GGT: DIABETES, SÍNDROME METABÓLICA, ESTRESSE OXIDATIVO E MORTALIDADE

GGT: DIABETES, SÍNDROME METABÓLICA, ESTRESSE OXIDATIVO E MORTALIDADE
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Como no nosso, não apresentaremos uma longa narrativa sobre cada sistema corporal afetado, mas resumiremos brevemente ou citaremos os pontos relevantes para levar para casa e / ou conclusões de pesquisa de cada estudo. Os títulos dos artigos estão vinculados a resumos arquivados na Biblioteca Nacional de Ciências dos EUA. Muitos artigos também têm links em PDF de texto livre completo. Nossas páginas da Iron Science Library incluem:


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O objetivo deste estudo de 2005 foi "examinar associações específicas de gênero entre a gama-glutamiltransferase (GGT) e o diabetes mellitus tipo 2 incidente em uma amostra representativa de base populacional na Alemanha". O estudo recrutou 1.851 homens e 1.836 mulheres durante sua linha de base. anos de 1984-1985. “Um total de 172 casos de diabetes tipo 2 incidente entre homens e 109 entre mulheres foram registrados durante um período médio de acompanhamento de 14,7 anos. Em ambos os sexos, o risco de diabetes tipo 2 aumentou com o aumento dos níveis séricos de GGT. Após o ajuste multivariável de RHs para diabetes tipo 2 incidente nas categorias GGT (<25º, <50º, <75º, <87.5th and > ou = 87,5º percentis) foram 1.0, 1.81, 2.37, 3.41 e 4.24 (Valor P para tendência <0,0001) nos homens e 1,0, 1,42, 1,48, 1,95 e 2,41 (Valor P para a tendência 0,0179) nas mulheres. ”Os pesquisadores concluíram”O GGT é um importante preditor de diabetes tipo 2 incidente em homens e mulheres da população em geral. ” (Nota Health-e-Iron: Quadros 2 e 3 deste estudo e uma associação derivada de dados Tabelas de análise de risco aparecem diretamente abaixo)

Tabela 2

Tabela de Análise de Risco 1

Tabela 3

Nota Health-e-Iron: (76% dos casos de diabetes diagnosticados recentemente ocorreram entre indivíduos com GGT acima da mediana na entrada do estudo, enquanto apenas 40% dos casos eram obesos na entrada do estudo.y.)

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Neste estudo de 2005 da Finlândia, os pesquisadores “estudaram o GGT sérico como um preditor da incidência de diabetes tipo 2 e uma possível interação entre obesidade e GGT no desenvolvimento de diabetes tipo 2 em homens e mulheres.” Neste estudo de 20.158 homens e mulheres em idade 25-64, seguidos por mais de 12 anos, "os pontos de corte de GGT foram estabelecidos nos percentis 25, 50, 75 e 90".Após o ajuste para fatores de risco conhecidos de diabetes tipo 2, os riscos relativos para diabetes incidente nas categorias GGT foram 1,0, 1,2, 2,3, 3,1 e 3,9 entre os homens e 1,0, 0,8, 1,7, 3,5 e 6,4 entre as mulheres (P para tendência <0,01, respectivamente). A equipe de pesquisa concluiu: "…em mulheres e homens, o nível sérico de GGT dentro da faixa normal previa o diabetes tipo 2 e pode modificar a associação bem conhecida entre índice de massa corporal e diabetes tipo 2. ” (Nota Health-e-Iron: figura 1 e Tabela 2 deste artigo aparecem diretamente abaixo. É importante notar aqui que o GGT na metade superior da faixa populacional aumentou o risco de diabetes em 100% nas faixas normais de IMC, em 150% na faixa de sobrepeso e em 268% nas faixas de IMC obesos (após o ajuste para vários fatores relevantes). Contudo, entre todos os assuntos, GGT na metade superior da faixa da população (21 U / L e acima para homens, ou 12 U / L ou acima para mulheres) aumentou o risco de diabetes incidente em 450%)

Tabela de análise de risco – A tabela abaixo foi derivada dos dados da Tabela 2 acima, a partir do texto completo.

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Em outro estudo de 2005 sobre enzimas hepáticas em uma população de 1.441 homens na Cidade do México, “O aumento do GGT sozinho foi associado a todas as características da síndrome metabólica. O aumento do GGT foi um preditor significativo de IGT (glicemia de jejum prejudicada) ou diabetes (razão de probabilidade 1,62 (IC95% 1,08-2,42) quartil superior vs. quartis inferiores, P <0,02) após o controle do sexo, idade, distribuição da adiposidade / gordura, consumo de álcool, níveis plasmáticos de insulina e pró-insulina em jejum e concentrações de glicose plasmática após 2 horas após a glicose. Os pesquisadores concluíram, com relação a outras enzimas hepáticas, “apenas GGT elevado é um preditor independente de deterioração da tolerância à glicose para IGT ou diabetes. Como o GGT sinaliza o estresse oxidativo, a associação ao diabetes pode refletir tanto a esteatose hepática quanto o estresse oxidativo aprimorado. ” (Nota Health-e-Iron; figura 1 deste artigo aparece abaixo)

Nota: NGT = tolerância normal à glicose; e IGT = tolerância à glicose diminuída.

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Neste estudo de 2009 sobre GGT e outra enzima hepática em 3.556 homens e mulheres não diabéticos, "em comparação com o primeiro quartil GGT, as razões de chances para o desenvolvimento de diabetes tipo 2 para o segundo, terceiro e quarto quartis GGT foram de 0,64 (IC 95%, 0,25-1,65), 1,12 (0,45-2,78) e 3.07 (1,21-7,76), respectivamente. Os pesquisadores concluíram:Níveis séricos elevados de GGT e ALT são fatores de risco aditivos independentes para o desenvolvimento de diabetes mellitus tipo 2 em indivíduos sem fígado gorduroso ou disfunção hepática. ”

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Este relatório de 2005 foi realizado por pesquisadores na Itália. “Duzentos e cinco sujeitos com índice de massa corporal normal (IMC), tolerância à glicose e sem nenhuma alteração metabólica foram estudados em 1.339 indivíduos, sem doenças hepáticas conhecidas, abuso de álcool ou uso de drogas hepatotóxicas, representante da população idosa de 45 a 64 anos de Asti (noroeste da Itália). ”“… Após ajustes para múltiplos fatores de confusão…, os níveis medianos de NT (um marcador de estresse oxidativo) estão significativamente associados ao aumento do tercil GGT…, mas não aos terteis AST e ALT ”Os pesquisadores concluíram:“A GGT, uma medida fácil, universalmente padronizada e disponível, pode representar um marcador precoce de inflamação subclínica e estresse oxidativo em indivíduos saudáveis.. ”Os pesquisadores declararam adicionalmente:“em indivíduos adultos saudáveis, sem qualquer alteração metabólica mensurável, aqueles com os mais altos níveis de GGT apresentam valores mais altos de glicose em jejum (mesmo dentro da normalidade) e evidência de algum estresse oxidativo ou inflamação." (Nota Health-e-Iron; figura 1 deste artigo aparece abaixo)

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Este estudo de 2009 envolveu 7.976 participantes do Inquérito Nacional de Saúde e Nutrição 1999-2002 nos EUA. Os autores relataram: “Diabetes mellitus foi definido como uma glicemia de jejum> ou = 126 mg / dl, glicemia não jejum> ou = 200 mg / dl, ou uso de medicação hipoglicêmica oral ou insulina (n = 805). Níveis mais altos de GGT sérico foram associados positivamente ao diabetes mellitus, independentemente do consumo de álcool, índice de massa corporal, hipertensão e outros fatores de confusão. Multivariável razão de probabilidade (Intervalo de confiança de 95%) comparando o quartil 4 de GGT (> 33 U / L) para quartil 1 (<15 U / L) era 2,33 (1,59-3,41), tendência P <0,0001. Essa associação persistiu em análises separadas entre homens e mulheres.Os autores concluíram: “Nos modelos, a associação positiva entre GGT sérico e diabetes parecia estar presente em toda a gama de GGT, sem nenhum efeito limiar. Níveis mais altos de GGT sérico estão associados positivamente ao diabetes mellitus. ” (Nota Health-e-Iron: Tabela 2 deste artigo aparece abaixo)



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O objetivo deste estudo de 2011 realizado no Irã “era avaliar a associação entre concentrações séricas de GGT e intolerância à glicose, no parentes de primeiro grau (FDR) de pacientes diabéticos tipo 2. Entre 551 parentes não diabéticos de pacientes com diabetes tipo 2, “(A) média de GGT foi de 25,3 ± 12,1 UI / L. De acordo com o teste de tolerância à glicose, 153 eram normais e 217 e 181 eram diabéticos e pré-diabéticos, respectivamente. A média de GGT em pacientes normais, pré-diabéticos e diabéticos foi de 23,5 ± 15,9 UI / L, 29,1 ± 28,1 UI / L e 30,9 ± 24,8 UI / L respectivamente (p = 0,000). Os pesquisadores concluíram, "A medição de GGT em FDRs de pacientes diabéticos tipo 2 pode ser útil na avaliação do risco de diabetes; aqueles com níveis cronicamente altos de GGT devem ser considerados como grupo de alto risco para diabetes. ” (Nota Health-e-Iron: Figura 1 deste estudo está abaixo)

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Neste estudo de 2006 da França, os investigadores declararam: "Entre os marcadores hepáticos, a gama-glutamiltransferase (GGT) é o principal preditor para o desenvolvimento de diabetes tipo 2, até o momento, não existem dados sobre alterações na incidência de GGT e diabetes tipo 2. ”Eles estudaram 2.071 homens e 2.130 mulheres sem diabetes basal. Em um modelo totalmente ajustado,“…associação entre diabetes tipo 2 incidente e aumento ou alteração inalterada (ao contrário de diminuído) Os níveis de GGT foram de 2,54 (1,38-4,68) em homens (p = 0,003) e 2,78 (1.20-6.42) nas mulheres (p = 0,02). ”A equipe concluiu:“Um nível inalterado ou aumentado de GGT ao longo do tempo, mesmo quando o GGT está na faixa normal, está correlacionado com o aumento da resistência à insulina e está associado a um risco de diabetes tipo 2 incidente em ambos os sexos, independentemente do GGT basal, que por si só é um fator de risco para diabetes. ”

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Neste estudo de 1997, “os níveis de GGT foram avaliados entre 8.043 trabalhadores da construção civil, com idades entre 25 e 64 anos, que foram submetidos a exames de saúde ocupacional em seis centros no sul da Alemanha entre 1986 e 1988. Os participantes do estudo foram acompanhados por mortalidade por todas as causas até 1994.”… “Houve uma forte relação dose-resposta entre os níveis séricos de GGT e a mortalidade por todas as causas (Valor P para tendência <0,001). Comparado com homens com níveis de GGT abaixo de 15 U / litro (medido a 25 ° C), os riscos relativos (IC95%) foram 1,46 (0,86-2,49), 1,78 (1,08-2,94), 2.09 (1,26-3,45) e 3,44 (2.20-5.38) para homens com níveis de GGT de 15-19, 20-29, 30-49 e> ou = 50 U / litro, respectivamente. Essa relação foi reduzida, mas não eliminada, pelo controle do índice de massa corporal, diabetes, hipertensão, consumo de álcool e outras covariáveis ​​na análise multivariável. Os pesquisadores concluíram:O GGT sérico é um forte indicador de risco de mortalidade por todas as causas. ” (Nota Health-e-iron: uma tabela demonstrando esses resultados aparece abaixo)

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Neste estudo de 2009 nos EUA, “A mortalidade em 12 anos com base no atestado de óbito foi analisada entre 14.950 participantes adultos na terceira Pesquisa Nacional de Saúde e Nutrição dos EUA, 1988-1994.” “…GGT anormal (foi definido) > 51 U / L em homens ou> 33 U / L em mulheres“A mortalidade por todas as causas aumentou com GGT elevado (HR, 1.5; IC95%, 1,2-1,8), assim como mortalidade por doença hepática (HR, 13,0; IC95%, 2,4-71,5), neoplasias (HR, 1.5; IC95%, 1,01-2,2) e diabetes (HR, 3.3.; IC95%, 1,4-7,6), mas não de doença cardiovascular (HR, 1.3; IC 95%, 0,80-2,0). Os pesquisadores concluíram:Na população dos EUA, o GGT elevado foi associado à mortalidade por todas as causas, doenças hepáticas, câncer e diabetes,… (Nota Health-e-Iron: embora as mortes cardiovasculares neste estudo não tenham atingido significância estatística, o achado de mortalidade por todas as causas alcançou. Você pode ver muitos artigos sobre doenças cardiovasculares e cardíacas do GGT, linkando a nossa página)

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Neste estudo prospectivo de 2008 do Reino Unido, “6.997 homens com idade entre 40 e 59 anos sem histórico de DCV (doença cardiovascular), (CHD) (doença cardíaca coronária ou derrame)) ou diabetes extraído de práticas gerais em 24 cidades britânicas (que foram) acompanhados por 24 anos, "O risco de mortalidade fatal por DCC e DCV foi elevado apenas no trimestre superior (22 U / L); o risco de acidente vascular cerebral tendia a aumentar com o aumento da GGT. Os riscos relativos ajustados (Q4 vs. Q1) foram de 1,43 (1.09,1.84) para eventos CHD fatais, 1,56 (1.20,2.04) para incidência de acidente vascular cerebral e 1,40 (1.16,1.70) para Mortalidade por DCV. Quando estratificadas por faixas etárias, foram observadas associações mais fortes entre a mortalidade por GGT e DCV nos homens mais jovens (<55 anos) (P = 0,01 para interação). ”Os pesquisadores concluíram:“O GGT elevado está associado a um risco significativamente aumentado de acidente vascular cerebral, eventos fatais de DCC e mortalidade por DCV, independente dos fatores de risco estabelecidos para DCV e pode ser um marcador adicional útil para o risco de DCV a longo prazo. ”


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Em 2009, essa equipe de pesquisa estudou uma coorte italiana e "avaliou possíveis interações entre o IMC e a concentração de GGT." … "em uma coorte de 3.633 indivíduos diabéticos tipo 2". Os pesquisadores observaram que “À medida que a concentração de GGT aumentou, a associação do IMC com dislipidemia aterogênica e controle glicêmico fortaleceu (P = 0,01 e 0,004 para interações, respectivamente): por outro lado, a associação do IMC com hipertensão, hipercolesterolemia e hiperuricemia não mudou substancialmente nos quartis de GGT. "…"no quartil GGT mais baixo, o IMC não se associou à dislipidemia aterogênica ou ao controle glicêmico deficiente, enquanto no quartil GGT mais alto, as taxas de prevalência variaram de 62,3 a 74,7% para dislipidemia e de 75,3 a 83% para controle glicêmico deficiente. Os pesquisadores concluíram com esta importante observação:Esses achados sugerem que a própria obesidade pode não ser um fator de risco suficiente para dislipidemia aterogênica ou controle glicêmico deficiente em pessoas com diabetes tipo 2. ” (Nota Health-e-Iron: figura 1 deste estudo aparece abaixo)


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Em um estudo de 2007 nos EUA, semelhante ao descrito imediatamente acima, os pesquisadores “analisaram 4.011 adultos> ou = 40 anos que participaram da 3ª Pesquisa Nacional de Saúde e Nutrição dos EUA."…"O IMC foi associado à diabetes prevalente apenas entre pessoas com alta atividade normal de GGT no soro (P para interação = 0,002). No maior quartil sérico de GGT, odds ratio ajustada para IMC 25-29,9, 30-34,5 e> ou = 35 kg / m (2) em comparação com IMC <25 kg / m (2) estavam 3.1., 5.1e 6.2, Respectivamente (P para tendência <0,001). No menor quartil sérico de GGT, o IMC não se associou ao diabetes; os odds ratio ajustados correspondentes foram 1,0, 0,9, 1,8 e 0,8 (P para tendência = 0,551). Semelhante à conclusão descrita acima, os pesquisadores concluíram: "O IMC não se associou ao diabetes tipo 2 prevalente quando o GGT estava baixo normal, sugerindo que a própria obesidade pode não ser um fator de risco suficiente para o diabetes tipo 2. Na prática, essa interação pode ser útil em contextos clínicos para identificar indivíduos com alto risco de diabetes tipo 2." (Nota Health-e-Iron: figura 1 deste estudo aparece diretamente abaixo)

Figura 1. Odds ratio ajustado (ORs) e ICs de 95% do diabetes recentemente reconhecido (205 casos) por categoria de IMC e quartis (Q) de GGT sérico. Os números na tabela são os números de casos e indivíduos em risco em cada categoria. As RUP foram ajustadas para idade, sexo, raça / etnia, índice de pobreza, tabagismo, atividade física no lazer e consumo de álcool; todos os ORs foram calculados com o grupo de referência de indivíduos com a categoria mais baixa de IMC e GGT sérico. O primeiro e o segundo quartis de GGT sérico foram combinados devido ao pequeno número de casos de diabetes recém-reconhecido.

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Neste artigo de revisão de 2007, os autores levantam a hipótese de que "associações de GGT dentro de sua faixa normal com diabetes tipo 2 podem refletir efeitos prejudiciais dos xenobióticos encontrados no ambiente, como poluentes orgânicos persistentes (POPs). Observações epidemiológicas mostraram que a atividade sérica de GGT dentro de sua faixa normal previa fortemente o diabetes tipo 2 futuro; a previsibilidade do diabetes devido à obesidade era baixa com GGT na extremidade inferior da faixa normal; e GGT mostraram associação positiva com marcadores conhecidos de estresse oxidativo ou inflamação. ”“… Postulamos uma hipótese em duas partes: que associações de GGT dentro de sua faixa normal com diabetes tipo 2 podem refletir efeitos prejudiciais dos xenobióticos encontrados no ambiente, "postulamos uma hipótese em duas partes: que a associação de GGT sérico com diabetes tipo 2 reflete a exposição a POPs, como estas substâncias, que têm uma meia-vida muito longa, pode influenciar o risco de diabetes residindo no tecido adiposo como desreguladores endócrinos; e que POPs ou substâncias similares podem interagir com a obesidade para causar diabetes tipo 2. Apoiando esta hipótese, A investigação transversal da exposição de fundo a POPs na Pesquisa Nacional de Exame de Saúde e Nutrição mostrou relações semelhantes às observadas para GGT, incluindo uma poderosa associação com diabetes prevalente e nenhuma associação entre obesidade e diabetes para concentrações muito baixas de POP. Nossa hipótese pode ser testada em estudos prospectivos e estudos toxicológicos. ”

