The development of diabetes complications is complex and multifactorial. Although advances in pharmacologic interventions and technology have improved diabetes management, nonmedical factors continue to drive persistent disparities in complications across the U.S. Using a socioecological framework, we examine how nonmedical factors operating at individual, organizational, community, and policy levels contribute to rising complications rates. We synthesize multilevel evidence-based interventions, real-world examples, and emerging opportunities that address these drivers. Approaches include culturally and linguistically tailored, digitally delivered diabetes education; systematic screening and documentation of social drivers within health care systems; use of health information systems technology; training for health care providers; multisector community partnerships that leverage social care resources; and policy incentives that integrate medical and social care. Coordinated interventions across socioecological levels are essential to move beyond traditional clinical approaches toward equitable, sustainable diabetes care that reduces complications.

Despite limitations in using BMI to assess obesity, little is known about central obesity's role in pregnancy and postpartum cardiometabolic conditions. We investigated associations of central obesity with perinatal cardiometabolic conditions, independently and jointly with BMI. We examined associations of early pregnancy central obesity measures (waist circumference, waist-to-hip ratio, waist-to-height ratio, and body roundness index) with gestational diabetes mellitus, hypertensive disorders of pregnancy, postpartum prediabetes/diabetes, and postpartum chronic hypertension using modified Poisson (prenatal outcomes) and Cox (postpartum outcomes) regression. Among the 3,055 individuals in the study, there was a dose-response relationship between increasing central obesity and all outcomes, even after adjusting for BMI. Among individuals with healthy prepregnancy BMI, central obesity was associated with a higher risk of gestational diabetes mellitus (relative risks 1.92-2.42), postpartum prediabetes/diabetes (hazard ratios [HRs] 1.50-2.16), and postpartum chronic hypertension (HRs 2.04-3.63). Early pregnancy central obesity measures may enhance perinatal cardiometabolic risk assessment, helping identify at-risk individuals who could be missed using BMI alone.

Type 2 diabetes mellitus (T2DM) amplifies liver disease burden, yet the comparative hepatic effects of antidiabetic drugs remain poorly defined. To compare associations between antidiabetic drug classes and major adverse liver outcomes (MALOs) in adults with T2DM. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched from December 1946 through 23 August 2025. Studies enrolling adults with T2DM that evaluated associations between antidiabetic drug classes with regard to MALOs were included. Data were extracted on study characteristics, drug exposures, and MALOs. A three-level Bayesian network meta-analysis with study- and database-level random effects was performed. Outcomes are reported as hazard ratios (HRs) and ranked using the surface under the cumulative ranking curve. Forty-six observational studies (N = 7,124,845) were included. Thiazolidinediones were least associated with hepatocellular carcinoma incidence and significantly lower than DPP-4 inhibitors (HR 0.50), GLP-1RAs (HR 0.72), insulin (HR 0.20), and sulfonylureas (HR 0.69). For decompensation (composite), GLP-1RAs were associated with the lowest hazard compared with all other classes (HRs 0.16-0.91; all significant). SGLT2 inhibitors were least associated with cirrhosis (HR 0.66 vs. DPP-4 inhibitors; HR 0.66 vs. GLP-1RAs). GLP-1RAs were least associated with variceal bleeding and hepatic encephalopathy, whereas SGLT2 inhibitors were least associated with liver-related mortality. All included studies were observational, precluding causal inference. Liver-specific risk reduction is not uniform across antihyperglycemic drug classes. Randomized trials are needed to determine whether these associations reflect true drug effects.

Diabetes-related disparities among U.S. racial and ethnic minority groups persist, despite decades of research on their causes and interventions in an attempt to reduce them. Research demonstrates a strong relationship between diabetes disparities and social determinants of health, the conditions where people are born, live, work, play, worship, and age. While these upstream factors strongly shape health outcomes, they are largely influenced by policy and community-level interventions with limited influence by clinicians or health systems. By contrast, health-related social needs (HRSN) are downstream consequences of adverse social and structural conditions that directly affect individuals and families. These immediate, actionable needs, such as food, housing, and transportation, can be addressed within health care settings. HRSN disproportionately affect racial and ethnic minority communities, with higher prevalence of diabetes, worse outcomes, and greater acute care use. These observations highlight the importance of addressing HRSN in diabetes care given the potential to improve outcomes and achieve diabetes equity. This narrative review summarizes current evidence on identifying and addressing HRSN in health care settings. Recently, significant progress has been made integrating medical and social care for adults with diabetes and HRSN. Specific examples of these efforts with reporting of diabetes outcomes are reviewed here. However, existing research has not yet demonstrated that HRSN interventions consistently reduce diabetes disparities. Additional infrastructure is needed to scale and sustain interventions, enhancing their feasibility, effectiveness, and long-term impact. We conclude with recommendations for research and practice to optimize social care integration for adults with diabetes and achieve diabetes equity.

