Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of these studies was to compare the pharmacokinetics, pharmacodynamics, counterregulatory hormone and symptom responses, as well as cognitive function during hypoglycaemia induced by s.c. injection of 0.15 IU/kg of regular human insulin (HI) and the monomeric insulin analogue [Lys(B28),Pro (B29)] (MI) in insulin-dependent-diabetic (IDDM) subjects. In these studies glucose was infused whenever needed to prevent decreases in plasma glucose below 3 mmol/l. After MI, plasma insulin increased earlier to a peak (60 vs 90 min) which was greater than after HI (294 +/- 24 vs 255 +/- 24 pmol/l), and plasma glucose decreased earlier to a 3 mmol/l plateau (60 vs 120 min) (p < 0.05). The amount of glucose infused to prevent plasma glucose falling below 3 mmol/l was approximately three times greater after MI than HI (293 +/- 26 vs 90 +/- 25 mumol.kg-1 x 60-375 min-1, p < 0.05). After MI, hepatic glucose production was more suppressed (0.7 +/- 1 vs 5.9 +/- 0.54 mumol.kg-1.min-1) and glucose utilization was less suppressed than after HI (11.6 +/- 0.65 vs 9.1 +/- 0.11 mumol.kg-1.min-1) (p < 0.05). Similarly, plasma NEFA, glycerol, and beta-OH-butyrate were more suppressed after MI than HI (p < 0.05), whereas plasma lactate increased only after MI, but not after HI. Responses of counterregulatory hormones, symptoms and deterioration in cognitive function during plasma glucose plateau of 3 mmol/l were superimposable after MI and HI (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM. 795 44

Insulin lispro [Lys (B28), Pro (B29) human insulin] is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0-4%) and approximately 10% had ISA, whereas 41-45% of patients with IDDM and 23-27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.
 ...
PMID:Immunologic effects of insulin lispro [Lys (B28), Pro (B29) human insulin] in IDDM and NIDDM patients previously treated with insulin. 892 61

[Nepsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i.v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed following subcutaneous (s.c.) doses of (A) 6 nmol/kg and (B) 1.2 nmol/kg (equivalent to 0.2 U/kg) in 9 subjects with IDDM. After overnight i.v. infusion of regular human insulin, morning glucose was (A) 6.9 +/- 0.1 and (B) 6.8 +/- 0.1 mmol/l. After the s.c. injection, i.v. human insulin or glucose was infused to maintain near-basal glycaemia and tracer glucose to assess hepatic glucose production (HGP). An activity profile was deduced for each study by expressing the glucose infusion rate at each time point, as a fraction (%) of the basal (measured) HGP, and the i.v. insulin infusion rate as a fraction (%) of the basal requirement. The two fractions are combined by adding the fractional glucose infusion rate and subtracting the fractional insulin infusion rate. Infusion rates of i.v. insulin in the morning were (A) 0.96 +/- 0.096 and (B) 1.22 +/- 0.09 pmol x kg(-1) x min(-1). After insulin injection, i.v. insulin requirements decreased and were below 10% of basal between 100 and 150 min. A constant activity profile of 0% represents a perfect substitution of the basal i.v. insulin infusion by the s.c. dose. The actual profile is defined by deviations from this (above) and was -17 +/- 11, 7 +/- 10, -9 +/- 6 and -18 +/- 18% for [Nepsilon-palmitoyl Lys (B29)] human insulin and 17 +/- 12, 5 +/- 6, -9 +/- 15, 22 +/- 18% for NPH insulin at 3, 6, 9 and 12 h after s.c. injection. HGP was similar for the two insulins, demonstrating similar metabolic actions and profiles both peripherally and at the liver.
 ...
PMID:Basal activity profiles of NPH and [Nepsilon-palmitoyl Lys (B29)] human insulins in subjects with IDDM. 949 40