Diabetes Mellitus Part One:
Symptoms, Diagnosis, Pathology, and Treatment
Dr. Salaheddin Sharif, MD, MS, RCEP
Diabetes mellitus
Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar
(hyperglycemia) resulting from defects in insulin secretion, insulin resistance or both. It is one
of the leading causes of death and disability in the United States, where there are about 24
million diagnosed cases of diabetes with an estimated 6 million additional undiagnosed cases
in the general population. The chronic high blood glucose of diabetes is associated with longterm damage, dysfunction, and failure of various organs, particularly the eyes, kidneys,
nerves, heart and blood vessels. The pathogenic processes that cause the development of
diabetes include autoimmune destruction of the B-cells of the pancreas with consequent
insulin deficiency to abnormalities that result in resistance to insulin action. The basis of the
abnormalities in carbohydrate, fat and protein metabolism in diabetes is ineffective action of
insulin on target tissues.
Symptoms of Diabetes
Symptoms of marked hyperglycemia include polyuria, polydipsia, weight loss, sometimes with
polyphagia and blurred vision. In addition, growth impairment and susceptibility to certain
infections may also accompany chronic hyperglycemia. Acute complications of uncontrolled
diabetes are hyperglycemia with ketoacidosis or the nonketotic hyperosmolar syndrome.
Long-term complications of diabetes are microvascular and macrovascular and include
retinopathy, nephropathy, peripheral neuropathy, autonomic neuropathy, atherosclerotic
cardiovascular disease, hypertension, peripheral arterial disease, dyslipidemia and
cerebrovascular disease.
Diagnosis of Diabetes
The diagnostic criteria of diabetes is a fasting plasma glucose ≥126 mg/l. Symptoms of
diabetes include polyuria, polydipsia and unexplained weight loss plus a casual plasma
glucose of ≥ 200 mg/dL and two hour plasma glucose more than 200 mg/dL during an oral
glucose tolerance test using 75 g of glucose. Currently, diabetes has a new classification
system that depends on etiology and pathogenesis rather than modalities of treatment.
Diabetes is divided into four major categories depending on etiology: Type 1, Type 2,
gestational and other types. For the purpose of this paper we will explore Type 2 diabetes.
Type 2 Diabetes
Type 2 diabetes accounts for 90-95% of all cases of diabetes. It is insulin resistance with
relative insulin deficiency. Previously, it was called non-insulin dependent diabetes, or adultonset diabetes, or patients who have insulin resistance. This population does not need insulin
treatment to survive.
Both genetic and environmental factors can contribute to an increased risk of type 2 diabetes.
Other risk factors for the disease include older age, obesity, minority ethnicity, family history,
lower socioeconomic status, fat distribution (specifically, intra-abdominal fat distribution) and
lifestyle factors (physical inactivity, sedentary life style, high fat diet).
It takes many years to diagnose type 2 because the hyperglycemia develops gradually.
Insulin resistance manifests as by decreased storage of glucose as glycogen in the liver and
muscle.
These deficiencies in insulin action may be either genetic or acquired through such factors as
abdominal obesity. Chronic hyperglycemia and increased free fatty acid levels are involved in
acquired insulin resistance. Each of these may cause decreased muscle glucose transport
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and phosphorylation and is reversible. Insulin secretion is abnormal in type 2 diabetes with
the first stage of insulin release generally being absent. High blood glucose levels may inhibit
insulin secretion. This theory has been termed glucose toxicity, and elevated products of fat
metabolism may also impair beta cell function. Glycated hemoglobin A1cn(HbA1c) is an
estimation of patient ‘s average blood glucose levels for the prior 2-3 months and is
considered the most good standard for monitoring blood glucose level (glycemic control).
The American Diabetes Association (ADA) and the American Association of Clinical
Endocrinologists/American College of Endocrinology (AACE/ACE) now recommend the use
of HbA1c for diagnosing DM. An increased HbA1c level has been shown to be a main
predictor of the development and progression of microvascular complications in patients with
Type 2 diabetes. Therefore, the International Diabetes Federation (IDF) recommends an
HbA1c level upper limit of 6.5%.
There are various treatment options for type 2 diabetes depending on the patient’s age,
duration of disease and complications. Generally, the first line of treatment is through diet and
physical exercise. The second is drug therapy using oral hypoglycemic agent (Metformin) or
insulin injections. Both treatment options have the common goal of maintaining near-normal
blood glucose levels and optimal lipid levels, in order to prevent or delay the microvascular,
macrovascular and neural complications.
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