第四章 討論
第一節 結果討論
Diabetes is traditionally known to predispose of atherosclerotic pathophysiology with its causal role in occlusive vascular disease. Since the publication of the ADAM by Lederle et al in 19977, the evidence of inverse relationship between diabetes and aortic aneurysm
development is addressed. It had point out a challenge to the traditional view of AAA as a manifestation since that time. Documented studies focused on a protective effect of diabetes have already increased currently. Several articles had reported that AAAenlargement
progresses more slowly in diabetic patients.15,16,17,18,19
Besides, the patients with carotid artery stenosis or aorto-iliac occlusive diseasehad significant negative association between the developmentof AAA and diabetes.20,21,22 Compared to reported researches, the overall incidence of AAA in our study was 23% lower in the DM cohort than in the non-DM cohort (2.76 vs. 3.60), with an adjusted HR of 0.57. Our data also revealed negative association between diabetes and AAA. However, this inverse association also had been challenged, as the consideration of ”competing risk”. The theory described that if AAA were particularly lethal in diabetics, more patients with both conditions might die before they could be identified at AAA screening. Nevertheless, the explanation has been opposed and potential reasons were explained7. If diabetics were more likely to have AAA diagnosed prior to screening, fewer AAA would be left for detection at screening. Following these described considerate, the prevalence of diabetes should be increased in patients with previously diagnosed AAA. But the same low rate of diabetes as in those with screening-detected AAA was found. The conclusions strongly suggested that the present ”competing risk” between diabetes and abdominal aortic aneurysm could not contribute the evident difference. 7 From our population-based data, sex-specific analysis showed higher protective effect from diabetic patients in men than women (IRR=0.68 vs. IRR=1.02). Hence, the adjusted HR was also higher protective benefit in men than in women. The documented similar results had been established. The large, population-based study assessed the relationship between
diabetes and AAA in men over the age of 65.23,24 A recent analysis, AAA events in a cohort of
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161,808 post-menopausal women followed-up for a mean of 7.8 years, found that women who suffered an AAA event had a lower prevalence of diabetes and the negative association between diabetes and AAA seen in men is also evident in women. 25In the United Kingdom Small Aneurysm Trial, the hazard ratio (HR) for risk of rupture was four times higher in women compared with men (HR 4.0, 95% CI 2.0-7.9; P<0.001), but the HR for the primary outcome of all-cause mortality was worse for immediate repair in women (0.99) than in men (0.80) 26 However, data from the ADAM screening program had a contrary result and showed that female sex is a negative risk factor for the presence of AAA (OR 0.17, 95% CI
0.07-0.48).27 The estrogen of women had also been researched and might occupy a possible role in the against effect of abdominal aortic aneurysm.28Different hormone therapy
contribute to significantly different abdominal aortic aneurysm eventswas also
documented.29,30These reports had offer a explanation in the different association between male and women in the inverse relationship between AAA and DM.
We supposed the reasons of patients with diabetes higher beneficial effect in men, and more significant with increased age through the NHIRD base.
The diminishing risk of abdominal aortic aneurysm with increasing duration of diabetes was observed in an article24: 3-5years (OR 0.50), 6 -12 years (OR 0.57), over 12 years (OR 0.37). The reason may be due to long diabetic duration, the more stiffed aneurysmal wall was expected to against aortic pressure. In this study, we compared the probability free of
abdominal aortic aneurysm for patients with and without diabetes mellitus. The Kaplan-Meier survival analysis showed that patients with DM had significantly lower rates in AAA than the comparisons. Invitingly, the curves for AAA become wider starting years 5. According to the prescribed mechanisms, we further analyzed the follow up duration in advanced DM group.
During the within five years after advanced DM diagnosis, the incidence rate of AAA was lower in the advanced DM cohort than non-DM cohort (0.63 vs. 0.91) and adjusted HR is 0.54 (95% CI=0.29-0.99) (Table 5). However, when follow-up duration is more than 5 years, the adjusted HR is 0.31, P valve cannot be significant. We considered that the too small rupture event (n=3) might contribute to the potential basis.
