Exercise in Type 1 (insulin-dependent) diabetic patients treated with continuous subcutaneous insulin infusion

Summary The study was performed to investigate the effects of mild to moderate exercise on blood glucose levels, metabolite concentrations and responses of counterregulatory hormones in tightly controlled Type 1 (insulin-dependent) diabetic patients treated by continuous subcutaneous insulin infusion, and to quantify the measures necessary to prevent acute and late exercise-induced hypoglycaemia. Seven male patients started a 60 min exercise period 90 min after an insulin bolus and a standard breakfast; they were monitored during a post-exercise resting period of 5 h 30 min. Different basal and premeal insulin infusion rates were applied. (Near)normoglycaemia prevailed throughout the study during the control protocol when the subjects did not exercise and received their usual insulin dose. When they exercised without changing the insulin dose, four patients were forced to stop due to hypoglycaemia. This effect of exercise could be attenuated but not completely avoided if the basal infusion rate of insulin was discontinued during the exercise period. The pronounced increase in catecholamine and growth hormone concentrations during exercise were not sufficient to prevent hypoglycaemic reactions. Hypoglycaemia during exercise could only be prevented when the premeal insulin bolus was reduced by 50% in addition to the discontinuation of the basal insulin infusion during exercise. In order to reduce late hypoglycaemic reactions after exercise the best measure proved to be a reduction of the basal insulin infusion rate by 25% during post-exercise hours. Administration of only 50% of the basal insulin infusion rate during this time was associated with blood glucose levels being raised up to 8 mmol/l. In conclusion, Type 1 diabetic patients treated with continuous subcutaneous insulin infusion at (near)normoglycaemia need to reduce their insulin dosage before, during, and after mild to moderate endurance exercise in order to minimize the risk of acute and late hypoglycaemia.     

Chronic continuous intraperitoneal insulin infusion (CIPII) in type I diabetic patients non-satisfactorily responsive to continuous subcutaneous insulin infusion (CSII)

Summary Six unstable C-peptide negative type I diabetic patients who had been previously treated with continuous subcutaneous insulin infusion (CSII) for at least one year without achieving satisfactory metabolic control, were admitted to this study and switched to continuous intraperitoneal insulin infusion (CIPII). The results obtained with the two treatments have been compared from the metabolic and clinical points of view. CIPII produced a decrease in HbA_1c (p<0.05), in MAGE value (p<0.005), in the percentage of blood glucose determinations above 14 mmol/l (p<0.05) and below 3.9 mmol/l (p<0.05); an increase in serum cholesterol, and a decrease in HDL-cholesterol (p<0.05) due to a reduction of the HDL₂ fraction (p<0.01). A mean body weight reduction of 3 kg was observed during CIPII (p<0.01), not related to dietary changes or to a reduction of the daily insulin dose. Twenty-four hour metabolic profiles during CIPII showed lower mean plasma glucose (p<0.001), serum free insulin (p<0.001), blood β-OH-butyrate (p<0.001), and higher serum glycerol (p<0.001) as compared to CSII. It is concluded that CIPII may be of clinical value in the out-patient management of unstable type I diabetic patients, and that metabolic modifications induced by CIPII are not limited to changes in glucose utilization and production, but include changes in triglyceride, cholesterol and lipid metabolism which may have clinical relevance. Supported by the National Research Council (CNR), Target Project ‘Preventive Medicine and Rehabilitation’, Subproject ‘4’ and by the Juvenile Diabetes Foundation, U.S.A., file No. 184066.     

Increased glucose carbon recycling in severely insulin deficient Type 1 (insulin-dependent) diabetic subjects

