We prospectively enrolled 3,681 patients with suspected AMI and stratified those by the presence of DM. The ESC 0/1-h and 0/3-h algorithms were used to calculate negative and positive predictive values (NPV, PPV). In addition, alternative cutoffs were calculated and externally validated in 2,895 patients.

In total, 563 patients (15.3%) had DM, and 137 (24.3%) of these had AMI. When the ESC 0/1-h algorithm was used, the NPV was comparable in patients with and without DM (absolute difference [AD] –1.50 [95% CI –5.95, 2.96]). In contrast, the ESC 0/3-h algorithm resulted in a significantly lower NPV in patients with DM (AD –2.27 [95% CI –4.47, –0.07]). The diagnostic performance for rule-in of AMI (PPV) was comparable in both groups: 0/1-h (AD 6.59 [95% CI –19.53, 6.35]) and 0/3-h (AD 1.03 [95% CI –7.63, 9.7]). Alternative cutoffs increased the PPV in both algorithms significantly, while improvements in NPV were only subtle.

Application of the ESC 0/1-h algorithm revealed comparable safety to rule out AMI comparing patients with and without DM, while this was not observed with the ESC 0/3-h algorithm. Although alternative cutoffs might be helpful, patients with DM remain a high-risk population in whom identification of AMI is challenging and who require careful clinical evaluation.

Of 20,418 individuals who underwent single-photon emission computed tomography myocardial perfusion imaging, 2,951 patients with diabetes were matched to 2,951 patients without diabetes based on risk factors using propensity score. TPD was categorized as TPD = 0%, 0% < TPD < 1%, 1% ≤ TPD < 5%, 5% ≤ TPD ≤ 10%, and TPD >10%. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, unstable angina, or late revascularization.

MACE risk was increased in patients with diabetes compared with patients without diabetes at each level of TPD above 0 (P < 0.001 for interaction). In patients with TPD >10%, patients with diabetes had greater than twice the MACE risk compared with patients without diabetes (annualized MACE rate 9.4 [95% CI 6.7–11.6] and 3.9 [95% CI 2.8–5.6], respectively, P < 0.001). Patients with diabetes with even very minimal TPD (0% < TPD < 1%) experienced a higher risk for MACE than those with 0% TPD (hazard ratio 2.05 [95% CI 1.21–3.47], P = 0.007). Patients with diabetes with a TPD of 0.5% had a similar MACE risk as patients without diabetes with a TPD of 8%.

For every level of TPD >0%, even a very minimal deficit of 0% < TPD < 1%, the MACE risk was higher in the patients with diabetes compared with patients without diabetes. Patients with diabetes with minimal ischemia had comparable MACE risk as patients without diabetes with significant ischemia.

Least squares mean difference (LSMD) in estimated glomerular filtration rate (eGFR) from baseline between the EQW and placebo groups was calculated for 13,844 participants. Cox regression models were used to estimate effects by group on incident macroalbuminuria, retinopathy, and major adverse CV events (MACE). Interval-censored time-to-event models estimated effects on renal composite 1 (40% eGFR decline, renal replacement, or renal death) and renal composite 2 (composite 1 variables plus macroalbuminuria).

EQW did not change eGFR significantly (LSMD 0.21 mL/min/1.73 m² [95% CI –0.27 to 0.70]). Macroalbuminuria occurred in 2.2% of patients in the EQW group and in 2.5% of those in the placebo group (hazard ratio [HR] 0.87 [95% CI 0.70–1.07]). Neither renal composite was reduced with EQW in unadjusted analyses, but renal composite 2 was reduced after adjustment (HR 0.85 [95% CI 0.74–0.98]). Retinopathy rates did not differ by treatment group or in the HbA_1c-lowering or prior retinopathy subgroups. CV outcomes in those with eGFR <60 mL/min/1.73 m² did not differ by group. Those with eGFR ≥60 mL/min/1.73 m² had nominal risk reductions for MACE, all-cause mortality, and CV death, but interactions by renal function group were significant for only stroke (HR 0.74 [95% CI 0.58–0.93]; P for interaction = 0.035) and CV death (HR 1.08 [95% CI 0.85–1.38]; P for interaction = 0.031).

