Metabolic Disorders Characterized By Hyperglycemia Biology Essay

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The word diabetes is from the Greek diabanein which means to pass through, in reference to the excessive urine produced as a symptom of these diseases. The term diabetes, without qualification, usually refers to diabetes mellitus, which roughly translates to excessive sweet urine.

History Of Diabetes Mellitus

The term diabetes was derived from the Greek verb, diabaínein, itself formed from the prefix dia-, "across, apart," and the verb bainein, "to walk, stand." Its derivative diabÄ“tÄ“s meant "one that straddles," or specifically "a compass, siphon." The sense "siphon" gave rise to the use of diabÄ“tÄ“s as the name for a disease involving the discharge of excessive amounts of urine.

Diabetes is first recorded in English, in the form diabete, in a medical text written around 1425. In 1675, Thomas Willis added the word mellitus, from the Latin meaning "honey", a reference to the sweet taste of the urine. Sushruta (6th century B.C.) identified diabetes with obesity and sedentary lifestyle, advising exercises to help "cure" it.[11] The ancient Indians tested for diabetes by observing whether ants were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha). In medieval Persia, Avicenna (980-1037) provided a detailed account on diabetes mellitus.

Although diabetes has been recognized since antiquity pathogenesis of diabetes has only been understood experimentally since about 1900. The role of the pancreas in diabetes was discovered in 1889 by experiments on dogs. Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas-he proposed calling this substance insulin, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.

The availability of an effective treatment-insulin injections could be made possible in 1922. The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made in January 1936. In 1980, U.S. biotech company Genentech developed human insulin. The insulin is isolated from genetically altered bacteria (the bacteria contain the human gene for synthesizing human insulin), which produce large quantities of insulin. The purified insulin is distributed to pharmacies for use by diabetes patients.

Epidemiology Of Diabetes Mellitus

In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, which accounts to 2.8% of the population. Its incidence is increasing rapidly, and it is estimated that by 2030, this number will almost double. [12, 13] Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030. The increase in incidence of diabetes in developing countries follows the trend of urbanization and lifestyle changes, perhaps most importantly a "Western-style" diet. This has suggested an environmental (i.e., dietary) effect, but there is little understanding of the mechanism(s) at present, though there is much speculation, some of it most compellingly presented. [14]

For at least 20 years, diabetes rates in North America have been increasing substantially. In 2010 nearly 26 million people have diabetes in the United States alone, from those 7 million people remain undiagnosed. Another 57 million people are estimated to have pre-diabetes.

The Centers for Disease Control has termed the change an epidemic. The American Diabetes Association cite the 2003 assessment of the National Center for Chronic Disease Prevention and Health Promotion (Centers for Disease Control and Prevention) that 1 in 3 Americans born after 2000 will develop diabetes in their lifetime.[15]

According to the American Diabetes Association, approximately 18.3% (8.6 million) of Americans age 60 and older have diabetes. Diabetes mellitus prevalence increases with age, and the numbers of older persons with diabetes are expected to grow as the elderly population increases in number. The National Health and Nutrition Examination Survey (NHANES III) demonstrated that, in the population over 65 years old, 18% to 20% have diabetes, with 40% having either diabetes or its precursor form of impaired glucose tolerance.[16]

Indigenous populations in first world countries have a higher prevalence and increasing incidence of diabetes than their corresponding non-indigenous populations. In Australia, the age-standardized prevalence of self-reported diabetes in Indigenous Australians is almost 4 times that of non-indigenous Australians. [17]

Classification Of Diabetes Mellitus

Most cases of diabetes mellitus fall into three broad categories: type 1, type 2, and gestational diabetes. A few other types are also described.

Type 1 diabetes

Type 1 diabetes is also referred to as insulin-dependent diabetes mellitus(IDDM) for short, and juvenile diabetes(because it represents a majority of the diabetes cases in children) .Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas leading to insulin deficiency. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, where beta cell loss is a T-cell mediated autoimmune attack [18].Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages.

