REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
12
VOLUME 11 NUMBER 1 • MARCH 2014
at risk of severe hypoglycaemia, those in whom an episode of
hypoglycaemia may be life-threatening, those who would not
benefit from intensive glucose control and, at least temporarily,
in patients without adequate warning signs until reversible
hypoglycaemia unawareness recovers (Table 5).
25,45
Reversal of
hypoglycaemia unawareness can occur with an increase in HbA
1c
level of approximately 1%, which correlates with an average
increase in blood glucose level of approximately 1.7 mmol/l.
Therefore, daily targets should be individualised and adjusted
with frequent SMBG and particular attention to the lowest blood
sugar values during the day. Attention to eating patterns, exercise
and insulin dosing is important. To avoid poor postprandial control
and nocturnal hypoglycaemia, it may be necessary to re-evaluate
the balance between basal and prandial insulin. Doses may need
to be carefully adjusted to control postprandial glucose levels while
avoiding overuse of basal insulin.
25
Conclusion
Hypoglycaemiaremainsamajorbarriertoachievingglycaemictargets
in patients with diabetes. Furthermore, hypoglycaemic episodes
may predispose to recurrent hypoglycaemia and hypoglycaemia
unawareness, which further jeopardises the patient’s safety and
well-being. Careful attention to appropriate individualised therapy
from the outset of the disease, combined with thorough patient
education and monitoring can help to reduce the risks of treatment,
while optimising glycaemic control and ensuring the best possible
long-term outcome.
References
1. De Galan BE, Schouwenberg BJJW, Tack CJ, Smits P. Pathophysiology and
management of recurrent hypoglycaemia and hypoglycaemia unawareness in
diabetes.
J Med
2006;
64
(8): 269–276.
2. Vignesh JP, Mohan V. Hypoglycaemia unawareness.
J Assoc Phys India
2004;
52
:
727–731.
3. The DCCT Research Group. Epidemiology of severe hypoglycaemia in the diabetes
and Complications Trial.
Am J Med
1991;
90
: 450–459.
4. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes.
Diabetes Care
2003;
26
(6): 1902–1912.
5. Whitmer RA, Karter AJ, Yaffe K,
et al.
Hypoglycemic episodes and risk of dementia
in older patients with type 2 diabetes mellitus.
J Am Med Assoc
2009;
301
(15):
1565–1572.
6. Frier BM. How hypoglycaemia can affect the life of a person with diabetes.
Diabetes Metab Res Rev
2008;
24
: 87–92.
7. Matthews DR, Dejager S, Ahren B,
et al.
Vildagliptin add-on tometformin produces
similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with
no weight gain: results from a 2-year study.
Diabetes Obes Metab
2010;
12
:
780–789.
8. Amiel SA, Dixon Y, Mann R, Jameson K. Hypoglycaemia in type 2 diabetes.
Diabet
Med
2008;
25
: 245–254.
9. Johnston SS, Connor C, Aagren M,
et al
. Association between hypoglycaemic
events and fall-related fractures in Medicare-covered patients with type 2
diabetes.
Diabetes Obes Metab
2012;
14
: 634–643.
10. Smith CB, Choudhary P, Pernet A,
et al.
Hypoglycemia unawareness is associated
with reduced adherence to therapeutic decisions in patients with type 1 diabetes:
evidence from a clinical audit.
Diabetes Care
2009;
32
: 1196–1198. Related
correspondence: Graveling AJ, Frier BM.
Diabetes Care
2010;
33
(1): e15.
11. Bakatselos SO. Hypoglycemia unawareness.
Diabetes Res Clin Pract
2011;
93S
:
S92–S96.
12. Heller SR. Hypoglycaemia: Its pathophysiology in insulin treated diabetes and
hypoglycaemia unawareness.
Br J Diabetes Vasc Dis
2011;
11
(Suppl 1): S6–S9.
13. Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes.
N Engl J Med
2013;
369
: 362–372.
14. Kubiak T, Hermanns N, Schreckling HJ,
et al
. Assessment of hypoglycaemia aware-
ness using continuous glucose monitoring.
Diabet Med
2004;
21
(5): 487–490.
15. Høi-Hansen T, Pedersen-Bjergaard U, Thorsteinsson B. Classification of
hypoglycemia awareness in people with type 1 diabetes in clinical practice.
J
Diabetes Complicat
2010;
24
: 392–397.
16. Schopman JE, Geddes J, Frier BM. Prevalence of impaired awareness of
hypoglycaemia and frequency of hypoglycaemia in insulin-treated type 2 diabetes.
Diabet Res Clin Pract
2010;
87
(1): 64–68.
17. Akram K, Pedersen-Bjergaard U, Carstensen B,
et al
. Frequency and risk factors of
severe hypoglycaemia in insulin-treated type 2 diabetes: a cross-sectional survey.
