Skip to main content
SpringerLink
Log in

Recent Developments in Insulin Delivery Techniques

Current Status and Future Potential

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Although single or multiple daily subcutaneous injections of insulin are the mainstay of insulin delivery techniques, several other methods of insulin delivery are now available or in development, including: (a) continuous subcutaneous insulin infusion by a wearable infusion pump; (b) total or segmental transplantation of a pancreas; (c) transplantation of isolated islet cells; (d) implantation of a programmable insulin pump; (e) oral, nasal, rectal and transdermal mechanisms of insulin delivery; (f) insulin analogues; (g) implantation of polymeric capsules which give continuous or time-pulsed release of insulin; and (h) implantation of a biohybrid artificial pancreas which uses encapsulated islets. Many of these methods of insulin delivery are aimed at achieving a more physiological means of delivery of the insulin, thus to improve glycaemic control and hopefully minimise the secondary complications of diabetes.

Techniques of multiple insulin injections and continuous subcutaneous insulin infusion pumps are already in widespread use and are resulting in improved glycaemic control. With the recent increased use of pancreatic transplantation, the rule of establishing euglycaemia will be elucidated in the treatment and prevention of microvascular and macrovascular complications of diabetes mellitus. Despite these advances, the ideal delivery of insulin to patients has yet to be developed. Subcutaneous methods of insulin delivery do not precisely mimic physiological insulin needs and transplantation requires risky immunosuppression. However, the future does look bright as glucose sensors are developed and insulin analogues synthesised.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albisser AM, Leibel BS, Ewart TG, Davidovac Z, Botz CK, et al. An artificial endocrine pancreas. Diabetes 23: 389–396, 1974a

    PubMed  CAS  Google Scholar 

  • Albisser AM, Leibel BS, Ewart TG, Davidovac Z, Botz CK, et al. Clinical control of diabetes by the artificial pancreas. Diabetes 23: 397–404, 1974b

    PubMed  CAS  Google Scholar 

  • Albisser AM, McAdam KP, Perlmen K, Carson S, Bahoric A, et al. Unanticipated amyloidosis in dogs infused with insulin. Diabetes 32: 1092–1101, 1983

    PubMed  CAS  Google Scholar 

  • Altman JJ, McMillan P, Callard P, Galetti PM. A bioartificial pancreas prevents chronic complication of diabetes in rats. Transactions of the American Society for Artificial Internal Organs 32: 145–147, 1986

    CAS  Google Scholar 

  • American Diabetes Association Policy Statement. Indications for use of continuous insulin delivery systems and self-measurement of blood glucose. Diabetes Care 5: 140–141, 1982

    Google Scholar 

  • American Diabetes Association Policy Statement. Position statement on Jet Injectors. Diabetes Care 11: 600–601, 1988

    Google Scholar 

  • Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effect of intensive insulin therapy on glycemic threshold for counterregulatory hormone release. Diabetes 37: 901–907, 1988

    PubMed  CAS  Google Scholar 

  • Amiel SA, Tamborlane WV, Simonson DC, Sherwin RS. Defective glucose counterregulation after strict glycemic control of insulin-dependent diabetes mellitus. New England Journal of Medicine 316: 1376–1383, 1987

    PubMed  CAS  Google Scholar 

  • Arrieta-Molero JF, Aleck K, Sinha MK, Bronnscheidle CM, Shapiro LJ, et al. Orally administered liposome-intrapped insulin in diabetic animals. Hormone and Metabolic Research 16: 249–256, 1982

    CAS  Google Scholar 

  • Aungst BJ, Roger NJ, Shefter TS. Comparison of nasal, rectal, buccal, sublingual, and intramuscular insulin efficacy and the effects of a bile salt absorption promoter. Journal of Pharmacology and Experimental Therapeutics 244: 23–27, 1988

    PubMed  CAS  Google Scholar 

  • Bak JF, Nielson OH, Pedersen O, Beck-Nielsen H. Multiple insulin injections using a pen injector versus insulin pump treatment in young diabetic patients. Diabetes Research 6: 155–158, 1987

    PubMed  CAS  Google Scholar 

  • Berger A, Saurbrey N, Kuhl C. Clinical experience with a new device that will simplify insulin injections. Diabetes Care 8: 73–76, 1985

    PubMed  CAS  Google Scholar 

  • Bilous RW, Mauer SM, Sutherland DER, Najarian JS, Goetz FC, et al. The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. New Engalnd Journal of Medicine 321: 80–85, 1989

    CAS  Google Scholar 

  • Binder C, Lauritzen T, Faber O, Pramming S. Insulin pharmacokinetics. Diabetes Care 7: 188–199, 1984

    PubMed  Google Scholar 

  • Binding JJ, Pickup JC, Rowe IF. Continuous subcutaneous insulin infusion does not include a significant acute phase respnse of serum A protein. Diabetologia 20: 113–115, 1985

    Google Scholar 

  • Blackard WG, Nelson NC. Portal and peripheral vein immuno-reactive insulin concentrations before and after glucose infusion. Diabetes 19: 302–306, 1970

    PubMed  CAS  Google Scholar 

  • Blackshear PJ, Rohde TD, Grotteng JC, Dorman FD, Perkins PK, et al. Control of blood glucose in experimental diabetes by means of totally implantable insulin infusion device. Diabetes 28: 634–639, 1979

    PubMed  CAS  Google Scholar 

  • Blackshear PJ, Rohde TD, Palmer JL, Wigness BD, Rupp WM, et al. Glycerol prevents insulin precipitation and interruption of flow in an implantable insulin infusion pump. Diabetes Care 6: 387–392, 1983

    PubMed  CAS  Google Scholar 

  • Bohman SO, Tyder G, Wilczek H, Lundgren G, Jaremko G, et al. Prevention of kidney graft diabetic nephropathy by pancreas transplantation in men. Diabetes 34: 306–308, 1985

    PubMed  CAS  Google Scholar 

  • Bohman SO, Wilczek H, Tyder G, Jaremko G, Lundgren G, et al. Recurrent diabetic nephropathy in renal allografts placed in diabetic patients and protective effect of simultaneous pancreas transplantation. Transplantation Proceedings 19: 2290–2293, 1987

