Long-term intensive insulin therapy in IDDM : effects of HbA1c, risk for severe and mild hypoglycaemia, status of counterregulation and awareness of hypoglycaemia

• Published in: Diabetologia 1996-06, Vol.39 (6), p.677-686
• Main Authors: PAMPANELLI, S, FANELLI, C, BARTOCCI, L, ANNIBALE, B, BRUNETTI, P, BOLLI, G. B, LALLI, C, CIOFETTA, M, DEL SINDACO, P, LEPORE, M, MODARELLI, F, RAMBOTTI, A. M, EPIFANO, L, DI VINCENZO, A
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid; Adult; Alanine - blood; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Epinephrine - blood; Fatty Acids, Nonesterified - blood; Female; Glucagon - blood; Glycated Hemoglobin A - analysis; Glycated Hemoglobin A - metabolism; Glycerol - blood; Hormones. Endocrine system; Human Growth Hormone - blood; Humans; Hydrocortisone - blood; Hydroxybutyrates - blood; Hypoglycemia - diagnosis; Hypoglycemia - drug therapy; Hypoglycemia - physiopathology; Insulin - blood; Insulin - metabolism; Insulin - therapeutic use; Lactic Acid - blood; Male; Medical sciences; Norepinephrine - blood; Pancreatic Polypeptide - blood; Perception; Pharmacology. Drug treatments; Risk Factors
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/BF00418539

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). 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%.