A cross-sectional study of 193 patients with type 2 diabetes and 20 age- and sex-matched controls. Cardiovascular magnetic resonance was used in order to evaluate left ventricular structure and function, and MBF at rest and during adenosine-induced stress. MBF was derived as the mean of the flow within all segments of a midventricular slice.

Patients with type 2 diabetes had higher global MBF at rest (0.81 ± 0.19 mL/min/g) and lower global MBF during stress (2.4 ± 0.9 mL/min/g) than did controls (0.61 ± 0.11 at rest, 3.2 ± 0.8 mL/min/g under stress; both P < 0.01). Patients with macroalbuminuria had lower MBF during stress (1.6 ± 0.5 mL/min/g) than did patients with microalbuminuria (2.1 ± 0.7 mL/min/g; P = 0.04), who in turn had lower MBF during stress than did normoalbuminuric patients (2.7 ± 0.9 mL/min/g; P < 0.01). Patients with severe retinopathy had lower MBF during stress (1.8 ± 0.6 mL/min/g) than did patients with simplex retinopathy (2.3 ± 0.7 mL/min/g; P < 0.05) and those who did not have retinopathy (2.6 ± 1.0 mL/min/g; P < 0.05). Albuminuria and retinopathy were associated with reduced MBF during stress in a multiple regression analysis. Stress-related MBF inversely correlated with myocardial extracellular volume (P < 0.001; R² = 0.37), a measure of diffuse myocardial fibrosis. A trend toward lower basal MBF was observed in patients treated with sodium–glucose cotransporter 2 inhibitors (P = 0.07).

Patients with type 2 diabetes have higher global MBF at rest and lower maximal MBF during vasodilator-induced stress than do controls. Reduced MBF during stress is associated with diabetes complications (albuminuria and retinopathy) and is inversely correlated with diffuse myocardial fibrosis.

We included 27 participants with a history of TNDM currently with (n = 24) or without (n = 3) relapse of diabetes, and 16 non-TNDM relatives known to be carriers of causal genetic defects and currently with (n = 9) or without (n = 7) diabetes. Insulin sensitivity and secretion were assessed by hyperinsulinemic-euglycemic clamp and arginine-stimulation testing in a subset of 8 TNDM participants and 7 relatives carrying genetic abnormalities, with and without diabetes, compared with 17 unrelated control subjects without diabetes.

In TNDM participants, age at relapse correlated positively with age at puberty (P = 0.019). The mean insulin secretion rate and acute insulin response to arginine were significantly lower in TNDM and relatives of participants with diabetes than in control subjects (4.7 [3.6–5.9] vs. 13.4 [11.8–16.1] pmol/kg/min, P < 0.0001; and 84.4 [33.0–178.8] vs. 399.6 [222.9–514.9] µIU/mL, P = 0.0011), but were not different between participants without diabetes (12.7 [10.4–14.3] pmol/kg/min and 396.3 [303.3–559.3] µIU/mL, respectively) and control subjects. Socioeducational attainment was lower in TNDM participants than in the general population, regardless of diabetes duration.

Relapse of diabetes occurred earlier in TNDM participants compared with relatives and was associated with puberty. Both groups had decreased educational attainment, and those with diabetes had lower insulin secretion capacity; however, there was no difference in insulin resistance in adulthood. These forms of diabetes should be included in maturity-onset diabetes of the young testing panels, and relatives of TNDM patients should be screened for underlying defects, as they may be treated with drugs other than insulin.

We included 2,236 adults aged ≥65 years without known diabetes from the 2005–2016 National Health and Nutrition Examination Survey. Diabetes was defined using: 1) the Endocrine Society approach (HbA_1c ≥6.5%, FPG ≥126 mg/dL, or 2-h plasma glucose ≥200 mg/dL among those with HbA_1c 5.7–6.4% or FPG 100–125 mg/dL); and 2) a standard approach (HbA_1c ≥6.5% or FPG ≥126 mg/dL). Treatment eligibility was defined using HbA_1c cut points (≥7 to ≥9%). OGTT screening costs were estimated using Medicare fee schedules.

Diabetes prevalence was 15.7% (~5.0 million) using the Endocrine Society’s approach and 7.3% (~2.3 million) using the standard approach. Treatment eligibility ranged from 5.4 to 0.06% and 11.8–1.3% for diabetes cases identified through the Endocrine Society or standard approach, respectively. By definition, diabetes identified exclusively through the Endocrine Society approach had HbA1_1c <6.5% and would not be recommended for glucose-lowering treatment. Screening all older adults with prediabetic HbA_1c/FPG (~18.3 million) with OGTT could cost between $737 million and $1.7 billion.

Adopting the 2019 Endocrine Society guidelines would substantially increase the number of older adults classified as having diabetes, require significant financial resources, but likely offer limited benefits.

