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Hypoglycemia: Symptoms, Treatments and Risk Factors - Pharmacology - Lecturio NursingHypoglycemic unawareness risk factors -
Bergenstal , Naomi S. Chaytor , Christina Peterson , Beth A. Olson , Medha N. Munshi , Alysa J. Perrin , Kellee M. Miller , Roy W. Beck , David R. Liljenquist , Grazia Aleppo , John B.
Buse , Davida Kruger , Anuj Bhargava , Robin S. Goland , Rachel C. Edelen , Richard E. Pratley , Anne L. Peters , Henry Rodriguez , Andrew J. Ahmann , John-Paul Lock , Satish K. Garg , Michael R. Rickels , Irl B. Hirsch , for the T1D Exchange Severe Hypoglycemia in Older Adults With Type 1 Diabetes Study Group; Risk Factors Associated With Severe Hypoglycemia in Older Adults With Type 1 Diabetes.
Diabetes Care 1 April ; 39 4 : — Severe hypoglycemia is common in older adults with long-standing type 1 diabetes, but little is known about factors associated with its occurrence.
A case-control study was conducted at 18 diabetes centers in the T1D Exchange Clinic Network. Data were analyzed for cognitive and functional abilities, social support, depression, hypoglycemia unawareness, various aspects of diabetes management, C-peptide level, glycated hemoglobin level, and blinded continuous glucose monitoring CGM metrics.
Glycated hemoglobin mean 7. On certain cognitive tests, case subjects scored worse than control subjects. In older adults with long-standing type 1 diabetes, greater hypoglycemia unawareness and glucose variability are associated with an increased risk of severe hypoglycemia.
A study to assess interventions to prevent severe hypoglycemia in high-risk individuals is needed. Older adults with type 1 diabetes T1D are a growing but underevaluated population 1 — 4.
Of particular concern in this age group is severe hypoglycemia, which, in addition to producing altered mental status and sometimes seizures or loss of consciousness, can be associated with cardiac arrhythmias, falls leading to fractures, and in some cases, death 5 — 7.
In Medicare beneficiaries with diabetes, hospitalizations related to hypoglycemia are now more frequent than those for hyperglycemia and are associated with high 1-year mortality 6. Emergency department visits due to hypoglycemia also are common 5. These reports likely underestimate the problem of hypoglycemia in older adults with T1D because they include individuals with type 2 diabetes in whom severe hypoglycemic events are considerably less frequent.
In addition, glucose levels at the time of falls hip fractures and the onset of cardiac events are frequently unavailable 8. The T1D Exchange clinic registry reported a remarkably high frequency of severe hypoglycemia resulting in seizure or loss of consciousness in older adults with long-standing T1D 9.
Unlike treatment guidelines in younger individuals with T1D, which focus on optimizing glycated hemoglobin HbA 1c levels, treatment approaches for older adults with T1D often focus on minimizing hypoglycemia rather than attempting to achieve low HbA 1c levels 10 , Despite the high frequency of severe hypoglycemia in older adults with long-standing T1D, little information is available about the factors associated with its occurrence.
The study was conducted at 18 diabetes centers participating in the T1D Exchange Clinic Network The centers are listed in the Supplementary Data.
The study adhered to the tenets of the Declaration of Helsinki and was approved by the respective multiple institutional review boards. Study participants provided written informed consent before study participation. Case subjects were required to have had at least one severe hypoglycemic event in the prior 12 months, defined as an event requiring assistance of another person as a result of altered consciousness or confusion, to administer carbohydrate or glucagon or other resuscitative actions.
Control subjects were required to have not had a severe hypoglycemic event in the past 3 years. Case and control subjects were frequency matched on clinic and age in 5-year bins. The cognitive test battery included measures of general mental status Montreal Cognitive Assessment [ 13 ] , psychomotor processing speed Symbol Digit Modalities Test [ 14 ] , executive functioning Trail Making Test—Trail A and B [ 15 , 16 ] , and verbal memory Hopkins Verbal Learning Test—Revised [ 17 ].
Raw scores were used because there were no significant differences in demographic factors between groups. Fine motor dexterity and speed Grooved Pegboard Test [ 18 ] , depression symptoms Geriatric Depression Scale Short Form [ 19 ] , instrumental activities of daily living Functional Activities Questionnaire [ 20 ] , social support Duke Social Support Index [ 21 ] , diabetes numeracy Diabetes Numeracy Test—15 question [ 22 ] , visual acuity Colenbrander Reading Card [English Continuous Text Near Vision Card] [ 23 ] , and physical frailty timed foot walk [ 24 ] were also assessed.
Diabetes-related questionnaires included hypoglycemia unawareness Clarke Hypoglycemia Unawareness Questionnaire [ 25 ] , hypoglycemia fear Hypoglycemia Fear Survey [ 26 ] , and hyperglycemia fear Preferring Hypoglycemia Scale; W.
