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The advanced and performing technologies of glucose monitoring systems provide a large amount of glucose data that needs to be properly read and interpreted by the diabetology team in order to make therapeutic decisions as close as possible to the patient’s metabolic needs. For this purpose, new parameters have been developed, to allow a more integrated reading and interpretation of data by clinical professionals. The new challenge for the diabetes community consists of promoting an integrated and homogeneous reading, as well as interpretation of glucose monitoring data also by the patient himself. The purpose of this review is to offer an overview of the glycemic status assessment, opened by the current data management provided by latest glucose monitoring technologies. Furthermore, the applicability and personalization of the different glycemic monitoring devices used in specific insulin-treated diabetes mellitus patient populations will be evaluated.

This study aimed to explore differences in vascular and structural parameters using optical coherence tomography angiography in patients with type 1 diabetes (DM1) with mild signs of diabetic retinopathy (DR) over a two-year follow-up period. Parafoveal vessel density (PVD) and foveal avascular zone (FAZ) area were analyzed. The thickness of three predefined retinal slabs was measured, including the inner limiting membrane (ILM)–inner plexiform layer (IPL), IPL–inner nuclear layer (INL), and the IPL–outer nuclear layer (ONL). Twenty-two patients with DM1 and 21 controls were included. There was no significant difference in the FAZ area, perimeter and acircularity index between cohorts over time. Baseline superficial capillary plexus PVD was approximately 10% lower in patients with diabetes than in controls ( p  = 0.001), and was 12% lower at 2 years ( p  = 0.002). There was no difference in the annual linear trend between the groups (− 0.5% in diabetics vs. controls, p  = 0.736). Baseline deep capillary plexus (DCP) PVD was slightly lower in diabetics than in controls (− 4.4%, p  = 0.047) and the difference increased at 2 years (− 12.6%, p  < 0.001). The annual linear trend was − 2.7% in diabetic patients compared to controls ( p  = 0.009) . In addition, the PVD of the DCP and the intermediate capillary plexus (ICP) were evaluated separately. Regarding the DCP PVD, no statistically significant difference at any time points in diabetic patients compared to controls and no statistically significant difference in the linear trend was found ( p  > 0.1). Conversely, no difference was recorded for parafoveal ICP density at individual time points ( p  > 0.1), but a statistically significant difference in the linear trend over time in diabetic patients compared to controls was recoded (− 3.2% per year, p  = 0.001). Despite the apparent intergroup differences at baseline in structural OCT parameters, the differences including ILM–IPL ( p  = 0.273), IPL–INL ( p  = 0.708), and IPL–ONL ( p  = 0.054) were modest and not statistically significant with time. Therefore, the microvascular change of the deeper vessels might be a robust biomarker to evaluate the clinical progression of DR in DM1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

OBJECTIVE: The effect of glycemic variability (GV) on cardiovascular risk has not been fully clarified in type 2 diabetes. We evaluated the effect of GV, blood pressure (BP), and oxidative stress on intima-media thickness (IMT), left ventricular mass index (LVMI), flow-mediated dilation (FMD), and sympathovagal balance (low frequency [LF]/high frequency [HF] ratio) in 26 type 2 diabetic patients (diabetes duration 4.41 ± 4.81 years; HbA₁c 6.70 ± 1.25%) receiving diet and/or metformin treatment, with no hypotensive treatment or complications. RESEARCH DESIGN AND METHODS: Continuous glucose monitoring (CGM) data were used to calculate mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA)-2, mean blood glucose (MBG), mean postprandial glucose excursion (MPPGE), and incremental area under the curve (IAUC). Blood pressure (BP), circadian rhythm, and urinary 15-F2t-isoprostane (8-iso-prostaglandin F₂α [PGF₂α]) were also evaluated. Subjects were divided into dipper (D) and nondipper (ND) groups according to ΔBP. RESULTS: IMT and LVMI were increased in ND versus D (0.77 ± 0.08 vs. 0.68 ± 0.13 [P = 0.04] and 67 ± 14 vs. 55 ± 11 [P = 0.03], respectively). MBG, MAGE, and IAUC were significantly associated with LF/HF ratio at night (r = 0.50, P = 0.01; r = 0.40, P = 0.04; r = 0.41, P = 0.04, respectively), MPPGE was negatively associated with FMD (r = -0.45, P = 0.02), and CONGA-2 was positively associated with LVMI (r = 0.55, P = 0.006). The Δsystolic BP was negatively associated with IMT (r = -0.43, P = 0.03) and with LVMI (r = -0.52, P = 0.01). Urinary 8-iso-PGF₂α was positively associated with LVMI (r = 0.68 P < 0.001). CONCLUSIONS: An impaired GV and BP variability is associated with endothelial and cardiovascular damage in short-term diabetic patients with optimal metabolic control. Oxidative stress is the only independent predictor of increased LV mass and correlates with glucose and BP variability.

To further characterize the protective profile of MHO individuals, we compared clinical characteristics, including cardiovascular risk factors, plasma IGF-1 levels, and intima-media thickness (IMT) of the common carotid artery, of a group of MHO women from a cohort of nondiabetic Italian Caucasians with those of two age-matched groups comprising healthy nonobese or IRO women. By definition, insulin-stimulated glucose disposal was higher in MHO subjects who also exhibited significant lower lean body mass, fasting and 2-h postchallenge plasma glucose, fasting insulin, triglycerides, systolic and diastolic blood pressure, and carotid IMT compared with IRO individuals.

