The ADA 2020 virtual poster hall

Visiting the poster hall in the American Diabetes Association annual meeting offers a wonderful opportunity to learn about new aspects of treatment - but, in typical years, seeing >1000 posters is next to impossible. This year there was ample time to browse the virtual poster hall, while sparing wear and tear on the feet! Here are summaries of some of the presentations I found interesting.* Gong et al (1471-P) compared the effect of the lifestyle intervention in the Da Qing study among the 287 vs 289 participants with baseline fasting plasma glucose <100 vs ≥100 mg/dL. Over 30-year follow-up from 1986, the reduction in development of diabetes was 37-46% in those with impaired glucose tolerance but not having impaired fasting glucose, similar to the 47-51% reduction among those with impaired fasting glucose. Identification of prediabetes without use of glucose tolerance testing may then miss a substantial group of persons who benefit from lifestyle intervention. Egan et al (1476-P) reported follow-up of 44 992 nondiabetic adults age 18-65 with at least two fasting glucose measurements from 2005-2017, finding that male sex, increasing age, and higher baseline fasting glucose were associated with greater likelihood of development of diabetes. Nielsen et al (1579-P) analyzed a longitudinal study of US families from 2001-2017, finding that obesity prevalence increased from 21% to 30% and diabetes prevalence increased from 8% to 12% in the population. The identification of type 2 diabetes (T2D) at the earliest stage appears increasingly important. Turning to diabetes among youth, Lawrence et al (1464-P) reported an increase in US type 1 diabetes (T1D) prevalence rates from 1.5 to 1.9 and 2.2 per 1000 population age 0-19 in 2001, 2009, and 2017, respectively, with highest rates among non-Hispanic whites. T2D prevalence rates were 0.3, 0.5, and 0.7 per 1000, with lowest rates among non-Hispanic whites and highest rates among those of non-Hispanic Black and American Indian ethnicity. The concept of “time in range” (TIR), the percentage of continuous glucose monitoring values between 70 and 180 mg/dL (3.9-10 mmoL/L) being a valuable proxy measure of glycemia, is becoming widely accepted. Bergenstal et al (21-LB) showed an association of TIR ≤ 30% with major adverse cardiovascular (CV) events, and of TIR ≥ 70% with reduction in hypoglycemia and microvascular outcomes in 5774 insulin-treated persons with T2D in a CV outcome study (CVOT) comparing insulin degludec with insulin glargine. Ranjan et al (28-LB) studied 26 persons with T1D and microalbuminuria on sensor-augmented insulin pump treatment, finding associations of TIR with reductions both in HbA1c and in urine albumin-creatinine ratio. Jendle et al (975-p) used the Glucose Rate Increase Detector algorithm to define meal times based on continuous glucose monitoring, in conjunction with a connected insulin pen, storing times of insulin bolus dosing in 96 adults with T1D over a total of 2238 days of treatment. Late dosing, taken >60 minutes