Diabetes Mellitus – History, Causes,Types and Treatment

Diabetes Mellitus – History, Causes,Types and Treatment

Diabetes Mellitus –Several hematological abnormalities have been defined in patients with diabetes mellitus, despite the lack of classic hematology pathologic findings in this condition (Narayan KM, et al, 2003). Studies of the erythrocyte and the formation of hemoglobin A1C have provided a means of documenting glycemia and a model reaction for diabetic sequelae. Oxygen affinity has been noted to be abnormal in the diabetic erythrocyte concomitant with decreased concentration of inorganic phosphorus. Red cell membrane viscosity has also been documented to be increased in the hyperglycemic subject (Warren S, et al, 1992). Abnormalities in the polymorphonuclear leukocyte have been described involving the properties of phagocytosis and killing. Lymphocyte has also been shown to have abnormal metabolic properties in diabetic patients.

 

Introduction

Diabetes mellitus is a complex, chronic disease. It is classed as a metabolic disorder in which the body does not produce enough or properly respond to insulin a hormone produced in the pancreas (IDF Atlas 2006). In 2030, the world health organization (WHO) predicts 366 million people with diabetes (5% of the world’s population) (McCarty D et al,, 1997).

The cause of diabetes depends on the type. The type 2 diabetes is primarily lifestyle factors and genetics (Riserusu et al, 2009) and type I diabetes is of immune-mediated nature where beta cell loss is a T-cell mediated anti immune attack. (Rother KI, 2007).

Symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). (Cook D W, et al, 2008). Symptoms may develop rapidly (weeks or months) in type I diabetes while in type 2 diabetes they usually develop much more slowly and may be subtle or absent. Hyperglycemia is a common effect of uncontrolled diabetes and overtime leads to serious damage to many of the body’s system especially the nerves and blood vessels (IDF, 2008).

Hematological parameter of diabetic mellitus patients varies when compared to the normal non-diabetic reference values. The parameters are gotten from a series of tests called complete blood count. (Ochei, A.2000). Some of the parameters used for diabetic and the normal diabetic values are:

1.)  White blood cell Count (x109) L: for diabetic mellitus patients 0.7-1.2, 4.5-11 for normal values.

2.)  RBC (x1012/L):  4.0-4.6 for diabetic mellitus patients.

4.9-5.9 for normal values.

3.) Hemoglobin g/L: 138-136 for diabetes

130-150 for normal values.

4.) Platelets x 109/L:   165-326 for diabetic patients

150-400 for normal values.

Some of the parameters also change according to the mode of treatments. This can be diet, insulin therapy and oral medication.

Conclusion:

The findings are compatible with the hypothesis that diabetic patients present normal responses hematological variations. These findings also suggest that the treatment of diabetes should target maintaining optimal parameters in order to lower cardiovascular risk.

        History of Diabetes

The term diabetes was coined from Aretaeus of cappadocia. It was derived from Greek verb diabainein. The verb diabainein means ‘to stride, walk or stand with legs asunder’. So diabetes means “one that straddles” or a “compass siphon”. The sense siphon gave rise to the use of diabetes as the name for a disease involving the discharge of excessive amount of urine.

Diabetes was first recorded in English in the form diabetes in a medical text written around 1425. In 1675, Thomas Willis added the world mellitus from the Latin meaning “honey” a reference to the sweet taste of the urine. This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians and Persians. In 1776, Mathew Bobson confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes (Dobson, M, 1776). Diabetes Mellitus appears to have been a death sentence in the ancient era. Hypocrites makes no mention of it, which may indicate that he felt the disease was incurable.

Aretaeus did attempt to treat it but could not give a good prognosis, he commented that “life with diabetes in short disgusting and painful. (Victor L, 1993). Sushita (6th century, BCE) identified diabetes and classified it as Medhumeha (Dwivedi et al, 2007). He further identified it with obesity and sedentary lifestyle, advising exercise to help “cure it”. (Dwivedi et al, 2007). The ancient Indians tasted for diabetes by observing whether ants were attracted to a person’s urine and called the ailment “sweet urine disease”.

Aricenna in 1980-1037 provided a detailed account on diabetes mellitus. He also recognized primary and secondary diabetes. Avicenna also described diabetes insipidus very precisely for the first time, though it was Johann Peter Frank (1745-1821) who first differentiated between diabetes mellitus and diabetes insipidus (Nabipour, 2003). The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph Von merring and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly after wards. (Von Mehring J. et al, 1890).

