American Diabetes Association Definition Research Articles

Diabetes remission in drug-naïve patients with type 2 diabetes after dorzagliatin treatment: A prospective cohort study.

To investigate the post-treatment effect of dorzagliatin in drug-naïve patients with type 2 diabetes (T2D) regarding the achievement of stable glycaemic control and drug-free diabetes remission. Patients who completed dorzagliatin treatment in the SEED trial and achieved stable glycaemic control were enrolled in this 52-week study without any antidiabetic medication. The primary endpoint was the diabetes remission probability at week 52 using the Kaplan-Meier method. The potential factors that contribute to stable glycaemic control and diabetes remission based on the characteristics of patients before and after treatment with dorzagliatin were analysed. A post hoc sensitivity analysis of diabetes remission probability using the American Diabetes Association (ADA) definition was conducted. The Kaplan-Meier remission probability was 65.2% (95% CI: 52.0%, 75.6%) at week 52. Based on the ADA definition, the remission probability was 52.0% (95% CI: 31.2%, 69.2%) at week 12. The significant improvements in the insulin secretion index ΔC30/ΔG30 (41.46 ± 77.68, P = .0238), disposition index (1.22 ± 1.65, P = .0030), and steady-state variables of HOMA2-β (11.49 ± 14.58, P < .0001) and HOMA2-IR (-0.16 ± 0.36, P = .0130) during the SEED trial were important factors in achieving drug-free remission. A significant improvement in time in range (TIR), a measure of glucose homeostasis, in the SEED trial from 60% to more than 80% (estimated treatment difference, 23.8%; 95% CI: 7.3%, 40.2%; P = .0084) was observed. In drug-naïve patients with T2D, dorzagliatin treatment leads to stable glycaemic control and drug-free diabetes remission. Improvements in β-cell function and TIR in these patients are important contributors to diabetes remission.

Prediabetes as atherapeutic challenge in internal medicine

The term prediabetes describes afasting blood glucose level that is elevated but not yet in the diabetic range, ablood glucose level that is elevated after 120 min in astandard 75‑g oral glucose tolerance test, or both. The American Diabetes Association definition also includes glycated hemoglobinA (HbA1c). The incidence of prediabetes is rapidly increasing. Progression from normal glucose tolerance to diabetes is acontinuous process. Insulin resistance and insulin secretory dysfunction, the simultaneous presence of which characterizes manifest diabetes, are already present in the prediabetic stage. Prediabetes is associated with an increased risk of diabetes; however, by no means all people with prediabetes go on to develop diabetes. Nevertheless, the identification of an increased risk of diabetes is still relevant insofar as it requires the adoption of diabetes prevention measures. Structured lifestyle intervention has been shown to be the most effective strategy for treating prediabetes. To increase its efficiency, it should, as far as possible, be made exclusively available to those people on whom it is most likely to confer abenefit. This would make it necessary to stratify people with prediabetes according to their risk profile. In apopulation of people at increased risk of diabetes (Tübingen Diabetes Family Study), acluster analysis was performed, resulting in six clusters/subgroups. Within these, three high-risk subgroups were identified: Two of these risk groupsshow predominant insulin secretory dysfunction or predominant insulin resistance and high diabetes and cardiovascular risk. The third group shows ahigh risk of nephropathy and high mortality, but acomparatively lower diabetes risk. In general, prediabetes cannot yet be treated in atargeted pathophysiologically oriented manner. The new classification of prediabetes-based on pathophysiology-is now opening up new avenues for diabetes prevention. Current and future studies should confirm the assumption that the effectiveness of established, or not yet established, preventive measures depends on the respective subgroup.

Pre-transplant HbA1c and risk of diabetes mellitus after kidney transplantation: a single center retrospective analysis.

Post-transplant diabetes mellitus occurs in 10-40% of kidney transplant recipients and is associated with increased risk ofdevelopingcardiovascular diseases. Early identification of patients with a higher risk of developing diabetescould allow to take timely measures. However, no validated model exists to predict the risk of post-transplant diabetes mellitus. This retrospective study includes 267 adult patients who underwent kidney transplantation at the Antwerp University Hospital between January 2014 and August 2021. Post-transplant diabetes mellitus was diagnosed based on the American Diabetes Association definition at 3months post-transplant. First, a logistic regression analysis was used to identify predictors for post-transplant diabetes mellitus. Second, criteria to identify patients with a high risk (> 35%) of developing post-transplant diabetes mellitus at 3months were established. At 3months post-transplantation, 54 (20.2%) patients developed post-transplant diabetes mellitus. Univariable analysis showed that age, body mass index and HbA1c on the day of transplantation were associated with post-transplant diabetes mellitus. However, in a multivariable model with the same parameters, only HbA1c remained statistically significant. An absolute increase in HbA1c of 0.1% increases the odds for developing post-transplant diabetes mellitus by 28% (95% confidence interval 1.15-1.42). An HbA1c level ≥ 5.3% at transplantation, regardless of age or body mass index, is sufficient to identify patients with a post-transplant diabetes mellitus risk of ≥ 35% with a positive predictive value of 39% and a negative predictive value of 88%. The HbA1c value at transplantation was the strongest predictor for post-transplant diabetes mellitus at 3months post-transplant. Furthermore, at least in our population,a pre-transplant HbA1c of ≥ 5.3% can be usedas an easy tool to identify patients at high risk of early post-transplant diabetes mellitus.

