Glucose Disposal Rate Research Articles

Manchester Intermittent and Daily diet Type 1 Diabetes App Study (MIDDAS-Type 1): protocol for a randomised feasibility trial of an intermittent and continuous low-energy diet in patients with type 1 diabetes and overweight and obesity

IntroductionRising levels of overweight and obesity among people with type 1 diabetes (T1D) contribute to insulin resistance, dyslipidaemia, retinopathy, cardiometabolic complications and psychological morbidity. Continuous low-energy diets (CLED) providing approximately...

Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction

BackgroundObesity and insulin resistance are prevalent in heart failure with preserved ejection fraction (HFpEF) and are associated with adverse cardiovascular outcomes. Measuring insulin resistance is difficult outside of research settings, and its correlation to parameters of myocardial dysfunction and functional status is unknown. MethodsA total of 92 HFpEF patients with New York Heart Association class II to IV symptoms underwent clinical assessment, 2D echocardiography, and 6-min walk (6 MW) test. Insulin resistance was defined by estimated glucose disposal rate (eGDR) using the formula: eGDR = 19.02 − [0.22 × body mass index (BMI), kg/m2] − (3.26 × hypertension, presence) − (0.61 × glycated hemoglobin, %). Lower eGDR indicates increased insulin resistance (unfavorable). Myocardial structure and function were assessed by left ventricular (LV) mass, average E/e’ ratio, right ventricular systolic pressure, left atrial volume, LV ejection fraction, LV longitudinal strain (LVLS), and tricuspid annular plane systolic excursion. Associations between eGDR and adverse myocardial function were evaluated in unadjusted and multivariable-adjusted analyses using analysis of variance testing and multivariable linear regression. ResultsMean age (SD) was 65 (11) years, 64 % were women, and 95 % had hypertension. Mean (SD) BMI was 39 (9.6) kg/m2, glycated hemoglobin 6.7 (1.6) %, and eGDR 3.3 (2.6) mg × kg−1 min−1. Increased insulin resistance was associated with worse LVLS in a graded fashion [mean (SD) −13.8 % (4.9 %), −14.4 % (5.8 %), −17.5 % (4.4 %) for first, second, and third eGDR tertiles, respectively, p = 0.047]. This association persisted after multivariable adjustment, p = 0.040. There was also a significant association between worse insulin resistance and decreased 6 MW distance on univariate analysis, but not on multivariable adjusted analysis. ConclusionOur findings may inform treatment strategies focused on the use of tools to estimate insulin resistance and selection of insulin sensitizing drugs which may improve cardiac function and exercise capacity.

Heterogeneity in the effect of marked weight loss on metabolic function in women with obesity.

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.

1517-P: Interactive Calculator to Estimate Insulin Sensitivity (IS) in Type 1 Diabetes

Introduction: Euglycemic hyperinsulinemic clamps, although costly, time- and labor-intensive, are “gold standard” in measuring insulin sensitivity (IS). Several formulae to estimate IS in people with Type 1 diabetes (T1D) exist (DOI: 10.1007/978-3-030-81303-1_18-1), using various routine and research assays, and with wide ranging IS results. Aim: To develop a free online tool to estimate IS using different metrics and existent formulae and compare estimated IS with measured glucose disposal rate (GDR) from 104 clamp studies. Methods: We prepared an online tool for calculating IS using 17 formulae. Suitable formula(e) are suggested based on available (clinical and research) data. We also compare calculated IS with measured IS (GDR) from clamp studies in 104 adults with T1D (mean±SD) age 34±7 yrs, T1D duration 10±4 yrs, HbA1c 7.7±1.5%, 33 with microvascular complications). Logistic regression was used to infer probability of calculated IS being below GDR=4.45 mg/kg/min or above GDR=6.5 mg/kg/min, which represent respectively the median and 75th percentile of measured GDR values. Results: A calculator is available at www.bit.ly/estimated-GDR and an example result in the Figure 1. Estimated IS varied widely, but results interpretation is generally consistent. Conclusion: We developed an interactive tool to estimate IS in T1D for clinical and research use. Disclosure A.S.Januszewski: None. P.Niedzwiecki: None. N.Sachithanandan: None. G.M.Ward: None. D.N.O'neal: None. D.Zozulinska-ziolkiewicz: Advisory Panel; Abbott, Lilly, Lilly, Novo Nordisk, Medtronic, Speaker's Bureau; Abbott, Ascensia Diabetes Care, Novo Nordisk, Medtronic, Boehringer-Ingelheim, AstraZeneca. A.Uruska: Other Relationship; Lilly, Boehringer-Ingelheim, AstraZeneca, Ascensia Diabetes Care, Sanofi. A.Jenkins: Advisory Panel; Insulet Corporation, Board Member; Insulin for Life, Research Support; Abbott Diabetes, Medtronic, Hemsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), National Institutes of Health.

829-P: Outcomes with Finerenone in People with CKD and T2D by Baseline Insulin Resistance—A FIDELITY Subgroup Analysis

Introduction Insulin resistance (IR) is associated with increased risk of T2D, CV disease and CKD. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has shown cardiorenal benefits in people with CKD and T2D. We investigated if IR is associated with risk of cardiorenal outcomes and if IR modifies finerenone efficacy in the pooled FIDELITY dataset. Methods People with T2D and CKD (UACR ≥30-&amp;lt;300 mg/g + eGFR ≥25-≤90 mL/min/1.73 m2 or UACR ≥300-≤5000 mg/g + eGFR ≥25 mL/min/1.73 m2) and optimized RAS blockade were randomized to finerenone or placebo. Estimated glucose disposal rate (eGDR), an inverse marker of IR, was calculated by 21.158 + (-0.09 × waist circumference [cm]) + (-3.407 × presence of hypertension) + (-0.551 × HbA1c [%]). Risk of CV (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (time to kidney failure, sustained ≥57% eGFR decline, or renal death) composite outcomes, and safety, were assessed by eGDR. Results Median baseline eGDR was 4.1 mg/kg/min in 12,964 participants. Analysis by continuous baseline eGDR showed a significantly lower risk of CV events at 3.5 years with increasing eGDR (HR 0.88 [95% CI 0.86-0.91] p&amp;lt;0.01); whereas eGDR was not associated with kidney outcomes. Analyses by eGDR subgroups showed no significant heterogeneity for the effect of finerenone on CV (eGDR &amp;lt;median: HR 0.82 [95% CI 0.72-0.92]; eGDR ≥median: HR 0.91 [95% CI 0.78-1.06]; p-interaction=0.29) or kidney outcomes (eGDR &amp;lt;median: HR 0.85 [95% CI 0.70-1.04]; eGDR ≥median: HR 0.69 [95% CI 0.57-0.84]; p-interaction=0.18). Consistent strength and direction of the associations were observed across sensitivity analyses. Adverse events were similar across eGDR subgroups; hyperkalaemia events were higher with finerenone than placebo. Conclusions A higher risk of CV, but not kidney, outcomes was observed with greater IR in people with T2D and CKD. Finerenone efficacy and safety were not modified by baseline IR. Disclosure T.Ebert: Advisory Panel; Sanofi, Bayer Inc., Research Support; AstraZeneca, Speaker's Bureau; CME-Verlag, Santis, Fresenius Medical Care. K.Rohwedder: Employee; Bayer Inc., AstraZeneca. P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. S.Anker: Advisory Panel; AstraZeneca, Novartis AG, Consultant; Bayer Inc., Boehringer Ingelheim Pharma GmbH&amp;Co.KG, Vifor Pharma Management Ltd., Research Support; Abbott, Vifor Pharma Management Ltd. L.M.Ruilope: Advisory Panel; Bayer Inc. P.Fioretto: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Bayer Inc. V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. A.L.Birkenfeld: None. R.Lawatscheck: Employee; Bayer Inc. C.Scott: None.

717-P: Unmet Needs and Communication Preferences for mHealth Self-Management Solutions in People with Type 1 Diabetes and Insulin Resistance

Insulin resistance (IR) is prevalent within type 1 diabetes (T1D) and associated with increased morbidity and mortality. Mobile health (mHealth) applications are useful platforms for delivering health behaviour interventions, but technologies focusing on addressing IR in T1D are absent. The aim of this formative study was to identity salient unmet patient needs, communication preferences, and barriers for mHealth self-management solutions in people with T1D and IR. 70 adults with type 1 diabetes (male=57%; HbA1c 8.1±3.4%; 28±5years) completed an online survey evaluating skills gaps in self-management and priorities for diabetes mHealth apps. Survey responses were ranked using a 9-point scale and analysed using descriptive and inferential statistics. Qualitative write-in responses were subsequently coded and analysed using inductive thematic analysis. IR was assessed using estimated glucose disposal rate (eGDR). Among all respondents, 49% (n=34) identified glycemic control/variability as the principle unmet self-management need. Fewer than 5% (n=3) reported having no self-perceived skills gaps. 89% (n=62) identified paternalistic communication and weight stigmatization as barriers to mHealth use. Real-life/situational feedback for glucose control/variability was reported as the single largest facilitator of mHealth use (65%, n=46). Preferred communication strategies were empathy, concern, and compassion (81%, n=57), and informal, open, and direct (77%, n=54). Our results highlight that glucose control/variability is the principle unmet self-management need in T1D adults with IR. Several communication barriers negatively impact mHealth acceptability and efficacy in this group, particularly paternalistic and weight-stigmatizing language. mHealth solutions that target glycemic control/variability and are non-weight stigmatizing are urgently needed for people with T1D and IR. Disclosure A.R.Wilson: None. M.Farrar: None. M.D.Campbell: None.

Estimated Glucose Disposal Rate Predicts Renal Progression in Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

Insulin resistance is a feature of type 2 diabetes mellitus (T2DM). The estimated glucose disposal rate (eGDR), a validated marker for insulin resistance, is associated with complications of diabetes, but few studies have explored the relationship between eGDR and renal outcomes in T2DM. This study investigated the value of eGDR in predicting renal progression in T2DM. A total of 956 T2DM patients with a baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 and 5 years of follow-up were enrolled. Primary outcomes were rapid eGFR decline, eGFR <60 mL/min/1.73 m2, and composite renal endpoint consisting of 50% eGFR decline, doubling of serum creatinine, or end-stage renal disease. A continuous scale with restricted cubic spline curves and a generalized linear model were applied to evaluate the associations between eGDR and primary outcomes. Rapid eGFR decline was experienced by 23.95% of patients, 21.97% with eGFR <60 mL/min/1.73 m2, and 12.13% with the composite renal endpoint. The eGDR showed a relationship with follow-up eGFR and percentage change in eGFR (P < .001). An eGDR <6.34 mg/kg/min was an independent risk factor for rapid eGFR decline, eGFR < 60 mL/min/1.73 m2, or the composite renal endpoint(P < .05). Compared with eGDR of 5.65∼6.91 mg/kg/min, eGDR levels >8.33 mg/kg/min decreased the risk of rapid eGFR decline by 75%, eGFR < 60 mL/min/1.73 m2 by 60%, and the composite renal endpoint by 61%. Subgroup analysis was performed by sex, age, and diabetes duration, which showed that eGDR was associated with primary outcomes. Lower eGDR is a predictive factor for renal deterioration in T2DM patients.

Metabolic Syndrome as a Factor of Impairment of Antioxidant Defense System in Youth with T1DM.

Research indicates that adolescents with type 1 diabetes mellitus (T1DM) may develop both metabolic syndrome (MetS) and oxidative stress. The purpose of this study was to test the hypothesis that MetS could potentially affect antioxidant defense parameters. The study recruited adolescents aged 10-17 who had been diagnosed with T1DM, and divided them into two groups: "MetS+" (n = 22), who had been diagnosed with MetS, and "MetS-" (n = 81), who did not have metabolic syndrome. A control group consisting of 60 healthy peers without T1DM was included for comparison. The study examined cardiovascular parameters, such as complete lipid profile and estimated glucose disposal rate (eGDR), as well as markers of antioxidant defense. The results revealed a statistically significant difference between the MetS+ and the MetS- group in terms of total antioxidant status (TAS) (1.186 mmol/L vs. 1.330 mmol/L), and oxidative stress index (OSI) levels (0.666 vs. 0.533). Furthermore, multivariate correspondence analysis identified individuals with HbA1c < 8%; eGDR > 8 mg/kg/min, using either flash or continuous glucose monitoring systems, as MetS- patients. The study also found that eGDR (AUC 0.85, p < 0.001), OSI and HbA1c (AUC 0.71, p < 0.001) markers may be useful for diagnosing the onset of MetS in adolescents with T1DM.

Relationship between visceral adiposity index and glycemic and metabolic control in children and adolescents with type 1 diabetes mellitus.

Visceral Adiposity Index (VAI) is a gender-specific mathematical model based on BMI, waist circumference (WC) and lipid parameters. No study has yet examined the relationship between this index and the glycemic and metabolic parameters in children and adolescents with Type 1 Diabetes Mellitus (DM). The current study aims at examining the relationship between glycemic and metabolic control and VAI in children and adolescents with Type 1 DM. A total of 150 children and adolescents aged 6-18years with Type 1 DM were included in this study. Anthropometric, glycemic and metabolic parameters were examined. VAI was calculated using gender-specific formulas. Statistical analysis was done by SPSS version 23. The average age of the participants was 12.2 ± 3.1years (females 53.0%). The females had higher rates of VAI, microalbuminuria and hypertension than males. Participants of both gender with higher VAI quartiles had higher anthropometric measurements, insulin usage, low-density lipoprotein cholesterol (LDL-C), triglycerides and urine microalbumin and had poor glycemic control. Sex adjusted correlation analysis showed that VAI is negatively correlated with estimated glucose disposal rate (eGDR), and positively correlated with insulin dose, LDL-C, triglycerides, glycosylated hemoglobin (HbA1c) and microalbuminuria. The present paper is the first study examining the relationship between Type 1 DM and VAI. Higher VAI values in children and adolescents with type 1 DM may adversely affect glycemic and metabolic control. VAI can be a useful and new method in evaluating glycemic and metabolic control in children and adolescents with Type 1 DM.

Utility of apolipoprotein ratio in predicting metabolic risk and microvascular complications in Indian children and young adults with type 1 diabetes mellitus.

To assess the relationship of apolipoproteins with glycemic control and insulin resistance (IR) in Indian children and youth with type-1 diabetes (T1D) and to assess its utility in predicting metabolic risk (MR) and microvascular complications in these subjects. This cross-sectional study included 152 participants aged 6-23 years with T1D. Demographic, anthropometric, clinical, biochemical and body composition data were obtained using standard protocols. IR was calculated using estimated glucose disposal rate (eGDR) and metabolic syndrome (MS) was diagnosed using the international diabetes federation consensus definition 2017. Apolipoprotein ratio in subjects with T1D had negative and positive correlation with eGDR and HbA1c respectively. Positive correlation of Apolipoproten B and apolipoprotein ratio with urinary albumin creatinine ratio is noted. The ratio had area under curve of 0.766 and 0.737 to predict MR and microvascular complications respectively. The ratio cut-off of 0.536 yielded 77.1 % sensitivity and 61 % specificity to predict MR. On adding the apolipoprotein ratio as a predictor to the regression model developed to predict MR, the R2 and accuracy improved. The apolipoprotein ratio had significant correlation with IR, microalbuminuria and glycaemic control. The ratio also predicts risk of development of microvascular complications and maybe used to predict MR in subjects with T1D.

Identification and phenotypic characterization of patients with LADA in a population of southeast Mexico

Latent autoimmune diabetes in adults (LADA) has clinical and metabolic features of type 1 and type 2 diabetes. LADA does not have specific features for its diagnosis apart from autoantibody detection; however, these tests are not affordable in clinical settings. In this cross-sectional study, we analyzed clinical criteria, metabolic control, pharmacological treatment, and diabetic complications in two groups of patients with diabetes -LADA and T2D- in order to identify specific characteristic of these clinical entities. Finally, we evaluated if the estimated glucose disposal rate (eGDR) and age at diagnosis of diabetes could be used as a diagnostic criterion for LADA. Demographic, biochemical, clinical and treatment were measured in 377 individuals with diabetes. The diagnostics of LADA were determined using Glutamic acid decarboxylase autoantibodies levels. Chi-square test or t-Student test were used to establish differences between groups. To identify factors associated with LADA, a logistic regression analysis was used. Finally, a ROC curve was plotted to assess the possible variables as diagnostic criteria for LADA. The 377 patients with diabetes were separated into 59 patients with LADA and 318 patients with T2D. Patients with LADA showed lower fasting glucose values, fewer diabetic complications, younger age at diagnosis of diabetes, higher insulin use, and higher eGDR in comparison to patients with T2D. Both groups had a mean BMI classified as overweight. The ROC evaluated the sensitivity and specificity, this analysis indicated that an age younger than 40.5 years and an eGDR value higher than 9.75 mg/kg/min correlated better with LADA. These parameters could be useful to identify patients suspected to have LADA at the first level of medical care in the population of southeastern Mexico and refer them to a second level of care.

Barriers to Exercise in Adults With Type 1 Diabetes and Insulin Resistance

ObjectiveOur aim in this study was to assess attitudes toward exercise and quality of life (QoL) in adults with type 1 diabetes (T1D) with and without insulin resistance (IR). MethodsWe pooled baseline pretreatment data from a subset of individuals with T1D from 2 randomized controlled trials. Estimated glucose disposal rate (eGDR), a validated surrogate marker of IR, was calculated using an established formula to classify individuals according to IR status with a cutpoint of <6 mg/kg/min for the determination of IR. Self-reported barriers to exercise were obtained using a validated questionnaire, the Barriers to Physical Activity in T1D (BAPAD-1). In addition, QoL was determined using the 36-item Short Form (SF-36) questionnaire. Differences between dichotomized variables were assessed using the independent t test, Mann–Whitney U test, or Fisher exact test. Linear regression was employed to explore the association of eGDR with BAPAD-1 and QoL scores, with sequential adjustment for potential confounders. ResultsOf the 85 individuals included in our study, 39 were classified as having IR. The mean BAPAD-1 total score was higher for individuals with IR (IR: 3.87±0.61; non-IR: 2.83±0.55; p<0.001). The highest exercise barrier scores for individuals with IR were risk of hypoglycemia (5.67±1.26) and risk of hyperglycemia (5.23±1.20), whereas the highest scoring exercise barrier scores for non-IR individuals were not diabetes-related, with low level of fitness (3.91±1.26) and physical health status, excluding diabetes (3.67±1.48), ranked highest. QoL scores were comparable between groups (p>0.05). ConclusionsRisk of hypoglycemia was the greatest barrier to exercise in individuals with T1D with IR, whereas non–diabetes-related barriers to exercise were more salient in individuals with T1D without IR.

High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals

Background and aimsHigh sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association. Methods and resultsIn a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using 23Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respectively. In obese individuals, insulin sensitivity negatively correlated with muscle (r = −0.45, p = 0.01) and skin sodium (r = −0.46, p = 0.01). In interaction analysis among obese individuals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction = 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction = 0.024 and 0.003 for muscle and skin Na+, respectively). In interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity was stronger with increasing levels of serum leptin (p-interaction = 0.01). ConclusionsHigher muscle and skin sodium are associated with insulin resistance in obese patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies.Clinicaltrials.gov registration: NCT02236520.

Insulin resistance is more frequent in type 1 diabetes patients with long disease duration.

To investigate the clinical status of insulin resistance (IR) and its correlation with disease duration in patients with type 1 diabetes (T1D). Cross-sectional data from a T1D cohort were obtained (n=923). IR-related metabolic disorders including hypertension, obesity, and dyslipidemia were used as outcome variables to explore the cut-off point for estimated glucose disposal rate (eGDR) by restricted cubic spline (RCS) curve. Regression models were used for multivariate analysis of the clinical factors associated with IR. The correlation between the status of IR and diabetes duration was depicted with the RCS curve. IR-related metabolic disorders were observed in 39.4% of patients, with 9.1% meeting the criteria for metabolic syndrome. Specifically, patients with ≥10years of T1D were more likely to have IR-related metabolic disorders (54.7% vs. 36.9%, p<0.05). The presence of IR, defined as an eGDR ≤9.0mg/kg/min, was observed in 42.2% of patients. Patients with IR had a longer diabetes duration (3.5 vs. 2.7, years, p=0.003) and higher insulin dose (0.5 vs. 0.4, units per kg per day, p<0.001). Moreover, the presence of IR showed a gradual increase during 10years' disease duration and further analysis showed that diabetes duration ≥10years was a key element behind the development of IR and IR-related metabolic disorders. The status of IR is common in T1D patients, especially in those with ≥10years of disease duration. Therapies targeting balancing glycaemic control and IR are needed to decrease the future risk of cardiovascular diseases in T1D. ClinicalTrials.gov NCT03610984 (cohort study of patients with type 1 diabetes).

Insulin resistance in patients with cancer: a systematic review and meta-analysis

Background Insulin resistance is a critical cause of metabolic dysfunctions. Metabolic dysfunction is common in patients with cancer and is associated with higher cancer recurrence rates and reduced overall survival. Yet, insulin resistance is rarely considered in the clinic and thus it is uncertain how frequently this condition occurs in patients with cancer. Methods To address this knowledge gap, we performed a systematic review and a meta-analysis guided by the Preferred Items for Systematic Review and Meta-Analyses (PRISMA) statement. We included studies assessing insulin resistance in patients with various cancer diagnoses, using the gold-standard hyperinsulinemic–euglycemic clamp method. Studies eligible for inclusion were as follows: (1) included cancer patients older than 18 years of age; (2) included an age-matched control group consisting of individuals without cancer or other types of neoplasms; (3) measured insulin sensitivity using the hyperinsulinemic–euglycemic clamp method. We searched the databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for articles published from database inception through March 2023 with no language restriction, supplemented by backward and forward citation searching. Bias was assessed using funnel plot. Findings Fifteen studies satisfied the criteria. The mean insulin-stimulated rate of glucose disposal (Rd) was 7.5 mg/kg/min in control subjects (n = 154), and 4.7 mg/kg/min in patients with a cancer diagnosis (n = 187). Thus, the Rd mean difference was −2.61 mg/kg/min [95% confidence interval, −3.04; −2.19], p<.01). Heterogeneity among the included studies was insignificant (p=.24). Interpretation These findings suggest that patients with a cancer diagnosis are markedly insulin resistant. As metabolic dysfunction in patients with cancer associates with increased recurrence and reduced overall survival, future studies should address if ameliorating insulin resistance in this population can improve these outcomes thereby improving patient care. Key points Metabolic dysfunction increases cancer recurrence rates and reduces survival for patients with cancer. Insulin resistance is a critical cause of metabolic dysfunctions. To date, no comprehensive compilation of research investigating insulin resistance in cancer patients has been produced. In this meta-analysis, we found that patients with various cancers were markedly insulin-resistant.

Estimated glucose disposal rate (eGDR) in rural Bangladeshi population and its correlation with cardiometabolic risks

Background and objectives: For decades type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are increasingly gaining importance as an underlying mechanism for increased risk of cardiovascular diseases (CVD). IR is related to various cardiometabolic adverse effects. Hyperinsulinemic-euglycemic clamp technique, the gold standard method for measuring IR, is an invasive and complex procedure. Estimation of glucose disposal rate (eGDR) is an easy alternative tool for measuring IR. There is no known study on eGDR level in Bangladeshi native population. Therefore, this study was undertaken to determine the eGDR values in a healthy working rural Bangladeshi population. Materials and methods: Six villages were selected purposively as the study sites. All healthy working people aged ≥20 years in selected rural community were considered eligible. Those who consented to participate in the study were enrolled. Investigations included a) interviewing for social and clinical history, b) anthropometry and measurement of blood pressure and d) estimation of HbA1c and biochemical indices. The eGDR (mg/kg/min) was calculated using formula: eGDR = 21.158 − (0.09 * WC) − (3.407 * HT) − (0.551 * HbA1c); where WC = waist circumference in cm, HT = hypertension (yes = 1/no = 0), and HbA1c = HbA1c (%). Results: A total of 93 (m/w = 29/64) participants were enrolled in the study. The prevalence rates of hypertension, diabetes and metabolic syndrome (MSyn) were 34%, 31.1% and 16.1%, respectively. The mean eGDR value was 9.9 (±0.149; 95% CI: 9.62–10.2) mg/kg/min. Most of the values of biophysical characteristics were normal. The comparison between participants with and without MSyn showed that the former had significantly lower eGDR (9.05±1.24 vs.10.10±1.37, p&lt;0.01). Inverse correlations of eGDR with the obesity, glycemia and lipidemia (weight, waist, FBG, T-chol, and TG) were significant. Declining eGDR were significant with rising WHR, WHtR, TG/HDLR and T-chol/HDLR (for all, p&lt;0.05). Conclusions: The study revealed the level of eGDR in a healthy working people of a rural community of Bangladesh. Moreover, eGDR was found to decrease significantly with the increasing cardiometabolic risks. The study revealed a higher prevalence of hypertension, diabetes and metabolic syndrome in apparently healthy working people highlighting susceptibility of Bangladeshi natives to non-communicable diseases. IMC J Med Sci. 2023; 17(2):005. DOI: https://doi.org/10.55010/imcjms.17.015 *Correspondence: M Abu Sayeed, Department of Community Medicine, Ibrahim Medical College, 1/A, Ibrahim Sarani, Segunbagicha, Dhaka 1000, Bangladesh. Email: sayeed1950@gmail.com

Estimated glucose disposal rate is associated with retinopathy and kidney disease in young people with type 1 diabetes: a nationwide observational study

AimsThe aim of this study was to investigate the association between estimated glucose disposal rate (eGDR), a proxy for insulin resistance, and retinopathy or kidney disease, i.e. micro-, or macroalbuminuria, in young individuals with type 1 diabetes (T1D).Material and MethodsUsing data from the Swedish pediatric registry for diabetes (SweDiabKids) and the registry for adults (NDR), all individuals with T1D with a duration of diabetes of less than 10 years between 1998 and 2017 were included. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) for two cohorts: retinopathy cohort or kidney disease cohort, stratified by eGDR categories: < 4, 4 to 5.99, 6 to 7.99, and ≥ 8 mg/kg/min (reference).ResultsA total of 22 146 (10 289 retinopathy cohort, and 11 857 kidney disease cohort with an overlapping of 9575) children and adults with T1D (median age 21 years, female 42% and diabetes duration of 6 and 7 years, respectively for the cohorts) were studied. During a median follow-up of 4.8 years (IQR 2.6–7.7) there were 5040 (24.7%), 1909 (48.1%), 504 (52.3%) and 179 (57.6%) events for retinopathy in individuals with an eGDR ≥ 8, 7.99 to 6, 5.99 to 4, and < 4 mg/kg/min, respectively. Corresponding numbers for kidney disease was 1321 (6.5%), 526 (13.3%), 255 (26.8%) and 145 (46.6%). After multiple adjustments for different covariates, individuals with an eGDR 7.99 to 6, 5.99 to 4 and < 4 mg/kg/min, had an increased risk of retinopathy compared to those with an eGDR ≥ 8 mg/kg/min (adjusted HRs, 95% CIs) 1.29 (1.20 to 1.40); 1.50 (1.31 to 1.71) and 1.74 (1.41 to 2.14). Corresponding numbers for kidney disease was (adjusted HRs, 95% CIs) 1.30 (1.11 to 1.52); 1.58 (1.25 to 1.99) and 1.33 (0.95 to 1.86), respectively.ConclusionseGDR, a proxy for insulin resistance, is associated with retinopathy and kidney disease in young adults with T1D. The risk of retinopathy increased with lower eGDR. The risk of kidney disease also increased with lower eGDR; however results show no association between the lowest eGDR and kidney disease. eGDR can be helpful to identify young T1D individuals at risk.

Relationship Between Estimated Glucose Disposal Rate and Type 2 Diabetic Retinopathy.

To investigate the association between diabetic retinopathy (DR), DR intensity, and estimated glucose disposal rate (eGDR) in individuals with type2diabetes mellitus (T2DM). This study comprised 1762 T2DM patients who were admitted between January and December, 2021. Overall, the DR was identified in 430 patients. Based on the eGDR, the participants were divided into four study groups. One-way analysis of variance was used to compare the groups. The correlations between eGDR and DR risk, eGDR, and DR severity were analyzed using regression analysis. Furthermore, these relationships were analyzed in different sex groups. Patients with T2DM had a 19.75% (348/1762) DR detection rate, whereas those with DR had a 22.41% (78/348) proliferative DR detection rate. The DR group had substantially reducedlevels of eGDR compared with the non-DR group. Multivariate logistic regression analysis demonstrated that reduced eGDR was an independent risk factor for DR, after adjusting forconfounding variables. eGDR correlated significantly with proliferative DR in women but not in men. In Chinese individuals with T2DM, lower eGDR was independently associated with a higher risk of DR.

Insulin resistance and hepatic steatosis in type 1 diabetes mellitus and their association with diabetic chronic complications.

The aim of this study was to evaluate insulin resistance and hepatic steatosis and their association with diabetes duration, control and chronic complications in patients with type 1 diabetes. We studied medical records of 181 consecutive hospitalized adult patients with type 1 diabetes. Estimated glucose disposal rate (eGDR), Insulin Sensitivity Score (ISS), Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) were calculated. Patients in the 1st tertile of eGDR (<4.1 mg/kg-1-min-1) and ISS (<4.8) had higher prevalence of ischemic cardiovascular disease (ICVD) (P<0.001), hepatic steatosis, higher gamma glutamyl transpeptidase, HSI, FLI compared with participants from the 2nd and 3rd tertile of eGDR and ISS. Compared with those without steatosis, patients with ultrasound-diagnosed steatosis (30.5%) had a lower ISS (4.4±1.9 vs. 6.3±2.4, P<0.001), eGDR (4.5±3.0 vs. 5.8±2.7, P=0.01), higher FLI (72.5±25.1 vs. 51.0±27.2, P<0.001), HSI (37.5±6.1 vs. 35.2±4.7, P=0.03) and prevalence of ICVD (71.7 vs. 45.7%, P=0.004) and retinopathy (69.6 vs. 52.4%, P=0.03). Factors independently associated with hepatic steatosis were only ICVD (OR=2.584, P=0.029), ISS (OR 0.148, P<0.001), aspartate aminotransferase (OR=1.025, P=0.038) and male gender (OR=2.726, P=0.016). Insulin resistance and hepatic steatosis are common in type 1 diabetes and have a significant association with ICVD, independently of diabetes duration, control and insulin doses.

Impact of overweight and obesity on epicardial adipose tissue in children with type 1 diabetes.

Epicardial adipose tissue (EAT) thickness, a novel marker of cardiovascular disease (CVD), is increased in children with a healthy weight and type 1 diabetes (T1D). The prevalence of obesity has increased in children with T1D and may confer additional CVD risk. The purpose of this study was to examine EAT thickness in youth with and without T1D in the setting of overweight/obesity. Youth with overweight/obesity and T1D (n=38) or without T1D (n=34) between the ages of 6-18 years were included in this study. Echocardiogram using spectral and color flow Doppler was used to measure EAT and cardiac function. Waist circumference, blood pressure, and HbA1c, were used to calculate estimated glucose disposal rate (eGDR) to estimate insulin resistance in children with T1D. EAT thickness was not significantly different in youth with T1D compared to controls (2.10±0.67mm vs. 1.90±0.59mm, p=0.19). When groups were combined, EAT significantly correlated with age (r=0.449, p≤0.001), BMI (r=0.538, p≤0.001), waist circumference (r=0.552, p≤0.001), systolic BP (r=0.247, p=0.036), myocardial performance index (r=-0.287, p=0.015), ejection fraction (r=-0.442, p≤0.001), and cardiac output index (r=-0.306, p=0.009). In the group with T1D, diastolic BP (r=0.39, p=0.02) and eGDR (r=-0.48, p=0.002) correlated with EAT. EAT was associated with measures of adiposity and insulin resistance but does not differ by diabetes status among youth with overweight/obesity. These findings suggest that adiposity rather than glycemia is the main driver of EAT thickness among youth with T1D.