REFERENCES 77Bott S, Bott U, Berger M, Muhlhauser I (1997). Intensified <strong>in</strong>sul<strong>in</strong> therapy and the risk of severehypoglycaemia. Diabetologia 40: 926–32.Boyle PJ, Schwartz NS, Shah SD, Clutter WE, Cryer PE (1988). Plasma glucose concentrations at theonset of hypoglycemic symptoms <strong>in</strong> patients with poorly controlled diabetes and <strong>in</strong> non-diabetics.New England Journal of Medic<strong>in</strong>e 318: 1487–92.Boyle PJ, Kempers SF, O’Connor AM, Nagy RJ (1995). Bra<strong>in</strong> glucose uptake and unawarenessof hypoglycemia <strong>in</strong> patients with <strong>in</strong>sul<strong>in</strong>-dependent diabetes mellitus. New England Journal ofMedic<strong>in</strong>e 333: 1726–31.Bulsara MK, Holman CDJ, van Bockxmeer FM, Davis EA, Gallego PH, Beilby JP, Palmer LJet al. (2007). The relationship between ACE genotype and risk of severe hypoglycemia <strong>in</strong> a largepopulation-based cohort of children and adolescents with type 1 diabetes. Diabetologia 50: 965–71.Chase HP, Lockspeiser T, Peery B, Shepherd M, MacKenzie T, Anderson J, Garg SK (2001). Theimpact of the <strong>Diabetes</strong> Control and Complications Trial and Humalog <strong>in</strong>sul<strong>in</strong> on glycohemoglob<strong>in</strong>levels and severe hypoglycemia <strong>in</strong> type 1 diabetes. <strong>Diabetes</strong> Care 24: 430–4.Clarke WL, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W (1995). Reducedawareness of hypoglycemia <strong>in</strong> adults with IDDM. A prospective study of hypoglycemic frequencyand associated symptoms. <strong>Diabetes</strong> Care 18: 517–22.Cox DJ, Irv<strong>in</strong>e A, Gonder-Frederick L, Nowacek G, Butterfield J (1987). Fear of hypoglycemia:quantification, validation and utilization. <strong>Diabetes</strong> Care 10: 617–21.Cox DJ, Kovatchev BP, Julian DM, Gonder-Frederick LA, Polonsky WH, Schlundt DG, Clarke WL(1994). Frequency of severe hypoglycemia <strong>in</strong> <strong>in</strong>sul<strong>in</strong>-dependent diabetes mellitus can be predictedfrom self-monitor<strong>in</strong>g blood glucose data. Journal of Cl<strong>in</strong>ical Endocr<strong>in</strong>ology and Metabolism 79:1659–62.Cryer PE (1992). Iatrogenic hypoglycemia as a cause of hypoglycemia-associated autonomic failure<strong>in</strong> IDDM. A vicious cycle. <strong>Diabetes</strong> 41: 255–260.Cryer PE (1994). Hypoglycemia: the limit<strong>in</strong>g factor <strong>in</strong> the management of IDDM. <strong>Diabetes</strong> 43:1378–89.Cryer PE, Davis SN, Shamoon H (2003). Hypoglycemia <strong>in</strong> diabetes. <strong>Diabetes</strong> Care 26: 1902–12.Dagogo-Jack SE, Craft S, Cryer PE (1993). Hypoglycemia-associated autonomic failure <strong>in</strong> <strong>in</strong>sul<strong>in</strong>dependentdiabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to,symptoms of, and defense aga<strong>in</strong>st subsequent hypoglycemia. Journal of Cl<strong>in</strong>ical Investigation 91:819–28.Davis EA, Keat<strong>in</strong>g B, Byrne GC, Russell M, Jones TW (1997). Hypoglycemia: Incidence and cl<strong>in</strong>icalpredictors <strong>in</strong> a large population-based sample of children and adolescents with IDDM. <strong>Diabetes</strong>Care 20: 22–5.Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R et al., for the DARTS/MEMOCollaboration (2005). Frequency and predictors of hypoglycaemia <strong>in</strong> type 1 and <strong>in</strong>sul<strong>in</strong>-treatedtype 2 diabetes: a population-based study. Diabetic Medic<strong>in</strong>e 22: 749–55.Feher MD, Grout P, Kennedy A, Elkeles RS, Touquet R (1989). <strong>Hypoglycaemia</strong> <strong>in</strong> an <strong>in</strong>ner-cityaccident and emergency department: a 12-month survey. Archives of Emergency Medic<strong>in</strong>e 6: 183–8.Galassetti P, Mann S, Tate D, Neill RA, Costa F, Wasserman DH, Davis SN (2001a). Effects ofantecedent prolonged exercise on subsequent counterregulatory responses to hypoglycemia. AmericanJournal of Endocr<strong>in</strong>ology 280: E908–17.Galassetti P, Neill AR, Tate D, Ertl AC, Wasserman DH, Davis SN (2001b). Sexual dimorphism<strong>in</strong> counterregulatory responses to hypoglycemia after antecedent exercise. Journal of Cl<strong>in</strong>icalEndocr<strong>in</strong>ology and Metabolism 86: 3516–24.Galassetti P, Tate D, Neill RA, Morrey S, Wasserman DH, Davis SN (2003). Effect of antecedenthypoglycemia on counterregulatory responses to subsequent euglycemic exercise <strong>in</strong> type 1 diabetes.<strong>Diabetes</strong> 52: 1761–9.Garg SK, Gottlieb PA, Hisatomi ME, D’Souza A, Walker AJ, Izuora KE, Chase HP (2004). Improvedglycemic control without an <strong>in</strong>crease <strong>in</strong> severe hypoglycemic episodes <strong>in</strong> <strong>in</strong>tensively treated patients
78 FREQUENCY, CAUSES AND RISK FACTORSwith type 1 diabetes receiv<strong>in</strong>g morn<strong>in</strong>g, even<strong>in</strong>g, or split dose <strong>in</strong>sul<strong>in</strong> glarg<strong>in</strong>e. <strong>Diabetes</strong> Researchand Cl<strong>in</strong>ical Practice 66: 49–56.Gerich J, Langlois M, Noacco C, Karam J, Forsham P (1973). Lack of glucagon response to hypoglycemia<strong>in</strong> diabetes: evidence for an <strong>in</strong>tr<strong>in</strong>sic pancreatic alpha-cell defect. Science 182: 171–3.Gerich JE, Mokan M, Veneman T, Korytkowski M, Mitrakou A (1991). Hypoglycemia unawareness.Endocr<strong>in</strong>e Reviews 12: 356–71.Gold AE, MacLeod KM, Frier BM (1994). Frequency of severe hypoglycemia <strong>in</strong> patients with type 1diabetes with impaired awareness of hypoglycemia. <strong>Diabetes</strong> Care 17: 697–703.Gold AE, Frier BM, MacLeod KM, Deary IJ (1997). A structural equation model for predictors ofsevere hypoglycaemia <strong>in</strong> patients with <strong>in</strong>sul<strong>in</strong>-dependent diabetes mellitus. Diabetic Medic<strong>in</strong>e 14:309–15.Gonder-Frederick L, Clarke WL, Cox DJ (1997). The emotional, social, and behavioural implicationsof <strong>in</strong>sul<strong>in</strong>-<strong>in</strong>duced hypoglycemia. Sem<strong>in</strong>ars <strong>in</strong> Cl<strong>in</strong>ical Neuropsychiatry 2: 57–65.Gonder-Frederick LA, Cox D (1997). The relationship between psychological depression and frequencyof severe hypoglycemia (SH) <strong>in</strong> IDDM. <strong>Diabetes</strong> 46: 268A(Abstract)Grimaldi A, Bosquet F, Davidoff P, Digy JP, Sachon C, Landault C et al. (1990). Unawareness ofhypoglycemia by <strong>in</strong>sul<strong>in</strong>-dependent diabetics. Hormone and Metabolic Research 22: 90–5.Hart SP, Frier BM (1998). Causes, management and morbidity of acute hypoglycaemia <strong>in</strong> adultsrequir<strong>in</strong>g hospital admission. Quarterly Journal of Medic<strong>in</strong>e 91: 505–10.Heller SR, Macdonald IA (1996). The measurement of cognitive function dur<strong>in</strong>g acute hypoglycaemia:experimental limitations and their effect on the study of