Steno Diabetes Center

Steno Diabetes Center

Offentligt hospital Steno Diabetes Center 5.500 patienter tilknyttet - 600-700 nye patienter hvert år Ca 25.000 ambulante konsultationer per år - læger, sygeplejersker, dietister, fodterapeuter, hjemme besøg Sengeafdelingen: 5-dags afsnit - 12 senge

Type 2 diabetes Frequency of macrovascular diseases at diagnosis Previous Cerebro-vascular attack 7% Abnormal ECG 18% Hypertension >70% Claudicatio intermittens 4.5% Abcence of palpable peripheral pulses 13%

CVD?? OSA DM?

A global pandemic Prevalence of diabetes among adults in 2010 (%) <4 4-5 5-7 7-9 9-11 12

A global pandemic Prevalence of diabetes among adults in 2030 (%) <4 4-5 5-7 7-9 9-11 12

The magnitude of the problem 2010 2030 Total number of people with diabetes (age 20-79) Prevalence of diabetes (age 20-79) 285 million 438 million 6.6 % 7.8 %

Diabetes Mellitus 2010 Skøn over udbredelse i Danmark 26.000 140.000 125.000 50.000 Type 1 Type 2 Insulin behandlet Type 2 Diæt/tbl. behandlet Type 2 Ikke diagnosticeret

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 1994 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 9

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 1998 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 10

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 2002 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 11

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 2006 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 12

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 2008 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 13

Once more!

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 1994 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 15

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 1998 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 16

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 2002 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 17

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 2006 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 18

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 2008 Obesity (BMI 30 kg/m 2 ) Diabetes Missing Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% 26.0% Missing data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 19

Insulin resistance is associated with abdominal obesity

Fat overflow hypothesis Caloric intake Saturated fat SC fat Free fatty acids Abdominal fat Free fatty acids adipokines Intrahepatic fat Intramyocellular fat Insulin resistance Beta-cell dysfunction

Why??

The usual suspects.. Ageing population Urbanization Obesogenic cultures Change in lifestyle Change in psychosocial environment?

years Ageing population Estimated life expectancy at birth by region (2002-2050) 90 80 70 60 50 2002 2025 2050 40 world africa asia europe latin america and carribean north america oceania Source: U.S. Census Bureau, Global Population Profile, 2002

% urban Urbanization Estimated urbanization by region (1950-2030) 90 80 70 60 1950 50 2000 40 30 2030 20 10 world africa asia europe latin america and carribean north america oceania Source: United Nations, World Urbanization Prospects: The 2003 Revision (medium scenario), 2004

Obesogenic cultures (sedentary life)

Diabetes epidemic the usual suspects.. Populations become more and more inactive!

Obesogenic cultures (food advertising)

Public health challenge Exporting obesity and diabetes since 2000! Number of people with diabetes (1995-2010) Weng & Bi, Diabetes Res Clin Pract, 2010

2.5 million years 50 years

Find 5 fejl

Lifestyle change

Psychosocial work stress

Social isolation

Hypothetical mechanisms psychosocial stressor impairment of brain neurotransmitters activation of neuroendocrine pathways high-fat/sugar diet alcohol consumption smoking physical activity adipose tissue blood pressure triglycerides HDL-cholesterol low-grade inflammation TYPE 2 DIABETES

0.80 0.85 0.90 0.95 1.00 0.80 0.85 0.90 0.95 1.00 Incidence of type 2 diabetes by baseline psychosocial work stress Whitehall II study, UK MEN Kaplan-Meier survival estimates, by work_stress WOMEN Kaplan-Meier survival estimates, by work_stress 0 5 10 15 analysis time 0 5 10 15 analysis time work_stress = no work_stress = yes work_stress = no work_stress = yes Log-rank test p=0.87 Log-rank test p=0.017

Cardiovascular death Schramm et al Circulation 2008

Survival (%) Survival (%) Survival Post-MI in Men and Women With and Without Diabetes Diabetes No diabetes 100 Men 100 Women 90 90 80 70 n=1628 80 70 n=568 60 60 50 40 n=228 50 40 n=156 0 10 20 30 40 50 60 0 10 20 30 40 50 60 Months Post-MI Months Post-MI Adapted from Sprafka JM et al. Diabetes Care 1991;14:537 543.

