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 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.

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.

Up to September 2018, 1.4 million office BP measurements in 79,849 children and adolescents (aged 5–20 years) with T1DM have been documented in the DPV (Diabetes Prospective Follow-up) registry. BP values of the most recent year were aggregated, and BP values of 74,677 patients without antihypertensive medication were analyzed (median age 16 years and diabetes duration 5.3 years and 52.8% boys). BP values were classified according to AAP 2017 and the references of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (2011) and the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (fourth report) (2004).

Of the patients, 44.1%, 29.5%, and 26.5% were hypertensive according to AAP 2017, KiGGS, and fourth report, respectively. Differences in prevalence of HTN were strongly age dependent: <10 years, AAP 2017 31.4%, KiGGS 30.7%, fourth report 19.6%; 10 to <15 years, AAP 2017 30.9%, KiGGS 31.2%, fourth report 22.4%; and ≥15 years, AAP 2017 53.2%, KiGGS 28.4%, fourth report 30.0%. Among teenagers ≥15 years, 59.1% of boys but only 46.3% of girls were classified as hypertensive by AAP 2017 but only 21.1%/26% of boys and 36.7%/34.4% of girls by KiGGS/fourth report, respectively.

Classification of BP as hypertension depends strongly on the normative data used. Use of AAP 2017 results in a significant increase in HTN in teenagers ≥15 years with T1DM, particularly in boys. AAP 2017 enhances the awareness of elevated BP in children, particularly in patients with increased risk for cardiovascular disease.

Cox regression models were constructed to analyze 20 years of data from the Danish National Patient Registry with respect to effect of the antihyperglycemic therapies on the three end points.

A total of 66,807 people with type 2 diabetes were treated with metformin (MET) including a combination of second- and third-line therapies. People on MET plus sulfonylurea (SU) had the highest risk of all end points, except for severe hypoglycemia, for which people on MET plus basal insulin (BASAL) had a higher risk. The lowest risk of major adverse cardiovascular events was seen for people on a regimen including a glucagon-like peptide 1 (GLP-1) receptor agonist. People treated with MET, GLP-1, and BASAL had a lower risk of all three end points than people treated with MET and BASAL, especially for severe hypoglycemia. The lowest risk of all three end points was, in general, seen for people treated with MET, sodium–glucose cotransporter 2 inhibitor, and GLP-1.

Findings from this study do not support SU as the second-line treatment choice for patients with type 2 diabetes. Moreover, the results indicate that adding a GLP-1 for people treated with MET and BASAL could be considered, especially if those people suffer from severe hypoglycemia.

We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI. Key secondary end points included other measures of LV remodeling and clinical and biochemical parameters.

In our cohort, dapagliflozin had no effect on LVESV or any other parameter of LV remodeling. However, it reduced diastolic blood pressure and loop diuretic requirements while increasing hemoglobin, hematocrit, and ketone bodies. There was a trend toward lower weight.

We were unable to determine with certainty whether dapagliflozin in patients with T2DM and HF had any effect on LV remodeling. Whether the benefits of dapagliflozin in HF are due to remodeling or other mechanisms remains unknown.

A total of 21 exons and exon-intron boundaries of ATP7B were identified by Sanger sequencing.

Two novel compound heterozygous mutations (c.525 dupA/ Val176Serfs*28 and c.2930 C>T/ p.Thr977Met) were detected in ATP7B. After d-penicillamine (D-PCA) therapy, serum aminotransferase and ceruloplasmin levels in this patient were normalized and levels of HbA_1c decreased. However, when the patient ceased to use D-PCA due to an itchy skin, serum levels of fasting blood glucose increased. Dimercaptosuccinic acid capsules were prescribed and memory recovered to some extent, which was accompanied by decreased insulin dosage for glucose control by 5 units.

This is the first report of diabetes caused by WD.

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.

In this phase 3, open-label, multicenter trial, 321 patients with HbA_1c≥7.5 to ≤10.0% (58–86 mmol/mol) and fasting plasma glucose (FPG) ≤13.8 mmol/L (250 mg/dL) were randomized 1:1 to iGlarLixi or Lixi for 52 weeks. The primary end point was change in HbA_1c at week 26.

Change in HbA_1c from baseline to week 26 was significantly greater with iGlarLixi (–1.58% [–17.3 mmol/mol]) than with Lixi (–0.51% [–5.6 mmol/mol]), confirming the superiority of iGlarLixi (least squares [LS] mean difference –1.07% [–11.7 mmol/mol], P < 0.0001). At week 26, significantly greater proportions of patients treated with iGlarLixi reached HbA_1c <7% (53 mmol/mol) (65.2% vs. 19.4%; P < 0.0001), and FPG reductions were greater with iGlarLixi than Lixi (LS mean difference –2.29 mmol/L [–41.23 mg/dL], P < 0.0001). Incidence of documented symptomatic hypoglycemia (≤3.9 mmol/L [70 mg/dL]) was higher with iGlarLixi (13.0% vs. 2.5%) through week 26, with no severe hypoglycemic events in either group. Incidence of gastrointestinal events through week 52 was lower with iGlarLixi (36.0% vs. 50.0%), and rates of treatment-emergent adverse events were similar.