hypoglycaemia unawareness. DiabeticMedic<strong>in</strong>e 13: 607–15.Hepburn DA, Patrick AW, Ead<strong>in</strong>gton DW, Ew<strong>in</strong>g DJ, Frier BM (1990). Unawareness of hypoglycaemia<strong>in</strong> <strong>in</strong>sul<strong>in</strong>-treated diabetic patients: prevalence and relationship to autonomic neuropathy. DiabeticMedic<strong>in</strong>e 7: 711–17.Hepburn DA, Patrick AW, Brash HM, Thomson I, Frier BM (1991). <strong>Hypoglycaemia</strong> unawareness<strong>in</strong> type 1 diabetes: a lower plasma glucose is required to stimulate sympatho-adrenal activation.Diabetic Medic<strong>in</strong>e 8: 934–45.Her<strong>in</strong>gs RMC, de Boer A, Stricker BHC, Leufkens HGM, Porsius A (1996). Hypoglycemia associatedwith the use of <strong>in</strong>hibitors of angiotens<strong>in</strong>-convert<strong>in</strong>g enzyme. Lancet 345: 1195–8.Hermansen K, Fonta<strong>in</strong>e P, Kukolja KK, Peterkova V, Leth G, Gall M-A (2004). Insul<strong>in</strong> analogues(<strong>in</strong>sul<strong>in</strong> detemir and <strong>in</strong>sul<strong>in</strong> aspart) versus traditional human <strong>in</strong>sul<strong>in</strong>s (NPH <strong>in</strong>sul<strong>in</strong> and regularhuman <strong>in</strong>sul<strong>in</strong>) <strong>in</strong> basal-bolus therapy for patients with type 1 diabetes. Diabetologia 47: 622–9.Hirsch BR, Shamoon H (1987). Defective ep<strong>in</strong>ephr<strong>in</strong>e and growth hormone responses <strong>in</strong> type 1diabetes are stimulus specific. <strong>Diabetes</strong> 36: 20–6.Hollander PA, Blonde L, Rowe R, Mehta AE, Milburn JL, Hershon KS et al., the Exubera Phase IIIStudy Group (2004). Efficacy and safety of <strong>in</strong>haled <strong>in</strong>sul<strong>in</strong> (Exubera) compared with subcutaneous<strong>in</strong>sul<strong>in</strong> therapy <strong>in</strong> patients with type 2 diabetes. <strong>Diabetes</strong> Care 27: 2356–62.Janssen MMJ, Snoek FJ, de Jongh RT, Casteleijn S, Deville W, He<strong>in</strong>e RJ (2000). Biological andbehavioural determ<strong>in</strong>ants of the frequency of mild, biochemical hypoglycaemia <strong>in</strong> patients with Type 1diabetes on multiple <strong>in</strong>sul<strong>in</strong> <strong>in</strong>jection therapy. <strong>Diabetes</strong> Metabolism Research and Reviews 16: 157–63.Johnson ES, Koepsell TD, Reiber G, Stergachis A, Platt R (2002). Increas<strong>in</strong>g <strong>in</strong>cidence of serioushypoglycemia <strong>in</strong> <strong>in</strong>sul<strong>in</strong> users. Journal of Cl<strong>in</strong>ical Epidemiology 55: 253–9.Jones TW, Porter P, Sherw<strong>in</strong> RS, Davis EA, O’Leary P, Frazer F et al. (1998). Decreased ep<strong>in</strong>ephr<strong>in</strong>eresponses to hypoglycemia dur<strong>in</strong>g sleep. New England Journal of Medic<strong>in</strong>e 338: 1657–62.Kerr D, Macdonald IA, Heller SR, Tattersall RB (1990). Alcohol causes hypoglycaemic unawareness<strong>in</strong> healthy volunteers and patients with type 1 (<strong>in</strong>sul<strong>in</strong>-dependent) diabetes. Diabetologia 33: 216–21.K<strong>in</strong>sley BT, Widom B, Simonson DC (1995). Differential regulation of counterregulatory hormonesecretion and symptoms dur<strong>in</strong>g hypoglycemia <strong>in</strong> IDDM. <strong>Diabetes</strong> Care 18: 17–26.Kong M-F, Macdonald IA, Tattersall RB (1996). Gastric empty<strong>in</strong>g <strong>in</strong> diabetes. Diabetic Medic<strong>in</strong>e 13:112–9.
