BACKGROUND: There is a dearth of studies on the association between diabetes mellitus (DM) and the risk of developing oral health complications in nonsmokers. Recent studies have presented a strong link between smoking and increased risk of periodontal disease in patients with T2DM. This study attempts to look at the risk of developing caries and poor oral health in nonsmokers who also have DM. Male and female subjects from the cross-sectional National Health and Nutrition Examination Survey (NHANES) 2017-2018 study who were 21+ years at the time of entering the study were included. The exposures are DM and smoking, and the outcome is oral health. HYPOTHESIS: DM-IFG will increase the risk of developing dental caries and tooth loss, thus lowering the quality of oral health in smokers compared to nonsmokers. METHODS: DM was defined as either the self-report of a doctor’s diagnosis of DM or a fasting glucose level of 126mg/dL or higher, or both. IFG was defined as a level of fasting glucose between 100mg/dL and 126mg/dL, as well as being informed by a medical doctor about having borderline DM. Subjects with IFG or DM were further combined into a DM-IFG group. Each subject’s status was classified on the basis of both DM-IFG status and smoking status, yielding four exposure groups: (1) no DM-IFG/non-smokers, (2) no DM-IFG/smokers, (3) DM-IFG/non-smokers, and (4) DM-IFG/smokers. Oral health outcomes were defined as a percent of missing teeth (due to dental health issues), percent of teeth with dental caries, and percent of teeth either missing or with caries. The primary statistical analysis for association between DM-IFG and smoking exposures and oral health outcomes was multivariable logistic regression. Adjusted models controlled for covariates such age, gender, Body Mass Index (BMI), education level, minutes of sedentary activity, race, HR, and percent of calories from fat intake. RESULTS: Overall, the prevalence of having 25% or more of teeth with dental caries was similar in those with and without DM-IFG (50.9% vs. 49.9%, respectively) and, surprisingly, was with higher among non-smokers than smokers (51.9% vs. 42.1%, respectively. Those with DM-IFG had a prevalence of missing teeth due to dental causes (≥ 15% missing) of 43.2% compared with a prevalence of 28.6% among those without DM-IFG. Since the majority of missing teeth were likely to be due to caries as well, the final outcome for these analyses consists of participants with either missing teeth or carious remaining teeth. Here, we found that 55.8% of those with DM-IFG had 40% of more of teeth missing vs. 44.8% of those without DM-IFG (p<0.0001). Similarly, 52.1% of smokers vs. 48.8% of non-smokers had more missing or carious teeth (p=0.1587). In the multivariable models, adjusting for age, race, HR, and percent of calories from fat, these analyses showed that DM-IFG alone (among non-smokers) was associated with a 1.42-fold increased risk of missing teeth while smoking along was associated with a 2.86-fold increased risk. The combined effects of the two factors were even stronger. Those who smoked cigarettes and who had DM-IFG (compared with those who did not smoke and had no DM-IFG) had a 3.88-fold increased risk of have 15% or more of their teeth missing due to dental health issues. Lastly, I examined these same effects on the risk of having either missing teeth or dental caries. In these analyses, smokers without DM-IFG had a 67% higher risk (95% CI: 1.27-2.19) of have 40% or more of their teeth missing or with caries while non-smokers with DM-IFG had no excess risk. Finally, those with DM-IFG who also smoked cigarettes had a 52% increased risk (95% CI: 1.08-2.14) of have 40% or more of their teeth missing or with caries compared with non-smokers who did not have DM-IFG. CONCLUSION: These results suggest that smoking was a more important risk factor for having missing teeth or dental caries than was DM or IFG.

No description available.

Background: This study was conducted to test the hypothesis that internal medicine residents at a northeast Tennessee university clinic were not compliant with the latest National Cholesterol Educational Program Adult Treatment Panel (NCEP-ATP) guidelines in treating hyperlipidemia in patients with diabetes and coronary artery disease. Methods: A retrospective medical record survey was conducted to evaluate residents' pattern in lowering low-density lipoprotein (LDL) cholesterol to below 100 mg/dL in patients with diabetes and coronary artery disease. The survey covered a 5-year period, from July 1998 to June 2003, and included 15 randomly chosen residents who were in training for 3 consecutive years. Charts were randomly selected from residents' clinics using International Classification of Diseases-9 codes for coronary artery disease or diabetes mellitus with hyperlipidemia. Five hundred fifty charts were reviewed. Only 41 (7.45%) met the inclusion criteria. Results: Analysis of data using Epi-Info 2002 (Centers for Disease Control and Prevention, Atlanta, GA) revealed that only 68.3% of patients with diabetes and coronary artery disease reached target LDL cholesterol levels. Of the patients who reached target levels, only 42.9% maintained them. Analysis of variance and chi-square tests revealed that the frequency of cholesterol measurement, but not the frequency of physicians' visits, was associated with a higher likelihood of reaching the target LDL level. Conclusion: There was a suboptimal compliance among internal medicine residents in the frequency of screening for, reaching, and maintaining the target LDL cholesterol level, according to the latest NCEP-ATP guidelines, among high-risk patients with hyperlipidemias.

