The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetes (original) (raw)
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Official journal of the South African Academy of Family Practice/Primary Care
Background There is increasing evidence that postprandial hyperglycaemia is implicated in the development of macro-and microvascular diabetic complications. Thus, control of postprandial glucose levels (PPG), in addition to control of fasting blood glucose (FBG), will ensure overall glycaemic control in diabetic patients. This study evaluated the effectiveness of a current anti-diabetic regimen on PPG in patients with type 2 diabetes mellitus. Method A total of 31 type 2 diabetic subjects on combination treatment of either Humulin N ® (HN), Monotard HM (ge) ® (M) or Humulin L ® (HL) insulin, with metformin, participated in a controlled, prospective, one-day visit study at a tertiary referral state diabetes clinic. The objective was to evaluate the effectiveness of the combination treatment of either M (n = 11) versus HN (n = 10) or HL (n = 10) insulin, each in combination with metformin, on PPG in this study cohort. Each subject was given a standardised meal after completing baseline procedures. Prescribed insulin doses were taken the night prior to the study day and metformin doses were taken with the standardised meal on the following morning, the study day. After completion of the meal, blood glucose levels were determined every half an hour at 0, 30, 60, 90, 120 and 150 minutes, thus providing a postprandial glucose profile for each subject. The data was analysed using ANOVA. Results The study cohort was South African, predominantly of Indian origin (54.8%), with a mean age of 59.2 ± 8 years, and 71% of the cohort was female. The subjects had a mean duration of diabetes of 11.4 ± 6.6 years, with 71% (n = 22) having a positive family history. The study cohort was obese (BMI 32.3 ± 6.2kg/m2, WHR 0.9 ± 0.1). A total of 61.3% (n = 19) of the study cohort was hypertensive, while 29% (n = 9) presented with at least one cardiovascular event and 48.3% (n = 15) had high total cholesterol. On entry to the study, the mean (± SD) FBG (10.3 ± 3.7mmol/l), fructosamine (369.9 ± 78.8mol/l) and glycosylated haemoglobin (9 ± 2%) were elevated. Each insulin group, HN, M and HL, was statistically matched for the above-mentioned and was therefore compared.
Comparison of two twice-daily insulin regimens: Ultralente/soluble and soluble/isophane
Diabetologia, 1981
The relative efficacy of two twice-daily insulin regimens using highly purified insulins, once daily Ultratard with twice daily Actrapid (ultralente/ soluble) and twice daily Actrapid with twice daily Retard (soluble/isophane), has been studied in 12 diabetics in a cross-over study. Control was optimised as an outpatient , and assessed by in-patient 24 hour profiles. Similar daytime glucose control was achieved, but the mean overnight plasma glucose concentrations were more steady on ultralente/soluble (
Pharmacokinetics, pharmacodynamics, and safety of prandial oral insulin (N11005) in healthy subjects
Frontiers in Endocrinology
AimsTo verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference.MethodsThis was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022.ResultsAfter administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the ...
Clinical and Experimental Pharmacology and Physiology, 2012
1. Few studies have evaluated the pharmacokinetics of rapid-acting insulin analogues in patients with type 2 diabetes, especially under clinical conditions. The aim of this study was to assess both the pharmacokinetics and pharmacodynamics of insulin aspart in type 2 diabetic patients who were being treated with the analogue alone. 2. Meal tolerance tests with and without self-injection of a customary dose of insulin aspart (0.05-0.22 U/kg) were conducted in 20 patients in a randomised crossover study. 3. The dose (per body weight) of insulin aspart was significantly correlated with both the maximum concentration (r 2 = 0.59, P < 0.01) and area under the concentration-time curve for insulin aspart (r 2 = 0.53, P < 0.01). However, the time to maximum concentration (t max), which varied widely from < 60 min to ≥ 120 min, was not associated with either dosage (r 2 = 0.02, P = 0.51) or body mass index (r 2 = 0.02, P = 0.57). Injection of insulin aspart exacerbated delayed hyperinsulinaemia after meal loading, mainly in patients with t max values ≥ 120 min. With regard to pharmacodynamics, insulin aspart had favourable effects on postprandial hyperglycaemia, hyperglucagonaemia, and hyperlipidaemia. 4. The t max for this insulin analogue differed greatly between individuals, and delayed hyperinsulinaemia was particularly exacerbated in patients with higher t max values. Identification of the factors contributing to inter-individual variation in the absorption lag time is essential for improving its efficacy and safety.
