bluuebunny/crossref_metadata_2025 huggingface dataset:
LBODP049 Clinical And Biochemical Markers In Early Pregnancy For Prediction Of Gestational Diabetes Mellitus
Authors: Manglunia Ankit , Kanwar Jaya Bhanu , Mangaraj Swayamsidha , Swain Jayashree , Sahoo Abhay Kumar , Sahoo Manisha , Pati Tapasi , Mishra Sujata , Pattnaik Tapan , Das Sasmita , Ray Subhashree , Panigrahy Rajashree , Gochhait Samanyoya
Published: November 2022

Background

Early identification of Gestational Diabetes Mellitus (GDM) is pivotal to reduce feto-maternal complications associated with the disease. Current risk prediction models that are based on maternal clinical and biochemical parameters lack a strong predictive value.

Objective

To evaluate the early trimester maternal parameters for prediction of gestational diabetes mellitus.

Methods

In this prospective observational study, we screened 581 consecutive healthy women with singleton pregnancy for GDM during their first antenatal visit. After informed consent, fasting blood samples were collected and stored at -800C. GDM was diagnosed as per IADPSG criteria. During prospective follow up, total 55 patients developed GDM. A total of 110 age and BMI matched controls were recruited for comparison. In all women, we measured Oral Glucose Tolerance test (OGTT) with 75 gm anhydrous glucose, fasting insulin, HbA1c, hsCRP, uric acid and Lipid Profile. HOMA-IR, HOMA-β and QUICKI were used to evaluate insulin sensitivity and β-cell function.

Results

Significant higher proportion of subjects in GDM cohort had presence of acanthosis nigricans and positive family history of Type 2 Diabetes Mellitus in first degree relative. The GDM cohort had significantly higher median waist circumference, 2hr plasma glucose (2hr PPG), HbA1c, fasting insulin, HOMA-IR, uric acid and serum triglyceride levels. The receiver operating characteristic (ROC) curve were as follows: HbA1c - 0.74 (95%CI: 0.661–0.819), Fasting Insulin - 0.748 (95%CI: 0.671–0.826), high sensitivity C-Reactive Protein (hsCRP) - 0.689 (95%CI: 0.605 - 0.773) and Uric acid - 0.718 (95%CI: 0.635–0.802). Multiple regression analysis revealed HbA1c (OR 5.264; p=0. 007), 2hr PPG (OR 1. 026; p=0. 035), QUIKI (OR 1. 057; p=0. 016), uric acid (OR 1. 039; p=0. 013) and neutrophil: lymphocyte ratio (OR 1.545; p=1. 008) to be independently associated with GDM outcome with combined area under the curve (AUC) of 0.850, a sensitivity of 72.7% and a specificity of 87.3%.

Conclusions

Fasting Insulin, HbA1c, HOMA-IR, hsCRP and Uric acid levels are significantly increased in early pregnancy in individuals who develop GDM subsequently, compared to women who did not develop GDM. Hence utilization of these parameters may identify at risk group in routine clinical care and help in improving feto-maternal outcome.

Presentation: No date and time listed
LBODP050 Examination Of The Effectiveness Of Diabetic Nephropathy Treatment Targeting Chrebp Activity
Authors: Suzuki Susumu , Yokoyama Atsushi , Sugawara Akira , Okamoto Koji , Iwabuchi Yoshiharu
Published: November 2022

Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and is characterized by elevated urinary albumin to creatinine ratio (UACR) and serum creatinine, and decreased glomerular filtration rate. Anti hypertensive agents are used for DN treatment, however, the effects of these drugs are insufficient, and the establishment of more effective treatment methods is desired. Carbohydrate responsive element binding protein (ChREBP) is one of the factors reported to be involved in the onset and progression of DN (1). Furthermore, whole body ablation of ChREBP suggested that the progression of DN was suppressed in the rodent model (2). On the other hand, the effectiveness of pharmaceutical ChREBP suppression is unclear, thus, we performed administration experiment to DN model mice using ChREBP activity inhibitor and examined the effects of pharmaceutical ChREBP activity suppression on renal function of diabetic mice. First, we established high-throughput screening system capable of detecting ChREBP activity and performed screening of Tohoku university compound library. The result compound, D-532, was ChREBP activity specific inhibitor without cell toxicity. D-532 directly binds to DNA-binding domain of ChREBP, and inhibits the transcriptional activity. We next performed administration experiment using type I DN model mice. D-532 treatment group showed an improvement tendency of the low body weight compared with that of vehicle treatment group, while it had no effect on blood glucose level. About renal functions, both of UACR and serum creatinine were significantly lower in D-532 treatment group. Importantly, renal tissues such as glomeruli and renal tubules were preserved in D-532 treatment group compared with in vehicle treatment group. In vivo as well, D-532 suppressed ChREBP target genes mRNA expression, and RNA-seq analysis with mice renal cortex RNA at the end of D-532 administration experiment indicated that D-532 suppressed excessive oxidative stress through the ChREBP activation under diabetes. These results indicate that ChREBP suppression is effective on DN rodent model, and ChREBP activity inhibitor D-532 may have potential as a new treatment for DN in the future. Reference: (1) Suzuki et al., Endocr J. 2019 Mar 28;67(3): 335-345. (2) Zhang et al., Eur Rev Med Pharmacol Sci. 2017 Jan;21(1): 42-47.

