Tight Glucose Control Research Articles

An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow.

Glucose homeostasis is the tight control of glucose in the blood. This complex control is important, due to its malfunction in serious diseases like diabetes, and not yet sufficiently understood. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modeling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes.

Hemi Chorea and Hemi Balllismus: A Rare Presentation of Prolonged Uncontrolled Hyperglycemia

Background: Hemi chorea and hemiballismus interestingly, are rare presentations of severe chronic persistent hyperglycemia which resolves with correction of hyperglycemia in most cases. Clinical Case: Here we report a case of a 67 YO woman with a PMH of prolonged uncontrolled DM evidenced by average baseline HbA1c of 14.6% (n<5.7%) presenting with dance-like movements of the left arm and mouth deviation. Initially the patient presented as a stroke code. Vital signs were unremarkable. On Physical exam, there was mild L face weakness and obvious abnormal hand movement. Other neurological exams were unremarkable for stroke. MRI showed the typical decreased T2/flair signal within the right frontal lobe, white matter, right caudate head, and bilateral lenticular nucleus with mild increased T1 signal of the right caudate and lenticular nucleus compatible with hyperglycemic nonketotic hemichorea hemiballismus. Her significant admission lab values of random blood glucose of 306mg/dl (n 74-200mg/dl), HbA1c of 18.7% (n<5.7%), urine sugar >1000 (n neg mg/dl), absence of ketonuria and acidosis also support the diagnosis. With improvement in her blood sugar control, there was a significant decrease in her abnormal hand movements. However, sugar control was not enough as there was the need for additional medications to improve the chorea such as risperidone and tetrabenazine. Eventually over the course of many months of tight glucose control, there was significant symptomatic improvement. While the exact etiology is unclear, the hyperintensity usually seen on head CT scan and the pathognomonic T1 hyperintensity of the basal ganglia on MRI is postulated to be related to metabolic abnormalities caused by hyper viscosity of the blood in the end arteries supplying the basal ganglia. Many case reports associated movement disorders to chronic persistent hyperglycemia but there are many other cases that described hemiballismus in acute cases of hyperglycemia or persisting despite adequate glycemic correction. Most of the patients described had an underlying markedly elevated HbA1c as a common factor which suggests that a prolonged period of uncontrolled hyperglycemia may be necessary to produce hemiballismus. When thinking of complications of diabetes, we often think of CAD, ESRD, CVD, DKA and HHS. We aim to create an awareness of this rare association and to recognize hemiballismus as one of the varying presentations of severe hyperglycemia in order to ensure early diagnosis and treatment of this condition. Conclusion: Hemichorea and hemiballismus are increasingly becoming popular as one of the many complications of severe chronic or acute hyperglycemia. This warrants recognition in literature.

