[Letter: Lactic acidosis during renal insufficiency in two diabetic patients treated with metformin].
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Biomedical subjects
Publications and source records attributed to J L Selam.
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The authors report one case of saturnism with chronic nephropathy. In a 49 years old Caucasian male, the diagnosis was suggested by the following findings. Two acute abdominal crisis associated with a severe increase in blood pressure and a slight but significant elevation in the lead concentration in blood (1 mg/l) and urine (0,42 and 0,60 mg/24 h). The chronic poisoning was explained by the high lead concentration in the drinking water used by the patient. Despite chronic renal failure, a significant lead urinary chelation was obtained after infusion of Edetate calcium disodium (8 mg/24 h). Although E.D.T.A. keep its value for diagnosis this chelating agent is less effective on lead removal than the peritoneal dialysis (15 mg over a 36 hour-period) which appears to be the most useful method for treatment in case of chronic nephropathy.
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The stability of a new insulin formulation (lyophilized U100 insulin, Organon) was investigated in vitro in conditions reproducing those of in vivo implanted devices, i.e., constant horizontal agitation at 37 degrees C for 4 wk in various containers and 8 wk in different solvents. Physical stability was assessed by ultraviolet absorption, chemical stability by HPLC, and biological stability by hypoglycemia tests in mice. Insulin precipitated in glass vials but remained clear and active in polyethylene reservoirs and after passage through catheter and pumps in motion, although only 83-90% of insulin was delivered chemically intact. In acidic solvent, insulin showed a major gradual transformation into deamidized derivatives (up to 78% after 8 wk), although still fully active and clear, as expected from previously published excellent in vivo results with acidic insulins. Heparin addition to neutral insulin solution (500 IU/ml) did not alter the properties of the two compounds and might thus be tried to prevent in vivo catheter obstruction due to fibrin deposition.
This work compares different routes of insulin infusion via portable pumps with chronically implanted catheters and evaluates the long-term feasibility of the technique. Six severely unstable (i.e., uncontrolled by optimized intensive insulin therapy) diabetic individuals (age range: 35 +/- 4 yr; duration: 11 +/- 2 yr) were selected. Promedos pumps (Siemens A. G., Erlangen, West Germany) were exclusively used because of their portability and long-life insulin reservoir (1-mo duration with U40 acidic Hoechst insulin). Each patient underwent three randomized 1-mo periods of insulin infusion: subcutaneous (s.c.), intravenous (i.v.), and intraperitoneal (i.p.) before the catheter was left indefinitely in one of these sites. Diabetic control was improved and insulin doses reduced whatever the route of infusion, although the s.c. route gave slightly higher values. These results did not deteriorate with time: mean blood glucose was 126 +/- 3 mg/dl and HbA1 was 8.3 +/- 0.6% after 10-18 mo of constant infusion versus 237 +/- 35 mg/dl and 10.0 +/- 0.8%, respectively, under conventional therapy. From a practical point of view, the i.p. route seems preferable since all s.c. catheters provoked local reactions after less than 1 mo and the two chronic i.v. catheters obstructed after 8 and 9 mo. All other incidents were minor and curable without removal of the catheters. All patients argued improvement of both diabetes and quality of life and no one has resigned so far. Thus, the i.p. infusion technique seems beneficial to unstable diabetic individuals and adaptable to long-term therapy, although intensive education and careful follow-up are necessary.
Fifty-nine chronic peritoneal catheters made of polyethylene covered with silastic were used to treat 43 IDDM patients peritoneally for 3-34 mo (mean 14 mo) with portable peristaltic pumps and U40 acidic insulin. The operative life of the catheters was determined by actuarial analysis. The mechanisms of catheter failure were determined by preremoval x-ray opacification, removal under laparoscopic examination, and electron microscopic analysis of the catheter. Factors such as age, sex, duration of diabetes, implantation and tunnelization procedures, length of the catheter, and rate of infusion were analyzed. The 50% survival rate of the catheters was 16 mo. Six catheters were irreversibly obstructed by intraluminal fibrin formation and/or extraluminal adhesions, although insulin precipitation was never encountered. Seven catheters had to be removed because of a persisting local infection. Other causes were negligible (misinsertion, irreparable break). The only factor significantly related to incidence of catheter failure was gender with respect to obstruction (1 obstruction among 24 women versus 5 among 19 men, P less than 0.03).
