Le PR - DIABTE Faut - il le dpister ? Faut - il le traiter ? Franoise - - PowerPoint PPT Presentation

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Le PR - DIABTE Faut - il le dpister ? Faut - il le traiter ? Franoise - - PowerPoint PPT Presentation

Le PR - DIABTE Faut - il le dpister ? Faut - il le traiter ? Franoise Fry ( ULB ) u Dfinition : cest quoi le prdiabte ? u u Frquence : est-ce frquent ? u u Histoire naturelle : risque de conversion vers un


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SLIDE 1

Le PRÉ-DIABÈTE

Faut-il le dépister ? Faut-il le traiter ?

Françoise Féry (ULB)

u u Définition : c’est quoi le prédiabète ? u u Fréquence : est-ce fréquent ? u u Histoire naturelle : risque de conversion vers un diabète avéré u u Peut-on ralentir l’évolution du prédiabète vers le diabète ? (études de prévention) u u Une hyperglycémie isolée non diabétique est-elle dangereuse ? u u Le prédiabète est-il associé à un risque cardiovasculaire accru ? u u Faut-il le dépister ? Chez qui et comment ? u u Faut-il le traiter ? Si oui, comment ?

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SLIDE 2

Clinical Practice Recommendations 2010

Diabetes Care. 33 (suppl 1): S62-S69, 2010

Qu’entend t-on par prédiabète ?

Before 1979 : Chemical, Latent, Borderline or Subclinical Diabetes 1979 : Impaired Glucose Tolerance (IGT) 1997 : Impaired Fasting Glucose (IFG) 2010 (with HbA1c) : Impaired → Increased Risk for Diabetes Prediabetes or Impaired Glucose Regulation, Non diabetic hyperglycemia, Dysglycemia, .....

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SLIDE 3

86 million American adults—more than 1 out of 3—have prediabetes

86

MILLION

1

OUT OF 3

COULD IT

BE YOU?

PREDIABETES

9

OUT OF10

people with prediabetes do not know they have it

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SLIDE 4

Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes. A prospective cohort study

Ligthart S et al. Lancet Diab & Endocrinol http://dx.doi.org/10.1016/S2213-8587(15)00362-9 2015

Lifetime risk in individuals aged 45 years, adjusted for the competing risk of death (data from 10 050 participants from the Rotterdam Study during a follow-up of up to 14.7 years)

Prediabetes Type 2 Diabetes

Cumula&ve ¡incidence ¡(%) ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡Cumula&ve ¡incidence ¡(%) ¡ n BMI ≥ 35 kg/m2 n BMI ≥ 30 to < 35 kg/m2 n BMI ≥ 25 to < 30 kg/m2 n BMI < 25 kg/m2

25% 15%

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SLIDE 5

Histoire Naturelle de l’Intolérance au Glucose

Evolution vers le Diabète Intolérance au Glucose persistante

En 10 ans

Intolérance au glucose 50% 25% 25% Tolérance au glucose normalisée

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SLIDE 6

10 20 30 40

Fasting plasma glucose 2-hour plasma glucose

<100 <140 100-110 140-165 110-125 165-200 Baseline Plasma Glucose (mg/dl)

5-year Cumulative Incidence of Diabetes (%) in Pima Indians ( n= 5023)

Le risque d’évolution vers le diabète augmente avec le degré de sévérité d’altération de la glycémie

Gabir MM et al. Diabetes Care. 23 1108-1112, 2000

4%

18% 37%

Cumulative Incidence of Diabetes (%)

4%

17% 39%

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SLIDE 7

Adjusted Hazard Ratios for Self-Reported Diagnosed Diabetes according to the Baseline Glycated Hemoglobin Value

Selvin E et al. NEJM. 362: 800-811, 2010

HbA1c (%)

Adjusted Hazard Ratio for Diagnosed Diabetes

The ¡Atherosclerosis ¡Risk ¡in ¡Communi&es ¡(ARIC) ¡study. ¡ 11,092 ¡adults ¡without ¡history ¡of ¡diabetes ¡or ¡cardiovascular ¡disease ¡ Median ¡follow-­‑up ¡&me ¡: ¡approximately ¡14 ¡years

5.7 ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡6.4 ¡

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SLIDE 8

Progression to Type 2 Diabetes characterized by moderate then rapid glucose increases

Mason CC et al. Diabetes 56: 2054-2061, 2007

  • 20 -16 -12 -8 -4 0

Years from diagnosis Longitudinal study in Pima Indians without diabetes at baseline Trajectories of glycemia before diagnosis of Type 2 Diabetes. An analysis from the Whitehall II study