    PubMed  CAS  Google Scholar 

  • Bolinder J, Tyden G. Indication, selection of patients and timing for pancreatic transplantation. Bailliere’s Clinical Gastroenterology 3: 825–833, 1989

    PubMed  CAS  Google Scholar 

  • Brange J, Owens DR, Kany S, Volund A. Monomeric insulins and their experimental and clinical implications. Diabetes Care 13: 923–954, 1990

    PubMed  CAS  Google Scholar 

  • Brange J, Ribel U, Hansen JF, Dobson G, Hansen MT, et al. Monomeric insulins obtained by protein engineering and their medical implications. Nature (London) 333: 679–682, 1988

    CAS  Google Scholar 

  • Bratusch-Marrain PR, Komjati M, Waldhausl W. Pulsatile insulin delivery: physiology and clinical implications. Diabetic Medicine 4(3): 197–200, 1987

    PubMed  CAS  Google Scholar 

  • Brekke IB, Ganes T, Syradalen P, Egge K, Dyrbekk D, et al. Combined renal and pancreatic transplantation: effects on advanced diabetic neuropathy and retinopathy. Life Support Systems 3(Suppl. 1): 680–684 (1985).

    PubMed  Google Scholar 

  • Brennan JR, Gebhart SP, Blackard G. Pump-induced insulin aggregation (a problem with the Biostator). Diabetes 34: 353–359, 1985

    PubMed  CAS  Google Scholar 

  • Brown J, Muller Y, Clark WR, Molnar IG, Neininger D. Importance of hepatic portal circulation for insulin action in streptozotocin-diabetic rats transplanted with fetal pancreases. Journal of Clinical Investigation 64: 1688–1694, 1979

    PubMed  CAS  Google Scholar 

  • Brown L, Munoz C, Siemer L, Edelman E, Langer R. Controlled release of insulin from polymer matrices. Diabetes 35: 692–697, 1986

    PubMed  CAS  Google Scholar 

  • Brownlee M, Cerami A. Glycosylated insulin complexed to Con A. Diabetes 32: 499–504, 1983

    PubMed  CAS  Google Scholar 

  • Brownlee M, Vlassara H, Cerami J, Martin T, Li JJ, et al. Association of insulin pump therapy with raised serum amyloid A in Type I diabetes mellitus. Lancet 1: 411–413, 1984

    PubMed  CAS  Google Scholar 

  • Buchwald H, Chute EP, Goldenberg FJ, Hitchcock CR, Hoogwerf BF, et al. Implantable infusion pump management of insulin resistant diabetes mellitus. Annals of Surgery 202: 278–283, 1985

    PubMed  CAS  Google Scholar 

  • Buchwald H, Rohde TD, Dorman FD, Skakoon JG, Wigness BJD, et al. A totally implantable drug infusion device: laboratory and clinical experience using a model with single flow rate and new design for modulated insulin infusion. Diabetes Care 3: 351–358, 1980

    PubMed  CAS  Google Scholar 

  • Buchwald H, Varco RL, Rupp WM, Goldenberg FJ, Barbosa J, et al. Treatment of a Type II diabetic by a totally implantable insulin infusion device. Lancet 1: 1233–1234, 1981

    PubMed  CAS  Google Scholar 

  • Champion MC, Shepherd GA, Rodger NW, Dupre J. Continuous subcutaneous infusion of insulin in the management of diabetes mellitus. Diabetes 29: 206–212, 1980

    PubMed  CAS  Google Scholar 

  • Chick W, Like A, Lauris V. Beta cell culture on synthetic capillaries: an artificial endocrine pancreas. Science 187: 847–849, 1975

    PubMed  CAS  Google Scholar 

  • Chien YW, Siddigui O, Sun Y, Shi WM, Liu JC. Transdermal iontophoretic delivery of therapeutic peptides/proteins. I. Insulin. Annals of the New York Academy of Sciences 507: 32–51, 1987

    PubMed  CAS  Google Scholar 

  • Chiou GCY, Chuang CY, Chang MS. Systemic delivery of insulin through eyes to lower the glucose concentration. Journal of Ocular Pharmacology 5: 81–91, 1989

    PubMed  CAS  Google Scholar 

  • Christiansen JS, Svendsen PA, Soegaard U, Frandsen M, Mathiesen E, et al. An artificial beta cell: assessment of the glucose analyser, infusion system and optimization of constants for the algorithms. Scandinavian Journal of Clinical Laboratory Investigation 41: 647–654, 1981

    CAS  Google Scholar 

  • Clemens AH, Chang PH, Myers RW. The development of Biostator, a glucose controlled insulin infusion system (GCIIS). Hormone and Metabolic Research 7(Suppl.): 22–33 (1977).

    Google Scholar 

  • Cosimi AB, Anchincloss H, Delmonico FL, Fang L, Natham DM, et al. Combined kidney and pancreas transplantation in diabetes. Archives of Surgery 123: 621–625, 1988

    PubMed  CAS  Google Scholar 

  • Cryer P, Gerich JE. Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. New England Journal of Medicine 313: 232–241, 1985

    PubMed  CAS  Google Scholar 

  • Dahl-Jorgensen K, Hanssen K, Kierulf P, Bjro T, Sandvik L, et al. Reduction of urinary albumin excretion after 4 years of continuous insulin infusion in insulin-dependent diabetes mellitus: the Oslo Study. Acta Endocrinologica 117: 19–25, 1988

    PubMed  CAS  Google Scholar 

  • DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study. Diabetes Care 10: 1–9, 1987

    Google Scholar 

  • DCCT Research Group. Are continuing studies of metabolic control and microvascular complications in insulin-independent diabetes mellitus justified? New England Journal of Medicine 318: 246–250, 1988

    Google Scholar 

  • DCCT Research Group. Diabetes Control and Complications Trial (DCCT): update. Diabetes Care 13: 427–433, 1990

    Google Scholar 

  • Deeb LC, Williams PE. Surveillance in Florida of continuous subcutaneous insulin infusion use in a cohort. Diabetes Care 9: 591–595, 1986