Abstract 12593: Type 2 Diabetes Mellitus Polygenic Score Predicts New Onset Diabetes in Patients With Established Atherosclerotic Cardiovascular Disease: A FOURIER Sub-Study

Introduction: Polygenic scores (PS) have been created to predict the risk of developing type 2 diabetes (T2D). We tested whether a contemporary T2D PS predicts new-onset T2D in individuals with established atherosclerotic cardiovascular disease (ACSVD) and across a range of HbA1c and BMI levels. Methods: We analyzed individuals without T2D at baseline with available genotyping data from the FOURIER trial. Genetic risk was characterized using a PS for T2D based on 554 previously identified genome-wide significant single nucleotide polymorphisms. PS was analyzed continuously and categorized as high (top 20%) vs. low (bottom 80%). New-onset T2D was pre-specified and adjudicated centrally according to the American Diabetes Association definitions. HRs were calculated and adjusted for baseline age, sex, BMI, HbA1c, SBP, DBP, HDL-C, and triglycerides. Results: The 9115 participants in this study had mean age of 63±9 yrs and 22.5% were women. Mean HbA1c and BMI were 5.6±0.4% and 28.7±5 kg/m 2 , respectively. A total of 641 new-onset diabetes cases occurred over a median of 2.3 years of follow up. T2D PS significantly predicted new-onset T2D (adjusted HR per 1-SD increase 1.13 95% CI 1.04-1.23, P=0.006). The rates of new-onset T2D in the high and low genetic risk categories were 10.8% vs. 6.6 %, respectively (adjusted HR 1.41 95% CI 1.18-1.69, P&lt;0.001, Panel A). The predictive strength of high genetic risk for T2D appeared strongest in those without key clinical risk factors, namely, those without pre-diabetes [HR 2.01 (1.03-3.89); Panel B] and those with normal weight [HR 2.77 (1.65-4.66); Panel C]. There was no treatment interaction with evolocumab for new-onset T2D. Conclusions: Within a relatively short follow up, we found that a contemporary T2D PS strongly predicted new-onset T2D in patients with established ASCVD. This genetic risk appeared more discriminatory in those lacking traditional clinical risk factors.

RF28 | PSUN184 New American Diabetes Association Definition of Diabetes Remission Does not Correlate with Time in Remission in Ketosis-Prone Diabetes

Abstract Introduction Approximately 50% of obese Black patients presenting with diabetic ketoacidosis (DKA) at new-onset of diabetes have immunologic and metabolic features of type 2 diabetes, also called ketosis-prone diabetes (KPDM). With intensive insulin treatment, ∼70% have improvements in beta-cell function and insulin sensitivity and achieve diabetes remission. The definition of remission in KPDM has been heterogeneous with our group defining remission as HbA1c &amp;lt; 7%, fasting blood glucose (BG) &amp;lt; 130 mg/dl and random BG &amp;lt; 180 mg/dl while off insulin injections for at least 1 week. In 2021, the American Diabetes Association (ADA) consensus recommended that the definition of diabetes remission as HbA1c &amp;lt; 6.5% or a fasting BG &amp;lt; 126 mg/dl while off medications for &amp;gt; 3 months. We hypothesized that patients who achieved the more intensive ADA definition of remission (HbA1c &amp;lt; 6.5%) will have longer time in remission compared to our previous non-intensive definition of remission (HbA1c 6.5-7%). Methods Forty obese Black patients (BMI ≥ 28 kg/m2) with newly diagnosed diabetes and unprovoked DKA had intensive insulin therapy until HbA1c &amp;lt; 7% without insulin therapy for at least one week. Patients were followed until hyperglycemia relapse (HbA1c &amp;gt; 6.5% or fasting BG &amp;gt; 126 mg/dl and/or requiring antidiabetic medications). Baseline characteristics and clinical time to hyperglycemia relapse-free survival were compared between patients with HbA1c &amp;lt; 6.5 (n= 24) and HbA1c 6.5-7% (n=16). Results Age, sex, family history of type 2 diabetes, BMI, HbA1C, weight change and insulin doses received between the two groups (HbA1c &amp;lt; 6.5 vs 6.5-7%) did not differ significantly. Median follow-up overall was 404 days with a range of 7-1099 days. In patients that experienced a hyperglycemia relapse, bivariate analysis shows that median days to hyperglycemia relapse was longer in HbA1c &amp;lt; 6.5% (411 days, range (17-804) vs HbA1c 6.5-7% (126 days, range (7-391), p= 0.05) but without a statistical difference. Survival analysis showed that time in remission did not statistically differ between the two groups (log rank, p=0.6853). Conclusion In obese Black patients with KPDM, HbA1c &amp;lt; 6.5% at time of insulin discontinuation does not prolong diabetes compared to patients that achieved HbA1c 6.5-7%, suggesting that predictors of prolonged remission may differ among diverse populations with diabetes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:44 p.m. - 12:49 p.m.

Predictive Efficiency of Prediabetes for Diabetes Among Chinese Middle-Aged and Older Populations: a 5-Year National Prospective Cohort Study.

Limited studies have explored the predictive efficiency of prediabetes based on two definitions for diabetes among Chinese middle-aged and older populations with prediabetes. To evaluate the predictive efficiency of prediabetes based on two definitions for diabetes and the clinical and public health benefit in Chinese middle-aged and older populations. A 5-year cohort study from the China Health and Retirement Longitudinal Study. A total of 5208 participants who had blood sample data at baseline in 2011. The exposure was prediabetes based on American Diabetes Association (ADA) and World Health Organization (WHO) definition. The main outcome was incident diabetes. The ability of prediabetes for predicting diabetes was assessed by sensitivity, specificity, positive predictive value, and negative predictive value. Cox proportional hazards regression was used to explore the associations between prediabetes and the 5-year risk of diabetes and all-cause mortality. Among those with prediabetes according to the ADA definition, only 426 (15.45%) with baseline prediabetes progressed to total diabetes, while according to the WHO definition, 208 (21.89%) progressed to total diabetes. In terms of the ability of predicting the incident total diabetes in 5 years, the ADA definition has a higher sensitivity than the WHO definition (70.76% versus 34.55%, P < 0.001), while the WHO definition has a higher specificity than the ADA definition (84.09% versus 49.35%, P < 0.001). Positive predictive values based on the two definitions were low (< 24%); negative predictive values were high (> 90%). Neither definition of prediabetes is robust for predicting diabetes development in Chineses middle-aged and older populations.

1323-P: Insulin Secretion at Diabetes Remission in Obese Blacks Presenting with Diabetic Ketoacidosis

In obese Blacks presenting with diabetic ketoacidosis (DKA) at new-onset of diabetes, intensive insulin treatment improves β-cell function so that ˜70% achieve near-normoglycemia remission (HbA1c &amp;lt; 7%, fasting blood glucose [BG]&amp;lt;130 mg/dl while off insulin for ≥1 week) and maintain glycemic control without medications. The 2021 American Diabetes Association (ADA) consensus defined diabetes remission as HbA1c &amp;lt;6.5% or BG 126 mg/dl while off medications for &amp;gt;3 months. It is unknown whether glycemic measures and insulin secretion differ between patients who achieve the new ADA definition of remission (intensive remission [IR]) compared to near-normoglycemia remission (non-intensive remission [NIR]) .We performed 75-g, 240-minute (min) oral glucose tolerance tests (OGTT) in 13 obese (BMI&amp;gt;30 kg/m2) Blacks who presented with DKA (BG&amp;gt;250 mg/dl, HCO3&amp;lt;18 mEq/L, pH&amp;lt;7.3) and achieved remission from insulin. Glucose and C-peptide levels were measured at -15, 0, 10, 20, 30, 60, 90, 120, 180 and 240 min during OGTT. Insulin secretory rates (ISR) , first phase (Φdynamic) , second phase (Φstatic) and total (Φtotal) insulin secretion were calculated using a previously published model. Data was compared between IR, (HbA1c&amp;lt;6.5%, n=7) vs. NIR, (HbA1c≥6.5%, n=6)) There were no differences in age, BMI and mean BG levels during OGTT between groups. Model estimates of Φdynamic were significant (P=0.046) and 5-fold higher in IR (Marginal Mean: 514.00, 95% CI: 134.53-893.47 [109]) vs. NIR (Marginal Mean: 100, 95% CI: 100.45, 95% CI: -41.97-242.87 [109]) . Estimates of Φstatic were significant (P=0.022) and 2-fold higher in the IR (Marginal Mean: 31.84, 95% CI: 19.88-43.80 [min-1]) vs. NIR (Marginal Mean: 14.59, 95% CI: 6.79-22.39 [min-1]) with no significant (P=0.058) group differences between Φtotal.In comparison to NIR, obese Blacks with IR exhibit marked preservation of β-cell function suggesting that HbA1c &amp;lt;6.5% should be targeted for insulin remission after presentation with DKA. Disclosure D.Stefanovski: None. O.Oladejo: None. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. P.Vellanki: n/a. Funding NIH/NIDDK K23 DK11324-01A1