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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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- 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
- Page 68 and 69: FREQUENCY OF HYPOGLYCAEMIA 55some i
- Page 70 and 71: FREQUENCY OF HYPOGLYCAEMIA 57Jansse
- Page 72 and 73: Table 3.2 Frequency of severe hypog
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- Page 88 and 89: CONCLUSIONS 75Other Risk FactorsThe
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- Page 94: REFERENCES 81Vervoort G, Goldschmid
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- Page 111 and 112: 98 NOCTURNAL HYPOGLYCAEMIAHolleman
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- Page 120 and 121: LIFESTYLE MODERATORS 107Growthhormo
- Page 122 and 123: LIFESTYLE MODERATORS 109mean change
- Page 124 and 125: MONITORING 111flow) while simultane
- Page 126 and 127: MONITORING 113• It is unclear whe
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- Page 130 and 131: REFERENCES 117CONCLUSIONS• Hypogl
- Page 132 and 133: REFERENCES 119MacDonald MJ (1987).
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DEFECTIVE HORMONAL GLUCOSE COUNTERR
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DEFECTIVE HORMONAL GLUCOSE COUNTERR
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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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PATHOGENESIS OF IMPAIRED AWARENESS
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PATHOGENESIS OF IMPAIRED AWARENESS
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PATHOGENESIS OF IMPAIRED AWARENESS
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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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196 HYPOGLYCAEMIA IN CHILDREN WITH
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198 HYPOGLYCAEMIA IN CHILDREN WITH
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200 HYPOGLYCAEMIA IN CHILDREN WITH
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202 HYPOGLYCAEMIA IN CHILDREN WITH
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204 HYPOGLYCAEMIA IN CHILDREN WITH
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206 HYPOGLYCAEMIA IN CHILDREN WITH
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208 HYPOGLYCAEMIA IN CHILDREN WITH
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210 HYPOGLYCAEMIA IN CHILDREN WITH
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212 HYPOGLYCAEMIA IN CHILDREN WITH
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214 HYPOGLYCAEMIA IN CHILDREN WITH
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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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CLINICAL MANAGEMENT BEFORE AND DURI
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CLINICAL MANAGEMENT BEFORE AND DURI
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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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242 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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244 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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246 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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Table 11.2a Prevalence of severe hy
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250 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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252 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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254 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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256 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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258 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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260 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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262 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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264 HYPOGLYCAEMIA IN TYPE 2 DIABETE
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266 MORTALITY, CARDIOVASCULAR MORBI
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268 MORTALITY, CARDIOVASCULAR MORBI
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270 MORTALITY, CARDIOVASCULAR MORBI
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272 MORTALITY, CARDIOVASCULAR MORBI
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274 MORTALITY, CARDIOVASCULAR MORBI
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276 MORTALITY, CARDIOVASCULAR MORBI
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278 MORTALITY, CARDIOVASCULAR MORBI
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280 MORTALITY, CARDIOVASCULAR MORBI
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282 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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FUNCTIONAL EFFECTS OF HYPOGLYCAEMIA
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FUNCTIONAL EFFECTS OF HYPOGLYCAEMIA
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STRUCTURAL AND FUNCTIONAL CHANGES I
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STRUCTURAL AND FUNCTIONAL CHANGES I
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STRUCTURAL AND FUNCTIONAL CHANGES I
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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