Place · Level 3 · Condition
Type 2 Diabetes & Prediabetes
中国 1.4 亿患者 · IR 三通路 · DiRECT 46% 缓解 · HbA1c / OGTT 解读 · 饮食 + 运动 + 药物完整谱
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Chapter 1
T2D · what + epidemiology
T2D · what + epidemiology
Type 2 diabetes (T2D) = chronic hyperglycemia caused by insulin resistance + relatively insufficient secretion. Distinct from T1D, which is autoimmune β-cell destruction → absolute insulin deficiency.
Diagnostic criteria (ADA + Chinese Diabetes Society):
HbA1c ≥ 6.5% (glycated hemoglobin, reflects 3-month average glucose)or fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL) × two occasionsor OGTT 2 h glucose ≥ 11.1 mmol/L (200 mg/dL)or random glucose ≥ 11.1 mmol/L + hyperglycemia symptoms
Prediabetes:
HbA1c 5.7-6.4%or fasting 5.6-6.9 mmol/L (100-125 mg/dL, IFG)or OGTT 2 h 7.8-11.0 mmol/L (IGT)about 5-10% per year progress to T2D, but reversible
Epidemiology (China, IDF 2021 + Wang 2017 JAMA):
T2D prevalence 11.2% (~ 140 million patients), the largest in the worldprediabetes 35-50% (400-500 million nationwide)undiagnosed rate 50%+ — half of T2D patients do not know they have itannual healthcare cost ~ 200 billion CNY
Asian-phenotype specificities:
At the same BMI, T2D risk is 2-3× higher vs Europeans (Hu 2011 Lancet)"Lean T2D" — BMI < 25 can still develop disease; Asian diagnostic cutoffs should be at lower BMI (China ≥ 24 = overweight, vs Western ≥ 25)Mechanism: at the same BMI, visceral fat + insulin resistance + β-cell decline are all more pronounced
"Diabetes = a disease of the elderly" no longer holds:
T2D prevalence in Chinese 20-39 y/o is 5-8% (2020)Pediatric and adolescent T2D is rising sharply with obesity + UPFEarly-onset T2D has a larger lifespan impact (every 10 years earlier onset → 5-10 years off life expectancy)
Atlas connections: this island pulls together endocrine/metabolic-syndrome L4 + carbs-fiber/glycogen + fructose-metabolism + UPF + exercise / protein and a dozen other stories into a single clinical scenario.
Diagnostic criteria (ADA + Chinese Diabetes Society):
HbA1c ≥ 6.5% (glycated hemoglobin, reflects 3-month average glucose)or fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL) × two occasionsor OGTT 2 h glucose ≥ 11.1 mmol/L (200 mg/dL)or random glucose ≥ 11.1 mmol/L + hyperglycemia symptoms
Prediabetes:
HbA1c 5.7-6.4%or fasting 5.6-6.9 mmol/L (100-125 mg/dL, IFG)or OGTT 2 h 7.8-11.0 mmol/L (IGT)about 5-10% per year progress to T2D, but reversible
Epidemiology (China, IDF 2021 + Wang 2017 JAMA):
T2D prevalence 11.2% (~ 140 million patients), the largest in the worldprediabetes 35-50% (400-500 million nationwide)undiagnosed rate 50%+ — half of T2D patients do not know they have itannual healthcare cost ~ 200 billion CNY
Asian-phenotype specificities:
At the same BMI, T2D risk is 2-3× higher vs Europeans (Hu 2011 Lancet)"Lean T2D" — BMI < 25 can still develop disease; Asian diagnostic cutoffs should be at lower BMI (China ≥ 24 = overweight, vs Western ≥ 25)Mechanism: at the same BMI, visceral fat + insulin resistance + β-cell decline are all more pronounced
"Diabetes = a disease of the elderly" no longer holds:
T2D prevalence in Chinese 20-39 y/o is 5-8% (2020)Pediatric and adolescent T2D is rising sharply with obesity + UPFEarly-onset T2D has a larger lifespan impact (every 10 years earlier onset → 5-10 years off life expectancy)
Atlas connections: this island pulls together endocrine/metabolic-syndrome L4 + carbs-fiber/glycogen + fructose-metabolism + UPF + exercise / protein and a dozen other stories into a single clinical scenario.
临床 · 化验单上怎么算糖尿病
2 型糖尿病 (T2D) = 胰岛素抵抗 + 相对分泌不足导致的慢性高血糖. 与 1 型不同 (T1D 是自身免疫 β 细胞破坏 → 绝对缺胰岛素).那化验单上到底怎么算糖尿病 — 诊断标准 (ADA + 中国糖尿病学会), 满足任一条即可:
HbA1c ≥ 6.5% (糖化血红蛋白, 反映 3 个月平均血糖)或空腹血糖 ≥ 7.0 mmol/L (126 mg/dL) × 两次或OGTT 2h 血糖 ≥ 11.1 mmol/L (200 mg/dL)或随机血糖 ≥ 11.1 mmol/L + 高血糖症状
还没到糖尿病、但已经偏高的中间地带 — 糖尿病前期 (Prediabetes):
HbA1c 5.7-6.4%或空腹 5.6-6.9 mmol/L (100-125 mg/dL, IFG)或OGTT 2h 7.8-11.0 mmol/L (IGT)每年约 5-10% 进展为 T2D, 但可逆 —— 这一段是干预的黄金窗口
数字 · 中国有多少人得
流行病学 (中国, IDF 2021 + Wang 2017 JAMA):T2D 患病率 10.9% (95% CI 10.4-11.5), 按 IDF 2021 估计约 1.4 亿患者, 居全球第一糖尿病前期 35-50% (全国 4-5 亿)未诊断率 50%+ — 一半 T2D 不知道自己有每年医疗成本 ~ 2,000 亿元
亚洲表型特殊性:
同 BMI 下 T2D 风险约 2-3 倍于欧洲人 (Hu 2011 Lancet)瘦型 T2D — BMI < 25 仍可患病, 亚洲诊断切点也应更低 (中国 ≥ 24 即算超重, 西方为 ≥ 25)机制: 同 BMI 下内脏脂肪更多, 胰岛素抵抗与 β 细胞功能下降都更明显
糖尿病 = 老年病 已不成立:
中国 20-39 岁 T2D 患病率 5-8% (2020)儿童 + 青少年 T2D 跟肥胖 + UPF 大幅上升早发 T2D 寿命影响更大 (每早 10 年发病, 寿命 - 5-10 年)
延伸 · 这一岛汇了哪些故事
Atlas 与其它岛的连接: 这一岛把已有的 endocrine/metabolic-syndrome L4 + carbs-fiber/glycogen + fructose-metabolism + UPF + 运动、蛋白等十几个故事汇成一个临床场景.Chapter 2
IR · 3 pathways
IR · 3 pathways
The plain version first: insulin is the "key" that lets blood sugar into your cells; insulin resistance means the cells go deaf to that key, so the body makes more and more insulin until the "key factory" (β-cells) burns out. Below is why the cells go deaf.
