I-CARE: Checkup Bibliography

Age Check

This measurement is performed by using a non invasive recent technique called skin autofluorescence, which has been reported to be a sensitive marker of the accumulation of advanced glycation end products, derived from glycemic and oxidative stress. An association between skin autofluorescence measure and type 2 diabetes micro- and cardio-vascular complications, as well as its independent predictive value for the aforementioned complications, has also been shown and reported in several valuable studies available in literature. More in details, the test is based on an autofluorescence reader that illuminates a small skin surface with a given excitation light intensity.
This emission light and the reflected skin light are then measured with a spectrometer and the final result is provided by specific calculations and expressed in units.
1. Mallipattu SK, Uribarri J. Advanced glycation end product accumulation: a new enemy to target in chronic kidney disease? Curr Opin Nephrol Hypertens. 2014 Nov;23(6):547-54.
2. McIntyre NJ, Fluck RJ , McIntyre CW, Taal MW. Skin autofluorescence and the association with renal and cardiovascular risk factors in chronic kidney disease stage 3. CJASN October 2011, 6 (10) 2356-2363
3. Oleniuc M, Secara I, Onofriescu M, Hogas S, Voroneanu L, Siriopol D, Covic A Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney
Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique –
Skin Autofluorescence. Mædica. 2011;6(4):298-307.
4. Wang AY, Wong CK, Yau YY, Wong S, Chan IH, Lam CW. Skin autofluorescence associates with vascular calcification in chronic kidney disease. Arterioscler Thromb Vasc Biol. 2014;34:1784-1790.

Body Check

This test utilizes worldwide commonly used measurements such as waist circumference, waist/hip and waist/height ratios and body mass index. These clinical anthropometric parameters have been reported as predictive scores for the risk of developing metabolic syndrome, type 2 diabetes and cardiovascular diseases. Many scientific societies support their clinical use in the prevention and screening of non communicable diseases, together with the evaluation of other well known risk factors such as physical activity. A large number of studies have also been published in highly reputed international scientific journals.
1. Cheong KC, Ghazali SM, Hock LK, Subenthiran S, Huey TC, Kuay LK, Mustapha FI, Yusoff AF, Mustafa AN. The discriminative ability of waist circumference, body mass index and waist-to-hip ratio in identifying metabolic syndrome: Variations by age, sex and race. Diabetes Metab Syndr. 2015 Apr-Jun;9(2):74-8.
2. Janiszewski, PM., Janssen I, Ross R. Does waist circumference predict diabetes and cardiovascular disease beyond commonly evaluated cardiometabolic risk factors?.” Diabetes care 30.12 (2007): 3105-3109.
3. Noble D, Mathur R, Dent T, Meads C, Greenhalgh T. Risk models and scores for type 2 diabetes: systematic review. BMJ. 2011 Nov 28;343:d7163.
4. Vazquez G, Duva Sl, Jacobs DR Jr, Silventoinen K. Comparison of Body Mass Index, Waist Circumference, and Waist/Hip Ratio in Predicting Incident Diabetes: A Meta-Analysis. Epidemiol Rev 2007;29 (1):115-128.
5. Wei M, Gaskill SP, Haffner SM, Stern MP. Waist Circumference as the Best Predictor of Noninsulin Dependent Diabetes Mellitus (NIDDM) Compared to Body Mass Index, Waist/hip Ratio and Other Anthropometric Measurements in Mexican Americans—A 7-Year Prospective Study. Obesity. 1997;5(1):16-23.

Body Composition

The evaluation of body composition has become more and more common in clinical practice, especially when physicians seek for nutritional and metabolic parameters which may correlate with the development of non communicable diseases later in life. In this regard, its predictive value has been clarified and demonstrated in several well designed studies reported in literature, which support the percentage of body fat as a better and more reliable predictor than body mass index.
1. Zeng Q, Dong SY, Sun XN, Xie J, Cui J. Percent body fat is a better predictor of cardiovascular risk factors than body mass index. Braz J Med Biol Res, 2012 (July); 45(7): 591-600.
2. Barreira TV, Staiano AE, Harrington DM, Heymsfield SB, Smith SR, Bouchard C, Katzmarzyk PT. Anthropometric Correlates of Total Body Fat,Abdominal Adiposity, and Cardiovascular Disease Risk Factors in a Biracial Sample of Men and Women. Mayo Clinic Proceedings. 2012;87(5):452-460.
3. Lichtash CT, Cui J, Guo X, Chen YDI, Hsueh WA, Rotter JI, Goodarzi MO. Body adiposity index versus body mass index and otheranthropometric traits as correlates of cardiometabolic risk factors. PLoS One. 2013 Jun 11;8(6):e65954.

