A multicenter, epidemiological study of the treatment patterns, comorbidities and hypoglycemia events of patients with type 2 diabetes and moderate or severe chronic kidney disease - the 'LEARN' study.

Objective Management of patients with type 2 diabetes (T2DM) and stage 3 to 5 chronic kidney disease (CKD) is challenging. The aim of the 'LEARN' study was to describe treatment patterns employed in this population and to record comorbidities, glycemic control and hypoglycemia episodes in routine clinical practice in Greece. Research design and methods 'LEARN' was a non-interventional, multicenter, cross-sectional study conducted in Greece between 15 February 2013 and 4 July 2013. A total of 120 adult patients were enrolled from four hospital sites in different geographic regions of Greece. Results Participants had a mean age of 69.1 ± 10.3 years and a male:female ratio of 2:1. Nearly all patients (99.2%) suffered from at least one comorbidity, with hypertension (95.8%) and hyperlipidemia/dyslipidemia (78.3%) being the most prevalent. Of the overall study population, 57.5% was managed with insulin therapy only, 30.8% with oral antidiabetics only and 11.7% with a combination of insulin and oral antidiabetics. The overall rate of glycemic control, defined as glycated hemoglobin (HbA1c) ≤ 7.0% during the most recent assessment, was 55.0%. This rate was significantly higher among those receiving oral antidiabetics only (73.0%) compared to insulin only (47.8%) or a combination of both types of treatment (42.9%) (p = 0.03). Moreover, patients receiving oral antidiabetics only had experienced fewer hypoglycemia episodes over the last 7 days prior to the study visit (0.1 ± 0.4) compared to patients receiving insulin only (0.9 ± 1.7) (p = 0.03). Conclusions Although this is an observational study, it seems that oral antidiabetic therapy might be advantageous for heavily burdened T2DM patients with moderate or severe CKD in terms of glycemic control and hypoglycemia episodes. More data preferably from randomized trials is needed in order to validate this hypothesis.

Treatment Compliance with Fixed-Dose Combination of Vildagliptin/Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study.

Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM) in Greece. Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid), participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A) and vildagliptin metformin free-dose combination (group B). Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR) 18.9 (95% CI: 6.2, 57.7; P < 0.001). In group A mean HbA1c decreased from 8.1% at baseline to 6.9% (P < 0.001) at the study end and from 7.9% to 6.8% (P < 0.001) in group B. Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment.

The Cost of Managing Type 2 Diabetes Mellitus in Greece: A Retrospective Analysis of 10-Year Patient Level Data "The HERCULES Study".

Objective. This study aimed to estimate the mean annual cost of treating type 2 diabetes mellitus patients (T2DM) including complications and comorbidities in Greece. Design. A noninterventional retrospective study was based on patient level data analysis (bottom-up approach) from medical records, with at least 10-year-follow-up data. Results. The total annual cost per patient for managing diabetes in Greece was estimated at € 7,111 and was, statistically significantly, higher for patients with inadequate glycemic control (Hba1c > 7%) versus patients with adequate control (Hba1c = 7%) (€ 7,783 versus € 6,366, resp.; P = 0.017). This was mainly attributed to difference in CV hospitalizations between groups 14/111 versus 4/100, respectively, OR = 3.46 (95% CI: 1.10-10.9) for inadequately controlled patients. The largest component of cost was management of comorbidities, accounting for 48% of costs, and pharmaceutical treatment at 35.9% while only 14.9% was attributed to diabetes treatment per se. Obese men and patients with poor education are the groups with higher treatment costs. Conclusions. This is the first study to capture all cost components and the real burden of diabetes in Greece. Comorbidities were found to account for almost half of total cost, significantly higher in nonoptimally controlled diabetes patients.

The prevalence of hypoglycemia and its impact on the quality of life (QoL) of type 2 diabetes mellitus patients (The HYPO Study).