    PubMed  CAS  Google Scholar 

  • Dimitridis GD, Gerich JE. Importance of timing of preprandial subcutaneous insulin administration in the management of diabetes mellitus. Diabetes Care 6: 374–377, 1983

    Google Scholar 

  • Dupre J. The entero-insulin axis and the metabolic effects of gastro-entero-pancreatic polypeptides. Clinical Gastroenterology 9: 711–732, 1980

    CAS  Google Scholar 

  • Field JB, Roidmark S, Harding P, Ishida T, Chou MC. Role of the liver in insulin physiology. Diabetes Care 3: 255–260, 1980

    PubMed  CAS  Google Scholar 

  • Fischel-Ghodsian F, Brown L, Mathiowitz E, Brandenburg D, Langer R. Enzymatically controlled drug delivery. Proceedings of the National Academy of Sciences of the United States 85: 2403–2406, 1988

    CAS  Google Scholar 

  • Flynn CT, Nanson JA. Intraperitoneal insulin with CAPD — an artificial pancreas. Transactions of the American Society for Artificial Internal Organs 25: 114–117, 1979

    PubMed  CAS  Google Scholar 

  • Freyse E-J, Fisher U, Albrecht G. Intraindividual comparison of short-term vs long-term portal and peripheral insulin infusion: differential effects on glucose carbon recycling. Diabetes Nutrition Metabolism 1: 103–112, 1988

    Google Scholar 

  • Friedman EA. Toward a hybrid artificial pancreas. Diabetes Care 12: 415–420, 1989

    PubMed  CAS  Google Scholar 

  • Gall M-A, Mathiesen ER, Skott P, Museaus L, Damm S, et al. Effect of multiple insulin injections with a pen injector on metabolic control and general well-being in insulin-dependent diabetes mellitus. Diabetes Research 11: 97–101, 1989

    PubMed  CAS  Google Scholar 

  • Gooch BR, Abumrad NN, Robinson RP, Petrik M, Campbell D, et al. The effect of continuous insulin infusion using the subcutaneous, intravenous, and intraperitoneal sites. Diabetes Care 6: 122–128, 1983

    PubMed  CAS  Google Scholar 

  • Grau U. Chemical stability of insulin in a delivery system environment. Diabetologia 28: 458–463, 1985

    PubMed  CAS  Google Scholar 

  • Grau U, Saudek CD. Stable insulin preparation for implanted insulin pumps: laboratory and animal trials. Diabetes 36: 1453–1459, 1987

    PubMed  CAS  Google Scholar 

  • Guinn TS, Bailey GJ, Mecklenburg RS. Factors related to discontinuation of continuous subcutaneous insulin-infusion therapy. Diabetes Care 11: 46–51, 1988

    PubMed  CAS  Google Scholar 

  • Gwinup G, Elias AN, Vaziri ND. A case for oral insulin therapy in the prevention of diabetic micro- and macroangiopathy. International Journal of Artificial Organs 13: 393–395, 1990

    PubMed  CAS  Google Scholar 

  • Hankiss J, Hadzary CS. Resorption von Insulin and Asthmolysion von der Nasenschleimhart. Academie Scientiarum Hungaricae 12: 107–114, 1958

    CAS  Google Scholar 

  • Hanna AK, Minuk HL, Albisser AM, Marliss EB, Leibel BS, et al. A portable system for continuous intravenous insulin delivery; characteristics and results in diabetic patients. Diabetes Care 3: 1–8, 1980a

    PubMed  CAS  Google Scholar 

  • Hanna AK, Zinman B, Nakhoda AF, Minuk HL, Stokes EF, et al. Insulin, glucagon and amino acids during glycemic control by the artificial pancreas in diabetic man. Metabolism 29: 321–322, 1980b

    PubMed  CAS  Google Scholar 

  • Hanssen KF, Dahl-Jorgensen D, Lauritzen T, Feldt-Rasmussen B, Brinchmann-Hansen O, et al. Diabetic control and micro-vascular complications: the near-normoglycemic experience. Diabetologia 29: 677–684, 1986

    PubMed  CAS  Google Scholar 

  • Harris MD, Davidson MB, Rosenberg CS. Simple solution to the problem of Biostator-induced insulin aggregation. Diabetes Care 9: 356–358, 1986

    PubMed  CAS  Google Scholar 

  • Haug CE, Babcock SK, Lafferty KJ, Weil III R. Islet cell function: comparison of portal versus sytemic venous insulin delivery. Transplantation 45: 992–994, 1988

    PubMed  CAS  Google Scholar 

  • Hellerstrom C, Andersson A, Korsgren O, Jansson L, Sandler S. Aspects of pancreatic islet transplantation in diabetes mellitus. Bailliere’s Clinical Gastroenterology 3: 851–863, 1989

    PubMed  CAS  Google Scholar 

  • Helve E, Koivisto VA, Lehtonen A, Pelkonen R, Hutturen JK, et al. A crossover comparison of continuous insulin infusion and conventional injection treatment of Type I diabetes. Acta Medica Scandinavica 221: 385–396, 1987

    PubMed  CAS  Google Scholar 

  • Hering BJ, Bretzel RG, Federlin K. Current status of clinical islet transplantation. Hormone and Metabolic Research 20: 537–545, 1988

    PubMed  CAS  Google Scholar 

  • Hirsch IB, Farkas-Hirsch R, Skyler JS. Intensive insulin therapy for treatment of Type I diabetes. Diabetes Care 12: 1265–1283, 1990

    Google Scholar 

  • Horwitz DL, Gonen B, Zeidler A, Langer B, Rodman D. An artificial beta cell for control of diabetes: comparison of glucose and free insulin levels with those achieved by subcutaneous insulin. Abstract no. 96. Diabetes 26(Suppl. 1): 376A 1977.

    Google Scholar 

  • Horwitz DL, Schwartz SS. Use of an artificial beta cell in surgery. Hormone and Metabolic Research 8 (Suppl. Series): 156–158 1979.

