Comparison of Two Estimated Glucose Disposal Rate Methods for Detecting Insulin Resistance in Adults with Type 1 Diabetes Mellitus.

Background: The presence of insulin resistance (IR) in patients with type 1 diabetes mellitus (T1DM) is a significant indicator of all chronic diabetic complications, independent of other risk factors. The estimated glucose disposal rate (eGDR) is a practical method that can be easily used in daily practice to determine IR. This study aimed to determine the cutoff values for two eGDR methods and compare their diagnostic value for determining IR in adult T1DM patients with metabolic syndrome (MetS). Methods: This cross-sectional study was performed on 184 adults admitted to the endocrinology outpatient clinic diagnosed with T1DM. Demographic characteristics, anthropometric measurements, and the presence of hypertension (HT) were recorded. The eGDR of all patients was calculated using two formulas based on HbA1c level, presence of HT, waist-to-hip ratio (WHR), or waist circumference (WC). Diagnostic cutoff values for both eGDRs were defined using receiver operating characteristic (ROC) analysis. Patients were divided into two groups according to the cutoff values. The accuracy of the diagnostic cutoffs for eGDRwhr and eGDRwc was compared using a Bland-Altman plot. Results: The cutoff value for eGDRwhr was 7.37 mg/(kg·min) with 83.3% specificity and 86.7% sensitivity [area under the curve (AUC) = 0.901; P < 0.001; 95% confidence interval (CI), 0.824-0.977] and for eGDRwc 7.50 mg/(kg·min) with 79.8% specificity and 83.3% sensitivity (AUC = 0.895; P < 0.001; 95% CI, 0.817-0.972) for the presence of MetS. Further ROC analysis showed that the difference between the two AUCs (0.901 and 0.895) was not significant (P = 0.923). Conclusion: Assessment of eGDR would lead to early prevention of diabetic complications. eGDR is measured using either WHR or WC. This study is the first to compare WHR and WC in calculating eGDR in adults. WHR and WC are not superior to each other for calculating eGDR in determining IR in T1DM.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

Progression of insulin resistance in individuals with type 1 diabetes: A retrospective longitudinal study on individuals from Thailand.

AIMS: To investigate temporal changes in glycaemic control and weight contributing to insulin resistance (IR), in Thai individuals with type 1 diabetes (T1D). METHODS: Longitudinal data of 69 individuals with T1D were retrospectively collected over a median follow-up of 7.2 years. The estimated glucose disposal rate (eGDR), a marker of IR, was calculated using an established formula. Individuals were assigned as insulin-sensitive T1D (the latest eGDR≥8 mg/kg/min), or insulin-resistant T1D/double diabetes (the latest eGDR<8 mg/kg/min). Generalised linear mixed model was employed to compare the temporal patterns of HbA1c, BMI, and eGDR between the two groups. RESULTS: 26 insulin-resistant T1D had a gradual decline in eGDR, corresponding with increased weight and HbA1c. In contrast, 43 insulin-sensitive T1D had stable insulin sensitivity with an improvement in HbA1c over time, associated with a modest weight gain. Fluctuations of glucose levels were observed during the early diabetes course leading to unstable eGDR, thus limiting the use of eGDR to classify insulin-resistant T1D. CONCLUSION: T1D individuals who eventually develop IR are likely to experience early increasing IR over time. In contrast, those who ultimately do not have IR, maintain their insulin sensitivity throughout their course at least in the medium term.

Estimated glucose disposal rate is associated with retinopathy and kidney disease in young people with type 1 diabetes: a nationwide observational study.

