Hypoglycemia in Type 2 Diabetes—Consequences and Risk Assessment
Table 1: Productivity Loss from a Non-severe Hypoglycemic Event US
UK NSHE outside working hours NSHE at work NSHE at sleep at night
$26.43 (SD 121.26) n=307
$31.12 (SD 124.91) n=278
$55.16 (SD 184.17) n=205
$46.30 (SD 157.60) n=287
$57.21 (SD 140.51) n=232
$83.59 (SD 177.30) n=153
NSHE = non-severe hypoglycemic event; SD = standard deviation. Costs provided for all countries in US dollars. Source: Brod et al., 2011.42
Germany
$15.50 (SD 67.24) n=173
$15.26 (SD 65.16) n=170
$35.58 (SD 130.27) n=88
France
$61.12 (SD 144.41) n=279
$48.33 (SD 111.58) n=283
$93.47 (SD 197.62) n=166
p value <0.001
<0.001 0.002
work, and function in ways that are important for quality of life (QoL).24 Mild hypoglycemia does not have serious clinical effects, other than the potential to induce defects in the CRR and impaired awareness of subsequent HEs.6
However, even clinically trivial events may reduce adherence to therapeutic regimens.6
Severe HEs have serious clinical consequences, particularly in elderly patients with diabetes. A prospective study of patients aged >80 years with well-controlled type 2 diabetes reported that hypoglycemia was responsible for 25 % of hospitalizations associated with diabetes.25
It has
also been associated with behavioral changes, cognitive impairment, seizures, coma, and a mortality rate estimated at between 4.9 and 9 %.6,18
In addition to the immediate risks associated with HEs, recurrent HEs can have serious consequences. In a retrospective study, patients with type 2 diabetes who experienced outpatient HEs as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), were also shown to have a 79 % higher odds ratio (OR) of experiencing acute cardiovascular events (OR 1.79) than patients without HEs. Because all HEs were identified through ICD-9-CM diagnosis coding, these events were likely to have been sufficiently severe to require medical intervention. Therefore, there were likely to have been many more episodes of hypoglycemia, especially episodes that were mild in nature, that were not captured in this study.17
Severe
hypoglycemia can cause neuronal cell death and may damage regions of the brain that oversee memory, particularly in brains already vulnerable due to age. A longitudinal cohort study found an association between a history of severe HEs and the risk of dementia among older patients (mean age 65 years) with type 2 diabetes: the more HEs a patient experiences, the greater the chance of developing dementia, with ≥3 episodes almost doubling the risk.22
A frequently overlooked problem in type 2 diabetes is nocturnal hypoglycemia. Although underreported, it increases with more intensified glucose control and in those with greater disease duration. Almost half of all severe HEs occur at night during sleep. Undetected nocturnal hypoglycemia often contributes to hypoglycemia unawareness, anxiety, loss of vitality, physical injury, poor QoL, and possibly, neurocognitive deficits.26
Nocturnal hypoglycemia can cause
convulsions and coma and has been associated with cardiac arrhythmias resulting in sudden death.27
Although it appears to have no
immediate detrimental effect on cognitive function, mood and wellbeing may be adversely affected by disturbed sleep secondary to nocturnal hypoglycemia. Recurrent nocturnal HEs may impair cognitive function.27
US ENDOCRINOLOGY
The increasing prevalence of hypoglycemia could pose a threat to the ability of patients with diabetes to drive. In the UK, HEs are responsible for five fatal road accidents a year and 45 serious events every month.28 Although the reported data does not distinguish between types 1 and 2 diabetes, it is likely that a proportion of these road accidents occur in patients with type 2 diabetes.
Hypoglycemia in individuals with type 2 diabetes may be associated with increased symptoms of chest pain and electrocardiographic abnormalities, and may account for sudden mortality.29–31
A case-control study evaluating
the effect of hypoglycemia in patients with type 2 diabetes demonstrated a 65 % increase in the odds of myocardial infarction (MI) with hypoglycemia within the previous two weeks, even following adjustment for possible confounding cofactors. It was also noted that the risk of MI remained elevated (by approximately 20 %) for up to six months following a hypoglycemic event.32
Social Impact of Hypoglycemia
Hypoglycemia in patients with type 2 diabetes is associated with significant reductions in QoL. The impact of hypoglycemia on QoL has been demonstrated in numerous surveys regardless of the measure of QoL.20,33–36
Patients who reported symptoms of hypoglycemia (n=286,
13.78 %) were significantly more likely to have a lower QoL in several parameters, including increased limitations on mobility (OR=1.93, p<0.0001) and usual activities (OR=1.78, p<0.0001), increased pain/discomfort (OR=2.00, p<0.0001), and anxiety/depression (OR=2.31, p<0.0001).36
Even relatively minor hypoglycemia symptoms (e.g., sweating, hunger, anxiety) can reduce QoL.37,38
Fear of hypoglycemia imposes an additional psychological burden. A US study assessed QoL according to the US-weighted summary score (utility) and worry subscale of the Hypoglycemia Fear Survey (HFS). The subscale comprises 18 questions that measure degree of patient fear in the past six months, and is scaled from 0 to 72 (from least to most worry). The EuroQoL-5D Questionnaire, a non-disease-specific instrument for assessing health-related QoL, was also administered. The unweighted summary scores were transformed into US preference-weighted index scores, -0.038–1.0, for the purposes of this study. Patients who reported HEs had a significantly lower mean utility score (0.78 versus 0.86, p<0.0001) and significantly higher mean HFS score (17.5 versus 6.2, p<0.0001) than those who did not report HEs. Differences in mean scores between those with and without HEs increased with the level of severity.35
The magnitude of fear of hypoglycemia is associated with the severity and frequency of HEs.39 97
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