Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka.

INTRODUCTION: While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean. METHODS: In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m2) NAFLD, non-lean (BMI ≥ 23 kg/m2) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case-control study between lean NAFLD cases and lean non-NAFLD controls. RESULTS: Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males (p < 0.001), and had a lower prevalence of hypertension (p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) (p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample. CONCLUSION: Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.

Risk estimates of cardiovascular diseases in a Sri Lankan community.

OBJECTIVES: Quantifying the risk of cardiovascular disease (CVD) in a community is important in planning preventive strategies, but such data are limited from developing countries, especially South Asia. We aimed to estimate the risks of coronary heart disease (CHD), total CVD, and CVD mortality in a Sri Lankan community. METHODS: A community survey was conducted in an urban health administrative area among individuals aged 35-64 years, selected by stratified random sampling. Their 10-year CHD, total CVD, and CVD mortality risks were estimated using three risk prediction tools: National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), Systematic Coronary Risk Evaluation (SCORE), and World Health Organisation/ International Society of Hypertension (WHO/ISH) charts. RESULTS: Among study participants (n=2985), 54.5% were females, and mean age (SD) was 52.4 (7.8) years. According to NCEP-ATP III ('hard' CHD risk), WHO/ISH (total CVD risk), and SCORE (CVD mortality risk) criteria, 25.4% (95% CI 23.6-27.2), 8.2% (95% CI 7.3-9.2), and 11.8 (95% CI 10.5-13.1) respectively were classified as at 'high risk'. The proportion of high risk participants increased with age. 'High risk' was commoner among males (30.3% vs 20.6%, p<0.001) according to NCEPATP III criteria, but among females (9.7% vs. 6.7%, p<0.001) according to WHO/ISH criteria. No significant gender difference was noted in SCORE risk categories. CONCLUSIONS: A large proportion of individuals in this community are at risk of developing cardiovascular diseases, especially in older age groups. Risk estimates varied with the different prediction tools, and were comparatively higher with NCEP-ATP III charts.

An ecological study for Sri Lanka about health effects of coconut.

An ecological correlation study was conducted to determine the association between consumption of coconut products and cardiovascular disease (CVD) deaths in Sri Lanka. Data on coconut consumption patterns from 1961 to 2006 were abstracted from the FAO database, and mortality data from reports of the Department of Census and Statistics, and UN databases. Correlational and regression analyses were carried out. There was no increase in the per capita consumption of coconut products from 1961 to 2006 (range 54.1-76.2kg/ capita/year). The CVD death rates and the proportionate mortality rate due to CVD increased from 1961 to 2006. CVD death rates were significantly associated with per capita GDP, percentage of urban population, and elderly dependency ratio but not consumption of coconut products after adjusting for the other variables (R2=0.94). The results do not provide evidence at the population level that consumption of coconut products increases mortality due to cardiovascular diseases.

Translational research for Diabetes Self-Management in Sri Lanka: A randomized controlled trial.

AIMS: The study tested the hypothesis that a theory driven Diabetes Self-Management (DSM) intervention delivered by trained nurses would result in a clinically significant improvement in glycaemic control. METHODS: Patients with an HbA1c >7.5% (58mmol/mol) and free of diabetes complications were enrolled into a randomized controlled trial (n=85). Intervention consisted of four sessions and monthly follow up for 6 months. Biochemical tests, and diet and physical activity assessments were done in both groups. Analysis of covariance was used to test the effectiveness of the intervention. RESULTS: At 6 months, there was a significant difference (P=0.001) in HbA1c between the groups controlling for baseline values and other variables. Based on the primary outcome, 28% in the intervention group achieved the target value of 6.5% HbA1c, compared to 8% in the "usual care" group (P<0.001; η(2)=0.65). The reduction in total energy intake and increase in physical activity was significant in the intervention group between baseline and follow up. CONCLUSIONS: The DSM intervention has resulted in a clinically significant impact on glycaemia, change in diet and physical activity, and has demonstrated the feasibility of using it within existing care arrangements in a developing country setting.

Incidence of inflammatory bowel disease in Gampaha district: details of the Sri Lankan component of the Asia-Pacific Crohn's and colitis epidemiology study.

The aim of this report is to provide details of the methodology and results of the Sri Lankan component of the Asia-Pacific Crohn's and Colitis Epidemiology Study. Fourteen state and private hospitals with specialist services in the Gampaha and Colombo districts were kept under surveillance over a 12 month period to recruit patients with newly diagnosed Inflammatory Bowel Disease (IBD) who were permanent residents of the Gampaha district. Thirty five cases (ulcerative colitis-21, Crohn's disease-13, IBD-undetermined-1) were detected, giving a crude annual IBD incidence of 1.59 per 100,000 population.

Outcome of patients with ST segment elevation myocardial infarction (STEMI) following percutaneous transluminal coronary angioplasty: a retrospective study.