Association of chemotactic cytokine receptor 5 (CCR5) gene polymorphism (59029 A/G, rs1799987) with diabetic kidney disease in patients with type 2 diabetes from Poland.

Diabetic kidney disease (DKD) pathogenesis is multifactorial and is a combination of metabolic, genetic, and environmental factors. Due to a long period of asymptomatic course, it is often diagnosed late when advanced stages of the disease are present. Among patients with diabetes, the presence of chemotactic cytokine receptor 5 (CCR5) gene polymorphism is suspected to be associated with the risk of DKD occurrence; however, the results of the research conducted so far are inconclusive. The aim of this study was to evaluate the CCR5 gene polymorphism (rs1799987, 59029 A/G) association with DKD among patients with type 2 diabetes mellitus (T2DM), who are residents of the Upper Silesia region of Poland. CCR5 gene polymorphism (rs1799987, 59029 A/G) was assessed among consecutive patients with type 2 diabetes mellitus (T2DM) treated in a single outpatient diabetology clinic in Upper Silesia, Poland. Its association with DKD was examined. Additionally, selected clinical and demographic data were included in the analysis. Among 467 eligible study patients, there was no association between examined CCR5 gene polymorphism and the presence of DKD in relation both to the American Diabetes Association definition (p = 0.6) and to the National Kidney Foundation definition (p = 0.3) of this complication. The presented study did not confirm the association between the examined gene polymorphism and the risk of DKD; further studies in this area are needed in order to establish or explicitly exclude this association.

Brain oxidative stress and cognitive function in older adults with diabetes and pre-diabetes who are at risk for dementia

AimsDiabetes is an established risk factor for dementia. This study aimed to examine the relationship between various cognitive domains, brain oxidative stress and markers of diabetes in older adults at risk for dementia. MethodsOlder adults at risk for dementia underwent comprehensive neuropsychological and medical assessment. At risk was defined as those with subjective and/or objective cognitive impairment. Pre-diabetes and type 2 diabetes were defined using American Diabetes Association definitions for fasting blood glucose and HbA1c. Brain oxidative stress as indicated by glutathione (GSH) was assessed via magnetic resonance spectroscopy in the anterior cingulate cortex. ResultsOne-hundred and forty-seven older adults completed a neuropsychological assessment and fasting blood sample with 63 also undergoing magnetic resonance spectroscopy. Those with pre-diabetes/diabetes according to FBG had impaired memory retention, set-shifting and response inhibition, compared to those with normal blood glucose. In contrast, there were no significant differences in any cognitive outcome using the HbA1c definition. Increasing glucose and HbA1c levels were associated with reduced GSH concentration in the anterior cingulate. ConclusionsThis study demonstrates that in older adults at risk for dementia, having pre-diabetes or diabetes is associated with impaired memory and executive dysfunction. It also highlights the potential role of oxidative stress as a pathophysiological mechanism that may underpin the link between diabetes and cognitive dysfunction.

Prediabetes and the risk of heart failure: A meta-analysis.

To determine the role of prediabetes in the incidence of heart failure (HF). We searched electronic databases (PubMed, Embase, Google Scholar and OpenGrey) for studies up to 31 December 2020. Studies were included for meta-analysis if they reported adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the risk of HF for prediabetes compared with normoglycaemia. Prediabetes was defined as impaired fasting glucose (IFG) according to the World Health Organization (WHO) criteria (IFG-WHO), or according to the American Diabetes Association (ADA) definition (IFG-ADA), impaired glucose tolerance (IGT), raised HbA1c according to the ADA criteria (HbA1c-ADA), or according to the International Expert Committee (IEC) recommendation (HbA1c-IEC). A total of 15 studies comprising 9,827,430 individuals provided data for this analysis. The median follow-up duration of the included studies was 8.0 years. Compared with normoglycaemia, prediabetes was associated with an increased risk for HF: IFG-ADA (RR: 1.09, 95% CI: 1.05-1.13), IFG-WHO (RR: 1.18, 95% CI: 1.07-1.30), IGT (RR 1.58, 95% CI 1.04-2.39), HbA1c-ADA (RR 1.28, 95% CI 1.16-1.41) or HbA1c-IEC (RR 1.40, 95% CI 1.09-1.79), respectively. Prediabetes is associated with an increased risk of HF. Future studies are needed to evaluate effective treatments for prediabetes to prevent the development and progression of HF.

