Hypoglycaemia in Clinical Diabetes

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4 Nocturnal HypoglycaemiaSimon R. HellerINTRODUCTIONPeople with type 1 diabetes, who owe their lives to insulin, worry as much abouthypoglycaemia as they do about the prospect of developing serious diabetic complications,and episodes occurring during sleep are feared more than any other. Several studies haveconfirmed how commonly hypoglycaemia occurs during the night, and the possibility ofthe development of severe nocturnal episodes can drive parents to sleep in their child’sbedroom for many years. However, nocturnal hypoglycaemia may have consequences beyonda domestic emergency. Asymptomatic episodes may contribute to impaired hypoglycaemiaawareness and deficient counterregulation, while nocturnal hypoglycaemia may also be associatedwith cognitive impairment and is implicated in the ‘Dead in Bed’ syndrome (seeChapter 12) with the increased risk of sudden death during sleep in young people with type1 diabetes. In this chapter, the reasons why nocturnal hypoglycaemia occurs so frequentlyin type 1 diabetes are discussed. Also, some clinical approaches are described that mighthelp to reduce its frequency and severity and some controversial topics are considered suchas the Somogyi effect.EPIDEMIOLOGY – HOW COMMON IS NOCTURNALHYPOGLYCAEMIA?Nocturnal hypoglycaemia has always been of major concern to individuals with diabetes,with many patients experiencing severe episodes, but it was not until the 1970s that thisproblem was studied systematically. Patients with type 1 diabetes on routine insulin therapywere admitted for overnight monitoring using intermittent venous blood sampling (Gale andTattersall, 1979). Nocturnal hypoglycaemia was reported in 22 of 39 adults, who had whatwould now be considered poorly controlled diabetes and were being treated with one ortwo injections of insulin each day. Since then a number of investigators have examined thefrequency of nocturnal hypoglycaemia, either using patients’ self-reports or by measuringblood glucose at intervals overnight. Although some studies have reported relatively lowrates, others have demonstrated how common nocturnal hypoglycaemia can be. Reportedrates of hypoglycaemia vary between 7 and 60% both in children and adults (Table 4.1).Hypoglycaemia in Clinical Diabetes, 2nd Edition.© 2007 John Wiley & Sons, LtdEdited by B.M. Frier and M. Fisher
Table 4.1 Frequency of nocturnal hypoglycaemia in insulin-treated diabetesStudy NumberAdults (A) orchildren (C) TreatmentSampling (bloodglucose (BG) orcontinuous(CGM))Percentage withglucose below:(mmol/l)3.0 2.5 2.0Proportionasymptomatic Mean HbA 1cGale andTattersall, 1979Dornan et al.,1981Pramming et al.,1985Whincup andMilner, 1987Bendtson et al.,1988Shalwitz et al.,1990Vervoort et al.,199639 A BD insulin BG 56 6482 A BD insulin BG 27 27 9.5 (A1)58 A Conventional BG 29 22 9 9 9.1 (A1)71 C BD insulin ODinsulinBG 34 111023 A MDI BG 30 9 9 57 8.3 (A1)25 CSII 44 36 12 66 7.0 (A1c)135 C Conventional BG 14 7 2 100 10.3 (A1)31 A Basal bolus BG 29 67 8.6 (A1c)Porter et al., 1997 61 C BD BG 17 13 8Beregszaszi et al., 150 C BD/MIT BG 47 491997Matyka et al., 29 C BD BG 45 100 8.8 (A1c)1999bBoland et al., 2001 56 C MIT/CSII CGM 70 100Kaufman et al.,200247 C MIT/CSII CGM 35 27 100 8.6BD = twice daily; CSII = continuous subcutaneous insulin infusion; OD = once daily; MDI = multiple doses of insulin; CGM = continuous glucose monitoring; MIT = multiple injection therapy;BG = blood glucose
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Hypoglycaemia in Clinical DiabetesS
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Hypoglycaemia in Clinical DiabetesS
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ToEmily, Ben and Marc
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viiiCONTENTS13 Long-term Effects of
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ContributorsProfessor Stephanie A.
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1 Normal Glucose Metabolismand Resp
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NORMAL GLUCOSE HOMEOSTASIS 3Box 1.2
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Fed state (Figure 1.1b)EFFECTS OF G
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COUNTERREGULATION DURING HYPOGLYCAE
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COUNTERREGULATION DURING HYPOGLYCAE
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HORMONAL CHANGES DURING HYPOGLYCAEM
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HORMONAL CHANGES DURING HYPOGLYCAEM
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PHYSIOLOGICAL RESPONSES 15hormones.
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PHYSIOLOGICAL RESPONSES 17Figure 1.
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PHYSIOLOGICAL RESPONSES 19We do not
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REFERENCES 21NORMAL GLUCOSE HOMEOST
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REFERENCES 23Hamilton-Wessler M, Be
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2 Symptoms of Hypoglycaemiaand Effe
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SYMPTOMS OF HYPOGLYCAEMIA 27appeare
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SYMPTOMS OF HYPOGLYCAEMIA 29aware o
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Page 58 and 59: REFERENCES 45Bremer JP, Baron M, Pe
Page 60 and 61: REFERENCES 47McAulay V, Deary IJ, F
Page 62 and 63: 3 Frequency, Causes and RiskFactors
Page 64 and 65: FREQUENCY OF HYPOGLYCAEMIA 51Box 3.
