Racial Disparities in Evidence-Based Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients With Type 2 Diabetes.

OBJECTIVE: To assess frequency of evidence-based management (EBM) of metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with type 2 diabetes (T2D), and to examine for racial/ethnic disparities in the receipt of EBM. METHODS: We conducted a cross-sectional analysis of patients with T2D and presumptive MASLD in an academic health care system between 2019 and 2021. Presumptive MASLD was defined as at least 1 alanine aminotransferase value ≥30 U/L with exclusions for alcohol overuse, viral hepatitis, liver transplantation, chemotherapy use, and liver disease other than MASLD. We calculated the proportion of patients receiving EBM, defined as a composite of liver ultrasound, transient elastography, or hepatology evaluation. We also examined the association between race/ethnicity and EBM via a logistic regression model. RESULTS: Our sample included 6532 patients; mean age was 58.0 (SD 13.1), 41.7% were female and 3.9%, 26.6%, 58.7%, and 5.8% were of Latino/a/x ethnicity, non-Latino (NL) Black race, NL White race, and NL Asian race, respectively. Rates of EBM were low overall (11.5%), with lower odds of EBM in NL Black versus NL White patients (adjusted odds ratio 0.75; 95% confidence interval 0.59, 0.96). Odds of hepatology evaluation and placement of MASLD diagnosis codes were also lower in NL Black versus NL White patients. CONCLUSION: Racial disparities exist in the receipt of EBM among patients with T2D and presumptive MASLD. These findings highlight the need for research to identify drivers of disparities, and to support development of clinical interventions that equitably facilitate EBM of MASLD in patients with T2D.

Evaluating Therapeutic Inertia in Two Telehealth Interventions for Type 2 Diabetes: Secondary Analyses of a Randomized Trial.

Introduction: Although therapeutic inertia is a known driver of suboptimal type 2 diabetes control, little is known about how to combat this phenomenon. We analyzed randomized trial data to determine whether a comprehensive telehealth intervention was more effective than a less structured telehealth approach (telemonitoring and care coordination) at promoting treatment intensification in poorly controlled diabetes. Methods: Patients with poorly controlled type 2 diabetes were randomized 1:1 to telemonitoring/care coordination or a comprehensive telehealth intervention, which included an active, study provider-guided medication management component. Prospectively collected medication lists were used to determine whether treatment intensification occurred for each patient during 3-month intervals throughout the study period. To examine between-arm differences in treatment intensification over time, we fit a generalized estimation equation model. In each arm, hemoglobin A1c levels at the beginning and end of each 3-month interval were used to distinguish between therapeutic inertia and potentially appropriate nonintensification of treatment. Results: The mean, model-estimated likelihood of treatment intensification during 3-month intervals was 61.3% in the comprehensive telehealth group versus 48.6% for telemonitoring/care coordination (odds ratio 1.7, 95% confidence interval 1.2-2.2; p = 0.0007), with no evidence that treatment effect varied over time (p = 0.54). Treatment intervals with observed therapeutic inertia were more common in the telemonitoring/care coordination arm than the comprehensive telehealth arm (116/300, 39% vs. 57/275, 21%). Conclusions: A comprehensive telehealth approach that integrated protocol-guided medication management increased treatment intensification and reduced therapeutic inertia compared with a less structured telehealth approach. The studied approaches may serve as examples of how systems might use telehealth to combat therapeutic inertia. Clinical Trial Registration: ClinicalTrials.gov NCT03520413.

Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Whether glycemic control, as opposed to diabetes status, is associated with the severity of NAFLD is open for study. We aimed to evaluate whether degree of glycemic control in the years preceding liver biopsy predicts the histological severity of NASH. APPROACH AND RESULTS: Using the Duke NAFLD Clinical Database, we examined patients with biopsy-proven NAFLD/NASH (n = 713) and the association of liver injury with glycemic control as measured by hemoglobin A1c (HbA1c). The study cohort was predominantly female (59%) and White (84%) with median (interquartile range) age of 50 (42, 58) years; 49% had diabetes (n = 348). Generalized linear regression models adjusted for age, sex, race, diabetes, body mass index, and hyperlipidemia were used to assess the association between mean HbA1c over the year preceding liver biopsy and severity of histological features of NAFLD/NASH. Histological features were graded and staged according to the NASH Clinical Research Network system. Group-based trajectory analysis was used to examine patients with at least three HbA1c (n = 298) measures over 5 years preceding clinically indicated liver biopsy. Higher mean HbA1c was associated with higher grade of steatosis and ballooned hepatocytes, but not lobular inflammation. Every 1% increase in mean HbA1c was associated with 15% higher odds of increased fibrosis stage (OR, 1.15; 95% CI, 1.01, 1.31). As compared with good glycemic control, moderate control was significantly associated with increased severity of ballooned hepatocytes (OR, 1.74; 95% CI, 1.01, 3.01; P = 0.048) and hepatic fibrosis (HF; OR, 4.59; 95% CI, 2.33, 9.06; P < 0.01). CONCLUSIONS: Glycemic control predicts severity of ballooned hepatocytes and HF in NAFLD/NASH, and thus optimizing glycemic control may be a means of modifying risk of NASH-related fibrosis progression.

Telehealth for the Longitudinal Management of Chronic Conditions: Systematic Review.

BACKGROUND: Extensive literature support telehealth as a supplement or adjunct to in-person care for the management of chronic conditions such as congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM). Evidence is needed to support the use of telehealth as an equivalent and equitable replacement for in-person care and to assess potential adverse effects. OBJECTIVE: We conducted a systematic review to address the following question: among adults, what is the effect of synchronous telehealth (real-time response among individuals via phone or phone and video) compared with in-person care (or compared with phone, if synchronous video care) for chronic management of CHF, chronic obstructive pulmonary disease, and T2DM on key disease-specific clinical outcomes and health care use? METHODS: We followed systematic review methodologies and searched two databases (MEDLINE and Embase). We included randomized or quasi-experimental studies that evaluated the effect of synchronously delivered telehealth for relevant chronic conditions that occurred over ≥2 encounters and in which some or all in-person care was supplanted by care delivered via phone or video. We assessed the bias using the Cochrane Effective Practice and Organization of Care risk of bias (ROB) tool and the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation. We described the findings narratively and did not conduct meta-analysis owing to the small number of studies and the conceptual heterogeneity of the identified interventions. RESULTS: We identified 8662 studies, and 129 (1.49%) were reviewed at the full-text stage. In total, 3.9% (5/129) of the articles were retained for data extraction, all of which (5/5, 100%) were randomized controlled trials. The CHF study (1/5, 20%) was found to have high ROB and randomized patients (n=210) to receive quarterly automated asynchronous web-based review and follow-up of telemetry data versus synchronous personal follow-up (in-person vs phone-based) for 1 year. A 3-way comparison across study arms found no significant differences in clinical outcomes. Overall, 80% (4/5) of the studies (n=466) evaluated synchronous care for patients with T2DM (ROB was judged to be low for 2, 50% of studies and high for 2, 50% of studies). In total, 20% (1/5) of the studies were adequately powered to assess the difference in glycosylated hemoglobin level between groups; however, no significant difference was found. Intervention design varied greatly from remote monitoring of blood glucose combined with video versus in-person visits to an endocrinology clinic to a brief, 3-week remote intervention to stabilize uncontrolled diabetes. No articles were identified for chronic obstructive pulmonary disease. CONCLUSIONS: This review found few studies with a variety of designs and interventions that used telehealth as a replacement for in-person care. Future research should consider including observational studies and studies on additional highly prevalent chronic diseases.

Duration of type 2 diabetes does not appear to moderate hypoglycaemia rate with insulin degludec versus insulin glargine U100.

In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during the maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes. In this post hoc analysis, data from 7635 individuals from DEVOTE and 720 individuals from SWITCH 2 were analysed by subgroups of diabetes duration at baseline (<10, ≥10-<15, ≥15-<20 and ≥20 years) using prespecified models from both trials. There was a trend towards lower rates of hypoglycaemia with degludec versus glargine U100 across all diabetes duration subgroups in both trials, with the difference being statistically significant in some subgroups in DEVOTE and SWITCH 2. Overall, however, no significant interaction was observed between diabetes duration and treatment (DEVOTE interaction, P = .496; SWITCH 2 interaction, P = .144). Therefore, in this post hoc analysis of DEVOTE and SWITCH 2, diabetes duration did not appear to affect the reduction in rates of hypoglycaemia observed with degludec compared with glargine U100.

