Serum adipokine levels in patients with type 1 diabetes are associated with degree of obesity but only resistin is independently associated with atherosclerosis markers.

PURPOSE: The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM. METHODS: A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed. RESULTS: Leptin and resistin levels were significantly higher in overweight and obese patients (p = 0.002 and p = 0.039, respectively). Adiponectin was the only adipokine negatively correlated with BMI (rs = - 0.41, p = 0.001). We report a bivariate association between serum adiponectin levels and retinopathy (p = 0.007). Resistin was the only adipokine that showed significant correlation with systolic (rs = 0.42, p = 0.001) and diastolic (rs = 0.29, p = 0.024) hypertension and PWV (p = 0.035). CONCLUSIONS: Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.

A Greek registry of current type 2 diabetes management, aiming to determine core clinical approaches, patterns and strategies.

BACKGROUND: To analyze data in terms of the glycaemic control and therapeutic regimens used for Type-2 Diabetes Mellitus (T2DM) management in Greece, identify factors that influence clinical decisions and determine the level of compliance of T2DM management with the latest international and local guidelines. METHODS: 'AGREEMENT' was a national-multicenter, non-interventional, cross-sectional disease registry. A total of 1191 adult T2DM patients were enrolled consecutively from 59 sites of the National Health System (NHS) or University Hospitals, representing the majority of Diabetes centers or Diabetes outpatient clinics in Greece with a broad geographic distribution. Patients were stratified by gender and analysis was done according to 3 treatment strategies: A (lifestyle changes or use of one oral antidiabetic agent), B (up to 3 antidiabetic agents including injectables but not insulin) and C (any regimens with insulin). RESULTS: Mean (±SD) HbA1c % of the total population was 7.1 (±1.2) while mean (±SD) FPG (mg/dl) was measured at 136 (±42). The proportion of patients who achieved HbA1c < 7% was 53% and ranged from 74.2% for group A, to 60.6% for group B and 35.5% for group C. Median age of the studied population was 65.0 year old (Interquartile Range-IQR 14.0) with an equal distribution of genders between groups. Patients on insulin therapy (treatment strategy C) were older (median age: 67 years vs 63 or 65 for A and B, respectively) with longer diabetes duration (mean duration: 15.3 years vs 5.2 and 10.1 for A and B, respectively). Patients who received insulin presented poor compliance. There was a consensus for a series of decision criteria and factors that potentially influence clinical decisions, used by physicians for selection of the therapeutic strategy among the three groups. Compliance with international and Greek guidelines received a high score among groups A, B and C. No significant differences were presented as per sites' geographic areas, NHS or University centers and physicians' specialty (endocrinologists, diabetologists and internists). CONCLUSIONS: The presented findings suggest the need for improvement of the glycaemic control rate, especially among insulin treated patients as this group seems to achieve low glycaemic control, by setting appropriate HbA1c targets along with timely and individualised intensification of treatment as well as post-therapy evaluation of the compliance with the proposed treatment.

The Real-Life Effectiveness and Care Patterns of Type 2 Diabetes Management in Greece.

AIM: To investigate the prevalence of hypoglycaemia during sulfonylurea (SU) treatment of type 2 diabetes mellitus (T2DM) in Greece and its influence on glycaemic control, treatment adherence and quality of life (QoL). PATIENTS AND METHODS: This was a retrospective cross-sectional study. We included 383 T2DM patients ≥30 years old on treatment with SU in monotherapy or in combination with metformin for at least 6 months. Patients were requested to fill in retrospective questionnaires on hypoglycaemia experience, adherence, weight gain and lifestyle/behavioural factors along with QoL (EQ-5D-3L), treatment satisfaction (TSQM), and fear of hypoglycaemia (HFS-II Worry scale). RESULTS: HbA1c<7% was found in 161 (42.0%) patients. In total, 165 (43.1%) patients reported hypoglycaemic symptoms during the previous 6 months: 41.6% (67/161) of those with HbA1c <7% and 44.1% (98/222) of those with HbA1c ≥7%. Glycaemic control was achieved by 43.1% (94/218) of patients without hypoglycaemia and 50.0% (41/82), 36.8% (25/68) and 6.7% (1/15) of patients with mild, moderate or severe hypoglycaemia, respectively (p=0.013). In multivariate analysis, both occurrence (none vs. mild/moderate/severe) and severity (none vs. mild vs. moderate vs. severe) of hypoglycaemia were significantly associated with impaired global treatment satisfaction (p=0.002 and p<0.0001 respectively) and HFS-II Worry scale scores (both p<0.0001), while lower QoL (EQ-5D (UK) Index) was related to hypoglycaemia severity (p=0.024) only. Finally, treatment adherence was associated with increased (none/mild vs. moderate/severe) hypoglycaemia severity in univariate analysis (p=0.019). CONCLUSION: A high prevalence of patient treated with SU reported hypoglycaemia in Greek healthcare settings with negative effects on treatment satisfaction, patient worry and adherence. Severity of hypoglycaemic symptoms was associated with reduced glycaemic control.