In 1910, Sir Edward Albert Sharpey Schafer suggested that people with diabetes were deficient in a single chemical that was produced by the pancreas he called the substance insulin. The endocrine role of the pancreas in metabolism and indeed the existence of insulin was not further clarified until 1921 when Sir Fredrick Grant Banting and Charles Herbert. Best repeated the work of Von merring and Minkowski and went further to demonstrate they could reserve induced diabetes in dogs by giving them an extract from the pancreatic islets of langerhans of healthy dogs (Banting FG, et al, 1991).

The distinction between what is now known as type I diabetes and type 2 diabetes was first clearly made by sir Harold Pervical (Harry) Himsworth and published in January 1936 (Hinsworth, 1936) despite the availability of treatment, diabetes has remained a major cause of death.

Classification of Diabetes Mellitus

Several attempts have been made to clarify diabetes mellitus and various classification symptoms have existed. However, the most widely accepted is the world health Organization (WHO) classification (WHO, 1980) which was originally proposed by Irvine (Irvine W.S. 1977) and later adopted by the national diabetes data group and was later updated in 1985. (WHO, 1985).

Diabetes Mellitus is either,

  1. Primary Idiopathic
  2. Secondary to other pathology (Pre diabetes) (Handelsman et al, 2009).

The primary idiopathic is either type I (Insulin dependent diabetes mellitus (IDDM) or type 2 (non-insulin dependent diabetes mellitus (NIDDM).

The three major types of diabetes are

A) Type1 diabetes (known as insulin-dependent or juvenile diabetes):

Is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas (Wilds et al, 2004). The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger) and weight loss (Lawrence J. M. et al, 2008).

It can also be called insulinopenic diabetes mellitus and the destruction of the pancreatic islet beta cell and it is characterized by absolute insulin deficiency (WHO, 1999).  This type of diabetes also known as juvenile-onset diabetes accounts for 10-50% of all people with the disease (WHO, 1992).

Most people who developed type I are other wise healthy. Although, the cause of type I diabetes still not fully understood it is believed to be immunological origin. There is a growing body of evidence that diet may play a role in the development of type I diabetes through influencing gut flora, intestinal permeability and immune function in the gut, wheat particular has been shown to have a connection of the development of type I diabetes, although the relationship is poorly understood (Rother K.I., 2007). Type I can be distinguished from type2 diabetes via a C-peptide assay, which measures endogenous insulin production.

A study showed that for identical twins, when one twin has type I diabetes, the other twin only that type 1, 30%-50% of the time. Despite having the exact same genome, one twin had the disease where the other did not, this suggests that environmental factors, in addition to genetic factors, can influence disease prevalence (Handelsman et al, 2009).

B) Type2 diabetes (Non-insulin dependent diabetes):

Type2 diabetes is the most common form of diabetes affecting 85-90% of all people with the disease. This type of diabetes is also known as late-onset diabetes and it’s characterized by insulin resistance and relative insulin deficiency.

It is also called insulinoplethoric diabetes mellitus which is caused by relative lack of insulin due to excess antagonizing hormones or other insulin inhibiting factors (WHO, 1992) the disease is strongly genetic in origin but life style factors such as excess weight, in activity, high blood pressure and poor diet are major risk factors for its, development. These groups of patients are judged clinically not to be in urgent need to insulin to preserve life (WHO, 1992).

Symptoms may not show for many years by the time they appear, significant problems may have developed. People with type 2 diabetes are twice as likely to suffer cardiovascular disease. Generally the patients do not produce enough insulin or the insulin is not working properly. It constitutes about 85% of all cases in developed countries. (Glattar, 1988) and the majority of cases is developing countries (Dowse and Zimmet, 1989).

C. Gestational Diabetes Mellitus (GDM):

It is first diagnosed during pregnancy through an oral glucose tolerance test. Between 5.5 and 8.8% of pregnant women develop gestational diabetes mellitus in Australia. Family of diabetes increasing maternal age, obesity and member of community or ethnic group with a high risk of developing type2 diabetes are among the people at risk for gestational diabetes. It is diabetes that develops only when you are pregnant (WHO, 1992).

Other Types

Pre-diabetes indicates a condition that occurs when a person’s blood glucose level is higher than normal but not high enough for a diagnosis of type 2 diabetes. Many people destined to develop type2 diabetes spend many years in state of pre-diabetes which has been termed “America’s largest health care epidemic. (Handelsman et al, 2009).

Causes of Diabetes

The cause of diabetes depends on the type. Type 2 diabetes is due to primarily to life style factors and genetics. (Reserusu, et al, 2009).

Type I diabetes is also partly inherited and then triggered by certain infections, with some evidence pointing at coxsackie B4 virus.

However, even in those who are inherited the susceptibility. Type 1 diabetes mellitus seems to require an environmental trigger. The majority of type I diabetes is of the immune-mediated nature, where beta cells loss is a T-cell mediated autoimmune attack. (Rother KI, 2007).

The Risk Factors (Those at Risk)

The risk is double. The risk of vascular problem including cardiovascular disease (Chang AM, 2003). According to one study, women with high blood pressure (hypertension) were three times more likely to develop type 2 diabetes as compared with women with optimal BP after adjusting for various factors such as age, ethnicity, smoking, alcohol intake, body mass index (BMI), exercise, family history of diabetes etc. (Top News, 2009).

Except in the case of type I diabetes, which always requires insulin replacement, the way type diabetes is managed may change with age. Insulin production decreases because of age-related impairment of pancreatic beta cells. Additionally, insulin resistance increases because of the loss of lean tissues and the accumulation of fat, particularly intra-abdominal fat, and the decreased tissue sensitivity to insulin. Glucose tolerance progressively declines with age, leading to a high prevalence of type2 diabetes and post challenge hyperglycemia the older population (Harris M.I. et al,, 1998).

Age-related glucose intolerance in human is often accompanied by insulin resistance, but circulatory insulin levels are similar to those of younger people (Chang A.M. et al, 2003). Treatment goals for older patients with diabetes vary with the individual, and take into account health status, as well as life expectancy, level of dependence, and willingness to adhere to a treatment regimen.(Diabetes and aging, 2002).

Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.

Symptoms of Diabetes

Symptoms of diabetes are polyuria (frequent urination), polydipsia(increased thirst) and polyphagia (increased hunger). (Cooke D.W. et al, 2008).

Symptoms may develop rapidly (weeks or months) in type I diabetes while in type2 diabetes they usually develop much more slowly and my be subtle or absent. Prolonged high blood glucose causes glucose absorption, which leads to changes in the shape of the lenses of the eyes, resulting in vision changes; sustained sensible glucose control usually returns the lens to its original shape.

Blurred vision is a common complacent leading to a diabetes diagnosis. Type I always is suspected in cases of rapid vision change, whereas with type 2 changes is generally more gradual but should still be suspected weight gain and initially is also experienced in the people.

Because of the presence of more sugar in the body, the ability of the body to recover from infection is affected hence there is more skin or yeast infection. Cuts and bruises do not heal properly or quickly because the glucose in the body is high and the healing rate is undermined. A number of skin rashes can occur in diabetes they are collectively known as diabetic dermadromes. Numbness and tingling in the feet or hands occurs as a result of too much sugar in the body and the nerves and tiny blood vessels that feeds the nerves becomes damaged.

Diagnosis of Diabetes Mellitus

The screening tests for diabetes including urine and blood glucose examination (Ochei A, 2000). The urine tests finds out whether excess glucose is present and blood test measures blood glucose levels and can confirm if the cause of the symptoms observed is diabetic.

2006 WHO DIABETES CRITERIA.

Conditions 2 hour glucose

Mmol/L(mg/dl)

Fasting glucose

Mmol/(mg/dl)

Normal <7.8(140) <6.1 (<110)
Impaired fasting glycaemia < 7.8 (140) ≥ 6.1 (≥ 110) and < 7.0 (<126)
Impaired glucose tolerance ≥ 7.8 9 (≥140) < 7.0 (<126)
Diabetes Mellitus ≥ 11.1 (≥ 200) ≥ 7.0 (≥ 126).

 

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia and is diagnosed by demonstrating anyone of the following: (WHO, 1999).

v Fasting plasma glucose level ≥ 7.0mmol/L(126mg/dl)

v Plasma glucose ≥ 11.1mmol/l (200mg/dl) two hours after a 75g oral glucose load as in a glucose tolerance test.

v Symptoms of hyperglycemia and casual plasma glucose ≥ 11.1mmol/L (200mg/dl).