Risk for Nephrogenic Systemic Fibrosis After Exposure to Newer Gadolinium Agents: A Systematic Review.

BACKGROUND: The risk for nephrogenic systemic fibrosis (NSF) after exposure to newer versus older gadolinium-based contrast agents (GBCAs) remains unclear. PURPOSE: To synthesize evidence about NSF risk with newer versus older GBCAs across the spectrum of kidney function. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science for English-language references from inception to 5 March 2020. STUDY SELECTION: Randomized controlled trials, cohort studies, and case-control studies that assessed NSF occurrence after GBCA exposure. DATA EXTRACTION: Data were abstracted by 1 investigator and verified by a second. Investigator pairs assessed risk of bias by using validated tools. DATA SYNTHESIS: Of 32 included studies, 20 allowed for assessment of NSF risk after exposure to newer GBCAs and 12 (11 cohort studies and 1 case-control study) allowed for comparison of NSF risk between newer and older GBCAs. Among 83 291 patients exposed to newer GBCAs, no NSF cases developed (exact 95% CI, 0.0001 to 0.0258 case). Among the 12 studies (n = 118 844) that allowed risk comparison between newer and older GBCAs, 37 NSF cases developed after exposure to older GBCAs (exact CI, 0.0001 to 0.0523 case) and 4 occurred (3 confounded) after exposure to newer GBCAs (exact CI, 0.0018 to 0.0204 case). Data were scant for patients with acute kidney injury or those at risk for chronic kidney disease. LIMITATIONS: Study heterogeneity prevented meta-analysis. Risk of bias was high in most studies because of inadequate exposure and outcome ascertainment. CONCLUSION: Although NSF occurrence after exposure to newer GBCAs is very rare, the relatively scarce data among patients with acute kidney injury and those with risk factors for chronic kidney disease limit conclusions about safety in these populations. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. (PROSPERO: CRD42019135783).

Racial Differences in the Effectiveness of a Multifactorial Telehealth Intervention to Slow Diabetic Kidney Disease.

BACKGROUND: African Americans are significantly more likely than non-African Americans to have diabetes, chronic kidney disease, and uncontrolled hypertension, increasing their risk for kidney function decline. OBJECTIVE: The objective of this study was to compare how African Americans and non-African Americans with diabetes responded to a multifactorial telehealth intervention designed to slow kidney function decline. RESEARCH DESIGN: Secondary analysis of a randomized trial. Primary care patients (N=281, 56% African American) were allocated to either: (1) a multifactorial, pharmacist-delivered phone-based telehealth intervention focused on behavioral and medication management of diabetic kidney disease; or (2) an education control. MEASURES: The primary study outcome was change in estimated glomerular filtration rate (eGFR). Linear mixed models were used to explore the moderating effect of race on the relationship between study arm and eGFR decline over time; the mean annual rate of eGFR decline was estimated by race and study arm. RESULTS: Findings demonstrated a differential intervention effect on kidney function over time by race (Pinteraction=0.005). Among African Americans, the intervention arm had significantly greater preservation of eGFR over time than the control arm (difference in the annual rate of eGFR decline=1.5 mL/min/1.73 m; 95% confidence interval: 0.04, 3.02). For non-African Americans, the intervention arm had a faster decline in eGFR over time than the control arm (difference in the annual rate of eGFR decline=-1.7 mL/min/1.73 m; 95% confidence interval: -3.3, -0.02). CONCLUSION: A multifactorial, pharmacist-delivered telehealth intervention for diabetic kidney disease may be more effective for slowing eGFR decline among African Americans than non-African Americans.

Triglycerides: Emerging Targets in Diabetes Care? Review of Moderate Hypertriglyceridemia in Diabetes.

PURPOSE OF REVIEW: Moderate hypertriglyceridemia is exceedingly common in diabetes, and there is growing evidence that it contributes to residual cardiovascular risk in statin-optimized patients. Major fibrate trials yielded inconclusive results regarding the cardiovascular benefit of lowering triglycerides, although there was a signal for improvement among patients with high triglycerides and low high-density lipoprotein (HDL)-the "diabetic dyslipidemia" phenotype. Until recently, no trials have examined a priori the impact of triglyceride lowering in patients with diabetic dyslipidemia, who are likely among the highest cardiovascular-risk patients. RECENT FINDINGS: In the recent REDUCE IT trial, omega-3 fatty acid icosapent ethyl demonstrated efficacy in lowering cardiovascular events in patients with high triglycerides, low HDL, and statin-optimized low-density lipoprotein (LDL). The ongoing PROMINENT trial is examining the impact of pemafibrate in a similar patient population. Emerging evidence suggests that lowering triglycerides may reduce residual cardiovascular risk, especially in high-risk patients with diabetic dyslipidemia.