Type 2 diabetes

Type 2 diabetes mellitus is also referred to as non-insulin-dependent diabetes mellitus (NIDDM) and adult-onset diabetes and is characterized by insulin resistance which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Type 2 diabetes is the most common type.

In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity. At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver.

Gestational diabetes

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2% - 5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20% - 50% of affected women develop type 2 diabetes later in life. Gestational diabetes is associated with a number of risks to the fetus and newborn.

Other types

Pre-diabetes indicates a condition that occurs when blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 diabetes. Many people destined to develop type 2 diabetes spend many years in a state of pre-diabetes which has been termed "America's largest healthcare epidemic."[19-21]

Latent autoimmune diabetes of adults is a condition in which Type 1 diabetes develops in adults. Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization when the current taxonomy was introduced in 1999[20, 21]

Genetic defects of β-cell Function

Mitochondrial DNA mutations

Maturity Onset Diabetes of the Young(MODY)

Genetic defects in insulin processing or insulin action

Defects in proinsulin conversion

Insulin gene mutations

Insulin receptor mutations

Exocrine Pancreatic Defects

Chronic pancreatitis


Pancreatic neoplasia

Cystic fibrosis


Fibrocalculous pancreatopathy


Growth hormone excess (acromegaly)

Cushing syndrome





Cytomegalovirus infection

Coxsackievirus B



Thyroid hormone

β-adrenergic agonists

Diagnosis Of Diabetes Mellitus [22]

Table 1: 2006 WHO Criteria for diagnosing Diabetes Mellitus

2006 WHO Diabetes criteria


2 hour glucose

Fasting glucose

m mol/l(mg/dl)

m mol/l(mg/dl)


<7.8 (<140)

<6.1 (<110)

Impaired fasting glycaemia

<7.8 (<140)

≥ 6.1(≥110) & <7.0(<126)

Impaired glucose tolerance

≥7.8 (≥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 any one of the following: [20] 

Fasting plasma glucose level ≥ 7.0 m mol/L (126 mg/ dL).

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

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

Glycated hemoglobin (Hb A1C) ≥ 6.5%.[23]

A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above listed methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. [ 24] According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes mellitus.

People with fasting glucose levels from 100 to 125 mg/dL (5.6 to6.9 mmol/L) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full blown diabetes mellitus as well as cardiovascular disease .[25]

Complications Of Diabetes Mellitus

The complications of diabetes mellitus are far less common and less severe in people who have well controlled blood sugar levels. [26, 27] Wider health problems accelerate the deleterious effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise.

Acute Complications:

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is an acute and dangerous complication that is always a medical emergency. Low insulin levels cause the liver to turn to fat for fuel (i.e., ketosis); ketone bodies are intermediate substrates in that metabolic sequence. Elevated levels of ketone bodies in the blood decrease the blood's pH, leading to DKA. Prompt, proper treatment usually results in full recovery, though death can result from inadequate or delayed treatment, or from complications (e.g., brain edema). Ketoacidosis is much more common in type 1 diabetes than type 2.

Hyperglycemia hyper osmolar state

With very high (usually considered to be above 300 mg/dl (16 mmol/L)) blood glucose levels, water is osmoticaly drawn out of cells into the blood and the kidneys eventually begin to dump glucose into the urine. This results in loss of water and an increase in blood osmolarity. The osmotic effect of high glucose levels, combined with the loss of water, will eventually lead to dehydration. Electrolyte imbalances are also common and are always dangerous. Lethargy may ultimately progress to a coma, though this is more common in type 2 diabetes than type 1.


Hypoglycemia, or abnormally low blood glucose, is an acute complication of several diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients. Clinical signs and symptoms range from feeling of intense hunger to altered state of consciousness and ultimately seizures, brain damage and death. In patients with diabetes, this may be caused by several factors, such as too much or incorrectly timed insulin, too much or incorrectly timed exercise (exercise decreases insulin requirements) or not enough food (specifically glucose containing carbohydrates).

Reduced sympathoadrenal responses can cause hypoglycemia unawareness. The concept of hypoglycemia associated autonomic failure (HAAF) in diabetes posits that recent incidents of hypoglycemia cause both defective glucose counter regulation and hypoglycemia unawareness.

