SPONTANEOUS RESOLUTION OF A NONFUNCTIONING PITUITARY ADENOMA OVER ONE-MONTH PERIOD: A CASE REPORT.

Spontaneous resolution of nonfunctioning pituitary adenoma after hemorrhagic apoplexy is a rare clinical entity of unknown etiology and is defined as disappearance of a tumor without any specific treatment. Here we present a 54-year-old male patient who presented with acute onset of severe headache, vomiting, photophobia, and sonophobia. He was referred to brain computed tomography, which showed a 16x12x16 mm tumor mass located in the sellar region with signs of hemorrhage. Endocrinologic evaluation was consistent with under-function of pituitary gonadotropic cells. Magnetic resonance imaging (MRI) performed ten days later was consistent with hemorrhagic apoplexy of the pituitary adenoma. The patient's symptoms resolved after conservative treatment with dexamethasone, but he was scheduled for elective pituitary surgery. Preoperative MRI was performed one month after the first one and disclosed normal pituitary gland without any signs of adenoma. Our case is remarkable due to the fact that spontaneous remission of pituitary adenoma occurred within the first month, which is the shortest interval reported to date. Our case highlights the importance of conservative therapy as the first-line treatment for pituitary apoplexy in the absence of neurological impairment, since spontaneous remission may occur in a short time interval.

THE ASSOCIATION OF SUBCLINICAL INSULIN RESISTANCE WITH THYROID AUTOIMMUNITY IN EUTHYROID INDIVIDUALS.

Hashimoto thyroiditis is characterized by anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies that gradually lead to thyroid cell destruction. As hypothyroidism has been associated with insulin resistance (IR), we aimed to investigate whether IR is associated with thyroid antibody presence and whether the degree of IR correlates with their concentration in euthyroid individuals. A total of 164 non-diabetic, euthyroid individuals, average age 34 years, were included in the study, divided into two groups according to Hashimoto thyroiditis and underwent 5-hour oral glucose tolerance test. The degree of IR was evaluated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The Hashimoto thyroiditis group had higher HOMA-IR (p=0.003) and lower glucose levels (p=0.04). HOMA-IR correlated positively with anti-TPO (p<0.001). Linear logistic regression revealed that anti-TPO concentration increased by 18.13 (p=0.001) with each HOMA-IR unit. IR might trigger thyroid antibody production and Hashimoto thyroiditis development, which needs to be evaluated in further larger scale follow up studies.

The differential influence of glimepiride and glibenclamide on insulin resistance and adiponectin levels in patients with type 2 diabetes.

Several studies have demonstrated the decreased insulin resistance (IR) in persons with type 2 diabetes mellitus (T2DM) treated with glimepiride. Those suggest this might be associated with observed higher concentrations of adiponectin. We assessed if there is a difference in IR and metabolic syndrome components between glimepiride and glibenclamide treatment as well as adiponectin concentration in T2DM. Our research observed 20 T2DM patients treated with glibenclamid and 20 switched to glimepiride (n = 20) treatment for 24 weeks. Anthropometric measurements and laboratory analysis were performed at the beginning and at the end of treatment while IR was accessed by homeostasis model assessment of insulin resistance (HOMA-IR). The glimepiride group revealed better glycaemic control compared to glibenclamide group. Moreover, the adiponectin concentration increased (23.9 ± 17.3 to 29.1 ± 12.2 ng/mL, p = 0.087) whereas it decreased in the glibenclamide group (34.3 ± 22.6 to 20.3 ± 11.3 ng/mL, p = 0.011) following 24 weeks of treatment. The serum adiponectin and HOMA-IR were inversely correlated within the group of glibenclamide (r = -0.667, p = 0.009). The present study demonstrates that glimepiride might have beneficial effect on IR compared to glibenclamide, as suggested. However, this observation needs further study investigation among other formulations of SU.

The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms.

BACKGROUND: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. METHODS: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. RESULTS: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. CONCLUSIONS: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

The Use of Anthropometric Measurements of Obesity in Prediction of Microvascular Complications in Obese Type 2 Diabetic Patients.

Waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) are superior to body mass index (BMI) in predicting type 2 diabetes mellitus (T2DM) development. The aim of this study was to investigate the predictive power of BMI, WC, WHR and WHtR for microvascular (chronic kidney disease (CKD), retinopathy and peripheral neuropathy) prevalence in obese (BMI ≥35 kg/m2) T2DM patients. This cross-sectional study included 125 T2DM patients of both genders. The validity of each test was assessed by Receiver Operating Characteristic (ROC) curves; the area under the curve (AUC) was calculated for each anthropometric parameter and microvascular complication. AUCs for WHtR were significantly higher than AUCs for WC with respect to CKD. Optimal cut-off for WHtR was >0.593 and WC >112 cm regarding CKD. The AUC for peripheral neuropathy was significant only for WHR and optimal cut-off for WHR was >1.409 with low sensitivity and high specificity. Our study demonstrated that WHtR, WC and WHR might be used as simple and noninvasive methods for detection of CKD and peripheral neuropathy in obese T2DM population.

Waist-to-height ratio is independently associated with chronic kidney disease in overweight type 2 diabetic patients.

OBJECTIVE: Chronic kidney disease (CKD) is one of the most serious complications in obesity-induced type 2 diabetes mellitus (T2DM). Body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC) and waist-to-height ratio (WHtR) are recognised as sensitive obesity measures. We aimed to investigate the association of BMI, WC, WHR and WHtR with CKD prevalence in overweight T2DM patients. DESIGN, SUBJECTS AND METHODS: We obtained 125 overweight T2DM patients coming for their in-patient annual visit. Metabolic profiles and anthropometric indices were measured and calculated. Urine albumin excretion (UAE) was determined as the mean of 24-h urine from two consecutive days. Serum creatinine was measured from fasting blood sample in order to calculate the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration formula. Patients were divided into two groups according to CKD prevalence. RESULTS: Thirty-six (28.8%) patients met diagnostic criteria for CKD. The WHtR and WC were higher in the group with CKD. WHtR correlated positively with UAE (r = 0.828, p < 0.001) and negatively with eGFR (r = -0.262, p = 0.015). No significant correlation was observed with WC in relation to UAE (p = 0.335) nor eGFR (p = 0.121). WHtR yielded the significant and great OR in association with nephropathy after adjustment for all confounding risk factors. CONCLUSION: WHtR might be of a greater importance in association to CKD compared to other anthropometric parameters that indicate central obesity. Whether it is a best measure of central obesity and its exact role in CKD pathology is yet to be investigated.

[Pathophysiological factors in the development of diabetic nephropathy--new insights]. / Patofizioloski cimbenici razvoja dijabeticke nefropatije--nove spoznaje.

Diabetic nephropathy (DN), also known as Kimmelstiel-Wilson syndrome, is a progressive kidney disease characterized by nephrotic syndrome and diffuse glomerulosclerosis. It affects about 30% of patients with diabetes mellitus and is a prime indication for dialysis in many Western countries as well as in Croatia. Moreover, it takes a high fourth place in total disease cost, thus it is a very important public health problem. Hyperglycemia, dyslipidemia and hypertension are well established risk factors for the disease development and progression. However, nowadays, the knowledge about the pathophysiology of the disease is expanded and recently focused on the role of growth factors. Well balanced local and plasma concentration of growth factors is important for achievement and maintenance of glomerular integrity and function, so any disturbances could be a contributing factor to the development of DN. There is a growing body of literature suggesting that bone morphogenic protein 7 (BMP7), fibroblast growth factor 23 (FGF23) and fibroblast growth factor 21(FGF21) may play an important role in the DN development and progression. BMP7 possesses antifibrotic and proteolytic activity, so it could diminish the action of profibrotic factors and play an inhibitory role in the disease pathogenesis. It has been demonstrated that plasma concentration of BMP7 is decreasing in parallel to the drop in glomerular filtration rate (GFR) and albumin excretion increase. The plasma concentration of FGF21 and FGF23 has been shown to increase in parallel to DN progression. Moreover, they are linked with hyperinsulinemia and insulin resistance as well as with other diabetic complications such as cardiovascular events and endothelial dysfunction and retinopathy conditions closely related to DN. However, the background of the disturbances is not well established; it is not clarified whether GFR lowering causes increase of FGF21 and FGF23 or the increase in FGF21 and FGF23 concentration causes GFR lowering. The loop is yet to be clarified in order to develop a possible novel therapeutic approach in the treatment of this disease with serious consequences for the individual as well as for the entire population.

[Acid-base status in patients treated with peritoneal dialysis]. / Acidobazni status u bolesnika lijecenih metodom peritonejske dijalize.

