The potential of glucose management indicator for the estimation of glucose disposal rate in people with type 1 diabetes.

BACKGROUND AND AIMS: Insulin resistance is a growing feature in type 1 diabetes (T1D). It can be quantified by calculating the estimated glucose disposal rate (eGDR) with the Epstein's formula, which includes laboratory-measured glycated hemoglobin (HbA1c). We aimed the current research to assess the agreement between the conventional eGDR formula and an alternative one (eGDR-GMI) incorporating the glucose management indicator (GMI) derived from continuous glucose monitoring (CGM). We also explored the relationship between eGDR-GMI, cardiovascular risk factors, and the prevalence of diabetes-related complications. METHODS AND RESULTS: We designed a cross-sectional study that included adults with T1D. eGDR-GMI and eGDR (mg/kg/min) were calculated using GMI or HbA1c, waist circumference, and hypertensive state. Clinical data were collected from electronic medical records. The analyses encompassed 158 participants with a mean age of 39 ± 13 years. The Bland-Altman analysis showed a good agreement between eGDR-GMI and eGDR. When we divided participants in eGDR-GMI tertiles we found a higher prevalence of diabetes-related complications and a less favorable metabolic profile in the lowest eGDR-GMI tertile. The relative risk of retinopathy, nephropathy, and neuropathy significantly increased by approximately 1 unit with each decrease in eGDR-GMI, regardless of age, sex, disease duration, lipids, and smoking habit. CONCLUSIONS: eGDR-GMI represents a valid and robust alternative to the eGDR to assess insulin resistance in T1D. Low eGDR-GMI is associated with diabetes complications and a less favorable metabolic profile. Incorporating the eGDR-GMI into clinical practice can enhance the characterization of T1D people and allow for a more personalized treatment approach.

Autoimmune thyroiditis and celiac disease do not worsen endothelial function in subjects with type 1 diabetes: an observational study.

BACKGROUND: Type 1 diabetes (T1D) is frequently associated with autoimmune thyroiditis (AT) and coeliac disease (CD). Whether the coexistence of multiple autoimmune diseases increases cardiovascular risk is uncertain. We evaluated the effects of AT and CD on arterial wall thickening and endothelial function in patients with T1D. METHODS: This observational study analyzed data from T1D patients regularly followed by the Diabetes Care Centre. Clinical and biochemical characteristics and micro and macrovascular complications were collected from the electronic medical records. All subjects performed Echo-Doppler to evaluate Intima-Media Thickness (IMT) of the common carotid artery (CCA) and endothelial function by the flow-mediated dilation (FMD) technique. The statistical analyses were performed by SPSS for Macintosh. Comparison between means was performed using the t-test for unpaired data and the Mann-Whitney U test. The ANalysis Of VAriance and the Tukey posthoc test were applied to compare patients with and without other autoimmune diseases, and control subjects. The p-value for statistical significance was set at p < 0.05. RESULTS: A total of 110 patients were enrolled. Among these, 69 had T1D and 41 T1D and AT and or CD, of whom 33 AT, 7 CD, and 1 both AT and CD. The mean age was 35 years, mean HbA1c was 7.6%, and mean diabetes duration 18 years. The IMT of the CCA was not significantly different between T1D patients with and without concomitant autoimmune diseases (with AT and CD: right CCA 603 ± 186 µ, left 635 ± 175 µ; without AT and CD: right CCA 611 ± 176 µ, left CCA 631 ± 200 µ). FMD was also comparable between T1D groups, with AT and CD 7.9 ± 4.2%; without AT and CD 8.8 ± 4.4%. CONCLUSION: Patients with T1D and concomitant AT and or CD show no worse morphological or functional vascular damage, evaluated by CCA IMT and brachial artery flow-mediated dilation, than patients with T1D alone.

Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy.

BACKGROUND: Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function. OBJECTIVE: We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness. METHODS: The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software. RESULTS: Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 µm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 µm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 µm; p = NS). CONCLUSIONS: This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.

Diabetes Data Management System to Improve Glycemic Control in People With Type 1 Diabetes: Prospective Cohort Study.

BACKGROUND: Smartphone and Web technology can improve the health care process, especially in chronic diseases. OBJECTIVE: The aim of this study was to investigate whether the use of blood glucose (BG) data management system, which enables connection to smartphones, the Web, the cloud, and downloading, can improve glycemic control in subjects with type 1 diabetes mellitus (T1DM). METHODS: This study was a prospective, single-arm, cohort feasibility study with 6 months of duration. T1DM subjects enrolled had experience in self-monitoring blood glucose, but were download data naïve. Fasting BG and glycated hemoglobin (HbA1c) were collected at the enrollment and at follow-up. Subjects were divided into Downloader (DL) and No-downloader (NDL). RESULTS: A total of 63 subjects were analyzed, of which 30 were classified as DL and 33 as NDL. At the end of the study, DL had significantly lower HbA1c, mean daily glucose, standard deviation, percentage of BG values above target, and pre- and postprandial (lunch and dinner) values compared with NDL (all P<.05). The percentage of BG values within treatment target was significantly higher in DL compared with NDL (47% [SD 9] vs 37% [SD 13]; P=.001). CONCLUSIONS: The findings suggest that, in T1DM, downloading of BG from data management system, which enables connection to smartphones, the Web, and the cloud, might be a valuable contributor to improved glycemic control.

Body fat and blood rheology: Evaluation of the association between different adiposity indices and blood viscosity.

BACKGROUND: In recent years, new measures of body adiposity have been introduced: lipid accumulation product (LAP), body adiposity index (BAI) and body shape index (ABSI). These indices have been demonstrated to better associate with cardiovascular disease than other measures of adiposity. OBJECTIVES: The aim of the present study was to evaluate if LAP or BAI better associate with blood viscosity than other measures of adiposity (body mass index, BMI; waist circumference, WC; waist-to-hip ratio, W/HR; waist-to-height ratio, W/HtR). METHODS: 344 subjects were recruited for the present investigation. Exclusion criteria were: diabetes, elevated triglycerides, smoking and drug use. Blood lipids and glucose were measured by routine methods. Blood and plasma viscosity were measured by a cone-plate viscometer. Adiposity measures were computed as previously described. RESULTS: In simple correlation analyses, blood viscosity (BV) correlated with BMI, BAI, and LAP in males and with LAP in females. Correlations between plasma viscosity and adiposity indices were weak and not statistically significant. Other variables significantly related with BV were: gender, HDL- and LDL-Cholesterol, and triglycerides (p < 0.05). In multiple regression analysis only LAP was associated with BV. CONCLUSIONS: Our data suggest that LAP index is strongly associated to blood viscosity. This result, along with previous evidence, identifies LAP index as a potential cardiovascular risk marker.

Hemorheological profiles of subjects with prehypertension.

High blood viscosity is associated with increased peripheral resistance and high blood pressure (BP). Prehypertension refers to a systemic BP of 120-139 mm Hg systolic (SBP) and/or 80-89 mm Hg diastolic (DBP). Subjects with prehypertension have an increased risk of overt hypertension and incident cardiovascular disease compared with subjects who have optimal BP. In the present study, we investigated the hemorheological profiles of subjects with prehypertension. A total of 418 apparently healthy subjects were enrolled. BP, plasma lipids and glucose were measured using routine methods. Blood and plasma viscosity were measured using a cone-plate viscometer. The participants were grouped according to BP into the following categories: 'normotensive' (n=100), 'prehypertensive' (n=172), and 'hypertensive' (n=146). The blood viscosity, plasma viscosity and hematocrit of the prehypertensive subjects were higher than those of the normotensive subjects (P<0.01), but they were comparable to those of the hypertensive subjects. In simple correlation analyses, SBP and DBP were directly and significantly correlated with age, body mass index (BMI), blood glucose, hematocrit, plasma viscosity and blood viscosity. In multiple regression analyses, age, fasting blood glucose and plasma viscosity were independently related with SBP, whereas blood viscosity, fasting blood glucose and BMI significantly predicted DBP. These data demonstrate that BP in the range of so-called prehypertension is accompanied by important hemorheological changes, which are similar to those observed in people with overt hypertension. These results could explain the increased cardiovascular risk observed in these subjects as well as their susceptibility to hypertension.

Brachial Low-Flow-Mediated Constriction is Associated with Delayed Brachial Flow-Mediated Dilation.

AIM: Flow-mediated vasodilation (FMD) of the brachial artery measures the ability of the artery to dilate after a forearm ischemia lasting for 5 min. During ischemia, and therefore in conditions of low flow, constriction of the brachial artery (L-FMC) has sometimes been reported. The meaning of L-FMC is still unclear. The aims of our study were to establish the prevalence of subjects with L-FMC, to determine whether the magnitude of L-FMC correlates with magnitude of FMD, and to determine whether L-FMC can be used to predict FMD timing. METHODS: A total of 179 outpatients were studied, and the brachial artery diameter was measured every minute during the 5 min forearm ischemia. Subjects who had at least one measurement showing a constriction of ＞ 1% during ischemia were defined as constrictors. FMD was evaluated at 50 s, 2 min, and 3 min after cuff release. On the basis of time, the subjects in whom maximal dilation had occurred were divided into Early, Late, or No dilators. RESULTS: The brachial artery diameter of 70 subjects (39%) constricted during ischemia. Higher the constriction during ischemia, lower was the dilation after ischemia. Constrictors were more likely to have Late (OR 2.6; ICs 95% 1.19-5.81, p=0.02) or No dilation (OR 4.8; ICs 95% 1.90-12-16, p=0.02) compared with no constrictors. CONCLUSIONS: The present study reveals that almost 40% of the subjects had brachial artery L-FMC and a more pronounced constriction during ischemia correlated with a lower dilation after ischemia. Finally, the prevalence of subjects showing L-FMC was significantly higher among subjects with delayed or no vasodilation, suggesting that L-FMC may be a marker of endothelial dysfunction.

Red blood cell distribution width predicts two-hours plasma glucose levels during OGTT.

OBJECTIVE: Red blood cell distribution width (RDW) is a numerical measure, reported as part of a standard complete blood count, usually employed for differential diagnosis of anemic state. Some lines of evidence demonstrate that RDW associates with type 2 diabetes incidence and its complications. To further explore the role of RDW as predictor of abnormal glucose metabolism, we have analyzed the relationship between RDW and 2-hours plasma glucose concentration during an oral glucose tolerance test (OGTT). METHODS: Forty-five outpatients were enrolled for the present study. Participants underwent 75 g OGTT and measurements of hematological parameters. Cardiovascular disease risk factors (blood pressure, blood lipids, cigarette smoking, obesity) were evaluated by routine methods. RESULTS: In simple regression analysis 2-hours post-load glucose was directly associated with age (r = 0.36, p = 0.01), fasting glucose levels (r = 0.40, p = 0.002) and RDW (r = 0.31, p = 0.037). In multiple regression analysis fasting glucose, RDW, triglycerides and age significantly and independently predicted 2-hours plasma glucose (p <  0.01 for all coefficients). CONCLUSION: The present findings demonstrate that RDW associates with plasma glucose concentration after a 75-g oral glucose tolerance test. Our results highlight the role of RDW as predictor of glucose metabolism disturbance.

Clinical Predictors of Progressive Beta-Cell Failure in Type 2 Diabetes.

OBJECTIVES: The aim of the study was to identify factors associated with progressive beta-cell failure in a cohort of nonselected subjects with type 2 diabetes. METHODS: Two hundred twenty-four medical records were evaluated. Progressive beta-cell failure was defined as the following: glycated hemoglobin is higher than 7.5% despite combined drug therapy and appropriate diet (ie, isocaloric or hypocaloric diet depending on body weight) and absence of any illness causing acute hyperglycemia. The following factors were considered as possible predictors: diabetes-related symptoms, fasting plasma glucose at the onset of disease, family history of type 2 diabetes, number of visits per year, and residency. Further potential predictors were disease duration, age, body mass index, estimated glomerular filtration rate, and hypertension and/or hyperlipidemia at the enrollment in the study. RESULTS: The prevalence of beta-cell failure was 41%. Independent predictors of failure were longer disease duration (hazard ratio [HR] for each year of diabetes, 1.03; confidence intervals (CIs), 1.01-1.05; P = 0.03), history of hypertension (HR, 1.90; CIs, 1.73-2.89; P = 0.04), hyperlipidemia (HR, 1.65; CIs, 1.06-2.58; P = 0.03), residence in suburb (HR, 1.78; CIs, 1.06-3.01; P = 0.03), and presence of symptoms at the onset of disease (HR, 2.47; CIs, 1.51-4.03; P = 0.0001). CONCLUSIONS: Patients with long disease duration, hypertension, and hyperlipidemia who are residents in suburbs and had diabetes-related symptoms at diagnosis might deserve intensive treatment to obtain adequate and stable glycemic control.

Management of Type 2 Diabetes Mellitus through Telemedicine.

BACKGROUND: Type 2 diabetes mellitus T2DM has a huge and growing burden on public health, whereas new care models are not implemented into clinical practice; in fact the purpose of this study was to test the effectiveness of a program of integrated care for T2DM, compared with ordinary diligence. METHODS: "Progetto Diabete Calabria" is a new organizational model for the management of patients with diabetes mellitus, based on General Practitioners (GPs) empowerment and the use of a web-based electronic health record, shared in remote consultations among GPs and Hospital Consultants. One-year change in glucose and main cardiovascular risk factors control in 104 patients (Cases) following this integrated care program has been evaluated and compared with that of 208 control patients (Controls) matched for age, gender, and cardiometabolic profile, and followed in an ordinary outpatient medical management by the Consultants only. Both patient groups had Day Hospitals before and after the study period. RESULTS: The mean number of accesses to the Consultants during the study was 0.6 ± 0.9 for Cases, and 1.3 ± 1.5 for Controls (p<0.0001). At follow-up, glycated hemoglobin (HbA1c) significantly decreased from 58 ± 6 to 54 ± 8 mmol/mol in Cases only (p=0.01); LDL cholesterol decreased in both groups; body mass index decreased in Cases only, from 31.0 ± 4.8 to 30.5 ± 4.6 kg/m(2) (p=0.03). CONCLUSIONS: The present study demonstrates that a health care program based on GPs empowerment and taking care plus remote consultation with Consultants is at least as effective as standard outpatient management, in order to improve the control of T2DM.