A multicenter, double-blind, randomized, parallel-group, 12-month study was conducted to determine if patients with diabetes could be transferred safely and effectively from semisynthetic human insulin (ssHI) to human insulin produced by recombinant DNA technology using baker's yeast as the host cell [rDNA HI (BY)]. Sixty-five patients who ranged in age from 19 to 67 years and who had been on a stable dose of NPH or Lente ssHI with or without Regular ssHI participated. Forty-three were transferred randomly to rDNA HI (BY) and 22 continued on ssHI. Evaluation at both six and 12 months of treatment indicated no statistically or clinically significant differences between the ssHI and rDNA HI (BY) groups with regard to the mean changes from baseline in glycosylated hemoglobin, total daily insulin dose, or body weight. In addition, the proportions of patients who had episodes of mild or moderate hypoglycemia, severe hypoglycemia, hyperglycemia, or other clinical experiences related to diabetes or treatment were similar in the ssHI and rDNA HI (BY) groups. No pattern of unexpected retinal changes occurred, nor were there any remarkable changes in human insulin antibody binding or in mean or individual yeast antibody values in either group. These results show that patients with diabetes can be safely and effectively transferred from semisynthetic human insulin to human insulin produced by rDNA technology from baker's yeast with no change expected in the insulin dose.
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12 recent acute-onset ketotic juvenile diabetics were optimally treated during 5 +/- days by means of an external artificial pancreas. Remission of diabetes occurred in 9 patients (75%). In a comparative group of 28 patients treated by conventional subcutaneous insulin, only 3 (11%) steady remissions were obtained. In a third group of 6 patients treated by insulin infusion without feed-back control, only 1 remission (17%) was obtained. The difference between these two groups and the first group (patients treated by the artificial pancreas) is significant (p less than 0.01). Urinary C-peptide/blood glucose ratio showed a steady improvement of insulin secretion during the remission period. At this time, actuarial analysis shows that the number of patients still in remission decreases during the first 10 months but seems to stabilize after this period. Duration of our remissions is equal to the duration of the "spontaneous" remissions taken from the literature. New treatment able to sustain the residual insulinsecretion during the remission phase (with presently can be induced frequently with our technique) are still to be found.
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We report our personal experience of chronic ambulatory insulin therapy via portable and implantable pumps in insulin-dependent diabetics. Fifteen patients, poorly controlled on conventional insulin injections, were equipped with portable Siemens pumps. These pumps offer compactness, safety means, portability, one-month insulin reservoir and variable insulin rates. The pump catheter was chronically inserted in the peritoneal space using a non-surgical personal technique. Our present experience, representing six patient-years of treatment (range 1 to 16 months), shows excellent steady blood glucose control (mean blood glucose is 115 +/- 5 mg/dl v. 187 +/- 21 mg/dl with conventional therapy). All incidents were minor and most were catheter related. However, there was no catheter removal or discontinuation of pump treatment. All patients declared that there was a marked improvement in their quality of life. One of the pump-treated patients agreed to be transferred to a totally implantable Siemens prototype. The pump was inserted in the muscular wall of abdomen, and the delivery catheter terminated in the peritoneal space. Refills are made percutaneously approximately every 20 days. Rates and functions of the pump are remotely controlled. Five months after implantation, results, compared with those of a portable pump, show similar excellent blood glucose control and pump precision with a further improvement in the patient's quality of life. Thus, although further miniaturization and longer autonomy are expected in the forthcoming devices, our present experience shows that, with careful patient instruction and follow up, insulin pumps could represent in the next years an alternative to conventional insulin therapy for poorly controlled diabetics.
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