Background. Patients with diabetes and end-stage kidney disease (ESKD) may experience “burnt-out diabetes”, defined as having a HbA1c <6.5% without antidiabetic therapy for >6 months. Methods. This pilot prospective study assessed glycemic control by continuous glucose monitoring (Dexcom CGM), HbA1c, glycated albumin and fructosamine in patients with burnt-out diabetes (n=20) and without a history of diabetes (n=20). Results. Patients with burnt-out diabetes had higher CGM-measured daily glucose, lower % time in range 70-180 mg/dL, higher % time above range >250 mg/dL, and longer duration of hyperglycemia >180 mg/dL (hours/day) compared to patients without diabetes (all p<0.01). HbA1c and fructosamine levels were similar; however, patients with burnt-out diabetes had higher levels of glycated albumin than patients without diabetes. Conclusion. The use of CGM demonstrated that patients with burnt-out diabetes have significant undiagnosed hyperglycemia. CGM and glycated albumin provide better assessment of glycemic control than HbA1c and fructosamine in patients with ESKD.

Patients with long-standing type 2 diabetes and end-stage kidney disease (ESKD) on dialysis may experience resolution of their hyperglycemia, as defined by an HbA1c < 6.5%, without antidiabetic therapy. This phenomenon is known as “burnt-out diabetes”. Because HbA1c may be falsely low in patients with ESKD/dialysis therapy, we conducted a prospective study to compare glycemic control as measured by Dexcom G6 CGM in patients with ESKD and burnt-out diabetes and those without history of diabetes. We hypothesize that the use of CGM may provide better assessment of glycemic control than HbA1c (standard-of-care) in these patients and clarify the glycemic characteristics of burnt-out diabetes. We included adults with ESKD on dialysis, with (n=20) and without (n=10) a known history of diabetes, and with HbA1c <6.5% without antidiabetic therapy for > 6 months. All subjects wore a blinded Dexcom G6 CGM for 10 days. Their clinical characteristics and CGM metrics are shown in Table 1. Conclusion: CGM provides better assessment of glycemic excursions, compared to HbA1c, in patients with ESKD and diabetes. Most patients with burnt-out diabetes (HbA1c <6.5%, off therapy) have frequent and significant hyperglycemic excursions as detected by CGM. Further research will need to examine whether these excursions require pharmacotherapy. Disclosure C.Kaminski: None. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. Z.E.Zabala: None. B.Moazzami: None. A.Y.G.Gerges: None. R.G.Mccoy: Consultant; Emmi. L.Peng: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. Funding Jacob's Fund for Education

Background: Reliability of HbA1c in subjects with end-stage kidney disease treated with hemodialysis is poor. Capillary blood glucose (CBG) is widely used, but is limited to 2-4 values/day. Clinical guidelines recommend using continuous glucose monitoring (CGM) to assess glycemic control in this population, but there is limited data. Methods: Prospective observational study of insulin treated adults with type-2 diabetes (T2D) receiving hemodialysis. Subjects were instructed to wear a Dexcom G6-Pro and perform Nova StatStrip CBG at least 2-4/d for 10-days. We compared mean glucose, hypoglycaemia, and hyperglycaemia rates, time-in-target range (TIR), time above range (TAR), and time below range (TBR) between testing methods. Results: Glucose metrics are shown in Table 1. Conclusion: Compared to CBG, CGM provides a comprehensive glycemic evaluation in insulin-treated subjects with T2D on hemodialysis. CGM was superior in assessing glycemic control (TIR), detection of severe hyperglycemia and hypoglycemic excursions, particularly nocturnal and prolonged events. Safer treatment options assessed by CGM metrics are needed for this high-risk population. Disclosure R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. A.Y.G.Gerges: None. B.Moazzami: None. L.Peng: None. K.R.Tuttle: Consultant; Lilly, AstraZeneca, Gilead Sciences, Inc., Research Support; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Novo Nordisk, Goldfinch Bio, Inc., Traveere Pharmaceuticals. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.

Background: Hemodialysis (HD) impacts glucose and insulin metabolism and increases hypoglycaemia rates. Glucose-containing dialysate decreases the risk, but studies using CGM metrics are lacking. Methods: Prospective observational study of insulin-treated adults with T2D, receiving hemodialysis (dialysate glucose 100mg/dl), at least thrice weekly. Subjects were instructed to wear a Dexcom G6-Pro for 10 days. We assessed CGM metrics (mean glucose, %TIR, %TAR, %TBR, and hypoglycemic and hyperglycemic rates) during three time periods: 20-hours before (PreHD), during (HD, ~4 hours), and 20-hours after (PostHD) hemodialysis sessions. Results: Among 56 subjects (mean age 57.3±9, HbA1c 7.2±1.4), mean glucose, %TAR, %TIR and rates of hypoglycaemia <70mg/dl were significantly better during HD. %TAR >180mg/dl and > 250mg/dl were significantly higher after HD, see Table 1. Other hypoglycaemia metrics were overall low, and not different in relation to HD timing. Conclusion: CGM patterns demonstrated improved glycemic control during dialysis, with tendency for higher glucose metrics before HD. Hypoglycaemia metrics were low, while severe hyperglycemia excursions are common across all HD-related periods. Future studies using newer CGM technology and providing longer duration of CGM monitoring are needed for subjects with T2D treated by HD. Disclosure R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. B.Moazzami: None. A.Y.G.Gerges: None. L.Peng: None. K.R.Tuttle: Consultant; Lilly, AstraZeneca, Gilead Sciences, Inc., Research Support; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Novo Nordisk, Goldfinch Bio, Inc., Traveere Pharmaceuticals. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.

