Determinants of Maternal Triglycerides in Women With Gestational Diabetes Mellitus in the Metformin in Gestational Diabetes (MiG) Study

OBJECTIVE

Factors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age, obesity, preeclampsia, and altered glucose metabolism. In a subgroup of women in the Metformin in Gestational Diabetes (MiG) trial, maternal plasma triglycerides increased more between enrollment (30 weeks) and 36 weeks in those treated with metformin compared with insulin. The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women.

RESEARCH DESIGN AND METHODS

Of the 733 women randomized to metformin or insulin in the MiG trial, 432 (219 metformin and 213 insulin) had fasting plasma triglycerides measured at enrollment and at 36 weeks. Factors associated with maternal triglycerides were assessed using general linear modeling.

RESULTS

Mean plasma triglyceride concentrations were 2.43 (95% CI 2.35–2.51) mmol/L at enrollment. Triglycerides were higher at 36 weeks in women randomized to metformin (2.94 [2.80–3.08] mmol/L; +23.13% [18.72–27.53%]) than insulin (2.65 [2.54–2.77] mmol/L, P = 0.002; +14.36% [10.91–17.82%], P = 0.002). At 36 weeks, triglycerides were associated with HbA_1c (P = 0.03), ethnicity (P = 0.001), and treatment allocation (P = 0.005). In insulin-treated women, 36-week triglycerides were associated with 36-week HbA_1c (P = 0.02), and in metformin-treated women, they were related to ethnicity.

CONCLUSIONS

At 36 weeks, maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin. Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study.Maternal metabolism in late pregnancy is catabolic, with increasing insulin resistance, decreased adipose tissue lipoprotein lipase (LPL) activity, and increased lipolysis (1). These processes combine to ensure the availability of maternal fuels such as glucose, fatty acids, and ketone bodies for fetal use (1). It is recognized that gestational age, maternal obesity (2), and preeclampsia (3) are associated with increases in lipids during pregnancy. Gestational diabetes mellitus (GDM) is also associated with abnormalities in maternal lipid metabolism (4–6), which may contribute to the elevated fat mass seen at birth in infants of women with GDM (7–10).Maternal glucose control and the pharmacological therapies used for treatment of GDM have the potential to influence these changes in maternal lipids (11). Insulin suppresses adipose tissue lipolysis and might be expected to reduce circulating triglycerides (12). Metformin reduces insulin resistance, but it has also been suggested to influence lipid metabolism (13), independent of glycemic control. In type 2 diabetes, metformin treatment is associated with a reduction in plasma triglyceride, total cholesterol, LDL cholesterol (13), and VLDL cholesterol concentrations (14). Metformin treatment in type 2 diabetes is also associated with increases in LPL mass level and LDL cholesterol particle size (15) and with a reduction in the release of free fatty acids from adipose tissue (16).We have recently examined maternal lipids in the Metformin in Gestational Diabetes (MiG) trial and found that maternal fasting plasma triglycerides and measures of glucose control at 36 weeks were the strongest predictors of customized birth weight >90th percentile (17). Interestingly, triglycerides increased more from randomization to 36 weeks'' gestation in women allocated to metformin than in those allocated to treatment with insulin, but there was no difference in customized birth weights or other neonatal anthropometry measures between the groups; there were also no differences in cord blood triglycerides (17). The aim of this study was to examine the known and putative determinants of maternal triglyceride concentrations and determine whether the difference seen in maternal plasma triglycerides at 36 weeks was due to treatment or other factors that may have differed between treatment groups.     

Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes

OBJECTIVEThe optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA_1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes.RESEARCH DESIGN AND METHODSOne hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA_1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks’ gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit).RESULTSHbA_1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks’ gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63–140 mg/dL [3.5–7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA_1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA_1c.CONCLUSIONSHbA_1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA_1c and increasingly available CGM metrics (TIR and TAR).     

