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Diabetes Mellitus, Type 2 – A Review

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Posted by on Tuesday, September 14, 2010, 23:45
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Introduction

Background

Diabetes mellitus is a chronic disease that requires long-term medical attention both to limit the development of its devastating complications and to manage them when they do occur.

Diabetes Mellitus
Diabetes Mellitus

It is a disproportionately expensive disease; in 2002, the per-capita cost of health care was $13,243 for people with diabetes, while it was $2560 for those without diabetes. The ED utilization rate by people with diabetes is twice that of the unaffected population.1

This article focuses on the ED evaluation and treatment of the acute and chronic complications of diabetes other than those directly associated with hypoglycemia and severe metabolic disturbances, such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). (Please see Hypoglycemia, Diabetic Ketoacidosis, and Hyperosmolar Hyperglycemic State for more information on these disorders.)
Pathophysiology

The 2 basic types of diabetes mellitus are type 1 and type 2. Type 1 diabetes mellitus is discussed in Diabetes Mellitus, Type 1 – A Review).

Type 2 diabetes mellitus was once called adult-onset diabetes. Now, because of the epidemic of obesity and inactivity in children, type 2 diabetes mellitus is occurring at younger and younger ages. Although type 2 diabetes mellitus typically affects individuals older than 40 years, it has been diagnosed in children as young as 2 years of age who have a family history of diabetes.

Type 2 diabetes is characterized by peripheral insulin resistance with an insulin-secretory defect that varies in severity. For type 2 diabetes mellitus to develop, both defects must exist: all overweight individuals have insulin resistance, but only those with an inability to increase beta-cell production of insulin develop diabetes. In the progression from normal glucose tolerance to abnormal glucose tolerance, postprandial glucose levels first increase. Eventually, fasting hyperglycemia develops as inhibition of hepatic gluconeogenesis declines.

About 90% of patients who develop type 2 diabetes mellitus are obese. Because patients with type 2 diabetes mellitus retain the ability to secrete some endogenous insulin, those who are taking insulin generally do not develop DKA if it is stopped. Therefore, they are considered to require insulin but not to depend on insulin. Moreover, patients with type 2 diabetes mellitus may not need treatment with oral antidiabetic medication or insulin if they lose weight.
Some forms of diabetes have been found to be due to genetic defects. A syndrome previously known as maturity onset diabetes of youth (MODY) has now been reclassified as individuals with a variety of defects in beta-cell function. This accounts for 2-5% of individuals with type 2 diabetes who present at a young age and have mild disease. The trait is autosomal dominant and can be screened for through commercial laboratories. The 6 currently identified mutation are: HNF-4-alpha, glycokinase gene, HNF-1-alpha, IPF-1, HNF-1-beta, and NEUROD1. The SURI-1 gene causes hyperglycemia in infancy, which is often misdiagnosed as type 1 diabetes, and there are genetic defects in mitochondrial DNA that cause type 2 diabetes and sensorineural hearing loss.

Various other types of diabetes, previously called secondary diabetes, are caused by other illnesses or medications. Depending on the primary process involved (eg, destruction of pancreatic beta cells or development of peripheral insulin resistance), these types of diabetes behave similarly to type 1 or type 2 diabetes. The most common are diseases of the pancreas that destroy the pancreatic beta cells (eg, hemochromatosis, pancreatitis, cystic fibrosis, pancreatic cancer), hormonal syndromes that interfere with insulin secretion (eg, pheochromocytoma) or cause peripheral insulin resistance (eg, acromegaly, Cushing syndrome, pheochromocytoma), and diabetes induced by drugs (eg, phenytoin, glucocorticoids, estrogens).

Diabetes Mellitus
Diabetes Mellitus

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Gestational diabetes mellitus is a complication of approximately 4% of all pregnancies in the United States. Untreated gestational diabetes mellitus can lead to fetal macrosomia, hypoglycemia, hypocalcemia, and hyperbilirubinemia. In addition, mothers with gestational diabetes mellitus have increased rates of cesarean delivery and chronic hypertension. To screen for gestational diabetes mellitus, a 50-g glucose screening test should be completed at 24-28 weeks of gestation.2 This is followed by a 100-g, 3-hour oral glucose tolerance test if the patient’s plasma glucose concentration at 1 hour after screening is greater than 140 mg/dL.

Although the pathophysiology of the disease differs between the types of diabetes, most of the complications, including microvascular, macrovascular, and neuropathic, are similar regardless of the type of diabetes.
Frequency
United States

In 2005, people with diabetes were estimated to account for 7% of the US population, or approximately 20.8 million people.3 Of these 20.8 million people, 14.6 million have a diagnosis of diabetes, and diabetes is undiagnosed in another 6.2 million. Approximately 5-10% have type 1 diabetes, 90-95% have type 2 diabetes, and 1-5% have other types. Additionally, an estimated 54 million people have pre-diabetes.