Background: Reliability of HbA1c in subjects with end-stage kidney disease treated with hemodialysis is poor. Capillary blood glucose (CBG) is widely used, but is limited to 2-4 values/day. Clinical guidelines recommend using continuous glucose monitoring (CGM) to assess glycemic control in this population, but there is limited data. Methods: Prospective observational study of insulin treated adults with type-2 diabetes (T2D) receiving hemodialysis. Subjects were instructed to wear a Dexcom G6-Pro and perform Nova StatStrip CBG at least 2-4/d for 10-days. We compared mean glucose, hypoglycaemia, and hyperglycaemia rates, time-in-target range (TIR), time above range (TAR), and time below range (TBR) between testing methods. Results: Glucose metrics are shown in Table 1. Conclusion: Compared to CBG, CGM provides a comprehensive glycemic evaluation in insulin-treated subjects with T2D on hemodialysis. CGM was superior in assessing glycemic control (TIR), detection of severe hyperglycemia and hypoglycemic excursions, particularly nocturnal and prolonged events. Safer treatment options assessed by CGM metrics are needed for this high-risk population. Disclosure R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. A.Y.G.Gerges: None. B.Moazzami: None. L.Peng: None. K.R.Tuttle: Consultant; Lilly, AstraZeneca, Gilead Sciences, Inc., Research Support; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Novo Nordisk, Goldfinch Bio, Inc., Traveere Pharmaceuticals. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.

Introduction The prevalence, severity, and quality of life (QoL) impact of diabetic retinopathy (DR) among African–Americans (AAs) with end-stage kidney disease (ESKD) undergoing dialysis are unknown.Research design and methods A cross-sectional study was conducted on 93 AA adults with diabetes and ESKD. The diagnosis of DR was based on a review of medical records and/or a positive photograph with a portable hand-held device reviewed by both artificial intelligence software and a retinal specialist. QoL, physical disability social determinants of health (SDoHs) were assessed by standardized questionnaires.Results The prevalence of DR was 75%, with 33% of participants having mild, 9.6% moderate and 57.4% severe DR. A total of 43% had normal visual acuity; 45% had moderate visual impairment; and 12% had severe visual impairment. We found a high burden of disease, multiple SDoH challenges, and low QoL and general health among patients with ESKD. The presence of DR had no significant impact on physical health and QoL compared with participants without DR.Conclusions DR is present in 75% of AA patients with diabetes and ESKD on haemodialysis. ESKD has a significant burden on general health and QoL; however, DR has a minor additional impact on the overall physical health and QoL in people with ESKD.

Background: Hemodialysis (HD) impacts glucose and insulin metabolism and increases hypoglycaemia rates. Glucose-containing dialysate decreases the risk, but studies using CGM metrics are lacking. Methods: Prospective observational study of insulin-treated adults with T2D, receiving hemodialysis (dialysate glucose 100mg/dl), at least thrice weekly. Subjects were instructed to wear a Dexcom G6-Pro for 10 days. We assessed CGM metrics (mean glucose, %TIR, %TAR, %TBR, and hypoglycemic and hyperglycemic rates) during three time periods: 20-hours before (PreHD), during (HD, ~4 hours), and 20-hours after (PostHD) hemodialysis sessions. Results: Among 56 subjects (mean age 57.3±9, HbA1c 7.2±1.4), mean glucose, %TAR, %TIR and rates of hypoglycaemia <70mg/dl were significantly better during HD. %TAR >180mg/dl and > 250mg/dl were significantly higher after HD, see Table 1. Other hypoglycaemia metrics were overall low, and not different in relation to HD timing. Conclusion: CGM patterns demonstrated improved glycemic control during dialysis, with tendency for higher glucose metrics before HD. Hypoglycaemia metrics were low, while severe hyperglycemia excursions are common across all HD-related periods. Future studies using newer CGM technology and providing longer duration of CGM monitoring are needed for subjects with T2D treated by HD. Disclosure R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. B.Moazzami: None. A.Y.G.Gerges: None. L.Peng: None. K.R.Tuttle: Consultant; Lilly, AstraZeneca, Gilead Sciences, Inc., Research Support; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Novo Nordisk, Goldfinch Bio, Inc., Traveere Pharmaceuticals. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.

