Uncovering undetected hypoglycemic events

Figures & data

Figure 1 Frequency of adverse clinical outcomes after the occurrence of severe hypoglycemia event.

Copyright © 2010, Massachusetts Medical Society. Reprinted with permission from Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363(15):1410–1418.

Figure 2 Diagrammatic representation of the concept of hypoglycemia-associated autonomic failure.

Copyright © 2011, Vendome Group. Reprinted with permission from Unger J, Parkin C. Hypoglycemia in insulin-treated diabetes: a case for increased vigilance. Postgrad Med. 2011;123(4):81–91.

Abbreviation: BG, blood glucose.

Table 1 Incidence of severe hypoglycemia requiring NHS resources

Type of diabetes	Treatment modality	Incidence
Type 1	Insulin	11.5 (9.4–13.6)
Type 2	Insulin	11.8 (9.5–14.1)
Type 2	SU tablets	0.9 (0.6–1.3)
Type 2	Metformin or diet	0.05 (0.01–0.2)

Note: Data are events expressed per 100 patient-years (95% CI).

Copyright © 2003, American Diabetes Association. Reprinted with permission from Leese GP, Wang J, Broomhall J, et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use. Diabetes Care. 2003;26(4):1176–1180.

Abbreviations: CI, confidence interval; NHS, Ninewells Hospital and Medical School (United Kingdom); SU, sulfonylurea.

Table 2 Episodes of severe and minor hypoglycemia in all study participants and according to treatment group

Variable	All participants (n = 11,140)	Intensive blood glucose control (n = 5571)	Standard blood glucose control (n = 5569)	Hazards ratio (95% CI)
Severe hypoglycemia				1.86 (1.40–2.40)
Patients (n, %)
Episodes (n)	231 (2.1)	150 (2.7)	81 (1.5)
1	184	120	64
2	35	22	13
≥3	12	8	4
Rate (person/year)	0.006	0.007	0.004
Minor hypoglycemia				1.58 (1.49–1.68)
Patients (n, %)
Episodes (n)	4975 (44.7)	2898 (52.0)	2077 (37.3)
1	2610	1529	1081
2	671	397	274
≥3	1694	972	722
Rate (person/year)	1.1	1.2	0.9

Copyright © 2010, Massachusetts Medical Society. Reprinted with permission from Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363(15):1410–1418.

Abbreviations: BG, blood glucose; CI, confidence interval.

Table 3 Annual total costs per patient attributable to hypoglycemia

Study	Cost year	Treatment arm	Mean (SD)	Median	Expected cost
Cobden^Citation75	2006	Insulin vial and syringe	$1528 ($2336)	$490
		Biphasic insulin analog pen	$620 ($899)	$142
Lee et al^Citation68	2006	Insulin vial and syringe	$1415 ($2556)	$533
		Insulin analog pen	$627 ($993)	$172
Misurski*,^Citation76	Data gathered 2006–2008	Exenatide			$78
		Insulin glargine			$196

Notes:

* Estimate derived from model using incidence rates (adjusted for patient characteristics) and estimated per event hypoglycemia costs based on mean and median costs per event pooled for both treatment groups. For ease of comparison in this table, reported cost per 100 patients has been converted to cost per patient.

Copyright © 2010, Turner White Communications, Inc. Reprinted with permission from Zhang Y, Wieffer H, Modha R, Balar B, Pollack M, Krishnarajah G. The burden of hypoglycemia in type 2 diabetes: a systematic review of patient and economic perspectives. J Clin Outcomes Manage. 2010;17(12):547–557.

Abbreviation: SD, standard deviation.

Table 4 Costs per hyperglycemic episode

Event severity	Estimated medical cost/event	Estimated work days lost	Estimated indirect cost/event
Mild: patient experiences hypoglycemic symptoms requiring assistance from a second person but no medical attention is needed	€26.0	0.22	37.0
Moderate: patient seeks medical attention for hypoglycemia but is not admitted to hospital overnight	€334.7	0.27	45.3
Severe: patient is admitted to hospital because of hypoglycemia	€2906.8	6.60	1110.6

Copyright © 2010, Turner White Communications, Inc. Reprinted with permission from Zhang Y, Wieffer H, Modha R, Balar B, Pollack M, Krishnarajah G. The burden of hypoglycemia in type 2 diabetes: a systematic review of patient and economic perspectives. J Clin Outcomes Manage. 2010;17(12):547–557.