Regression to the Mean Contributes to the Apparent Improvement in Glycemia 3.8 Years After Screening: The ELSA-Brasil Study.

OBJECTIVEGlycemic regression is common in real-world settings, but the contribution of regression to the mean (RTM) has been little investigated. We aimed to estimate glycemic regression before and after adjusting for RTM in a free-living cohort of adults with newly ascertained diabetes and intermediate hyperglycemia (IH).RESEARCH DESIGN AND METHODSThe Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a cohort study of 15,105 adults screened between 2008 and 2010 with standardized oral glucose tolerance test and HbA1c, repeated after 3.84 ± 0.42 years. After excluding those receiving medical treatment for diabetes, we calculated partial or complete regression before and after adjusting baseline values for RTM.RESULTSRegarding newly ascertained diabetes, partial or complete regression was seen in 49.4% (95% CI 45.2–53.7); after adjustment for RTM, in 20.2% (95% CI 12.1–28.3). Regarding IH, regression to normal levels was seen in 39.5% (95% CI 37.9–41.3) or in 23.7% (95% CI 22.6–24.3), depending on use of the World Health Organization (WHO) or the American Diabetes Association (ADA) definition, respectively; after adjustment, corresponding frequencies were 26.1% (95% CI 22.4–28.1) and 19.4% (95% CI 18.4–20.5). Adjustment for RTM reduced the number of cases detected at screening: 526 to 94 cases of diabetes, 3,118 to 1,986 cases of WHO-defined IH, and 6,182 to 5,711 cases of ADA-defined IH. Weight loss ≥2.6% was associated with greater regression from diabetes (relative risk 1.52, 95% CI 1.26–1.84) and IH (relative risk 1.30, 95% CI 1.17–1.45).CONCLUSIONSIn this quasi–real-world setting, regression from diabetes at ∼4 years was common, less so for IH. Regression was frequently explained by RTM but, in part, also related to improved weight loss and homeostasis over the follow-up.

Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: comparison between American Diabetes Association and World Health Organization diagnostic criteria

IntroductionPre-diabetes, a status conferring high risk of overt diabetes, is defined differently by the American Diabetes Association (ADA) and the WHO. We investigated the impact of applying definitions of pre-diabetes...

Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study.

Multifactorial pathogenesis of diabetic kidney disease (DKD) consists of a combination of metabolic, environmental, and genetic factors. A genome-wide association study has shown that ELMO1 is a candidate gene for DKD occurrence and progression. The aim of this study was to assess the association of a single nucleotide polymorphism (rs741301) of the ELMO1 gene with DKD in Polish patients with type 2 diabetes (T2DM). This was a case/control study of 272 T2DM patients with or without DKD. Patients were divided into groups depending on DKD definition according to the American Diabetes Association (ADA) and the National Kidney Foundation (NKF). The association of the rs741301 polymorphism with DKD was assessed in the whole study group as well as in the subgroups stratified according to the presence of DKD. There was no association between rs741301 polymorphisms and the presence of DKD in relation to the ADA definition (p = 0.6) or the NKF definition (p = 0.5) of DKD and with estimated glomelural filtration rate (eGFR) value reflecting the stage of the chronic kidney disease (p = 0.8). Even though the results of this study are negative, there is still a great need for larger studies assessing the genetic susceptibility to DKD to identify patients who are particularly prone to this complication.

Post-Pancreatectomy Diabetes Index: A Validated Score Predicting Diabetes Development after Major Pancreatectomy