Abstract Hypoglycemia and hyperglycemia are associated with poor outcomes among hospitalized patients with type 2 diabetes (T2D). Until 2012, the American Diabetes Association (ADA) and Endocrine Society hospital clinical guideline recommended a target blood glucose (BG) of 70-140 mg/dl; however, more recently a relaxed target of 140-180 mg/dl has been recommended by the ADA. Little data from randomized clinical trials (RTC) is available to support an intensive vs relaxed BG target. Accordingly, we performed a post-hoc analysis on 9 RCTs to assess hospital outcomes in non-critically ill insulin-treated patients with T2D targeting BG 70-140 mg/dl vs. 140-180 mg/dl. Methods Among 1446 patients, 640 were treated to a target of 70-140 mg/dl and 806 to a target of 140-180 mg/dl. Propensity score matching was used to reduce the bias due to confounding in the estimation of the effect of BG target. The propensity score dependent variables upon model selection included sex, admission HbA1c, and home insulin use. The final propensity score matched study sample consisted of 1,146 patients (573 patients in each BG target group). Results There were no differences in age, gender, BMI, diabetes duration, home insulin use or hospital admission service (medicine/surgery). Patients in the intensive target BG group had lower mean BG (day 2-10: 163.73 ± 39.79 mg/dl vs 170.15 ± 39.94 mg/dl, p=0.004), less hyperglycemia (any BG >180: 86% vs 92%, p=0.003; any BG >240: 51% vs 62%, p<.001), similar rates of hypoglycemia (BG <70: 12% vs 15%, p=0.11; BG <54: 2.5% vs 4.0%, p=0.14), and trended towards greater time in range <180 mg/dl (62.00 ± 28.14% vs 59.23 ± 27.38%, p=0.06). The composite of complication rate (acute renal failure, infection, myocardial infarction, respiratory failure and stroke) was lower (3.7% vs 6.8%, p=0.02) in the intensive control group, with similar rates of inpatient death (0.9% vs 0.3%, p=0.36). Hospital length of stay was shorter in the intensive control group (4.0 vs 6.0 days, p<.001). Conclusion Our results indicate that tighter glycemic target of 70-140 mg/dl leads to lower mean daily BG, less severe hyperglycemia events, similar rates of hypoglycemia, and lower length of stay and complication rates compared to a higher target of 140-180 mg/dl. Further RCTs are indicated to elucidate optimal glycemic targets in hospitalized patients with T2D. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Abstract 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.

Background and Methods: This cross-sectional study determined the prevalence of diabetic retinopathy (DR) in non-Hispanic African Americans (AA) with end-stage-kidney disease (ESKD) and their impact on quality of life. A total of 95 adults with type 1 (n= 10) and type 2 (n= 85) on dialysis diabetes were assessed for DR using portable hand-held (Optomed Aurora) with artificial intelligence report with AEYE Diagnostic System (AEYE-DS) , visual acuity using a Snellen chart, and social determents of health, and standardized questionnaires (Kidney Disease Quality of Life (KDQoL) , depression screening (Patient health Questionaire-9) and food insecurity. Results: Among the 95 participants (female 51%, mean age 59.5 ±12.3 years, duration of diabetes (DM) 18.2 ± 12.0 years and duration of dialysis 4.5±3.6 years) . A total of 55% of patients had a diagnosis of (DR+) , who had a longer duration of DM (18.8±9.5 vs. 15.8±12.2 years, p=0.20 and shorter duration of dialysis (3.6±2.7 vs. 5.9±5.0 years compared to DR negative (DR-) , p=0.09. Kidney Disease Quality of Life score on symptoms/problems related to ESKD and greater effect of kidney disease in daily life were lower compared to the general US, AA population with ESKD, p <.0001) . DR+ had worse physical health (p: 0.09) , greater rate of severe vision impact on quality of life (p= 0.01) , similar rates below the federal poverty level per household income (25% vs. 30%) , non-statistically significantly higher Ph-Q9 depression (6.9±5.3 vs. 4.8±4.1, p=0.16) , and food insecurity scores compared to without DR (1.07±1.51 vs. 0.83±1.56, p=0.33) . Overall, the prevalence of diabetic retinopathy was 55% based on the AEYE artificial intelligence system. Diabetic retinopathy was associated with poor quality of life and physical health, higher rates of poverty, and greater impact of vision impairment on quality of life compared to DR negative. Our preliminary finding highlights the increased disease burden of DR in AAs with ESKD, indicating an alarming gap in care. Disclosure M. Egeolu: None. G. E. Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. E. Manishimwe: None. Z. E. Zabala: None. B. Moazzami: None. R. L. Caleon: None. R. J. Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. J. E. Navarrete: None. A. Y. G. Gerges: None. L. Peng: None.