Diabetes results from a complex interaction of genetic, environmental, and lifestyle factors. In type 1 diabetes, an autoimmune-mediated process triggered by an environmental factor and occurring in genetically susceptible people causes destruction of the pancreatic β cells. People with type 1 diabetes do not produce insulin and they must receive daily injections of insulin to survive. Type 2 diabetes is caused by lifestyle factors (obesity being the most important) and, to a small degree, by genetic factors. The pancreatic β cells are not destroyed, but they do not produce sufficient insulin to maintain healthy glycemic control, and people with type 2 diabetes also do not utilize the insulin they do produced. Type 2 diabetes can initially be managed with a special diet, some lifestyle changes, and oral medications, but most patients will eventually need insulin.
Case Study #1: A 13-year-old male with no prior medical history (PMH) is noticed by his parents to have an increased appetite, excessive thirst, and excessive urination. He has been in his usual state of health and maintaining his normal activities. He has two older siblings and both are healthy. His mother is healthy, but his father has type 1 diabetes. Laboratory tests show fasting plasma glucose of 145 mg/dL and one week later, 151 mg/dL, and his HbA1C is 7.3%. He is started on intensive insulin therapy (basal insulin plus as needed short-acting insulin through the day) and exercise and diet prescriptions are made.
Case Study #2: A 57-year-old female with a PMH of HTN visits her primary care physician because she has developed an ulcer on her foot (the result of an injury) that does not seem to be healing, and pins and needles sensation in the same extremity. She currently takes lisinopril and HCTZ for HTN; her blood pressure is 166/88 mm Hg. She does not smoke or use alcohol. Her body weight is 125 kg (classifying her as obese), and she never exercises. Her fasting plasma glucose is 191 mg/dL, and one week later, 211 mg/dL, her HbA1C is 8.1%, and her total serum cholesterol is 246 mg/dL. She is diagnosed with diabetic neuropathy, hypercholesterolemia, metabolic syndrome, type 2 diabetes, and uncontrolled hypertension.
Learning Break: Diabetes is diagnosed and monitored using three tests: fasting plasma glucose, oral glucose tolerance test, and glycated hemoglobin (HbA1C). Normal fasting plasma glucose is 70-99 mg/dL. A normal oral glucose tolerance test should be ≤ 140 mg/dL two hours after receiving 50 grams of glucose. The HbA1C test reflects the average amount of glucose in the blood over a period of weeks, so it is a useful test for monitoring the effectiveness of therapy and assessing the long-term risk for complications. The HbA1C should be ≤ 6%.
The epidemiology of diabetes is best understood in the context of these categories: diabetes in the population, type 1 diabetes, type 2 diabetes, diabetes and age, diabetes and gender, diabetes and ethnic background, and morbidity and mortality associated with diabetes.
Learning Break: Diabetes is typically classified as either type 1 or type 2, but there are actually many other types of diabetes (e.g., gestational, drug-induced, infection-induced, or disease-induced, etc.). However, these represent a very, very small minority of the total number of cases of diabetes and they will not be discussed here. There is also a condition called pre-diabetes. Pre-diabetes is a condition in which the HbA1C, the plasma glucose, and other markers of diabetes are persistently elevated, but are not high enough to require treatment. People with pre-diabetes have an increased risk of developing type 2 diabetes, heart disease, and stroke.
Type 1 diabetes is caused by autoimmune destruction of the β cells of the pancreas. This process occurs in genetically susceptible people and is (presumably) triggered by an environmental factor or factors (Skyler, Ricordi, 2011). When the majority (approximately 80%-90%) of the β cells have been destroyed, a normal level of serum glucose cannot be maintained and signs and symptoms of type 1 diabetes will become evident.
Learning Break: Type 1 diabetes is caused by an interaction of genetics and environment, and there are multiple genetic and environmental factors that may contribute to the development of the disease.
Type 2 diabetes is characterized by insulin resistance and a progressive decline in pancreatic β cell insulin production. There is no autoimmune-mediated pancreatic β cell damage and most patients with type 2 diabetes do not need insulin during the initial stages of the disease.
Insulin resistance is a condition in which insulin is produced, but is not used properly: a given amount of insulin does not produce the expected result. In people who are obese it may be that the chronic inflammation associated with obesity affects the function of the insulin receptors on the cells in the liver, muscles, etc., decreases the number of insulin receptors, affects insulin signaling pathways, or inactivates insulin receptors (Allende-Vigo, 2010; Olatunbosun, 2011).
The progressive decline in pancreatic β cell function is due to decreased β cell mass caused by apoptosis (Butler, Janson, Bonner-Weir, Ritzel, Rizza, Butler, 2003); this may be a consequence of aging, genetic susceptibility, and insulin resistance itself (Unger, Parkin, 2010). The etiology of type 2 diabetes is complex and involved genetic and lifestyle factors.
The question of who to test for type 1 diabetes usually resolves itself. People with type 1 diabetes present with signs and symptoms that are distinctive and the fasting plasma glucose is markedly elevated, so most cases are diagnosed very soon after onset. Autoantibody levels can be measured and this might be advisable in high-risk individuals.
Testing for type 2 diabetes should be performed in any asymptomatic adult, regardless of age, who is obese or has one or more risk factors such as sedentary lifestyle, ethnic risk factor, a first-degree relative who has diabetes, an HbA1C ≥ 5.7%, hypertension, etc. (American Diabetes Association, 2010). People who are not obese and do not have risk factors should be tested starting at age 45. Fasting plasma glucose, oral glucose tolerance test, or HbA1C testing can be used and if the values are normal, the tests can be repeated in three years. Adults should also have serum lipids measured, blood pressure should be checked, an evaluation for the presence of cardiovascular disease should be performed, and if needed, evaluation for the presence/possibility of diabetic nephropathy, neuropathy, and retinopathy. Children who are obese and who have risk factors should be evaluated starting at age 10.
Diabetes can be a devastating disease, it is a progressive disease, and there is no cure. Patients with diabetes must monitor their diet, their activity level, their plasma glucose, and almost without exception they must take medications forever.
Type 1 diabetes cannot be prevented or (effectively) cured; it can only be managed. However, with conscientious effort patients can delay the onset and/or slow the progression and severity of the complications of the disease.
But type 2 diabetes can, in many instances, be prevented. It has clearly been shown that lifestyle alterations such as diet, exercise and weight loss especially weight loss can prevent the development of type 2 diabetes; unfortunately, it is well known that many people find initiating and maintaining an exercise and weight loss program very difficult. So with the incidence of obesity at epidemic proportions and predicted to increase, the population getting older and more sedentary, the already very high incidence of type 2 diabetes is going to become even higher.
Given these facts, identification of people at risk and vigorous screening of these people is essential, and health care professionals need to know who these people are and provide them with education and testing.
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