Summary Six Type 1 (insulin-dependent) diabetic subjects were studied in order to determine the contribution of recycling of glucose carbon to the overproduction of glucose which is characteristic of the fasting hyperglycaemia produced by insulin withdrawal. The subjects were studied on two occasions, once after an overnight insulin infusion and once following 24 h of insulin withdrawal. The difference in turnover rates of 1-¹⁴C-glucose and 3-³H-glucose was used as a measure of glucose recycling. Insulin withdrawal caused a marked metabolic derangement with a rise in non-esterified fatty acids from 0.69±0.23 to 1.11±0.21 mmol/l (mean±SEM, p<0.05), total ketones from 0.27±0.06 to 2.06±0.51 mmol/l (p<0.01), cortisol from 341±43 to 479±31 nmol/l (p<0.05) and growth hormone from 1.1±0.3 to 19+5-mu/l (p<0.05). Glucose turnover rose from 13.8±2.3 mol·kg^–1·min^–1 at a glucose of 6.9±0.7 mmol/l in the insulin infused study to 25.8±4.4 mol·kg^–1·min^–1 (p<0.05) at a glucose of 16.4±0.7 mmol/l in the insulin withdrawn study. Recycling also rose from 3.0±0.4 mol· kg^–1·min^–1 to 9.4±2.2 mol·kg^–1·min^–1 (p<0.05) when insulin withdrawn, accounting for 23±3% and 36±3% of glucose turnover, respectively. We conclude that in the severely insulin deficient Type 1 diabetic subject recycling of glucose carbon is a major contributor to the excess glucose production.     

Hepatic glucose production during intraperitoneal and intravenous closed-loop insulin regulation of blood glucose in Type 1 (insulin-dependent) diabetic patients

Summary Intraperitoneal infusion of insulin should be more physiological than intravenous insulin since part of the insulin is directed toward the portal vein, which allows the liver to retain its major role in glucose homeostasis. The regulation of hepatic glucose production during the intraperitoneal and intravenous infusions of insulin were compared in eight Type 1 (insulin-dependent), C-peptide-deficient diabetic patients. Primed, continuous infusions of [6,6-²H] glucose were given in the postabsorptive state and during continuous infusion of unlabelled glucose at 1.5 and 4 mg/kg· min, while normoglycaemia was maintained by closed-loop intraperitoneal and intravenous insulin delivery. During all three periods, plasma glucose concentrations remained near normal (variations 3.8–6.1%). The insulin infusion rates required for normal plasma glucose concentrations were essentially the same for the intravenous and intraperitoneal routes in all cases, although the variations were greater with intraperitoneal insulin. Plasma free-insulin levels were only slightly, non-significantly lower with intraperitoneal infusion than with intravenous infusion. Hepatic glucose production was significantly lower with intraperitoneal insulin during all three conditions: basal: 1.71±0.14, i.p. vs 2.37±0.26 mg/kg · min, i.v.; 1.5 mg/kg · min glucose infusion: 0.49±0.23, i.p. vs 0.88±0.18 mg/kg · min, i.v.; 4 mg/kg · min glucose infusion: 0.31±0.10, i.p. vs 0.56±0.12 mg/kg · min, i.v. These results, obtained with steady-state conditions for plasma glucose, isotopic plasma glucose enrichments and unlabelled glucose infusion rates, suggest that better control of hepatic glucose production leading to normoglycaemia was achieved with the intraperitoneal infusion.     

The effect of intraperitoneal insulin delivery on carbohydrate metabolism in type 1 (insulin-dependent) diabetic patients.

Patients with type 1 diabetes are usually given insulin subcutaneously, but this does not mimic the physiological route of pancreatic insulin release, which may be better achieved with intraperitoneal insulin. Five C-peptide negative type 1 diabetic patients were studied on two occasions, once with intravenous (IV) and once with intraperitoneal (IP) insulin. Normoglycaemia was maintained from 1700 h with variable insulin infusion, and glucose turnover and recycling assessed from 0600 to 0800 h. A 4-h hyperinsulinaemic (25 mU kg-1 h-1) euglycaemic clamp was then performed, with IP or IV insulin delivery. During the night similar insulin infusion rates were needed to achieve equal blood glucose concentrations. Glucose turnover was identical (IV: 2.4 +/- 0.2 vs IP: 2.3 +/- 0.1 mg kg-1 min-1) (+/- SE) with glucose/carbon recycling 8.8 +/- 4.7 and 12.8 +/- 2.9% (NS). Blood lactate, pyruvate and alanine concentrations were significantly higher with IP than IV insulin (P less than 0.05). During the clamp, insulin concentration was 28 +/- 3 mU/l with IV insulin and 15 +/- 1 mU/l with IP insulin (P less than 0.05) and glucose requirement 2.0 +/- 0.5 and 0.8 +/- 0.3 mg kg-1 min-1, respectively (P less than 0.05). Glucose carbon recycling was higher with IP insulin (P less than 0.05). We conclude that: (1) in type 1 (insulin-dependent) diabetic patients hepatic glucose production could be normalized with both routes of insulin administration, and (2) at the same insulin infusion rate, the relative peripheral hypoinsulinaemia with IP route is sufficient to increase the rate of release of gluconeogenic precursors, or decrease their hepatic uptake.     