after meal start, correlated with higher mean and with greater coefficient of variation of the glucose concentration. Edwards (375-P) found negative association of TIR with missed bolus doses, similarly ascertained with a connected insulin pen. Mueller et al (95-LB) reported that the use of a closed-loop technology was associated with improvement in TIR among 1659 insulin pump-treated persons. Soupal (852-P) studied 60 persons with T1D using real-time vs intermittently scanned continuous glucose monitoring, finding that the former system was associated with significantly less hypoglycemia and significantly greater TIR. Brown et al (983-P) reported performance of a closed-loop algorithm using the Omnipod insulin pump and Dexcom 6 continuous glucose monitoring system in 18 adults with well-controlled T1D, finding no hypoglycemia and modest improvement in TIR at 130 and 110 mg/dL (7.2 and 6.1 mmoL/L) glucose targets. Arora and Agrawal (109-LB) studied 500 diabetic persons injecting insulin for at least 2 years, finding lipohypertrophy (LH) on clinical examination in 45%, and on ultrasound imaging in 58%, with 2 of 100 skin and subcutaneous tissue punch biopsies revealing insulin-derived amyloidosis showing positive immunostaining with anti-insulin antibody. Reuse of insulin needles and incorrect site rotation were associated with greater likelihood of LH. Xu et al (674-P) found that 81% of 260 insulin-treated persons had ultrasound evidence of LH, based on the presence of thickening of subcutaneous fat, diffuse areas of increased echogenicity, and nodular hyperechoic foci, with 39% of these missed on physical examination, particularly in persons with high body mass index (BMI). Perez-Nieves et al (1033-P) summarized data from an insurance claims database on insulin use and glucose monitoring from 2009-2018. Insulin pump use increased from about 40% to more than half, and use of insulin vials without pumps decreased from about 40% to <20%, of persons with T1D; disposable pens increased from <40% to ~80% and use of insulin vials without pumps decreased from about 70% to <20% among insulin-treated persons with T2D. Continuous glucose monitoring increased from ~10% to 40% of persons with T1D but was used infrequently among persons with T2D. Höskuldsdottir et al (1975-P) compared 5321 persons with T2D undergoing Roux-en-Y gastric bypass (RYGB) with 5321 controls with T2D in the Swedish hospital admission dataset; RYGB was associated with 41% lower likelihood of development of atrial fibrillation and 73% lower likelihood of development of heart failure over up to 8 years of follow-up. Mingrone et al (121-LB) reviewed the hypothesis that duodenal mucosal hypertrophy accompanies nutrient excess and is a mediator of insulin resistance. In a trial of endoscopic duodenal mucosal resurfacing in 39 persons with T2D, HbA1c decreased from 8.1% by 0.6% and 0.7%, and body weight decreased by 2.4 and 2.1 kg from a baseline of 93 kg, at 24 and 48 weeks, respectively; results in 36 persons undergoing a sham control procedure were not reported. Parks