Siphon Effects on Continuous Subcutaneous Insulin Infusion Pump Delivery Performance

Background

The objective was to quantify hydrostatic effects on continuous subcutaneous insulin infusion (CSII) pumps during basal and bolus insulin delivery.

Methods

We tested CSII pumps from Medtronic Diabetes (MiniMed 512 and 515), Smiths Medical (Deltec Cozmo 1700), and Insulet (OmniPod) using insulin aspart (Novolog, Novo Nordisk). Pumps were filled and primed per manufacturer''s instructions. The fluid level change was measured using an inline graduated glass pipette (100 μl) when the pipette was moved in relation to the pump (80 cm Cosmo and 110 cm Medtronics) and when level. Pumps were compared during 1 and 5 U boluses and basal insulin delivery of 1.0 and 1.5 U/h.

Results

Pronounced differences were seen during basal delivery in pumps using 80–100 cm tubing. For the 1 U/h rate, differences ranged from 74.5% of the expected delivery when the pumps were below the pipettes and pumping upward to 123.3% when the pumps were above the pipettes and pumping downward. For the 1.5 U/h rate, differences ranged from 86.7% to 117.0% when the pumps were below or above the pipettes, respectively. Compared to pumps with tubing, OmniPod performed with significantly less variation in insulin delivery.

Conclusions

Changing position of a conventional CSII pump in relation to its tubing results in significant changes in insulin delivery. The siphon effect in the tubing may affect the accuracy of insulin delivery, especially during low basal rates. This effect has been reported when syringe pumps were moved in relation to infusion sites but has not been reported with CSII pumps.     

Comparison of Subcutaneous Regular Insulin and Lispro Insulin in Diabetics Receiving Continuous Nutrition: A Numerical Study

Background:

Optimal management of non–critically ill patients with diabetes maintained on continuous enteral feeding (CEN) is poorly defined. Subcutaneous (SQ) lispro and SQ regular insulin were compared in a simulated type 1 and type 2 diabetic patient receiving CEN.

Method:

A glucose-insulin feedback mathematical model was employed to simulate type 1 and type 2 diabetic patients on CEN. Each patient received 25 SQ injections of regular insulin or insulin lispro, ranging from 0-6 U. Primary endpoints were the change in mean glucose concentration (MGC) and change in glucose variability (GV); hypoglycemic episodes were also reported. The model was first validated against patient data.

Results:

Both SQ insulin preparations linearly decreased MGC, however, SQ regular insulin decreased GV whereas SQ lispro tended to increase GV. Hourly glucose concentration measurements were needed to capture the increase in GV. In the type 2 diabetic patient, “rebound hyperglycemia” occurred after SQ lispro was rapidly metabolized. Although neither SQ insulin preparation caused hypoglycemia, SQ lispro significantly lowered MGC compared to SQ regular insulin. Thus, it may be more likely to cause hypoglycemia. Analyses of the detailed glucose concentration versus time data suggest that the inferior performance of lispro resulted from its shorter duration of action. Finally, the effects of both insulin preparations persisted beyond their duration of actions in the type 2 diabetic patient.

Conclusions:

Subcutaneous regular insulin may be the short-acting insulin preparation of choice for this subset of diabetic patients. Clinical trial is required before a definitive recommendation can be made.     

Basal Insulin Requirements on Continuous Subcutaneous Insulin Infusion During the First 12 Months After Diagnosis of Type 1 Diabetes Mellitus

Introduction

While the endogenous first-phase insulin response has disappeared by the time of diagnosis of type 1 diabetes mellitus (T1DM), anecdotal evidence suggests that these patients can continue to have a second-phase insulin response during the first 12 months after diagnosis. We hypothesized that patients who are started on continuous subcutaneous insulin infusion (CSII) at the time of diagnosis of T1DM would have a lower basal insulin requirement than the 40-60% usually expected.

Methods

We analyzed 38 patients with T1DM, age 9.9 ± 6.4 years, 71% male, who were started on CSII within the first month of diagnosis.

Results

Average basal insulin requirements were 47–49% of total daily dose during the first 12 months after diagnosis and decreased from 0.30 U/kg/day at diagnosis to 0.20 U/kg/day by 12 months. Baseline percentage of basal insulin was significantly correlated with hemoglobin A1c at baseline and at six months. The percentage of basal insulin requirement at 12 months after diagnosis was significantly correlated with baseline body mass index (BMI) and current BMI. No other correlations between percentage of basal insulin requirements and any other factors were seen.

