Intramuscular diacylglycerol accumulates with acute hyperinsulinemia in insulin-resistant phenotypes.

Elevated skeletal muscle diacylglycerols (DAG) and ceramides can impair insulin signaling, and acylcarnitines (acylCN) reflect impaired fatty acid oxidation, thus the intramuscular lipid profile is indicative of insulin resistance. Acute (i.e., postprandial) hyperinsulinemia has been shown to elevate lipids in healthy muscle and is an independent risk factor for type 2 diabetes (T2D). It is unclear how the relationship between acute hyperinsulinemia and the muscle lipidome interacts, thus contributing to or exacerbating insulin resistance. We investigated the impact of acute hyperinsulinemia on the muscle lipidome in order to help characterize the physiological basis in which hyperinsulinemia elevates T2D risk. Endurance athletes (n=12), sedentary lean adults (n=12), and individuals with obesity (n=13) and T2D (n=7) underwent a hyperinsulinemic-euglycemic clamp with muscle biopsies. While there were no significant differences in total 1,2-DAG fluctuations, there was a 2% decrease in athletes versus a 53% increase in T2D. C18 1,2-DAGs increased during the clamp with T2D only, which negatively correlated with insulin sensitivity. Basal muscle C18:0 ceramides were elevated with T2D, but not altered by clamp. Acylcarnitines were universally lowered during hyperinsulinemia, with more robust reductions of 80% in athletes compared to only 46% with T2D. Similar fluctuations with acute hyperinsulinemia increasing 1,2 DAGs in insulin-resistant phenotypes and universally lowering acylcarnitines were observed in male mice. In conclusion, acute hyperinsulinemia elevates muscle 1,2-DAG levels with insulin-resistant phenotypes. This suggests a possible dysregulation of intramuscular lipid metabolism in the fed state in individuals with low insulin sensitivity, which may exacerbate insulin resistance.

Reduced Efficacy of Glucagon-Like Peptide-1 Receptor Agonists Therapy in People With Type 1 Diabetes and Genetic Forms of Obesity.

BACKGROUND: Once weekly Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) have been shown to improve glycemic outcomes and cause significant weight loss. However, 9% to 27% of individuals have little or no response to these drugs. In this article, we investigated the efficacy of GLP-1 RA therapy among adults with type 1 diabetes and obesity likely related to genetic mutations compared with obesity likely unrelated to genetic mutations. METHODS: In this retrospective study, we compared body weight and glycated hemoglobin (HbA1c) change with the use of GLP-1 RA therapy (including a dual agonist, Tirzepatide) over six months among adults with type 1 diabetes and obesity likely (n = 11, median age 39.5 years with a median BMI of 43.0 kg/m2) versus unlikely related to genetic mutation(s) (n = 15, median age 45.8 years with a median BMI of 38.7 kg/m2). RESULTS: Six months of GLP-1 RA treatment resulted in a numerically lower reduction of weight (-5.75 ± 9.46 kg vs -8.65 ± 9.36 kg, P = .44) and HbA1c (-0.28 ± 0.96% vs -0.43 ± 0.57%, P = .64) among individuals with obesity likely versus unlikely related to a genetic mutation(s), respectively. Fewer individuals with genetic obesity met goal weight loss ≥5% or HbA1c decrease ≥0.4% than did individuals with obesity unlikely related to a genetic cause (36.4% vs 80.0%, P = .04). CONCLUSIONS: The weight loss and glycemic lowering effects of GLP-1 RA therapy may be decreased in people with type 1 diabetes and obesity likely related to genetic causes. Further research is needed to understand GLP-1 RA mechanisms via energy regulating genes.

Longitudinal associations of the alternative healthy eating index with coronary artery calcification and pericardial adiposity in US adults with and without type 1 diabetes.

