Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia.

BACKGROUND: A protein that is expressed on capillary endothelial cells, called GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1), binds lipoprotein lipase and shuttles it to its site of action in the capillary lumen. A deficiency in GPIHBP1 prevents lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides, and severe hypertriglyceridemia (chylomicronemia). During the characterization of a monoclonal antibody-based immunoassay for GPIHBP1, we encountered two plasma samples (both from patients with chylomicronemia) that contained an interfering substance that made it impossible to measure GPIHBP1. That finding raised the possibility that those samples might contain GPIHBP1 autoantibodies. METHODS: Using a combination of immunoassays, Western blot analyses, and immunocytochemical studies, we tested the two plasma samples (as well as samples from other patients with chylomicronemia) for the presence of GPIHBP1 autoantibodies. We also tested the ability of GPIHBP1 autoantibodies to block the binding of lipoprotein lipase to GPIHBP1. RESULTS: We identified GPIHBP1 autoantibodies in six patients with chylomicronemia and found that these autoantibodies blocked the binding of lipoprotein lipase to GPIHBP1. As in patients with GPIHBP1 deficiency, those with GPIHBP1 autoantibodies had low plasma levels of lipoprotein lipase. Three of the six patients had systemic lupus erythematosus. One of these patients who had GPIHBP1 autoantibodies delivered a baby with plasma containing maternal GPIHBP1 autoantibodies; the infant had severe but transient chylomicronemia. Two of the patients with chylomicronemia and GPIHBP1 autoantibodies had a response to treatment with immunosuppressive agents. CONCLUSIONS: In six patients with chylomicronemia, GPIHBP1 autoantibodies blocked the ability of GPIHBP1 to bind and transport lipoprotein lipase, thereby interfering with lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins and causing severe hypertriglyceridemia. (Funded by the National Heart, Lung, and Blood Institute and the Leducq Foundation.).

Multimerization of glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) and familial chylomicronemia from a serine-to-cysteine substitution in GPIHBP1 Ly6 domain.

GPIHBP1, a glycosylphosphatidylinositol-anchored glycoprotein of microvascular endothelial cells, binds lipoprotein lipase (LPL) within the interstitial spaces and transports it across endothelial cells to the capillary lumen. The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structure containing 10 cysteines and a conserved pattern of disulfide bond formation. Here, we report a patient with severe hypertriglyceridemia who was homozygous for a GPIHBP1 point mutation that converted a serine in the GPIHBP1 Ly6 domain (Ser-107) to a cysteine. Two hypertriglyceridemic siblings were homozygous for the same mutation. All three homozygotes had very low levels of LPL in the preheparin plasma. We suspected that the extra cysteine in GPIHBP1-S107C might prevent the trafficking of the protein to the cell surface, but this was not the case. However, nearly all of the GPIHBP1-S107C on the cell surface was in the form of disulfide-linked dimers and multimers, whereas wild-type GPIHBP1 was predominantly monomeric. An insect cell GPIHBP1 expression system confirmed the propensity of GPIHBP1-S107C to form disulfide-linked dimers and to form multimers. Functional studies showed that only GPIHBP1 monomers bind LPL. In keeping with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free binding assays. We conclude that an extra cysteine in the GPIHBP1 Ly6 motif results in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia.

A prospective, longitudinal, multicenter, observational study to assess insulin treatment patterns in diabetic patients in Thailand: results from the TITAN Study.

OBJECTIVE: To assess usage patterns, effectiveness, andsafety of newly prescribed insulin treatment in patients with diabetes in Thailand MATERIAL AND METHOD: Type 1 or type 2 diabetes mellitus patients who failed achievement of HbA1c <7%, and were about to start or switch to a new insulin treatment were enrolled into this prospective, longitudinal, multicenter observational study. Data regarding insulin usage pattern, HbA1c, fasting plasma glucose (FPG), and hypoglycemia were collected at enrollment, three and six-month. RESULTS: Between July 2008 and February 2010, 751 patients were recruited Mean (SD) age was 57.0 (12.8) years. Mean BMI was 26.1 (5.0) kg/m2. At enrollment, 269 (35.8%), 241 (32.1%), 206 (27.4%), and 35 (4.7%) patients were prescribed neutral protamine Hagedorn (NPH) insulin, long-acting insulin analogues (LAA), premixed insulin (Premixed), and insulin combinations, respectively. Significant HbA1c and FPG reductions were noted at six-month (-1.4% and -56.2 mg/dl, respectively, p<0.01). After stratifying patients into three subgroups according to insulin, the patients could continue throughout six months (588 patients, 211 NPH-group, 201 LAA-group, and 176 Premixed-group). Patients in LAA-group attained higher rate of achievement HbA1c <7% without any hypoglycemia (18.9%) than NPH-group (7.1%) and Premixed-group (6.3%; p<0. 001). Mild-to-moderate hypoglycemic events were reported at 638 events (1.9 events/patient-year) while severe hypoglycemia was reported at 10 events (3.0 event/l00 patient-year). CONCLUSION: In this observational study of real-life clinical practice in Thailand, most common newly prescribed insulin for patients having inadequate glycemic control was NPH, followed by LAA and premixed insulin. More patients on LAA achieved target HbA1c without hypoglycemic events than those on NPH and premixed insulin.

