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The article discusses the Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC). It explains how the DCCT demonstrated that intensive treatment of type 1 diabetes reduced the risk of microvascular complications, such as retinopathy, neuropathy, and albuminuria. However, it also found that intensive treatment had adverse effects, including an increase in severe hypoglycemia. The EDIC study showed that the benefits of intensive treatment persisted over time, leading to reductions in severe complications and mortality. The findings of these studies have greatly influenced diabetes treatment guidelines and improved outcomes for people with type 1 diabetes. [Extracted from the article]

OBJECTIVE: We evaluated the effect of long-term intensive metabolic control with hybrid closed-loop (CL) on residual C-peptide secretion and glucose control compared with standard insulin therapy in youth with type 1 diabetes over 48 months. RESEARCH DESIGN AND METHODS: Following the 24-month primary phase of a multicenter, randomized, parallel trial of 96 newly diagnosed youth aged 10 to 16.9 years, participants were invited to an extension phase using treatment allocated at randomization. They continued with hybrid CL using the Cambridge algorithm or standard insulin therapy (control) until 48 months after diagnosis. Analysis was by intention-to-treat. RESULTS: At 24 months after diagnosis, 81 participants (mean ± SD age 14 ± 2 years) continued in the extension phase (47 CL, 34 control). There was no difference in fasting C-peptide corrected for fasting glucose at 48 months between groups (CL: 5 ± 9 vs. control: 6 ± 14 pmol/L per mmol/L; mean adjusted difference −2 [95% CI −7, 4; P = 0.54]). Central laboratory HbA1c remained lower in the CL group by 0.9% (10 mmol/mol [95% CI 0.2, 1.5; 3, 17 mmol/mol); P = 0.009). Time in target range of 3.9 to 10.0 mmol/L was 12 percentage points (95% CI 3, 20; P = 0.008) higher in the CL group compared with control. There were 11 severe hypoglycemic events (6 CL, 5 control) and 7 diabetic ketoacidosis events (3 CL, 4 control) during the extension phase. CONCLUSIONS: Improved glycemic control was sustained over 48 months after diagnosis with CL insulin delivery compared with standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes. RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c <6.5%) were randomized to receive subcutaneous semaglutide (2.4 mg weekly) or placebo. Major glycemic outcomes were HbA1c and proportions achieving biochemical normoglycemia (HbA1c <5.7%) and progressing to biochemical diabetes (HbA1c ≥6.5%). RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference of −0.32 percentage points (95% CI −0.33 to −0.30; −3.49 mmol/mol [−3.66 to −3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001). Body weight plateaued at 65 weeks and was 8.9% lower with semaglutide. At week 156, a greater proportion treated with semaglutide were normoglycemic (69.5% vs. 35.8%; P < 0.0001) and a smaller proportion had biochemical diabetes by week 156 (1.5% vs. 6.9%; P < 0.0001). The number needed to treat was 18.5 to prevent a case of diabetes. Both regression and progression were dependent on glycemia at baseline, with the magnitude of weight reduction important in mediating 24.5% of progression and 27.1% of regression. CONCLUSIONS: In people with preexisting cardiovascular disease and overweight or obesity but without diabetes, long-term semaglutide increases regression to biochemical normoglycemia and reduces progression to biochemical diabetes but does not slow glycemic progression over time. 6357437865112 dc240491video1 Video 1. This image is from a video available online at https://bcove.video/3WedKuq. American Diabetes Association 84th Scientific Sessions: SELECT Trial—New Looks at Glycemia, Inflammation, and Heart Failure. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether continuous glucose monitoring (CGM)-derived glycemic patterns can characterize pregnancies with gestational diabetes mellitus (GDM) as diagnosed by standard oral glucose tolerance test at 24–28 weeks' gestation compared with those without GDM. RESEARCH DESIGN AND METHODS: The analysis includes 768 individuals enrolled from two sites prior to 17 weeks' gestation between June 2020 and December 2021 in a prospective observational study. Participants wore blinded Dexcom G6 CGMs throughout gestation. Main outcome of interest was a diagnosis of GDM by oral glucose tolerance test (OGTT). Glycemic levels in participants with GDM versus without GDM were characterized using CGM-measured glycemic metrics. RESULTS: Participants with GDM (n = 58 [8%]) had higher mean glucose (109 ± 13 vs. 100 ± 8 mg/dL [6.0 ± 0.7 vs. 5.6 ± 0.4 mmol/L], P < 0.001), greater glucose SD (23 ± 4 vs. 19 ± 3 mg/dL [1.3 ± 0.2 vs. 1.1 ± 0.2 mmol/L], P < 0.001), less time in range 63–120 mg/dL (3.5–6.7 mmol/L) (70% ± 17% vs. 84% ± 8%, P < 0.001), greater percent time >120 mg/dL (>6.7 mmol/L) (median 23% vs. 12%, P < 0.001), and greater percent time >140 mg/dL (>7.8 mmol/L) (median 7.4% vs. 2.7%, P < 0.001) than those without GDM throughout gestation prior to OGTT. Median percent time >120 mg/dL (>6.7 mmol/L) and time >140 mg/dL (>7.8 mmol/L) were higher as early as 13–14 weeks of gestation (32% vs. 14%, P < 0.001, and 5.2% vs. 2.0%, P < 0.001, respectively) and persisted during the entire study period prior to OGTT. CONCLUSIONS: Prior to OGTT at 24–34 weeks' gestation, pregnant individuals who develop GDM have higher CGM-measured glucose levels and more hyperglycemia compared with those who do not develop GDM. [ABSTRACT FROM AUTHOR]

The article discusses the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), which compared glucose-lowering agents for type 2 diabetes (T2D) patients already on metformin. It highlights that glargine and liraglutide showed slightly better glycemic control than oral agents, the differences were minimal, suggesting they could be recommended as second-line therapy for T2D patients not controlled with metformin.