Literature is varied regarding risk factors associated with diabetes development after major pancreatic resection. The aim was to develop and validate a scoring index that preoperatively predicts the development of diabetes after pancreaticoduodenectomy and distal pancreatectomy. In this prospective study, perioperative fasting and postprandial (OGTT, oral glucose tolerance test) plasma glucose, glycated hemoglobin A1c (HbA1c), insulin, and c-peptide were measured in select consecutive patients undergoing pancreaticoduodenectomy and distal pancreatectomy by the senior author, from 2007 to 2018. American Diabetes Association definitions were used for glycemic classifications. Statistical analyses included multivariate generalized estimated equation for factor identification and variable weighting; area under the receiver operating curve (ROC) c-statistic for predictive ability, and survival analysis risk score grouping. Of 1,083 included patients with preoperative normoglycemia (253; 23.4%), prediabetes (362; 33.4%), and diabetes (468; 43.2%), the overall postoperative incidence of each diabetic class at 120 months was 152 (14.0%), 466 (43.0%), and 465 (42.9%), respectively. The development and validation groups included 1,023 and 60 patients, respectively. Five factors were identified predicting diabetes development, with a total possible score of 8. The C-statistics for development and validation groups were 0.727 (CI 0.696 to 0.759, p<0.001) and 0.823 (CI 0.718 to 0.928, p < 0.001), respectively. At a cut point of 3(sensitivity 0.691, specificity 0.644) the Post-pancreatectomy Diabetes Index (PDI) independently predicted diabetes in development (odds ratio [OR] 4.298, relative risk [RR] 2.486, CI 1.238 to 5.704, p < 0.001) and validation (OR 6.970, RR 2.768, CI 2.182 to 22.261, p < 0.001) groups. The PDI similarly predicted pre-diabetes in development (OR 1.961, RR 1.325, CI 1.202 to 2.564, p < 0.001) and validation (OR 4.255, RR 1.798, CI1.247 to 14.492, p= 0.021) groups. The Post-pancreatectomy Diabetes Index predicts the development of diabetes and pre-diabetes in patients undergoing major pancreatectomy using routine endocrine laboratories and pre-surgical clinical data.

Heart failure with insulin degludec versus glargine U100 in patients with type 2 diabetes at high risk of cardiovascular disease: DEVOTE 14

BackgroundHeart failure (HF) is a common cardiovascular complication of type 2 diabetes (T2D). This secondary analysis investigated baseline factors and treatment differences associated with risk of hospitalization for HF (hHF), and the possible association between severe hypoglycemia and hHF.MethodsDEVOTE was a treat-to-target, double-blind cardiovascular outcomes trial in patients (n = 7637) with T2D and high cardiovascular risk randomized to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). The main endpoint of this secondary analysis was time to first hHF (standardized MedDRA Query definition). Severe hypoglycemia was adjudicated (American Diabetes Association definition). The main endpoint and the temporal association between severe hypoglycemia and hHF were analyzed with a Cox proportional hazards regression model. Predictors of time to first hHF were identified using baseline variables.ResultsOverall, 372 (4.9%) patients experienced hHF (550 events). There was no significant difference in the risk of hHF between treatments (hazard ratio [HR] 0.88 [0.72;1.08]95% CI, p = 0.227). Prior HF (HR 4.89 [3.90;6.14]95% CI, p ≤ 0.0001) was the strongest predictor of future hHF events. The risk of hHF significantly increased after (HR 2.2), and within a week after (HR 11.1), experiencing a severe hypoglycemic episode compared with before an episode.ConclusionsIn patients with T2D and high cardiovascular risk there were no treatment differences in terms of hHF. Prior HF was the strongest predictor of future hHF events, and there was an association between severe hypoglycemia and subsequent hHF. Further research should evaluate whether the risk of hHF can be modified by treatments aimed at reducing hypoglycemia.Trial Registration NCT01959529

Type 2 Diabetes Mellitus (T2DM) "Remission" in Non-bariatric Patients 65 Years and Older.

Objective: To analyze the factors associated with type 2 diabetes mellitus (T2DM) “remission” in non-bariatric Medicare patients 65 years and older.Research Design and Methods: A retrospective cohort analysis of a Medicare Advantage health plan was conducted using administrative data. An individual was identified as T2DM if the individual had: ≥ 2 medical claims for T2DM coded 250.xx excluding type 1 diabetes; or ≥ 2 pharmacy claims related to T2DM; or ≥ 2 combined medical claims, pharmacy claims for T2DM in 12 months. A T2DM individual was in “remission” if they had no T2DM related claims for more than 12 months continuously. This is different from the standard American Diabetes Association (ADA) definition of remission which includes HbA1c values and hence is represented in quotation (as “remission”). 10,059 T2DM individuals were evaluated over a period of 8 years from 2008 to 2015. Cox proportional hazards was used to identify significant variables associated with T2DM “remission.”Results: 4.97% of patients studied met the definition of T2DM “remission” in the study cohort. After adjusting for covariates this study found a number of variables associated with T2DM “remission” that were not previously reported: no statin use; low diabetes complications severity index score; no hypertension; no neuropathy; no retinopathy; race (non-white and non-African American); presence of other chronic ischemic heart disease (IHD) and females (p < 0.05).Conclusion: T2DM “remission” in Medicare patients 65 years and older is observed in a community setting in a small proportion of non-bariatric patients.

