Presentations at the 81st scientific sessions of the American Diabetes Association (ADA), Part 1

1 HEALTH CARE

Trief and coauthors gave a sobering reminder of the prevalence of low medication adherence in a survey of 381 young adults (mean age 26) with type 2 diabetes (T2D), most with low income and poor glycemic control (mean HbA1c 9.4%). Of 212 taking oral hypoglycemic agents, 70% had low (<80% of doses) adherence, and of 192 taking insulin, 37% had low adherence (abstract 42-LB). In further assessment of factors related to glycemic control in young adults, Pihoker et al found mean HbA1c 11% and 10.3% among relatively small numbers of those with T1D and T2D, respectively, not having health insurance, somewhat higher than that among those with public or private insurance (abstract 142-OR). Chen et al used data from the 2001-2018 National Health Interview Surveys to show that income-related inequalities were associated with higher diabetes prevalence, showing a trend to progression through the period of study in those over age 64 and an initial improvement through 2011 with subsequent worsening of the association of diabetes with income inequality in those age 45-64 (abstract 326-OR). In an analysis of costs of care among persons with T2D after a first cardiovascular disease (CVD) hospitalization, 1712 of whom initiated a glucagon-like peptide-1 receptor agonist (GLP-1RA) vs 122 334 who received older standard of treatment agents, annual drug costs were $1201 vs$705, but inpatient costs were $1070 vs $1374 and outpatient costs $1712 vs $1979, leading to similar overall expenditures; Evans et al (abstract 82-LB) observed that GLP-1RA treatment might then be “budget neutral,” suggesting further rationale for their use among the one-third of persons with T2D who have CVD, given the evidence of improvement in outcome in such a setting. It is striking to observe the low use of GLP-1RA, in just over 1% of persons with T2D and CVD requiring hospitalization. Shao and coworkers used evidence from mortality follow-up of the 2011-2012 National Health and Nutrition Examination Survey to estimate that the greatest gains in life expectancy would come from weight loss, with blood pressure-lowering treatment secondarily of benefit, and with little mortality benefit of lipid- or glucose-lowering agents (abstract 139-OR); this model does not include substantial numbers of persons receiving GLP-1RA and sodium glucose cotransporter 2 inhibitors (SGLT2i), agents found to be associated with reduction in mortality subsequent to the initial study.

2 CONTINUOUS GLUCOSE MONITORING

Mueller-Korbsch et al analyzed Dexcom continuous glucose monitoring (CGM) readings from sensors placed on the upper arm, abdomen, and thigh during a strenuous 50-mile bicycle ride, finding lower bias and lower mean absolute relative difference from capillary glucose with the former location (abstract 28-LB), and Hester et al noted that acute worsening of critical illness with decreased tissue perfusion led to rapid reduction in CGM values in eight hospitalized persons on mechanical ventilation (abstract 74-LB); although these are extreme examples, in clinical use of CGM potential factors affecting sensor accuracy must be taken into account in a variety of settings. Bergenstal et al analyzed 4727 CGM profiles from 484 persons enrolled in the Cornerstone4Care (C4C) a freely available patient support program, finding mean time in range (TIR) 63% and 68% among persons with T1D and T2D; less than half achieved ≥70% TIR, and less than one-third had both TIR≥70% and <1% time with glucose<54, showing that even in this self-selected population there is potential for improvement in care (abstract 65-LB). Norman et al estimated costs of care among 571 persons with T2D initiating CGM, finding ~25% reduction in overall medical costs, in part because of reduction in requirement for hospitalization (abstract 66-LB). Miller et al compared persons using rapid- or short-acting insulin starting CGM with propensity score matched controls, finding that both with T1D and T2D, and with baseline HbA1c ≥7% and ≥8%, HbA1c decreased significantly over 6 months, without difference between the Dexcom and Freestyle Libre devices (abstract 67-LB); a similar comparison by Hirsch et al of 3564 persons with T1D and 3930 persons with T2D vs propensity score-matched controls showed progressive reduction over time in hospitalizations and in acute diabetes events, again without difference between the Dexcom and Freestyle Libre devices (abstract 68-LB). McQueen et al cross-tabulated glucose coefficient of variability (CV) on CGM vs HbA1c groupings among 466 adults with T1D over 1648 visits from 2014-2020, finding that the weekly number of episodes of glucose<54 increased as expected with higher CV and lower HbA1c; with CV <36%, even at HbA1c <6.5% fewer than one episode of glucose<54 would be expected, whereas with CV >45%, even at HbA1c ≥8% more than two episodes per week were predicted, and with CV >45%, at HbA1c 6.5%, nearly five episodes per week would occur (abstract 59-LB). In an interesting study suggesting an approach to reducing such variability, Secher et al treated persons with T1D on multiple daily injections either with CGM, with an automated bolus calculation based on carbohydrate counting, with both, or with usual care; the combined treatment led to reduction both in HbA1c and in CV (abstract 150-OR).