OBJECTIVE: To estimate the impact of hypoglycemia on the Quality of Life (QoL) and its prevalence in patients with type 2 diabetes mellitus (T2DM) in Greece. DESIGN: A cross-sectional epidemiological study was conducted in 6631 patients with T2DM. QoL was assessed with the patient self-administered ADDQoL-19. Reliability analysis of patients' outcomes was performed to assess internal consistency of the ADDQoL-19. Patients were categorized according to hypoglycemia experience and diabetes control. Controlled patients were considered as having Hb1Ac <7% (53 mmol/mol) and hypoglycemic episodes were defined as laboratory-confirmed clinical symptomatic events. RESULTS: In total, 59% of the sample had HbA1c >7% (53 mmol/mol) and 20.4% of patients had a history of laboratory-confirmed hypoglycemia. The mean age was 60 years and the mean T2DM duration was 10 years. The mean QoL score was -3.09±1.9 for the total sample and the mean score of non-hypoglycemic patients was -3.05±2, while the respective score of hypoglycemic patients was -3.26 ±1.8, (p≤0.001). Similar results were observed in the group of controlled and uncontrolled patients, who scored -2.73±1.7 and -3.33±1.9, respectively (p≤0.001). Comparable results were identified in the majority of the ADDQoL-19 instrument dimensions. CONCLUSIONS: The QoL of T2DM patients is affected significantly by hypoglycemia and the level of disease control. In diabetes treatment, the ultimate goal should be optimal glycemic control without debilitating hypoglycemic episodes which compromise patients' QoL.

Markers of bone metabolism in eugonadal female patients with beta-thalassemia major.

Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) have been recently implicated in the pathogenesis of various types of osteoporosis. The aim of this study was to investigate bone turnover in eugonadal female patients with this disease and characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. Markers of bone turnover and bone mineral density (BMD) were measured in 16 eugonadal young females with beta-thalassemia major and 18 age- and sex-matched healthy controls. Bone turnover was significantly increased in thalassemic patients compared to controls but OPG was significantly higher in healthy subjects. BMD values negatively correlated with urine markers of bone resorption but not with OPG/sRANKL system.

Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in patients with beta-thalassemia major.

Osteoporosis represents an important cause of morbidity in patients with beta-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-kappaB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age +/- SEM, 24.26 +/- 1.29 years; range, 13-41 years) and females (n = 31; age, 24.59 +/- 0.95 years; range, 12-34 years) with beta-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 +/- 0.12 vs. 3.25 +/- 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 +/- 0.03 vs. 0.295 +/- 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = -0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = -0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in beta-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.

Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs.

Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.

Effect of enhanced iron chelation therapy on glucose metabolism in patients with beta-thalassaemia major.

Recently introduced chelation regimens that combine deferoxamine (DFO) and deferiprone have been shown to have greater efficacy in promoting iron excretion than either chelator alone and have been associated with rapid reduction of the iron load in the heart and liver, and with reversal of cardiac dysfunction. It is unclear whether this combined therapy could be associated with a reduction in iron load or decline in the severity of iron-induced endocrinopathies. Starting in January 2001, 42 patients with beta-thalassaemia major, previously maintained on subcutaneous DFO only, were switched to combined treatment with DFO and deferiprone. The primary endpoint was to investigate the effects of this therapy on the glucose metabolism characteristics of this population. Combination therapy markedly decreased ferritin levels (638 +/- 1345 vs. 2991 +/- 2093 microg/l, P < 0.001). Glucose responses were improved at all times during an oral glucose tolerance test, particularly in patients in early stages of glucose intolerance. Glucose quantitative secretion also decreased significantly with combined therapy, while no significant change occurred in insulin levels in any group. Insulin secretion, according to the homeostasis assessment model, markedly increased in all groups, while overall reduction in insulin sensitivity did not reach statistical significance. This study showed that the combination of DFO and deferiprone was associated with an improvement in liver iron deposition and glucose intolerance.

Evaluation of bone mineral density of the lumbar spine in patients with beta-thalassemia major with dual-energy x-ray absorptiometry and quantitative computed tomography: a comparison study.

