Severe hypoglycemia and hypoglycemia awareness are associated with preclinical atherosclerosis in patients with type 1 diabetes without an estimated high cardiovascular risk.

AIMS: To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated. RESULTS: We included 634 patients (52.4% men, age 48.3 ± 10.8 years, T1D duration 27.4 ± 11.1 years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p < 0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n = 192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n = 436; ≥2 plaques: OR 1.2 [1.0-1.5], p = 0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p = 0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p = 0.036). CONCLUSIONS: In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach.

Adherence to an energy-restricted Mediterranean diet is associated with the presence and burden of carotid atherosclerosis in people with type 1 diabetes.

AIMS: People with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD). The Mediterranean diet is associated with reduced CVD; however, the evidence in T1D is scarce. We aimed to analyse the relationships between adherence to the energy-restricted Mediterranean diet (erMEDd) and carotid atherosclerosis. MATERIALS AND METHODS: We included children with T1D without CVD, with ≥1 of the following: age ≥40 years, diabetic kidney disease, or ≥10 years of disease duration with another risk factor. Plaque presence (intima-media thickness ≥1.5 mm) was determined by ultrasonography. The PREDIMED-Plus 17-item questionnaire (PP-17) was used to assess adherence to the erMEDd. RESULTS: Four hundred one individuals were included (48% males, age 48.3 ± 11 years, diabetes duration 26.8 ± 11.4 years). Those harbouring plaques (42%) showed lower adherence to the erMEDd (PP-17: 8.9 ± 2.3 of a maximum of 17 vs. 9.8 ± 2.5, p < 0.001). Greater adherence to the erMEDd was correlated with an overall better metabolic profile. After adjusting for multiple confounders, adherence to the erMEDd was independently associated with carotid atherosclerosis (OR 0.86 [0.77-0.95] for plaque presence and OR 0.85 [0.75-0.97] for ≥2 plaques). The consumption of fruit and nuts and preference of white over red meat was higher in individuals without atherosclerosis (p < 0.05). Fruit and nut consumption was associated with lower plaque prevalence in the fully adjusted models (OR 0.38 [0.19-0.73] and 0.51 [0.29-0.93]). CONCLUSIONS: Greater adherence to the erMEDd is associated with less carotid atherosclerosis in children with T1D at high risk of CVD. Strategies to improve and implement healthy dietary patterns in this population should be encouraged.

Tacrolimus's Time Below Therapeutic Range Is Associated With Acute Pancreatic Graft Rejection and the Development of De Novo Donor-specific Antibodies.

Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.

Neutrophil-to-lymphocyte ratio is independently associated with carotid atherosclerosis burden in individuals with type 1 diabetes.

BACKGROUND AND AIMS: Recent studies have identified a relationship between innate versus. Adaptative immunity and cardiovascular disease (CVD) in the general population, but information on type 1 diabetes (T1D) is lacking. We aimed to study the relationship between inflammatory biomarkers and preclinical atherosclerosis in this population. METHODS AND RESULTS: Cross-sectional study in T1D individuals without CVD and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of diabetes duration with classical CVD risk factors. Carotid plaques were evaluated by ultrasonography. C-reactive protein, total leukocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index were assessed as inflammatory markers. Multivariate-adjusted models including age, sex, and other CVD risk factors were constructed to test their independent associations with atherosclerosis burden. We included 602 subjects (52.8% men, 48.7 ± 10.2 years old and 27.0 ± 10.5 years of diabetes duration). Carotid plaques were found in 41.2% of the individuals (12.8%, ≥3 plaques). The number of carotid plaques (none, 1-2, ≥3 plaques), was directly associated with the leukocyte count (6570 [5445-8050], 6640 [5450-8470] and 7310 [5715-8935] per mm3, respectively; p for trend = 0.021) and the NLR (1.63 [1.28-2.13], 1.78 [1.38-2.25] and 2.14 [1.58-2.92], respectively; p for trend <0.001), but only the NLR remained directly associated in fully-adjusted models (presence of plaques; OR 1.285 [1.040-1.587]; ≥3 plaques, OR 1.377 [1.036-1.829]). CONCLUSIONS: The NLR was independently and directly associated with carotid plaque burden in T1D individuals. Our data support the role of innate versus. Adaptative immunity in atherosclerosis also among the T1D population.

