Increased Insulin Resistance Research Articles

Evaluation of cardiovascular risk factors in long-term survivors of adult- and childhood-onset brain tumours: a pilot study.

Survivors of childhood brain tumours (SCBT) and teenage and young adult cancer survivors have an adverse cardiovascular risk profile, which translates into an increased vascular mortality. Data on cardiovascular risk profiles in SCBT are limited, and furthermore, there are no data in adult-onset (AO) brain tumours. methods: Fasting lipids, glucose, insulin, 24-h blood pressure (BP), and body composition were measured in 36 brain tumour survivors (20 AO; 16 childhood-onset (CO)) and 36 age- and gender-matched controls. Compared with controls, patients had elevated total cholesterol (5.3 ± 1.1 vs 4.6 ± 1.0 mmol/L, P = 0.007), LDL-C (3.1 ± 0.8 vs 2.7 ± 0.9 mmol/L, P = 0.011), insulin (13.4 ± 13.1 vs 7.6 ± 3.3 miu/L, P = 0.014), and increased insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR) 2.90 ± 2.84 vs 1.66 ± 0.73, P = 0.016). Patients showed adverse body composition, with increased total body fat mass (FM) (24.0 ± 12.2 vs 15.7 ± 6.6 kg, P < 0.001) and truncal FM (13.0 ± 6.7 vs 8.2 ± 3.7 kg, P < 0.001). After stratification by timing of onset, CO survivors showed significantly increased LDL-C, insulin, and HOMA-IR compared with controls. Body composition was characterized by the increased total body and truncal FM. Truncal fat mass was increased by 84.1% compared with controls. AO survivors showed similar adverse cardiovascular risk profiles, with increased total cholesterol and HOMA-IR. Truncal FM was increased by 41.0% compared with matched controls (P = 0.029). No difference in mean 24-h BP was noted between patients and controls irrespective of the timing of cancer diagnosis. The phenotype of both CO and AO brain tumour survivors is characterized by an adverse metabolic profile and body composition, putatively placing long-term survivors at increased risk of vascular morbidity and mortality.

Excellent Blood Glucose Levels for 5 Years with Well Maintained Insulin Secretion by the Treatment Comprising a Once-Weekly Injection of Dulaglutide: GLP- 1RA Alone in a Patient with Type 2 Diabetes Mellitus

As a result of worsening of diabetes mellitus control to 9.1% hemoglobin A1c, a 61-year-old male Japanese patient began treatment with once-weekly subcutaneous injection of 0.75mg dulaglutide (a glucagon-like peptide-1 receptor agonist) alone. As a result, he demonstrated excellent diabetes mellitus control at an approximate 6.0% to 6.7% hemoglobin A1c level with this treatment alone for 5 years. The insulin secretion activity was well maintained as assessed by the HOMA-β score from 2.7 to 10.2. Interestingly, slight increase of insulin resistance, as assessed by the HOMA-IR was observed from 0.7 to 1.1. Taken together, the mild increase of insulin secretion may have been a positive reaction to keep good control of diabetes mellitus in response to slightly increased insulin resistance. Thus, a long-lasting favorable effect of treatment with dulaglutide alone, not only for diabetes mellitus control, but also for keeping insulin secretion, was demonstrated by this patient.

