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The Hypoglycemia Risk Calculator is provided free of charge for informational purposes only. The content is based on on Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (Seaquist ER, Anderson J, Childs B, et al. Diabetes Care. 2013;36(5):1384-1395. doi:10.2337/dc12-2480). Knighten Health has used all reasonable care in compiling the information but makes no warranty as to its accuracy.
Your patient has [Diabetes type II] with a disease duration of [2 years] and [is not taking] [a sulfonylurea]. Your patient has been taking [insulin] for [2 years]. Your patient [has] had an glucose concentration less than 70 mg/dL and [has] experienced symptoms consistent with hypoglycemia.
Recurrent hypoglycemia has been shown to reduce the glucose level that precipitates the
counterregulatory response necessary to restore euglycemia during a subsequent episode of
hypoglycemia. As a result, patients with frequent hypoglycemia do not experience the symptoms from
the adrenergic response to a fall in glucose until the blood glucose reaches lower and lower levels. For
some individuals, the level that triggers the response is below the glucose level associated with
neuroglycopenia. The ﬁrst sign of hypoglycemia in these patients is confusion, and they often must rely
on the assistance of others to recognize and treat low blood glucose. Such individuals are said to have
developed hypoglycemia unawareness.
Defective glucose counterregulation (the result of loss of a decrease in insulin production and an increase in glucagon release along with an attenuated increase in epinephrine) and hypoglycemia unawareness (the result of an attenuated increase in sympathoadrenal activity) are the components of hypoglycemia-associated autonomic failure (HAAF) in patients with diabetes. HAAF is a form of functional sympathoadrenal failure that is most often caused by recent antecedent iatrogenic hypoglycemia and is at least partly reversible by scrupulous avoidance of hypoglycemia.
Defective glucose counterregulation and hypoglycemia unawareness substantially increase the risk of severe hypoglycemia with its morbidity and potential mortality. A particularly low plasma glucose concentration might trigger a robust, potentially fatal sympathoadrenal discharge. Life-threatening episodes of hypoglycemia need not be frequent to be devastating.
Hypoglycemia is a common problem in children with type 1 diabetes because of the challenges
presented by insulin dosing, variable eating patterns, erratic activity, and the limited ability of small
children to detect hypoglycemia. The infant, young child, and even the adolescent typically exhibit
unpredictable feeding, not eating all the anticipated food at a meal and snacking unpredictably between
meals, and have prolonged periods of fasting overnight that increase the risk of hypoglycemia.
Infants and toddlers may not recognize the symptoms of hypoglycemia and lack the ability to effectively communicate their distress. Caregivers must be particularly aware that changes in behavior such as a loss of temper may be a sign of hypoglycemia.
Puberty is associated with insulin resistance, while at the same time the normal developmental stages of adolescence may lead to inattention to diabetes and increased risk for hypoglycemia. As children grow, they often have widely ﬂuctuating levels of activity during the day, which puts them at risk for hypoglycemia. Minimizing the impact of hypoglycemia on children with diabetes requires the education and engagement of parents, patients, and other caregivers in the management of the disease.
Landmark data on the impact of hypoglycemia on adults with type 1 diabetes come from the Diabetes Control and Complications Trial (DCCT) and its follow-up study, where cognition has been systematically measured over time. In this cohort, performance on a comprehensive battery of neurocognitive tests at 18 years of follow-up was the same in participants with and without a history of severe hypoglycemia. Despite such reassuring ﬁndings, recent investigation with advanced imaging techniques has demonstrated that adults with type 1 diabetes appear to call upon a greater volume of the brain to perform a working memory task during hypoglycemia. These ﬁndings suggest that adults with type 1 diabetes must recruit more regions to preserve cognitive function during hypoglycemia than adults without the disease. More work will be necessary to understand the signiﬁcance of these observations on the long-term cognitive ability of adults with type 1 diabetes.
There is growing evidence that patients with type 2 diabetes might be particularly vulnerable to adverse
events associated with hypoglycemia. Over the last decade, three large trials examined the effect of
glucose lowering on cardiovascular events in patients with type 2 diabetes: ACCORD (Action to Control
Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and
Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial).