Diabet Med
2006;
23
(7): 750–756.
18. Akram K, Pedersen-Bjergaard U, Borch-Johnsen K, Thorsteinsson B. Frequency
and risk factors of severe hypoglycemia in insulin-treated type 2 diabetes: a
literature survey.
J Diabetes Complicat
2006;
20
(6): 402–408.
19. Reno CM, Litvin M, Clark AL, Fisher SJ. Defective counterregulation and hypogly-
caemia unawareness in diabetes.
Endocrinol Metab Clin N Am
2013;
42
:15–38.
20. Hepburn DA, Patrick AW, Eadington DW,
et al
. Unawareness of hypoglycaemia
in insulin-treated diabetic patients: prevalence and relationship to autonomic
neuropathy.
Diabet Med
1990;
7
(8): 711–717.
21. Cryer PE. The barrier of hypoglycaemia in diabetes.
Diabetes
2008;
57:
3169–3176.
22. Cryer PE. Mechanisms of hypoglycaemia-associated autonomic failure and its
component syndromes in diabetes.
Diabetes
2005;
54
: 3592–3601.
23. Gold AE, Macleod KM, Frier BM. Frequency of severe hypoglycemia in patients
with type 1 diabetes with impaired awareness of hypoglycemia.
Diabetes Care
1994;
17
(7): 697–703.
24. Hepburn D, Brian BM. Unawareness of hypoglycaemia.
Br Med J
1990;
301
:
1101.
25. McCall AL. Insulin therapy and hypoglycemia.
Endocrinol Metab Clin N Am
2012;
41
: 57–87.
26. Rogers HA, de Zoysa N, Amiel SA. Patient experience of hypoglycaemia
unawareness in Type 1 diabetes: are patients appropriately concerned?
Diabet
Med
2012;
29
: 321–327.
27. Hopkins D, Lawrence I, Mansell P,
et al
. Improved biomedical and psychological
outcomes 1 year after structured education in flexible insulin therapy for people
with type 1 diabetes.
Diabetes Care
2012;
35
: 1638–1642.
28. Cryer PE. Hypoglycemia: Still the limiting factor in the management of diabetes.
Endocrine Pract
2008;
14
(6): 750–756.
29. Stratton IM, Adler AI, Neil AW,
et al.
Association of glycemia with macrovascular
and microvascular complications of type 2 diabetes (UKPDS 35): prospective
observational study.
Br Med J
2000;
321
: 405–412.
30. Holman RR, Paul SK, Bethel MA,
et al
. 10-year follow-up of intensive glucose
control in type 2 diabetes.
N Engl J Med
2008;
359
(15): 1577–1589.
31. Barnett AH. Avoiding hypoglycaemia while achieving good glycaemic control in
type 2 diabetes through optimal use of oral agent therapy.
Curr Med Res Opin
2010;
26
(6): 1333–1342.
32. Khunti K, Davies M. Glycemic goals in patients with type 2 diabetes: current
status, challenges and recent advances.
Diabetes Obes Metab
2010;
12
: 474–
484.
33. Liu S-C, Tu Y-K, Chien M-N, Chien K-L. Effect of antidiabetic agents added to
metformin on glycaemic control, hypoglycaemia and weight change in patients
with type 2 diabetes: a network meta-analysis.
Diabetes Obes Metab
2012;
14
:
810–820.
34. DeVries JH, Bain SC, Rodbard HW,
et al
. Sequential intensification of metformin
treatment in type 2 diabetics with liraglutide followed by randomized addition of
basal insulin prompted by A1C targets.
Diabetes Care
2012;
35
(7): 1446–1454.
35. Berlie H, Hurren KM, Pinelli NR. Glucagon-like peptide-1 receptor agonists as
add-on therapy to basal insulin in patients with type 2 diabetes: a systematic
review.
Diabetes, Metab Synd Obes: Targets Ther
2012;
5
: 165–174.
36. Li C-j, Li J, Zhang Q-m,
et al
. Efficacy and safety comparison between liraglutide
as add-on therapy to insulin and insulin dose-increase in Chinese subjects with
poorly controlled type 2 diabetes and abdominal obesity.
Cardiovasc Diabetol
2012;
11
:142 Published online at
.
37. Henderson JN, Allen KV, Deary IJ, Frier BM. Hypoglycaemia in insulin-treated type
2 diabetes: frequency, symptoms and impaired awareness.
Diabet Med
2003;
20
(12): 1016–1021.
Table 5.
Clinical indications for relaxed glycaemic goals.
19
Hypoglycaemia unawareness
Advanced age
Paediatric patients
Frequent severe hypoglycaemia
Limited life expectancy
Advanced macrovascular complications
Renal failure
Extensive co-morbidities
