Reduction of severe hypoglycemic events in type I (insulin dependent) diabetic patients using continuous subcutaneous insulin infusion.

In order to evaluate the safety and effectiveness of insulin pump treatment and to establish criteria for its use, we retrospectively studied 45 patients from a referral university diabetes clinic who were treated with either intensive subcutaneous insulin injections or continuous subcutaneous insulin infusion. Hemoglobin A1C was 8.5 +/- 0.3% (SEM) before and 8.1 +/- 0.1% during continuous subcutaneous insulin infusion (p = NS), but rose to 10.0 +/- 0.2% at a 16-month post-study follow-up. The frequency of ketoacidosis was 0.17 events/year before and 0.20 during infusion pump use (p = NS) and declined to 0.10 at the follow-up (p = NS). Severe hypoglycemia was reduced from 2.73 events/year to 0.22 during continuous subcutaneous infusion treatment (p less than 0.001), and from 3.72-0.32 (p less than 0.001) in a subgroup of 23 patients who initiated insulin pump treatment because of frequent and severe hypoglycemic events during intensive insulin injection treatment. Insulin pump use, compared to intensive insulin injections in a non-research setting, (a) is equally effective for maintenance of near normal glycosylated hemoglobin levels, (b) need not result in increased ketoacidosis, and (c) is effective for reducing hypoglycemic events. Thus, insulin pump treatment can benefit larger and randomized studies are needed to confirm these results.

The interrelationships of radioimmunoassayable urinary albumin, renal function and diabetes.

Urinary albumin, measured by radioimmunoassay, was evaluated as a method to assess early renal impairment in 76 insulin (IDD) and 36 noninsulin (NIDD)-dependent diabetic patients. Mean albumin excretion in IDD and NIDD patients was significantly higher at 23 and 12 micrograms/100 ml glomerular filtrate (GF) respectively, compared to 4 micrograms/100 ml GF in normal subjects (P less than 0.001 and P less than 0.05). Abnormal albumin excretion from 20 to 200 micrograms/100 ml GF was observed in 30% of IDD patients (P less than 0.001) and 15% of NIDD patients (P less than 0.03). Albumin excretion was significantly increased in hypertensive IDD and NIDD patients. Significant correlations between albumin excretion and age, duration of diabetes and creatinine clearance were observed, but albumin excretion did not correlate with hemoglobin A1C. These data indicate that (1) 30% of IDD patients not clinically recognized as having renal impairment have abnormal albumin excretion, (2) albumin excretion may reflect renal impairment, since albumin excretion levels independently correlate with duration of diabetes and hypertension in both diabetic subgroups and to glomerular function in NIDD patients, and (3) measurement of urinary albumin by radioimmunoassay may be the most sensitive test to evaluate early renal disease in diabetes.

Comparison of porcine and semisynthetic human insulins using euglycemic clamp-derived glucose-insulin dose-response curves in insulin-dependent diabetes.

In order to compare the biologic effectiveness of porcine and semisynthetic human insulins, a euglycemic clamp method was used in eight insulin-dependent diabetic subjects. Each subject was tested for each insulin on separate days. In order to derive glucose-insulin dose-response curves for both insulins, sequential but constant infusion rates of 0.2, 0.5, 1.0, and 2.0 mU/kg/min were performed. Plasma glucose levels attained during the euglycemic clamp were 96 +/- 3 mg/dL. At each insulin infusion rate, the steady-state glucose infusion rate required to maintain euglycemia was measured. At each increment of insulin infused, steady-state glucose infusion rates for porcine insulin were 1.12 +/- 0.22, 1.90 +/- 0.59, 4.28 +/- 0.61, and 9.37 +/- 0.66 mg/kg/min compared with 1.27 +/- 0.42, 2.38 +/- 0.20, 4.25 +/- 0.43, and 8.87 +/- 0.67 mg/kg/min for semisynthetic human insulin. By ANOVA, no significant difference was noted between the two insulins. Because insulin infusion rates may not result in predictable circulating free insulin levels in subjects who have circulating insulin antibodies, free insulin levels were determined. When steady-state glucose infusion rates were compared with free insulin levels achieved at the four insulin infusion rates, dose-response curves for both porcine and semisynthetic human insulins were virtually identical. These data suggest that semisynthetic human insulin has equivalent biologic effects on overall glucose metabolism compared with porcine insulin in insulin-dependent diabetes.

Comparison of the biologic activity of porcine and semisynthetic human insulins using the glucose-controlled insulin infusion system in insulin-dependent diabetes.

Semisynthetic human insulin is prepared from porcine pancreas by chemical methods involving the substitution of porcine B-30 alanine with threonine. To compare the effectiveness of porcine and semisynthetic human insulins, eight insulin-dependent diabetic patients were evaluated during two separate periods using a glucose-controlled insulin infusion system. During each 36-h period, patients received either porcine or semisynthetic human insulin. Patients ingested mixed meals. The mean daily insulin requirements for porcine and semisynthetic human insulins were 84 +/- 9 U and 85 +/- 6 U (+/- SEM), respectively (P = NS). Mean blood glucose values were similar at 95 +/- 1 mg/dl for porcine and 101 +/- 3 mg/dl with semisynthetic human insulin (P = NS). Prior metabolic control or insulin antibody levels did not correlate with intravenous insulin requirements. These studies indicate that semisynthetic human insulin is as effective as porcine insulin in maintaining near-normal blood glucose control in short-term intravenous studies using artificial pancreas techniques in insulin-dependent diabetes.

Comparison of porcine insulin and human insulin (Novo) using the glucose-controlled insulin infusion system, glucose-insulin dose-response curves, and the outpatient effectiveness of human insulin (Novo) in insulin-dependent diabetes.

The usefulness of human insulin (Novo) in the treatment of diabetes was studied in eight insulin-dependent diabetic patients. Evaluation was carried out through three methods: (1) glucose-controlled insulin infusion system on two separate days during the patients' ingestion of mixed meals; (2) euglycemic clamp method; and (3) evaluation of patients for 3 mo using short- and intermediate-acting insulins. Employing the glucose-controlled insulin infusion system resulted in mean daily insulin requirements of 84 +/- 9 U and 85 +/- 6 U SEM for porcine and human insulin, respectively (P = NS). Plasma glucose levels attained during the euglycemic clamp were 96 +/- 3 mg/dl. At each insulin infusion rate, the steady-state glucose infusion rates for porcine insulin were 1.12 +/- 0.22, 1.90 +/- 0.58, 4.28 +/- 0.61, and 9.37 +/- 0.66 mg/kg/min compared with 1.27 +/- 0.42, 2.38 +/- 0.20, 4.25 +/- 0.43, and 8.87 +/- 0.67 mg/kg/min for human insulin. No complications of either insulin preparation were observed in the 3-mo patient evaluation. Human insulin was associated with lower levels of circulating insulin antibody (P less than 0.03). In addition, hemoglobin A1c levels decreased from 8.4 to 6.9% (P less than 0.035), and normal hemoglobin A1c levels were maintained in patients using portable insulin infusion pumps.

Outpatient use of intermediate- and short-acting semisynthetic human insulins.

To determine if semisynthetic human insulins are useful in the outpatient management of insulin-dependent diabetes, the conditions of eight patients were evaluated for three months using short- and intermediate-acting insulins. No complications of either insulin preparation were observed. Hemoglobin A1c levels were decreased from 8.4% to 6.9% during human insulin use, and, in addition, normal hemoglobin A1c levels were maintained in patients using portable insulin infusion pumps. These results were achieved because of the health care provision team and were not directly the result of human insulin. Semisynthetic human insulins were also associated with lower levels of circulating insulin antibody. These data indicate that both short- and intermediate-acting semisynthetic human insulins are effective in stringent diabetes metabolic control, provided adequate health care provision is available.