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Non-Diabetic Hypoglycemia

Hypo-Glyce-mia, Hypo means low, Glyce is from word Glucose (sugar), and Mia means Blood, so hypoglycemia is a condition when blood sugar levels are too low. What level is too low for blood sugar? Low if plasma glucose concentration below 70 mg/dL; however, signs and symptoms may not occur until plasma glucose concentrations drop below 55 mg/dL.

Non-Diabetic Hypoglycemia
illustration Non-Diabetic Hypoglycemia
Source picture: https://www.thehealthsite.com

Hypoglycemia often occurs in people with Diabetic Mellitus. In some cases, hypoglycemia occurs in people without having Diabetic Mellitus.  Hypoglycemia in people without having diabetic Mellitus is called Non-Diabetic Hypoglycemia.

There are two kinds of Non-Diabetic Hypoglycemia
a. Reactive Hypoglycemia
b. Fasting Hypoglycemia

Reactive Hypoglycemia

Reactive hypoglycemia is low blood sugar levels that occur within a few hours (3-5 hours) after a meal. So this condition is also called postprandial hypoglycemia. Reactive hypoglycemia can be caused by disorders of certain enzymes, such as fructose intolerance and galactosemia. The condition after Upper Gastrointestinal Surgery (example: gastrectomy) also can cause reactive hypoglycemia because it increases glucose absorption in the intestine and makes insulin secretion excessively.
Insulinoma, a neuroendocrine tumor can cause reactive hypoglycemia. Nonetheless, cases of insulinoma cause less reactive hypoglycemia than fasting hypoglycemia.

Fasting hypoglycemia (fasting hypoglycemia)

The pathophysiology of fasting hypoglycemia is the body's failure to regulate so that there is no euglycemia during fasting. Fasting hypoglycemia is usually caused by certain diseases that interfere with glucose metabolism, such as:

1. Nesidioblastosis (very rare): disorders of cells that secrete insulin in the pancreas.
2. Insulinoma, can occur independently or be part of the syndrome of multiple endocrine neoplasia type I (MEN 1).
3. Non-beta-cell tumors, for example, malignant mediastinal or retroperitoneal mesenchymal tumors, fibromas, carcinoids, myeloma, lymphomas, and hepatocellular and colorectal carcinomas. These secrete insulin-like growth factor (IGF-2).
4. Congenital liver enzyme disorders such as glucose-6-phosphate (G6PD) deficiency and fructose-1,6-diphosphatase
5. Impaired fatty acid oxidation as occurs in systemic carnitine deficiency and defects in ketogenesis
6. Autoimmune hypoglycemia on insulin antibodies and insulin receptors
7. There has been a reported pulmonary sarcoma (metastatic synovial cell sarcoma) which produces paraneoplastic compounds insulin-like growth factor (ILG-F) which makes a whole weakness due to hypoglycemia
8. The imbalance of certain hormones can cause hypoglycemia, such as hypoadrenalism, low growth hormone in children, glucagon, and epinephrine deficiency (very rare).
9. Hypoglycemia can also be found in critical conditions, such as multiple organ failure and sepsis

Some medications can cause hypoglycemia.

The following drugs are studied in association with the incidence of hypoglycemia:

a. Quinolone (826 patients)
- Gatifloxacin (OR 2.0, 95% CI 0.9 - 4.1)
- Other quinolones (such as ciprofloxacin, levofloxacin, and moxifloxacin) have a low quality of evidence, incidence rates range from 1-6%
b. Pentamidine (330 patients; OR 41.9, 95% CI, 7.7 - 227.7)
c. Quinine group (326 patients; OR 1.71, 95% CI 0.72 - 4.02)
d. Beta-blockers (131 patients; OR 1.9; 95% CI 0.4 - 9.4, very low quality)
e. Angiotensin-converting enzyme inhibitors or ACEI (129 patients; OR 3.0, CI 95% 1.7 - 5.3, very low quality)
f. Tramadol in noncancerous pain compared with codeine use has a double risk in the incidence of hypoglycemia that requires treatment.
g. Excessive alcohol consumption can cause hypoglycemia. The process of ethanol metabolism that occurs in the liver can reduce the NAD + / NADH ratio through oxidation-reduction reactions. Decreasing this ratio can reduce the process of liver gluconeogenesis. Ketone body formation occurs in response to hypoglycemia and makes alcoholic ketosis conditions.

Management of Hypoglycemia

In patients with acute hypoglycemia, the treatment does not look at the etiology, which is given a 50 mL D50 bolus (dextrose 50%) via the intravenous route. Glucagon or oral glucose paste can be given via intramuscular or subcutaneous pathways, if available. One of the maintenance fluid choices used is D10W (10% dextrose with water).

In chronic hypoglycemia, the underlying cause must be managed. Examples of tumors, tumors should be removed if possible. The following procedures can be carried out to maintain supportive euglycemia conditions:

- Nutrition and diet therapy by increasing the frequency of eating and especially complex carbohydrates at night
- Reducing activity
- In hospitalization, dextrose can be given intravenously
- Oreotides can be given, but because they can cause paradoxical hypoglycemia, you should do a trial dose first
- In a report, dexamethasone was given to chronic hypoglycemia due to pulmonary sarcoma undergoing palliative therapy because of the side effects of steroids, which can increase blood sugar. Dexamethasone 4 mg is given once a day (along with other drugs), and blood sugar levels can be maintained above 100 mg / dL.

In reactive hypoglycemia management, you should avoid simple sugars. It is recommended to consume 6 small portions of heavy food with 2-3 times of snacks per day. In some cases, the use of acetose and miglitol can help because it can inhibit sugar absorption and reduce postprandial hyperglycemia.

Conclusion

- Hypoglycemia is rarely found in conditions not related to diabetes, but in hospitalized conditions, the mortality rate will be higher than in hypoglycemia due to diabetes.
- If the patient comes in good general condition and has symptoms of hypoglycemia, to distinguish between 2 types of hypoglycemia (reactive hypoglycemia and fasting), do a mixed meal test or an extended fast (up to 72 hours, so it needs to be done at the hospital). Both of these examinations are intended to prove the Whipple triad.
- Reactive hypoglycemia or postprandial hypoglycemia is hypoglycemia that occurs within a 4-hour postprandial period. It can be caused by congenital enzyme disorders and upper gastrointestinal postoperative conditions.
- Fasting hypoglycemia (fasting hypoglycemia) is usually caused by certain diseases. Some examples are tumors and hormonal disorders.
- Hypoglycemia can also be found in critical conditions, such as multiple organ failure and sepsis
- Drugs that can cause hypoglycemia include quinolones, pentamidines, quinine groups, beta-blockers, ACEI, and tramadol.
- Excessive alcohol consumption in its metabolism can reduce gluconeogenesis, thus causing hypoglycemia.
- Management of hypoglycemia in acute conditions does not regard etiology, which can be given as much as 50 mL D50 bolus.
- Management of chronic hypoglycemia, differentiated, and treated based on the cause. Proper diet and nutrition and decreased activity can be done. Oreotides can be considered with supervision.
- Dexamethasone has been reported to maintain blood sugar above 100 mg / dL, given along with other drugs in patients with pulmonary sarcoma undergoing palliative therapy.
- In reactive hypoglycemia, you should avoid simple sugars. It is recommended to consume 6 small portions of heavy food with 2-3 times snacks per day

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