AIM: The aim of this study was to prepare insulin-loaded poly(lactic acid)-polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model.
METHODS: The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin 30/70 as a reference product in streptozotocin-induced diabetic rats.
RESULTS: The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 microm and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix.
CONCLUSIONS: The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.
Rosiglitazone is an oral hypoglycaemic agent of the thiazolidinedione group. This study aimed to assess changes in the diabetic prothrombotic state via plasminogen activity and changes in surrogate markers of atherosclerotic burden via ankle-brachial pressure index (ABPI) measurements after rosiglitazone was added to a pre-existing type 2 diabetes mellitus treatment regime. A nonblinded interventional study was designed. Fifty-nine patients were enrolled. Rosiglitazone-naïve patients were prescribed oral rosiglitazone 4 mg daily for 10 weeks. ABPI, plasminogen activity, glycosylated haemoglobin (HbA1c) and fasting lipid profile were measured pretreatment and post-treatment. Forty-eight patients completed the study. At the end of this study, mean plasminogen activity improvement was nearly 16% (P<0.05), mean ABPI improvement was 0.01 (P=0.439), mean HbA1c reduction was 0.51% (P<0.05), mean total cholesterol (TC) increase was 0.36 mmol/l (P<0.05), mean high-density lipoprotein cholesterol (HDL-C) increase was 0.15 mmol/l (P<0.05) and mean low-density lipoprotein cholesterol increased by 0.19 mmol/l (P=0.098). Rosiglitazone significantly improved plasminogen activity. There was also significant HbA1c reduction, and rise in both TC and HDL-C. Thus, rosiglitazone potentially improves the atherosclerotic burden and prothrombotic state. In future, more studies are needed to confirm the relationship between rosiglitazone, fibrinolytic system and atheromatous reduction in type 2 diabetes mellitus.
OBJECTIVE: To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).
METHODS: In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.
RESULTS: Rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.
CONCLUSIONS: Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.
AIM: To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia.
METHODS: Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore.
RESULTS: The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA.
CONCLUSION: Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.
Objective: Examine the formation of pectin-insulin nanoparticles and their blood glucose lowering properties.
Methods: The calcium pectinate nanoparticles were prepared by ionotropic gelation method, with alginate, sodium chloride or Tween 80 as additive. Their in vitro physicochemical, drug release and in vivo blood glucose lowering characteristics were evaluated.
Key findings: Spherical calcium pectinate-insulin nanoparticles were characterized by size, zeta potential, insulin content and insulin association efficiency of 348.4 ± 12.9 nm, -17.9 ± 0.8 mV, 8.4 ± 1.0% and 63.8 ± 7.4%, respectively. They released less than 25% insulin following 24 h in simulated intestinal medium and exhibited delayed blood glucose lowering effect in rats. Incorporation of solubilizer sodium chloride or Tween 80 into nanoparticles did not enhance blood glucose lowering capacity owing to sodium chloride reduced matrix insulin content and Tween 80 interacted with water and had its blood glucose dilution effect negated. Combination of nanoparticles with alginate gel to allow prolonged intestinal residence and more insulin release did not enhance their blood glucose lowering capacity because of calcium alginate-cross-linked gel formation that could retard insulin release and migration into systemic circulation.
Conclusion: Physicochemical responses of additives in vivo affected blood glucose regulation property of pectin-insulin nanoparticles.
Novel LNCs (lipid nanocrystals) were developed with an aim to improve the solubility, stability and targeting efficiency of the model drug glibenclamide (GLB). PEG 20000, Tween 80 and soybean lecithin were used as polymer, surfactant and complexing agent, respectively. GLB nanocrystals (NCs) were prepared by precipitation process and complexed using hot and cold melt technique. The LNCs were evaluated by drug loading, saturation solubility (SL), optical clarity, in vitro dissolution, solid state characterization, in vivo and stability analysis. LNCs exhibited a threefold increase in SL and a higher dissolution rate than GLB. The percentage dissolution efficiency was found to decrease with increase in PEG 20000. The average particle size was in the range of 155-842 nm and zeta potential values tend to increase after complexation. X-ray powder diffractometry and differential scanning calorimetry results proved the crystallinity prevailed in the samples. Spherical shaped particles (<1000 nm) with a lipid coat on the surface were observed in scanning electron microscopy analysis. Fourier transform infrared results proved the absence of interaction between drug and polymer and stability study findings proved that LNCs were stable. In vivo study findings showed a decrease in drug concentration to pancreas in male Wistar rats. It can be concluded that LNCs are could offer enhanced solubility, dissolution rate and stability for poorly water soluble drugs. The targeting efficiency of LNCs was decreased and further membrane permeability studies ought to be carried out.
The aim of the present study was to assess the hypoglycaemia risk and safety of dapagliflozin compared with sulphonylurea during the fasting month of Ramadan. In this 12-week, randomized, open-label, two-arm parallel group study, 110 patients with type 2 diabetes who were receiving sulphonylurea and metformin were randomized either to receive 10 mg (n = 58) of dapagliflozin daily or to continue receiving sulphonylurea (n = 52). The primary outcome was to compare the effects of dapagliflozin and sulphonylurea on the proportions of patients with at least one episode of hypoglycaemia during Ramadan, as well as to assess the safety of dapagliflozin when used to treat patients observing Ramadan. A lower proportion of patients had reported or documented hypoglycaemia in the dapagliflozin group than in the sulphonylurea group: 4 (6.9%) versus 15 (28.8%); p = 0.002. The relative risk of any reported or documented hypoglycaemia in the 4th week of Ramadan was significantly lower in the dapagliflozin group: RR=0.24, 95%CI: 0.09, 0.68; p=0.002. No significance differences were observed between the two groups regarding postural hypotension (13.8 vs 3.8%; p = 0.210) or urinary tract infections (10.3 vs 3.8%; p = 0.277). In conclusion, fewer patients exhibited hypoglycaemia in the dapagliflozin group than in the sulphonylurea group.
To evaluate the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin or metformin in combination with sulphonylurea.