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Continuous Intraperitoneal Insulin Infusion for People With Type 1 Diabetes: A Literature Review and International Position Statement.

Achieving glucose targets without hypoglycaemia is the treatment goal in type 1 diabetes. Structured education, intensified insulin injection regimens, continuous glucose monitoring, automated insulin delivery, and ongoing support from a multidisciplinary team all support people with type 1 diabetes to achieve this goal. Despite these advances, significant barriers to achieving optimal management remain. Continuous intraperitoneal insulin infusion has comparable or better glucose outcomes to continuous subcutaneous insulin infusion and may reduce the frequency of hypoglycaemia, including severe episodes. Intraperitoneal insulin may be considered as a treatment modality for children and adults with type 1 diabetes using optimised intensive insulin therapy for whom subcutaneous insulin has failed due to lipoatrophy, -dystrophy or -hypertrophy, local allergy, subcutaneous insulin resistance or co-existing skin conditions. Failure of subcutaneous insulin may result in recurrent or unexplained severe hypoglycaemia or hyperglycaemia. Intraperitoneal insulin may also be considered as a treatment modality for people with type 1 diabetes with severe needle-phobia, and for those being considered for islet cell or pancreatic transplantation, or where transplantation is not available. This paper summarises current intraperitoneal insulin delivery technology, its potential risks and benefits, and an expert position statement. It is intended for use by diabetes specialist healthcare professionals, and as a reference for other healthcare professionals, commissioners, payors, people with diabetes, their carers, and advocates.

Humans

Early Worsening of Diabetic Retinopathy Following Initiation of Hybrid Closed-Loop/Automated Insulin Delivery Systems in Type 1 Diabetes: A Systematic Review and Structured Study-Level Synthesis.

BACKGROUND: Hybrid closed-loop (HCL) systems achieve rapid, algorithm-driven improvements in glycaemia in type 1 diabetes (T1D). Paradoxically, rapid improvement in glycaemic control is associated with early worsening of diabetic retinopathy (EWDR), a phenomenon established in the intensive insulin therapy era. Whether HCL initiation carries a clinically meaningful EWDR risk is unknown. No systematic review has previously addressed this question. METHODS: A systematic review and structured quantitative synthesis was performed using study-level estimates only (PROSPERO CRD:420261391951). MEDLINE, SCOPUS and Web of Science were searched to 14th May 2026. Studies reporting retinal outcomes in people with T1D initiating any HCL system were eligible. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS-I and certainty of evidence using the GRADE framework. EWDR incidence was summarised using study-level proportions, and comparative studies were summarised using study-specific risk ratios for HCL versus control therapy. Given substantial heterogeneity in EWDR definitions, retinal assessment timing, follow-up duration, and comparator groups, no pooled or meta-analytic estimates were derived. RESULTS: Eight studies (n = 1487 participants; 860 HCL users) were included; all were observational and six were retrospective. EWDR varied markedly with the timing of retinal assessment. In studies assessing the retina within ≤ 12 months of HCL initiation, EWDR rates ranged from 8.9% to 26.5%. Studies with longer follow-up reported lower rates of retinal worsening or incident DR, 6.7% at 24 months and 6.1% over a mean follow-up of 4.9 years, suggesting that these studies may capture background DR progression rather than true early worsening. Three comparative studies included 177 HCL users and 315 controls; EWDR study-specific risk ratios were directionally inconsistent, ranging from 0.32 to 1.51, and were therefore not pooled. The most consistently identified risk factors were higher baseline HbA1c and older age. The magnitude of HbA1c reduction was not a consistent predictor of EWDR in the HCL context, in contrast to pre-HCL era evidence. Risk of bias ranged from moderate to critical and certainty of evidence was very low for all outcomes. CONCLUSIONS: Study-defined retinal worsening was reported in a minority of participants. The current evidence base is dominated by retrospective studies, variable retinal assessment timing, and inconsistent EWDR definitions. Well-designed prospective studies with protocol-specified retinal surveillance anchored to HCL initiation are required to generate reliable incidence estimates, identify risk factors, determine visual consequences, and inform standardised screening guidance.