OBJECTIVE: To compare demographic, clinical, and therapeutic characteristics of children with type 1 diabetes age <6 years across three international registries: Diabetes Prospective Follow-Up Registry (DPV; Europe), T1D Exchange Quality Improvement Network (T1DX-QI; U.S.), and Australasian Diabetes Data Network (ADDN; Australasia). RESEARCH DESIGN AND METHODS: An analysis was conducted comparing 2019–2021 prospective registry data from 8,004 children. RESULTS: Mean ± SD ages at diabetes diagnosis were 3.2 ± 1.4 (DPV and ADDN) and 3.7 ± 1.8 years (T1DX-QI). Mean ± SD diabetes durations were 1.4 ± 1.3 (DPV), 1.4 ± 1.6 (T1DX-QI), and 1.5 ± 1.3 years (ADDN). BMI z scores were in the overweight range in 36.2% (DPV), 41.8% (T1DX-QI), and 50.0% (ADDN) of participants. Mean ± SD HbA1c varied among registries: DPV 7.3 ± 0.9% (56 ± 10 mmol/mol), T1DX-QI 8.0 ± 1.4% (64 ± 16 mmol/mol), and ADDN 7.7 ± 1.2% (61 ± 13 mmol/mol). Overall, 37.5% of children achieved the target HbA1c of <7.0% (53 mmol/mol): 43.6% in DPV, 25.5% in T1DX-QI, and 27.5% in ADDN. Use of diabetes technologies such as insulin pump (DPV 86.6%, T1DX 46.6%, and ADDN 39.2%) and continuous glucose monitoring (CGM; DPV 85.1%, T1DX-QI 57.6%, and ADDN 70.5%) varied among registries. Use of hybrid closed-loop (HCL) systems was uncommon (from 0.5% [ADDN] to 6.9% [DPV]). CONCLUSIONS: Across three major registries, more than half of children age <6 years did not achieve the target HbA1c of <7.0% (53 mmol/mol). CGM was used by most participants, whereas insulin pump use varied across registries, and HCL system use was rare. The differences seen in glycemia and use of diabetes technologies among registries require further investigation to determine potential contributing factors and areas to target to improve the care of this vulnerable group. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe rescue insulin use and associated factors in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS: GRADE participants (type 2 diabetes duration <10 years, baseline A1C 6.8%–8.5% on metformin monotherapy, N = 5,047) were randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin and followed quarterly for a mean of 5 years. Rescue insulin (glargine or aspart) was to be started within 6 weeks of A1C >7.5%, confirmed. Reasons for delaying rescue insulin were reported by staff-completed survey. RESULTS: Nearly one-half of GRADE participants (N = 2,387 [47.3%]) met the threshold for rescue insulin. Among participants assigned to glimepiride, liraglutide, or sitagliptin, rescue glargine was added by 69% (39% within 6 weeks). Rescue aspart was added by 44% of glargine-assigned participants (19% within 6 weeks) and by 30% of non-glargine-assigned participants (14% within 6 weeks). Higher A1C values were associated with adding rescue insulin. Intention to change health behaviors (diet/lifestyle, adherence to current treatment) and not wanting to take insulin were among the most common reasons reported for not adding rescue insulin within 6 weeks. CONCLUSIONS: Proportionately, rescue glargine, when required, was more often used than rescue aspart, and higher A1C values were associated with greater rescue insulin use. Wanting to use noninsulin strategies to improve glycemia was commonly reported, although multiple factors likely contributed to not using rescue insulin. These findings highlight the persistent challenge of intensifying type 2 diabetes treatment with insulin, even in a clinical trial. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine the benefit of starting continuous glucose monitoring (CGM) in adult-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) with regard to longer-term glucose control and serious clinical events.Research design and methodsA retrospective observational cohort study within the Veterans Affairs Health Care System was used to compare glucose control and hypoglycemia- or hyperglycemia-related admission to an emergency room or hospital and all-cause hospitalization between propensity score overlap weighted initiators of CGM and nonusers over 12 months.ResultsCGM users receiving insulin (n = 5,015 with T1D and n = 15,706 with T2D) and similar numbers of nonusers were identified from 1 January 2015 to 31 December 2020. Declines in HbA1c were significantly greater in CGM users with T1D (-0.26%; 95% CI -0.33, -0.19%) and T2D (-0.35%; 95% CI -0.40, -0.31%) than in nonusers at 12 months. Percentages of patients achieving HbA1c

The prevalence of gestational diabetes mellitus (GDM) has increased over the past two decades, leading to concerns about adverse pregnancy outcomes. The diagnosis and treatment of GDM typically occur in the third trimester, which may be too late to prevent all the adverse effects associated with maternal hyperglycemia. Researchers have attempted to diagnose GDM earlier in pregnancy, but reliable approaches have not been developed. Continuous glucose monitoring (CGM) has the potential to provide insight into the relationship between early glycemic patterns and GDM diagnosis, as well as maternal and perinatal outcomes. A recent study found that individuals diagnosed with GDM had higher mean glucose values and greater variability in their glucose levels prior to diagnosis, as well as consistently higher mean glucose levels during both the daytime and overnight periods. CGM metrics obtained prior to an oral glucose tolerance test had the ability to predict GDM. These findings contribute to our understanding of maternal glycemia across gestation and suggest that CGM could be an alternative to traditional GDM testing in the future. However, further research is needed to determine the impact of early diagnosis and treatment on perinatal outcomes. [Extracted from the article]

OBJECTIVE: To explore the associations among mannose, indexes of insulin resistance (IR) and secretion, and long-term cardiovascular outcomes. RESEARCH DESIGN AND METHODS: Fasting mannose was assayed in 1,403 participants, one-half of which had a first myocardial infarction (MI) with either normal glucose tolerance (n = 1,045) or newly detected dysglycemia (i.e., impaired glucose tolerance or type 2 diabetes; n = 358). Regression models were used to explore mannose associations with surrogate indexes of IR/insulin secretion. Multivariate Cox models were used to investigate the independent association between high (higher quartile) versus low (lower three quartiles) mannose and major adverse cardiac events (MACE) (n = 163) during the 10-year follow-up. RESULTS: Mannose was independently associated with IR indexes (all P ≤ 0.001). High versus low mannose was independently associated with MACE (hazard ratio 1.54, 95% CI 1.07–2.20) in the overall population. CONCLUSIONS: Mannose might represent a new biomarker able to track early, potentially detrimental glucometabolic alterations independently of glycemic state. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The hyperosmolar hyperglycemic state (HHS) is a rare and life-threatening complication of diabetes. We aimed to estimate the incidence of HHS and describe the clinical and biomarker profiles of patients with HHS, including subgroups with acidosis and acute kidney injury. RESEARCH DESIGN AND METHODS: This nationwide, descriptive cohort study used Danish registry data during years 2016–2018 to identify acutely admitted patients fulfilling the hyperglycemia and hyperosmolarity criteria of HHS (glucose ≥33 mmol/L and osmolarity [2 × sodium + glucose] ≥320 mmol/L). RESULTS: We identified 634 patients (median age, 69 years (first quartile; third quartile: 58; 79) who met the criteria of HHS among 4.80 million inhabitants aged ≥18 years. The incidence rates were 16.5 and 3.9 per 10,000 person-years among people with known type 1 (n = 24,196) and type 2 (n = 251,357) diabetes, respectively. Thirty-two percent of patients with HHS were not previously diagnosed with diabetes. Patients were categorized as pure HHS (n = 394) and combined HHS and diabetic ketoacidosis (HHS-DKA; n = 240). The in-hospital mortality rate for pure HHS was 17% and 9% for HHS-DKA. CONCLUSIONS: The incidence of HHS was higher among patients with type 1 diabetes compared with type 2 diabetes. HHS is a spectrum of hyperglycemic crises and can be divided in pure HHS and HHS-DKA. In one-third of patients, HHS was the debut of their diabetes diagnosis. [ABSTRACT FROM AUTHOR]

The article discusses the advancements in automated insulin delivery (AID) systems for the management of type 1 diabetes. It highlights the benefits of AID in improving glycemic control and reducing the burden of diabetes management. However, the article also acknowledges the limitations and challenges of AID, such as the risk of severe hypoglycemia and disparities in access to diabetes technology. The authors suggest that further technological advancements and research are needed to drive improved outcomes and address these challenges. Additionally, the article mentions the potential for cell therapies to restore insulin production in the body as a future treatment option for type 1 diabetes. [Extracted from the article]