Presentation: No date and time listed
LBODP052 A Novel Hnf4α Corepressor Irf2bp2: Its Role In The Gluconeogenic Gene Regulation Via Biochemically Labile Interaction
Authors: Kouketsu Takumi , Sugawara Akira , Yokoyama Atsushi , Igarashi Kazuhiko , Shima Hiroki , Sawatsubashi Shun
Published: November 2022

Hepatocyte nuclear factor 4α (HNF4α) has an essential role in controlling the expression of variety of genes involved in key metabolic pathways including gluconeogenesis in the liver. Though mechanistic and physiological significance of proliferator-activated receptor-gamma co-activator-1α (PGC-1α) for HNF4α-mediated transcriptional activation models for gluconeogenic genes is well characterized, transcriptional repression of HNF4α for those genes still remains to be examined. In this study, we applied novel proteomic techniques to evaluate the HNF4α interactome including biochemically labile binding proteins. From the experiment, we identified interferon regulatory factor 2 binding protein 2 (IRF2BP2) as a novel HNF4α corepressor, with which its interaction could not be detected by conventional immunoprecipitation. IRF2BP2 repressed transcriptional activity of HNF4α dependent on its E3 ubiquitin ligase activity. Deficiency of IRF2BP2 gene in HepG2 cells induced gluconeogenic genes comparable to the forskolin-treated wild type HepG2 cells. Together, these results suggest the role of IRF2BP2 as a novel class of nuclear receptor coregulator.

Presentation: No date and time listed
LBODP053 Significance Of Insulin Resistance And Development Of Type 2 Diabetes Mellitus
Authors: Rusalenka Mariya , Wisham Mohamed , Savasteeva Irina
Published: November 2022

A study was conducted via Clinical and laboratory parameters affecting the formation of insulin resistance(IR) and development of Type 2 Diabetes Mellitus. Data was collected in 140 patients below the age of 50, noted as overweight or obese. The results of the analysis demonstrated a significant direct correlation of the size of pre-peritoneal fat with fasting glycemia (rS=0.35, p<0. 05) and insulin level (rS=0.33, p<0. 05). The calculated risk of developing insulin resistance increased with increasing thickness of pre-peritoneal fat (b=1.46) (exp(b)=4.29 (1.54÷1.90), p=0. 005). Thus, with a size of pre-peritoneal fat of more than 1.5 cm, the relative risk (RR) of IR formation was 5.60 (2.48÷37.11). It should be noted that the linear size of subcutaneous fat did not significantly affect the development of IR. It was also noted that the risk of developing IR (exp (b) = 0.43 (0.91÷2.55), p = 0. 08)) had a steady upward trend with an increase in triglyceride levels, and amounted to 2.86 (1, 03÷7.91). At triglyceride levels above 1.75 mmol/l, the risk of developing IR was significant. When assessing the risk of developing type 2 diabetes mellitus, a steady upward trend was obtained with an increase in the thickness of pre-peritoneal fat (b=0.35; exp(b)=1.15 (0.82÷3.89; p<0.10) and the level of triglycerides (b=0.56; exp(b)=1.75(0.85 ÷3.83); p<0.10). In addition, the risk of developing type 2 diabetes significantly increased with age (b=0.11; exp(b)=1.12 (1. 01÷1.23), p<0. 03) and amounted to 1.52 (1 . 09÷15.39) for individuals over 37.74 years. Thus, individuals over 37.74 years with linear size of pre-peritoneal fat more than 1.5 cm and level of triglycerides above 1.75 mmol/l, has a significant risk for the developing insulin resistance, type 2 diabetes mellitus and can be recommended for targeted screening.

Presentation: No date and time listed
LBODP057 Association Between DKA And Live Abscess: Results From The National Inpatient Sample
Authors: Muammar Ahmad , Mahfouz Ratib
Published: November 2022

Background

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes, it can be the initial sign of unrecognized type 1 or type 2 diabetes; however, it occurs more frequently in patients with established disease, liver abscess is a life-threatening disease with an increasing rate of incidence in patient with uncontrolled diabetes, in this study we examined the association between DKA and liver abscess as formal evidence is limited, Methods This is a retrospective study using the National Inpatient Sample database from 2016 to 2019. A 20% probability sample was collected and subsequently weighted to ensure that the selected population was nationally representative. Using ICD-10-CM codes, all patients diagnosed with liver abscess were identified and considered the study population while excluding patients < 18 years old. Furthermore, baseline demographic data, comorbidities, in-hospital mortality, hospital charges, and hospital length of stay were extracted and compared based on the presence or absence of a concurrent diagnosis of DKA. Statistical analyses were done using t-test and Chi-squared analysis. Finally, multivariate analysis for the mortality odds ratio was calculated after adjusting for possible confounders.

Results

From a total sample of 140 million patients, 94,600 met the criteria for this analysis and were diagnosed with liver abscess. A 0.96% of this population had a concurrent diagnosis of DKA during the same admission. Patients with liver abscess with DKA were younger than patients without DKA (58 vs. 62.17, p-value 0. 0013). The male gender was predominant in both groups without significant difference between these two groups (58.81% vs. 58.33%, respectively, p-value 0.8962). The white race was dominant in both groups, but more prevalent in non DKA group (62% vs. 44%, respectively, p-value <0. 0001) The mortality rate was significantly higher in the liver abscess with DKA group (7.78% vs. 4.42%, p-value 0. 0289). Patients with DKA incurred higher costs of hospitalization ($213,792 vs. $128,730; P <0. 0001) and longer length of stay (14.5 days vs. 11 days; P 0. 001) than the non-DKA group. The multivariate analysis concluded that DKA carries an odds ratio (OR) of 1.74 (CI 95% 1-3. 03, p-value 0. 049) in patients with liver abscess. In addition to DKA, age greater than 65 years, non-white race and CHF were independently associated with higher mortality. HTN, smoking and obesity were associated with decreased risk of mortality (p-value <0. 001), Discussion: Our retrospective study identified association between DKA and liver abscess. DKA with liver abscess were associated with longer length of stay and higher mortality rate, treatment of the triggering factor is an essential component of the management of DKA, and liver abscess must be considered if sepsis source in DKA patient was unclear.

