Contextualização: As complicações agudas do diabetes, embora em grande parte evitáveis, apresentavam considerável mortalidade em diversas localidades do mundo no século passado. No Brasil, a organização do Sistema Único de Saúde pode ter resultado em importante queda na mortalidade por esta causa. Objetivos: Descrever a mortalidade por complicações agudas do diabetes no Brasil entre 1991 e 2010. Métodos: Os óbitos declarados no Sistema de Informações sobre Mortalidade por complicações agudas do diabetes (CID-9 249 e 250, seguidos pelos dígitos 1, 2 ou 3, e CID-10 E10 a E14, seguidos pelos dígitos 0 ou 1) foram corrigidos para causas mal definidas e sub-registro. A partir da população obtida do Instituto Brasileiro de Geografia e Estatística, foram calculadas taxas de mortalidade padronizadas de acordo com a população mundial. Correlações lineares foram realizadas para descrever a relação entre mortalidade e idade, e regressões Joinpoint foram utilizadas para descrever tendências. Resultados: Houve queda de 70,9% na mortalidade por complicações agudas do diabetes no Brasil entre 1991 e 2010, de 8,42 para 2,45 óbitos por 100.000 habitantes. A redução ocorreu em ambos os sexos, todas as faixas etárias, todas as regiões e quase todas as unidades federativas. O declínio foi menor nos últimos anos, quando as taxas já estavam bem mais baixas. A mortalidade aumentou exponencialmente com a idade e foi maior nas regiões Norte e Nordeste. Conclusões: A marcante redução na mortalidade por complicações agudas do diabetes no Brasil nas últimas duas décadas indica que a cobertura ampla e gratuita adotada pelo sistema nacional de saúde do Brasil, com disponibilização de insulina e organização do cuidado, foi capaz de reduzir substancialmente as complicações agudas dessa doença. Entretanto, considerando especialmente as iniquidades regionais existentes, ainda há espaço para redução na mortalidade por essas complicações no Brasil. / Background: Acute complications of diabetes, though largely preventable, presented considerable mortality in various locations around the world in the 20th Century. In Brazil, the organization of the national health system may have resulted in an important decline in this cause of mortality. Objectives: To describe mortality rates from acute complications of diabetes in Brazil from 1991 to 2010. Methods: The deaths reported in the Mortality Information System for acute complications of diabetes (ICD-9 249 and 250, followed by the digits 1, 2 or 3, and ICD-10 E10 to E14, followed by the digits 0 or 1) were corrected for ill-defined and under-reporting. Using the population obtained from national censuses, we calculated mortality rates standardized to the world population. Linear correlations were performed to describe the relationship between mortality and age, and Joinpoint regressions were used to characterize trends. Results: Mortality from acute complications of diabetes decreased 70.9%, from 8.42 to 2.45 deaths / 100000 inhabitants, in Brazil from 1991 to 2010. The reduction occurred in both sexes, all ages, all regions and almost all states. The decline was less marked in recent years. Mortality rates increased exponentially with age and were higher in the North and Northeast regions. Conclusions: The marked reduction in mortality from acute complications of diabetes in Brazil over the last two decades suggests that the universal coverage adopted by the national health system of Brazil, provided without charge and in an increasingly organized fashion, coupled with greater availability of insulin, was able to substantially reduce deaths due to the acute complications of diabetes. However, especially considering regional inequities, much room still exists for further reduction in mortality from these complications in Brazil.

