Diabetes mellitus
iabetes mellitus is a disease caused by insufficient insulin or insulin effect giving rise to significantly elevated levels of blood glucose. Diabetes comes from the Latin diabetes, meaning a "siphon," derived from the Greek diabetes, meaning a "to pass through." Medically, diabetes means "passing large amounts of water (urine)." Mellitus comes from the Latin mellifer = "honey." Patients with diabetes mellitus have high levels of blood sugar, which pull large amounts of water, spilling through the kidneys as a cataract of sweet urine.
In previous centuries, physicians dipped a finger in the urine of patients with excessive urination and tasted it-if it was sweet, the diagnosis was diabetes mellitus-if not, diabetes insipidus. For the remainder of this discussion, the term "diabetes" will refer to diabetes mellitus.
Normal Glucose Metabolism
The human pancreas contains glands which secrete digestive enzymes, such as amylase (starch buster) and lipase (fat buster)-sent to the small intestine to digest food. This is called the exocrine function of the pancreas.
The pancreas also has nested in its Islets of Langerhans clusters of cells secreting endocrine hormones. One such cell type is known as the beta cell, which secretes insulin to regulate blood sugar (glucose) before, during, and after meals. The insulin is released directly into the blood stream, and therefore this activity represents an endocrine function of the pancreas.
When a meal is taken, signals are sent to the beta cells to release insulin. Other hormones are released when the food bolus enters the stomach, which help raise the insulin secretion and slow emptying of the stomach. There is a spike in the blood insulin level paralleling the prandial (eating a meal) glucose spike. The liver goes from fasting glucose release to glucose storage mode, as insulin drives glucose into the liver, skeletal muscle, and lipocytes (fat cells). This causes a fall in the fasting glucose to less than 100 mg/dL, known as the basal glucose level.
The two paragraphs above describe nondiabetic glucose processing. Next follow sketches of processes found in each of the two types of diabetes mellitus.
Type 1 Diabetes mellitus
Type 1 diabetes, also called insulin dependent diabetes, lacks insulin. The disease often starts in childhood or early teens. There appears to be genetic predisposition, with the disease often following a viral infection, with the ill individual genetically predisposed to mounting a brisk antibody response to viral antigens, which cross-react with and attack the Islet beta cells, wiping them out relatively quickly.
The loss of the body's beta cell population means loss of insulin storage, secretion and basal level maintenance. The blood sugar rises and high levels of glucose in the urine cause large losses of fluid, causing excessive thirst.
Lack of available energy from the diet induced by absence of insulin causes hunger and weight loss. Hence, these are the major symptoms of diabetes: diuresis (Polyuria), thirst (Polydipsia), and hunger (Polyphagia)-known in medicine as the "3 P's."
Complications
In Type 1 diabetes, lack of insulin causes a number of metabolic problems. In addition to very high levels of glucose, which can cause coma, the metabolic apparatus of the liver is unhooked in the absence of insulin, fat metabolism is unlinked, and molecules called ketoacids accumulate, producing metabolic acidosis. Extremely high levels of glucose and acid may create life-threatening DKA (Diabetic KetoAcidosis) with coma.
The foundation of treatment for all these Type 1 complications is insulin. Given by sub Q injection, pump, or IV in the case of DKA. Since insulin is made up of chains of amino acids, oral formulations are digested and useless.
Various methods have been tried unsuccessfully to bypass the need for needle use, such as inhaled insulin, fat-coated insulin, jet injectors and more. Current injections utilize ultrafast preparations, such as Humalog, and ultra slow formulations, such as glargine insulin (Lantus), which maintains baseline blood insulin levels for nearly 24 hours after a single bedtime dose.
Complications of long-standing Type 1 diabetes include the microangiopathies: retinopathy, which affects micro blood vessels of the retina-regular dilated eye exams are necessary to catch the blood vessel changes early, allowing treatment with laser photocoagulation.
Neuropathy-micro vessels feeding the nerve sheath are interrupted causing loss of sensation, burning, and pain in the feet-nylon filament testing of sensation on the sole of the foot is needed to detect neuropathy early. Nephropathy-micro vessels of the kidney affect the glomeruli (filtering bodies of the kidney)-checking urine microalbumin regularly will help detect this early.
What can be done to prevent or reduce the occurrence and progression of microangiopathy. Diabetic diet, walking, proper use of insulin, keeping the average blood glucose near 100 mg/dL, or equivalent Hemoglobin A1C (HA1C) at 6.5%. ACE inhibitors help protect the kidneys. ARBs appear helpful.
Another type of diabetic complication is related to macroangiopathy-atherosclerosis or hardening of the medium or large coronary, cerebral, leg and foot arteries. This process causes heart attacks, angina pectoris, strokes, blocked leg arteries, foot and toe ulcers. The feet should be checked daily by the diabetic patient or a reliable observer, and at 3 monthly doctor visits.
Hypertension is a problem seen frequently in diabetes, and this should be controlled to 120/75. ACE inhibitors, ARBs, and other agents are often used for this purpose. Hyperlipidemia (high chlolesterol, LDL-C, low HDL-C, high triglycerides) are often seen and contribute to the macroangiopathy. Statins, diet and other treatments help with control of hyperlipidemia and prevention of complications.
