Improvement of basal hepatic glucose production and fasting hyperglycemia of type I diabetic patients treated with human recombinant ultralente insulin.

OBJECTIVE: To test whether a suppertime injection of human ultralente insulin in patients with type I diabetes would result in a larger inhibition of basal hepatic glucose production (HGP) and improvement in fasting and mean daily plasma glucose levels. RESEARCH DESIGN AND METHODS: We studied 16 type I diabetic patients (41 +/- 4 years of age; body mass index [BMI] = 23.3 +/- 0.3 kg/m2; diabetes duration > 3 years) with a crossover protocol of therapy with an intermediate and ultralente insulin. All patients were already treated with three injections per day of regular insulin in addition to intermediate-acting (NPH) insulin at suppertime. After a 14-day run-in period, patients were randomly assigned to treatment with equivalent doses (10.8 +/- 0.8 U, at 1900) of intermediate (Humulin I) or ultralente (Humulin U) insulin. After 1 month of treatment, patients were crossed over. No change of the insulin dosage was performed during the study period. Basal HGP was measured by D-(6,6-2H2)-glucose infusion. Plasma glucose concentration was measured in the fasting state and monitored during the day. RESULTS: Before starting the study period, fasting plasma glucose was 13.4 +/- 1.1 mM and plasma free-insulin was 48.0 +/- 4.8 pM. Daily plasma glucose concentration averaged 10.3 +/- 0.3 mM and the area under the curve (AUC) was 1.41 +/- 0.05 mol/14 h. NPH insulin, given at suppertime for a month, did not induce significant changes in fasting plasma insulin (40.2 +/- 4.8 pM), glucose concentration (14.0 +/- 0.9 mM) or HGP (20.2 +/- 2.2 mumol.kg-1.min-1). Accordingly, no change occurred in the average daily plasma glucose (10.3 +/- 0.3 mM) or AUC (1.41 +/- 0.9 mol/14 h). Glycated hemoglobin also was not affected (8.2 +/- 0.4 vs. 8.2 +/- 0.3%). On the contrary, a 4-week treatment with ultralente insulin, also given at suppertime, was associated with a decline in the basal HGP (16.0 +/- 1.3 mumol.kg-1.min-1), fasting (11.3 +/- 0.9 mM) and average daily (9.4 +/- 0.3 mM) plasma glucose concentrations, and AUC (1.29 +/- 0.07 mol/14 h) of plasma glucose level (all P < 0.05). Glycated hemoglobin was reduced (7.9 +/- 0.4%). In each condition, fasting plasma glucose concentration was correlated with the average daily plasma glucose level (basal = 0.78; intermediate = 0.89; ultralente = 0.62; all P < 0.05), which suggests that ultralente insulin likely induces the improvements of metabolic control through reducing fasting plasma glucose. CONCLUSIONS: Our results suggest that treating type I diabetic patients with ultralente insulin at suppertime provides a better modulation of basal HGP so that lower fasting plasma glucose levels are ensured. The reduction of fasting hyperglycemia is likely to affect positively daily plasma glucose control.

Use of premixed insulin among the elderly. Reduction of errors in patient preparation of mixtures.

OBJECTIVE: To evaluate the accuracy of elderly patients in their mixing of regular and intermediate insulins, to assess the safety and efficacy of premixed insulins compared with extemporarily mixed insulins, and to determine patients' preferences. RESEARCH DESIGN AND METHODS: We conducted a crossover multicenter study of 5 mo duration. Premixed insulins and patient-mixed, human biosynthetic (rDNA) insulins were used among 64 insulin-treated patients with NIDDM. After a 4-wk run-in period, eligible patients were randomly assigned to treatment 1 (extemporarily mixed insulins) or treatment 2 (premixed insulins) for 8 wk. After that period, the two treatments were crossed for an additional 8-wk period. A blood glucose profile was recorded monthly and HbA1c was measured at the beginning and at the end of each treatment period. An in vitro skills test was performed to assess the accuracy and reproducibility of the patient preparation of insulin doses, and a questionnaire was used to determine their personal preferences for premixed versus extemporarily mixed insulin. RESULTS: In our study, the quality of the metabolic control was the same whether patients used self-mixed or premixed insulin. The differences in blood glucose profiles and HbA1c were negligible between type and periods of treatment. The overall number of hypoglycemic episodes increased during the trial in both groups, but the difference between treatments was not significant. The in vitro skills test, however, indicated that the accuracy in the preparation of insulin doses was significantly higher when patients aspirated from one vial compared with preparation from two vials (P < 0.001). The CVs were 3.7% when drawing up a single dose and 5.0% when preparing a mixture, but the ranges were rather elevated (0.1-20.7 and 0.6-35.8%, respectively). Forty-two patients described the preparation of their daily insulin dose as very easy and 21 described it as easy when using premixed insulins versus 11 and 43, respectively, when using extemporarily mixed insulins (P < 0.001). CONCLUSIONS: While the quality of the metabolic control was the same whether patients used self-mixed or premixed insulin, the in vitro skills test indicated that insulin preparation by elderly patients is highly inaccurate. In some patients, a modification of the contents of the insulin is likely to occur in a few days. The use of premixed insulins should lessen the errors that occur in mixing insulins and from the contamination of the second insulin vial. Draw-up errors could partially account for the lack of improvement of glucose control during the period when patients received premixed insulins. A longer observation period probably is needed to assess appreciable changes in the quality of diabetes control.

Plasma biguanide levels are correlated with metabolic effects in diabetic patients.

Metabolic abnormalities occur in biguanide-treated diabetic patients. We investigated the relationship between plasma metformin and phenformin concentrations and metabolic effects. Drug levels were measured in 37 type II diabetic patients by HPLC. The method was sensitive, specific, and linear over a wide range of drug concentrations. Metformin and phenformin values ranged from 236 to 718 ng/ml and from 28 to 114 ng/ml, respectively. The plasma metformin level was correlated with triglycerides (r = -0.55; P less than 0.05) but not with drug dosage, plasma glucose, HbA1, creatinine, creatinine clearance, lactate, pyruvate, lipid, and clinical parameters. Plasma phenformin concentrations correlated with lactate (r = 0.49; P less than 0.05) and HbA1 (r = 0.50; P less than 0.05) but not with drug dosage, parameters of diabetes control, creatinine, creatinine clearance, pyruvate, and clinical parameters. The clinical usefulness of this HPLC method, the evidence that the increase of lactate is related to the circulating phenformin levels, and the demonstration that the metformin effect on triglyceride metabolism is correlated to plasma drug levels are the positive findings of this work.

[A case of factitious hypoglycemia with unusual presentation]. / Su di un caso di ipoglicemia factitia dalla presentazione insolita.

In this paper the Authors describe a case of factitious hypoglycemia in a 30-year-old nurse who came to the practitioner saying she was drug-addict. A careful history and the clinical examinations showed that the symptoms were due to hypoglycemic episodes. The finding of high plasma insulin levels together with low plasma C-peptide concentrations enabled us to exclude organic causes of hypoglycemia, suggesting the diagnosis of factitious hypoglycemia. After the patient was told we suspected a case of factitious hypoglycemia, the symptoms disappeared.