Tabák AG et al. Lancet 373:2215-2221, 2009

2-hour glucose (mg/dl)

The mode of onset of diabetes follows a non-linear trajectory

135 - 130 - 125 - 120 - 115 - 110 - 105 - 100 - 95 - 90 -

Time until end of follow-up (years)

Fasting glucose (mg/dl) l Non-diabetics l Incident diabetes Prospective cohort study of 6538 British civil servants without diabetes at baseline

400 – 300 – 200 – 100 – 0 –

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SLIDE 9

PREVENTION of TYPE 2 DIABETES in IFG and/or IGT

  • 54%
  • 31%
  • 63%

+ 7%

  • 20%
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SLIDE 10

Control Intervention

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Follow-up time (years) 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Cumulative Incidence of Diabetes

Improved lifestyle and decreased diabetes risk over 13 years Long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS)

Lindström J et al. Diabetologia 56: 284-293, 2013

Intervention Follow-up

Risk of developping diabetes Intervention period HR = 0.40 (95% CI 0.30-0.70 ; P<0.001) Post intervention period HR = 0.67 (95% CI 0.48-0.95 ; p=0.023)

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SLIDE 11

Diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study. A 23-year follow-up study

Guangwei Li et al. Lancet Diabetes Endocrinol 2: 474–480, 2014

Cumulative incidence of diabetes incidence over the 23-year follow-up Intervention

HR 0.55 95%CI (0.40-0.76)

  • --- Control Group
  • --- Intervention Group

Propor&on ¡of ¡par&cipants ¡(%) ¡ Follow-­‑up ¡(years) ¡

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SLIDE 12

Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up The Diabetes Prevention Program Outcomes Study

Diabetes Prevention Program Research Group. Lancet Diabetes Endocrinol 3: 866-875, 2015

Over the entire 15-year study Average annual incidence Cumulative incidence vs placebo 7.0% in the placebo group 5.7% in the metformin group

  • 18% (p<0.0001)

5.2% in the lifestyle group

  • 27% (p<0.0001)

no difference between the lifestyle and metformin groups

Cumulative incidence of diabetes (%) Incidence of diabetes (per 100 person-years) Placebo 11.0 Metformin 7.8

  • 31%

Lifestyle 4.8

  • 58%

DPP ¡ DPPOS ¡

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SLIDE 13

Effect of Weight Loss With Lifestyle Intervention on Risk of Diabetes

Hamman RF et al. Diabetes Care. 29: 2102-2107, 2006

Diabetes incidence (per 100 person-years) by change in weight after baseline among DPP participants

Changes in weight from baseline (kg) Incidence rate

  • f diabetes

(per 100 person-years)

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SLIDE 14

u u Définition : c’est quoi le prédiabète ? une hyperglycémie chronique infra-diabétique u u Fréquence : est-ce fréquent ? oui u u Risque de conversion vers un diabète avéré : élevé u u Peut-on ralentir l’évolution du prédiabète vers le diabète ? (études de prévention) oui u u Une hyperglycémie chronique non diabétique est-elle dangereuse ? u u Le prédiabète est-il associé à un risque cardiovasculaire accru ? u u Faut-il le dépister ? Chez qui et comment ? u u Faut-il le traiter ? Si oui, comment ?

Le PRÉ-DIABÈTE

Faut-il le dépister ? Faut-il le traiter ?

Françoise Féry (ULB)

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SLIDE 15

Patients with Glucokinase Mutations have prolonged, mild Hyperglycemia

Steele AM et al. JAMA. 311: 279-286, 2014

Scatterplot of HbA1c by Age in Patients and Controls Linear regression lines show increasing HbA1c with age

Pa'ents ¡with ¡GCK ¡ muta'ons ¡(n=117) ¡

¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡

Unaffected ¡family ¡ members ¡(n=105) Age (year) HbA1c (%)

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SLIDE 16

Prevalence and Severity of complications in GCK mutations

Steele AM et al. JAMA. 311: 279-286, 2014

Characteristics

GCK

(n=99)

Controls

(n=91)

Young Onset T2D (n=83)

GCK vs Controls GCK vs T2D

Current age (yr) 49

(40-63)

52

(42-65)

55

(49-62) NS NS

Fasting glucose (mg/dl) 117

(126-135)

94

(86-101)