Management of Preexisting Diabetes in Pregnancy: A Review.

Importance: The presence of preexisting type 1 or type 2 diabetes in pregnancy increases the risk of adverse maternal and neonatal outcomes, such as preeclampsia, cesarean delivery, preterm delivery, macrosomia, and congenital defects. Approximately 0.9% of the 4 million births in the United States annually are complicated by preexisting diabetes. Observations: Women with diabetes have increased risk for adverse maternal and neonatal outcomes, and similar risks are present with type 1 and type 2 diabetes. Both forms of diabetes require similar intensity of diabetes care. Preconception planning is very important to avoid unintended pregnancies and to minimize risk of congenital defects. Hemoglobin A1c goals are less than 6.5% at conception and less than 6.0% during pregnancy. It is also critical to screen for and manage comorbid illnesses, such as retinopathy and nephropathy. Medications known to be unsafe in pregnancy, such as angiotensin-converting enzyme inhibitors and statins, should be discontinued. Women with obesity should be screened for obstructive sleep apnea, which is often undiagnosed and can result in poor outcomes. Blood pressure goals must be considered carefully because lower treatment thresholds may be required for women with nephropathy. During pregnancy, continuous glucose monitoring can improve glycemic control and neonatal outcomes in women with type 1 diabetes. Insulin is first-line therapy for all women with preexisting diabetes; injections and insulin pump therapy are both effective approaches. Rates of severe hypoglycemia are increased during pregnancy; therefore, glucagon should be available to the patient and close contacts should be trained in its use. Low-dose aspirin is recommended soon after 12 weeks' gestation to minimize the risk of preeclampsia. The importance of discussing long-acting reversible contraception before and after pregnancy, to allow for appropriate preconception planning, cannot be overstated. Conclusions and Relevance: Preexisting diabetes in pregnancy is complex and is associated with significant maternal and neonatal risk. Optimization of glycemic control, medication regimens, and careful attention to comorbid conditions can help mitigate these risks and ensure quality diabetes care before, during, and after pregnancy.

Specialist Perspectives on Delivering High-Quality Telemedicine for Diabetes: A Mixed Methods Survey Study.

Background: Recent recommendations guiding appropriate use of telemedicine for endocrinology care have largely relied on expert opinion due to limited evidence on factors that increase quality of telemedicine care. In this study, we assessed the perspectives of front-line specialists on factors and strategies perceived to increase quality of diabetes care delivered via telemedicine after more than 2 years of widespread use. Methods: Adult diabetes specialists in 2 academic health systems who recently used video-based telemedicine to provide diabetes care were invited to participate in an online survey study between March and April 2022. Likert-style questions, followed by related open-ended questions, assessed perspectives on availability of key resources, factors affecting quality, and anticipated benefits from telemedicine for diabetes. Results: Response rate was 52% (56/111). More than half (54%) of participants reported better overall quality of diabetes care with face-to-face care vs telemedicine. Participants reported clinical data supporting high-quality care, such as home blood glucose readings and vital signs, were often not available with telemedicine. Patient factors, including comorbidities and communication barriers, reduced anticipated benefit from telemedicine, while geographic and mobility barriers increased expected benefit. Providers described multiple health care setting resources that could promote high-quality telemedicine diabetes care, including greater support for sharing patient-generated health data and coordinating multidisciplinary care. Conclusions: After 2 years of sustained use, diabetes specialists identified telemedicine as an important way to enhance access to care. However, specialists identified additional supports needed to increase appropriate use and delivery of high-quality telemedicine care for patients with complex clinical needs.

Prescribing of evidence-based diabetes pharmacotherapy in patients with metabolic dysfunction-associated steatohepatitis.