OBJECTIVE: Diabetes may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined insulin clearance and its possible determinants in individuals with recent-onset diabetes. RESEARCH DESIGN AND METHODS: Participants of the German Diabetes Study (GDS) with type 1 diabetes (T1D) (n = 306), type 2 diabetes (T2D) (n = 489), or normal glucose tolerance (control [CON]) (n = 167) underwent hyperinsulinemic-euglycemic clamps for assessment of whole-body insulin sensitivity (M value) and insulin clearance (ICCLAMP). Insulin clearance rates were further calculated during intravenous glucose tolerance tests (ICIVGTT) and mixed-meal tests (ICMMT). Hepatocellular lipid content (HCL) was quantified with 1H-MRS. RESULTS: Both T1D and T2D groups had lower ICCLAMP (0.12 ± 0.07 and 0.21 ± 0.06 vs. 0.28 ± 0.14 arbitrary units [a.u.], respectively, all P < 0.05) and ICMMT (0.71 ± 0.35 and 0.99 ± 0.33 vs. 1.20 ± 0.36 a.u., all P < 0.05) than CON. In T1D, ICCLAMP, ICIVGTT, and ICMMT correlated negatively with HbA1c (all P < 0.05). M value correlated positively with ICIVGTT in CON and T2D (r = 0.199 and r = 0.178, P < 0.05) and with ICMMT in CON (r = 0.176, P < 0.05). HCL negatively associated with ICIVGTT and ICMMT in T2D (r = −0.005 and r = −0.037) and CON (r = −0.127 and r = −0.058, all P < 0.05). In line, T2D or CON subjects with steatosis featured lower ICMMT than those without steatosis (both P < 0.05). CONCLUSIONS: Insulin clearance is reduced in both T1D and T2D within the first year after diagnosis but correlates negatively with liver lipid content rather in T2D. Moreover, insulin clearance differently associates with glycemic control and insulin sensitivity in each diabetes type, which may suggest specific mechanisms affecting insulin kinetics. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify predictors of body weight (BW) reduction of ≥15% with tirzepatide treatment and to describe associated clinical parameters of participants with type 2 diabetes (T2D) who achieved different categorical measures of BW reduction (<5%, ≥5 to <10%, ≥10 to <15%, and ≥15%) across four studies from the phase 3 SURPASS clinical trial program for T2D. RESEARCH DESIGN AND METHODS: The multivariate model for predictor of a BW reduction of ≥15% included age, sex, race, BW, HbA1c, tirzepatide dose and baseline metformin use, fasting serum glucose, and non-HDL cholesterol. Baseline characteristics and change from baseline to week 40/42 for efficacy parameters were described and analyzed in treatment-adherent participants (≥75% doses administered and on treatment at week 40/42) receiving once weekly tirzepatide (5 mg, 10 mg, or 15 mg) (N = 3,188). RESULTS: Factors significantly associated with achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, and lower HbA1c, fasting serum glucose, and non-HDL cholesterol at baseline. With higher categorical BW reduction, there were greater reductions in HbA1c, triglycerides, ALT, waist circumference, and blood pressure. CONCLUSIONS: Baseline factors associated with a higher likelihood of achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, better glycemic status, and lower non-HDL cholesterol. With greater BW reduction, participants with T2D achieved larger improvements in glycemia and cardiometabolic risk parameters. These findings help inform which people with T2D are most likely to achieve greater BW reduction with improved cardiometabolic risk factors with tirzepatide. [ABSTRACT FROM AUTHOR]

BACKGROUND: Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. APPROACH: An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association for Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. CONTENT: Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (HbA1c) in the blood. Glycemic control is monitored by the people with diabetes measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring (CGM) devices and also by laboratory analysis of HbA1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. SUMMARY: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Post–bariatric surgery hypoglycemia (PBH) is a metabolic complication of Roux-en-Y gastric bypass (RYGB). Since symptoms are a key component of the Whipple's triad to diagnose nondiabetic hypoglycemia, we evaluated the relationship between self-reported symptoms and postprandial sensor glucose profiles. RESEARCH DESIGN AND METHODS: Thirty patients with PBH after RYGB (age: 50.1 [41.6–60.6] years, 86.7% female, BMI: 26.5 [23.5–31.2] kg/m2; median [interquartile range]) wore a blinded Dexcom G6 sensor while recording autonomic, neuroglycopenic, and gastrointestinal symptoms over 50 days. Symptoms (overall and each type) were categorized into those occurring in postprandial periods (PPPs) without hypoglycemia, or in the preceding dynamic or hypoglycemic phase of PPPs with hypoglycemia (nadir sensor glucose <3.9 mmol/L). We further explored the relationship between symptoms and the maximum negative rate of sensor glucose change and nadir sensor glucose levels. RESULTS: In 5,851 PPPs, 775 symptoms were reported, of which 30.6 (0.0–59.9)% were perceived in PPPs without hypoglycemia, 16.7 (0.0–30.1)% in the preceding dynamic phase and 45.0 (13.7–84.7)% in the hypoglycemic phase of PPPs with hypoglycemia. Per symptom type, 53.6 (23.8–100.0)% of the autonomic, 30.0 (5.6–80.0)% of the neuroglycopenic, and 10.4 (0.0–50.0)% of the gastrointestinal symptoms occurred in the hypoglycemic phase of PPPs with hypoglycemia. Both faster glucose dynamics and lower nadir sensor glucose levels were related with symptom perception. CONCLUSIONS: The relationship between symptom perception and PBH is complex, challenging clinical judgement and decision-making in this population. [ABSTRACT FROM AUTHOR]

The article focuses on the importance of personalized physical activity for managing glucose levels in individuals with type 2 diabetes, emphasizing the need to understand the optimal dose and types of physical activities for different glycemic control statuses. It mentions while guidelines recommend specific durations and types of physical activity, the optimal dose-response relationship remains unclear.