We report the resource utilization, costs, and effectiveness measures from the ongoing ASK program compared with usual care (i.e., no screening). Additionally, we report a practical screening scenario by including utilization and costs relevant to routine screening in clinical practice. Finally, we project the potential cost-effectiveness of ASK and routine screening by identifying clinical benchmarks (i.e., diabetic ketoacidosis [DKA] events avoided, HbA_1c improvements vs. no screening) needed to meet value thresholds of $50,000–$150,000 per quality-adjusted life-year (QALY) gained over a lifetime horizon.

Cost per case detected was $4,700 for ASK screening and $14,000 for routine screening. To achieve value thresholds of $50,000–$150,000 per QALY gained, screening costs would need to be offset by cost savings through 20% reductions in DKA events at diagnosis in addition to 0.1% (1.1 mmol/mol) improvements in HbA_1c over a lifetime compared with no screening for patients who develop type 1 diabetes. Value thresholds were not met from avoiding DKA events alone in either scenario.

Presymptomatic type 1 diabetes screening may be cost-effective in areas with a high prevalence of DKA and an infrastructure facilitating screening and monitoring if the benefits of avoiding DKA events and improved HbA_1c persist over long-run time horizons. As more data are collected from ASK, the model will be updated with direct evidence on screening effects.

Each method was used to evaluate nine insulin formulations, purchased at four pharmacies, within five geographic locations in the U.S.

All human and analog insulins measured by the USP methods (n = 174) contained the expected quantity of active insulin (100 ± 5 units/mL). When using isotope dilution SPE-LC-MS, units-per-milliliter values were well below product labeling due to unequal recovery of the internal standard compared with target insulin.

Insulin purchased from U.S. pharmacies is consistent with product labeling.

5,181 participants from the cross-sectional Metabolic Syndrome in Men (METSIM) study that included Finnish men (age 57 ± 7 years, BMI 26.5 ± 3.5 kg/m²) having metabolomics data available were included in our study. Metabolomics analysis was performed based on fasting plasma samples. On the basis of an oral glucose tolerance test, Matsuda ISI and Disposition Index values were calculated as markers of insulin sensitivity and insulin secretion. A total of 4,851 participants had a 7.4-year follow-up visit, and 522 participants developed type 2 diabetes.

Creatine, 1-palmitoleoylglycerol (16:1), urate, 2-hydroxybutyrate/2-hydroxyisobutyrate, xanthine, xanthurenate, kynurenate, 3-(4-hydroxyphenyl)lactate, 1-oleoylglycerol (18:1), 1-myristoylglycerol (14:0), dimethylglycine, and 2-hydroxyhippurate (salicylurate) were significantly associated with an increased risk of type 2 diabetes. These metabolites were associated with decreased insulin secretion or insulin sensitivity or both. Among the metabolites that were associated with a decreased risk of type 2 diabetes, 1-linoleoylglycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes.

Several novel and previously reported microbial metabolites related to the gut microbiota were associated with an increased risk of incident type 2 diabetes, and they were also associated with decreased insulin secretion and insulin sensitivity. Microbial metabolites are important biomarkers for the risk of type 2 diabetes.

A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal interval [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio). We compared the risk of diabetes until 2017 according to tertiles of heart rate and HRV variables, with tertile 1 serving as the reference group.

During 243,758.2 person-years, 1,369 subjects were diagnosed with diabetes. Both time and frequency domain variables were lower in the group with diabetes, with the exception of those with normalized LF and LF/HF ratio. In Cox analysis, as SDNN, RMSSD, and normalized HF tertiles increased, the risk of diabetes decreased (hazard ratios [95% CIs] of tertile 3: 0.81 [0.70–0.95], 0.76 [0.65–0.90], and 0.78 [0.67–0.91], respectively), whereas the risk of diabetes increased in the case of heart rate, normalized LF, and LF/HF ratio (hazard ratios [95% CIs] of tertile 3: 1.41 [1.21–1.65], 1.32 [1.13–1.53], and 1.31 [1.13–1.53), respectively) after adjusting for age, sex, BMI, smoking, drinking, systolic blood pressure, lipid level, CRP, and HOMA of insulin resistance.

Abnormal HRV, especially decreased vagal activity and deviation in sympathovagal imbalance to sympathetic activity, might precede incident diabetes.

This age-, sex-, BMI-, and diabetes duration–matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA.

A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3–5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed.

Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.

FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine [8-OHdG]), lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]), and acrylamide exposure (N-acetyl-S-[2-carbamoylethyl]-l-cysteine [AAMA], N-acetyl-S-[2-carbamoyl-2-hydroxyethyl]-l-cysteine [GAMA]) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis.