妊娠期糖尿病与血清胎球蛋白A的关系

目的:探讨妊娠期糖尿病(GDM)患者血清中胎球蛋白A(Fetuin-A)、脂联素及游离脂肪酸(FFA)水平的变化.方法:用酶链免疫吸附法(ELISA)测定GDM患者正常孕妇及正常人群外周血血清中Fetuin-A、脂联素及FFA水平.结果:GDM患者血清中Fetuin-A及FFA的水平显著高于非妊娠和健康妊娠妇女(P＜0.05).而其血清糖化血红蛋白和脂联素水平差异无统计学意义.结论:血清Fetuin-A联合FFA能更好地反映体内的胰岛素抵抗状态.     

Maternal and Neonatal Circulating Markers of Metabolic and Cardiovascular Risk in the Metformin in Gestational Diabetes (MiG) Trial: Responses to maternal metformin versus insulin treatment

OBJECTIVE

This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.

RESEARCH DESIGN AND METHODS

Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks’ gestation, and 6–8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.

RESULTS

Maternal plasma triglycerides increased more from randomization to 36 weeks’ gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.

CONCLUSIONS

There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.Gestational diabetes mellitus is carbohydrate intolerance first diagnosed during pregnancy (1) and affects up to 18% of pregnancies. The prevalence varies depending on maternal demographics and diagnostic criteria (2). The prevalence of gestational diabetes mellitus is increasing, which is likely driven by the rising population prevalence of overweight and obesity and increasing maternal age at pregnancy (3). Gestational diabetes mellitus increases maternal and infant morbidity and mortality during pregnancy (4). Women with a history of gestational diabetes mellitus are at risk for metabolic syndrome, type 2 diabetes (5), and cardiovascular disease in later life (6). Children born to women with gestational diabetes mellitus have higher rates of type 2 diabetes and obesity (7).Treating gestational diabetes mellitus improves pregnancy outcomes for both mother and infant (8). Current therapies include modification of diet, increased physical activity, and drug therapy with insulin and oral hypoglycemic agents, including metformin. In addition to improving insulin sensitivity and hyperglycemia, metformin therapy in the setting of type 2 diabetes reduces triglycerides (9), total cholesterol, LDL cholesterol (10), and VLDL cholesterol; increases HDL cholesterol (9); and reduces markers of inflammation and thrombosis (11). Metformin therapy in gestational diabetes mellitus achieves maternal glucose control and pregnancy outcomes similar to insulin therapy (12,13).In contrast to insulin, metformin crosses the placenta (14) and, therefore, could directly influence fetal metabolism. Our recent follow-up studies in 2-year-old offspring of women enrolled in the Metformin in Gestational Diabetes (MiG) trial showed increased subcutaneous fat measurements with no increase in abdominal adiposity or total fat (15). Further assessments are required to determine whether metformin actually reduces visceral/ectopic fat. Therefore, we hypothesized that metformin would be more effective than insulin in improving markers of insulin sensitivity and cardiovascular risk during pregnancy and postpartum in women with gestational diabetes mellitus and in their newborns.     

妊娠糖尿病患者血脂水平及其与体质量变化的关系

【目的】探讨妊娠糖尿病（GDM ）患者妊娠期血脂水平及其与孕期体质量变化的关系。【方法】选择159例妊娠24～28周孕妇,根据口服葡萄糖糖耐量试验（OGTT）结果,将其分为GDM 组（n＝70）及健康孕妇组（n＝89）;记录孕前、孕期体质量,测量身高,计算孕前及孕期体质量指数（BMI）、孕期增重;测定血浆总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL‐C）、低密度脂蛋白胆固醇（LDL‐C）、空腹胰岛素（FINS）、糖化血红蛋白（HbA1c）等水平;比较两组间血脂水平、体质量变化的差异及相关性。【结果】GDM 组 TC、LDL‐c显著低于健康孕妇组（均 P ＜0．05）,HDL‐C显著高于健康孕妇组（ P ＜0．05）,健康孕妇组TG水平高于GDM 组,但无显著性差异（ P＞0．05）;但健康孕妇中,TC与体质量增加（ r ＝0．249,P＝0．017）、孕期BMI（ r＝0．224,P＝0．033）及BMI增加（ r ＝0．259,P＝0．013）相关;GDM 组中,TC与BMI（ P ＝0．241,P ＝0．041）相关。【结论】GDM患者存在血脂代谢紊乱,但孕期营养摄入及体质量增加过多可能对血脂的影响更大。     