Accuracy of continuous subcutaneous glucose monitoring with the GlucoDay in type 1 diabetic patients treated by subcutaneous insulin infusion during exercise of low versus high intensity

AIM: The GlucoDay allows continuous glucose monitoring by subcutaneous microdialysis in sedentary conditions. To validate it when glycaemia may undergo rapid and dramatic changes, we investigated its accuracy during two exercise sessions with markedly different glucose disposal rates. METHODS: Nine male diabetic patients, aged 32-61, treated by insulin pumps, first underwent a standard maximal exercise-test designed for determining the maximal oxygen consumption and the first ventilatory threshold (Vt1). Then two 30 min steady-state workloads at 15% below and 15% above the Vt1 were performed in random order with the GlucoDay, and measurement of CHO oxidation rates was made by indirect calorimetry. RESULTS: CHO oxidation during exercise at +15% Vt1 was higher (+943.5 mg/min, ie +45.5%, P<0.01) than during exercise at -15% Vt1 No hypoglycaemia occurred. Due to breakages of 39% of subcutaneous probes, eleven steady-state sessions in 7 subjects allowed to compare 141 paired glucose (sensor vs. venous) determinations. The Clarke error grid situates 92.9% of glucose values within the A zone and 6.4% within the B zone, while only one pair of values (0.7%) falls in the D zone. Venous glucose tended to decrease more rapidly than sensor glucose during exercise. Bland-Altman plots evidence for a few cases of underestimation of venous glucose at high intensity. CONCLUSIONS: This study showed satisfactory accuracy of the GlucoDay during exercise. A slight lag time in sensor values likely explains a few discrepancies that do not appear as clinically meaningful. Reduction of probe fragility and confirmed sensor accuracy in hypoglycaemia would further support applicability of GlucoDay at exercise.     

Diurnal variation of carbohydrate insulin ratio in adult type 1 diabetic patients treated with continuous subcutaneous insulin infusion

To estimate the carbohydrate‐to‐insulin ratio (CIR), a formula dividing a constant, usually 300–500, by the total daily dose (TDD) of insulin, is widely utilized. An appropriate CIR varies for each meal of the day, however. Here, we investigate diurnal variation of CIR in hospitalized Japanese type 1 diabetic patients treated with continuous subcutaneous insulin infusion. After optimization of the insulin dose, TDD and total basal insulin dose (TBD) were 34.9 ± 10.2 and 9.3 ± 2.8 units, respectively, with a percentage of TBD to TDD of 27.3 ± 6.0%. The products of CIR and TDD at breakfast, lunch and dinner were 311 ± 63, 530 ± 161, and 396 ± 63, respectively, suggesting that in the formula estimating CIR using TDD, the constant should vary for each meal of the day, and that 300, 500, and 400 are appropriate for breakfast, lunch, and dinner, respectively.     

Minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in Type 1 (insulin-dependent) diabetic pancreas allograft recipients

Summary Decreased insulin sensitivity and glucose-dependent glucose disposal (glucose effectiveness) have been demonstrated in poorly-controlled Type 1 (insulin-dependent) diabetic patients. We have therefore examined the effects of successful pancreas transplantation that results in long-term physiologic normoglycaemia as measured by insulin sensitivity index and glucose effectiveness in 14 Type 1 diabetic recipients (Group 1) using the Bergman minimal model method. Their results were compared with those of five non-diabetic patients with kidney transplant alone (Group 2) and 10 healthy control subjects (Group 3). Mean plasma glucose levels were indistinguishable in Group 1 when compared to Groups 2 and 3. However, mean basal plasma insulin levels were two-and eight-fold greater in Group 1 (36±6 U/ml) than in Group 2 (17±7 U/ml) and Group 3 (4.5±0.6 U/ml), respectively. Following intravenous glucose (t=0 min) and tolbutamide (t=20), peak incremental insulin levels were significantly (p<0.001) greater in Group 1 vs Groups 2 and 3. Mean insulin sensitivity index was 65% and 50% lower in Group 1 (2.89±0.45) and Group 2 (4.11±1.30), respectively, when compared to GroupS (8.40±1.24×10^–1 min^–1 (U/ml)^–1. In contrast, glucose effectiveness was similar in the three groups (Group 1, 2.48±0.26; Group 2, 2.05±0.21; and Group 3, 2.10±0.17×10^–2·min^–1). We conclude that, despite prednisone-induced insulin resistance, normal glucose tolerance is achieved by hyperinsulinaemia and normalisation of glucose-dependent glucose disposal following pancreas-kidney transplantation in Type 1 diabetic patients.     

Retrospective analysis of daily glucose profile in type 1 diabetic patients with continuous subcutaneous insulin infusion (CSII).

A retrospective analysis of blood glucose control was performed in 17 type 1 diabetic patients who regularly monitored their blood glucose concentration by visual strips over a period of 3-83 months. Analysis was performed by a patient management software loaded on a personal computer. In this cohort of patients the average daily blood glucose reading was 1.6 +/- 0.3. Blood glucose readings were collected more frequently following meal ingestion (40.3%) than in the post-absorptive state (24.6%; P less than 0.05). Blood glucose concentration fluctuated from a basal level of 146 +/- 5 mg/dl to 167 +/- 4 mg/dl in the post-prandial phases with an average daily value of 156 +/- 2 mg/dl. Blood glucose values below 80 mg/dl were evenly distributed throughout the day, while hyperglycemia (greater than 300 mg/dl) occurred more commonly after meals (42%). Daily blood glucose was higher during weekends (164 +/- 5 mg/dl) than during weekdays (155 +/- 2 mg/dl; P less than 0.05). A weak correlation was found between the number of blood glucose readings/day and daily blood glucose level. These results suggest that long-term maintenance of satisfactory metabolic control is attainable in type 1 diabetic patients and that this is mainly dependent upon subject self awareness.     

Comparison between multi-injection and continuous subcutaneous insulin therapy in insulin-dependent diabetic inpatients

Summary Circadian blood glucose profiles have been evaluated in 8 insulin-dependent diabetic inpatients on their usual home insulin therapy, on a 3-injection regimen (ultralente in the morning plus 3 injections of regular insulin at meals), on continuous subcutaneous insulin infusion by portable micropumps (Mill Hill 1001) and, again, on a 3-injection regimen at the same insulin dose as during continuous subcutaneous insulin infusion. The 3-injection regimen achieved a mean daily blood glucose level comparable to that obtained by continuous subcutaneous insulin infusion, even if significantly more insulin was needed. At comparable insulin doses, continuous subcutaneous insulin infusion provided a significantly lower mean daily blood glucose. Glycemic control at 06⁰⁰ and 08⁰⁰ was better during continuous subcutaneous insulin infusion. Low acceptance by the patients of the home use of portable micropumps was evidenced because of the practical and psychological problems involved.Deceased on March 3, 1981.     

Accuracy assessment of online glucose monitoring by a subcutaneous enzymatic glucose sensor during exercise in patients with type 1 diabetes treated by continuous subcutaneous insulin infusion

AimOnline continuous glucose monitoring (CGM) during physical exercise would be highly useful in patients with insulin-treated diabetes. For this reason, this study assessed whether such a goal could be reached with a subcutaneous ‘needle-type’ enzymatic sensor.MethodsTen patients (five women/five men), aged 51 ± 12 years, with type 1 diabetes for 24 ± 11 years treated by continuous subcutaneous insulin infusion (CSII) for more than 1 year (HbA_1c: 7.5 ± 0.8%) performed a 30-min bout of exercise at a constant high-intensity load (15% above their individual ventilatory threshold) on a cycle ergometer. All patients wore a subcutaneous ‘needle-type’ enzymatic glucose sensor linked to a portable monitor (Guardian^® RT, Medtronic-MiniMed, Northridge, CA, USA) that had been inserted the previous evening. Sensor calibration was performed against capillary blood glucose immediately before the exercise. CGM values were recorded every 5 min from T_–10 to T₊₃₀, then every 10 min during the recovery period from T₊₃₀ to T₊₉₀. These recorded values were compared with blood glucose assays performed on simultaneously collected venous samples.ResultsSensor functioning and tolerability raised no problems except for one sensor that could not be adequately calibrated. Data from this patient were excluded from the data analysis. An average blood glucose decrease of 63 ± 63 mg/dL (3.5 ± 3.5 mmol/L) (median decrease: 58 mg/dL [3.22 mmol/L]; range: –3 mg/dL [0.16 mmol/L] to 178 mg/dL [9.8 mmol/L]) occurred during exercise bouts, while CGM values decreased by 38 ± 49 mg/dL (2.11 ± 2.72 mmol/L) (median: 32 mg/dL [1.7 mmmol/L]; range: –15 mg/dL [0.83 mmol/L] to 58 mg/dL [3.22 mmol/L]). Cumulative paired glucose values (n = 135) could be analyzed. The correlation factor between CGM and blood glucose values was 0.957 with an intercept of 0.275. The mean difference between paired values according to Bland–Altman analysis was 10 ± 31 mg/dL (0.56 ± 1.72 mmol/L). Clarke error grid analysis showed 91% of paired points in A and B zones, while 0%, 9% and 0% of paired points were in the C, D and E zones, respectively.ConclusionBlood glucose changes during intensive physical-exercise bouts performed by CSII-treated type 1 diabetes patients can be estimated with acceptable clinical accuracy by online CGM.     