Diabetic Myonecrosis: A Rare Condition That Present With Pain

Abstract Diabetic myonecrosis is the term used for spontaneous ischemic necrosis of skeletal muscle, unrelated to atheroembolism or occlusion of major arteries. This is an uncommon manifestation of long-standing and poorly controlled diabetes mellitus. A 65-year-old Hispanic female presented to the Hospital with one-week history of worsening right thigh pain. She denied associated fever, trauma, history of blood clots, past surgery, recent travel, ect. Patient has history of uncontrolled diabetes type 2, diabetic neuropathy and End-Stage Kidney Disease on hemodialysis for the last 3 years. Home medications include gabapentin 300 mg daily and insulin 70/30 20 units twice a day. On physical exam, vital signs appeared within normal limits. There was right medial and anterior thigh fullness, warmth and tenderness without erythema or fluctuance. Laboratory studies are pertinent for HbA1C 8.8% (n &amp;lt;6.5%), C-reactive protein (CRP) 12.97 (n &amp;lt;0.5 mg/dL), Erythrocyte sedimentary rate (ESR) &amp;gt;130 (n 0–30 mm/hr), Creatinine: 6.2 (n 0.57–1.11 mg/dL), BUN 77 (n 6–20 mg/dL), CO2 19 (n 22–29 mEq/L) and albumin 2.7(n 3.5–5.0 gm/dL). Other labs including CPK, glucose, ANA panel and CBC are within normal limits. Patient was admitted with initial diagnosis of cellulitis without improvement in clinical status after 3 days of antibiotics. MRI of the right thigh showed proximal thigh muscle, cutaneous and subcutaneous edema. Right thigh muscle biopsy showed marked myonecrosis with surrounding endomysial edema, foci of histiocytes, fibroblasts, and regenerating muscle fibers. Histologic features, together with localized muscle pain, normal CPK, negative microbiologic studies and uncontrolled diabetes are consistent with diabetic myonecrosis. Insulin was adjusted for tight glucose control and patient was started on low dose aspirin with outpatient follow-up. Diabetic myonecrosis presents with acute onset of painful swelling that evolves over days or weeks. The most common affected areas are the front and back of the thigh and calf. The pathophysiology is not well understood but appears related to thromboembolic events secondary to microvascular endothelial damage leading to tissue ischemia, which triggers an inflammatory cascade causing local tissue damage and ischemic necrosis. Common laboratory findings include elevated ESR, CRP and HbA1C level. Treatment involves symptomatic management, rest, glycemic control, analgesia and low-dose aspirin. The optimal approach is uncertain and current treatment is based upon published case reports and case series; there have been no randomized trials to compare approaches or specific agents. Close patient follow-up and tight glycemic control are key elements to prevent progression of this condition.

Plasma heat shock protein response to euglycemia in type 2 diabetes

IntroductionGlucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved....

The optimal medical therapy for glycemic control in covid-19

Diabetes is highly linked to the severity of coronavirus disease 2019 (COVID-19). My recent meta-analysis also suggested a higher prevalence of diabetes in severe COVID-19 as compared with non-severe COVID-19. Recent observational studies have shown that hyperglycemia was significantly associated with severity of COVID-19 in both diabetic and non-diabetic patients. To prevent worse outcome of COVID-19, more tight glucose control is required. I studied the association between hyperglycemia and worse outcome of COVID-19, the putative beneficial and harmful effects, and clinical outcomes of oral hypoglycemic drugs and insulin use in glycemic control among COVID-19 patients, by searching literatures. Although there were some negative studies, the meta-analysis reported that the treatment using metformin was associated with reduction in mortality due to COVID-19. One study showed that treatment with sitagliptin, one of dipeptidyl peptidase-4 (DPP4) inhibitors, during hospitalization was associated with reduction of mortality, with a clinical improvement as compared with patients on the standard care. There were no clinical studies showed effects of glucagon-like peptide-1 receptor agonists, pioglitazone and sulfonylurea on COVID-19 outcomes. Regarding sodium-glucose cotransporter 2 (SGLT2) inhibitors, a case of euglycemic diabetic ketoacidosis (DKA) associated with COVID-19 and a case of DKA that was difficult to distinguish from COVID-19 were reported. COVID-19 patients who need hospital care may deteriorate rapidly, an early and appropriate initiation of insulin therapy in hyperglycemic COVID-19 patients may be to be encouraged. J Endocrinol Metab. 2021;11(1):1-7 doi: https://doi.org/10.14740/jem718

Using Virtual Reality to Improve Health Care Providers' Cultural Self-Efficacy and Diabetes Attitudes: Pilot Questionnaire Study.

