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.

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.

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 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 thoroughly characterized 6,726 patients with recently diagnosed diabetes. After a median of 2.8 years, we sent a detailed questionnaire on neuropathy, including the Michigan Neuropathy Screening Instrument questionnaire (MNSIq), to identify possible DPN (score ≥4) and the Douleur Neuropathique en 4 Questions (DN4) questionnaire for possible associated neuropathic pain (MNSIq ≥4 + pain in both feet + DN4 score ≥3).

Among 5,249 patients with data on both DPN and pain, 17.9% (n = 938) had possible DPN, including 7.4% (n = 386) with possible neuropathic pain. In regression analyses, central obesity (waist circumference, waist-to-hip ratio, and waist-to-height ratio) was markedly associated with DPN. Other important metabolic factors associated with DPN included hypertriglyceridemia ≥1.7 mmol/L, adjusted prevalence ratio (aPR) 1.36 (95% CI 1.17; 1.59); decreased HDL cholesterol <1.0/1.2 mmol/L (male/female), aPR 1.35 (95% CI 1.12; 1.62); hs-CRP ≥3.0 mg/L, aPR 1.66 (95% CI 1.42; 1.94); C-peptide ≥1,550 pmol/L, aPR 1.72 (95% CI 1.43; 2.07); HbA_1c ≥78 mmol/mol, aPR 1.42 (95% CI 1.06; 1.88); and antihypertensive drug use, aPR 1.34 (95% CI 1.16; 1.55). Smoking, aPR 1.50 (95% CI 1.24; 1.81), and lack of physical activity (0 vs. ≥3 days/week), aPR 1.61 (95% CI 1.39; 1.85), were also associated with DPN. Smoking, high alcohol intake, and failure to increase activity after diabetes diagnosis associated with neuropathic pain.

Possible DPN was associated with metabolic syndrome factors, insulin resistance, inflammation, and modifiable lifestyle habits in early type 2 diabetes.

This was a cohort study using an active-comparator, new-user design and nationwide register data from Sweden, Denmark, and Norway during 2010–2016. The cohort included 38,731 new users of GLP-1 receptor agonists (liraglutide 92.5%, exenatide 6.2%, lixisenatide 0.7%, and dulaglutide 0.6%), matched 1:1 on age, sex, and propensity score to a new user of the active comparator, dipeptidyl peptidase 4 (DPP-4) inhibitors. The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospitalization for renal events. Secondary outcomes were the individual components of the main outcome. Hazard ratios (HRs) were estimated using Cox models and an intention-to-treat exposure definition. Mean (SD) follow-up time was 3.0 (1.7) years.

Mean (SD) age of the study population was 59 (10) years, and 18% had cardiovascular disease. A serious renal event occurred in 570 users of GLP-1 receptor agonists (incidence rate 4.8 events per 1,000 person-years) and in 722 users of DPP-4 inhibitors (6.3 events per 1,000 person-years, HR 0.76 [95% CI 0.68–0.85], absolute difference –1.5 events per 1,000 person-years [–2.1 to –0.9]). Use of GLP-1 receptor agonists was associated with a significantly lower risk of renal replacement therapy (HR 0.73 [0.62–0.87]) and hospitalization for renal events (HR 0.73 [0.65–0.83]) but not death from renal causes (HR 0.72 [0.48–1.10]). When we used an as treated exposure definition in which patients were censored at treatment cessation or switch to the other study drug, the HR for the primary outcome was 0.60 (0.49–0.74).

In this large cohort of patients seen in routine clinical practice in three countries, use of GLP-1 receptor agonists, as compared with DPP-4 inhibitors, was associated with a reduced risk of serious renal events.

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.

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.

We performed exploratory analyses to identify potential mediators of the effect of liraglutide on major adverse CV events (MACE; composite of CV death, nonfatal myocardial infarction, or nonfatal stroke) from the following candidates: glycated hemoglobin (HbA_1c), body weight, urinary albumin-to-creatinine ratio (UACR), confirmed hypoglycemia, sulfonylurea use, insulin use, systolic blood pressure, and LDL cholesterol. These candidates were selected as CV risk factors on which liraglutide had an effect in LEADER such that a reduction in CV risk might result. We used two methods based on a Cox proportional hazards model and the new Vansteelandt method designed to use all available information from the mediator and to control for confounding factors.

Analyses using the Cox methods and Vansteelandt method indicated potential mediation by HbA_1c (up to 41% and 83% mediation, respectively) and UACR (up to 29% and 33% mediation, respectively) on the effect of liraglutide on MACE. Mediation effects were small for other candidates.

These analyses identify HbA_1c and, to a lesser extent, UACR as potential mediators of the CV effects of liraglutide. Whether either is a marker of an unmeasured factor or a true mediator remains a key question that invites further investigation.

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.