Advanced lipoprotein profile identifies atherosclerosis better than conventional lipids in type 1 diabetes at high cardiovascular risk.

BACKGROUND AND AIMS: People with type 1 diabetes (T1D) present lipoprotein disturbances that could contribute to their increased cardiovascular disease (CVD) risk. We evaluated the relationship between lipoprotein alterations and atherosclerosis in patients with T1D. METHODS AND RESULTS: Cross-sectional study in subjects with T1D, without previous CVD, but high-risk (≥40 years, nephropathy, or ≥10 years of evolution of diabetes with another risk factor). The presence of plaque (intima-media thickness ≥1.5 mm) in the different carotid segments was determined by ultrasound. The advanced lipoprotein profile was analysed by magnetic resonance imaging (1H NMR). We included 189 patients (42% women, 47.8 ± 10.7 years, duration of diabetes 27.3 ± 10.1 years, HbA1c 7.5% [7-8]). Those with carotid plaques (35%) were older, with longer diabetes duration, had a higher prevalence of hypertension, and showed lower and smaller LDL particles (LDL-P) and HDL particles (HDL-P), but higher VLDL particles (VLDL-P). Some LDL, HDL and VLDL-related parameters were associated with atherosclerosis in sex, age and statin use adjusted models (p < 0.05), but after adjusting for multiple confounders, including conventional lipid parameters, only HDL-P (OR 0.440 [0.204-0.951]; p = 0.037), medium HDL-P (OR 0.754 [0.590-0.963]; p = 0.024), HDL-P cholesterol content (OR 0.692 [0.495-0.968]; p = 0.032), 1H NMR LDL-P number/conventional LDL-cholesterol (OR 1.144 [1.026-1.275]; p = 0.015), and 1H NMR non-HDL particle number/conventional non-HDL-cholesterol ratios (OR 1.178 [1.019-1.361], p = 0.026) remained associated with atherosclerosis. CONCLUSIONS: In adults with T1D at high-risk, variables related to HDL, LDL and total atherogenic particle number are independently associated with preclinical atherosclerosis. Advanced lipoprotein profiling could be used to identify those at the highest risk of CVD.

Results of a multidisciplinary strategy to improve the management of cardiovascular risk factors after liver transplantation.

Although liver transplantation (LT) recipients are at high cardiovascular risk (CVR), the management of CVR factors (CVRF) after LT is far from optimal and needs to be improved. For this reason, we developed a multidisciplinary protocol to standardize the identification, risk stratification, management, and targets of therapy of CVRF during the first post-LT year. The grade of identification and control of CVRF 12 months after LT in the postintervention cohort (LT January 2018-January 2020, n = 150) were compared with a control cohort who underwent LT between July 2015 and December 2016 (n = 100). Before LT, the prevalence of metabolic-associated fatty liver disease as the indication of LT and the presence of obesity were significantly higher in the postintervention cohort, whereas the prevalence of other CVRF and renal dysfunction tended to be higher. Cyclosporine A was used less frequently in the postintervention cohort, whereas everolimus tended to increase. At 12 months after LT, the proportion of patients with measured blood pressure (88% vs. 56%), glycosilated hemoglobin (HbA1c; 96% vs. 72%), and high-density lipoprotein/low-density lipoprotein cholesterol (67% vs. 33%) was higher in the postintervention than in the control cohort (all p < 0.001). Blood pressure (64% vs. 36%, p = 0.02) and HbA1c (85% vs. 70%, p = 0.1) were within target in more individuals with hypertension and diabetes mellitus, respectively, in the postintervention cohort. Median total cholesterol levels were lower in the postintervention (184 mg/dl; interquartile range [IQR], 160-210 mg/dl) than in the control cohort (212 mg/dl; IQR, 186-240 mg/dl; p = 0.02). At 2 years after LT, the incidence of cardiovascular events was 14% in the control cohort and 6% in the postintervention cohort (p = 0.063). In conclusion, a multidisciplinary, multiprofessional strategy can achieve a higher grade of assessment and management of post-LT CVR despite a worsening metabolic profile of LT recipients.