妊娠期糖尿病的管理与妊娠结局相关性分析

目的分析妊娠期糖尿病(GDM)的管理与妊娠结局的相关性。方法回顾性分析87例GDM患者的临床资料,根据血糖控制程度分为满意组和不满意组,对比两组孕产妇并发症率、剖宫产率及新生儿病率。结果不满意组妊高征、酮症、羊水过多、早产、胎儿发育迟缓的发生率及剖宫产率明显高于满意组,新生儿巨大儿、低血糖、呼吸窘迫综合征、畸形、新生儿窒息的发生率明显高于满意组,差异均有显著性意义(P<0.05)。结论重视围产保健,争取GDM的早期诊断和治疗,加强管理,以饮食控制为基础,必要时加用胰岛素,适当放宽剖宫产指征,有利于获得良好妊娠结局。     

Antenatal Depression and Gestational Diabetes: A Review of Maternaland Fetal Outcomes

Depression and gestational diabetes are common and serious problems during pregnancy. While information exists regarding maternal and fetal outcomes in women who have either depression or gestational diabetes, there is a paucity of data regarding outcomes in women who have both. This article reviews and summarizes studies examining depression during pregnancy as well as an analysis of six studies examining depression in women with gestational diabetes, and discusses implications for clinicians and future research needs.     

Genetic Risk of Progression to Type 2 Diabetes and Response to Intensive Lifestyle or Metformin in Prediabetic Women With and Without a History of Gestational Diabetes Mellitus

OBJECTIVE

The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.

RESEARCH DESIGN AND METHODS

We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.

RESULTS

β-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention.

CONCLUSIONS

These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to β-cell dysfunction.     

不同诊断标准诊断妊娠期糖尿病与不良妊娠结局关系的探讨

目的 探讨国际糖尿病与妊娠研究组织（IADPSG）标准和美国国家糖尿病数据组（NDDG）标准诊断妊娠期糖尿病（GDM）与不良妊娠结局关系.方法 随机选择从2012年1月-2014年1月在门诊完成产检,住院分娩且临床资料完整的单胎孕妇.在孕24-28周时进行口服75 g葡萄糖耐量试验（oral glucose tolerance test,OGTT）,分别采用IADPSG及NDDG两种标准确诊为GDM患者的共323例（GDM组）,其中达到NDDG标准的为A组（174例）,达到IADPSG标准但未达到NDDG标准的为B组（149例）,另选择同期住院分娩的非GDM正常孕妇323例为对照组,分别统计分析各组新生儿高胆红素血症、新生儿低血糖、新生儿呼吸窘迫、子痫前期、胎膜早破、羊水过多及巨大儿不良结局的发生率.分别分析两组间差异有无显著统计学意义.结果 统计分析比较各组不良结局的发生率.其中,GDM组：高胆红素血症（2.8％ vs 0.6％）,新生儿低血糖（2.2％ vs o.3％）,子痫前期（1.9％ vs 0.0％）及胎膜早破率（2.2％ vs 0.0％）的发生率明显高于正常对照组,两组间差异有统计学显著性意义（χ^2=4.5-7.5,P值均＜0.05）,新生儿呼吸窘迫（2.2％ vs 0.6％）,羊水过多（1.5％ vs 0.3％）和巨大儿（3.1％vs 1.2％）的发生率高于对照组,但两组间差异无统计学意义（（χ^2=2.6-2.9,P值均＞0.05）;A组：新生儿高胆红素血症（2.9％vs 2.7％）,新生儿低血糖（2.3％ vs 2.0％）,新生儿呼吸窘迫（2.3％vs 2.0％）,痫前期（2.3％vs 1.3％）,胎膜早破（1.7％vs 0.7％）,羊水过多（1.7％vs 1.3％）及巨大儿（3.4％vs 2.7％）的发生率均高于B组,但两组间差异无统计学显著性意义（χ^2=0.01-0.80,P值均＞0.05）.结论 IADPSG诊断标准的敏感度比NDDG标准高,将达不到NDDG标准的轻型GDM患者纳入妊娠期血糖管理中,有效地降低其不良妊娠结局的发生率.     

妊娠期糖尿病产妇脐血胰岛素及脂联素与新生儿结局的相关性研究进展

妊娠期糖尿病(GDM)的发生与胰岛素抵抗和胰岛素分泌受损有关,胰岛素抵抗是一个亚临床炎症过程,胰岛素及脂联素在这个过程中与其他炎症因子共同作用。收集近年来对GDM产妇脐血胰岛素、脂联素及对GDM孕妇所生新生儿预后影响的相关的研究文献,对它们之间的相关性进行探讨,为临床的诊断、治疗和改善新生儿预后提供参考。     

孕期营养指导对妊娠期糖尿病患者母婴结局的影响

目的探索孕期营养指导对于妊娠期糖尿病患者母婴结局的影响。方法选取我院2015年10月~2016年12月收治的400例妊娠期糖尿病患者。两组患者接受常规治疗,根据孕期管理方法的不同分入到观察组和对照组中,对照组患者给予常规孕期管理,观察组患者给予孕期营养指导,对比分析两组产妇并发症发生率、新生儿并发症发生率。结果观察组孕妇的并发症发生率(胎膜早破、羊水过多、产褥期感染)以及新生儿并发症发生率(巨大儿、新生儿窒息、新生儿低血糖、新生儿呼吸窘迫综合症)均比对照组更低,差异有统计学意义(P<0.05)。结论孕期营养指导用于妊娠期糖尿病患者有助于改善母婴结局,具有临床推广应用价值。     

不同糖化血红蛋白控制水平对妊娠糖尿病妊娠结局的影响分析

目的 探讨不同糖化血红蛋白控制水平对妊娠糖尿病妊娠结局的影响.方法 选取深圳市人民医院2008～2009年住院分娩妊娠糖尿病患者136例,以糖化血红蛋白≥6.0%为A组,<6.0%为B组,比较两组的空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、胰岛素(FINS)、稳态模式法的胰岛素抵抗指数(HOMA-IR)以及妊娠结局的差异.结果 A组的FBG,TC,TG,LDL-C,FINS,HOMA-IR均高于B组,差异有统计学意义.除胎膜早破和巨大儿两者差异不明显外,A组的妊高征、羊水过多、剖宫产、新生儿窒息、高胆红素血症均显著高于B组.HbA1c与FPG显著正相关,相关系数为0.912 (P<0.05).结论 GDM患者的HbA1c水平与妊娠结局相关.     