Calorimetric Check

In the field of clinical nutrition, physicians cannot avoid to check patients’ energy expenditure in order to calculate their personal energy requirements and design a proper diet. With respect to this need, the calorimeter is the most utilized apparatus worldwide. There is a large consensus within the scientific community about the recommendation to prefer this method rather than other energy expenditure tests currently available.
1. Lam YY, Ravussin E. Indirect calorimetry: an indispensable tool to understand and predict obesity. Eur J Clin Nutr. 2017 Mar;71(3):318-322.
2. Oshima T, Berger MM, De Waele E, Guttormsen AB, Heidegger CP, Hiesmayr M, Singer P, Wernerman J, Pichard C. Indirect calorimetry in nutritional therapy. A position paper by the ICALIC study group. Clin Nutr. 2017 Jun;36(3):651-662.
3. Purcell SA, Elliott SA, Ryan AM, Sawyer MB, Prado CM. Accuracy of a Portable Indirect Calorimeter for Measuring Resting Energy Expenditure in Individuals With Cancer. JPEN J Parenter Enteral Nutr. 2018 Jun 5.
4. Yavelberg L, Zaharieva D, Cinar A, Riddell MC, Jamnik V. A Pilot Study Validating Select Research-Grade and Consumer-Based Wearables Throughout a Range of Dynamic Exercise Intensities in Persons With and Without Type 1 Diabetes: A Novel Approach. J Diabetes Sci Technol. 2018 May;12(3):569-576.

Densi Check

The estimation of bone density is of utmost importance for the evaluation of bone health and the prevention of osteoporosis. Its measure is also relevant for monitoring possible side effects of specific “by exclusion diets”, either in health or in disease related regimens, as well as those linked to the use of some specific drugs or subsequent to hormonal changes or to some inherited metabolic disorder. Therefore, it should be always assessed when evaluating the nutritional status of a subject presenting with risk factors for bone health. Many different methods are currently available to measure bone density. Among these, heel ultrasound densitometry has been demonstrated to be a quick, non invasive, safe, reliable, validated and easy to learn method, sometimes even more accurate than other techniques used for bone densitometry evaluation.
1. Coaccioli S, Sabatini C, Ponteggia M, Giuliani M, Tomassi A, Pinoca F, Landucci P, Fatati G, Puxeddu A. Osteoporosis and anorexia nervosa: ultrasonometric and biochemical evaluation–preliminary data. Clin Ter. 2007 Jan-Feb;158(1):17-20.
2. Gregg EW, Kriska AM, Salamone LM, Roberts MM, Aderson SJ, Ferrell RE, Kuller LH, Cauley JA. The epidemiology of quantitative ultrasound: A review of the relationships with bone mass, osteoporosis and fracture risk. Osteoporosis Int. 1997; 7(2): 89-99.
3. Ponteggia M, Di Cato L, Ponteggia F, Pica M, Puxeddu A, Coaccioli S. Evaluation of the peak bone mass by quantitative heel ultrasound in young women of the centre of Italy. Reumatismo. 2003;55(1):34-8.
4. Sapthagirivasan V1, Anburajan M. Heel bone mass of a young South Indian population with a Nigerian population residing in a South Indian suburban neighborhood: a comparative study. Osteoporos Int. 2012 Nov;23(11):2661-9. 

Food Detective

This assay is claimed to be able to identify the presence of food intolerance to a large number of common foods, by measuring related IgG antibodies. As a matter of fact, the method is not validated by any international or national scientific society of Allergology or Nutrition, though it is supported by some papers published in literature.
1. Jian L, Anqi H, Gang L, Litian W, Yanyan X, Mengdi W, Tong L. Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study. Inflamm Bowel Dis. 2018 May 16.
2. Calderon TE, Ferrero M, Marino GM, Cordoba A, Beltramo D, Muino JC, Rabinovich GA, Romero MD. Meat-specific IgG and IgA antibodies coexist with IgE antibodies in sera from allergic patients: clinical association and modulation by exclusion diet. J Biol Regul Homeost Agents. 2010 Jul-Sep; 24(3):261-71.
3. Shakoor Z, AlFaifi A, AlAmro B, AlTawil LN, AlOhaly RY. Prevalence of IgG-mediated food intolerance among patients with allergic symptoms. Ann Saudi Med. 2016 NovDec;36(6):386-390.