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program.

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components.

Linoleic Acid Status in Cell Membranes Inversely Relates to the Prevalence of Symptomatic Carotid Artery Disease.

BACKGROUND AND PURPOSE: The red blood cell fatty acid composition objectively reflects the long-term dietary intake of several fatty acids. In patients undergoing carotid endarterectomy, we explored whether red blood cell status of selected fatty acids related to symptomatic carotid artery disease. METHODS: We included patients with symptomatic (n=22) and asymptomatic (n=23) carotid artery disease. We determined all-C18:1 trans, linoleic acid (LA, C18:2n6), alpha-linolenic acid (C18:3n3), and the omega-3 index (sum of eicosapentaenoic [C20:5n3] and docosahexaenoic [C22:6n3] acids) in both red blood cells and carotid plaque phospholipids by gas-chromatography. RESULTS: In a multivariate logistic regression analysis, we only observed a significant association for LA, whose red blood cell status was inversely related to symptomatic carotid artery disease (odds ratio, 0.116 [95% CI, 0.022-0.607], P=0.011, for each 1-SD increase). A similar result was observed for LA in carotid plaque phospholipids. CONCLUSIONS: Cell membrane enrichment in LA, which reflects its intake, was inversely related to symptomatic carotid disease. This increases evidence supporting a favorable role of dietary LA in vascular health.

Nuclear magnetic resonance lipoproteins are associated with carotid atherosclerosis in type 1 diabetes and pre-eclampsia.

AIMS: Persistence of lipoprotein abnormalities in type 1 diabetes (T1D) and/or pre-eclampsia could be associated with cardiovascular disease (CVD). We assessed differences in the advanced lipoprotein profiles according to the presence of both conditions and their differential association with atherosclerosis. MATERIAL AND METHODS: We recruited 112 women without CVD and last pregnancy ≥5 years previously, divided into four groups (n = 28 per group): (a) T1D and previous pre-eclampsia; (b) T1D without pre-eclampsia; (c) pre-eclampsia without T1D; and (d) controls (without T1D/pre-eclampsia). Groups were matched by several risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥1.5 mm) were assessed by ultrasonography. The lipoprotein profile was evaluated by nuclear magnetic resonance (NMR) spectroscopy. RESULTS: The participants were 44.9 ± 7.8 years old. Carotid plaque presence was 20.5%, with a higher prevalence in T1D and/or pre-eclampsia vs controls (P < .05). High-density lipoprotein (HDL)-related variables differed among groups, mainly driven by an increase in T1D (P < .05), whereas triglyceride-related variables were increased in pre-eclampsia [medium very low-density lipoprotein (VLDL) particles and triglyceride enrichment in HDL and low-density lipoprotein (LDL)]. Overall, in multivariate-adjusted models, LDL-related variables were the most strongly associated with atherosclerosis (P < .05). In age- and statin-adjusted models, previous pre-eclampsia showed an independent association with triglyceride-related variables (plaque: medium-VLDL-particles, OR 1.550 [1.013-2.374]; HDL-cholesterol/HDL-triglycerides ratio, OR 0.411 [0.175-0.967]). Regarding T1D, HDL-parameters were also differentially associated (maximum-IMT: HDL-cholesterol/HDL-particles ratio, ß = -.258, P = .036). CONCLUSIONS: NMR lipoproteins were differentially and independently associated with atherosclerosis in T1D/pre-eclampsia. Further studies are needed to ascertain the role of NMR parameters as CVD biomarkers in this high-risk population.

Biomarkers of fatty acid intake are independently associated with preclinical atherosclerosis in individuals with type 1 diabetes.

