressing and displacing the islet cells.

By electron microscopy, the amyloid has a fibrillar appearance, and it is deposited between the two basement membranes separating the islet cells from the capillaries.

Previously, this change was called "hyalinization of the islets of Langerhans" and was one of the earlier morphologic findings observed in diabetic patients.

Amyloidosis does not involve all the islets within a single pancreas, but has a patchy distribution.

The lesion is not limited to diabetic patients.

It has been found in about 2% of nondiabetic persons over 40 years of age.

It is unlikely that this pathologic change has a primary role in the cause of type II diabetes, however, it may play a role in delaying the release of insulin from affected islets in these persons.

Long-term complications of diabetes mellitus (mostly after 10 to 15 years):

Visit: 'Sugary Urine' the subtle killer- Devastating Complications of Diabetes Mellitus

Diabetes mellitus causes long-term complications in blood vessels, kidneys, eyes and nerves leading to morbidity & mortality.

1. Arteries:  Atherosclerosis - (i) Myocardial infarct   (ii) Gangrene foot.

2. Basement membrane of small vessels:  Microangiopathy - cerebral infarct and hemorrhage.

3. Kidney: Diabetic nephropathy.

4. Retina: Retinopathy ; Cataract ; Glaucoma.

5. Nerves:  Diabetic neuropathy - Peripheral symmetric neuropathy of hands and feet. Autonomic neuropathy - disturbance of bladder and bowel functions.

Visit: Pancreatic Pathology Online

 

Further reading:

Anatomical study of peripheral neuropathies of diabetes mellitus.

Vascular changes in diabetes.

Functional microangiopathy in diabetes mellitus.

Diagnosis of diabatic retinopathy and its significance in diabetes.

Diabetes mellitus in the elderly: from the epidemiological challenge to a personalized approach.

Impaired angiogenesis and lymphangiogenesis in diabetes mellitus.

 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

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