144

(112-187) <0.001 <0.001

HbA1c (%) 6.9

(6.5-7.1)

5.8

(5.5-5.9)

7.8

(7.2-8.7) <0.001 <0.001

Duration of hyperglycemia (yr) 49

(40-63)

NA 17

(9-23) <0.001

Albuminuria (%) 1% 2% 25%

NS <0.001

Background retinopathy (%) 27% 12% 34%

NS <0.05

Pre/proliferative retinop (%) 0% 0% 15%

NS <0.002

Maculopathy (%) 0% 0% 17%

NS <0.001

Significant microvascular complic (%)

1% 2% 30%

NS <0.001

Significant macrovascular complic (%)

4% 10% 25%

NS <0.001

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SLIDE 17

Clinical and Metabolic Characteristics in 35-70-year-old Subjects according to their Glucose Tolerance Status (Botnia Study)

Isomaa B et al. Diabetes Care 24: 683-689, 2001

BMI (kg/m2) Insulin Resistance (HOMA IR)

NGT (n = 1988) IFG/IGT (n = 798)

Systolic BP (mm Hg) Diastolic BP (mm Hg) HDL chol (mg/dl) Triglycerides (mg/dl)

Le prédiabète, c’est plus qu’une hyperglycémie

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SLIDE 18

Profile of the Immune and Inflammatory Response in Individuals with Prediabetes and Type 2 Diabetes

Grossmann V et al. Diabetes Care. 38: 1356-1364, 2015

Impact of inflammatory and immune biomarkers on the presence of prediabetes and diabetes.

A logistic model with diabetes or prediabetes vs. normoglycemia as dependent variable was calculated for each biomarker Adjusted for sex and age.

Normoglycemia vs Prediabetes Normoglycemia vs Diabetes

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SLIDE 19

Fasting blood glucose Number of Number concentration participants

  • f cases

≥126 mg/dl 7240 452 110 to <126 mg/dl 19607 1011 100 to <110 mg/dl 32008 1631 70 to <100 mg/dl 185590 9508 <70 mg/dl 15916 646 HR [95% CI] 1.78 [1.56-2.03] 1.17 [1.08-1.26] 1.11 [1.04-1.18] 1.00 [0.95-1.06] 1.07 [0.97-1.18]

HRs for CHD by clinically defined categories of baseline Fasting Plasma Glucose concentration in participants with no known diabetes at baseline

HRs were adjusted for age, smoking status, BMI, and systolic blood pressure, and, where appropriate, stratified by sex.

HR (95% CI) in people with fasting glucose 100-125 mg/dl was 1.12 (1.06-1.18).

Revisiting the links between glycaemia, diabetes and cardiovascular disease

Sattar N. Diabetologia. 56: 686-695, 2013

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SLIDE 20

Revisiting the links between glycemia and cardiovascular disease

Sattar N. Diabetologia. 56: 686-695, 2013

La relation entre la glycémie ou l’HbA1c dans le range non diabétique et le risque cardiovasculaire est incertaine car les études rapportent des résultats variables, soit :

  • Relations linéaires
  • Courbes en J
  • Effet de seuil
  • Pas de relation

et, dans toutes, un risque marginal La glycémie et l’HbA1c sont utiles pour diagnostiquer un diabète existant ou évaluer un risque futur de diabète mais pas pour évaluer le risque cardiovasculaire Les études sont inconclusives

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SLIDE 21

Dépistage du (pré)diabète

Quelles sont les recommandations en 2015 ?

  • 1. Qui dépister ?

European Association for the Study of Diabetes (EASD) Dépistage recommandé chez les individus avec maladie cardiovasculaire avérée, chez les femmes avec antécédents de diabète gestationnel et chez ceux à risque élevé sur base d’un score de risque (FINDRISC suggéré)

European Heart Journal 34: 3035–3087, 2013

American Diabetes Association (ADA) Dépistage recommandé chez les tous les adultes de ≥ 45 ans et indépendamment de l’âge chez ceux avec 1 ou plusieurs facteurs de risque.

Diabetes Care 38 (suppl 1): S8-S16, 2015

  • 2. Quel(s) test(s) utiliser pour le dépistage ?