We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG (except GAMA with FPG) and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, AAMA + GAMA (UAAM), or 8-iso-PGF2α was associated with a 0.17, 0.15, or 0.23 mmol/L increase in FPG, respectively (P and/or P trend < 0.05). Each 1% increase in AAMA, GAMA, or UAAM was associated with a 0.19%, 0.27%, or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48%, or 0.44% increase in 8-iso-PGF2α, respectively (P and P trend < 0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA- and UAAM-associated FPG increases, respectively.

Exposure of the general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage, and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation.

Asymptomatic patients (8–45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA_1c and continuous glucose monitoring over 12 months.

Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9–8.2%, N = 1,298] vs. 4.7% [95% CI 3.4–5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA_1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI –0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4–2.7; P = 0.014) emerged with a GFD.

CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Up to 4,761 offspring from the Avon Longitudinal Study of Parents and Children were studied. Linear models were used to examine effects of a genetic risk score (162 variants) for adult type 2 diabetes on 229 metabolomic traits (lipoprotein subclass–specific cholesterol and triglycerides, amino acids, glycoprotein acetyls, others) measured at age 8 years, 16 years, 18 years, and 25 years. Two-sample Mendelian randomization (MR) was also conducted using genome-wide association study data on metabolomic traits in an independent sample of 24,925 adults.

At age 8 years, associations were most evident for type 2 diabetes liability (per SD-higher) with lower lipids in HDL subtypes (e.g., –0.03 SD, 95% CI –0.06, –0.003 for total lipids in very large HDL). At 16 years, associations were stronger with preglycemic traits, including citrate and with glycoprotein acetyls (0.05 SD, 95% CI 0.01, 0.08), and at 18 years, associations were stronger with branched chain amino acids. At 25 years, associations had strengthened with VLDL lipids and remained consistent with previously altered traits, including HDL lipids. Two-sample MR estimates among adults indicated persistent patterns of effect of disease liability.

Our results support perturbed HDL lipid metabolism as one of the earliest features of type 2 diabetes liability, alongside higher branched-chain amino acid and inflammatory levels. Several features are apparent in childhood as early as age 8 years, decades before the clinical onset of disease.

A total of 4,699 people with diabetes who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 were recruited for this study. Energy and macronutrient intake was measured by a 24-h dietary recall. The differences () in energy and macronutrient intake between dinner and breakfast ( = dinner – breakfast) were categorized into quintiles. Death information was obtained from the National Death Index until 2015. Cox proportional hazards regression models were developed to evaluate the survival relationship between and diabetes, cardiovascular disease (CVD), and all-cause mortality.

Among the 4,699 participants, 913 deaths, including 269 deaths due to diabetes and 314 deaths due to CVD, were documented. After adjustment for potential confounders, compared with participants in the lowest quintile of in terms of total energy and protein, participants in the highest quintile were more likely to die due to diabetes (hazard ratio [HR]_energy 1.92, 99% CI 1.08–3.42; HR_protein 1.92, 99% CI 1.06–3.49) and CVD (HR_energy 1.69, 99% CI 1.02–2.80; HR_protein 1.96, 99% CI 1.14–3.39). The highest quintile of total fat was related to CVD mortality (HR 1.67, 99% CI 1.01–2.76). Isocalorically replacing 5% of total energy at dinner with breakfast was associated with 4% and 5% lower risk of diabetes (HR 0.96, 95% CI 0.94–0.98) and CVD (HR 0.95, 95% CI 0.93–0.97) mortality, respectively.

Higher intake of energy, total fat, and protein from dinner than breakfast was associated with greater diabetes, CVD, and all-cause mortality in people with diabetes.

The association between CD34⁺ cell migration and cardiovascular mortality was reassessed at 6 years after revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow CD34⁺ cells were profiled for miRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated miRNA-21 and its proapoptotic target, PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34⁺ cells to endothelial cells.

Multivariable regression analysis confirmed that CD34⁺ cell migration forecasts long-term cardiovascular mortality. CD34⁺ cells from T2D-CLI patients were more apoptotic and less proangiogenic than control subjects and featured miRNA-21 downregulation, modulation of several long noncoding RNAs acting as miRNA-21 sponges, and upregulation of the miRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control subject CD34⁺ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34⁺ cells imprinted naïve endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/miRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging reactive oxygen species protected endothelial cells from the negative influence of T2D-CLI CD34⁺ cells.

Migration of CD34⁺ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signaling conveys antiangiogenic and proapoptotic features from CD34⁺ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.

A total of 291 subjects aged 35–60 years with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT), or type 2 diabetes were screened by a standard 2-h oral glucose tolerance test (OGTT) with the use of traditional measures to evaluate β-cell function. From these participants, 74 subjects were recruited for an oral minimal model test, and β-cell function was assessed with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit.

Circulating RBP4 levels were significantly and inversely correlated with β-cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indices, but not with HOMA of β-cell function, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β-cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion.

Circulating RBP4 levels are inversely and independently correlated with β-cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.