INTRODUÇÃO: a ação dos hormônios contrarreguladores da insulina na cetoacidose diabética tem sido estudada desde a década 1970-80, e é sabido que seus níveis elevados, aumentando a resistência à insulina, têm papel importante na gênese da CAD. Leptina e ghrelina foram mais recentemente associadas à homeostase da glicose, no entanto, seu papel na CAD ainda é controverso. Os objetivos deste estudo foram: avaliar as alterações nas concentrações séricas de leptina e ghrelina presentes ao diagnóstico da CAD durante os primeiros três dias de seu tratamento e após a estabilização completa do quadro, as correlações com a insulina e outros contrarreguladores, comparando com indivíduos saudáveis. MÉTODOS: foram analisados 25 episódios de cetoacidose diabética em 22 pacientes admitidos no setor de emergência pediátrica de um hospital terciário em São Paulo, Brasil, entre março de 2010 e julho de 2013. Os episódios de cetoacidose foram manejados com reposição endovenosa de fluidos e eletrólitos e análogos de ação ultrarrápida de insulina subcutânea intermitente. Amostras para glicose, insulina, leptina, ghrelina, GH, cortisol e catecolaminas foram obtidas no momento da admissão (T0), durante o tratamento da cetoacidose (após 2, 4, 6, 12, 24 e 72 horas) e em um momento estável após a alta (TE). Os dados foram analisados utilizando-se os testes ANOVA ou Kruskal-Wallis para a comparação de variáveis contínuas durante o tratamento, Teste t de Student ou Mann Whitney para a comparação entre pacientes e grupo controle, e testes de Pearson ou Spearman para correlação entre as variáveis; p < 0.05 foi considerado significativo. RESULTADOS: observamos três fases distintas (a): o diagnóstico de CAD (T0) em que prevalecem hiperglicemia, insulinopenia e elevação de hormônios contrarreguladores; nesse momento, as concentrações de leptina foram menores que no grupo controle, provavelmente relacionadas à insuficiência de energia, estado hipercatabólico e elevação dos hormônios contrarreguladores; as concentrações de ghrelina foram menores que no grupo controle, apesar do hipercatabolismo, da hipoinsulinemia e da hiperglucagonemia, todas situações que fisiologicamente elevariam seus níveis, possivelmente devido à hiperglicemia marcante do momento; (b) durante o tratamento da CAD (T2 a T72): com redução gradual da glicemia até T24, elevação gradual da insulina, redução de glucagon, GH, cortisol e norepinefrina; nesse período, ocorreu elevação gradual da leptina após o início do tratamento com insulina, que atingiu níveis comparáveis ao GC no T72; redução da ghrelina (T4 menor que T72), provavelmente inibida pela hiperglicemia e por doses suprafisiológicas de insulina; e (c) após a resolução da CAD (TE): com hiperinsulinização; GH, cortisol e norepinefrina comparáveis ao GC, glucagon reduzido em relação ao GC, possivelmente supresso pelos altos níveis de insulina; as concentrações de leptina foram maiores que em T0 e comparáveis ao GC; os níveis de ghrelina, comparáveis ao diagnóstico e durante o tratamento da CAD, ainda significativamente menores que no GC, provavelmente influenciados pela hiperglicemia, hiperinsulinemia e baixos níveis de glucagon. CONCLUSÕES: as concentrações de leptina diminuídas ao diagnóstico de CAD tornam-se semelhantes em pacientes com DM1 estáveis em relação a indivíduos saudáveis, podendo ser um marcador de hipercatabolismo. As concentrações de ghrelina permaneceram baixas durante todo o estudo em pacientes diabéticos, independentemente da descompensação / INTRODUCTION: The role of glucoregulatory hormones in diabetic ketoacidosis have been investigated since 1970-80s and the elevation of growth hormone, cortisol and norepinephrine reduce the sensitivity to insulin. Leptin and Ghrelin have more recently been shown to regulate glucose and insulin metabolism; however, their functions in DKA are still controversial. The aims of this study were to analyze leptin, ghrelin and their relationships with other glucoregulatory hormones on diagnosis of diabetic ketoacidosis, during the first 72 hours of treatment and after recovery compared with healthy subjects. METHODS: We examined 25 DKA episodes in 22 patients who were admitted to the pediatric emergency department of a tertiary hospital in