Sympathetic and baroreflex abnormalities in the uncomplicated prediabetic state.

BACKGROUND: Neurogenic abnormalities characterize overt diabetic state. However, how early is their appearance in the clinical course of the disease is unclear. METHODS: In 26 normotensive and normoweight prediabetic patients, aged 45.2 ±â€Š3.2 years (mean ±â€ŠSEM), we assessed efferent postganglionic muscle sympathetic nerve traffic (MSNA, microneurography), spontaneous baroreflex sensitivity, and a number of hemodynamic and metabolic variables, including homeostatic model assessment (HOMA) index. Measurements were compared with those obtained in a group of 30 healthy controls of similar age. RESULTS: For similar clinic and ambulatory blood pressure and BMI values, prediabetic patients displayed significantly greater MSNA values than controls, both when expressed as bursts incidence over time (33.3 ±â€Š2.0 vs. 25.6 ±â€Š1.2 bursts/min, P < 0.01) and when corrected for heart rate values (49.6 ±â€Š1.9 vs. 36.7 ±â€Š1.4 bursts/100 heart beats, P < 0.01). This neurogenic abnormality was associated with a reduced spontaneous baroreflex MSNA sensitivity (-3.20 ±â€Š0.2 vs. -4.72 ±â€Š0.2 a.u., P < 0.01) and significantly greater HOMA index values (3.73 ±â€Š0.1 vs. 1.65 ±â€Š0.1 a.u., P < 0.01). In the multivariate analysis, performed in prediabetic patients, MSNA values were directly and significantly related to HOMA index and inversely and significantly to baroreflex-MSNA sensitivity. CONCLUSION: These data provide evidence that sympathetic and reflex abnormalities are of early appearance in the clinical course of the diabetic disease. The adrenergic overdrive and the baroreflex impairment may thus participate at the disease progression, favoring the development of the hypertensive state and adversely affecting the disease prognosis.

Long-term Saxagliptin Treatment Improves Endothelial Function but not Pulse Wave Velocity and Intima-Media Thickness in Type 2 Diabetic Patients.

INTRODUCTION: Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes. AIM: We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables. METHODS: In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls. RESULTS: The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P < 0.05) greater in the S-treated patients. In the S-group glucose metabolism and FMD significantly improved during the follow-up (from 169.3 ± 8 to 157.1 ± 9 mg/dl, P < 0.05, from 7.9 ± 0.1 to 6.9 ± 0.2%, P < 0.001 and from 3.6 ± 0.3 to 7.4 ± 0.8%, respectively P < 0.05). No significant difference was detected in the other parameters, including blood pressure. CONCLUSIONS: Thus treatment with S added-on to metformin results in beneficial effects on endothelial function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process.

Association between depression and neuropathy in people with type 2 diabetes: a meta-analysis.

OBJECTIVE: Depression and neuropathy are frequent complications of type 2 diabetes. The current meta-analysis aimed to estimate the association between depression and neuropathy in subjects with type 2 diabetes. METHODS: We systematically searched electronic databases for articles published up to February 2015, providing data on the association between depression and neuropathy in individuals with type 2 diabetes. No language restrictions were applied. The meta-analysis generated random-effect odds ratios with 95% confidence intervals (95% CI). Risk of publication bias and heterogeneity were estimated using the Egger test and I(2) index, respectively. Leave-one-out analysis was performed. Data were analysed using stata. RESULTS: Thirteen studies were included in the meta-analysis. Data on the association between depression and neuropathy were available for 3898 individuals with type 2 diabetes. Pooled analysis showed an association between depression and neuropathy, with an odds ratio of 2.01 (95% CI: 1.60-2.54; p < 0.001). There was no risk of publication bias (p = 0.064), and heterogeneity was moderate (I(2) = 44.5%). Leave-one-out analysis confirmed consistency of the findings. The association appeared partly influenced by age, because studies selecting older people (sample mean age > 65 years) showed a slightly higher estimate for the association. CONCLUSIONS: We found an association between depression and neuropathy among people with type 2 diabetes. Because of the cross-sectional nature of included studies, the relationship between these two conditions might be bidirectional. Further research exploring factors that might moderate or mediate this association is needed. Targeted interventions for comorbid depression and neuropathy should be implemented in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of blood glucose variability on carotid artery intima media thickness and distensibility in type 1 diabetes mellitus.

AIMS: Diabetes mellitus is characterized by structural and functional alterations of the large- and medium-size arteries. Whether blood glucose variability, i.e. the glycemic oscillations occurring during the 24-h period, represents a risk factor for vascular alterations additional to and independent on HbA1c in type 1 diabetes mellitus is still undefined. The present study was carried out with the aim at investigating the impact of different measures of blood glucose variability on arterial structure and function. We studied 17 non-complicated type 1 diabetic patients (11 males, six females) with an age of 40.8 ± 7.6 years (mean ± SD). In each patient, 24-h glucose profile was obtained by continuous glucose monitoring system and glucose variability was expressed as mean ± SD of 24-h blood glucose levels, mean amplitude of glycemic excursions and postprandial hyperglycemic spikes. Arterial structure and function was measured as carotid IMT and stiffness. MAJOR FINDINGS: The different approaches to assessing blood glucose variability well correlated between and with HbA1c. Carotid IMT and stiffness showed significant correlations with age, blood pressure, heart rate and daily insulin intake but a non- significant correlation with blood glucose variability. PRINCIPAL CONCLUSION: Thus, in type 1 diabetes mellitus, measures of glycemic variability are useful in predicting both actual and long-lasting glycemic control. In absence of diabetes-related complications and of any intima-media thickness alterations, the major predictors of arterial distensibility are represented by traditional risk factors beside glycemic 24-h control.

Increased arterial stiffness in normoglycemic normotensive offspring of type 2 diabetic parents.

Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid diameters at diastole and a reduced increase in carotid diameter at systole (-16%), a reduced carotid artery distensibility (-30%), and an increased pulse pressure (+21.8%), all differences being statistically significant (P<0.05) and persisting in subgroups with elevated or normal body mass index values (<25 and >or=25 kg/m(2)). Carotid artery wall thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism, body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.

Emotional and affective disturbances in patients with epilepsy.

We sought to assess whether epilepsy is associated with a higher risk of emotional reactions to frustrating stimuli, aggressive behavior, apathy, and depression, and whether these psychiatric patterns are specific to the epileptic condition. The study population consisted of referral patients 17 years and older with idiopathic or cryptogenic epilepsy (i.e., epilepsy not caused by a detectable brain lesion) without significant cognitive dysfunction. A first control was selected for each patient among patients with insulin-dependent diabetes and a second among normal blood donors. Aggressiveness in response to stressful stimuli was assessed with the Picture Frustration Study (PFS). Depression was tested by the Beck Depression Inventory. The Aggressive Behavior Scale (assessing irritability and rumination) and the Apathy Scale were also used. Odds Ratios (ORs) with 95% Confidence Intervals (95% CI) were used as the risk measure. Statistical analysis included between-group comparisons. In patients with epilepsy, the test scores were correlated to the main demographic (age, sex, education, marital status, and occupation) and clinical features (seizure types, disease duration, seizure control, and treatments). The sample included 55 patients with epilepsy, 56 diabetics, and 59 normal individuals. Patients with epilepsy and the two control groups had similar PFS scores and similar aggressiveness. Scores were also similar for the Aggressive Behavior and Apathy Scales, with similar numbers of individuals with aggressive conduct and excess rumination. Patients with epilepsy had higher depression scores. Moderate to severe depression was present in 9 cases (diabetes, 2; blood donors, 1) (P=0.004). Relative to blood donors, the OR for moderate to severe depression (95% CI) was 2.1 (0.1-61.7) for diabetes and 11.3 (1.4-247.8) for epilepsy. No significant correlation was detectable between test scores and patient and disease characteristics.