    Google Scholar 

  • Horwitz DL, Starr JI, Make ME, Blackbard WG, Rubenstein AH. Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. Journal of Clinical Investigation 55: 1278–1283, 1975

    PubMed  CAS  Google Scholar 

  • Houtzagers CMGJ, Berntzen PA, van der Stap H, Heine PJ, van der Veen FA. Absorption kinetics of short- and intermediateacting insulins after jet injection with Medi-jector II. Diabetes Care 11: 739–742, 1988a

    PubMed  CAS  Google Scholar 

  • Houtzagers CMG, Visser APh, Berntzen PA, van der Veen FA. The Medi-Jector II: Efficacy and acceptability in insulin dependent diabetic patients with and without needle phobia. Diabetic Medicine 5: 135–138, 1988b

    PubMed  CAS  Google Scholar 

  • Irsigler K, Kritz H. Long-term continuous intravenous insulin therapy with a portable insulin dosage-regulating apparatus. Diabetes 28: 196–203, 1979

    PubMed  CAS  Google Scholar 

  • Irsigler K, Kritz H, Hagmuller G, Franetzki M, Prestele K, et al. Long-term continuous intraperitoneal insulin infusion with an implantable remote-controlled insulin infusion device. Diabetes 30: 1072–1075, 1981

    PubMed  CAS  Google Scholar 

  • Irsigler K, Kritz H, Hagmuller G, Franetzki M, Prestele K, et al. Implanted remote controlled insulin infusion device for long term continuous intraperitoneal insulin infusion. In Petal (Ed.) Artificial systems for insulin delivery, pp. 317–333, Raven Press, New York, 1983

    Google Scholar 

  • Jefferson IG, Martean TM, Smith MA, Baum JD. A multiple injection regimen using an insulin injection pen and prefilled cartridged soluble human insulin in adolescents with diabetes. Diabetic Medicine 2: 493–495, 1985

    PubMed  CAS  Google Scholar 

  • Jorgensen S, Vaag A, Langkjaer L, Hougaard P, Markusen J. NovoSol Basal: pharmacokinetics of a novel soluble long-acting insulin analogue. British Medical Journal 299: 415–419, 1989

    PubMed  CAS  Google Scholar 

  • Kang S, Owens DR, Vora JP, Brange J. Comparison of insulin analogue B9Asp B27Glu and soluble human insulin in insulin-treated diabetes. Lancet 335: 303–306, 1990

    PubMed  CAS  Google Scholar 

  • Kari B. Control of blood glucose levels in alloxan-diabetic rabbits by iontophoresis of insulin. Diabetes 35: 217–221, 1986

    PubMed  CAS  Google Scholar 

  • Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 61: 827–837, 1967

    PubMed  CAS  Google Scholar 

  • Kerner W, Bruckel J, Zier H, Arias P, Thun C, et al. Similar effects of pulsatile and constant intravenous insulin delivery. Diabetes Research and Clinical Practice 4: 269–274, 1988

    PubMed  CAS  Google Scholar 

  • Kerner W, Moll V, Navascues I, Pfeiffer EF. Importance of early postprandial insulin delivery in insulin-dependent diabetics. Klinische Wochenschrift 62: 738–744, 1984

    PubMed  CAS  Google Scholar 

  • Kerner W, Schultz M, Schock D, Pfeiffer EF. Variations of insulin requirements in insulin-dependent diabetics for meals taken at different times of the day. Hormone and Metabolic Research 12 (Suppl.): 228–230 (1982).

    Google Scholar 

  • Kerner W, Thum C, Tamas G, Beischer W, Clemens AH, et al. Attempts at perfect normalization of glucose tolerance test of severe diabetes by the artificial beta cell. Hormone and Metabolic Research 8: 256–261, 1976

    PubMed  CAS  Google Scholar 

  • Knatterud GL, Fisher M. International study group on implantable insulin delivery devices registry. Diabetes, Nutrition and Metabolism 1: 323–328, 1988

    Google Scholar 

  • Koivisto VA, Teppo AM, Maury CP, Taskinen MR. No evidence of amyloidosis in Type I diabetes treated with continuous subcutaneous insulin infusion. Diabetes 32: 88–90, 1983

    PubMed  CAS  Google Scholar 

  • Kraegen EW, Chisholm DJ. Closure of the loop by glucose sensing: physiological and practical considerations. Hormones and Metabolic Research (Suppl. 20): 1–4, 1988

    Google Scholar 

  • Kritz H, Hagmuller G, Lovett R, Irsigler K. Implanted constant basal-rate insulin infusion devices for Type I (insulin-dependent) diabetic patients. Diabetologia 25: 78–81, 1983

    PubMed  CAS  Google Scholar 

  • Kryshak EJ, Butler PC, Marsh C, Miller A, Barr D, et al. Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery. Diabetes 39: 142–148, 1990

    PubMed  CAS  Google Scholar 

  • Land W, Landgraf R (Eds). Clinical pancreas transplantation, the world experience. Transplantation Proceedings 19(Suppl. 14): 37–91 1987.

    Google Scholar 

  • Landgraf R, Nusser J, Scheuer R, Fiedler A, Scheider A, et al. Metabolic control and effect on secondary complications of diabetes mellitus by pancreatic transplantation. Bailliere’s Clinical Gastroenterology 3: 865–876, 1989

    PubMed  CAS  Google Scholar 

  • Lauritzen T, Pramming S, Deder T, Binder C. Pharmacokinetics of continuous subcutaneous insulin infusion. Diabetologia 24: 326–329, 1983

    PubMed  CAS  Google Scholar 

  • LeBlanc H, Chauvet D, Lombrail P, Robert J. Glycemic control with closed-loop intraperitoneal insulin in Type I diabetes. Diabetes Care 9: 124–128, 1986

    PubMed  CAS  Google Scholar 

  • Lim F, Sun AM. Microencapsulated islets as bio-artificial endocrine pancreas. Science 210: 908–910, 1980

    PubMed  CAS  Google Scholar 

  • Longhead WD, Wonlfe-Flanagan H, Clement JR, Albisser AM. Insulin aggregation in artificial delivery systems. Diabetologia 19: 1–9, 1980

    Google Scholar 

  • Major RH. The intranasal application of insulin. Journal of Laboratory and Clinical Medicine 21: 278–280, 1935