INTRODUCTION: Metabolic dysfunction-associated steatohepatitis (MASH) is highly prevalent in type 2 diabetes (T2D). Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) are medications used in T2D that can resolve MASH and should be considered in all patients with T2D and MASH. We assessed prescription rates of evidence-based T2D pharmacotherapy (EBP) in MASH, and ascertained racial/ethnic disparities in prescribing. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study on patients in Duke University Health System with diagnosis codes for T2D and MASH between January 2019 and January 2021. Only patients with ≥1 primary care or endocrinology encounter were included. The primary outcome was EBP, defined as ≥1 prescription for pioglitazone and/or a GLP-1RA during the study period. A multivariable logistic regression model was used to examine the primary outcome. RESULTS: A total of 847 patients with T2D and MASH were identified; mean age was 59.7 (SD 12) years, 61.9% (n=524) were female, and 11.9% (n=101) and 4.6% (n=39) were of Black race and Latino/a/x ethnicity, respectively. EBP was prescribed in 34.8% (n=295). No significant differences were noted in the rates of EBP use across racial/ethnic groups (Latino/a/x vs White patients: adjusted OR (aOR) 1.82, 95% CI 0.78 to 4.28; Black vs White patients: aOR 0.76, 95% CI 0.44 to 1.33, p=0.20). CONCLUSIONS: EBP prescriptions, especially pioglitazone, are low in patients with T2D and MASH, regardless of race/ethnicity. These data underscore the need for interventions to close the gap between current and evidence-based care.

Simplifying therapy to assure glycemic control and engagement (STAGE) in poorly-controlled diabetes: A pilot study.

In this single-arm pilot study, we demonstrated feasibility and acceptability of an insulin simplification intervention in patients with persistent, poorly-controlled type 2 diabetes on complex insulin regimens. While not powered to assess clinical outcomes, we observed neither worsened glycemic control nor increased hypoglycemia.

Time to internal fixation of femoral neck fractures in patients under sixty years--does this matter in the development of osteonecrosis of femoral head?

PURPOSE: Osteonecrosis of femoral head remains a major complication of femoral neck fractures. It has been postulated that early internal fixation drastically reduces the incidence of osteonecrosis of the femoral head. However, there is a paucity of literature looking at the effect of time delay to internal fixation on the development of this late complication. In this study, we aim to assess the effect of time delay and method of internal fixation on the development of osteonecrosis in those less than 60 years of age. METHODS: We retrospectively analysed 92 patients less than 60 years of age who presented with intracapsular neck of femur fractures that underwent internal fixation between 1999 and 2009. RESULTS: Of the 92 intracapsular fractures, 50 underwent fixation using cannulated screws, 32 using a dynamic hip screw, and ten using a dynamic hip screw with a derotation screw. In total, 13 patients (14.1 %) developed osteonecrosis of the femoral head, the highest incidence being in the cannulated screw fixation group with an osteonecrosis rate of 24 %. We did not find the time delay to internal fixation to be a significant predictor of the development of osteonecrosis. CONCLUSION: Our study demonstrated that the method of internal fixation rather than delay in internal fixation was more predictive of osteonecrosis of the femoral head. We did not find support to the current belief that early surgical fixation of neck of femur fractures reduces the risk of osteonecrosis in patients less than 60 years.

Factors associated with non-adherence to insulin and non-insulin medications in patients with poorly controlled diabetes.

OBJECTIVES: To evaluate differences in factors associated with self-reported medication non-adherence to insulin and non-insulin medications in patients with uncontrolled type 2 diabetes. METHODS: In this secondary analysis of a randomized trial in patients with obesity and uncontrolled type 2 diabetes, multivariable logistic regression was used to evaluate associations between several clinical factors (measured with survey questionnaires at study baseline) and self-reported non-adherence to insulin and non-insulin medications. RESULTS: Among 263 patients, reported non-adherence was 62% (52% for insulin, 55% for non-insulin medications). Reported non-adherence to non-insulin medications was less likely in white versus non-white patients (odds ratio (OR) = 0.42; 95%CI: 0.22,0.80) and with each additional medication taken (OR = 0.75; 95%CI: 0.61,0.93). Non-adherence to non-insulin medications was more likely with each point increase in a measure of diabetes medication intensity (OR = 1.43; 95%CI: 1.01,2.03), the Problem Areas in Diabetes (PAID) score (OR = 1.06; 95%CI: 1.02,1.12), and in men versus women (OR = 3.03; 95%CI: 1.06,8.65). For insulin, reporting non-adherence was more likely (OR = 1.02; 95%CI: 1.00,1.04) with each point increase in the PAID. DISCUSSION: Despite similar overall rates of reported non-adherence to insulin and non-insulin medications, factors associated with reported non-adherence to each medication type differed. These findings may help tailor approaches to supporting adherence in patients using different types of diabetes medications.