Insulin resistance (IR) sits at the core of T2D pathophysiology. The endocrine/metabolic-syndrome L4 covers it in detail; here is the condensed version:
Normal insulin signaling:
```
insulin → receptor → IRS-1 → PI3K → Akt → GLUT4 → glucose into cell
```
In IR, IRS-1 Ser307 is mis-phosphorylated → the entire downstream cascade is weakened.
Three upstream drivers (mutually reinforcing):
① Lipid (lipotoxicity):
Visceral adipose tissue (VAT) → releases FFA → ectopic lipid accumulation in muscle + liver + β-cellsDiacylglycerol (DAG) + ceramide → activate PKCθ + JNK → phosphorylate IRS-1 Ser307 → signal blockThe fructose DNL pathway (atlas fructose-metabolism) is upstream of this step
② Inflammation:
VAT releases tumor necrosis factor alpha: A strong pro-inflammatory signal molecule that runs high in chronic inflammation. / interleukin-6: A pro-inflammatory signal molecule (cytokine) released by immune cells during inflammation. / leptin / resistin → low-grade systemic chronic inflammationMacrophage infiltration of adipose tissue (M1 polarization)nuclear factor kappa B: The cell's inflammation master switch (a transcription factor) — when flipped, it turns inflammation on. activation → IRS-1 Ser phosphorylation → signal block
③ Androgen / sex-hormone imbalance:
PCOS women: androgens ↑ → worsens IR (see atlas PCOS L4)Men with low T (middle-aged abdominal obesity) → also promotes IR (bidirectional)SHBG ↓ is a marker of IR + MetSyn
β-cell decompensation:
Early: β-cells secrete 2-3× more insulin compensatorily → glucose stays normal → but insulin is already elevatedMiddle: β-cell function declines + cell number falls → impaired glucose tolerance → prediabetesLate: β-cell function < 50% → diabetes → some require exogenous insulin
Key insights:
"Diabetes = eating too much sugar" is a wrong simplification — the real cause is lipid + inflammation + hormonal systemic metabolic imbalance → β-cell decompensationHbA1c is the result, not the cause — treating by HbA1c alone is insufficient; look upstream (weight / VAT / FFA / inflammation)Early-stage reversibility: prediabetes + early T2D (HbA1c < 7.5, < 5 years) → 10-15% weight loss can produce substantial remission
Insulin resistance (IR) sits at the core of T2D pathophysiology. The endocrine/metabolic-syndrome L4 covers it in detail; here is the condensed version:
Normal insulin signaling:
```
insulin → receptor → IRS-1 → PI3K → Akt → GLUT4 → glucose into cell
```
In IR, IRS-1 Ser307 is mis-phosphorylated → the entire downstream cascade is weakened.
Three upstream drivers (mutually reinforcing):
① Lipid (lipotoxicity):
Visceral adipose tissue (VAT) → releases FFA → ectopic lipid accumulation in muscle + liver + β-cellsDiacylglycerol (DAG) + ceramide → activate PKCθ + JNK → phosphorylate IRS-1 Ser307 → signal blockThe fructose DNL pathway (atlas fructose-metabolism) is upstream of this step
② Inflammation:
VAT releases tumor necrosis factor alpha: A strong pro-inflammatory signal molecule that runs high in chronic inflammation. / interleukin-6: A pro-inflammatory signal molecule (cytokine) released by immune cells during inflammation. / leptin / resistin → low-grade systemic chronic inflammationMacrophage infiltration of adipose tissue (M1 polarization)nuclear factor kappa B: The cell's inflammation master switch (a transcription factor) — when flipped, it turns inflammation on. activation → IRS-1 Ser phosphorylation → signal block
③ Androgen / sex-hormone imbalance:
PCOS women: androgens ↑ → worsens IR (see atlas PCOS L4)Men with low T (middle-aged abdominal obesity) → also promotes IR (bidirectional)SHBG ↓ is a marker of IR + MetSyn
β-cell decompensation:
Early: β-cells secrete 2-3× more insulin compensatorily → glucose stays normal → but insulin is already elevatedMiddle: β-cell function declines + cell number falls → impaired glucose tolerance → prediabetesLate: β-cell function < 50% → diabetes → some require exogenous insulin
Key insights:
"Diabetes = eating too much sugar" is a wrong simplification — the real cause is lipid + inflammation + hormonal systemic metabolic imbalance → β-cell decompensationHbA1c is the result, not the cause — treating by HbA1c alone is insufficient; look upstream (weight / VAT / FFA / inflammation)Early-stage reversibility: prediabetes + early T2D (HbA1c < 7.5, < 5 years) → 10-15% weight loss can produce substantial remission
机制 · 三股上游力量
