Gong et al.¹ conducted a post hoc analysis to examine the effects of a lifestyle intervention among 576 adults with impaired glucose tolerance (IGT) in the Da Qing Diabetes Prevention Outcome Study. They divided the participants into those with impaired fasting glucose (IFG) (n = 289) and those without IFG (n = 287) at baseline. IFG was defined as fasting plasma glucose (FPG) of 100 mg/dL or higher. The intervention objectives were to increase participants' vegetable intake, lower alcohol and sugar intake, lose weight in overweight or obese individuals by reducing total calorie intake, and increase leisure-time physical activity. The intervention reduced diabetes incidence significantly in both groups (IGT only and IGT + IFG) at the end of the 6-year intervention and throughout the 30 years of follow-up (hazard ratios [HRs]: 0.49-0.63). This study's findings add to the existing literature that lifestyle interventions are effective in reducing diabetes incidence in people with IGT, regardless of the presence of IFG. However, the available evidence suggests that such interventions are not effective in those with IFG in the absence of IGT (i.e. isolated IFG).

Isolated IFG is defined as FPG 100-125 mg/dL by the American Diabetes Association (ADA) and as FPG 110-125 mg/dL by the World Health Organization among those without IGT.² A recent meta-analysis of 24 studies showed that isolated IFG constitutes a substantial proportion of the glucose-defined prediabetes population (44%-58% of Caucasians and 29%-48% of Asians, depending on the criteria).³ The proportional prevalence of isolated IFG (ADA criteria) is much larger in certain other ethnic groups; 84% in Asian Indians, for example.⁴ Most importantly, in addition to being at high risk of developing type 2 diabetes,⁵ people with isolated IFG are also at an increased risk of cardiovascular disease and all-cause mortality.⁶ Thus, it is crucial to examine the effectiveness of lifestyle interventions in those with isolated IFG.

In addition to the Da Qing study, other randomized controlled trials (RCTs) have shown that lifestyle interventions (e.g. at least 5%-7% weight loss, ≥150 minutes of moderately intense physical activity a week, <30% of daily calorie intake from fat) can significantly reduce the incidence of type 2 diabetes in people with IGT with or without IFG.² However, it should be noted that there was heterogeneity in the components included in the intervention programmes of these trials. Yet the efficacy of such interventions has not been shown in people with isolated IFG.² In the Zensharen Study for Prevention of Lifestyle Diseases, an RCT conducted among 641 overweight Japanese adults with IFG, lifestyle intervention significantly reduced diabetes incidence at 3 years (HR: 0.56, 95% CI 0.36-0.87).⁷ Among these participants, the intervention was effective in the IFG + IGT group (n = 262, HR: 0.41, 95% CI 0.24-0.69), but not in those with isolated IFG (n = 379, HR: 1.17, 95% CI 0.50-2.74). Similarly, in the Diabetes Community Lifestyle Improvement Program (D-CLIP) from India, lifestyle intervention followed by metformin (for those who were at high risk after 4 months) significantly reduced diabetes incidence in the IFG + IGT group (n = 222, HR: 0.64, 95% CI 0.43-0.97) at 3 years, but not in people with isolated IFG (n = 166, HR: 0.88, 95% CI 0.43-1.20).⁸ In the recent Norfolk Diabetes Prevention Study (NDPS), which was conducted at 135 general practices in England, in those with IFG (n = 631), the odds ratio for diabetes incidence in the lifestyle intervention group versus usual care was 0.53 (95% CI 0.29-0.95) at 2 years.⁹ In NDPS, the IFG group almost certainly included some people with IGT, and it may well be that the reduction in diabetes incidence was driven primarily by the beneficial effect seen in those with IGT.

IGT and IFG are two distinct prediabetes phenotypes. While β-cell function is impaired in both, IGT is characterized by severe muscle insulin resistance, whereas marked hepatic insulin resistance is seen in IFG.¹⁰ Consequently, 2-hour plasma glucose on an oral glucose tolerance test (OGTT) is increased in IGT, while FPG is elevated in IFG, although both are below the diabetes thresholds.¹¹ Because of these differences in underlying abnormalities, IGT and IFG may respond differently to the same set of lifestyle interventions.

The evidence base for national diabetes prevention programmes in countries such as the UK¹² and United States¹³ comes primarily from lifestyle intervention trials conducted in people with IGT.² However, these programmes mainly use HbA1c and FPG to recruit high-risk individuals, as performing a 2-hour OGTT is cumbersome. Of note, it has been consistently shown in different populations that the overlap of people with elevated HbA1c, IFG, and IGT (who can only be identified with an OGTT) is poor.^{14, 15} Thus, using FPG alone would fail to identify a substantial proportion of people with IGT and might result in significant numbers of people enrolling in intensive lifestyle-change programmes with little chance of benefit. The use of a 1-hour OGTT is probable to be more convenient and acceptable to identify people with IGT.¹⁶ Further, artificial intelligence using non-invasive imaging techniques may be a promising approach in the future to distinguish prediabetes phenotypes, given that such a strategy has been shown to predict a person's HbA1c from a retinal image alone.¹⁷ Whatever screening approaches are used, it is critical to ensure that people enrolled in lifestyle-based diabetes prevention programmes are aligned with the phenotypes tested in the RCTs.

To conclude, based on the currently available evidence, it is important to recognize that lifestyle interventions may not be effective in reducing diabetes incidence in those with IFG in the absence of IGT.^{2, 10} However, it should be noted that such evidence is based on subgroup analyses of RCTs with limited power. Thus, an individual participant meta-analysis of data from lifestyle intervention trials that included people with isolated IFG or adequately powered RCTs among people with isolated IFG is urgently needed.