São Paulo, Brazil, from March 2010 to July 2013. These episodes were managed with fluids and electrolytes replacement and intermittent subcutaneous fast-acting insulin analogues. Samples for blood glucose, insulin, leptin, ghrelin, GH, cortisol, and catecholamines were obtained on admission (T0), during treatment (after 2, 4, 6, 12, 24 and 72 hours) and after discharge (TS). The control group (CG) was comprised by 21 healthy subjects, who submitted a single blood sample. Data were analyzed by ANOVA or Kruskal-Wallis to compare continuous variables during treatment, student t-test or Mann Whitney for comparisons between patients and controls, and Pearson or Spearman correlations between variables; p < 0.05 was considered to be significant. RESULTS: we observed three distinct phases: (a) on diagnosis of DKA (T0) where hyperglycemia, insulinopenia, and elevated glucoregulatory hormones prevail; leptin concentrations were lower than CG at this moment, probably related to energy insufficiency, hypercatabolic state, and elevated glucoregulatory hormones; ghrelin concentrations were lower than CG at this moment, despite hypercatabolism, hypoinsulinemia and hyperglucagonemia, situations that physiologically would increase them, possibly related to marked hyperglycemia at T0; (b) during DKA treatment (T2 to T72): with gradual reduction of blood glucose until T24, gradual rise of insulin; reduction of glucagon, GH, cortisol and norepinephrine. Leptin levels rises gradually after the start of insulin treatment and is comparable to control group at T72; reduction of ghrelin (T4 lower than T72), possibly inhibited by hyperglycemia and supraphysiological doses of insulin, all lower than CG; and (c) After DKA (TS), in an outpatient setting: with marked hyperinsulinization, GH, cortisol and norepinephrine were comparable to CG. Glucagon was lower than CG, possibly suppressed by high insulin levels; leptin was higher than T0 and comparable to CG; ghrelin levels were comparable to all samples during DKA treatment, and still significantly lower than CG, probably influenced by hyperglycemia, hyperinsulinemia and low glucagon levels. CONCLUSIONS: Low leptin levels were a marker of hypercatabolic state, with normalization of its concentrations with DKA resolution. Ghrelin was low in diabetic patients independent of metabolic derangements

INTRODUÇÃO: a ação dos hormônios contrarreguladores da insulina na cetoacidose diabética tem sido estudada desde a década 1970-80, e é sabido que seus níveis elevados, aumentando a resistência à insulina, têm papel importante na gênese da CAD. Leptina e ghrelina foram mais recentemente associadas à homeostase da glicose, no entanto, seu papel na CAD ainda é controverso. Os objetivos deste estudo foram: avaliar as alterações nas concentrações séricas de leptina e ghrelina presentes ao diagnóstico da CAD durante os primeiros três dias de seu tratamento e após a estabilização completa do quadro, as correlações com a insulina e outros contrarreguladores, comparando com indivíduos saudáveis. MÉTODOS: foram analisados 25 episódios de cetoacidose diabética em 22 pacientes admitidos no setor de emergência pediátrica de um hospital terciário em São Paulo, Brasil, entre março de 2010 e julho de 2013. Os episódios de cetoacidose foram manejados com reposição endovenosa de fluidos e eletrólitos e análogos de ação ultrarrápida de insulina subcutânea intermitente. Amostras para glicose, insulina, leptina, ghrelina, GH, cortisol e catecolaminas foram obtidas no momento da admissão (T0), durante o tratamento da cetoacidose (após 2, 4, 6, 12, 24 e 72 horas) e em um momento estável após a alta (TE). Os dados foram analisados utilizando-se os testes ANOVA ou Kruskal-Wallis para a comparação de variáveis contínuas durante o tratamento, Teste t de Student ou Mann Whitney para a comparação entre pacientes e grupo controle, e testes de Pearson ou Spearman para correlação entre as variáveis; p < 0.05 foi considerado significativo. RESULTADOS: observamos três fases distintas (a): o diagnóstico de CAD (T0) em que prevalecem hiperglicemia, insulinopenia e elevação de hormônios contrarreguladores; nesse momento, as concentrações de leptina foram menores que no grupo controle, provavelmente relacionadas