那是谁动的手脚? 主要是三股上游力量, 而且它们互相加强:脂: 内脏脂肪把脂肪酸源源不断倒进血里, 在肌肉、肝、β 细胞里堆成本不该有的异位脂肪; 这些脂肪的中间产物 (二酰甘油 DAG、神经酰胺 ceramide) 会激活几种激酶 (PKCθ、JNK), 正是它们去把 IRS-1 这把锁改坏的。果糖走的新生脂肪通路在这一步是上游 (atlas fructose-metabolism)。炎: 内脏脂肪还像个发炎的器官, 放出一批促炎信号 (tumor necrosis factor alpha: A strong pro-inflammatory signal molecule that runs high in chronic inflammation.、interleukin-6: A pro-inflammatory signal molecule (cytokine) released by immune cells during inflammation. 等), 招来巨噬细胞, 把全身拖进低度慢性炎症; 炎症信号 (经 nuclear factor kappa B: The cell's inflammation master switch (a transcription factor) — when flipped, it turns inflammation on. 通路) 同样落到 IRS-1 上, 让它更不灵。激素: 性激素失衡推波助澜 —— PCOS 女性雄激素偏高会加剧胰岛素抵抗 (atlas pcos L4), 中年腹型肥胖男性睾酮偏低则反过来促进它; SHBG 偏低是这一整套代谢紊乱的标志。
进程 · β 细胞怎么被拖垮
β 细胞失代偿 (decompensation):早期: β 细胞代偿性分泌 2-3 倍胰岛素 → 维持血糖正常 → 但胰岛素水平已经升高中期: β 细胞功能下降 + 数量减少 → 葡萄糖耐量减弱 → 糖尿病前期晚期: β 细胞功能 < 50% → 糖尿病 → 部分需要外源胰岛素
关键洞察:
糖尿病 = 糖吃多了 过度简化 — 真因是脂质、炎症与激素叠加的全身代谢失衡, 最终把 β 细胞推到失代偿HbA1c 是结果而非原因 — 治疗只看 HbA1c 不够, 要看上游 (体重 / VAT / FFA / 炎症)早期可逆: 糖尿病前期与早期 T2D (HbA1c < 7.5, 病程 5 年内), 通过减重 10-15% 可显著缓解
Lab interpretation
HbA1c (glycated hemoglobin):Reflects average glucose over the past 8-12 weeks (set by red cell lifespan)Pros: no fasting needed, single blood draw, stableLimits: anemia / abnormal hemoglobin (thalassemia / sickle): falsely lowIron deficiency / B12 deficiency: falsely highChronic kidney disease: unreliable
Fasting plasma glucose (FPG):
8+ hours fastingReflects hepatic glucose output + basal insulin resistance"Dawn phenomenon": early-morning cortisol + growth hormone → hepatic glucose ↑ → fasting reading elevated
OGTT (oral glucose tolerance test):
Fast + drink 75 g anhydrous glucose + retest at 2 hMost sensitive — catches early IR presentation (postprandial spikes)Some people have normal HbA1c + FPG but abnormal OGTT — important early signalRecommendation: 35+ y/o + any MetSyn marker, every 3 years
Insulin + C-peptide:
Fasting insulin > 12 µIU/mL suggests IR (Reaven 1988)HOMA-IR = (fasting insulin × fasting glucose) / 22.5; ≥ 2.5 suggests IRC-peptide reflects endogenous β-cell secretion; useful in insulin-treated patients to assess residual function
CGM (continuous glucose monitoring):
24-hour continuous subcutaneous interstitial glucose"Normal HbA1c" + high GI postprandial peaks → early IRMassive individual variation: the same banana + milk produces totally different glucose responses across peopleNew tool: 1-2 weeks of CGM can help healthy people understand their personal food responses
Self-check checklist (priority 35+ y/o):
Annually: HbA1c + fasting + waist + lipids + ALTAny abnormality: + OGTT + insulin + C-peptide"This year's check-up is normal" ≠ "next year will still be normal" — early-onset T2D forms over 5-10 years
Chapter 3
DiRECT · T2D reversibility
DiRECT · T2D reversibility
The DiRECT trial (Lean et al 2018 Lancet) is one of the most important RCTs in the atlas's cardiovascular + diabetes series — the first proof that T2D can be put into remission.
Design:
49 primary-care clinics in Scotland + EnglandN = 298 T2D patients (diagnosed ≤ 6 years, BMI 27-45, not insulin-dependent)Randomised: Very-low-calorie diet (VLCD) protocol vs standard care
VLCD protocol:
3-5 months: 825-853 kcal/day (protein shakes + vitamins)Refeeding phase: gradual reintroduction of solid food (2-8 weeks)Long-term maintenance: monthly dietitian follow-up + weight-maintenance strategy
Results (1 year):
46% T2D remission (HbA1c < 6.5%, off medication)vs standard-care 4% remissionAverage weight loss 10 kg (VLCD vs 1 kg control)Those losing ≥ 15 kg: 86% remissionThose losing 10-15 kg: 57% remission
Results (2 years, follow-up):
36% maintained remission (vs 3% standard care)Sustained remitters had fewer medications + improved cardiovascular markers + greatly improved quality of life
Results (5 years, 2024 update):
About 1/3 of remitters maintained remission — weight regain is the main cause of relapseNon-remitters who lost weight: still had substantially reduced cardiovascular risk
Mechanism (twin-cycle hypothesis, Lim 2011):
Excess weight → ectopic lipid (liver + pancreas) → β-cell function suppression + hepatic glucose output ↑Major weight loss → rapid depletion of ectopic lipid → β-cell recovery + liver normalisationEarly T2D (< 6-8 years) is reversible by this process; long-standing T2D has too much β-cell death → irreversible
Clinical translation:
UK NHS adopted the DiRECT protocol in 2020 as a standard option for early T2DSome Chinese hospitals run similar programs, but insurance coverage + dietitian resources are the implementation bottleneckKey point: this is not "dieting" — it is "structured medical nutrition therapy + long-term follow-up"; losing weight on your own ≠ DiRECT
Mediterranean diet + exercise (PREDIMED 2018, Look AHEAD 2013):
Slower weight loss than VLCD but more sustainablePREDIMED: Mediterranean + olive oil / nuts → cardiovascular events -30%Suited to populations who cannot do VLCD
Conclusion: the old view that T2D is "chronically progressive and irreversible" has been falsified — early stage + weight loss = real remission is possible.