AIMS: The aim of this study was to investigate the association between estimated glucose disposal rate (eGDR), a proxy for insulin resistance, and retinopathy or kidney disease, i.e. micro-, or macroalbuminuria, in young individuals with type 1 diabetes (T1D). MATERIAL AND METHODS: Using data from the Swedish pediatric registry for diabetes (SweDiabKids) and the registry for adults (NDR), all individuals with T1D with a duration of diabetes of less than 10 years between 1998 and 2017 were included. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) for two cohorts: retinopathy cohort or kidney disease cohort, stratified by eGDR categories: < 4, 4 to 5.99, 6 to 7.99, and ≥ 8 mg/kg/min (reference). RESULTS: A total of 22 146 (10 289 retinopathy cohort, and 11 857 kidney disease cohort with an overlapping of 9575) children and adults with T1D (median age 21 years, female 42% and diabetes duration of 6 and 7 years, respectively for the cohorts) were studied. During a median follow-up of 4.8 years (IQR 2.6-7.7) there were 5040 (24.7%), 1909 (48.1%), 504 (52.3%) and 179 (57.6%) events for retinopathy in individuals with an eGDR ≥ 8, 7.99 to 6, 5.99 to 4, and < 4 mg/kg/min, respectively. Corresponding numbers for kidney disease was 1321 (6.5%), 526 (13.3%), 255 (26.8%) and 145 (46.6%). After multiple adjustments for different covariates, individuals with an eGDR 7.99 to 6, 5.99 to 4 and < 4 mg/kg/min, had an increased risk of retinopathy compared to those with an eGDR ≥ 8 mg/kg/min (adjusted HRs, 95% CIs) 1.29 (1.20 to 1.40); 1.50 (1.31 to 1.71) and 1.74 (1.41 to 2.14). Corresponding numbers for kidney disease was (adjusted HRs, 95% CIs) 1.30 (1.11 to 1.52); 1.58 (1.25 to 1.99) and 1.33 (0.95 to 1.86), respectively. CONCLUSIONS: eGDR, a proxy for insulin resistance, is associated with retinopathy and kidney disease in young adults with T1D. The risk of retinopathy increased with lower eGDR. The risk of kidney disease also increased with lower eGDR; however results show no association between the lowest eGDR and kidney disease. eGDR can be helpful to identify young T1D individuals at risk.

Longitudinal trends in lipid profile in indian children and youth with type-1 diabetes: a 5-year follow up from a single centre.

INTRODUCTION: High prevalence of dyslipidaemia in children and adolescents with type-1 diabetes (T1D) places them at increased risk of developing atherosclerosis leading to mortality caused by cardiovascular disease(CVD). Thus, screening for fasting blood lipids when diabetes is stabilized in children aged 11 years and above is routinely recommended with follow-up every 5 years. OBJECTIVES: (1) To characterize the lipid profile of children and adolescents with respect to diabetes duration. (2) To describe longitudinal changes in lipid profile over a 5-year period in patients with T1D. METHODS: This longitudinal 5-year follow-up study included 112 patients with T1D aged 3-18 years. Demographic data, anthropometry and laboratory measurements were performed using standard protocols at baseline and endline. P value < 0.05 was considered significant. RESULTS: The prevalence of dyslipidaemia in our study was 49.5% with abnormal LDL as the most frequently deranged parameter. Duration of illness played a major role in deterioration of lipid profile mediated by triglyceride and VLDL. Duration of illness and fibre intake in diet significantly predicted the change in lipid profile which were driven by triglycerides and VLDL. Glycemic control, insulin sensitivity and serum TSH also significantly altered components of lipid profile with no impact on overall dyslipidaemia. A total of 6.5% subjects had LDL concentrations >130 mg/dl and the same proportion had non-HDL cholesterol concentrations >145 mg/dl at baseline while at endline, 11.9% subjects had LDL concentrations >130 mg/dl and 15.6% subjects had non-HDL cholesterol concentrations >145 mg/dl. 28.6% subjects with LDL > 130 mg/dl and non-HDL cholesterol >145 mg/dl at baseline had persistently elevated concentrations while 10.3% and 14.4% additional subjects developed elevated LDL and non-HDL cholesterol concentrations respectively during the study period. CONCLUSIONS: The deterioration of lipid profile in T1D, due to increase in disease duration was chiefly mediated by increase in serum triglyceride and VLDL concentrations which may be prevented by improving glycaemic control, insulin sensitivity and fibre intake in diet.

Estimated glucose disposal rate and risk of cardiovascular disease: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVES: Previous studies had reported that insulin resistance (assessed by estimated glucose disposal rate; eGDR) was associated with higher risk of cardiovascular events (CVD) in diabetes patients. The aim of present study was to investigate the potential association between eGDR and CVD in general population. METHODS: The China Health and Retirement Longitudinal Study with 8,267 individuals were included in analysis. Participants were divided into four subgroups according to eGDR quartile. Cox proportional hazards regression models were used to examine the associations of eGDR with CVD (stroke or cardiac events). RESULTS: During 6 years of follow-up, a total of 1,476 respondents experienced a CVD (494 stroke and 1,110 cardiac events). In multivariable-adjusted analyses, the corresponding hazard ratio (95% confidence intervals) for the highest eGDR versus lowest quartile of eGDR was 0.58(0.49-0.67) for CVD. Each 1-SD increase of eGDR was associated with 16% (HRs = 0.84; 0.79-0.88) decreased risk of CVD. There was also a significant linear association between eGDR and CVD (P for linearity < 0.001). Similar associations were also found between eGDR and stroke and cardiac events. CONCLUSION: A higher eGDR (a measure of insulin resistance) was associated with a decreased risk of CVD, stroke and cardiac events in general Chinese population, suggesting that eGDR could be considered as a preferential predictor and treatment target of CVD. Future well-designed prospective clinical studies are needed to verify our findings and to assess the effect of eGDR interventions in CVD prevention and therapy.