Ube4A maintains metabolic homeostasis and facilitates insulin signaling in vivo

ObjectiveDefining the regulators of cell metabolism and signaling is essential to design new therapeutic strategies in obesity and NAFLD/NASH. E3 ubiquitin ligases control diverse cellular functions by ubiquitination-mediated regulation of protein targets, and thus their functional aberration is associated with many diseases. The E3 ligase Ube4A has been implicated in human obesity, inflammation, and cancer. However, its in vivo function is unknown, and no animal models are available to study this novel protein. MethodsA whole-body Ube4A knockout (UKO) mouse model was generated, and various metabolic parameters were compared in chow- and high fat diet (HFD)-fed WT and UKO mice, and in their liver, adipose tissue, and serum. Lipidomics and RNA-Seq studies were performed in the liver samples of HFD-fed WT and UKO mice. Proteomic studies were conducted to identify Ube4A's targets in metabolism. Furthermore, a mechanism by which Ube4A regulates metabolism was identified. ResultsAlthough the body weight and composition of young, chow-fed WT and UKO mice are similar, the knockouts exhibit mild hyperinsulinemia and insulin resistance. HFD feeding substantially augments obesity, hyperinsulinemia, and insulin resistance in both sexes of UKO mice. HFD-fed white and brown adipose tissue depots of UKO mice have increased insulin resistance and inflammation and reduced energy metabolism. Moreover, Ube4A deletion exacerbates hepatic steatosis, inflammation, and liver injury in HFD-fed mice with increased lipid uptake and lipogenesis in hepatocytes. Acute insulin treatment resulted in impaired activation of the insulin effector protein kinase Akt in liver and adipose tissue of chow-fed UKO mice. We identified the Akt activator protein APPL1 as a Ube4A interactor. The K63-linked ubiquitination (K63-Ub) of Akt and APPL1, known to facilitate insulin-induced Akt activation, is impaired in UKO mice. Furthermore, Ube4A K63-ubiquitinates Akt in vitro. ConclusionUbe4A is a novel regulator of obesity, insulin resistance, adipose tissue dysfunction and NAFLD, and preventing its downregulation may ameliorate these diseases.

Subclinical hypothyroidism increases insulin resistance in normoglycemic people.

To investigate the effect of simple subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM) combined with SCH on insulin resistance. A total of 622 people with newly diagnosed T2DM were selected as the study subjects, and 621 normoglycemic people were selected as control subjects. According to the diagnostic criteria of thyroid diseases, the subjects were divided into a normal thyroid function group and a subclinical hypothyroidism group. Both groups received a physical examination, and blood samples were collected. The measurement indexes included FPG, FINS, OGTT2hPG, OGTT2hINS, HbA1c, TC, TG, HDL-C, LDL-C, TSH, FT3 and FT4. HOMA-IR, HOMA-β, and TFQI (thyroid feedback quantile index) were calculated. There was no significant difference in age or sex distribution between the T2DM group and the normoglycemic group (P>0.05). The prevalence of thyroid dysfunction in the T2DM group was significantly higher than that in the normoglycemic group (16.39% vs. 11.27%, P<0.05), and among the different types of thyroid dysfunction, the prevalence of SCH was the highest at 14.95% (P<0.05). There was no significant difference in BMI, waist-hip ratio, blood lipid profile, HOMA-β, and HOMA-IR values between the T2DM with subclinical hypothyroidism group (T2DM+SCH+ group) and the normal thyroid function group (T2DM+SCH- group) (P>0.05). The BMI, waist-hip ratio and HOMA-IR values of the normoglycemic group with subclinical hypothyroidism (T2DM-SCH+ group) were significantly higher than those of the normoglycemic group with normal thyroid function (T2DM-SCH- group) (P<0.05), and there were no significant differences between the T2DM+SCH- and T2DM+SCH+ groups (P>0.05). HOMA-β values were significantly higher in the T2DM-SCH+ group than in the T2DM-SCH-, T2DM+SCH- and T2DM+SCH+ groups (P<0.05). As the TFQI value increased, the body weight, waist-hip ratio, diastolic blood pressure, FPG, OGTT2hPG and HbA1c values gradually increased in the T2DM group and normoglycemic group (P<0.05). HDL-C, FINS, OGTT2hINS and HOMA-β values gradually decreased (P<0.05). Subclinical hypothyroidism only increases insulin resistance in normoglycemic people. As the sensitivity of the central thyroid decreases, the risk of developing diabetes increases.

Role of Genetic Polymorphisms in the Efficacy and Adverse Effects of Metformin in the Treatment of Type 2 Diabetes Mellitus

Role of Genetic Polymorphisms in the Efficacy and Adverse Effects of Metformin in the Treatment of Type 2 Diabetes Mellitus

Assessment of Insulin Secretion and Insulin Resistance

Impaired insulin secretion and increased insulin resistance are major contributors to the pathogenesis of diabetes mellitus (DM). Because pancreatic β-cell function and insulin resistance play an important role in the prevention, diagnosis, treatment, and prognosis of DM, several methods for measuring them have been developed based on dynamic and static tests. Because dynamic tests are time consuming and labor intensive, they are not suitable for use in practice. Static tests are simple and less invasive but do not reflect the complex processes of glucose and insulin metabolism. To easily measure insulin secretion capacity, insulinogenic index calculated from oral glucose tolerance test or mixed meal tolerance test and HOMA-β (homeostasis model assessment for β-cell function) can be used. To assess insulin resistance, HOMA-IR (homeostasis model assessment for insulin resistance) can be used. To measure insulin secretion and insulin resistance more accurately, efficiently, and easily, standardized insulin assay should be establishment and new tests should be continuously developed.

A CORRELATIVE STUDY OF FASTING BLOOD SUGAR, BODY MASS INDEX AND DURATION OF DIABETES WITH FASTING C-PEPTIDE LEVEL IN TYPE 2 DIABETES MELLITUS PATIENTS

Background: Diabetes mellitus refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. It occurs either due to insulin deficiency or insulin resistance. It is an ongoing progressive disorder. The long term complications can be prevented by early screening of diabetes and initiating treatment. Progression of the disease is depicted in the form of worsening hyperglycemia, which may either be due to decreasing secretory activity of beta cells of pancreas or increasing insulin resistance, or in the form of progression of complications. The worldwide prevalence of diabetes mellitus has risen dramatically over the past two decades, from an estimated 30 million cases in 1985 to 415 million in 2017. Adding to this burden is the increasing incidence of type 2 diabetes mellitus. Hence, there is a need to understand the pathophysiology of diabetes, insulin secretion and insulin resistance and overcome them. One such way is to measure beta cell secretory activity. Measurement of C-peptide, which is secreted along with Insulin, provides a better index of endogenous insulin production and pancreatic beta cell function. Materials And Methods: It is a prospective interventional study done by simple random procedure, over a period of 18 months (1st March 2021 to 31st August 2022) with 200 cases. Results: Study reveals that there is no statistically significant difference of mean FBS with Quantile C-peptide levels. But there is statistically significant negative correlation between duration of diabetes and C-peptide levels in the study population (p&lt;0.05). As duration of diabetes increases, C-peptide value decreases. And, there was statistically highly significant positive correlation between BMI and C-peptide levels in the study population (p&lt;0.001). As BMI value increases, C-peptide level also increases. Conclusion: This study suggests that BMI and duration of diabetes are major factors in ß cell function in people with diabetes.

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.

1585-P: MAFLD in Obesity with Deteriorating Glucose Control

The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rising in parallel with increasing bodyweight and loss of glucose control, implicating a high risk of hepatic and extra-hepatic complications. This longitudinal observational study analysed several indicators for MAFLD in 240 overweight subjects (body mass index (BMI) &amp;gt; 28 kg/m²) at 2 visits within in average 16 months. Subjects were categorised according to their insulin sensitivity (HOMAIR) and diabetic status. Liver fat and liver stiffness were measured with sonographic elastography (FibroScan®), and by calculation of Fatty Liver Index (FLI), and NAFLD Fibrosis Score (NFS). Parameters indicative for liver steatosis, i.e., the controlled attenuation parameter (CAP) and the FLI, were significantly higher in the T2DM group compared to the normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) groups (p&amp;lt;0.05). FLI values and the HOMAIR significantly correlated with sonographic liver fat content (CAP) (r=0.53, p&amp;lt;0.0001; r=0.34, p&amp;lt;0.001, respectively). An inverse correlation was observed between serum adiponectin levels and CAP (r=-0.20; p&amp;lt;0.019) and adiponectin levels and FLI (r=-0.37; p&amp;lt;0.0001). Over 16 months, fasting insulin levels and HOMAIR score increased mainly driven by the group of obese subjects with T2DM. No significant change in liver fat or stiffness was observed that period. In subjects with a BMI ≥ 28kg/m², the prevalence of MAFLD increases in line with increasing insulin resistance and loss of glucose control. Despite some further deterioration in insulin sensitivity, liver fat content appeared relatively unchanged over 16 months. Disclosure T.Forst: Consultant; Pfizer Inc., Speaker's Bureau; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Inc., Cipla Inc., Daiichi Sankyo, Eli Lilly and Company, MSD Life Science Foundation, Novo Nordisk, Sanofi. I.Botz: None. M.Berse: None. S.K.Baumann: None. A.Schultz: None.

1321-P: Screening for Liver Fibrosis in Diabetes—Assessing the Performance of Current Recommendations in a Large Unselected Population

American Diabetes Association’s Standard of Care 2023 recommended screening patients with T2D for significant liver fibrosis with FIB-4 and transient elastography (TE). However, the evidence supporting this approach is controversial. The aim of this study was to assess the use of FIB-4, and its correlation with TE, in an unselected population of patients with diabetes. Adult patients from NHANES 2017-2020 with complete data on FIB-4 and TE were included. Diabetes was defined based on FPG, A1c or prior history. Patients with secondary causes of liver steatosis were excluded. NAFLD was defined as a controlled attenuation parameter ≥274 dB/m, while clinically significant and advanced liver fibrosis were defined as TE ≥9.6 and ≥12 kPa, respectively. Among 1193 patients with diabetes (Age: 61 ± 13; BMI: 32.6 ± 7.3 kg/m2; A1c: 7.4 ± 1.7%), the prevalence of NAFLD, clinically significant liver fibrosis, and advanced fibrosis were 68%, 15% and 8%, respectively. These were significantly higher than in patients without diabetes even after stratifying for BMI (all p&amp;lt;0.001). Liver fibrosis worsened with increasing insulin resistance (HOMA-IR), but were not associated with A1c levels. FIB-4 performed poorly to predict significant or advanced liver fibrosis in diabetes (AUC: 0.59 [0.54-0.64] and AUC: 0.63 [0.56-0.69], respectively). Moreover, it performed numerically worse than plasma AST alone (AUC: 0.63, p=0.10 and AUC: 0.68, p=0.10, respectively). Among patients with significant and advanced fibrosis based on TE, FIB-4 was &amp;lt;1.30 (suggested cut-off for screening) in 51% and 47% of patients (i.e., false negatives), suggesting a significant disagreement between these tests. Patients with diabetes are at high risk of liver disease, and therefore, screening for liver fibrosis is warranted. However, our results suggest that current screening strategies based on FIB-4 and TE may not be adequate, as they may miss a significant number of patients with advanced fibrosis. Disclosure F.Bril: None. M.Gray: Advisory Panel; Takeda Pharmaceutical Co., Ltd., Theratechnologies, Consultant; Novo Nordisk.

1508-P: ZnPP-Laden Nanoparticles Improve Glucose Homeostasis and Chronic Inflammation during Obesity

Type 2 diabetes mellitus (T2DM) characterized by insulin resistance has become a serious health threat. Chronic inflammation is believed to play a pivotal role in the development of T2DM. Previous study has shown that HO-1 plays an anti-inflammatory role, suggesting HO-1 inhibition could be an effective strategy to treat T2DM. However, application of HO-1 inhibitors is restricted due to their low solubility. In this study, we detected the role of HO-1 inhibitor, ZnPP, in regulating glucose homeostasis and inflammation during obesity. We encapsulated ZnPP with nanoparticles to increase its water solubility and delivered ZnPP-laden nanoparticles (Nano-ZnPP) to the obese mice. We found that inhibition of HO-1 by Nano-ZnPP significantly decreases adiposity, increases insulin resistance, and improves glucose tolerance in diet-induced obesity mice. Moreover, Nano-ZnPP treatment attenuated both local and systematical inflammatory levels during obesity. Mechanistically, Nano-ZnPP significantly attenuated glucagon, TNF, and fatty acid synthesis signaling pathway in liver. In white adipose tissue, oxidative phosphorylation signaling pathway was enhanced and inflammation signaling pathway was diminished by Nano-ZnPP. Our results showed that Nano-ZnPP has a better effect on improving glucose homeostasis and attenuating chronic inflammation, as compared to DMSO-dissolved ZnPP. These results indicate that ZnPP-laden nanoparticles could be a potential therapeutic agent to treat T2DM. Disclosure W.Yang: None. Y.Sun: None. S.Guo: None. M.Arora: None. H.Han: None. W.Jiang: None. D.Kim: None. W.Ai: None. Q.Pan: None. M.Kumar: None. W.Brashear: None. Funding National Institutes of Health (R01DK095118, R01DK120968, R01DK118334, R01AG064869)

Insulin Resistance Associated with Impaired Fasting Glycaemia in Anti-Retroviral Therapy Patients

Background: Insulin resistance was associated with type-2 diabetes mellitus regardless of HIV status. However, an association of insulin resistance in prediabetes with HIV-infected subjects undergoing anti-retroviral therapy (ART) has been reported in very few studies. Methods: Serum insulin and insulin resistance (HOMA-IR) were measured in ART patients with impaired fasting glycemia (IFG) and those with normal glucose tolerance (NGT) along with other biochemical parameters. Results: There was increased insulin resistance in the ART IFG group when compared to their ART NGT counterparts. There was a positive correlation of HOMA-IR with serum creatinine, triglycerides, and ALT levels. However, serum HDL showed a negative correlation with HOMA-IR. Conclusion: Present study showed that there is association of insulin resistance in IFG associated with HIV-infected subjects on ART. Hence, monitoring the insulin resistance in ART patients may help in early prevention of type 2 diabetes mellitus. Keywords: Human Immunodeficiency Virus, anti-retroviral therapy, impaired fasting glycemia, serum Insulin, HOMA-IR

#3781 INSULIN RESISTANCE IS ASSOCIATED WITH INCIDENT CHRONIC KIDNEY DISEASE IN POPULATION WITH NORMAL RENAL FUNCTION

Abstract Background and Aims Insulin resistance is prevalent in chronic kidney disease (CKD) and may accelerate its progression. This study aimed to investigate whether insulin resistance was associated with the development of incident CKD in a population with normal renal function. Method A total of 3,331 individuals with normal renal function from a community-based cohort formed the study population. We determined the relationship between insulin resistance indices and incident CKD using Cox proportional hazard model and Kaplan-Meier survival analysis. Results During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 414 (12.4%) participants. The high homeostasis model assessment-insulin resistance (HOMA-IR) level group had an increased risk of incident CKD (HR, 1.40; 95% CI, 1.13-1.74; p = 0.002) compared to the normal group after adjusting for confounding factors The risk of incident CKD also increased with lower quantitative insulin sensitivity check index (QUICKI) levels (HR, 0.62; 95% CI, 0.41-0.92; p = 0.018) and higher leptin-adiponectin ratio (LAR) levels (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Conclusion Higher insulin resistance indices were associated with the incidence of CKD. Our data suggests that increased insulin resistance may be involved in the development of incident CKD in individuals with normal renal function.

Menopause, lipids and cardiovascular risk

The greatest mortality burden for women in Europe is due to cardiovascular diseases (CVD), such as stroke and coronary heart disease. Women develop CVD on average 10 years later than men. Premenopausal women have a more favorable CVD risk factor profile characterized by lower cholesterol levels and blood pressure and a lower prevalence of diabetes. During the transition to menopause, women experience changes in phenotype and metabolism associated with an increased risk of CVD; including increase in abdominal fat, increase in low-density lipoprotein-cholesterol (LDLC) and systolic blood pressure, and increased insulin resistance. It has been a matter of debate whether menopause per se is a risk factor of CVD or if it is merely aging.

Role of microRNAs in Metabolic Diseases

MicroRNAs regulate a number of processes by controlling the gene expression at the post-transcriptional level. These small, non-coding RNA molecules play an important role in predisposition to metabolic diseases by maintaining glucose, lipid, and cholesterol metabolism. miRNAs are synthesized as double-stranded RNA, the two strands are separated to produce functional single-stranded miRNAs. The miRNAs are part of a large silencing complex called RNA-induced silencing complex (RISC). miRNAs regulate adipogenesis, the accumulation and droplet size of triacylglycerols, and PPAR gene expression. Dysfunction or higher expression of certain miRNAs (e.g., miR-222) silences the glucose transporter mRNAs resulting in a decrease in the surface receptors for glucose uptake hence predisposing to diabetes. miR-222 has also been reported to increase insulin resistance. Certain miRNAs are upregulated in obese mice as well as obese humans including miR143-145, miR29a, etc. The most important regulatory miRNA for lipid metabolism is miR-122, in addition, miR-33a and miR-33b exert their effect through sterol regulatory element binding proteins. The naturally occurring miRNAs can be silenced by chemically modified anti-miRNA oligonucleotides (AMOs) to alter their cellular expression levels. Another therapeutic oligonucleotide type called miRNA sponges compete with miRNAs for binding sites on the target mRNAs. The nuclease-resistant locked nucleic acids (LNAs) can also reduce the expression of certain miRNAs and have been shown to reduce cholesterol levels in mice. In conclusion, miRNAs appear to be faithful therapeutic targets for altering the gene expression of many target genes involved in lipid and fat metabolism in the future.

Correlation between type 2 diabetes mellitus and pancreatic steatosis

Objective. To study the features of endocrine function in non-alcoholic fatty disease of the pancreas in patients with chronic pancreatitis in remission.&#x0D; Materials and methods. There were examined 62 patients with chronic pancreatitis without exacerbation, who were admitted to the day hospital department of the City Clinical Hospital № 9 (Izhevsk). The data of laboratory and instrumental research methods, the features of the pancreatic endocrine function in patients with chronic pancreatitis, accompanied by fatty degeneration of the organ were analyzed.&#x0D; Results. Pancreatic steatosis was detected in 80.8 % of cases in patients with chronic pancreatitis in remission with metabolically complicated obesity. Violation of endocrine function was diagnosed in 19.3 % of cases. In the presence of insulin resistance, 6 (16.7 %) of the examined patients were diagnosed type 2 diabetes for the first time. At high insulin levels, 4 (6.5 %) patients had no changes in the indicators of fasting sugar.&#x0D; Conclusions. All patients with increased insulin resistance and metabolically complicated obesity require a comprehensive clinical and laboratory-instrumental study for the early detection of non-alcoholic fatty pancreatic disease. When establishing the signs of fatty degeneration of the pancreas, dispensary observation as well as prophylactic and therapeutic measures are necessary to prevent the development of type 2 diabetes mellitus.

Associations of estrogen therapy and non-estrogen anti-resorptive therapy with diabetes mellitus risk: A classical and Bayesian meta-analysis.

Anti-resorptive therapy (AT) increases insulin resistance and decrease insulin secretion through reduced undercarboxylated osteocalcin in mice. However, there are inconsistent findings regarding the impact of AT use on the risk of diabetes mellitus in humans. We examined the association between AT and incident diabetes mellitus using classical and Bayesian meta-analysis. We searched Pubmed, Medline, Embase, Web of Science, Cochrane, and Google Scholar for studies listed from database inception to 25 February 2022. Randomized controlled trials (RCTs) and cohort studies reporting associations of estrogen therapy (ET) and non-estrogen anti-resorptive therapy (NEAT) with incident diabetes mellitus were included. Two reviewers independently extracted research data such as ET and NEAT, diabetes mellitus, risk ratios (RRs), and 95% confidence intervals (CIs) for incident diabetes mellitus associated with ET and NEAT from individual studies. This meta-analysis included data from nineteen original studies, consisting of fourteen ET and five NEAT studies. ET was associated with reduced risk of diabetes mellitus in the classical meta-analysis (RR: 0.90; 95% CI: 0.81-0.99). Slightly stronger results were found in the meta-analysis of RCTs (RR: 0.83; 95% CI: 0.77-0.89). The probability that RR<1.0 was 95% in the overall analysis and 99% in RCTs under weakly informative prior. Although NEAT was associated with reduced risk of diabetes mellitus overall (RR: 0.80; 95% CI: 0.67-0.97), this was not found in the RCT meta-analysis (RR: 0.90; 95% CI: 0.75-1.10). Under weakly informative prior, the probabilities that NEAT reduces diabetes mellitus by >0% were 99%, and 73% in the overall and RCT meta-analysis, respectively. In conclusion, meta-analysis provided consistent evidence against the hypothesis that AT increases diabetes risk. ET may reduce the risk of diabetes mellitus. Whether NEAT reduces the risk of diabetes mellitus is uncertain and requires additional evidence from RCTs.

Screening for Late-Onset Gestational Diabetes: Are There Any Clinical Benefits?

(Abstracted from BJOG 2022;129(13):2176–2183 Gestational diabetes mellitus (GDM) affects approximately 1 in 16 women in the United Kingdom. Screening for GDM involves a 2-hour, 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks of gestation; a fasting value of plasma glucose of ≥5.6 mM or 2-hour plasma glucose level of ≥7.8 mM indicates GDM. However, as pregnancy progresses, levels of hormones, particularly placental lactogen, change and increase insulin resistance.

0757 Associations between Objective Sleep Health and Cardiovascular Health in Adolescents with Type 1 Diabetes

Abstract Introduction Adolescents with type 1 diabetes (T1D) are at risk for early-onset cardiovascular disease due to increased arterial stiffness, decreased endothelial function, and early-stage hypertension compared to healthy peers. Poor sleep health has been associated with greater glycemic variability, increased insulin resistance, and poorer cardiovascular health; however, the relationship between sleep and vascular health has not been studied in adolescents with T1D. The aim of this study was to evaluate associations between objectively measured sleep and cardiovascular health in this population. We hypothesized that better sleep health would correlate with better cardiovascular health. Methods Twenty-four adolescents with T1D completed the study during the academic year. Sleep was monitored for one week at home with actigraphy. Watchpat-assessed apnea hypopnea index (AHI) and vascular measures were obtained during an overnight study visit. EndoPAT estimated reactive hyperemia index (RHI) and augmentation index (AI). Dynapulse measured systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), heart rate (HR), pulse wave velocity (PWV), and brachial distensibility and resistance (BrachD, BrachR). Correlations between sleep and vascular measures were examined. Results Participants were an average age of 15.5±1.1 years (54.2% female, 83.3% White non-Hispanic, BMI 58.8 ±25.8%ile, HbA1c 7.5±1.2%). Average school night (weekday) sleep duration was 6.7±0.8 hours and average sleep efficiency (SE) was 82.8±6.9%. The majority (87.5%) of participants slept less than the clinical recommendation of 8-10 hours per night. Worse actigraphy-estimated SE was associated with higher DBP (r=-0.52, p=0.02; mean= 59.2±6.7mmHg) and MAP (r=-0.46, p=0.04; mean= 79.5±7.5mmHg). Higher AHI was associated with higher BrachR (r=0.81, p&amp;lt; 0.001). No significant associations were identified between sleep variables and RHI, AI, HR, PWV, or BrachD (all p&amp;gt;0.05). Conclusion Poorer SE and higher AHI were associated with poorer indicators of vascular health in adolescents with T1D, consistent with prior literature linking poorer sleep health with risk factors for hypertension in adults with T1D. Further research is needed to determine if improving sleep can improve cardiovascular comorbidities in adolescents with T1D. Support (if any) JDRF 2-SRA-2019-848-S-B; JDRF 2-SRA-2022-1144-M-B; Ludeman Center for Women’s Health Research COVID-19 Relief Supplemental Grant; Colorado Clinical &amp; Translational Research Center Maternal &amp; Child Health Pilot Award; CTSA UL1 TR002535

(206) Erectile Dysfunction and Hypogonadism in Men with Spina Bifida

Abstract Introduction Spina Bifida is a congenital neurological defect associated with genitourinary anomalies, requiring comprehensive urological care from pediatrics to adulthood. For men with spina bifida, a significant focus is on urinary tract surveillance to maintain continence, preserve kidney and bladder health, and optimize fertility and sexual function. While men with SB have an increasing interest in exploring their sexuality and sexual health, these concerns may be under-discussed and undertreated depending on their burden of illness. ED is associated with diminished body image and low self-confidence resulting in poor sexual health. Additionally, it creates barriers to maintaining intimate relationships. Current data tackling the prevalence of erectile dysfunction demonstrates variations in value, yet low quantifications of treatment for SB patients. Prior studies have shown a positive response to phosphodiesterase-5 (PDE5) inhibitor therapy (80%). Concurrently, the impact of hypogonadism on the SB is unknown. Hypogonadism is associated with increased insulin resistance in young males, hyperlipidemia, and other adverse vascular effects. These risk factors play a role in the vascular etiology of erectile dysfunction and can be a burden on sexual health. With a scarcity of men’s sexual health data focused on the adult SB male population, there is a need to illustrate the prevalence of ED and HG in men with SB while investigating treatment utilization. We hypothesize that men with SB will experience a higher rate of diagnosis of ED and HG compared to the general adult male population, and lower treatment utilization rates. Objective To calculate the estimated prevalence of erectile dysfunction and hypogonadism in adult men with spina bifida Methods This retrospective claims study used the MarketScan® databases from 2008 to 2017 to derive prevalence estimates for erectile dysfunction and hypogonadism in men with spina bifida, to compare these estimates to those in men without spina bifida, and to describe treatment patterns in this cohort. All men in aged 18 years and older with a diagnosis of SB were included for analysis. Patients with congenital hormonal disorders were excluded. To analyze treatment utilization, the National Drug Codes for pharmacotherapies for ED or HG and Current Procedural Terminology (CPT) codes for penile prosthesis were used. Results The estimated prevalence of erectile dysfunction and hypogonadism in men with spina bifida was 7.83% and 7.71%, respectively. Men with spina bifida in the sample exhibited high rates of smoking and metabolic comorbidities, but were diagnosed less frequently with erectile dysfunction when controlling for age and metabolic comorbidities than men without spina bifida. Most men with spina bifida and ED (66.6%) or hypogonadism (77.4%) do not receive treatment. However, a diagnosis of spina bifida did not appear to affect the likelihood of treatment for either condition on multivariate analysis. Conclusions Based on the results, claims data suggest that HG and ED are diagnosed less frequently than expected. While there are some limitations to the population being examined in this database, improving health care delivery of sexual health concerns during the surveillance of men with spina bifida will enhance their quality of life and optimize their sexual and metabolic function. Disclosure No