BackgroundIn southeastern Appalachian Ohio, the prevalence of diabetes is 19.9%, nearly double that of the national average of 10.5%. Here, people with diabetes are more likely to have a delayed diagnosis, limited access to health care, and lower health literacy. Despite the high rates of diabetes in the region, the availability of endocrinologists and certified diabetes care and education specialists is limited. Therefore, innovative strategies to address the growing diabetes care demands are needed. One approach is to train the primary care workforce in new and emerging therapies for type 2 diabetes to meet the increasing demands and complexity of diabetes care.ObjectiveThe aim of this study was to assess the effectiveness of a virtual reality training program designed to improve cultural self-efficacy and diabetes attitudes.MethodsHealth care providers and administrators were recruited from large health care systems, private practices, university-owned hospitals or clinics, Federally Qualified Health Centers, local health departments, and AmeriCorps. Providers and administrators participated in a 3-hour virtual reality training program consisting of 360-degree videos produced in a professional, cinematic manner; this technique is called virtual reality cinema (cine-VR). Questionnaires measuring cultural self-efficacy, diabetes attitudes, and presence in cine-VR were administered to providers and administrators before and after the program.ResultsA total of 69 participants completed the study. The mean age of the sample was 42.2 years (SD 13.7), 86% (59/69) identified as female, 83% (57/69) identified as White, 86% (59/69) identified as providers, and 25% (17/69) identified as nurses. Following the training program, we observed positive improvements in all three of the cultural self-efficacy subscales: Cognitive (mean change –1.29; t65=–9.309; P<.001), Practical (mean change –1.85; t65=–9.319; P<.001), and Affective (mean change –0.75; t65=–7.067; P<.001). We observed the largest magnitude of change with the subscale, with a Cohen d of 1.16 indicating a very large effect. In addition, we observed positive improvements in all five of the diabetes attitude subscales: Need for special training (mean change –0.21; t67=–6.154; P<.001), Seriousness of type 2 diabetes (mean change –0.34; t67=–8.114; P<.001), Value of tight glucose control (mean change –0.13; t67=–3.029; P=.001), Psychosocial impact of diabetes (mean change –0.33; t67=–6.610; P<.001), and Attitude toward patient autonomy (mean change –0.17; t67=–3.889; P<.001). We observed the largest magnitude of change with the Psychosocial impact of diabetes subscale, with a Cohen d of 0.87 indicating a large effect. We observed only one significant correlation between presence in cine-VR (ie, Interface Quality) and a positive change score (ie, Affective self-efficacy) (r=.285; P=.03).ConclusionsOur findings support the notion that cine-VR education is an innovative approach to improve cultural self-efficacy and diabetes attitudes among health care providers and administrators. The long-term impact of cine-VR education on cultural self-efficacy and diabetes attitudes needs to be determined.

The Optimal Medical Therapy for Glycemic Control in COVID-19

Diabetes is highly linked to the severity of coronavirus disease 2019 (COVID-19). My recent meta-analysis also suggested a higher prevalence of diabetes in severe COVID-19 as compared with non-severe COVID-19. Recent observational studies have shown that hyperglycemia was significantly associated with severity of COVID-19 in both diabetic and non-diabetic patients. To prevent worse outcome of COVID-19, more tight glucose control is required. I studied the association between hyperglycemia and worse outcome of COVID-19, the putative beneficial and harmful effects, and clinical outcomes of oral hypoglycemic drugs and insulin use in glycemic control among COVID-19 patients, by searching literatures. Although there were some negative studies, the meta-analysis reported that the treatment using metformin was associated with reduction in mortality due to COVID-19. One study showed that treatment with sitagliptin, one of dipeptidyl peptidase-4 (DPP4) inhibitors, during hospitalization was associated with reduction of mortality, with a clinical improvement as compared with patients on the standard care. There were no clinical studies showed effects of glucagon-like peptide-1 receptor agonists, pioglitazone and sulfonylurea on COVID-19 outcomes. Regarding sodium-glucose cotransporter 2 (SGLT2) inhibitors, a case of euglycemic diabetic ketoacidosis (DKA) associated with COVID-19 and a case of DKA that was difficult to distinguish from COVID-19 were reported. COVID-19 patients who need hospital care may deteriorate rapidly, an early and appropriate initiation of insulin therapy in hyperglycemic COVID-19 patients may be to be encouraged. J Endocrinol Metab. 2021;11(1):1-7 doi: https://doi.org/10.14740/jem718

Chronic hyperglycemia before acute ischemic stroke impairs the bilateral cerebrovascular response to exercise during the subacute recovery period.