A C-peptide assay is a test used to distinguish type I from type 2. It measures endogenous insulin production.

Treatment of Diabetes Mellitus

Diabetes mellitus is a chronic disease which is difficult to cure. Management concentrates on keeping blood sugar level as close to normal as possible without presenting undue patient danger. This can usually be with close dietary management, exercise, and use of appropriate medications (insulin only in the case of type I diabetes mellitus. Oral medication may be used in the case of type2 diabetes as well as insulin).

Patient education, understanding and participation is vital since the complications of diabetes are far less common and less severe in people who have well managed blood sugar levels. (Nathan D.M. et al, 2005).

Wider health problems may accelerate the deleterious effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure and lack of regular exercise. Type I diabetes is fatal unless treated with insulin. Injection is the most common method of administering insulin, insulin pumps and inhaled insulin have been available at various times.

Pancreas transplants have been used to treat type I diabetes. However this procedure is currently still at the experimental trial stage (Rother Kl, 2007). Some of the medications used for treating type 2 diabetes include:

  1. Sulfonylurea drugs
  2. Meglitinides
  3. Biguanides
  4. Alpha glycosidase inhibitors.
  5. Thiazolidinediones.

 

Hematological Studies on the Diabetic Patients 

        Several hematological changes affecting the red blood cells, white blood cells and the coagulation factors are shown to be associated with diabetes mellitus. Some of these are directly related to the diabetic state, while others are simply coincidental with the disease. (Bern MM., 1982) Various types of anemia have been reported to occur in patients with diabetes mellitus. Some of these anemia result as a complication of long term diabetes, affecting uptake or utilization of Iron, or absorption of nutrient in the gastro – intestinal tract, or as a result of diabetic nephropathy. However, studies have shown that elevated glucose level may induce anemia and hence diabetes could be a primary cause of anemia. (Pelerson C.M.).

The anemia associated with diabetic kidney disease is proportional to the seventy of the renal failure. It is generally normocytic normochomic but if there is also associated Iron deficiency then microcytic and hypochromic red alls may be seen. Reticulocytopenia is reported due to suppression of bone marrow in diabetic patients. Patients who develop gastrointestinal neuropath have anemia resulting from malabsorption.

In diabetic patients changes in PH and in the levels of 2, 3 diphosphoglycerate (2,3 DPG) and salt have an effect on the binding of oxygen to hemoglobin (Clanutin A, et al, 1967) hyperglycemic state itself also alter oxygen  delivery since it causes an elevation in the levels of 2,3, DPG. (Dilzel J. et al, 1973). This effect is balanced by an elevation in the level of Hb A1C, which has a higher affinity for oxygen then the non – glycosylated hemoglobin molecule.

Other hematological defects that have been reported in the diabetic patients include white blood cell functional defects including defects in cell migration, phagocytosis, intracellular bactericidal activities and responses to mitogenic substances in diabetic patients following an infection. Whole blood is used to determine the hematological parameters. (Ochei J, et al, 2000). Some of the hematological parameters include:

1. Estimation of hemoglobin

2. Red blood cell (RBC) count.

3. White blood cell (WBC) count

4. Platelet Count.

The test can be performed by complete blood count (CBC). A complete blood count is a series of test used to evaluate the composition and concentration of the cellular components of blood. (Ochei J, et al, 2000). Complete blood count is commonly performed on an automate d hematology analyzer using well mixed well mixed whole blood that is added to a chemical called EDTA to prevent clotting. Some laboratories perform the test manually. The whole is collected in a bottle containing different anticoagulant depending on the type of test to be performed.

1.     Red Cell Count (Manual Method): Here 0.02ml of whole blood anticoagulated with ethylene diamine tetra acetic acid (EDTA) is added to 3.98ml of diluting fluid. (Ochei J, et al, 200). Improved Neubeaur counting is used for counting the cells. The improved Neubeaur counting chamber is charged the well mixed diluted blood is added to the Neubeaur chamber covered with cover slip (2 -3 drops). The chamber is placed on a moist chamber for 3 – 4minutes (Monica, 2000). X 10 objective is used to focus and x 40 objective is used to court. Calculation:-

Total red cell=

 

Area counted (mm)

Depth(mm)

No of cell counted x          1         x        1        x    Dilution.