CVD risk factor profile in diabetes Hyperglycaemia Blood pressure Dyslipidaemia Urinary albumin excretion rate Smoking BMI Left ventricular hypertrophy Autonomic dysfunction??? Endothelial dysfunction Insulin resistance / Hyperinsulinaemia Familial predisposition to CVD Obstructive sleep apnea? OSA

Insulin resistance is associated with abdominal obesity

MR scan of distribution of neck fat control subject non-obese patient with OSA

Obstructive sleep apnea in diabetes 305 Americans referred for sleep AHEAD obese (BMI 36.5 kg/m2) Foster et al, Diab Care 2009 35 30 25 20 15 10 5 0 no moderate AHI: <5 5-15 15-30 >30 86 % 279 Americans unselected obese (BMI 33.5 kg/m2) Einhorn et al, Endocrine Prac 2007 40 35 30 25 20 15 10 5 0 72 %

OSAID Obstructive sleep apnea in diabetes Aim: To estimate the prevalence of OSA in type 2 diabetes patients in Denmark Patients: Unselected clinic based cohort of all newly referred patients with type 2 diabetes Design: 3 step approach Collaboration between: - Patientcare center at Steno Diabetes Center - Clinical Research Unit at SDC - Respiration Center East, Rigshospitalet

OSAID 3 step approach: 1) Berlin questionnaire 2) ApneaLink 3) Referral for sleep clinic

OSAID status (9.marts 2011) 143 Berlin questionnaires 57 without symptoms of OSA 77 ApneaLink handed out 57 % 21 without signs of OSA 43 referred to sleep clinic 34 % 10 / 11 has OSA AHI: 18 (5-43) CPAP indicated!!!

Health, social and economical consequences of OSA - in Denmark Higher rates of - health related contact - medication use - unemployment Annual excess (direct/indirect cost): 28 950 DKK - 250 000 pts with type 2 diabetes - 34% has OSA - ~ 2.5 mia DKK per year Jennum and Kjellberg, Thorax 2011

behandling?

Improved glycaemic control and mortality Intensive (SU/Ins) vs. Conventional glucose control HR (95%CI)

DIABOSA study Background OSA is associated with: hyperglycaemia insulin resistance in non-diabetic subjects hypertension dyslipidaemia CPAP treatment improves insulin sensitivity in non-diabetic subjects reduces nighttime blood glucose in T2DM no change in HbA1c or insulin resistance in T2DM

NT-proBNP in type 2 diabetes Elevated in type 2 diabetes with BP, UAE, LVDD and dysfunction Independent predictor of all cause mortality cardiovascular mortality Risk marker for CVD and heart failure in type 2 diabetic patients with microalbuminuria

Proportion died (%) All cause mortality in 315 type 2 diabetic patients according to NT-proBNP tertiles 100 1 0,9 0,8 80 0,7 p<0.0001 Upper tertile (>103ng/l) 0,6 60 0,5 0,4 40 0,3 0,2 20 Middle tertile Lower tertile (<41 ng/l) 0,1 0 0 2 4 6 8 10 12 14 16 18 Follow-up (years)

DIABOSA study Design Doubleblind,randomised,cross-over,placebo-controlled Intervention CPAP versus sham CPAP Endpoint: change in NT-proBNP Patients (n=50) type 2 diabetes OSA (AHI > 10) stable blood glucose and blood pressure therapy

285 mio pts with diabetes increasing - prevalence ~ 7% OSA and diabetes? Prevalence of OSA in T2DM: 34 %??? DIABOSA - CPAP treatment effect?