à insuficiência de energia, estado hipercatabólico e elevação dos hormônios contrarreguladores; as concentrações de ghrelina foram menores que no grupo controle, apesar do hipercatabolismo, da hipoinsulinemia e da hiperglucagonemia, todas situações que fisiologicamente elevariam seus níveis, possivelmente devido à hiperglicemia marcante do momento; (b) durante o tratamento da CAD (T2 a T72): com redução gradual da glicemia até T24, elevação gradual da insulina, redução de glucagon, GH, cortisol e norepinefrina; nesse período, ocorreu elevação gradual da leptina após o início do tratamento com insulina, que atingiu níveis comparáveis ao GC no T72; redução da ghrelina (T4 menor que T72), provavelmente inibida pela hiperglicemia e por doses suprafisiológicas de insulina; e (c) após a resolução da CAD (TE): com hiperinsulinização; GH, cortisol e norepinefrina comparáveis ao GC, glucagon reduzido em relação ao GC, possivelmente supresso pelos altos níveis de insulina; as concentrações de leptina foram maiores que em T0 e comparáveis ao GC; os níveis de ghrelina, comparáveis ao diagnóstico e durante o tratamento da CAD, ainda significativamente menores que no GC, provavelmente influenciados pela hiperglicemia, hiperinsulinemia e baixos níveis de glucagon. CONCLUSÕES: as concentrações de leptina diminuídas ao diagnóstico de CAD tornam-se semelhantes em pacientes com DM1 estáveis em relação a indivíduos saudáveis, podendo ser um marcador de hipercatabolismo. As concentrações de ghrelina permaneceram baixas durante todo o estudo em pacientes diabéticos, independentemente da descompensação / INTRODUCTION: The role of glucoregulatory hormones in diabetic ketoacidosis have been investigated since 1970-80s and the elevation of growth hormone, cortisol and norepinephrine reduce the sensitivity to insulin. Leptin and Ghrelin have more recently been shown to regulate glucose and insulin metabolism; however, their functions in DKA are still controversial. The aims of this study were to analyze leptin, ghrelin and their relationships with other glucoregulatory hormones on diagnosis of diabetic ketoacidosis, during the first 72 hours of treatment and after recovery compared with healthy subjects. METHODS: We examined 25 DKA episodes in 22 patients who were admitted to the pediatric emergency department of a tertiary hospital in São Paulo, Brazil, from March 2010 to July 2013. These episodes were managed with fluids and electrolytes replacement and intermittent subcutaneous fast-acting insulin analogues. Samples for blood glucose, insulin, leptin, ghrelin, GH, cortisol, and catecholamines were obtained on admission (T0), during treatment (after 2, 4, 6, 12, 24 and 72 hours) and after discharge (TS). The control group (CG) was comprised by 21 healthy subjects, who submitted a single blood sample. Data were analyzed by ANOVA or Kruskal-Wallis to compare continuous variables during treatment, student t-test or Mann Whitney for comparisons between patients and controls, and Pearson or Spearman correlations between variables; p < 0.05 was considered to be significant. RESULTS: we observed three distinct phases: (a) on diagnosis of DKA (T0) where hyperglycemia, insulinopenia, and elevated glucoregulatory hormones prevail; leptin concentrations were lower than CG at this moment, probably related to energy insufficiency, hypercatabolic state, and elevated glucoregulatory hormones; ghrelin concentrations were lower than CG at this moment, despite hypercatabolism, hypoinsulinemia and hyperglucagonemia, situations that physiologically would increase them, possibly related to marked hyperglycemia at T0; (b) during DKA treatment (T2 to T72): with gradual reduction of blood glucose until T24, gradual rise of insulin; reduction of glucagon, GH, cortisol and norepinephrine. Leptin levels rises gradually after the start of insulin treatment and is comparable to control group at T72; reduction of ghrelin (T4 lower than T72), possibly inhibited by hyperglycemia and supraphysiological doses of insulin, all lower than CG; and (c) After DKA (TS), in an outpatient setting: with marked hyperinsulinization, GH, cortisol and norepinephrine were comparable to CG. Glucagon was lower than CG, possibly suppressed by high insulin levels; leptin was higher than T0 and comparable to CG; ghrelin levels were comparable to all samples during DKA treatment, and still significantly lower than CG, probably influenced by hyperglycemia, hyperinsulinemia and low glucagon levels. CONCLUSIONS: Low leptin levels were a marker of hypercatabolic state, with normalization of its concentrations with DKA resolution. Ghrelin was low in diabetic patients independent of metabolic derangements

