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


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 ≤ 5.5% (Group I, n=10), between 6.1–7.0% (Group II, n=12), and ≥ 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). In conclusion: 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 ≤ 7.0%, but also to prevent, recognize and reverse iatrogenic H unawarenes during long-term IT of IDDM by maintaining HbA1c>6.0%.

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Insulin-dependent diabetes mellitus


Diabetes Control and Complications Trial


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Correspondence to G. B. Bolli.

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Pampanelli, S., Fanelli, C., Lalli, C. et al. Long-term intensive insulin therapy in IDDM: effects on HbA1c, risk for severe and mild hypoglycaemia, status of counterregulation and awareness of hypoglycaemia. Diabetologia 39, 677–686 (1996).

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  • Hypoglycaemia
  • intensive insulin therapy
  • hypoglycaemia unawareness
  • counterregulation
  • IDDM
  • glycaemic thresholds