Diabetes Care, 1984
Where adjustments of diet, physical activity, and dosage of insulin are well known to diabetologists and diabetic patients, present-day knowledge of factors of importance to the pharmacokinetics of insulin is frequently ignored. The pharmacokinetics of insulin comprise the absorption process, the distribution including binding to circulating insulin antibodies, if present, and to insulin receptors, and its ultimate degradation and excretion. The distribution and metabolism of absorbed insulin follow that of endog' enous insulin. The distribution and metabolism cannot be actively changed, except in the case of circulating insulin antibodies, which in rare cases also may cause insulin resistance. The use of insulin preparation of low immunogeneity will avoid or reduce this course of variation in action. The absorption process, the detailed mechanisms of which are still unknown, is influenced by many variables where some can be controlled, thereby reducing the intrapatient variability in insulin absorption, which may reach 35%, causing a corresponding metabolic lability. Besides the known differences in timing among different preparations, the size of dose, the injected volume, and the insulin concentration are determinants of absorption role. Fortuitous injection technique contributes to variance, as do changes in blood flow of the injected tissue. This may be induced by changes in ambient temperature, exercise of injected limb, or local massage. Regional differences are also due to differences in blood flow. Serum insulin peaks may peak up to 1 h after injection of soluble insulin into the thigh versus into the abdominal wall. Local degradation of insulin seems of less importance but may, in rare cases, be the cause of high insulin "requirements." Available evidence is reviewed and the importance of implementing the consequences in the daily care of the insulin-treated patient is emphasized, DIABETES CARE
Diabetes Care, 1993
OBJECTIVE-To determine whether tight glycemic control can be obtained using intensive conventional split-dose insulin therapy in the outpatient management of type II diabetes without development of unacceptable side effects. RESEARCH DESIGN AND METHODS-Fourteen type II diabetic subjects were treated with an intensive program of conventional insulin (subcutaneous NPH and regular insulin before breakfast and supper) for 6 mo. Insulin dose adjustments were based on an algorithm built on frequent CPG measurements (4-6 times/day). Patients were monitored biweekly as outpatients and admitted 1 day/mo for metabolic evaluation. RESULTS-Glycemic control was achieved by 1 mo (mean plasma glucose fell from 17.5 ± 0.9 to 7.7 ± 0.7 mM, P < 0.001) and remained in this range thereafter. Hypoglycemic events at 1 mo were infrequent (mean ± SE events per patient per month: 4.1 ± 0.3) and mild in nature, and progressively decreased to 1.3 ± 0.5 events/mo by 6 mo. After treatment, basal HGO fell 44% from 628 ± 44 to 350 ± 17 jimol • m~2 • min" 1 (P < 0.001), and maximal rates of glucose disposal measured by hyperinsulinemic euglycemic clamp (1800 pmol • m~2 • min" 1) improved from 1418 ± 156 to 1657 ± 128 |xmol • m~2 • min" 1 (P < 0.05). The total dose of exogenous insulin required was 86 ± 13 U at 1 mo and 100 ± 24 U at 6 mo. During treatment, mean serum insulin levels increased from 308 ± 80 to 510 ± 102 pM (P < 0.05), while body weight increased from 93.5 ± 5.8 to 102.2 ± 6.8 kg (P < 0.001). Both pre-and posttreatment glucose disposal rates correlated with the total exogenous insulin dose required to achieve glycemic control (r =-0.75 and-0.78, both P < 0.005). Weight gain was inversely related to the pretreatment glucose disposal rate (r =-0.53, P < 0.05) and directly correlated with both mean day-long serum insulin level (r = 0.67, P < 0.01) and total exogenous insulin dose (r = 0.62, P < 0.02). CONCLUSIONS-Intensive CIT, when combined with CBG measurements, can be used to rapidly improve glycemic control in type II diabetes without development of unacceptable hypoglycemia. This degree of metabolic improvement, however, requires large doses of exogenous insulin to overcome peripheral insulin resistance and results in greater hyperinsulinemia with progressive weight gain.