title: Long-term intensive insulin therapy in IDDM: effects on HbA1c, risk for severe and mild hypoglycaemia, status of counterregulation and awareness of hypoglycaemia.
abstract: The present studies were designed to assess the percentage of HbA1c, frequency, and awareness of hypoglycaemia (H) during long-term intensive therapy (IT) of insulin-dependent diabetes mellitus (IDDM). From 1981 to 1994, 112 IDDM patients were on IT. HbA1c was 7.17 +/- 0.16% (non-diabetic subjects 3.8-5.5%), the frequency of severe H 0.01 +/- 0.009 episodes/patient-year, frequency of mild symptomatic H 35.6 +/- 2.9 episodes/patient-year. IDDM patients with HbA1c < or = 5.5% (Group I, n = 10), between 6.1-7.0% (Group II, n = 12), and > or = 7.6% (Group III, n = 11) were studied to assess responses of counterregulatory hormones, symptoms and cognitive function during experimental, stepped H. Compared to 18 non-diabetic subjects, Group I exhibited high thresholds (plasma glucose had to decrease more than normal to evoke responses), and impaired responses of adrenaline, unawareness of H and delayed onset of cognitive dysfunction at the lowest glycaemic plateau (2.3 mmol/l). Group II had normal thresholds and responses, whereas Group III had low thresholds. Frequency of mild H was higher in Group I (54.5 +/- 1.9 episodes/patient-year) than in Group II and III (33.7 +/- 3.5 and 20.4 +/- 2.5 episodes/patient-year, respectively, p < 0.001) and correlated with percentage of HbA1c (r = -0.82).
  
  
  CONCLUSIONS
  IT can maintain near-normal HbA1c and is compatible with low frequency of severe H. However, if HbA1c is less than 6.0%, mild, symptomatic H is excessively frequent and causes impaired counterregulation and H unawareness. Efforts should be made not only to maintain HbA1c < or = 7.0%, but also to prevent, recognize and reverse iatrogenic H unawareness during long-term IT of IDDM by maintaining HbA1c > 6.0%.
authors.affiliation: Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, University of Perugia, Perugia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Pampanelli
authors.forename: C
authors.initials: C
authors.lastname: Fanelli
authors.forename: C
authors.initials: C
authors.lastname: Lalli
authors.forename: M
authors.initials: M
authors.lastname: Ciofetta
authors.forename: P D
authors.initials: PD
authors.lastname: Sindaco
authors.forename: M
authors.initials: M
authors.lastname: Lepore
authors.forename: F
authors.initials: F
authors.lastname: Modarelli
authors.forename: A M
authors.initials: AM
authors.lastname: Rambotti
authors.forename: L
authors.initials: L
authors.lastname: Epifano
authors.forename: A
authors.initials: A
authors.lastname: Di Vincenzo
authors.forename: L
authors.initials: L
authors.lastname: Bartocci
authors.forename: B
authors.initials: B
authors.lastname: Annibale
authors.forename: P
authors.initials: P
authors.lastname: Brunetti
authors.forename: G B
authors.initials: GB
authors.lastname: Bolli
mesh_terms: D020155:3-Hydroxybutyric Acid; D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006885:Hydroxybutyrates / Q000097:blood; D007003:Hypoglycemia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010191:Pancreatic Polypeptide / Q000097:blood; D010465:Perception; D012307:Risk Factors
chemical_list: D020155:3-Hydroxybutyric Acid; D000409:Alanine; D001786:Blood Glucose; D004837:Epinephrine; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D006442:Glycated Hemoglobin; D005990:Glycerol; D019382:Human Growth Hormone; D006854:Hydrocortisone; D006885:Hydroxybutyrates; D007328:Insulin; D019344:Lactic Acid; D009638:Norepinephrine; D010191:Pancreatic Polypeptide