Novel biomarkers are needed to better predict coronary artery calcification (CAC), a marker of subclinical atherosclerosis, and diabetic kidney disease (DKD) in type 1 diabetes. We evaluated the associations between serum uromodulin (SUMOD [a biomarker associated with anti-inflammatory and renal protective properties]), CAC progression, and DKD development over 12 years. RESEARCH DESIGN AND METHODS Participants (n = 527, 53% females) in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were examined during 2002-2004, at a mean age of 39.6 6 9.0 years and a median duration of diabetes of 24.8 years. Urine albumin-tocreatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) determined by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation were measured at baseline and after a mean follow-up period of 12.1 6 1.5 years. Elevated albumin excretion was defined as ACR ‡30 mg/g, rapid GFR decline (>3 mL/min/1.73 m 2 /year), and impaired GFR as eGFR <60 mL/min/1.73 m 2. SUMOD was measured on stored baseline plasma samples (Meso Scale Discovery). CAC was measured using electron beam computed tomography. CAC progression was defined as a change in the square root-transformed CAC volume of ‡2.5. RESULTS Higher baseline SUMOD level conferred lower odds of CAC progression (odds ratio 0.68; 95% CI 0.48-0.97), incident elevated albumin excretion (0.37; 0.16-0.86), rapid GFR decline (0.56; 0.35-0.91), and impaired GFR (0.44; 0.24-0.83) per 1 SD increase in SUMOD (68.44 ng/mL) after adjustment for baseline age, sex, systolic blood pressure, LDL cholesterol, and albuminuria/GFR. The addition of SUMOD to models with traditional risk factors also significantly improved the prediction performance for CAC progression and incident DKD. CONCLUSIONS Higher baseline SUMOD level predicted lower odds of both CAC progression and incident DKD over 12 years in adults with type 1 diabetes.

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Adolescents with type 2 diabetes (T2D) have severe insulin resistance (IR) secondary to obesity, genetics, and puberty, and IR predicts metabolic comorbidities. Adults with T2D have multitissue IR, which has guided therapeutic developments, but this is not established in youth. We sought to assess adipose, hepatic, and peripheral insulin sensitivity in adolescents with and without T2D. Twenty-seven youth with T2D [age: 15.6 ± 0.4 yr; female: 78%; body mass index (BMI) percentile: 96.1 (52.6, 95.9), late puberty; hemoglobin A1c (HbA1c) 7.3% (6.2, 10.1)] and 21 controls of similar BMI, pubertal stage, and habitual activity were enrolled. Insulin action was measured with a four-phase hyperinsulinemic-euglycemic clamp (basal, 10, 16, and 80 mU·m−2·min−1 for studying adipose, hepatic, and peripheral IR, respectively) with glucose and glycerol isotope tracers. Total fat mass, fat-free mass, liver fat fraction, and visceral fat were measured with dual-energy x-ray absorptiometry (DXA) and MRI, respectively. Free fatty acids (FFAs), lipid profile, and inflammatory markers were also measured. Adolescents with T2D had higher lipolysis ( P = 0.012), endogenous glucose production ( P < 0.0001), and lower glucose clearance ( P = 0.002) during hyperinsulinemia than controls. In T2D, peripheral IR positively correlated to FFA ( P < 0.001), inflammatory markers, visceral ( P = 0.004) and hepatic fat ( P = 0.007); hepatic IR correlated with central obesity ( P = 0.004) and adipose IR ( P = 0.003). Youth with T2D have profound multitissue IR compared with BMI-equivalent youth without T2D. The development of multitissue interactions appears crucial to the pathogenesis of T2D. Therapeutic targets on multitissue IR may be of benefit, deserving of further research.

The use of rapid DNA sequencing technology in severely ill children in developed countries can accurately identify diagnoses and positively impact patient outcomes. This study sought to evaluate the outcome of Thai children and adults with unknown etiologies of critical illnesses with the deployment of rapid whole exome sequencing (rWES) in Thailand. We recruited 54 unrelated patients from 11 hospitals throughout Thailand. The median age was 3 months (range, 2 days–55 years) including 47 children and 7 adults with 52% males. The median time from obtaining blood samples to issuing the rWES report was 12 days (range, 5–27 days). A molecular diagnosis was established in 25 patients (46%), resulting in a change in clinical management for 24 patients (44%) resulting in improved clinical outcomes in 16 patients (30%). Four out of seven adult patients (57%) received the molecular diagnosis which led to a change in management. The 25 diagnoses comprised 23 different diseases. Of the 34 identified variants, 15 had never been previously reported. This study suggests that use of rWES as a first‐tier investigation tool can provide tremendous benefits in critically ill patients with unknown etiology across age groups in Thailand.

Youth with type 1 diabetes (T1D) carry greater cardiovascular disease (CVD) risk than their nondiabetic peers. Low serum uromodulin (SUMOD) associates with increased CVD mortality in adults. We found that T1D youth have low SUMOD. Lower SUMOD correlated with aortic stiffness, suggesting its potential as a CVD biomarker in T1D.

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Objective We sought to evaluate copeptin concentrations in adolescents with and without type 1 diabetes (T1D) and examine the associations between copeptin and measures of arterial stiffness and kidney dysfunction. Research design and methods This analysis included 169 adolescents with T1D (12‐19 years of age, 59% girls, mean HbA1c 9.0 ± 1.5% and diabetes duration of 8.6 ± 2.9 years), in addition to 61 controls without T1D. Arterial stiffness including carotid‐femoral pulse wave velocity (CF‐PWV), carotid‐radial PWV (CR‐PWV), augmentation index normalized to heart rate of 75 bpm (AIx@HR75), and brachial artery distensibility (BAD). Serum copeptin, urinary albumin‐to‐creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) by serum creatinine and cystatin C were also assessed. Results Compared to controls, adolescents with T1D had higher median (Q1‐Q3) copeptin (7.5 [5.2‐11.3] vs 6.4 [4.8‐8.3] pmol/L, P = .01), mean ± SD eGFR (121 ± 23 vs 112 ± 16 mL/min/1.73m2, P = .002) and lower BAD (7.1 ± 1.3 vs 7.2 ± 1.2%, P = .02). Adolescents with T1D in the in high tertile copeptin group (>9.1 pmol/L) had higher AIx@HR75 (10.7 ± 1.2 vs 5 ± 1.2, P = .001), CR‐PWV (5.30 ± 1.0 vs 5.18 ± 1.0 m/s, P = .04), and UACR (12 ± 1 vs 8 ± 1 mg/g, P = .025) compared to those in low tertile (<5.8 pmol/L) after adjusting for age, sex, and eGFR. Copeptin inversely associated with CF‐PWV independent of age, sex, eGFR, SBP, and HbA1c in T1D adolescents. Conclusions Our data demonstrate that elevated copeptin was associated with worse arterial stiffness in adolescents with T1D. These findings suggest that copeptin could improve CVD risk stratification in adolescents with T1D.

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