Type 2 diabetes mellitus (T2DM) is a global health concern affecting six to ten percent of adults worldwide, with the number of diagnosed individuals projected to double in the next 25 years. However, effective public health strategies can help mitigate its impact on quality of life, morbidity, mortality and the associated social and economic burden. In Sweden, screening programs classify individuals with Impaired fasting glucose (IFG) as high-risk individuals, however scholars argue that preventative measures should also include those at lower fasting plasma glucose (FPG) concentrations as some evidence suggests that the disease begins developing several years before the current threshold. A systematic review and meta-analysis of cohort and case-control studies was conducted with the purpose of exploring the IFG threshold from a longitudinal perspective. Eleven studies on the incidence rates of T2DM in normoglycemic individuals and seven studies on pre-diagnostic trajectories of FPG concentrations were analyzed. Incidence rates increased progressively across the normoglycemic range, with a twelve-fold difference between the low and high end. FPG concentrations in eventual progressors and non-diabetic controls were significantly different twelve years prior to diagnosis. Mildly increasing FPG concentrations were observed in eventual progressors until three years before diagnosis, at which a larger increase followed. In the last year before diagnosis, FPG concentrations rose dramatically in this group. The findings imply that a lowering of the threshold would extend the time spent in the IFG state, allowing for earlier identification of at-risk individuals. In addition, further stratification of normoglycemic range may enhance the accuracy of T2DM risk assessment.

Background Type 2 diabetes mellitus (T2DM) is a globally prevalent disease anticipated to double from 500 million diagnosed cases in 2021 to more than one billion by 2050. The investigation of the potentially protective effects of skeletal muscle mass on glucose intolerance may lead to the development of more precise screening protocols. Purpose This thesis aimed to address the lack of clear consensus in existing literature by exploring the relationship between skeletal muscle mass and glucose intolerance. Methods Fifteen healthy young adults were recruited to partake in a prospective correlational study. The participants underwent anthropometric measurements and an oral glucose tolerance test (OGTT). Anthropometric data was collected using an bioelectrical impedance analysis (BIA) scale. Blood glucose levels were measured using capillary sampling before and after ingestion of a 75 g/200 mL glucose solution. Statistical analysis included Spearman’s rank correlation test and Pearson’s correlation coefficient test. Results All associations between skeletal muscle mass and glucose intolerance were of moderate strength. Skeletal muscle mass (SMM) correlated significantly with glucose concentrations two hours (2hPG) following ingestion of the glucose solution and an adjusted measure of SMM was significantly associated with glucose area under the curve (AUC). Statistical significance was also found between Sex and incremental glucose area under the curve (iAUC). Conclusion This thesis suggests an inverse relationship between skeletal muscle mass and glucose intolerance in a group of healthy young adults. The results imply the potential usefulness of incorporating muscle mass when determining the glucose load during an OGTT, especially in preventive contexts. Nevertheless, further research with larger samples is crucial to establish precise cutoff levels for clinical applications. / Bakgrund Typ 2 diabetes mellitus (T2DM) är en global sjukdom och antalet diagnostiserade individer förväntas fördubblas från 500 miljoner fall 2021 till över en miljard år 2050. En undersökning av muskelmassans potentiellt skyddande effekt på glukostolerans kan leda till utvecklandet av noggrannare screeningmetoder. Syfte Syftet med denna uppsats var att bemöta den bristfälliga konsensus som råder bland befintlig forskning genom att undersöka sambandet mellan muskelmassa och glukosintolerans. Metod Femton friska yngre vuxna rekryterades för att delta i en prospektiv korrelationsstudie. Deltagarna genomgick antropometriska mätningar samt ett oralt glukostoleranstest (OGTT). Antropometriska värden mättes med hjälp av en bioelektrisk impedansanalysvåg. Blodglukosnivåer mättes kapillärt före och efter intag av en 75 g/200 mL glukoslösning. Statistisk analys inkluderade Spearmans rangkorrelationstest och Pearsons korrelationskoefficientstest. Resultat Alla samband mellan muskelmassa och glukosintolerans var av måttlig styrka. Muskelmassa (SMM) korrelerade signifikant med blodglukos två timmar (2hPG) efter intag av glukoslösningen och ett justerat SMM-mått (adjSMM) var signifikant associerat med arean under glukoskurvan (AUC). Statistisk signifikans hittades även mellan kön och den inkrementella arean under glukoskurvan (iAUC). Slutsats Resultaten från denna uppsats antyder att ett omvänt samband existerar mellan muskelmassa och glukosintolerans hos en grupp friska yngre vuxna. Resultatet innebär en potentiell möjlighet att använda muskelmassan vid bestämmandet av mängden glukos som administreras vid ett OGTT, särskilt i preventiva syften. Ytterligare forskning med fler studiedeltagare är avgörande för att fastställa exakta gränsvärden för klinisk tillämpning.