Background and PurposeChronic hyperglycemia contributes to cerebrovascular dysfunction by damaging blood vessels. Poor glucose control has been tied to impairments in cerebral blood flow, which may be particularly detrimental for people recovering from major cerebrovascular events such as acute ischemic stroke. In this secondary analysis, we explore for the first time the connection between chronic hyperglycemia before acute stroke and the cerebrovascular response (CVR) to exercise 3 and 6 month into the subacute recovery period.MethodsWe recorded middle cerebral artery velocity (MCAv) using transcranial Doppler ultrasound bilaterally at rest and during moderate‐intensity exercise in stroke patients at 3 (n = 19) and 6 (n = 12) months post‐stroke. We calculated CVR as the difference between MCAv during steady‐state exercise and resting MCAv. We obtained hemoglobin A1c levels (HbA1c; a measure of blood glucose over the prior 3 months) from the electronic medical record (EMR) and divided participants by HbA1c greater or less than 7%.ResultsParticipants with high HbA1c (>7%) at the time of acute stroke had significantly lower CVR to exercise for both the stroke‐affected (p = .009) and non‐affected (p = .007) hemispheres at 3 months post‐stroke. These differences remained significant at 6 months post‐stroke (stroke‐affected, p = .008; non‐affected, p = .016).ConclusionsPatients with chronic hyperglycemia before acute ischemic stroke demonstrated impaired cerebrovascular function during exercise months into the subacute recovery period. These findings highlight the importance of maintaining tight glucose control to reduce morbidity and improve recovery post‐stroke and could have implications for understanding cerebrovascular pathophysiology.

Nicotinamide: Oversight of Metabolic Dysfunction Through SIRT1, mTOR, and Clock Genes.

Metabolic disorders that include diabetes mellitus present significant challenges for maintaining the welfare of the global population. Metabolic diseases impact all systems of the body and despite current therapies that offer some protection through tight serum glucose control, ultimately such treatments cannot block the progression of disability and death realized with metabolic disorders. As a result, novel therapeutic avenues are critical for further development to address these concerns. An innovative strategy involves the vitamin nicotinamide and the pathways associated with the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and clock genes. Nicotinamide maintains an intimate relationship with these pathways to oversee metabolic disease and improve glucose utilization, limit mitochondrial dysfunction, block oxidative stress, potentially function as antiviral therapy, and foster cellular survival through mechanisms involving autophagy. However, the pathways of nicotinamide, SIRT1, mTOR, AMPK, and clock genes are complex and involve feedback pathways as well as trophic factors such as erythropoietin that require a careful balance to ensure metabolic homeostasis. Future work is warranted to gain additional insight into these vital pathways that can oversee both normal metabolic physiology and metabolic disease.

Adjustments to an Existing Colorectal Surgical Site Infection Prevention Bundle Lead to Fewer Infections

