多因素介入對糖尿病的影響課件

1、Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes Gde, P., Lund-Anderen, H., Hans-Henrik, P., and O. PedersenN Engl J Med 2008;358:580-91Peter KarackiGIM Journal ClubMarch 25, 2008Diabetes BackgroundIn 2005, U.S. prevalence of DM = 20.8 million people or 7% of the population6th

2、 leading cause of death in the U.S. in 2004Risk of death is 2x for an individual with diabetes vs. one without it at the same ageFrom 1991 to 2001, the CDC found a 61% increase in diagnosis of diabetesDiabetes ComplicationsHeart Disease 2-4x death rates vs. adults w/o DMCVA risk = 2-4x higher vs. ad

3、ults w/o DMRetinopathy #1 cause of blindness in adults 20-74 yoa.Nephropathy #1 cause of CRFNervous system damageAcute hypoglycemia or hyperglycemiaPeripheral vascular diseaseComplications during pregnancySteno-2 Study: Intensive therapy vs. conventional therapy for DMII (2003)Intensive therapyBenef

4、its: (n = 80)Hazard ratioConfidence Interval1. CV Disease0.470.24 to 0.732. Nephropathy0.390.17 to 0.873. Retinopathy0.420.21 to 0.864. Autonomic neuropathy0.370.18 to 0.79Gde et al. Multifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes. NEJM. 2003;348:383-393Steno-

5、2 Follow-up: Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes (2008)Steno-2 mean length = 7.8 yrs Steno-2 f/u mean length = +5.5 yrs“Where are they now?”Study PopulationEnd of Steno II Beginning of f/uSteno IISteno-II Treatment ObjectivesGde et al. Multifactorial Intervention

6、and Cardiovascular Disease in Patients with Type 2 Diabetes. NEJM. 2003;348:383-393Steno-II f/u goals for both groupsSteno-II Intensive Therapy (cont)If HTN thiazide, CCBs, BB, or ACE-I/ARBDaily MVI Vit. C, D-tocopherol, folic acid, + chrome picolinateFat 30% of daily calorie intake (saturated 10%)L

7、ight-to-mod. exercise x 30 min 3-5x/week encouragedSmokers or smoking spouses smoking cessation classesSteno-II f/u Endpoints2 Endpoints1. Death from a CV cause2. CVD events: a. nonfatal CVA b. nonfatal MI c. CABG d. PCI/PVD int. e. amputation 3 Endpoints1. Incident nephropathy2. Development/progres

8、sion: a. Diabetic retinopathy b. Peripheral neuropathy c. Autonomic neuropathy1 Endpoint = Time to death from any causeStatistical AnalysisStatistical analysis to begin when 60 patients or of a group had died1/2 Outcomes 1. Kaplan-Meier time to 1st event 2. Treatments compared by log-rank test 3. Pr

9、oportion-hazards model to generate hazard ratios + CIs3 Outcomes Proportional-hazards model w/adjustment for age, duration of diabetes, sex + microvascular status at baseline to determine relative risksChanges in measured values 1. Analysis of covariance2. Mann-Whitney testClinical Characteristics (

10、cont)Fig. 2A Changes in Selected Risk factors during the Interventional study and Follow-up Period7.71.2/8.01.414734/1553214014/146187129/7728748/73799 (29-1148)148 (35-318)Intensive therapyConventional therapy1 Endpoint: Cumulative Incidence of DeathFig. 3A Cumulative risk of death from any causeIn

11、tensive Group: 24 deaths (30%)Conventional Group: 40 deaths (50%)ARR = 20% (P=0.02)Hazard ratio = 0.5495% CI = 0.32 to 0.89 (P=0.02) 2 Endpoints: Number of CVD eventsFig. 3C Number of deaths from a CV cause and number of CVD eventsNumber of CVD EventsIntensive Group: 51 events in 25 patients (31%) o

12、r 0.6/PatientConventional Group: 158 events in 48 patients (60%) or 2.0/patientARR = 29%Hazard ratio = 0.4195% CI = 0.25 to 0.67 (P=0.001) 3 Endpoints: Microvascular Complications20/37RR = 0.44 (P=0.004) 95% CI = 0.25 0.77RR = 0.57 (P=0.01) 95% CI = 0.37 0.8841/5439/52RR = 0.53 (P=0.004) 95% CI = 0.

13、34 0.8144/46RR = 0.97 (P=0.89) 95% CI = 0.62 1.511 Endpoint 30% death rate in intensive therapy group vs. 50% in the conventional group over 13.3 years (ARR = 20%, P = 0.02).Discussion2 Endpoints 51 CV events in 25 patients in the intensive-therapy group vs. 158 in 48 patients in the conventional gr

14、oup = a mean of 0.6 events per patient vs. 2.0, respectively. (ARR = 29%). 3 Endpoints Statistically significant in progression of nephropathy, retinopathy, and autonomic neuropathy in intensive-therapy group. No in progression of diabetic neuropathy.Clinical characteristics Fewer differences in ris

15、k factors in the f/u study vs. the original one. Excellent LDL values obtained. Mediocre HbA1c values and poor SBP control. 1. Length of the studyStrengths2. Excellent retention of patients given the study duration3. Comprehensiveness of the study in terms of measuring multiple outcomes and complica

16、tions of diabetes4. The majority of the outcome measures reached statistical significanceWeaknesses/Limitations1. The patient population only included white Danes3. The therapies received by the conventional group were ill-defined and inconsistent versus the intensive-therapy group 2. The overall sa

17、mple size of 160 is relatively small4. NPH and regular insulin are arguably inferior to glargine and ultra-short acting insulins in terms of risk of complications and stable management of blood glucose5. Further data analysis should have been done to determine if individual risk factors (such as SBP

18、 or LDL) had a statistical effect on the different measured outcomesImpact on Clinical Practice4. 2008 ADA Diabetes Treatment Goals1. Diabetes management is not just fixing BG2. The intensive therapy group benefited from constant education (4x a year during Steno 2) that likely has an immeasurable i

19、mpact on their outcomes in complications of diabetes 3. It appears as if many diabetics “forget” what they have learned over time.ReferencesGde, P., Lund-Anderen, H., Hans-Henrik, P., and O. Pedersen. Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes. NEJM. 2008;358:580-912005 National Diabetes Fact Sheet, CDCMinino, A., Heron, M., Murphy, S., and K. Kochanek. Deaths: Final Data for 2004. CDC National Vitals Statistics Report. 2004;55;19 Mokdad, A., Bowman, B., Ford, E., Vi