Costs and outcomes of "intermediate" vs "minimal" care for youth-onset type 1 diabetes in six countries.

OBJECTIVE: Data are needed to demonstrate that providing an "intermediate" level of type 1 diabetes (T1D) care is cost-effective compared to "minimal" care in less-resourced countries. We studied these care scenarios in six countries. METHODS: We modeled the complications/costs/mortality/healthy life years (HLYs) associated with "intermediate" care including two blood glucose tests/day (mean HbA1c 9.0% [75 mmol/mol]) in three lower-gross domestic product (GDP) countries (Mali, Tanzania, Pakistan), or three tests/day (mean HbA1c 8.5% [69 mmol/mol]) in three higher-GDP countries (Bolivia, Sri Lanka, Azerbaijan); and compared findings to "minimal" care (mean HbA1c 12.5% [113 mmol/mol]). A discrete time Markov illness-death model with age and calendar-year-dependent transition probabilities was developed, with inputs of 30 years of complications and Standardized Mortality Rate data from the youth cohort in the Pittsburgh Epidemiology of Diabetes Complications Study, background mortality, and costs determined from international and local prices. RESULTS: Cumulative 30 years incidences of complications were much lower for "intermediate care" than "minimal care", for example, for renal failure incidence was 68.1% (HbA1c 12.5%) compared to 3.9% (9%) and 2.4% (8.5%). For Mali, Tanzania, Pakistan, Bolivia, Sri Lanka, and Azerbaijan, 30 years survival was 50.1%/52.7%/76.7%/72.5%/82.8%/89.2% for "intermediate" and 8.5%/10.1%/39.4%/25.8%/45.5%/62.1% for "minimal" care, respectively. The cost of a HLY gained as a % GDP/capita was 141.1%/110.0%/52.3%/41.8%/17.0%/15.6%, respectively. CONCLUSIONS: Marked reductions in complications rates and mortality are achievable with "intermediate" T1D care achieving mean clinic HbA1c of 8.5% to 9% (69-75 mmol/mol). This is also "very cost-effective" in four of six countries according to the WHO "Fair Choices" approach which costs HLYs gained against GDP/capita.

Reducing the incidence of predictors of cardio-metabolic disease and dysglycaemia with lifestyle modification in at-risk persons - results of further analyses of DIABRISK-SL in those below 18 years of age.

BACKGROUND: We have previously demonstrated in the DIABRISK-SL trial that a trimonthly pragmatic lifestyle modification (P-LSM), as compared to a 12-monthly LSM advice (C-LSM), significantly reduced the primary composite endpoint of predictors of cardio-metabolic disease (new onset type 2 diabetes (T2DM), hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia and markers of cardio-renal disease) in urban participants aged below 40 years with risk factors for T2DM. MAIN TEXT: We now report results of post hoc analyses for those aged below 18 (n = 1725) in three age groups, specifically of 6-10 years (P-LSM n = 77, C-LSM n = 59), 10-14 years (P-LSM n = 534, C-LSM n = 556) and 14-18 years (P-LSM n = 239, C-LSM n = 260). There was no effect of P-LSM on the primary endpoint in participants aged below 10 years. Participants aged 10-14 years in the P-LSM intervention as compared to C-LSM had a lower incidence of the primary combined endpoint (87 vs. 106 cases; incident rate ratio (IRR) = 0.85, 95% confidence intervals (CI) 0.72-1.01; P = 0.07), driven mainly by the lower incidence of new onset hypertension (24 vs. 37 cases; IRR = 0.67, 95% CI 0.49-0.91; P = 0.012). Participants aged 14-18 years in the P-LSM intervention had a lower incidence of the composite endpoint (36 vs. 54 cases; IRR = 0.73, 95% CI 0.57-0.94; P = 0.015) as well as a lower incidence of IGT (12 vs. 21 cases; IRR = 0.6, 95% CI 0.39-0.92; P = 0.02), new onset hypertension (6 vs. 15 cases; IRR = 0.43, 95% CI 0.25-0.76; P = 0.004), and new onset dysglycaemia (composite of new T2DM, IGT and impaired fasting glycaemia) (30 vs. 46 cases; IRR = 0.74, 95% CI 0.56-0.97; P = 0.03) compared to those assigned to the C-LSM intervention. Limitations of the analyses are the post hoc approach and the small number of events in each group. There were no differences in retention between the two groups. CONCLUSIONS: Our results suggest that, in young South Asians aged between 10 and 18 years at risk of T2DM, a pragmatic lifestyle modification programme may reduce the incidence of predictors of T2DM and hypertension. There is a need for further studies in younger populations to evaluate the impact and feasibility of interventions to reduce the burden of T2DM and associated cardio-metabolic risk. Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0905-6.

