식영기본둘째장

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1 pissn eissn Korean J. Food Nutr. Vol. 29. No. 2, 290~299 (2016) THE KOREAN JOURNAL OF 한국식품영양학회지 FOOD AND NUTRITION 숭의여자대학교식품영양과 Dietary Calcium Intake is associated with Blood Lipid Profile, Blood Pressure, Inflammatory State and Insulin Resistance in Type 2 Diabetes Patients Hae-Yun Chung Dept. of Food and Nutrition, Soongeui Women s College, Seoul , Korea Abstract This study was conducted to determine the association between dietary calcium intake and biomarkers related to lipid and glucose metabolism and inflammation in Korean patients with type 2 diabetes. Seventy-five subjects (41 males, 34 females) were recruited from a group of patients who had visited the department of endocrine medicine. Data on anthropometric characteristics, clinical indices such as hemoglobin A1c and C-reactive protein (CRP), and dietary nutrient intakes were collected. Subjects were divided into three groups on the basis of their calcium intake [<EAR (below estimated average requirement), EAR-RNI (between EAR and recommended nutrient intake), >RNI (above RNI)]. Average calcium intake of <EAR, EAR-RNI, >RNI groups were 462.7±18.7, 649.7±12.8, and 895.7±21.7 mg, respectively. Energy intake was not different among groups but intakes of protein, total and saturated fatty acids were significantly higher in >RNI group than <EAR group. Analysis of covariance revealed that HDL cholesterol level was significantly higher in EAR-RNI group, as compared to <EAR group after adjustment with confounders such as age, sex, BMI and energy intake (p<0.05). Levels of CRP and homeostasis model assessment 2-insulin resistance (HOMA2-IR) were significantly lower in EAR-RNI group. Total cholesterol level was higher in EAR-RNI and >RNI groups, although within the normal range. Our results suggest that dietary calcium intake may influence the levels of HDL-cholesterol, CRP and HOMA2-IR and subsequently, help management/treatment of type 2 diabetes patients. Key words: type 2 diabetes, dietary calcium intake, HDL-cholesterol, C-reactive protein, homeostasis model assessment 2-insulin resistance 제2형당뇨병은비만과운동부족의증가로인해전세계적으로유병률이증가하고있으며, 향후 10년간당뇨병으로인한사망률이 50% 이상상승할것으로예측된다. 고혈당은시간이흐를수록심장, 혈관, 눈, 신장, 신경등에손상을끼치며, 특히심혈관및뇌혈관질환발생과그로인한사망의위 험을증가시킨다. 따라서혈당을적절하게유지하는것은사망위험감소와합병증예방을위해매우중요하다. 우리나라역시 30세이상성인의당뇨병유병율이 12.4% 로상당히높지만, 한국인당뇨병환자의 27.9% 만이혈당조절목표에도달한다고보고되었고, 고혈압과이상지질혈증등의합병증을갖고있는당뇨병환자의각각 40% 와 20% 만이조절목표수준을유지하고있었다 (Korean Diabetes Association 2013). Corresponding author: Hae-Yun Chung, Dept. of Food and Nutrition, Soongeui Women s College, Seoul , Korea. Tel: , Fax: , hchung02@sewc.ac.kr

