2型糖尿病＋心血管疾患のobesity paradox

2型糖尿病＋心血管疾患患者における体重・体重変化と罹患率・死亡率の逆相関に関する論文を紹介します。
Doehner W, Erdmann E, Cairns R, Clark AL, Dormandy JA, Ferrannini E, Anker SD. Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: An analysis of the PROactive study population. Int J Cardiol. 2011 Oct 29. [Epub ahead of print]

PROactiveという2型糖尿病＋心血管疾患患者のRCTのデータを使用した二次研究です。死亡率がもっとも低かったのは BMI 30-35の群で、BMI22未満とBMI22-25の群は BMI 30-35の群より有意に死亡率が高いという結果でした。また、体重減少は死亡率の増加と有意に関連していましたが、体重増加は有意な関連を認めませんでした。以上より2型糖尿病＋心血管疾患患者においてobesity paradoxがあるかもしれないという結論です。

obesity paradoxは慢性炎症を生じる疾患（CKD、COPD、CHFなど）で指摘されています。2型糖尿病も単独で慢性炎症を生じる可能性がありますが、心血管疾患による要素のほうが大きいのではと思います。また、体重減少の原因が意図した減量目的なのか、併存疾患や慢性炎症によるものなのかで異なると感じます。筋肉量を減らさないほうがよいことは確かだと考えますが。

Abstract
CONTEXT: Although weight reduction is a recommended goal in type 2 diabetes mellitus (T2DM), weight loss is linked to impaired survival in patients with some chronic cardiovascular diseases.

OBJECTIVE: To assess the association of weight and weight change with mortality and non-fatal cardiovascular outcomes (hospitalisation, myocardial infarction and stroke) in T2DM patients with cardiovascular co-morbidity and the effect of pioglitazone-induced weight change on mortality.

SETTING AND PARTICIPANTS: We assessed in a post hoc analysis body weight and weight change in relation to outcome in 5202 patients from the PROactive trial population who had T2DM and evidence of pre-existing cardiovascular disease. Patients were randomized to treatment with pioglitazone or placebo in addition to their concomitant glucose-lowering and cardiovascular medication. Mean follow up was 34.5months.

MAIN OUTCOME MEASURE: The impact of body weight and body weight change on all-cause mortality, cardiovascular mortality, on non-fatal cardiovascular events and on hospitalisation.

RESULTS: The lowest mortality was seen in patients with BMI 30-35kg/m(2) at baseline. In comparison to this (reference group), patients in the placebo group with BMI <22kg/m(2) (Hazard Ratio (95% confidence intervals) 2.96 [1.27 to 6.86]; P=0.012) and BMI 22 to 25kg/m(2) (HR 1.88 [1.11 to 3.21]; P=0.019) had a higher all-cause mortality. Weight loss was associated with increased total mortality (HR per 1% body weight: 1.13 [1.11 to 1.16]; P<0.0001), with increased cardiovascular mortality, all-cause hospitalisation and the composite of death, myocardial infarction and stroke. Weight loss of ≥7.5% body weight (seen in 18.3% of patients) was the strongest cut-point to predict impaired survival (multivariable adjusted HR 4.42 [3.30 to 5.94]. Weight gain was not associated with increased mortality. Weight gain in patients treated with pioglitazone (mean+4.0±6.1kg) predicted a better prognosis (HR per 1% weight gain: 0.96 [0.92 to 1.00] P=0.037) compared to patients without weight gain.

CONCLUSION: Among patients with T2DM and cardiovascular co-morbidity, overweight and obese patients had a lower mortality compared to patients with normal weight. Weight loss but not weight gain was associated with increased mortality and morbidity. There may be an "obesity paradox" in patients with type 2 diabetes and cardiovascular risk. The original PROactive trial is registered as an International Standard Randomized Controlled Trial (Number ISRCTN NCT00174993).