Contextualização: As complicações agudas do diabetes, embora em grande parte evitáveis, apresentavam considerável mortalidade em diversas localidades do mundo no século passado. No Brasil, a organização do Sistema Único de Saúde pode ter resultado em importante queda na mortalidade por esta causa. Objetivos: Descrever a mortalidade por complicações agudas do diabetes no Brasil entre 1991 e 2010. Métodos: Os óbitos declarados no Sistema de Informações sobre Mortalidade por complicações agudas do diabetes (CID-9 249 e 250, seguidos pelos dígitos 1, 2 ou 3, e CID-10 E10 a E14, seguidos pelos dígitos 0 ou 1) foram corrigidos para causas mal definidas e sub-registro. A partir da população obtida do Instituto Brasileiro de Geografia e Estatística, foram calculadas taxas de mortalidade padronizadas de acordo com a população mundial. Correlações lineares foram realizadas para descrever a relação entre mortalidade e idade, e regressões Joinpoint foram utilizadas para descrever tendências. Resultados: Houve queda de 70,9% na mortalidade por complicações agudas do diabetes no Brasil entre 1991 e 2010, de 8,42 para 2,45 óbitos por 100.000 habitantes. A redução ocorreu em ambos os sexos, todas as faixas etárias, todas as regiões e quase todas as unidades federativas. O declínio foi menor nos últimos anos, quando as taxas já estavam bem mais baixas. A mortalidade aumentou exponencialmente com a idade e foi maior nas regiões Norte e Nordeste. Conclusões: A marcante redução na mortalidade por complicações agudas do diabetes no Brasil nas últimas duas décadas indica que a cobertura ampla e gratuita adotada pelo sistema nacional de saúde do Brasil, com disponibilização de insulina e organização do cuidado, foi capaz de reduzir substancialmente as complicações agudas dessa doença. Entretanto, considerando especialmente as iniquidades regionais existentes, ainda há espaço para redução na mortalidade por essas complicações no Brasil. / Background: Acute complications of diabetes, though largely preventable, presented considerable mortality in various locations around the world in the 20th Century. In Brazil, the organization of the national health system may have resulted in an important decline in this cause of mortality. Objectives: To describe mortality rates from acute complications of diabetes in Brazil from 1991 to 2010. Methods: The deaths reported in the Mortality Information System for acute complications of diabetes (ICD-9 249 and 250, followed by the digits 1, 2 or 3, and ICD-10 E10 to E14, followed by the digits 0 or 1) were corrected for ill-defined and under-reporting. Using the population obtained from national censuses, we calculated mortality rates standardized to the world population. Linear correlations were performed to describe the relationship between mortality and age, and Joinpoint regressions were used to characterize trends. Results: Mortality from acute complications of diabetes decreased 70.9%, from 8.42 to 2.45 deaths / 100000 inhabitants, in Brazil from 1991 to 2010. The reduction occurred in both sexes, all ages, all regions and almost all states. The decline was less marked in recent years. Mortality rates increased exponentially with age and were higher in the North and Northeast regions. Conclusions: The marked reduction in mortality from acute complications of diabetes in Brazil over the last two decades suggests that the universal coverage adopted by the national health system of Brazil, provided without charge and in an increasingly organized fashion, coupled with greater availability of insulin, was able to substantially reduce deaths due to the acute complications of diabetes. However, especially considering regional inequities, much room still exists for further reduction in mortality from these complications in Brazil.