Table 5 Questions about hypoglycemic events to consider at every patient visit

When did the event(s) occur? (daytime versus overnight) Under what circumstances did they occur? (missed meal, following exercise, excess medication) What were the symptoms? What was the blood glucose reading? How did patient treat the hypoglycemia? Did the patient require assistance from another person in order to reverse the hypoglycemia? Did the hypoglycemic event reoccur later within a 24-hour period? What was done? (eg, carbohydrates ingested, follow-up blood glucose monitoring) How soon did hypoglycemia resolve? (blood glucose levels rose to 3.9 mmol/L [70 mg/dL]) How fearful is the patient or the family of hypoglycemia? Do they test before driving? Do patients “stack insulin” (re-bolus rapid insulin analog within 3 hours of a similar injection)? At what glycemic level does the patient perceive hypoglycemia? (If <0.8 mmol/L [<50 mg/dL], patient may have hypoglycemia-associated autonomic failure) Some patients prefer being “low” rather than “high” because they fear the consequences of acute or chronic hyperglycemia. Does your patient understand the consequences of hypoglycemia?

Copyright © 2011, Dove Medical Press, Ltd. Reprinted with permission from Unger J. Insulin initiation and intensification in patients with type 2 diabetes mellitus for the primary care physician. Diabetes Metab Syndr Obes. 2011;4:253–261.

Abbreviation: HAAF, hypoglycemia-associated autonomic failure.

Table 6 Interpretation of structured glucose testing readings

Delta value (mg/dL)	Delta value (mmol/L)	Interpretation	Intervention
0–50	0–2.7	Correct insulin given for amount of carbohydrates consumed Correct lag time procedure followed	None
51–100	2.8–5.5	Insulin-to-carbohydrate mismatch Incorrect lag time Possible snacking in between end of meal and 2-hour test	Increase prandial insulin dose 1–2 units next time this type of food is eaten Make sure to inject insulin at least 15 minutes prior to meals
100–200	5.5–11.1	Possibly had elevated blood glucose prior to mealtime and did not give a correction dose Insulin-to-carbohydrate mismatch Was insulin omitted? Errors in blood glucose monitoring technique	Teach patient how to use a premeal insulin sensitivity factor If patient omitted insulin they will see the error of their ways If postmeal delta is consistently elevated, increase baseline insulin dose by 1 unit per day until delta is 0–2.7 mmol/L (0–50 mg/dL) or 2-hour postprandial blood glucose value is 7.7 mmol/L (<140 mg/dL) Educate patient on proper BG monitoring. Touching fruit, cakes, or ice cream after a meal may result in false elevation of BG values
Any negative delta value (eg, –25)	Any negative delta value	Miscalculation of insulin-to-carbohydrate ratio: too much insulin administered for amount of carbohydrate eaten. Patient is likely to become hypoglycemic in the next 1–2 hours	Educate patient regarding insulin absorption principles: 1 hour after bolus administration, 90% of rapid-acting insulin analog remains in depot. Based upon the pharmacokinetics of rapid-acting insulins (lispro, aspart, and glulisine), the percentage of insulin remaining to be absorbed from the depot postbolus are as follows: 90% at 1 hour, 60% at 2 hours, and 40% at 3 hours. Thus, if 10 units of insulin are given at 8 am, at 10 am 6 units (60% of the initial bolus) remains to be absorbed. A premeal blood glucose value of 6.6 mmol/L (120 mg/dL) and a 2-hour postmeal blood glucose value of 4.9 mmol/L (90 mg/dL) gives a delta of −1.6 mmol/L (−30 mg/dL). Because 6 units of rapid-acting insulin remains to be absorbed, a significant decline in blood glucose has been noted at 2 hours after eating, and the patient is trending towards hypoglycemia. Self-monitoring should be repeated at 3 and 4 hours postinjection to identify and correct any hypoglycemia (<3.3 mmol/L [<60 mg/dL]) events proactively

Abbreviation: BG, blood glucose.

Figure 3 Action profile of rapid-acting and long-acting insulin analogs and insulin analog premixes.

Copyright © 2009, UBM Medica LLC. Reprinted with permission from Brunton S. Safety and effectiveness of modern insulin therapy: the value of insulin analogs. Consultant. 2009;Suppl:S13–S19.

Cobden D Lee WC Balu S Health outcomes and economic impact of therapy conversion to a biphasic insulin analog pen among privately insured patients with type 2 diabetes mellitus Pharmacotherapy 2007 27 7 948 962 17594200

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Lee WC Balu S Cobden D Joshi AV Pashos CL Medication adherence and the associated health-economic impact among patients with type 2 diabetes mellitus converting to insulin pen therapy: an analysis of third-party managed care claims data Clin Ther 2006 28 10 1712 1725 17157128

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Misurski D Lage MJ Fabunmi R A comparison of costs among patients with type 2 diabetes who initiated therapy with exenatide or insulin glargine Appl Health Econ Health Policy 2009 7 4 245 254 19905038

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