Metabolic Check

The prevention of cardiovascular diseases must take into account the evaluation of specific metabolic biochemical parameters which have turned to be considered as major risk factors. The assessment of blood lipid profile, including total cholesterol, HDL and LDL cholesterol and triglycerides is the mainstay of cardiovascular and cardiometabolic risk evaluation, as recommended by many outstanding international scientific societies as well as by WHO. A huge amount of papers has been published to support the value of this check in prevention and/or in monitoring therapeutic interventions.
1. Mahmood SS, Levy D, Vasan RS, Wang TJ. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet. 2014 Mar 15;383(9921):999-1008.
2. Menotti A, Puddu PE, Kromhout D, Kafatos A, Tolonen H. Coronary heart disease mortality trends during 50 years as explained by risk factor changes: The European cohorts of the Seven Countries Study. Eur J Prev Cardiol. 2019 Jan 6:2047487318821250. doi: 10.1177/2047487318821250 [Epub ahead of print].
3. Nicholls SJ, Nelson AJ. HDL and cardiovascular disease. Pathology. 2019 Jan 3. pii: S0031-3025(18)30512-9. [Epub ahead of print].1
4. Tsao CW, Vasan RS. Cohort Profile: The Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology. Int J Epidemiol. 2015 Dec;44(6):1800-13.

Skin Check

As declared by the authors, these dermo-cosmetic checks have no diagnostic value for skin health or disease, rather they just represent an aesthetic evaluation. In this regard, the use of medical devices is not required, except for a digital microscope and a device for the detection of moisture and skin elasticity. Therefore, I have no further comment on this point.

Trico Check

As declared by the authors, these dermo-cosmetic checks have no diagnostic value for skin health or disease, rather they just represent an aesthetic evaluation. In this regard, the use of medical devices is not required, except for a digital microscope and a device for the detection of moisture and skin elasticity. Therefore, I have no further comment on this point.

Nail Check

As declared by the authors, these dermo-cosmetic checks have no diagnostic value for skin health or disease, rather they just represent an aesthetic evaluation. In this regard, the use of medical devices is not required, except for a digital microscope and a device for the detection of moisture and skin elasticity. Therefore, I have no further comment on this point.

UV Check

As declared by the authors, these dermo-cosmetic checks have no diagnostic value for skin health or disease, rather they just represent an aesthetic evaluation. In this regard, the use of medical devices is not required, except for a digital microscope and a device for the detection of moisture and skin elasticity. Therefore, I have no further comment on this point.

Pulmonary Check

Spirometric pattern evaluation is of utmost importance in the assessment of lung functions, according to the international recommendations by different scientific societies of Pneumology and Allergology. The reference and cut-off values of the parameters to evaluate have been fully agreed and adopted worldwide. Should a subject need a pneumological evaluation, this must include the assessment of spirometric parameters to define pulmonary functions, obstruction or restriction severity scores and prescribe adequate therapeutic intervention. The check is also commonly used in the clinical follow up for monitoring drug efficacy and response and may also have predictive value for lung function later in life.
1. Cahana-Amitay D, Lee LO, Spiro A 3rd, Albert ML. Breathe Easy, Speak Easy: Pulmonary Function and Language Performance in Aging. Exp Aging Res. 2018 Oct-Dec;44(5):351- 368.
2. Gonzalez L, Stolz D. Spirometry in the GP-Office. Praxis (Bern 1994). 2016 Feb 17;105(4):201-6.
3. Griffith KA, Sherrill DL, Siegel EM, Manolio TA, Bonekat HW, Enright PL. Predictors of loss of lung function in the elderly: the Cardiovascular Health Study. Am J Respir Crit Care Med. 2001 Jan;163(1):61-8.
4. Kjeldgaard P, Lykkegaard J, Spillemose H, Ulrik CS. Multicenter study of the COPD-6 screening device: feasible for early detection of chronic obstructive pulmonary disease in primary care? Int J Chron Obstruct Pulmon Dis. 2017 Aug 4;12:2323-2331.
5. Vandevoorde J, Verbanck S, Schuermans D, Kartounian J, Vincken W. Obstructive and restrictive spirometric patterns:fixed cut-offs for FEV1/FEV6 and FEV6. Eur Respir J. 2006 Feb;27(2):378-83.

Sat Check

It’s undisputed that oxidative stress plays a major role in determining many diseases affecting the whole body from the skin, to the brain and the heart, as well as a number of metabolic pathways and reactions. It may also have mutagenic effects on DNA, in turn involved in cancer onset and progression. Oxidative stress may affect protein and lipid metabolism as well as DNA via the deleterious effect of free radicals substances, which should be counteracted by a proper action of antioxidant compounds to maintain an healthy balance. The different harmful effect of oxidative stress may also underlie very common oral diseases, such as periodontitis, precancerous lesions and dental caries. As the latter is thought to be the most common, chronic, non communicable, preventable oral disease in the world, a number of studies have been designed to find adequate salivary markers of oxidative stress to prevent the onset of such and of other preventable oral diseases. As a diagnostic fluid, saliva has the advantage to allow non-invasive, easy collection and even repeated sampling. It has been assessed that saliva contains products of lipid and protein peroxidation and of DNA oxidation and fragmentation, which can be used for the assessment of oxidative stress. On the other hand, various antioxidant compounds are present in saliva including glutathione, ascorbic, and uric acid and some antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A simple, non invasive test of the salivary “redox” status may therefore be considered as a useful tool in the prevention of common oral diseases, according to many scientific studies published in literature.
Kamodyova N, Tothova L, Celec P. Salivary markers of oxidative stress and antioxidant status:influence of external factors. Dis Markers. 2013;34(5):313-321. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010; Jul-Dec 4(8):118-126. Motamayel-Ahmadi F, Goodarzi MT, Mahdavinezhad A, Jamshidi Z, Darvishi M. Salivary and serum antioxidant and oxidative stress markers in dental caries. Caries Res. 2018; 52(6):565-569.

Vascular Age

Arterial stiffness, measured as pulse wave velocity, has been described as associated to brain lesions detected as white matter hyperintensities in nuclear magnetic resonance T2 imaging. More recently, it has been clarified that these lesions may be associated to the progression of cognitive decline and functional disabilities, which in turn are typical features of the so called geriatric syndrome. Evidence has been accumulating to suggest that diabetes mellitus may favour the progression of these brain lesions, in addition to other already known risk factors such as hypertension, dyslipidemia and old age. Given the above, it seems obvious that the periodical check of the vascular age and stiffness may represent a valuable preventive tool, especially in subjects with the aforementioned risk factors.
1. Khoshdel AR, Eshtiaghi R. Assessment of Arterial Stiffness in Metabolic Syndrome Related to Insulin Resistance in Apparently Healthy Men. Metab Syndr Relat Disord. 2019 Jan 8. doi: 10.1089/met.2018.0090. [Epub ahead of print].
2. Saji N, Ogama N, Toba K, Sakurai T. White matter hyperintensities and geriatric syndrome: An important role of arterial stiffness. Geriatr Gerontol Int. 2015 Dec;15 Suppl 1:17-25.
3. Skrzypczyk P, Pańczyk-Tomaszewska M. Methods to evaluate arterial structure and function in children – State-of-the art knowledge. Adv Med Sci. 2017 Sep;62(2):280-294.
4. Tsao CW, Himali JJ, Beiser AS, Larson MG, DeCarli C, Vasan RS, Mitchell GF, Seshadri S. Association of arterial stiffness with progression of subclinical brain and cognitive disease. Neurology. 2016 Feb 16;86(7):619-26.
5. Vallée A, Petruescu L, Kretz S, Safar ME, Blacher J. Added value of aortic pulse wave velocity index in a predictive diagnosis decision tree of coronary heart disease. Am J Hypertens. 2019 Jan 9. doi: 10.1093/ajh/hpz004. [Epub ahead of print].

Vein Check

The measure of the elasticity of venous system, especially of leg veins, has been described as a useful tool to prevent venous insufficiency. Some studies have been carried out and published in literature so far, showing that reduced vein elasticity may predispose to varicose veins and precede valvular incompetence.
Hoang P, Wallace A, Sugi M, Fleck A, Pershad Y, Dahiya N, Albadawi H, Knuttinen G, Naidu S, Oklu R. Elastography techniques in the evaluation of deep vein thrombosis. Cardiovasc Diagn Ther. 2017 Dec;7(Suppl 3):S238-S245. Maeda Y1, Sekine M, Tamura T, Moriya A, Suzuki T, Kameyama K. Comparison of reflected green light and infrared photoplethysmography. Conf Proc IEEE Eng Med Biol Soc. 2008;2008:2270-2. Mumoli N, Mastroiacovo D, Giorgi-Pierfranceschi M, Pesavento R, Mochi M, Cei M, Pomero F, Mazzone A, Vitale J, Ageno W, Dentali F. Ultrasound elastography is useful to distinguish acute and chronic deep vein thrombosis. J Thromb Haemost. 2018 Dec;16(12):2482-2491. Njoum H, Kyriacou PA. Photoplethysmography for the Assessment of Haemorheology. Sci Rep. 2017 May 3;7(1):1406. Wardhan R, Shelley K. Peripheral venous pressure waveform. Curr Opin Anaesthesiol. 2009 Dec;22(6):814-21.