et al (39-LB) reported a meta-analysis of foot ulcer healing among the standard-of-care controls, with offloading, debridement, and dressing changes, in 14 randomized controlled trials of novel approaches, finding that before 1999 24% of wounds healed at 12 weeks, whereas after 2000, 37% healed. Although an improvement, this low rate of healing suggests that better treatment approaches are needed. Petersen (31-LB) reported 3-month follow-up of 216 persons with refractory painful diabetic neuropathy randomized to an implanted spinal cord stimulation device, finding 79% vs 5% of controls having ≥50% pain relief at 3 months and with significant increase in walking distance over 6 minutes. Chen et al (1436-P) analyzed the relationship between self-reported sleep duration and mortality among ~250 000 nondiabetic and ~ 25 000 diabetic persons in the National Health Interview Survey 2004-2013, finding a U-shaped relationship with and without diabetes, with an optimal 7-hour sleep duration. Among persons with diabetes, this was particularly seen with diabetes duration >20 years, and both short (≤5 hours) and long (≥10 hours) sleep duration were associated with CV mortality. Inzucchi et al (132-LB) examined the common clinical issue of the initial fall in estimated glomerular filtration rate (eGFR) with sodium glucose cotransporter-2 inhibitor (SGLT2i) treatment. In the EMPA-REG OUTCOME trial, 28% of those receiving empagliflozin had a >10% initial decline, associated with greater age, lower initial eGFR, and greater level of albuminuria, and with more frequent use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, diuretics, and insulin; 31% had a decline that was <10% of baseline, and only 31% had no decline in eGFR. Only 1.4% of persons receiving empagliflozin (and 0.9% of those receiving placebo) had a >30% initial decline. After the initial decline in the >10% group, eGFR increased toward baseline, and the reduction in cardiovascular death and in nephropathy rates seen with empagliflozin was neither negated nor improved among those with greater initial decline in eGFR. Ferannini et al (139-LB) analyzed associations of baseline metabolites in the CANVAS CVOT, showing that higher free fatty acid (FFA) levels were associated with lower likelihood of development of heart failure, whereas higher lactate and pyruvate were associated with greater development of heart failure. Interestingly, over the first 2 years of the study, FFA levels increased and pyruvate levels decreased with canagliflozin treatment, suggesting that changes in energy metabolism might underlie the CV benefit. Dumartin and Frundi (137-LB) compared 100 people with T2D treated with an SGLT2i in a 28-day in-patient rehabilitation facility with 100 not receiving SGLT2i, matched for age, sex, BMI, and functional status. The SGLT2i group had greater improvement in 6-minute walking distance, in perceived exertion during the 6-minute walk, and in fatigue, intriguing observations suggesting functional benefit. Gautam et al (140-LB) reported a potentially useful