Conclusion

Our data suggest that, even though some endogenous insulin production remains during the first year after diagnosis of T1DM, the distribution of basal versus total daily insulin requirements remains the same as in the general population of people with diabetes. There may be benefits to starting patients on a higher basal rate at time of diagnosis for overall glycemic control during the first six months. Further research is needed to optimize starting insulin doses to maximize their potential in preserving beta-cell function.     

Practical Experience with Continuous Subcutaneous Insulin Infusion Therapy in a Pediatric Diabetes Clinic

Continuous subcutaneous insulin infusion therapy (CSII) is an increasingly popular form of intensive insulin administration in pediatric patients. The use of CSII commenced at our large tertiary referral diabetes clinic as recently as 2002. In the intervening years, demand and enthusiasm from both patients and physicians alike have resulted in a steady ongoing increase in CSII use at our clinic. We currently have >200 active patients using insulin pump therapy. This article reviews our experience with CSII and outlines our current multidisciplinary approach to optimizing glycemic control and outcomes in this patient group.     

胰岛素泵皮下注射和多次胰岛素皮下注射治疗妊娠期糖尿病的疗效比较

目的 分析经胰岛素泵开展皮下注射与多次皮下注射胰岛素对妊娠期糖尿病(GDM)的疗效.方法 将2017年1月—2019年8月该院收治的GDM患者共72例为研究对象,依据随机数表法分成对照组(多次皮下注射胰岛素)和观察组(经胰岛素泵开展皮下注射),各36例,比较两组治疗前后空腹血糖(FPG)、餐后2 h血糖(2 hPG)、...     

Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects

Background:

An 8-mm needle length is commonly used for insulin injections; however, recent recommendations suggest shorter needles may help patients avoid intramuscular injections and reduce pain, while maintaining adequate glucose control. The goal of these analyses was to compare the pharmacokinetics (PK) and glucodynamics (GD) of insulin lispro after a 5-mm or an 8-mm injection depth administration in 2 populations: normal weight (study 1) or obese (study 2).

Methods:

In both open-label, randomized, 2-period crossover euglycemic clamp studies, subjects received single 0.25 U/kg insulin lispro doses on 2 occasions (at 5-mm and 8-mm injection depths); samples for PK and GD analyses were collected up to 6 hours postdose. Noncompartmental PK parameters AUC_0-tlast, AUC_0-∞, C_max and GD parameters G_tot, R_max, t_Rmax were log-transformed prior to analysis using a mixed effects model.

Results:

There were no apparent differences between PK profiles at the 5-mm or 8-mm injection depth in either study, demonstrated by the ratios of geometric means of AUC_0-tlast, AUC_0-∞, and C_max being close to 1, with 90% confidence intervals (CI) within (0.80, 1.25). There were no apparent differences between GD profiles at either injection depth with the ratios of G_tot and R_max near unity and 90% CIs that included 1. In both studies, the t_Rmax values were similar between injection depths, with a small median of pairwise differences and a 90% CI that included zero.

Conclusions:

Injection depths in the 5-8 mm range did not affect the PK or GD of insulin lispro in normal weight or obese subjects.     

Diabetes Technologies and Hospital Care: Comparison of Insulin Pump Therapy (Continuous Subcutaneous Insulin Infusion) to Alternative Methods for Perioperative Glycemic Management in Patients with Planned Postoperative Admissions

Background

Patients with diabetes who use insulin pumps [continuous subcutaneous insulin infusion (CSII)] undergo surgeries that require postoperative hospital admission. There are no defined guidelines for CSII perioperative use.

Methods

This retrospective single-institution study identified type 1 and type 2 diabetes subjects by electronically searching 2005–2010 anesthesia preoperative assessments for “pump.” Surgical cases (n = 92) were grouped according to intraoperative insulin delivery method: (a) CSII continuation of basal rate with/without correctional insulin bolus(es) (n = 53); (b) conversion to intravenous insulin infusion (n = 20); and (c) CSII suspension with/without correctional insulin bolus(es) (n = 19). These groups were compared on mean intraoperative blood glucose (BG) and category of most extreme intraoperative BG.