Humans

Changes in glucagon levels after four to five weeks of glucoregulation by portable insulin infusion pumps.

Near-normal glucoregulation was maintained in five patients with juvenile-onset diabetes mellitus for 4--5 wk with a preprogrammed, continuous, subcutaneous insulin infusion using a portable battery-powered infusion pump. This form of therapy significantly lowered immunoreactive glucagon (IRG) levels below those observed while on conventional insulin treatment at several times during the 24-h profile. The maximum IRG levels were also reduced in all five subjects. Thus, a flexible system of insulin delivery, as is provided by certain open-loop pump systems, can overcome inappropriate glucagon secretion that occurs with conventional insulin therapy.

Adolescent

Restoration of normal lipid and aminoacid metabolism in diabetic patients treated with a portable insulin-infusion pump.

To determine whether abnormalities of lipid and aminoacid metabolism observed in diabetes are corrected when plasma-glucose levels are restored to normal, eight insulin-dependent diabetics were treated for 7-14 days with a portable infusion pump which delivers insulin subcutaneously in basal (between-meal) doses with pulse-dose increments before meals. Mean plasma-glucose (206 +/- 24 mg/dl during conventional insulin treatment) fell to 89 +/- 3 mg/dl at day 7 and 84 +/- 2 mg/dl at day 14 of pump treatment; glycosuria was eliminated. Plasma cholesterol, triglycerides, and free fatty acids were elevated during conventional insulin treatment but fell to normal after 7 days of pump treatment. Plasma-levels of branched-chain aminoacids were 50-60% above control levels during conventional treatment but fell to normal after 7 days of pump therapy. Aminoacids were reduced from their high postprandial levels to normal values after insulin-pump treatment. In addition to restoring plasma-glucose to normal, treatment of diabetes with a portable insulin-infusion system results in restoration of normal lipid and aminoacid metabolism. Long-term use of this system may determine whether metabolic changes resulting from insulin lack cause the complications of diabetes.

Adolescent

Continuous intravenous insulin therapy with a miniaturized open-loop system.

For the continuous intravenous application of insulin, a portable open-loop system was developed consisting of a delivery unit with a miniaturized pump and an insulin reservoir which is connected with an electronic control unit. The infusion rates were either preprogrammed or patient-controlled. Blood glucose control with both systems was tested in eight juvenile-type diabetics, among them two of the brittle type. Diabetic control during a 1-2-day pre-infusion period was compared with 2-3 days of continuous insulin infusion; as judged by the mean blood glucose value (MBG), the mean amplitude of glycemic excursions (MAGE), and glucosuria, all patients were significantly better controlled by the open-loop systems than by conventional therapy with subcutaneous insulin. The use of portable open-loop systems offers a promising approach to an improvement of metabolic control in insulin-requiring diabetics.

Adult

[Artificial endocrine pancreas (author's transl)].

16 years ago Kadish (1963) Trans. Amer. Soc. Artif. Org. 9, 363--367) published his first pioneering experiments with an extracorporal blood glucose regulating machine. These experiments were fundamental to the development of an artificial endocrine pancreas that replaces the natural regulator of the blood glucose. Enormous improvements have been done as far as analytical and computer technology and algorithms are concerned. Satisfactory but time-limited insulin therapy of problematic diabetics is feasable and benefical. However, in spite of a very great miniaturization of the analytical device, of the computer system, or of the insulin delivery pump, we are still far away from a durable, or at least long-term implantation of an artificial endocrine pancreas.

Artificial Organs

Evaluation of a portable insulin infusion pump for outpatient management of brittle diabetes.

Three "brittle" diabetic patients were given constant subcutaneous insulin infusion with a portable battery-driven pump, and their plasma glucose and hemoglobin A1 were measured at frequent intervals during inpatient or outpatient periods. Mean plasma glucose decreased significantly in all inhospital patients and remained significantly less than before pump therapy in two of three as outpatients during the 8--12 wk of follow-ups; however, complete normalization of glucose metabolism was not accomplished in any. All three demonstrated a progressive decline in hemoglobin A1 levels to normal or near-normal values. The need for long-term studies of open loop infusion systems in a research setting before their adaptation to routine care is emphasized.