2 Vol. 29, No. 2(2016) 제 2 형당뇨병환자의칼슘섭취와임상지표 291 제2형당뇨병의발병을예방혹은지연하는데에는건강한식사와정기적인운동, 정상체중유지와금연이도움이된다고알려져있다. 식사는제2형당뇨병의발병에중요한역할을하는데, 식사패턴에관한연구들에서는과일, 채소, 전곡류등이제2형당뇨병에대해보호효과를나타낸다고하였다 (van Dam 등 2002). 개별영양소와제2형당뇨병의상관관계에대한연구들은 ω3계지방산, 베타카로틴, 비타민 E 등이당뇨병예방효과를나타낸다고하였고 (Ärnlöv 등 2009; Fedor & Kelley 2009), Nurses Health Study 등몇몇연구는칼슘섭취와당뇨병위험사이에역관계가존재한다고하였다. Nurses Health Study 의결과에따르면칼슘섭취가가장많은집단은가장적은집단에비해당뇨병의상대위험도가 0.79로낮았으며 (Pittas 등 2006), Women s Health Study 연구도칼슘이풍부한유제품, 특히저지방유제품의섭취가제2형당뇨병의발병위험을낮춘다고보고하였다 (Liu 등 2006). 칼슘섭취는당뇨병의발병위험에영향을미칠뿐만아니라, 당뇨병합병증과연관이깊은임상지표와도관련성을나타낸다. 제2형당뇨병환자는인슐린저항지표와혈당이높을뿐만아니라염증지표수준도높은데이는고혈당이체내에서염증반응을유발하기때문이다. 염증지표는혈압, 혈중지질과함께당뇨병의대표적인합병증인심혈관질환의발병률과사망률을상승시킨다 (Korean Diabetes Association 2013). 칼슘섭취의효과에대한연구들은식이칼슘섭취가많을경우혈당및혈청지질수준, 염증지표등이낮게유지된다고하였다 (Ditscheid 등 2005; Sun & Zemel 2008; Richart 등 2011). 칼슘섭취와당뇨병위험의상관관계에대한연구대부분은서구사회인구집단을대상으로한것인데이들은칼슘섭취량이한국인에비해많고주요칼슘급원식품이한국을비롯한아시아국가와다르다. 우리나라의경우채소류로섭취하는칼슘의양이 mg으로가장많았고우유류 (116.4 mg), 어패류, 곡류가그다음으로중요한급원식품이다. 반면, 서구사회에서는지방, 특히포화지방함량이높은유제품이칼슘의주요급원인데, 고지방섭취는당뇨병위험을높이는위험요인으로작용하여칼슘섭취와당뇨병사이의상관관계에대한해석을어렵게한다 (van Dam 등 2002; Yu 등 2013; Ministry of Health and Welfare 2014). 본연구에서는서구에비해칼슘과유제품섭취가적고, 칼슘의주요급원식품이서구와다른한국인당뇨병환자를대상으로칼슘섭취가당뇨병의임상지표에미치는영향에대해연구하고자한다. 본연구에포함된임상지표는체질량지수, 혈청지질, 혈압, 염증지표, 혈당및인슐린저항지표등이다. 1. 본연구는 2009 년 6월부터 2009 년 9월까지서울소재대학병원내분비내과에내원한만 30세이상 80세이하의당뇨병환자 76명 ( 남자 42명, 여자 34명 ) 을대상으로실시하였다. 본인의동의하에개별면담을통하여성별, 연령, 흡연여부 ( 현재흡연, 과거흡연경험 ), 음주여부 ( 현재음주, 과거음주경험 ), 약복용력 ( 고혈압, 당뇨병, 고지혈증등 ) 등을조사하였다. 대상자중 1명은칼슘섭취가이상치에해당하여통계분석에서제외하였다. 2. 대상자의신장과체중은신체자동계측기를이용하여측정하였고, 체질량지수 (Body Mass Index, BMI) 는체중 (kg)/ 신장 (m) 2 으로계산하였다. 혈압은 10분이상안정을취한상태에서자동혈압측정기를이용하여수축기혈압 (Systolic Blood Pressure, SBP) 과이완기혈압 (Diastolic Blood Pressure, DBP) 을측정하였다 시간이상금식한상태에서상완정맥에서혈액을채취한후 4, 3,000 rpm에서 20분간원심분리하여혈청을얻었다. 진단검사의학과에서자동분석기 (Fuji DRI-CHEM 3500i, Tokyo, Japan) 를이용하여분석한일반혈액검사자료를통계분석에사용하였다. 검사항목은혈당, 중성지방, 콜레스테롤및염증지표인 C-reactive protein(crp) 등이었다. 그외에 C-peptide 와 hemoglobin A1c(HbA1c) 는각각화학발광면역분석법 (E170, Roche Diagnostics, Mannheim, Germany) 과고성능액체크로마토그래피 (Variant II, Bio-Rad Laboratories, Hercules, CA, USA) 를이용하여분석하였다. 인슐린저항지표인 homeostasis model assessment 2-insulin resistance(homa2-ir) 는 HOMA Calculator 프로그램에공복혈당농도와 C-peptide 농도를대입하여계산하였다 (The Oxford Centre for Diabetes, Endocrinology & Metabolism. Diabetes Trials Unit. HOMA Calculator). 4. 식이섭취는 24시간회상법을이용하여조사하였다. 숙련된임상영양사가대상자와일대일개별면담하였으며, 비연속된 3일동안아침, 점심, 저녁, 간식으로섭취한모든종류의음식과섭취량을기록하였다. 조사한식이섭취내용은한국영양학회의영양평가프로그램 CAN-Pro 3.0에입력하여칼슘섭취는물론열량및영양소섭취량을산출하였다. 본조사에는영양보충제를통한섭취량은포함되지않았다.