Design:
49 primary-care clinics in Scotland + EnglandN = 298 T2D patients (diagnosed ≤ 6 years, BMI 27-45, not insulin-dependent)Randomised: Very-low-calorie diet (VLCD) protocol vs standard care
VLCD protocol:
3-5 months: 825-853 kcal/day (protein shakes + vitamins)Refeeding phase: gradual reintroduction of solid food (2-8 weeks)Long-term maintenance: monthly dietitian follow-up + weight-maintenance strategy
Results (1 year):
46% T2D remission (HbA1c < 6.5%, off medication)vs standard-care 4% remissionAverage weight loss 10 kg (VLCD vs 1 kg control)Those losing ≥ 15 kg: 86% remissionThose losing 10-15 kg: 57% remission
Results (2 years, follow-up):
36% maintained remission (vs 3% standard care)Sustained remitters had fewer medications + improved cardiovascular markers + greatly improved quality of life
Results (5 years, 2024 update):
About 1/3 of remitters maintained remission — weight regain is the main cause of relapseNon-remitters who lost weight: still had substantially reduced cardiovascular risk
Mechanism (twin-cycle hypothesis, Lim 2011):
Excess weight → ectopic lipid (liver + pancreas) → β-cell function suppression + hepatic glucose output ↑Major weight loss → rapid depletion of ectopic lipid → β-cell recovery + liver normalisationEarly T2D (< 6-8 years) is reversible by this process; long-standing T2D has too much β-cell death → irreversible
Clinical translation:
UK NHS adopted the DiRECT protocol in 2020 as a standard option for early T2DSome Chinese hospitals run similar programs, but insurance coverage + dietitian resources are the implementation bottleneckKey point: this is not "dieting" — it is "structured medical nutrition therapy + long-term follow-up"; losing weight on your own ≠ DiRECT
Mediterranean diet + exercise (PREDIMED 2018, Look AHEAD 2013):
Slower weight loss than VLCD but more sustainablePREDIMED: Mediterranean + olive oil / nuts → cardiovascular events -30%Suited to populations who cannot do VLCD
Conclusion: the old view that T2D is "chronically progressive and irreversible" has been falsified — early stage + weight loss = real remission is possible.
试验 · 它到底怎么做的
设计:苏格兰 + 英格兰 49 家初级保健诊所N = 298 T2D 患者 (诊断 ≤ 6 年, BMI 27-45, 不依赖胰岛素)随机: 极低热量饮食 (VLCD) 协议 vs 标准护理
VLCD 协议:
3-5 个月: 每天 825-853 kcal (蛋白冲剂 + 维生素)复食阶段: 渐进引入固体食物 (2-8 周)长期维持: 每月营养师随访 + 体重维持策略
结果 · 一年后, 五年后
结果 (1 年):46% 缓解 T2D (HbA1c < 6.5%, 无药物)vs 标准护理组 4% 缓解平均减重 10 kg (VLCD vs 1 kg 对照)减重 ≥ 15 kg 者 86% 缓解减重 10-15 kg 者 57% 缓解
结果 (2 年, 后续随访):
36% 维持缓解 (vs 标准护理 3%)维持缓解者减药 + 心血管标志改善 + 生活质量大幅提升
结果 (5 年, 2024 更新):
继续接受低强度支持的 85 人平均仍比基线轻 6.1 kg, 其中 11 人 (13%) 处于缓解 —— 比 2 年时的 36% 明显回落, 体重回弹是主要复发原因这一档数字提醒的是: DiRECT 证明的是可缓解, 不是一次搞定
落地 · 不是自己在家节食
临床转化:英国 NHS 2020 起把 DiRECT 协议作为早期 T2D 的标准选项之一中国部分医院在做类似项目, 但保险覆盖与营养师资源仍是落地瓶颈注意: 这不是节食, 而是结构化的医疗营养干预 + 长期随访 — 自己减肥并不等于 DiRECT
地中海饮食 + 运动 (PREDIMED 2018, Look AHEAD 2013):
不如 VLCD 减重快, 但更可持续PREDIMED: 地中海 + 橄榄油、坚果 → 心血管事件 -30%适合不能 VLCD 的人群
结论: T2D 的慢性进展不可逆 旧观点已被证伪——早期 + 减重 = 真缓解可能.
Chapter 4
Meds · GLP-1 era
Meds · GLP-1 era
T2D drug landscape by mechanism (2024-2025 consensus):
First-line: Metformin:
Invented 1957, US launch 1995, 60+ years of safety dataMechanism: AMP-activated protein kinase: The cell's 'low fuel' sensor — switches on when energy is low to make energy and pause building. activation + suppression of hepatic glucose output + improved IR (see atlas berberine L4 for the head-to-head)HbA1c ↓ 1-2%Side effects: GI (~ 25%, extended-release improves it) + long-term B12 deficiency (see atlas vitamin-b12)Price: ¥4-15/month, globally available
Second-line option 1: glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. receptor agonists (Liraglutide / Semaglutide / Tirzepatide):
Ozempic (semaglutide, since 2017) / Wegovy (weight-loss version) / Mounjaro (tirzepatide, GLP-1 + GIP, 2022)Mechanism: delayed gastric emptying + central satiety + β-cell insulin secretion + glucagon suppressionHbA1c ↓ 1-2% + weight ↓ 10-20% over 12-24 monthsAdditional hard-endpoint benefits: atherosclerotic cardiovascular disease: The plaque-clogged-artery family of disease — heart attack, stroke, peripheral artery disease. secondary prevention, heart failure, chronic kidney disease protection (SUSTAIN-6, REWIND, LEADER, etc.)2024 STEP-HFpEF, FLOW: significant reductions in all-cause + cardiovascular mortalitySide effects: GI (nausea / vomiting, 20-40%) + rare pancreatitisPrice: ¥800-1500/month, partial Chinese reimbursement; USA $700-1200/month
SGLT2 inhibitors (Empagliflozin / Dapagliflozin / Canagliflozin):
Inhibit renal glucose reabsorption → urinary glucose loss + weight loss + cardiovascular protectionHbA1c ↓ 0.7-1.0% + weight ↓ 2-3 kgEMPA-REG / DAPA-HF / DAPA-CKD: ↓ HF hospitalisation, ↓ CKD progressionSide effects: UTI + rare DKA (diabetic ketoacidosis)Important: used not only for T2D but also for non-diabetic HF + CKD
Others: sulfonylureas (hypoglycemia-prone, fading from first-line) / DPP-4 inhibitors (moderate efficacy, safe) / thiazolidinediones (Pioglitazone, fat-reducing + weight-increasing) / acarbose (postprandial) / insulin (later line)
Major 2024 consensus shift:
GLP-1 / SGLT2 have shifted from "T2D drugs" to "comprehensive cardiometabolic protective agents"A growing number of RCTs show benefit in non-diabetic obesity / HF / CKD patientsControversies: long-term safety? GLP-1 + sarcopenia (muscle loss) + price + post-discontinuation rebound