Pre-diabetes, as defined by the American Diabetes Association, is that state in which blood glucose levels are higher than normal but not high enough to be diagnosed as diabetes. It is presumed that most persons with elevated glucose levels approaching the level needed for the diagnosis of diabetes will subsequently progress to diabetes.
International

Rates of diabetes are increasing worldwide. At least 171 million people currently have diabetes, and this figure is likely to more than double to 366 million by 2030. The top 10 countries, in numbers of people with diabetes, are currently India, China, the United States, Indonesia, Japan, Pakistan, Russia, Brazil, Italy, and Bangladesh. The greatest percentage increase in rates of diabetes will occur in Africa over the next 20 years. However, at least 80% of people in Africa with diabetes are undiagnosed, and many in their 30s to 60s will die from diabetes there.
Mortality/Morbidity

The morbidity and mortality associated with diabetes are related to the short- and long-term complications. Complications include the following:

* Hypoglycemia and hyperglycemia
* Increased risk of infections
* Microvascular complications (eg, retinopathy, nephropathy)
* Neuropathic complications
* Macrovascular disease (eg, coronary artery disease, stroke)

Diabetes is the major cause of blindness in adults aged 20-74 years, as well as the leading cause of nontraumatic lower-extremity amputation and end-stage renal disease (ESRD).
Race

Type 2 diabetes mellitus is more prevalent among Hispanics, Native Americans, African Americans, and Asians/Pacific Islanders than in non-Hispanic whites.
Sex

The incidence of type 2 diabetes is essentially equal in women and men in all populations.
Age

* Type 2 diabetes mellitus is becoming increasingly common because people are living longer and because the prevalence of diabetes increases with age.
* It is also seen more frequently now than before in young people, in association with the rising prevalence of childhood obesity.
* Although type 2 diabetes mellitus still occurs most commonly in adults aged 40 years or older, the incidence of disease is increasing more rapidly in adolescents and young adults than in other age groups.

Clinical
History

Correctly determining whether a patient has type 1 or type 2 diabetes is important because patients with type 1 diabetes are dependent on a continuous source of exogenous insulin and carbohydrates for survival. Patients with type 2 diabetes may not need treatment of hyperglycemia during periods of fasting or decreased oral intake. A patient whose diabetes is controlled with diet or an oral antidiabetic agent clearly has type 2 diabetes. A lean patient who has had diabetes since childhood, who has always been dependent on insulin, or who has a history of DKA almost certainly has type 1 diabetes.

Distinguishing the type of diabetes can be difficult in (1) patients who are treated with insulin and are young but clinically appear to have type 2 diabetes and (2) older patients with late onset of diabetes who nonetheless take insulin and seem to share characteristics of patients with type 1 diabetes. (This latter group is now said to have latent autoimmune diabetes of the adult [LADA]). When in doubt, the patient should be treated with insulin and his or her glucose levels should be closely monitored. Some adolescents or young adults, mostly Hispanic or African American patients, who present as with classic DKA are subsequently found to have type 2 diabetes.

Many patients with type 2 diabetes are asymptomatic, and their disease is undiagnosed for many years. Studies suggest that the typical patient with new-onset type 2 diabetes has had diabetes for at least 4-7 years before it is diagnosed.4 Among patients with type 2 diabetes, 25% are believed to have retinopathy; 9%, neuropathy; and 8%, nephropathy at the time of diagnosis.

Pre-diabetes often precedes overt type 2 diabetes. Pre-diabetes is defined by a fasting blood glucose level of 100-125 mg/dL or a 2-hour post oral glucose tolerance test (OGTT) glucose level of 140-200 mg/dL. Patients who have pre-diabetes have an increased risk for macrovascular disease as well as diabetes.2

Often confused with pre-diabetes is the metabolic syndrome (also called syndrome X or the insulin-resistance syndrome). Metabolic syndrome, thought to be due to insulin resistance, can occur in patients with overtly normal glucose tolerance, prediabetes, or diabetes. It is characterized by central obesity, then by dyslipidemia. Hypertension is a common feature. Eventually, clinically apparent insulin resistance develops. Unfortunately, insulin resistance is not measured clinically, except in research settings. An elevated fasting blood glucose level is the first indication of insulin resistance, but fasting insulin levels are generally increased long before this occurs. Measurement of fasting insulin levels are not yet recommended for the diagnosis of insulin resistance. An effort to standardize insulin assays is underway and may allow for the use of fasting insulin levels to diagnose insulin resistance in the future.

See Workup for more information on diagnosis of diabetes. See Diabetes Mellitus, Type 1 – A Review for more information on distinguishing type 2 diabetes mellitus from type 1 diabetes mellitus.

Inquire about the type and duration of the patient’s diabetes and about the care the patient is receiving for diabetes.