PURPOSE: Information on the association between diet and cardiovascular disease (CVD) in type 1 diabetes (T1D) is scarce. We assessed the association between biomarkers of fatty acid (FA) intake and the presence of carotid plaques (a surrogate marker of future CVD events) in this high-risk population. METHODS: Cross-sectional study in 167 consecutive T1D patients without CVD and with at least one of the following: ≥ 40 years, diabetic nephropathy, or ≥ 10 years of T1D duration with another CVD risk factor. The FA profile of erythrocyte membranes was determined by gas chromatography, and the number of carotid plaques (intima-media thickness ≥ 1.5 mm) was assessed by ultrasonography. Regression models were constructed adjusting for classical (age, gender, blood pressure, smoking habit, LDL-cholesterol, body mass index and statins) and T1D-specific risk factors (diabetes duration, HbA1c and chronic complications). RESULTS: A total of 58.7% were men (mean age 48.3 ± 10.3 years, T1D duration 27.2 ± 10.1 years). Sixty-one patients (36.5%) showed carotid plaque. Linoleic acid decreased and all-C18:1trans increased with the number of carotid plaques (none, 1-2, ≥ 3 plaques; p for trend < 0.05). In multivariate regression models, linoleic acid remained inversely associated with the presence of plaque [1% increase of total FAs; OR 0.71 (0.53-0.95), p = 0.021] and ≥ 2 plaques [OR 0.70 (0.51-0.98), p = 0.039]; whereas, all-C18:1trans was positively associated with ≥ 3 plaques (0.1% increase of total FAs; OR 1.51 [1.05-2.16], p = 0.026). CONCLUSIONS: Erythrocyte FA composition, as a biomarker of FA intake, was independently associated with preclinical atherosclerosis in T1DM. Our data support the potential role of an unfavorable pattern of fat intake and CVD risk in this population.

Novel glycoproteins identify preclinical atherosclerosis among women with previous preeclampsia regardless of type 1 diabetes status.

BACKGROUND AND AIMS: Information regarding inflammation and cardiovascular disease (CVD) risk in type 1 diabetes (T1D) or preeclampsia (PE) is scarce. We assessed differences in inflammation markers according to the presence of both conditions and their association with atherosclerosis. METHODS AND RESULTS: We recruited 112 women without CVD and last pregnancy ≥5 years previously (n = 28 per group): a)T1D and PE; b)T1D without PE; c)PE without T1D; and d)Controls (without T1D or PE). Groups were matched by several CVD risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by ultrasonography. Inflammatory markers included classical variables (leucocytes and high-sensitivity C-reactive protein [hsCRP]) and glycoproteins by nuclear magnetic resonance (1H-NMR) spectroscopy (GlycA, GlycB, GlycF and the height/width [H/W] ratios of GlycA and GlycB). The age of the participants was 44.9 ± 7.8 years, and 20.5% harbored plaque. There were no differences in inflammatory markers among the four study groups. Overall, in multivariate-adjusted models, all 1H-NMR-glycoproteins (except GlycB) were positively associated with IMT measures (IMT of bulb and maximum-IMT of any carotid segment; p < 0.05). After dividing the sample according to PE status, previous findings remained largely unchanged. Furthermore, GlycF was independently associated with carotid plaque only in PE group (OR 5.08 [1.03-25.01] per 0.1 log-increments, p = 0.046). Neither leucocytes nor hsCRP were related to atherosclerosis. Regarding T1D status, non-uniform results were observed. CONCLUSIONS: High 1H-NMR-glycoprotein concentrations have a negative impact on carotid atherosclerosis among women with preeclampsia, regardless of T1D status.

Quantification of glycoproteins by nuclear magnetic resonance associated with preclinical carotid atherosclerosis in patients with type 1 diabetes.