Debunking "Berberine = Nature's Ozempic" (covered in atlas berberine):
Berberine -2-5% body weight vs GLP-1 -15-20% — 3-5× difference, not comparableBerberine is a metformin alternative, not a GLP-1 alternative
Natural intervention vs drugs:
DiRECT 10-15 kg weight loss ≈ semaglutide weight-loss magnitudeBut DiRECT requires strict protocol + dietitian + a lot of effortDrugs are easier but more expensive + have less long-term dataBest combined: drug to initiate + lifestyle to maintain
First-line: Metformin:
Invented 1957, US launch 1995, 60+ years of safety dataMechanism: AMP-activated protein kinase: The cell's 'low fuel' sensor — switches on when energy is low to make energy and pause building. activation + suppression of hepatic glucose output + improved IR (see atlas berberine L4 for the head-to-head)HbA1c ↓ 1-2%Side effects: GI (~ 25%, extended-release improves it) + long-term B12 deficiency (see atlas vitamin-b12)Price: ¥4-15/month, globally available
Second-line option 1: glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. receptor agonists (Liraglutide / Semaglutide / Tirzepatide):
Ozempic (semaglutide, since 2017) / Wegovy (weight-loss version) / Mounjaro (tirzepatide, GLP-1 + GIP, 2022)Mechanism: delayed gastric emptying + central satiety + β-cell insulin secretion + glucagon suppressionHbA1c ↓ 1-2% + weight ↓ 10-20% over 12-24 monthsAdditional hard-endpoint benefits: atherosclerotic cardiovascular disease: The plaque-clogged-artery family of disease — heart attack, stroke, peripheral artery disease. secondary prevention, heart failure, chronic kidney disease protection (SUSTAIN-6, REWIND, LEADER, etc.)2024 STEP-HFpEF, FLOW: significant reductions in all-cause + cardiovascular mortalitySide effects: GI (nausea / vomiting, 20-40%) + rare pancreatitisPrice: ¥800-1500/month, partial Chinese reimbursement; USA $700-1200/month
SGLT2 inhibitors (Empagliflozin / Dapagliflozin / Canagliflozin):
Inhibit renal glucose reabsorption → urinary glucose loss + weight loss + cardiovascular protectionHbA1c ↓ 0.7-1.0% + weight ↓ 2-3 kgEMPA-REG / DAPA-HF / DAPA-CKD: ↓ HF hospitalisation, ↓ CKD progressionSide effects: UTI + rare DKA (diabetic ketoacidosis)Important: used not only for T2D but also for non-diabetic HF + CKD
Others: sulfonylureas (hypoglycemia-prone, fading from first-line) / DPP-4 inhibitors (moderate efficacy, safe) / thiazolidinediones (Pioglitazone, fat-reducing + weight-increasing) / acarbose (postprandial) / insulin (later line)
Major 2024 consensus shift:
GLP-1 / SGLT2 have shifted from "T2D drugs" to "comprehensive cardiometabolic protective agents"A growing number of RCTs show benefit in non-diabetic obesity / HF / CKD patientsControversies: long-term safety? GLP-1 + sarcopenia (muscle loss) + price + post-discontinuation rebound
Debunking "Berberine = Nature's Ozempic" (covered in atlas berberine):
Berberine -2-5% body weight vs GLP-1 -15-20% — 3-5× difference, not comparableBerberine is a metformin alternative, not a GLP-1 alternative
Natural intervention vs drugs:
DiRECT 10-15 kg weight loss ≈ semaglutide weight-loss magnitudeBut DiRECT requires strict protocol + dietitian + a lot of effortDrugs are easier but more expensive + have less long-term dataBest combined: drug to initiate + lifestyle to maintain
二线 · 减重最猛的那一类
glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. 受体激动剂 (利拉鲁肽、司美格鲁肽/Ozempic、替尔泊肽/Mounjaro 等) 是二线里最亮眼的一类: 它同时延缓胃排空、让大脑更快饱、促 β 细胞分泌胰岛素、压住胰高糖素, 12-24 个月里能把 HbA1c 降 1-2%、体重降 10-20%。更重要的是硬终点收益 —— SUSTAIN-6 等试验显示它能降低心血管事件, 并对心衰、慢性肾病有保护。主要副作用是恶心、呕吐等胃肠反应 (20-40%), 罕见胰腺炎; 价格偏贵 (国内约 ¥800-1500/月, 部分医保覆盖)。二线 · 让糖从尿里走掉的那一类
SGLT2 抑制剂 (恩格列净、达格列净等) 换一条路: 堵住肾脏对葡萄糖的重吸收, 让糖随尿排掉, 顺带减重和保护心肾, HbA1c 降 0.7-1.0%、体重降 2-3 kg。EMPA-REG 等试验证明它能降低心衰住院和慢性肾病进展 —— 正因如此, 它现在连没有糖尿病的心衰、CKD 患者也在用。副作用主要是泌尿生殖系感染, 罕见酮症酸中毒。其余的药各有位置, 但不再是主角: 磺脲类易低血糖、正逐渐淡出, DPP-4 中等效而安全, 吡格列酮减脂肪但增体重, 阿卡波糖管餐后, 胰岛素是后线。
观念 · 从降糖药到护心护肾
把观念转变说透: glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. 和 SGLT2 已经从降糖药升级成心肾代谢的综合保护药, 越来越多证据支持没有糖尿病的肥胖、心衰、CKD 患者也用它们; 争议留在长期安全性、GLP-1 带来的肌肉流失、价格和停药反弹上。至于网红把小檗碱吹成天然版 Ozempic: 小檗碱减重只有 2-5%, GLP-1 是 15-20%, 差 3-5 倍 —— 它顶多算二甲双胍的平替, 不是 GLP-1 的平替 (atlas berberine 详拆)。而 DiRECT 那种减 10-15 kg 的生活方式干预, 减重幅度其实接近司美格鲁肽, 只是更费力; 通常的建议是药物起步、生活方式维持。Chapter 5
Decision tree
Decision tree
🚩 Safety first · when to seek emergency care
Diabetes has several acute emergencies — get emergency care immediately (do not wait) if you have:
Diabetic ketoacidosis (DKA): thirst / frequent urination + nausea & vomiting + abdominal pain + deep rapid or "fruity"-smelling breath + confusionSevere hypoglycemia: cold sweat / shaking / palpitations / altered consciousness / seizure — if awake and able to swallow, take 15 g of fast sugar now; if it does not improve or consciousness is impaired, call an ambulanceHyperosmolar hyperglycemic state (HHS): extreme thirst + heavy urination + drowsiness / altered consciousness (more common in older adults)
The safety floor on meds and diet: any starting, changing, or stopping of medication must be discussed with your doctor first; a very-low-calorie diet (like the DiRECT ~825 kcal) must be done under medical + dietitian supervision — it can put early patients into remission, but it is not a do-it-yourself-at-home plan.
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"I have prediabetes / T2D — what do I do?" — a decision path:
Q1: What stage are you in?
HbA1c 5.7-6.4%: prediabetes — golden window, focus on lifestyleHbA1c 6.5-7.5% + < 6 years duration: early T2D — DiRECT remission candidateHbA1c 7.5-9% + 5-10 years duration: mid-stage — lifestyle + medication (start with metformin)HbA1c > 9% / > 10 years duration / serious complications: multi-drug combinations + possibly insulin
Q2: What is your goal?
Remission (off medication): for early patients, 10-15 kg weight loss is the strongest interventionControl (maintain HbA1c < 7%): most patients, drugs + lifestyle combinedReduce complications + longevity: focus on cardiovascular + renal + retinal protection
Q3: What is your weight and capacity for weight loss?
Can do strict weight loss (time + resources): DiRECT protocol + dietitian + long-term supportModerate weight loss (5-10% target): Mediterranean diet + strength training + walkingDifficulty losing weight (psychological / time / appetite): consider glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. (if indicated)
Q4: Drug choice:
First-line: metformin (unless contraindicated)Second-line + cardiovascular disease / HF / CKD: GLP-1 or SGLT2 (hard-endpoint benefit)Second-line + main goal is weight loss: GLP-1Second-line + high postprandial glucose: acarbose / SGLT2Third-line: multi-drug combinations + insulinNote (ADA 2024/2025): if atherosclerotic cardiovascular disease: The plaque-clogged-artery family of disease — heart attack, stroke, peripheral artery disease., heart failure, or CKD is already present, a GLP-1 or SGLT2 with proven cardiorenal benefit should be started early and need not be preceded by metformin — for these comorbidities the drug order is no longer decided by HbA1c or by metformin first (uncomplicated T2D still starts with metformin)
Core intervention list (do at any stage):
Cut sugar-sweetened beverages + milk tea (atlas SSDs chapter — single highest-ROI move)30 minutes aerobic daily + 2-3 strength sessions per weekVegetables and protein first, carbs last at each meal (Shukla 2015)No eating after 10 PM + 7-8 hours sleepStop smoking + limit alcohol (alcohol + T2D = severe acceleration of hepatic complications)B12 monitoring (annually if on metformin)
Mental health + diabetes:
T2D + depression comorbidity rate 30-40%"Diabetes distress" — treatment burden + self-blame + anxietyIt is not "lack of self-discipline"; it is the psychological burden of a chronic illness — deserves psychological support
Self-management tools:
Continuous glucose monitor (CGM): 1-2 weeks can help understand personal food responsesApps: ADA-recommended in the US; Dingxiang Doctor / Tang Hu Shi in ChinaCommunity support: patient groups + dietitians + endocrinologists
Closing the loop with other atlas stories:
endocrine/metabolic-syndrome L4 (5-step reversibility mechanism)carbs-fiber/glycogen L4 (GLUT4 + insulin signaling)fructose-metabolism + UPF + alcohol (dietary drivers)sleep-apnea + insomnia + shift-work-circadian (sleep drivers)hashimoto / pcos (other endocrine comorbidities)exercise + protein + strength training (Batch IV)These 12 stories converge on this one condition island to form a complete teaching path
Atlas position: T2D is not the destiny tied to the label "diabetes" — it is a state of the metabolic system, and in most early / mid-stage patients it is interveneable and improvable. The atlas gives you mechanism + evidence so you can understand your own metabolism and decide together with your doctor (it does not replace medical care).
Diabetes has several acute emergencies — get emergency care immediately (do not wait) if you have:
Diabetic ketoacidosis (DKA): thirst / frequent urination + nausea & vomiting + abdominal pain + deep rapid or "fruity"-smelling breath + confusionSevere hypoglycemia: cold sweat / shaking / palpitations / altered consciousness / seizure — if awake and able to swallow, take 15 g of fast sugar now; if it does not improve or consciousness is impaired, call an ambulanceHyperosmolar hyperglycemic state (HHS): extreme thirst + heavy urination + drowsiness / altered consciousness (more common in older adults)
The safety floor on meds and diet: any starting, changing, or stopping of medication must be discussed with your doctor first; a very-low-calorie diet (like the DiRECT ~825 kcal) must be done under medical + dietitian supervision — it can put early patients into remission, but it is not a do-it-yourself-at-home plan.
---
"I have prediabetes / T2D — what do I do?" — a decision path:
Q1: What stage are you in?
HbA1c 5.7-6.4%: prediabetes — golden window, focus on lifestyleHbA1c 6.5-7.5% + < 6 years duration: early T2D — DiRECT remission candidateHbA1c 7.5-9% + 5-10 years duration: mid-stage — lifestyle + medication (start with metformin)HbA1c > 9% / > 10 years duration / serious complications: multi-drug combinations + possibly insulin
Q2: What is your goal?
Remission (off medication): for early patients, 10-15 kg weight loss is the strongest interventionControl (maintain HbA1c < 7%): most patients, drugs + lifestyle combinedReduce complications + longevity: focus on cardiovascular + renal + retinal protection
Q3: What is your weight and capacity for weight loss?
Can do strict weight loss (time + resources): DiRECT protocol + dietitian + long-term supportModerate weight loss (5-10% target): Mediterranean diet + strength training + walkingDifficulty losing weight (psychological / time / appetite): consider glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. (if indicated)
Q4: Drug choice:
First-line: metformin (unless contraindicated)Second-line + cardiovascular disease / HF / CKD: GLP-1 or SGLT2 (hard-endpoint benefit)Second-line + main goal is weight loss: GLP-1Second-line + high postprandial glucose: acarbose / SGLT2Third-line: multi-drug combinations + insulinNote (ADA 2024/2025): if atherosclerotic cardiovascular disease: The plaque-clogged-artery family of disease — heart attack, stroke, peripheral artery disease., heart failure, or CKD is already present, a GLP-1 or SGLT2 with proven cardiorenal benefit should be started early and need not be preceded by metformin — for these comorbidities the drug order is no longer decided by HbA1c or by metformin first (uncomplicated T2D still starts with metformin)
Core intervention list (do at any stage):
Cut sugar-sweetened beverages + milk tea (atlas SSDs chapter — single highest-ROI move)30 minutes aerobic daily + 2-3 strength sessions per weekVegetables and protein first, carbs last at each meal (Shukla 2015)No eating after 10 PM + 7-8 hours sleepStop smoking + limit alcohol (alcohol + T2D = severe acceleration of hepatic complications)B12 monitoring (annually if on metformin)
Mental health + diabetes:
T2D + depression comorbidity rate 30-40%"Diabetes distress" — treatment burden + self-blame + anxietyIt is not "lack of self-discipline"; it is the psychological burden of a chronic illness — deserves psychological support
Self-management tools:
Continuous glucose monitor (CGM): 1-2 weeks can help understand personal food responsesApps: ADA-recommended in the US; Dingxiang Doctor / Tang Hu Shi in ChinaCommunity support: patient groups + dietitians + endocrinologists
Closing the loop with other atlas stories:
endocrine/metabolic-syndrome L4 (5-step reversibility mechanism)carbs-fiber/glycogen L4 (GLUT4 + insulin signaling)fructose-metabolism + UPF + alcohol (dietary drivers)sleep-apnea + insomnia + shift-work-circadian (sleep drivers)hashimoto / pcos (other endocrine comorbidities)exercise + protein + strength training (Batch IV)These 12 stories converge on this one condition island to form a complete teaching path
Atlas position: T2D is not the destiny tied to the label "diabetes" — it is a state of the metabolic system, and in most early / mid-stage patients it is interveneable and improvable. The atlas gives you mechanism + evidence so you can understand your own metabolism and decide together with your doctor (it does not replace medical care).
路径 · 你在哪个阶段, 想要什么
我有糖尿病前期 / T2D, 怎么办 — 路径决策:Q1: 你处在什么阶段?
HbA1c 5.7-6.4%: 糖尿病前期 — 黄金窗口, 重点是生活方式HbA1c 6.5-7.5% + 病程 < 6 年: 早期 T2D — DiRECT 缓解候选HbA1c 7.5-9% + 病程 5-10 年: 中期 — 生活方式 + 药物 (二甲双胍起步)HbA1c > 9% / 病程 > 10 年、严重并发症: 多药联合 + 可能胰岛素
Q2: 你的目标?
缓解 (停药): 早期患者, 减重 10-15 kg 是最强干预控制 (维持 HbA1c < 7%): 大多数患者, 药物 + 生活方式综合减并发症 + 长寿: 重点是心血管 + 肾 + 眼底保护
路径 · 能减多少, 药怎么选
Q3: 你的体重 + 减重能力?能严格减重 (有时间 + 资源): DiRECT 协议 + 营养师 + 长期支持温和减重 (5-10% 目标): 地中海饮食 + 力量训练 + 步行难以减重 (心理 / 时间、食欲): 考虑 glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. (有适应症)
Q4: 药物选择:
一线: 二甲双胍 (除禁忌)二线 + 有心血管病、心衰 / CKD: GLP-1 或 SGLT2 (硬终点收益)二线 + 主要要减重: GLP-1二线 + 餐后血糖高: 阿卡波糖 / SGLT2三线: 多药联合 + 胰岛素注意 (ADA 2024/2025): 若已有 atherosclerotic cardiovascular disease: The plaque-clogged-artery family of disease — heart attack, stroke, peripheral artery disease.、心衰或 CKD, 具心肾获益证据的 GLP-1 或 SGLT2 应尽早启用, 且无需先用二甲双胍打底 —— 这类合并症的用药顺序不再由 HbA1c 或二甲双胍先后决定 (无合并症的单纯 T2D 仍以二甲双胍起步)
GLP-1 RA · mechanism + RCTs
The biggest revolution in diabetes care since 2015 — two classes of glucose-lowering drugs with simultaneous "cardiovascular / renal hard-endpoint" benefits have changed the treatment hierarchy. First, glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar..GLP-1 receptor agonists (Glucagon-Like Peptide-1 RA):
Semaglutide (Ozempic / Wegovy) — weekly injection / oralLiraglutide (Victoza) — daily injectionDulaglutide (Trulicity) — weekly injectionTirzepatide (Mounjaro / Zepbound) — dual GLP-1 + GIP agonist, weekly injection, available in China from 2024
Mechanism (5 pathways):
Pancreatic β-cells: glucose-dependent insulin secretion ↑ (very low hypoglycemia risk)Pancreatic α-cells: glucagon ↓Stomach: delayed emptying → smoother postprandial glucose + stronger satietyHypothalamus: appetite center ↓Cardiovascular + renal: direct protection (mechanism not fully attributable to glucose lowering)
Key RCTs:
LEADER (Liraglutide): MACE ↓ 13% / CV death ↓ 22% / all-cause death ↓ 15%SUSTAIN-6 (Semaglutide): MACE ↓ 26%STEP-1 (Semaglutide 2.4 mg for weight loss): weight ↓ 14.9% over 68 weeks (Wegovy indication)SURMOUNT-1 (Tirzepatide): weight ↓ 22.5% over 72 weeks (strongest weight-loss drug to date)SELECT (Semaglutide cardiovascular, non-diabetic): MACE ↓ 20% — pushes GLP-1 into the "anti-cardiovascular disease drug" category
Side effects:
