IL DIABETE NEL TERZO MILLENNIO. MIGLIORA LA PROGNOSI MA AVANZANO LE FORME GIOVANILI

Claudio Borghi

Cattedra di Medicina Interna Università degli Studi di Bologna

The Human (d)evolution

WHO Diabetes: Key facts• The number of people with diabetes has risen from 108 million in 1980 to 422million in 20141.

• The global prevalence of diabetes* among adults over 18 years of age has risenfrom 4.7% in 1980 to 8.5% in 20141 and more rapidly in middle- and low-incomecountries1

• Diabetes is a major cause of blindness, kidney failure, heart attacks, strokeand lower limb amputation1.

• In 2012, an estimated 1.5 million deaths were directly caused by diabetes andanother 2.2 million deaths were attributable to high blood glucose**1.

• WHO projects that diabetes will be the 7th leading cause of death in 2030 2.

• Diabetes can be treated and its consequences avoided or delayed with diet,physical activity, medication and regular screening and treatment for complications1.

1 Global report on diabetes. World Health Organization, Geneva, 2016.2 Projections of global mortality and burden of disease from 2002 to 2030. Mathers CD, Loncar D. PLoS Med, 2006

Type 2 diabetes is increasingly prevalent

• Globally, 387 million people are living with diabetes1

• At least 68% of people >65 years with diabetes die of heart disease2

This will rise to 592 million by 20351

Mortality risk associated with diabetes (n=820,900)3

1 Global report on diabetes. World Health Organization, Geneva, 2016.2 Projections of global mortality and burden of disease from 2002 to 2030. Mathers CD, Loncar D. PLoS Med, 2006

CI = confidence interval.a Numbers for subgroups may not add up to the total because of rounding.b Data are crude, not age-adjusted.

Estimated number and percentage of diagnosed and undiagnosed DM among adults aged ≥18 years, United States, 2015

Data source: 2011–2014 National Health and Nutrition Examination Survey and 2015 U.S. Census Bureau data.

Diabetes is associated with significant loss of life years

.

0

7

6

5

4

3

2

1

040 50 60 70 80 90

Age (years)

Year

s of

life

lost

Men7

6

5

4

3

2

1

040 50 60 70 80 900

Age (years)

WomenNon-vascular deathsVascular deaths

On average, a 50-year-old individual with diabetes and no history of vascular disease will die 6 years earlier compared to someone without diabetes

1 Global report on diabetes. World Health Organization, Geneva, 2016.2 Projections of global mortality and burden of disease from 2002 to 2030. Mathers CD, Loncar D. PLoS Med, 2006

Comparison of the estimated effects of glicemia and DM on the risk of CHD. Results of Mendelial randomization

Ross S et al, Eur Heart J, 2015

Modifiable RF’s for CV disease in DM

• Hypertension• Lipid abnormalities• Physical inactivity• OSAS• SUA/Gout• Metabolic syndrome

Effect of intensive glucose-lowering and multifactorial interventions on CV and mortality outcomes in patients with Type 2 DM:

random effects meta-analysis

Seidu S et Al., Diabet. Med. 2016;33:280–289

From: Temporal Trends in Mortality in the United States, 1969-2013

JAMA. 2015;314(16):1731-1739. doi:10.1001/jama.2015.12319

Age-Standardized Death Rate by Sex and Cause of Death in the United States, 1969-2013

Efficacy and safety of new antidiabetic drugs

Trial ELIXA SAVOR-TIMI 53 EXAMINE TECOS EMPA-REG CANVAS

Reference Pfeffer et al, 2015 Scirica et al, 2013 White et al, 2013 Green et al, 2015 Zinman et al, 2015 Neal et al, 2017

Treatment lixisenatide saxagliptin alogliptin sitagliptin empagliflozin canagliflozin

CV outcomes(MACE)

HR 1,02, IC 95%(0,89-1,17)p <0,001

HR 1,00, IC 95%(0,89-1,12)p = 0,001

HR 0,96 (≤1,16)upper boundary 1-sided rep IC 95%p ≤0,001

HR 0,98, IC 95%(0,88-1,09)p <0,001

HR 0,86, IC 95%(0,74-0,99)p <0,001

HR 0,86, IC 95%(0,75-0,97)p <0,001

Hospitalizationfor HF

HR 0,96, IC 95%(0,75-1,23)p = 0,75

HR 1,27, IC 95%(1,07-1,51)p = 0,007

HR 1,19, IC 95%(0,90-1,58)p = 0,220

HR 1,00, IC 95%(0,83-1,20)p = 0,98

HR 0,65, IC 95%(0,50-0,85)p = 0,002

HR 0,67, IC 95%(0,52-0,87)p = 0,002

DeathHR 0,94, IC 95%(0,78-1,13)p = 0,50

HR 1,11, IC 95%(0,96-1,27)p = 0,15

HR 0,88, IC 95%(0,71-1,09)p = 0,23

HR 1,01, IC 95%(0,90-1,14)p = 0,88

HR 0,68, IC 95%(0,57-0,82) p <0,001

HR 0,78, IC 95%(0,67-0,91) p <0,002

Pfeffer et al. N Engl J Med 2015;373:2427; Scirica et al. N Engl J Med 2013;369:1317; White et al. N Engl J Med 2013;369:1327;Green et al. N Engl J Med 2015;373:232; Zinman et al. N Engl J Med 2015;373:2117; Neal B New Engl J Med 2017; 377:644