When compared to hemodialysis, peritoneal dialysis is very simple yet low cost method of renal replacement therapy. Series of studies have shown its superiority in preserving residual renal function, postponing uremic complications, maintaining the acid-base balance and achieving better post-transplant outcome in patients treated with this method. Despite obvious advantages, its role in the treatment of chronic kidney disease is still not as important as it should be. Metabolic acidosis is an inevitable complication associated with progressive loss of kidney function. Its impact on mineral and muscle metabolism, residual renal function, allograft function and anemia is very complex but can be successfully managed. The aim of our study was to evaluate the efficiency in preserving the acid-base balance in patients undergoing peritoneal dialysis at Zagreb University Hospital Center. Twenty-eight patients were enrolled in the study. The mean time spent on the treatment was 32.39 ± 43.43 months. Only lactate-buffered peritoneal dialysis fluids were used in the treatment. Acid-base balance was completely maintained in 73.07% of patients; 11.54% of patients were found in the state of mild metabolic acidosis, and the same percentage of patients were in the state of mild metabolic alkalosis. In one patient, mixed alkalosis with respiratory and metabolic component was present. The results of this study showed that acid-base balance could be maintained successfully in patients undergoing peritoneal dialysis, even only with lactate-buffered solutions included in the treatment, although they were continuously proclaimed as inferior in comparison with bicarbonate-buffered ones. In well educated and informed patients who carefully use this method, accompanied by the attentive and thorough care of their physicians, this method can provide quality continuous replacement of lost renal function as well as better quality of life.

Association between red blood cell count and renal function exist in type 1 diabetic patients in the absence of nephropathy.

Anemia is a prevalent finding in patients with type 1 diabetes, particularly in those with albuminuria or reduced renal function. We investigated the relationship between red blood cell count (RBC) and renal function in type 1 diabetic patients with normal or mildly impaired renal function and urinary albumin excretion rate (UAE) < 30 mg/24 h. Study included 313 type 1 diabetic patients with estimated glomerular filtration rate (eGFR) > 60 mL min(-1) 1.73 m(-2), and before any interventions with statins, ACE inhibitors or angiotensin II receptor blockers. UAE was measured from at least two 24-h urine samples. Hemoglobin (Hb), hematocrit (Hct), erythrocytes (E), serum iron and ferritin levels were significantly lower in subjects in the highest quartile of serum creatinine compared to those in lowest quartile (132 vs 148 g/L, 0.39 vs 0.42 L/L, 4.5 vs 4.8 x 10(12)/L, 13 vs 18 micromol/L, and 25 vs 103 microg/L, respectively, for all p < 0.001). Hb and Hct levels were significantly lower in subjects in the highest quartile of UAE compared to those in lowest quartile (135 vs 140 g/L, and 0.40 vs 0.41 L/L, respectively, for all p = 0.03). Finally, those with mildly impaired eGFR had significantly lower levels of Hb, Hct and E compared to those with normal eGFR or hyperfiltrating subjects (133 vs 140 g/L, 0.38 vs 0.41 L/L, and 4.4 vs 4.7 x 10(12)/L, respectively, for all p = 0.01). We have detected that interplay between RBC and renal function parameters occurs even in type 1 diabetic patients with normal or mildly impaired renal function.

Association between symptoms of depression, diabetes complications and vascular risk factors in four European cohorts of individuals with type 1 diabetes - InterDiane Consortium.

AIMS: To investigate the association between depressive symptomatology and health markers in type 1 diabetes. METHODS: Four countries from the InterDiane Consortium had adopted the Finnish Diabetic Nephropathy Study protocol, including the Beck Depression Inventory (BDI). Associations between depression symptomatology, diabetes complications (diabetic nephropathy, proliferative retinopathy, major adverse cardiovascular events [MACE]) and vascular risk factors (metabolic syndrome, body mass index, glycaemic control) were investigated. RESULTS: In a sample of 1046 participants (Croatia n = 99; Finland n = 314; Latvia n = 315; Lithuania n = 318), 13.4% displayed symptoms of depression (BDI score ≥ 16) with no statistically significant difference in the prevalence of depression among the cohorts. The highest rates of diabetic nephropathy (37.1%) and proliferative retinopathy (36.3%) were observed in Lithuania. The rates of MACE and metabolic syndrome were highest in Finland. In joint analyses, individuals exhibiting depression symptomatology had higher HbA1c (79 vs. 72 mmol/mol, p < 0.001) and higher triglyceride concentration (1.67 vs. 1.28 mmol/l, p < 0.001), than those without. In the multivariable model, BDI score was positively associated with the presence of diabetic nephropathy, proliferative retinopathy, MACE, and metabolic syndrome and its triglyceride component. Moreover, BDI score was positively associated with the number of metabolic syndrome components, triglyceride concentration, and HbA1c. CONCLUSIONS: Comorbid depression should be considered a relevant factor explaining metabolic problems and vascular outcomes. Causality cannot be inferred from this cross-sectional study.