A Type 2 Diabetes Subtype Responsive to ACCORD Intensive Glycemia Treatment

OBJECTIVECurrent type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed, suggesting potential benefit for some individuals.RESEARCH DESIGN AND METHODSACCORD was a randomized controlled trial that investigated whether intensively treating glycemia in individuals with T2D would reduce CVD outcomes. Using a novel approach to cluster HbA_1c trajectories, we identified groups in the intensive glycemia arm with modified CVD risk. Genome-wide analysis and polygenic score (PS) were developed to predict group membership. Mendelian randomization was performed to infer causality.RESULTSWe identified four clinical groupings in the intensive glycemia arm, and clinical group 4 (C4) displayed fewer CVD (hazard ratio [HR] 0.34; P = 2.01 × 10⁻³) and microvascular outcomes (HR 0.86; P = 0.015) than those receiving standard treatment. A single-nucleotide polymorphism, rs220721, in MAS1 reached suggestive significance in C4 (P = 4.34 × 10⁻⁷). PS predicted C4 with high accuracy (area under the receiver operating characteristic curve 0.98), and this predicted C4 displayed reduced CVD risk with intensive versus standard glycemia treatment (HR 0.53; P = 4.02 × 10⁻⁶), but not reduced risk of microvascular outcomes (P < 0.05). Mendelian randomization indicated causality between PS, on-trial HbA_1c, and reduction in CVD outcomes (P < 0.05).CONCLUSIONSWe found evidence of a T2D clinical group in ACCORD that benefited from intensive glycemia treatment, and membership in this group could be predicted using genetic variants. This study generates new hypotheses with implications for precision medicine in T2D and represents an important development in this landmark clinical trial warranting further investigation.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a landmark trial to examine the effect of intensive glycemia treatment targeting glycated hemoglobin A_1c (HbA_1c) <6% versus more modest therapy targeting HbA_1c 7.0–7.9%. The study was conducted in patients with type 2 diabetes (T2D) at high cardiovascular risk, with a primary end point of time to first occurrence of major adverse cardiovascular events (MACE), specifically nonfatal myocardial infarction (MI), nonfatal stroke, or cardiovascular death. Notably, the intensive glycemia arm of the trial was terminated prematurely because of an increase in cardiovascular and overall mortality (1). The findings from ACCORD have had important implications regarding guidelines for glycemic management (2–4). Although there was a significant increase in mortality in the intensive glycemia arm, heterogeneity was observed (5–8). In addition, potential benefits in some measures of neuropathy, eye complications, and microalbuminuria were observed (9). Epidemiological analysis of ACCORD demonstrated that individuals at greatest risk of mortality and MACE were those intensively treated who did not reach the target HbA_1c (10).We previously developed a risk score based on two genetic variants that predicted White individuals with modified risk of cardiovascular mortality and displayed a significant interaction with glycemia control (5). Here, we expanded our approach to a racially diverse population, characterizing a glycemia-responsive group in the intensive glycemia arm of ACCORD using a novel application of dynamic time warping to measure the similarity of patient HbA_1c trajectories. We then clustered patients into clinical groups based on HbA_1c trajectory and identified a group of patients intensively treated in ACCORD with significantly lower risk of mortality, MACE, and multiple other cardiovascular disease (CVD) outcomes compared with other intensively treated patients. We also demonstrated causal inference regarding this relationship using Mendelian randomization. Furthermore, we performed a genome-wide association study (GWAS) to identify genetic variants associated with membership in a low-risk clinical group and used machine learning to construct a polygenic score (PS) to predict patients likely to benefit from ACCORD-like intensive intervention. Importantly, this study generates new hypotheses that patients predicted to be in this low-risk clinical group have significantly lower risk of CVD outcomes compared with the same predicted group receiving standard glycemia treatment.     

妊娠期糖尿病对母婴的影响及护理

目的探讨妊娠期糖尿病(GDM)对母婴影响及护理。方法观察妊娠期糖尿病患者25例及同期正常孕妇50例,分析其妊娠结局。结果 GDM组妊娠期高血压疾病、早产、巨大儿及剖宫产发生率分别为30.0%、32.0%、28.0%及88.0%,明显高于对照组10.0%、6.0%、6.0%及40.0%,差异有统计学意义(P0.05)。结论 GDM是危害孕产妇和围产儿的妊娠并发症,早期诊断及控制血糖是减少母婴并发症的关键。产后要加强产妇及新生儿护理。     

妊娠糖尿病患者血清脂联素与炎症因子的关系及临床意义

目的 检测妊娠糖尿病(GDM)患者血清脂联素(APN)与炎症因子IL-6,IL-17,C-反应蛋白(CRP)的水平并分析其关系,探讨炎症因子在妊娠糖尿病发展进程中的作用.方法 按照ADA诊断标准选取GDM组60例,妊娠糖耐量正常组(非GDM组)39例,健康对照组(NGT组)45例.分别采用ELISA检测空腹血清APN,IL-6,IL-17,免疫比浊法测CRP水平.结果 ①与NGT组比较,非GDM组、GDM组APN水平明显下降(P<0.05,P<0.01),且GDM组较非GDM组下降更明显(P<0.01),而CRP,IL-6,IL-17在非GDM组明显上升(P<0.01,P<0.01,P<0.05),且GDM组较非GDM组明显升高,差异有统计学意义(P<0.05,P<0.05,P<0.01);②GDM患者妊娠中期与晚期比较,APN水平下降明显(P<0.05),CRP,IL-6,IL-17明显上升(P<0.01,P<0.01,P<0.01);③相关性分析显示:APN与炎症因子CRP,IL-6,IL-17在GDM患者中晚期均呈负相关.结论 脂联素与炎症因子的负相关,提示炎症与抗炎症失衡机制参与妊娠糖尿病的发生发展.     

