Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Novel Automated Self-adjusting Subcutaneous Insulin Algorithm Improves Glycemic Control and Physician Efficiency in Hospitalized Patients.

BACKGROUND: Hyperglycemia occurs in 22% to 46% of hospitalized patients, negatively affecting patient outcomes, including mortality, inpatient complications, length of stay, and hospital costs. Achieving inpatient glycemic control is challenging due to inconsistent caloric intake, changes from home medications, a catabolic state in the setting of acute illness, consequences of acute inflammation, intercurrent infection, and limitations in labor-intensive glucose monitoring and insulin administration. METHOD: We conducted a retrospective cross-sectional analysis at the University of California San Francisco hospitals between September 3, 2020 and September 2, 2021, comparing point-of-care glucose measurements in patients on nil per os (NPO), continuous total parenteral nutrition, or continuous tube feeding assigned to our novel automated self-adjusting subcutaneous insulin algorithm (SQIA) or conventional, physician-driven insulin dosing. We also evaluated physician efficiency by tracking the number of insulin orders placed or modified. RESULTS: The proportion of glucose in range (70-180 mg/dL) was higher in the SQIA group than in the conventional group (71.0% vs 69.0%, P = .153). The SQIA led to a lower proportion of severe hyperglycemia (>250 mg/dL; 5.8% vs 7.2%, P = .017), hypoglycemia (54-69 mg/dL; 0.8% vs 1.2%, P = .029), and severe hypoglycemia (<54 mg/dL; 0.3% vs 0.5%, P = .076) events. The number of orders a physician had to place while a patient was on the SQIA was reduced by a factor of more than 12, when compared with while a patient was on conventional insulin dosing. CONCLUSIONS: The SQIA reduced severe hyperglycemia, hypoglycemia, and severe hypoglycemia compared with conventional insulin dosing. It also improved physician efficiency by reducing the number of order modifications a physician had to place.

Effect of semaglutide on weight loss and glycaemic control in patients with Prader-Willi Syndrome and type 2 diabetes.

Prader-Willi Syndrome (PWS) is the most common genetic cause of obesity, occurring in approximately 1 in 15,000 newborns. It results from the lack of expression of genes on the paternal allele of the chromosomal region 15q-11q13 (65-75% due to type 1 or type 2 deletion). Individuals with PWS experience associated symptoms such as hypotonia, hyperphagia, and early-onset obesity (before 5 years of age). Around 20% of adults with PWS also develop type 2 diabetes. Previous studies have shown the beneficial effects of GLP1-RA medications, such as exenatide and liraglutide, in treating type 2 diabetes in PWS. However, there is limited information available on the use of semaglutide in PWS. This study aimed to evaluate the effects of semaglutide on weight loss and glycaemic control in four patients with PWS and type 2 diabetes associated with obesity. The patients were started on weekly subcutaneous progressive doses of semaglutide.

The Effects of Preoperative Glycaemic Control (HbA1c) on Bariatric and Metabolic Surgery Outcomes: Data from a Tertiary-Referral Bariatric Centre in the UK.

BACKGROUND: Current recommendations advocate the achievement of an optimal glucose control (HbA1c < 69 mmol/mol) prior to elective surgery to reduce risks of peri- and post-operative complications, but the relevance for this glycaemic threshold prior to Bariatric Metabolic Surgery (BMS) following a specialist weight management programme remains unclear. METHODS: We undertook a retrospective cohort study of patients with type 2 diabetes mellitus (T2DM) who underwent BMS over a 6-year period (2016-2022) at a regional tertiary referral following completion of a specialist multidisciplinary weight management. Post-operative outcomes of interest included 30-day mortality, readmission rates, need for Intensive Care Unit (ICU) care and hospital length of stay (LOS) and were assessed according to HbA1c cut-off values of < 69 (N = 202) and > 69 mmol/mol (N = 67) as well as a continuous variable. RESULTS: A total of 269 patients with T2D were included in this study. Patients underwent primary Roux en-Y gastric bypass (RYGB, n = 136), Sleeve Gastrectomy (SG, n = 124), insertion of gastric band (n = 4) or one-anastomosis gastric bypass (OAGB, n = 4). No significant differences in the rates of complications were observed between the two groups of pre-operative HbA1c cut-off values. No HbA1c threshold was observed for glycaemic control that would affect the peri- and post-operative complications following BMS. CONCLUSIONS: We observed no associations between pre-operative HbA1C values and the risk of peri- and post-operative complications. In the context of a specialist multidisciplinary weight management programme, optimising pre-operative HbA1C to a recommended target value prior to BMS may not translate into reduced risks of peri- and post-operative complications.