BACKGROUND AND AIM: Long-term associations between the alternative healthy eating index (AHEI) score and two predictive indicators for CVD, pericardial adipose tissue (PAT) and coronary artery calcification (CAC) volume, are lacking. Our study aims to investigate the longitudinal associations of the AHEI score with measures of CAC and PAT in adults with and without type 1 diabetes (T1D). METHODS AND RESULTS: The prospective Coronary Artery Calcification in T1D (CACTI) study included 652 people with T1D and 764 people without diabetes (non-DM) (19-56 years old) and was conducted in 2000-2002, 2003-2004, and 2006-2007. At each visit, food frequency questionnaires were collected and PAT and CAC were measured using electron beam computed tomography. Two variables were used for CAC analyses: a continuous variable for the square-root tranformed volume (SRV) for each visit and a second variable identified CAC progression from baseline to visit 3. Mixed effect models and a logistic regression model were used to conduct statistical analyses. A one-point increase in the AHEI score was significantly associated with a -0.12 cm3 (95% CI: -0.17, -0.08; p-value<0.0001) decrease in PAT volume in combined analyses, a -0.16 cm3 (95% CI: -0.22, -0.09; p-value<0.0001) decrease in the non-DM group, a marginally significant -0.07 cm3 (95% CI: -0.14, 0.002; p-value = 0.0571) decrease in the T1D group, and was not associated with either CAC outcome. CONCLUSION: The AHEI score is inversely associated with PAT; the association revealed greater magnitude of PAT reduction in the non-DM group. The AHEI score did not associate with CAC progression.

Sleep duration and association with cardiometabolic health in adolescents and adults with type 1 diabetes: Results from the BCQR-T1D study.

AIM: Type 1 diabetes (T1D) increases the risk of morbidity and mortality from cardiovascular disease, and insufficient sleep is prevalent. Emerging evidence suggests a link between sleep and cardiometabolic health, but this has not been examined across the lifespan in individuals with T1D. We aimed to examine associations between sleep and cardiometabolic health in adolescents and adults with T1D in a secondary analysis of data from a 4-week double-blind, random-order, placebo-controlled crossover trial of bromocriptine quick release (BCQR) therapy with a 4-week washout in between conditions. MATERIALS AND METHODS: Forty-two adults (19-60 years) and 42 adolescents (12-18 years) with T1D >9 months completed 1 week of home monitoring with wrist-worn actigraphy to estimate sleep duration and continuous glucose monitoring, anthropometrics, arterial stiffness, magnetic resonance imaging (adolescents only), and fasting laboratory testing at each treatment phase. RESULTS: Sixty-two per cent of adolescents and 74% of adults obtained <7 h of sleep per night at baseline. After adjustment for age, sex and diabetes duration, baseline sleep <7 h per night was associated with a higher body mass index, a higher waist circumference, a higher systolic blood pressure, worse arterial stiffness and a lower estimated insulin sensitivity (all p < .05). When examined by age group, associations between sleep duration and cardiometabolic health outcomes remained significant, predominantly for adolescents. In adolescents only, wake time was significantly later (p = .027) and time in bed was significantly longer with BCQR versus placebo (p = .049). CONCLUSIONS: Objectively measured sleep <7 h per night was prevalent in adolescents and adults with T1D and associated with poorer cardiometabolic health markers. Small changes in sleep were seen following BCQR treatment in adolescents only. Sleep may be an important and novel target for improving cardiometabolic health in individuals with T1D.

Clinical Effectiveness of Continuous Glucose Monitoring in Pregnancies Affected by Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) improves neonatal outcomes in type 1 diabetes pregnancies; however, its effectiveness has not been assessed in a real-world setting in the United States. Objective: The Triple C Study aimed to examine the clinical effectiveness, assessed through maternal glucose control and gestational health outcomes, of CGM use compared with self-monitoring of blood glucose (SMBG) in pregnancies associated with type 1 diabetes in a real-world setting. Research Design and Methods: We retrospectively identified 160 type 1 diabetes pregnancies at the Barbara Davis Center for Diabetes managed with CGM therapy (n = 109) or SMBG (n = 51) over a 6.5-year period (2014-2020). Obstetric care was provided at multiple practices. CGM use was defined as ≥60% wear in the second and third trimesters of pregnancy. Data were obtained from the electronic medical record system, hospital records, and vital statistics departments (Colorado and Wyoming). We used Student's t-test for continuous variables and chi-square test for categorical variables to compare outcomes between groups. Results: The CGM group had more participants meeting trimester-specific hemoglobin A1C (HbA1c) goals throughout pregnancy and postpartum (P < 0.01 in each time period). The CGM group had fewer participants never meeting HbA1c goals in any trimester than the SMBG group (P < 0.001). There were no significant differences in neonatal outcomes between groups, other than for macrosomia (12.8% CGM vs. 29.4% SMBG, P = 0.01). Infants of CGM users required a neonatal intensive care unit admission less often (52.9% CGM vs. 68.3% SMBG, P = 0.0989). Conclusions: CGM use was associated with improved maternal glucose levels in a diverse real-world cohort.