OBJECTIVE: We sought to examine the mediating role of changes in depressive symptoms in the association between chronic hyperglycemia and longitudinal cognition in a sample of older adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We conducted a longitudinal mediation analysis using structural equation modeling of observational data collected over 6 years from 2,155 participants with T2D (aged ≥51 years) in the U.S.-wide Health and Retirement Study. T2D was defined using self-reported diagnosis, and HbA1c was assessed at study baseline. Self-reported depressive symptoms were assessed at two time points 4 years apart. Episodic memory was measured using a list-learning test administered at three time points over 6 years. We adjusted for sociodemographics, chronic health comorbidities, medication adherence, study enrollment year, and prior years' depressive symptoms and memory scores. RESULTS: At baseline, participants' mean age was 69.4 (SD = 9.1), mean HbA1c was 7.2% (SD = 1.4%), 55.0% were women, 19.3% were non-Latinx Black, and 14.0% were Latinx. Higher baseline levels of HbA1c were associated with increases in depressive symptoms over 4 years, which, in turn, were associated with poorer memory 2 years later. Depressive symptoms accounted for 19% of the longitudinal effect of HbA1c on memory over the 6-year period. Sensitivity analyses ruled out alternative directions of associations. CONCLUSIONS: Incident elevations in depressive symptoms mediated the longitudinal association between hyperglycemia and 6-year episodic memory scores. For older adults with T2D, interventions to prevent HbA1c-related incident depressive symptoms may be beneficial in reducing the neurotoxic effects of chronic hyperglycemia on cognition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess whether increased genetic risk of type 2 diabetes (T2D) is associated with the development of hyperglycemia after glucocorticoid treatment. RESEARCH DESIGN AND METHODS: We performed a retrospective analysis of individuals with no diagnosis of diabetes who received a glucocorticoid dose of ≥10 mg prednisone. We analyzed the association between hyperglycemia and a T2D global extended polygenic score, which was constructed through a meta-analysis of two published genome-wide association studies. RESULTS: Of 546 individuals who received glucocorticoids, 210 developed hyperglycemia and 336 did not. T2D polygenic score was significantly associated with glucocorticoid-induced hyperglycemia (odds ratio 1.4 per SD of polygenic score; P = 0.038). CONCLUSIONS: Individuals with increased genetic risk of T2D have a higher risk of glucocorticoid-induced hyperglycemia. This finding offers a mechanism for risk stratification as part of a precision approach to medical treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Little is known about the impact of early attainment of tight glycemic control on long-term β-cell function and glycemic control in youth-onset type 2 diabetes. We examined the effect of the initial 6 months of glycemic control on β-cell function and glycemic control longitudinally over 9 years and the impact of sex, race/ethnicity, and BMI on these relationships in adolescents with youth-onset type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. RESEARCH DESIGN AND METHODS: Oral glucose tolerance tests were performed longitudinally through year 9 to derive estimates of insulin sensitivity and secretion. Early glycemia was defined by mean HbA1c during the first 6 months postrandomization, categorized into five HbA1c groups (<5.7%, 5.7 to <6.4%, 6.4 to <7.0%, 7.0 to <8.0%, and ≥8.0%). The long-term period was defined as the period between years 2 and 9. RESULTS: A total of 656 participants (64.8% female, baseline mean age 14 years, diabetes duration <2 years) had longitudinal data available over an average of 6.4 ± 3.2 years of follow-up. HbA1c significantly increased in all early glycemic groups during years 2–9, with a steeper increase (+0.40%/year) among participants with the tightest initial control (mean early HbA1c <5.7%), in parallel to a decline in the C-peptide–derived disposition index. Nevertheless, the lower HbA1c categories continued to have relatively lower HbA1c over time. CONCLUSIONS: Early tight glycemic control in the TODAY study was related to β-cell reserve and translated to better long-term glycemic control. However, tight early glycemic control on the randomized treatment in the TODAY study did not prevent deterioration of β-cell function. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Racial/ethnic-specific estimates of the influence of gestational diabetes mellitus (GDM) on type 2 diabetes remain underexplored in large population-based cohorts. We estimated racial/ethnic differences in the influence of GDM on diabetes risk and glycemic control in a multiethnic, population-based cohort of postpartum women. RESEARCH DESIGN AND METHODS: Hospital discharge and vital registry data for New York City (NYC) births between 2009 and 2011 were linked with NYC A1C Registry data between 2009 and 2017. Women with baseline diabetes (n = 2,810) were excluded for a final birth cohort of 336,276. GDM on time to diabetes onset (two A1C tests of ≥6.5% from 12 weeks postpartum onward) or glucose control (first test of A1C <7.0% following diagnosis) was assessed using Cox regression with a time-varying exposure. Models were adjusted for sociodemographic and clinical factors and stratified by race/ethnicity. RESULTS: The cumulative incidence for diabetes was 11.8% and 0.6% among women with and without GDM, respectively. The adjusted hazard ratio (aHR) of GDM status on diabetes risk was 11.5 (95% CI 10.8, 12.3) overall, with slight differences by race/ethnicity. GDM was associated with a lower likelihood of glycemic control (aHR 0.85; 95% CI 0.79, 0.92), with the largest negative influence among Black (aHR 0.77; 95% CI 0.68, 0.88) and Hispanic (aHR 0.84; 95% CI 0.74, 0.95) women. Adjustment for screening bias and loss to follow-up modestly attenuated racial/ethnic differences in diabetes risk but had little influence on glycemic control. CONCLUSIONS: Understanding racial/ethnic differences in the influence of GDM on diabetes progression is critical to disrupt life course cardiometabolic disparities. [ABSTRACT FROM AUTHOR]

The article discusses the importance of clinical trials in advancing medical care, specifically in the field of diabetes. It highlights the Diabetes Control and Complications Trial (DCCT), which demonstrated the benefits of intensive glycemic control in reducing complications for people with type 1 diabetes. The article also mentions the long-term observational follow-up study, Epidemiology of Diabetes Complications (EDIC), which further supported the benefits of glycemic lowering. The authors express gratitude to the participants of these studies and emphasize the crucial role they play in advancing medical knowledge and improving patient care. [Extracted from the article]

ObjectiveThis study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors.Research design and methodsWe prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled.ResultsAmong all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, P < 0.001), item-color recall (β = -0.08, P = 0.010), and forward digit span (β = -0.06, P = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, P = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (β = -0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for.ConclusionsA single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.

The article explores gestational diabetes mellitus (GDM), rising due to global obesity, presenting two studies examining insulin secretion and resistance in pregnancy. Topics include gestational diabetes, insulin secretion, insulin resistance in pregnancy. Thaweethai et al. assess early-onset GDM, introducing a new b-cell index, while Mittendorfer et al. explore insulin dynamics in overweight pregnant women.

OBJECTIVE: Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODS: We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTS: A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline. CONCLUSIONS: Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the associations between modifiable risk factors and glycemic status changes in individuals with prediabetes. RESEARCH DESIGN AND METHODS: A total of 10,358 individuals with prediabetes defined by their fasting blood glucose and HbA1c levels from the Health Examinees-Gem study were included in the present study. Modifiable factors, including BMI, abdominal obesity, smoking status, physical activity, alcohol consumption, diet quality, hypertension, and dyslipidemia, were examined to determine their associations with changes in glycemic status during follow-up. In addition, modifiable-factor scores were calculated, and their association with changes in glycemic status was also analyzed. RESULTS: The median follow-up time for this study was 4 years (range, 1–7 years). BMI ≥25 kg/m2 (adjusted odds ratio [OR] 0.71 [95% CI 0.63–0.79]), abdominal obesity (OR 0.76 [95% CI 0.68–0.86]), heavy drinking (OR 0.74 [95% CI 0.60–0.91]), hypertension (OR 0.71 [95% CI 0.64–0.79]), and dyslipidemia (OR 0.78 [95% CI 0.70–0.85]) were associated with a lower possibility of normoglycemia reversion. BMI ≥25 kg/m2 (OR 1.58 [95% CI 1.29–1.94]), abdominal obesity (OR 1.31 [95% CI 1.11–1.55]), current smoking (OR 1.43 [95% CI 1.07–1.91]), and hypertension (OR 1.26 [95% CI 1.07–1.49]) were associated with a higher probability of type 2 diabetes progression. Having more favorable modifiable factors was also associated with normoglycemia reversion (OR 1.46 [95% CI 1.30–1.64]) and type 2 diabetes progression (OR 0.62 [95% CI 0.49–0.77]). CONCLUSIONS: More favorable modifiable factors were related to a higher probability of returning to normoglycemia and a lower probability of progression to type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article presents a summary of revisions to the American Diabetes Association's (ADA) 2023 Standards of Care in Diabetes. Topcis of the changes include improvement of care and health promotion, classification and diagnosis of diabetes, prevention or delay of type 2 diabetes and associated comorbidities, medical evaluation and assessment of comorbidities, health behaviors and well-being to improve health outcomes, glycemic targets, diabetes technology, diabetes and weight management.