A pragmatic lifestyle modification programme reduces the incidence of predictors of cardio-metabolic disease and dysglycaemia in a young healthy urban South Asian population: a randomised controlled trial.

BACKGROUND: There is an increasing incidence of type 2 diabetes mellitus (T2DM) in young urban South-Asians. We tested the effect of a pragmatic trimonthly lifestyle modification (LSM) programme (P-LSM) versus a less-intensive 12-monthly control LSM (C-LSM) intervention on a primary composite endpoint of predictors of cardio-metabolic disease (new onset T2DM, hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and markers of cardio-renal disease) in participants aged 5-40 years with risk factors for T2DM. METHODS: This was a randomised controlled trial performed at the National Diabetes Centre, Sri-Lanka. We individually randomised 4672 participants at risk of T2DM, of whom 3539 (mean age 22.5 (range 6-40 years, 48% males) received either trimonthly (P-LSM n = 1726) or 12-monthly (C-LSM n = 1813) peer educator advice aimed at reducing weight, improving diet, reducing psychological stress and increasing physical activity. RESULTS: During a median follow-up of 3 years, the cumulative incidence of the primary endpoint was n = 479 in P-LSM (74 per 1000 person years) vs. 561 in C-LSM (96 per 1000 person years), with an incident rate ratio (IRR) of 0.89 (95% CI 0.83-0.96, P = 0.02). In post hoc analyses, new onset dysglycaemia (T2DM, IFG and IGT), was the major contributor to the composite and was significantly reduced by P-LSM (IRR 0.9, 95% CI 0.83-0.97, P = 0.01). A significant impact of P-LSM on the incidence of the composite endpoint was noted in 1725 participants (P-LSM n = 850, C-LSM n = 875) aged below 18; P-LSM n = 140 (48 per 1000 person years) versus C-LSM n = 174 (55.4 per 1000 person years), with an IRR of 0.83 (95% CI 0.73-0.94, P = 0.004). CONCLUSIONS: In a young at-risk South-Asian population, a pragmatic LSM programme significantly reduces the incidence of predictors of cardio-metabolic disease. Our results highlight the importance of early intervention in young at-risk subjects. TRIAL REGISTRATION: World Health Organization international clinical trial registry platform ( SLCTR/2008/003 ). Registration Date: March 28, 2008. Retrospectively registered.

The effect of dietary changes on distinct components of the metabolic syndrome in a young Sri Lankan population at high risk of CVD.

South Asian populations are predisposed to early onset of the metabolic syndrome. Lifestyle intervention programmes have demonstrated a reduction in the metabolic syndrome and CVD risk; however, the most effective components of the multi-faceted lifestyle interventions are unknown. We studied 2637 Sri Lankan males (n 1237) and females (n 1380), with a mean BMI of 23·9 (sd 4·2) kg/m2, aged 22·5 (sd 10·0) years, who had participated in a 5-year lifestyle-modification programme to examine the effect of dietary changes on distinct components of the metabolic syndrome. The dietary intervention comprised advice to replace polished starches with unpolished starches, high-fat meat and dairy products with low-fat products and high-sugar beverages and snacks with low-sugar varieties. For the purposes of this analysis, data from the control and intensive lifestyle groups were combined. Anthropometric and biochemical data were recorded, and a FFQ was completed annually. Multiple regression was used to determine the effect of the dietary changes on distinct components of the metabolic syndrome. The ratio unpolished:polished rice was inversely related to change in fasting glucose (ß=-0·084, P=0·007) and TAG (ß=-0·084, P=0·005) and positively associated with change in HDL-cholesterol (ß=0·066, P=0·031) at the 5-year follow-up after controlling for relevant confounders. Red meat intake was positively associated with fasting glucose concentrations (ß=0·05, P=0·017), whereas low-fat (ß=-0·046, P=0·018) but not high-fat dairy products (ß=0·003, P=0·853) was inversely related to glucose tolerance at the follow-up visit. Replacement of polished with unpolished rice may be a particularly effective dietary advice in this and similar populations.

