Uptake of the IV bolus of dextrose improved the patient's level of consciousness, but she still had focal neurological symptoms, including hemiparesis and aphasia.

Fifteen minutes after the initiation of treatment with serum dextrose, she was responsive to pain and stimulation. Thus, a CT scan to rule out vascular events was deferred. After regaining consciousness, the patient mentioned having T1DM since the age of 18 years and receiving regular treatment with insulin and Neutral Protamine Hagedorn insulin NPH.

In this setting, non-beta cell tumors are unlikely to be diagnosed. The patient also claimed experiencing HU for the previous 2 years. She also mentioned at least three episodes of severe hypoglycemic episodes weekly during the last 3 months that may have necessitated the assistance of others. These episodes mostly happened at night.

The patient claims that she was very active during her work shift and did not have time to eat adequately, but she injected insulin at the usual dose.

The injection regimen of the patient consisted of multiple insulin injections day: regular insulin, 10 U before breakfast and dinner, and 6 U before lunch; NPH insulin, 25 U in the morning and 10 U at night.

Her dose had been adjusted at her last visit to her endocrinologist 3 months previously, but she has had several severe hypoglycemic attacks during the last 4 weeks.

She was examined by a neurologist in the morning for her focal neurological symptoms, and the examination revealed no deficits. Her medical history was also concerning for hpoglycemia-associated autonomic failure HAAF , and she was recommended to have this condition evaluated as outpatient.

To avoid recurrent hypoglycemia, further laboratory tests and a follow-up evaluation with an endocrinologist were recommended, as well a switch from human insulins to analog insulins.

Hypoglycemia is a common side effect of various diabetes medications, such as insulin and sulfonylureas [ 8 , 11 ]. This condition can cause life-threatening episodes, significant morbidity, and a lack of optimal glycemic control. Many routine activities, such as driving, job performance, and sporting competitions, can be affected by hypoglycemia [ 12 ].

This clinical scenario necessitates additional investigation and a review of the medical regimen. The true prevalence of hypoglycemia in persons with T1DM is unknown [ 2 , 8 , 19 ]. HU happens more often in those who: 1 repeatedly have low blood sugar episodes which can cause the patient to stop sensing the early warning signs of hypoglycemia ; 2 have had diabetes for an extended time; and 3 tightly control their diabetes which intensifies their probabilities of having low blood sugar reactions [ 15 , 16 , 18 ].

Changes to insulin regimen. Decreased glucose that enters the bloodstream. The possible explanation of the hypoglycemia in our patient is expected to be delayed meals due to work shifts and lack of carbohydrates at night before sleeping [ 1 , 2 , 6 , 8 , 11 ].

Increased glucose uptake. Other possible causes, in the present case, are due to increased physical activity following work shifts [ 1 , 2 , 6 , 8 , 11 ]. Decreased endogenous glucose production following alcohol consumption. The medical history of our patient and test results did not confirm this possibility [ 1 , 2 , 6 , 8 , 11 ].

Decreased renal insulin excretion following renal failure. The medical history of our patient and test results did not confirm renal insufficiency [ 1 , 2 , 6 , 8 , 11 ].

Increased insulin sensitivity following weight loss or exercise or severe glycemic control. She also mentioned beginning sports activities in the last 6 months [ 1 , 2 , 6 , 8 , 11 ].

Previous studyies have linked both tight glycemic control [ 22 , 23 , 24 ] and attempts to rapidly control hemoglobin A1c HbA1c levels [ 22 , 25 ] to increased hypoglycemic events [ 26 ].

Our patient had an HbA1c of 5. According to related studies in patients with insulin-dependent diabetes, the incidence of hypoglycemic attacks in patients taking regular insulin is higher than that in patients taking newer insulins, including lispro [ 27 , 28 , 29 ], which is consistent with our reported case.

Our patient had also been given regular insulin and NPH. The risk of hypoglycemia is higher with human insulin than with analog insulin such as Lantus and Novorapid [ 30 ], and therefore the preferred type of insulin in T1DM is analog insulin.