 

0.2

0.1

= Number of cells counted x 1   x    1    x 200

= Number of cell counted x 10, 000

The Range = 4. 9 – 5. 9 for Normal range (Ochei 2000)

For Diabetic patients, the no of red blood cells is reduced to 0. 7 – 1. 2. The normal range is 4. 9- 5. 9 x 1012 /L

The Diabetic range is 4.0 – 4. 6 x 1012 /L

Because of this reduced no of red cells various types of anemia have been reported to occur in patients with diabetes mellitus (Volk BW, 1990). Some of these anemia result as a complication of long term diabetes, affecting uptake or utilization of Iron. (Bern MM, 1982).

2. Estimation of Hemoglobin: The Drabkin & Austin (method was used (Reid et al,, 1987). Here, 0.02ml of whole blood was added to 4.0ml of the modified diluents (Drabkin’s solution) in a tube. (Monica, 2000). The tube was then stopped and inverted for several times after which it was allowed to standard sample were then read at 540nm against the absorbance values were used to calculate the Hb level.

The Normal range in g/L = 130 – 150

Diabetic patients = 118 – 136.

It was observed that the hemoglobin levels of diabetic patients were reduced.

3. White blood Cell Count (Total) Manual Method: 0.02ml of the whole blood anticoagulated with EDTA is added to 0.38ml of diluting solution contain acetic acid and gentian violet. (Ochei J, et al, 2000). The blood is well mixed and New Improved Neubeaur chamber is used for the counting. 2–3 drops of the mixed blood is added to the Neubeaur chamber covered with cover ship and placed or a moisted chamber for about 20mins. The cells in the four larger corner square is counted using x 40 objectives and its then calculated (Ochei J et al,, 2000).

Calculation:-

 

Depth(mm3 

Area counted (mm3)  

No of cells counted x     1              x     1        x  dilution

 

 

0.1

4

= No of cells counted x   1    x 1      x 20

= No of cells counted x 50

White cell count x 109/L is the unit (Ochei J. et al, 2000)

The Normal valued = (4. 5 – 11) x 109/L

Diabetic patients = (0.7 – 1.2) x 109/L

The no of white cell in the diabetic patients is reduced. This reduction makes the body to be prom to infections.

4. Platelet count (Manual Method):

0.02ml of blood anticoagulated with EDTA is added to 0.38ml of diluting fluid which is ammonium oxalate (Monica, 2000). The Neubeaur chamber is charged and 2- 3 drops of the mixed blood is added and allowed to stand in a moist chamber for 20 minutes. The cell is counted using the x 40 objectives and the center square is the part counted. The platelet is then calculated calculation:

= Number of platelets counted x

X dilution

= No of platelet counted x

= No of platelet counted x 500.

The Normal range is 150 – 400 x 109 /L

The Diabetic range is 165 – 326 x 109/L.

The low platelet count causes the injuries like bruises and cuts not to heal properly or fest.

Discussion

Diabetic Induced polyuria could cause hyponatraemia (Fitz Simons, 1979). In hyponatraemia, the sodium and chloride concentrations in the plasma are usually Ion, while the plasma globulin proteins and the hematocrit values are high (Gray and Howarth, 1979).

In a case reported by Montgomery et al, 1977, a 21 year old female with a four year history of insulinopenic diabetes mellitus had plasma sodium, potassium, PCV and PH values of 134mmol/L, 6.4mmol/L, 49% and 6.8 respectively. They explained that the values indicated dehydration probably caused by the excess polyuria that characterized the life of diabetics and the ph showed that the plasma wars acidotic, possibly due to oxidation of fatty acids in lieu of glucose to yield energy. Dietary and drug control therefore could only be effective if the recommended traditional diet and drug dosage are strictly adhered to.

Conclusion

The findings are compatible with the hypothesis that diabetic patients present normal responses to hematocrit variation and therefore blood viscosity and shear stress in mediating the release of vasodilators and lack the ability to autoregulate blood pressure relative to difference in hematocrit by Comparism to non – diabetic subjects. These finding also suggest that the treatment of diabetes should target maintaining an optimal hematocrit in order to lower cardiovascular risk.

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One Comment on “Diabetes Mellitus – History, Causes,Types and Treatment”

  1. Treatment of Diabete says:

    This is very informative post and helpful for those who are searching for it.I away get wonderful information from your blog.I hope you will provide more information in future.Thank you for sharing.

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