Objective: The temporal pattern of cognitive and functional change before and after incident diabetes remains unknown.Research Design and Methods: Data from wave 2 to wave 9 (2004-2018) of the English Longitudinal Study of Ageing were used. Global cognition (assessed by orientation, memory, and executive function) and daily functioning (calculated as the sum of impaired basic and instrumental activities of daily living) were measured in each wave. Incident diabetes was defined as glycated hemoglobin A1c ≥6.5% (47.5 mmol/mol), self-reported doctor diagnosis of diabetes, or glucose-lowering medication use during follow-up.Results: Among the 6,342 participants (mean age 65.0 years, 57.8% women) included, 576 participants (9.1%) with incident diabetes were identified during a median follow-up of 13.3 years. The annual rates of change in global cognition (β = -0.035 SD/year; 95% CI -0.054 to -0.015), orientation (-0.031 SD/year; -0.060 to -0.002), memory (-0.016 SD/year; -0.029 to -0.003), and executive function (-0.027 SD/year; -0.042 to -0.013) were accelerated after diabetes diagnosis compared with before the event. The postdiabetes annual changes in daily functioning (0.093 points/year; 95% CI 0.056-0.131) were also accelerated compared with the prediabetes diagnosis. However, the rate of cognitive and functional decline before the diabetes diagnosis in participants with future incident diabetes was similar to the rate in participants without diabetes. Also, no significant acute change was observed during its onset.Conclusions: Incident diabetes is associated with accelerated cognitive and functional decline after, but not before, the event. We suggest careful monitoring for cognitive and physical dysfunction after a diabetes diagnosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Pregnant individuals are universally screened for gestational diabetes mellitus (GDM). Gestational glucose intolerance (GGI) (an abnormal initial GDM screening test without a GDM diagnosis) is not a recognized diabetes risk factor. We tested for an association between GGI and diabetes after pregnancy. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of individuals followed for prenatal and primary care. We defined GGI as an abnormal screening glucose-loading test result at ≥24 weeks' gestation with an oral glucose tolerance test (OGTT) that did not meet GDM criteria. The primary outcome was incident diabetes. We used Cox proportional hazards models with time-varying exposures and covariates to compare incident diabetes risk in individuals with GGI and normal glucose tolerance. RESULTS: Among 16,836 individuals, there were 20,359 pregnancies with normal glucose tolerance, 2,943 with GGI, and 909 with GDM. Over a median of 8.4 years of follow-up, 428 individuals developed diabetes. Individuals with GGI had increased diabetes risk compared to those with normal glucose tolerance in pregnancy (adjusted hazard ratio [aHR] 2.01 [95% CI 1.54–2.62], P < 0.001). Diabetes risk increased with the number of abnormal OGTT values (zero, aHR 1.54 [1.09–2.16], P = 0.01; one, aHR 2.97 [2.07–4.27], P < 0.001; GDM, aHR 8.26 [6.49–10.51], P < 0.001 for each compared with normal glucose tolerance). The fraction of cases of diabetes 10 years after delivery attributable to GGI and GDM was 8.5% and 28.1%, respectively. CONCLUSIONS: GGI confers an increased risk of future diabetes. Routinely available clinical data identify an unrecognized group who may benefit from enhanced diabetes screening and prevention. [ABSTRACT FROM AUTHOR]

Objective: To assess whether low doses of empagliflozin as adjunct to hybrid closed-loop therapy improve glycemia compared with placebo in adults with type 1 diabetes (T1D) who are not able to achieve targets with the system alone.Research Design and Methods: A double-blind crossover randomized controlled trial was performed in adults with suboptimally controlled T1D (HbA1c 7.0-10.5%) who were not able to achieve a target time in range (3.9-10.0 mmol/L) ≥70% after 14 days of hybrid closed-loop therapy. Three 14-day interventions were performed with placebo, 2.5 mg empagliflozin, or 5 mg empagliflozin as adjunct to the McGill artificial pancreas. Participants were assigned at a 1:1:1:1:1:1 ratio with blocked randomization. The primary outcome was time in range (3.9-10.0 mmol/L). Analysis was by intention to treat, and a P value <0.05 was regarded as significant.Results: A total of 24 participants completed the study (50% male; age 33 ± 14 years; HbA1c 8.1 ± 0.5%). The time in range was 59.0 ± 9.0% for placebo, 71.6 ± 9.7% for 2.5 mg empagliflozin, and 70.2 ± 8.0% for 5 mg empagliflozin (P < 0.0001 between 2.5 mg empagliflozin and placebo and between 5 mg empagliflozin and placebo). Mean daily capillary ketone levels were not different between arms. There were no serious adverse events or cases of diabetic ketoacidosis or severe hypoglycemia in any intervention.Conclusions: Empagliflozin at 2.5 and 5 mg increased time in range during hybrid closed-loop therapy by 11-13 percentage points compared with placebo in those who otherwise were unable to attain glycemic targets. Future studies are required to assess long-term efficacy and safety. [ABSTRACT FROM AUTHOR]

The article presents the case of a 13-year-old female with childhood-onset obesity and type 1 diabetes to discuss the feasibility of insulin omission for weight loss in patients treated with advanced hybrid closed-loop system. She was admitted to the hospital due to impaired consciousness when she was 15 years old. Also cited are the potential risk factors for deliberate insulin restriction or omission in patients like female gender, increased weight concerns, and body dissatisfaction.

ObjectiveWe aimed to identify hemoglobin A1c (HbA1c)-associated genetic variants and examine their implications for glycemic status evaluated by HbA1c in U.S. Hispanics/Latinos with diverse genetic ancestries.Research design and methodsWe conducted a genome-wide association study (GWAS) of HbA1c in 9,636 U.S. Hispanics/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos, followed by a replication among 4,729 U.S. Hispanics/Latinos from three independent studies.ResultsOur GWAS and replication analyses showed 10 previously known and novel loci associated with HbA1c at genome-wide significance levels (P < 5.0 × 10-8). In particular, two African ancestry-specific variants, HBB-rs334 and G6PD-rs1050828, which are causal mutations for sickle cell disease and G6PD deficiency, respectively, had ∼10 times larger effect sizes on HbA1c levels (β = -0.31% [-3.4 mmol/mol]) and -0.35% [-3.8 mmol/mol] per minor allele, respectively) compared with other HbA1c-associated variants (0.03-0.04% [0.3-0.4 mmol/mol] per allele). A novel Amerindian ancestry-specific variant, HBM-rs145546625, was associated with HbA1c and hematologic traits but not with fasting glucose. The prevalence of hyperglycemia (prediabetes and diabetes) defined using fasting glucose or oral glucose tolerance test 2-h glucose was similar between carriers of HBB-rs334 or G6PD-rs1050828 HbA1c-lowering alleles and noncarriers, whereas the prevalence of hyperglycemia defined using HbA1c was significantly lower in carriers than in noncarriers (12.2% vs. 28.4%, P < 0.001). After recalibration of the HbA1c level taking HBB-rs334 and G6PD-rs1050828 into account, the prevalence of hyperglycemia in carriers was similar to noncarriers (31.3% vs. 28.4%, P = 0.28).ConclusionsThis study in U.S. Hispanics/Latinos found several ancestry-specific alleles associated with HbA1c through erythrocyte-related rather than glycemic-related pathways. The potential influences of these nonglycemic-related variants need to be considered when the HbA1c test is performed.

The article focuses on the analysis of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) by Garvey et al., revealing baseline factors associated with glycemic outcomes. It reports that younger age and baseline Glycated hemoglobin (HbA1c) increased the risk of reaching glycemic outcomes, with treatment group associations. It highlights for more aggressive treatment and follow-up, especially in patients with younger onset and high HbA1c values.