Pas de recommandation spécifique Glycémie à jeun, 2h post charge orale de 75 g de glucose (HGPO) ou HbA1c

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SLIDE 22

Prediction models for risk of developing type 2 diabetes: systematic literature search and independent external validation study

Abbasi A et al. BMJ 2012;345:e5900

25 prediction models were identified

12 basic models (based on variables that can be assessed non-invasively) 13 extended models (including biomarkers such as glucose concentration)

Conclusions

Most basic prediction models can identify people at high risk of developing diabetes in a time frame of 5 to 10 years. Models including biomarkers classified cases slightly better than basic ones. Most models overestimated the actual risk of diabetes

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SLIDE 23

Type 2 diabetes risk assessment form

Circle the right alternative and add up your points

  • 1. Age

0 p Under 45 years 2 p 45-54 years 3 p 55-64 years 4 p Over 64 years

  • 2. Body Mass Index

0 p Lower than 25 kg/m2 1 p 25-30 kg/m2 3 p Higher than 30 kg/m2

  • 3. Waist circumference measured below

the ribs (usually at the level of the navel) MEN WOMEN 0 p Less than 94 cm Less than 80 cm 3 p 94-102 cm 80-88 cm 4 p More than 102 cm More than 88 cm

  • 4. Do you usually have daily at least 30

min physical activity at work and/or during leisure time (including normal daily activity) ? 0 p Yes 2 p No

  • 5. How often do you eat vegetables, fruit,
  • r berries ?

0 p Every day 1 p Not every day

  • 6. Have you ever taken anti-hypertensive

medication regularly ? 0 p No 2 p Yes

  • 7. Have you ever been found to have high

blood glucose (e.g. in a health examination, during an illness, during pregnancy) ? 0 p No 5 p Yes

  • 8. Have any of the members of your

immediate family or other relatives been diagnosed with diabetes (type 1 or type 2) ? 0 p No 3 p Yes : grandparent, aunt, uncle or first cousin (but no own parent, brother, sister or child) 5 p Yes : parent, brother, sister or own child)

Total Risk Score

The risk of developing type 2 diabetes within 10 years is Lower than 7 Low: estimated 1 in 100 will develop disease 7-11 Slightly elevated: estimated 1 in 25 will develop disease 12-14 Moderate: estimated 1 in 6 will develop disease 15-20 High: estimated 1 in 3 will develop disease Higher Very High: than 20 estimated 1 in 2 will develop disease

FINnish Diabetes RIsk SCore (FINDRISC) to assess the 10-year risk of type 2 diabetes in adults

(www.diabetes.fi/english)

Predicts the 10-year risk of T2 diabetes (including asymptomatic diabetes and IGT) with 85% accuracy Validated in most European populations No laboratory assays No specially trained personnel needed No special equipments Inexpensive, easy, fast and accurate

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SLIDE 24

Prise en charge du Prédiabète

Quelles sont les recommandations en 2015 ? Tout le monde recommande des mesures hygiénodiététiques

European Association for the Study of Diabetes (EASD) Mesures hygiénodiététiques : Régime hypocalorique + Exercice (Reco classe I, niveau A)

European Heart Journal 34: 3035–3087, 2013

American Diabetes Association (ADA) Mesures hygiénodiététiques : Régime hypocalorique visant à une perte de ≥ 7% du poids + Exercice d’intensité modérée pendant au moins 150 min par semaine (A pour IGT – E pour IFG

  • u HbA1C 5.7–6.4%)

La metformine peut être envisagée dans l’IGT (reco A), l’IFG ou HbA1C 5.7-6.4% (reco E) en particulier chez les personnes avec BMI > 35 kg/m2, agés de < 60 ans et les femmes avec antécédents de diabète gestationnel

Diabetes Care 38 (suppl 1): S8-S16, 2015

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SLIDE 25

Study Objectives : to evaluate the effect of adding metformin to the usual care of participants with non-diabetic hyperglycemia on major macrovascular events Study Population 12,898 individuals aged ≥40 years with an estimated 10-year CVD risk ≥20% with non-diabetic hyperglycemia (HbA1c ≥5.5% and <6.5%) Duration : 5-7 years Primary endpoints : CV events Composite endpoint defined as the time to the first occurrence after randomisation of any of

  • Cardiovascular death
  • Non-fatal MI
  • Non-fatal stroke

Secondary endpoints

  • Incidence of and death from non-melanoma cancer
  • Incidence of diabetes
  • Patient satisfaction with treatment

The GLiNT Trial

Glucose Lowering In Non-diabetic hyperglycemia Trial

Results in 2022

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SLIDE 26

u u Définition : c’est quoi le prédiabète ?