* Type of diabetes: The diagnosis is based on history, therapy, and clinical judgment, as described above.
* Duration of diabetes: The chronic complications of diabetes are related to the length of time the patient has had the disease.
* Diabetes care: Inquire about the patient’s current treatment of diabetes.

A focused diabetes history should also include the following questions:

* Is the patient’s diabetes generally well controlled (with near-normal blood glucose levels)? Patients with poorly controlled blood glucose levels heal more slowly and are at increased risk for infection and other complications.
* Does the patient have severe hypoglycemic reactions? If the patient has episodes of severe hypoglycemia and therefore is at risk for losing consciousness, this possibility must be addressed, especially if the patient drives.
* Does the patient have diabetic nephropathy that might alter the use of medications or intravenous radiographic contrast material?
* Does the patient have macrovascular disease, such as coronary artery disease (CAD) that should be considered in the ED?
* Treatment monitoring
o Does the patient self-monitor his or her blood glucose levels? Note the frequency and range of values at each time of day.
o When was the patient’s hemoglobin A1C (HbA1C) value (an indicator of long-term glucose control) last measured? What was it?

As circumstances dictate, additional questions may be warranted.

* Hyperglycemia: Does the patient give a history of recent polyuria, polydipsia, nocturia, or weight loss?
* Hypoglycemia
o Has the patient had episodes of unexplained hypoglycemia? If so, when, how often, and how does the patient treat these episodes?
o Does the patient have hypoglycemia unawareness (ie, does the patient lack the adrenergic warning signs of hypoglycemia)? Hypoglycemia unawareness indicates an increased risk of subsequent episodes of hypoglycemia.
* Microvascular complications
o Retinopathy: When was the patient’s last dilated eye examination? What were the results?
o Nephropathy: Does the patient have known kidney disease? What were the dates and results of the last measurements of urine protein and serum creatinine levels?
* Macrovascular complications
o Hypertension: Does the patient have hypertension (defined as a blood pressure of >130/80)? What medications are taken?
o CAD: Does the patient have CAD?
o Peripheral vascular disease: Does the patient have symptoms of claudication or a history of vascular bypass?
o Cerebrovascular disease: Has the patient had a stroke or transient ischemic attack?
o Hyperlipidemia: What are the patient’s most recent lipid levels? Is the patient taking lipid-lowering medication?
* Neuropathy: Does the patient have a history of neuropathy or are symptoms of peripheral neuropathy or autonomic neuropathy present (including impotence if the patient is male)?
* Diabetic foot disease: Does the patient have a history of foot ulcers or amputations? Are any foot ulcers present?
* Infections: Are frequent infections a problem? At what site?

Physical

A diabetes-focused examination includes vital signs, funduscopic examination, limited vascular and neurologic examinations, and a foot assessment. Other organ systems should be examined as indicated by the patient’s clinical situation.

* Assessment of vital signs
o Is the patient hypertensive or hypotensive? Orthostatic vital signs may be useful in assessing volume status and in suggesting the presence of an autonomic neuropathy.
o If the respiratory rate and pattern suggest Kussmaul respiration, DKA must be considered immediately, and appropriate tests ordered.
* Funduscopic examination
o The funduscopic examination should include a careful view of the retina, including both the optic disc and the macula.
o If hemorrhages or exudates are seen, the patient should be referred to an ophthalmologist as soon as possible. Examiners who are not ophthalmologists tend to underestimate the severity of retinopathy, especially if the patients’ pupils are not dilated.
* Foot examination
o The dorsalis pedis and posterior tibialis pulses should be palpated and their presence or absence noted. This is particularly important in patients who have foot infections because poor lower-extremity blood flow can delay healing and increase the risk of amputation.
o Documenting lower-extremity sensory neuropathy is useful in patients who present with foot ulcers because decreased sensation limits the patient’s ability to protect the feet and ankles. This can be assessed with a monofilament, or more readily by assessment of reflexes, position, and vibration sensation.
o If peripheral neuropathy is found, the patient should be made aware that foot care (including daily foot examination) is very important for the prevention of foot ulcers and lower-extremity amputation.

Causes

The major risk factors for type 2 diabetes mellitus are the following:

* Age – Older than 45 years (though, as noted above, type 2 diabetes mellitus is occurring with increasing frequency in young individuals)
* Obesity – Weight greater than 120% of desirable body weight (true for approximately 90% of patients with type 2 diabetes mellitus)
* Family history of type 2 diabetes in a first-degree relative (eg, parent or sibling)
* Hispanic, Native American, African American, Asian American, or Pacific Islander descent
* History of previous impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
* Hypertension (>140/90 mm Hg) or dyslipidemia (high-density lipoprotein [HDL] cholesterol level <40 mg/dL or triglyceride level >150 mg/dL)
* History of gestational diabetes mellitus or of delivering a baby with a birth weight of >9 lb
* Polycystic ovarian syndrome (which results in insulin resistance)

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