Deintensification of Treatment With Sulfonylurea and Insulin After Severe Hypoglycemia Among Older Adults With Diabetes.

Importance: Practice guidelines recommend deintensification of hypoglycemic agents among older adults with diabetes who are at high risk of hypoglycemia, yet real-world treatment deintensification practices are not well characterized. Objective: To examine the incidence of sulfonylurea and insulin deintensification after a hypoglycemia-associated emergency department (ED) visit or hospitalization among older adults with diabetes and to identify factors associated with deintensification of treatment. Design, Setting, and Participants: This retrospective cohort study included a random sample of 20% of nationwide fee-for-service US Medicare beneficiaries aged 65 years and older with concurrent Medicare parts A, B, and D coverage between January 1, 2007, and December 31, 2017. Individuals with diabetes who had at least 1 hypoglycemia-associated ED visit or hospitalization were included. Data were analyzed from August 1, 2020, to August 1, 2021. Exposures: Baseline medication for the treatment of diabetes (sulfonylurea, insulin, or both). Main Outcomes and Measures: Incidence of treatment deintensification (yes or no) in the 100 days after a severe hypoglycemic episode requiring an ED visit or hospitalization, with treatment deintensification defined as (1) a decrease in sulfonylurea dose, (2) a change from long-acting to short-acting sulfonylurea (glipizide), (3) discontinuation of sulfonylurea, or (4) discontinuation of insulin based on pharmacy dispensing claims. Results: Among 76 278 distinct Medicare beneficiaries who had a hypoglycemia-associated ED visit or hospitalization, the mean (SD) age was 76.6 (7.6) years. Of 106 293 total hypoglycemic episodes requiring hospital attention, 69 084 (65.0%) occurred among women, 26 056 (24.5%) among Black individuals; 4761 (4.5%) among Hispanic individuals; 69 704 (65.6%) among White individuals; and 5772 (5.4%) among individuals of other races and ethnicities (comprising Asian, North American Native, unknown race or ethnicity, and unspecified race or ethnicity). A total of 32 074 episodes (30.2%) occurred among those receiving sulfonylurea only, 60 350 (56.8%) occurred among those receiving insulin only, and 13 869 (13.0%) occurred among those receiving both sulfonylurea and insulin. Treatment deintensification rates were highest among individuals receiving both sulfonylurea and insulin therapies at the time of their hypoglycemic episode (6677 episodes [48.1%]), followed by individuals receiving sulfonylurea only (14 192 episodes [44.2%]) and insulin only (14 495 episodes [24.0%]). Treatment deintensification rates increased between 2007 and 2017 (sulfonylurea only: from 41.4% to 49.7%; P < .001 for trend; insulin only: from 21.3% to 25.9%; P < .001 for trend; sulfonylurea and insulin: from 45.9% to 49.6%; P = .005 for trend). Lower socioeconomic status (as indicated by the receipt of low-income subsidies) was associated with lower odds of deintensification, regardless of baseline hypoglycemic regimen (sulfonylurea only: adjusted odds ratio [AOR], 0.74 [95% CI, 0.70-0.78]; insulin only: AOR, 0.71 [95% CI, 0.68-0.75]; sulfonylurea and insulin: AOR, 0.72 [95% CI, 0.66-0.78]). A number of patient factors were associated with higher odds of treatment deintensification: higher frailty (eg, ≥40% probability of needing assistance with activities of daily living among those receiving sulfonylurea and insulin: AOR, 1.50; 95% CI, 1.32-1.71), chronic kidney disease (eg, sulfonylurea and insulin: AOR, 1.29; 95% CI, 1.19-1.40), a history of falls (eg, sulfonylurea and insulin: AOR, 1.20; 95% CI, 1.09-1.33), and depression (eg, sulfonylurea and insulin: AOR, 1.11; 95% CI, 1.02-1.20). Conclusions and Relevance: In this cohort study, deintensification of sulfonylurea and/or insulin therapy within 100 days after a hypoglycemia-associated ED visit or hospitalization occurred in fewer than 50% of older adults with diabetes; however, these deintensification rates may be increasing over time, and deintensification of insulin was likely underestimated because of challenges in capturing changes to insulin dosing using administrative claims data. These results suggest that greater efforts are needed to identify individuals at high risk of hypoglycemia to encourage appropriate treatment deintensification in accordance with current evidence.