3 292 정혜연 한국식품영양학회지 5. 모든자료는평균 ± 표준오차 (SEM) 로나타내었고, 정규분포를따르지않는변수는통계분석전에로그변환하였다. 대상자를칼슘섭취가평균필요량미만인 <EAR군 (Estimated Average Requirements) 과권장섭취량보다많은 >RNI 군 (Recommended Nutrient Intake) 그리고섭취량이평균필요량에서권장섭취량사이인 EAR-RNI 군으로분류하여각군사이의차이를비교하였다. 이산형변수는 Chi-square test를이용하여비교하였고, 연속형변수는분산분석을이용하여비교하였다. 연령, 성별, BMI, 에너지섭취및기타교란변수의영향을통제하기위해공분산분석을실시하였다. Model 1에는본연구에서통계분석결과, 교란변수로판명된연령, 성별, BMI, 에너지섭취를공분산분석에포함하였으며, Model 2에는각종문헌에서종속변수에영향을미치는것으로보고된흡연, 음주, 운동및약물복용을추가하였다. 공분산분석결과, 군간유의적차이가나타난경우 Bonferroni 방법을사용하여사후검정을실시하였다. SPSS(Statistical Package for Social Science, v. 15.0) 를사용하여통계분석하였고, 모든결과는 p<0.05 일때통계적으로유의한것으로판정하였다. 1. 본연구에서는대상자를칼슘섭취량에따라 <EAR 군, EAR- RNI군, >RNI 군의세군으로분류하였다. 각군의일반적특성을비교한결과, 성별, 연령, BMI, 약물복용여부등에있어서는군간차이를보이지않았다. 그러나음주, 흡연여부등은군에따라유의적차이를보였는데, 칼슘섭취가적은 <EAR 군이다른군에비해흡연자의비율이유의적으로높았으며, 운동을하지않는비율도높은경향을보였다. 한편, 칼슘섭취가권장섭취량이상인 >RNI 군은다른군에비해음주비율이유의적으로낮았다 (Table 1). 이러한분석결과는칼슘섭취가많은사람들이더건강한생활습관을갖고있음을시사한다. 2. 전체연구대상자의평균칼슘섭취량은 736.0±24.7 mg으로이중 438.1±13.0 mg은식물성식품에서, 297.9±21.7 mg은동물성식품으로부터섭취한것으로조사되었다. 남자대상자의평균섭취량은 707.5±36.8 mg이었고, 여자는 770.4±31.1 mg으로나타났는데, 이는 50~64 세한국인의평균섭취량인 521.1±9.9 mg을상회할뿐만아니라, 50세이상남성의권장섭취량인 700 mg보다도많은양이다. 여성의경우, 50세이상의권장섭취량인 800 mg보다는약간적었다. 이는본연구의 Table 1. Characteristics of participants according to calcium intake 1) 1) 2) <EAR (n=18) EAR-RNI (n=17) >RNI (n=40) Age (yr) 58.5±3.3 2) 55.5± ± Sex (%) 0.14 Female Male Height (cm) 165.1± ± ± Weight (kg) 64.1± ± ± Body mass index (kg/m 2 ) 23.4± ± ± Alcohol drinking (%) 0.04 Never Past Current Cigarette smoking (%) <0.01 Never Past Current Exercise (%) 0.08 Yes No Medication (%) Diabetes mellitus Hypertension Hyperlipidemia Calculated by chi-square test for the prevalence of population characteristics and by ANOVA for age, height, weight, and body mass index Mean±S.E.M. 대상자들이한국인평균에비해더많은식품을섭취해서가 아니라, 당뇨병관리에유익한식생활을하기위해노력했기 때문으로보인다. 본연구진의이전연구와 2013 년국민건강 영양조사결과를비교해보면 50~64 세한국인의평균에너지 및탄수화물섭취량은각각 2,033.4±24.5 kcal 와 325.7±4.0 g 으 로본연구대상자에비해더많았는데, 비타민 A 와 C 그리고 식이섬유의섭취는본연구대상자에서더많았다는사실이 이런추측을뒷받침한다 (Kwon & Chung 2013; Ministry of Health and Welfare 2014). 또한본연구에는다수의폐경기 여성이참여하였는데, 이들이골다공증예방및관리를위해 다량의칼슘을섭취한것으로보인다. 군별칼슘섭취량을살펴보면 <EAR 군의칼슘섭취는평 균 462.7±18.7 mg 이었고, EAR-RNI 군과 >RNI 군의섭취량은 P

