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Severe insulin resistance treated with insulin lispro

1997; Elsevier BV; Volume: 349; Issue: 9046 Linguagem: Inglês

10.1016/s0140-6736(05)60957-9

1474-547X

Geoffrey Gill, Gareth Williams,

Diabetes, Cardiovascular Risks, and Lipoproteins

Henrichs and colleagues (Nov 2, p 1248)1Henrichs HR Unger H Trautmann ME Pfützner A Severe insulin resistance treated with insulin lispro.Lancet. 1996; 348: 1248Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar describe the case of a 38-year-old woman with severely unstable insulin-dependent diabetes (IDDM) and apparent subcutaneous insulin resistance, which dramatically improved after the introduction of the human insulin analogue, insulin lispro. Several points deserve mention. First, these workers have not investigated or even speculated on the possible cause of their patient's insulin resistance. They seem unaware of the many publications about brittle diabetic patients with recurrent ketoacidosis,2Kent LA Gill GV Williams G Mortality and outcome of patients with brittle diabetes and recurrent ketoacidosis.Lancet. 1994; 344: 778-781Summary PubMed Scopus (74) Google Scholar, 3Gill GV Lucas S Kent LA Prevalence and characteristics of brittle diabetes in Britain.Q J Med. 1996; 89: 839-843Crossref Scopus (44) Google Scholar and, curiously, have not cited any of the reports that have effectively discredited the notion of subcutaneous insulin resistance. These patients are almost exclusively young women with various psychosocial problems, and many have been shown to induce frequent episodes of metabolic decompensation by direct manipulation of their therapeutic regimens; for example, by omitting or faking injections, and by tampering with insulin infusion pumps. In a detailed and systematic investigation of a group of such patients from America, Schade and Duckworth4Schade DS Duckworth WC In search of the subcutaneous insulin resistance syndrome.New Engl J Med. 1986; 315: 147-153Crossref PubMed Scopus (65) Google Scholar were unable to substantiate the diagnosis of subcutaneous insulin resistance in any patient referred to them. They measured plasma insulin and blood glucose responses to standardised subcutaneous and intravenous insulin injections, and compared these with normal ranges derived from stable IDDM patients. The subcutaneous insulin absorption studies presented by Henrichs and colleagues are difficult to interpret. They do not follow the protocol of Schade and Duckworth.4Schade DS Duckworth WC In search of the subcutaneous insulin resistance syndrome.New Engl J Med. 1986; 315: 147-153Crossref PubMed Scopus (65) Google Scholar Additionally, they are one-off observations, and the patient was presumably closely supervised. Additionally, the variability in plasma insulin concentrations after subcutaneous insulin injection, even in stable diabetic patients, is considerable.4Schade DS Duckworth WC In search of the subcutaneous insulin resistance syndrome.New Engl J Med. 1986; 315: 147-153Crossref PubMed Scopus (65) Google Scholar Finally, we are puzzled as to how insulin lispro delivered by continuous subcutaneous infusion (CSII) can offer advantages over standard soluble insulin delivered in the same manner. As Henrichs and colleagues point out, insulin lispro has more rapid subcutaneous absorption than other short-acting insulins,5Howy DC Bowsher RR Brunelle RL Woodworth JR [Lys (B28), Pr (B29)]—human insulin—a rapidly absorbed analogue of human insulin.Diabetes. 1994; 43: 396-402Crossref PubMed Scopus (533) Google Scholar but once stable steady-state subcutaneous delivery was achieved by the pump, it is difficult to see how insulin bioavailability could be improved, especially since subcutaneous losses of standard insulin delivered by CSII are negligible. The patient's improved metabolic stability coincided with striking weight reduction and fall in insulin dosage. Henrichs suggests that this was attributable to lispro treatment. In fact, the data suggest that she was previously overinsulinised, which is well known to induce obesity, insulin resistance, and poor metabolic control. We therefore suggest that it was the reduction in insulin dosages, perhaps motivated by the patient's apparent response to lispro, that led to the improvement in glycaemic control, rather than treatment with insulin lispro per se. Severe insulin resistance treated with insulin lisproAuthors' reply Full-Text PDF