Page 66 and 67: Table 3.1 Frequency of mild hypogly
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Page 70 and 71: FREQUENCY OF HYPOGLYCAEMIA 57Jansse
Page 72 and 73: Table 3.2 Frequency of severe hypog
Page 74 and 75: CAUSES OF HYPOGLYCAEMIACAUSES OF HY
Page 76 and 77: RISK FACTORS FOR SEVERE HYPOGLYCAEM
Page 88 and 89: CONCLUSIONS 75Other Risk FactorsThe
Page 90 and 91: REFERENCES 77Bott S, Bott U, Berger
Page 92 and 93: REFERENCES 79Leckie AM, Graham MK,
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Page 111 and 112: 98 NOCTURNAL HYPOGLYCAEMIAHolleman
Page 114 and 115: 5 Moderators, Monitoring andManagem
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Page 130 and 131: REFERENCES 117CONCLUSIONS• Hypogl
Page 132 and 133: REFERENCES 119MacDonald MJ (1987).
Page 134 and 135: 6 Counterregulatory Deficienciesin
Page 136 and 137: NORMAL GLUCOSE COUNTERREGULATION 12
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Page 140 and 141: DEFECTIVE HORMONAL GLUCOSE COUNTERR
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Page 144 and 145: MECHANISMS OF COUNTERREGULATORY FAI
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AGE, OBESITY AND GLUCOSE COUNTERREG
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TREATMENT OF COUNTERREGULATORY FAIL
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REFERENCES 137Bingham EM, Dunn JT,
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REFERENCES 139McCall AL, Fixman LB,
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7 Impaired Awareness ofHypoglycaemi
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NORMAL RESPONSES TO HYPOGLYCAEMIA 1
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IMPAIRED AWARENESS OF HYPOGLYCAEMIA
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PREVALENCE OF IMPAIRED AWARENESS OF
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PATHOGENESIS OF IMPAIRED AWARENESS
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Table 7.3 Studies of antecedent hyp
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IMPAIRED AWARENESS OF HYPOGLYCAEMIA
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TREATMENT STRATEGIES 163or unexplai
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CONCLUSIONS 165Box 7.5 Treatment st
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REFERENCES 167Boyle PJ (1997). Alte
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REFERENCES 169Kerr D, Sherwin RS, P
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8 Risks of Strict GlycaemicControlS
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CONTRIBUTORS TO INCREASED RISK OF S
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CONTRIBUTORS TO INCREASED RISK OF S
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CEREBRAL ADAPTATION 177severe, are
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CEREBRAL ADAPTATION 179hypoglycaemi
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THERAPEUTIC MANIPULATION 181Figure
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PATIENTS UNSUITABLE FOR STRICT CONT
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REFERENCES 185It is the patient who
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REFERENCES 187Egger M, Davey Smith
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REFERENCES 189Simonson DC, Tamborla
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192 HYPOGLYCAEMIA IN CHILDREN WITH
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Table 9.2 Summary of studies examin
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10 Hypoglycaemia in PregnancyAnn E.
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FREQUENCY OF HYPOGLYCAEMIA IN DIABE
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FREQUENCY OF HYPOGLYCAEMIA IN DIABE
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CLINICAL MANAGEMENT BEFORE AND DURI
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Figure 10.2 Example of home blood g
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MATERNAL COMPLICATIONS OF DIABETES
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COMPLICATIONS IN THE INFANT OF THE
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REFERENCES 235Akazawa M, Akazawa S,
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REFERENCES 237Ray JG, O’Brien TE,
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240 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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Table 11.2a Prevalence of severe hy
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266 MORTALITY, CARDIOVASCULAR MORBI
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13 Long-term Effects ofHypoglycaemi
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COGNITIVE FUNCTION AND HYPOGLYCAEMI
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FUNCTIONAL EFFECTS OF HYPOGLYCAEMIA
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STRUCTURAL AND FUNCTIONAL CHANGES I
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REFERENCES 303disease (Fisher and F
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REFERENCES 305Fisher M, Frier BM (1
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REFERENCES 307Seidl R, Birnbacher R
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310 LIVING WITH HYPOGLYCAEMIAPSYCHO
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312 LIVING WITH HYPOGLYCAEMIABox 14
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314 LIVING WITH HYPOGLYCAEMIAprophy
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316 LIVING WITH HYPOGLYCAEMIAMost t
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318 LIVING WITH HYPOGLYCAEMIAfor pu
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320 LIVING WITH HYPOGLYCAEMIAVocati
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322 LIVING WITH HYPOGLYCAEMIAif the
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324 LIVING WITH HYPOGLYCAEMIAestabl
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326 LIVING WITH HYPOGLYCAEMIAwith g
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328 LIVING WITH HYPOGLYCAEMIAalcoho
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330 LIVING WITH HYPOGLYCAEMIAChante
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332 LIVING WITH HYPOGLYCAEMIASonger
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334 INDEXanterior pituitary gland,
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336 INDEXcomplications due to diabe
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338 INDEXemployment aspects, 323-32
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340 INDEXhypopituitarism, 74, 102,
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342 INDEXmood changes due to hypogl
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344 INDEXpsychological factors, and
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346 INDEXtrain drivers, 323, 324tra
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