Prevention of complications: are we winning or losing the battle. Naveed Sattar Professor of Metabolic Medicine

Transcription

1 Prevention of complications: are we winning or losing the battle Naveed Sattar Professor of Metabolic Medicine

2 Duality of Interest Declaration Consultant or speaker for: Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Roche Diagnostics, Sanofi Grants: Boehringer Ingelheim

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4 Top line: lots good news, yet rising challenges Once upon a time. T2DM = CHD risk equivalent Average life expectancy 12 years less CVD risks down: perhaps non-fatal >> fatal relative to general population More focus on HF as MI rates down Lifetime risks greater: younger onset T2DM, Type 1 diabetes

5 HR mortality in people with vs. without diabetes by decade of entry into the baseline survey ERFC (2011) NEJM

6 Trends in rates of all-cause mortality in those with diagnosed type 2 DM Gregg EW, Sattar N, Ali MK. Lancet Diabetes & Endocrinology. 2016

7 44% 29% Rashwani et al (2017) NEJM

8 Diabetes-related CV complications have declined with improved care, but substantial burden remains Years CV, cardiovascular; MI, myocardial infarction. Adapted from Gregg EW, et al. N Engl J Med. 2014;370:

9 Shah A et al (2015) Lancet Diabetes Endo

10 Risk factors for CVD changed most so CVD rates most declined; BMI and glucose changed less High Glucose T2DM High BMI Lifestyle We can do better Lean et al (2018) Lancet DiRECT trial HBP Altered lipids CVD Risks

11 Rethinking diabetes to cardio-renal complications Traditional focus T2DM Lipids Glucose BP Thrombotic tendency Accelerated Atherogenesis MI, CVA, PAD Obesity Novel Insights Insulin Renal SGLT2 Glomerular hyperfiltration TGF other mechanisms? Na + & glucose retention Intravascular volume increase Volume Status/ Hemodynamic & Glomerular stress Heart Failure Kidney disease Sattar N, McGuire D (2018) Circulation

12 Magnitude of Improvement in Risk Factors and Control among the US Diabetic Population, (Large: 15+ % point; Moderate: 5-14 % point; Small/None: <5 % point) Gregg, Sattar, Ali (2016) Lancet D/E Compared to Persons without Diabetes Lower smoking rates and higher smoking cessation/quit rates. Better (20+point) HTN control levels. Much Higher statin use and greater LDL improvement. Exception: Adults age References: Ali et al., NEJM, 2014; Imperatore et al., Am J Epidemiol; Wang et al., Diabetes Care, 2010; Gu et al., Hypertension 2012; Fan et al., Prev Chronic Dis 2013; Ford et al., Cardiovascular Diabetol 2013;

13 DRCP 2013

14 Improved risk factors over 10 years NZ (2010 vs 2001) Risk factors HbA1c 0.2% SBP 5 mmhg Chol 30 mg/dl Alb /Creat ratio 1.3 unit BMI 1 unit 1 year older average Double number of T2DM Admissions / Rate ratios Ketoacidosis 56% IHD 41% PVD 65% Nephropathy 50% Renal 98% Neurological 56% Tomlin DRCP 2013

15 Lower-Extremity Amputations Scotland: A nationwide study Kennon et al (2012) Diabetes Care 40% reduction 2004 to 2008

16 Any DR 19% UKPDS 39%

17 CHD RISK Diabetes and CVD risk: improving picture CHD equivalent Lower retinopathy Diagnosis ~ 5-15 years Age Sattar (2013) Diabetologia (several studies support concept)

18 Summary part 1: Big successes but future challenges Atherothrombotic CVD declined ++ Better risk management, earlier diagnosis Non-atherothrombotic modes of CVD less well? Haemodynamic? /Treatment-induced hypos? /other? Slowing glycaemic progression but as living longer, overall hyperglycaemia exposure higher? Renal disease, neuropathy increase? T2DM prevalence 3 times as high higher incidence initially, now better survival

19 Heterogeneity in CVD risks are common by simple characteristics Age of T2DM onset T1 vs T2DM

20 DM: double CVD risk on average ERFC (2010) Lancet Hazard ratios for vascular outcomes DM vs. no DM

21 ERFC (2011) NEJM

22 Far higher when T2D in young Steinarsson et al (2018) Diabetologia

23 Younger T2DM higher HbA1c diagnosis and faster deterioration Steinarsson et al (2018) Diabetologia

24 4. Type 1 higher absolute risks and life losses T2 more toxic than T1DM, only IF Develop at same age heavier, higher BP, worse lipids etc BUT Average T1DM age diagnosis 14 (vs T2DM) so absolute risk and life years lost far greater

25 Constantino et al (20xx) Diabetes Care

26 HF data Scotland-wide data: HF rates HIGHER in T1DM McAllister et al (2018) Circulation

27 Rashwani et al (2017) NEJM Gains in both Fatal and non-fatal disease relative to background population BUT gap remains large Highest risk earlier onset T1DM independent of duration Rawshani, Sattar et al (In press) Lancet

28 LMIC challenges High income countries 70s 2000s Data from Mexico Younger onset Faster progression Lack even basic drugs Herrington (2018) Lancet Diabetes Endocrinol

29 Conclusion: CVD, total mortality in DM Big gains MI, CVA, less so HF? BP and LDL-c reduction >> glucose reduction Earlier diagnosis, less retinopathy Age of onset major risk stratifier (later better) Risks down but lifetime risks higher T1DM But big challenges Huge increase T2DM numbers (+ younger, obese) More T2DM living with co-morbidities (CVD+non-CVD) Will newer meds help to further slow renal, HF? LMIC countries, risks greater due to lack of basics

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