    Google Scholar 

  • Malone J, Lowitt S, Grone N, Shah S. Comparison of insulin levels after injection by jet stream and disposable insulin syringe. Diabetes Care 9: 637–640, 1986

    PubMed  CAS  Google Scholar 

  • Marshall SM, Home PD, Taylor R, Alberti KGMM. Continuous subcutaneous insulin infusion versus injection therapy: a randomised cross-over trial under usual diabetic clinic conditions. Diabetic Medicine 4: 521–525, 1987

    PubMed  CAS  Google Scholar 

  • Mauer SM, Buchwald H, Groppoli TJ. Failure to find amyloidosis in dogs treated with long-term intravenous insulin delivery by a totally implantable pump. Diabetologia 25: 448–450, 1983

    PubMed  CAS  Google Scholar 

  • McMurry JF. The artificial pancreas today. Henry Ford Hospital Medical Journal 31: 77–83, 1982

    Google Scholar 

  • Mecklenburg RS, Benson FA, Benson Jr JW. Longer-term metabolic control with insulin pump therapy: report of experience with 27 patients. New England Journal of Medicine 313: 465–468, 1985

    PubMed  CAS  Google Scholar 

  • Mecklenburg RS, Benson FA, Benson JW, Fredlund PN, Guinn T, et al. Acute complications associated with insulin infusion pump therapy: report of experience with 161 patients. Journal of the American Medical Association 252: 3265–3269, 1984

    PubMed  CAS  Google Scholar 

  • Metcalf J. The administration of insulin by continuous injection. MD Thesis, University of Cambridge, 1934

  • Meyer BR, Katzeff HL, Eschbach JC, Trimmer J, Zacharias SB, et al. Transdermal delivery of human insulin to albino rabbits using electrical current. American Journal of Medical Sciences 297: 321–325, 1989

    CAS  Google Scholar 

  • Micossi P, Galimberti G, Librenti MC, Petrella G, Dozio N, et al. Glycerol-insulin raises circulating insulin antibodies in Type I diabetic patients treated with permanently implanted devices. Metabolism 37: 1029–1032, 1988

    PubMed  CAS  Google Scholar 

  • Mirouze J, Selam JL, Slingeneyer A, Chaptal PA, Franetzki M, et al. One year continuous run with a totally implantable insulin infusion pump in a human diabetic. Transactions of the American Society for Artificial Internal Organs 29: 709–712, 1983

    PubMed  CAS  Google Scholar 

  • Miyazaki S, Yokouchi C, Takada M. External control of drug release: controlled release of insulin from a hydrophilic polymer implant by ultrasound irradiation in diabetic rats. Journal of Pharmacy and Pharmacology 40: 716–717, 1988

    PubMed  CAS  Google Scholar 

  • Moses AC, Flier JS. Nasal insulin: an approach to peri-prandial control of blood glucose. In Larkins RG et al. (Eds) Diabetes 1988, pp. 81–84, Elsevier Press, Amsterdam, 1989

    Google Scholar 

  • Moses AC, Gordon GS, Carey MC, Flier JF. Insulin administered intranasally as an insulin-bile salt aerosol. Diabetes 32: 1040–1047, 1983

    PubMed  CAS  Google Scholar 

  • Murray DP, Keenan P, Gayer E, Salmon P, Tonkin GH, et al. A randomized trial of the efficacy and acceptability of a pen injector. Diabetic Medicine 5: 750–754, 1988

    PubMed  CAS  Google Scholar 

  • Nolte MS, Taboga C, Salamon E, Moses A, Longenecker J, et al. Biological activity of nasally administered insulin in normal subjects. Hormonesand Metabolic Research 22: 170–174, 1990

    CAS  Google Scholar 

  • Nishihata T, Kamada A, Sakai K, Yagi T, Kawamori R, et al. Effectiveness of insulin suppositories in diabetic patients. Journal of Pharmacy and Pharmacology 4: 799–801, 1989

    Google Scholar 

  • Paolisso G, Sgambato S, Torella R, Varricchio M, Scheen A, et al. Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with Type I diabetes. Journal of Clinical Endocrinology Metabolism 66: 1220–1226, 1988

    PubMed  CAS  Google Scholar 

  • Patel HM, Ryman BE. Oral administration of insulin by encapsulation within liposomes. FEBS Letters 62: 60–63, 1976

    PubMed  CAS  Google Scholar 

  • Paterson KR, Campbell IN, MacRury SM, Gilmour DG, MacCuish AC. Management of diabetes resistant to subcutaneous insulin with intravenous insulin via an implanted infusion pump. Scottish Medical Journal 33: 239–243, 1988

    PubMed  CAS  Google Scholar 

  • Peden NR, Braaten JT, McKendry JBR. Diabetic ketoacidosis during long-term treatment with continuous subcutaneous insulin infusion. Diabetes Care 7: 1–5, 1984

    PubMed  CAS  Google Scholar 

  • Pehling GB, Gerich JE. Comparison of plasma insulin profiles after subcutaneous administration of insulin by jet spray and conventional needle injection in patients with insulin-dependent diabetes mellitus. Mayo Clinical Proceedings 59: 751–754, 1984

    CAS  Google Scholar 

  • Perkins PR, Dorman FD, Rohde TD, Blackshear PJ, Blackshear PL, et al. Design and initial testing of a totally implantable transcutaneously controllable insulin delivery device. Transactions of the American Society for Artificial Internal Organs 24: 229–234, 1978

    PubMed  CAS  Google Scholar 

  • Pfeiffer EF. On the way to the automated (blood) glucose regulation in diabetes: the dark past, they grey present and the rosy future. Diabetologia 30: 51–65, 1987

    PubMed  CAS  Google Scholar 

  • Pfeiffer EF. Artificial endocrine pancreas (closed-loop system for blood sugar control in diabetes mellitus): introduction to the subject. Artificial Organs 12: 310–319, 1988

    PubMed  CAS  Google Scholar 

  • Pfeiffer EF, Kerner W. Use of artificial pancreas and portable insulin infusion pumps in diabetes therapy: past, present, and future. Artificial Organs 9: 129–137, 1985