Efficacy and Safety of Tirzepatide in Adults With Type 1 Diabetes: A Proof of Concept Observational Study.

BACKGROUND: Tirzepatide is approved by the United States Food and Drug Administration (FDA) for the management of type 2 diabetes. The efficacy and safety of this drug have not been studied in people with type 1 diabetes (T1D). METHODS: In this single-center, retrospective, observational study, hemoglobin A1C (HbA1c), weight, body mass index (BMI), and continuous glucose monitoring (CGM) data were collected from electronic health records of adults with T1D at initiation of tirzepatide and at subsequent clinic visits over 8 months. Primary outcomes were reduction in HbA1c and percent change in body weight and secondary outcomes were change in CGM metrics and BMI over 8 months from baseline. RESULTS: The mean (±SD) age of the 26 adults (54% female) with T1D was 42 ± 8 years with a mean BMI of 36.7 ± 5.3 kg/m2. There was significant reduction in HbA1c by 0.45% at 3 months and 0.59% at 8 months, and a significant reduction in body weight by 3.4%, 10.5%, and 10.1% at 3, 6, and 8 months after starting tirzepatide. Time in target range (TIR = 70-180 mg/dL) and time in tight target range (TITR = 70-140 mg/dL) increased (+12.6%, P = .002; +10.7%, P = .0016, respectively) and time above range (TAR >180 mg/dL) decreased (-12.6%, P = .002) at 3 months, and these changes were sustained over 8 months. The drug was relatively safe and well tolerated with only 2 patients discontinuing the medication. CONCLUSIONS: Tirzepatide significantly reduced HbA1c and body weight in adults with T1D. A randomized controlled trial is needed to establish efficacy and safety of this drug in T1D.

Time in Range Is Associated with Incident Diabetic Retinopathy in Adults with Type 1 Diabetes: A Longitudinal Study.

Abstract Objective: To evaluate the association between continuous glucose monitoring (CGM)-based time in various ranges and the subsequent development of diabetic retinopathy (incident DR) in adults with type 1 diabetes. Methods: Between June 2018 and March 2022, adults with type 1 diabetes with incident DR or no retinopathy (control) were identified. CGM data were collected retrospectively for up to 7 years before the date of eye examination defining incident DR or control. Associations between incident DR and CGM metrics were evaluated using logistic regression models. Results: This analysis included 71 adults with incident DR (mean age 27 years, 52% females, and mean diabetes duration 15 years) and 92 adults without DR (mean age 38 years, 48% females, and mean diabetes duration 20 years). Adjusting for age, diabetes duration, and CGM type, each 0.5% increase in glycated hemoglobin (HbA1c), 10 mg/dL increase in mean glucose, 5% decrease in time in target range 70-180 mg/dL (TIR), 5% decrease in time in tight target range 70-140 mg/dL (TITR), and 5% increase in time above 180 mg/dL (TAR) were associated with 24%, 22%, 18%, 28%, and 20% increase in odds of incident DR, respectively. Spearman correlations of TIR, TITR, TAR, and mean glucose with each other were all ≥0.97. Conclusion: Similar to HbA1c, TIR, TITR, TAR, and mean glucose were associated with increased risk for incident DR in adults with type 1 diabetes. These CGM metrics are highly correlated indicating that they provide similar information on glycemic control and diabetic retinopathy risk.

Rosiglitazone improves insulin resistance but does not improve exercise capacity in individuals with impaired glucose tolerance: A randomized clinical study.

Dysmetabolic states, such as type 2 diabetes (T2D), characterized by insulin resistance (IR), are associated with fatty liver, increased cardiovascular disease (CVD) risk, and decreased functional exercise capacity (FEC). Rosiglitazone (RO) improves exercise capacity and IR in T2D. However, the effects of RO on FEC and other markers of CVD risk in prediabetes are unknown. We hypothesized that insulin sensitization with RO would improve exercise capacity and markers of CVD risk in participants with impaired glucose tolerance (IGT). Exercise performance (peak oxygen consumption and oxygen uptake kinetics), IR (homeostasis model assessment of IR and quantitative insulin sensitivity check index), and surrogate cardiovascular endpoints (coronary artery calcium (CAC) volume and density and C-reactive protein (CRP)) were measured in participants with IGT after 12 and 18 months of RO or placebo (PL). RO did not significantly improve exercise capacity. Glycemic measures and IR were significantly lower in people on RO compared to PL at 18 months. CAC volume progression was not different between PL and RO groups. RO did not improve exercise capacity during an 18-month intervention despite improved IR and glycemia in people with IGT. Future studies should explore why effects on FEC with RO occur in T2D but not IGT. Understanding these questions may help in targeting therapeutic approaches in T2D and IGT.

Longitudinal Associations of Dietary Fiber Intake with Glycated Hemoglobin and Estimated Insulin Sensitivity in Adults with and without Type 1 Diabetes.

Dietary fiber, an essential bioactive compound in plant-based diets, is of public health concern based on habitual low intakes in the general population. Not much data are available on how habitual dietary fiber is associated with glycemic control in type 1 diabetes (T1D) as well as in prediabetes and normoglycemic adults. To address this gap, we conducted a six-year longitudinal analysis of an original cohort in adults with and without T1D (n = 1255; T1D: n = 563; non-diabetes mellitus (non-DM): n = 692). Dietary data were collected from a validated food frequency questionnaire, biochemical measures were obtained after an overnight fast, and anthropometric measurements were collected at baseline as well as after three and six years for the follow-up study. Glycated hemoglobin (HbA1c) and estimated insulin sensitivity (eIS) were the main outcomes examined. In adjusted analyses, dietary fiber intake was inversely associated with HbA1c in a minimally adjusted model, but it was positively associated with eIS in a model involving all relevant covariates in non-DM adults. These associations were not significant in the T1D group. Furthermore, when examined by HbA1c cut-offs for glycemic control, an inverse association with dietary fiber was only observed in adults with prediabetes (all p < 0.05). At a six-year mean (±SD) dietary fiber intake of 17.4 ± 8.8 g for non-DM and 17.0 ± 8.2 g for the T1D group, protective associations against poor glycemic control were observed in those without diabetes and in prediabetes.

Bone Structure and Turnover in Postmenopausal Women With Long-Standing Type 1 Diabetes.

Compromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double-labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy. An expert blinded to the study group performed histomorphometry. Static and dynamic histomorphometry measurements were performed and compared between the two groups. The analysis included 9 postmenopausal women with T1D (mean age 58.4 ± 7.1 years with 37.9 ± 10.9 years of diabetes and HbA1c 7.1% ± 0.4%) and 7 postmenopausal women without diabetes (mean age 60.9 ± 3.3 years and HbA1c 5.4% ± 0.2%). There were no significant differences in serum PTH (38.6 ± 8.1 versus 51.9 ± 23.9 pg/mL), CTX (0.4 ± 0.2 versus 0.51 ± 0.34 ng/mL), or P1NP (64.5 ± 26.2 versus 87.3 ± 45.3 ng/mL). Serum 25-hydroxyvitamin D levels were higher in T1D than in controls (53.1 ± 20.8 versus 30.9 ± 8.2 ng/mL, p < 0.05). Bone structure metrics (bone volume, trabecular thickness, trabecular number, and cortical thickness) were similar between the groups. Indices of bone formation (osteoid volume, osteoid surface, and bone formation rate) were 40% lower in T1D and associated with lower activation frequency. However, the differences in bone formation were not statistically significant. Long-standing T1D may affect bone turnover, mainly bone formation, without significantly affecting bone structure. Further research is needed to understand bone turnover and factors affecting bone turnover in people with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Longitudinal associations of physical activity with inflammatory markers in US adults with and without type 1 diabetes.

