Safety and efficacy of an oral insulin (Capsulin) in patients with early-stage type 2 diabetes: A dose-ranging phase 2b study

Aim

To compare the pharmacodynamic properties of different doses of regular human insulin administered in capsule form twice daily in a randomised twelve-week open-label study.

Methods

A total of 100 individuals (48 males, 52 females) with type 2 diabetes on metformin completed the study according to the protocol. The mean (SD) age was 48.5 (6.7) years, body mass index 25.7 (2.8) kg/m² and HbA1c 8.10% (0.65%). Subjects randomized upon admission were assigned to one of three groups receiving formulated regular insulin at dose levels of 75 iu BD, 150 iu insulin BD, or 300 iu BD, all in enteric-coated capsules. The primary and secondary endpoints were change from baseline in HbA1c and fasting plasma glucose (FPG), respectively.

Results

The study met its primary clinical endpoint of a decrease in HbA1c of 0.5% or higher (least square mean decrease 0.52%; P = .004, median decrease 0.6%) in the dose group receiving 150 iu BD. In a subset of this population, with starting HbA1c values of 9% to 9.5%, an average decrease of 1.575% was observed. In the total population, least square mean decreases in HbA1c for the 75 and 300 iu BD groups were −0.11% and −0.42%, respectively. Mean change in FPG in the 150 iu BD dose group was −18.8 mg/dl (P = .017) and −14.8 and −2.7 mg/dl for the 75 and 300 iu BD groups, respectively. A decrease of 20% for triglycerides (−40 mg/dl) was observed in the 150 iu BD dose group. No significant increases in body weight were observed, and significant decreases in systolic blood pressure were seen in all groups. No serious treatment-related adverse events were recorded, and no incidence of hypoglycaemia was reported throughout the entire 12-week study period.

Conclusions

Capsulin oral insulin administered twice per day at a dose of 150 iu per capsule is safe, with no confirmed treatment-linked hypoglycaemic events, and results in significant decreases from baseline in HbA1c, FPG and triglycerides.     

Polymorphisms in PDCD1 gene are not associated with Wegener’s granulomatosis

Genetic association of programmed cell death-1 (PDCD1) has been implicated in several autoimmune inflammatory disorders. Hence, in this study, our main objective is to evaluate the association of PDCD1 gene to Wegener’s granulomatosis (WG). We, thus, analyzed three single nucleotide polymorphisms (SNPs) in PDCD1 gene among WG patients and controls. Further, we quantified circulating serum levels of soluble (s) PD-1 in patients and controls. The methodologies used were ABI Taqman allelic discrimination and restriction fragment length polymorphism for genotyping and in-house ELISA for quantifying sPD-1. Statistical relevance was analyzed by Fischer’s exact test. As a result, reduced AA homozygote for SNP in intron-1 was observed, among the patients. However, no association was demonstrated after Bonferroni correction. Also, no differences in genotype and allele frequency were elucidated for SNPs in intron-4 and exon-5. Moreover, we could not demonstrate circulating sPD-1. In conclusion, we show no association of selected SNPs in PDCD1 gene with WG.     

Zinc, iron and phytic acid levels of some popular foods consumed by rural children in Sri Lanka

Zinc (Zn) and iron (Fe) deficiencies may prevail in populations dependent on cereal-based diets containing few animal products. The contribution of Zn and Fe from foods of preschool children of a hill country village in Sri Lanka, is discussed as it is known that the presence of phytic acid (PA) in the diet limits bioavailability of micronutrients. The Zn, Fe and PA contents of cereal-based (rice or wheat flour) composite meals (n=12), wheat flour-based products (n=5), pulses used as staples, snacks or accompaniments (n=6) and other miscellaneous accompaniments (n=4) were determined. Additionally, 20 rice and 3 paddy varieties consumed were also analysed. Although the Zn and Fe levels were reasonable in the composite meals, the PA to Zn molar ratios (5–43) were relatively high, in a majority of meals. Composite meals containing wheat flour (refined) had lower PA levels (<6 mg/100 g) in the absence of pulses and scraped coconut, than rice meals. All rice varieties were partially polished but the PA to Zn molar ratios varied. The major contributors of PA appeared to be soy-textured vegetable protein, all types of jak fruit and scraped coconut kernel. Potable water was a poor source of Zn and Fe. These diets could potentially lead to marginal Zn and Fe deficiencies, and dietary diversification and counselling would be beneficial.     

Outcome of biliary atresia in Malaysia: A single-centre study

Aim:   This study aimed to determine the outcome of the operation of children with biliary atresia (BA) at a tertiary paediatric referral centre in Malaysia.
Methods:   A prospective study on all patients with BA referred to the University of Malaya Medical Centre (UMMC), Kuala Lumpur, from 1996 to 2005 was conducted. Survival with native liver, liver transplantation (LT) or death at 2 years of age was determined.
Results:   The median age at referral of the 57 patients with BA seen at University of Malaya Medical Centre was 62 days. Kasai procedure was not performed in nine patients who were all referred late (median age of referral 180 days). The median age at hepatoportoenterostomy (HPE) of the remaining 48 patients was 70 days. A total of 53 (93%) patients had type 3 BA, while only 1 (2%) patient had BA splenic malformation. At 2 years, the survival rate with native liver for the 48 patients who had HPE was 37%, while the overall survival (native liver and LT) rate was 40%. Two of the four patients who had LT survived with a liver graft at 2 years.
Conclusions:   The 2-year survival with native liver following corrective surgery for BA in UMMC, Malaysia, compares favourably with other international figures, but the overall survival rate was adversely affected by a lack of timely LT. The outcome of BA in Malaysia may be further improved by increasing the awareness among child-health professionals on the importance early referral for appropriate surgery in infants suspected of having BA.     

Management of Hirschsprung's disease with reference to one-stage pull-through without colostomy

BACKGROUND/PURPOSE: The authors evaluated the safety and benefits of 1-stage pull-through in comparison with staged repair of Hirschsprung's disease under circumstances prevailing in a developing country. METHODS: Forty-nine patients were treated for Hirschsprung's disease during a 7-year period between January 1991 and March 1998 at our institution, which is a tertiary referral center. Nine patients were excluded from the study, and the medical records of the remaining 40 patients were reviewed. RESULTS: Eighteen patients including 7 neonates underwent 1-stage pull-through, and 22 patients underwent staged correction. There was no mortality for patients undergoing one-stage treatment, but there was 1 death caused by anastamotic leak after a 2-stage repair. There was no substantial difference in the incidence of complications (38.8% v 45.45%) and the need for additional surgical procedures (33.5% v 45.45%) between the 2 groups. Seventy-one percent after 1-stage treatment and 80% after staged treatment had a satisfactory functional result, and the incidence of incontinence was 14% and 10%, respectively. Overall, the incidence of postoperative enterocolitis was low (7.5%). CONCLUSIONS: One-stage correction of Hirschsprung's disease is a safe procedure in all age groups. It offers economical and social advantages to families in developing countries. Benefits of 1-stage treatment include avoidance of multiple operations, elimination of complications associated with a colostomy, shorter duration of hospital stay, and completion of treatment at an earlier age. It is advisable to continue postoperative anal dilatation for a minimum period of 6 months to 1 year to reduce the incidence of enterocolitis.     

Twisted fate of bladder catheters

Catheter knotting is a rare complication of bladder catheterisation. Retention of catheter parts resulting in calculus formation is even rarer. We report a case of a vesical calculus formed over a broken and retained supra-pubic catheter which to the best of our knowledge has yet to be reported, along with three other cases of bladder catheter knotting.