    PubMed  CAS  Google Scholar 

  • Pickup JC. Amyloid and insulin infusion pumps. Diabetic Medicine 2: 12–16, 1985

    Google Scholar 

  • Pickup JC, Keen H, Parsons JA, Alberti KG. Continuous subcutaneous insulin infusion: an approach to achieving normo-glycemia. British Medical Journal 1(6107): 204–207 1978

    PubMed  CAS  Google Scholar 

  • Pickup J, Keen H, Vibert GC, White MC, Kohner EM, et al. Continuous subcutaneous insulin infusion in the treatment of diabetes mellitus. Diabetes Care 3: 290–300, 1980

    PubMed  CAS  Google Scholar 

  • Pickup JC, Shaw GW, Claremont DJ, In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer. Diabetologia 32: 213–217, 1989

    PubMed  CAS  Google Scholar 

  • Pietri A, Raskin P. Cutaneous complications of chronic continuous subcutaneous insulin infusion therapy. Diabetes Care 4: 624–626, 1981

    PubMed  CAS  Google Scholar 

  • Piwernetz K, Selam JL, Mirouze J, Renner R, Hepp KD. Hybrid control of intraperitoneal insulin infusion. Diabetes, Nutrition and Metabolism 1: 49–55, 1988

    Google Scholar 

  • Pontioroli AE, Alberetto M, Secchi A, Dossi G, Bosi I, et al. Insulin given intranasally induces hypoglycemia in normal and diabetic subjects. British Medical Journal 284: 303–306, 1982

    Google Scholar 

  • Poulsen JSD, Smith M, Deckert M, Deckert T. Comparison of intraperitoneal, intraportal and intravenous insulin infusion. Acta Endocrinologica 95: 500–504, 1980

    PubMed  CAS  Google Scholar 

  • Pozza G, Secchi A. Evaluation of endocrine function in pancreas transplant recipients. In van Schilfgaarde R & Hardy MA (Eds) Transplantation of the endocrine pancreas in diabetes mellitus, pp. 337–345, Elsevier Press, Amsterdam, New York, 1988

    Google Scholar 

  • Pyke D. Pancreas transplantation for diabetes? Lancet 1: 816–817, 1988

    PubMed  CAS  Google Scholar 

  • Ramsay RC, Goetz FC, Sutherland DER, Mauer SM, Robinson LL, et al. Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus. New England Journal of Medicine 318: 208–214, 1988

    PubMed  CAS  Google Scholar 

  • Ravnik-Oblak M, Babie D, Granic M. Closed-loop systems in the management of diabetes. Diabetologia Croatica 17(2): 73–91 1988

    Google Scholar 

  • Rayman G, Walker R, Day JL. Patient experience with a jet injector. Diabetic Medicine 6: 274–276, 1989

    PubMed  CAS  Google Scholar 

  • Raz I, Kidron M, Bar-On H, Ziv E. Rectal administration of insulin. Israel Journal of Medical Sciences 20: 173–175, 1984

    PubMed  CAS  Google Scholar 

  • Reach G. Bioartificial pancreas: status and bottlenecks. International Journal of Artificial Organs 13: 329–336, 1990

    PubMed  CAS  Google Scholar 

  • Reach G, Jaffrin MY. Les pancreas bioartificiels. Medecine/Science 2: 87–93, 1986

    Google Scholar 

  • Reeves ML, Seigler DE, Ryan EA, Skyler JS. Glycemic control in insulin-dependent diabetes mellitus: comparison of outpatient intensified conventional therapy with continuous subcutaneous insulin infusion. American Journal of Medicine 72: 673–680, 1982

    PubMed  CAS  Google Scholar 

  • Regal H, Koivisto VA, Maury CP, Irsigler K. No sign of amyloidosis in pump-treated diabetics. Diabetes Research 9: 195–199, 1988

    Google Scholar 

  • Ritschel WA, Ritschel GB, Ritschel BEC, Lucker PW. Rectal delivery system for insulin. Methods and Findings in Experimental and Clinical Pharmacology 10: 645–656, 1988

    PubMed  CAS  Google Scholar 

  • Rizza RA. Treatment options for insulin-dependent diabetes mellitus: a comparison of the artificial endocrine pancreas, continuous subcutaneous insulin infusion, and multiple daily insulin injections. Mayo Clinic Proceedings 61: 796–805, 1986

    PubMed  CAS  Google Scholar 

  • Rizza RA, Gerich JE, Haymond MW, Westland RE, Hall LD, et al. Control of blood sugar in insulin-dependent diabetes: comparison of an artificial endocrine pancreas, continuous subcutaneous insulin infusion, and intensified conventional insulin therapy. New England Journal of Medicine 303: 1313–1318, 1980

    PubMed  CAS  Google Scholar 

  • Rizza RA, Mandarino LJ, Gerest J, Baker BA, Gerich JF. Production of insulin resistance by hyperinsulinemia in man. Diabetologia 28: 70–75, 1985

    PubMed  CAS  Google Scholar 

  • Rizza RA, Westland RE, Hall DK, Patton G, Haymond MW, et al. Subcutaneous versus intraperitoneal administration of insulin on postprandial hyperglycemia and glucose turnover in alloxan diabetic dogs. Daibetologia 23: 61–64, 1982

    CAS  Google Scholar 

  • Roos AN, Meinders AE. Does an insulin pen improve the metabolic control of type I diabetes mellitus if added to conventional treatment? Netherlands Journal of Medicine 34: 116–125, 1989

    PubMed  CAS  Google Scholar 

  • Rupp WM, Barbosa JJ, Blackshear PJ, McCarthy HB, Rohde TD, et al. The use of an implantable insulin pump in the treatment of Type II diabetes. New England Journal of Medicine 307: 265–270, 1982

    PubMed  CAS  Google Scholar 

  • Saffran M, Kumar GS, Savariar C, Burnham JC, Williams F, et al. A new approach to the oral administration of insulin and other peptide drugs. Science 233: 1081–1084, 1986