The prognostic value of red blood cell characteristics on diabetic retinopathy development and progression in type 2 diabetes mellitus.

BACKGROUNDAlthough it is considered that the pathogenesis of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) is primarily due to chronic hyperglycemia resulting in vascular changes and retinal ischemia, the red blood cells (RBCs) disorders might also represent an important pathophysiological risk factor.OBJECTIVETo evaluate whether the RBC properties contribute to DR development and progression in T2DM.METHODSThis prospective observational study comprised 247 persons with T2DM free of DR or with non proliferative DR without any signs of anaemia. The patients were reacessed after 60-months.RESULTSThe mean age of our study population was 56 years, 54.9% males with diabetes duration of 11,18±1,28 years. During the follow up, 16 (5.84%) participants developed non proliferative DR and 9 (3.64%) progressed to PDR while the mean corpuscular volume (MCV) and red cell distribution width (RDW) MCV rose. Both MCV and RDW correlated positively with HbA1c (r = 0,468, p = 0.003 and r = 0.521, p < 0.001), while Cox regression analysis revealed that besides age, diabetes duration, HbA1c, hypertension and dyslipidemia presence, MCV and RDW are also associated with the risk of DR development and progression (HR 1.057 and 1.237, p < 0.001).CONCLUSIONSWe clearly demonstrated that RBC's characteristics might represent a risk factor for DR development and progression.

Treatment approach to type 2 diabetes: Past, present and future.

Type 2 diabetes mellitus (DM) is a lifelong metabolic disease, characterized by hyperglycaemia which gradually leads to the development and progression of vascular complications. It is recognized as a global burden disease, with substantial consequences on human health (fatality) as well as on health-care system costs. This review focuses on the topic of historical discovery and understanding the complexity of the disease in the field of pathophysiology, as well as development of the pharmacotherapy beyond insulin. The complex interplay of insulin secretion and insulin resistance developed from previously known "ominous triumvirate" to "ominous octet" indicate the implication of multiple organs in glucose metabolism. The pharmacological approach has progressed from biguanides to a wide spectrum of medications that seem to provide a beneficial effect on the cardiovascular system. Despite this, we are still not achieving the target treatment goals. Thus, the future should bring novel antidiabetic drug classes capable of acting on several levels simultaneously. In conclusion, given the raising burden of type 2 DM, the best present strategy that could contribute the most to the reduction of morbidity and mortality should be focused on primary prevention.

A score derived from routine biochemical parameters increases the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms.

BACKGROUND: Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs. METHODS: This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs. RESULTS: CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713-0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430). CONCLUSIONS: CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.

Dipeptidyl peptidase-4 activity is associated with urine albumin excretion in type 1 diabetes.

AIMS: The inability of kidneys to prevent urinary protein leakage represents the earliest sign of renal damage in diabetic kidney disease (DKD). Recent data suggest the possible nephroprotective role of the dipeptidyl peptidase-4 (DPP-4) inhibitors. We aimed to investigate whether serum DPP-4 activity is associated with urine albumin excretion (UAE) in patients with type 1 diabetes (type 1 DM). METHODS: DPP-4 activity and UAE measurement were performed in 113 patients with type 1 DM and glomerular filtration rate (GFR) within normal range. They were divided into three groups according to UAE tertiles. RESULTS: Worse lipid profile and higher waist circumference were observed in the group with highest DPP-4 activity. Patients within lowest UAE tertile group had lowest DPP-4 activity value (p<0.001) compared to group within second and third tertile of UAE. DPP-4 activity correlated with systolic blood pressure (ρ=0.142; p=0.001), HbA1c (ρ=0.133; p=0.013) and UAE (ρ=0.349; p<0.001). In the linear regression analysis when DPP-4 activity was adjusted for age, gender, disease duration, HbA1c, waist circumference, the use of ACEI and hypolipemic agents the association remained significant; UAE increased for 8.136mg/24h by each increase of DPP-4 activity of 1U/L (p<0.008). CONCLUSION: Our results indicate that serum DPP-4 activity is associated with albuminuria in type 1 diabetes. This arises the question whether the use of DPP-4 inhibitors might serve as an additional therapeutic strategy to prevent proteinuria in patients with DKD.

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.

Prediabetes awareness among Southeastern European physicians.

AIMS/INTRODUCTION: Prediabetes (PD) represents a transitional state where the glucose levels are higher than normal, but not enough for diabetes mellitus diagnosis. As there is a growing number of the population with PD, its early detection and treatment could prevent the development of diabetes mellitus and its complications. We aimed to assess the overall knowledge of PD among medical professionals of different varieties. MATERIALS AND METHODS: A questionnaire-based study addressing PD and type 2 diabetes mellitus knowledge among Southeastern European general practitioners, postgraduates, physicians and superior specialists was carried out. RESULTS: A total of 397 physicians completed the questionnaire. The total rate of correct answers from diabetologists, non-diabetologist internists, residents and general practitioners was 69, 56.1, 54 and 53%, respectively. Questions related to the PD definition achieved a total of 46.6% correct answers. Correct responses considering the numerical definition of impaired fasting glucose and impaired glucose tolerance were 46.3 and 46.8%, respectively. Younger physicians had better knowledge of numerical values regarding PD and type 2 diabetes mellitus criteria (P < 0.001). CONCLUSIONS: The present results show that overall knowledge of PD is poor among Southeastern European physicians, which necessitates adequate educational programs on PD in this region.

Dipeptidyl peptidase-4 inhibitors improve arterial stiffness, blood pressure, lipid profile and inflammation parameters in patients with type 2 diabetes mellitus.

BACKGROUND: This uncontrolled open label study evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i): sitagliptin and vildagliptin on augmentation index standardized for 75 beats per minute (cAiX@75), blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) in patients with type 2 diabetes mellitus (T2DM). METHODS: Fifty-one well-regulated T2DM patients were randomly assigned to either sitagliptin or vildagliptin (100 mg/day) for 3 months continuing their previous treatment. Lipid profile, cAiX@75, hsCRP, glycated hemoglobin (HbA1c) were measured at baseline at 4, 8 and 12th week were accessed. cAiX@75 and pulse wave velocity (PWV) were determined by SphygmoCor device. RESULTS: Following DPP-4 treatment there was a significant reduction in total serum cholesterol (5.18 vs 4.62 mmol/L), low-density lipoprotein (2.89 vs 2.54 mmol/L), hsCRP (3.21 vs 1.95 mg/L), cAiX@75 (24.5 vs 22.3) and central systolic BP (131.8 vs 119.5 mmHg). The sitagliptin treated group reached cAiX@75 reduction earlier in the study period while neither sitagliptin or vildagliptin use resulted in the significant HbA1c reduction. CONCLUSION: The treatment with DPP-4i: sitagliptin and vildagliptin provides favorable metabolic and vascular effects beyond glucose-control. Further studies are required to elucidate their implication in metabolic pathways.

Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study.

BACKGROUND: Statins are effective in the primary and secondary prevention of cardiovascular events in individuals with and without diabetes. Emerging evidence, however, suggests that statins might reduce insulin sensitivity and secretion in healthy population and in type 2 diabetes. OBJECTIVE: We aimed to investigate the effect of statin therapy introduction on insulin sensitivity in patients with type 1 diabetes mellitus (T1DM). METHODS: This prospective observational 56-month long study included 832 randomly selected T1DM patients aged 25 to 61 years. Uncontrolled dyslipidemia and clinician-perceived need for treatment, rather than randomization, were basis for individuals being started on either atorvastatin or simvastatin (10-40 mg); N = 345, 41.47%. Patients on statin treatment were compared with those unexposed to statin. Insulin sensitivity was assessed using equation derived from euglycemic-hyperinsulinemic clamp studies-estimated glucose disposal rate. RESULTS: Patients who started statin therapy (N = 345, 59.42% atorvastatin and 40.58% simvastatin) experienced a greater decrease in insulin sensitivity (19.27% vs 12.82% P < .001) and metabolic control deterioration compared with statin-free group. The risk of decrease in insulin sensitivity attributable to statin use was 36.7% (hazard ratio 1.36; 95% confidence interval 1.31-1.43) after adjustment for age, gender, disease duration, smoking status, and the concomitant antihypertensive therapy. CONCLUSION: Although there is still a lack of a clear molecular explanation on the adverse effects of statin therapy on insulin sensitivity, we showed that it deteriorates insulin sensitivity in T1DM. The cardiovascular benefits of statin treatment might outweigh the risk of developing insulin resistance, but, the possible metabolic control worsening merits to be considered.

Plasma Homocysteine is Associated with Retinopathy in Type 1 Diabetic Patients in the Absence of Nephropathy.

INTRODUCTION: Previous cross-sectional studies suggested that plasma total homocysteine (tHcy) is associated with retinopathy in patients with type 1 diabetes (T1DM) only in cases of impaired renal function. The objective of this study was to examine whether there is an independent relationship between tHcy and retinopathy in normoalbuminuric T1DM patients with normal estimated glomerular filtration rate (eGFR). METHODS: The study included 163 normoalbuminuric patients with T1DM and normal renal function (eGFR >60 ≤ 125 ml min(-1) 1.73 m(-2)). Urinary albumin excretion rate (UAE) was measured from at least two 24 h urine samples. Photodocumented retinopathy status was made according to the EURODIAB protocol. tHcy level was measured with the chemiluminescent immunoassay. RESULTS: Retinopathy was present in 48% of normoalbuminuric patients. Patients with retinopathy were older (49 vs 42 years, p = 0.001), had higher systolic blood pressure (130 vs 120 mmHg, p = 0.001), triglycerides (0.89 vs 0.77 mmol/L, p = 0.01), tHcy (9.8 vs 9.1 µmol/L, p = 0.04), and lower eGFR (100 vs 106 ml min(-1) 1.73 m(-2), p = 0.03). In multivariate logistic regression analysis, after adjustment for variables that reached statistical significance in the univariate analysis, only tHcy was significantly associated with a risk of retinopathy in our subjects (p = 0.02), with odds ratios of 1.02 to 1.43. CONCLUSION: These data suggest that tHcy is independently associated with retinopathy in normoalbuminuric T1DM with normal eGFR. The mechanisms relating tHcy and retinopathy in T1DM are not clear. Prospectives studies are needed to confirm whether higher tHcy in normoalbuminuric T1DM patients has predictive value for development of retinopathy.

Dipeptidyl peptidase-4 activity might be a link between tumour necrosis factor alpha and insulin resistance in type 1 diabetes.

Tumour necrosis factor alpha (TNF α) leads to ß cell damage in type 1 diabetes (T1DM) but also causes insulin resistance (IR). It modulates dipeptidyl peptidase-4 (DPP-4) activity, adipokine linked with both IR and T1DM. We were interested if there is an association of TNF α in conjunction with DPP-4 and IR in T1DM. DPP-4 activity, TNF α concentration measurements, and insulin sensitivity calculation using estimated glucose disposal rate (eGDR) equation were performed in 70 T1DM patients. They were divided into two groups according to eGDR median. The group with higher IR had higher value of DPP-4 activity (27.57 ± 1.77 vs. 18.33 ± 1.14, p < 0.001) and TNF α concentration (12.91 ± 0.83 vs. 6.72 ± 0.36, p < 0.001). TNF α concentration and DPP-4 activity negatively correlated with eGDR (r = -0.616, p < 0.001 and r = -0.643, p < 0.001) while correlating positively with each other (r = 0.422; p = 0.001). The linear regression showed that eGDR decreases for 0.166 mg kg(-1) min(-1) by TNF α concentration increase of 1 pg/mL (p < 0.001) and for 0.090 mg kg(-1) min(-1) by DPP-4 activity increase of 1 U/L (p = 0.001) when adjusted for age, gender disease duration, glycated haemoglobin, body mass index and waist-to-hip ratio. eGDR decreased by additional 0.60 mg kg(-1) min(-1) (B = -0.150, p < 0.001) when DPP-4 activity was additionally adjusted for TNF α. TNF α concentration is associated with IR, correlates with its severity and increases the drop in insulin sensitivity modulated by DPP-4 activity. Whether TNF α involvement in the insulin signalling pathway is mediated by DPP-4 activity needs to be further evaluated.