AIMS: To investigate the longitudinal associations of different levels of moderate-to-vigorous physical activity (MVPA) with C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen. METHODS: We conducted longitudinal analyses with data from the Coronary Artery Calcification in T1D (CACTI) cohort, which included individuals with type 1 diabetes (T1D, n = 563) and without diabetes mellitus (non-DM, n = 692) with ∼ 3 years follow-up. Individuals were divided into groups to perform two analyses: 1) those who performed any MVPA and those who were sedentary (0 mins/week) and 2) those who performed 1-149 mins/week, ≥150 mins/week, or who were sedentary. Mixed effect models with an unstructured covariance structure were applied. RESULTS: Compared to sedentary individuals, any MVPA was associated with a -2.96 % decrease in fibrinogen (p-value = 0.0043) and a -11.23 % decrease in PAI-1 (p-value = 0.0007) in combined analyses. Stratified analyses found 1-149 mins/week and ≥ 150 mins/week were associated with significant decreases in fibrinogen, -5.31 % and -3.44 %, respectively, in those with T1D. Both the non-DM and T1D groups had significant decreases in PAI-1 associated with ≥ 150 mins/week (-9.11 % and -16.96 %, respectively). CONCLUSIONS: Our findings highlight that meeting ≥ 150 mins/week of MVPA is inversely associated with inflammatory markers linked with increased CVD risk.

Association Between Diabetes Technology Use and Glycemic Outcomes in Adults With Type 1 Diabetes Over a Decade.

OBJECTIVE: To evaluate change in mean clinic HbA1c from 2014 to 2021 with diabetes technology use in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: In this single-center study, we analyzed diabetes technology use and mean clinic HbA1c among unique adults (age ≥18 years) with type 1 diabetes (last visit of the year per patient) between 1 January 2014 and 31 December 2021 from the electronic medical record. Diabetes technology use was defined as the use of continuous glucose monitors (CGMs) without an automated insulin delivery (AID) system or an AID system. Diabetes technology use and HbA1c over time were analyzed using mixed models adjusted for age, sex, and visit year. RESULTS: A total of 15,903 clinic visits over 8 years (mean 1,988 patients per year, 4,174 unique patients, 52.7% female, 80.0% Non-Hispanic White) showed significant increases in CGM and AID use (P < 0.001 for both), resulting in an increase of diabetes technology use from 26.9% in 2014 to 82.7% in 2021. These increases were associated with a lower mean clinic HbA1c (7.7-7.5%, P < 0.001) and a higher percentage of adults achieving an HbA1c <7.0% (32.3-41.7%, P < 0.001) from 2014 to 2021. The HbA1c difference between technology users and nonusers increased over time from 0.36% (95% CI 0.26-0.47%, P < 0.001) in 2014 to 0.93% (95% CI 0.80-1.06%, P < 0.001) in 2021. CONCLUSIONS: Adopting diabetes technology in adults with type 1 diabetes decreased HbA1c and increased the number of people achieving an HbA1c <7.0%, supporting the current international recommendation to offer AID systems to most individuals with type 1 diabetes.

Ultra-processed food consumption and obesity indicators in individuals with and without type 1 diabetes mellitus: a longitudinal analysis of the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) cohort study.

