持续皮下胰岛素注射在糖尿病酮症酸中毒早期应用的合理性探讨

目的:比较持续皮下胰岛素注射(CSⅡ)和持续静脉胰岛素输注(CVⅡ)在合并糖尿病酮症酸中毒(DKA)患者早期治疗中的有效性和合理性.方法:比较两组血糖达标时间、胰岛素用量、酮体和酸中毒纠正的时间、低血糖发生率及治疗前5 d血糖水平波动情况.结果:两组血糖达标的时间类似,但CSⅡ组前5 d血糖稳定于靶目标值(11.1±2.0 mmol/L)比例更高,且血糖的波动更小,前3 d胰岛素的用量更小(P均＜0.05);两组在酮体转阴、酸中毒纠正的时间以及低血糖的发生上无显著性差异(P均＞0.05).结论:CSⅡ和CVⅡ都能纠正DKA早期的代谢紊乱,但CSⅡ能使血糖更平稳、波动更小,临床使用须根据病情而定.     

Substitution of night-time continuous subcutaneous insulin infusion therapy for bedtime NPH insulin in a multiple injection regimen improves counterregulatory hormonal responses and warning symptoms of hypoglycaemia in IDDM

Summary In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean ± SEM): 16.1 ± 3.1 vs 23.6 ± 3.3) episodes during the last 6 weeks of treatment, p = 0.03 (CSII vs NPH)) with maintenance of good glycaemic control (HbA_1c 7.2 ± 0.2 vs 7.1 ± 0.2 %, p = 0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study. [Diabetologia (1998) 41: 322–329] Received: 21 July 1997 and in revised form: 7 October 1997     

Suppression of counterregulatory hormone response to hypoglycemia by insulin per se

Although assessment of counterregulatory hormone responses to hypoglycemia relies upon insulin to lower the glucose level, it is not known if the exogenous insulin does used itself influences the magnitude of the hormone response. To assess this, 12 normal subjects randomly received 2 hypoglycemic clamp studies in which the only variable was the insulin dose (0.6 or 5.0 mU/kg-min). Despite 10-fold differences in circulating insulin (265 +/- 29 vs 2576 +/- 222 pmol/L respectively), the hypoglycemic stimulus did not vary. Glucose levels fell over one hour, and then were maintained for two hours at the same hypoglycemic plateau (approximately 3.1 mmol/L for each study) by a variable glucose infusion. Although basal counterregulatory hormone levels in low and high dose studies were indistinguishable, during hypoglycemia the response of epinephrine, growth hormone, and glucagon was significantly suppressed when the degree of hyperinsulinemia was increased. We conclude that raising the magnitude of hyperinsulinemia suppresses the magnitude of the counterregulatory hormone response to hypoglycemia in normal subjects. This modulating effect of insulin per se is yet another variable in the interpretation of hypoglycemic counterregulation.     

Counterregulatory responses in CSII

Normally, glucose is the only substrate used by the brain to meet its metabolic requirements. Therefore, a continuous supply of circulatory glucose is a necessary prerequisite for normal cerebral metabolism. Acute hypoglycemia produces several physiological responses, known as counterregulatory, symptomatic and behavioral responses, that aim at preventing further decrease in plasma glucose and thus correct hypoglycemia. Subjects with type 1 diabetes mellitus under intensive insulin treatment either with multiple daily injections (MDI) or with continuous subcutaneous insulin infusion (CSII) exhibit defects in these responses, mainly the adrenaline response, which may increase the recurrence of hypoglycemia in daily life. Unfortunately, recurrence of hypoglycemia [i.e. blood glucose < 70 mg/dl (3.9 mmol/L)], including mild hypoglycemia, does further impair such hormonal responses and the awareness of hypoglycemia resulting in additional risk for severe hypoglycemia. CSII, which for several reasons, including subjects' preferences and higher costs, is less widespread than MDI, allows achievment of good glycemic control while reducing the risk of hypoglycemia and of hypoglycemia induced blunted counterregulatory and symptomatic responses (hypoglycemia-associated autonomic failure). For that reason, CSII would be particularly indicated in people suffering from recurrence of severe hypoglycemia and hypoglycemia unawareness under a MDI treatment regimen.     

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.     

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.     

Metabolic control in newly kidney transplanted insulin-dependent diabetics: Improvement by insulin pump treatment (CSII)

Management of glucose homeostasis in newly kidney transplanted insulin-dependent diabetic patients is difficult. To examine whether continuous subcutaneous insulin infusion (CSII) could reverse this problem, six consecutive kidney-transplanted Type I diabetic patients either proceeded with conventional insulin therapy (CIT) or were changed to CSII beginning on the third postoperative day. After a mean of 13 days, the insulin administration mode was changed from CIT to CSII (n=3) or from CSII to CIT (n=3), and continued for a further 15 days. Mean blood glucose calculated on the basis of four daily measurements (8.00, 12.00, 17.00, 22.00 h) during the study periods was significantly lower during CSII (8.0±0.4 mmol/l, mean±SEM) than on CIT (11.0±0.6 mmol/l; p<0.005). Moreover, the variability of blood glucose expressed as the M-value was lower during the pump treatment compared to CIT (p<0.001), while the number of blood glucose values below 3.0 mmol/l was similar (3.8 vs. 4.4%). Diurnal metabolic and hormonal profiles were twice determined on each regimen with 2 hourly sampling. Glycemic control was again found to be improved during CSII therapy as compared to CIT (p<0.01 or 0.05<p<0.10). Moreover, insulin pump treatment resulted in a significant reduction of two major intermediary metabolites, lactate and glycerol (p<0.05 and p<0.01, respectively). The improved metabolic state during CSII was probably due 1) to a more physiologic serum-free insulin pattern, which exhibited postprandial plasma peaks mimicking that of non-diabetic subjects; and 2) to an increased ability to combat varying insulin resistance post-transplantation. In conclusion, in newly kidney transplanted insulin-dependent diabetics, insulin pump therapy results in improved (almost normal) metabolic control compared to that achieved with CIT.     

Protective effect of insulin against hypoglycemia-associated counterregulatory failure.

Antecedent hypoglycemic episodes reduce the counterregulatory neuroendocrine response to hypoglycemia. The role of insulin in the mechanism responsible for the antecedent hypoglycemia causing subsequent counterregulatory failure has not been elucidated. We performed antecedent hypoglycemic clamps (56 mg/dL) lasting 2 h with differing degrees of hyperinsulinemia, which were followed by 6-h stepwise hypoglycemic clamps (76-66-56-46 mg/dL) on the next day. Experiments were carried out in 30 young, healthy men. Fifteen of these subjects were tested on 2 occasions. On 1 occasion the antecedent hypoglycemia was induced by insulin infusion at a rate of 1.5 mU/min x kg (low insulin-ante-hypo); on the other occasion the insulin infusion rate was 15.0 mU/min x kg (high insulin-ante-hypo). Both sessions were separated by at least 4 weeks, and their order was balanced across subjects. The remaining 15 subjects (control group) received the same stepwise hypoglycemic clamp as the other subjects, but without antecedent hypoglycemia. During the stepwise hypoglycemic clamp, the counterregulatory increases in ACTH, cortisol, and norepinephrine were significantly blunted after the low insulin-ante-hypo (P < 0.01, P < 0.05, and P < 0.05, respectively) but not after the high insulin-ante-hypo (P = 0.12, P = 0.92, and P = 0.19, respectively) compared to that in the control group. The cortisol, norepinephrine, and glucagon responses were greater after the high than after the low insulin-ante-hypo (all P < 0.05). In conclusion, the present study clearly demonstrates that even a single episode of mild hypoglycemia reduces neuroendocrine counterregulation 18-24 h later. Insulin has a moderate protective effect on subsequent counterregulation.     

Insulin pump therapy improves blood glucose control during hyperalimentation

The present study investigated the feasibility of basal continuous subcutaneous insulin infusion (CSII) in four patients with postoperative sepsis or extensive burns during continuous enteral hyperalimentation with 2,500 to 3,000 calories/day, containing approximately 390 g of simple carbohydrates. The mean duration of CSII treatment was 16.8 days (range, seven to 32 days). The mean capillary blood glucose level fell from 322 +/- 52 mg/dL during pre-CSII therapy to 195 +/- 33 mg/dL during CSII therapy. Only 1.3% of 1,254 capillary blood glucose values were less than 60 mg/dL. Most values (61.6%) were between 61 and 200 mg/dL. The mean insulin infusion rate was 2.5 +/- 1.5 units/hr. These preliminary observations suggest that basal infusion CSII is a safe and effective means of improving blood glucose control in patients receiving enteral hyperalimentation despite the high glucose intake and presence of insulin resistance. Thus, CSII therapy can enhance the metabolic response to hyperalimentation without requiring an intravenous access route.     

Continuous basal insulin infusion without premeal boluses in insulin-dependent diabetes mellitus therapy

Summary Six insulin-dependent diabetic patients, poorly controlled on conventional insulin therapy (CIT), underwent continuous basal insulin infusion (CBII) and continuous subcutaneous insulin infusion (CSII) during 2 subsequent periods of 1 month each, employing a Betatron II insulin infusion pump (Lilly, CPI). During CSII, insulin was infused at a continuous basal rate with 3 premeal boluses. During CBII, from 22⁰⁰ to 06⁰⁰ a continuous basal nocturnal insulin infusion rate and from 06⁰⁰ to 22⁰⁰ a diurnal one, which was approximately twice the former, were maintained and total daily calorie intake was subdivided into 6 isoglycidic and isocaloric meals, taken at regular intervals. We obtained better blood glucose control both by CSII and CBII than by CIT, with significant reduction of HbA₁ values. Mean blood glucose levels were lower during CBII than during CSII, while M-index, number of hypo- and hyperglycemic events and insulin requirement were not different. However, daily blood glucose excursions were narrower and percent blood glucose increment after the noon meal was reduced during CBII. CBII insulin profile was characterized by a plateau trend with lower levels at meals in comparison with CSII. Our data show that the subdivision of daily calorie intake into 6 isocaloric and isoglycidic meals allows to achieve good metabolic control by continuous basal insulin infusion without need for premeal boluses and could be especially useful in brittle diabetic patients, whose brittle condition may be caused by erratic absorption of subcutaneous boluses of insulin.     

A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion

Aim: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety.
Methods: In this open, randomized, controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized to CIPII or CSII. The aim was to obtain the best possible blood glucose while avoiding hypoglycemia.
Results: The frequency of any hypoglycemia was similar (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910). The incidence of severe hypoglycemia with CSII was more than twice the one with CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean blood glucose, and glucose fluctuations were not statistically different. Treatment-related severe complications occurred mainly during CIPII: port infections (0.47 events / patient year), abdominal pain (0.21 events / patient year), insulin underdelivery (0.14 events / patient year). Weight gain was greater with CSII (+ 1.5 kg vs. − 0.1 kg, p = 0.013), quality of life better with CIPII.
Conclusions: In type 1 diabetes CIPII with DiaPort reduces the number of severe episodes of hypoglycemia and improves quality of life with no weight gain. Because of complications, indications for CIPII must be strictly controlled. CIPII with DiaPort is an alternative therapy when CSII is not fully successful and provides an easy method of intraperitoneal therapy.     

Counterregulatory response to hypoglycemia differs according to the insulin delivery route, but does not affect glucose production in normal humans

The magnitude of the counterregulatory response to insulin-induced hypoglycemia is primarily determined by the degree of hypoglycemia. We examined whether the route of acute insulin delivery (portal or peripheral venous) is also important in determining the magnitude of the counterregulatory response to hypoglycemia in nine healthy nondiabetic men. Pancreatic insulin secretion, stimulated by an i.v. tolbutamide infusion (portal insulin study), was matched with an exogenous insulin infusion into the peripheral vein 4-6 weeks later (peripheral insulin study). Each study consisted of a 150-min baseline tracer equilibration period, a 180-min euglycemic hyperinsulinemic (portal or peripheral insulin delivery) period, a 60-min hypoglycemic period in which insulin secretion diminished during tolbutamide or was reduced during exogenous insulin, and a 30-min recovery period. Peripheral venous glucose concentrations were well matched in the portal and peripheral studies during euglycemia and hypoglycemia (glucose nadir, 2.9 +/- 0.1 mmol/L in the portal and 2.7 +/- 0.1 mmol/L in the peripheral; mean +/- SEM; P = NS), and insulin concentrations were about 1.5-fold higher throughout the experiment in the peripheral vs. the portal insulin study due to the first pass extraction of insulin in the portal study. There was a much greater increment (P < 0.0001) in FFA in the portal vs. the peripheral study (area under the curve: portal, 19.5 +/- 3.9 mmol/L x 90 min; peripheral, 3.3 +/- 1.1 mmol/L x 90 min), whereas plasma glucagon and GH were higher in the peripheral study (P = 0.01 for glucagon; P = 0.015 for GH). There was no significant difference between studies in epinephrine and norepinephrine responses to hypoglycemia or stimulation of endogenous glucose production (area under the curve: portal, 636 +/- 103 micromol/kg x 90 min; peripheral, 705 +/- 69 micromol/kg x 90 min; P = NS). In summary, we have shown that the glucagon, GH, and FFA responses to hypoglycemia during insulin dissipation are affected by the route of insulin delivery and are not controlled exclusively by the nadir blood glucose level. The clinical importance of these observations in diabetic subjects as they relate to route of insulin delivery (portal or peripheral) during insulin dissipation remains to be determined.     

Insulin pump therapy in adults

Restoration of the physiological insulin secretion is a current medical challenge and a dream for patients with Diabetes Mellitus. Continuous insulin therapy using pumps was the first step to the development of artificial pancreas. The aim of diabetes treatment is to achieve strict glycemic control in order to avoid the development of long-term diabetic complications while reducing the frequency of hypoglycemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump, offers both a better blood glucose stability as compared to multiple daily injections and a broader flexibility in life mode, and reduces the frequency of severe hypoglycemia. The advantages of the insulin pump (consistency of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Finally, the use of CSII in patients with Diabetes Mellitus type 2 now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients.     

Improved blood glucose variability, HbA1c insuman Infusat and less insulin requirement in IDDM patients using insulin lispro in CSII. The Swedish Multicenter Lispro Insulin Study

The aim of the study was to compare lispro (LP) and Insuman(R) (I) insulin in continuous subcutaneous insulin infusion (CSII) therapy with respect to blood glucose control as expressed by the standard deviation of blood glucose (SD(BG) ) and HbA(1c) and to monitor the well-being (WBQ) and treatment satisfaction (DTSQ) parameters during such treatment. Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label, randomized, cross-over, multicenter study for 4 months (2 months LP and 2 months I or vice versa). Boluses with LP were given 5 min before each meal and with I 30 min before each meal. During LP administration compared with I, the SD(BG) of all blood glucose values (3.6 mmol/l vs. 3.9 mmol/l, p=0.012), as well as the SD(BG) of the postprandial, blood glucose values (3.6 mmol/l vs. 4.0 mmol/l, p=0.006), were significantly reduced. The HbA(1c) was significantly lower during LP administration (7.4% vs. 7.6%, p=0.047). The incidence of hypoglycemic events per 30 days (capillary blood glucose<3.0 mmol/l and/or symptoms) did not significantly differ between LP and I (9.7 vs. 8.0 per month, p=0.23). The total amount of daily insulin was slightly but significantly lower with LP, compared to I (38.0 IU vs. 40.3 IU, p=0.004). There was no treatment effects of LP compared to I concerning WBQ and DTSQ. It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control, a lower HbA(1c), a less insulin requirement without increasing the frequency of hypoglycemia.     

An Analysis of the Glucagon Response to Hypoglycaemia in Patients with Type 1 Diabetes and in Healthy Subjects

The study aimed to analyse the glucagon response during hypoglycaemia in relation to gender, level of hypoglycaemia, and hyperinsulinaemia as well as its relation to other counterregulatory hormones in patients with Type 1 diabetes and in nondiabetic subjects. Mild hypoglycaemia was induced by an i.v. insulin infusion (244 pmol kg^?1h^?1) for 180 min in 43 Type 1 diabetic patients and 22 nondiabetic subjects. Venous blood glucose, plasma free insulin, glucagon, adrenaline, noradrenaline, growth hormone, and cortisol were measured every 15–30 min. The hormonal responses during hypoglycaemia were evaluated from the incremental areas under their respective curves. There was a linear correlation between the glucagon response and the decremental area of blood glucose (p < 0.005), but the slope of the regression line in the diabetic group was less steep than in the controls (p < 0.5), and, in spite of the deeper hypoglycaemia in the diabetic groups, their glucagon response was diminished (p < 0.05). Plasma, adrenaline, growth hormone and cortisol all increased during hypoglycaemia. The glucagon response correlated with the responses of growth hormone and cortisol in both groups, while it was positively correlated with the adrenaline response (p < 0.001) and inversely with the plasma insulin (p < 0.001) only in the diabetic patients. Although the insulin infusion rate was identical, the female diabetic patients had a lower metabolic clearance rate of insulin as compared with the males (p < 0.05). There was no statistical difference in the counterregulatory hormone responses between males and females in neither of the groups. In conclusion, this study suggests that the glucagon response to hypoglycaemia in Type 1 diabetic patients, may be suppressed by circulating insulin within its therapeutic range, and stimulated by the simultaneously secreted adrenaline. Furthermore, female Type 1 diabetic patients have a lower metabolic clearance rate of insulin than males, yielding a more pronounced hypoglycaemia in response to the same dose of insulin, although this study does not provide evidence of a gender difference in the responsiveness of counterregulatory hormones to hypoglycaemia.     

胰岛素泵和多次胰岛素皮下注射治疗对糖尿病酮症酸中毒和高渗昏迷的疗效比较

目的比较不同胰岛素给药方法对糖尿病酮症酸中毒（DKA）和糖尿病高渗性昏迷（DHC）的疗效。方法对DKA和DHC患者首先用静脉泵小剂量胰岛素持续输注,在生命体征平稳并能进半流食后分别用不同的胰岛素给药方式进行治疗：（1）持续皮下胰岛素输注（CSII）组;（2）常规4次皮下注射胰岛素（MSII）组。治疗目标为FBG≤7.0mmol/L、2hBG≤10mmol/L。结果两组每日胰岛素用量无统计学差异（P〉0.05）,但平均达标天数CSII组较MSII组明显缩短（P〈0.01）,CSII组血糖波动小,发生低血糖次数明显减少,且FBG及晚餐后2hBG控制亦明显优于MSII组（P〈0.01）。结论在治疗DKA和DHC时采用静脉泵连续小剂量胰岛素输注急救后,使用CSII较MSII能更快、更平稳、更有效地控制高血糖。     

Intensive insulin therapy in preschool-aged diabetic children: from multiple daily injections to continuous subcutaneous insulin infusion through indwelling catheters

In this study, glycemic control, diabetes care indices and quality of life (QoL) were assessed in 2 groups of newly diagnosed Type 1 diabetic subjects <6 yr old who were randomized to multiple daily injections with (Group A) or without (Group B) an indwelling catheter. Group A [12 males (M)/8 females (F), mean age 3.2+/-1.4 yr] and Group B (9M/11F, mean age 3.9+/-1.8 yr) were evaluated at baseline and after 6 and 12 months of treatment. No significant difference was observed in metabolic control (glycosylated hemoglobin) or in the number of hypoglycemic events between the groups. Patients in Group A had a greater number of daily insulin injections, monitored blood glucose more frequently and had a lower total daily insulin dose per kg (p<0.05). QoL was better in group A. At the end of the study 30% of group A patients progressed to continuous sc insulin infusion (CSII), while no child in Group B switched to a different insulin regimen. Based on these findings, indwelling catheter therapy may be helpful for selected CSII candidates.     

Use of continuous subcutaneous insulin infusion pump in patients with type 2 diabetes mellitus

PURPOSE: In patients with type 2 diabetes, the control of hyperglycemia is often difficult despite full doses of oral hypoglycemic agents and extremely large doses of insulin. These patients pose a major management problem. The authors therefore investigated whether insulin given as a subcutaneous continuous infusion of insulin (CSII) would result in an improvement in glucose homeostasis. METHODS: Four patients with badly controlled type 2 diabetes, on treatment with extremely high doses of insulin and oral hypoglycemic agents, were started on CSII. RESULTS: All four patients had a marked improvement in plasma glucose concentrations with a corresponding fall in HbA1c levels. This improvement was associated with a marked fall in the insulin doses necessary to maintain adequate glucose homeostasis. CONCLUSIONS: Since HbA1c levels fell from levels that would be associated with diabetic complications to those at which complications are markedly reduced, we recommend that patients with type 2 diabetes uncontrolled on extremely high doses of insulin be given a trial of treatment with CSII.     

Mechanisms of acute and chronic hypoglycemic action of gliclazide

An extrapancreatic effect of sulfonylureas has been postulated. However, in vivo results have been disputed because the amelioration of insulin action that follows sulfonylurea may represent the relief from glucose toxicity rather than a direct effect of the drug. Therefore, we studied the hypoglycemic action of gliclazide acutely and after 2 months of therapy in seven type 2 diabetic patients. All patients received a 240-minute IV glucose infusion with [3-³H]glucose. In a random order, 160 mg gliclazide (study 1) or placebo (study2) was given orally before glucose infusion. Finally, the effect of 160 mg gliclazide was reassessed after a two-month treatment with the same sulfonylurea (80 mg t. i. d.). Basal plasma glucose, insulin, C-peptide and endogenous glucose production (EGP) were similar before the two initial studies. During glucose infusion, EGP was more suppressed after gliclazide in spite of comparable increase in plasma insulin and C-peptide. After the two-month therapy, basal plasma glucose levels and HbA_1c were lower while plasma insulin and C-peptide were higher with respect to baseline (p < 0.05). Gliclazide further reduced plasma glucose, the incremental area above baseline, and EGP during glucose infusion, while plasma insulin and C-peptide achieved higher plateaus (p < 0.05). When data were pooled, plasma glucose concentration and EGP correlated both in the basal state (r = 0.71) and during the last hour of glucose infusion (r = 0.84; both p < 0.05). These data suggest that gliclazide enhances the suppression of EGP induced by insulin and that this effect is greater with chronic treatment because of concomitant improvement of insulin secretion. Received: 1 June 2000 / Accepted in revised form: 5 December 2000     

A Crossover Comparison of Continuous Insulin Infusion and Conventional Injection Treatment of Type I Diabetes

ABSTRACT. Helve E, Koivisto VA, Lehtonen A, Pelkonen R, Huttunen JK, NikkilÄ EA (Third Department of Medicine, University of Helsinki, and National Public Health Institute, Helsinki, Finland). A crossover comparison of continuous insulin infusion and conventional injection treatment of type I diabetes. We evaluated the feasibility and effectiveness of continuous subcutaneous insulin infusion therapy (CSII) as compared to conventional injection treatment (CIT) in an ordinary diabetic clinic in a one-year randomized crossover study of 65 type I diabetic patients. Home blood glucose levels were lower during CSII (8.6±0.2 mmol/1, mean ± SEM) than during CIT (9.1±0.3 mmol/1, p<0.05). During the first six months, HbA₁ fell on CSII therapy (from 10.6±0.4 to 9.7±0.3%, p<0.001), whereas no change occurred during CIT. After the crossover, HbA₁ decreased again on CSII (p<0.05), but rose in patients shifted from CSII to CIT (p<0.05). The fall in glycosylated haemoglobin during CSII correlated with the initial HbA₁ level (r=0.54, p<0.001). Ketoacidosis was more common during CSII (16 vs. 2 verified episodes). Hypoglycaemia occurred infrequently, without difference between CSII and CIT. Fifty-six per cent of the patients preferred CSII after the study. In conclusion, while CSII slightly improves the metabolic control, the improvement in the unselected study population is less than previously reported among highly selected patients.