Relationship Between Lipohypertrophy, Glycemic Control, and Insulin Dosing: A Systematic Meta-Analysis.

Background: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.

A case of rapidly declining glycemic control and diabetic ketoacidosis in a newly diagnosed diabetes patient after starting teprotumumab for thyroid eye disease.

PURPOSE: Teprotumumab for thyroid eye disease has a known hyperglycemic adverse effect through its impact on the insulin-like growth factor-1 receptor. While most cases are mild and easily managed by adjusting diabetes medications, it appears some patients have a more dramatic response. The purpose of this case report is to highlight an example of rapidly declining glycemic control and diabetic ketoacidosis (DKA) in a patient with newly diagnosed diabetes after starting teprotumumab for thyroid eye disease. METHODS: This was a single-patient case report assessing a severe episode of hyperglycemia leading to new-onset diabetes. The case report was approved by Atrium Health Wake Forest Baptist's IRB committee. The patient was closely monitored by a pharmacist-led pharmacotherapy clinic after initial diagnosis and periodically since then to adjust therapy and assess glucose and hemoglobin A1c (HbA1c) trends. RESULTS: After the acute episode of DKA was managed inpatient, the patient was discharged with insulin outpatient, but this was ultimately weaned off, and the patient's glucose and HbA1c are stable on metformin alone. This patient decided to not continue teprotumumab due to extensive side effects including but not limited to severe hyperglycemia. CONCLUSION: While additional research is needed as to the cause of severe hyperglycemia in select patients, providers should consider proactively monitoring glucose throughout treatment with teprotumumab by ensuring that patients have baseline labs and labs at every visit and access to a glucometer with education for its use.

Association between continuous glucose monitoring-derived glycemic control indices and urinary biomarkers of diabetic kidney disease: Hyogo Diabetes Hypoglycemia Cognition Complications study.

AIMS: Glomerular damage and proximal tubular damage play an important role in the pathogenesis of diabetic kidney disease. This study aimed to investigate the relationship between the urinary markers of proximal tubular injury, including urinary liver-type fatty acid-binding protein-to-creatinine ratio (uL-FABP/Cr) and urinary N-acetyl-ß-D-glucosaminidase-to-creatinine ratio (uNAG/Cr), and glycemic control status. METHODS: This cross-sectional study included 245 and 39 patients with type 2 diabetes mellitus (T2DM) and non-T2DM (NDM), respectively. The participants of this study were fitted with retrospective CGM, and glycemic control indices, such as time in range (TIR) and glycemia risk index (GRI), were calculated. RESULTS: The results were presented as medians (interquartile ranges). The uL-FABP/Cr was significantly higher in the microalbuminuria than in the normo-albuminuria group [4.2 (2.7-7.1) and 2.2 (1.4-3.4) µg/gCr, respectively, P < 0.001], while the uNAG/Cr in the normo-albuminuria group [6.3 (4.5-10.1) U/gCr] was significantly higher than that in the NDM group [5.3 (3.8-6.3) U/gCr, P = 0.048] but significantly lower than that in the microalbuminuria group [9.2 (6.4-11.1) U/gCr, P = 0.004]. The multivariate logistic regression analysis indicated that CGM-derived TIR was significantly associated with the urinary albumin-to-creatinine ratio [uAlb/Cr, odds ratio (OR) 0.985, 95% confidence interval (CI) 0.971-0.998, P = 0.029] and uNAG/Cr (OR 0.973, 95% CI 0.957-0.989, P = 0.001) independent of renal function. GRI was similarly associated with uAlb/Cr and uNAG/Cr. CONCLUSION: The findings of this study indicated that uNAG/Cr was elevated before albuminuria development and was associated with CGM-derived TIR and GRI.