Diabetic coma

Diabetic coma is a medical emergency in which a person with diabetes mellitus is comatose (unconscious) because of one of the acute complications of diabetes:

Severe diabetic hypoglycemia

Diabetic ketoacidosis advanced enough to result in unconsciousness from a combination of severe hyperglycemia, dehydration and shock, and exhaustion

Hyper osmolar non ketotic coma in which extreme hyperglycemia and dehydration alone are sufficient to cause unconsciousness.

Respiratory infections

The immune response is impaired in individuals with diabetes mellitus which leads to an increase in susceptibility to respiratory infections such as pneumonia and influenza among individuals with diabetes. [28]

Chronic Complications

Chronic elevation of blood glucose level leads to damage of blood vessels (angiopathy). The endothelial cells lining the blood vessels take in more glucose than normal, since they do not depend on insulin. They then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker. In diabetes, the resulting problems are grouped under "micro vascular disease" (due to damage to small blood vessels) and "macro vascular disease" (due to damage to the arteries).

However, some research challenges the theory of hyperglycemia as the cause of diabetic complications. The fact that 40% of diabetics who carefully control their blood sugar nevertheless develop neuropathy, [29] and that some of those with good blood sugar control still develop nephropathy, [30] requires explanation. It has been discovered that the serum of diabetics with neuropathy is toxic to nerves even if its blood sugar content is normal.[31] Recent research suggests that in type 1 diabetics, the continuing autoimmune disease which initially destroyed the beta cells of the pancreas may also cause retinopathy,[32] neuropathy,[33] and nephropathy[34]. Non-diabetic offspring of type 2 diabetics have been found to have increased arterial stiffness and neuropathy despite normal blood glucose levels [35], and elevated enzyme levels associated with diabetic renal disease have been found in non-diabetic first-degree relatives of diabetics. Even rapid tightening of blood glucose levels has been shown to worsen rather than improve diabetic complications, though it has usually been held that complications would improve over time with more normal blood sugar, provided this could be maintained. [36]

Microvascular Complications:

The damage to small blood vessels leads to a microangiopathy , which can cause one or more of the following: [37]

Diabetic cardiomyopathy leading to diastolic dysfunction and eventually heart failure.

Diabetic nephropathy, damage to the kidney which can lead to chronic renal failure, eventually requiring dialysis. Diabetes mellitus is the most common cause of adult kidney failure worldwide in the developed world.

Diabetic neuropathy, abnormal and decreased sensation, usually in a 'glove and stocking' distribution starting with the feet but potentially in other nerves, later often fingers and hands. When combined with damaged blood vessels this can lead to diabetic foot . Other forms of diabetic neuropathy may present as mononeuritis or autonomic neuropathy. Diabetic amyotrophy is muscle weakness due to neuropathy.

Diabetic retinopathy, growth of friable and poor-quality new blood vessels in the retina as well as macular edema (swelling of the macula), which can lead to severe vision loss or blindness. Retinal damage (from microangiopathy) makes it the most common cause of blindness among non-elderly adults in the US.

Macrovascular Complications:

Macro vascular disease leads to cardiovascular disease, to which accelerated atherosclerosis is a contributor: [37]

Coronary artery disease, leading to angina or myocardial infarction

Diabetic myonecrosis

Peripheral vascular disease, contributing to intermittent claudication and diabetic foot.

Stroke (mainly the ischemic type)

Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increases rates of skin ulcers (diabetic foot ulcers) and infection and, in serious cases, necrosis and gangrene. It is why diabetics are prone to leg and foot infections and why it takes longer for them to heal from leg and foot wounds. It is the most common cause of non-traumatic adult amputation, usually of toes and or feet, in the developed world.

Diabetic encephalopathy is the increased cognitive decline and risk of dementia observed in diabetes. Various mechanisms are proposed, including alterations to the vascular supply of the brain and the interaction of insulin with the brain itself [38]. Carotid artery stenosis does not occur more often in diabetes, and there appears to be a lower prevalence of abdominal aortic aneurysm. [39]