We retrospectively analyzed records of patients presenting with a first type 1 MI at age ≤50 years from 2000 to 2016. Diabetes was defined as a hemoglobin A_1c ≥6.5% (48 mmol/mol) or a documented diagnosis of or treatment for diabetes. Vital status was ascertained for all patients, and cause of death was adjudicated.

Among 2,097 young patients who had a type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), diabetes was present in 416 (20%), of whom 172 (41%) were receiving insulin. Over a median follow-up of 11.2 years (interquartile range 7.3–14.2 years), diabetes was associated with a higher all-cause mortality (hazard ratio 2.30; P < 0.001) and cardiovascular mortality (2.68; P < 0.001). These associations persisted after adjusting for baseline covariates (all-cause mortality: 1.65; P = 0.008; cardiovascular mortality: 2.10; P = 0.004).

Diabetes was present in 20% of patients who presented with their first MI at age ≤50 years and was associated with worse long-term all-cause and cardiovascular mortality. These findings highlight the need for implementing more-aggressive therapies aimed at preventing future adverse cardiovascular events in this population.

Data for 3,129 U.S. counties, obtained from the Small Area Health Insurance Estimates and Area Health Resources Files, were used to analyze trends in uninsured rates among populations with a household income ≤138% of the federal poverty level. Multivariable analysis adjusted for the percentage of county populations aged 50–64 years, the percentage of women, Distressed Communities Index value, and rurality.

In 2012, 39% of the population in the Diabetes Belt and 34% in non-Belt counties were uninsured (P < 0.001). In 2016 in states where Medicaid was expanded, uninsured rates declined rapidly to 13% in Diabetes Belt counties and to 15% in non-Belt counties. Adjusting for county demographic and economic factors, Medicaid expansion helped reduce uninsured rates by 12.3% in Diabetes Belt counties and by 4.9% in non-Belt counties. In 2016, uninsured rates were 15% higher for both Diabetes Belt and non-Belt counties in the nonexpansion states than in the expansion states.

ACA-driven Medicaid expansion was more significantly associated with reduced uninsured rates in Diabetes Belt than in non-Belt counties. Initial disparities in uninsured rates between Diabetes Belt and non-Belt counties have not existed since 2014 among expansion states. Future studies should examine whether and how Medicaid expansion may have contributed to an increase in the use of health services in order to prevent and treat diabetes in the Diabetes Belt.

Patients with type 1 diabetes receiving regular care were recruited in this observational cross-sectional study and divided into four groups according to their Lp(a) levels in nmol/L (very low <10, low 10–30, intermediate 30–120, high >120). Prevalence of vascular complications was compared between the groups. In addition, the association between metabolic control, measured as HbA_1c, and Lp(a) was studied.

The patients (n = 1,860) had a median age of 48 years, diabetes duration of 25 years, and HbA_1c of 7.8% (61 mmol/mol). The median Lp(a) was 19 (interquartile range 10–71) nmol/L. No significant differences between men and women were observed, but Lp(a) levels increased with increasing age. Patients in the high Lp(a) group had higher prevalence of complications than patients in the very low Lp(a) group. The age- and smoking-status–adjusted relative risk ratio of having any macrovascular disease was 1.51 (95% CI 1.01–2.28, P = 0.048); coronary heart disease, 1.70 (95% CI 0.97–3.00, P = 0.063); albuminuria, 1.68 (95% CI 1.12–2.50, P = 0.01); and calcified aortic valve disease, 2.03 (95% CI 1.03–4.03; P = 0.042). Patients with good metabolic control, HbA_1c <6.9% (<52 mmol/mol), had significantly lower Lp(a) levels than patients with poorer metabolic control, HbA_1c >6.9% (>52 mmol/mol).

Lp(a) is a significant risk factor for macrovascular disease, albuminuria, and calcified aortic valve disease in patients with type 1 diabetes. Poor metabolic control in patients with type 1 diabetes is associated with increased Lp(a) levels.

We examined 590 participants with diabetes [399 type 1 diabetes (T1D) and 191 type 2 diabetes (T2D)] and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the fifth percentile of the control patients without diabetes.

Control patients without diabetes were 37.9 ± 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was –0.1% (90% CI, –5.9 to 5.0%). RCNFL was defined by values exceeding the fifth percentile of 6% loss. Participants with T1D were 39.9 ± 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was –0.8% (90% CI, –14.0 to 9.9%). Participants with T2D were 60.4 ± 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was –0.2% (90% CI, –14.1 to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type [64 T1D (16.0%), 37 T2D (19.4%), P = 0.31]. RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA_1c or its change over follow-up.