OBJECTIVES: To study the characteristics and long term outcome of patients who had segment elevation myocardial infarction (STEMI) and treated with PTCA in a fee levying hospital in Sri Lanka. METHODS: A retrospective study was conducted among patients diagnosed with STEMI and treated with PTCA in a fee levying private hospital in Colombo from 1st January 2009 to 1st November 2012. Details of patients were obtained from medical records and the survival status, cause of death and date of death where relevant, were obtained from records, patients or close relatives. RESULTS: 197 patients (153 men; 77.7%) were included. More than 50% had a history of diabetes, dyslipidaemia or hypertension. The three year survival was 82.7% (95% CI: 77.9%-90.5%). Based on the Cox's Proportional Hazards model, site of arterial occlusion (proximal vs distal segment of left anterior descending artery [LAD] was significantly associated with mortality due to all causes [HR 10.98; 95% CI: 1.09-110.20]. Low ejection fraction, not on regular medication and delay of more than 3 hours between onset to door time were associated with death due to cardiovascular causes in patients whose right coronary artery or left circumflex artery was the culprit artery. CONCLUSIONS: The three year survival of patients with STEMI and who had PTCA was 83%. Patients with proximal LAD occlusion were 11 times more likely to die within 3 years of PTCA as compared to those who had a distal LAD occlusion.

The burden of diabetes mellitus and impaired fasting glucose in an urban population of Sri Lanka.

AIMS: To describe the burden of diabetes mellitus and impaired fasting glucose in middle-aged residents (35-64 years) in an urban area of Sri Lanka. METHODS: A cross-sectional survey was conducted in the Ragama Medical Officer of Health area, from which 2986 participants (1349 men and 1637 women) were randomly selected from the electoral registry between January and December 2007. The participants underwent a physical examination and had their height, weight, waist and hip circumferences and blood pressure measured by trained personnel. Fasting blood samples were taken for measurement of glucose, HbA(1c) and lipids. The prevalence of diabetes (fasting plasma glucose > 7 mmol/l) and impaired fasting glycaemia (fasting plasma glucose 5.6-6.9 mmol/l) and major predictors of diabetes in Sri Lanka were estimated from the population-based data. RESULTS: Age-adjusted prevalence of diabetes mellitus in this urban population was 20.3% in men and 19.8% in women. Through the present screening, 263 patients with diabetes and 1262 with impaired fasting glucose levels were identified. The prevalence of newly detected diabetes was 35.7% of all patients with diabetes. Among patients with diabetes, only 23.8% were optimally controlled. In the regression models, high BMI, high waist circumference, high blood pressure and hypercholesterolaemia increased the fasting plasma glucose concentration, independent of age, sex and a family history of diabetes. CONCLUSIONS: Our data demonstrate the heavy burden of diabetes in this urban population. Short- and long-term control strategies are required, not only for optimal therapy among those affected, but also for nationwide primary prevention of diabetes.

Consumption pattern of iodised salt in households and serum TSH levels among 5-9 year old children in the plantation sector of Sri Lanka.

INTRODUCTION: Salt is the main source of iodine in areas with high rainfall and iodine deficiency is the main cause of preventable hypothyroidism. Iodisation of salt increases iodine intake, but will depend on how salt is handled. This study was carried out to assess the pattern of salt consumption in the estate population and to ascertain the relationship between household salt iodine concentration and TSH levels in children. METHODS: A descriptive cross sectional study was carried out in 20 randomly selected estates in the Ratnapura district of Sri Lanka, from August to November 2009. 1683 households with at least one child between 5-9 years were surveyed to determine patterns of salt usage. A salt sample from each household was tested for adequacy of iodine (concentration ≥ 30 ppm). In phase two, 519 children were randomly selected from these households and serum TSH levels were assayed. RESULTS: Salt powder (54.5%) was preferred to salt crystals. Salt crystals were washed before use in 20% households. Salt was kept away from the fire-place in 90.4% of households. Salt samples of 88.7% households had an adequate iodine concentration. Salt iodine concentration was significantly lower when salt was stored near a fire-place and washed before use (p<0.001). The median TSH level of children from households with adequate salt iodine concentrations was significantly lower than that of children from households with inadequate salt iodine concentration (p<0.001). CONCLUSIONS: A significant number of households did not have adequate iodine in salt samples probably due to inappropriate handling and storage. Consumption of salt low in iodine is associated with high serum TSH levels.

Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations.

AIMS/HYPOTHESIS: To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations. METHODS: We genotyped five common variants previously reported in Europeans: rs1799884 (GCK), rs780094 (GCKR), rs560887 (G6PC2-ABCB11) and both rs1387153 and rs10830963 (MTNR1B) in the general Japanese (n = 4,813) and Sri Lankan (n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples. RESULTS: Fasting glucose association was replicated for the five single nucleotide polymorphisms (SNPs) at p < 0.05 (one-tailed test) in South Asians (Sri Lankan) as well as in East Asians (Japanese). In fine-mapping by GWA scan data, we identified in the G6PC2-ABCB11 region a novel SNP, rs3755157, with significant association in Japanese (p = 2.6 x 10(-8)) and Sri Lankan (p = 0.001) populations. The strength of association was more prominent at rs3755157 than that of the original SNP rs560887, with allelic heterogeneity detected between the SNPs. On analysing the cumulative effect of associated SNPs, we found the per-allele gradients (beta = 0.055 and 0.069 mmol/l in Japanese and Sri Lankans, respectively) to be almost equivalent to those reported in Europeans. CONCLUSIONS/INTERPRETATION: Fasting glucose association at four tested loci was proven to be replicable across ethnic groups. Despite this overall consistency, ethnic diversity in the pattern and strength of linkage disequilibrium certainly exists and can help to appreciably reduce potential causal variants after GWA studies.