Adolescent

[Treatment of ambulatory unstable diabetic patients by continuous subcutaneous infusion of insulin: preliminary results (author's transl)].

The aim of the present work was to examine the possibility of improving the metabolic control of ambulatory unstable diabetic patients by continuous subcutaneous infusion of insulin. For this purpose, a simple portable pump infusing insulin at a constant rate of 0.8 or 1.1 U/h was utilized. Pulses of a more concentrated insulin solution were superimposed 30-60 min. before meals. Blood glucose control during conventional insulin therapy and during continuous infusion was compared by measuring the mean blood glucose and the M-value of Schlichtkrull. Blood glucose fluctuations were estimated by the MAGE index of Service and Molnar. Three patients were submitted to continuous subcutaneous infusion of insulin during periods of 1, 5 and 6 weeks. In two cases, the application of this technic considerably improved the metabolic control as evidenced by a remarkable decrease of the three measured parameters. In one patient, continuous infusion of insulin was stopped after one week since it did not lead to an improvement of diabetic equilibrium. This failure was apparently due to emotional intolerance of the new technic. On two occasions, infection at the site of infusion was noted. These results should encourage longer-term studies involving a larger number of patients.

Ambulatory Care

Validation of I.V. small-dose insulin infusion therapy in diabetic ketoacidosis of depancreatized dogs.

A validation of small-dose insulin infusion therapy was studied by the constant i.v. infusion of various doses of insulin into ketoacidotic depancreatized dogs. Constant insulin infusion of 5 x B, 10 X B, 30 X B and 50 X B (B = 225 microunit/kg/min) was performed for 3 h by mechanical pump. The following results were obtained: (1) plasma concentrations of immunoreactive insulin (IRI) increased proportionally to the dose of infused insulin, but the higher IRI did not result in a greater fall in plasma glucose concentration, correspondingly; the mean rate of fall in plasma glucose concentration of 5 x B was not significantly lower than that of 50 x B; beta-hydroxybutyrate and arterial pH improvements were observed in each group during the 3-h insulin infusion. These data suggested that for the improvement of diabetic ketoacidosis, the insulin infusion rate of more than 30 x B, which raised the plasma IRI levels above the physiological range, was not essential; (2) the necessity of potassium supplementation during the small-dose insulin infusion was suggested if the pre-treatment level of serum potassium was low. These results confirmed that in the absence of infection or severe acidosis small-dose insulin infusion therapy is as effective as the conventional large-dose insulin therapy.

Animals

A portable precision pumping system for chronic, programmed insulin infusion.

This paper provides some details of a new insulin delivery system which includes a reservoir, a pump and a power pack. The reservoir holds 50 ml and is coupled to a precision peristaltic pump whose delivery can be set to any one of 128 different mean flow rates from 0 to 80 microliter/min (+/- 1.6% over 10 months) using the flow rate controller included in the battery power pack. The system weighs 525 g consuming 60 mW at the maximum pumping rate, proportionately less at lower rates. Ten pumps have undergone bench tests for 30 days. One has been subjected to an extended life test of 11 months while seven complete systems have been used on dogs to demonstrate their capability for precise longterm intravenous insulin therapy. With this system experimental diabetes has been reversed in 4 dogs for periods now extending beyond 6 months. This device now qualifies for long-term studies on hospitalized patients with diabetes mellitus.

Animals

Criteria for choosing amino acid therapy in acute renal failure.

Metabolic studies were performed on 19 patients with acute renal failure. Therapy included intravenous hyperalimentation using 15 to 20 g of essential amino acids or 20 to 40 g of essential plus nonessential amino acids and hypertonic glucose (37 to 50%). The effect of this parenteral feeding appears to be primarily pharmacological. Hypertonic glucose promotes the hyperinsulinemia important to be membrane function, the operation of the sodium pump, and cell metabolism. Administration of high biological value crystalline amino acdis potentiates the effect of insulin by inhibiting protein breakdown and promoting protein synthesis, particularly in muscle. This reduces tissue catabolism and urea formation, and promotes potassium, magnesium, and phosphate homeostasis. The branched-chain ketogenic amino acids valine, leucine, and isoleucine may be of particular importance. When indicated, administration of renal failure hyperalimentation and peritoneal or hemodialysis can be expected to complement each other and accelerate recovery. This intravenous fluid therapy, in turn, must be coordinated with proper hemodynamics, usually requiring a colloidal solution to maintain intravascular volume, and cardiotrophic agents such as digitalis and dopamine. Early use of renal failure can be expected to demonstrate the most striking response in terms of survival, early recovery from acute renal failure, and the preservation of physiological homeostasis.

