Hypoglycemia is a disorder caused by low blood glucose levels that can have many potential causes. Symptoms range from mild symptoms like hunger and fatigue at mild levels to more severe symptoms like blurred vision, confusion, and seizures at lower levels. Treatment depends on the underlying cause but initially involves raising blood glucose through ingesting carbohydrates or administering glucose intravenously or through glucagon injections. Long term treatment aims to prevent future hypoglycemic episodes by addressing the underlying cause, adjusting medications, patient education, and new technologies to monitor glucose levels.

1. HYPOGLYCEMIA, A GLUCOSE METABOLISM
DISORDER
Research by: Norseen Hosameldeen Lotfy
Id: 221101448
Group no. 6
Abstract
Hypoglycemia is a disorder with manifold potential etiologies, from environmental to inherited,
from presenting in isolation to presenting as a small part of a clinical syndrome, from insulin
excess to defects in counterregulatory hormones or endogenous glucose production pathways,
and from simple Mendelian disorders to those with more complex modes of inheritance,
including imprinted conditions. Classic neuroglycopenic and adrenergic symptoms may be
absent in infants, where hypoglycemia often presents with nonspecific symptoms. Diagnosis
requires evaluating the response to hypoglycemia by means of obtaining a critical sample at the
time of hypoglycemia, whether spontaneous or elicited by a diagnostic fast; however, a
diagnostic fast should never be undertaken without first excluding the possibility of a fatty acid
oxidation defect via an acylcarnitine profile. Molecular genetic testing can confirm the
underlying genetic diagnosis. Hypoglycemia treatment is specific to the cause of the
hypoglycemia, which is why proper diagnosis is crucial, causes of hypoglycemia include
medications or toxins capable of decreasing blood glucose, disorders associated with fasting
hypoglycemia, and postprandial hypoglycemic disorders. The most common type of
hypoglycemia is insulin-induced hypoglycemia in diabetics. Insulinoma is rare; however, it is the
most common hormone-secreting islet cell tumor.1
1
Javier Morales and Doron Schneider, ‘Hypoglycemia’, The American Journal of Medicine, Insulin Therapy in Type 2
Diabetes: A Reflection Upon the State of the Art Today, and the Potential Journeys yet to Come, 127.10,
Supplement (2014), S17–24 <https://doi.org/10.1016/j.amjmed.2014.07.004>.

2. Introduction
Hypoglycemia is often defined by a plasma glucose concentration below 70 mg/dL; however,
signs and symptoms may not occur until plasma glucose concentrations drop below 55 mg/dL.
The symptoms of Whipple's triad have been used to describe hypoglycemia since 1938. For
Whipple's triad, the practitioner must first recognize symptoms of hypoglycemia, then obtain
low blood glucose, and finally, demonstrate immediate relief of symptoms by the correction of
the low blood glucose with glucose treatment.
Glucose is the primary metabolic fuel for the brain under physiologic conditions. Unlike other
tissues of the body, the brain is very limited in supplying its glucose. Expectedly, the brain
requires a steady supply of arterial glucose for adequate metabolic function. Potential
complications can arise from an interruption in the glucose supply. As such, protective
mechanisms to guard against low serum blood glucose (hypoglycemia) have evolved in the
body.
During fasting states, serum glucose levels are maintained via gluconeogenesis and
glycogenolysis in the liver. Gluconeogenesis is the pathway in which glucose is generated from
non-carbohydrate sources. These non-carbohydrate sources could be protein, lipids, pyruvate,
or lactate. In contrast, glycogenolysis is the breakdown of glycogen stored into glucose
products. Much of glycogenolysis occurs in hepatocytes (liver) and myocytes (muscle).
Hypoglycemia is most often seen in patients who have diabetes that undergoing pharmacologic
intervention. Among this group, patients with type 1 diabetes are three times as likely to
experience hypoglycemia than patients with type 2 diabetes when receiving treatment.2
2
Philip Mathew and Deepu Thoppil, ‘Hypoglycemia’, in StatPearls (Treasure Island (FL): StatPearls Publishing,
2022) <http://www.ncbi.nlm.nih.gov/books/NBK534841/> [accessed 20 May 2022].