Polonsky, personal communication. All questionnaires and functional testing were scored using recommended approaches, except for the Clarke Questionnaire Supplementary Table 1. Because this survey includes questions regarding recent hypoglycemic events, an overall score would be invalid; therefore, scores for pertinent items were tabulated individually.
Measurements of HbA 1c , random C-peptide, glucose, and creatinine levels were performed at a central laboratory. A SEVEN PLUS CGM Dexcom, Inc. Excluding the data from one case subject who used acetaminophen frequently despite instructions to the contrary acetaminophen can affect the accuracy of the Dexcom sensor and one control subject with no available CGM glucose data, the median interquartile range amount of CGM data was h — for case subjects and h — for control subjects.
CGM metrics were computed overall and separately for daytime 6 a. to midnight and nighttime midnight to 6 a. Characteristics between the case and control subjects were compared with the χ 2 test, Fisher exact test, t test, and Wilcoxon test dependent on variable distribution.
Adjusted regression models were run to assess the relationship between case-control status and various clinical factors, diabetes management factors, CGM data, and assessments. All statistical analyses were performed using SAS 9.
All P values are two-sided. The study included participants case subjects and control subjects enrolled between August and April Demographics for case and control subjects were similar for most factors, including sex, age, race, diabetes duration, education, income, and BMI Table 1.
This did not differ by case and control subjects. Total daily insulin amounts were similar median 0. ϑThe government and commercial insurance group includes those with government insurance Medicare, Medigap, Medicaid, TRICARE, Indian Health Service Plan, State Children's Health Insurance Program, etc.
and commercial insurance commercial, fee-for-service, health maintenance organization, preferred provider organization, point-of-service or a single-service plan e.
The only commercial insurance group includes those with commercial insurance only, and the only government insurance group includes those with government insurance only. There was a trend toward more frequent self-reported home blood glucose meter testing in case subjects compared with control subjects mean 6 vs.
ϑIncludes oral and ophthalmologic β-blockers; P value adjusted for age and T1D duration. Mean HbA 1c was 7. Ω Additional CGM data missing for 4 case and 2 control subjects due to less than 24 h of nighttime CGM readings available.
Case subjects performed worse than control subjects on the written version of the Symbol Digit Modalities Test mean There was a trend for slightly lower scores in case than in control subjects on the Montreal Cognitive Assessment mean score No large differences were found between case and control subjects for other cognitive tests, functional testing, or diabetes numeracy Table 4.
Assessments §. Additional scoring details are listed in the Supplementary Data. α P value adjusted for insulin method pump vs.
injections , in addition to age and site. ϑ P value adjusted for use of assistive devices during the test, in addition to age and site.
ΦEnglish Continuous Text Near Vision Card; P value obtained from treating reading vision as an ordinal variable and adjusting for visual aids used during the test such as a magnifying glass , in addition to age and site.
Case and control subjects had similar depression scores, but there was a trend for slightly lower scores on the Duke Social Support Scale in case versus control subjects mean score Case subjects scored higher on the Hypoglycemia Fear Survey than control subjects mean score Case subjects were substantially more likely than control subjects to have significant hypoglycemia unawareness Fig.
A : How low does your blood glucose need to go before you feel symptoms? B : To what extent can you tell by your symptoms that your blood glucose is low? Hypoglycemia Unawareness Questionnaire response missing for two case subjects and one control subject. This case-control study of older adults with long-standing T1D found that the occurrence of recent severe hypoglycemia was associated with greater hypoglycemia unawareness and higher glucose variability but not with lower HbA 1c or mean glucose levels.
The latter finding indicates that the risk of severe hypoglycemia in this age group was not due to tighter glycemic control. The greater risk also was not due to less fear of hypoglycemia, and in fact, those with recent severe hypoglycemia, not surprisingly, had greater fear of hypoglycemia.
The slightly higher daily frequency of blood glucose monitoring in case subjects compared with control subjects might be related to their higher fear of hypoglycemia. Hypoglycemia unawareness, which is associated with altered counterregulation, is more common in older adults with long-duration T1D than in younger individuals or those with type 2 diabetes Individuals with reduced hypoglycemia awareness are more prone to severe hypoglycemia and high morbidity and mortality, particularly in the elderly 5 — 7 , Current insulin therapies are unable to eliminate this risk.
Routine screening for hypoglycemia unawareness in this population is recommended and can be accomplished using a brief questionnaire Whether the glucose counterregulatory failure that characterizes hypoglycemia unawareness may explain the greater glucose variability reported here requires further study, and future work should explore strategies to correct defective glucose counterregulation in T1D.
The finding of greater glucose variability in case subjects than in control subjects is a concern, particularly when combined with a lack of awareness of hypoglycemia. Earlier studies examining limited glucose data from self-monitoring of blood glucose in younger patients suggested that blood glucose variance was related to hypoglycemia 29 , A more recent study in long-standing T1D complicated by reduced awareness of hypoglycemia showed that glucose variability as determined by h CGM was related to the severity of clinically problematic hypoglycemia Although the percentages of participants with measurable C-peptide levels were not different between the two groups, single C-peptide measurements are not as sensitive as provocative testing.