BACKGROUND AND AIMS: Glycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. METHODS AND RESULTS: We selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7-55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p < 0.05), with no association in patients receiving this drug (p for interaction <0.05; in ≥2 plaques). Finally, in models adjusted for other classical and T1D-specific risk factors, GlycA and GlycB H/W ratios remained associated with carotid plaque (OR 1.39 [1.12-1.90] and OR 6.89 [1.85-25.62], respectively). CONCLUSION: In T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.

Advanced lipoprotein profile disturbances in type 1 diabetes mellitus: a focus on LDL particles.

BACKGROUND: Lipoprotein disturbances have been associated with increased cardiovascular disease (CVD) risk in type 1 diabetes mellitus (T1DM). We assessed the advanced lipoprotein profile in T1DM individuals, and analysed differences with non-diabetic counterparts. METHODS: This cross-sectional study involved 508 adults with T1DM and 347 controls, recruited from institutions in a Mediterranean region of Spain. Conventional and advanced (assessed by nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analysed. Crude and adjusted (by age, sex, statin use, body mass index and leukocyte count) comparisons were performed. RESULTS: The median (interquartile range) age of the study participants was 45 (38-53) years, 48.2% were men. In the T1DM group, the median diabetes duration was 23 (16-31) years, and 8.1% and 40.2% of individuals had nephropathy and retinopathy, respectively. The proportion of participants with hypertension (29.5 vs. 9.2%), and statin use (45.7% vs. 8.1%) was higher in the T1DM vs. controls (p < 0.001). The T1DM group had a better conventional (all parameters, p < 0.001) and NMR-lipid profile than the control group. Thus, T1DM individuals showed lower concentrations of atherogenic lipoproteins (VLDL-particles and LDL-particles) and higher concentrations of anti-atherogenic lipoproteins (HDL-particles) vs. controls, even after adjusting for several confounders (p < 0.001 for all). While non-diabetic women had a more favourable lipid profile than non-diabetic men, women with T1DM had a similar concentration of LDL-particles compared to men with T1DM (1231 [1125-1383] vs. 1257 [1128-1383] nmol/L, p = 0.849), and a similar concentration of small-LDL-particles to non-diabetic women (672.8 [614.2-733.9] vs. 671.2 [593.5-761.4] nmol/L, respectively; p = 0.790). Finally, T1DM individuals showed higher discrepancies between NMR-LDL-particles and conventional LDL-cholesterol than non-diabetic subjects (prevalence of LDL-cholesterol < 100 mg/dL & LDL-particles > 1000 nmol/L: 38 vs. 21.2%; p < 0.001). All these differences were largely unchanged in participants without lipid-lowering drugs (T1DM, n = 275; controls, n = 317). CONCLUSIONS: Overall, T1DM participants showed a more favourable conventional and NMR-lipid profile than controls. However, the NMR-assessment identified several lipoprotein derangements in LDL-particles among the T1DM population (higher discrepancies in NMR-LDL-particles vs. conventional LDL-cholesterol; a worse profile in T1DM women) that were overlooked in the conventional analysis. Further studies are needed to elucidate their role in the development of CVD in this population.

Insulin resistance is associated with preclinical carotid atherosclerosis in patients with type 1 diabetes.

AIM: Although insulin resistance (IR) is a growing trait among type 1 diabetes (T1D) population, its relationship with atherosclerosis has been scarcely studied. We assessed the association between IR indexes and carotid atherosclerosis in T1D, a population at high cardiovascular disease (CVD) risk. MATERIALS AND METHODS: We evaluated 191 participants with T1D and no prior CVD with at least one of the following criteria: ≥40 years old; diabetic nephropathy; or T1D duration ≥10 years harbouring ≥1 additional CVD risk factor. IR was assessed with the metabolic syndrome (MetS) harmonized definition proposed in 2009 and the estimated glucose disposal rate (eGDR), a T1D-specific IR surrogate marker (lower values indicating higher IR). Standardized carotid ultrasonography was performed, recording intima-media thickness (IMT), plaque presence and maximum height of plaque. Comparisons between patients according to their MetS status as well as concerning eGDR values were performed. RESULTS: The participants' median age was 47.4 (41.1-53.3) years and diabetes duration 25.7 (21.6-32.5) years. Plaque prevalence was higher in patients with greater IR (49.1%, 29.1% and 20%, P = .001, for any plaque according to decreasing eGDR tertiles). Conversely, no statistically significant higher plaque prevalence was found in participants with MetS. In multivariate analyses (adjusted for general- and T1D-specific risk factors, and statin treatment), MetS was associated with neither IMT nor plaque. On the contrary, eGDR was independently related to ≥2 plaques (P = .018) and maximum plaque height (P < .01). CONCLUSIONS: In T1D, IR assessed through eGDR but not by MetS definition was independently associated with plaque burden, a predictor of CVD.

