Clinical Endocrinology (1977) 7,301-305.

COMPARISON BETWEEN THE PLASMA INSULIN AND GLUCOSE RESPONSES TO FIVE DIFFERENT INSULIN REGIMES IN DIABETIC PATIENTS R. GOKAL, P. H A R D I N G AND R. C. T U R N E R

Nuffield Department o f Clinical Medicine, Radcliffe Infirmary, Oxford (Received 7 February 19 77; revised 24 May I 9 77; accepted 28 May I 9 77)

SUMMARY

Diurnal plasma insulin and glucose concentrations were studied in six diabetic patients, each treated with five different insulin regimes. Subcutaneous soluble insulin was too slow and long acting for physiological replacement of the normal insulin response to meals, but the peak insulin levels were higher than the postprandial levels of normal subjects. Intramuscular insulin, though absorbed more quickly than subcutaneous insulin, was not clinically advantageous. Three rather than two injections of soluble insulin gave improved blood glucose control but two combined injections of short and medium acting insulins gave nearly as good results. A long acting insulin was needed to prevent raised plasma glucose levels ovemight. Many different insulin regimes are used in diabetes, but very few comparisons have been made between the plasma insulin and glucose responses. Plasma insulin levels have been measured following single injections of soluble (Ginsberg et al., 1973; Galloway et al., 1973), Isophane (Ginsberg et al., 1973; Quickel & Feldman, 1971; Belmonte et al., 1971) and Lente (Rasmussen et al., 1975) insulin, but n o comparative studies of blood glucose control have been made. A single daily injection of along acting insulin may give moderately good control as judged by lack of glycosuria and symptoms. Some physicians, however, prefer to prescribe two or three injections per day in an attempt t o improve control and provide a more ‘physiological’ fluctuation of plasma insulin concentrations (Job et al., 1976). We have compared the plasma insulin and glucose responses over 24 h t o five different insulin regimes in six diabetic patients. METHODS

Six male, non-obese diabetics, aged 18-34 years, who presented with acute onset ketotic diabetes were treated with monocomponent insulin (Novo) for 3-6 months prior to study. All were judged t o have ‘good control’ (no glycosuria at any time, and random plasma glucose levels less than 10 mmol/l). They were treated with 26, 36, 40, 42, 54 and 60 u/day respectively. In each patient all studies were made with the same total daily dose of insulin. Correspondence: Dr R . C. Turner, Department of Regius Professor of Medicine, Radcliffe Infimary, Oxford, U.K.

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They were in hospital for the study, dressed and ambulant, taking their usual diabetic diet, except for a standard breakfast (SB) (Turner et ul., 1977). Four different insulin regimes were tested; day 1, twice daily subcutaneous Actrapid insulin (mean doses 24 and 20 u); days 2 and 3, three times a day subcutaneous or intramuscular Actrapid insulin (mean doses 14, 10 and 20 u); day 4, subcutaneous Actrapid arid Leo Retard insulin twice daily (mean doses 14/10 and loll0 u, respectively). The patients were discharged on the same total dose of Lente MC insulin and re-admitted for a further study day. All insulin injections were given 30 min before a meal. Blood samples were taken from an i.v. Teflon cannula. Plasma glucose and insulin responses to meals, including a standard breakfast, were assessed in eight non-obese normal subjects aged 39-49 years (Holman & Turner, 1977). Plasma glucose was measured using glucose oxidase and an oxygen electrode (Analox), plasma insulin and C-peptide by radioimmunoassay, using charcoal phase separation (Albano, et ul., 1972, Holman & Turner, 1977). None of the patients had anti-insulin antibodies as determined by lack of binding of radioactive insulin by the patient’s plasma in assay tubes without added antiserum. RESULTS The patients studied had a little endogenous insulin contributing to the measured plasma insulin. Fasting plasma C-peptide concentrations in the patients (with total insulin doses, insulin

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Fig. 1. Mean plasma glucose and insulin values for six patients during a 24 h period on three different subcutaneous insulin regimes. Thick line with dots, subcutaneous Actrapid-insulin twice daily ;dotted line, subcutaneous Actrapid and Leo-Retard insulins twice daily; thin line, subcutaneous Lente insulin daily.

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u/day, in parenthesis) were 0.12 (26), 0.13 (36), 0.08 (40), 0.06 (42), 0.02 (54), 0.01 (60) pmol/ml (normal fasting concentration: mean 0.38, range 0.19-0.58 pmol/ml). The 1 h increment in C-peptide following breakfast was mean 0.04, range 0-0.08 pmol/ml (normal increment 0.72, range 0.49-1.22 pmollml). The mean plasma glucose and insulin concentrations during the different regimes are shown in Figs 1 and 2, which also contain data from normal subjects. After subcutaneous soluble insulin the plasma insulin rose in all subjects by 15 min. It rose from a mean basal level of 4 mull to a mean of 22 mu/l by the time breakfast was eaten at 30 min. Plasmainsulin reached a peak (mean of peak in each patient, 59 mull) 40-70 min after breakfast, which was greater (P

Comparison between the plasma insulin and glucose responses to five different insulin regimes in diabetic patients.

Clinical Endocrinology (1977) 7,301-305. COMPARISON BETWEEN THE PLASMA INSULIN AND GLUCOSE RESPONSES TO FIVE DIFFERENT INSULIN REGIMES IN DIABETIC PA...
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