La prévalence du diabète ne cesse d’augmenter et la détection de sujets à risque de développer cette maladie reste une préoccupation importante afin qu’un programme de prévention leur soit proposé. Le dosage de l’HbA1c est utilisé pour l’évaluation de l’efficacité du traitement pris par les diabétiques. Il n’était pas utilisé pour le diagnostic des dysglycémies car les méthodes de ce dosage n’étaient pas standardisées. Actuellement l’IFCC (International Federation of Clinical Chemistry) propose une nouvelle méthode de référence pour cette mesure, et l’OMS (Organisation Mondiale de la Santé) a intégré ce paramètre dans les critères diagnostiques du diabète. but Evaluer la capacité de l’HbA1c à prédire un diabète incident, chercher des seuils, d’HbA1c, de GAJ et de glycémie deux heures (G2H) après un test d’hyperglycémie provoquée par voie orale (HGPO), au delà desquels les sujets sont plus à risque de développer un diabète incident et, enfin, étudier l’influence du tabac sur les variations de ces mesures. Méthodes Pour l’évaluation de la prédiction du diabète et la recherche de seuils, nous avons utilisé les données de l’étude australienne AusDiab, de l’étude danoise Inter99 et de l’étude française D.E.S.I.R. avec plus de 5500, 4500 et 3550 sujets, respectivement. Dans la troisième partie, nous avons utilisé les données du projet DETECT-2 (12 études, 26 000 sujets), ainsi que celles des études françaises D.E.S.I.R. et TELECOM (3700 sujets). Les distributions de l’HbA1c dans les trois premières études étaient différentes, nous avons donc, dans les deux premières parties d’analyses, ajusté les moyennes d’HbA1c à l’inclusion et après le suivi. Nous avons utilisé un modèle logistique pour la comparaison du pouvoir prédictif de l’HbA1c et de GAJ ; l’intervalle de confiance des Odds Ratios (ORs) à été obtenu par bootstrap. Pour rechercher les seuils de prédiction du diabète, nous avons comparé le modèle logistique (avec la variable glycémique) sans seuil au modèle avec seuil. Enfin, nous avons utilisé un modèle linéaire mixte pour évaluer la différence entre les moyennes d’HbA1c, de GAJ et de G2H en fonction du tabagisme, en attribuant un effet aléatoire à la variable ‘centre’. Résultats Avant ajustement des moyennes d’HbA1c, l’incidence du diabète (défini par la prise de traitement antidiabétique, une HbA1c≥6.5% ou une GAJ≥7mmol/l) était de 3.1% dans AusDiab, 2.7% dans Inter99 et 2.5% dans D.E.S.I.R. Les sujets dépistés comme étant diabétiques par l’HbA1c et par la GAJ n’étaient pas toujours les mêmes. L’incidence estimée du diabète augmente bien avec l’augmentation du taux de l’HbA1c et de la GAJ à l’inclusion. Pour chaque critère, l’aire sous la courbe de ROC (Receiver Operating Characteristic) était supérieure à 0.80 témoignant d’une bonne discrimination des deux tests entre les diabétiques incidents et les non diabétiques et le test de Hosmer-Lemeshow témoigne d’une bonne adéquation des modèles utilisés (p>0.05). Dans les trois populations, les ORs qui mesurent l’association entre les taux d’HbA1c et de GAJ et la survenue du diabète étaient presque toujours supérieurs pour l’HbA1c. Les seuils d’HbA1c et de GAJ au-delà desquels les sujets étaient plus à risque de développer un diabète variaient en fonction de la définition du diabète incident sauf pour l’HbA1c dans l’étude D.E.S.I.R. (5.3%) et la GAJ dans l’étude AusDiab (5.5mmol/l). Enfin, la moyenne d’HbA1c chez les fumeurs actuels était 0.10%(0.08,0.12) plus élevée que chez ceux qui n’ont jamais fumé ; la moyenne de G2H était -0.44(-0.51,-0.36) moins élevée chez les fumeurs actuels que chez ceux qui n’ont jamais fumé.Conclusion Ces résultats soulignent : 1) l’importance de l’utilisation de l’HbA1c comme critère diagnostique de dysglycémies, 2) la nécessité de mieux explorer les limites inférieures des stades intermédiaires qui précèdent la survenue du diabète, 3) l’importance de prendre en considération les facteurs qui peuvent influencer les taux d’HbA1c / The increasing prevalence of diabetes worldwide makes the detection of people at risk of developing diabetes a major concern, so that they can benefit from diabetes prevention programs. HbA1c is used to evaluate the effectiveness of treatment taken by diabetic patients. HbA1c had not been used to diagnose dysglycemia because the assay methods were not standardized. The International Federation of Clinical Chemistry has proposed a reference method, and in 2011 the World Health Organization included HbA1c as one of the criteria for the diagnosis of diabetes. aims: 1) To evaluate the ability of HbA1c to predict incident diabetes compared with fasting plasma glucose (FPG); 2) to find thresholds for HbA1c, FPG and two hour plasma glucose (G2H) after an oral glucose tolerance test (OGTT) beyond which subjects are more at risk for developing incident diabetes and finally; 3) to study the influence of smoking on HbA1c, FPG and G2H.Methods: Several populations were studied. To evaluate the prediction of diabetes and the search for thresholds, we used data from the Australian study (AusDiab), a Danish study (Inter99) and a French study (D.E.S.I.R.) with respectively more then 5500, 4500 and 3550 participants. In the third part, we used data from the DETECT-2 consortium (12 studies with more than 26 000 men and women) and from two French studies: D.E.S.I.R. and TELECOM (with more than 3700 participants). The distribution of HbA1c in AusDiab, Inter99 and D.E.S.I.R. differed, so in the first two parts of this thesis, we adjusted HbA1c so that all three studies had the same mean HbA1c at baseline and the same mean HbA1c at follow-up. We used a logistic model to quantify the predictive ability of HbA1c and FPG for diabetes, and then derived confidence intervals for the difference in Odds Ratios (ORs) by bootstrap. To search for thresholds to predict incident diabetes, based on HbA1c, FPG and G2H at inclusion, we compared logistic regression models that were linear in the glycaemic variable, without a threshold, with a spline model with a threshold. Linear mixed models with ‘centre’ as a random variable, were used to assess the difference between the means of HbA1c, FPG and G2H in current-, ex- and never-smokers.Results: With unadjusted HbA1c data, the incidence of diabetes (defined by treatment, HbA1c≥6.5% or FPG≥7 mmol/l) was 3.1% in AusDiab, 2.7% in Inter99 and 2.5% in D.E.S.I.R.. Subjects detected as having diabetes by HbA1c and FPG were not always the same. The incidence of diabetes increased with increasing HbA1c and FPG at baseline. For each test, the area under the Receiver Operating Characteristic curve was greater than 0.80, indicating good discrimination for these two measures between those with and without incident diabetes, and the Hosmer-Lemeshow test indicated that the models fitted well (p>0.05). In all three populations, the ORs measuring the association between HbA1c and FPG and the development of diabetes were almost always higher for HbA1c than for FPG. The thresholds of HbA1c and FPG above which the incidence of diabetes were higher, varied according to the definition of incident diabetes - except for HbA1c in D.E.S.I.R. (always 5.3%) and for FPG in AusDiab (always 5.5mmol/l). Finally, in current-smokers, the mean HbA1c was 0.10%(0.08,0.12) higher than in never-smokers; the mean G2H was 0.44( 0.51,-0.36) lower in current-smokers than in never-smokers. Conclusion: The results that we found emphasize: 1) the importance of using HbA1c as a diagnostic criterion for dysglycemia, as those diagnosed diabetic by HbA1c did not have always an FPG ≥ 7 mmol/l, 2) the need to better explore the lower limits of the “pre-diabetic” stage as the thresholds of HbA1c, FPG and 2H-PG that we found were lower than those used in clinical practice, 3) the importance to consider factors that may influence HbA1c and G2H, such as smoking.

Pre-diabetes is a serious health problem in the United States. Distinguished by plasma glucose levels that are above the normal threshold, patients with pre-diabetes are 10 times more likely to develop type 2 diabetes. Patients with pre-diabetes suffer the same complications as patients with diabetes including diabetic retinopathy, nephropathy, and microalbuminuria. There is considerable evidence to support the idea that early identification and aggressive treatment of pre-diabetes has the potential to delay disease progression. The American Diabetes Association’s clinical practice guideline recommends management of with lifestyle modification and metformin for patients who are at risk for developing type 2 diabetes. The purpose of this project was to evaluate the implementation of the 2012 ADA clinical practice guidelines regarding the management of patients with pre-diabetes by the health care providers at a volunteer-run clinic located in a large metropolitan area in the southeastern United States. This study, even with a small sample size (n=26) revealed that the providers at the clinic had not implemented the 2012 ADA clinical practice guidelines. Clinical practice guidelines promote health care interventions that have proven benefits and improve the consistency of care provided to patients. The greatest benefits of implementing clinical practice guidelines for patients with pre-diabetes are early diagnosis and aggressive disease management. This would improve patient outcomes and in the long run, decrease the cost of medical care.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.