Lifestyle and clinical risk factors in relation with the prevalence of diabetes in the Indonesian urban and rural populations: The 2018 Indonesian Basic Health Survey.

Aims: To investigate the differences between Indonesian urban and rural populations in the association of lifestyle and clinical factors with diabetes prevalence. Methods: Using database of the 2018 Indonesian Basic Health Survey, which was conducted in April-May 2018, non-pregnant respondents aged ≥15 years old with available blood glucose data (n urban = 17,129, n rural = 16,585) were included in this study. The diagnosis of diabetes was based on the combination of known diabetes, i.e., a previous history of diabetes or use of anti-diabetes medication, and unknown diabetes based on blood glucose criteria. We performed logistic regression analyses separately for the urban and rural populations to examine the association of lifestyle and clinical factors with prevalent diabetes. Results: Indonesian urban population was less physically active, had a lower proportion of adequate fruit and vegetable intake, and had higher individuals with obesity than rural population. Although there were no differences in the total prevalence of diabetes between the two populations (10.9 % vs. 11.0 %, for urban and rural, respectively), the prevalence of known diabetes was twice higher in urban than in rural population (3.8 % vs. 1.9 %). Physical activity was associated with lower risk of diabetes, especially in the urban population [prevalence OR (95 %CI): 0.91 (0.85; 0.98) for urban and 0.94 (0.89; 1.00) for rural). Obesity, hypertension, and dyslipidemia were risk factors for prevalent diabetes in both populations. Conclusions: Indonesian rural population showed relatively better lifestyle and clinical profiles compared to their urban counterparts. However, no differences were observed between the two populations in the relation between risk factors and diabetes. Special attention needs to be addressed to the high prevalence of undiagnosed and untreated diabetes in Indonesia.

Increased intestinal-fatty acid binding protein in obesity-associated type 2 diabetes mellitus.

BACKGROUND: Obesity is a traditional risk factor for type 2 diabetes mellitus (T2DM). However, recent studies reported that metabolically unhealthy obesity (MUO) exerts a higher risk of developing T2DM than metabolically healthy obesity (MHO) because of its higher state of insulin resistance. This may happen due to metabolic endotoxemia through gut dysbiosis and increased intestinal permeability. Our study aimed to know the association of intestinal permeability using intestinal fatty acid-binding protein (I-FABP) with obesity-related T2DM patients in Indonesia. METHODS: This was a cross-sectional study that recruited 63 participants with obesity defined using body mass index (BMI) classification for the Asia-Pacific population (BMI ≥25 kg/m2). All participants were then grouped into T2DM and non-T2DM based on American Diabetes Association (ADA) diagnostic criteria. The I-FABP levels were measured using the enzyme-linked immunosorbent assay method. RESULTS: The I-FABP level of T2DM group was higher compared to non-T2DM group, namely 2.82 (1.23) ng/mL vs. 1.78 (0.81) ng/mL (p<0.001; mean difference 1.033 with 95% CI 0.51-1.55). This difference was not attenuated even after adjustment for age. The fitted regression model using linear regression was: i-FABP = 1.787+1.034*(DM) (R2 = 18.20%, standardized ß = 0.442, p<0.001). CONCLUSIONS: This study underscores the association of intestinal permeability with T2DM in people with obesity and supports the evidence of the potential role of intestinal permeability in the pathogenesis of obesity-related T2DM.

Autologous intraarterial pancreatic bone-marrow mononuclear cells infusion in T2D patients: Changes on beta-cells function, insulin resistance, and inflammatory marker.

BACKGROUND: Type 2 diabetes (T2D) is a progressive disease. Many drugs currently being used for the management of T2D have minimal effect on pancreatic beta cells regeneration. Cell-based therapies might provide potential benefits in this aspect. METHODS: A pilot study in five T2D patients with 12 months follow-up was performed to evaluate the effect of autologous bone marrow mononuclear stem cells (BM-MNCs) infusion into pancreatic arteries on the insulin requirement, beta-cell function, insulin resistance, and systemic inflammatory marker (CRP). RESULTS: The primary endpoint, a 50 % reduction of total insulin doses from baseline, was not achieved in this study. However, a trend of increasing fasting C-peptide (p = 0.07) and C-peptide 60' (p = 0.07) and 90' (p = 0.07) after a mixed-meal tolerance test was observed 12 months post-infusion compared to baseline levels. A similar result was observed for the homeostatic model assessment of beta cell function (HOMA1-B), an index for beta cell function. No improvement was observed for insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA1-IR) and systemic inflammatory parameter. CONCLUSION: Intraarterial pancreatic autologous BM-MNCs infusion might potentially improve beta cell function in T2D patients, although further study is needed to confirm this finding.