Clinical associations of an updated medication effect score for measuring diabetes treatment intensity.

OBJECTIVES: The medication effect score reflects overall intensity of a diabetes regimen by consolidating dosage and potency of agents used. Little is understood regarding how medication intensity relates to clinical factors. We updated the medication effect score to account for newer agents and explored associations between medication effect score and patient-level clinical factors. METHODS: Cross-sectional analysis of baseline data from a randomized controlled trial involving 263 Veterans with type 2 diabetes and hemoglobin A1c levels ≥8.0% (≥7.5% if under age 50). Medication effect score was calculated for all patients at baseline, alongside additional measures including demographics, comorbid illnesses, hemoglobin A1c, and self-reported psychosocial factors. We used multivariable regression to explore associations between baseline medication effect score and patient-level clinical factors. RESULTS: Our sample had a mean age of 60.7 (SD = 8.2) years, was 89.4% male, and 57.4% non-White. Older age and younger onset of diabetes were associated with a higher medication effect score, as was higher body mass index. Higher medication effect score was significantly associated with medication nonadherence, although not with hemoglobin A1c, self-reported hypoglycemia, diabetes-related distress, or depression. DISCUSSION: We observed several expected associations between an updated medication effect score and patient-level clinical factors. These associations support the medication effect score as an appropriate measure of diabetes regimen intensity in clinical and research contexts.

Underrecognition of Nonalcoholic Fatty Liver Disease in Poorly Controlled Diabetes: A Call to Action in Diabetes Care.

Individuals with type 2 diabetes (T2DM) are at high risk for nonalcoholic fatty liver disease (NAFLD), and evidence suggests that poor glycemic control is linked to heightened risk of progressive NAFLD. We conducted an observational study based on data from a telehealth trial conducted in 2018-2020. Our objectives were to (1) characterize patterns of NAFLD testing/care in a cohort of individuals with poorly controlled T2DM; and (2) explore how laboratory based measures of NAFLD (eg, liver enzymes, fibrosis-4 [FIB-4]) vary by glycemic control. We included individuals with poorly controlled T2DM (n = 228), defined as hemoglobin A1c (HbA1c) ≥ 8.5% despite clinic-based care. Two groups of interest were (1) T2DM without known NAFLD; and (2) T2DM with known NAFLD. Demographics, medical history, medication use, glycemic control (HbA1c), and NAFLD testing/care patterns were obtained by chart review. Among those without known NAFLD (n = 213), most were male (78.4%) and self-identified as Black race (68.5%). Mean HbA1c was 9.8%. Most had liver enzymes (85.4%) and platelets (84.5%) ordered in the outpatient department over a 2-year period that would allow for FIB-4 calculation, yet only 2 individuals had FIB-4 documented in clinical notes. Approximately one-third had abnormal liver enzymes at least once over a 2-year period, yet only 7% had undergone liver ultrasound and 4.7% had referral to hepatology. Among those with known NAFLD (n = 15), mean HbA1c was 9.5%. Only 4 individuals had undergone transient elastography, half of whom had advanced fibrosis. NAFLD is underrecognized in poorly controlled T2DM, even though this is a high-risk group for NAFLD and its complications.

Newer second-line glucose-lowering drugs versus thiazolidinediones on cirrhosis risk among older US adult patients with type 2 diabetes.