Objective: Hyperglycemia can increase urinary zinc excretion. We evaluated the association of higher urinary zinc level with new diagnosis of incident type 2 diabetes mellitus (T2DM) in adult populations with a high burden of T2DM from AZ, OK, and ND and SD. We also assessed the cross-sectional association of urinary zinc levels with prevalent prediabetes.Research Design and Methods: We included 1,339 adults free of T2DM at baseline (1989-1991) followed through 1998-1999 in the Strong Heart Study (SHS) and 1,905 family members of SHS participants followed as part of the Strong Heart Family Study (SHFS) through 2006-2009.Results: T2DM incidence was 14.7% (mean follow-up 6.6 years) in the SHS and 13.5% (mean follow-up 5.6 years) in the SHFS. After adjustment for sex, site, education, smoking status, BMI, and estimated glomerular filtration rate, the hazard ratio of T2DM in comparing 75th vs. 25th percentiles of urinary zinc distribution was 1.21 (95% CI 1.08, 1.36) in the SHS and 1.12 (0.96, 1.31) in the SHFS. These associations were attenuated but significant in the SHS after adjustment for HOMA of insulin resistance (HOMA-IR) score. With exclusion of participants with prediabetes at baseline, urinary zinc remained significantly associated with T2DM in the SHS. In cross-sectional analyses, prediabetes was associated with higher urinary zinc levels.Conclusions: Urinary zinc levels were associated with T2DM incidence and prediabetes prevalence even after adjustment for HOMA-IR in populations with a high burden of T2DM. These results highlight the importance of zinc metabolism in diabetes development. [ABSTRACT FROM AUTHOR]

Objective: To examine whether the effect of a 3-year lifestyle intervention on body weight and cardiometabolic risk factors differs by prediabetes metabolic phenotype.Research Design and Methods: This post hoc analysis of the multicenter, randomized trial, PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World (PREVIEW), included 1,510 participants with prediabetes (BMI ≥25 kg ⋅ m-2; defined using oral glucose tolerance tests). Of these, 58% had isolated impaired fasting glucose (iIFG), 6% had isolated impaired glucose tolerance (iIGT), and 36% had IFG+IGT; 73% had normal hemoglobin A1c (HbA1c; <39 mmol ⋅ mol-1) and 25% had intermediate HbA1c (39-47 mmol ⋅ mol-1). Participants underwent an 8-week diet-induced rapid weight loss, followed by a 148-week lifestyle-based weight maintenance intervention. Linear mixed models adjusted for intervention arm and other confounders were used.Results: In the available-case and complete-case analyses, participants with IFG+IGT had greater sustained weight loss after lifestyle intervention (adjusted mean at 156 weeks -3.5% [95% CI, -4.7%, -2.3%]) than those with iIFG (mean -2.5% [-3.6%, -1.3%]) relative to baseline (P = 0.011). Participants with IFG+IGT and iIFG had similar cardiometabolic benefits from the lifestyle intervention. The differences in cardiometabolic benefits between those with iIGT and IFG+IGT were minor or inconsistent in different analyses. Participants with normal versus intermediate HbA1c had similar weight loss over 3 years and minor differences in cardiometabolic benefits during weight loss, whereas those with normal HbA1c had greater improvements in fasting glucose, 2-h glucose (adjusted between-group difference at 156 weeks -0.54 mmol ⋅ L-1 [95% CI -0.70, -0.39], P < 0.001), and triglycerides (difference -0.07 mmol ⋅ L-1 [-0.11, -0.03], P < 0.001) during the lifestyle intervention.Conclusions: Individuals with iIFG and IFG+IGT had similar improvements in cardiometabolic health from a lifestyle intervention. Those with normal HbA1c had greater improvements than those with intermediate HbA1c. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Diabetes and the outpatient diabetes treatment regimen have been identified as risk factors for poor outcomes in patients with sepsis. However, little is known about the effect of tight inpatient glycemic control in the setting of coronavirus disease 2019 (COVID-19). Therefore, we examined the effect of hyperglycemia in patients with diabetes hospitalized because of COVID-19. RESEARCH DESIGN AND METHODS: We analyzed data from 1,938 COVID-19 patients with diabetes hospitalized for COVID-19 from March to May 2020 at a large academic medical center in New York City. Patients were divided into two groups based on their inpatient glycemic values, and a Cox proportional hazards regression model was used to assess the independent association of inpatient glucose levels with mortality (primary outcome) and the risk of requiring mechanical ventilation (MV) (secondary outcome). RESULTS: In our analysis, 32% of the patients were normoglycemic and 68% hyperglycemic. Moreover, 31% of the study subjects died during hospitalization, and 14% required MV, with inpatient hyperglycemia being significantly associated with both mortality and the requirement for MV. Additionally, in the Cox regression analysis, after adjustment for potential confounders, including age, sex, race, BMI, HbA1c, comorbidities, inflammatory markers, and corticosteroid therapy, patients with uncontrolled hyperglycemia had a higher risk of dying (hazard ratio [HR] 1.54, 95% CI 1.00–2.36, P = 0.049) and of requiring MV (HR 4.41, 95% CI 1.52–2.81, P = 0.006) than those with normoglycemia. CONCLUSIONS: A tight control of inpatient hyperglycemia may be an effective method for improving outcomes in patients with diabetes hospitalized for COVID-19. [ABSTRACT FROM AUTHOR]

Objective: Dysglycemia influences hospital outcomes and resource utilization. Clinical decision support (CDS) holds promise for optimizing care by overcoming management barriers. This study assessed the impact on hospital length of stay (LOS) of an alert-based CDS tool in the electronic medical record that detected dysglycemia or inappropriate insulin use, coined as gaps in care (GIC).Research Design and Methods: Using a 12-month interrupted time series among hospitalized persons aged ≥18 years, our CDS tool identified GIC and, when active, provided recommendations. We compared LOS during 6-month-long active and inactive periods using linear models for repeated measures, multiple comparison adjustment, and mediation analysis.Results: Among 4,788 admissions with GIC, average LOS was shorter during the tool's active periods. LOS reductions occurred for all admissions with GIC (-5.7 h, P = 0.057), diabetes and hyperglycemia (-6.4 h, P = 0.054), stress hyperglycemia (-31.0 h, P = 0.054), patients admitted to medical services (-8.4 h, P = 0.039), and recurrent hypoglycemia (-29.1 h, P = 0.074). Subgroup analysis showed significantly shorter LOS in recurrent hypoglycemia with three events (-82.3 h, P = 0.006) and nonsignificant in two (-5.2 h, P = 0.655) and four or more (-14.8 h, P = 0.746). Among 22,395 admissions with GIC (4,788, 21%) and without GIC (17,607, 79%), LOS reduction during the active period was 1.8 h (P = 0.053). When recommendations were provided, the active tool indirectly and significantly contributed to shortening LOS through its influence on GIC events during admissions with at least one GIC (P = 0.027), diabetes and hyperglycemia (P = 0.028), and medical services (P = 0.019).Conclusions: Use of the alert-based CDS tool to address inpatient management of dysglycemia contributed to reducing LOS, which may reduce costs and improve patient well-being. [ABSTRACT FROM AUTHOR]