Background: Surgical site infections (SSI) related to colorectal procedures are detrimental to patients and publicly reportable events. Our institution implemented a successful bundle of interventions to decrease SSI rates in 2014. In 2018, compliance started to wane, with a concurrent increase in infections. In an effort to enhance compliance and incorporate up-to-date information, we convened a multidisciplinary team to streamline this process. Methods: Our team evaluated published studies on successful bundle components and updates to professional guidelines for SSI prevention to determine adjustments. Modifications included allowing surgeon preference for (rather than mandating) wound protector use and simplification of clean closure protocol (determined by intraoperative contamination, leading to more efficient closure time). In addition, measures were added to achieve perioperative patient optimization (maintenance of normothermia, prevention of intraoperative hypoxia, tighter glucose control and postoperative bathing). The bundle was implemented in stages starting January 2019. SSI rates were monitored throughout the process using NHSN definitions, and rates were compared using χ2 analysis (Epi Info, CDC). Results: From 2015 to 2017, bundle compliance was 90%, and 8 SSIs (rate, 3.8 per 100 procedures) were detected (Table 1). In 2018, compliance was 82%, with 4 SSIs (rate, 6.6 per 100 procedures). From January through September 2019, SSI rates decreased to a rate of 4.8 per 100 procedures, with notable increase in superficial SSI, with zero cases of deep or organ-space infections. Feedback from operating-room personnel indicated their commitment to bundle compliance and perceived intraoperative time savings. Conclusions: Revamping an existing colorectal SSI bundle, including relaxation of time-intensive and expensive intraoperative measures and increased focus on evidence-based guidelines, resulted in decreased deep-organ space SSI rates, as well as increased satisfaction from procedural team members. Successful implementation of care pathways to prevent infections is an iterative process and requires the engagement of practitioners.Funding: NoneDisclosures: None

Comparison of the Effects of Standard and Diabetesspecific Dietary Products on Tight Blood Glucose Control in Critically Ill Patients

Comparison of the Effects of Standard and Diabetesspecific Dietary Products on Tight Blood Glucose Control in Critically Ill Patients

Effective Initiation and Treatment With Basal Insulin in People With Type 2 Diabetes: Focus on Mitigating Hypoglycemia in Patients at Increased Risk: Executive Summary.

Many people with type 2 diabetes are treated with insulin with the goal of achieving a specific A1C target. The most prominent risk for people on insulin therapy is hypoglycemia. When basal insulin analogs are used appropriately, the risk of hypoglycemia can be reduced while still achieving individualized glycemic goals. In a series of short videos now available on the Clinical Diabetes website, the authors discuss approaches to optimizing basal insulin initiation and treatment in people with type 2 diabetes, including those at high risk such as individuals with renal impairment and older adults, with a focus on reaching A1C goals while mitigating the risk for hypoglycemia. This article is intended to briefly summarize those discussions, and readers are encouraged to view the videos in their entirety at https://clinical.diabetesjournals.org/content/basal-insulin-videos. ### Introduction (Available at https://bcove.video/2Q2Rb9b) Approximately 50% of people with type 2 diabetes have poorly controlled disease and are vulnerable to long-term micro- and macrovascular complications (1). As type 2 diabetes progresses, many patients will require insulin to maintain glycemic control. The appropriate use of insulin requires a balance between the need for tight glucose control and the potential risk for hypoglycemia. Definitions of hypoglycemia have evolved over time, and the American Diabetes Association (ADA) now uses a three-level classification of hypoglycemia severity (2). Mitigating the risk for hypoglycemia is crucial to the successful treatment of people with type 2 diabetes. In the following series of videos, the authors discuss the use of available insulin formulations in the context of hypoglycemia risk. ### Basal Insulin Therapy—Balancing Glycemic Control With Risk for Hypoglycemia (Available at https://bcove.video/3h3Y85h) The achievement of tight glycemic control reduces micro- and macrovascular complications, and adherence to treatment improves quality of life and decreases health care costs (3–9). The authors discuss the association between A1C reduction and microvascular complications, as reported in the UK …

Does Tight Glucose Control During the First 24 hours of Hospitalization Reduce Scintigraphic Infarct Size in STEMI Patients?

Abstract Background Hyperglycemia at the time of admission is related to increased mortality and poor prognosis in patients diagnosed with ST-segment elevation myocardial infarction (STEMI). Objective We aimed to investigate whether tight glucose control during the first 24 hours of STEMI decreases the scintigraphic infarct size. Methods The study population consisted of 56 out of 134 consecutive patients hospitalized with STEMI in a coronary care unit. Twenty-eight patients were treated with continuous insulin infusion during the first 24 hours of [...]