Osteoporosis is a common, multifactorial cause of morbidity in patients with beta-thalassemia. The present study was performed to compare bone mineral density (BMD) results in the lumbar spine of thalassemic patients measured by both dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT), and to determine their correlations with the markers of bone turnover. BMD was measured in the lumbar spine of 13 regularly transfused patients with beta-thalassemia major by both DEXA and QCT. Blood and urine samples were obtained for the determination of biochemical and hormonal profiles. Both T-scores and Z-scores were higher when measured by QCT (T-score = -0.41 +/- 1.31, Z-score = -0.56 +/- 1.08, mean +/- SD) compared with the values given by DEXA (T-score = -2.57 +/- 0.88, Z-score = -2.32 +/- 1.11, P = 0.0005). In comparison to DEXA, QCT T-scores were more closely correlated with age (r = -0.19 vs. r = -0.70, P = 0.0068). Strong negative correlation was found between QCT values and age (r = -0.67, P = 0.01). In comparison to DEXA T-scores, QCT T-scores were more closely correlated with osteocalcin, urine N-telopeptide cross-links of type I collagen, and deoxypyridinoline, but without statistical significance. DEXA T-scores were better correlated only with urine C-terminal telopeptides of type I collagen, but again without statistical significance. These results imply that the two methods cannot be used interchangeably in assessing BMD in thalassemic patients. However, which one of these two techniques more precisely determines the overall strength of vertebrae in patients with beta-thalassemia remains to be investigated.

Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia.

Hypoparathyroidism is thought to be a rare consequence of iron overload seen in beta-thalassemic transfused patients. This study was conducted to determine the prevalence of hypoparathyroidism in a large number of beta-thalassemic patients, and its potential correlation with the presence of other endocrinopathies caused by iron overload. Serum and urine biochemical parameters were measured in 243 thalassemic patients (136 females and 107 males) in order to determine the prevalence of hypoparathyroidism and evaluate bone turnover. The patients were divided into two groups according to the presence of hypoparathyroidism. We compared the prevalence of other endocrinopathies and disease complications in the two groups. Hypoparathyroidism was detected in 13.5% of the patients (33 subjects; 17 males and 16 females). Serum-intact parathyroid hormone, and total and ionized calcium were significantly lower, while phosphorus was significantly higher in thalassemic patients with hypoparathyroidism. The reduction in BMD was more prominent in normal thalassemic patients (Z score = -2.246 +/- 0.97) compared with those with hypoparathyroidism (Z score = -1.975 +/- 0.89), although the difference was not statistically significant. Disturbed glucose metabolism was more common in patients with hypoparathyroidism (P < 0.05). In addition, heart dysfunction was statistically more frequent in this group (odds ratio = 2.51, P < 0.05). Hypoparathyroidism is a not infrequently observed complication in thalassemic patients. Since the concentration of ferritin is not a valuable tool in the prediction of the development of hypoparathyroidism, parathyroid function should be tested periodically, particularly when other iron overload-associated complications occur.

Endocrine pancreatic insufficiency in chronic pancreatitis.

Chronic pancreatitis (CP) is considered to be a rare cause of diabetes mellitus. However, in both the developed and developing world, there is an increasing number of patients suffering from pancreatitis probably due to lifestyle changes, which is partially associated with both social factors and the poor health status of immigrants. Owing to these circumstances, CP has evolved with one of the possible causes of diabetes in a selected group of patients and should be included in the differential diagnosis of diabetes. Several studies have shown that the long-term rate of diabetic complications in patients with CP and insulin-dependent diabetes is similar to that in patients with type 1 diabetes of equal duration. The hypothesis that early diagnosis of CP should result in better prognosis is not validated and may complicate the issue, since the risk of diabetes has been shown to increase significantly only once pancreatic calcification has developed. Accumulative evidence suggests that the risk of diabetes is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy. The lack of contemporary data points to the urgent need for large prospective studies in order to accurately evaluate the special characteristics of disorders in glucose homeostasis in patients with CP.