A study by Smith et al. revealed that reduced compliance to changes in insulin regimen in hypoglycemia unawareness is consistent with hypoglycemic stress habituation. These authors concluded that therapies aimed at altering repetitive risky behavior could be beneficial in restoring hypoglycemia awareness and preserving toward severe hypoglycemia [ 31 ].

HAAF is another possible explanation for the hypoglycemic episodes experience by our patient. HAAF is a type of functional sympathoadrenal failure caused most commonly by recent antecedent iatrogenic hypoglycemia and is at least partially reversible by careful avoidance of hypoglycemia.

HAAF can be maintained by recurrent iatrogenic hypoglycemia [ 32 ]. It is vital to distinguish HAAF from conventional autonomic neuropathy, which can also be caused by diabetes. Sympathoadrenal activation appears to be inhibited only in response to hypoglycemia, while autonomic activities in organs, such as the heart, gastrointestinal tract, and bladder, are unaffected [ 32 ].

Our case was examined for this possibility due to her long history of severe hypoglycemic attacks, which needed further evaluation to rule out having HAAF after an evaluation of sympathoadrenal response to hypoglycemia.

People with HU are unable to detect drops in their blood sugar level, so they are unaware that they require treatment. Unawareness of hypoglycemia increases the risk of severe low blood sugar reactions when they need someone to help them recover. People who are unaware of their hypoglycemia are also less likely to be awakened from sleep when hypoglycemia occurs at night.

People who are hypoglycemic but are unaware of it must take extra precautions to monitor their blood sugar levels regularly. This is especially true before and during critical tasks, such as driving.

When blood sugar levels are low or begin to fall, a CGM can sound an alarm. Such a device can be a great assistance to people with HU [ 12 , 15 ]. With continuous BG monitoring, children and adults with T1DM spend less time in hypoglycemia and simultaneously decrease their HbA1c level [ 33 , 34 ].

A prior study showed that diabetic patients with reduced beta-adrenergic sensitivity may be unaware of hypoglycemia, and the best suggestion for these patients is to strictly avoid hypoglycemia [ 35 , 36 ].

Our patient was also advised to have emergency glucose tablets, intermuscular, or intranasal glucagon injections at her disposal all of the time to avoid hypoglycemic attacks.

The glucagon injection pen was not available in Iran at the time of the episode described here, neither was a CGM, so she was recommended to follow educational sessions on carbohydrate counting and perform excessive SBGM. The patient was given strict advice based on her job and profession, as well as the need to control her blood sugar level to the extent that it did not interfere with her professional and daily functioning [ 12 ].

She was advised to see her endocrinologist to adjust her insulin dose based on her unawareness of hypoglycemia attacks and her work schedule, which may not allow her enough time to rest and consume enough carbohydrates, potentially leading to life-threatening attacks, especially since her coworkers were unaware of her medical condition.

It is strongly advised that people with diabetes, especially patients like this case, wear some sort of identification, such as a bracelet, or carry a card that state their condition [ 15 ]. Normalization of autonomic response takes 7—14 days on average, but it can take up to 3 months to normalize the threshold of symptoms, neuroendocrine response, and glucagon response although glucagon response is never fully recovered [ 37 , 38 ].

Another suggestion was to switch human insulin to the analog type of insulin. Hypoglycemia is a fairly common complication in diabetic patients receiving oral or insulin therapy.

However, in a subset of patients who are unaware of hypoglycemia for a variety of reasons, these warning signs do not exist, resulting in severe and life-threatening hypoglycemic episodes.

As a result, patients who have multiple episodes of HU are advised to raise their blood sugar control threshold for at least 2 weeks and to wear at all times a bracelet or label indicating their medical condition.

In addition, in these patients, the use of CGM equipped with alarms in the occurrence of severely low blood sugar can be a perfect option. Patient data and information can be accessed for review after obtaining permission from the patient without any disclosure of her name.

Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. Article CAS Google Scholar. Cryer PE. Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness.