Acute Kidney Injury

Long-term continuous intravenous insulin therapy with a portable insulin dosage-regulating apparatus.

A portable insulin dosage-regulating apparatus (PIDRA) was used with five volunteer diabetic subjects for periods ranging from 1 wk to more than 3 months to explore the possibilities of achieving near normoglycemic control over long time periods with such an apparatus. PIDRA consists of a matchbox size pump with insulin reservoir and a pocket size electronic control box. It can infuse a preprogrammed basal rate of insulin plus externally manipulated supplementary doses in rectangular profiles. The quality of blood glucose control was monitored with the Miles Biostator and through self-testing by the patient in the outpatient phases. Under inpatient conditions, the relatively simple PIDRA insulin administration profile was almost as effective in achieving normoglycemia as the Biostator, and good control could be maintained over long periods of time. The apparatus allows considerably greater ease in variation of insulin dosage with less risk of hypoglycemic epidoses as compared with conventional subcutaneous injections. Several technical problems remain to be solved, but it is concluded that PIDRA represents a viable alternative as a means of achieving tight control, at least as a step toward the goal of an implanted glucose-contingent insulin infusion system.

Adolescent

An open-loop insulin delivery device for the control of experimental diabetes.

A new insulin delivery device has been developed and tested. It includes a reservoir, a pump, and a power pack. The reservoir holds 75 ml and is coupled to a precision peristaltic pump whose delivery can be set to any one of 128 different flow rates from 0 to 80 microliter/min (+/- 1.6% over 10 months) using the flow rate controller included in the battery power pack. The system weighs 525 g, consuming 50 mW at the maximum pumping rate, proportionately less at lower rates. Ten pumps have undergone bench tests for 30 days. One has been subjected to an extended life test of 16 months without change of tubing while seven complete systems have been used on dogs to demonstrate their capability for precise long-term (up to 16 months) intravenous insulin therapy. With this system, experimental diabetes has been controlled in 7 dogs for periods now extending beyond 16 months. This device now qualifies for-long term studies on hospitalized patients with diabetes mellitus.

Animals

Extended Use of the Omnipod 5 Automated Insulin Delivery System in Adults With Type 1 Diabetes: 12-Month Extension of a Randomized Controlled Trial.

BACKGROUND: The Omnipod 5 Automated Insulin Delivery (AID) System is safe and effective for individuals managing Type 1 diabetes (T1D). Longer-term studies may provide additional evidence of sustained effectiveness and safety of AID system use in T1D. METHODS: This 12-month extension study was conducted following a multicenter randomized controlled trial (RCT) where participants used either AID (Omnipod 5) or standard therapy (current non-automated pump therapy) for 13&#x2009;weeks. Participants in France (n&#x2009;=&#x2009;76) could transition to or continue with AID for an additional 12&#x2009;months. Glycemic, safety, and psychosocial outcomes during or at the end of the extension phase were compared with baseline or end of RCT, as appropriate. RESULTS: Seventy-five participants enrolled in the extension phase. From RCT baseline to the end of the extension phase, time in range 70-180&#x2009;mg/dL increased by 17.9% (p&#x2009;<&#x2009;0.0001) or 4.3&#x2009;h/day to 62.3%. Time above range&#x2009;>&#x2009;180&#x2009;mg/dL and mean sensor glucose decreased by 17.7% and 27.8&#x2009;mg/dL (both p&#x2009;<&#x2009;0.0001), respectively. HbA1c decreased from 8.33% to 7.18% (-1.14%; p&#x2009;<&#x2009;0.0001). Glycemic improvements were maintained for those continuing with AID from the RCT intervention group and for those transitioning to AID from standard therapy. Diabetes Quality of Life-brief and Hypoglycemia Confidence Scale scores were maintained or improved at 6 and 12&#x2009;months compared to RCT baseline. Adverse events were infrequent (12 per 100 person-years). CONCLUSIONS: Findings support the RCT results, demonstrating safety and sustained improvements in glycemic and psychosocial outcomes with the Omnipod 5 System in adults in France with T1D over 12&#x2009;months. TRIAL REGISTRATION: ClinicalTrials.gov NCT05409131.