4 Vol. 29, No. 2(2016) 제 2 형당뇨병환자의칼슘섭취와임상지표 293 Table 2. Dietary intake of participants according to calcium intake 1) <EAR EAR-RNI >RNI Energy (kcal) 1,857.9±64.2 1,959.1±49.4 1,950.7±41.9 Carbohydrate (g) 266.1±11.3 a 299.0±7.5 b 292.0±6.0 ab Protein (g) 68.8±3.0 a 82.6±3.0 b 85.6±2.3 b Vegetable protein 39.4±1.5 a 48.1±1.3 b 45.5±1.4 b Animal protein 29.4±2.6 a 34.5±3.1 ab 40.2±2.2 b Fat (g) 37.5± ± ±2.3 Vegetable fat 19.5± ± ±1.1 Animal fat 17.9± ± ±1.8 Cholesterol (mg) 220.2± ± ±23.7 Total fatty acid (g) 20.0±2.3 a 25.6±2.3 ab 29.4±2.1 b SFA (g) 2) 5.9±0.9 a 7.8±0.9 ab 10.7±0.9 b MUFA (g) 3) 7.5± ± ±0.9 PUFA (g) 4) 6.6± ± ±0.5 Calcium (mg) 462.7±18.7 a 649.7±12.8 b 895.7±21.7 c Vegetable Ca 349.6±12.2 a 456.8±15.1 b 470.0±20.4 b Animal Ca 113.1±12.0 a 193.0±17.7 b 425.7±25.6 c 1) All values are mean±s.e.m. Values in a row with different superscript letters are significantly different, P < 0.05 (one-way ANOVA followed by a Bonferroni test). 2) SFA: Saturated fatty acid 3) MUFA: Monounsaturated fatty acid 4) PUFA: Polyunsaturated fatty acid 각각 649.7±12.8 mg 과 895.7±21.7 mg 이었다. 식물성칼슘의 섭취량도군에따라약간차이가있었으며, 특히동물성칼슘 의차이가컸는데, 이는각군의우유섭취에차이가있음을 시사한다. 열량섭취량은군간유의적차이를나타내지않았지만, 탄 수화물과단백질섭취는 <EAR 군에서유의적으로낮게나타 났다. 한편, 지방산, 특히포화지방산섭취는 <EAR 군에비해 >RNI 군에서높게나타났는데, 이는이군의우유섭취가많 다는추측을뒷받침한다. 3. BMI 역학연구결과는칼슘및유제품섭취와비만, 특히복부 비만사이에역관계가존재한다는것을보여준다 (Eilat-Adar 등 2007). 칼슘과비만사이의상관관계에대한기전은아직 잘밝혀져있지않지만, 칼슘이장에서지방과불용성복합체 를형성하여대변으로지방의배설을증가시킨다는이론과 칼슘을부족하게섭취하는경우혈청칼시트리올농도가상 승하고, 이것이지방세포로의칼슘유입을증가시켜비만위 험을높인다는이론이많은지지를받고있다 (Xue 등 2001). 비만한인체지방세포에서칼슘이온농도의상승이관찰되었는데, 세포내칼슘농도가상승하면지방산합성효소를증가시켜지방합성을촉진하고, hormone-sensitive lipase를방해함으로써지방분해를저해한다고한다. Xue 등 (2001) 은세포내칼슘농도가증가하면 phosphodiesterase 3B가활성화되고, camp 농도가감소하는데, 이는작용제가 hormone sensitive lipase 를자극하는능력을감소시킴으로써지방분해를억제한다고설명하였다. 또한칼시트리올이인체지방세포에서 11β-hydroxysteroid dehydrogenase-1 의발현을촉진하여코티솔생산을증가시킴으로써복부비만을악화한다는이론도있다 (Morris & Zemel 2005). 코티솔은식욕을증진시킬뿐만아니라, 지방세포분화를촉진하고, 복부지방에유리지방산을공급하여비만, 특히복부비만을촉진하는호르몬이다 (Bjorntorp P 2001). 따라서식이칼슘섭취가적을때칼시트리올에의해코티솔생산이증가하고, 내장지방이증가한다고제안하였다. 한편, 칼시트리올이지방세포의 nuclear vitamin D 수용체에작용하여 uncoupling protein-2 의발현을억제한다는연구결과도있는데, uncoupling protein 은미토콘드리아에존재하며, 열발생을증가시켜에너지소비를촉진하는역할을하므로이단백질의저하는비만위험을높이게된다 (Bjorntorp P 2001; Dougkas 등 2011). 이와반대로칼슘섭취와복부비만사이에상관성이없다는연구결과도있다. 일례로 Barr SI(2003) 는체중및체조성과칼슘섭취와의상관성에대해연구한수십편의논문을분석한결과, 대개의연구들이체중, 지방량, 근육량등의지표에서칼슘섭취량에따른차이를발견하지못했다고하였다. 본연구에서도칼슘섭취에따라군간유의적차이가발견되지않았고, 오히려 <EAR군의 BMI가약간낮은경향을보였다 (Table 3). 칼슘섭취실태및 BMI에서한국인과더유사한일본인을대상으로한연구에서도칼슘섭취와비만도사이에상관관계가나타나지않았는데, 연구자들은이들의평균 BMI가서구에비해낮고칼슘섭취가적기때문이라고설명하였다 (Murakami 등 2006). 4. 칼슘과혈청지질에대한초창기의연구에서는건강한성인에게하루 900 mg의칼슘보충제를투여했을때혈청콜레스테롤과중성지방이각각 15.4 mg/dl 와 32.2 mg/dl 감소하였다고보고하였다 (Yacowitz 등 1965). 연구자들은칼슘을섭취하면장내에서칼슘이포화지방산과결합하여불용성 soap 을형성하므로대변을통한배설이많아진다고설명하였다. 또한칼슘은대변을통한담즙의배설을증가시키는데, 담즙산이배설되면간콜레스테롤로부터담즙합성이증가하고, 이를통해혈액콜레스테롤제거가촉진된다 (Govers 등 1996).

