Going on the Defensive

I signed on tonight to write a few short sentences about my much improved health, but after reading my latest comments I’m feeling rather frustrated and will do some venting instead.

Blaire seems to be very upset that some of the symptoms I’ve been having of late may be attributed to something other than mental illness.  In her efforts to convince me that all of my health problems have a psychological basis, she’s simply coming off as one of those people who would tell someone with fibromyalgia or autoimmune disease that they are just depressed.  Since the focus of one of her comments was dismissing my hypoglycemia, I would like to share an article by Vasudevan A Raghavan, MBBS, MD, MRCP from the Division of Endocrinology at Ohio State University (because someone clearly needs educated on the difference between reactive and fasting hypoglycemia):

Hypoglycemia is a syndrome characterized by a reduction in plasma glucose concentration to a level that may induce symptoms of low blood sugar. Hypoglycemia typically arises from abnormalities in the mechanisms involved in glucose homeostasis. To diagnose hypoglycemia, the Whipple triad characteristically is present. This triad includes the documentation of low blood sugar, presence of symptoms, and reversal of these symptoms when the blood sugar level is restored to normal.

Hypoglycemic symptoms are related to the brain and the sympathetic nervous system. Decreased levels of glucose lead to deficient cerebral glucose availability (ie, neuroglycopenia) that can manifest as confusion, difficulty with concentration, irritability, hallucinations, focal impairments (eg, hemiplegia), and eventually, coma and death. Stimulation of the sympatho-adrenal nervous system leads to sweating, palpitations, tremulousness, ANXIETY, and hunger. [hmmm... that all sounds very familiar, huh]

The adrenergic symptoms often precede the neuroglycopenic symptoms and, thus, provide an early warning system for the patient. Studies have shown that the primary stimulus for the release of catecholamines is the absolute level of plasma glucose. The rate of decrease of glucose is less important. Previous blood sugar levels can influence an individual’s response to a particular level of blood sugar. However, one must appreciate that a patient with chronic hypoglycemia can have almost no symptoms.

Symptoms of hypoglycemia may be categorized as neurogenic (adrenergic) or neuroglycopenic.

• Symptoms due to sympatho-adrenal activation include sweating, shakiness, tachycardia, anxiety, and a sensation of hunger.
• Neuroglycopenic symptoms include weakness, tiredness, or dizziness; inappropriate behavior (sometimes mistaken for inebriation), difficulty with concentration; confusion; blurred vision; and, in extreme cases, coma and death.
• The timing of onset of these symptoms relative to the time of meal ingestion is crucial in the evaluation of a patient with hypoglycemia. Fasting hypoglycemia typically occurs in the morning before eating or during the day, particularly in the afternoon if meals are missed or delayed. Postprandial hyperglycemia typically occurs 2-4 hours after eating food, especially when meals contain high levels of simple carbohydrates. Postprandial symptoms are typically due to reactive causes, but some patients with insulinoma also may present with postprandial symptoms. About 4-6 hours after food ingestion, plasma glucose concentrations are 80-90 mg/dL, and rates of glucose utilization and production are approximately 2 mg/kg/min. Glucose production is primarily (70-80%) from hepatic glycogenolysis, with a lesser contribution (20-25%) from hepatic gluconeogenesis.