Incretin-based pharmacology has revolutionized the medical treatment of type 2 diabetes and obesity. The most effective drug to date is tirzepatide, a dual incretin receptor agonist that engages both the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). While the relative contributions of GIPR and GLP-1R actions to the clinical effects of tirzepatide have not been established, the potency of this agent has reignited interest in the clinical potential of GIPR agonism. Here, we discuss incretin biology as it relates to metabolic pharmacology and contextualize the mechanisms by which GIPR activity could contribute to the development of new and effective drugs. We explore current and future applications of GIPR agonists and antagonists, to underscore the potential that this signaling system could add to treatment of type 2 diabetes and obesity.

Hyperglycemia during acute pancreatitis (HDAP) likely reflects both stress hormone responses and pancreatic islet injury, distinguishing it from typical stress-induced hyperglycemia. The aim of this study was to determine the prevalence of HDAP and its prognostic significance for early-onset diabetes following acute pancreatitis (AP). Diabetes Related to Acute Pancreatitis and Its Mechanisms (DREAM) is a prospective multicenter study examining the development of diabetes following AP. This analysis included 395 participants without prior diabetes with an AP episode, focusing on their glucose levels during the event. Two definitions of HDAP were examined: peak glucose >140 mg/dL (HDAP140) and >200 mg/dL (HDAP200). Outpatient glycemic status after recovery (median: 111 days post-AP) was evaluated using fasting glucose, oral glucose tolerance test, and HbA1c. HDAP140 and HDAP200 were present in 37.5% and 7.1% of participants, respectively. Age, race, etiology, and AP severity were significant predictors of HDAP140. Among participants with HDAP140, 14.8% developed early-onset diabetes after AP recovery vs. 1.2% in those without (P = 0.0001). In those with HDAP200, 42.9% developed early-onset diabetes vs. 3.5% in those without (P = 0.0001). The absence of HDAP140 and HDAP200 was associated with negative predictive values of 99% and 97%, respectively, for diabetes. HDAP can be common in individuals without diabetes and is associated with early-onset diabetes following AP. Individuals without HDAP have a low risk of diabetes short term, while those with HDAP200 are at high risk. Monitoring glycemia during AP can identify individuals best suited for early targeted postdischarge care.

Glucagon-based polyagonists improve metabolic dysfunction-associated steatotic liver disease (MASLD), which could result from glucagon-stimulated hepatic lipid oxidation. Nevertheless, people with long-standing type 2 diabetes (T2D) exhibit a paradoxical rise in both hepatic lipid content (HLC) and glucagon levels, which has been related to disturbed hepatic metabolism generating glucagonotropic metabolites such as amino acids and nonesterified fatty acids (NEFAs). We examined these relationships in individuals with normal glucose tolerance (NGT) and newly diagnosed T2D. Fifty individuals with newly diagnosed T2D and 50 age-, sex-, BMI-matched individuals with NGT underwent liquid mixed-meal tolerance tests to measure glucagon and metabolites, hyperinsulinemic-euglycemic clamps with stable isotope dilution, indirect calorimetry to assess insulin sensitivity and lipid oxidation, and 1H/31P magnetic resonance spectroscopy and MRI to quantify HLC, ATP, and visceral adipose tissue (VAT) volume. Individuals with T2D had an ∼65% higher HLC as well as higher fasting and postprandial glucagonemia (∼30% and ∼75%) than those with NGT. Multivariable linear regression analyses revealed that the presence of MASLD, but not T2D, was associated with higher fasting glucagonemia. Interestingly, postprandial glucagon was related to HLC only in T2D, leading to ∼47% higher early postprandial glucagonemia in individuals with combined MASLD and T2D. These differential associations were independent of insulin sensitivity or VAT volume, and neither were mediated by amino acids or NEFAs. Hyperglucagonemia in the face of higher HLC in early T2D is not due to differences in insulin sensitivity or glucagonotropic metabolites but could suggest hepatic glucagon resistance.