Dietary polyunsaturated fatty acids mediate the inverse association of stearoyl-CoA desaturase activity with the risk of fatty liver in dyslipidaemic individuals.

PURPOSE: The activity of stearoyl-CoA desaturase-1 (SCD1) is increased in non-alcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) inhibit SCD1, but clinical studies on whether all dietary PUFA species are equal in SCD1 inhibition are scarce. Serum phospholipids are an objective proxy of dietary intake of plant-derived PUFA (C18:2n-6, C18:3n-3) and marine-derived PUFA (C20:5n-3, C22:6n-3). In 355 participants with primary dyslipidemia, we cross-sectionally investigated whether the presumed association between surrogate markers of NAFLD and SCD1 activity is mediated by intake of PUFA, and, if it is, what PUFA species are relevant in this regard. METHODS: We determined the fatty acid profile of serum phospholipids by gas chromatography, and used the ratio C16:1n-7/C16:0 as a marker of SCD1 activity. NAFLD was diagnosed by values ≥ 60 in the fatty liver index (FLI), a surrogate recently validated against ultrasonography. RESULTS: FLI ≥ 60 was detected in 37.5% (n = 133) of study participants. In a multivariate model, SCD1 activity showed an expected significant association with the risk of NAFLD, with odds ratio (OR) (95% confidence interval) of 1.44 (1.04-2.01) for each 0.01 increase. In a model further allowing the stepwise inclusion of plant-derived PUFA, marine-derived PUFA, and total PUFA (vegetable + marine), total PUFA replaced SCD1 activity as a significant (inverse) association of NAFLD, with OR 0.89 (0.81-0.99). CONCLUSIONS: Total PUFA, regardless of their origin, mediates the relationship between SCD1 activity and NAFLD. This provides a new insight in the protective effects of PUFA against NAFLD, heretofore mostly focussed on PUFA species from marine origin.

Relationship Between Total Serum Bilirubin Levels and Carotid and Femoral Atherosclerosis in Familial Dyslipidemia.

OBJECTIVE: Bilirubin is a potent antioxidant that has been inversely related to cardiovascular disease. There is little information on serum total bilirubin (TB) in relation to atherosclerosis in familial dyslipidemia. We assessed the association between TB and carotid and femoral atherosclerosis in this high-risk group. APPROACH AND RESULTS: We evaluated 464 individuals with familial dyslipidemia (56% men; median age, 48 years), 322 with familial hypercholesterolemia, and 142 with familial combined hyperlipidemia. Carotid and femoral arteries were imaged bilaterally with a standardized ultrasonographic protocol. Mean and maximum intima-media thickness and plaque presence (≥1.2 mm) and height were recorded. Cross-sectional associations between TB and atherosclerosis variables were investigated in multivariable-adjusted models, including lipid values and hypolipidemic drug use. Inflammatory markers (C-reactive protein, total leukocyte count, and lipoprotein[a]) were also determined. Increasing TB levels were associated with decreasing intima-media thickness of all carotid segments (P<0.05, all). TB also related to carotid plaque, present in 78% of individuals, and to plaque burden (≥3 plaques), with odds ratios (95% confidence interval) 0.59 (0.36-0.98) and 0.57 (0.34-0.96) for each increase of 0.5 mg in TB, respectively. Findings were confirmed in a validation cohort of 177 subjects with nonfamilial dyslipidemia. Only the familial combined hyperlipidemia group, with higher inflammation-related markers, showed an inverse association between TB and femoral plaque height (ß=-0.183; P=0.030). CONCLUSIONS: TB was inversely and independently associated with carotid plaque burden in familial and nonfamilial dyslipidemia. These findings support the use of TB as a biomarker of atherosclerosis in this high-risk group.