3. Causes of hypoglycemia
The principal causes of hypoglycemia can be grouped into two categories: insulin-dependent
and insulin-independent. Insulin-dependent hypoglycemia is caused by too much insulin
(hyperinsulinemia), usually attributed to the intake of a sulfonylurea drug or to the presence of
excess insulin in a patient with diabetes. Other, much less common causes of insulin-dependent
hypoglycemia may include an insulin-secreting tumour of the islets of Langerhans or a tumour,
usually of fibrous tissue, that secretes insulin-like growth factor 2 (IGF-2), which activates
insulin receptors. Insulin-independent hypoglycemia is caused by disorders that result in
impaired glucose mobilization during fasting (defects in gluconeogenesis or glycogenolysis).
Impaired glucose mobilization may be caused by adrenal insufficiency, severe liver disease,
glycogen storage disease, severe infections, and starvation. Insulin-dependent hypoglycemia is
diagnosed by an inappropriately high serum insulin concentration when symptoms of
hypoglycemia are present. Conversely, insulin-independent hypoglycemia is diagnosed by an
inappropriately low serum insulin concentration when symptoms of hypoglycemia are present.
Many people have hypoglycemia-like symptoms three to five hours after a meal. However, few
of these people have hypoglycemia when symptomatic, and their symptoms may not improve
with the administration of glucose. Symptoms can often be controlled by eating small snacks
every few hours, exercising regularly, and managing weight. A known cause of post-meal
hypoglycemia is gastrectomy (removal of the stomach) or gastric bypass surgery for obesity,
which results in rapid absorption of glucose into the blood, thereby triggering excessive insulin
secretion and hypoglycemia
Not eating or drinking enough carbohydrates (carbs). When you eat foods or drink beverages
that contain carbohydrates, your digestive system breaks down the sugars and starches into
glucose. Glucose then enters your bloodstream and raises your blood glucose level. If you don’t
eat enough carbohydrates or skip or delay any meals, your blood glucose level could drop lower
than what is healthy for you.
Fasting. Continuing to take medicines that lower your glucose level while fasting for a medical
procedure or for other purposes can also increase the risk for low blood glucose.
Increasing physical activity. Increasing your physical activity level beyond your usual routine can
lower your blood glucose level for up to 24 hours after the activity. Learn more about diabetes,
eating, and physical activity.
Drinking too much alcohol without enough food. Alcohol makes it harder for your body to keep
your blood glucose level steady, especially if you haven’t eaten in a while. Alcohol can also keep
you from feeling the first symptoms of low blood glucose, which can lead to severe symptom.3
3
‘Hypoglycemia | Pathology | Britannica’ <https://www.britannica.com/science/hypoglycemia> [accessed 20 May
2022].

4. What causes low blood glucose in people with diabetes?
Low blood glucose levels can be a side effect of insulin or some other medicines that help your
pancreas release insulin into your blood. Taking these can lower your blood glucose level.
Two types of diabetes pills can cause low blood glucose
sulfonylureas, usually taken once or twice per day, which increase insulin over several hours
meglitinides, taken before meals to promote a short-term increase in insulin.4
Manifestations of hypoglycemia
The manifestations of hypoglycemia evolve in a characteristic pattern. Mild hypoglycemia—for
example, blood glucose concentrations less than 55 mg per 100 ml (3 mmol/l)—causes hunger,
fatigue, tremour, rapid pulse, and anxiety. These symptoms are known as sympathoadrenal
symptoms because they are caused by activation of the sympathetic nervous system, including
the adrenal medulla. Activation of the sympathetic nervous system increases blood glucose
concentrations by mobilizing liver glycogen, which is the principal storage form of carbohydrate
in liver and muscle. More severe hypoglycemia—for example, blood glucose concentrations less
than 45 mg per 100 ml (2.5 mmol/l)—causes blurred vision, impaired thinking and
4
‘Low Blood Glucose (Hypoglycemia) | NIDDK’ <https://www.niddk.nih.gov/health-
information/diabetes/overview/preventing-problems/low-blood-glucose-hypoglycemia> [accessed 20 May 2022].