Objective: Administration of supplemental sliding scale insulin for correction of hyperglycemia in non-intensive care unit (ICU) patients with type 2 diabetes is frequently used with basal-bolus insulin regimens. In this noninferiority randomized controlled trial we tested whether glycemic control is similar with and without aggressive sliding scale insulin treatment before meals and bedtime in patients treated with basal-bolus insulin regimens.Research Design and Methods: Patients with type 2 diabetes with admission blood glucose (BG) 140-400 mg/dL treated with basal-bolus insulin were randomized to intensive (correction for BG >140 mg/dL, n = 108) or to nonintensive (correction for BG >260 mg/dL, n = 107) administration of rapid-acting sliding scale insulin before meals and bedtime. The groups received the same amount of sliding scale insulin for BG >260 mg/dL. Primary outcome was difference in mean daily BG levels between the groups during hospitalization.Results: Mean daily BG in the nonintensive group was noninferior to BG in the intensive group with equivalence margin of 18 mg/dL (intensive 172 ± 38 mg/dL vs. nonintensive 173 ± 43 mg/dL, P = 0.001 for noninferiority). There were no differences in the proportion of target BG readings of 70-180 mg/dL, <70 or <54 mg/dL (hypoglycemia), or >350 mg/dL (severe hyperglycemia) or total, basal, or prandial insulin doses. Significantly fewer subjects received sliding scale insulin in the nonintensive (n = 36 [34%]) compared with the intensive (n = 98 [91%] [P < 0.0001]) group with no differences in sliding scale insulin doses between the groups among those who received sliding scale insulin (intensive 7 ± 4 units/day vs. nonintensive 8 ± 4 units/day, P = 0.34).Conclusions: Among non-ICU patients with type 2 diabetes on optimal basal-bolus insulin regimen with moderate hyperglycemia (BG <260 mg/dL), a less intensive sliding scale insulin treatment did not significantly affect glycemic control. [ABSTRACT FROM AUTHOR]

ObjectiveSevere hyperglycemia and hypoglycemia ("severe dysglycemia") are serious complications of type 1 diabetes (T1D). Depression has been associated with severe dysglycemia in type 2 diabetes but has not been thoroughly examined specifically in T1D. We evaluated bidirectional associations between depression and severe dysglycemia among older people with T1D.Research design and methodsWe abstracted depression and severe dysglycemia requiring emergency room visit or hospitalization from medical health records in 3,742 patients with T1D during the study period (1996-2015). Cox proportional hazards models estimated the associations between depression and severe dysglycemia in both directions, adjusting for demographics, micro- and macrovascular complications, and HbA1c.ResultsDuring the study period, 41% had depression and 376 (11%) and 641 (20%) had hyperglycemia and hypoglycemia, respectively. Depression was strongly associated with a 2.5-fold increased risk of severe hyperglycemic events (hazard ratio [HR] 2.47 [95% CI 2.00, 3.05]) and 89% increased risk of severe hypoglycemic events (HR 1.89 [95% CI 1.61, 2.22]). The association was strongest within the first 6 months (HRhyperglycemia 7.14 [95% CI 5.29, 9.63]; HRhypoglycemia 5.58 [95% CI 4.46, 6.99]) to 1 year (HRhyperglycemia 5.16 [95% CI 3.88, 6.88]; HRhypoglycemia 4.05 [95% CI 3.26, 5.04]) after depression diagnosis. In models specifying severe dysglycemia as the exposure, hyperglycemic and hypoglycemic events were associated with 143% (HR 2.43 [95% CI 2.03, 2.91]) and 74% (HR 1.75 [95% CI 1.49, 2.05]) increased risk of depression, respectively.ConclusionsDepression and severe dysglycemia are associated bidirectionally among patients with T1D. Depression greatly increases the risk of severe hypoglycemic and hyperglycemic events, particularly in the first 6 months to 1 year after diagnosis, and depression risk increases after severe dysglycemia episodes.

Objective: The 2018-2019 federal government partial shutdown resulted in a one-time disruption to the usual disbursement schedule of Supplemental Nutrition Assistance Program (SNAP) benefits nationwide. We assessed the relationship between this disruption and hyperglycemia and hypoglycemia medical encounters among beneficiaries with diabetes.Research Design and Methods: To estimate whether the one-time change in benefit disbursement affected the monthly cycle of hyperglycemia or hypoglycemia encounter rates, we used linked administrative Medicaid claims and SNAP disbursement data from West Virginia in a fixed-effects model with interactions between week of the month and the two months of interest-January and February 2019. We controlled for week, month, year, and county effects as well as individual characteristics, and we clustered SEs by individual.Results: We found that the early disbursement of SNAP benefits in January 2019 resulted in a spike in hyperglycemia four times the rate in a typical month. Further, we found a decrease in both hyperglycemia and hypoglycemia in late February.Conclusions: Our findings suggest that the early distribution of benefits led to a temporary increase in food consumption among West Virginia Medicaid beneficiaries with diabetes. Findings from late February also imply that individuals may have a way to prepare for reduced food resources. These results shed new light on the effects of unexpected changes to the timing of safety net payments as well as an understanding of unintended consequences of government shutdowns. [ABSTRACT FROM AUTHOR]

Objective: To estimate time with diabetes distress using ecological momentary assessment (EMA) in people with type 1 diabetes and analyze its associations with glycemic management based on continuous glucose monitoring (CGM).Research Design and Methods: We used EMA to assess diabetes distress in a sample of recently hospitalized adults with type 1 diabetes once a day for 17 consecutive days in an ambulatory setting. Additionally, participants were asked daily about hypoglycemia distress (<70 mg/dL [3.9 mmol/L]), hyperglycemia distress (>180 mg/dL [10 mmol/L]), and variability distress (glucose fluctuations). Per person, the percentage of days with elevated distress was calculated (time with distress). Multilevel regression was used to analyze daily associations of distress ratings with CGM-derived parameters. EMA-derived associations between diabetes distress and glycemic outcomes were compared with questionnaire-derived associations.Results: Data of 178 participants were analyzed. Participants spent a mean (SD) of days in a state of diabetes distress, 54.6 ± 26.0% in hyperglycemia distress, 45.2 ± 27.5% in variability distress, and 23.0 ± 19.3% in hypoglycemia distress. In multilevel analyses, higher daily ratings of diabetes distress were significantly associated with hyperglycemia (β = 0.41). Results showed high between-person variability as explanation of variance of the models ranged between 22.2 and 98.8%. EMA-derived diabetes distress showed a significant association with mean glucose (r = 0.25), while questionnaire-based diabetes distress did not (r = 0.10). Prospectively, time with diabetes distress was associated with HbA1c at the 3-month follow-up (r = 0.27), while questionnaire-based distress showed no association (r = 0.11).Conclusions: Time with distress as assessed with EMA showed a comparative advantage over distress as determined by questionnaire-based assessment of diabetes distress regarding associations with glycemic management. [ABSTRACT FROM AUTHOR]

The article informs about the lack of predictability of immune checkpoint inhibitor-induced type 1 diabetes (ICIT1D) through routine blood glucose monitoring. Topic include Despite the increased incidence of ICIT1D, particularly after anti-PD-1 or anti-PD-L1 therapy, blood glucose levels often remain normal before the onset of hyperglycemia, emphasizing the need for alternative screening methods like T1D-associated antibodies or HLA typing.