This phase 3 study demonstrated superior glycemic control and fewer gastrointestinal adverse events with iGlarLixi than with Lixi, which may support it as a new treatment option for Japanese patients with T2DM that is inadequately controlled with OADs.

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.

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.

We included 84,285 postmenopausal women without a history of diabetes from the national Women’s Health Initiative Observational Study (WHI-OS). Replication analysis was then conducted among 62,338 women who participated in the WHI-Clinical Trial (WHI-CT). Additionally, data from a case-control study of 3,749 women nested in the WHI-OS with information on biomarkers of inflammation and endothelial dysfunction were examined using mediation analysis to determine the relative contributions of these known biomarkers by which manganese affects type 2 diabetes risk.

Compared with the lowest quintile of energy-adjusted dietary manganese, WHI-OS participants in the highest quintile had a 30% lower risk of type 2 diabetes (hazard ratio [HR] 0.70 [95% CI 0.65, 0.76]). A consistent association was also confirmed in the WHI-CT (HR 0.79 [95% CI 0.73, 0.85]). In the nested case-control study, higher energy-adjusted dietary manganese was associated with lower circulating levels of inflammatory biomarkers that significantly mediated the association between dietary manganese and type 2 diabetes risk. Specifically, 19% and 12% of type 2 diabetes risk due to manganese were mediated through interleukin 6 and hs-CRP, respectively.

Higher intake of manganese was directly associated with a lower type 2 diabetes risk independent of known risk factors. This association may be partially mediated by inflammatory biomarkers.

Four years of data were extracted from a hospital electronic health record system. This included laboratory and point-of-care blood glucose (BG) values to identify biochemical and clinically significant hypoglycemic episodes (BG ≤3.9 and ≤2.9 mmol/L, respectively). We used patient demographics, administered medications, vital signs, laboratory results, and procedures performed during the hospital stays to inform the model. Two iterations of the data set included the doses of insulin administered and the past history of inpatient hypoglycemia. Eighteen different prediction models were compared using the area under the receiver operating characteristic curve (AUROC) through a 10-fold cross validation.

We analyzed data obtained from 17,658 inpatients with diabetes who underwent 32,758 admissions between July 2014 and August 2018. The predictive factors from the logistic regression model included people undergoing procedures, weight, type of diabetes, oxygen saturation level, use of medications (insulin, sulfonylurea, and metformin), and albumin levels. The machine learning model with the best performance was the XGBoost model (AUROC 0.96). This outperformed the logistic regression model, which had an AUROC of 0.75 for the estimation of the risk of clinically significant hypoglycemia.

Advanced machine learning models are superior to logistic regression models in predicting the risk of hypoglycemia in inpatients with diabetes. Trials of such models should be conducted in real time to evaluate their utility to reduce inpatient hypoglycemia.

All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT samples in NaF tubes were centrifuged within 10 min (early centrifugation).

A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P < 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887).

The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood samples used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.

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.

The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP), a two-by-two factorial randomized controlled trial, examined effects of SBP (<120 vs. <140 mmHg) and glycemic (HbA_1c <6% vs. 7.0–7.9% [<42 vs. 53–63 mmol/mol]) control on cardiovascular events in T2DM (N = 4,731). We examined whether effects of SBP control on cardiovascular composite were modified by baseline DBP and glycemic control.

Intensive SBP lowering decreased the risk of the cardiovascular composite (hazard ratio [HR] 0.76 [95% CI 0.59–0.98]) in the standard glycemic arm but not in the intensive glycemic arm (HR 1.06 [95% CI 0.81–1.40]). Spline regression models relating the effects of the intervention on the cardiovascular composite across the range of baseline DBP did not show evidence of effect modification by low baseline DBP for the cardiovascular composite in the standard or intensive glycemic arms. The relation between the effect of the intensive SBP intervention and baseline DBP was similar between glycemic arms for the cardiovascular composite three-way interaction (P = 0.83).

In persons with T2DM, intensive SBP lowering decreased the risk of cardiovascular composite end point irrespective of baseline DBP in the setting of standard glycemic control. Hence, low baseline DBP should not be an impediment to intensive SBP lowering in patients with T2DM treated with guidelines recommending standard glycemic control.

Patients with T2DM received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), keratin-18 (K-18), procollagen III (Pro-C3), and adiponectin were analyzed in a modified intention-to-treat population.

Significant (P < 0.05) reductions from baseline in ALT (all groups), AST (all groups except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg), and Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg) and with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from baseline with tirzepatide compared with placebo (10, 15 mg).

In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.

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.