Need for less tight glucose control in early pregnancy after embryogenesis due to high risk of maternal hypoglycaemia in women with pre-existing diabetes can be compensated by good control in late pregnancy.

Poor glucose control is associated with adverse outcomes in pregnancies with pre-existing diabetes. However, strict glucose control increases the risk of severe hypoglycaemia, particularly in the first trimester. Therefore, we aimed to investigate whether less tight glucose control in the first trimester determines adverse outcomes or can be compensated for by good control in late pregnancy. Retrospective data were collected from 517 singleton pregnancies complicated by pre-existing diabetes delivering between 2010 and 2017. Three hundred and thirty-six pregnancies fulfilled the inclusion criteria of having available HbA1c values either pre-conception or in the first trimester (65% type 1 diabetes, 35% type 2 diabetes). Higher HbA1c values in the first trimester were associated with increasing rates of large for gestational age (LGA) neonates, preterm delivery or neonatal intensive care unit admissions. Multiple regression analysis demonstrated third trimester HbA1c , type 1 diabetes, multiparity and excess weight gain, but not first trimester HbA1c , to be independently predictive for LGA. Pre-eclampsia and third trimester HbA1c increased the risk for preterm delivery. If HbA1c was ≤ 42 mmol/mol (6.0%) in the third trimester, rates of adverse outcomes were not significantly higher even if HbA1c targets of ≤ 48 mmol/mol (6.5%) had not been met in the first trimester. Good first trimester glucose control did not modify the rates of adverse outcomes if HbA1c was >42 mmol/mol (6.0%) in the third trimester. Less tight glycaemic control, for example due to high frequency of severe hypoglycaemia in the first trimester, does not lead to increased adverse neonatal events if followed by tight control in the third trimester. Besides glycaemic control, excess weight gain is a modifiable predictor of adverse outcome.

Palliative and End-of-Life Care: Vital Aspects of Holistic Diabetes Care of Older People With Diabetes.

Palliative and end-of-life care and advance care planning are important components of holistic diabetes management, especially for older people with a long duration of diabetes and comorbidities who experience unpleasant symptoms and remediable suffering. Many diabetes clinicians do not have conversations about advance care planning with people with diabetes, often because they are reluctant to discuss these issues and are not familiar with palliative care. This article outlines palliative, terminal, and end-of-life care for older people with type 1 or type 2 diabetes and suggests when to consider changing the focus on tight blood glucose control to a focus on safety and comfort. It proposes strategies to incorporate palliative and end-of-life care into personalized holistic diabetes care, determined with older people with diabetes and their families through shared decision-making.

51-LB: Young Adults with T1DM: Is Fear a Mediator between Self-Efficacy and Quality of Life?

It has been reported that the many demands of young adulthood in addition to the complex treatment regimen required to manage T1DM impacts quality of life (QoL). It has also been stated in the literature that self-efficacy (SE), fear of complications (FOC) and fear of hypoglycemia (FOH) are predictive of quality of life. However, is fear a mediator in the relationship between SE and QoL? The literature to no extent has reported on whether FOC and FOH mediate the relationship between SE and QoL. Therefore, the aim of this study was to determine if fear mediates the relationship between SE and QoL in young adults with T1DM. This descriptive, cross-sectional study examined SE among young adults with T1DM. The subjects included 201 young adults (age: 27.4 ± 5; gender: 163(F) 38 (M); A1C: 7.4 ± 1.5%; age of diagnosis: 14 ± 8 years). The subjects completed a general health survey and six self-report instruments accessed via the web including the Diabetes Knowledge Test (DKT), Hypoglycemia Fear Scale (HFS), the Fear of Complications Questionnaire (FCQ), Self-Efficacy for Diabetes Self-Management (SEDM), the Diabetes Behavior Rating Scale (DBRS), the Diabetes Quality of Life Measure (DQoL). This study explored the relationship between SE and QoL and found the FOC and FOH significantly mediated the relationship between SE and QoL (p&amp;lt;.000). This study suggests that although the higher ones SE is, the higher the reported QoL is, FOC and FOH impact this relationship when present. The young adults in this study reported a high level of fear centered around complications from their diabetes as well as fear of hypoglycemia in trying to maintain tight glucose control. Therefore, it is important for researchers and clinicians working to improve QoL in young adults to consider mediating factors such as FOC and FOH when designing interventions aimed to impact QoL. Disclosure D.A. Kent: None. C.G. Park: None. C. Fritschi: None. L.T. Quinn: None.