From: Management of Type 2 Diabetes in 2017Getting to Goal

JAMA. Published online March 01, 2017. doi:10.1001/jama.2017.0241

Glucose Management for Patients With Type 2 Diabetes

″Regression to disease″

Type 2 Diabetes Mellitus in youth

• T2DM in youth has increased over the past 20 years

• ~5,000 new cases per year in the U.S.

• T2DM in youth is different from both T1DM in youth and T2DM inadults

• Disproportionally impacts youth of ethnic and racial minorities

• Additional risk factors include:

• Adiposity, family history of diabetes, female sex, and lowsocioeconomic status, (other?)

Children and Adolescents: Standards of Medical Care in Diabetes - 2018. Diabetes Care

2018; 41 (Suppl. 1): S126-S136

Estimated prevalence of diagnosed DM among the total population and among children and adolescents, United States, 2015

CI = confidence interval. Note: Data rounded to nearest thousand and not age-adjusted

Data source: 2013–2015 National Health Interview Survey and 2015 U.S. Census Bureau data.

Prevalenza del DM in funzione del sesso e dell’età in Italia

Osservatorio ARNO Diabete, Il profilo assistenziale della popolazione con diabete, 2017

Type 1 and Type 2 DM among Youths, 2002–2012, United States:model-adjusted incidence estimates per 100,000 youths in the

SEARCH for Diabetes in Youth Study

The incidence of type 1 diabetes was assessed among participants who were 0 to 19 years of age, and the incidence of type 2 diabetesamong participants who were 10 to 19 years of age. P values are for the linear trend tests in each racial or ethnic group, according totype of diabetes. Significant results suggest a positive annual rate of increase during the study period.

Mayer-Davis EJ et Al., N Engl J Med 2017;376:1419-29.

Prevalence of complications and comorbidities among teen-agers and young adults who had been diagnosed with DM during childhood or

adolescence in the SEARCH for Diabetes in Youth study

Dabelea D et Al., JAMA. 2017;317(8):825-835.

Some Pathways through Which Excess Adiposity Leads to Major Risk Factors and Common Chronic Diseases.

Heymsfield SB, Wadden TA. N Engl J Med 2017;376:254-266

Body-Mass Index (BMI) during Adolescence and Subsequent Cardiovascular Mortality.

Twig G et al. N Engl J Med 2016;374:2430-2440

Serum uric acid and risk of incident type 2 diabetes

Fix-effects model analysis for the overall RR (1.56, 95% CI = 1.39–1.76) of incident type 2diabetes for the highest compared with the lowest category of serum uric acid level. Noevidence of heterogeneity across tudies was found (I2 = 0.0%, P = 0.571). The squaresizes are proportional to the weight of each study in the meta-analysis; the horizontal linesrepresent 95% CIs; the diamond represents the overall RR with its 95% CI.

Lu et al. PLoS One. 2013;8(2):e56864

Sugar-Sweetened Soft Drinks, Diet Soft Drinks, and Serum Uric Acid Level: The Third National Health and Nutrition Examination Survey (14,761 participants age >20 years)

Jee Woong J. Choi, et al. Arthritis & Rheumatism, 2008

Johnson RJ, et al. JASN 2012 (mod)

A pathway by which fructose is metabolized into uric acid

KHK, ketohexokinase.

Oxidative stress

INS-RESISTANCE

XO

InflammationSRA activationXO

Screening criteria for type 2-DM in adolescents

Type 2 DM: Recommendations

Screening and Diagnosis:• Risk-based screening for prediabetes and/or type 2 DM

should be considered in children and adolescents afterthe onset of puberty or ≥10 years of age, whicheveroccurs earlier.

• If tests are normal, repeat testing at minimum of 3-yearintervals (E), or more frequently if BMI is increasing (C)

Children and Adolescents: Standards of Medical Care in Diabetes - 2018. Diabetes

Care 2018; 41 (Suppl. 1): S126-S136

Take home messages

• Diabetes (type-2) is one of the most prominent RF’s forcardiovascular and renal disease and its prevalence isincreasing across the world.

• The most recent treatment strategies have improved theclinical outcome of patients with Type-2 DM

• The prevalence of diabetes is increasing in the adolescentpopulation and associated with a high risk of complications

• A more comprehensive approach to DM involvingidentification and prevention of the risk factors for the diseasein the younger generations cannot be further delayed