Hyperglycemia

Etiology

Factors contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization, and increased glucose production. Glucose homeostasis is a balance between hepatic glucose production and peripheral glucose uptake and utilization. Insulin is the most important regulator of glucose homeostasis.[3][4]

Secondary Cause of Hyperglycemia

The secondary causes of hyperglycemia include the following:

• Destruction of the pancreas from chronic pancreatitis, hemochromatosis, pancreatic cancer, and cystic fibrosis
• Endocrine disorders that cause peripheral insulin resistance like Cushing syndrome, acromegaly, and pheochromocytoma
• Use of medications like glucocorticoids, phenytoin, and estrogens
• Gestational diabetes is known to occur in 4% of all pregnancies and is primarily due to decreased insulin sensitivity
• Total parental nutrition and dextrose infusion
• Reactive as seen postoperatively or in critically ill patients

Major Risk Factors for Hyperglycemia

• Weight more than 120% of the desired body weight
• Family history of type 2 diabetes
• Native Americans, Hispanics, Asian Americans, Pacific Islanders, or African Americans
• Presence of hyperlipidemia or hypertension
• History of gestational diabetes[5]
• Presence of polycystic ovarian syndrome

Epidemiology

The incidence of hyperglycemia has increased dramatically over the last two decades due to increased obesity, decreased activity level, and an aging population. The prevalence is equal between men and women. The countries with the greatest number of patients with diabetes included China, India, United States, Brazil, and Russia. Hyperglycemia is more prominent in low to medium-income households.

The latest data released by the Centers for Disease Control and Prevention indicate that there are nearly 30.5 million Americans with diabetes and nearly 84 million Americans with prediabetes. These numbers are set to increase significantly over the next decade.[6][7]

Pathophysiology

Hyperglycemia in a patient with type 1 diabetes is a result of genetic, environmental, and immunologic factors. These lead to the destruction of pancreatic beta cells and insulin deficiency. In a patient with type 2 diabetes, insulin resistance and abnormal insulin secretion lead to hyperglycemia.

According to recent studies, metabolic disturbances like type 2 diabetes mellitus increases the risk of cognitive decline and Alzheimer dementia. Alzheimer dementia is also a risk factor for diabetes type 2. Recent studies have indicated these diseases are connected both at clinical and molecular levels. Like peripheral insulin resistance leading to type 2 diabetes, brain insulin resistance is linked to neuronal dysfunction and cognitive impairment in Alzheimer dementia.[8]

History and Physical

Symptoms of severe hyperglycemia include polyuria, polydipsia, and weight loss. As the patient's blood glucose increases, neurologic symptoms can develop. The patient may experience lethargy, focal neurologic deficits, or altered mental status. The patient can progress to a comatose state. Patients with diabetic ketoacidosis may present with nausea, vomiting, and abdominal pain in addition to the above symptoms. They also may have a fruity odor to their breath and have rapid shallow respirations, reflecting compensatory hyperventilation for the acidosis.

The physical examination can reveal signs of hypovolemia like hypotension, tachycardia, and dry mucous membranes.

Evaluation

When evaluating a patient for hyperglycemia, the focus should be on the patient's cardiorespiratory status, mental status, and volume status. Bedside serum glucose can be obtained quickly. Testing includes serum electrolytes with the calculation of the anion gap, blood urea nitrogen and creatinine, and complete blood count. Urinalysis by dipstick assesses glucose and ketones in the urine. Arterial blood gas or venous blood gas may be necessary if serum bicarbonate is substantially reduced.[9]

Blood Glucose Determination

To determine if the patient has developed type 2 diabetes the patient needs to have the following outcomes on these tests:

• A fasting plasma glucose level of 126 mg/dL or higher

• A 2-hour plasma glucose level of 200 mg/dL or higher during a 75-g oral glucose tolerance test (OGTT)

• Random plasma glucose of 200 mg/dL or higher in the presence of symptoms of hyperglycemia

• A hemoglobin A1c level of 6.5% or higher

Treatment / Management

The treatment goals of hyperglycemia involve eliminating the symptoms related to hyperglycemia and reducing long-term complications. Glycemic control in patients with type 1 diabetes is achieved by a variable insulin regimen along with proper nutrition. Patients with type 2 diabetes are managed with diet and lifestyle changes as well as medications. Type 2 diabetes also may be managed on oral glucose-lowering agents. Patients with hyperglycemia need to be screened for complications including retinopathy, nephropathy, and cardiovascular disease.

Goals of Treatment

Treatment goals are to reduce the following complications associated with hyperglycemia:

• Kidney and eye disease by regulation of blood pressure and lowering hyperglycemia
• Ischemic heart disease, stroke, and peripheral vascular disease by control of hypertension, hyperlipidemia, and cessation of smoking
• Reduce the risk of metabolic syndrome and stroke by control of body weight and control of hyperglycemia

Patients who have hyperglycemia and are confirmed to have type 2 diabetes need to be referred to an endocrinologist. Unless there is a contraindication, the drug of choice to lower hyperglycemia is metformin. In addition, some patients may require insulin therapy in combination with other agents.

Prevention of Complications

To prevent complications of hyperglycemia, the following preventive approaches are recommended:

• Refer to an ophthalmologist for yearly eye exams
• Monitor hemoglobin A1c levels every 3-6 months
• Check urinary albumin levels every 12 months
• Examine the feet at each clinic visit
• Maintain the Blood pressure to less than 130/80 mmHg
• Initiate statin therapy if the patient has hyperlipidemia

Some patients are prone to greater glycemic variability of their blood sugars within a day and also variability for the same time on different days, thereby causing frequent episodes of hypoglycemia and hyperglycemia. These patients need close monitoring by an endocrinologist with a treatment plan intended to reduce both the risks or at least maintain one risk while reducing the other.

Differential Diagnosis

There are many conditions that can present with hyperglycemia. Differential diagnosis of hyperglycemia include:

• Diabetes mellitus type 1 and 2
• Stress-induced hyperglycemia
• Medications induced like steroids
• Acromegaly
• Cushing disease
• Iatrogenic (from intravenous fluids with dextrose and tube feeds)

Prognosis

The prognosis of individuals with hyperglycemia depends on how well the levels of blood glucose are controlled. Chronic hyperglycemia can cause severe life- and limb-threatening complications. Changes in lifestyle, regular physical exercise, and changes in diet are the keys to a better prognosis. Individuals who maintain euglycemia have a markedly better prognosis and an improved quality of life compared to individuals who remain hyperglycemic. Once the complications of hyperglycemia have developed, they are basically irreversible. Countless studies have shown that untreated hyperglycemia shortens lifespan and worsens the quality of life. Thus, an aggressive lowering of hyperglycemia must be initiated, and patients must be closely followed. Studies suggest that one should try to achieve an A1C level of less than 7%. However, controlling blood sugars too tightly can result in hypoglycemia which is not well tolerated by elderly individuals who already may have a pre-existing cardiovascular disease.[10]

Complications

Complications of untreated or uncontrolled hyperglycemia over a prolonged period of time include:

Microvascular Complications

• Retinopathy
• Nephropathy
• Neuropathy

Macrovascular Complications

• Coronary artery disease
• Cerebrovascular disease
• Peripheral vascular disease

Patients with diabetes are more prone to depression than those without diabetes. This is more so in newly diagnosed diabetics and young patients due to significant lifestyle changes that are needed.[11]