Dysglycemia after distal pancreatectomy: Results of a 10-year series using prospective endocrine evaluation

Background: Distal pancreatectomy (DP) is a commonly utilized procedure by hepatopancreatobiliary surgeons for the management of pancreatic body and tail lesions. While associated with low mortality rates, the development of postoperative diabetes represents a challenge to both patient and physician. Limited literature is available regarding the development or reversibility of impaired glucose tolerance and/or type-II diabetes mellitus (IGT/DM) in this patient population. The primary aim was to define the post-surgical clinical evolution of IGT/DM and the association with the pre-operative glycemic profile of patients following DP. Methods: In this prospective study, pre and postoperative fasting and 2-hour postprandial oral glucose challenge testing (OGTT) laboratories including plasma glucose, glycated hemoglobin (A1c), insulin, and c-peptide were measured in consecutive non-diabetic patients undergoing DP by the senior author from 2007 to 2017. Benign, pre-malignant, and malignant indications were included. Differences in postprandial chemistries from fasting values are denoted with delta (Δ) prefix. American Diabetes Association definitions were used for glycemic classifications. Univariate and multivariate risk factor analysis was performed overall and for individual diabetic classes in determining the development of IGT/DM. Kaplan-Meier survival curves were constructed for onset to endocrine and exocrine dysfunctions, and patient survival. Results: Among 216 patients included (mean age 63 ± 13.7 years, 71.3% Caucasians, 56% female, mean BMI 28.5 m/kg2); 29.6% (n = 64), 31% (n = 67), 39.5% (n = 85) were pre-operatively diagnosed with no-diabetes (No-DM), with pre-diabetes (Pre-DM), or diabetes (DM), respectively. At 120-months of follow-up, 17 (13.5%), 86 (39.0%), and 115 (53.2%) patients were classified as No-DM, Pre-DM or DM, respectively. Based on preoperative laboratories, patients with Pre-DM had 85% increased risk of developing post-op dysglycemia (RR = 1.85, CI 1.126-3.041, p = 0.021), compared to those with no-DM, while 80% (68/85) patients with preoperative DM retained there IGT/DM status postoperatively. Patients developing post-operative IGT/DM demonstrated higher preoperative fasting glucose, OGTT-glucose, and A1c (all p ≤ 0.010), and a greater Δglucose compared to those classified as Pre-DM and No-DM, respectively (Δ64.5±38.0 vs Δ32.5±37.9 vs Δ4.33 ± 6.03; p 130, Δglucose >30, A1c >6.0, HOMA-IR ≥2, and surgical pathology of chronic pancreatitis as risk factors for developing IGT/DM. In patients with No-DM preoperatively, a HOMA-IR >1 was identified as a risk factor for development of postoperative IGT/DM after adjusting for multiple co-variates. For patients classified with DM preoperatively by fasting or OGTT chemistries but whom still retained an A1c ≤ 6.4, multivariate analysis identified an A1c ≤ 6.1 and the absence of a history of smoking as predictors of these diabetics returning to euglycemia postoperatively. There was no association between advancing age, BMI, race, or pancreatic ductal adenocarcinoma and post-operative IGT/DM development. Conclusion: Approximately 40% and 53% of patients undergoing distal pancreatectomy develop post-operative IGT and DM, respectively over 10-years. Higher pre-op fasting glucose, OGTT glucose, A1c, HOMA-IR, and chronic pancreatitis are significant risk factors for development of diabetes. Alternatively, diabetics diagnosed by fasting or OGTT glucose values but non-diabetic A1c values, a preoperative A1c ≤ 6.1 and absence of a history of smoking may indicate postoperative conversion to a euglycemic state. The development of new-onset IGT/DM or persistent diabetes diagnosis following distal pancreatectomy is multifactorial and assessment of pre-operative glycemic status is paramount when counseling patients on their risk of developing postoperative IGT/DM.

Development of Diabetes after Pancreaticoduodenectomy: Results of a 10-Year Series Using Prospective Endocrine Evaluation