Thresholds of Glycemia and the Outcomes of COVID-19 Complicated With Diabetes: A Retrospective Exploratory Study Using Continuous Glucose Monitoring

OBJECTIVEAlthough elevated glucose levels are reported to be associated with adverse outcomes of coronavirus disease 2019 (COVID-19), the optimal range of glucose in patients with COVID-19 and diabetes remains unknown. This study aimed to investigate the threshold of glycemia and its association with the outcomes of COVID-19.RESEARCH DESIGN AND METHODSGlucose levels were assessed through intermittently scanned continuous glucose monitoring in 35 patients for an average period of 10.2 days. The percentages of time above range (TAR), time below range (TBR), time in range (TIR), and coefficient of variation (CV) were calculated. Composite adverse outcomes were defined as either the need for admission to the intensive care unit, need for mechanical ventilation, or morbidity with critical illness.RESULTSTARs using thresholds from 160 to 200 mg/dL were significantly associated with composite adverse outcomes after adjustment of covariates. Both TBR (<70 mg/dL) and TIR (70–160 mg/dL), but not mean sensor glucose level, were significantly associated with composite adverse outcomes and prolonged hospitalization. The multivariate-adjusted odds ratios of the CV of sensor glucose across tertiles for composite adverse outcomes of COVID-19 were 1.00, 1.18, and 25.2, respectively.CONCLUSIONSPatients with diabetes and COVID-19 have an increased risk of adverse outcomes with glucose levels >160 mg/dL and <70 mg/dL and a high CV. Therapies that improve these metrics of glycemic control may result in better prognoses for these patients.     

Effects of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes: The HEART2D trial

OBJECTIVE—Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI).RESEARCH DESIGN AND METHODS—Patients (type 2 diabetes, aged 30–75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose <7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose <6.7 mmol/l).RESULTS—A total of 1,115 patients were randomly assigned (PRANDIAL n = 557; BASAL n = 558), and the mean patient participation after randomization was 963 days (range 1–1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n = 174, 31.2%) and BASAL (n = 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8–1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 ± 0.1 vs. 7.8 ± 0.1%; P = 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P < 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P < 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P < 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P = 0.233) versus the PRANDIAL group.CONCLUSIONS—Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with diabetes, for which ∼65% of deaths are attributable to heart disease or stroke (1,2). Among individuals with type 2 diabetes, those with a previous myocardial infarction have a particularly high risk of additional cardiovascular events (3).The higher prevalence of classic cardiovascular risk factors in type 2 diabetes only partly explains the increased cardiovascular risk associated with diabetes (2,3). Chronic hyperglycemia increases this risk (4–7) and postchallenge/postprandial hyperglycemia has been associated with CVD independent of A1C or fasting blood glucose (FBG) (8,9). Increased oxidative stress has been suggested as a pathophysiologic mechanism to explain this relationship (10). Furthermore, acarbose, an α-glucosidase inhibitor that specifically reduces postprandial hyperglycemia, reduced cardiovascular mortality in a diabetes prevention trial (11).The Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial (12) demonstrated a reduction in mortality in patients with type 2 diabetes and recent acute myocardial infarction (AMI) after intensive insulin treatment, and this study was developed to determine the impact of postprandial hyperglycemia on CVD in a similar high-risk population. Thus, the primary objective of the Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) study was to demonstrate a difference between two insulin strategies, one targeting postprandial hyperglycemia and the other targeting fasting and interprandial hyperglycemia, on time until the first combined adjudicated cardiovascular event (primary outcome defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndrome).