Marijana Vučić Lovrenčić

Does treatment of subsyndromal depression improve depression-related and diabetes-related outcomes? A randomised controlled comparison of psychoeducation, physical exercise and enhanced treatment as usual

BackgroundElevated depressive symptoms that do not reach criteria for a clinical diagnosis of depression are highly prevalent in persons with diabetes. This study was aimed at determining the efficacy of psychoeducation and physical exercise compared with enhanced treatment as usual on 1-year changes in depressive symptoms, diabetes distress and self-management, and quality of life and metabolic control in type 2 diabetes patients with subsyndromal depression.MethodsAdult type 2 diabetes patients who screened positively for depression and expressed a need for professional help with mood-related issues were eligible. Exclusion criteria were clinical depression, current psychiatric treatment and advanced diabetes complications. Out of 365 eligible patients 209 consented to either 6 weekly sessions of psychoeducation (A) and physical exercise (B), or to enhanced treatment as usual (C). Computer-generated sequences for block randomisation stratified by gender were used. Depressive symptoms (primary outcome) and diabetes distress, diabetes self-care, metabolic control and health-related quality of life (secondary outcomes) were analysed at 6-month and 12-month follow-up using repeated-measures ANOVAs.ResultsOut of the 74 patients randomised into group A, 66 into B and 69 into group C, 203 completed the interventions, and 179 patients with all 3 assessments were analysed. Depressive symptoms in participants from the psychoeducational, physical exercise and the enhanced treatment as usual groups improved equally from baseline to 12-month follow-up (time versus time x group effect; F = 12.51, p < 0.001, η2 = 0.07 and F = 0.609, p = 0.656, η2 = 0.007 respectively), as did diabetes distress and quality of life (all p < 0.001), diabetes self-care (p < 0.001 to < 0.05), triglycerides, and total cholesterol and LDL-cholesterol (p < 0.001).ConclusionsThe employed interventions had comparable positive effects on 12-month psychological and diabetes-related outcomes suggesting that even minimal intervention addressing patients’ diabetes-related problems and concerns had favourable clinical implications and might be sufficient to treat subsyndromal depression. Further investigation is warranted to clarify possible mechanisms of improvement.Trial registrationCurrent Controlled Trials ISRCTN05673017The message on assigning the above mentioned ISRCTN was received on 11 August 2010

Validation of Point-of-Care Glucose Testing for Diagnosis of Type 2 Diabetes

Point-of-care (POC) glucose technology is currently considered to be insufficiently accurate for the diagnosis of diabetes. The objective of this study was to investigate the diagnostic accuracy of an innovative, interference-resistant POC glucose meter (StatStrip glucose hospital meter, Nova Biomedical, USA) in subjects with a previous history of dysglycaemia, undergoing a 75 g diagnostic oral glucose tolerance test (oGTT). Venous and capillary blood sampling for the reference laboratory procedure (RLP) and POC-glucose measurement was carried out at fasting and 2 h oGTT, and categories of glucose tolerance were classified according to 2006 WHO diagnostic criteria for the respective sample type. We found an excellent between-method correlation at fasting (r = 0.9681, P < 0.0001) and 2 h oGTT (r = 0.9768, P < 0.0001) and an almost perfect diagnostic agreement (weighted Kappa = 0.858). Within a total of 237 study subjects, 137 were diagnosed with diabetes with RLP, and only 6 of them were reclassified as having glucose intolerance with POC. The diagnostic performance of POC-fasting glucose in discriminating between the normal and any category of disturbed glucose tolerance did not differ from the RLP (P = 0.081). Results of this study indicate that StatStrip POC glucose meter could serve as a reliable tool for the diabetes diagnosis, particularly in primary healthcare facilities with dispersed blood sampling services.

Redefinition of gestational diabetes mellitus: implications for laboratory practice in Croatia

An increasing prevalence of gestational diabetes has become a very challenging task in prenatal care worldwide. International Association of Diabetes and Pregnancy Study Groups (IADPSG) has recently issued recommendations on the diagnosis and classification of hyperglycaemia in pregnancy. These recommendations, the first to provide harmonised, evidence-based criteria for the diagnosis and classification of diabetes in pregnancy, are currently being discussed and accepted worldwide by the relevant authorities. As the acceptance of the proposed criteria has major implications for both clinical and laboratory settings, a concerted action towards necessary changes in practice has to be carefully planned and adjusted to national health-care specificities. IADPSG criteria have been strongly advocated by the Croatian Perinatology Society, resulting in a new strategy for the detection and diagnosis of hyperglycaemic disorders in pregnancy. To address the respective laboratory requirements, in April 2012, the Croatian Chamber of Medical Biochemists appointed a Working Group to provide a standardised procedure for the diagnosis of gestational diabetes, applicable to all laboratories involved in prenatal care, in both primary and specialised health-care facilities. In this paper we discuss key laboratory-related issues regarding succesful implementation of the IADPSG criteria in Croatia.