Triple burden of malnutrition and role of anaemia in the development of complications associated with type 1 diabetes in Indian children and youth.

OBJECTIVES: The double burden of malnutrition accompanied by micronutrient deficiency is referred to as the triple burden of malnutrition (TBM). Very few studies have highlighted the TBM in children with type-1 diabetes. We conducted this study with the objective of estimating the TBM in Indian children and youth with type-1 diabetes (T1D) and to study role of anaemia in the development of complications associated with T1D. METHODS: This cross-sectional observational study included 394 subjects with T1D. Demographic data, anthropometry, blood pressure, biochemical measurements, dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography were performed using standard protocols. Estimated glucose disposal rate (eGDR) and estimated glomerular filtration rate (eGFR) were calculated for all subjects. RESULTS: We report a 16, 5.8, and 16.2% prevalence of anaemia, underweight and overweight/obese suggesting TBM with microcytic hypochromic anaemia as the most common morphological form. Haemoglobin concentrations showed positive correlation with systolic and diastolic blood pressure. The presence of anaemia was a significant predictor of eGDR and macrovascular complications in T1D which could not be attributed to glycemic control. Bone health of anaemic T1D subjects was poor than subjects without anaemia on DXA scan after adjusting for confounders. No systematic pattern between Hb concentrations and eGFR or ACR was found. CONCLUSIONS: TBM in Indian children and youth with T1D is a significant health problem and anaemia is an important predictor in the development of macrovascular complications and poor bone health associated with T1D. However, its role in development of microvascular complications remains to be explored.

The relationship between estimated glucose disposal rate and bone turnover markers in type 2 diabetes mellitus.

PURPOSE: To investigate the relationship between estimated glucose disposal rate (eGDR) and bone turnover markers in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This is a cross-sectional study, which recruited 549 patients with T2DM. The eGDRs of patients were calculated based on the presence of hypertension, glycated hemoglobin, and body mass index. All patients were divided into high-eGDR group and low-eGDR group using the median of eGDR as the boundary. The patients were further divided into two subgroups: males and postmenopausal females. RESULTS: The lower the eGDR, the more severe was insulin resistance. The levels of osteocalcin (OC), type I collagen carboxyl-terminal peptide (ß-CTX), and type I procollagen amino-terminal peptide (PINP) were significantly lower in the low-eGDR group than those in the high-eGDR group. The eGDR was positively correlated with OC, ß-CTX, and PINP in all patients, and in the male subgroups. In the postmenopausal female subgroup, there was no correlation between eGDR and OC, ß-CTX, or PINP. In addition, this positive correlation remained after adjusting for other factors in multilinear regression analysis. CONCLUSION: Our study was the first to demonstrate that eGDR is positively correlated with bone turnover markers in patients with T2DM. This correlation was observed among the male patients with T2DM but not among postmenopausal female patients with T2DM.

A pilot study to determine association of parental metabolic syndrome with development of metabolic risk in Indian children, adolescents and youth with Type-1 diabetes.

BACKGROUND AND AIMS: Prevalence of metabolic syndrome (MS) is increasing in children with type-1 diabetes (T1D). Genetic and environmental factors shared among family members are considered significant risk factors. We conducted this study to assess the association of parental MS with development of metabolic risk (MR) in patients with T1D. METHOD: This cross-sectional study included 29 patients with T1D along with their parents (29 triads). Demographic data, anthropometry, blood pressure, biochemical measurements and body composition measurements were performed using standard protocols. Insulin resistance was calculated using estimated glucose disposal rate (eGDR) in patients and using HOMA-IR in their parents. MS was diagnosed using International Diabetes Federation Consensus Definition, 2017. RESULTS: Of total study participants, 44.8% patients with T1D had MR while 25.3% of parents had MS. Low HDL was identified as the most common component of MS. 64.3% patients with T1D, who had parents with MS, had MR. The odds ratio (OR) for development of MR in patients with T1D with parents affected by MS was 4.9 (95% confidence interval 1.0-24.1) while relative risk (RR) was 2.4 (95% confidence interval 0.9-6.1). MR in patients with T1D was found to have a strong correlation with parental MS and also with development of double diabetes (DD). CONCLUSION: In conclusion, parental MS increases the risk of development of metabolic abnormalities in patients with T1D. Thus, positive family history may serve as a useful indicator for targeted screening to detect DD.

Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis.

PURPOSE: To determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D). METHODS: We reanalysed baseline pretreatment data in a subset of patients with T1D from two previous RCTs, consisting of a panel of thrombotic markers, including fibrinogen, tissue factor (TF) activity, and plasminogen-activator inhibitor (PAI)-1, and TNFα, and clinical factors (age, T1D duration, HbA1c, insulin requirements, BMI, blood pressure, and eGDR). We employed univariate linear regression models to investigate associations between clinical parameters and eGDR with thrombotic biomarkers. RESULTS: Thirty-two patients were included [mean ± SD age 31 ± 7 years, HbA1c of 58 ± 9 mmol/mol (7.5 ± 0.8%), eGDR 7.73 ± 2.61]. eGDR negatively associated with fibrinogen (P < 0.001), PAI-1 concentrations (P = 0.005), and TF activity (P = 0.020), but not TNFα levels (P = 0.881). We identified 2 clusters of patients displaying significantly different characteristics; 56% (n = 18) were categorised as 'higher-risk', eliciting significantly higher fibrinogen (+ 1514 ± 594 µg/mL; P < 0.001), TF activity (+ 59.23 ± 9.42 pmol/mL; P < 0.001), and PAI-1 (+ 8.48 ± 1.58 pmol/dL; P < 0.001), HbA1c concentrations (+ 14.20 ± 1.04 mmol/mol; P < 0.001), age (+ 7 ± 3 years; P < 0.001), duration of diabetes (15 ± 2 years; P < 0.001), BMI (+ 7.66 ± 2.61 kg/m2; P < 0.001), and lower mean eGDR (- 3.98 ± 1.07; P < 0.001). CONCLUSIONS: Compared to BMI and insulin requirements, classical surrogates of insulin resistance, eGDR is a suitable and superior thrombotic risk indicator in T1D. TRIAL REGISTRATION: ISRCTN4081115; registered 27 June 2017.

Variants in HSD11B1 gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes.

BACKGROUND AND AIM: 11ß-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. MATERIALS AND METHODS: Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). RESULTS: The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96; P = .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37; P = .028). A follow-up study revealed that 29% of the individuals lost ≥5 mL min-1 × 1.73 m2 per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89; P = .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42; P = .004). CONCLUSION: SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals.

Estimated insulin sensitivity in Type 1 diabetes adults using clinical and research biomarkers.

AIMS: Insulin resistance in people with type 1 diabetes (T1D) is associated with increased risk of chronic complications and death. The gold standard to quantify insulin sensitivity, a euglycaemic hyperinsulinaemic clamp, is not applicable to clinical practice. We have employed clamp studies to develop a panel of formulae to estimate insulin sensitivity in adults with T1D for use in clinical practice and trials. METHODS: Clamps were conducted in 28 adults with T1D, who were also characterised with 38 clinical and research biomarkers. Exhaustive search analysis was used to derive equations correlating with clamp-quantified glucose disposal rate (GDR), GDR/plasma insulin (M/I) and log10M/I. RESULTS: Measured insulin sensitivity correlated with BMI, WHR, HDL-C, adipokines and inflammation markers on univariate analysis. Exhaustive search analysis derived three formulae correlating with clamp-derived GDR and logM/I (p < 0.0001), accounting for ≈62% of their variability. A formula using gender, age, HDL-C, pulse pressure and WHR performed as well as those containing inflammation and adipokine measures. CONCLUSIONS: The performance of formulae using routinely available parameters with/without research biomarkers in clinical studies and trials, particularly related to future complications, relevant lifestyle interventions, insulin delivery modes and insulin sensitisers is merited.

Serum Dipeptidyl peptidase-4 level is related to adiposity in type 1 diabetic adolescents.