Abstract The aim of this work was to evaluate the frequency of diabetic ketoacidosis (DKA) in children &#60;15 years of age at the time of diagnosis of type 1 diabetes (T1D) at Oulu University Hospital over a period of 33 years (1982−2014) and throughout Finland in 2002−2005. The aim was to assess the effect of certain host characteristics (age at diagnosis, family history of T1D, T1D-associated HLA risk genotypes and participation in T1D prediction and prevention trials) on the frequency on DKA. A further aim was to assess temporal changes in the frequency of DKA. The overall frequency of diabetic ketoacidosis at the diagnosis of T1D in children &#60;15 years was low both at Oulu University Hospital and over the whole country. A decrease in the frequency of DKA was observed at the university hospital during the years 1982−2001, but it then seemed to stabilize at just under 20.0%. The frequency in the whole of Finland during the period 2002−2005 was similar, i.e. 19.4%. The frequency of DKA at diagnosis in very young children (&#60;2 years of age) at Oulu University Hospital decreased markedly during the period in question, being 50.0% in 1982−1991, 39.1% in 1992−2001 and 17.1% in 2002−2014 (p=0.021), and a similar decrease was seen in children &#60;5 years (32.1% in 1982−1991, 17.7% in 1992−2001 and 13.0% in 2002−2014, p=0.007). The children aged 10−14.9 years at diagnosis, however, had an increased risk of DKA over the whole period studied here, and more attention should definitely be paid to this group in the future to reduce its DKA frequency. In the analysis of the data based on all children in Finland diagnosed with T1D in 2002−2005 the risk of DKA at diagnosis was lower in those with a first-degree relative affected by T1D. The children carrying a higher HLA-conferred risk of T1D had DKA less frequently at the manifestation of the disease. Prospective studies based on screening for HLA-DQB1-associated genetic susceptibility to T1D from cord blood and subsequent regular clinical, immunological and metabolic follow-up have been going on in Oulu University Hospital since 1995, and the children taking part have been found to have a reduced frequency of DKA (5%) at diagnosis. Genetic screening without follow-up did not prevent DKA at disease presentation. / Tiivistelmä Väitöstyön tarkoituksena oli tutkia diabeettisen ketoasidoosin (DKA) esiintymistä alle 15–vuotiailla lapsilla tyypin 1 diabeteksen toteamisvaiheessa Oulun yliopistollisessa sairaalassa vuosina 1982–2014 ja koko Suomessa vuosina 2002–2005. Tavoitteena oli selvittää tiettyjen lapsen erityispiirteiden (ikä diagnoosihetkellä, perheen diabeteshistoria, diabetekseen liittyvien HLA riskigenotyyppien esiintyminen ja osallistuminen prospektiivisiin tyypin 1 diabeteksen seurantatutkimuksiin) vaikutusta ketoasidoosin esiintymiseen. Lisäksi tärkeänä tavoitteena oli tutkia mahdollisia ajallisia muutoksia ketoasidoosin esiintymisessä. Kaikkiaan ketoasidoosin esiintyminen oli matala alle 15–vuotiailla lapsilla tyypin 1 diabeteksen diagnoosihetkellä Oulun yliopistollisessa sairaalassa tutkimusjakson aikana. Ketoasidoosin esiintymisessä nähtiin vähenemistä kahden ensimmäisen 10–vuotisjakson aikana (1982–1991 ja 1992–2001), minkä jälkeen sen esiintyminen vakiintui alle 20 %:n tasolle. Koko Suomessa ketoasidoosin kokonaisesiintyvyys vuosina 2002–2005 oli 19,4 % mikä vastasi Oulun yliopistollisessa sairaalassa havaittua esiintyvyyttä. Pienillä, alle 2–vuotiailla lapsilla ketoasidoosin esiintyminen diabeteksen toteamisvaiheessa väheni huomattavasti tutkimusjakson aikana Oulun yliopistollisessa