Results

Differences were found on baseline characteristics of diabetes duration (p = .010), anesthesia time (p = .011), proportions receiving general anesthesia (p = .013), and preoperative BG (p = .033). The conversion group had the longest diabetes duration and anesthesia time; it had a higher proportion of general anesthesia recipients and a higher mean preoperative BG than the continuation group. There was no significant difference in mean BG/surgical case between continuation (163.5 ± 58.5 mg/dl), conversion (152.3 ± 28.9 mg/dl), and suspension groups (188.3 ± 44.9 mg/dl; p = .128). The suspension group experienced a greater percentage of cases (84.2%) with one or more intraoperative BG > 179 mg/dl than continuation (45.3%) and conversion (40%) groups Figure 1 groupings (p = .034).Open in a separate windowFigure 1Comparison of insulin delivery methods to percentage of surgical cases with intraoperative hypoglycemia and hyperglycemia. Chi-square = 13.43, p = .034; continuation group, n = 53; conversion group, n = 20; suspension group, n = 19. All groupings were mutually exclusive. Intraoperative BG is defined as all BG measurements performed in the operating room and the first postoperative anesthesia care unit measurement

Conclusions

In this limited sample, preliminary findings are consistent with similar intraoperative glycemic control between CSII continuation and CSII conversion to intravenous insulin infusions. Continuous subcutaneous insulin infusion suspension had a greater rate of hyperglycemia. Preoperative differences between insulin delivery groups complicate interpretations of findings.     

Insulin Depot Formation in Subcutaneous Tissue

Background

The size and geometry of an insulin depot that is formed during subcutaneous administration by an insulin pump is evaluated. A novel method is used to visualize accurately the depot formation for small volumes of insulin (of the order of 10–100 µl) at a given point in time. Conventional visualization methods such as magnetic resonance imaging are unable to provide such accurate measurements because of their coarse imaging resolution and long measurement time.

Methods

The described method consists of subcutaneously infusing dyed insulin into porcine tissue and subsequently shock freezing it with liquid nitrogen. The frozen sample is then sliced into thin layers using a cryomicrotome. A digital image of each layer is taken and then processed with proprietary software, which identifies the dyed areas on each layer and reconstructs a three-dimensional model of the insulin depot with a planar resolution of 30 × 30 µm² and a depth resolution of 100 µm. Since this process is not viable for living organisms, porcine tissue was used immediately following slaughter of the animal.

Results

To date, it is most often assumed that the insulin depot takes the shape of a sphere around the tip of the cannula (e.g., 50 µl insulin equates to a spherical radius of 2.3 mm). However, in practice, such a depot form is never observed. Instead, the insulin depot initially spreads laterally (i.e., parallel) to the skin surface and in the collagen matrix that binds the adipose cells together. The depot outreach increases with larger infused volumes, e.g., maximum outreach measured at 5.0/5.7/7.1 mm (quartiles, n = 17) for 50 µl of infused insulin. Beyond a given infused volume (approximately 100 µl), the insulin also starts to spread perpendicular to the skin surface.

Conclusions

It is concluded that formation of the insulin depot depends on the opening of channels at the boundaries between adipose cells. Hence the insulin follows a path of least resistance and depot formation is determined by the local structure of the subcutaneous tissue.     

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.     

Advances in Insulin Pen Technologies: Evolution of Diabetes Insulin Delivery Devices

The first manufactured insulin pump was introduced in the 1970s and the first insulin pens in 1985; since then, many improvements have been made to both devices. The advantages of pens over syringes have been confirmed in numerous studies and include greater accuracy, ease of use, patient satisfaction, quality of life, and adherence. United States claims database analyses indicate that the improved adherence made possible by use of an insulin pen has the potential to reduce diabetes care costs when compared with using a vial and syringe. Features of certain advanced pump models include the ability to connect wirelessly to a blood glucose meter or to a subcutaneous interstitial glucose sensor for semicontinuous glucose-driven insulin rate adjustment. A new trend in the design of insulin pumps is the tubing-free patch pump that adheres directly to the skin. The low rate of insulin pen usage in the United States compared with European countries and the fact that many patients report that they are not offered the option of an insulin pen by their physician suggest that there is a need to increase patient and provider awareness of the currently available devices for insulin administration.     

Pharmacokinetics and Postprandial Glycemic Excursions following Insulin Lispro Delivered by Intradermal Microneedle or Subcutaneous Infusion

Background

Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery.

Method

The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design. One arm established each subject’s optimal meal dose. In six additional arms, the optimal, higher, and lower doses (+30%, -30%) were each given ID and SC delivery, in random order. The final arm assessed earlier timing for the ID optimal dose (-12 versus -2 min). The PK/PD data were collected for 6 h following meals. Intravenous basal regular insulin was given throughout, and premeal blood glucose (BG) adjusted to 115 mg/dl.