Foot care, including treatment of toenail fungus infection with PenLac (See link "A" below.) and clotrimazole 1% cream helps reduce toe and foot infection. Prompt treatment of signs of early or impending skin breakdown is important. Properly fitting diabetic shoes are essential (Rx).
Screening for coronary artery lesions, carotid ultrasound, regular laboratory follow up, charting of blood glucose levels diurnally-all are important, as are regular dental exams and hygiene.
Type 2 Diabetes Mellitus
The second type of diabetes shares symptoms (the 3 P's) and high fasting and postprandial blood sugars with Type 1. However, Type 2 diabetics, unlike Type 1 diabetics, are more often overweight or obese (BMI > 30 kg/m2).
Type 2 diabetics have highly positive family histories-often parents, siblings, offspring, and/or grandparents have the disease. Women with this disease frequently have had gestational diabetes, with delivery of high birth weight infants.
In Type 2 diabetes, the beta cells are lost over a decade or more, causing a quiet time in which no symptoms are seen, but postprandial hyperglycemia is present. Postprandial hyperglycemia is found when a blood sugar measurement is made 2 hours after a meal or a glucose load by mouth. Hyperglycemia or glucose intolerance is found when the blood glucose is 140 to 199 mg/dL.
A two hour postprandial blood glucose of 200 mg/dL or more is DIABETES. As more beta cells are lost by the stress of insulin resistance from obesity, the pancreas fails to keep the fasting glucose below 100 mg/dL. A fasting (12 hour) blood glucose between 100 and 126 mg/dL is diagnostic of impaired fasting glucose.
A fasting blood glucose of 126 mg/dL or more is DIABETES.1 An HA1C over 6.5% indicates an average blood glucose of over 100 mg/dL and impaired glucose tolerance is often present. All these findings indicate beta cell dysfunction.
Treatment
What can be done about beta cell dysfunction? For those with a BMI in the overweight or obese range, a carbohydrate-controlled, weight loss diet and walking program will reduce metabolically active body fat mass, and reduce insulin resistance. A weight loss of 7% or more of body weight will significantly improve postprandial and fasting glucose, as well as HA1C.
The metabolic syndrome represents a time of early beta cell dysfunction and insulin resistance. People with this syndrome have high BMIs, hypertension, increased abdominal girth, high triglycerides, low HDL-Cholesterol, beta cell dysfunction, such as impaired glucose tolerance and/or impaired fasting glucose.
Treatment includes measures designed to reduce weight, abdominal girth, blood fats and glucose-mostly nonpharmacological interventions, such as diet, exercise, and/or medication-metformin represents a pharmacological therapy which may help, associated with weight stabilization or weight loss, decreased insulin resistance, reduced insulin requirements, and a lower coronary mortality.
By the time a Type 2 diabetic presents with symptoms, over 50% of the beta cells are gone, and high insulin resistance faces falling insulin levels. All of the complications discussed above in the section on Type 1 diabetes apply here.
Proper ADA (American Diabetic Association) nutritional intervention is indicated with weight loss goals, walking program, eye, dental, foot, renal, heart, lipid, blood pressure, skin and other monitoring and care. The patient is instructed in the use of medication as indicated.
If the patient has normal renal function and is not in DKA, metformin, an insulin sensitizer, can be started, along with twice daily finger stick blood glucose monitoring-first thing in the morning (fasting) and 2 hours after supper (postprandial)-these results are recorded and brought to the provider at appropriate intervals.
A secretogogue (causing secretion of insulin), such as the sulfonylurea Glyburide, may be needed at some point-it can cause hypoglycemia because it squeezes the remaining beta cells to secrete insulin. It causes weight gain, fluid retention, and has not been shown to be cardioprotective.
TZDs, such as Actos, are insulin sensitizers and cause weight gain, fluid retention and are contraindicated in heart failure or left ventricular dysfunction-not shown to be cardioprotective.
Byetta or exenatide, is an incretin mimetic, a synthetic version of exendin-4, a hormone found in Gila monster saliva . The incretin is GLP-1, a hormone found in the human body, released when food reaches the stomach, causing delayed stomach emptying and increased insulin release, lowering blood glucose. Nausea is a problem. Weight loss is seen. It has to be given by sub Q injection twice daily, short half-life-lowers HA1C 0.7%, with lowered insulin resistance secondary to weight loss.2
Januvia is a molecule that protects the body's intrinsic incretins such asGLP-1, so that GLP-1 effects last longer-oral preparation is an advantage-reduce with CKD (chronic kidney disease).
Insulin comes in long-acting forms, given once at night, and ultra fast insulins given with meals. Insulin can cause hypoglycemia (low blood glucose), weight gain (less with long-acting insulin), and fluid retention (not shown to be cardioprotective).
Resources
A. http://www.associatedcontent.com/article/1356299/using_antifungal_nail_polish_to_clear.html?cat=5
1. Diabetes Mellitus Washington Manual of Medical Therapeutics 2007; page 601
2. Physician's Drug Handbook LWW 2008; page 205