3 INSULIN TREATMENT

Piras de Oliveira et al studied >1000 persons with T1D treated with basal insulin plus prandial lispro vs ultrarapid lispro; 1 mmol/L lower fasting glucose was associated with 0.12% vs 0.11% lower HbA1c, whereas the same reduction in postprandial glucose was associated with 58% vs 82% as great an HbA1c reduction, and, using 10-point self-monitored blood glucose profiles, a 1 mmol/L lower fasting and postprandial glucose was associated with 10% and 8.6% greater TIR, respectively, with both insulin lispro and ultrarapid lispro (abstract 107-LB); the “ultrarapid” formulation does not then appear to offer much in the way of clinical benefit. Two studies of once-weekly basal insulin preparations were reported. Silver et al studied differing protocols comparing insulin icodec with insulin glargine given once daily in treat-to-target 16-week trials of >350 persons with T2D, showing similar durations of hypoglycemia using CGM (abstract 191-OR); Kazda et al similarly compared the once weekly basal insulin Fc vs daily insulin degludec in 399 persons with T2D using CGM, showing 62% vs 63% TIR and <1% hypoglycemia with both approaches (abstract 192-OR). Finally, a 2-year randomized crossover trial of 149 persons with T1D and recurrent severe nocturnal hypoglycemia used CGM to show that insulin degludec was associated with less than half the likelihood of nocturnal hypoglycemia seen with insulin glargine (Brøsen et al, abstract 131-OR), confirming a number of previous studies of an approach used for avoiding hypoglycemia in such persons.

4 OTHER TREATMENT APPROACHES

Peng et al performed metaanalyses of glycemic effects of proton pump inhibitors; in seven studies totaling 342 persons with diabetes, these agents led to 0.4% and 10 mg/dL reductions in HbA1c and fasting glucose, respectively, but in five studies totaling 244 439 nondiabetic persons no significant change was seen in the development of diabetes (abstract 180-LB). Pittas et al carried out an individual participant-level metaanalysis of three trials of over a minimum 2-year period, comparing 2097 persons receiving oral vitamin D supplementation and 2093 controls, finding a significant ~15% reduction in diabetes risk, without causing hypercalcemia, hypercalciuria, or nephrolithiasis (abstract 34-LB). Dote Montero et al compared early in day, late in day, and self-selected 8-hour time-restricted eating schedules in 22 overweight/obese adults, finding 0.8-1.7 kg body weight reduction, without significant difference between the groups (abstract 35-LB).

Next month, further notes from the ADA meeting, on studies of GLP-1RA, SGLT2i, and chronic kidney disease.

1 保健

Trief等在一项对381名患有2型糖尿病(T2D)平均年龄26岁的年轻人的调查中提出了一个发人深省的问题，即服药依从性普遍较低，其中大多数人收入较低，血糖控制较差(平均HbA1c为9.4%)。212例口服降糖药患者中，70%的患者依从性较低(<80%的剂量)，192例使用胰岛素的患者中，37%的患者依从性较低。在进一步评估与年轻人血糖控制相关的因素时，Pihoker等人发现，在没有医疗保险的相对较少的T1D和T2D患者中，平均糖化血红蛋白HbA1c分别为11%和10.3%，略高于有公共或私人保险的患者。Chen等人利用2001-2018年国民健康访谈调查的数据显示，与收入相关的不平等与糖尿病患病率上升有关，在64岁以上的患者中显示出在整个研究期间呈进展趋势，并在2011年之前有初步改善，而在45-64岁的人中，糖尿病与收入不平等的相关性程度加重。在对首次心血管疾病(CVD)住院后T2D患者的治疗费用进行分析后[其中1712人首次服用胰高血糖素样肽-1受体激动剂(GLP-1RA)；122 334人接受较旧标准治疗药物]，每年的药费分别为1201美元和705美元，但住院费用为1070美元和1374美元，门诊费用为1712美元和1979美元，导致类似的总体支出。Evans等人观察到，GLP-1RA治疗可能是“中等预算的”，建议在三分之一患有心血管疾病的T2D患者中使用GLP-1RA，因为有证据表明在这种情况下预后有所改善。值得注意的是，GLP-1RA的使用率很低，在有T2D和CVD需要住院的患者中仅超过1%。Shao和他的同事们利用2011-2012年全国健康与营养调查中死亡随访的证据估计，预期寿命的最大增长将来自减肥，降压治疗次之，降脂或降糖药物对死亡率几乎没有好处；但该模型不包括大量服用GLP-1RA和葡萄糖协同转运蛋白2抑制剂(SGLT2i)的患者，这两种药物经过初步研究后发现与死亡率的降低有关。