Challenges in the diagnosis of insulin resistance: Focusing on the role of HOMA-IR and Tryglyceride/glucose index.

BACKGROUND AND AIMS: Metabolic Syndrome (MS) prevalence is increasing worldwide in line with the growing prevalence of obesity. The underlying mechanism of MS is insulin resistance which can be diagnosed by measuring Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Triglyceride/Glucose (TyG) Index. This review will focus on comparing studies assessing the HOMA-IR and TyG index cut-off points. METHODS: We carried out a comprehensive review of the literature using suitable keywords on the search engines of PubMed, Scopus, Research Gate, and Google Scholar in the month of October 2020. RESULTS: There is a high degree of variability in determining threshold levels of HOMA-IR for defining insulin resistance. The distribution of the HOMA-IR varies according to the demographic characteristics of the subjects, such as age, sex, and race, making it difficult to estimate the optimal cut-off point. Another simpler method without requiring the use of insulin assays is TyG Index. Similar to HOMA-IR, the TyG Index cut-off point from existing data shows varying results. CONCLUSION: The HOMA-IR and the TyG index are simple and widely used methods for determining insulin resistance. However, an issue that arises is determining the insulin resistance cut-off point for both methods. Further studies are needed to assess the cut-off point of insulin resistance for various ethnicities associated with the risk of developing MS later in life.

Urbanization and Unfavorable Changes in Metabolic Profiles: A Prospective Cohort Study of Indonesian Young Adults.

The substantial increase in the prevalence of non-communicable diseases in Indonesia might be driven by rapid socio-economic development through urbanization. Here, we carried out a longitudinal 1-year follow-up study to evaluate the effect of urbanization, an important determinant of health, on metabolic profiles of young Indonesian adults. University freshmen/women in Jakarta, aged 16−25 years, who either had recently migrated from rural areas or originated from urban settings were studied. Anthropometry, dietary intake, and physical activity, as well as fasting blood glucose and insulin, leptin, and adiponectin were measured at baseline and repeated at one year follow-up. At baseline, 106 urban and 83 rural subjects were recruited, of which 81 urban and 66 rural were followed up. At baseline, rural subjects had better adiposity profiles, whole-body insulin resistance, and adipokine levels compared to their urban counterparts. After 1-year, rural subjects experienced an almost twice higher increase in BMI than urban subjects (estimate (95%CI): 1.23 (0.94; 1.52) and 0.69 (0.43; 0.95) for rural and urban subjects, respectively, Pint < 0.01). Fat intake served as the major dietary component, which partially mediates the differences in BMI between urban and rural group at baseline. It also contributed to the changes in BMI over time for both groups, although it does not explain the enhanced gain of BMI in rural subjects. A significantly higher increase of leptin/adiponectin ratio was also seen in rural subjects after 1-year of living in an urban area. In conclusion, urbanization was associated with less favorable changes in adiposity and adipokine profiles in a population of young Indonesian adults.

Characteristics of Diabetic Foot Ulcer Patients Pre- and During COVID-19 Pandemic: Lessons Learnt From a National Referral Hospital in Indonesia.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most terrifying diabetic complications for patients, due to the high mortality rate and risk for amputation. During the COVID-19 pandemic, many diabetic patients limited their visits to the hospital, resulting in delays for treatment especially in emergency cases. OBJECTIVE: This study aimed to compare the characteristics of patients with DFU pre- and during COVID-19 pandemic period. Methods: This study was a retrospective cohort study using foot registry data. We compared our patients' characteristics pre-COVID-19 pandemic period (1 March 2019-28 February 2020) and during COVID-19 pandemic period (1 March 2020-28 February 2021). RESULTS: Cohorts of 84 and 71 patients with DFU pre- and during COVID-19 pandemic period, respectively, were included in this study. High infection grade (66.7% vs 83.1%, P = .032), osteomyelitis event (72.6% vs 87.3%, P = .04), leukocyte count (15 565.0/µL vs 20 280.0/µL, P = .002), neutrophil-to-lymphocyte ratio (7.7 vs 12.1, P = .008), waiting time-to-surgery (39.0 h vs 78.5 h, P = .034), and number of major amputation (20.2% vs 39.4%, P = .014) were significantly higher during the COVID-19 pandemic period. CONCLUSION: During the COVID-19 pandemic, patients with DFU had more severe infection, higher proportion of osteomyelitis, longer waiting time for getting surgical intervention, and higher incidence of major amputation.