Results

The primary end point, postprandial time in range (70–180 mg/dl), showed no route-based differences with a high level of overall BG control for both SC and ID delivery. Secondary insulin PK end points showed more rapid ID availability versus SC across doses and meals (∆Tmax -16 min, ∆T50rising -7 min, ∆T50falling -30 min, all p < .05). Both intrasubject and intersubject variability for ID Tmax were significantly lower. Intradermal delivery showed modest, statistically significant secondary PD differences across doses and meals, generally within 90–120 min postprandially (∆12 mg/dl BG at 90 min, ∆7 mg/dl BGmax, ∆7 mg/dl mean BG 0–2 h, all p < .05).

Conclusions

This study indicates that ID insulin delivery is superior to SC delivery in speed of systemic availability and PK consistency and may improve postprandial glucose control.     

Biodistribution of Insulin Following Massive Insulin Subcutaneous Injection

A man in his 30s injected insulin several times into his abdomen and was found dead several hours later. Micropathological findings showed alveolar injury with hemorrhaging and cerebral parietal lobe nerve cell edema. Biochemical examinations showed that the blood insulin level was high, significantly so at the insulin injection sites. The blood glucose and C-peptide levels were low. The insulin level in the kidneys was low. In forensic medicine, a postmortem diagnosis of insulin subcutaneous injection is often difficult. When insulin injection is suspected, particularly high insulin levels can be expected at the insulin injection site, rather than in the blood.     

Continuous Subcutaneous Insulin Infusions vs. Multiple Daily Injections of Insulin in Hospitalized Patients: Glycemic Trends in the First 24 Hours of Admission

Background:Continuous subcutaneous insulin infusion (CSII) is a common diabetes treatment modality. Glycemic outcomes of patients using CSII in the first 24 hours of hospitalization have not been well studied. This timeframe is of particular importance because insulin pump settings are programmed to achieve tight outpatient glycemic targets which could result in hypoglycemia when patients are hospitalized.Methods:This retrospective cohort study evaluated 216 hospitalized adult patients using CSII and 216 age-matched controls treated with multiple daily injections (MDI) of insulin. Patients using CSII did not make changes to pump settings in the first 24 hours of admission. Blood glucose (BG) values within the first 24 hours of admission were collected. The primary outcome was frequency of hypoglycemia (BG < 70 mg/dL). Secondary outcomes were frequency of severe hypoglycemia (BG < 40 mg/dL) and hyperglycemia (BG ≥ 180 mg/dL).Results:There were significantly fewer events of hypoglycemia [incident rate ratio (IRR) 0.61, 95% confidence interval (CI) 0.42–0.88, p = 0.007] and hyperglycemia (IRR 0.79, 95% CI 0.65–0.96, p = 0.02) in the CSII group compared to the MDI group. There was a trend toward fewer events of severe hypoglycemia in the CSII group (IRR 0.15, 95% CI 0.02–0.93, p = 0.06).Conclusions:Patients using CSII experienced fewer events of both hypoglycemia and hyperglycemia in the first 24 hours of hospital admission than those treated with MDI. Our study demonstrates that CSII use is safe and effective for the treatment of diabetes within the first 24 hours of hospital admission.     

Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

Introduction

AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described.

Methods

This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done.

Results

Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as well as for insulin doses up to 50 IU.

Discussion

The methodology to be adopted for implementing the generic absorption model within AIDA has been overviewed, and the first plasma insulin profiles based on this approach have been demonstrated. Ideas for future work and development are discussed. It is expected that an updated release of AIDA (v4.5), based on this collaborative approach, will become available for free—in due course—via the www.2aida.org Web site. Readers who wish to be informed when the new software is launched can join the very low volume AIDA announcement list by sending a blank email note to gro.adia2@ebircsbus.     

Stability and Performance of Rapid-Acting Insulin Analogs Used for Continuous Subcutaneous Insulin Infusion: A Systematic Review

Aim:

We review and summarize the literature on the safety and stability of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion (CSII) in patients with diabetes.

Methods

Two predefined search strategies were systematically implemented to search Medline and the Cochrane Register of Clinical Trials for publications between 1996 and 2012.

Results

Twenty studies were included in the review: 13 in vitro studies and 7 clinical studies. In vitro studies investigated the effects of extreme CSII conditions (high temperature and mechanical agitation) on the risk of catheter occlusions and insulin stability factors, such as potency, purity, high molecular weight protein content, pH stability, and preservative content (m-cresol, phenol). Under these conditions, the overall stability of rapid-acting insulin analogs was similar for insulin lispro, insulin aspart, and insulin glulisine, although insulin glulisine showed greater susceptibility to insulin precipitation and catheter occlusions. A limited number of clinical trials were identified; this evidence-based information suggests that the rate of catheter occlusions in patients with type 1 diabetes using CSII treatment may vary depending on the rapid-acting analog used.