2 连续血糖监测

Mueller-Korbsch等人分析了Dexcom连续血糖监测(CGM)读数，这些读数来自放置在上臂、腹部和大腿上的传感器，在高强度50英里骑行过程中，发现与先前毛细血管血糖相比，存在较低的偏差和较低的平均绝对相对差值。Hester等人指出，危重疾病的急性恶化和组织灌注的减少导致了8名接受机械通气的住院患者的CGM值迅速降低；虽然这些都是极端的例子。Bergenstal等人分析了参加Cornerstone4Care(C4C)研究的484人的4727份CGM档案，发现T1D和T2D患者的平均血糖目标范围内时间(TIR)分别为63%和68%。不到一半的人达到了≥70%TIR，不到三分之一的人同时具有TIR≥70%和<1%时间血糖在54以下，这表明即使是在这部分人群中，医疗保健也有改善的潜力。Norman等人估计了571名T2D患者CGM的护理成本，发现总体医疗成本降低了约25%，部分原因是住院需求的减少。Miller等人比较了使用快速或短效胰岛素CGM的人和倾向评分匹配的对照组，发现基线HbA1c分别≥7%和≥8%的T1D和T2D患者，HbA1c在6个月内显著下降，使用Dexcom和Freestyle Libre设备之间没有差异。Hirsch等人对3564名T1D患者和3930名T2D患者与倾向性得分匹配的对照组进行了类似的比较，结果显示住院和急性糖尿病事件随着时间的推移而逐渐减少，同样在Dexcom和Freestyle Libre设备之间也没有区别。McQueen等人从2014年到2020年对466名患有T1D的成年人进行了CGM和HbA1c组之间交叉列表血糖变异系数(CV)分析，发现每周血糖<54mg/dL的发作次数与预期的一样增加，CV较高，则HbA1c较低；CV<36%时，即使HbA1c<6.5%，预计血糖<54的发作也会少于一次，而CV>45%，HbA1c为 6.5%时，每周会有近五次的预计血糖<54mg/dL的发作。有一项研究提出了一种减少这种变异性的方法，Secher等人每天给T1D患者以CGM的方法多次注射，根据碳水化合物计数进行自动推注计算，或者在常规的护理下进行治疗，或者同时使用这两种方法，结果发现联合这两种方法可以使得HbA1c和CV降低。

3 胰岛素治疗

Piras de Oliveira等人研究了1000多名T1D患者接受基础胰岛素加餐时lispro治疗与超速效lispro治疗的对比；发现，空腹血糖降低1 mmol/L与HbA1c降低0.12%与0.11%相关，而餐后血糖的显著降低同样与HbA1c降低58%与82%相关，并且无论是用lispro胰岛素还是超速效lispro，从10点自我监测血糖曲线看，空腹和餐后血糖降低1 mmol/L与10%和8.6%较高的TIR相关。因此，这种“超快速”的配方似乎并不能提供太多的临床益处。另外报告了有两项每周一次的基础胰岛素制剂研究。Silver等人研究了不同的方案以比较icodec胰岛素和甘精胰岛素，在目标达标的16周治疗试验中，超过350名T2D患者使用CGM，结果显示相似的低血糖持续时间；Kazda等人也使用CGM比较了399名T2D患者每周一次基础胰岛素Fc和每日德谷胰岛素的疗效，显示两种方法的TIR分别为62%和63%，并且低血糖都<1%。最后，一项为期两年的随机交叉试验对149名患有T1D并反复出现严重夜间低血糖的患者进行了CGM试验，结果表明，与甘精胰岛素相比，德谷胰岛素与夜间低血糖发生的可能性降低一半有关，证实了先前的多项研究结果，即通过此方法可以避免此类患者出现低血糖。

4 其他治疗方法

Peng等人对质子泵抑制剂的升糖作用进行了meta分析；在总共342名糖尿病患者的7项研究中，这些药物导致HbA1c和空腹血糖分别降低了0.4%和10 mg/dL，但在总共244439名非糖尿病患者的5项研究中，糖尿病的发生没有明显变化。Pittas等人对三项试验进行了个体参与者水平的meta分析，试验持续至少两年，对2097名服用维生素D补充剂的人和2093名对照组进行比较，发现糖尿病风险显著降低约15%，且不会导致高钙血症、高钙尿或肾结石。Dote Montero 等人比较了22名超重/肥胖成年人的8小时限时进食计划，分别在清晨、晚间和随机选择的8小时内进食，结果发现体重减轻了0.8-1.7公斤，但组间没有显著差异。