5 294 정혜연 한국식품영양학회지 Table 3. Serum lipid levels, blood pressure, inflammation index and blood glucose profiles according to calcium intake 1) <EAR EAR-RNI >RNI Serum calcium (mg/dl) 8.6± ± ±0.1 Model 1 2) p Model 2 3) BMI (kg/m 2 ) 23.4± ± ± Cholesterol (mg/dl) 157.4±11.0 a 205.9±7.6 b 199.5±7.7 b LDL-Cholesterol (mg/dl) 98.4± ± ± HDL-Cholesterol (mg/dl) 39.1±2.3 a 49.5±2.4 b 47.9±2.0 ab LHR 4) 2.6± ± ± TG (mg/dl) 171.7± ± ± SBP (mmhg) 5) 125.1± ± ± DBP (mmhg) 6) 71.4±2.3 a 80.4±2.4 b 78.9±1.2 b CRP (mg/dl) 7) 3.4±1.1 a 1.0±0.4 b 2.4±1.2 ab NLR 8) 3.2± ± ± Glucose (mg/dl) 169.3± ± ± HbA1c (%) 9) 9.0± ± ± C-peptide (ng/ml) 3.4± ± ± HOMA2-IR 10) 3.5±0.5 a 2.0±0.3 b 2.2±0.2 ab ) All values are mean±s.e.m. Values in a row with different superscript letters are significantly different, P<0.05 (ANCOVA followed by Bonferroni test) 2) Adjusted with age, sex, BMI and energy intake 3) Adjusted with age, sex, BMI, smoking, alcohol consumption, exercise, medication uses and energy intake 4) LHR: LDL to HDL ratio, 5) SBP: Systolic blood pressure, 6) DBP: Diastolic blood pressure, 7) CRP: C-reactive protein 8) NLR: Neutrophil to lymphocyte ratio, 9) HbA1c: Hemoglobin A1c, 10) HOMA2-IR: Homeostasis model assessment 2-insulin resistance p 한편, 고칼슘군은혈청 HDL- 콜레스테롤농도가더높다는연구결과도있다 (da Silva Ferreira 등 2013). 칼슘혹은유제품이 HDL에미치는영향은분명치않으나, 고칼슘그룹은저칼슘그룹에비해유제품의섭취가많고, 따라서 HDL- 콜레스테롤농도를상승시키는단일불포화지방산의섭취가많을수도있다. 유지방의 25% 가량은단일불포화지방산인 oleic acid 로구성되어있다 (Rice 등 2011). 반면, Karandish 등 (2009) 은칼슘보충시비만여성의혈청콜레스테롤에변화가없었다고하였고, Li 등 (2013b) 은폐경기여성에게칼슘을보충했을때혈청콜레스테롤이오히려유의적으로증가하였다고보고하였다. Li 등 (2013a) 은세포와쥐를이용한후속연구에서에스트로겐이결핍된상태에서칼슘보충제를투여하면콜레스테롤을담즙산을만드는데필요한 7α-수산화효소가감소하여콜레스테롤의분해대사가저하됨을보여주었다. 본연구에서도위의결과들과유사하게 EAR-RNI 군과 >RNI 군에서총콜레스테롤수치가더높게나타났다. 심혈관질환의위험요인인 LDL- 콜레스테롤도높은경향을보였으나, 통계적으로유의적이지는않았고, 반면심혈관질환에보호효과가있는 HDL- 콜레스테롤은 <EAR 군에비해 EAR-RNI 군에서유의적으로높게나타났다. >RNI군도 <EAR군에비하면 HDL의농도가높았지만통계적으로유의적이지는않았다. 연령, 성별, BMI, 흡연, 음주, 운동, 약물복용여부및에너지섭취로보정한 Model 2에서는 HDL- 콜레스테롤농도의유의적차이가사라졌지만이는과도한보정의결과로보이며본연구에서통계분석결과, HDL- 콜레스테롤농도에영향을미치는것으로밝혀진교란요인으로만보정을한경우에는유의적차이를보였다 (p<0.05, Table 3). 한편, 식이콜레스테롤섭취량을통계분석모델에포함한경우, 연령, 성별, BMI, 에너지섭취로보정한 Model 1의경우에는통계적유의성이유지되었으나 Model 2의경우에는군간혈청총콜레스테롤및 HDL- 콜레스테롤농도가유의적차이를나타내지않았다. EAR-RNI 군과 >RNI 군에서총콜레스테롤수준이높게나타났지만, HDL- 콜레스테롤역시높았으므로심혈관질환위험의지표가되는 LDL 에대한 HDL 의비율 (LDL to HDL ratio, LHR) 은군간유의한차이를나타내지않았다. 5. Dietary Approaches to Stop Hypertension(DASH) 등여러연

6 Vol. 29, No. 2(2016) 제 2 형당뇨병환자의칼슘섭취와임상지표 295 구는칼슘혹은유제품섭취와혈압사이에역관계가존재함을보여주었다. DASH 연구에따르면저지방유제품을충분히섭취하고과일과채소를많이섭취하는경우약한고혈압에대해약물섭취와비슷한정도의효과를나타낸다 (Appel 등 1997). 칼슘의혈압상승억제효과는칼시트리올이세포내칼슘이온농도에미치는영향에의해설명할수있다. 칼슘섭취가적으면혈액에순환하는칼시트리올농도가상승하는데, 이는혈관평활근세포로의칼슘이온유입을자극한다. 혈관평활근세포의칼슘이온농도상승은혈관수축과혈압상승으로이어질수있다 (Zemel MB 2001). 또한식이칼슘은 renin-angiotensin system의활성을저하하여혈압을낮춘다고한다 (Weiss & Taylor 2008). 나아가칼슘은체중감소를도와주고 (Dougkas 등 2011), 인슐린민감성을자극하는데 (Pittas 등 2007), 이들은모두혈압강하와연관되어있다. 칼슘의혈압강하효과는경우에따라차이가있을수있다. 칼슘보충은수축기, 이완기혈압의강하로이어지지만강하효과는수축기혈압에더큰효과가있는것으로보인다. 칼슘에대한반응에는개인차가존재하는데혈압이소금섭취에민감하게반응하는사람들이칼슘에대해가장잘반응하는것으로알려져있다 (Resnick LM 1999). Alonso 등 (2005) 은유제품을통해칼슘을섭취하는경우, 저지방유제품섭취가가장많은군이적은군에비해고혈압위험이 54% 낮았다고보고하였는데, 고지방유제품을섭취하는경우에는고혈압과상관관계가발견되지않았다고하였다. 칼슘과칼시트리올보충이혈압에악영향을가져온다는연구결과도있다. Hsia 등 (2007) 은폐경기여성을대상으로연구한논문에서 2년동안칼슘과칼시트리올을보충한그룹은수축기혈압이 1.1±12.4% 상승한반면, 위약군은단지 0.7± 12.4% 만상승하였다고보고하였다. 또한이완기혈압은보충군에서는 0.2±12.4% 감소하였고, 위약군에서는 0.6±12.4% 로더많이감소하였다. 본연구에서는수축기혈압은군간차이가없었으나, 이완기혈압의경우칼슘섭취가많은 EAR-RNI 군과 >RNI 군에서더높게나타났고, EAR-RNI 군과 >RNI 군사이에는차이가없었다 (Table 3). 대한당뇨병학회가발표한당뇨병진료지침에따르면수축기혈압은 130 mmhg, 이완기혈압은 80 mmhg 미만으로유지하는것이바람직하다 (Korean Diabetes Association 2013). 본연구에서 EAR-RNI 군과 >RNI군의이완기혈압이약간더높게나타나기는했지만세군모두조절목표수준을유지하고있음을알수있다. 6. 여러연구들에따르면제2형당뇨병환자는시토카인, 케모카인뿐만아니라, CRP 나피브리노겐과같은염증관련급성기단백질의혈액농도가높다 (Spranger 등 2003). 또한 Stanley 등 (2011) 은대사증후군을갖고있는비만인에게항염증작용을하는종양괴사인자억제제를투여한경우, 인슐린민감성이좋아진다고보고하여염증반응이당뇨병의발병및진행과밀접한관련이있다는것을보여주었다. 칼슘이풍부한식사는산화적손상과염증반응을완화한다고하는데유제품을통해칼슘을섭취한비만인은대조군에비해혈액 CRP 농도가낮다고보고되었다 (Pittas 등 2007). 비만쥐를이용한연구에서도고칼슘식이를주면지방조직의염증성시토카인유전자발현이억제되는것이관찰되었는데, 이러한식이칼슘의항염증효과에는칼시트리올이관여하는것으로보인다. Sun & Zemel(2008) 은칼시트리올이지방세포와대식세포에서염증성시토카인생산을증가시킨다는것을입증하고, 충분한양의칼슘을섭취하는경우혈청칼시트리올농도가낮아지므로염증반응이억제된다고설명하였다. 반면, Wamberg 등 (2013) 은비만인에게 26주동안 7,000 IU 의칼시트리올을투여했을때혈액과지방조직의염증지표가변화하지않았다고보고하였고, 한연구는칼시트리올이지방조직에서염증촉진성시토카인의분비를오히려억제한다는것을보여주었다 (Lorente-Cebrian 등 2012). 