The associations between different level diabetic condition and the risks of AAAW and AAAR were presented in our study. The hospital discharge data claimed from New York and Florida showed that diabetics were less likely to have an ruptured abdominal aortic aneurysm at the time of repair.31 We specific pay attention to the severity of diabetes and partitioned as advanced and uncomplicated status according to coexist DM-related disease. Present diabetic
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related complications such as nephropathy, retinopathy, neuropathy were defined as the advanced.
Varieties of studies potentially provide the possible mechanism to find out the relation of aneurysm rupture. Norman et al.9 described mechanisms involving the aortic wall that result in aneurysmal disease. Intraluminal thrombus (ILT) and ILT growth are also considered to associate with the rate of expansion of AAAs10,11 In small molecular mechanisms, the advanced glycation has been shown to induce cross-linking of collagen lattices in theaortic media in diabetic patients, and this cross-linking resists proteolysis and inhibits secretion of the matrix metalloproteinases (MMP). They are thought to mediate abdominal aortic aneurysmal formation.32Diabetes also suppresses plasmin, itself an activator of matrix metalloproteinases.33 The effect decrease aortic wall degradation directly and may also explain the thicker abdominal aortic wall observed in diabetes. A thicker aortic wall reduces wall stress by the Law of LaPlace,34 and wall stress is considered fundamental to abdominal aortic aneurysm progression.35 We considered that the advanced diabetes has persistent highest quartile of blood sugars. They reflected the existence that higher quartile blood sugar has higher advanced glycation. Under the mentioned description in above articles, lower abdominal aorta ruptured rate could be expected in advanced diabetic status. The results were observed from our study. In un-ruptured abdominal aortic aneurysm group, the advanced DM patients cannot reveal a higher protective effect than uncomplicated DM (adjusted HR = 0.67 vs. 0.44) when compared to the non-DM cohort. However, considering aneurysm rupture, the advanced diabetic patients revealed a lower aneurysm ruptured rate than uncomplicated DM (adjusted HR = 0.51 vs. 0.71).
The advanced diabetic status always react much potency of medication. The doubt focused on medication use rather than diagnoses19 have a negative effect onAAA growth has been queried. Studies suggest that hyperglycemia itself rather than its treatment retard aneurysm progression. The explanations could be concluded as below. The study reported a negative association between fasting glucose and aortic diameter in 2859 non-diabetics.24 Investigators at Stanford reported that hyperglycemia in mice was associated with
slowerAAA enlargement, and this effect was diminished by insulintherapy.36These
explanations could further provide a basis of theory in our study. The advanced diabetes itself
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not the much potency of medication effect in this advanced disease condition occupy the major protective role in abdominal aortic aneurysm rupture.
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第二節 研究限制
The study was subject to some limitations, which must be mentioned. First, the NHIRD does not provide detailed information on patients such as their smoking habits, alcohol
consumption, body mass index (BMI), physical activity, socioeconomic status, and family history of systemic diseases. All of these are major risk factors for abdominal aortic aneurysm.
Second, the evidence derived from a cohort study is generally of a lower methodological quality than that from randomized trials because a cohort study design is subject to many biases related to adjustment for confounds. Despite our meticulous study design with adequate control of confounding factors, a key limitation was that bias could still remain because of possible unmeasured or unknown confounders. Third, the diagnoses in NHI claims primarily serve the purpose of administrative billing, and do not undergo verification for scientific purposes. We were unable to contact the patients directly to obtain more information because of the anonymity assured by the identification numbers.
Although the data that we obtained on NIDDM and abdominal aortic aneurysm diagnoses were highly reliable, underlying mechanisms must still be explored and identified. Additional large population-based unbiased studies are required, and it would be essential to confirm our current findings before drawing any firm conclusions.
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