1295-P: Newly Diagnosed Pediatric Patients with Type 1 Diabetes Show Steady Decline in Glucose Time-in-Range (TIR) over 1 Year: Pilot Study

Optimal glycemic control is associated with improved T1D outcomes. However, in the U.S. over the last decade, glycemic control has worsened. We aimed to monitor glucose time-in-range (TIR) in the first year after diagnosis in pediatric T1D to identify the time when glucose control worsens. Newly diagnosed patients (N=67) with T1D were commenced on continuous glucose monitoring (CGM). Data was uploaded to Dexcom Clarity and analyzed retrospectively. Sample size differences at each time period vary due to patient enrollment start dates. All data was analyzed by mixed model and Tukey’s multiple comparison test. In 67 children (mean age 10±5 yrs, A1c at onset 12.1±1.9%) glucose TIR decreased from 64±21% to 55±18% at 10±9 days to 361±23 days post-diagnosis (P=0.03, Table). Mean glucose increased from 146±28 mg/dL at nadir to 172±29 mg/dL at 361±23 days post-diagnosis (P=0.001). CGM wear time also increased from 83±20% to 95±9% at 10±9 days to 361±23 days post-diagnosis (P=0.04). Time spent &amp;lt;70 mg/dL was 2±3% throughout. Newly diagnosed pediatric T1D patients continue to wear CGM throughout the first year of diagnosis. The apparent increase in mean CGM glucose and decrease in TIR as early as 205±9 days post-diagnosis presents an opportunity for more frequent monitoring and unified education by healthcare providers to target tighter glucose control for this population. Disclosure D. Zaharieva: Speaker’s Bureau; Self; Ascensia Diabetes Care, Insulet Corporation, Medtronic. P. Prahalad: None. A. Addala: None. D. Scheinker: None. M. Desai: None. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ. B. Leverenz: None. D.M. Maahs: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S. Consultant; Self; Abbott, Sanofi. Research Support; Self; Bigfoot Biomedical, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care.

386-P: Acute Hypoglycemia Does Not Alter Serum Levels of Amyloid-Related Proteins Associated with Dementia

Objective: Hypoglycemia is a common complication of tighter glucose control regimens in type 2 diabetes (T2D) and may increase the risk of dementia, Alzheimer’s disease being the most common form. We measured amyloid-related proteins during induced hypoglycemia in a cohort of subjects with and without T2D, hypothesizing that these protein levels would be further elevated during hypoglycemia in T2D subjects. Methods: A prospective, parallel study was conducted in individuals with T2D (n=23) and controls (n=22). Hypoglycaemia (&amp;lt;2.2mmol/l: &amp;lt;40mg/dl) was achieved by intravenous infusion of soluble insulin. Blood samples were collected at baseline and at 0, 30, 60, 120, 240 minutes and 24 hours following hypoglycaemia and proteomic (Somalogic) analysis of four amyloid-related proteins (Amyloid P component [APCS], Amyloid precursor protein [APP], Pappalysin [PAPPA] and Serum amyloid A1 [SAA1]) at baseline, at hypoglycemia and at 24-hours post-clamp was undertaken. Results: No changes from baseline in serum levels of the four amyloid-related proteins were seen in subjects with or without T2D, either at the time of hypoglycemia or at 24-hours post-clamp. Conclusions: Induced hypoglycemia is not associated with a significant increase in serum levels of amyloid-related proteins. Thus, no clear mechanistic link based on serum proteins between T2D-related hypoglycemic episodes and Alzheimer’s disease emerged from this study, although it is important to consider that protein levels in the cerebrospinal fluid may differ. Disclosure A. Moin: None. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals. S. Atkin: None. A.E. Butler: None.