또한고지방식이를준쥐에게칼시트리올을투여했을때에도지방조직의 Interleukin-6 수준이저하되었다는보고도있다 (Lira 등 2011). 본연구에서는염증및심혈관계질환위험의지표인 CRP 수치가칼슘섭취가낮은 <EAR 군에서더높은것을관찰할수있다. 칼슘섭취가가장많은 >RNI군은 EAR-RNI 군에비해 CRP 수치가오히려약간상승하여칼슘섭취와 CRP 농도사이에선형관계가존재하지않는다는것을보여준다. CRP 역시연령, 성별, BMI, 흡연, 읍주, 운동, 약물복용여부및에너지섭취로보정한경우에는통계적차이가유의적이지않았다 (Table 3). 또다른염증지표인 neutrophil to lymphocyte ratio는군간차이를나타내지않았다. 7. 최근의연구결과는칼슘섭취가인슐린저항에대해보호효과를나타냄을보여준다. 칼슘을많이섭취하는사람은공복혈당이낮다고보고된바있고 (Richart 등 2011), 칼슘및칼시트리올섭취와 HbA1c 농도사이에역관계가존재한다는연구결과도있다 (Sabherwal 등 2010). 칼슘과칼시트리올이어떤기전을통해제2형당뇨병의위험에영향을미치는지는잘알려져있지않지만칼슘이인

7 296 정혜연 한국식품영양학회지 슐린분비와인슐린민감성모두에영향을미치는것으로보인다. 건강한성인에게식사와함께체중 1 kg 당 3 mg 혹은 15 mg의칼슘을섭취하도록한후혈액인슐린농도를측정한연구에서다량의칼슘을섭취한경우, 인슐린분비가더많았음이관찰되었다 (Gonzalez & Stevenson 2014). 또한칼슘과칼시트리올보충후 HOMA-IR 이개선되었다는연구는이들영양소가인슐린저항을완화함으로써당뇨병발병위험을낮춘다는것을보여준다 (Pittas 등 2007). 그러나일부연구는식사칼슘이당뇨병발병에영향을미치지않는다고하였고 (Gagnon 등 2011), 칼슘혹은칼시트리올보충이포도당내성에미치는영향을연구한중재연구들도일관적인결과를보여주지못했다. 공복혈당수치가다양한사람들에게칼슘과칼시트리올보충제를투여하고 3년동안추적관찰한결과, 애초에공복혈당장애를갖고있던대상자는인슐린저항이예방되는효과를나타냈지만공복혈당수치가정상범위에있던사람은어떤효과도보지못하여연구대상자에따라칼슘보충의효과가다르다고제안하기도하였다 (Pittas 등 2007). 본연구의결과에따르면혈당, HbA1c, C-peptide 등의농도는칼슘섭취에따라차이를나타내지않았으나인슐린저항의지표인 HOMA2-IR 는 <EAR 군에서비해 EAR-RNI 군에서유의적으로낮았다. >RANI 군도 <EAR 군보다는 HOMA2-IR 이낮았지만, 그차이는유의적이지않았다 (Table 3). 본연구에서는제2형당뇨병환자들을칼슘섭취량에따라세군으로분류하고, 각군의체중, 혈청지질, 혈압, 염증지표및혈당관리지표를비교함으로써당뇨병의관리및치료에미치는칼슘의영향을파악하고자하였다. 전체연구대상자의평균칼슘섭취량은 736.0±24.7mg 이었고, <EAR군, EAR-RNI 군과 >RNI 군의섭취량은각각 ±18.7 mg, 649.7±12.8 mg, 그리고 895.7±21.7 mg이었다. <EAR 군은칼슘외에탄수화물, 단백질, 총지방산및포화지방산의섭취가다른군보다적었으나, 열량섭취의차이는유의적이지않았다. 연구된임상지표중체중, LDL-콜레스테롤, 중성지방, 수축기혈압, 혈당및 HbA1c 와 C-peptide 는군에따라유의적차이를나타내지않았다. 반면, HDL- 콜레스테롤은 <EAR군에비해칼슘섭취가많은 EAR-RNI 군에서높게나타나충분한칼슘섭취가 HDL- 콜레스테롤농도상승에도움이된다는것을알수있다. HDL- 콜레스테롤은심혈관계질환에대해보호효과를나타내므로칼슘섭취가당뇨병환자에서심혈관계합병증을예방하는 데도움이될것으로사료된다. 한편, 칼슘섭취가가장많은 >RNI 군의경우 HDL- 콜레스테롤농도가 <EAR 군보다높기는했지만그차이는통계적으로유의하지않았다. 염증지표인 CRP 역시 <EAR 군에비해 EAR-RNI 군에서낮게나타나칼슘이염증반응을완화하는데도움이된다는것을보여주었다. 한편, 칼슘섭취가가장많은 >RNI 군이유의적이지는않지만, EAR-RNI 군에비해 CRP 농도가높은점은일정수준이상의칼슘섭취가증상완화에도움이되지않는다는것을시사한다. 인슐린저항의지표인 HOMA2-IR 도 EAR-RNI 군에서가장낮게나타나칼슘섭취가인슐린저항을완화하는데도움이됨을입증하였다. 