Impact of diabetes mellitus on COVID-19 clinical symptoms and mortality: Jakarta's COVID-19 epidemiological registry.

BACKGROUND AND AIMS: While the higher prevalence of diabetes mellitus (DM) at younger age in Indonesia might contribute to the relatively higher COVID-19 mortality rate in Indonesia, there were currently no available evidence nor specific policy in terms of COVID-19 prevention and management among DM patients. We aimed to find out the association between diagnosed diabetes mellitus (DM) with COVID-19 mortality in Indonesia. METHODS: We performed a retrospective cohort study using Jakarta Province's COVID-19 epidemiological registry within the first 6 months of the pandemic. All COVID-19 confirmed patients, aged >15 years with known DM status were included. Patients were assessed for their clinical symptoms and mortality outcome based on their DM status. A multivariate Cox-regression test was performed to obtain the relative risk (RR) of COVID-19 mortality in the diagnosed DM group. RESULTS: Of 20,481 patients with COVID-19, 705 (3.4%) had DM. COVID-19 mortality rate in DM group was 21.28%, significantly higher compared to 2.77% mortality in the non-DM group [adjusted RR 1.98 (CI 95% 1.57-2.51), p < 0.001]. In addition, COVID-19 patients with DM generally developed more symptoms. CONCLUSIONS: DM is associated not only with development of more COVID-19 clinical symptoms, but also with a higher risk of COVID-19 mortality. This finding may provide a basis for future policy regarding COVID-19 prevention and management among diabetes patients in Indonesia.

The urgency in proposing the optimal obesity cutoff value in Indonesian population: A narrative review.

In developing nations such as Indonesia, obesity and central obesity have emerged as major public health issues. Many studies have revealed that morbidity and death from obesity-related diseases are already significant in some "Asian" communities at low body mass index (BMI) levels. A recent study showed that the obesity prevalence in Indonesia is underestimated when using the current BMI cutoff (obese ≥ 27.0). Indonesia faced an increase in obesity-related chronic diseases despite having a lower obesity prevalence than developed countries, which may be explained by the underestimation of obesity levels in Indonesia. This creates a huge global health problem, as well as an economic burden. Another recent study on the Indonesian population depicted the new proposed cutoff of waist circumference (WC), which is lower than the World Health Organization (WHO) standard for detecting the early detection of type 2 diabetes mellitus (T2DM), one of the comorbidities and a strong correlation with obesity. An analysis of 58 studies in 2021 that included Indonesian adult subjects revealed enormous differences and ambiguities in defining obesity cutoffs values among Indonesian researchers. Additionally, we advocate adding the Edmonton Obesity Staging System (EOSS) staging to the anthropometric classification for a better clinical evaluation of obesity. Considering the urgency of obesity determination in Indonesia for clinical application and study purposes, this review highlights the need to revise the optimal cutoff value for obesity to warrant early prevention and control of diabetes complications.

The impact of Ramadan fasting on Fetuin-A level in type 2 diabetes mellitus.

BACKGROUND/AIMS: Ramadan fasting creates changes in lifestyle, causing biochemical alterations that affect glucose metabolism and insulin sensitivity. This study aims to assess the impact of Ramadan fasting on glycemic control and Fetuin-A, a glycoprotein that affects insulin resistance, in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This was a prospective study done among 37 patients with T2DM from Internal Medicine Polyclinic in a hospital in Jakarta, Indonesia. Anthropometric data as well as Hemoglobin A1c (HbA1c), Fasting Blood Glucose (FBG), and Fetuin-A levels of the subjects were measured in three time points: before, during, and after Ramadan fasting. A bivariate analysis was done to see the effect of Ramadan fasting on those parameters. RESULTS: Ramadan fasting reduced Fetuin-A levels [median (minimum-maximum), 5.35 (2.91-7.81) vs. 3.22 (2.35-5.60) mg/dl; p = 0.039] four weeks after the end of Ramadan compared to pre-Ramadan. After two weeks of Ramadan fasting, we found a significant reduction in body weight, BMI, FBG, and HbA1c levels which rebounded to baseline level after Ramadan. CONCLUSION: Ramadan fasting was associated with a significant decrease in Fetuin-A level post Ramadan.

Autologous Bone-Marrow vs. Peripheral Blood Mononuclear Cells Therapy for Peripheral Artery Disease in Diabetic Patients.