OBJECTIVE: To evaluate the associations of ultra-processed food (UPF) consumption and obesity indicators among individuals with and without type 1 diabetes mellitus (T1DM) from the Coronary Artery Calcification in Type 1 Diabetes cohort study. DESIGN: A secondary analysis. The consumption of UPF was assessed using the dietary data collected with the Harvard FFQ, and each food item was categorised according to the NOVA food processing classification. Height, weight and waist circumference were measured at baseline and after a mean of 14·6-year follow-up. Generalised estimating equations stratified by diabetes status were used to assess the associations between UPF intake and obesity indicators over 14 years of follow-up. SETTING: USA. PARTICIPANTS: A total of 600 adults (256 T1DM and 344 non-diabetic controls) aged 39 ± 9·1 years at baseline and followed up for over 14 years were included. RESULTS: Participants with T1DM consumed significantly more UPF than non-diabetic controls at baseline: 7·6 ± 3·8 v. 6·6 ± 3·4 servings per day of UPF, respectively (P < 0·01). Participants with T1DM and with the highest UPF intake had the highest weight (ßQ4 v. Q1 = 3·07) and BMI (ßQ4 v. Q1 = 1·02, all P < 0·05) compared with those with the lowest UPF intake. Similar positive associations were observed in non-diabetic controls. CONCLUSIONS: Individuals with T1DM may consume more UPF than non-diabetic controls. Positive associations between UPF consumption and obesity indicators suggest that limiting UPF can be recommended for obesity prevention and management. Further research is needed to confirm these findings.

Periodontitis and cardiovascular risk factors in subjects with and without type 1 diabetes: A cross sectional analysis.

AIMS: This cross-sectional analysis explored the relationships between periodontal disease (PD) and subclinical CVD in a cohort of patients with type 1 diabetes and non-diabetic controls. METHODS: Data were collected from adults enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study or enrolled through the Barbara Davis Center for Diabetes Adult Clinic. A clinical periodontal exam measured attachment loss and probing depth. Brachial artery distensibility (brachD), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV) were assessed as measures of subclinical cardiovascular structure and function. RESULTS: 144 participants with T1D and 148 non-diabetics were enrolled. Compared to non-diabetic controls, T1D participants had a higher probing depth (2.6 mm vs. 2.5 mm; p = 0.04), higher attachment loss (2.7 mm vs. 2.4 mm; p < 0.01), lower brachD (mean 5.8 vs. 6.4 mmHg; p < 0.01), a higher cIMT (mean 0.68 vs. 0.64 mm; p < 0.01), and a higher PWV (mean 8.3 vs. 7.8 m/s; p < 0.01). There were no significant associations between PD and CVD metrics. CONCLUSIONS: Periodontal and cardiovascular health was worse in participants with T1D compared to non-diabetics. No significant associations between PD measures and CVD were identified.

Longitudinal Associations of Healthy Dietary Pattern Scores with Coronary Artery Calcification and Pericardial Adiposity in United States Adults with and without Type 1 Diabetes.

BACKGROUND: Pericardial adipose tissue volume (PAT) and coronary artery calcification (CAC) are prognostic indicators for future cardiovascular events; however, no studies have assessed the long-term associations of adherence to dietary patterns (DPs) with PAT and CAC in adults with and without type 1 diabetes (T1D). OBJECTIVES: We investigated the longitudinal associations of the Mediterranean Diet (MedDiet) and Dietary Approaches to Stop Hypertension (DASH) diet with PAT and CAC progression in adults with and without T1D. METHODS: The Coronary Artery Calcification in Type 1 Diabetes (CACTI) study is a population-based, prospective study of 652 T1D and 764 nondiabetic mellitus (nonDM) (19-56 y) participants that began in 2000-2002 with follow-up visits in 2003-2004 and 2006-2007. At each visit, food frequency questionnaires were collected and used to develop adherence scores for the MedDiet and DASH diets. PAT and CAC were measured at each visit using electron beam computed tomography. CAC progression was defined as a ≥2.5 mm square root-transformed volume. Mixed effect models were used to conduct statistical analyses. RESULTS: Combined models found a significant-0.09 cm3 (95% CI: -0.14, -0.03; P = 0.0027) inverse association in PAT for every 1-point increase in the MedDiet score and a significant-0.26 cm3 (95% CI: -0.38, -0.14; P < 0.0001) inverse association in PAT for every 1-point increase in the DASH score. In combined models, the DPs were not significantly associated with lower odds of CAC progression; however, both DPs had significant interactions by diabetes status for CAC. Only the DASH diet was associated with lower odds of CAC progression in the nonDM group (OR: 0.96; 95% CI: 0.93, 0.99; P = 0.0224). CONCLUSIONS: These data suggest that the DPs are associated with lower PAT, which may reduce future cardiovascular events. The DASH diet may be beneficial for lower odds of CAC progression in those without T1D.