Causes of Fasting Hypoglycemia

• Nesidioblastosis is characterized by a diffuse budding of insulin-secreting cells from pancreatic duct epithelium and pancreatic microadenomas of such cells; it is a rare cause of fasting hypoglycemia in infants and an extremely rare cause in adults.
• Causes of fasting hypoglycemia usually diagnosed in infancy or childhood include inherited liver enzyme deficiencies that restrict hepatic glucose release (deficiencies of glucose-6-phosphatase, fructose-1,6-diphosphatase, phosphorylase, pyruvate carboxylase, phosphoenolpyruvate carboxykinase, or glycogen synthetase). Inherited defects in fatty acid oxidation, including that resulting from systemic carnitine deficiency and inherited defects in ketogenesis (3-hydroxy-3-methylglutaryl-CoA lyase deficiency) cause fasting hypoglycemia by restricting the extent to which nonneural tissues can derive their energy from plasma FFA and ketones during fasting or exercise. This results in an abnormally high rate of glucose uptake by nonneural tissues under these conditions.
• Drugs – Ethanol, haloperidol, pentamidine, quinine, salicylates, and sulfonamides
• Insulin-producing tumors of pancreas: Islet cell adenoma or carcinoma (insulinoma) is an uncommon and usually curable cause of fasting hypoglycemia and is most often diagnosed in adults. It may occur as an isolated abnormality or as a component of the type I multiple endocrine neoplasia (MEN) syndrome. Carcinomas account for only 10% of insulin-secreting islet cell tumors. Hypoglycemia in patients with islet cell adenomas results from uncontrolled insulin secretion, which may be clinically determined during fasting and exercise. Approximately 60% of patients with insulinoma are female. Insulinomas are uncommon in persons younger than 20 years and are rare in those younger than 5 years. The median age at diagnosis is about 50 years, except in patients with MEN syndrome, in which it is in the mid 20s. Ten percent of patients with insulinoma are older than 70 years.
• Non–beta-cell tumors: Hypoglycemia may also be caused by large non–insulin-secreting tumors, most commonly retroperitoneal or mediastinal malignant mesenchymal tumors. The tumor secretes abnormal insulinlike growth factor (large IGF-II), which does not bind to its plasma binding proteins. This increase in free IGF-II exerts hypoglycemia through the IGF-I or the insulin receptors. The hypoglycemia is corrected when the tumor is completely or partially removed and usually recurs when the tumor regrows.
• Autoimmune hypoglycemia – Insulin antibodies and insulin receptor antibodies
• Surreptitious sulfonylurea use/abuse
• Hormonal deficiencies – Hypoadrenalism (Cortisol), hypopituitarism (growth hormone) (in children), glucagons deficiency (rare), and epinephrine (very rare)
• Critical illnesses – Cardiac, hepatic, and renal diseases; sepsis with multiorgan failure
• Combination of one or more of the above, for example, chronic renal failure and sulphonylurea ingestion

Diet

• Dietary therapy may be effective for improving symptoms in patients with fasting hypoglycemia. Frequent meals/snacks are preferred, especially at night, with complex carbohydrates.
• For patients with reactive hypoglycemia, initiate a carbohydrate restriction. Patients should avoid simple sugars, increase the frequency of their meals, and reduce the size of their meals. Patients may require 6 small meals and 2-3 snacks per day.

Activity

Because exercise burns carbohydrates and increases sensitivity to insulin, patients with fasting hypoglycemia should avoid significant activity. On the other hand, patients with reactive hypoglycemia often find that their symptoms improve after embarking on a routine exercise program.

Further Outpatient Care

• If the patient has fasting hypoglycemia and the cause is treatable, long-term follow-up usually is not needed. If the cause cannot be treated definitively (eg, inoperable pancreatic insulinoma), diazoxide can be used to elevate blood glucose levels and chemotherapy that specifically targets the beta cell (ie, using cytotoxic agents such as streptozotocin) should be considered.
• If the patient has reactive hypoglycemia, periodic outpatient monitoring is warranted to assess the continued presence of symptoms.

Complications

• Untreated fasting hypoglycemia can lead to severe neuroglycopenia and, possibly, death.
• Untreated reactive hypoglycemia may cause significant discomfort to the patient, but long-term sequelae are not likely.

Prognosis

• Prognosis depends on the CAUSE of the hypoglycemia. If the cause of fasting hypoglycemia is identified and curable, prognosis is excellent. If the problem is not curable, such as an inoperable malignant tumor, long-term prognosis is poor. [wonder what the prognosis is if your doctors don't even bother to look for the cause?] However, note that these tumors may progress rather slowly.
• If the patient has reactive hypoglycemia, symptoms often spontaneously improve over time, and long-term prognosis is very good.