Presentation: No date and time listed
LBODP058 Evaluation Of Factors Associated With The Development Of Diabetic Retinopathy Based On A Case-control Study
Authors: Nathani Pratiksha Shankarlal , Kharat Pratik R , Wadde Satish , Kamdar Sheetal
Published: November 2022

Objectives

Diabetic Retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) and one of the leading causes of irreversible vision loss, particularly in the most productive age group. Several epidemiological studies have found that diabetics worldwide and in India have a high prevalence of DR. Risk estimation of various factors has been performed earlier however there is dearth of case control studies among the diabetics who developed DR and those who were unaffected. This study was planned to identify the sociodemographic, disease related and lifestyle related risk factors for development of DR among diabetics which could broadly be categorized under modifiable and non-modifiable factors. Findings from the study could help clinicians develop predictors and risk-based screening programs for early detection of DR.

Material & Methods

In this age and gender matched case control study, total 256 diabetes mellitus patients (96% type 2) were recruited equally in groups with diabetic retinopathy (DR) and without it. Diagnosis of DR was done by fundal examination as per the Early Treatment for Diabetic Retinopathy Study (ETDRS) standard. Adherence to diabetes medications was measured using four items in vernacular language adapted from the MMAS-4 (Morisky Medication Adherence Scale). Univariate and multivariate binary logistics regression was performed to find the independent risk (Odd's ratio) and modified Odd's ratio respectively.

Results

There was parity between cases and controls in terms of gender distribution and age. Mean age of DR and non-DR group was 63.7 ± 9.5 and 63.3 ± 10.4 years respectively. Independent risk factors for development of DR were presently on insulin therapy (OR=2.87,p=0. 0001), smoking (OR=1.92,p=0. 02), alcoholism(OR=2.62,p=0. 03), sedentary lifestyle(OR=2.72,p=0. 0008), non-adherence to diabetes medications (OR=14. 08,p=0. 0001), non-adherence to dietary advice (OR=4.41,p=0. 0001), presence of other microvascular complications (OR=3.79,p=0. 0001), dyslipidemia (OR=1.85,p=0. 02) and hypertension (OR=5.91,p=0. 0001). On multivariate logistics regression analysis, non-adherence to medicine (Exp(B)=7.89,p=0. 0001) and hypertension (Exp(B)=1.16,p=0. 0001) were predictors of development of DR . Type of occupation, education, socioeconomic status and type of diabetes did not have any correlation with development of DR among diabetics.

Conclusion

Diabetics under insulin therapy and with hypertension have a seriously increased risk of developing DR. Smoking, alcohol abuse, sedentary lifestyle, failure to take diabetes medications, and failure to follow dietary advice are independent risk factors for developing DR that can be modified through lifestyle changes in diabetics. DR should be monitored more closely in patients with other microvascular complications and dyslipidemia.

Presentation: No date and time listed
LBSUN151 The Impact Of The COVID-19 Pandemic On Diabetes & Weight Management
Authors: Hashmi Hiba Z , Malham Sarah Bou , Alameddine Hind
Published: November 2022

COVID-19 was declared a pandemic on 03/11/2020 by the WHO and the State of Minnesota issued a stay-at-home mandate on 03/27/2020. While individuals with diabetes mellitus (DM) and severe obesity were identified as more likely to be infected and at higher risk of complications from COVID-19, access to outpatient clinics was limited during this time, with a shift towards telemedicine. In June 2020, the WHO reported that in 49% of 155 surveyed countries, diabetes treatment was disrupted. However, the impact on diabetes care in the US was poorly characterized, particularly among underserved groups.

Aim

To study the impact of the pandemic and telemedicine on medical treatment of patients with DM at Hennepin County Medical Center (HCMC), a teaching hospital in Minneapolis, Minnesota serving a diverse inner-city population.

Methods

Retrospective cohort study design with 710 participants. We compared A1C and weight changes before and after the pandemic. The study group (n=344) included patients, 18 years of age or older, with DM Type 1 or Type 2 who presented for an HCMC diabetes clinic visit between 12/2019-02/2020 and a follow up visit between 6/2020 -10/2020. The control group (n=366) included patients with DM who presented for an HCMC diabetes clinic visit between 12/2018 - 02/2019 and a follow up visit between 6/2019 - 10/2019.

Results

There was a significantly lower A1C reduction in the cases as compared to the control group (-0.34 [CI -0.59, -0. 09] p value 0. 007), adjusted for inpatient admission, continuous glucose monitor use, diabetes type 1, insurance status, insulin use, GLP-1 agonist use, smoking status and hypertension. Weight reduction during the pandemic was lower as compared to the control but did not achieve statistical significance (-0.96 [CI -3. 02, 1. 09] p value 0.36). Telemedicine use among the study group resulted in an insignificant A1c reduction of -0.24 (p value 0.23). There was statistically significant weight gain of 0.42 among the group who used telemedicine, while nonusers had weight loss of -3.24 (p value 0. 04). Telemedicine users had higher insulin utilization (92.6% vs 83.3%, p value 0. 017) and lower self-pay and Medicaid enrollment (1.7% vs 5.9% and 33.8% vs 40.6% respectively, p value 0. 011) as compared to nonusers.