GI: nausea (30-40% on initiation) + vomiting + constipation + diarrhea — dose titration + time to adaptMedullary thyroid carcinoma warning (rodent data, no confirmed human signal): contraindicated in MTC / MEN2 family historyPancreatitis risk: small relative increase, low absolute riskGallstones: associated with rapid weight lossMuscle loss ~ 20-40% of lost weight is lean mass — see atlas sarcopenia warning
SGLT2 + ADA 2024 order
SGLT2 inhibitors (Sodium-Glucose Co-transporter 2):Dapagliflozin (Farxiga)Empagliflozin (Jardiance)Canagliflozin (Invokana)
Mechanism: blocks glucose reabsorption in the renal proximal tubule → urinary glucose loss ~ 80-100 g/day → glucose ↓ + ~ 300 kcal/day calorie loss
Unexpected benefits: HF + renal protection (mechanism not fully attributable to glucose lowering)
Key RCTs:
EMPA-REG (Empagliflozin): CV death ↓ 38%, HF hospitalisation ↓ 35%DAPA-HF (Dapagliflozin in HF, non-diabetic): HF worsening ↓ 26% — SGLT2 also becomes an HF drugDAPA-CKD: CKD progression ↓ 39% — SGLT2 also becomes a kidney-disease drug
Side effects:
Genital candidiasis (high urinary glucose): women 10-20% / men 2-5%UTI slightly ↑Ketoacidosis (DKA): rare; vigilance in T1D / very-low-carb diet usersAmputation risk (canagliflozin CANVAS): slight ↑, follow-up evidence neutral
T2D treatment order (ADA 2024):
First-line: metformin (unless contraindicated)Second-line (with cardiovascular / renal / HF comorbidity): glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. or SGLT2 (choose by comorbidity, no longer by HbA1c alone)Second-line (primary need is weight loss): GLP-1 (especially semaglutide / tirzepatide)Third-line: multi-drug combinations, potentially insulin later
Pricing + GLP-1 miracle-drug caveats
Price + accessibility (China 2024-2025):Semaglutide (Nuotai): ¥800-1200/month, partial reimbursement from 2024Tirzepatide (Duyida): launched 2024, not yet reimbursed, ¥1500-3000/monthDomestic SGLT2 (Hengrui / Innovent / Fosun): substantially cheaper, ¥30-100/month, reimbursement covered
Risks of the "glucagon-like peptide-1: A gut hormone released after eating that makes you feel full and helps lower blood sugar. miracle weight-loss drug" narrative:
Rebound after discontinuation: STEP-4 shows that 1 year after stopping, 67% of lost weight is regainedMuscle loss: ~ 25% of lost weight is lean mass — must be paired with strength training + high proteinLong-term (10+ year) safety data still accumulating"Influencer / cross-border purchase" risks: counterfeit + dose errors + no medical oversight — strong warning
Atlas closure: endocrine/metabolic-syndrome + sarcopenia (GLP-1 + protein + strength) + DiRECT (weight-loss remission) + obesity / weight-loss island.
清单 · 任何阶段都该做的事
重点干预清单 (任何阶段都做):砍含糖饮料 + 奶茶 (atlas SSDs 章, 单一最高性价比)每天 30 分钟有氧 + 每周 2-3 次力量训练餐前蔬菜 + 蛋白先吃, 碳水后吃 (Shukla 2015)晚上 10 后不吃 + 睡眠 7-8 小时戒烟 + 限酒 (酒精 + T2D = 严重肝并发症加速)B12 监测 (服二甲双胍者每年查)
心理健康 + 糖尿病:
T2D 与抑郁共病率 30-40%糖尿病窘困 (diabetes distress) — 治疗负担、自责与焦虑这不是自律不够, 是慢性病自带的心理负担, 值得专门的心理支持
自我管理工具:
连续血糖监测 (CGM): 1-2 周可帮助理解食物个人反应APP: 美国 ADA 推荐 + 中国丁香医生、糖护士 等社区支持: 病友群 + 营养师 + 内分泌科医生
闭环 · 这一岛汇到哪里去
和 atlas 其它故事的闭环:endocrine/metabolic-syndrome L4 (5 步可逆机制)carbs-fiber/glycogen L4 (GLUT4 + 胰岛素信号)fructose-metabolism + UPF + alcohol (饮食驱动)sleep-apnea + insomnia + shift-work-circadian (睡眠驱动)hashimoto / pcos (其它内分泌共病)运动 + 蛋白 + 力量训练 (Batch IV)这 12 个故事汇集到这一个条件岛, 形成完整教学路径
Atlas 立场: T2D 不是糖尿病 这个标签判定的命运, 而是一种代谢系统状态, 在大多数早期与中期患者中可干预、可改善. atlas 提供机制与证据, 帮助你理解自己的代谢, 并和医生一起做决定 (本站为科普, 不构成诊疗建议, 请遵医嘱).
References · 9
- American Diabetes Association. (2024). Standards of Medical Care in Diabetes — 2024. Diabetes Care, 47(Suppl. 1). diabetesjournals.org/care/issue/47/Supplement_1
- Wang, L., Gao, P., Zhang, M., Huang, Z., Zhang, D., Deng, Q., et al. (2017). Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA, 317(24), 2515-2523. 10.1001/jama.2017.7596
- DeFronzo, R. A. (2009). From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes, 58(4), 773-795. Insulin acts via insulin receptor → IRS-1 → PI3K → Akt → GLUT4 translocation in muscle/adipose; suppresses hepatic gluconeogenesis; T2DM involves defects in 8 organs (muscle, liver, beta-cell, fat cell, gut, alpha-cell, kidney, brain). 10.2337/db09-9028
- Rosmond, R. (2005). Role of stress in the pathogenesis of the metabolic syndrome. Psychoneuroendocrinology, 30(1), 1-10. 10.1016/j.psyneuen.2004.05.007
- Lean, M. E. J., Leslie, W. S., Barnes, A. C., et al. (2018). Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet, 391(10120), 541-551. 10.1016/S0140-6736(17)33102-1
- Lim, E. L., Hollingsworth, K. G., Aribisala, B. S., Chen, M. J., Mathers, J. C., & Taylor, R. (2011). Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia, 54(10), 2506-2514. 10.1007/s00125-011-2204-7
- Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., et al. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). New England Journal of Medicine, 375(19), 1834-1844. 10.1056/NEJMoa1607141
- Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., et al. (2015). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes (EMPA-REG OUTCOME). New England Journal of Medicine, 373(22), 2117-2128. 10.1056/NEJMoa1504720
- Shukla, A. P., Iliescu, R. G., Thomas, C. E., & Aronne, L. J. (2015). Food order has a significant impact on postprandial glucose and insulin levels. Diabetes Care, 38(7), e98-e99. 10.2337/dc15-0429