BACKGROUND: Insulin resistance (IR) plays a great role in type 1 diabetes (T1DM) disease process than is commonly recognized. Dipeptidyl peptidase-4 (DPP-4) is an enzyme that deactivates many bioactive peptides involved in glucose regulation. AIMS: This study evaluates DPP-4 level in adolescent patients with T1DM compared to controls and investigates the relationship between DPP-4 level and IR in these patients. MATERIALS AND METHODS: We measured serum DPP-4 level in 50 patients with T1DM recruited from the Diabetes Endocrine Metabolism Pediatric Unit, and in 80 healthy controls. IR was assessed by the equation for estimated glucose disposal rate (eGDR). Biochemical evaluation including glycated haemoglobin (HbA1C) and lipid profile were included. RESULTS: IR was found in 80% of patients with T1DM. DPP-4 was significantly higher in control group than patients with T1DM. Patients with T1DM were classified into 3 groups according to DPP-4 tertiles showing significant increase in BMI SDS and total cholesterol across the 3 groups. Significant correlation was found between DPP-4 levels and insulin dose. DPP-4 was significantly higher in patients with T1DM with good glycemic control. CONCLUSION: In sample of individuals researched by us, serum DPP-4 was related to adiposity and not to the hyperglycemia in patients with T1DM. Larger sample should be researched to make firm conclusions.

Ethnic variation in the correlation between waist to height ratio and total daily insulin requirement in children with type 1 diabetes: a cross-sectional study.

INTRODUCTION: Total daily insulin required to achieve glycaemic control in type 1 diabetes (T1D) depends on numerous factors. Correlation of insulin requirement to body mass index and waist circumference has been variably reported in the literature and that of waist-to-height ratio has not been studied. AIMS: To study the correlation between daily insulin requirement [total daily dose (TDD)] and waist-to-height ratio (WHtR) in a multiethnic population. METHODS: A cross-sectional study of children (5-18 years) with T1D attending a diabetes clinic in a multiethnic population in Bradford, UK was conducted. Physical measurements were undertaken in the clinic setting and data collected from case notes and patients/carers. RESULTS: Sixty nine patients with mean age 12.7(±3.1) yr, duration of diabetes 5.4(±3.5) yr and hemoglobin A1c (HbA1c) 80(±18)mmol/mol(9.5 ± 1.6%) were recruited. Nearly 54% (n = 37) were white and 46% were non-white (29 Asian Pakistani; 1 Indian; 2 mixed White Afro-Caribbean). The two groups had similar demographics and disease profiles. Non-whites compared with whites had a higher prevalence of obesity (15 vs 5%, p < 0.01), family history of type 2 diabetes (T2D) (49% vs. 33%), microalbuminuria (22% vs. 11%, p < 0.05) and deprivation (mean index of multiple deprivation score 42 vs. 30, p < 0.001). WHtR and TDD were poorly correlated in the whole group. There was however a significant positive correlation in Caucasians (r = 0.583, N = 37, p < 0.01) and a negative correlation in Asian Pakistanis (r = -0.472, N = 32, p < 0.01); with a significant negative correlation seen in subjects with relatives with T2D (r = -0.86, N = 6, p = 0.02). CONCLUSIONS: The variation in correlations highlights that the two ethnic groups behave differently and should therefore be studied separately with regards to factors influencing insulin requirements with careful consideration to the presence of parental IR. Further prospective studies are required to explore the reasons for these differences.

Type 1 diabetes, metabolic syndrome and cardiovascular risk.

Patients with type 1 diabetes mellitus (T1DM) traditionally had a low body mass index and microangiopathic complications were common, while macroangiopathy and the metabolic syndrome were exceptional. The Diabetes Control and Complications Trial, published in 1993, demonstrated that therapy aimed at maintaining HbA1c levels as close to normal as feasible reduced the incidence of microangiopathy. Since then, the use of intensive insulin therapy to optimize metabolic control became generalized. Improved glycemic control resulted in a lower incidence of microangiopathy; however, its side effects included a higher rate of severe hypoglycemia and increased weight gain. Approximately 50% of patients with T1DM are currently obese or overweight, and between 8% and 40% meet the metabolic syndrome criteria. The components of the metabolic syndrome and insulin resistance have been linked to chronic T1DM complications, and cardiovascular disease is now the leading cause of death in these patients. Therefore, new therapeutic strategies are required in T1DM subjects, not only to intensively lower glycemia, but to control all associated metabolic syndrome traits.