Cost-Effectiveness of Peer-Educator-Delivered Lifestyle Modification for Type 2 Diabetes Prevention in a Young Healthy Population in Sri Lanka: A Trial-Based Economic Evaluation and Economic Model.

BACKGROUND: This study evaluated the cost effectiveness of an intensive lifestyle modification (LSM) intervention delivered by peer educators for the prevention of type 2 diabetes mellitus in a young at-risk population in a low healthcare resource setting. OBJECTIVE: The aim of this study was to evaluate the short-term and long-term cost effectiveness of an intensive lifestyle modification intervention for type 2 diabetes prevention in a young urban at-risk population in Sri Lanka. METHODS: This was an economic evaluation using cost and outcome data from a randomized controlled trial. We randomized 3539 healthy individuals aged 5-40 years with risk factors for type 2 diabetes to either 3-monthly (P-LSM n = 1727) or 12-monthly (C-LSM n = 1812) peer-educator advice aimed at reducing weight, improving diet, reducing psychological stress and increasing physical activity. A cost-effectiveness analysis was conducted from a health system perspective with outcomes expressed as disability-adjusted life-years (DALYs). Intervention costs and outcomes were collected during a median clinical trial period of 3 years and extrapolated to a lifetime horizon using economic modelling. Uncertainty in the lifetime model was explored by structural and probabilistic sensitivity analyses. RESULTS: The costs of the more intensive peer support programme were partially offset by reduced costs of type 2 diabetes complications recorded over the trial period and completely offset by lifetime cost savings of 6000 LKR. The more intensive P-LSM also averted more DALYs, estimated at 0.456 DALYs over the lifetime of participants. CONCLUSIONS: In a young at-risk Sri Lanka population, an intensive LSM programme was cost effective, averting more DALYs at an acceptable additional cost than a much less intensive LSM programme. Early intervention in young at-risk people represents good value for money from the Sri Lankan health care payer perspective.

The metabolic syndrome in South Asians: continuing escalation & possible solutions.

The metabolic syndrome is a crucial factor in causation of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) in South Asians. Approximately 20-25 per cent of urban South Asians have evidence of the metabolic syndrome. Furthermore, insulin resistance was reported to be present in nearly 30 per cent of children and adolescents in India, more so in girls. At the same time many young individuals have clustering of other risk factors/conditions related to insulin resistance (e.g., non-alcoholic fatty liver disease, obstructive sleep apnoea, etc.). Rapid nutritional and lifestyle transition in urbanized areas in various countries in South Asia are prime reasons for increasing prevalence of obesity and the metabolic syndrome. It is particularly important to effectively implement and strengthen population-based primary prevention strategies for the prevention of 'epidemic' of obesity and the metabolic syndrome. The lifestyle factor modification to prevent the metabolic syndrome and T2DM in South Asians should start in early childhood. Finally, there is an urgent need to conduct research studies regarding the correct definitions of the metabolic syndrome and genetic and perinatal factors related to insulin resistance in South Asians.

High prevalence of cardio-metabolic risk factors in a young urban Sri-Lankan population.