All three trials clearly demonstrated that an episode of severe hypoglycemia was associated with an increased risk of subsequent mortality. In ACCORD, those who had one or more severe hypoglycemic episodes had higher rates of death than those without such episodes across both study arms (hazard ratio 1.41 [95% CI 1.03–1.93]). One-third of all deaths were due to cardiovascular disease, and hypoglycemia was associated with higher cardiovascular mortality. In VADT, a recent severe hypoglycemic event was the strongest independent predictor of death at 90 days. In ADVANCE, where rates of hypoglycemia were low, a similar pattern was found. Of course, in post hoc analyses a causal relationship cannot be established with certainty. It is possible that the association between hypoglycemia and death may be merely an indicator for vulnerability for death from any cause.
The relationship between hypoglycemia and subsequent cognitive function in patients with type 2 diabetes has also been investigated. … The possibility that mild cognitive dysfunction might increase the risk of experiencing severe hypoglycemia has been supported by analyses from the ACCORD study. In the ACCORD MIND (Memory IN Diabetes) study, in which cognitive function was assessed longitudinally, no difference was noted in the rate at which cognitive performance declined over time in subjects randomly assigned to the intensive versus the standard glucose arms despite the fact that they experienced three times as much hypoglycemia. Future investigation will need to ad- dress this question because the existing data are somewhat contradictory.
Patients in the older age-groups are especially vulnerable to hypoglycemia. Epidemiological studies
show that hypoglycemia is the most frequent metabolic complication experienced by older adults in the
U.S. Although severe hypoglycemia is common in older individuals with both type 1 and type 2 diabetes,
patients with type 2 diabetes tend to have longer hospital stays and greater medical costs. The most
signiﬁcant predictors of this condition are advanced age, recent hospitalization, and polypharmacy, as
shown in a study of Tennessee Medicare patients. Age-related declines in renal function and hepatic
enzyme activity may interfere with the metabolism of sulfonylureas and insulin, thereby potentiating
their hypoglycemic effects. The vulnerability of the elderly to severe hypoglycemia may be partially
related to a progressive age-related decrease in b-adrenergic receptor function. Age-related impairment
in counterregulatory hormone responses has been described in elderly patients with diabetes, especially
with respect to glucagon and growth hormone. Symptoms of neuroglycopenia are more prevalent. With
the prolonged duration of type 2 diabetes as is often seen in the elderly patient, the glucagon response
to hypoglycemia is virtually absent. The intensiﬁcation of glycemic control in the elderly patient is
associated with an increased reduction in the plasma glucose thresholds for epinephrine release and for
the appearance of hypoglycemia. As a result, changes in the level of glycemic control have a marked
impact on the risk of developing hypoglycemia in the elderly.
Older adults with diabetes have a disproportionately high number of clinical complications and comorbidities, all of which can be exacerbated by and sometimes contribute to episodes of hypoglycemia. Older adults with diabetes are at much higher risk for the geriatric syndrome, which includes falls, incontinence, frailty, cognitive impairment, and depressive symptoms. The cognitive and executive dysfunction associated with the geriatric syndrome interferes with the patient’s ability to perform self-care activities appropriately and follow the treatment regimen.
To minimize the risk of hypoglycemia in the elderly, careful education regarding the symptoms and treatment of hypoglycemia, with regular reinforcement, is extremely important because of the recognized gaps in the knowledge base of these individuals. In addition, it is important to assess the elderly for functional status as part of the overall clinical assessment in order to properly apply individualized glycemic control goals...
Maintaining blood glucose control in pregnancy as close to that of healthy pregnant women is important
in minimizing the negative effects on the mother and the fetus. This is true for women with
pregestational type 1 or type 2 diabetes, as well for those with gestational diabetes mellitus. Normal
blood glucose levels during pregnancy are 20% lower than in nonpregnant women, making the
deﬁnition and detection of hypoglycemia more challenging.
For women with type 1 diabetes, severe hypoglycemia occurs 3–5 times more frequently in the ﬁrst trimester and at a lower rate in the third trimester when compared with the incidence in the year preceding the pregnancy. Risk factors for severe hypoglycemia in pregnancy include a history of severe hypoglycemia in the preceding year, impaired hypoglycemia awareness, long duration of diabetes, low HbA1c in early pregnancy, ﬂuctuating plasma glucose levels, and excessive use of supplementary insulin between meals.
Hypoglycemia is generally without risk for the fetus as long as the mother avoids injury during the episode. For women with preexisting diabetes, insulin requirements rise throughout the pregnancy and then drop precipitously at the time of delivery of the placenta, requiring an abrupt reduction in insulin dosing to avoid postdelivery hypoglycemia. Breastfeeding may also be a risk factor for hypoglycemia in women with insulin-treated diabetes.