    PubMed  CAS  Google Scholar 

  • Salzman R, Mansor JE, Griffmg GT, Kimmerle R, Rudermen N, et al. Intranasal aerosolized insulin. Mixed-meal studies and long-term use in Type I diabetes. New England Journal of Medicine 312: 1078–1084, 1985

    PubMed  CAS  Google Scholar 

  • Santiago JV, Clemens AH, Clark WL, Kipnis DM. Closed-loop and open-loop devices for blood glucose control in normal and diabetic subjects. Diabetes 27: 71–81, 1979

    Google Scholar 

  • Saudek CD. Implantable insulin pumps: current look. Diabetes Research and Clinical Practice 10: 109–114, 1990

    PubMed  CAS  Google Scholar 

  • Saudek CD, Selam JL, Pitt HA, Waxman K, Rubio M, et al. A preliminary trial of the programmable implantable medication system for insulin delivery. New England Journal of Medicine 321: 574–579, 1989

    PubMed  CAS  Google Scholar 

  • Schade DS, Eaton RP. Remotely controlled implantable versus manually controlled external insulin pump. Western Journal of Medicine 140: 948–951, 1984

    PubMed  CAS  Google Scholar 

  • Schade DS, Eaton RP, Carlson GA, Bair RE, Gaona JI, et al. Future therapy of the insulin-dependent diabetic patient: the implantable insulin delivery system. Diabetes Care 4: 319–324, 1981a

    PubMed  CAS  Google Scholar 

  • Schade DS, Eaton RP, Davis T. The kinetics of peritoneal insulin absorption. Metabolism 30: 149–155, 1981b

    PubMed  CAS  Google Scholar 

  • Schade DS, Eaton RP, Edwards WS, Dobemecle RC, Spencer WJ, et al. Successful short term implantation of a remotely programmable insulin delivery system in man. Journal of the American Medical Association 247: 1848–1853, 1982

    PubMed  CAS  Google Scholar 

  • Schade DS, Eaton RP, Friedman NB, Spencer WJ. Normalization of plasma insulin profiles with intraperitoneal insulin in diabetic man. Diabetologia 19: 35–39, 1980

    PubMed  CAS  Google Scholar 

  • Schade DS, Santiago J, Skyler J, Rizza R (Eds). Intensive insulin therapy, Excerpta Medica, Amsterdam, 1983

    Google Scholar 

  • Scharp DW. Islet transplantation. Diabetes 39(Suppl. 1): 323–325 1989

    Google Scholar 

  • Schiffrin A, Belmonte MM. Comparison between continuous subcutaneous insulin infusion and multiple injections of insulin: a one-year prospective study. Diabetes 31: 255–264, 1982

    PubMed  CAS  Google Scholar 

  • Sefton MV. Implantable pumps. Critical Reviews in Biomedical Engineering 14: 201–240, 1987

    PubMed  CAS  Google Scholar 

  • Selam JL. Insulin therapy of diabetics with implantable infusion pumps: clinical aspects. International Journal of Artificial Organs 13: 261–266, 1990

    PubMed  CAS  Google Scholar 

  • Selam JL, Charles MA. Devices for insulin administration. Diabetes Care 13: 955–979, 1990

    PubMed  CAS  Google Scholar 

  • Selam JL, Slingeneyer P, Hedon B, Mares P, Berand JJ, et al. Long-term ambulatory peritoneal insulin infusion of brittle diabetes with portable pumps: comparison with intravenous and subcutaneous routes. Diabetes Care 6: 105–111, 1983

    PubMed  CAS  Google Scholar 

  • Service FJ. Normalization of plasma glucose of unstable diabetes studies under ambulatory, fed conditions with pumped intravenous insulin. Journal of Laboratory and Clinical Medicine 91: 480–489, 1978

    PubMed  CAS  Google Scholar 

  • Shettigar UR. Theoretical studies on self-regulating insulin delivery system. Artificial Organs 10(5): 404–410 1986

    PubMed  CAS  Google Scholar 

  • Shichiri M, Kawamori R, Hakui N, Yamasaki Y, Abe H. Closed-loop glycemic control with a wearable artificial endocrine pancreas (variations in daily insulin requirements to glycemic response). Diabetes 33: 1200–1202, 1984

    PubMed  CAS  Google Scholar 

  • Siddiqui O, Sun Y, Lin JC, Chien YW. Facilitated transdermal transport of insulin. Journal of Pharmaceutical Sciences 76: 341–345, 1987

    PubMed  CAS  Google Scholar 

  • Silver RD, Flier JS. Intranasal insulin: a unique approach to insulin therapy. IDF Bulletin 34: 94–96, 1990

    Google Scholar 

  • Simonson DC, Tamborlane WV, Defronzo RA, Sherwin RS. Intensive insulin therapy reduces the counterregulatory hormone responses to hypoglycemia in patients with type I diabetes. Annals of Internal Medicine 103: 184–190, 1985

    PubMed  CAS  Google Scholar 

  • Sinay IR, Schlimovich S, Damilano S, Cagide AL, Faingold MC, et al. Intranasal insulin administration in insulin dependent diabetes: reproducibility of its absorption and effects. Hormone and Metabolic Research 22: 307–308, 1990

    PubMed  CAS  Google Scholar 

  • Slams G, Hautecouverture M, Assan R, Tchobroutsky G. One to five days of continuous intravenous insulin infusion on seven diabetic patients. Diabetes 23: 732–738, 1974

    Google Scholar 

  • Soeldner JS. Treatment of diabetes mellitus by devices. American Journal of Medicine 70: 183–194, 1981

    PubMed  CAS  Google Scholar 

  • Solders G, Wilczek H, Gunnarsson R, Ryden G, Persson A, et al. Effects of combined pancreatic and renal transplantation on diabetic neuropathy: a two-year follow-up study. Lancet 2: 1232–1235, 1987

    PubMed  CAS  Google Scholar 

  • Spangler RS. Insulin administration via liposomes. Diabetes Care 13: 911–922, 1990

    PubMed  CAS  Google Scholar 

  • Stephen RL, Kim SW, Jacobsen SC. Potential novel methods for insulin administration. II: Self-regulating internal drug delivery systems. Biomedica Biochemica Acta (Berlin) 43: 559–560, 1984