5. consciousness, confusion, seizures, and coma. These symptoms are known as neuroglycopenic
symptoms because they are indicative of glucose deprivation in the brain. Sympathoadrenal
symptoms and neuroglycopenic symptoms are nonspecific and should be attributed to
hypoglycemia only when relieved by either oral or intravenous administration of glucose
TREATMENT
Immediate treatment should be focused on reversing the hypoglycemia. If the patient is able to
ingest carbohydrates 15 to 20 grams of glucose should be given every 15 minutes until the
hypoglycemia has resolved.
If the patient is unable to ingest carbohydrates, or if the hypoglycemic episode is severe then
parenteral glucose should be administered. In a healthcare setting intravenous dextrose is
used. Twenty-five gram boluses of 50% dextrose are given until the hypoglycemia has resolved.
If needed, an infusion of 10% or 20% dextrose can be used to sustain euglycemia in patients
with recurrent episodes of hypoglycemia. In the outpatient setting, glucagon, given as an
intramuscular injection, is used to correct hypoglycemia. Glucose gel and other forms of oral
glucose should be used in impaired patients with caution and only in circumstances where no
alternative is available, as they pose an aspiration risk.

6. Long-term treatment should be tailored to the specific hypoglycemic disorder, taking into
account the burden of hypoglycemia on well-being and patient preferences. Offending
medications should be discontinued and underlying illnesses treated, whenever possible.
Surgical resection can be curative for insulinomas, and can alleviate hypoglycemia in non-islet
cell tumors, even if the malignancy cannot be cured. Partial pancreatectomy can be considered
in patients with β-cell disorders. Medical treatment with frequent feedings, α-glucosidase
inhibitors, diazoxide, or octreotide can be used if resection is not possible, or as a temporizing
measure. New drugs that may be helpful include long-acting somatostatin analogs, mTOR
inhibitors, and GLP-1 antagonists.
Autoimmune hypoglycemic conditions may be treated with either glucocorticoids or
immunosuppressants, but these disorders may be self-limited.
For adults taking insulin or insulin secretagogues for diabetes mellitus risk factors for
hypoglycemia, such as advanced age and renal insufficiency, should be considered. The
treatment regimen and glycemic goals should be reviewed and adjusted if needed. Patients
should be instructed on how to manage hypoglycemia, either by the ingestion of carbohydrates
if possible, or by parenteral glucagon or glucose.
If the patient has hypoglycemia unawareness, a 2-to 3 week period of strict avoidance of
hypoglycemia should be maintained, as hypoglycemia awareness will return in many patients.
For individuals with type 1 diabetes and a history of serious hypoglycemia, the use of a personal
continuous glucose monitoring device, sensor-augmented insulin pump therapy, or a hybrid
closed loop system should be considered.5
5
Marisa E. Desimone and Ruth S. Weinstock, ‘Hypoglycemia’, in Endotext, ed. by Kenneth R. Feingold and others
(South Dartmouth (MA): MDText.com, Inc., 2000) <http://www.ncbi.nlm.nih.gov/books/NBK279137/> [accessed
20 May 2022].

7. Conclusions
Hypoglycemia, an often neglected complication of diabetes therapy, has far-reaching clinical,
economical, and social impacts. Mild hypoglycemia reduces QoL, while severe hypoglycemia is
life-threatening and can precipitate major cardiovascular and cerebrovascular events. Careful
attention should be paid while deciding upon a treatment regimen for the management of
diabetes such that adequate glycemic control measures can be implemented against the life-
threatening complication of hypoglycemia. To improve diabetes-related outcomes, including
reducing the risk and consequences of hypoglycemia, effective patient education is essential.
Physician-patient collaboration is vital to develop and modify a treatment plan that is
acceptable to the patient. The use of newer antidiabetic medications with little or no risk of
hypoglycemia will reduce the future risk of hypoglycemia. Empowering patients with the tools
to monitor hypoglycemia, making them aware of the risks of hypoglycemia and the available
preventive strategies, together with an individualized plan of treatment, can decrease the
frequency and severity of hypoglycemia.6
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784865/#!po=0.490196
https://www.ncbi.nlm.nih.gov/books/NBK279137/
https://www.sciencedirect.com/science/article/abs/pii/S0002934314005841
https://www.ncbi.nlm.nih.gov/books/NBK534841/
https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/low-
blood-glucose-hypoglycemia
https://www.britannica.com/science/hypoglycemia
6
Sanjay Kalra and others, ‘Hypoglycemia: The Neglected Complication’, Indian Journal of Endocrinology and
Metabolism, 17.5 (2013), 819–34 <https://doi.org/10.4103/2230-8210.117219>.