Evaluation of changes in glycemic control and diabetic complications over time and factors associated with the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

BACKGROUND: This study aimed to evaluate the changes in glycemic control and diabetic complications over time in Japanese patients with juvenile-onset type 1 diabetes mellitus and to clarify the factors associated with the progression of diabetic complications. METHODS: We tracked 129 patients with type 1 diabetes mellitus (21.8 ± 4.1 years old [mean ± SD] with a diabetes duration of 12.6 ± 5.7 years) for up to 19 years and analyzed data on glycated hemoglobin (HbA1c) and indicators related to the severity of diabetic complications (estimated glomerular filtration rate [eGFR], urinary albumin excretion rate [UAE], carotid intima-media thickness [CIMT], and brachial-ankle pulse wave velocity [baPWV]) using linear mixed model and decision tree analysis. RESULTS: Although the HbA1c and UAE levels improved over time, the eGFR, CIMT, and baPWV worsened. Decision tree analysis showed that HbA1c and the glycoalbumin/HbA1c ratio for eGFR; HbA1c and systolic blood pressure for UAE; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, glycoalbumin/HbA1c ratio, and body mass index (BMI) for CIMT; and HbA1c for baPWV were associated factors. CONCLUSIONS: In this retrospective observational study, glycemic control and albuminuria improved; however, renal function and arteriosclerosis worsened over time. HbA1c levels, glycemic excursion, and blood pressure are associated with nephropathy progression. HbA1c levels, glycemic excursion, lipid levels, and BMI are associated with the progression of atherosclerosis.

The evolution of type 2 diabetes management: glycemic control and beyond with SGLT-2 inhibitors and GLP-1 receptor agonists.

Diabetes mellitus (DM) is one of the most prevalent diseases encountered by the primary care physician on a daily basis. Complications associated with DM can include nephropathy, neuropathy, and retinopathy ("microvascular complications"), along with cardiovascular disease (CVD), which can include myocardial infarction (MI) and strokes ("macrovascular complications"). In the 1990s, landmark clinical trials demonstrated that intensive glycemic control can reduce the risk of developing microvascular complications, but reduction in macrovascular complications with intensive glycemic control was not clearly demonstrated. At this point, intensive glycemic control became the standard of care (SOC). In the 2000s, additional trials evaluating the effect of intensive glycemic control in patients with type 2 diabetes mellitus (T2D) and established CVD, or risk factors for CVD, subsequently failed to identify a macrovascular benefit from intensive glycemic control, and one of the trials was terminated early because of an increase in the risk of mortality observed among patients assigned to receive intensive glycemic control. These results led to less strict glycemic targets being recommended in older patients, particularly those with established CVD. In 2007, everything changed after a report surfaced suggesting that rosiglitazone was associated with a significant increase in the risk of MI, as well as an increase in the risk of cardiovascular death that was of borderline significance. As a result, in 2008, the FDA mandated that all new diabetes medications must exclude an unacceptable level of risk for atherosclerotic cardiovascular disease (ASCVD) prior to drug approval, and thus undergo additional cardiovascular safety trials. Accordingly, through these trials, some of the newer agents, particularly sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), were demonstrated to reduce the risk of major adverse cardiovascular events (MACEs), independent of their effect on glycemic control. These findings subsequently led to further trials to evaluate the effects of some of these therapies on the risk of chronic kidney disease (CKD) progression, as well as adverse heart failure-related outcomes. SGLT-2 inhibitors have been demonstrated to reduce the risk of CKD progression, as well as a reduction in the risk of cardiovascular death or hospitalization secondary to heart failure in patients with both reduced ejection and preserved ejection fractions. A trial evaluating the effects of GLP-1RA on CKD outcomes is ongoing. The aim of this narrative review article, compiled by identifying relevant studies via the utilization of PubMed, is to provide a broad overview over the various clinical trials and analyses that have led to current diabetes management guidelines, and ultimately, help guide primary care physicians in selecting therapies that will not only improve glycemic control and reduce the risk of microvascular complications, but also reduce the risk of macrovascular disease in their patients with T2D.

HCC is associated with diabetes and longitudinal blood glucose control in a national cohort with cirrhosis.