Humans

The external artificial pancreas: an instrument to induce remissions in severe recent juvenile diabetes. Comparison with a preprogrammed insulin infusion system.

Remission of juvenile insulin-dependent diabetes is a rare, temporary, and partial phenomenon which seems to be related to an improvement of the residual insulin secretion supported by prompt and rigorous insulin therapy. Thus, remissions allowing the replacement of insulin by oral drugs were attempted in 23 insulin dependent ketotic juvenile diabetics (age 10 +/- 2 years) of recent onset (apparent duration of diabetes 71 +/- 5 days) treated by an external artificial pancreas during 5 +/- 1 days and compared with 10 control diabetics treated by a less effective technique (preprogrammed insulin pump without feedback control) during 6 +/- 1 days. 18 (78%) remissions of long duration (1-26 months) occurred after artificial pancreas compared with 3 (30%) in the control group. Measurement of daily urinary C-peptide excretion confirmed the improvement of the residual insulin secretion in patients with insulin-induced remissions. Thus, the excellent blood glucose control given by an artificial pancreas seems necessary to lead to much more frequent remissions of diabetes than usually reported.

Acute Disease

[Progress and developments in insulin therapy].

BANTING and BEST revolutionized diabetes therapy with the discovery of insulin 57 years ago. Since then, progress in this area has been slow despite tremendous reseach efforts. The subcutaneous injection of a depot insulin does not provide optimal control of blood sugar. True progress has been brought about by intravenous insulin administration for the management of diabetic coma. The authors do not recommend ultra low dose therapy. The prognosis of diabetic coma is much better than 20 years ago, in particular because of much improved and continuous supervision of the circulation (CVP, ECG, K+ etc.). Pancreas and islet transplantation fail in man due to immunological rejection. The "artificial pancreas" with a glucose sensor is useful for research purposes, and for controlling blood sugar for a few days at most. The implantable glucose sensor is not yet in sight. The authors have treated diabetics successfully with a programmable flexible open loop infusion program. The basal insulin infusion rate can be varied from 0.25 to 2 U/h, and rectangular one hour extra insulin infusions between 2 and 10 U/h are superimposed by pushing a button on the steering unit. The pump automatically switches back to the basal rate after one hour. No hypoglycemic reactions have been observed in patients on ths program on the ward or at home. At present, technical problems with the catheter remain to be solved before this simple therapeutic approach can be applied routinely.

Adolescent

[Experimental pancreas transplantation].

Pancreatic auto- and allotransplantation of the pancreas tail were successfully performed in dogs. Malnutrition related to pancreatic exocrine hypofunction occurs initially in pancreatic-autotransplantation but gradual recovery by 3 months is normal. Tolbutamide showed a significant prolongation of hypoglycemia, glucose tolerance curves were normal in pancreatic autotransplantation. Denervation and lymphatic interruption of the pancreas may cause a transient but not definitive influence on pancreatic functions. In pancreatic allotransplantations there was a slight extension of survival time in the immunosuppressive treated group (Imuran 6 mg/kg). The results suggest that hyperglycemia, a poor response of the islets after glucose stimulation and a low circulating plasma-insulin level along with a low amylase level indicated the end point of rejection. The canine pancreas has been perfused for 3 hours with a membrane oxygenator, a pulsatile pump and a heat exchanger at a temperature of 37 degrees C. Among the criteria used in this study the insulin output into the venous blood in response to glucose administration as well as a pancreas secretion after secretin stimulation were found to be the most reliable indicators as to the viability of the pancreas. This is further supported by an average oxygen consumption of 0,77 ml O2/100 g/min at a constant flow of 80 ml/min and a pressure of 75 mmHg.

Animals