Conclusions

Based on a limited amount of available data, the safety, stability, and performance of the three available rapid-acting insulin analogs available for use with CSII were similar. However, there is limited evidence suggesting that the risk of occlusion may vary with the insulin preparation under certain circumstances.     

Characterizing Normal-use Temperature Conditions of Pumped Insulin

In this study, the temperature profiles of insulin pump reservoirs during normal wear conditions across multiple seasons were characterized. Thermocouples secured in reservoirs filled with insulin diluent were loaded in infusion pumps worn by volunteers. Reservoir and ambient environmental temperature data and activity levels were logged during the course of normal daily activities in February (winter), April (spring), and August (summer). Each seasonal data set comprised 7 to 14 days of wear from 3 to 5 volunteers. Reservoir temperature profiles were generally higher than ambient temperatures, likely due to heat transfer from the wearer when the pump was placed close to the body. Temperature conditions inside pump reservoirs fluctuated between 25°C and 37°C regardless of seasonal variations. The average reservoir temperature remained close to 30°C across all seasons, notably lower than used in previously published compatibility and stability protocols (37°C). Results from this study could be utilized to develop more accurate stability and compatibility testing procedures for new insulin formulations and/or delivery devices.     

Evolving Approaches to Intensive Insulin Therapy in Type 1 Diabetes: Multiple Daily Injections,Insulin Pumps and New Methods of Monitoring

Reviews in Endocrine and Metabolic Disorders -     

Technology for Hospital Management of Diabetes: Use of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Hospital: A Review of One Institution's Experience

Background

This article reviews the performance of our hospital''s inpatient insulin pump policy.

Methods

Twenty-five hospital admissions of 21 unique patients receiving outpatient insulin pump therapy were reviewed.

Results

Between November 1, 2005, and November 30, 2006, there were 25 hospital admissions involving 21 patients receiving outpatient insulin pump therapy. The average age and duration of diabetes among these 21 patients was 50 and 29 years, respectively; 67% were women, 90% had type 1 diabetes, and all were white. The mean length of hospital stay was 4 days, and the average reported length of insulin pump therapy was 4 years. Patients in 16 of the admissions were identified as candidates for continued use of the insulin pump during the hospital stay. Over 90% of patients remaining on the insulin pump had documentation by nursing of the presence of the pump at the time of admission; 100% of the patients had an admission glucose recorded; 88% had a record of signed patient consent; 81% had evidence of completed preprinted insulin pump orders; 75% received a required endocrine consultation; and 75% of cases had documentation of completed bedside flow sheet. A high frequency of both hypoglycemic and hyperglycemic events occurred in the patients; however, no adverse events were related directly to the insulin pump.

Conclusions

Insulin pump therapy can be safely continued in the hospital setting. While staff compliance with required procedures was high, there was still room for improvement. More data are needed, however, on whether this method of insulin delivery is effective for controlling hyperglycemia in hospitalized patients.     

A Controlled Study of the Influence of Continuous Subcutaneous Insulin Infusion Treatment on Diabetic Retinopathy during Pregnancy

ABSTRACT. Laatikainen L, Teramo K, Hieta-Heikurainen H, Koivisto V, Pelkonen R (Department of Ophthalmology, I and II Departments of Obstetrics and Gynaecology, III Department of Medicine, Helsinki University Hospital, Helsinki, Finland). A controlled study of the influence of continuous subcutaneous insulin infusion treatment on diabetic retinopathy during pregnancy. Forty consecutive pregnant patients with insulin-dependent (Type I) diabetes mellitus were randomized at the end of the first trimester for treatment with conventional insulin therapy (CIT) or continuous subcutaneous insulin infusion therapy (CSII). Nine patients randomized into the CSII group declined the pump treatment. The mean glycosylated haemoglobin (Hb A_1c) decreased (p<0.001) both in the CIT and the CSII groups with no difference between the groups. Some deterioration in retinopathy was found in 2/18 patients in the CIT group, in 5/13 in the CSII group, and in 3/9 of those who declined the pump treatment. The proportion of patients whose retinopathy progressed did not differ significantly between the groups, and in the majority the deterioration was mild. However, two patients in the CSII group developed acute ischaemic retinopathy, which progressed to proliferative stage in spite of laser treatment. In these two cases the decrease in the Hb A_lc level was among the greatest and fastest in the study. These data suggest that a rapid near normalization of glycaemic control by CSII during pregnancy can accelerate the progress of retinopathy in poorly controlled diabetic patients.