    CAS  Google Scholar 

  • Stephen RL, Petelenz TJ, Jacobsen SC. Potential novel methods for insulin administration. I. Iontophoresis. Biomedica Biochimica Acta (Berlin) 43: 553–558, 1984b

    CAS  Google Scholar 

  • Stevenson RW, Parsons JA, Alberti KGMM. Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs. American Journal of Physiology 244: E190–E195, 1983

    PubMed  CAS  Google Scholar 

  • Stolar MW. Atherosclerosis in diabetes: the role of hyperinsulinemia. Metabolism 37(Suppl. 1): 1–9 1988

    PubMed  CAS  Google Scholar 

  • Stout RW. The role of insulin in atherosclerosis in diabetes and non-diabetes: a review. Diabetes 30(Suppl. 2): 54–57 1981

    PubMed  CAS  Google Scholar 

  • Sutherland DER, Kendall DM, Moudry KC, Navarno X, Kennedy WR, et al. Pancreas transplantation in nonuremic, Type I diabetic recipients. Surgery 104: 453–464, 1988

    PubMed  CAS  Google Scholar 

  • Sutherland DER, Moudry-Munns KC. International pancreas transplantation registry analysis. Transplantation Proceedings 22: 571–574, 1990

    PubMed  CAS  Google Scholar 

  • Tamas GY, Bojta J, Baayai Z, Petrangi G, Szalay J. Use of an artificial endocrine pancreas in diabetic pregnancy. Hormone and Metabolic Research 8 (Suppl. Series) 166–167, 1979

    Google Scholar 

  • Tamborlane WV, Champion MC, Rizza RA, Service FJ, Bergenstal RM. Observations or control of glycemia with conventional insulin therapy or continuous subcutaneous insulin infusion. Diabetes 34(Suppl. 3): 22–26 1985

    PubMed  Google Scholar 

  • Tamborlane WV, Sherwin RS, Genel M, Felig P. Reduction to normal or plasma glucose in juvenile diabetes by subcutaneous administration of insulin with a portable infusion pump. New England Journal of Medicine 300: 573–578, 1979

    PubMed  CAS  Google Scholar 

  • Taylor R, Home PD, Alberti KG. Plasma free insulin profiles after administration of insulin by jet and conventional syringe injections. Diabetes Care 4: 377–379, 1981

    PubMed  CAS  Google Scholar 

  • Tchobroutsky G. Relation of diabetes control to development of microvascular complications. Diabetologia 15: 143–152, 1978

    PubMed  CAS  Google Scholar 

  • Teutsch SM, Herman WH, Dwyer DM, Lane JM. Mortality among diabetic patients using continuous subcutaneous insulin-infusion pumps. New England Journal of Medicine 310: 361–368, 1984

    PubMed  CAS  Google Scholar 

  • Unger RH. Meticulous control of diabetes: benefits, risks, and precautions. Diabetes 31: 479–483, 1982

    PubMed  CAS  Google Scholar 

  • University of Michigan Pancreas Transplant Evaulation Committee. Pancreatic transplantation as treatment for IDDM: proposed candidate criteria before end-stage diabetic nephropathy. Diabetes Care 11: 669–675, 1988

    Google Scholar 

  • van der Vliet JA, Navarno X, Kennedy WR, Goetz FC, Najarian JS, et al. The effect of pancreas transplantation on diabetic polyneuropathy. Transplantation 45: 368–370, 1988

    PubMed  Google Scholar 

  • Velosa JA, Frohnert PP, Perkins JD, Zimmerman BR, Fromme GA, et al. Pancreas transplantation at Mayo: in patient selection. Mayo Clinical Proceedings 65: 475–482, 1990

    CAS  Google Scholar 

  • Verdonk CA, Rizza RA, Westland RE, Nelson RL, Gerich JE, et al. Glucose clamping using the Biostator GCIIS. Hormone and Metabolic Research 12: 133–135, 1980

    PubMed  CAS  Google Scholar 

  • Vora JP, Owens DR, Dolben J, Atiea JA, Dean JD, et al. Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects. British Medical Journal 297: 1236–1239, 1988

    PubMed  CAS  Google Scholar 

  • Walters DP, Simith PA, Martean TM, et al. Experience with NovoPen, an injection device using cartridged insulin for diabetic patients. Diabetic Medicine 2: 496–497, 1985

    PubMed  CAS  Google Scholar 

  • Watkins PJ. Pros and cons of continuous subcutaneous insulin infusion. British Medical Journal 290: 655–656, 1985

    PubMed  CAS  Google Scholar 

  • Weingarten C, Monfti A, Desjeux JF, Luong TT, Durand G, et al. Oral ingestion of insulin liposomes: effects of the administration route. Life Science 28: 2747–2752, 1981

    CAS  Google Scholar 

  • White NH, Skor DA, Cryer PE, Levandoski LA, Bier DM, et al. Identification of Type I diabetic patients at increased risks for hypolgycemia during intensive therapy. New England Journal of Medicine 308: 485–491, 1983

    PubMed  CAS  Google Scholar 

  • Yamamoto A, Luo AM, Dodd-Kashi S, Lee VHL. The ocular route for systemic insulin delivery in the albino rabbit. Journal of Pharmacology and Experimental Therapeutics 249: 249–255, 1989

    PubMed  CAS  Google Scholar 

  • Yamasake Y, Shichiri M, Kawamori R, Kikuchi M, Yagi T, et al. The effectiveness of rectal administration of insulin suppository in normal and diabetic subjects. Diabetes Care 4: 454–458, 1981

    Google Scholar 

  • Zimmerman BR. Influence of the degree of control of diabetes on the prevention, postponement, and amelioration of late complications. Drugs 38: 941–956, 1989

    PubMed  CAS  Google Scholar 

  • Zinman B. The physiologic replacement of insulin: an elusive goal. New England Journal of Medicine 321: 363–370, 1989

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

    Frank P. Kennedy

Authors
  1. Frank P. Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kennedy, F.P. Recent Developments in Insulin Delivery Techniques. Drugs 42, 213–227 (1991). https://doi.org/10.2165/00003495-199142020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199142020-00004

Search

Navigation