observation among 80 postmenopausal women treated with SGLT2i: those using vaginal estrogen had 6% lower rate of urinary infection. SGLT2i have not been shown to be associated with urinary infection in most studies, so that this might simply be an effect of vaginal estrogen per se, but it might be interesting to extend this observation to see whether vulvovaginal candidiasis was similarly reduced. Bethel et al (944-P) presented meta-regression analysis of six glucagon-like peptide-1 receptor agonists (GLP-1RA) CVOTs, showing that greater degrees of reduction in HbA1c were associated with greater likelihood of development of retinopathy, with each 0.1% decrease in HbA1c associated with an 8% increased likelihood of retinopathy, suggesting that rather than being an agent-specific adverse effect, retinopathy status should be considered in all patients when glucose-lowering therapy is intensified. Mody et al (928-P and 929-P), in “real-world” studies, compared 3852 persons initiating dulaglutide with propensity score-matched persons initiating semaglutide, and 1879 persons initiating dulaglutide with propensity score-matched persons initiating exenatide, showing 6-month adherence rates of 75%, 67%, and 63% with the three agents, with similar patterns among persons less than and greater than age 65, and with or without baseline insulin use. Among 27 038 persons initiating dulaglutide, of 4172 continuing treatment for 24 months, 872 had HbA1c results at baseline and at follow-up, showing a reduction from 8.7% to 7.4% that was sustained over the period of observation. Desouza et al (931-P) analyzed 23 467 persons with T2D taking two oral agents in a claims/electronic medical records database. Propensity score matching allowed comparison of 530 intensified by addition of a GLP-1RA with 530 who had the addition of a third oral agent, and 398 persons with addition of a GLP-1RA compared with 398 who added insulin. GLP-1RA use was associated with greater reduction in HbA1c (from baseline levels averaging 8.5% and higher) and in weight; only approximately half of participants met criteria for adherence. Which should we choose, SGLT2i or GLP-1RA? Patorno et al (133-LB) used insurance claims and Medicare data to compare propensity score matched cohorts of 11 579 persons with T2D age > 65 treated with empagliflozin and the same number receiving a dipeptidyl peptidase 4 inhibitor (DPP-4i), and 17 500 persons treated with empagliflozin and the same number receiving a GLP-1RA. In the comparison with DPP-4i, myocardial infarction, stroke, mortality, and heart failure occurred 29%, 36%, 48%, and 43% less often with empagliflozin. In the comparison with GLP-1RA, myocardial infarction and mortality occurred with the same frequency, stroke 45% more often (95% confidence interval 1.0-2.11), and heart failure occurred 17% less often with empagliflozin. Lee et al (402-P) compared a propensity score matched subset of 91 259 SGLT2i vs 122 349 thiazolidinedione-treated persons in Korea from 2014-2018, finding no difference in stroke, myocardial infarction, or CV mortality, a reminder that thiazolidinediones are also cardioprotective, although as expected there was a 37% lower likelihood of heart failure with SGLT2i. Often, the choice involves cost, particularly for seniors. Lipska et al (1157-P) reported that adjusted health plan annual spending per person with T2D in a >1.5 million person data set increased from $73 and $87 for commercial and Medicare Advantage in 2006 to $186 and $138, respectively, in 2018. Bhatt et al (4-LB) looked at the effect of icosapent ethyl on CV outcome among persons with diabetes in a subset analysis of the CVOT including those with diabetes and risk factors without established atherosclerotic CV disease (ASCVD), those with diabetes and having ASCVD, and nondiabetic persons with ASCVD. There was no statistically significant evidence of between group differences, but those with diabetes and established ASCVD had a significant ~30% fall in CV end points during the 5-year period of observation, whereas those with diabetes without established ASCVD had a nonsignificant ~12% decrease. We should be aware, then, that CV risk alone may not justify prescribing expensive medicines for persons with diabetes. This may particularly be the case with the SGLT2i and GLP-1RA classes: Luo et al (1162-P) calculated likely annual per-person expenditures to exceed $1100 for Medicare beneficiaries prescribed SGLT2i, and $1600 with prescription of GLP-1RA. Consultant/advisor: Astra Zeneca, Boehringer Ingelheim. Stockholder: Johnson & Johnson, Humana, Novartis. 参观美国糖尿病协会(ADA)年会的海报展厅是学习糖尿病治疗新观点的绝好机会。以往要看超过1 000张海报几乎是不可能的, 但今年有足够的时间浏览虚拟海报大厅。以下是一些我觉得重要的演讲摘要。 1. 糖尿病前期和糖尿病的进展 Gong等人(1471-P)在287名基线空腹血糖<100 mg / dl的参与者和289名基线空腹血糖≥100mg / dl的参与者中, 比较了“大庆研究”中生活方式干预的效果。 从1986年开始的30多年的随访中, 在那些糖耐量受损但没有空腹血糖受损的人中, 糖尿病发病率降低了37%~46%, 与空腹血糖受损者的降幅类似(47%~51%)。如果不使用糖耐量试验来识别糖尿病前期, 那么可能会错过一大批受益于生活方式干预的人群。Egan等人(1476-P)报告了从2005年到2017年对44 992名年龄在18~65岁之间的非糖尿病成年人, 每年进行至少两次空腹血糖检测的随访, 发现男性、年龄增长和较高的基线空腹血糖水平与发生糖尿病更相关。Nielsen等人(1579-P)对2001-2017年美国家庭进行了纵向研究, 发现人群中肥胖症患病率从21%上升到30%, 糖尿病患病率从8%上升到12%。2型糖尿病(T2D)的早期诊断显得越来越重要。关于年轻人中的糖尿病, Lawrence等人(1464-P)报告说, 2001年、2009年和2017年, 美国0~19岁人群中, 每1 000人1型糖尿病(T1D)的患病率从1.5上升到1.9和2.2, 其中非西班牙裔白人的患病率最高。T2D的患病率分别为0.3/1000、0.5/1000和0.7/1000, 它在非西班牙裔白人中发病率最低, 而在非西班牙裔黑人和美国印第安族中最高。 2.1 型糖尿病与胰岛素治疗 连续血糖监测值在70~180 mg/dl (3.9~10 mmol/L)之间的百分率, 也就是“目标范围内时间”(time in range, TIR)的概念正在被广泛接受, 这是一种有价值的血糖替代指标。Bergenstal等人(21-LB)在一项比较德谷胰岛素和甘精胰岛素的心血管不良事件结果研究中发现, 5 774名接受T2D胰岛素治疗的患者, TIR≤30%与主要心血管不良事件(CV)相关, TIR≥70%与低血糖和微血管结局减少相关。Ranjan等人(28-LB)研究了26名T1D和微量白蛋白尿并接受增强传感器胰岛素泵治疗的患者, 发现TIR与糖化血红蛋白(HbA1c)和尿白蛋白/肌酐比值的降低有关。Jendle等人(975-p)使用葡萄糖速率增加监测算法定义进餐时间, 该算法基于连续血糖监测, 结合连接的胰岛素笔, 在总共2 238天的治疗中, 记录了96名T1D成人患者胰岛素推注的时间。结果发现在餐后60 min以上使用的餐后剂量, 与较高的血糖平均值和较大的葡萄糖变异系数相关。Edwards(375-P)通过类似的连接胰岛素笔的方式, 发现TIR与错过的餐前剂量呈负相关。Mueller等人(95-LB)报告说, 在1 659名接受胰岛素泵治疗的患者中, 闭环技术的使用与TIR的改善有关。Soupal(852-P)研究了60名T1D患者, 使用实时和间歇扫描的连续血糖监测, 发现前者的低血糖明显减少, TIR显著增加。Brown等人(983-P)报告了使用OmniPod胰岛素泵和Dexcom 6连续血糖监测系统在18名T1D控制良好的成年患者中的闭环算法的性能, 发现在130和110 mg/dl(7.2和6.1 mmol/L)的血糖目标下, 没有低血糖的发生, TIR略有改善。 Arora和Agrawal(109-LB)研究了500名注射胰岛素的糖尿病患者至少2年, 在临床检查中发现脂肪增生(lipohypertrophy , LH)占45%, 在超声成像中占58%, 在100例皮肤和皮下组织穿刺活检中有2例显示胰岛素衍生的淀粉样变性, 免疫染色示抗胰岛素抗体阳性。重复使用胰岛素针头和不正确的轮换注射位置与发生LH更相关。 Xu等(674-P)发现, 在260名接受胰岛素治疗的患者中, 有81%的超声表现为LH, 这是由于存在皮下脂肪增厚, 弥散性增强的回声区域和结节性高回声灶, 而其中的39%, 特别是高体重指数(BMI)的患者在体检中漏诊。 Perez-Nieves等人(1033-P)汇总了2009~2018年间保险索赔数据库中胰岛素使用和葡萄糖监测的数据。 T1D患者的胰岛素泵使用率从约40%增加到一半以上, 不带泵的胰岛素使用率从约40%降低到<20%；在接受胰岛素治疗的T2D患者中, 一次性笔的使用率从<40%增加到约80%, 不带泵的胰岛素使用率从大约70%下降到<20%。持续血糖监测在T1D患者中从约10%增加到40%, 但在T2D患者中很少使用。 3.肠道和2型糖尿病 Höskuldsdottir等人(1975-P)在瑞典医院入院数据中比较了5 321例接受Roux-en-Y胃旁路手术(RYGB)的T2D患者和5 321例T2D患者。在长达8年的随访中, 行RYGB的患者发生房颤的可能性降低了41%, 发生心力衰竭的可能性降低了73%。 Mingrone等人(121-LB)回顾了以下假设:十二指肠粘膜肥大伴有营养过剩介导了胰岛素抵抗。在一项针对39例T2D患者内镜下十二指肠粘膜表面置换试验中, 在24周到48周时, HbA1c分别从8.1%降低到0.6%和0.7%, 体重分别从基线93 kg降低了2.4和2.1 kg, 但没有报告对照组的36人的结果。 4.糖尿病神经病变 Parks等人(39-LB)在14种新方法的随机对照试验中, 根据护理标准, 对减压、清创和包扎处理的足部溃疡愈合情况进行了meta分析, 发现在1999年之前, 有24%的伤口在12周时愈合, 而在2000年之后, 37%的伤口愈合了。尽管有所改善, 但低治愈率表明还是需要更好的治疗方法。 Petersen(31-LB)对216名难治性痛性糖尿病神经病患者进行了为期3个月的随访, 患者被随机分配植入脊髓刺激装置, 发现3个月内79%的实验组疼痛缓解≥50%, 而对照组中仅5%, 此外实验组的6分钟内步行距离显著增加。 Chen等人(1436-P)在2004~2013年的《美国国家健康访问调查》中分析了约25万非糖尿病和约25 000糖尿病患者自我报告的睡眠时间与死亡率, 发现两者间存在U型关系, 尤其是糖尿病持续时间> 20年。在糖尿病患者中, 7小时为最佳睡眠时长。睡眠时间短(≤5小时)和睡眠时间长(≥10小时)均与CV死亡率相关。 5.糖尿病的心脏保护治疗 Inzucchi等人(132-LB)研究了一个常见的临床问题:在使用葡萄糖共转运蛋白2抑制剂(SGLT2i)治疗过程中导致估计肾小球滤过率(eGFR)的初始下降。 在EMPA-REG OUTCOME试验中, 接受恩格列净治疗的患者中有28%的患者初始下降> 10%, 这与年龄较大、初始eGFR较低, 蛋白尿水平较高, 以及经常使用血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂、利尿剂和胰岛素有关； 有31%的患者eGFR下降水平低于基线的10%, 只有31%的eGFR没有下降。接受恩格列净治疗的患者中, 只有1.4%(而接受安慰剂的患者有0.9%)人初始下降> 30%。在eGFR最初下降较大(> 10%)的患者中, 初始下降后, eGFR朝基线增加, 此外恩格列净治疗相关的心血管死亡率和肾病发生率的降低既未消除也未改善。 Ferannini等人(139-LB)分析了CANVAS CVOT中基线代谢物的相关性, 显示较高的游离脂肪酸(FFA)水平更不容易发生心力衰竭, 而较高的乳酸和丙酮酸与心力衰竭的发展趋势相关。在研究的前2年中, 使用卡格列净治疗时, FFA水平升高而丙酮酸水平降低, 这表明能量代谢的改变可能是CV获益的基础。 Dumartin和Frundi(137-LB)在28天的住院康复患者中比较了100名接受SGLT2i治疗的T2D患者与100名对照者, 按照其年龄、性别、BMI和功能状态一一匹配, 其中100名未接受SGLT2i的治疗。SGLT2i组在6分钟步行过程中感觉到的劳累和疲劳方面都有较大的改善, 观察结果表明该治疗方式是有益的。 Gautam等人(140-LB)报告了在80名接受SGLT2i治疗的绝经后妇女中的结果:使用阴道雌激素的妇女尿路感染率降低了6%。在大多数研究中, 尚未证明SGLT2i与尿路感染有关, 因此这可能仅仅是阴道雌激素本身的作用, 进一步观察是否同样减少了阴道念珠菌也许是有趣的。 Bethel等人(944-P)对六种胰高血糖素样肽1受体激动剂(GLP-1RA)的CVOTs进行了meta回归分析, 结果表明HbA1c降低程度越大, 发生视网膜病变的可能性就越大, 每降低0.1% HbA1c, 视网膜病变可能性就增加8%, 这表明在加强降糖治疗后, 应在所有患者中排查视网膜病变, 而不是将其作为药物特异性不良反应。 Mody等人(928-P和929-P)在真实世界研究中, 将3 852名使用杜拉鲁肽的患者与使用索马鲁肽的倾向得分匹配的患者进行比较, 以及1 879名使用杜拉鲁肽者与使用艾塞那肽的倾向得分匹配者比较, 结果显示这三种药物的6个月依从率分别为75%、67%和63%, 在65岁以下和大于65岁的人群中以及使用或不使用基础胰岛素的人群中也有类似的模式。在27 038名开始接受杜拉鲁肽治疗的患者中, 有4 172名患者连续治疗了24个月, 其中872名在基线和随访时具有HbA1c的检查结果, 显示在观察期内HbA1c从8.7%降至7.4%。 Desouza等人(931-P)在索赔/电子病历数据库中分析了服用两种口服药物的23 467名T2D患者。通过倾向得分匹配比较了530名使用GLP-1RA的患者与增加了第三种口服药物的530名患者, 以及398名使用GLP-1RA的患者与增加使用胰岛素的398患者。结果显示:使用GLP1RA降低了更多的HbA1c(从基线平均8.5%或以上)和体重, 但只有大约一半的参与者符合顺应性标准。 我们应该选择SGLT2i还是GLP-1RA?Patorno等人(133-LB)使用保险索赔和医疗保险数据, 比较了T2D患者中年龄>65岁的倾向得分匹配队列, 11 579名接受恩格列净治疗以及相同数量接受二肽基肽酶4抑制剂(DPP-4i)治疗, 17 500人接受恩格列净治疗以及相同数量的接受GLP-1RA治疗的患者。与DPP-4I相比, 服用恩格列净的心肌梗死、中风、死亡率和心力衰竭发生率分别降低了29%、36%、48%和43%。与GLP1RA相比, 服用恩格列净的心肌梗死和死亡率的发生率相同, 卒中发生率增加45%(95%可信区间1.0~2.11), 心力衰竭发生率降低17%。Lee等人(402-P)比较了2014~2018年韩国91 259名SGLT2i与122