EQW had no impact on unadjusted retinopathy or renal outcomes. CV risk was modestly reduced only in those with eGFR ≥60 mL/min/1.73 m² in analyses unadjusted for multiplicity.

The concentration of 239 biochemical markers was measured in stored serum from participants in the biomarker substudy of Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Repeated-measures mixed-effects models were used to compute the annual change in eGFR (measured as mL/min/1.73 m²/year) for the 7,482 participants with a recorded baseline and follow-up eGFR. Linear regression models using forward selection were used to identify the independent biomarker determinants of the annual change in eGFR after accounting for baseline HbA_1c, baseline eGFR, and routinely measured clinical risk factors. The incidence of the composite renal outcome (i.e., renal replacement therapy, renal death, renal failure, albuminuria progression, doubling of serum creatinine) and death within each fourth of change in eGFR predicted from these models was also estimated.

During 6.2 years of median follow-up, the median annual change in eGFR was –0.18 mL/min/1.73 m²/year. Fifteen biomarkers independently predicted eGFR decline after accounting for cardiovascular risk factors, as did 12 of these plus 1 additional biomarker after accounting for renal risk factors. Every 0.1 mL/min/1.73 m² predicted annual fall in eGFR predicted a 13% (95% CI 12, 14%) higher mortality.

Adding up to 16 biomarkers to routinely measured clinical risk factors improves the prediction of annual change in eGFR in people with dysglycemia.

This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information–Diabetes Collaboration (SCI-DC) who were observable from the diagnosis of diabetes and had at least five HbA_1c measurements before the outcomes were evaluated. We used the previously reported HbA_1c variability score (HVS), calculated as the percentage of the number of changes in HbA_1c >0.5% (5.5 mmol/mol) among all HbA_1c measurements within an individual. The association between HVS and 10 outcomes was assessed using Cox proportional hazards models.

We included 13,111–19,883 patients in the analyses of each outcome. The patients with HVS >60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, HVS >80 to ≤100 vs. HVS ≥0 to ≤20, hazard ratio 2.38 [95% CI 1.61–3.53] for major adverse cardiovascular events, 2.4 [1.72–3.33] for all-cause mortality, 2.4 [1.13–5.11] for atherosclerotic cardiovascular death, 2.63 [1.81–3.84] for coronary artery disease, 2.04 [1.12–3.73] for ischemic stroke, 3.23 [1.76–5.93] for heart failure, 7.4 [3.84–14.27] for diabetic retinopathy, 3.07 [2.23–4.22] for diabetic peripheral neuropathy, 5.24 [2.61–10.49] for diabetic foot ulcer, and 3.49 [2.47–4.95] for new-onset chronic kidney disease). Four sensitivity analyses, including adjustment for time-weighted average HbA_1c, confirmed the robustness of the results.

Our study shows that higher HbA_1c variability is associated with increased risks of all-cause mortality, cardiovascular events, and microvascular complications of diabetes independently of high HbA_1c.

We identified 8,528 patients with diabetes (self-report, medication use, or electronic medical record diagnosis) from the Henry Ford Exercise Testing Project (FIT Project). Patients with a BMI <18.5 kg/m² or cancer were excluded. Fitness was measured as the METs achieved during a physician-referred treadmill stress test and categorized as low (<6), moderate (6–9.9), or high (≥10). Adjusted hazard ratios for mortality were calculated using standard BMI (kilograms per meter squared) cutoffs of normal (18.5–24.9), overweight (25–29.9), and obese (≥30). Adjusted splines centered at 22.5 kg/m² were used to examine BMI as a continuous variable.