1159-P: Cost of Achieving A1C Treatment Goals in Patients with Type 2 Diabetes: Results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

American Diabetes Association (ADA) guideline on glycemic control recommends an A1c &amp;lt;7% in most adults with diabetes and 7-8% for those with history of hypoglycemia, limited life expectancy, or comorbid conditions. From 2013-2016, 64% of U.S. adults with diabetes met ADA A1c goals. Using data from the ACCORD trial, we estimated the cost of achieving the two A1c goals, defined as reaching the goal for two consecutive follow-up visits. Costs of the diabetes drugs were estimated from Marketscan data. Costs by baseline A1c levels were estimated using a generalized linear model with Gamma distribution and log link. 3698 participants in the control arm achieved the goal of 7-7.9%, and 4135 in the intervention arm achieved the goal of &amp;lt;7%. Estimated monthly cost increased by baseline A1c level and was higher for achieving A1c&amp;lt;7% than 7-7.9% (Figure). In patients with a baseline A1c of 11%, the estimated cost was $610 per month ($7320 per year) for achieving &amp;lt;7% and $413 per month ($4956 per year) for achieving 7-7.9%. In patients with a baseline A1c level of 9%, the corresponding estimates were $430 per month ($5160 per year) and $266 per month ($3192 per year). Our study provides critical cost estimates needed for assessing the cost-effectiveness of tighter glucose control in the U.S. Disclosure P. Zhang: None. H. Shao: None. A. Bertoni: None. L. Lovato: None. H. Chen: None.

High-sensitivity C-reactive protein, Malondialdehyde and their association with Glycated hemoglobin (HbA1c)in type 2 diabetes patients

Type 2 diabetes mellitus is a major public health problem worldwide and accompanied by enduring vascular complications, which leads to morbidity and mortality. Inflammation play major role in the pathogenesis of type 2 diabetes mellitus. High sensitivity C-reactive protein is an acute phase protein synthesized by the liver and has been revealed as sensitive, systemic inflammatory marker . Oxidative stress, low grade systemic inflammation contributes to insulin resistance and is linked to the characteristics of metabolic syndrome and type 2 diabetes mellitus. The present study was to evaluate hs - CRP, malondialdehyde (MDA) levels in type 2 diabetic patients compare with healthy controls and correlate these levels with glycated hemoglobin (HbA1C) and insulin resistance Fifty type 2 diabetic patients with age group of 35 to 45 years were selected for this study and 50 age matched healthy subjects were selected as controls. Ser um hs- CRP and insulin was assessed by ELISA, malondialdehyde (MDA) was assessed by Thiobarbituric Acid Reactive Substances (TBARS) method and other routine investigations were carried out by standardized protocols with ERBA EM-360 fully automated analyzer. The mean serum hs - CRP and MDA levels were significantly increa sed in type 2 diabetic patients com pared with healthy controls. Hs-CRP and MDA levels w ere shown significant positive correlation with glyc osylated hemoglobin (HbA1C), insulin resistance, triglycerides and negative correlation with HDL cholesterol. Elevated hs - CRP, MDA levels are potentially important diagnostic markers for the assessment of endothelial dysfunction in type 2 diabetic patients. Tight blood glucose control, regular monitoring of hs-CRP, MDA levels within normal range might be useful for reduction of vascular complications in type 2 diabetic patients.