Dicky Tahapary

Challenges in diabetes management in Indonesia: a literature review

Background and objectivesThe expanding diabetes epidemic worldwide could have potentially devastating effects on the development of healthcare systems and economies in emerging countries, both in terms of direct health care costs and loss of working time and disability. This study aims to review evidence on the burden, expenditure, complications, treatment, and outcomes of diabetes in Indonesia and its implications on the current health system developments.MethodsWe conducted a comprehensive literature review together with a review of unpublished data from the Ministry of Health and a public health insurer (Askes). Studies presenting evidence on prevalence, incidence, mortality, costs, complications and cost of complications, treatment, and outcomes were included in the analysis.ResultsA limited number of international, national and local studies on the burden and cost of diabetes in Indonesia were identified. National survey data suggests that in 2007 the prevalence of diabetes was 5.7%, of which more than 70% of cases were undiagnosed. This estimate hides large intracountry variation. There was very limited data available on direct costs and no data on indirect costs. The most commonly-identified complication was diabetic neuropathy.DiscussionThere were a number of limitations in the data retrieved including the paucity of data representative at the national level, lack of a clear reference date, lack of data from primary care, and lack of data from certain regions of the country.ConclusionsIf left unaddressed, the growing prevalence of diabetes in the country will pose a tremendous challenge to the Indonesian healthcare system, particularly in view of the Government’s 2010 mandate to achieve universal health coverage by 2014. Essential steps to address this issue would include: placing diabetes and non-communicable diseases high on the Government agenda and creating a national plan; identifying disparities and priority areas for Indonesia; developing a framework for coordinated actions between all relevant stakeholders.

Helminths, hygiene hypothesis and type 2 diabetes.

Worldwide, there is little overlap between the prevalence of soil‐transmitted helminths and type 2 diabetes (T2D). Helminth‐induced type 2 immune responses and immune regulatory network might modulate the obesity‐induced activation of inflammatory pathways that are associated with the development of insulin resistance, a strong predictor of the development of T2D. However, other factors such as helminth‐associated changes in adiposity and gut microbiome might also contribute to improved metabolic outcomes. In this review, we summarize epidemiological evidence for the link between helminths and T2D and discuss the potential mechanisms, based on findings from experimental studies as well as the limited number of studies in humans.

Effect of Anthelmintic Treatment on Insulin Resistance: A Cluster-Randomized, Placebo-Controlled Trial in Indonesia

Background Emerging evidence suggests that helminth infections are associated with lower insulin resistance (IR). Current deworming programs might remove this helminth-associated protective effect. Therefore, we evaluated the anthelmintic treatment effect on changes in IR. Methods We conducted a double-blind, household-cluster-randomized, placebo-controlled clinical trial on Flores island, Indonesia, an area endemic for soil-transmitted helminths (STHs). All subjects received 4 rounds of albendazole or matching placebo with 3-month intervals, for 3 consecutive days. The primary outcome was the change in homeostatic model assessment of IR in those aged >16 years. An intention-to-treat analysis was performed involving all subjects and ad hoc in the helminth-infected subjects. Results We examined 797 (in 329 households) and 872 (in 353 households) subjects, who were assigned randomly into the albendazole and placebo arms, respectively. Albendazole was associated with a significant reduction in STH prevalence, total immunoglobulin E (IgE), and eosinophil count. Whereas albendazole had no effect on IR (estimated treatment effect, 0.006 [95% confidence interval, -.010 to .021]; P = .48) at the community level, it was associated with a significant increase in IR (estimated treatment effect, 0.031 [95% confidence interval, .004 to .059]; P = .04) (P value for interaction = .01) among helminth-infected subjects as detected by microscopy. Pathway analysis suggested that this might in part be due to an increased body mass index or a reduced eosinophil count. Conclusions Anthelmintic treatment reduces STH prevalence, total IgE, and eosinophil count but has no effect on IR at the community level. In helminth-infected subjects, treatment significantly increases IR, highlighting the need for metabolic health monitoring with ongoing deworming programs. Clinical Trials Registration ISRCTN 75636394.

The effect of three-monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL-5

Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL‐5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1‐mediated pathologies when the counterbalancing helminth‐induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2‐mediated responses in a household‐clustered randomized controlled trial in Indonesia. Total plasma IgE and whole‐blood IL‐5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three‐monthly single‐dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole‐ compared to placebo‐treated subjects. IL‐5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole‐treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B‐cell (IgE levels) and T‐cell (IL‐5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2‐mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases.

Impact of rural-urban environment on metabolic profile and response to a 5-day high-fat diet

Epidemiological studies have indicated that rural living might be protective against type 2 diabetes development. We compared the metabolic profile and response to a short-term high-fat high-calorie diet (HFD) of men with the same genetic background living in an urban and rural area of Indonesia. First, we recruited 154 Floresian male subjects (18–65 years old), of whom 105 lived in a rural area (Flores) and 49 had migrated and lived in urban area (Jakarta) for more than 1 year. The urban group had significantly higher whole-body insulin resistance (IR), as assessed by homeostatic-model-assessment of IR (HOMA-IR), [mean difference (95% CI), p-value: 0.10 (0.02–0.17), p = 0.01]. Next, we recruited 17 urban and 17 rural age-and-BMI-matched healthy-young-male volunteers for a 5-day HFD challenge. The HOMA-IR increased in both groups similarly −0.77 (−2.03–0.49), p = 0.22]. Neither rural living nor factors associated with rural living, such as current helminth infection or total IgE, were associated with protection against acute induction of IR by HFD.