An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.

We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18–65 years, mean BMI >40 kg/m², mean follow-up >4.5 years). The risks of postoperative outcomes were assessed with Cox regression models.

During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR <30 mL/min/1.73 m².

Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.

We used logistic regression to examine associations of comorbidities with elevations in either troponin (≥85th percentile) among 1,835 participants in the Atherosclerosis Risk in Communities (ARIC) Study with diabetes (ages 67–89 years, 43% male, 31% black) at visit 5 (2011–2013). We used Cox models to compare associations of high cardiac troponins with mortality across comorbidity levels.

Elevations in either troponin (≥9.4 ng/L for hs-cTnI, ≥25 ng/L for hs-cTnT) were associated with prevalent coronary heart disease, heart failure, chronic kidney disease, pulmonary disease, hypoglycemia, hypertension, dementia, and frailty. Over a median follow-up of 6.2 years (418 deaths), both high hs-cTnI and high hs-cTnT further stratified mortality risk beyond comorbidity levels; those with a high hs-cTnI or hs-cTnT and high comorbidity were at highest mortality risk. Even among those with low comorbidity, a high hs-cTnI (hazard ratio [HR] 3.0 [95% CI 1.7, 5.4]) or hs-cTnT (HR 3.3 [95% CI 1.8, 6.2]) was associated with elevated mortality.

Many comorbidities were reflected by both hs-cTnI and hs-cTnT; elevations in either of the troponins were associated with higher mortality risk beyond comorbidity burden. High-sensitivity cardiac troponins may identify older adults at high mortality risk and be useful in guiding clinical care of older adults with diabetes.

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 studied the effects of more intensive glycemic control in 11,071 patients with type 2 diabetes (T2D), without missing values, in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, using Cox models.

During 5 years’ follow-up, intensive glycemic control reduced major vascular events (hazard ratio [HR] 0.90 [95% CI 0.83–0.98]), with the major driver being a reduction in the development of macroalbuminuria. There was no evidence of differences in the effect, regardless of baseline ASCVD risk or HbA_1c level (P for interaction = 0.29 and 0.94, respectively). Similarly, the beneficial effects of intensive glycemic control on all-cause mortality were not significantly different across baseline ASCVD risk (P = 0.15) or HbA_1c levels (P = 0.87). The risks of severe hypoglycemic events were higher in the intensive glycemic control group compared with the standard glycemic control group (HR 1.85 [1.41–2.42]), with no significant heterogeneity across subgroups defined by ASCVD risk or HbA_1c at baseline (P = 0.09 and 0.18, respectively).

The major benefits for patients with T2D in ADVANCE did not substantially differ across levels of baseline ASCVD risk and HbA_1c.

Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.

FDA revealed that women using RT-CGM had significantly lower glucose (0.4–0.8 mmol/L [7–14 mg/dL]) for 7 h/day (0800 h–1200 h and 1600 h–1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4–0.9 mmol/L [7–16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4–0.7 mmol/L (7–13 mg/dL) for 4.5 h/day at baseline; by 0.4–0.9 mmol/L (7–16 mg/dL) for 16 h/day at 24 weeks; and by 0.4–0.7 mmol/L (7–13 mg/dL) for 14 h/day at 34 weeks.

FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.

Using a group-based modeling approach, we identified sleep duration trajectories based on sleep duration in ages 20–25, 26–35, 36–45, and 46+ years, which were retrospectively assessed in 2009 among 60,068 women from the Nurses’ Health Study II (median age 54.9 years) who were free of diabetes, cardiovascular disease, and cancer. We investigated the prospective associations between sleep duration trajectories and diabetes risk (2009–2017) using multivariable Cox proportional hazards models.

We documented 1,797 incident diabetes cases over a median follow-up of 7.8 years (442,437 person-years). Six sleep duration trajectories were identified: persistent 5-, 6-, 7-, or 8-h sleep duration and increased or decreased sleep duration. After multivariable adjustment for diabetes risk factors, compared with the persistent 7-h sleep duration group, the hazard ratio was 1.43 (95% CI 1.10, 1.84) for the 5-h group, 1.17 (1.04, 1.33) for the 6-h group, 0.96 (0.84, 1.10) for the 8-h group, 1.33 (1.09, 1.61) for the increased sleep duration group, and 1.32 (1.10, 1.59) for the decreased sleep duration group. Additional adjustment for time-updated comorbidities and BMI attenuated these associations, although a significantly higher risk remained in the decreased sleep duration group (1.24 [1.03, 1.50]).