sairaalassa ollen 50,0 % 1982–2001, 39,1 % 1992–2001 ja 17,1 % 2002–2014 (p=0,021). Samanlainen laskeva suunta havaittiin tuona ajanjaksona myös alle 5–vuotiailla lapsilla (32,1 % 1982–1991, 17,7 % 1992–2001 ja 13,0 % 2002–2014, p=0,007). Sen sijaan ketoasidoosiriski pysyi huomattavan korkeana yli 10–vuotiailla lapsilla koko tutkimusjakson ajan. Tulevaisuudessa on tärkeä kiinnittää erityishuomio tähän ikäluokkaan ketoasidoosin vähentämiseksi. Analysoitaessa kaikkia Suomessa 2002–2005 tyypin 1 diabetekseen sairastuneita lapsia, havaittiin lapsilla, joilla oli ensimmäisen asteen tyypin 1 diabetesta sairastava sukulainen (vanhemmat, sisarukset), ketoasidoosiriski matalammaksi. Lisäksi niillä lapsilla, joilla oli korkeaan sairastumisriskiin liittyvä HLA–genotyyppi, oli ketoasidoosin esiintyminen vähäisempää tyypin 1 diabeteksen diagnoosihetkellä. Prospektiivinen tyypin 1 diabeteksen kehittymistä selvittävä seurantatutkimus aloitettiin Oulussa 1995. Tutkimuksessa lapsen napaverinäytteestä analysoidaan perinnöllinen diabetesalttius ja riskiryhmiä seurataan säännöllisesti. Seurantatutkimukseen osallistuneiden lasten ketoasidoosiriski diabeteksen diagnoosihetkellä oli vähentynyt taudin toteamishetkellä (5,0 %). Pelkkä geneettiseen seulontatutkimukseen osallistuminen ei kuitenkaan suojannut lasta ketoasidoosilta.

The management of patients hospitalised with diabetes mellitus is neglected in South Africa. The research on which this thesis is based assessed factors contributing to glycaemic control as well as evaluated an intervention aimed at improving of such control in diabetic inpatients. A survey of doctors and nurses measuring their perceptions, knowledge and attitudes regarding care of diabetic inpatients was done. This indicated a need for special training in inpatient diabetes care, where 90.5% of respondents realised that diabetes is a serious condition and 92.2% valued the importance of tight glycaemic control. Despite these perceptions, the knowledge of doctors and nurses caring for diabetic inpatients was suboptimal. A before and after study regarding an intervention to improve glycaemic control of diabetic inpatients consisted of a training programme and the introduction of an inpatient management protocol. The mean blood glucose on day one of admission after the intervention was significantly higher than before the intervention (p < 0.001). A significant improvement in mean blood glucose from day 1 to day 7 of hospitalisation was seen after the intervention (p < 0.001), which was not significant before (p = 0.33). The proportion of patients achieving glycaemic control did not significantly differ before and after the intervention (43.0% versus 43.7%, p = 0.97). A double blind randomised controlled trial to assess superiority of Ringer’s lactate solution compared to 0.9% Sodium chloride solution in the normalisation of pH in patients with diabetic ketoacidosis was done. The outcome of this study indicated that the time to normalisation of venous pH (pH > 7.32) (HR: 1.863, CI: 0.937 to 3.705, p = 0.758) was not significantly different between the two resuscitation fluid groups The time to reach a blood glucose of 14 mmol/L was significantly longer in the Ringer’s lactate group (p = 0.044) and patients needed significantly more insulin (p = 0.02). The overall conclusion of this study is that there is no significant benefit in using Ringer’s lactate solution as initial resuscitation fluid compared to the currently advised 0.9% Sodium chloride solution. / Thesis (PhD)--University of Pretoria, 2012. / Internal Medicine / unrestricted