Expert Opinion: A Call for Basal Insulin Titration in Patients with Type 2 Diabetes in Daily Practice: Southeast European Perspective.

Therapeutic inertia related to insulin treatment, i.e. delays in initiation, especially titration of basal insulin, is a significant problem in daily practice in Southeast European countries. This phenomenon can be traced back to several patient-, physician- and health system-related factors. In recognition of the issue of inadequate insulin titration, 11 leading experts from countries in this region held a consensus-seeking meeting to review the current status of insulin initiation after non-insulin treatment and the potential barriers to insulin titration to provide an algorithm and tools for outpatient physicians and for patients aimed at optimizing basal insulin titration. The experts reached a consensus on the majority of the topics and proposed recommendations on how clinical inertia can be overcome. The outcomes of the meeting have been summarized in this paper.

Fine-scale haplotype mapping of MUT, AACS, SLC6A15 and PRKCA genes indicates association with insulin resistance of metabolic syndrome and relationship with branched chain amino acid metabolism or regulation.

Branched chain amino acids (BCAA) are essential elements of the human diet, which display increased plasma levels in obesity and regained particular interest as potential biomarkers for development of diabetes. To define determinants of insulin resistance (IR) we investigated 73 genes involved in BCAA metabolism or regulation by fine-scale haplotype mapping in two European populations with metabolic syndrome. French and Romanians (n = 465) were genotyped for SNPs (Affymetrix) and enriched by imputation (BEAGLE 4.1) at 1000 genome project density. Initial association hits detected by sliding window were refined (HAPLOVIEW 3.1 and PHASE 2.1) and correlated to homeostasis model assessment (HOMAIR) index, in vivo insulin sensitivity (SI) and BCAA plasma levels (ANOVA). Four genomic regions were associated with IR located downstream of MUT, AACS, SLC6A15 and PRKCA genes (P between 9.3 and 3.7 x 10-5). Inferred haplotypes up to 13 SNPs length were associated with IR (e.g. MUT gene with P < 4.9 x 10-5; Bonferroni 1.3 x 10-3) and synergistic to HOMAIR. SNPs in the same regions were also associated with one order of magnitude lower P values (e.g. rs20167284 in the MUT gene with P < 1.27 x 10-4) and replicated in Mediterranean samples (n = 832). In French, influential haplotypes (OR > 2.0) were correlated with in vivo insulin sensitivity (1/SI) except for SLC6A15 gene. Association of these genes with BCAA levels was variable, but influential haplotypes confirmed implication of MUT from BCAA metabolism as well as a role of regulatory genes (AACS and PRKCA) and suggested potential changes in transcriptional activity. These data drive attention towards new regulatory regions involved in IR in relation with BCAA and show the ability of haplotypes in phased DNA to detect signals complimentary to SNPs, which may be useful in designing genetic markers for clinical applications in ethnic populations.

Branched-Chain Amino Acid Database Integrated in MEDIPAD Software as a Tool for Nutritional Investigation of Mediterranean Populations.

Branched-chained amino acids (BCAA) are essential dietary components for humans and can act as potential biomarkers for diabetes development. To efficiently estimate dietary intake, we developed a BCAA database for 1331 food items found in the French Centre d'Information sur la Qualité des Aliments (CIQUAL) food table by compiling BCAA content from international tables, published measurements, or by food similarity as well as by calculating 267 items from Greek, Turkish, Romanian, and Moroccan mixed dishes. The database embedded in MEDIPAD software capable of registering 24 h of dietary recalls (24HDR) with clinical and genetic data was evaluated based on archived 24HDR of the Saint Pierre Institute (France) from 2957 subjects, which indicated a BCAA content up to 4.2 g/100 g of food and differences among normal weight and obese subjects across BCAA quartiles. We also evaluated the database of 119 interviews of Romanians, Turkish and Albanians in Greece (27⁻65 years) during the MEDIGENE program, which indicated mean BCAA intake of 13.84 and 12.91 g/day in males and females, respectively, comparable to other studies. The MEDIPAD is user-friendly, multilingual, and secure software and with the BCAA database is suitable for conducting nutritional assessment in the Mediterranean area with particular facilities for food administration.

The effect of physical activity in glycemia in patients with diabetes mellitus.