Objective: To determine trends in the incidence of major diabetes-related complications in Australia.Research Design and Methods: This study included 70,885 people with type 1 and 1,089,270 people with type 2 diabetes registered on the Australian diabetes registry followed from July 2010 to June 2019. Outcomes (hospitalization for myocardial infarction [MI], stroke, heart failure [HF], lower-extremity amputation [LEA], hypoglycemia, and hyperglycemia) were obtained via linkage to hospital admissions databases. Trends over time in the age-adjusted incidence of hospitalizations were analyzed using joinpoint regression and summarized as annual percent changes (APCs).Results: In type 1 diabetes, the incidence of all complications remained stable, except for stroke, which increased from 2010-2011 to 2018-2019 (financial years; APC: +2.5% [95% CI 0.1, 4.8]), and hyperglycemia, which increased from 2010-2011 to 2016-2017 (APC: +2.7% [1.0, 4.5]). In type 2 diabetes, the incidence of stroke remained stable, while the incidence of MI decreased from 2012-2013 to 2018-2019 (APC: -1.7% [95% CI -2.8, -0.5]), as did the incidence of HF and hypoglycemia from 2010-2011 to 2018-2019 (APCs: -0.8% [-1.5, 0.0] and -5.3% [-6.7, -3.9], respectively); the incidence of LEA and hyperglycemia increased (APCs: +3.1% [1.9, 4.4], and +7.4% [5.9, 9.0]). Most trends were consistent by sex, but differed by age; in type 2 diabetes most improvements were confined to individuals aged ≥60 years.Conclusions: Trends in admissions for diabetes-related complications were largely stable in type 1 diabetes. In type 2 diabetes, hospitalization rates for MI, HF, and hypoglycemia fell over time, while increasing for LEA and hyperglycemia. [ABSTRACT FROM AUTHOR]

Objective: In recent years, some studies have indicated that a novel marker described as the stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with the short-term poor prognosis in patients with acute myocardial infarction. In the current study we evaluated the association of SHR with adverse cardiovascular events among patients with acute coronary syndrome (ACS).Research Design and Methods: We consecutively enrolled 5,562 ACS patients who underwent drug-eluting stent (DES) implantation. All subjects were divided into five groups according to SHR, which was determined by the following formula: ABG / [(28.7 × HbA1c %) - 46.7], where ABG is admission blood glucose level. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE) at the 2-year follow-up, and the secondary end point included major adverse cardiovascular events (MACE) at 2-year follow-up, cardiac death, and nonfatal myocardial infarction (MI) at 2-year follow-up and in-hospital cardiac death and nonfatal MI.Results: A total of 643 MACCE were recorded during a median follow-up of 28.3 months. Kaplan-Meier survival analysis showed the lowest MACCE incidence in quintile 3 (P < 0.001). Moreover, the outcomes of restricted cubic spline analysis suggested that there was a U-shaped or J-shaped association between the SHR and early and late cardiovascular outcomes even after adjustment for other confounding factors.Conclusions: There were U-shaped associations of SHR with MACCE rate and MACE rate at 2-year follow-ups and J-shaped associations of SHR with in-hospital cardiac death and MI and that at 2-year follow-up in ACS patients who underwent DES implantation, and the inflection point of SHR for poor prognosis was 0.78. [ABSTRACT FROM AUTHOR]

Objective: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear.Research Design and Methods: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy.Results: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels.Conclusions: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate long-term glycemic outcomes of continuous glucose monitoring (CGM) initiation within the first year of type 1 diabetes diagnosis.Research Design and Methods: Patients with type 1 diabetes (N = 396) were divided into three groups: 1) CGM (CGM use within 1 year of diabetes diagnosis and continued through the study), 2) no-CGM (no CGM use throughout the study), and 3) new-CGM (CGM use after 3 years since diabetes diagnosis). Patients were followed up to 7 years.Results: A1c was significantly lower in the CGM compared with the no-CGM group throughout 7 years of follow-up (least squares mean A1c values: 6 months, 7.3% vs. 8.1%; 1 year, 7.4% vs. 8.6%; 2 years, 7.7% vs. 9.1%; 3 years, 7.6% vs. 9.3%; 4 years, 7.4% vs. 9.6%; 5 years, 7.6% vs. 9.7%; 6 years, 7.5% vs. 10.0%; and 7 years, 7.6% vs. 9.8%; for all, P < 0.001) adjusting for age at diagnosis, sex, and insulin delivery method.Conclusions: CGM initiation within first year of type 1 diabetes diagnosis results in long-term improvement in A1c. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to 1) identify the frequency of severe and level 2 hypoglycemia presenting in individuals with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting and 2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population.Research Design and Methods: A cross-sectional survey study in adults with type 1 diabetes using CGMs >6 months was conducted at a large tertiary academic center. Participant demographics, 6-month severe hypoglycemia history, hypoglycemia beliefs (with the Attitude to Awareness of Hypoglycemia questionnaire), and 4-week CGM glucose data were collected. Statistical analysis was performed to assess the presentation of severe and level 2 hypoglycemia and identify associated risk factors.Results: A total of 289 participants were recruited (including 257 participants with CGM data within the last 3 months). Of these, 25.6% experienced at least one severe hypoglycemic episode in the last 6 months, and 13.6% presented with ≥1% of time in level 2 hypoglycemia on CGMs. Reporting beliefs about prioritizing hyperglycemia avoidance was associated with severe hypoglycemia development (P < 0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (P = 0.038).Conclusions: Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in individuals with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may continue to impact the effectiveness of glucose self-management. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycemic, lipid, and other metabolic biomarkers were associated with future type 1 diabetes risk in adults.Research Design and Methods: We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design.Results: We identified 1,122 type 1 diabetes cases during follow-up (average age of patient at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the ratio of apolipoprotein (apo)B to apoA-I, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. Higher apoA-I was associated with lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared with control subjects.Conclusions: Alterations in biomarker levels related to glycemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis. [ABSTRACT FROM AUTHOR]

Objective: We characterized annual trends of severe hypoglycemic and hyperglycemic crises (diabetic ketoacidosis/hyperglycemic hyperosmolar state) in patients with diabetes and end-stage kidney disease (ESKD).Research Design and Methods: This was a nationwide, retrospective study of adults (≥18 years old) with diabetes/ESKD, from the United States Renal Data System registry, between 2013 and 2017. Primary outcome was annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1,000 person-years. Event rates and risk factors were adjusted for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen, and U.S. region.Results: Among 521,789 adults with diabetes/ESKD (median age 65 years [interquartile range 57-73], 56.1% male, and 46% White), overall adjusted rates of hypoglycemic and hyperglycemic crises were 53.64 and 18.24 per 1,000 person-years, respectively. For both hypoglycemia and hyperglycemia crises, respectively, the risks decreased with age and were lowest in older patients (≥75 vs. 18-44 years old: incidence rate ratio 0.35, 95% CI 0.33-0.37, and 0.03, 0.02-0.03), women (1.09, 1.06-1.12, and 1.44, 1.35-1.54), and those with smoking (1.36, 1.28-1.43, and 1.71, 1.53-1.91), substance abuse (1.27, 1.15-1.42, and 1.53, 1.23-1.9), retinopathy (1.10, 1.06-1.15, and 1.36, 1.26-1.47), and insulin therapy (vs. no therapy; 0.60, 0.59-0.63, and 0.44, 0.39-0.48). For hypoglycemia, specifically, additional risk was conferred by Black race (1.11, 1.08-1.15) and amputation history (1.20, 1.13-1.27).Conclusions: In this nationwide study of patients with diabetes/ESKD, hypoglycemic crises were threefold more common than hyperglycemic crises, greatly exceeding national reports in nondialysis patients with chronic kidney disease. Young, Black, and female patients were disproportionately affected. [ABSTRACT FROM AUTHOR]