BACKGROUND: Diabetes is associated with HCC; however, the impact of longitudinal blood glucose (BG) control on HCC risk in cirrhosis is not well known. We investigated this knowledge gap in a cohort of United States Veterans with cirrhosis from 2015 to 2021. METHODS: We used repeated hemoglobin A1c measurements to categorize follow-up time according to BG control (defined as hemoglobin A1c < 7%) state over time: uncontrolled, nonsustained control (≤2 y), or sustained control (>2 y). We performed a sensitivity analysis using hemoglobin A1c < 8% to define BG control. We used Fine and Gray Cox proportional hazards regression with death and transplant as competing events to compare rates of incident HCC. RESULTS: Our study included 81,907 individuals, 56.2% of whom had diabetes at baseline. There were 8,002 incident HCCs. The rate of HCC was 18% higher in diabetes (95% CI: 13% - 24%), and the relative increase in the rate of HCC varied by etiology of cirrhosis from nonsignificant (HCV) to an increase of 120% (HBV). Uncontrolled and nonsustained BG control was associated with 1.80 (95% CI: 1.70-1.91) and 2.34 (95% CI: 2.21-2.48) times the rate of HCC compared to sustained BG control, respectively. Using Hgb A1c < 8% to define BG control, HCC rates in uncontrolled and nonsustained BG control were 2.43 (2.28-2.58) and 2.23 (2.11-2.36) times that observed in sustained BG control. CONCLUSIONS: Associations between diabetes and HCC in cirrhosis vary according to the longitudinal BG control state. Inadequate BG control is consistently associated with a higher risk of HCC, and long-term BG control should be considered in comprehensive cirrhosis care.

Predictive value of different glycemic control markers in total hip or knee arthroplasty: A prospective study.

OBJECTIVE: The optimal glycemic control marker before total hip or knee arthroplasty remains inconclusive. Hemoglobin A1c (HbA1c) is widely used, while fructosamine may be valuable for predicting periprosthetic joint infection (PJI). Fructosamine levels can be affected by serum albumin levels; albumin-corrected fructosamine (AlbF) can be calculated to overcome this issue. The objective of this study was to evaluate the predictive value of different markers for complications after primary total hip or knee arthroplasty. METHODS: This prospective cohort study included 304 patients (mean age: 65 years [range, 16-85), mean follow-up: 32 months (range, 12-49)] who underwent primary total hip or knee arthroplasty between 2018 and 2021. Of them, 156 patients had diabetes. Mean HbA1c was 6.5% (range, 4.8%-13%), fructosamine 244 µmol/L (range, 98-566 µmol/L), and AlbF 632 (range, 238-2308). Patients who did and did not have diabetes were matched 1 : 1. Hemoglobin A1c 7% and fructosamine 292 µmol/L were used as cutoff. Complications were documented. Glycemic markers were compared using logistic regression analyses, with a special focus on PJI. RESULTS: In the logistic regression analyses, HbA1c was strongly associated with total complications [adjusted odds ratio (OR): 3.61; 95% CI, 1.65-7.91, P = .001], while fructosamine was associated with PJI (adjusted OR: 13.68; 95% CI, 1.39-134.89, P = .025). Albumin-corrected fructosamine did not show any additional benefits. CONCLUSION: Preoperative assessment before total hip or knee arthroplasty must not focus on a single marker; HbA1c is a good predictor of total complications, while fructosamine is a better predictor of PJI. To the best of our knowledge, in its first orthopedic study, AlbF did not show any advantages. LEVEL OF EVIDENCE: Level II, Prognostic Study.

Impact of diabetes mellitus severity, treatment regimen and glycaemic control on atrial fibrillation prevalence in the Polish population aged ≥ 65.

Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF), but the mechanism(s) by which DM affects AF prevalence remains unclear. This study aims to evaluate the impact of diabetes mellitus severity (expressed as its known duration), antihyperglycemic treatment regimen and glycaemic control on AF prevalence. From the representative sample of 3014 participants (mean age 77.5, 49.1% female) from the cross-sectional NOMED-AF study, 881 participants (mean age 77.6 ± 0.25, 46.4% female) with concomitant DM were involved in the analysis. AF was screened using a telemonitoring vest for a mean of 21.9 ± 9.1 days. The mean DM duration was 12 ± 0.35 years, but no significant impact of DM timespan on AF prevalence was observed. No differences in the treatment pattern (oral medication vs insulin vs both oral + insulin) among the study population with and without AF were shown (p = 0.106). Metabolic control reflected by HbA1c levels showed no significant association with AF and silent AF prevalence (p = 0.635; p = 0.094). On multivariate analyses, age (Odds Ratio (OR) 1.35, 95%CI: 1.18-1.53, p < 0.001), p = 0.042), body mass index (BMI; OR 1.043, 95%CI: 1.01-1.08, p = 0.027) and LDL < 100 mg/dl (OR 0.64, 95%CI: 0.42-0.97, p = 0.037) were independent risk factors for AF prevalence, while age (OR 1.45, 95%CI: 1.20-1.75, p < 0.001), LDL < 100 mg/dl (OR 0.43, 95%CI 0.23-0.82, p = 0.011), use of statins (OR 0.51, 95%CI: 0.28-0.94, p = 0.031) and HbA1c ≤ 6.5 (OR 0.46, 95%CI: 0.25-0.85, p = 0.013) were associated with silent AF prevalence. Diabetes duration, diabetic treatment pattern or metabolic control per se did not significantly impact the prevalence of AF, including silent AF detected by prospective continuous monitoring. Independent predictors of AF were age, BMI and low LDL levels, with statins and HbA1c ≤ 6.5 being additional independent predictors for silent AF.Trial registration: NCT03243474.