Patients had a mean age of 58 ± 11 years (49% women) with 1,319 deaths over a mean follow-up of 10.0 ± 4.1 years. Overall, obese patients had a 30% lower mortality hazard (P < 0.001) compared with normal-weight patients. In adjusted spline modeling, higher BMI as a continuous variable was predominantly associated with a lower mortality risk in the lowest fitness group and among patients with moderate fitness and BMI ≥30 kg/m². Compared with the lowest fitness group, patients with higher fitness had an ~50% (6–9.9 METs) and 70% (≥10 METs) lower mortality hazard regardless of BMI (P < 0.001).

Among patients with diabetes, the obesity paradox was less pronounced for patients with the highest fitness level, and these patients also had the lowest risk of mortality.

The myocardial metabolic rate of glucose (MRGlu) was measured by using dynamic ¹⁸F-fluorodeoxyglucose positron emission tomography combined with a euglycemic-hyperinsulinemic clamp in 30 volunteers without coronary artery disease. Three groups were studied: 1) those with 1-h postload glucose <155 mg/dL (NGT 1-h low) (n = 10), 2) those with NGT 1-h high (n = 10), 3) and those with IGT (n = 10).

After adjusting for age, sex, and BMI, both subjects with NGT 1-h high (23.7 ± 6.4 mmol/min/100 mg; P = 0.024) and those with IGT (16.4 ± 6.0 mmol/min/100 mg; P < 0.0001) exhibited a significant reduction in global myocardial MRGlu; this value was 32.8 ± 9.7 mmol/min/100 mg in subjects with NGT 1-h low. Univariate correlations showed that MRGlu was positively correlated with insulin-stimulated whole-body glucose disposal (r = 0.441; P = 0.019) and negatively correlated with 1-h (r = –0.422; P = 0.025) and 2-h (r = –0.374; P = 0.05) postload glucose levels, but not with fasting glucose.

This study shows that myocardial insulin resistance is an early defect that is already detectable in individuals with dysglycemic conditions associated with an increased risk of type 2 diabetes, such as IGT and NGT 1-h high.

A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI ≥30 kg/m² and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.

The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient’s data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.

The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.

A total of 24 T1D patients (median age 5.1 years) received a single intravenous infusion of autologous UCB cells and underwent metabolic and immunologic assessments.

No infusion-related adverse events were observed. β-Cell function declined after UCB infusion. Area under the curve C-peptide was 24.3% of baseline 1 year postinfusion (P < 0.001) and 2% of baseline 2 years after infusion (P < 0.001). Flow cytometry revealed increased regulatory T cells (Tregs) (P = 0.04) and naive Tregs (P = 0.001) 6 and 9 months after infusion, respectively.

Autologous UCB infusion in children with T1D is safe and induces changes in Treg frequency but fails to preserve C-peptide.

In this double-blind study, 587 patients taking stable-dose insulin glargine (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) to MK-0941 10, 20, 30, or 40 mg or matching placebo t.i.d. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week treatment phase during which patients were to be uptitrated as tolerated to 40 mg (or placebo) t.i.d. a.c. The primary efficacy end point was change from baseline in A1C at Week 14.

At Week 14, A1C and 2-h postmeal glucose (PMG) improved significantly versus placebo with all MK-0941 doses. Maximal placebo-adjusted least squares mean changes from baseline in A1C (baseline A1C 9.0%) and 2-h PMG were –0.8% and –37 mg/dL (–2 mmol/L), respectively. No significant effects on fasting plasma glucose were observed at any dose versus placebo. By 30 weeks, the initial glycemic responses noted at 14 weeks were not sustained. MK-0941 at one or more doses was associated with significant increases in the incidence of hypoglycemia, triglycerides, systolic blood pressure, and proportion of patients meeting criteria for predefined limits of change for increased diastolic blood pressure.

In patients receiving stable-dose insulin glargine, the GKA MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood pressure.