Conclusion

The COVID-19 pandemic led to a significant deterioration of glycemic control but had no effect on weight. Telemedicine use led to A1c reduction but did not reach statistical significance potentially due to the small sample size and short duration of follow up. Significant weight gain was observed in telemedicine users influenced by greater insulin use and insurance coverage as compared to weight loss amongst nonusers which may be attributed to socioeconomic barriers such as food scarcity among those without the means to access telemedicine.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN161 Relationship Of Shape Of Glucose OGTT Curves With Measures Of Cardiometabolic Health In African American Adolescents
Authors: Thaker Vidhu , Gidding Samuel , Keith Scott , Falkner Bonita
Published: November 2022

Background and Aims

Studies in youth and adults have shown that the shape of oral glucose tolerance test (OGTT) response curve may be a biomarker for insulin secretion and insulin sensitivity (IS). Individuals with monophasic (MPh) glucose response curve have lower IS and decreased beta-cell function compared to those with biphasic (BPh) pattern. The aim of this study was to assess if the shape of the glucose response curve of OGTT is associated with 2-D ECHO based indices of heart structure and function.

Methods

In a cross-sectional study, African American (AA) adolescents with and without obesity between the ages of 13-18 years were recruited to assess the relationship of blood pressure, obesity, and measures of cardiac health. Metabolic and inflammatory markers, 2-D ECHO and OGTT data were collected. The shape of the OGTT glucose response was classified based on a change from nadir to glucose-120 min of ≥ 4.5 mg/dL, and its association with cardiac health indices was calculated. R v.4.1.2 was used for analysis.

Results

Of the 276 individuals with available OGTT data (mean age 16.18 ± 1.70 years, 47.5% females), 39 (14.1%) had BPh curve. The individuals with BPh were lower in age (15.61 ± 1.68 vs 16.28 ± 1.68, p=0. 02), but similar in sex, BMI, BMIz and metabolic parameters. There was no difference in impaired glucose tolerance (27% [BPh] vs 15% [MPh], p=. 08). At 120 min, glucose (6.96 ± 0. 07 vs 6.31 ± 0. 07 mmol/L, p=. 05), and insulin (362.86 ± 13.69 vs 276.48 ± 13.61 uIU/mL, p=. 04) levels were higher in BPh. The glucose area under the curve (AUC) was lower in individuals with BPh (13.2 ± 1.23 vs 14.7 ± 1.16 mmol/L/hr, p <. 001) while the insulinogenic index (1.5 ± 3.79 vs 1.17 ± 2.74, p =. 03) and oral glucose disposition index were higher in both univariate analyses and after adjusting for age, sex and BMIz. The aortic root size was associated with the shape of the curve adjusting for age, sex and BMIz (p=. 03), but not ventricular or atrial mass, systolic or diastolic function.

Conclusions

There was lower proportion of individuals with BPh in this cohort of AA adolescents compared to published studies. Individuals with BPh had healthier beta-cell function indices. No significant relationship of the shape of the OGTT curve was seen with the metrics of heart structure or function at this age. Replication of results in adult cohort(s) is ongoing.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN211 The Importance Of Early Opportunities To Identify And Treat Prediabetes Or Even Change The Diagnostic Threshold For Diabetes
Authors: Schwartz Stanley S , Larson Sharon , Kjelstrom Stephanie , Beaupre Justin , Hartz William
Published: November 2022

Introduction

34.5% of US adults meet criteria for prediabetes, while 13% of US adults have diabetes. Diabetes increases the risk for many serious conditions. Recommendations for early screening and management of prediabetes have recently been updated.

Hypothesis

Diabetes has been associated with higher frequency use of emergency department (ED) services and inpatient admission, leading to higher costs associated with diabetes. We compare patients with diabetes or prediabetes for use of ED and inpatient care hypothesizing that prediabetic patients will have fewer visits to the ED and hospital. We additionally described differences in characteristics between these two groups to identify health inequities. Research Design: Data on people with Type 2 diabetes (DM) or prediabetes (PD) who seen in the ED March 2018 and December 2019 were extracted from an EHR. Descriptive statistics were compared between people with DM and PD using t-test or chi square tests. Linear and logistic regression analyses were conducted to compare DM to PD frequency of ED visits, high utilization of ED (3+ ED visits per year), admission to inpatient care. A p-value of 0. 05 or less is considered significant.

Major Results

PD patients were younger, and female compared to DM patients. Bivariate analysis show PD patients had fewer ED visits per year on average (1.2 v 1.5, (p<. 0001) compared to DM, and were less than half as likely to have 4+ visits per year (2. 0% v 5.4%, p <. 0001). Several comorbidities were examined, and all were significantly higher amongst DM patients. PD patients were more likely to have 0 or 1 comorbidities (69.6% vs. 55.3%, p <. 0001) compared to DM. In the linear regression analysis, PD was negatively associated with ED visits (-0.2 (-0.3, -0.1, p <. 0001) after adjusting for age, gender, race, and poverty, as well as multiple comorbidities. Similar findings emerged in a logistic regression analysis of high ED utilization, and linear regression analysis of inpatient admission.

Interpretation of Results and Conclusions

Our data suggest that adverse outcomes of hyperglycemia accrue prior to current HgA1c cut-off for the diagnosis of diabetes, deserve therapy, and even changing the threshold of diagnosis of diabetes to HgA1c= 5.7. Considering previously reported costs associated with ED visits (averaging $2200 per visit nationally) and inpatient care, early management of prediabetes represents an important health economic priority. Management of PD offers an opportunity to improve outcomes and reduce morbidity and early mortality associated with DM. Our study found that PD was associated with fewer ED visits, fewer debilitating comorbidities such as retinopathy, COPD, CKD, and CHF. PD patients were less likely to have any comorbidities in comparison to DM patients.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP604 | LBSUN287 Ketosis-prone Type 2 Diabetes (Flatbush Diabetes) In Remission: Report Of Two Cases
Authors: Ji Beisi , Suresh Sumatha Channapatna , Naher Kamrun , Banerji MaryAnn
Published: November 2022

Diabetic ketoacidosis (DKA) is a triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration1. Diabetic ketoacidosis (DKA) is a well-known manifestation of Type 1 diabetes2; however, there has been an increase in the incidence of DKA as the first presentation in Type 2 diabetes. This subtype of diabetes is typically seen in non-Caucasian middle-aged obese males due to non-autoimmune disruption of glucose metabolism, which requires an initial intensive insulin regimen. After initial insulin treatment for several weeks to several months, a significant percentage of people can become insulin independent with an oral hypoglycemic agent(OHA) and /or just lifestyle modification, and in remission for many years3. This hybrid form of diabetes sharing the characteristics of T1DM and T2DM is called "Flatbush diabetes", also known as "ketosis-prone T2DM4 5. This article aims to emphasize the importance of early recognition of this heterogeneous syndrome through the two representative case reports of Ketosis-prone T2DM.

Case presentation

We describe two cases of African American men (elderly and young adult) with no past medical histories, who presented to the Emergency Department with a few days history of polyphagia, polydipsia, polyuria and fatigue. New onset of Type 2 diabetes and unprovoked DKA were diagnosed. Both of them received standard treatment with intravenous fluid and insulin drip, recovered uneventfully and discharged with insulin. Both of them followed up closely in our endocrinology clinic, their GAD antibodies were 0. 00(n<=0. 02nmol/L), Islet cell antibody<1: 4(n<1: 4) and C-peptide were 2.6ng/mL and 6ng/mL(1.1-4.4ng/mL) respectively. Their insulin was gradually withdrawn with the addition of an oral hypoglycemic agent. Both the patients are currently insulin independent for more than 15 months.

Conclusion

This is an important clinical entity to recognize ketosis-prone T2DM as insulin independence positively impacts quality of life and decreases economic burden on the health care system. For patients with suspected ketosis-prone T2DM, B-cell autoantibodies and C-peptide level should be obtained 1-3 weeks at the first outpatient visit, as it can predict patients’ prognosis. These patients should also be referred to an endocrinologist and need careful follow-up. Among all ketosis-prone T2DM patients, those with preserved B-cell function are more likely to be insulin independent and go into remission phase.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN294 Insulin-induced Abdominal Acanthosis Nigricans From High Doses Of Insulin U-500
Authors: Yap Sara Elizabeth , Gerges Amany , Oliva Joseph , Idrees Thaer
Published: November 2022

Introduction

Dermatological complications associated with insulin therapy include lipoatrophy, lipohypertrophy, and acanthosis nigricans. We have a rare case of severe acanthosis nigricans from repeated insulin injection.

Case

A 63-year-old man with diabetes mellitus type 2 presented with an elevated blood glucose of 584mg/dL. He reported "high" glucose levels, despite adherence to his insulin regimen. He only injected insulin in his abdomen. Over 20 years, his insulin doses increased from Lantus 65 units BID and Humalog 35 units TID to Lantus units 110 BID and Humalog 65 units TID. It was later changed to U-500 at 160 units TID. His Hba1c ranged from 10.7% to 15.4%, most recently 13.6%. Physical examination revealed hyperpigmented and thickened plaques, localized to two large areas lateral to his umbilicus. During his hospital stay, insulin was administered on his arms and thighs. Glucose levels improved on Levemir 55 units daily and Lispro 20 units TID. He was discharged on Insulin U-500 40 units TID with instructions to avoid injecting on his abdomen and to rotate injection sites.

Discussion

Acanthosis nigricans is associated with insulin resistance or hyperinsulinemia. Insulin has a similar structure to insulin-like growth factor (IGF-1). At higher insulin concentrations, it can bind to IGF-1 receptors on keratinocytes and fibroblasts, leading to skin proliferation. Other suggested mechanisms include the involvement of fibroblast and epidermal growth factor. Histopathological findings show hyperkeratosis, papillomatosis, and thickened dermis. Immunochemical findings show positive IGF-1 antibodies in basal epithelial and prickle cell layers. In patients with poor glycemic control and increasing doses of insulin, it is important to assess for insulin-related skin changes. Besides routine visual inspection, skin thickening can be assessed by stroking the skin side-to-side in a sweeping motion instead of palpation.

Conclusion

Our patient with poorly type 2 diabetes required escalating doses of insulin over the years. He developed severe acanthosis nigricans on his abdomen leading to poor absorption of insulin. This case highlights the importance of routine visual inspection and tactile examination of insulin injection sites for skin changes, as well as repeated counseling regarding insulin site rotation. References: Buzási K, Sápi Z, Jermendy G. Acanthosis nigricans as a local cutaneous side effect of repeated human insulin injections. Diabetes Res Clin Pract. 2011;94: E34-E36. Mailler-Savage EA, Adams BB. Exogenous insulin-derived acanthosis nigricans. Arch Dermatol 2008;144: 126-7. Yahagi E, Mabuchi T, Nuruki H, et al. Case of exogenous insulin-derived acanthosis nigricans caused by insulin injections. Tokai J Exp Clin Med. 2014;39: 5-9

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN307 A Randomized Controlled Pilot Study Of The Food Order Behavioral Intervention In Prediabetes
Authors: Shukla Alpana P , Karan Ampadi , Graves Maya , Steller Ian , Abel Brittany , Zecca Christina , Hayashi Lauren , O’Connor Madlen , Tils Jamie , Giannita Ashley , Truong Wanda , Casper Anthony , D’Angello Debra , Hootman Katie , Aronne Louis J
Published: November 2022

Background and Objectives

Ordering the ingestion of carbohydrate-rich foods after protein/vegetables (carbohydrate-last food order) significantly reduced postprandial glucose and insulin excursions over 180 min in patients with prediabetes and type 2 diabetes, compared with the reverse food order (carbohydrate-first) in previous research. We implemented a 16-week food order behavioral intervention, assessing its feasibility and impacts on glucose tolerance (GT), HbA1c, and weight (wt) in adults with prediabetes.

Methods

Participants with overweight/obesity and prediabetes (HbA1c 5.7-6.4%) were randomized to receive either standard nutritional counseling (control group) or standard nutritional counseling plus carbohydrate-last food order counseling (FO group). Participants were instructed to maintain their usual level of exercise throughout the study; this was assessed by the Godin Leisure-Time Exercise questionnaire at baseline and wk 16. Participants in both groups received 4 in-person brief counseling sessions at 1-month intervals. Due to the Covid-19 pandemic, later participants received some or all of their counseling via telemedicine. Oral GT was tested at baseline and week 16. Feasibility was assessed via a questionnaire.

Results

Of the 45 randomized subjects, 39 completed the study (control 21, FO 18). Demographics and baseline variables including wt (190.8 lbs vs 191.1 lbs) and HbA1c (6% vs 6%) were similar between groups. Exercise levels did not differ between groups at baseline and wk 16. Within FO group, body wt declined (-3.6 ±5.7 lbs, p=0. 017; -1.8% ±2.8, p=0. 012), and there was a trend towards improvement in HbA1c (-0.1 ±0.2, p=0. 054). Control group wt changed (-2.6 ±6.8 lbs, p=0.102; -1.6% ±3.5, p=0. 048) without altering HbA1c (-0. 03 ±0.3, p=0.605). Changes in wt, HbA1c, and GT were not significantly different between groups. At week 16, 17 FO group subjects (94%) reported high intervention adherence, 13 (74%) reported it was easy to eat protein/vegetables before carbohydrates, and 14 (78%) reported they would continue eating protein/vegetables before carbohydrates.

Conclusions

Carbohydrate-last food order is a feasible behavioral strategy in individuals with prediabetes. More research with a larger sample size and longer duration is needed to delineate its clinical impact.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP161 Adipose mitochondrial complex I deficiency modulates inflammation and glucose homeostasis in a sex-dependent manner
Authors: Yoon John , Choi Kyung-Mi , Ryan Karen
Published: November 2022

Mitochondrial dysfunction in adipose tissue has been associated with type 2 diabetes, but it is unclear whether it is a cause or the consequence. Mitochondrial complex I is a major site of reactive oxygen species generation and a therapeutic target. Here we report that genetic deletion of the complex I subunit Ndufs4 specifically in adipose tissue results in an increased propensity to develop diet-induced weight gain, glucose intolerance, and elevated levels of fat inflammatory genes. This outcome is apparent in young males but not in young females, suggesting that females are relatively protected from the consequences of adipose mitochondrial dysfunction for metabolic health. Mutant mice of both sexes exhibit defects in brown adipose tissue thermogenesis. Fibroblast growth factor 21 (FGF21) signaling in adipose tissue is selectively blunted in male mutant mice relative to wild-type littermates, consistent with sex-dependent regulation of its autocrine/paracrine action in adipocytes. Together, these findings support that adipocyte-specific mitochondrial dysfunction is sufficient to induce tissue inflammation and can cause systemic glucose abnormalities in male mice.

Presentation: No date and time listed
ODP163 Association of HbA1c and Comfort with Diabetes Self-Management Among Adolescents and Young Adults with Type 1 Diabetes
Authors: Onwukwe Obichi , Lundgrin Erika , Zimmerman Teresa N
Published: November 2022

Glycemic targets are not met by many individuals with type 1 diabetes (T1D), especially among adolescents and young adults (AYA). To date, research is limited regarding comfort with diabetes self-management in this vulnerable demographic preparing to transition from pediatric to adult care. The purpose of this study was to examine levels of self-reported comfort with diabetes management tasks among AYA with T1D, and to describe the relationships among comfort levels, sociodemographic factors, and HbA1c. As a part of a quality improvement initiative at an academic pediatric hospital, AYA aged 15-23 years old with T1D received a transition survey to self-assess their comfort level with sixteen different diabetes management tasks on a 5-point Likert scale during a routine diabetes care visit. A chart review was subsequently performed to obtain sociodemographic factors and HbA1c. Among 161 participants who completed the survey (median age 17, median diabetes duration 7 years, 82.3% white, 59% female, 66.5% with private insurance, and median HbA1c 8.8%), comfort with diabetes management tasks was generally rated highly (median overall comfort level of 4.5 out of 5) and did not differ by race or insurance type. Regression analysis revealed that higher self-reported comfort level with diabetes management tasks was associated with a higher HbA1c (p=0.006), after controlling for age, sex, race, insurance type, and diabetes duration. These findings suggested that self-reported comfort with independently managing T1D may not be a sufficient metric in assessing AYA patients’ need for further intervention to optimize glycemic outcomes as they transition from pediatric to adult providers, and highlighted the importance of continuity of care to optimize diabetes management during this transitional period.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.
ODP165 Atypical DKA? Think Cannabis!
Authors: Albashaireh Arwa , Henske Joseph
Published: November 2022

Diabetic ketoacidosis (DKA) can be life threatening if not recognized and treated promptly. DKA is characterized by hyperglycemia, acidosis, ketosis and elevated anion gap. The presence of these metabolic derangements is essential to make the diagnosis. The use of cannabis has been associated with atypical acid-base profile in DKA which may contribute to confusion in diagnosis and treatment.

Case

A 20-year-old man with type 1 diabetes since age 10 presented to the emergency department with 4 days of nausea, vomiting and elevated blood glucose (BG). Emesis occurred up to 6 times daily and started 2 days prior to hyperglycemia. He was unable to correct BG with rapid acting insulin. Moderate urine ketones were present. He denied symptoms of diarrhea, fever, sore throat, runny nose or cough and reported adherence to insulin regimen. Physical exam was remarkable for dry mucous membranes and mild epigastric tenderness. Lab evaluation showed BG of 268 (70-110mg/dL), sodium 133 (135-145 mmol/L), potassium 3.6 (3.5- 5.1 mmol/L), chloride 95 (98-107 mmol/L), bicarbonate 22 (22-32 mmol/L), creatinine 0.8 (0.6–1.2 mg/dL), Anion gap 16, beta-hydroxybutyrate 3.38 (<0.27 mmol/L). He had normal white blood cell count and infectious work up was unremarkable. The patient was started on continuous IV fluids and was managed with intermittent subcutaneous rapid acting insulin in addition to basal insulin. After anion gap closure he was transitioned to his home doses of insulin. Prior to discharge, the patient discretely asked about the effects of smoking marijuana on BG and subsequently disclosed he had increased his use of marijuana recently.

Discussion

Diabetic keto-alkalosis may present as a result of recurrent vomiting that leads to gastric acid loss. Cannabis use has been linked to an increased risk of diabetic keto-alkalosis. The underlying mechanism is hypothesized to be related to cannabis effects on the stomach causing delayed gastric emptying and leading to cyclic nausea and vomiting. One study conducted to investigate acid-base parameters seen in atypical DKA in Type 1 Diabetes referred to this as "Hyperglycemic Ketosis due to Cannabis Hyperemesis Syndrome" (HK-CHS) recommending obtaining urine drug screen in patients with atypical DKA 1 . Attention should be drawn to this phenomenon as cannabis use has grown with its legalization in many states. Individuals with T1D presenting with ketosis but normal or elevated pH and/or serum bicarbonate may confuse clinicians and delay proper diagnosis. When the patient does not disclose cannabis use voluntarily, taking a thorough social history is critical to making the correct diagnosis. Reference: 1. Akturk HK, Snell-Bergeon J, Kinney GL, Champakanath A, Monte A, Shah VN. Differentiating diabetic ketoacidosis and hyperglycemic ketosis due to cannabis hyperemesis syndrome in adults with type 1 diabetes. Diabetes Care 2021 December 8,: dc211730

Presentation: No date and time listed
ODP166 Autoantibody Positivity and Random C-peptide Profile in Young Ethnic South Indian Population with Diabetes Mellitus
Authors: Kamalanathan Sadishkumar , SS Sarayu Gopal , Sahoo Jayaprakash , Naik Dukhabandhu , Negi Vir Singh
Published: November 2022

The islet cell autoantibody and beta-cell reserve profiles of young-onset diabetes patients in India are not only heterogeneous but also differ from those in the rest of the world. We sought to assess 3 standard islet cell autoantibodies and random C-peptide in the young ethnic South Indian population with diabetes mellitus attending the Endocrinology OPD of our tertiary care. A total of 190 young diabetes patients aged between 12-30 years were screened for inclusion in the study. Known cases of gestational diabetes and those on diabetogenic drugs were excluded. Additionally, those with clinical features suggestive of pancreatic diabetes or maturity-onset diabetes of young (MODY), or any diabetes-associated syndromic disorders were also excluded. Finally, 138 eligible young diabetes patients were included in the study. The islet cell autoantibodies against glutamic acid decarboxylase (GAD), insulinoma-associated protein-2 (IA-2), zinc transporter (ZnT8)was measured by sandwich ELISA technique using a human GAD ELISA kit (Euroimmun, Germany), human IA2 ELISA kit (Euroimmun, Germany), human ZnT8 ELISA kit (RSR diagnostics, USA) respectively. Random C-peptide was measured with chemiluminescence immunoassay analyser Advia Centaur XP. Diagnosis of T1DM was based on the requirement of immediate insulin replacement therapy for hyperglycemia with or without acute-onset ketosis with random C-peptide (<0.6 ng/ml) with /without any of islet cell antibodies. Diagnosis of T2DM is based on the history of control of hyperglycemia with oral hypoglycemic agents with documentation of adequate beta-cell reserve (random C-peptide ≥ 0.6 ng/ml) while maintaining euglycemia. Based on the patient characteristics, treatment profile, islet cell antibody status, and beta-cell reserve as assessed by random C-peptide levels, 82 were classified as T1DM, and 48 were classified as T2DM. The rest 8 patients were categorized as unclassified diabetes. GAD antibody was seen in 54(66%) of 82 T1DM patients. Islet cell autoantibody negativity was documented in 21(26%) of T1DM patients. IA-2 and ZnT8 antibodies contributed to an additional 7(8%) to islet cell antibody positivity in T1DM patients. IA-2 antibody positivity was low and random C-peptide was undetectable in many cases of T1DM in our study and is probably due to prolonged duration of diabetes in many T1DM patients. Autoantibody positivity was seen in 4(8%) T2DM patients. These patients need to be followed up for possible evolution of latent autoimmune diabetes in adults. References: Sahoo SK, Zaidi G, Vipin VP, Chapla A, Thomas N, Yu L,et al. Heterogeneity in the aetiology of diabetes mellitus in young adults: A prospective study from north India. Indian J Med Res 2019; 149: 479-88.

Presentation: No date and time listed
ODP175 COVID-19 Induced Euglycemic Diabetic Ketoacidosis in a Patient taking Sodium-Glucose Cotransporter-2 Inhibitors
Authors: Alqaisi Sura , Rahman Ali
Published: November 2022

From the U.S., under to American Diabetes Association, diabetic ketoacidosis (DKA) is accountable for around 6.3 percent of all hospitalization and 0.4% of all mortality annually. Unregulated hyperglycemia (>250 mg/dL), significant anion gaps, metabolic acidosis, and an increased plasma ketone concentration are the manifestations of diabetic ketoacidosis. Despite this, DKA can occur in the vicinity of an average bloodstream sugar level (less than 200 mg/dL); this is described as euglycemic DKA (eu-DKA). The Sodium-glucose Cotransporter-2 (SGLT2) inhibitors are being used in the management of type 2 diabetes, given its favorable side effect of weight loss and improved cardiovascular mortality. Still, at the same, can cause in rare occasions eu-DKA. The hospitalization of a patient taking Empagliflozin at home presented to the emergency department complaining of shortness of breath, fever, chills, and productive cough for one week with eu-DKA and extreme acidemia in the setting of a confirmed COVID-19 infection that had remained persistent for eight days before presentations are described in this medical abstract. Eu-DKA is uncommon in the population, which increases the possibility of misdiagnosis in patients. In light of the COVID-19 epidemic, there is an immediate demand for increased public knowledge of the condition. Keywords: COVID-19, Diabetes, Glucose Metabolism, SARS-2, SGLT2 Inhibitor, Type 2 Diabetes

Presentation: No date and time listed
ODP183 Diabetic Ketoacidosis Precipitated by Ketogenic Diet and SGLT-2 Inhibitor Use in an Individual with T2DM
Authors: Mason Timothy , Ansar Sameer
Published: November 2022

Background

SGLT-2 inhibitors have been associated with increased risk of ketoacidosis even with normal blood glucose levels. A ketogenic diet is a low-carb, high-fat diet which has recently gained popularity for weight loss by producing a state of ketosis. We present this case to emphasize the risk of ketoacidosis in patients on SGLT-2 inhibitors and a ketogenic diet.

Clinical Case

A 48-year-old woman with a 16-year history of T2DM presented to the ER with a 3-day history of upper abdominal cramping and headaches, decreased urine output, and progressively worsening nausea and vomiting. Her glycated hemoglobin level was 9.4% (n: 4-6%) and her blood glucose readings were not elevated during this time. Other medical issues include dyslipidemia, transaminitis and hypertension. She does not smoke or drink alcohol. She takes glimepiride 0.5 mg daily and canagliflozin was added approximately 1.5 weeks prior to presentation. She was on a ketogenic diet. A few days prior to these symptoms she was in the process of moving out of her home, spending long days physically exerting herself. On exam she was in mild distress with dry mucous membranes. Vitals showed tachycardia (119BPM) but otherwise were stable. Labs revealed that she was severely acidotic with an anion gap of >27 and pH < 6.9 (n: 7.34-7.43), with urinalysis positive for ketones (2+, n: negative), protein (3+, n: negative), and glucose (3+, n: negative). Complete blood count showed leukocytosis (WBC: 18,000, n: 4. 00-12. 00*10 3 /mcL). Complete metabolic panel showed hyponatremia (130, n: 136-145mmol/L), elevated glucose (305, n: 70-99,g/dL), and low bicarbonate (<5, n: 22-30mmol/L). A chest X-ray, lumbar puncture and CT of head and abdomen were unrevealing. She was admitted to the ICU for treatment of suspected DKA with severe acidosis and hypovolemia. She was hydrated with IV fluids and was started on an insulin drip according to DKA protocol. Her anion gap closed in 22 hours. The patient spent 3 days in the ICU and 1 day on general floor before discharge on home medications and was advised to follow up with endocrinology. At follow up 2 months later her C-peptide was 2.14 (0.78-5.19 ng/mL) and GAD65 antibody assay was 0. 00 (<0. 02 nmol/L), the SGLT-2 inhibitor was discontinued, and she was instead started on a GLP-1 agonist.

Conclusion

The mechanism behind DKA with SGLT-2 inhibitor use involves glycosuria and volume depletion, lowering the insulin-to-glucagon ratio, while stimulating lipolysis. The addition of a low carbohydrate or ketogenic diet produces a state of ketosis as fat is utilized for energy and ketones are produced, further promoting DKA. With increased use of SGLT-2 inhibitors in patients with and without diabetes mellitus extreme caution should be exercised in prescribing SGLT-2 inhibiters in a patient on a low carbohydrate diet.

Presentation: No date and time listed