Persistent hypoglycemia in patients with liver cancer.

Summary: Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child-Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon. Learning points: Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF). Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor. The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon. Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH-IGF axis.

Physio-cognitive decline syndrome among middle-aged diabetes patients: Handgrip strength significantly correlates with glycaemic control and cognitive score.

Aims: To investigate the correlation between glycaemic control with component of Physio-Cognitive Decline Syndrome (PCDS) and among each component of PCDS itself. Methods: A cross sectional study was conducted (January 2021-November 2022) at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia on consecutively recruited T2DM outpatients aged 40-59 years old. Data on the latest three months HbA1c, hand grip strength (HGS), usual gait speed (GS), and Indonesian Montreal Cognitive Assessment (MoCA-Ina) were evaluated. Pearson or Spearman's test was used to analyse the correlations. Results: There were 133 subjects with median age 53 (40-59) years. The PCDS was found in 48.1 % subjects, of which 64.1 % with uncontrolled glycaemia. Significant correlations were found between HGS and HbA1c (r = -0.24, R2 = 0.06, p < 0.01) and MoCA-Ina score (r = 0.21, R2 = 0.04, p < 0.05). Conclusion: The higher HbA1c and the lower MoCA-Ina score, the weaker handgrip strength was.

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.

Dysregulation of adipokines levels among healthy first-degree relatives of type 2 diabetes patients.

Background: Leptin, adiponectin and its ratio (L/A), as well as adipocyte fatty acid binding protein (A-FABP) have shown association to type 2 diabetes and atherosclerosis. Since first degree relatives (FDR) of type 2 diabetes are known to have higher risks of developing aforementioned diseases, this study aimed to see differences in adipokines profiles between FDR of type 2 diabetes and non-FDR counterpart. Methods: Age, sex and body mass index (BMI)-matched normotensive-normoglycemic subjects, aged 19-39 years with BMI<30 kg/m2, were included in this cross-sectional study. Serum adiponectin, leptin, and A-FABP levels were measured by sandwich ELISA while HOMA-IR was calculated from fasting blood glucose and insulin levels. Results: Of 116 subjects recruited, there were significant difference of insulin level (6.00 vs 5.00 µIU/mL, P = 0.029) and HOMA-IR (1.27 vs 1.10, P = 0.028). Adiponectin, leptin, L/A ratio, and A-FABP levels were not statistically different between FDR and non-FDR groups. Stratified by BMI, non-obese FDR had higher L/A ratio (0.83 vs 0.49, P = 0.020) compared to those of corresponding non-FDR. In multivariate analysis, after adjusting for age, sex, waist circumference, BMI, and metabolic profiles (HbA1C, HOMA-IR, LDL-C, HDL-C, and triglyceride levels), FDR status became significantly associated with adiponectin level, and in non-obese subgroup, remained its significance with L/A ratio. Conclusion: The FDR status was independently associated with adiponectin level. Furthermore, higher L/A ratio was more pronounced in non-obese FDR than those of non-FDR subjects, suggesting that FDR status may already contribute to the development of adipokines dysregulation before obesity occurs.

Impact of the source of hematopoietic stem cells on immune reconstitution after transplantation: A systematic review.

Hematopoietic stem cell (HSC) transplantation's success lies in its ability to induce immune reconstitution. To date, there is no review published to compare the immune reconstitution among the three sources of HSC: umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PB). The review aims to analyze the kinetic of immune reconstitution among UCB, PB, and BM in HSC transplant patients by focusing on natural killer (NK) cells, B and T lymphocytes, and neutrophils. A systematic review was conducted through five databases, searching for clinical trials and randomized control trials (RCTs) which analyze the kinetics of immune reconstitution in at least two sources. Selected studies were assessed with Cochrane RoB 2.0. This review included 14 studies, with a total of 2539 subjects. The PB group achieved the fastest time to neutrophil recovery, while the B-cell count was the highest in the UCB group. The T-cell count is the lowest in the BM group, and the NK-cell count does not differ significantly among the three HSC sources. Among the three sources of HSC, there is no superior HSC source for any immune reconstitution parameter. More studies must be conducted to compare the immune reconstitution and clinical outcomes of all HSC sources in specific diseases.