INTRODUCTION: Diabetes mellitus (DM) is the most common endocrine disease and it is a major problem in medicine, not only for diabetic patients, but also as a general health problem. Physical activity was accepted as a therapeutic approach in diabetic patients. AIM OF THE STUDY: The objective of this study was to assess the role of physical activity in DM patients and in their values of glycaemia. The other objective of our study was to see the reduction of medicament's therapy in these patients by physical activity. METHODS: The study was done in Service of Endocrinology, Internal Medicine Clinic and in Clinic of Physiatry and Orthopedy, University Clinic Center in Prishtina, from January 2003 till March 2004. In our study were included 96 (58 female and 38 male) consecutive patients diagnosed with diabetes mellitus, according to the diagnostic criteria by new definition from of World Health Organization and American Society of Diabetes, (fast glycaemia > or = 7 mmol/L, founded two times consequently). According to these criteria, 46 patients were with type 1 diabetes mellitus, whereas 50 patients were with type 2 diabetes mellitus. Physical activity is applied 10 days consequently, after a psychological preparation and treatment of the patient according the standard protocol to physic activity for diseased with diabetes mellitus. The assessment of glycaemia was done before and after physic acctivity. RESULTS: The glycaemia level was decreased by physical activity in DM type 1 patients for 25.0 mg/dl in male and for 30.4 mg/dl in female, respectively. Also in DM type 2 patients, the glycaemia was decreased by physical activity 25.4 mg/dl in male and for 18.0 mg/dl in female, respectively. At female patients with diabetes mellitus-type 1 after physical activity there was a decrease in glycaemia levels compared to patients with diabetes mellitus-type 2. There was not significant difference between male and female in the decrease f the glycaemia by physical activity. CONCLUSION: in diabetes mellitus patients, physical activity decreases the level of glycaemia. There is no important difference between gender and type in the effect of physical activity on glycaemia, in these patients. Physical activity in these patients does not need the important circumstances and has a low cost effectiveness. We recommend that physical activity should be a part of the treatment of diabetes mellitus patients.

HLA alleles and type 1 diabetes mellitus in low disease incidence populations of Southern Europe: a comparison of Greeks and Albanians.

Type 1 diabetes mellitus (DM1) is caused by environmental factors acting on genetically susceptible individuals. HLA-DQA1 and -DQB1 are major genetic determinants of the disease. Greece and Albania represent the low DM1 incidence countries of South-Eastern Europe. The HLA-DQA1 and -DQB1 associations with DM1 were investigated in these two groups, as reference for comparisons to the high-risk populations of Northern Europe. One hundred and thirty Greeks and 64 Albanians with DM1 were studied; 1,842 Greeks and 186 Albanians were analysed as controls. The samples were typed for six HLA-DQB1 alleles, using time-resolved fluorometry to detect the hybridisation of lanthanide labelled oligonucleotides with PCR products. Individuals positive for DQB1*0201 were selectively typed for three DQA1 alleles. In both populations DQB1*0201 increased the risk for DM1 while DQB1*0301 was protective. DQB1*0302 was associated with lower risk than *0201, while *0602 and *0603 were protective in Greeks but not in Albanians. It was also shown that DQA1 has a modifying effect, altering the risk conferred by the susceptible DQB1*0201. The low incidence of DM1 in these two countries correlates with the high frequency of the protective allele DQB1*0301 and the low impact of the susceptible DQB1*0302.

Body weight patterns in a country in transition: a population-based survey in Tirana City, Albania.

OBJECTIVE: This paper reports the distribution and determinants of body mass index (BMI) and obesity in Tirana City (Albania). DESIGN: Cross-sectional survey conducted in mid-2001. SETTING: Tirana City. SUBJECTS: One thousand one hundred and twenty adults aged 25 years and over (response rate 72.7%), selected using multi-stage cluster sampling. RESULTS: Over three-quarters of male and female respondents had an excess body weight. The overall population prevalence of obesity in Tirana was estimated to be 22.0% in men and 30.9% in women. Obesity affected both genders (age-standardised prevalence in males 22.0%, females 30.9%; age-adjusted odds ratio (OR) 1.89; 99% confidence interval (CI) 1.33-2.67) and all age groups, but most particularly middle-aged women. The age-standardised overall prevalence of central obesity was 21.6% in men and 29.4% in women (age-adjusted OR 1.58; 99% CI 1.11-2.25), increasing with age (P<0.01). In women, the likelihood of being obese was inversely related to educational achievement (trend P=0.001) and alcohol consumption (trend P=0.009). Income, smoking and leisure-time physical activity were not associated with obesity. CONCLUSIONS: Excess weight and obesity are major public health problems in the adult population of Tirana, but most particularly in middle-aged women. The high obesity prevalence observed along with the recent decrease in physical activity, dietary changes and increase in smoking prevalence make it probable that there will be substantial increases in many non-communicable diseases in Albania in the coming decades. Health promotion strategies are needed that prevent excess weight gain in the Albanian population.