Limited literature is available on the development of impaired glucose tolerance and diabetes mellitus after pancreaticoduodenectomy. The primary aim was to define the diabetic phenotype and correlate preoperative glycemic laboratory results to new-onset diabetes after pancreaticoduodenectomy. In this prospective study, perioperative fasting and postprandial (oral glucose tolerance test) plasma glucose, glycated hemoglobin, insulin, and c-peptide were measured in consecutive patients undergoing pancreaticoduodenectomy by the senior author from 2006 to 2017. American Diabetes Association definitions were used for glycemic classifications. Multivariate risk factor analysis was performed. Of 774 identified patients, 371 diabetics were excluded and 403 patients were included: 167 and 236 were preoperatively classified as nondiabetic and prediabetic, respectively. The incidence rates of diabetes at 120 months post pancreaticoduodenectomy were 9.0% (nondiabetics), 22.0% (prediabetics), and 16.6% (overall). Patients in whom diabetes developed demonstrated a 3-fold larger difference between oral glucose tolerance test and fasting glucose (Δ), and 2-fold larger Δinsulin and Δc-peptide values. Tiered multivariate analysis identified glycated hemoglobin >5.4% with a relative risk (RR) of 2.944 (p= 0.047) as an independent predictor of impaired glucose tolerance and diabetes mellitus. Analysis of patients stratified by preoperative classification identified fasting glucose >95 mg/dL (nondiabetics, RR 1.925; p= 0.002), and glycated hemoglobin ≥5.4% (prediabetics, RR 3.125; p= 0.040) as independent risk factors for diabetes. Compared with nondiabetics, prediabetics classified by any laboratory results demonstrated an RR of 2.471 (p=0.001) for diabetes developing postoperatively. There was no association between primary pathology, advancing age, or BMI and increased risk of diabetes development. Diabetes will develop after pancreaticoduodenectomy in approximately 16.6% of patients. A preoperative glycated hemoglobin >5.4% independently predicts new-onset diabetes. Pre- and postoperative endocrine analysis remains paramount for proper patient risk stratification.

494: Early hemoglobin A1c as a screening test for gestational diabetes among overweight and obese women

Overweight and obese pregnant woman are known to be at increased risk of developing gestational diabetes. However, little is known about early screening in this population. The objective of this study was to determine early (< 20 gestational age) hemoglobin A1c values between overweight and obese pregnant women who develop gestational diabetes (GDM) compared those who do not develop GDM. A case-control study comparing overweight and obese women with GDM to overweight and obese women without GDM (non-GDM) in a 3:1 ratio between 2011 and 2014 at Oregon Health and Sciences University to determine if early hemoglobin A1C (HbA1C; obtained < 20 weeks gestational age) differs between the two cohorts. Chi squared, Pearson correlation, and Wilcoxon rank-sum test were used to compare GDM and non-GDM pregnancies. Receiver Operating Characteristic (ROC) curve was analyzed to plot the true positive rate against the false positive rate for the different possible cut-points of early HbA1C to predict the diagnosis of GDM among overweight and obese women. A total of 443 subjects were analyzed (n=139 cases and n=304 controls). Women with GDM were more likely to be non-white, older in age, multiparous and have a higher pre-pregnancy BMI (see Table). Women with GDM had a significant difference in early HbA1C compared to non-GDM pregnancies (5.6 and 5.3%, P<0.01). Early HbA1C is more significantly correlated with GDM diagnosis than pre-pregnancy BMI (0.34 vs 0.13; p<0.01). The curve point at which the area under the ROC curve was maximized was an early HbA1C of 5.6% with an AUC = 0.725 (see Figure). Overweight and obese women who develop GDM have significantly different HbA1C than non- GDM pregnancies. The mean HbA1C is lower than the American Diabetes Association definition for pre-diabetes. When using A1c as a screening tool, these data suggest lower cut-points should be considered among overweight and obese pregnant women to perform early diagnostic diabetes testing in pregnancy. However, further studies are needed to determine a reliable, predictive HbA1C.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Biological and socioeconomic determinants of prediabetes in youth: an analysis using 2007 to 2011 Canadian Health Measures Surveys

To describe rates of prediabetes among youth in Canada and the associated social and biological characteristics. We analyzed the cross-sectional data from the first (2007-2009) and second (2009-2011) cycles of the Canadian Health Measures Survey (CHMS) for youth aged 6-19 years. Prediabetes was defined using the glycated hemoglobin (A1C) guidelines set out by the American Diabetes Association (ADA) and the Canadian Diabetes Association (CDA) of A1C ranges 5.7-6.4% (38.8-46.4 mmol/mol) and 6.0-6.4% (42.1-46.4 mmol/mol), respectively. An elevated A1C was observed in 22.8% of our sample (n = 3449) based on the ADA definition and 5.2% of youth using the CDA definition. Independent predictors in a fully adjusted model for prediabetes were non-White (odds ratio (OR) 2.62: 95% Confidence intervals 2.05-3.35), obese (OR 1.53: 1.19-1.96), less physically active youth (0.97: 0.95-0.99), and parents with high school education or less (1.34: 1.02-1.74). Moreover, significant regional variations were noted with higher rates for all regions except Ontario. Prediabetes is relatively common in Canada and associated with common biologic and socioeconomic factors. Importantly, regular physical activity was significantly associated with reduced odds of prediabetes. Targeted screening and continued emphasis on physical activity may help curb the increasing rates of prediabetes.