Sexual activity in diabetic patients treated by continuous subcutaneous insulin infusion therapy

Background and aimsAs concerns over interference with sexual activity may be an obstacle to initiating pump therapy in diabetic patients, the aim of the study was to assess the impact of continuous subcutaneous insulin infusion (CSII) therapy on sexual activity.Patients and methodsPatients filled out a questionnaire on their demographic data, diabetes history, pump-treatment history, metabolic control, inconvenience/convenience of the pump and catheter, and information on sexual activity.ResultsA total of 271 diabetic patients (aged 44 ± 17 years, 51% women, 22% single), treated with CSII for 4.2 ± 5.9 years and with a diabetes duration of 19 ± 11 years, filled out the questionnaire. Their HbA_1c was 7.7 ± 1.1%, with 2.4 ± 2.1 mild hypoglycaemic episodes over the past week, and their frequency of sexual activity was: never 29.9%; < 1/month 12.3%; > 1/month and < 1/week 18.2%; and > 1/week 39.6%. Age and cohabitation were independently correlated with frequency of sexual activity (P < 0.0001 and P < 0.0003, respectively), but not diabetes duration or complications. To the question “Does the pump have an influence on your sexual activity?”, The answer was “no” in 90% and “yes” in 10%. However, intercourse frequency was significantly decreased in the latter (P = 0.04). On multivariate analyses, this negative influence of CSII was correlated with HbA_1c (P < 0.05), discomfort with the pump (P < 0.05) and the number of mild hypoglycaemic episodes (P < 0.01).ConclusionFrequency of sexual activity appears to be unaffected by pump therapy or diabetes, but is decreased by the expected characteristics–namely, age and being single. Also, only 10% of patients believe that CSII is an obstacle during sexual activity and, in particular, because of the catheter.     

Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion,and impact on glucose control

The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti‐insulin antibodies (IAs). Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), continuous peritoneal insulin infusion (CPII) and more recently inhaled insulin administration, appear to significantly increase circulating levels of immunoglobulin G (IgG) anti‐IAs in diabetic patients. However, the increase is usually moderate and mostly transient as compared to previous observations with poorly purified animal insulin preparations. The clinical impact of these circulating anti‐IAs remains unclear. Nevertheless, several studies have suggested that antibodies could retard insulin action, leading to a worsening of postprandial hyperglycaemia and/or serve as a carrier, thus leading to unexpected hypoglycaemia. CPII may be associated with more marked and sustained increase in IAs levels, possibly related to the use of an unstable insulin and the formation of immunogenic aggregates of insulin. The possible clinical consequences of these high levels of IAs remain to be evaluated because a low‐glucose morning syndrome or severe insulin resistance with ketone bodies production have been reported in some cases. In conclusion, even if CSII and CPII may promote the development of circulating IAs, this increase does not lead to immunological insulin resistance, compared to that previously described with animal non‐purified insulin preparations, and seems to have only marginal influence on blood glucose control or complications in most diabetic patients. Copyright © 2009 John Wiley & Sons, Ltd.     