그러나 >RNI 군은 EAR-RNI 군과유의적차이를나타내지않아역시일정수준이상의칼슘섭취가더이상도움이되지않음을보여주었다. 체중과칼슘섭취와의상관성을보면체중과체조성에대해더이상의유익한효과가나타나지않는칼슘섭취의역치가존재한다고추정하고있다. Boon 등 (2005) 은이역치를 800 mg/d 정도로, Dougkas 등 (2011) 은 500~700 mg/d일것으로추정하고있다. 한편, 혈청콜레스테롤과이완기혈압은기대와달리칼슘섭취가많은군에서더높게나타났다. Wennersberg 등 (2009) 은성인에게우유를보충한결과, 콜레스테롤농도가상승하였다고보고하였고, Huth & Park(2012) 도전지방유제품을섭취하는경우 LDL-콜레스테롤이증가하지만 HDL 역시증가한다고하였다. 본연구에서도고칼슘섭취군은우유를많이섭취하였다고추정되는데총콜레스테롤이유의적으로높았지만, HDL- 콜레스테롤역시높아 LHR은군간차이가없었다. 중년이상의성인, 특히폐경기여성에게칼슘을보충한연구들은칼슘보충군에서혈청콜레스테롤, 관상동맥석회화등이증가하고, 심혈관계질환의위험이상승한다고보고하였다 (Bolland 등 2010). 이들은칼슘의상한섭취량을 1,500 mg으로조정해야한다고제안하였으며최근미국의의학협회도 51세이상성인의상한섭취량을 2,000 mg으로하향하였다 (Institute of Medicine 2011). 본연구에서는칼슘섭취량과급원식품이서구인과는다른한국인당뇨병환자를대상으로칼슘섭취가염증지표및인슐린저항지표등을개선함으로써질병의관리에도움을줄수있다는것을보여주었다. 그러나일정수준이상의칼슘을섭취한다고해서더큰효과가나타나는것은아니고, 오히려지나칠경우혈청지질수준등의측면에서악영향을끼칠수있다는점을지적하였다. 본연구에서는칼슘보충제를통한섭취를조사하지않아대상자의실제칼슘섭취량이조사된바와다를수있고, 비타민 D 섭취에대한자료가없

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10 Vol. 29, No. 2(2016) 제 2 형당뇨병환자의칼슘섭취와임상지표 299 levels - results from a randomized trial. Eur J Intern Med 24: Weiss D, Taylor WR Deoxycorticosterone acetate salt hypertension in apolipoprotein E2/2 mice results in accelerated atherosclerosis: The role of angiotensin II. Hypertension 51: Wennersberg MH, Smedman A, Turpeinen AM, Retterstol K, Tengblad S, Lipre E, Aro A, Mutanen P, Seljeflot I, Basu S, Pedersen JI, Mutanen M, Vessby B Dairy products and metabolic effects in overweight men and women: Results from a 6-mo intervention study. Am J Clin Nutr 90: Xue B, Greenberg AG, Kraemer FB, Zemel MB Mechanism of intracellular calcium ([Ca 2+ ]i) inhibition of lipolysis in human adipocytes. FASEB J 15: Yacowitz H, Fleischman AI, Bierenbaum ML Effects of oral calcium upon serum lipids in man. Br Med J 1: Yu A, Yang YJ, Jeong S, Kim J, Kim YJ, Kwon O, Oh SE, Kim J Calcium intakes in Korean and American populations. J Korean Diet Assoc 19:46-58 Zemel MB Calcium modulation of hypertension and obesity: Mechanisms and implications. J Am Coll Nutr 20:428S- 435S Received 15 April, 2016 Revised 18 April, 2016 Accepted 19 April, 2016