Persistent short sleep duration or changes in sleep duration from early to middle adulthood were associated with higher risk of type 2 diabetes in later life. These associations were weaker after obesity and metabolic comorbidities were accounted for.

This multicenter, double-blind, treat-to-target trial randomized participants to faster aspart (n = 546) or IAsp (n = 545). All available information, regardless of treatment discontinuation or use of ancillary treatment, was used for evaluation of effect.

Noninferiority for the change from baseline in HbA_1c 16 weeks after randomization (primary end point) was confirmed for faster aspart versus IAsp (estimated treatment difference [ETD] –0.04% [95% CI –0.11; 0.03]; –0.39 mmol/mol [–1.15; 0.37]; P < 0.001). Faster aspart was superior to IAsp for change from baseline in 1-h postprandial glucose (PPG) increment using a meal test (ETD –0.40 mmol/L [–0.66; –0.14]; –7.23 mg/dL [–11.92; –2.55]; P = 0.001 for superiority). Change from baseline in self-measured 1-h PPG increment for the mean over all meals favored faster aspart (ETD –0.25 mmol/L [–0.42; –0.09]); –4.58 mg/dL [–7.59; –1.57]; P = 0.003). The overall rate of treatment-emergent severe or blood glucose (BG)–confirmed hypoglycemia was statistically significantly lower for faster aspart versus IAsp (estimated treatment ratio 0.81 [95% CI 0.68; 0.97]).

In combination with insulin degludec, faster aspart provided effective overall glycemic control, superior PPG control, and a lower rate of severe or BG-confirmed hypoglycemia versus IAsp in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.

Forty-five patients with poorly controlled (HbA_1c 7–11%) type 2 diabetes mellitus (T2DM) on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-³H]glucose infusion, after which they were randomized to receive 1) liraglutide 1.2 mg/day (LIRA); 2) canagliflozin 100 mg/day (CANA); or 3) liraglutide 1.2 mg plus canagliflozin 100 mg (CANA/LIRA) for 16 weeks. At 16 weeks, the EGP measurement was repeated.

The mean decrease from baseline to 16 weeks in HbA_1c was –1.67 ± 0.29% (P = 0.0001), –0.89 ± 0.24% (P = 0.002), and –1.44 ± 0.39% (P = 0.004) in patients receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight was –6.0 ± 0.8 kg (P < 0.0001), –3.5 ± 0.5 kg (P < 0.0001), and –1.9 ± 0.8 kg (P = 0.03), respectively. CANA monotherapy caused a 9% increase in basal rate of EGP (P < 0.05), which was accompanied by a 50% increase (P < 0.05) in plasma glucagon-to-insulin ratio. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP. In CANA/LIRA-treated patients, EGP increased by 15% (P < 0.05), even though the plasma insulin response was maintained at baseline and the CANA-induced rise in plasma glucagon concentration was blocked.

These results demonstrate that liraglutide failed to block the increase in EGP caused by canagliflozin despite blocking the rise in plasma glucagon and preventing the decrease in plasma insulin concentration caused by canagliflozin. The failure of liraglutide to prevent the increase in EGP caused by canagliflozin explains the lack of additive effect of these two agents on HbA_1c.

This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (~810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison.

Eighty-seven participants with T2D (age 51 ± 7 years, HbA_1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s^–1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731).

In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.

We studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA_1c variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI.

Compared with the standard therapy group (n = 4,728), the intensive therapy group (n = 4,755) had significantly lower mean HbA_1c (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], P < 0.0001) and lower CV, VIM, and ARV (P < 0.0001). In multivariate adjusted analysis, all three HbA_1c variability indices were significantly associated with total mortality in all patients as well as in the standard- and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA_1c variability indices for the all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA_1c mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI, 1.17–3.61; P < 0.01) only in the intensive-therapy group.

Long-term visit-to-visit HbA_1c variability was a strong predictor of all-cause mortality. HbA_1c VIM combined with HbA_1c mean conferred an increased risk for all-cause mortality in the intensive-therapy group.