短期胰岛素泵治疗初诊2型糖尿病患者的随访研究

目的 观察短期应用胰岛素泵治疗初诊2型糖尿病的中远期疗效及不良反应.方法 观察、随访、回顾性分析256例初诊2型糖尿病患者经胰岛素泵(CSII)强化治疗2周后控制血糖情况、不服用药物血糖达标(空腹血糖:3.9～7.0 mmol/L,餐后2h血糖:3.9～10.0 mmol/L)持续时间(缓解期)等.结果 CSII治疗3 d血糖达标率46.7%,7 d达标率78.4%,2周达标率92.2%;拆除胰岛素泵缓解期超过3个月的患者共192例(75%),超过6个月166例(64.8%),超过12个月137例(53.5%),超过24个月79例(30.9%),超过36个月26例(10.2%),无1例超过48个月.缓解期少于3个月的患者,其停用胰岛素时的剂量明显高于缓解期超过3个月的患者(P＜0.01),停用胰岛素时的剂量与缓解期的长度呈负相关(r=-0.63,P＜0.01).结论 CSII可迅速有效使初诊2型糖尿病患者血糖达标,消除高血糖的毒性作用,使受糖毒性损伤的残存胰岛β细胞功能得到一定程度恢复,可延缓胰岛β细胞功能的衰退.     

Metabolic and hormonal responses to exercise in type 1 diabetic patients during continuous subcutaneous, as compared to continuous intraperitoneal, insulin infusion

This study was performed to determine whether metabolic and hormonal responses during moderate exercise differ between continuous intraperitoneal insulin infusion (CIPII) and continuous subcutaneous insulin infusion (CSII). In seven Type 1 diabetic patients, treatment was changed from CSII to CIPII. Prior to the change, these patients performed an ergometer exercise at 60% of VO2max for 40 min followed by a 200-min rest. About one year later, when the procedure was repeated during CIPII, HbA1c had improved from 8.5 to 7.1%. Arterial blood glucose, venous lactate and hormonal responses were analysed. Although a regimen with a higher basal insulin infusion rate was applied during the exercise test on CIPII, corresponding venous insulin levels were lower (28.0 +/- 2.2 vs. 48.1 +/- 7.9 pmol L-1, p = 0.04). Exercise caused a more marked decline in blood glucose during CIPII, with nadir blood glucose at the end of exercise (3.6 +/- 0.4 vs. 5.1 +/- 0.4 mmol L-1, p = 0.005). Both exercise tests yielded significant and similar increases in plasma levels of adrenaline, noradrenaline, cortisol and growth hormone. A significant rise in plasma glucagon (15.1 +/- 4.5 pg mL-1, p = 0.01) was observed during CIPII, but not during CSII (7.4 +/- 3.5, pg mL-1, n.s.). It is concluded that patients on CIPII should reduce their insulin infusion rate during exercise. CIPII appears to have favourable effects on counterregulatory capacity; in particular, a more prominent glucagon response to exercise may prove important.     

Prostaglandin E1 accelerates subcutaneous insulin absorption in insulin-dependent diabetic patients

The powerful vasodilator, prostaglandin E1 (PGE1), was added to Actrapid insulin to try to accelerate the early phase of subcutaneous insulin absorption through increasing injection site blood flow. Actrapid insulin alone (6U) and insulin containing PGE1 (7.5 X 10(-6) M) were injected on different days into 13 fasting insulin-dependent diabetics. With the insulin/PGE1 mixture, increases in both free and total plasma insulin concentrations were greater at all times up to 120 minutes after injection than with insulin alone, with significant differences in the first 40 minutes. With insulin/PGE1 the area under the total plasma insulin curve increased significantly more rapidly between 80 and 120 minutes. Plasma glucose concentrations fell consistently more rapidly with insulin/PGE1 than with insulin alone although the differences were small (mean fall +/- S.E.M. at 120 minutes: 4.9 +/- 0.5 mmol/l vs 4.0 +/- 0.6; p = 0.02). Addition of local hyperaemic agents to short-acting insulin preparations could be therapeutically useful in hastening insulin entry to the circulation at mealtimes.     