Diabetes mellitus (DM) remains one of the most important risk factors for peripheral artery disease (PAD), with approximately 20% of DM patients older than 40 years old are affected with PAD. The current standard management for severe PAD is endovascular intervention with or without surgical bypass. Unfortunately, up to 40% of patients are unable to undergo these revascularization therapies due to excessive surgical risk or adverse vascular side effects. Stem cell therapy has emerged as a novel therapeutic strategy for these 'no-option' patients. Several types of stem cells are utilized for PAD therapy, including bone marrow mononuclear cells (BMMNC) and peripheral blood mononuclear cells (PBMNC). Many studies have reported the safety of BMMNC and PBMNC, as well as its efficacy in reducing ischemic pain, ulcer size, pain-free walking distance, ankle-brachial index (ABI), and transcutaneous oxygen pressure (TcPO2). However, the capacity to establish the efficacy of reducing major amputation rates, amputation free survival, and all-cause mortality is limited, as shown by several randomized placebo-controlled trials. The present literature review will focus on comparing safety and efficacy between BMMNC and PBMNC as cell-based management in diabetic patients with PAD who are not suitable for revascularization therapy.

Effect of anthelmintic treatment on serum free IGF-1 and IGFBP-3: a cluster-randomized-controlled trial in Indonesia.

In children, soil-transmitted helminth infections have been linked to poor nutritional status and growth retardation in association with lower levels of IGF-1. In adults, IGF-1 has an anabolic and metabolic function and is related to nutritional status. Here, we assessed the impact of helminth infection on free IGF-1 and its major binding protein, IGFBP-3, in adults. The levels of IGF-1 and IGFBP3 were measured in 1669 subjects aged ≥ 16 years, before and after receiving four rounds of albendazole 400 mg/day or matching placebo for three consecutive days. Helminth infection status was assessed by microscopy (Kato-Katz) and PCR. Serum free IGF-1 level was significantly lower in helminth-infected subjects [mean difference and 95% CI - 0.068 (- 0.103; - 0.033), P < 0.001 after adjustment for age, sex, body mass index, and fasting insulin level]. There was no difference in IGFBP-3 level between helminth infected versus non-infected subjects. In the whole study population, albendazole treatment significantly increased serum free IGF-1 level [estimate and 95% CI 0.031 (0.004; - 0.057), P = 0.024] whereas no effect was found on the IGFBP-3 level. Our study showed that helminth infection in adults is associated with lower free IGF-1 levels but not with IGFBP-3 and albendazole treatment significantly increases free IGF-1 levels in the study population.Clinical Trial Registration: https://www.isrctn.com/ISRCTN75636394 .

The impact of Ramadan fasting on glucose variability in type 2 diabetes mellitus patients on oral anti diabetic agents.

Ramadan fasting is associated with changes in eating, physical activity, sleeping patterns, and medication. Unfortunately, only limited studies examine glucose variability in subjects with type 2 diabetes who fast in Ramadan. Our study aims to evaluate glucose variability in subjects with type 2 diabetes on oral antidiabetic agents using continuous glucose monitoring system (CGMS) during and after Ramadan fasting. This observational study was done in The Indonesian Medical Education and Research Institute, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia, which recruited 10 subjects with type 2 diabetes who underwent Ramadan fasting in 2019. These subjects were free from cardiovascular disease, kidney disease, severe liver disease, chronic gastrointestinal disease and autoimmune disease. Insertion of CGMS for measuring interstitial glucose was performed after at least 2 weeks of Ramadan fasting and 4 weeks after the end of the Ramadan fasting, with a minimum of 3 days observation. The mean amplitude of glycemic excursion (MAGE) during and after Ramadan were similar (p = 0.94). In line with this, the average interstitial glucose (p = 0.48), the maximum interstitial glucose (p = 0.35), the minimum interstitial glucose (p = 0.24), and the duration of hypoglycemia (p = 0.25) were also similar in both periods. Overall, nutritional intake and energy expenditure during both periods were comparable. Ramadan fasting is not associated with increased glucose variability in subjects with type 2 diabetes. Thus, Ramadan fasting is safe in subjects with type 2 diabetes with no complications.

Diagnostic Approach for Thyroid Nodules.

Thyroid nodule is a health problem which commonly found in daily practice, therefore clinical guidance is needed. This guideline was compiled by a multidisciplinary team and expected to be a guideline in diagnosing thyroid nodules on daily clinical practice.

Practical Guidelines Management of Graves Ophthalmopathy.

Graves' ophthalmopathy is the most common extra-thyroid manifestation in patients with Graves' disease, based on inflammatory and autoimmune conditions in orbital tissue. This practical guideline was formed by a multidiciplinary team, and is intended to provide guidance for diagnosis and management of Graves' ophthalmopathy in daily clinical practice to improve quality of care and treatment outcome.

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.