Prevalence, prevention and addressing hypoglycaemia

Why address hypoglycemia in diabetes?

• Reducing HbA1c levels associated with prevention or delay in complications and death

• Hypoglycemia is a limiting factor in achieving glycaemic targets

• Hypoglycemia is associated with morbidity and rarely even be fatal

• Optimizing glycaemic control is of obvious importance:• $376 billion USD spent to treat diabetes and its

complications in 2010; hypoglycemia is cost-intensive

• 6.8% of global all-cause mortality attributed to diabetes in 2010 (4 million deaths)

Cryer et al 2003. Diabetes Care; 26,6: 1902-1912 IDF Diabetes Atlas 4th ed., 2009

Roglic and Unwin 2010. Diabetes Research and Clinical Practice; 87: 15-19

Symptoms of Hypoglycemia

• Neurogenic (ANS) Symptoms• (Caused by Falling Glucose

Level)• Shakiness• Trembling• Anxiety• Nervousness• Palpitations• Clamminess• Sweating• Dry mouth• Hunger• Pallor• Pupil dilation

• Neuroglycopenic Symptoms• (Caused by Brain Neuronal Glucose• Deprivation)• Abnormal mentation• Irritability• Confusion• Difficulty in thinking• Difficulty speaking• Paresthesias• Headaches• Stupor• Seizures• Coma• Death (if untreated)

Sequalae of hypoglycaemia

• Mild symptomatic hypoglycaemia • No direct serious clinical effects • May impair subsequent hypoglycaemia awareness

• Severe hypoglycaemia associated with• Stroke and transient ischaemic attacks• Memory loss/cognitive impairment• Myocardial infarction• Injury (direct/indirect)• Death

Hypoglycemia unawareness

• Patients with long-standing diabetes and onomic neuropathy, might not subjectively sense symptoms of hypoglycemia even in the presence of low glucose concentrations

• Glycemic targets of therapy should be adjusted upward in these patients because they are at particularly high risk for hypoglycemia

Hypoglycemia RiskFactors• Missed or delayed meal

• Eating less food at a meal than planned

• Vigorous exercise without carbohydrateCompensation

• Taking too much diabetes medicine (e.g., insulin, insulin secretagogues, and meglitinides)

• Drinking alcohol

SU should be discontinued

• There is evidence of feedback by exogenous insulin upon endogenous insulin secretion

• Combining insulin and SU in patients with significant residual endogenous insulin secretion might incur a high risk of hypoglycaemia

Hypoglycaemia: a barrier to insulin use?

Nakar et al. J Diab Compl 2007;21:220−6

Patients not treated with insulin

Physicians

Insulin makes one fat

Fear of hypoglycaemia

Pain from injection

Pain from blood tests

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Keys to addressing hypoglycaemia

• Patient education• Perception vs. reality: rates of hypoglycaemia are much lower in type 2

patients than type 1 patients, even on intensified insulin therapy

• Educate patients to properly self-monitor blood glucose (SMBG); actively monitoring BG to mitigate fear of hypoglycaemia

• Regimen selection and dosage• Physicians must tailor insulin therapy to the patient, while considering

glycaemic level and patient feedback

• Choice of insulin• Modern insulin analogues incur less hypoglycaemia at equivalent levels

of glycaemic control, thus offering the possibility of titrating more safely to target

Korytkowski M. Int J Obes Relat Metab Disord 2002;26:S18–S24

Danne T. MedscapeCME Diabetes & Endocrinology, 2009-09-21

Tips for Preventing Hypoglycemia• If blood glucose is < 70 mg/dl, give 15–20 g of quick-

acting carbohydrate (1–2 teaspoons of sugar or honey, 5–6 pieces of hard candy

• glucose gel or tablets as directed, or 1 cup of milk).• Test blood glucose 15 minutes after treatment. If it

is still < 70 mg/dl, re-treat with 15 g of additional carbohydrate.

• Keep glucagon injection kit available for patients who are unconscious or unable to take in oral carbohydrate

Treatment hints

• Intravenous glucose (25 g) should be given if the patient is unable or unwilling to take carbohydrates orally.

• If intravenous therapy is not practical, subcutaneous or intramuscular Glucagon can be used.

• This treatment raise plasma glucose concentrations only transientlytransiently, and patients should therefore be urged to eat as soon as is practical to replete glycogen stores.

Changing the dose: some general rules

Combating hypoglycaemia

• Reduce insulin dose by at least 20% and review after 1 week

• Preventing hypoglycaemiaPreventing hypoglycaemia takes priority over correcting hyperglycaemiacorrecting hyperglycaemia

http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf

HYPOGLYCAEMIA & MODERN INSULIN

Do modern insulins offer any advantages over traditional insulins?

NovoMix® 30 effectively reduces HbA1c in T2 patients; low hypo rates

OnceMix, Strojek et al 2009. Curr Med Res Opin; 25; 2887-941-2-3 Garber A et al. Diab Obesity Metab 2006; 8(1):58-66

EUROMIX, Kann et al. Exp Clin Endocrinol Diabetes 2006; 114:527-532REFORM Lund S et al. BMJ 2009;339: 2-11

INITIATE Raskin P et al. Diabetes Care 2005; 28:260-5ACTION Raskin et al. Diabetes Obes Metab. 2009 Jan; 11(1):27-32PREFER Liebl et al. Diabetes Obes Metab. 2009 Jan; 11(1):45-52

Aspart (NovoRapid®) maintains glycaemic control†: 3-year data...

Home et al. Diabetes Res Clin Pract 2006;71:131–9

8.5

8.0

7.5

0

HbA

1c

(%)

Months0 6 12 18 2

430 36

*

p=0.035 at 30 months

n=753

Insulin aspart (IAsp)Human insulin (HI)

† Study conducted in patients with T1 diabetes

…and incurs a low risk of hypoglycaemia

Hypoglycaemia rate (event/patient-month)

RR (IAsp/HI) [95% CI], p-value

IAsp HI

Major 0.08 0.08 1.00 [0.72–1.39] NS

Minor 2.46 2.03 1.24 [1.09–1.39] p=0.02

Despite significant differences in glycaemic control, the risk of major hypoglycaemia did not

differ between the two treatments†

Home et al. Diabetes Res Clin Pract 2006;71:131–9

†Study conducted in patients with T1 diabetes;IAsp = NovoRapid®

Aspart significantly reduced major nocturnal hypoglycaemia vs. HI†

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Heller et al. Diabet Med 2004;21:769–75

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72%* risk reduction with insulin aspart

† Study conducted in patients with T1 diabetes* P = 0.001

Modern analogues incur fewer hypos at equivalent levels of glycaemic control

• Hypoglycaemia is a major perceived barrier to insulin use for patients and physicians

• Modern insulin analogues incur less hypoglycaemia at equivalent levels of glycaemic control, thus offering the possibility of titrating more safely to target

• These findings have been reported both in clinical trials, and in observational studies