Lipoprotein(a) predicts progression of carotid artery intima-media thickening in patients with type 2 diabetes: A four-year follow-up

ZusammenfassungHINTERGRUND: Ziel dieser Studie war es, herauszufinden ob erhöhtes Serum Lipoprotein(a) (Lpa) bei Patienten mit Diabetes mellitus Typ 2 signifikant zu einem Anstieg der Intima-Media-Dicke und der Zahl der Plaques der Carotiden beiträgt und so das kardiovaskuläre Risiko dieser Patienten erhöht. METHODEN: Bei 146 Patienten mit Diabetes mellitus Typ 2 wurden die Lipoprotein(a)-Spiegel, die Intima-Media-Dicke und die Zahl der Plaques in den Carotiden erhoben. Die Intima-Media-Dicke und die Anzahl der Plaques wurde nach 4 Jahren Follow-up kontrolliert. Die Patienten wurden entsprechend ihrem Serum-Lipoprotein(a)-Spiegel in 2 Gruppen (> oder ≤30 mg/dl) eingeteilt. Die Intima-Media-Dicke wurde mit hochauflösendem B-Mode Ultraschall erhoben. ERGEBNISSE: Anfangs bestand kein signifikanter Unterschied in der Intima-Media Dicke der Carotiden der beiden Gruppen. Bei der Kontrolle waren die Intima-Media-Dicken der Gruppe mit höherem Lipoprotein(a)-Spiegel signifkant höher als jene der Gruppe mit niedrigem Lipoprotein(a) Spiegel (1,24 + 0,22 vs. 1,15 + 0,17 mm; p = 0.005), Die mittlere Zunahme der Intima-Media Dicke betrug in der Gruppe mit niedrigem Lipoprotein(a) Spiegel nach 4 Jahren 0,12 mm (0,030 mm/Jahr) und in der Gruppe mit höherem Lipoprotein(a) Spiegel 0,17 mm (0,043 mm/Jahr). Die Multivarianzanalyse ergab, dass die Intima-Media Dicke nur vom Lipoprotein(a)- und nicht vom Triglyzerid- beziehungsweise vom HDL-Cholesterin-Spiegel oder dem Taille-Hüfte Quotienten abhing. Die Anzahl der Plaques unterschied sich weder bei der Erstuntersuchung noch bei der Kontrolle zwischen den beiden Gruppen signifikant (p = 0,276 respektive p = 0,355). In der Gruppe mit höherem Lipoprotein(a)-Spiegel traten mehr kardiovaskuläre Ereignisse ein als in der anderen Gruppe – der Unterschied war allerdings statistisch nicht signifikant. SCHLUSSFOLGERUNGEN: Unsere Ergebnisse weisen daraufhin, dass Lipoprotein(a) ein unabhängiger, genetisch determinierter Risikofaktor ist, der eng mit der Zunahme der Intima-Media-Dicke bei Diabetes mellitus Typ 2 assoziiert ist.SummaryBACKGROUND: The aim of the study was to establish whether increased levels of serum lipoprotein(a) significantly contribute to an increase in intima-media thickness and the number of carotid artery plaques, and consequently to cardiovascular risk in patients with type 2 diabetes mellitus. METHODS: Lipoprotein(a) levels, intima-media thickness and the number of carotid artery plaques were determined at the beginning of the study in 146 patients with type 2 diabetes. Patients were divided into two groups according to serum lipoprotein(a) levels (> or ≤30 mg/dl). Intima-media thickness and the number of plaques were again determined after four years of follow-up. Intima-media thickness was assessed using high-resolution B-mode ultrasound. RESULTS: The two groups of patients revealed no significant differences in baseline intima-media thickness (P = 0.112) in relation to lipoprotein(a) level. After follow-up, intima-media thickness was significantly greater in patients with higher lipoprotein(a) levels (1.24 + 0.22 vs. 1.15 + 0.17 mm, respectively; P = 0.005). The mean increase in thickness over four years was 0.12 mm (0.030 mm/year) in the group with low lipoprotein(a) levels and 0.17 mm (0.043 mm/year) in the group with high lipoprotein(a). Multivariate analysis indicated that intima-media thickness depended on lipoprotein(a), and not on triglyceride, HDL-cholesterol levels or waist-to-hip ratio. No significant difference in baseline and follow-up number of plaques was observed between the study groups (P = 0.276 vs. P = 0.355, respectively). Although the group with lipoprotein(a) >30 mg/dl had more cardiovascular events, the difference was not statistically significant. CONCLUSIONS: These results indicate that lipoprotein(a) is an independent, genetically determined risk factor closely associated with progression of intima-media thickness in type 2 diabetes.