Longitudinal trajectories of branched chain amino acids through young adulthood and diabetes in later life.

BACKGROUNDElevated circulating branched chain amino acids (BCAAs), measured at a single time point in middle life, are strongly associated with an increased risk of developing type 2 diabetes mellitus (DM). However, the longitudinal patterns of change in BCAAs through young adulthood and their association with DM in later life are unknown.METHODSWe serially measured BCAAs over 28 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of apparently healthy Black and White young adults at baseline. Trajectories of circulating BCAA concentrations from years 2-30 (for prevalent DM) or years 2-20 (for incident DM) were determined by latent class modeling.RESULTSAmong 3,081 apparently healthy young adults, trajectory analysis from years 2-30 revealed 3 distinct BCAA trajectory groups: low-stable (n = 1,427), moderate-stable (n = 1,384), and high-increasing (n = 270) groups. Male sex, higher body mass index, and higher atherogenic lipid fractions were more common in the moderate-stable and high-increasing groups. Higher risk of prevalent DM was associated with the moderate-stable (OR = 2.59, 95% CI: 1.90-3.55) and high-increasing (OR = 6.03, 95% CI: 3.86-9.43) BCAA trajectory groups in adjusted models. A separate trajectory group analysis from years 2-20 for incident DM after year 20 showed that moderate-stable and high-increasing trajectory groups were also significantly associated with higher risk of incident DM, after adjustment for clinical variables and glucose levels.CONCLUSIONBCAA levels track over a 28-year span in most young adults, but serial clinical metabolomic measurements identify subpopulations with rising levels associated with high risk of DM in later life.FUNDINGThis research was supported by the NIH, under grants R01 HL146844 (JTW) and T32 HL069771 (MRC). The CARDIA study is conducted and supported by the NIH National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), the University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I).

Hemoglobin A1c Variability Metrics Predict Coronary Artery Calcium and Cardiovascular Events in Type 1 Diabetes: The CACTI Study.

CONTEXT: Interventions that decrease mean glucose have reduced rates of micro- and macrovascular complications in type 1 diabetes (T1D). However, the difference in cardiovascular risk between people with T1D and the general population endures, suggesting that factors beyond hemoglobin A1C (HbA1c) normalization drive cardiovascular outcomes. OBJECTIVE: To determine whether various HbA1c metrics predict anatomic cardiovascular disease (CVD) risk factors and/or CVD events in people with T1D. METHODS: We used linear regression to analyze the relationship of several HbA1c metrics to anatomic CVD risk factors and then used Cox regression to model their relationship to incident CVD events in the CACTI Study (ClinicalTrials.gov Identifier: NCT00005754). RESULTS: In linear regression models adjusted for age, sex, and T1D duration, baseline Hba1c (b = 0.3998, P = 0.0236), mean HbA1c (b = 0.5385, P = 0.0109), and HbA1c SD (b = 1.1521, P = 0.0068) were each positively associated with square root transformed coronary artery calcium volume. Conversely, only mean HbA1c (b = 1.659, P = 0.0048) positively associated with pericardial adipose tissue volume. In survival models adjusted for age, sex, and T1D duration, baseline HbA1c [hazard ratio (HR): 1.471, 95% CI: 1.257-1.721], mean HbA1c (HR: 1.850, 95% CI: 1.511-2.264), time-varying HbA1c (HR: 1.500, 95% CI: 1.236-1.821), and HbA1c SD (HR: 1.665, 95% CI: 1.022-2.711) each independently predicted CVD events over 14.3 ± 5.2 person-years of follow-up. CONCLUSIONS/INTERPRETATION: We found that various HbA1c metrics positively correlated with CAC volume and independently predicted incident CVD events in the CACTI T1D cohort. These associations with CVD events persisted for baseline HbA1c, mean HbA1c, and time-varying HbA1c even after adjustment for numerous CVD risk factors.

Femoral neck structural properties are altered in adults with type 1 diabetes.