Detailed description of a prepregnancy care program and its impact on maternal glucose control, weight gain, and dropouts.

BACKGROUND: The aim of this study was to analyze the clinical and metabolic changes observed during a prepregnancy care (PPC) program. METHODS: We performed a retrospective, observational, cohort study of 104 women with type 1 diabetes initiating a PPC program from 2011 to 2014. The outcomes measured were changes in HbA1c levels, weight and hypoglycemic events during PPC. Risk factors associated with severe hypoglycemia events, achieving the HbA1c target and dropouts were evaluated. RESULTS: HbA1c decreased from 7.2 ± 0.8% (55.3 ± 8.8 mmol/mol) to 6.7 ± 0.9% (49.8 ± 10.3 mmol/mol) (P < .001) within a median of 14.2 months (interquartile interval 5.4-23.2); 71.2% obtained HbA1c  < 7% (53 mmol/mol). HbA1c at the end of PPC was associated with baseline HbA1c (ß = .318, P = .001) and the number of previous pregnancies (ß = .224, P = .038), PPC was accompanied by 1.4 ± 4.0 kg weight gain (P = .003) without changes in severe hypoglycemic events. The risk factors for severe hypoglycemia were severe hypoglycemic events during the 2 years before (odds ratio [OR] 11.99, confidence interval 95% 1.89-75.95) and PPC duration (OR 1.09, 1.03-1.16). A total of 33 patients (31.7%) dropped out from PPC during follow-up, with dropout being associated with age (OR 1.17, 1.04-1.36) and PPC duration (OR 1.06, 1.02-1.11). CONCLUSIONS: Our PPC program was associated with an improvement in glycemic control without a significant increase in severe hypoglycemic events, although with some weight gain. A considerable number of patients dropped out during follow-up, this being related to older age and a longer duration of the program. This information could be of help to design new and more effective PPC approaches. Copyright © 2016 John Wiley & Sons, Ltd.

The Effect of Corticosteroid Withdrawal on Glucose Metabolism and Anti-GAD Antibodies in Simultaneous Pancreas-Kidney Transplant Patients.

CONTEXT: Corticosteroid withdrawal may reduce insulin resistance; however, it could also influence pancreatic autoantibody profile in simultaneous pancreas-kidney (SPK) transplant patients. OBJECTIVE: To evaluate the effect of corticosteroid withdrawal on glucose metabolism and anti-glutamic acid decarboxylase (GAD) antibody titers in SPK patients with type 1 diabetes after 12 months of follow-up. DESIGN: In this retrospective study, fasting glucose and glycated hemoglobin (A1c) were compared before and after 3, 6, and 12 months of corticosteroid withdrawal in 80 SPK patients. In addition, weight, anti-GAD, and C-peptide levels were compared before and after withdrawal. Finally, fasting and postglucose, insulin, and C-peptide levels were compared before and after withdrawal in 25 patients undergoing oral glucose tolerance test (OGTT). RESULTS: Fasting glucose levels did not change during corticosteroid discontinuation. After 12 months, A1c slightly increased from 4.6% (0.4%) to 4.8% (0.6%) (P < .01) and C-peptide decreased from 2.8 (1.1) ng/mL to 2.4 (1.3) ng/mL (P <. 01). In patients submitted to OGTT, glucose, insulin, and C-peptide levels did not change. There was no alteration in the proportion of anti-GAD positive tests (41% vs 45%). Anti-GAD titers remained stable or decreased in 70% of positive patients. CONCLUSION: Corticosteroid withdrawal has no significant effect on glucose metabolism and on anti-GAD profile among SPK patients.