Inverse Levels of Adiponectin in Type 1 and Type 2 Diabetes Are in Accordance with the State of Albuminuria

Aims. To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabetic nephropathy. Methods. ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER), and creatinine clearance (CrCl) categories in 219 type 1 and type 2 diabetic patients. Results. Significant differences among ApN levels according to AER were found in both types of diabetes (F = 8.45, df = 2, P < 0.001). With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (F = 12.7, df = 1, P < 0.001). The best model for ApN (R 2 = 0.9002) obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes (R 2 = 0.2882) it included ppPG, LDL, and UA. Conclusion. ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabetes and decreasing in type 2 diabetes. It was however increased in the subgroups with decreased CrCl in both types of diabetes. Albuminuria seems to be more important than renal insufficiency in the definition of ApN levels in type 1 and type 2 diabetes.

Improvement in Depressive Symptoms Is Associated with Reduced Oxidative Damage and Inflammatory Response in Type 2 Diabetic Patients with Subsyndromal Depression: The Results of a Randomized Controlled Trial Comparing Psychoeducation, Physical Exercise, and Enhanced Treatment as Usual.

Aims. To examine one-year changes in oxidative damage and inflammation level in type 2 diabetic patients undergoing behavioral treatment for subsyndromal depression. Materials and Methods. A randomized controlled comparison of psychoeducation (A), physical exercise (B), and enhanced treatment as usual (C) was performed in 209 eligible subjects in a tertiary diabetes care setting. Depressive symptoms (primary outcome) and selected biomarkers of oxidative damage and inflammation (secondary outcomes) were assessed at baseline and six- and twelve-month follow-up. Results. Out of the 74, 67, and 68 patients randomised into groups A, B, and C, respectively, 201 completed the interventions, and 179 were analysed. Participants in all three groups equally improved in depressive symptoms from baseline to one-year follow-up (repeated measures ANOVA; F = 12.51, p < 0.0001, η 2 = 0.07). Urinary 8-oxo-deoxyguanosine (u-8-oxodG) decreased (F = 10.66, p < 0.0001, η 2 = 0.06), as did sialic acid and leukocytes (F = 84.57, η 2 = 0.32 and F = 12.61, η 2 = 0.07, resp.; p < 0.0001), while uric acid increased (F = 12.53, p < 0.0001, η 2 = 0.07) in all subjects during one year. Improvement of depressive symptoms at 6 months significantly predicted one-year reduction in u-8-oxodG (β = 0.15, p = 0.044). Conclusion. Simple behavioral interventions are capable not only of alleviating depressive symptoms, but also of reducing the intensity of damaging oxidative/inflammatory processes in type 2 diabetic patients with subsyndromal depression. This trial is registered with ISRCTN05673017.

Validation of a laboratory and hospital information system in a medical laboratory accredited according to ISO 15189

Introduction The aim of the study was to present a protocol for laboratory information system (LIS) and hospital information system (HIS) validation at the Institute of Clinical Chemistry and Laboratory Medicine of the Merkur University Hospital, Zagreb, Croatia. Materials and methods: Validity of data traceability was checked by entering all test requests for virtual patient into HIS/LIS and printing corresponding barcoded labels that provided laboratory analyzers with the information on requested tests. The original printouts of the test results from laboratory analyzer(s) were compared with the data obtained from LIS and entered into the provided template. Transfer of data from LIS to HIS was examined by requesting all tests in HIS and creating real data in a finding generated in LIS. Data obtained from LIS and HIS were entered into a corresponding template. The main outcome measure was the accuracy of transfer obtained from laboratory analyzers and results transferred from LIS and HIS expressed as percentage (%). Results: The accuracy of data transfer from laboratory analyzers to LIS was 99.5% and of that from LIS to HIS 100%. Conclusion: We presented our established validation protocol for laboratory information system and demonstrated that a system meets its intended purpose.

