Gemma Llauradó

Arterial Stiffness Is Increased in Patients With Type 1 Diabetes Without Cardiovascular Disease: A potential role of low-grade inflammation

OBJECTIVE To investigate the relationship between arterial stiffness and low-grade inflammation in subjects with type 1 diabetes without clinical cardiovascular disease. RESEARCH DESIGN AND METHODS Sixty-eight patients with type 1 diabetes and 68 age- and sex-matched healthy subjects were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (aPWV). Serum concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and soluble fractions of tumor necrosis factor-α receptors 1 and 2 (sTNFαR1 and sTNFαR2, respectively) were measured. All statistical analyses were stratified by sex. RESULTS Subjects with diabetes had a higher aPWV compared with healthy control subjects (men: 6.9 vs. 6.3 m/s, P < 0.001; women: 6.4 vs. 6.0 m/s, P = 0.023). These differences remained significant after adjusting for cardiovascular risk factors. Men with diabetes had higher concentrations of hsCRP (1.2 vs. 0.6 mg/L; P = 0.036), IL-6 (0.6 vs. 0.3 pg/mL; P = 0.002), sTNFαR1 (2,739 vs. 1,410 pg/mL; P < 0.001), and sTNFαR2 (2,774 vs. 2,060 pg/mL; P < 0.001). Women with diabetes only had higher concentrations of IL-6 (0.6 vs. 0.4 pg/mL; P = 0.039). In men with diabetes, aPWV correlated positively with hsCRP (r = 0.389; P = 0.031) and IL-6 (r = 0.447; P = 0.008), whereas in women with diabetes no significant correlation was found. In men, multiple linear regression analysis showed that the following variables were associated independently with aPWV: age, BMI, type 1 diabetes, and low-grade inflammation (R2 = 0.543). In women, these variables were age, BMI, mean arterial pressure, and type 1 diabetes (R2 = 0.550). CONCLUSIONS Arterial stiffness assessed as aPWV is increased in patients with type 1 diabetes without clinical cardiovascular disease, independently of classical cardiovascular risk factors. In men with type 1 diabetes, low-grade inflammation is independently associated with arterial stiffness.

Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes

OBJECTIVES Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects. MATERIALS AND METHODS We compared 32 overweight adult T1DM patients and 32 nondiabetic subjects matched for age, body mass index (BMI), and gender. Liver fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS), body composition by magnetic resonance imaging, and insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique (insulin 0.4 mU/kg · min combined with infusion of D-[3-(3)H]glucose). We also hypothesized that low liver fat might protect from obesity-associated increases in insulin requirements and, therefore, determined insulin requirements across BMI categories in 3164 T1DM patients. RESULTS Liver fat content was significantly lower in T1DM patients than in nondiabetic subjects (0.6% [25th-75th quartiles, 0.3%-1.1%] vs 9.0% [3.0%-18.0%]; P < .001). The endogenous rate of glucose production (R(a)) during euglycemic hyperinsulinemia was significantly lower (0.4 [-0.7 to 0.8] mg/kg fat-free mass · min vs 0.9 [0.2-1.6] fat-free mass · min; P = .012) and the percent suppression of endogenous Ra by insulin was significantly greater (89% [78%-112%] vs 77% [50%-94%]; p = .009) in T1DM patients than in nondiabetic subjects. Serum nonesterified fatty acid concentrations during euglycemic hyperinsulinemia were significantly lower (78.5 [33.0-155.0] vs 306 [200.0-438.0] μmol/L; P < .001) and the percent suppression of nonesterified fatty acids significantly higher (89.1% [78.6%-93.3%] vs 51.4% [36.5%-71.1%]; P < .001) in T1DM patients than in nondiabetic subjects. Insulin doses were similar across BMI categories. CONCLUSIONS T1DM patients might be protected from steatosis and hepatic insulin resistance. Obesity may not increase insulin requirements in T1DM.

Altered Expression of miR-181a-5p and miR-23a-3p Is Associated With Obesity and TNFα-Induced Insulin Resistance

Context The proinflammatory cytokine TNFα is a key player in insulin resistance (IR). The role of miRNAs in inflammation associated with IR is poorly understood. Objective To investigate miR-181a-5p and miR-23a-3p expression profiles in obesity and to study their role in TNFα-induced IR in adipocytes. Design Two separate cohorts were used. Cohort 1 was used in adipose tissue (AT) expression studies and included 28 subjects with body mass index (BMI) <30 kg/m2 and 30 with BMI ≥30 kg/m2. Cohort 2 was used in circulating serum miRNA studies and included 101 subjects with 4 years of follow-up (48 case subjects and 53 control subjects). miR-181a-5p and miR-23a-3p expression was assessed in subcutaneous and visceral AT. Functional analysis was performed in adipocytes, using miRNA mimics and inhibitors. Key molecules of the insulin pathway, AKT, PTEN, AS160, and S6K, were analyzed. Results Expression of miR-181a-5p and miR-23a-3p was reduced in adipose tissue from obese and diabetic subjects and was inversely correlated to adiposity and homeostasis model assessment of IR index. Overexpression of miR-181a-5p and miR-23a-3p in adipocytes upregulated insulin-stimulated AKT activation and reduced TNFα-induced IR, regulating PTEN and S6K expression. Serum levels of miR-181a-5p were reduced in case vs control subjects at baseline, suggesting a prognostic value. Variable importance in projection scores revealed miR-181a-5p had more effect on the model than insulin or glucose at 120 minutes. Conclusion miR-181a-5p and miR-23a-3p may prevent TNFα-induced IR in adipocytes through modulation of PTEN and S6K expression.