Prevalence of Atopy following Mass Drug Administration with Albendazole: A Study in School Children on Flores Island, Indonesia

Background: In many rural areas of tropical countries such as Indonesia, the prevalence of soil-transmitted helminths (STH) infections remains high. At the same time, the burden of allergic disorders in such rural areas is reported to be low and inversely associated with helminth infections. To reduce the morbidity and transmission of helminth infections, the world health organization recommends preventive treatment of school children by providing mass drug administration (MDA) with albendazole. Here, we had an opportunity to evaluate the prevalence of skin reactivity to allergens before and after albendazole treatment to get an indication of the possible impact of MDA on allergic sensitization. Methods: A study was conducted among 150 school children living in an area endemic for STH infections. Before and 1 year after anthelminthic treatment with albendazole, stool samples were examined for the presence of STH eggs, skin prick tests (SPT) for cockroach and house dust mites were performed, blood eosinophilia was assessed, and total immunoglobulin E (IgE) and C-reactive protein (CRP) were measured in plasma. Results: Anthelminthic treatment significantly reduced the prevalence of STH from 19.6 before treatment to 6% after treatment (p < 0.001). Levels of total IgE (estimate: 0.30; 95% CI 0.22–0.42, p < 0.0001), CRP (estimate: 0.60; 95% CI 0.42–0.86, p = 0.006), and eosinophil counts (estimate: 0.70; 95% CI 0.61–0.80, p < 0.001) decreased significantly. The prevalence of SPT positivity increased from 18.7 to 32.7%. Multivariate analysis adjusted for confounding factors showed an increased risk of being SPT positive to any allergen (OR 3.04; 95% CI 1.338–6.919, p = 0.008). Conclusions: This study indicates that 1 year of MDA with albendazole was associated with a reduced prevalence of STH infections. This study shows that the prevalence of allergic sensitization increases after 1 year of albendazole treatment. Placebo-controlled and larger studies are needed to further substantiate a role of deworming treatment in an increased risk of allergic sensitization.

The Association of Lipoprotein Changes and the Development of Plasma Leakage in Dengue Infection

There’s interrelationship between infection and lipoprotein. This is a cohort prospective study which conducted November 2010 – February 2011. This study aimed to assess the changes of HDL-C, LDL-C, total cholesterol (TC), triglyceride (TG), in acute and critical phase of dengue infection and its association with plasma leakage. Subjects who had fever 48 hours or less and Dengue NS1 antigen test positive were admitted to Cipto Mangunkusumo Hospital Jakarta. We examined clinical and CBC daily; level of albumin, HDL-C, LDL-C, TC, TG; ultrasound to find ascites and pleural effusion. Among 51 subjects, 21 subjects (41%) had plasma leakage. There were significant lower of HDL-C, LDL-C, and higher TG in critical phase than acute phase. In critical phase, subjects with plasma leakage had a significant lower HDL-C level [26.3 (8.2) vs 33.1 (12.1) mg/dL, p=0.029] but not for LDL-C, TC, and TG. They also had a significantly higher reduction in HDL-C [19.6 (9.1) vs 11.5 (5.8) mg/dL, p<0.0001] and TC [25.1 (20.0) vs 15.2 (14.5) mg/dL, 0.045] over the course of acute to critical phase. Lipoprotein changes during dengue infection were more pronounced among subjects who developed plasma leakage. The higher reduction in HDL-C is associated with the development of plasma leakage. Normal 0 false false false IN X-NONE X-NONE

Effect of anthelmintic treatment on leptin, adiponectin and leptin to adiponectin ratio: a randomized-controlled trial

Emerging evidence suggests that helminths might confer protection against the development of type 2 diabetes. We aimed to assess the role of adipokines in mediating the effect of helminths on insulin resistance. Serum samples were obtained from a randomized-controlled trial of anthelmintic treatment in an area endemic for soil-transmitted helminths (STH), Flores Island, Indonesia. In STH-infected subjects, anthelmintic treatment significantly increased the ratio of leptin to adiponectin (treatment effect factor (95% confidence interval (CI)), P-value for interaction: 1.20 (1.06–1.35), P=0.010), which largely stemmed from a significant reduction in adiponectin (0.91 (0.85–0.98), P=0.020) and a trend for an increase in leptin level (1.10 (1.00–1.21), P=0.119). No significant effect on resistin level was observed. This increase in leptin to adiponectin ratio seemed to contribute to the observed effect of deworming on increased insulin resistance (IR) as adjustment for leptin to adiponectin ratio attenuated the effect on IR from 1.07 (1.01–1.14, P=0.023) to 1.05 (0.99–1.11, P=0.075). Anthelmintic treatment in STH-infected subjects increases leptin to adiponectin ratio which may in small part contribute to the modest increase in IR. Further studies will be needed to assess the effect of the changes in adipokine levels on the host immune response and metabolism.