AIMS: Type 2 diabetes (T2D) accelerates progression of chronic liver disease to cirrhosis, yet the effects of most glucose-lowering drugs (GLDs) on cirrhosis risk in T2D are unknown. To address this gap, we compared cirrhosis risk following initiation of newer second-line GLDs vs. thiazolidinediones (TZDs), which improve histology in non-alcoholic fatty liver disease. MATERIALS AND METHODS: Using the US Medicare Fee-for-Service database (2007-2015) and an active comparator, new-user design, we estimated crude incidence rates (IRs) and propensity-score adjusted hazard ratios (aHR) for incident cirrhosis, comparing newer GLDs (dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i)) vs. TZDs. RESULTS: Among 239,549 total initiators, we observed 318, 151, and < 30 cirrhosis events when comparing DPP4i vs. TZD, GLP1RA vs. TZD, and SGLT2i vs. TZD, respectively. IRs ranged from 1.7 [95% CI, 0.8-3.6] to 3.6 [2.5-5.2] events per 1000 person-years. Point aHR estimates for cirrhosis were elevated among newer GLD initiators vs. TZD (DPP4i: 1.15 [0.89-1.50]; GLP1RA: 1.34 [0.82-2.20]; SGLT2i: 1.16, [0.44-3.08]), although estimates were imprecise due to short durations of drug exposure. CONCLUSIONS: We observed mildly elevated cirrhosis risk with newer GLDs vs. TZD; however, uncertainty remains due to imprecise and statistically non-significant effect estimates.

Initial injectable therapy in type 2 diabetes: Key considerations when choosing between glucagon-like peptide 1 receptor agonists and insulin.

Managing type 2 diabetes is complex and necessitates careful consideration of patient factors such as engagement in self-care, comorbidities and costs. Since type 2 diabetes is a progressive disease, many patients will require injectable agents, usually insulin. Recent ADA-EASD guidelines recommend glucagon-like peptide 1 receptor agonists (GLP-1 RAs) as first injectable therapy in most cases. The basis for this recommendation is the similar glycemic efficacy of GLP-1 RAs and insulin, but with GLP-1 RAs promoting weight loss instead of weight gain, at lower hypoglycemia risk, and with cardiovascular benefits in patients with pre-existing cardiovascular disease. GLP-1 RAs also reduce burden of glucose self-monitoring. However, tolerability and costs are important considerations, and notably, rates of drug discontinuation are often higher for GLP-1 RAs than basal insulin. To minimize risk of gastrointestinal symptoms patients should be started on lowest doses of GLP-1 RAs and up-titrated slowly. Overall healthcare costs may be lower with GLP-1 RAs compared to insulin. Though patient-level costs may still be prohibitive, GLP-1 RAs can replace 50-80 units of insulin daily and reduce costs associated with glucose self-monitoring. Decisions regarding initiating injectable therapy should be individualized. This review provides a framework to guide decision-making in the real-world setting.

Clinical factors associated with persistently poor diabetes control in the Veterans Health Administration: A nationwide cohort study.

OBJECTIVE: Patients with persistent poorly-controlled diabetes mellitus (PPDM) despite engagement in clinic-based care are at particularly high risk for diabetes complications and costs. Understanding this population's demographics, comorbidities and care utilization could guide strategies to address PPDM. We characterized factors associated with PPDM in a large sample of Veterans with type 2 diabetes. METHODS: We identified a cohort of Veterans with medically treated type 2 diabetes, who received Veterans Health Administration primary care during fiscal years 2012 and 2013. PPDM was defined by hemoglobin A1c levels uniformly >8.5% during fiscal year (FY) 2012, despite engagement with care during this period. We used FY 2012 demographic, comorbidity and medication data to describe PPDM in relation to better-controlled diabetes patients and created multivariable models to examine associations between clinical factors and PPDM. We also constructed multivariable models to explore the association between PPDM and FY 2013 care utilization. RESULTS: In our cohort of diabetes patients (n = 435,820), 12% met criteria for PPDM. Patients with PPDM were younger than better-controlled patients, less often married, and more often Black/African-American and Hispanic or Latino/Latina. Of included comorbidities, only retinopathy (OR 1.68, 95% confidence interval (CI): 1.63,1.73) and nephropathy (OR 1.26, 95% CI: 1.19,1.34) demonstrated clinically significant associations with PPDM. Complex insulin regimens such as premixed (OR 10.80, 95% CI: 10.11,11.54) and prandial-containing regimens (OR 18.74, 95% CI: 17.73,19.81) were strongly associated with PPDM. Patients with PPDM had higher care utilization, particularly endocrinology care (RR 3.56, 95% CI: 3.47,3.66); although only 26.4% of patients saw endocrinology overall. CONCLUSION: PPDM is strongly associated with complex diabetes regimens, although heterogeneity in care utilization exists. While there is evidence of underutilization, inadequacy of available care may also contribute to PPDM. Our findings should inform tailored approaches to meet the needs of PPDM, who are among the highest-risk, highest-cost patients with diabetes.