To investigate previous gestational diabetes mellitus (GDM) as a potential risk factor for diabetic retinopathy (DR) in women with diabetes, including the potential role of GDM severity and hypertension after pregnancy. A nationwide, register-based cohort study including all women giving birth in Denmark in 1997-2018. We defined GDM and DR using ICD-10 codes. GDM severity was a proxy based on insulin treatment during GDM pregnancy. Subsequent diabetes and hypertension were based on ICD-10 codes and/or medication postpregnancy. Statistical analyses included Cox regression. The complete study population comprised 708,250 women. The GDM prevalence was 3.4%, and the overall median follow-up was 12 years. Diabetes developed subsequently in 18,556 women, and DR occurred in 655 of these. In the women who developed diabetes, previous GDM was associated with a threefold higher risk of DR (adjusted hazard ratio [aHR] 3.0 [95% CI 2.6-3.6]). The risk increased with increasing GDM severity (aHRs 5.6 [95% CI 4.5-6.9] and 2.4 [95% CI 2.0-2.9]) in women with previous GDM with and without insulin treatment, respectively, compared with women without previous GDM [reference group]). In women with subsequent hypertension, GDM exposure was associated with a 2.7-fold higher DR risk (aHR 2.7 [95% CI 2.1-3.5]). This large population-based study identified GDM as significant risk factor for DR in parous women with diabetes, a risk that increased with increasing GDM severity and postpregnancy hypertension development. On the basis of this study, planning of DR screening strategies should include awareness of GDM history.

Glycemic management metrics derived from continuous glucose monitoring (CGM) are increasingly recognized as important therapeutic targets. We performed one of the first comparisons of CGM metrics and achievement of CGM targets among four classes of glucose-lowering medications in combination with metformin. The Glycemia Reduction Approaches in Diabetes (GRADE) study randomly assigned participants with type 2 diabetes and taking metformin to add one of four glucose-lowering medications (insulin glargine, glimepiride, liraglutide, or sitagliptin) and followed them for glycemic outcomes for 5 ± 1.3 years. A 2-week masked CGM analysis was conducted midstudy in 1,080 participants to evaluate CGM metrics, 24-h ambulatory glucose profile, and achievement of consensus goals. Treatment effects among the four groups were compared. The sitagliptin and liraglutide groups had the highest time in range 70-180 mg/dL (TIR70-180) and the lowest time below range <70 mg/dL (TBR<70) and percentage coefficient of variation (%CV). The glimepiride group had the lowest TIR70-180, and the highest %CV, TBR<70, and number of CGM-derived hypoglycemic events (P < 0.001), and was the only drug showing daytime hypoglycemia. Sitagliptin and liraglutide were best for achieving consensus goals of very low TBR<54 <1% and the combined metric of TIR70-180 >70% and TBR<70 <4% (P < 0.001). When stratified by HbA1c, mean glucose did not differ among treatments, but %CV and TBR<70 were higher with glargine and glimepiride within each HbA1c stratum. Incretin class drugs had the lowest %CV, the least hypoglycemia, and best achievement of CGM-based glycemic targets. CGM metrics and profiles provide clinical insights, beyond HbA1c, to guide diabetes management.

Adult-onset type 1 diabetes is not well characterized, especially after 40 years of age, and is commonly misdiagnosed as type 2 diabetes. We evaluated the differences in clinical presentation, islet autoantibodies, and HLA genetics between pediatric- and adult-onset type 1 diabetes. Individuals who were newly diagnosed with type 1 diabetes were tested for islet autoantibodies within 1 year of diagnosis in this retrospective study. Islet autoantibodies against GAD, insulin, islet antigen 2, and zinc transporter 8 were measured using fluid-phase radiobinding assays. High-resolution HLA class I (n = 655) and II (n = 1,196) typing was performed in a subset of participants. In total, 414 adults (aged ≥20 years) and 2,000 children were included. Adults were aged 20 to 76 years and had a mean BMI of 23.5 ± 4.7 kg/m2 at onset. Compared with children, adults presented with diabetic ketoacidosis (DKA) less frequently (32.6% vs. 56.0%; P < 0.001) and with slightly lower HbA1c values (11.3% ± 2.6% vs. 12.0% ± 2.4%; P < 0.001). Notably, adults older than 40 years (n = 84) presented with DKA only 13.1% of the time. Adults more often presented with zero or one islet autoantibodies compared with children (43.0% vs. 20.2%; P < 0.001). There were no differences in high-risk HLA haplotypes between adults and children (DR4-DQ8: 57.1% vs. 63.7%; P = 0.060; DR3-DQ2: 43.6% vs. 46.1%; P = 0.482). Adult-onset type 1 diabetes is characterized by a reduced frequency of DKA and by fewer total islet autoantibodies. Our findings can help in the accurate diagnosis of type 1 diabetes in adults.