Peripheral neuropathy could complicate diabetes mellitus (DM). confocal microscopy (IVCM) is an ocular examination for the diagnosis of small fiber neuropathies and the detection of the earliest corneal sub-basal nerve plexus (SBP) alterations. Corneal SBP characteristics include focal enlargement along with the nerve fiber, called corneal beadings. These dilatations represent a mitochondrial accumulation induced by the reactive oxygen stress, as a consequence of hyperglycemia. For this reason, corneal beadings are considered indicative of metabolic activity. This study aimed to describe the corneal characteristics of a population of type 1 diabetes mellitus (T1DM) well metabolically controlled, using a new algorithm for the analysis of corneal beading size (BS). Patients aged ≥18 years affected by T1DM were compared with healthy subjects who underwent IVCM (Confoscan 4; Nidek Technologies Padova, Italy). Starting from the coordinates of the beadings detected by the IVCM, we implemented a new algorithm for automatically measuring BS in corneal SBP images. We compared 20 eyes of T1DM patients with 26 healthy controls. The corneal nerves' fiber length ( = 0.008), corneal nerves' fiber length density ( = 0.008), and the number of fibers ( = 0.017) were significantly lower in the diabetic group compared with controls. There was no difference between diabetic and healthy eyes in the mean number of corneal beadings both in the frame of analysis ( = 0.606) and for 0.1 mm of SBP nerve ( = 0.145). Regarding the BS, patients with T1DM had corneal beadings larger than controls ( = 0.036). We found that the corneal beadings parameters are similar in healthy and T1DM individuals. Nevertheless, measuring the BS with our algorithm, we showed that corneal beadings are enlarged in patients affected by T1DM when compared with healthy controls. Identifying beading expansion in corneal nerve fiber using IVCM should become a useful tool to predict peripheral neuropathy at an early stage.

Purpose. The purpose of our study is to describe the in vivo corneal confocal microscopy characteristics of subbasal nerve plexus in a highly selected population of patients affected by type 1 diabetes mellitus (T1DM) without any microvascular diabetes complications. Methods. We included 19 T1DM patients without diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria. All patients underwent in vivo corneal confocal microscopy and blood analysis to determine subbasal nerve plexus parameters and their correlation with clinical data. We compared the results with 19 healthy controls. Results. The T1DM group showed a significant decrease of the nerve fiber length (P=0.032), the nerve fiber length density (P=0.034), the number of fibers (P=0.005), and the number of branchings (P=0.028), compared to healthy subjects. The nerve fiber length, nerve fiber length density, and number of fibers were directly related to the age at onset of diabetes and inversely to the duration of DM. BMI (body mass index) was highly related to the nerve fiber length (r = −0.6, P=0.007), to the nerve fiber length density (r = −0.6, P=0.007), and to the number of fibers (r = −0.587, P=0.008). No significant correlations were found between the corneal parameters and HbA1c. Conclusions. Early subclinical fiber corneal variation could be easily detected using in vivo corneal confocal microscopy, even in type 1 diabetes without any microvascular diabetes complications, including diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria.

The role of the autonomic nervous system in obesity and insulin-resistant conditions has been largely explored. However, the exact mechanisms involved in this relation have not been completely elucidated yet, since most of these mechanisms display a bi-directional effect. Insulin-resistance, for instance, can be caused by sympathetic activation, but, in turn, the associated hyperinsulinemia can activate the sympathetic branch of the autonomic nervous system. The picture is made even more complex by the implicated neural, hormonal and nutritional mechanisms. Among them, leptin plays a pivotal role, being involved not only in appetite regulation and glucose homeostasis but also in energy expenditure. The purpose of this review is to offer a comprehensive view of the complex interplay between leptin and the central nervous system, providing further insights on the impact of autonomic nervous system balance on adipose tissue and insulin-resistance. Furthermore, the link between the circadian clock and leptin and its effect on metabolism and energy balance will be evaluated.

Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl) at 1 h during an oral glucose tolerance test (OGTT) can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high). The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low). To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001) and insulin clearance (P = 0.006) after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02) in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

Metabolically healthy obese (MHO) are relatively insulin sensitive and have a favorable cardio-metabolic risk profile compared with metabolically abnormal obese (MAO). To evaluate whether MAO individuals have a decreased insulin clearance compared with MHO individuals, 49 MHO, 147 MAO, and 172 non-obese individuals were analyzed in this cross-sectional study. Insulin clearance and insulin sensitivity were assessed through euglycemic hyperinsulinemic clamp. MHO subjects exhibited significant lower triglycerides, total cholesterol, 2-h post-challenge glucose, fasting and 2-h post-challenge insulin, steady-state plasma insulin, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase as compared with MAO individuals. Disposition index was higher in MHO subjects as compared with MAO individuals after adjusting for gender and age ( P  = 0.04). Insulin clearance was significantly lower in MAO individuals as compared with MHO and non-obese individuals. The difference between the two obese subgroups remained significant after adjusting for gender, age, waist circumference, fat mass, and insulin-stimulated glucose disposal ( P  = 0.03). The hepatic insulin extraction (C-peptide/insulin) in the fasting state was significantly higher in MHO subjects as compared with MAO individuals ( P  < 0.0001). In univariate analysis adjusted for gender and age, insulin clearance was correlated with hepatic insulin extraction ( P  = 0.01). In conclusion, insulin clearance differs among obese subjects with different metabolic phenotypes. Impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia observed in MAO individuals.