AIMS: To determine differences in hip geometry in adults with type 1 diabetes (T1D) compared with healthy adults without diabetes. METHODS: In this cross-sectional study, 43 adults with T1D (mean age 56 years, 84 % female, 92 % White, mean duration of diabetes of 39 years, A1c of 7.8 %) and 40 adults without diabetes (mean age 60 years, 80 % female, 77 % white) who had hip dual-energy x-ray absorptiometry (DXA) scans from previous studies were included. Areal bone mineral density (aBMD) and measures of hip structural properties at the narrow neck, intertrochanteric and femoral shaft regions of the left proximal femur were analyzed between adults with T1D and controls using linear models controlled for age, sex, and body mass index. RESULTS: There were no significant differences in DXA-based aBMD at the hip (0.769 ± 0.132 vs. 0.900 ± 0.139 g/cm2, p = 0.07) or femoral neck (0.722 ± 0.116 vs. 0.849 ± 0.114 g/cm2, p = 0.09) regions between adults with T1D and controls. When controlling for age, sex, and BMI, DXA-based aBMD at the hip (0.880 ± 0.022 vs. 0.943 ± 0.020 g/cm2, p = 0.02) and femoral neck (0.750 ± 0.021 vs. 0.812 ± 0.020 g/cm2, p = 0.02) regions were significantly lower in adults with T1D than controls. Cortical thickness was significantly lower in all three hip regions in adults with T1D than in controls (narrow-neck: 0.169 ± 0.005 vs. 0.186 ± 0.005 cm, p = 0.011; intertrochanteric: 0.388 ± 0.013 vs. 0.425 ± 0.012 cm, p = 0.017; femoral shaft: 0.529 ± 0.017 vs. 0.586 ± 0.016 cm, p = 0.006). Moreover, adults with T1D had a smaller cross-sectional area at the narrow-neck (3.06 ± 0.09 vs. 3.32 ± 0.08 cm2, p = 0.015), a higher femoral shaft endocortical diameter (2.23 ± 0.07 vs. 2.02 ± 0.06 cm, p = 0.011), and higher buckling ratios (an indicator of cortical instability) at the intertrochanteric (9.22 ± 0.34 vs. 8.23 ± 0.32, p = 0.016) and femoral shaft (3.32 ± 0.15 vs. 2.89 ± 0.14, p = 0.016) regions. CONCLUSIONS: Adults with T1D have several significant differences in proximal femur morphology compared with controls. These morphological differences may adversely affect the mechanical integrity of the proximal femur, thereby contributing to an increased risk of fracture in the event of a fall.

Continuous Glucose Monitor, Insulin Pump, and Automated Insulin Delivery Therapies for Type 1 Diabetes: An Update on Potential for Cardiovascular Benefits.

PURPOSE OF REVIEW: The incidence of type 1 diabetes (T1D) is rising in all age groups. T1D is associated with chronic microvascular and macrovascular complications but improving glycemic trends can delay the onset and slow the progression of these complications. Utilization of technological devices for diabetes management, such as continuous glucose monitors (CGM) and insulin pumps, is increasing, and these devices are associated with improvements in glycemic trends. Thus, device use may be associated with long-term prevention of T1D complications, yet few studies have investigated the direct impacts of devices on chronic complications in T1D. This review will describe common diabetes devices and combination systems, as well as review relationships between device use and cardiovascular outcomes in T1D. RECENT FINDINGS: Findings from existing cohort and national registry studies suggest that pump use may aid in improving cardiovascular risk factors such as hypertension and dyslipidemia. Furthermore, pump users have been shown to have lower arterial stiffness and better measures of myocardial function. In registry and case-control longitudinal data, pump use has been associated with fewer cardiovascular events and reduction of cardiovascular disease (CVD) and all-cause mortality. CVD is the leading cause of morbidity and mortality in T1D. Consistent use of diabetes devices may protect against the development and progression of macrovascular complications such as CVD through improvement in glycemic trends. Existing literature is limited, but findings suggest that pump use may reduce acute cardiovascular risk factors as well as chronic cardiovascular complications and overall mortality in T1D.