Previous Gestational Diabetes Increases Atherogenic Dyslipidemia in Subsequent Pregnancy and Postpartum

In a cohort of women with previous gestational diabetes mellitus (GDM), we aimed to ascertain whether women with abnormal glucose tolerance 1-year postdelivery had a more atherogenic lipid profile during and after pregnancy than those with normal glucose tolerance. A prospective cohort study with longitudinal design between January 2004 and March 2016 was conducted. Three hundred and six (56.8%) of 537 women diagnosed with GDM during the studied period attended a control visit during the first year after delivery. Of these, 112 (36.6%) had prediabetes and 16 (5.2%) had type 2 diabetes mellitus. No significant differences during pregnancy were found in total, low-density lipoprotein, high-density lipoprotein (HDL) cholesterol, and triacylglycerol (TAG) concentrations among the three groups. Only HDL cholesterol and TAG levels differed significantly among groups at 2 and 12 months after delivery. Logistic regression analysis revealed pregnancy HDL and glucose metabolism status to be associated with the HDL cholesterol concentration 1-year postdelivery. Furthermore, the only independent factor associated with TAG levels 1 year after delivery was the gestational TAG concentration. In summary, an overweight multiethnic group of women with prior GDM presented a high incidence of postpartum dysglycemia (41.8%). HDL-cholesterol and TAG levels, both components of the metabolic syndrome, differed significantly among the three study groups in the glucose-metabolism status at 2 and 12 months after delivery. Women with previous GDM must be followed up in the postpartum period for early detection and management of lipid and glucose disorders.

Incidencia y factores asociados al metabolismo alterado de la glucosa un año después del parto en una población multiétnica de mujeres con diabetes mellitus gestacional en España

BACKGROUND AND AIM Women with history of gestational diabetes mellitus (GDM) are at increased risk for diabetes. Ethnicity may modify such risk, but no studies have been conducted in our environment. The aim of this study was to assess the incidence of type 2 diabetes mellitus and prediabetes one year after delivery in women with GDM and in a multiethnic background and to identify the associated factors. PATIENTS AND METHODS A retrospective analysis of a prospective, observational cohort of women with GDM who attended annual postpartum follow-up visits at Hospital del Mar from January 2004 to March 2016. RESULTS Three hundred and five women attended postpartum follow-up visits. Of these, 47.2% were Caucasian, 22% from South-Central Asia, 12% from Latin America, and 10% from Morocco and East Asia. Incidence rates of type 2 diabetes mellitus and prediabetes in these patients were 5.2 and 36.6%, respectively. In a multivariate analysis, non-Caucasian origin (OR=3.15, 95% CI [1.85-5.39]), recurrent gestational diabetes (OR=2.26, 95% CI [1.11-4.59]), and pre-pregnancy body mass index (OR=1.09, 95% CI [1.04-1.15]) were independent predictors of impaired glucose tolerance. CONCLUSIONS In a multiethnic Spanish population of women with GDM, incidence of impaired glucose tolerance in the first year after delivery was 41.8%, with a three-fold increased risk for women of non-Caucasian ethnicity.

Serum Insulin Bioassay Reflects Insulin Sensitivity and Requirements in Type 1 Diabetes

Context Insulin resistance could increase insulin requirements in type 1 diabetes (T1D). Current insulin immunoassays do not detect insulin analogs. Kinase insulin receptor (IR) activation (KIRA) bioassays specific for human IR isoforms A (IR-A) and B (IR-B) permit assessment of all circulating insulin bioactivity. We studied whether IR-A and IR-B KIRA assays are related to direct measures of insulin sensitivity or insulin doses in T1D. Design We evaluated 31 adult patients with T1D (age 45.7 ± 1.6 years, body mass index 28.8 ± 0.7 kg/m2). Serum IR-A and IR-B bioactivities were measured by KIRA bioassays. Insulin sensitivity of glucose production (Ra) was measured by the euglycemic hyperinsulinemic clamp technique in which a low insulin dose (0.4 mU/kg/min for 240 minutes) was combined with D-[3-3H] glucose infusion to measure rates of Ra and utilization and insulin action on antilipolysis from suppression of serum free fatty acids. Results Baseline circulating IR-A bioactivity was 53 ± 7 pmol/L, and IR-B bioactivity was 81 ± 11 pmol/L. Compared with baseline, insulin infusion significantly increased IR-A (P < 0.001) and IR-B (P < 0.001) bioactivities. Fasting IR-A and IR-B bioactivities were positively related to endogenous Ra (r = 0.44, P = 0.01 and r = 0.38, P < 0.05). Fasting IR-A (r = 0.43, P = 0.02) and IR-B (r = 0.47, P = 0.01) bioactivities were significantly correlated with insulin requirements and glycosylated hemoglobin (IR-A: r = 0.52, P = 0.002; IR-B: r = 0.48, P = 0.006). Conclusions Circulating IR-A and IR-B bioactivities are associated with insulin resistance, high insulin requirements, and poor glycemic control in T1D. Measurement of IR bioactivity by KIRA assays provides a tool to assess the amount of biologically active insulin in groups of T1D patients treated with insulin analogs.

Ethnic Differences in the Risk of Developing Metabolic Syndrome or itsComponents in Women with a History of Gestational Diabetes Mellitus

Women with a history of gestational diabetes mellitus (GDM) are known to be at increased risk for diabetes and cardiovascular disease. Other cardiovascular risk factors that integrate the metabolic syndrome also seem to be more prevalent in this group of women. On the other hand, several studies have shown that there is an ethnic effect on disease risk. Prevalence of type 2 diabetes, gestational diabetes and other cardiovascular risk factors vary greatly in populations of different ethnicity. Therefore, we have reviewed the available evidence on the prevalence of the metabolic syndrome components in women with previous GDM along with the differential characteristics of each ethnic group.