Further research is required to determine if endogenous insulin secretion can assist in explaining our findings. β-Blockers, which are commonly used in older patients with diabetes for a variety of indications, were more commonly used by case subjects than by control subjects. In younger age groups with shorter durations of diabetes than in our report, the adverse effect of selective and nonselective β-blockers on hypoglycemia unawareness has been studied 32 , 33 , although we did not find an association between hypoglycemia unawareness and β-blocker use.
We also note that there are no data about hypoglycemia risks in elderly patients with T1D, although one report of 13, subjects with type 2 diabetes did not find that β-blockers significantly increased the risk of severe hypoglycemia Use of β-blockers in that report included oral and eye drop preparations, and the indications for use were not recorded.
Further research is needed to better understand the possible influence of nonselective β-blocker use on hypoglycemia in this population. The study found some differences in executive function and psychomotor processing speed between case and control subjects.
These could be contributory factors for severe hypoglycemia, could result from recurrent hypoglycemia, or could be part of a vicious cycle involving both. Those with cognitive impairment may be less able to determine and self-administer the correct insulin doses for meals and correction of hyperglycemia and amounts of carbohydrate for falling glucose levels.
They may fail to anticipate the consequences of exercise or missed meals. This may be particularly problematic in those who lack physiological symptoms to alert them of hypoglycemia. Conversely, hypoglycemia could be related to the development of these cognitive impairments.
No differences between case and control subjects were seen in functional activities score, numeracy, vision testing, depression, or social support.
A potential limitation of the study is that participants were from specialized diabetes centers; however, because case and control subjects were matched within centers, this was not likely a source of bias. Nevertheless, it is possible that results could differ in patients meeting study eligibility criteria receiving care in other settings.
There is also the possibility of survivor bias. Individuals with a history of more severe hypoglycemia could have had earlier mortality.
The study excluded users of CGM at home because frequency of use in this age group is low and it would be inappropriate to pool data from CGM and non-CGM users. Because hypoglycemia is a major problem in older adults with longstanding T1D, current guidelines suggest higher HbA 1c goals for this population based on the assumption that this will lead to less hypoglycemia 9.
Our results suggest that raising HbA 1c goals in many patients will be insufficient to reduce severe hypoglycemia in this population due to the presence of hypoglycemia unawareness and increased glucose variability.
Therefore, until an artificial pancreas or β-cell replacement therapy becomes available, frequent home glucose measurements may be an important strategy for these patients.
Other methods to reduce hypoglycemic exposure 35 and minimize β-blocker use should be considered. The use of current technologies, such as CGM and threshold suspend pumps, in this population requires further study.
Funding was provided by the Leona M. and Harry B. Helmsley Charitable Trust. The nonprofit employer of R. has received grant funding from the National Institutes of Health and the Leona M. The nonprofit employer of N. has received grant funding from the National Institutes of Health.
Duality of Interest. receives royalties from the Betty Crocker Diabetes Cookbook and holds stock in Merck. has received lecture fees from BRIOmed. has received consultancy payments and stock from PhaseBio. has received payments as a board member for Eli Lilly, Merck, Novartis, and Sanofi and consultancy payments from Roche Diagnostics.
No other potential conflicts of interest relevant to this article were reported. Author Contributions. researched data and wrote and edited the manuscript. researched data, wrote and edited the manuscript, and performed statistical analyses. researched data and reviewed and edited the manuscript.
is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.
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Ruth Hypoglycemic unawareness risk factors. WeinstockStephanie Unawarenees. DuBoseRichard M. BergenstalNaomi S. ChaytorChristina PetersonBeth A. This may be manifested by bizarre Hypoglycemic unawareness risk factors, Hupoglycemic Low GI dinner vehicle ffactors or activities, loss of Htpoglycemic, seizures, or even death. The first symptom, often noticed by others, unawareness is Fast metabolism boosters. When Hypoglycemuc unawareness occurs during sleep, patients Organic Coconut Oil Hypoglycemic unawareness risk factors only unawzreness Low GI dinner blood factprs levels the Somogyi effect due to enhanced counterregulatory effects to correct for the overnight low levels. The most common risk factor for hypoglycemia unawareness is hypoglycemia-associated autonomic failure HAAFwhich is a generally reversible metabolic adaptation to frequent hypoglycemia. This adaptation may develop rapidly and has been shown to occur after as few as three 2-hour periods of hypoglycemia within 30 hours. Generalized autonomic neuropathy, which may or may not be reversible, also may manifest similarly to HAAF but often is accompanied by other autonomic dysfunction symptoms eg, gastroparesis, orthostatic hypotension, bladder dysfunction.
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