Simple anthropometric measures to predict visceral adipose tissue area in middle-aged Indonesian men.

The diagnosing of central obesity requires ethnic-specific cut-offs of waist circumference (WC) and body mass index (BMI). This study aims to develop formulas to predict visceral adipose tissue (VAT) area based on WC and BMI to determine the cut-off points of central obesity in Indonesia. We conducted a cross-sectional study among 32 middle-aged Indonesian men. VAT area was measured using an abdominal CT scan, whereas WC and BMI were assessed through anthropometric measurements. Linear regression analysis was performed to define the formulas to predict VAT area using WC and BMI. Next, the optimal cut-off values of WC and BMI were determined using ROC curve analysis. Strong positive correlations were found between WC and VAT as well as BMI and VAT (r = 0.78; r = 0.67, p <0.001). The formula to predict VAT area from WC was -182.65 + (3.35 × WC), whereas the formula to predict VAT area from BMI was -57.22 + (6.95 × BMI). These formulas predicted WC of 88.5 cm and BMI of 23.9 kg/m2 as the optimal cut-off values for central obesity in middle-aged Indonesian men.

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.

New proposed cut-off of waist circumference for central obesity as risk factor for diabetes mellitus: Evidence from the Indonesian Basic National Health Survey.

BACKGROUND: Waist circumference (WC) measurement is practical to define central obesity. However, WC cut-off point might be differ based on different race or ethnicity. This study aims to analyze the optimal WC cut-off point to identify T2DM risk among Indonesian population. METHOD: We analyzed the secondary data of national based cross-sectional study of the Indonesian Basic National Health Research 2013, comprising 24,660 adults aged ≥ 18 years who were assessed for fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). The new proposed cut-off point for WC was calculated using ROC curve analysis and Youden index. The odds ratio of having T2DM was calculated using logistic regression analysis. RESULTS: Increased WC was associated with worsening dysglycemia status among men and women (p<0.001). The optimal cut-off point of WC for detecting T2DM from ROC analysis was 76 for men and 80 for women. Based on this WC cut-off point, the odds ratio for having T2DM was 1.64 [95% CI 1.45-1.86, p<0.01] for men and 1.90 [95% CI 1.71-2.11 p<0.01] for women. CONCLUSION: The newly proposed WC cut-off point of 76 for men and 80 women can be used to screen the risk of T2DM among Indonesian population.

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.

Visceral fat thickness of erosive and non-erosive reflux disease subjects in Indonesia's tertiary referral hospital.

BACKGROUND: There has been an increasing number of reports regarding the correlation between obesity and gastroesophageal reflux disease (GERD). Visceral fat thickness is thought to be a risk factor for GERD and its severity. Several studies have conflicting results, so this study aimed to determine visceral fat thickness difference between erosive and non-erosive reflux disease. METHODS: A cross-sectional study of 56 adult subjects with GERD symptoms was held at Cipto Mangunkusumo National General Hospital between April and November 2018. Gastroesophageal Reflux Disease Questionnaires (GERDQ) were utilized to determine the presence of GERD. Ultrasonography was used to determine visceral fat thickness. Esophageal erosions were diagnosed using upper gastrointestinal endoscopy. The difference in visceral fat thickness between esophagitis and non-esophagitis group was analysed using T-test. RESULTS: From 56 total subjects, 55.4% have erosive reflux disease (ERD), in which were dominated by subjects with grade A esophagitis (64.5%) based on Los Angeles Classification of Esophagitis (LA classifications). There was no significant difference of visceral fat thickness between non-erosive reflux disease (NERD) and ERD (p = 0,831). There was, however, an increasing trend of visceral fat thickness with the advancing severity of esophagitis, although statistical significance was not reached. CONCLUSION: Visceral fat thickness as measured by ultrasonography has no significant difference between NERD and ERD.

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.

Challenges in diabetes management in Indonesia: a literature review.

BACKGROUND AND OBJECTIVES: The 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. METHODS: We 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. RESULTS: A 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. DISCUSSION: There 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. CONCLUSIONS: If 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.