龚等人。¹在大庆糖尿病预防结果研究中，进行了一项事后分析，以检查生活方式干预对 576 名糖耐量受损 (IGT) 成年人的影响。他们将参与者分为基线时空腹血糖受损 (IFG) (n = 289) 和无 IFG (n = 287) 的参与者。IFG 定义为空腹血糖 (FPG) 为 100 mg/dL 或更高。干预目标是增加参与者的蔬菜摄入量，降低酒精和糖的摄入量，通过减少总热量摄入来减轻超重或肥胖个体的体重，并增加休闲时间的体育活动。在 6 年干预结束时和整个 30 年随访期间，干预显着降低了两组（仅 IGT 和 IGT + IFG）的糖尿病发病率（风险比 [HR]：0.49-0.63）。这项研究' s 发现增加了现有文献，即生活方式干预可有效降低 IGT 患者的糖尿病发病率，无论是否存在 IFG。然而，现有证据表明，此类干预措施对没有 IGT（即孤立性 IFG）的 IFG 患者无效。

美国糖尿病协会 (ADA) 将孤立的 IFG 定义为 FPG 100-125 mg/dL，世界卫生组织将无 IGT 的患者定义为 FPG 110-125 mg/dL。²最近对 24 项研究的荟萃分析表明，孤立性 IFG 占葡萄糖定义的前驱糖尿病人群的很大一部分（44%-58% 的白种人和 29%-48% 的亚洲人，取决于标准）。³孤立性 IFG（ADA 标准）的比例患病率在某些其他种族群体中要大得多；例如，在亚洲印度人中为 84%。⁴最重要的是，除了患 2 型糖尿病的高风险外，⁵名孤立性 IFG 患者患心血管疾病和全因死亡率的风险也增加。⁶ 因此，检查生活方式干预对孤立性 IFG 患者的有效性至关重要。

除了大青研究外，其他随机对照试验 (RCT) 也表明生活方式干预（例如至少减轻 5%-7% 的体重、每周≥150 分钟的中等强度体育活动、<30% 的每日卡路里摄入量）来自脂肪）可以显着降低 IGT 患者有或没有 IFG 的 2 型糖尿病的发病率。²然而，应该指出的是，这些试验的干预计划中包含的成分存在异质性。然而，此类干预措施的有效性尚未在孤立性 IFG 患者中得到证实。²在 Zensharen 生活方式疾病预防研究中，一项 RCT 在 641 名患有 IFG 的超重日本成年人中进行，生活方式干预显着降低了 3 年的糖尿病发病率（HR：0.56，95% CI 0.36-0.87）。⁷在这些参与者中，干预对 IFG + IGT 组有效（n = 262，HR：0.41，95% CI 0.24-0.69），但对孤立性 IFG 无效（n = 379，HR：1.17，95% CI 0.50-2.74)。同样，在来自印度的糖尿病社区生活方式改善计划 (D-CLIP) 中，生活方式干预后使用二甲双胍（对于 4 个月后处于高风险的患者）显着降低了 IFG + IGT 组的糖尿病发病率（n = 222，HR : 0.64, 95% CI 0.43-0.97) 在 3 年时，但不适用于孤立性 IFG 患者（n = 166，HR：0.88，95% CI 0.43-1.20）。⁸最近在英格兰 135 家全科诊所进行的诺福克糖尿病预防研究 (NDPS) 中，IFG 患者（n = 631）中，生活方式干预组与常规护理组糖尿病发病率的优势比为 0.53（95% CI 0.29-0.95) 在 2 年。⁹在 NDPS 中，IFG 组几乎肯定包括一些 IGT 患者，很可能糖尿病发病率的降低主要是由 IGT 患者的有益效果驱动的。

IGT 和 IFG 是两种不同的前驱糖尿病表型。虽然两者的 β 细胞功能均受损，但 IGT 的特征是严重的肌肉胰岛素抵抗，而 IFG 中可见明显的肝脏胰岛素抵抗。¹⁰因此，口服葡萄糖耐量试验 (OGTT) 的 2 小时血浆葡萄糖在 IGT 中升高，而 FPG 在 IFG 中升高，尽管两者都低于糖尿病阈值。¹¹由于这些潜在异常的差异，IGT 和 IFG 对同一组生活方式干预措施的反应可能不同。

英国¹²和美国¹³等国家的国家糖尿病预防计划的证据基础主要来自对 IGT 患者进行的生活方式干预试验。²然而，这些程序主要使用 HbA1c 和 FPG 来招募高危个体，因为执行 2 小时的 OGTT 很麻烦。值得注意的是，在不同人群中一致表明，HbA1c、IFG 和 IGT（只能通过 OGTT 识别）升高的人的重叠很差。^14、15因此，单独使用 FPG 将无法识别大部分 IGT 患者，并可能导致大量人参加强化生活方式改变计划，而受益的机会很小。使用 1 小时的 OGTT 可能更方便和更容易被接受来识别 IGT 患者。¹⁶此外，使用非侵入性成像技术的人工智能可能是未来区分前驱糖尿病表型的一种很有前途的方法，因为这种策略已被证明可以仅从视网膜图像中预测一个人的 HbA1c。¹⁷无论使用何种筛查方法，确保参加基于生活方式的糖尿病预防计划的人与 RCT 中测试的表型一致至关重要。

总之，根据目前可用的证据，重要的是要认识到生活方式干预可能无法有效降低在没有 IGT 的 IFG 患者中的糖尿病发病率。^{2, 10}然而，应该指出的是，此类证据是基于功效有限的 RCT 的亚组分析。因此，迫切需要对生活方式干预试验的数据进行个体参与者荟萃分析，这些试验包括孤立性 IFG 患者或孤立性 IFG 患者中具有足够效力的 RCT。