Effect of vildagliptin on hsCRP and arterial stiffness in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the effect of dipeptidyl-peptidase-4 (DPP-4) inhibitor vildagliptin on high sensitivity C-reactive protein (hsCRP) and arterial stiffness (AS) in patients with type 2 diabetes (T2DM). DESIGN: Sixty-four drug-naive diabetic patients, with inadequate glycemic control, participated in this randomized, open-label study. Half of the patients received metformin 1700 mg/d and the other half of them received metformin 1700 mg/d plus vildagliptin 100 mg/d. AS was measured by carotid-femoral Pulse Wave Velocity (cfPWV). Body weight (BW), body mass index (BMI), blood pressure (BP), hsCRP, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), lipid profile, albumin/creatinine ratio (ACR), fasting insulin, C-peptide, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) were also assessed at baseline and after 6 months. RESULTS: Vildagliptin in combination with metformin had a beneficial influence on hsCRP, HbA1c, C-peptide and HOMA-ß index (p <0.05) but had no effect on cfPWV, BP, BW, BMI, lipid profile, ACR and HOMA-IR compared with metformin alone (p=NS). CONCLUSIONS: We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP, improved glycemic control and ß-cell function but had no effect on AS in drug-naive patients with T2DM.

Study of the lipidemic profile of diabetic patients. Negative correlation of cholesterol levels of diabetes type I patients with serum amylase concentration.

Diabetes Mellitus type I (DM1) and II (DM2) share the common characteristic of high blood glucose concentration and the health complications resulting from uncontrolled hyperglycemia such as hyperlipidemia, cardiovascular problems, stroke, ketoacidosis, kidney failure and blindness but have different etiology. DM1 is practically an autoimmune disease. Genetic susceptibility together with environmental factors leads to disease development. The main characteristics of Diabetes type II (DM2) is insulin resistance in muscle and liver cells accompanied by loss of ß-cell function. However, adipose tissue, gastro-intestinal tract, pancreatic a-cell activity, may be involved in disease development. In parallel to the impairment of endocrine pancreatic function, a reduction in exocrine function has also been observed in all types of Diabetes Mellitus. A decrease in amylase and lipase activity has been mentioned by many authors, although cases with elevated amylase have been referred. Most recently a trend for positive correlation between HDL cholesterol and amylase in Diabetes type II patients was shown. In the present study we evaluated the lipidemic profile and related factors such as cortisol, total serum antioxidant capacity (TAC) and amylase in patients suffering from diabetes type I and II. The relationship between different parameters was examined. Blood serum from 20 DM1 patients and 45 DM2 patients was used. Serum from 50 healthy individuals was used as control. Total cholesterol and triglycerides were measured using an enzymatic colorimetric method. Serum cortisol, auto-antibodies and anti-Neu5Gc antibodies were measured using immunoenzyme assays and TAC measurement was made using the ABTS method. Mean total cholesterol was 245.5mg/dL in Diabetes I patients and was significantly elevated compared to healthy individuals as well as Diabetes II patients (168.71±76.0mg/dL). The observed difference was statistically significant (P=0.0004). On the contrary, triglyceride values were within normal range in both cases (123.7±63.2mg/dL in DM1 and 168.1±76.0mg/dL in DM2 patients). Cortisol levels were elevated in both cases with higher values observed in Diabetes type I (280.5±162.9ng/mL in DM1 and 248.5±100.1ng/mL in DM2), while total antioxidant capacity was significantly reduced compared to healthy individuals, 1.470mM, with lower values observed in Diabetes type I (0.680±0.116mM in DM1 and 0.849±0.126mM in DM2). Amylase determination revealed a mean amylase value, 81.7U/ml, within normal range and a negative correlation between cholesterol levels and amylase (r=-0.770) in DM1 patients. No correlation was observed between the determined values or the presence of autoantibodies and antibodies against Neu5Gc in the samples. In conlusion, the lipidemic profile and overall atherogenic and cardiovascular risk factors were worse in Diabetes I compared to Diabetes II patients. Most interestingly, cholesterol levels exhibited a negative correlation with serum amylase values. Since, amylase is not known to be involved in lipid metabolism, cholesterol levels and serum amylase activity may have a common modulator related to Diabetes development.

Postexercise phosphocreatine recovery, an index of mitochondrial oxidative phosphorylation, is reduced in diabetic patients with lower extremity complications.

OBJECTIVE: To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications. METHODS: We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed. RESULTS: The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-α (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-α were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time. CONCLUSIONS: Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups.