ANSWERS AND EXPLANATIONS
1. Hypoglycemia is typically defined in diabetes as a glucose level below 70 mg/dL. The complete definition of hypoglycemia is the triad of (1) signs and symptoms of hypoglycemia; (2) a blood glucose measured to be low; and (3) resolution of those symptoms with treatment.1
Innate counterregulatory physiologic responses start at a glucose level of 70 mg/dL to protect from further drops in blood sugar. Progressive hypoglycemia below this threshold poses an increased health risk for the person.2
People without any glucose or insulin abnormalities can have glucose readings in the 60s mg/dL, particularly at night.4
This is because physiologic glucose management during fasting and while asleep is a balance between hepatic glucose release and pancreatic insulin production. Typically, the liver generates just enough glucose to meet the basal metabolic needs of the body (primarily the brain) and pancreatic insulin production is just enough to assist in the cellular uptake of available glucose.
Symptomatic hypoglycemia is defined by Whipple triad: a measured glucose less than 55 mg/dL, typical signs and symptoms of hypoglycemia, and resolution of symptoms with normalization of glucose.1
Hypoglycemia is relatively uncommon in people who are not taking antidiabetic medications, as the body possesses multiple physiologic layers of defense to prevent hypoglycemia from occurring (Table 5.1
). Ironically, the body has fewer defenses to prevent hyperglycemia. Symptomatic hypoglycemia, while very distressing for the patient, is rarely
dangerous to someone who does not have diabetes. However, hypoglycemia can be immediately life-threatening.
TABLE 5.1 Physiologic Response to Hypoglycemia5,6
Suppression of insulin secretion
Primary defense—stops most
Increased glucagon secretion
Primary counterregulatory response
Increased secretion of epinephrine
Primary response for those who do not take insulin
Increase in cortisol and growth hormone
Slower system: minor role
Increase in exogenous glucose
Compromises further responses
The patient presenting in this scenario has typical symptoms; however, it is necessary to confirm that she is indeed becoming hypoglycemic and identify a cause if possible.
2. There are many things other than hypoglycemia that could cause this patient’s symptoms (dysrhythmias, hypotension, seizures, etc). This patient’s fingerstick glucose helps to narrow our differential. Now we need to focus on her diagnosis.
These can be determined in several ways. Perhaps the simplest option would be to provide the patient with a glucometer and instructions to check glucose levels upon the occurrence of each “spell.” Another option is to have the patient use a CGM and maintain a log of when she is symptomatic. There are professional versions of CGM systems available that will allow the patient to continuously record 7 to 14 days of glucose readings that can either be downloaded or accessed remotely. This is particularly useful as it allows the physician to see if symptoms correspond in time with hypoglycemia. Alternatively, the patient could be asked to complete a glucose tolerance test.
If hypoglycemic episodes are found, the next step is to understand their relationship to eating. One way to further define hypoglycemia is by the time it occurs. Postprandial hypoglycemia is most likely to occur within 4 hours of ingestion of food. Postabsorptive hypoglycemia is hypoglycemia that occurs in the fasting state and is more likely to present while the person is sleeping (Figure 5.1
This CGM download appears to show that this person is dropping low most often after eating. The hypoglycemic spells are relatively short-lived.
3. People with prediabetes typically have insulin resistance and hyperinsulinemia. For many, the initial defect of glucose regulation is a blunted first-phase insulin response. The first-phase response is a rapid, short-duration release of insulin in response to an increase in serum glucose concentration. Subsequently, the initial blunted first-phase insulin release is followed by an exaggerated second phase of insulin release. The second-phase insulin response starts concurrently with first-phase response and typically reaches a plateau 2 hours after the initial rise in glucose. When this second phase of insulin release lasts longer than the glucose rise itself, the person is at risk for “reactive hypoglycemia.”
FIGURE 5.1. CGM for postprandial hypoglycemia.
4. In general, it is recommended that people with reactive hypoglycemia do the following:
Eat 3 to 5 small meals per day
Make sure each meal consists of mixed nutrients (carbohydrate/fat/protein) to allow for longer absorption times
Avoid simple carbohydrate ingestion alone, as carbohydrate-only meals induce significant insulin spikes leading to rapid glucose uptake followed by second-phase mismatches
Avoid intake of alcohol for similar reasons
While it is antidotal and off label, the use of DPP-4 inhibitors can help reduce the frequency and severity of these spells.
Finally, if the person has prediabetes, physical activity and weight loss (at least 5%) improve insulin sensitivity and reduce progression to type 2 diabetes and reduce risk of reactive hypoglycemia.7
Case Summary and Closing Points
In this case a person with prediabetes was experiencing postprandial hypoglycemia because of a mismatch between glucose absorption and insulin secretion. These types of episodes are often mild, but the symptom severity does not always match the level of the glucose. Assuming that there are no competing etiologies, this patient can be managed with lifestyle changes.
1. Whipple’s triad. Found in Melmed, S. Williams Text Book of Endocrinology. 13th ed. Elsevier; 2016:1582-1607. ISBN 978-0-323-29738-7.
2. International Hypoglycaemia Study Group. Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should Be reported in clinical trials: a joint position statement of the American diabetes association and the European association for the study of diabetes. Diabetes Care. 2017;40(1):155-157. doi:10.2337/dc16-2215
3. Agiostratidou G, Anhalt H, Ball D, et al. Standardizing clinically meaningful outcome measures beyond HbA1c for type 1 diabetes: a consensus report of the American association of clinical endocrinologists, the American association of diabetes educators, the American diabetes association, the endocrine society, JDRF International, the Leona M. and Harry B. Helmsley charitable trust, the pediatric endocrine society, and the T1D exchange. Diabetes Care. 2017;40(12):1622-1630. doi:10.2337/dc17-1624
4. Service FJ. Hypoglycemic disorders. NEJM. 1995;332(17):1114-1152.
5. Cryer PE. Hypoglycemia-associated autonomic failure in Diabetes. Am J Physiol Endocrinol Metab. 2001;281(6):E1115-E1121.
6. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003;26(6):1902-1912. doi:10.2337/diacare.26.6.1902
7. The Diabetes Prevention Program (DPP) Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
ANSWERS AND EXPLANATIONS
1. A normal fasting blood sugar for someone with diabetes is 80 to 130 mg/dL (4.4-7.2 mmol/L).1
Based on his fasting fingerstick readings, he is hypoglycemic most mornings. It is important to recognize his symptoms are result of his current medication regimen.
2. This person is taking too much medication and is experiencing hypoglycemic episodes. Both glipizide (sulfonylurea) and degludec (basal insulin) can cause hypoglycemia. In fact, his basal insulin dose is quite high (>0.7 U/kg/d). We could consider him “overbasalized.” It is generally ill-advised to utilize sulfonylureas when patients are taking large insulin doses. It is important to note that some of the sulfonylureas are considered Beers list medications and should be avoided in elderly patients.2
While some of his glucose readings in the morning are ideal, it is highly likely that he is dropping low overnight, which in turn is leading to glucose variability in the morning. He is also experiencing what sounds like hypoglycemia during the day based on his reported “shaky spells.”
3. Hypoglycemia signs and symptoms can vary considerably between people and even within the same person. Therefore, it is important to ask patients and their family what signs and symptoms they notice with hypoglycemic episodes. Sometimes the patient’s family members will notice changes before the patient experiences symptoms. For this reason, if possible, it is important to obtain information from both the patient and their family (Table 5.2
For most people, a combination of adrenergic and cholinergic symptoms will present first. Then, if the glucose continues to drop to the point that the brain does
not have enough glucose to function, the person will develop neuroglycopenic symptoms. Neuroglycopenia refers to alteration of neuronal function in the brain because of a shortage of available glucose. Many people need assistance once the neuroglycopenic symptoms start.
TABLE 5.2 The Most Common Symptoms of Hypoglycemia3,4
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