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Em 2010, este grupo de pesquisa relatou o seguinte: “O objetivo desta pesquisa foi examinar a associação da gama-glutamiltransferase (GGT) e suas interações com o consumo de álcool (álcool), índice de massa corporal (IMC) e / ou alanina aminotransferase (ALT) na incidência de diabetes tipo 2 (DM) no Japão. ”“ O número total de indivíduos nesta coorte foi de 39.563. ”“.os HRs (razões de risco) do terceiro e quarto quartis de GGT em mulheres e o quarto quartil de GGT em homens foram significativamente maiores do que os do primeiro quartil de GGT. A associação entre o IMC e a incidência de DM (diabetes mellitus) foi aumentada pelo aumento dos níveis de GGT em mulheres. Quando os níveis de GGT estavam no segundo ao quarto quartil, as FCs de indivíduos obesos eram significativamente maiores do que as de indivíduos com baixo peso. ”Além disso, em mulheres, a obesidade não é mais um fator de risco para Diabetes Mellitus quando o nível de GGT é baixo. ” (Nota Health-e-Iron: Figura 2 deste estudo aparece abaixo)


Figura 2 Relação entre IMC e risco de DM entre as categorias GGT. Os HRs foram calculados e ajustados para idade, histórico familiar de diabetes, tabagismo, tipo basal de glicose, consumo de álcool e ALT. O primeiro, segundo, terceiro e quarto quartis de GGT <16, 16 a <24, 24 a <41 e ≥41 U / L para homens e <9, 9 a <13, 13 a <19 e ≥19 U / L para mulheres são expressas como linha pontilhada cinza, linha sólida cinza, linha pontilhada preta e linha sólida preta, respectivamente. P <0,05, P <0,01, P <0,001; comparado com o sujeito com baixo peso usando análise de regressão de Cox. A interação entre GGT e IMC na incidência de DM é limítrofe significativa em mulheres (valor de P para interação = 0,070), mas não em homens (valor de P para interação = 0,978). IMC, índice de massa corporal; DM, diabetes tipo 2; GGT, gama-glutamiltransferase; HR, taxa de risco; ALT, alanina aminotransferase.

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Neste estudo de laboratório de março de 2012 de “células humanas de hepatoblastoma C3A (fígado) tratadas com várias combinações de octanoato, lactato (L), (P) e (N) aguda ou por 72h, antes das medições da concentração de triglicerídeos, respiração celular , Produção de EROs (espécies reativas de oxigênio), potencial de membrana mitocondrial e análise e microscopia eletrônica. A equipe de pesquisa do Reino Unido relatou: Agudamente, LPON tratamento (isto é, as substâncias acima) respiração mitocondrial melhorada e Formação ROS. Após 72h, apesar das semelhanças na acumulação de triglicerídeos, o tratamento com LPON, mas não o oleato, afetou dramaticamente a função mitocondrial, como evidenciado pela diminuição da respiração, aumento do potencial da membrana mitocondrial e formação de ERO com cetogênese aprimorada concomitante. A adição do antioxidante evitou a disfunção mitocondrial e reverteu as alterações metabólicas observadas com o LPON, sugerindo fortemente o envolvimento da ERO na mediação do comprometimento mitocondrial. Os pesquisadores concluíram, "Nossos dados indicam que a formação de ERO, em vez da esteatose celular per se, prejudica a função mitocondrial. Assim, a redução na esteatose celular pode nem sempre ser o resultado desejado sem melhora concomitante da função mitocondrial e / ou redução da formação de ERO. ”

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Este estudo de laboratório de 2008 foi realizado no Japão. O objetivo era "tInvestigar os principais fatores correlacionados com a atividade sérica de gama-glutamiltransferase".Medimos a atividade sérica de gama-glutamiltransferase em 248 japoneses saudáveis ​​e determinamos suas correlações com antioxidantes séricos, outros fatores plasmáticos ou séricos, 8-hidroxi-desoxiguanina urinária e fatores do estilo de vida. ”“ A atividade sérica média de gama-glutamiltransferase foi de 29 UI / L. As atividades de gama-glutamiltransferase de homens e pessoas com mais de 45 anos foram significativamente maiores que cada uma das contrapartes. Os níveis de gama-glutamiltransferase aumentaram significativamente com o número de cigarros fumados por dia e a frequência do consumo de álcool, exceto para as pessoas que não tomavam álcool. Além disso, gama-glutamiltransferase correlacionou-se significativamente com a 8-hidroxi-desoxiguanina urinária, e com mais fatores sanguíneos, incluindo tocoferóis séricos, carotenóides, enzimas antioxidantes, peróxido lipídico, e ácidos graxos livres do que a 8-hidroxi-desoxiguanina. Em análises de regressão múltipla, a gama-glutamiltransferase teve associações significativas com retinol, 8-hidroxi-desoxigananina, ácido docosahexaenóico e tabagismoOs pesquisadores concluíram:Nossos achados atuais sustentam a hipótese de que a gama-glutamiltransferase pode ser usada como um marcador relacionado ao estresse oxidativo."

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Este é um estudo de 2012 relatado na Turquia. "Após exclusões apropriadas, uma coorte de 1.667 adultos de uma população em geral (idade de 52 ± 11 anos) foi avaliada prospectivamente no seguimento de 4 anos, usando regressões de risco proporcional em parte de Cox. “A atividade mediana (intervalo interquartil) da GGT foi 24,9 (17,0; 35,05) U / l nos homens, 17,0 (12,3; 24,0) U / l em mulheres. ”“ Na análise de regressão linear, Embora o tabagismo não tenha sido associado, sexo (masculino), idade dependente de sexo, uso de álcool, IMC, triglicerídeos em jejum e proteína C reativa (PCR) foram determinantes independentes significativos da GGT circulante. ”“ A associação independente mais forte existia com diabetes (HR 1.3 (IC 95% 1,1; 1,5)) enquanto a atividade GGT tendia a predizer marginalmente a DCC independentemente da bilirrubina total, mas não do IMC. ”Os pesquisadores concluíram:“… que o GGT sérico elevado confere, além do IMC, risco de hipertensão, SM e diabetes tipo 2, mas medeia a adiposidade contra o risco de doença coronariana. ”

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Neste estudo relatado em 1998, os pesquisadores “realizaram um estudo de coorte prospectivo de casos incidentes de NIDDM diagnosticado por médico em um grupo de 7.458 homens não diabéticos (40-59 anos) seguidos por uma média de 12,8 anos (intervalo 11,5-13,0). Os homens foram selecionados aleatoriamente nas listas de prática geral em 24 cidades britânicas. Os casos de NIDDM foram apurados por repetidos questionários postais aos homens e por uma revisão sistemática regular dos registros da atenção primária. ” Durante o seguimento, 194 homens desenvolveram diabetes. "GGT sérico médio no início do estudo (média geométrica (IC95%)) foi significativamente maior nos pacientes com DMNID do que no restante da coorte (20,9 (19,3-22,6) vs. 15,3 U / l (15,0-15,6), P <0,0001). Houve um aumento suave e gradual no risco de NIDDM ajustado à idade com o aumento dos níveis de GGT, com um risco relativo no quinto topo da distribuição de 6,8 (3.5-12.9) em relação ao quinto inferior (tendência P <0,0001). Essa associação foi independente da glicose sérica e do IMC e de outros preditores de DMNID aos quais a GGT está associada, incluindo ingestão de álcool e nível de atividade física (ajustado para o quinto risco relativo superior ao menor: 4,8 (2,0-11,8), tendência P <0,0001)). Os investigadores concluíram:Esses achados sugerem que um nível sérico elevado de GGT é um fator de risco independente para NIDDM. O nível sérico de GGT pode ser um marcador simples e confiável de gordura visceral e hepática e, por inferência, de resistência hepática à insulina. ” (Nota Health-e-Iron: as pesquisas deste 1998 Um estudo inferiu que a relação entre GGT elevado e diabetes pode estar relacionada à gordura abdominal e hepática. Conforme observado em outros estudos mais recentes nesta página, a relação entre GGT e diabetes ainda existe quando são feitos ajustes apropriados para a gordura. Os estudos mais recentes sugerem que essa relação é provavelmente mediada por estresse oxidativo. figura 1 deste estudo aparece abaixo. O próximo artigo desta página (#18) é uma carta ao editor escrita b por dois dos mesmos autores do editorial (artigo #2) em nossa página. Este editorial foi publicado em 2007 e sugeriu que o GGT, como um fator no aumento do estresse oxidativo, poderia explicar uma observação muito semelhante à encontrada aqui.)


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Os autores observaram “Estudos epidemiológicos populacionais recentes mostraram convincentemente que a atividade sérica da glutamiltransferase (GGT) está associada a muitos fatores de risco para doenças cardiovasculares e prevê diabetes tipo 2, hipertensão, acidente vascular cerebral e infarto do miocárdio de início recente. ”“ Lemos com interesse o artigo recente de Lim et al. (veja o estudo acima #13) em a possível interação entre GGT e obesidade e sua associação com o risco de diabetes tipo 2 prevalecente, achados indicando que a própria obesidade pode não ser um fator de risco suficiente para diabetes quando as concentrações de GGT se aproximam do limite inferior do intervalo de referência. ”As implicações clínicas dessa conclusão são dignas de nota, porque pessoas obesas com sobrepeso e com concentrações de GGT no limite inferior do intervalo de referência (por exemplo, 20 U / L) deixaria de ser considerado com alto risco de desenvolver diabetes. ”O pesquisador realizou uma análise retrospectiva dos resultados em uma coorte de pacientes ambulatoriais consecutivamente encaminhados por clínicos gerais para exames de sangue de rotina nos 9 meses anteriores. "Resultados cumulativos para GGT, FPG (glicemia de jejum), e triglicerídeos foram recuperados em 7.267 pacientes ambulatoriais> 35 anos durante um período de 9 meses. Conforme mostrado na Tabela 1 (veja abaixo), as concentrações de FPG e triglicerídeos aumentaram acentuadamente entre as categorias GGT. Da mesma forma, a frequência daqueles com FPG ≥7,0 mmol / L, um ponto de corte sugestivo para o diagnóstico de diabetes de acordo com as diretrizes da Associação Americana de Diabetes e daqueles com hipertrigliceridemia (≥1,7 mmol / L pelo critério do Painel de Tratamento para Terceiros Adultos) aumentou constantemente em todo o espectro dos limiares de GGT de 16% para 31% para FPG e de 14% para 39% para triglicerídeos, respectivamente. ”No geral, concordamos com as sugestões de Lim et al. (veja o estudo acima #13) que a medição da GGT pode ser útil em contextos clínicos para detectar subpopulações de alto risco de diabetes tipo 2 e / ou hipertrigliceridemia. SEsses indivíduos podem se beneficiar de uma abordagem terapêutica mais intensiva para diminuir o risco cardiovascular global, independentemente dos possíveis efeitos não medidos do estilo de vida ou da obesidade.. Concebivelmente, a associação significativa das concentrações séricas de GGT com FPG e triglicerídeos, observada em nossa investigação, pode ser biologicamente explicada por alguns mecanismos subjacentes, como esteatose hepática, resistência à insulina e aumento do estresse oxidativo. (Nota Health-e-Iron: figura 1 deste estudo aparece abaixo)

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“Esta revisão de 2010 examina evidências de uma associação de atividade sérica normal alta da enzima GGT, principalmente dentro da faixa de referência, com risco de mortalidade e grandes (ou seja, morbimortalidade cardiovascular) e resultados não vasculares (ou seja, diabetes incidente tipo 2, doença renal crônica e câncer), independente do consumo de álcool e outros fatores prognósticos. ”


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Neste estudo de 2010, “foi investigada a relação entre GGT ou consumo de álcool e incidência de DM (diabetes mellitus), considerando o índice de massa corporal (IMC) em trabalhadores japoneses saudáveis”. "Seguimos 3.095 homens que não tinham DM na linha de base por 4 anos."Participantes com maior GGT (GGT> ou = 27 U / L) mostraram um risco aumentado de incidência de diabetes, mesmo quando seu nível de IMC era baixo. ”Os pesquisadores concluíram, "Maior GGT foi associado a uma maior incidência de DM, independentemente do estado de bebida ou obesidade. Embora tenha sido observada uma relação em forma de U entre consumo de álcool e diabetes incidente, o risco de bebedores leves a moderados não era baixo se eles estavam acima do peso ou apresentavam GGT mais alto. ”

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Pesquisadores do estudo francês de 2010 analisaram “marcadores hepáticos associados a diabetes incidente em homens e mulheres com IMC <27 kg / m (2) e compará-los com os de indivíduos com IMC de> ou = 27 kg / m (2). ”“ Os fatores de risco para diabetes incidente de 9 anos foram comparados nos dados franceses de um estudo epidemiológico sobre a coorte da síndrome de resistência à insulina (DESIR). Comparações foram feitas entre os 2.947 participantes com IMC <27 kg / m (2) e o 879 com um IMC> ou = 27kg / m (2). ”GGT, seja considerada uma variável contínua ou em níveis> ou = 20 U / l, foi associado a diabetes incidente, com um efeito mais forte no grupo IMC <27 kg / m (2): OU 1,59 (IC95% 1,29-1,97, p <0,001) em comparação com OR 1.07 (IC 95% 0,82-1,38, p = 0,63) para aqueles com IMC> ou = 27 kg / m (2) " (Nota Health-e-Iron: Tabela 3 deste estudo aparece abaixo)


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O objetivo desta investigação francesa de 2007 era “… estudar a associação de GGT com o desenvolvimento da síndrome metabólica (SM). Os pesquisadores estudaram "dados de três anos do estudo prospectivo de Dados do Estudo Epidemiológico sobre a Síndrome de Resistência à Insulina de 1.656 homens e 1.889 mulheres sem SM na linha de base …" a razão de chances para a SM incidente aumentou nos quartis basais de GGT (1, 1,96, 2,25 e 3,81 em homens, P <0,03; e 1, 1,23, 1,80 e 1,58 em mulheres, P <0,05). ”Após os ajustes dos marcadores de resistência à insulina,“… os homens no mais alto em comparação ao quartil mais baixo de GGT mantiveram um risco significativo de SM incidente. Nas mulheres, não havia mais um risco significativo. O GGT foi significativamente associado à incidência de três anos de componentes individuais da SM. Os pesquisadores concluíram:GGT, um preditor de diabetes tipo 2, foi associado a um risco de SM incidente. Essa associação estava principalmente relacionada à resistência à insulina, mas era independente de outros fatores de confusão. ” (Nota Health-e-Iron: Uma tabela de análise de risco derivado dos dados deste estudo aparece abaixo)

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Em 2009, este grupo de pesquisadores coreanos “hipotetizou que as concentrações séricas de GGT e ALT estão associadas ao desenvolvimento de SM. Eles estudaram "15.250 homens (média de 38 anos) e 6.280 mulheres(média de 41 anos) ", em 2002 e" analisou o desenvolvimento de SM nos dados de acompanhamento em 2006 ". Quando os dados coletados em 2002 foram divididos em quartis." "Neste grande estudo prospectivo em coreanos, altas concentrações basais de GGT e ALT previram o desenvolvimento futuro de SM (Nota Health-e-Iron: os pesquisadores deste estudo prepararam uma ilustração Apresentação de slide que pode ser visualizado clicando aqui)

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Neste estudo de 2008 da China, “um total de 5.404 indivíduos com idade ≥ 40 anos foram recrutados de dois comunidades urbanas em Xangai para análises transversais. Um subgrupo de 681 participantes sem SM na linha de base foi incluído nas análises longitudinais. ”Tanto o GGT quanto o ALT foram associados forte e positivamente aos riscos de SM em análises simples e multivariadas. Ajustes adicionais para HOMA-IR e ALT não alteraram materialmente a associação de GGT e SM, Considerando que o ajustamento para HOMA-IR e GGT atenuou substancialmente a associação ALT-MetS. ” Os valores médios de GGT para cada quartil foram 14, 20, 28.e 50.. Nas análises longitudinais, os riscos de desenvolver SM foram aumentados nos quartis de GGT de maneira dependente da dose após ajustes extensivos (odds ratio de 1,00, 1,38, 1,62 e 2,29 para GGT, quartil 1 a quartil 4; P para tendência = 0,01). ”Os pesquisadores concluíram:“Nosso estudo confirmou associações significativas e independentes de GGT e ALT com SM em adultos chineses. Além disso, o GGT pode ser mais eficaz para indicar o desenvolvimento futuro de SM. ” (Nota Health-e-Iron: Tabela 3 deste estudo aparece abaixo)

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Este estudo de 2003 investigou "a associação entre GGT sérico e risco de desenvolvimento de diabetes" em japonês homens. Os investigadores estudaram a incidência de glicemia de jejum comprometida (IFG) e diabetes tipo 2 durante um período de sete anos. “Com o ajuste de possíveis fatores de risco para diabetes, o risco relativo de IFG comparado com GGT sérico <16 U L-1 foi 1,23 (95% CI, 0.79-1.90), 1.50 (CI, 0.97-2.32) and 1.70 (CI, 1.07-2.71) with serum GGT of 16-24, 25-43 and >/=44 U L-1, respectively (P for trend = 0.014). The respective relative risks for type 2 diabetes compared with serum GGT <16 U L-1 were 2.54 (CI, 1.29-5.01), 2.64 (CI, 1.33-5.23) and 3.44 (CI, 1.69-6.70) (P for trend = 0.002).” The researchers concluded, “The risk for development of IFG or type 2 diabetes increased in a dose-dependent manner as serum GGT increased in middle-aged Japanese men. The increased relative risk for IFG or type 2 diabetes associated with serum GGT was more pronounced in obese men. ” (Health-e-Iron note: Table 2 from this study appear below)

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In this 2008 reported study the investigators “sought to examine the association between plasma concentrations of liver enzymes gamma-glutamyltransferase (GGT) and alanine transaminase (ALT) and incident diabetes, prospectively.” “We conducted a case-cohort analysis of data from participants mainly aged 35-65 years in the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. The analytic sample included 787 participants with incident diabetes and 2,224 participants without diabetes.” “Concentrations of GGT and ALT were significantly associated with incident diabetes after extensive adjustment. Compared with participants in the lowest quintile of GGT, the adjusted hazard ratios for increasing quintiles were 1.13 (95% CI 0.66-1.93), 1.67 (1.01-2.77), 2.77(1.71-4.49), and 2.67 (1.63-4.37), respectivamente (P for linear trend <0.001).” Similar but slightly weaker associations were found for ALT. "The magnitude of the associations were higher among men than women for GGT (P = 0.004) but did not differ significantly between men and women for ALT (P = 0.307).” The investigators concluded, “Concentrations of GGT and ALT were significant predictors of incident diabetes in this study, even at concentrations still considered to be within the normal range. ” (Health-e-Iron note: Tables 2 and 3 from this study appear below)


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In this 2007 study, investigators in the U.K. studied data from the British Women’s Health and Heart Study. “…a random sample of British women aged 60-79 years (N = 3,394; 3,086 without diabetes and 308 with diabetes) was used. “Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulinare stronger in women with diabetes compared to women without diabetes (P for interaction < 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status.” “Associations did not differ substantially between obese and non-obese non-diabetic women.” The investigators concluded, “elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population. ” (Health-e-Iron note: Table 1 e Figure 1 from this study appear below)

Figure 1

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In a study 2007 in japan of 1,804 non-diabetic subjects 40 to 79 years of age who were followed prospectively for a mean of 9.0 years, 135 subjects developed diabetes. "In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly with elevating quartiles of serum gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) levels.” “after adjusting for comprehensive risk factors and other liver enzymes, the risk of developing diabetes was significantly higher in the highest GGT quartile than in the lowest quartile (odds ratio (OR), 2.54; 95% confidence interval (CI), 1.03 to 6.26 for homens; OR, 5.73; 95% CI, 1.62 to 20.19 for mulheres).” The researchers concluded, "Our findings suggest that serum GGT and ALT concentrations are strong predictors of diabetes in the general population, independent of known risk factors. ” (Health-e-Iron note; Figure 1 from this article appears below)

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The investigators in this 2008 reported study “analyzed the National Health and Nutrition Examination Survey, 1999 to 2004, a nationally representative sample of the noninstitutionalized US population. Among adults (aged >20 years of age) who were not problem drinkers, we examined hepatitis B and C antibodies and the liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamyl transaminase (GGT) with impaired fasting glucose and undiagnosed diabetes (unweighted, n 5234; weighted, n 172,626,805). "In unadjusted analyses 51% of individuals with undiagnosed diabetes have elevated GGT versus 20% of individuals without diabetes or impaired fasting glucose (P = .01). Similarly, 43% of individuals with undiagnosed diabetes have elevated ALT versus 23% of individuals without diabetes or impaired fasting glucose (P = .01).” “In adjusted analyses, elevated GGT (odds ratio, 2.15; 95% CI, 1.44 –3.20) and ALT (odds ratio, 1.84; 95% CI, 1.06 –3.20) are associated with undiagnosed diabetes. Similarly, in adjusted analyses, elevated GGT (odds ratio, 1.23; 95% CI, 1.00 –1.53) and ALT (odds ratio, 1.44;95% CI, 1.15–1.79) are associated with impaired fasting glucose.” The investigators concluded, “Liver function is associated with undiagnosed diabetes and impaired fasting glucose and may justify further investigation as a risk stratification variable for undiagnosed diabetes or impaired fasting glucose. ” (Health-e-Iron note: Table #4 from this study appears below)

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Reported in 2010, a team of researchers from Italy “performed a cross-sectional analysis of 500 subjects (199 men/301 women, age 47 +/- 11 years, body mass index (BMI) 28.6 +/- 5.5 kg/m(2)) referred to Diabetes Clinics because of potential risk of type 2 diabetes mellitus (T2DM).” “Subjects with normal glucose tolerance showed lower gamma-glutamyltransferase levels compared with those with impaired glucose tolerance (IGT), impaired fasting glucose (IFG)+ IGT and T2DM (ANOVA, p < 0.0001), but not those with IFG.” “After further adjustment for BMI, alcohol intake, family history of diabetes, cigarette smoking and physical activity, the top quartile of gamma-glutamyltransferase remained an independent predictor of IFG + IGT (OR 2.62; 95% CI: 1.13-6.07) and T2DM (OR 2.39; 95% CI: 1.20-4.76).” The researchers concluded, “GGT is closely related to insulin resistance, reduced beta-cell function and deterioration of glucose tolerance. ”

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In this 2012 reported meta-analysis of nine prospective cohort studies that included 47,499 participants and 5,009 cases of metabolic syndrome, “the association between GGT and MetS was analysed in qualitative and quantitative manners.” “When comparing the risk of MetS between the highest versus the lowest category of GGT levels, the pooled RR (Relative Risk) of MetS was 1.63 (95% CI: 1.43-1.82; p < 0.000). The second dose-response analysis of GGT levels per 5 U/l increment with risk of MetS showed that the summary RR of MetS was 1.09 (95% CI: 1.06-1.13; p < 0.000).” “Sensitivity analyses showed that no single study significantly influenced the pooled RRs. “Conclusions: Our results show that GGT levels are positively associated with risk of MetS independently of alcohol intake. GGT may be a promising marker for predicting MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms in future.”

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The objective of this 2012 published study undertaken in Malaysia was “To evaluate gamma-glutamyltransferase (GGT), alanine transaminases (ALT) and aspartate transaminases (AST) levels and prevalent gestational diabetes mellitus (GDM).” “Random plasma glucose, GGT, ALT and AST and the 50-g glucose challenge test were done on antenatal women followed by diagnostic 3-point 75-g oral glucose tolerance test within two weeks. GDM was diagnosed by ADA (2011) criteria.” “The risk for GDM was higher for women in the highest GGT quartile band compared to the lowest: RR 1.3595%CI 1.0-1.8; P=0.04. However, after adjustment for confounders, GGT was no longer associated with GDM. There was no correlation between ALT and AST levels and GDM.

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In another gestational diabetes study from Malaysia that was reported in 2008 the reseachers set out “To evaluate the relationship between gamma-glutamyltransferase (GGT) level in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of gestational diabetes (GDM).” “GGT level correlated positively with the 2-hour glucose level (Spearman’s rho = 0.112: P < 0.05). GGT values that were stratified into quartiles demonstrated a significant trend with diagnosis of GDM (chi(2) for trend; P = 0.03). Multivariable logistic regression analysis taking into account maternal age, gestational age at OGTT, body mass index and a positive 50-g glucose challenge test (GCT) indicated that high GGT was an independent risk factor for GDM (adjusted odds ratio (AOR) 2.1 95% CI 1.2-3.8: P = 0.01). In the subset of women identified by a positive GCT, on multivariable logistic regression analysis, only high GGT was an independent risk factor for GDM (AOR 2.3 95% CI 1.3-4.2: P = 0.007).” The researchers concluded, “Raised GGT level is an independent risk factor for GDM in high risk pregnant women undergoing OGTT. ”

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In another 2012 similar gestational diabetes study reported in Turkey, “The aim of this study was to evaluate plasma gamma-glutamyltransferase (GGT) in gestational diabetes mellitus (GDM) in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of GDM and to explore whether this activity is associated with metabolic parameters.” “his prospective control study included 37 women with GDM and 42 women with normal glucose tolerance in pregnancy (control group). In the study group (GDM), blood was taken for analyzing 100 g OGTT from women who have abnormal 50 g glucose challenge test (GCT).” “Compared with the controls, the GDM group had significantly higher mean values for serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglyceride and GGT. Within the GDM group, GGT levels were only negatively correlated with high-density lipoprotein (r = -0.41, p = 0.01). GGT was determined to be an independent metabolic parameter for GDM. The researchers concluded, “The increase at GGT level is an independent risk factor for GDM and identified as high-risk women for diagnosis of GDM. ”

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The objective of this 2010 study undertaken in Israel was “to evaluate the range of prevalence of MetS in apparently healthy individuals whose liver enzyme concentrations were all within-normal-range.” “Analyzed were a cohort of 6,561 men and 3,389 women.” “In our study, we found that the prevalence of the MetS doubles if a comparison is made between the first, second and third quintiles of both GGT and ALT. In these quintiles the concentrations of the enzymes are not only regarded as being absolutely normal, but are actually even in the lower range of the “normal" values.” In their conclusion the researchers state the following, “Moreover, our findings suggest that even minute changes, still within the so called "normal range" could point towards a potential dysmetabolic state. These observations could therefore lead to avoiding the usage of cut-off values for normalcy for these two biomarkers. In addition, they should encourage the use of both GGT and ALT as continuous biomarkers that could be used for early signaling of dysmetabolism. Finalmente, our results support the notion that in the era of early detection, prevention and treatment of metabolic disorders, one cannot be confident that relatively low concentrations of liver enzymes exclude the presence of dysmetabolic changes. A practical consequence might therefore be to follow these enzyme concentrations as continuous biomarkers and take into consideration the possibility that even small changes in their concentrations might be of relevance. ” (Health-e-Iron note: Figure 1 e Table 4 appear below)

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This study from Turkey was reported in 2010. “The aim of this study is to know if the liver function tests (LFT), especially gamma glutamyl transferase (GGT), have a predictive value in diagnosis of metabolic syndrome (MS).” “A cross-sectional, single-center study was carried out with 908 subjects.” “The mean values of alanine amino transferase (ALT), aspartate aminotransferase (AST) and GGT levels were statistically significantly higher in MS group. The mean values of liver enzymes, for female/ male subjects in MS group, AST; ALT and GGT respectively, estavam; 20.5/19.7 U/l; 25.9/28.5 U/l; 35.9/42.1 U/l. When the sample is divided into quartiles of the GGT levels, increase in GGT is positively correlated with increased MS prevalence. In ROC analysis GGT is as strongly associated with the IDF diagnostic components as is each individual IDF component, except elevated systolic blood pressure. In covariance analysis, there was significant relationship between elevated GGT levels and MS presence after adjustment for age, sex and MS diagnostic criteria; but not AST and ALT levels. In multivariance analysis, in MS group, a high GGT was positively associated with CVD prevalance (odds ratio: 2.011, 95% CI 1.10-4.57) compared to low GGT group independent of age, sex and smoking habits.” The researchers concluded, “Elevated liver enzymes, although in normal ranges, especially at upper quartiles, play a central role in early diagnosis of fat overflow to the liver. Regarding the availability and simplicity of these tests in routine clinical practice, eles, especially GGT, have potential to be considered in algorithms for metabolic syndrome. ”

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In this 2008 U.S. study, the research objective was “To establish the relation of oxidized LDL with metabolic syndrome in the general community.” “We studied 1,889 participants who were between the ages of 18 and 30 years at the time of recruitment in 1985 and 1986 and living in 1 of 4 US metropolitan areas (41% African American; 56% women) and were seen both at year 15 … and year 20 examinations (2005-2006).” “The adjusted ORs for incidence of dichotomous components of metabolic syndrome in the highest vs the lowest quintile of oxidized LDL were 2.1 (95% CI, 1.2-3.6) for abdominal obesity, 2.4 (95% CI, 1.5-3.8) for high fasting glucose, and 2.1 (95% CI, 1.1-4.0) for high triglycerides. Low-density lipoprotein cholesterol was not associated with incident metabolic syndrome or with any of its components in the fully adjusted model containing oxidized LDL.” The researchers concluded, "Higher concentration of oxidized LDL was associated with increased incidence of metabolic syndrome overall, as well as its components of abdominal obesity, hyperglycemia, and hypertriglyceridemia. ”

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This study was reported in 2001. The researchers “…examined dietary correlates of serum GGT activity.” “Study subjects were 3,146 black and white men and women aged 17-35 y in 1985-1986. A diet history was taken at years 0 and 7. Food items were classified into alcohol; breaded, battered, or canned vegetables; fruit; fruit juice; refined grain; whole grain; dairy; legumes; meat; poultry; fish; fresh or frozen vegetables; nuts; and coffee.” “After adjustment for nondietary factors and other food groups, GGT was positively associated with alcohol consumption and meat intake.” “Among meat constituents, total dietary heme iron but not saturated fat was positively associated with the serum GGT concentration; saturated fat showed a nonsignificant inverse trend
(Figure 1). Neither monounsaturated nor polyunsaturated fat was significantly associated with serum GGT (Figure 1). Geometric means of year 10 GGT across categories of alcohol consumption (0, 1-9, 10-19, 20-29, and > or = 30 g/d) were 17.7, 18.8, 20.4, 21.8, e 24.8 U/L (P for trend < 0.01); corresponding means across quintiles of meat intake estavam 19.2, 20.2, 20.5, 21.8, e 21.2 times/wk (P for trend < 0.01). GGT was inversely associated with fruit intake. Among possible meat constituents, dietary heme iron, but not saturated fat, was associated with GGT. Dietary constituents typical of plant foods showed an inverse association. In contrast, vitamin supplements were positively associated with GGT.” The researchers concluded, “Serum GGT activity increased in a dose-response manner as alcohol and meat consumption increased and fruit consumption decreased. Heme iron contained in meats and micronutrients contained in fruits may influence GGT metabolism. Contudo, micronutrients taken as supplements had a positive association with GGT. ” (Health-e-Iron note: Table 1 e Figure 3 from this research appear below)

FIGURE 3. Geometric x (± SE) of year 10 у-glutamyltransferase (GGT) concentrations according to intake of micronutrients from vitamin and mineral supplements, after adjustment for alcohol consumption, heme iron, vitamin C from food, Beta-carotene from food, folate from food, fiber from food, -tocopherol from food, total energy intake, study center, race, sex, age, BMI, cigarette smoking, and physical activity in CARDIA Study subjects. P for trend is based on logarithmic transformations of the continuous micronutrient variables. Cutoffs of micronutrients from supplements were the recommended dietary allowances (RDA; 46) among men and women aged 19–30 y (vitamin C: 90 mg for men, 75 mg for women; vitamin A: 900 μg for men, 700 μg for women; folate: 400 mg for men, 400 mg for women; and Alpha-tocopherol: 15mg for men, 15mg for women). CARDIA, Coronary Artery Risk Development in Young Adults.

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In this 2004 reported study, based on a CARDIA study cohort 3,128 black and white men and women 17-35 years of age in 1985-1986, Serum carotenoids and tocopherols were measured at years 0 and 7, and serum GGT was measured at years 0 and 10.” “Circulating concentrations of alpha-carotene, beta-carotene, and beta-cryptoxanthin inversely predicted the serum GGT concentration measured 10 years later in a dose-response manner (P for trend <0.01).” “Adjusted geometric means of serum GGT at year 10 according to quintile of the sum of four carotenoids at year 0 (alpha-carotene, beta-carotene, beta-cryptoxanthin, and zeaxanthin/lutein) were 19.9, 19.4, 18.9, 17.8, and 17.3 U/L (P for trend <0.01). Year 0 alpha-tocopherol was also a significant inverse predictor of year 10 serum GGT concentration (P for trend = 0.03), whereas gamma-tocopherol showed an inconsistent or possibly U-shaped association. However, year 0 serum GGT did not predict serum antioxidants measured 7 years later.” The researchers concluded, “Our present findings support the contention that serum GGT concentration is a marker related with oxidative stress. ” (Health-e-Iron note: Table 3 from this study appears below)

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In this 2005 prospective study of 2,478 black and white men and women without  at year 10 of the CARDIA study, “Among individuals who ever had hypertension or diabetes, year 10 serum GGT showed a clear positive dose-response association with incident microalbuminuria (P <0.01 for trend), whereas among individuals with neither hypertension nor diabetes during the study, year 10 GGT showed a U-shaped association with it (P = 0.01 for quadratic term). When the long-term risk was evaluated in 3,895 participants based on serum GGT at year 0 and prevalence of microalbuminuria at year 10 or year 15, the trends were similar but weaker than those of short-term incidence risk. The researchers concluded, “Serum GGT within the physiologic range predicted microalbuminuria among patients with hypertension or diabetes and may act as a predictor of microvascular and/or renal complications in these vulnerable groups. GGT showed a U-shaped association with microalbuminuria among persons who did not develop either hypertension or diabetes. ”

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This study from China was reported in 2011. “A population-based cross-sectional study was conducted in 2006 in Qingdao, China. Data of 1,143 men and 1,689 women aged 35-74 years and free of diabetes at baseline were analyzed. Multivariable logistic regression analysis was performed to estimate the odds ratio (OR) and its 95% confidence interval (CI).” “Compared with the lowest quartile, the ORs (95%CI) for IFG/IGT corresponding to the highest quartile were 0.89 (0.61,1.28) in men and 0.87 (0.64,1.18) in women for CRP and 2.12(1.40,3.38) and 1.87(1.32,2.62) for GGT, when the two were fitted simultaneously in a model adjusting for age, school years, alcohol-drinking, smoking, family history of diabetes, systolic blood pressure, waist circumference, triglycerides and high-density lipoprotein.” The researchers concluded, “The elevated GGT, but not CRP, was independently associated with the presence of the IFG/IGT in both genders in this Chinese population. ”

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This study was published in the U.K. in 2009. The aim of the researchers was “To estimate and compare associations of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) with incident diabetes.” “ALT and GGT were studied as determinants of diabetes in the British Women’s Heart and Health Study, a cohort of 4,286 women 60-79 years old (median follow-up 7.3 years).” In addition, “A systematic review and a meta-analysis of 21 prospective, population-based studies of ultrasonography, which diagnosed nonalcoholic fatty liver disease (NAFLD), ALT, and GGT as determinants of diabetes, were conducted, and associations of ALT and GGT with diabetes were compared.” The results indicated that, “ALT and GGT both predicted diabetes.” “For ALT, the HR was 2.02 (1.59-2.58, I(2) = 27%), and for GGT the HR was 2.94 (1.98-3.88, I(2) = 20%), suggesting that GGT may be a better predictor (P = 0.05).” The researchers concluded, “Findings are consistent with the role of liver fat in diabetes pathogenesis. GGT may be a better diabetes predictor than ALT, but additional studies with directly determined liver fat content, ALT, and GGT are needed to confirm this finding. ” (Health-e-Iron note: Figure 2 from this article appears directly below)

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In this 2006 study reported by a team of investigators in Turkey the “role of serum gamma glutamyltransferase (GGT) activity as a cardiovascular risk marker was studied basically cross-sectionally.” “After appropriate exclusions, 754 men and 802 women were available for analysis who were followed up briefly yielding only 16% of overall cases of coronary heart disease (CHD). By analyzing the sample in tertiles, doubling in GGT activity was found associated with a rise of 74% in metabolic syndrome (MS) likelihood-independent of salient confounders (P < 0.001). This association was mediated by waist circumference. Individuals in the top versus the bottom tertile exhibited an odds ratio for CHD likelihood of 1.81 (95% CI 1.09; 3.02)-independent of age, sex, total cholesterol, systolic blood pressure, impaired fasting glucose, smoking status, alcohol usage and, notably, of waist circumference. This indicated that a doubling in serum GGT activity corresponded to a 45% excess in CHD likelihood, after adjustment for standard risk factors.” The researchers concluded, “...waist circumference is a major determinant of serum GGT activity among Turkish adults. Doubling in activity is associated with a (largely waist girth mediated) rise by over one-half in the multiadjusted MS likelihood, and by nearly one-half in the CHD likelihood, independent of waist girth and major risk factors. ”

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The complete abstract from this 2012 study from Austria follows: “To study the effects of a supervised exercise program on serum gamma-glutamyl transferase (GGT), glycemic control and cardiovascular risk factors in pre-diabetic patients with isolated glicemia de jejum prejudicada (IFG) and those with IFG plus impaired glucose tolerance (IGT)Out of 60 pre-diabetic patients (30 with isolated IFG and 30 with IFG + IGT) 24 were randomly assigned to the supervised exercise program (1 h twice a week) and 36 only obtained counselling on the risk of diabetes and its prevention. Patients have been followed over a 12-month period. The main findings were that patients with IFG + IGT had increased GGT levels at baseline (49.2±27.4 U/L) compared to subjects with isolated IFG (28.1±21.9 U/L) (p<0.01), and that GGT levels improved only after the supervised exercise intervention within the IFG + IGT subjects ( – 17.7±19.6 U/L). Similarly, baseline triglyceride levels were also higher in IFG + IGT patients (p<0.001) and there was a decrease through exercise intervention in these patients only (p<0.05). GGT is an unspecific marker of oxidative stress and both high plasma glucose and triglycerides levels may produce oxidative stress. Thus, patients with IFG + IGT seem to have higher levels of oxidative stress than those with isolated IFG. Based on the known association between GGT levels and cardiovascular risk factors, IFG + IGT patients may be at higher risk for the development of cardiovascular diseases. The specific effect of regular exercise on GGT in pre-diabetic patients may contribute to the understanding of the preventive effects related to exercise. ”

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This 2012 reported study was undertaken in Africa to “evaluate the impact of acute tuberculose pulmonar (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. The researchers noted, “Tuberculosis is, therefore, characterized by poor antioxidants defense that exposes to oxidative host tissue damage.” And “With the current and increasing interest in oxidative stress, emphasis is to develop functional biomarkers of oxidative stress with epidemiological and clinical implications such as gamma-glutamyltransferase (GGT)…” “A prospective followup of 40 adults with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n = 1) developed a transient and benign ADR (Adverse Drug Reaction) at day 30 without interruption of anti-TB treatment.” “Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0-day 60, there was a significant, negative, and independent association between GGT and AST.” The researchers concluded, “The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR. ” (Health-e-Iron note: The researchers in this study made these observations that are consistent with other reports on this web site: “If serum GGT is a marker of oxidative stress targeted by anti-TB during the initial phase, it might have important implications both clinically and epidemiologically because measurement of serum GGT is easy, reliable, and inexpensive. It is important to evaluate in tuberculosis patients on DOTS intake of fruits and vegetables, which are rich in antioxidants.” And “Clinicians should be vigilant for conditions related to oxidative stress and deficiency of antioxidant systems.”)

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In this 2009 report the research team undertook to evaluate the biomarkers associated with an increased risk of metabolic syndrome and cardiovascular disease. “We thus compared biomarkers and their association with metabolic syndrome.” “We measured the white blood cell count, high-sensitivity C-reactive protein, homeostasis model assessment of insulin resistance (HOMA-IR), homocysteine, cystatin C, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and uric acid levels in 4,624 adults without a medical history of cardiovascular disease.” “The HOMA-IR and GGT were most strongly correlated with metabolic syndrome.” “The best cut-off value of HOMA-IR and GGT for identifying metabolic syndrome was (1.22, 30 IU/l (men), 1.28, 15 IU/l (women)).” The researchers concluded, “HOMA-IR and GGT are most strongly associated with metabolic syndrome, suggesting that theses biomarkers may contribute to identifying metabolic syndrome more than other factors. ”

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This was a Korean study re(ported in 2012. The research noted, “Serum gamma-glutamyltransferase (GGT) has been suggested as a predictor for development of the metabolic syndrome in non-Korean population, but studies in Korean population are scarce.” “The study population consisted of 32,692 office workers who underwent health checkups in both 2005 and 2009. A total of 17,583 with elevated GGT levels, the presence of metabolic syndrome, medication history at baseline, and female office workers were excluded. Finalmente, 15,109 subjects were included in the final analysis. We measured serum GGT levels and individual metabolic components.” “As a quartile of serum GGT increased, 4-year follow-up incidence of the metabolic syndrome increased. After adjustment for age, alcohol drinking status and smoking status in 2005, logistic regression analysis showed that the odds ratios (95% confidence interval) for incident metabolic syndrome in 2009 compared to the lowest quartile and upper quartiles were 1.00 (reference), 1.57 (1.24-2.00), 2.73 (2.17-3.43), 3.78(3.02-4.74), and statistically significant (P < 0.001), respectively. The research concluded, “These results showed that the higher serum GGT predicted the future development of metabolic syndrome. In Korean male office workers without the metabolic syndrome, the serum GGT levels despite normal levels were associated with an increased risk of incident metabolic syndrome. ” (Health-e-Iron note: Table #4 from this study appears below)



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The objective of this 2012 reported study was “To investigate the relationship of liver enzymes with hyperglycemia in a large population in Shanghai and identify the association between liver enzymes and insulin resistance.” “A total of 3,756 participants were enrolled. Each participant underwent an oral glucose tolerance test and completed a questionnaire. Anthropometric indices were recorded and serum samples were collected for measurement.” “Liver enzymes concentrations were independently associated with i-IGT, IFG+IGT, and diabetes. With the increase of ALT and GGT concentrations, ORs for i-IGT, IFG+IGT, and diabetes increased gradually. By comparing patients in the highest quartile of GGT concentrations or ALT concentrations with those in the lowest quartile (Q1), ORs for i-IGT, IFG+IGT, or diabetes was significant after adjustment. Both ALT and GGT concentrations were linearly correlated with HOMA-IR and independently associated with HOMA-IR (ALT OR (95% CI): 2.56 (1.51-4.34) P=0.00; GGT OR (95% CI): 2.66 (1.53-4.65) P=0.00).” The researchers concluded, “Serum ALT and GGT concentrations were closely related to pre-diabetes and diabetes in the Shanghai population and positively associated with insulin resistance. ” (Health-e-Iron note: Figure #1 from this study appears below)

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This study from Korea was reported in 2010. The researcher first noted, “Diabetic peripheral polyneuropathy (DPP) is one of the common complications of diabetes mellitus (DM) and can lead to foot ulcers or amputation. The pathophysiology of DPP includes several factors such as metabolic, vascular, autoimune, oxidative stress and neurohormonal growth-factor deficiency and recent studies have suggested the use of serum gamma-glutamyl transferase (GGT) as an early marker of oxidative stress. Therefore,we investigated whether serum GGT may be useful in predicting DPP.” “We assessed 90 patients with type 2 DM who were evaluated for the presence of DPP using clnical neurologic examinations including nerve conduction velocity studies. We evaluated the association between serum GGT and the presence of DPP.” “The prevalence of DPP was 40% (36 cases) according to clinical neurological examinations. The serum GGT concentration was significantly elevated in type 2 diabetic patients with DPP compared to patients without DPP (P < 0.01). There were other factors significantly associated with DPP including smoking (P = 0.019), retinopathy (P = 0.014), pressão sanguínea (P < 0.05), aspartato aminotransferase (P = 0.022), C-reactive protein (P = 0.036) and urine microalbumin/creatinine ratio (P = 0.004). Serum GGT was independently related with DPP according to multiple logistic analysis (P < 0.01).” The researcher concluded, “This study shows that increased levels of serum GGT may have important clinical implications in the presence of DPP in patients with type 2 diabetes. ”

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(Health-e-Iron note: we have not included pediatric studies in our Science Libraries because it is our intention to primarily focus on risk factors among adult between the approximate ages of 20 and 75. We’ve added this 2012 study from Finland, a 2006 study of Pima Indian children in the U.S. and a 2012 study of elementary school children in Korea (studies numbered 53 e 57 below) to emphasize current findings that are consistent with reports from many public health agencies that report dietary habits formed at an early age do not often improve. Several studies on our web site demonstrate that the relative risk of the diseases and early mortality associated with elevated GGT is greatest among individuals under 30 years of age.)

The investigators in this study “studied the associations of clustering of metabolic risk factors with plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in healthy prepubertal children. Methods: The subjects were a representative population sample of 492 children 6-8 years of age.” “Children with overweight or obesity, defined by International Obesity Task Force (IOTF) criteria, had a 2.1-times higher risk of having ALT and a 4.5-times higher risk of having GGT in the highest fifth of its distribution than normal weight children. Children in the highest sex-specific third of metabolic syndrome score, percentual de gordura corporal, circunferência da cintura, and insulin had a two to three times higher risk of being in the highest fifth of ALT and GGT.” The researchers concluded, “Clustering of metabolic risk factors, particularly excess body fat, is associated with high-normal levels of ALT and GGT in prepubertal children. High-normal levels of liver enzymes, especially GGT, and systemic low-grade inflammation could be considered features of metabolic syndrome among children. Subtle changes in liver function may play an important role in the pathogenesis of metabolic syndrome beginning in childhood. ”

GGT and Diabetes among the Pima Indians of Arizona

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The researchers in this 2006 reported study undertook to “establish whether independent relationships exist between either adiposity or IR (insulin resistance) and hepatic enzymes in a group of Pima Indian children.” “In a cross-sectional study, 44 children (22 males and 22 females; 7-11 yr old) were measured for weight (WT), height, percent body fat, and serum activities of ALT, AST, and GGT. Body mass index (kilograms per meter squared) was calculated. IR was calculated from fasting plasma concentrations of glucose and insulin using the homeostasis model assessment (HOMA-IR).” “Hepatic enzymes were positively associated with obesity measures, fasting insulin, and HOMA-IR. GGT was additionally associated with serum lipids and white blood cell count. GGT, but not AST or ALT, was a significant determinant of HOMA-IR independently of age, sex, and WT, índice de massa corporal, or percent body fat. The model that accounted for the largest portion of the variance in HOMA-IR included WT (beta = 0.004; P = 0.008) and GGT (beta = 0.20; P = 0.004; total R(2) = 0.62; P < 0.0001).” The researchers concluded, “Significant relationships between adiposity and hepatic enzyme activities exist during childhood in Pima Indians. Whether serum GGT activity predicts the development of T2DM in these children remains to be determined in follow-up studies. ” (Health-e-Iron note: The Pima Indian population in the U.S. has the highest incidence of type 2 diabetes in the world, approximately five-fold that of their “cousins” in Mexico. We have added Table #1 from this study below to illustrate that GGT levels in these very young children already have reached the high and very high risk categories for diabetes, heart diseases and early mortality among adults. The respective Pima boy and girl mean (average) GGT levels were 24.5 e 22.8 U/L. We’ve compared these GGT levels with those of comparably aged Korean children (see study #57below, Table#2) The young Korean boys and girls had mean mean GGT levels of ~ 14.1 and 13.4 U/L respectively, significantly lower than those of the Pima children.

We have added several more Pima Indian studies below that further define the extent of this major public health problem. We believe there’s a dietary solution to this problem that can be achieved by providing healthier foods to this very high-risk community, inclusive of nutrient dense and antioxidant replete whole foods inclusive of fresh fruits, vegetables, nuts, berries, legumes cocoa beverages and dark chocolate. This is truly a community where the term “overfeed & undernourished” applies. This will likely require a proactive strategy to replace packaged, high calorie, high-fructose, nutrient-poor foods, which likely caused this problem in the first place, with healthier foods. More on the science behind lowering GGT through healthy food choices can be read on our  page and on our  page.)

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(Health-e-Iron note: This was a study of reported in 2002. Importantly, this study was reported before knowledge regarding the prognostic capability of GGT to forecast developing type 2 diabetes had been widely reported. At that time little was known about the dose-relationship of GGT with incident diabetes. As noted on this page and elsewhere on this web site, that relationship appears at relatively low levels of GGT, even those well-within standard laboratory references ranges.)

The researchers stated: “The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma -glutamyltranspeptidase (GGT)) are associated with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians.” “We measured ALT, AST, and GGT in 451 nondiabetic Pima Indians (aged 30 +/- 6 years, body fat 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l (mean +/- SD)) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output (HGO) during the low-dose insulin infusion of a hyperinsulinemic clamp) and acute insulin response (AIR) (25-g intravenous glucose challenge).” “Sixty-three subjects developed diabetes over an average follow-up of 6.9 +/- 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGTwere related to percent body fat (r = 0.16, 0.17, and 0.11, respectively), M (r = -0.32, – 0.28, and -0.24), and HGO (r = 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT (relative hazard 90th vs.10th centiles (95% CI): 1.9 (1.1-3.3), P = 0.02), but not AST or GGT, predicted diabetes. The researchers concluded, “Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver in the pathogenesis of type 2 diabetes. ” (Health-e-Iron note: In 2002, when this study was reported, GGT was known mainly as a marker of liver disease or alcohol consumption, but generally only when GGT exceeded the upper interval of standard laboratory reference ranges. Although ~ 21% of the study group had become diabetic during the nearly 7 year follow-up period (somewhat more than half the rate of diabetes in the U.S. Pima community). Table 1 from this study appears below. This study population was relatively young at follow up (~ 30 yrs. of age), consisted of ~ 38% men and ~ 62% women. The researchers used combined gender GGT measures that indicated GGT increased over time, was higher among the individuals that became diabetic during the period and reached a mean level of ~ 50 U/L. Measured in either men or women, GGT of 50 U/L or greater, independent of other risk factors, is predictive of incident diabetes, heart disease and premature mortality as demonstrated in the more recent studies referenced on this web site.)

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In 2010 another group of investigators reported on the high incidence of insulin resistance as a major risk factor in the development of type 2 diabetes in the U.S. Pima Indian community. This research team noted that the U.S. Pima Indians as “a population with the highest prevalence of type 2 diabetes mellitus in the world. Their Mexican counterpart, living a traditional lifestyle in the mountains of Sonora, have at least 5 times less diabetes than the U.S. Pima Indians.” “We evaluated whether Mexican Pima Indians had lower insulin resistance than U.S. Pima Indians.” “We compared fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) in 194 Mexican Pima Indians (100 females, 94 males) and 449 U.S. Pima Indians (246 females, 203 males) with normal glucose tolerance from a cross-sectional study.” “Unadjusted fasting insulin and HOMA-IR were much lower in the Mexican Pima Indians than in their U.S. counterparts. After adjusting by obesity, era, and sex, significar (95% confidence interval) for fasting insulin was 6.22 (5.34-7.24) vs. 13.56 μU/ml (12.27-14.97) and for HOMA-IR 1.40 (1.20-1.64) vs. 3.07 (2.77-3.40), respectivamente, for Mexican Pima and U.S. Pima Indians. Results were confirmed in subset matched for age, sex, and body fat.” Notably, this research team did not report on comparative liver enzymes. The researchers concluded, “…our results indicate that Mexican Pima Indians with normal glucose tolerance have lower insulin resistance in comparison with their genetically related counterparts U.S. Pima Indians, even after controlling for differences in obesity, era, and sex. This finding underscores the importance of lifestyle factors as direct protecting factors against insulin resistance in nondiabetic populations. ” (Health-e-Iron note: Since this investigations was limited in terms of scope, and did not include biochemical measurements such as GGT, their finding respecting lifestyle factors is consistent with those of other research teams. Certainly lifestyle factors play an important role in the development of insulin resistance and diabetes. In regard to lifestyle factors, this study is consistent with many others in that it does not differentiate nor weight lifestyle factors much beyond the somewhat standard measures of body fat and waistline circumference values and differences in physical activity levels. The authors’ referenced literature search as well appears to have been limited in scope. Relative measures of both iron and GGT would likely have added significant prognostic value within the broad scope of “lifestyle factors.”  Qualitative and quantitative nutritional differences are most likely the major lifestyle factors that underlay this very significant difference in disease prevalence. This would have been an ideal context in which to measure the unanswered question from the above Pima Indian children’s study reported four years earlier, “Whether serum GGT activity predicts the development of T2DM in these children remains to be determined in follow-up studies.”)

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The investigators who published this study in 2006 noted that, “Type 2 diabetes and obesity have genetic and environmental determinants. We studied the effects of different environments on these diseases in Pima Indians in Mexico and the U.S.” “Adult Pima-Indian and non-Pima populations in the Sierra Madre mountains of Mexico were examined using oral glucose tolerance tests and assessments for obesity, physical activity, and other risk factors. Results were compared with those from Pima Indians in Arizona. Both Pima populations were typed for DNA polymorphisms to establish their genetic similarity.” “The age- and sex-adjusted prevalence of type 2 diabetes in the Mexican Pima Indians (6.9%) was less than one-fifth that in the U.S. Pima Indians (38%) and similar to that of non-Pima Mexicans (2.6%) The prevalence of obesity was similar in the Mexican Pima Indians (7% in men and 20% in women) and non-Pima Mexicans (9% in men and 27% in women) but was much lower than in the U.S. Pima Indians. Levels of physical activity were much higher in both Mexican groups than in the U.S. Pima Indians. The two Pima groups share considerable genetic similarity relative to other Native Americans.” The researchers conclude, “The much lower prevalence of type 2 diabetes and obesity in the Pima Indians in Mexico than in the U.S. indicates that even in populations genetically prone to these conditions, their development is determined mostly by environmental circumstances, thereby suggesting that type 2 diabetes is largely preventable. This study provides compelling evidence that changes in lifestyle associated with Westernization play a major role in the global epidemic of type 2 diabetes. ”

(Health-e-Iron note: we have placed three video links below that describe the historical and cultural framework which led to the serious diabetes problem among the U.S. Pima Indian’s. The fourth video suggests the first step toward a healthy solution. These and other similar videos and transcripts can be found at this web page: )

The Problem – How and Why, and What can be done?

CLICK ON TITLE FOR VIDEO LINK

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This was a study reported in Korea in 2009.  “This study was a cross-sectional study using data on 390 4th grade students of elementary schools in Gunpo, Korea.” “Children (mean age = 9.8 yrs.) were divided into 4 groups according to gender-specific quartiles of serum GGT level. Body mass index, waist circumference and body fat percentage were quantified as adiposity indices.” “All adiposity indices in children of the highest GGT level quartile were higher than those in children of the lowest quartile. Adjusted odd ratios on overweight of the highest quartile of GGT level compared to the lowest quartile were 14.40 (95% confidence interval (CI), 4.43 to 46.83) in boys and 2.94 (95% CI, 1.06 to 8.16) in girls.” The researchers concluded, “This study shows that high serum GGT level is related with overweight in Korean urban children and this relationship is stronger in boys compared to girls. ” (Health-e-Iron note: Table#2 from this study appears below)

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The aim of this German study reported in 2009 “was to investigate the association of serum gamma-glutamyltransferase (GGT) levels with all-cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association.” “We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population-based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis.” “Elevated GGT levels were associated with increased risk of mortality in men (hazard ratio (HR) 1.49; 95% confidence interval (CI), 1.08-2.05), but not in women (HR 1.30; 95% CI, 0.80-2.12). This association was even stronger in men with hepatic steatosis (HR 1.98; 95% CI, 1.21-3.27). Cause-specific mortality analysis by cardiovascular disease deaths confirmed the sex-specific association. Adjustment for cardiometabolic risk factors did not affect the estimates.” The researchers concluded, “In the case of increased GGT levels, liver ultrasound should be performed, not only for diagnosis, but also for further risk stratification. ” (Health-e-Iron note: Table #3 from this study appears below)

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The researchers in this 2003 reported study of Korean men noted that, “Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses.” “Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes.” “A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication.” “There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l estavam 8.0, 13.3, 12.6, 19.6 e 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration.” The researchers concluded, “This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes. ” (Health-e-Iron note: Table #2 for this paper appears below)

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