Impact of creatinine methodology on glomerular filtration rate estimation in diabetes

AIM To evaluate the influence of creatinine methodology on the performance of chronic kidney disease (CKD)-Epidemiology Collaboration Group-calculated estimated glomerular filtration rate (CKD-EPI-eGFR) for CKD diagnosis/staging in a large cohort of diabetic patients. METHODS Fasting blood samples were taken from diabetic patients attending our clinic for their regular annual examination, including laboratory measurement of serum creatinine and eGFR. RESULTS Our results indicated an overall excellent agreement in CKD staging (kappa = 0.918) between the Jaffé serum creatinine- and enzymatic serum creatinine-based CKD-EPI-eGFR, with 9% of discordant cases. As compared to the enzymatic creatinine, the majority of discordances (8%) were positive, i.e., associated with the more advanced CKD stage re-classification, whereas only 1% of cases were negatively discordant if Jaffé creatinine was used for eGFR calculation. A minor proportion of the discordant cases (3.5%) were re-classified into clinically relevant CKD stage indicating mildly to moderately decreased kidney function (< 60 mL/min per 1.73 m2). Significant acute and chronic hyperglycaemia, assessed as plasma glucose and HbA1c levels far above the recommended glycaemic goals, was associated with positively discordant cases. Due to a very low frequency, positive discordance is not likely to present a great burden for the health-care providers, while intensified medical care may actually be beneficial for the small number of discordant patients. On the other hand, a very low proportion of negatively discordant cases (1%) at the 60 mL/min per 1.73 m2 eGFR level indicate a negligible possibility to miss the CKD diagnosis, which could be the most prominent clinical problem affecting patient care, considering high risk of CKD for adverse patient outcomes. CONCLUSION This study indicate that compensated Jaffé creatinine procedure, in spite of the glucose-dependent bias, is not inferior to enzymatic creatinine in CKD diagnosis/staging and therefore may provide a reliable and cost-effective tool for the renal function assessment in diabetic patients.

Analytical verification and quality assessment of the Tosoh HLC-723GX HbA1c analyzer

Objectives Ion-exchange high-performance liquid chromatography (IE-HPLC) has long been used as a reproducible and versatile analytical tool for HbA1c measurement. In this study, we performed analytical verification and quality assessment of the recently introduced small IE-HPLC Tosoh HLC-723GX HbA1c analyzer, and a comparison of results to immunoassay (IA) and capillary electrophoresis (CE). Design and methods The total imprecision of Tosoh HLC-723GX was verified according to CLSI EP15-A2 protocol using commercial control materials (C-QC) and pooled human whole blood samples (HWB). The Sigma metric was used for the evaluation of quality targets. HbA1c results were compared to automated CE (MiniCap Flex Piercing, Sebia, France) and IA (Tina-quant HbA1c Gen 2, Cobas Integra 400+, Roche Diagnostics, USA) procedures. Results The total imprecision of Tosoh HLC-723GX-HbA1c for IFCC(mmol/mol) and NGSP(%) units was: 1.91/1.25% (HbA1c=31 mmol/mol/5.0%) and 0.51/0.63% (HbA1c=84 mmol/mol/9.8%) for C-QC, and 0.39/0.2% (HbA1c=47 mmol/mol/6.5%) and 0.77/0.46% (HbA1c=94 mmol/mol/10.8%) in HWB samples, respectively. Bland-Altman analysis did not reveal any deviation of the results between Tosoh HLC-723GX and CE: mean difference 0.0% (95%CI: −0.02927 to 0.02653%), while the mean HbA1c difference against IA was −0.07% (95%CI: −0.1039 to −0.02765). At the selected HbA1c clinical decision level (48 mmol/mol/6,5%), six sigma analysis gave σ value of 3.91, within a desirable classification of performance. Conclusion The analytical performance of the Tosoh HLC-723GX complies with the rigorous quality criteria for clinical use of HbA1c, with the results comparable to the CE procedure. Tosoh HLC-723GX provides a plausible analytical choice for reliable HbA1c measurement in low-volume laboratories.

Age-dependent systemic DNA damage in early Type 2 Diabetes mellitus

Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM. Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, gamma-glutamyl transpeptidase (GGT), uric acid, C-reactive protein (CRP), total leukocyte/neutrophil count, and urinary 8-hidroxy-deoxyguanosine (u-8-OHdG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications. BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-OHdG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Higher 8-OHdG in older subjects with T2DM suggests that both aging process and diabetes could contribute to the development of DNA damage. Oxidative DNA damage cannot serve as an universal early marker of T2DM.