Improved glycemic control after the use of flash glucose monitoring accompanied by improved treatment satisfaction in patients with non-insulin-treated type 2 diabetes: A post-hoc analysis of a randomized controlled trial.

AIMS: In our previously reported randomized controlled trial in patients with noninsulin-treated type 2 diabetes, the use of flash glucose monitoring (FGM) improved glycated hemoglobin (HbA1c), and the improvement was sustained after the cessation of glucose monitoring. In this post-hoc analysis, we examined data from our trial to identify the factors that influenced FGM efficacy. METHODS: We analyzed data for 48 of 49 participants of the FGM group who completed the trial to clarify the changes in various parameters and factors related to HbA1c improvement with the use of FGM. RESULTS: Analyses of the FGM data during the 12-week FGM provision period showed that the weekly mean blood glucose levels considerably decreased as early as at 1 week compared with the baseline values, and this decline continued for 12 weeks. An enhancement in the Diabetes Treatment Satisfaction Questionnaire regarding "willingness to continue the current treatment" score was significantly associated with the improvement in HbA1c at 12 (p = 0.009) and 24 weeks (p = 0.012). CONCLUSIONS: Glycemic control was improved soon after FGM initiation, accompanied by improved satisfaction with continuation of the current treatment in patients with noninsulin-treated type 2 diabetes.

Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU.

BACKGROUND: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency. METHODS: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome. RESULTS: Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control. CONCLUSIONS: In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.).

Blood glucose control in the burn intensive care unit: A narrative review of literature.

Burn survivors undergoing complex glycemic derangements in the acute period after burn are at significantly increased risk of worse outcomes. Although most critical care investigations recommend intensive glycemic control to prevent morbidity and mortality, conflicting recommendations exist. To date, no literature review has studied outcomes associated with intensive glucose control in the burn intensive care unit (ICU) population. This review addresses this gap to improve practice guidelines and support further research regarding glycemic control. This is a narrative review of literature utilizing PubMed for articles published at any time. Inclusion criteria were English studies describing glucose management in ICU adult burn patients. Studies involving pediatric patients, non-human subjects, care non-ICU care, case reports, editorials, and position pieces were excluded. Our literature search identified 2154 articles. Full text review of 61 articles identified eight meeting inclusion criteria. Two studies reported mortality benefit of intensive glucose control ( mg/dL) compared to controls ( mg/dL), while two studies showed no mortality differences. Three studies reported reduced infectious complications such as pneumonia, urinary tract infection, sepsis, and bacteremia. A majority of the studies (6/8) reported higher risk for hypoglycemia with tight glucose control, but few reported instances of adverse sequela associated with hypoglycemia. Intensive glucose control may provide benefit to burn patients, but complications associated with hypoglycemia must be considered. This review recommends an individualized patient-centered approach factoring comorbidities, burn injury characteristics, and risk factors when determining whether to employ intensive glucose control.

Prevalence of Hearing Loss in Type 2 Diabetes Mellitus and Its Association with Severity of Diabetic Neuropathy and Glycemic Control.