Identifying the biting species in snakebite by clinical features: an epidemiological tool for community surveys.

The outcome of snakebite is related to the biting species but it is often difficult to identify the biting snake, particularly in community settings. We have developed a clinical scoring system suitable for use in epidemiological surveys, with the main aim of identifying the presumed biting species in those with systemic envenoming who require treatment. The score took into account ten features relating to bites of the five medically important snakes in Sri Lanka, and an algorithm was developed applying different weightings for each feature for different species. A systematically developed artificial data set was used to fine tune the score and to develop criteria for definitive identification. The score was prospectively validated using 134 species-confirmed snakebites. It correctly differentiated the bites caused by the three snakes that commonly cause major clinical problems (Russell's viper (RV), kraits and cobra) from other snakes (hump-nosed viper (HNV) and saw-scaled viper (SSV)) with 80% sensitivity and 100% specificity. For individual species, sensitivity and specificity were, respectively: cobra 76%, 99%; kraits 85%, 99%; and RV 70%, 99%. As anticipated, the score was insensitive in the identification of bites due to HNV and SSV.

Underestimation of snakebite mortality by hospital statistics in the Monaragala District of Sri Lanka.

Estimates of snakebite mortality are mostly based on hospital data, although these may considerably underestimate the problem. In order to determine the accuracy of hospital-based statistics, data on snakebite mortality in all hospitals in the Monaragala District of Sri Lanka were compared to data on snakebite as the certified cause of death for the district, for the 5-year period between 1999 and 2003. Data were cross-checked in a sample of hospitals and divisional secretariats within the district. Hospital statistics did not report 45 (62.5%) of the true number of snakebite deaths in the Monaragala District. Twenty-six (36.1%) of the victims either did not seek, or had no access to, a hospital. Another 19 (26.4%) had arrived at hospital, but had done so too late to receive treatment. Our study confirms the limitations of official hospital-based mortality data on snakebite.

Morbidity pattern and household cost of hospitalisation for non-communicable diseases (NCDs): a cross-sectional study at tertiary care level.

OBJECTIVE: To determine the pattern of morbidity and the demographic and socioeconomic characteristics of patients seeking in-patient services for noncommunicable diseases (NCDs) in medical units of a tertiary care hospital, and to estimate the economic burden imposed by these admissions on the households. METHODS: A descriptive cross-sectional study was conducted in medical units of the Colombo North Teaching Hospital, Ragama. Data were collected using a pre-tested interviewer-administered questionnaire. Morbidity patterns and demographic and socio-economic characteristics of patients with NCDs were determined. Direct and indirect components of the household cost of hospital stay were estimated. RESULTS: Fifty five per cent of the patients men male and the largest age group (11%) was 50-54 years. Seventy per cent were above 40 years of age, and 63% represented social classes 4 and 5. Diseases of the circulatory system were the commonest (31%). Median household cost of the total hospital stay was Rs. 852.00 (inter-quartile range Rs. 351.00-1885.00) of which 70% were direct costs. Median daily cost was Rs. 340.00 (interquartile range Rs.165.00-666.00). Only 44% of patients incurred an indirect cost. Cost of travelling was the main contributor (36%) to the household cost. Laboratory investigations contributed 16%. CONCLUSIONS: Most patients seeking in-patient services were from a poor socioeconomic background. The economic burden imposed by the admission to the household was mainly due to direct costs incurred for travelling and investigations.

Estimates of disease burden due to land-snake bite in Sri Lankan hospitals.

Snake bite is a common cause of hospital admission in Sri Lanka. Despite this, there have been no countrywide studies or national estimates of disease burden due to snake bites in Sri Lankan hospitals. We assessed the disease burden due to snake bite in our hospitals and estimated the frequency of admissions due to bites by different snake species. Sri Lanka was divided into four zones based on climate and topography. Hospital morbidity and mortality data, which are available on an administrative district basis, were collated for the four zones. A survey of opinion among specialist physicians (the Delphi technique) was used to estimate the proportion of bites by different species, and requirements for anti-venom (AV) and intensive care facilities for management of snake bites in hospitals in each of the four zones. A study of hospital admissions due to snake bites in seven selected hospitals was also performed to validate the opinion survey. There was a clear difference in the incidence of hospital admissions due to snake bites in the different zones. Estimates of hospital admissions due to bites by different species also varied considerably between zones. These trends corresponded to estimates of requirements of AV and other supportive health care. Health care planning using data based on environmental information, rather than merely on political boundaries, could lead to targeted distribution of AV and intensive care requirements to manage snake bites.