BACKGROUND: South-Asian's are predisposed to early onset type 2 diabetes (T2DM). The prevalence of cardio-metabolic risk-factors in young Sri-Lankans is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine by questionnaire and anthropometry the prevalence of first degree family history (FH) of T2DM, physical inactivity, raised waist circumference (WC) and raised body mass index (BMI) in a representative healthy urban population selected by cluster sampling. Those with ≥ 2 risk-factors were evaluated for metabolic syndrome (MS) and recruited for an intervention trial. Of 23,296 participants screened, 22,507 (53% Female) were eligible [8,497 aged 10-14 yrs, 4,763 aged 15-19 yrs and 9,247 aged 20-40 yrs]. 51% had none of the 4 risk-factors, 26% 1 risk-factor and 23% (5,163) ≥ 2 risk-factors of whom 4,532 were assessed for MS. Raised BMI was noted in 19.7% aged 10-14 yrs, 15.3% between 15-19 yrs, and between 20-40 yrs, 27.4% of males vs. 21.8% of females p<0.001. Prevalence of raised WC was greater in females for each age group: 42.7% vs. 32.1%; 28.1% vs. 16.1%; 34.5% vs. 25.7% (p<0.05 for all) as was physical inactivity: 39.9% vs. 14.5%; 51.7% vs. 20.0%; 62.7% vs. 41.3% which rose in both sexes with age (p<0.05 for all). FH of T2DM was present in 26.2%. In 4532 (50%<16 yrs) with ≥ 2 risk-factors, impaired fasting glycaemia/impaired glucose tolerance (pre-diabetes) prevalence was 16%. MS was more prevalent in males [10-16 yrs (13.0% vs. 8.8%), 16-40 yrs (29.5% vs. 20.0%) p<0.001 for both]. CONCLUSIONS/SIGNIFICANCE: There is a high prevalence of modifiable cardio-metabolic risk-factors in young urban Sri-Lankans with significant gender differences. A primary prevention intervention trial is ongoing in this cohort. Clinical Trial Registration Number SLCTR/2008/World Health Organization (WHO) international clinical trial registry platform.

DIABRISK-SL prevention of cardio-metabolic disease with life style modification in young urban Sri Lankan's--study protocol for a randomized controlled trial.

BACKGROUND: Urban South-Asian's are predisposed to early onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There is an urgent need for country specific primary prevention strategies to address the growing burden of cardio-metabolic disease in this population. The aim of this clinical trial is to evaluate whether intensive (3-monthly) lifestyle modification advice is superior to a less-intensive (12 monthly; control group) lifestyle modification advice on a primary composite cardio-metabolic end point in 'at risk' urban subjects aged between 5-40 years. METHODS/DESIGN: This is an open randomised controlled parallel group clinical trial performed at a single centre in Colombo, Sri-Lanka. A cluster sampling strategy was used to select a large representative sample of subjects aged between 5-40 years at high risk of T2DM and CVD for the intervention study. We have screened 23,298 (males 47% females 53%) healthy subjects for four risk factors: obesity, elevated waist circumference, family history of diabetes and physical inactivity, using a questionnaire and anthropometry. Those with two or more risk-factors were recruited to the intervention trial. We aim to recruit 4600 subjects for the intervention trial. The primary composite cardio-metabolic end point is; new onset T2DM, impaired glucose tolerance, impaired fasting glycaemia, new onset hypertension and albuminuria, following 5 years of intervention. The effect of the intervention on pre-specified secondary endpoints will also be evaluated. The study will be conducted according to good clinical and ethical practice, data analysis and reporting guidelines. DISCUSSION: DIABRISK-SL is a large population based trial to evaluate the prevalence of diabetes, pre-diabetes and cardio-metabolic risk factors among young urban Sri-Lankans and the effect of a primary prevention strategy on cardio-metabolic disease end points. This work will enable country specific and regional cardio-metabolic risk scores to be derived. Further if the proposed intervention is successful the results of this study can be translated and implemented as a low-cost primary prevention tool in Sri-Lanka and other low/middle income developing countries. TRIAL REGISTRATION: The trial is registered with the World Health Organisation and Sri-Lanka clinical trial registry number SLCTR/2008/003.

The Kathmandu Declaration: "Life Circle" approach to prevention and care of diabetes mellitus.

OBJECTIVES: To formulate strategies and action plans for the prevention and care of diabetes mellitus as part of the implementation of the International Diabetes Federation (IDF) United Nations Resolution (UNR) 61/225 through a unique concept of a "Life Circle" approach. METHOD: Consensus following review of evidence available and presented at a meeting convened to achieve the objective co-chaired by the IDF President and President elect and diabetologists from several countries in the IDF regions. CONCLUSIONS: The Kathmandu Declaration presents the concept of a "Life Circle" approach to prevention and care of diabetes--a continuum beginning from preconception, pregnancy, infancy and childhood to adult life in an integrated manner. Emphasis is on the benefits on entering the circle at any point and formulates guidelines that could be incorporated in any national diabetes prevention and care programme, indicating the interactive role of all known aetiological factors.