Pulsatile insulin infusion and glucose-homeostasis in well-controlled type 1 (insulin-dependent) diabetic patients

Pulsatile, intravenous insulin infusion designed to mimic the portal insulin concentrations that emerge physiologically after a meal, has been postulated to improve glucose tolerance in Type 1 (insulin-dependent) diabetic patients. We studied the effects of insulin pulsing (10 i.v. pulses of human insulin of 0.035 U kg-1 idealised body weight were given, each of 20 s duration, with intervals of 6 min, three times per day covered with adequate administration of glucose) on 2 successive days on glucose-tolerance in nine well-controlled Type 1 diabetic patients on continuous subcutaneous insulin infusion therapy (age 26 (7) years, mean (SD); duration of diabetes 10 (7) years; body mass index 23.4 (2.3) kg m-2; HbA1c 6.0 (0.6)%). On the days before and after the insulin pulsing, the patients were subjected to metabolic assessments by an oral glucose tolerance test (1 g glucose kg-1 body weight) 30 min after the subcutaneous injection of 0.15 U kg-1 body weight regular human insulin and a subsequent bicycle-ergometer test. During these metabolic assessments, plasma free insulin concentrations, plasma glucagon and the non-protein respiratory quotient remained unaffected by the insulin pulsing. However, glucose tolerance deteriorated significantly (maximal glucose concentration 120 min after glucose load was 10.0 mmol l-1 before and 13.9 mmol l-1 after insulin pulsing, P less than 0.01). In conclusion, the pattern of insulin pulsing used in this study did not ameliorate oral glucose homeostasis in well-controlled Type 1 (insulin dependent) diabetic patients.     

Effects of a novel short-term continuous subcutaneous insulin infusion program evaluated by continuous glucose monitoring on young adult type 1 diabetic patients in Taiwan

The aim of this study is to evaluate the effectiveness of blood sugar control by a short-course reinforcement program, consisting of using continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) for young adult type 1 diabetic patients. Twenty-six pump-na?ve type 1 diabetic patients were successively enrolled in two years. The mean disease duration was 13 years and the mean HbA1c was 8.8 %. Initially, a 3-day course of CGM was used to evaluate the baseline glycemic status of the subjects, followed by 6-day intensive insulin adjustment by CSII therapy. Thereafter, a second course of CGM was performed to evaluate the effectiveness of our outcomes in comparison to the initial measurements. All participants received necessary education and instruction as required throughout the course of the program. The glucose variability as measured by standard deviation of plasma glucose and mean amplitude of glucose excursion decreased significantly (67.8 ± 2.7 to 52.0 ± 1.8 mg/dL and 140.4 ± 6.5 to 105.5 ± 5.3 mg/dL, p < 0.001). The hypoglycemic events noted per patient were reduced by 46.4% (p = 0.003) and occurred significantly less often during nocturnal periods (-63.2%, p = 0.002). Following the adjustment, the mean daily insulin requirement was reduced by 28.05% (from 0.82 to 0.59 IU/kg) and the new proportion of 40% as basal insulin was found. The short-term CSII program provided significant improvement in blood sugar control for type 1 diabetic patients, by reducing hypoglycemic events, glucose excursion, and insulin dosage in our examined subjects.     

Low subcutaneous degradation and slow absorption of insulin in insulin-dependent diabetic patients during continuous subcutaneous insulin infusion at basal rate

Summary As information on the absorption kinetics and local degradation of infused insulin is relevant to programming strategies for continuous subcutaneous insulin infusion, we examined the time relationship of systemic insulin appearance and quantitated subcutaneous degradation during a near-basal rate of continuous subcutaneous insulin infusion in five insulin-dependent diabetic patients. Plasma free insulin was monitored for 8 h during and 3 h after a subcutaneous (abdominal wall) infusion of neutral insulin at 2.4 U/h. An identical intravenous infusion (2–4 h) was given on a separate occasion. Plateau levels of free insulin were not significantly different during the subcutaneous (37±8 mU/l) and intravenous (40±7 mU/l) infusions. Fitting of the free insulin data to our two-pool model of the subcutaneous space gave a mean estimate of 9.2 units insulin (= 3.8 h infusion) for the subcutaneous depot after 8 h. Model estimates of systemic insulin appearance, as a percentage of subcutaneous infusion rate, were 59% and 93% after 4 and 8 h respectively, and 76% 2 h after cessation of infusion. In insulin-dependent diabetic patients subcutaneous degradation of infused insulin is negligible but local accumulation in the subcutaneous space is considerable. The delay in absorption has important clinical implications for interruption and resumption of continuous subcutaneous insulin infusion and also for programming of variable basal rates.