Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial

Objective: For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS^®, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. Research Design and Methods: This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose ≤100 mg/dl (≤5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A_1c (HbA_1c). Results: Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA_1c decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (−1.4%, p < 0.001; algorithm 1 −1.3% vs. algorithm 2 −1.5%; p = 0.03) and glargine plus >1 OAD (−1.7%, p < 0.001; algorithm 1 −1.5% vs. algorithm 2 −1.8%; p = 0.001). Conclusions: This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA_1c with a low risk of hypoglycaemia. The greater reduction in HbA_1c was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD.     

Deprivation of dietary nucleotides decreases protein synthesis in the liver and small intestine in rats

BACKGROUND & AIMS: Dietary nucleotides are reported to influence the growth and functioning of the liver and small intestine. The aim of this study was to examine the mechanism by which nucleotides exert their effects in these tissues by assessing protein synthesis activity and related parameters in the presence or absence of dietary nucleotides. METHODS: Rats were fed a purified diet with or without nucleotides for 10 days. Fractional protein synthesis rate, RNA and DNA concentrations, polysome size distribution, and number of ribosomes were assessed. RESULTS: Fractional protein synthesis rates of the liver and small intestine were lower in the nucleotide-deprived group than in the control group. In the liver, RNA concentration was also lower in the nucleotide-deprived group, but values in the small intestine were similar in the two groups. In the liver, deprivation of nucleotides resulted in a reduction in the number of ribosomes and in polysome breakdown. Protein and DNA concentrations did not vary in the liver; however, the concentration of DNA was lower in the small intestine of the nucleotide-deprived group than in the control group. CONCLUSIONS: Dietary nucleotides can modulate protein synthesis in the liver and small intestine as a result of tissue-specific nucleic acid changes. (Gastroenterology 1996 Jun;110(6):1760-9)     

Paraoxonase1 55 and 192 gene polymorphisms in an Egyptian population with diabetic complications

Type 2 diabetes is a polygenic disease characterized by interaction of environmental and genetic factors. The paraoxonase 1 gene (PON1) 55 and 192 polymorphisms have been reported to be associated with type 2 diabetes and its complications. Our aim is to study the PON1 55, 192 gene polymorphisms and enzyme activity in type 2 diabetic Egyptian population with complications. 100 type 2 diabetic patients with complications (34 with cardiac and 66 with microvascular complications (neuropathy, retinopathy and/or nephropathy)). This was in addition to 100 healthy control subjects of matched age and sex were taken. PON1 55 L?M and 192 Q?R gene polymorphisms and PON1 enzyme activity serum levels were detected. The LL genotype of PON1 55 polymorphism and QR and QQ genotypes of PON1 192 polymorphism were more frequent among the patients with diabetic complications. The PON1 enzyme activity levels were lower among the diabetic patients than in control subjects. PON1 55 and 192 polymorphisms and enzyme activity seems to be related to diabetic complications in this population.     

Adaptation of adult bone marrow transplant recipient long-term survivors

Although there is a small literature on psychosocial and psychiatric aspects of bone marrow transplants (BMT) in adult recipients during the BMT hospitalization phase, adaptation of long-term adult BMT recipient survivors has received little study. This study surveyed the adaptation of BMT recipient survivors over age 17 who were an average of 42 months posttransplant. Study variables included the recipients' current self-reported health status, mood state, social role function, self esteem, life satisfaction, and relationships with their BMT donors and other family members. A companion study of those who donated BMT to the recipients eligible for this study was also performed. The study participants were preponderantly young adults who currently were in an intimate relationship and vocationally active. About 1/4 of the subjects reported ongoing medical problems. Also, 15-25% reported significant emotional distress, low self-esteem, and less-than-optimal life satisfaction. The subjects' current quality of relationship with their donors was highly correlated with many measures of their psychosocial status. The findings indicate that about 75% of BMT recipient long-term survivors are doing well from a psychosocial as well as a medical standpoint, that the recipient-donor relationship may be sensitive to any changes in the recipient's status, and that 15-20% of BMT recipient survivors report a degree of psychological distress that might benefit from specific psychological/psychiatric intervention.     

Comparison of weekly and daily incremental protocols of narrowband ultraviolet B phototherapy for psoriasis

BACKGROUND: Different protocols have been used for narrowband ultraviolet B (UVB) therapy, commonly used in the treatment of psoriasis; however, more effective and reliable protocols are still required. OBJECTIVE: The aim of this study was to compare the weekly and daily dose increment protocols of narrowband UVB phototherapy in psoriasis patients. METHODS: Thirty patients with plaque psoriasis underwent narrowband UVB treatment three times a week and 15 patients selected consecutively among these patients underwent a weekly (once in three treatments) dose increment whereas the remaining 15 patients underwent a daily dose increment. Patients were monitored for 10 weeks and evaluated by the Psoriasis Area Severity Index (PASI). RESULTS: When the two groups were evaluated according to median PASI scores prior to the treatment and during 10 weeks of treatment, there was no statistically significant difference between the groups (P > 0.05). During the treatment lasting for 10 weeks, four patients in the group with a weekly dose increment and three patients in the group with a daily dose increment recovered and no statistically significant difference was detected between the groups (P > 0.05). The groups were also evaluated according to the median cumulative dose. The median cumulative dose was higher in the group with a daily dose increment and the difference between the groups was statistically significant (P = 0.002). CONCLUSION: The application of daily dose increments was no better than that of weekly dose increments in narrowband UVB treatment for psoriasis. Therefore, although our results may need to be supported by large-series studies, we conclude that application of weekly dose increments with a lower cumulative dose having the same efficacy is preferred in narrowband UVB treatment of psoriasis.