OBJECTIVES: This study assessed the prevalence of hearing loss (HL) in patients with type 2 diabetes mellitus (T2DM) and its relationship with the presence and severity of diabetic neuropathy. MATERIALS AND METHODS: Patients between the ages of 30 and 60 years (both ages inclusive) with T2DM were recruited and divided into three groups. Group I included patients without neuropathy. Group II had patients with mild neuropathy. Group III had patients with moderate and severe neuropathy. After informed consent hearing threshold was assessed using pure tone audiometry (PTA). RESULTS: Of the 200 patients recruited, the prevalence of HL was overall 81%. The prevalence was 66.7% in group I, 80.9% in group II, and 87.6% in group III (p = 0.009). Among patients with moderate to severe neuropathy (group III), 33.3% had clinically significant HL (CSHL) (p = 0.015). Age, gender, presence of neuropathy, and severity of neuropathy were associated with an increased risk of developing HL. CONCLUSION: Among patients with diabetes, age, nephropathy, and neuropathy were associated with HL. The severity of HL worsened with the worsening severity of neuropathy and increase in glycated hemoglobin (Hba1c) levels. Patients with moderate to severe neuropathy might benefit from screening for HL.

Glycemic control and outcome after carotid intervention in patients with T2D: A Swedish nationwide cohort study.

AIMS: To investigate the association between glycemic control and outcome in people with type 2 diabetes (T2D) after carotid intervention due to carotid stenosis. METHODS: Observational nationwide population-based cohort study using inverse probability treatment weighting (IPTW) and Cox regressions with covariates, that is, 4 stepwise models, investigating the relationship between terciles of glycated hemoglobin (HbA1c) levels and stroke or death. RESULTS: 1115 subjects with T2D undergoing carotid intervention were included during Jan 1st 2009 to Dec 31st 2015. Divided into terciles, with a mean HbA1c level of 44 (tercile 1), 53 (tercile 2), and 72 (tercile 3) mmol/mol. By using IPTW and Cox regression, each model was stepwise introduced for the investigating of relative risks, that is, hazard ratios (HRs) with associated 95% confidence intervals (CI). There was a significant increased risk for stroke or death, in every model observed for tercile 3, compared to tercile 1: HR for model 4: 1.35 (95% CI 1.02-1.78). No difference for stroke or death within 30 days was observed between the groups. CONCLUSION: Poor glycemic control in people with T2D after carotid intervention is associated with an increased long-term risk for stroke or death.

Influence of Gestational Diabetes Mellitus on Diabetes Risk and Glycemic Control in a Retrospective Population-Based Cohort.

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.

Intermittent closed-loop blood glucose control for people with type 1 diabetes on multiple daily injections.

BACKGROUND AND OBJECTIVES: Recent advances in Automated Insulin Delivery systems have been shown to dramatically improve glycaemic control and reduce the risk of hypoglycemia in people with type 1 diabetes. However, they are complex systems that require specific training and are not affordable for most. Attempts to reduce the gap with closed-loop therapies using advanced dosing advisors have so far failed, mainly because they require too much human intervention. With the advent of smart insulin pens, one of the main constraints (having reliable bolus and meal information) disappears and new strategies can be employed. This is our starting hypothesis, which we have validated in a very demanding simulator. In this paper, we propose an intermittent closed-loop control system specifically intended for multiple daily injection therapy to bring the benefits of artificial pancreas to the application of multiple daily injections. METHODS: The proposed control algorithm is based on model predictive control and integrates two patient-driven control actions. Correction insulin boluses are automatically computed and recommended to the patient to minimize the duration of hyperglycemia. Rescue carbohydrates are also triggered to avoid hypoglycemia episodes. The algorithm can adapt to different patient lifestyles with customizable triggering conditions, closing the gap between practicality and performance. The proposed algorithm is compared with conventional open-loop therapy, and its superiority is demonstrated through extensive in silico evaluations using realistic cohorts and scenarios. The evaluations were conducted in a cohort of 47 virtual patients. We also provide detailed explanations of the implementation, imposed constraints, triggering conditions, cost functions, and penalties for the algorithm. RESULTS: The in-silico outcomes combining the proposed closed-loop strategy with slow-acting insulin analog injections at 09:00 h resulted in percentages of time in range (TIR) (70-180 mg/dL) of 69.5%, 70.6%, and 70.4% for glargine-100, glargine-300, and degludec-100, respectively, and injections at 20:00 h resulted in percentages of TIR of 70.5%, 70.3%, and 71.6%, respectively. In all the cases, the percentages of TIR were considerably higher than those obtained from the open-loop strategy, being only 50.7%, 53.9%, and 52.2% for daytime injection and 55.5%, 54.1%, and 56.9% for nighttime injection. Overall, the occurrence of hypoglycemia and hyperglycemia was notably reduced using our approach. CONCLUSIONS: Event-triggering model predictive control in the proposed algorithm is feasible and may meet clinical targets for people with type 1 diabetes.