Une hyperglycémie chronique infra-diabétique u u Fréquence : est-ce fréquent ? Oui u u Risque de conversion vers un diabète avéré : Élevé u u Peut-on ralentir l’évolution du prédiabète vers le diabète ? Oui u u Une hyperglycémie chronique non diabétique est-elle dangereuse ? Non u u Le prédiabète est-il associé à un risque cardiovasculaire accru ? Peut-être mais faiblement u u Faut-il le dépister ? Chez qui et comment ? Chez les individus à risque, par une glycémie à jeun u u Faut-il le traiter ? Si oui, comment ? Par des mesures hygiénodiététiques

Le PRÉ-DIABÈTE

Faut-il le dépister ? Faut-il le traiter ?

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SLIDE 27

Mais, surtout

Ne pas oublier de dépister et traiter les autres facteurs de risque cardiovasculaire (Cholestérol, HTA, Tabac, ....) mieux validés que la glycémie

sBP LDL-chol HbA1c per 4 mm Hg per 39 mg/dl per 0.9% lower lower lower CV events prevented

  • 5
  • 10
  • 15
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SLIDE 28
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SLIDE 29

10-year follow-up of Diabetes Incidence and Weight Loss in the Diabetes Prevention Program Outcomes Study

Diabetes Prevention Program Research Group. Lancet, 2009

Change in Weight (kg) Cumulative Incidence of Diabetes (%)

Age at randomisation 25-44 years 45-59 years ≥ 60 years

Lifestyle Metformin Placebo

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SLIDE 30

Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects

Carlsson LMS et al. N Engl J Med 367:695-704, 2012

Cumulative Incidence of Type 2 Diabetes

Kaplan–Meier unadjusted estimates of the cumulative incidence of type 2 diabetes in the bariatric-surgery group and the control group. The light shading represents the 95% confidence interval. The adjusted hazard ratio with bariatric surgery was 0.17 (95% confidence interval, 0.13 to 0.21).

Cumulative Incidence of Type 2 Diabetes Follow-up (years)

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SLIDE 31

Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific Death

The Emerging Risk Factors Collaboration. N Engl J Med; 364:829-841, 2011

Hazard ¡ra'o ¡(95% ¡CI) ¡

History o

  • f d

diabetes a at b baseline n n Ye Yes n n No No Hazard Ratios for Vascular Death, according to baseline levels of Fasting Glucose (50 studies, 16 211 deaths) All analyses were stratified or adjusted for sex, age, smoking status and body-mass index. Participants with known preexisting cardiovascular disease at baseline were excluded from all analyses. Mean Fasting Glucose (mmol/l)

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SLIDE 32

Association between HbA1c and All-Cause Mortality: Results of the Mortality Follow-up of the German National Health Interview and Examination Survey 1998

Paprott R et al. Diabetes Care. 38: 249-256, 2015

Risk for all-cause mortality according to restricted cubic spline regression among participants without known diabetes Total population : 5,986 including 461 deaths. Excess mortality risk was not observed for participants with HbA1c between 5.7-6.4%

HR (95% CI) HbA1c (%)

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SLIDE 33

Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up The Diabetes Prevention Program Outcomes Study

Diabetes Prevention Program Research Group. Lancet Diab & Endocrinol 3: 866-875, 2015

Prevalence of aggregate microvascular complications and individual microvascular components at DPPOS-end All participants. None of the treatment group differences were significant for the aggregate or the microvascular components. The aggregate microvascular complications outcome is expressed as the average prevalence among the three components of nephropathy, retinopathy, and neuropathy.

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SLIDE 34

The 10-Year Cost-Effectiveness of Lifestyle Intervention or Metformin for Diabetes Prevention. An intent-to-treat analysis of the DPP/DPPOS

The Diabetes Prevention Program Research Group Diabetes Care. 35: 723-730, 2012

Medical costs of the DPP/DPPOS interventions Lifestyle 4 572 $ Metformin 2 281$ Placebo 752 $ Medical costs received

  • utside the DPP/DPPOS

Lifestyle 26 810 $ Metformin 27 384 $ Placebo 29 007 $

Total medical costs ($)

(per participant during 10 years) Lifestyle 31 382 $ Metformin 29 665 $ Placebo 29 759 $

Cumulative quality of well- being score gained over 10 years was Lifestyle 6.89 Metformin 6.79 Placebo 6.74

Cost of lifestyle (per QALY gained) compared with placebo = $13 000 compared with metformin = $15 000 CONCLUSION Over 10 years, from a payer perspective, lifestyle was cost-effective and metformin was marginally cost-saving compared with placebo.