Endocrinol Metab Clin North Am. Hoeldtke RD, Boden G. Epinephrine secretion, hypoglycemia unawareness, and diabetic autonomic neuropathy. Ann Intern Med. Greenspan SL, Resnick MN.

Geriatric endocrinology. In: Greenspan FS, Strewler GJ, editors. Basic and clinical endocrinology. Stamford: Appleton and Lange; Mitrakou A, Ryan C, Veneman T, Mokan M, Jenssen T, Kiss I, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction.

Am J Physiol-Endocrinol Metabol. Wilson JD, Foster DW, Kronenberg HM, Larsen PR. The anterior pituitary. Williams textbook of endocrinology. Philadelphia: WB Saunders Co; Joslin EP, Kahn CR. Ronald Kahn Hypoglycemia: pathophysiology, diagnosis, and treatment.

Oxford:: Oxford University Press; Google Scholar. Veneman T, Mitrakou A, Mokan M, Cryer P, Gerich J. Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia. Kalra S, Mukherjee JJ, Venkataraman S, Bantwal G, Shaikh S, Saboo B, et al.

Hypoglycemia: the neglected complication. Indian J Endocrinol Metabol. Article Google Scholar. Cryer P. Hypoglycemia in diabetes: pathophysiology, prevalence, and prevention.

Arlington County: American Diabetes Association; In: Loriaux L, Vanek C, editors. Endocrine emergencies: recognition and treatment. Cham: Springer International Publishing; Chapter Google Scholar. Liu J, Wang R, Ganz ML, Paprocki Y, Schneider D, Weatherall J.

The burden of severe hypoglycemia in type 1 diabetes. Curr Med Res Opin. Whipple AO. Thesurgical therapy of hyperinsu-linism. J Int Chir. American Diabetes Association. Glycemic targets: standards of medical care in diabetes— Lamounier RN, Geloneze B, Leite SO, Montenegro R, Zajdenverg L, Fernandes M, et al.

Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil. Diabetol Metab Syndr. Amiel SA, Choudhary P, Jacob P, Smith EL, De Zoysa N, Gonder-Frederick L, et al.

Hypoglycaemia awareness restoration programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care HARPdoc : protocol for a group randomised controlled trial of a novel intervention addressing cognitions.

BMJ Open. Hopkins D, Lawrence IA, Mansell P, Thompson G, Amiel S, Campbell M, et al. Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the UK DAFNE experience.

Binder C, Bendtson I. Endocrine emergencies. Pedersen-Bjergaard U, Pramming S, Heller SR, Wallace TM, Rasmussen ÅK, Jørgensen HV, et al. Severe hypoglycaemia in adult patients with type 1 diabetes: influence of risk markers and selection.

Diabetes Metab Res Rev. Zammitt NN, Geddes J, Warren RE, Marioni R, Ashby JP, Frier BM. Serum angiotensin-converting enzyme and frequency of severe hypoglycaemia in Type 1 diabetes: does a relationship exist?

Diabet Med. McCulloch D. Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus. Up to Date Medical , Becker K. Endocrine drugs and values. Principles and practice of endocrinology and metabolism. Philadelphia: JB Lippincott; Hypoglycemia in the diabetes control and complications trial.

Diamond MP, Reece EA, Caprio S, Jones TW, Amiel S, DeGennaro N, et al. Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus. Am J Obstet Gynecol. Some health care professionals may prefer to use newer basal insulins in patients at risk of hypoglycemia because these insulins seem to have less risk of hypoglycemia than the older ones, but they can still cause hypoglycemia, and we need to be aware of that.

I think that for many people, it is easier to administer mealtime insulin when they have an insulin pump. It is also important to remember that some patients may be afraid to report episodes of hypoglycemia to their doctors because of legal implications.

For example, some states may require people with diabetes to not have a hypoglycemia episode for 6 to 12 months before they can drive a vehicle. Health care professionals should emphasize to patients that they should know what their blood glucose level is before they drive a car, and that they should have food on hand, so if their glucose level drops, they can manage it.

Q: What research is being conducted on hypoglycemia unawareness? A: Researchers are interested in different aspects of hypoglycemia unawareness such as the cause, complications, and treatments.

Some groups are studying why recurrent hypoglycemia leads to impaired awareness. Is it a problem with brain adaptation to hypoglycemia, or is it only a problem with people who have severe glucagon deficiency?

Other groups are doing research on the long-term effects of recurrent hypoglycemia on the function of other organs. I just finished a study where we gave people naloxone during an episode of exercise to determine if they recognize their hypoglycemia the next day, but the study was just completed, so we do not have results yet.

We welcome comments; all comments must follow our comment policy. Blog posts written by individuals from outside the government may be owned by the writer and graphics may be owned by their creator. In such cases, it is necessary to contact the writer, artist, or publisher to obtain permission for reuse.

Q: What is hypoglycemia? Q: What is hypoglycemia unawareness, and how common is it? What is your experience managing hypoglycemia unawareness? Tell us in the comments below. Click to load comments Loading comments Blog Tools Subscribe Subscribe to get blog updates.

Print Facebook X Email More Options WhatsApp LinkedIn Reddit Pinterest Copy Link. Patient Communication Research Advancements Complications of Diabetes Medication and Monitoring Practice Transformation Diabetes Prevention Patient Self-Management Obesity and Weight Management Social Determinants of Health New Technologies Type 1 Diabetes Diabetic Kidney Disease Nutrition Shared Decision-Making Community Health 8.

July 1. June 2. May 1. April 1. March 1. July 2. May 2. April 2. March 2. June 3. July 3. May 4.

When patients report that they have been experiencing low blood glucose, it is important to define hypoglycemia together. What do patients consider to be a low blood glucose level? Is this based solely on feelings or have they been able to actually check their blood glucose at the moment of symptoms?

If self-monitoring of blood glucose SMBG records are available, at what point or level of blood glucose do individuals start to experience symptoms of hypoglycemia? People with consistently high blood glucose levels will feel hypoglycemic at blood glucose levels higher than the normal range, whereas those with tight glycemic control may feel hypoglycemic at lower levels.

Discussing these concepts with patients provides practical motivation and support for the role of SMBG in medication adjustment and safety. Another area worthy of inquiry is patients' actions leading up to hypoglycemic events.

It may seem obvious that changes in food choices, physical activity, or medication can produce hypoglycemia, but letting patients verbalize their patterns or changes in patterns can allow them to discover this for themselves.

Eating a smaller meal or one containing less carbohydrate than normal may result in a low postprandial blood glucose level.

If changes in food choices lead to hypoglycemic events, patients likely did not do this on purpose. Have they been less hungry lately, or are they trying to lose weight? Has there been a change in their oral health?

Many individuals do not understand the complexity of factors affecting postprandial glucose levels or are not able to consistently identify a low-carbohydrate or high-carbohydrate meal or to accurately estimate the number of calories in their meals.

For patients who are doing basic carbohydrate counting, explore the potential impact of the presence or absence of protein and fat in meals. These individuals may not recognize or may easily forget the role of protein and fat because they are concentrating more closely on carbohydrates.

For patients who are counting calories or using some overall means of portion control, explore the impact of significant changes in carbohydrate content and assess their ability to identify foods that are rich in carbohydrates. These individuals may not understand the importance of carbohydrate budgeting.

In these discussions, providers may find patients to be at a point of readiness to be referred to a registered dietitian or certified diabetes educator for more nutrition education. Changes in physical activity that can lead to hypoglycemia can include more than just intentional exercise. Particularly for people who are usually sedentary, an increase in overall energy and stamina that leads to doing more errands, gardening, or housework than normal may result in hypoglycemia.

In contrast, athletes with diabetes who have temporary periods of two-a-day practices might need help learning how to adjust their medication to deal with the increase in insulin sensitivity and glucose uptake that results from increased exercise.

Asking open-ended questions about the timing and dosing of medication or asking patients to demonstrate or describe their injection technique also may reveal potential causes of hypoglycemia. Finally, it is important to ask exactly how patients treat low blood glucose. This question often reveals a tendency to consume more than the recommended 15—20 g of carbohydrate or may uncover a misunderstanding of what types of foods and substances will most quickly raise the blood glucose level.

Table 2 reviews the recommended treatment guidelines for hypoglycemia. Discussing patients' knowledge of food choices, physical activity, and medication can help prevent future hypoglycemia and allow providers to best determine any necessary changes in medication and identify education needs.

Lipohypertrophy is a buildup of fat at the injection site. Injecting insulin into lipohypertrophy usually causes impaired absorption of insulin. However, injecting into sites of lipohypertrophy can result in erratic and unexplained fluctuations in blood glucose.

When advising patients to rotate to new injection sites, HCPs should note the need for caution. Because insulin injected into a fresh site likely will be absorbed more efficiently, doses may need to be decreased. Regular rotation of insulin injection sites may prevent lipohypertrophy from occurring.

Keep in mind that some patients, especially children, may be hesitant to inject in areas other than one with lipohypertrophy because they report that area is less sensitive to injections.

Many alcohol-containing drinks contain carbohydrate and can cause initial hyperglycemia. However, alcohol also inhibits gluconeogenesis, which becomes the main source of endogenous glucose about 8 hours after a meal. Therefore, there is increased risk of hypoglycemia the morning after significant alcohol intake if there has not been food intake.

Alcohol consumption can also interfere with the ability to feel hypoglycemia symptoms. For patients whose blood glucose is well controlled, the ADA guidelines for alcohol intake suggest a maximum of one to two drinks per day, consumed with food. Close monitoring of blood glucose for the next 10—20 hours may be beneficial.

Insulin and sulfonylurea clearance is decreased with impaired hepatic or renal function. Decreasing the dosages of some anti-hyperglycemic medications and avoiding others may be necessary. Of the oral agents, sulfonylureas are more likely to cause hypoglycemia. Glimepiride may be a safer choice than glyburide or glipizide in elderly patients and those with renal insufficiency because it is completely metabolized by the liver; cytochrome P reduces it to essentially inactive metabolites that are eliminated renally and fecally.

As kidney function declines, exogenous insulin has a longer duration and is more unpredictable in its action, and the contribution of glucose from the kidney through gluconeogensis is reduced. Patients who have had diabetes for many years or who have had poor control are at risk for autonomic neuropathy, including gastroparesis, or slow gastric emptying.

It is thought that delayed food absorption increases the risk of hypoglycemia, although evidence is lacking. Intercurrent gastrointestinal problems such as gastroenteritis or celiac disease can also be causes of altered food absorption.

Medications such as metoclopramide or erythromycin are used to increase gastric emptying time. Giving mealtime insulin after meals or using an extended bolus on an insulin pump may also help to prevent potential hypoglycemia related to delayed gastric emptying.

Hypothyroidism slows the absorption of glucose through the gastrointestinal tract, reduces peripheral tissue glucose uptake, and decreases gluconeogenesis.

For people with diabetes, this can cause increased episodes of hypoglycemia. Measuring the level of thyroid-stimulating hormone is the most accurate method of evaluating primary hypothyroidism.

As hypothyroidism is treated, an increase in insulin dose will likely be needed to meet the increased metabolic need. The risk of severe hypoglycemia increases with age. Slowed counter-regulatory hormones, erratic food intake, and slowed intestinal absorption place older adults at higher risk of hypoglycemia.

The incidence of mild and severe hypoglycemia is highest between 8 and 16 weeks' gestation in type 1 diabetes. Severe hypoglycemia in early pregnancy is three times more frequent than during preconception.

Providing preconception counseling, including information about a potential increase in hypoglycemia early in pregnancy, may help reduce the incidence of hypoglycemia for women planning to become pregnant.

Intentional insulin overdose is thought to be relatively rare, but the actual prevalence is difficult to measure. A common method used to estimate the number of deliberate insulin overdoses is to analyze data from regional poison control centers.

In the annual report of the American Association of Poison Control Centers, only 3, of the 2,, inquiries 0. Although rare, most cases of insulin overdose reported to poison control centers have occurred during suicide attempts.

HCPs who are unable to identify other reasons for persistent hypoglycemia may not be able to rule out intentional induction of hypoglycemia. Patients who are suspected of intentionally inducing hypoglycemia should be referred to a behaviorist for evaluation and treatment.

Individuals with diabetes and, ideally, their care partners who have received diabetes self-management education should have a better understanding of how their medication, meal plan, and physical activity interact to achieve optimal glucose control while limiting hypoglycemia. They also will be better equipped to prevent and treat hypoglycemia should it occur.

HCPs should help individuals who have not had an opportunity to work with a diabetes educator or dietitian to identify educational resources in their area. Table 3 provides a list of resources for locating local diabetes educators and dietitians.

Patients who have not had a recent diabetes education update may benefit from a refresher course. Hypoglycemia education includes not only appropriate treatment and prevention, but also driving precautions, including performing SMBG before driving and frequently while driving for individuals who are prone to hypoglycemia.

People with diabetes also should keep glucose tabs, gel, or other appropriate oral treatment options in their vehicle. Encouraging individuals to wear a medical identification listing diabetes and any other diagnoses they may have is also important.

Using a pattern-management approach for reviewing SMBG data will allow individuals with diabetes and their HCPs to adjust medications to better match food intake and physical activity. Reviewing SMBG results that include fasting, postprandial, and nocturnal test results will allow HCPs to craft a more physiological medication regimen for patients.

SMBG also allows individuals to take appropriate preventive and follow-up actions related to hypoglycemia. Today, the use of continuous glucose monitoring CGM systems can also help to limit hypoglycemia, especially in those who have frequent episodes with hypoglycemia unawareness and nocturnal hypoglycemia.

HCPs may order a diagnostic CGM study to determine whether nocturnal hypoglycemia is occurring and to better identify patterns of hyperglycemia and hypoglycemia around the clock.

An increasing number of individuals with insulin-requiring diabetes are wearing CGM sensors as a part of their routine diabetes management.

Blood Glucose Awareness Training should be considered for patients with recurrent, severe hypoglycemia. Hypoglycemia can be a limiting factor to optimal diabetes control. However, the risk of hypoglycemia can be minimized through adequate diabetes self-management education, SMBG, and individualization of medication regimens employing physiological insulin replacement and appropriate medication management.

HCPs' careful consideration of all potential factors associated with hypoglycemia will help patients reduce their hypoglycemia risk and achieve optimal glycemic control, thereby reducing their risk of long-term diabetes complications.

Reducing the risks of hypoglycemia and empowering individuals and their families to prevent and treat it appropriately will ultimately help to reduce patients' fear of hypoglycemia and could result in improved diabetes control and quality of life.

Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Clinical Diabetes. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation.

Volume 30, Issue 1. Previous Article Next Article. Defining Hypoglycemia. Investigating the Causes and Effects of Hypoglycemia. The American Diabetes Association Page. Accessed 1SEP 2 The system is intended to complement, not replace, information obtained from standard blood glucose monitoring devices.

All therapy adjustments should be based on measurements obtained from standard blood glucose monitoring devices. All therapy adjustments should be based on measurements obtained using a home blood glucose meter and not on values provided by the system.

The system is intended to complement, not replace, information obtained from standard blood glucose monitoring devices, and is not recommended for people who are unwilling or unable to perform a minimum of two meter blood glucose tests per day, or for people who are unable or unwilling to maintain contact with their healthcare professional.

The system requires a functioning mobile electronic device with correct settings. If the mobile device is not set up or used correctly, you may not receive sensor glucose information or alerts.

Feeling shaky Being nervous or anxious Sweating, chills and clamminess Irritability or impatience Confusion Fast heartbeat. Tingling or numbness in the lips, tongue, or cheeks Headaches Coordination problems, clumsiness Nightmares or crying out during sleep Seizures.

Hypoglycemia unawareness As unpleasant as they may be, these symptoms are useful as they help let you know that action is needed to correct a low blood sugar. They are also less likely to wake up from an overnight low.