Nordic Walking in Water on Cerebrovascular Reactivity and Cognitive Function in Elderly Patients with Type 2 Diabetes.

INTRODUCTION: Aquatic Nordic walking (ANW) is a novel whole-body low-impact exercise that can be practiced by a variety of older adults with chronic conditions. However, its efficacy on several aspects of health is largely unknown. PURPOSE: This study aimed to determine the effects of regular ANW on glycemic control and vascular function in older adults with type 2 diabetes and mild cognitive impairment. METHODS: Thirty-three older adults with type 2 diabetes age 60-75 yr were randomly allocated to nonexercising control ( n = 17) or ANW ( n = 17) groups. Nordic walking was performed in a pool at water temperature of 34°C-36°C, three times per week for 12 wk. RESULTS: Measures of functional physical fitness including chair stand, timed up and go, chair sit and reach, reach and back scratch, and 6-min walk test scores were all improved after ANW (all P < 0.05). Plasma glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance decreased (all P < 0.05) in ANW. Vascular reactivity as assessed by brachial flow-mediated dilation increased, and arterial stiffness as assessed by brachial-ankle pulse wave velocity decreased in ANW (all P < 0.05). No significant changes were observed in the control group. Middle cerebral artery pulsatility index decreased with ANW under normocapnia condition ( P < 0.05). Cerebrovascular conductance increased with ANW under hypercapnia condition. Montreal Cognitive Assessment score increased in the ANW group ( P < 0.001). Changes in Montreal Cognitive Assessment scores were positively associated with corresponding changes in brain-derived neurotrophic factor ( r = 0.540, P = 0.031). CONCLUSIONS: Nordic walking in water was a safe and effective innovative exercise modality to improve glycemic control, vascular function, physical fitness, cerebrovascular reactivity, and cognitive function in older adults with type 2 diabetes.

Multiplex recombinase polymerase amplification for high-risk and low-risk type HPV detection, as potential local use in single tube.

High rates of new cervical cancer cases and deaths occur in low- and middle-income countries yearly, and one reason was found related to limitation of regular cervical cancer screening in local and low-resource settings. HPV has over 150 types, yet certain 14-20 high-risk and 13-14 low-risk types are common, and, thus, most conventional HPV nucleic acid assays, for examples, Cobas 4800 HPV test (Roche Diagnostics, New Jersey, USA) and REBA HPV-ID (Molecules and Diagnostics, Wonju, Republic of Korea) were developed to cover these types. We thereby utilized bioinformatics combined with recent isothermal amplification technique at 35-42 °C to firstly describe multiplex recombinase polymerase amplification assay that is specific to these common 20 high-risk and 14 low-risk types, and also L1 and E6/E7 genes that target different stages of cervical cancer development. Multiplex primer concentrations and reaction incubation conditions were optimized to allow simultaneous two gene detections at limit of detection of 1000 copies (equivalent to 2.01 fg) for L1 and 100 copies (0.0125 fg) for E6/E7, respectively. The assay was validated against urogenital and other pathogens, normal flora, and human control. In 130 real clinical sample tests, the assay demonstrated 100% specificity, 78% diagnostic accuracy, and 75% sensitivity compared with REBA HPV-ID test, and is much more rapid (15-40 min), less expensive (~ 3-4 USD/reaction) and does not require instrumentation (35-42 °C reaction condition so hand holding or tropical temperature is possible). Hence, the developed novel assay provides alternative screening tool for potential local screening. Furthermore, as this assay uses safe chemical reagents, it is safe for users.

Gaps in the Care of Subjects with Familial Hypercholesterolemia: Insights from the Thai Familial Hypercholesterolemia Registry.

AIMS: Familial hypercholesterolemia (FH) is currently underdiagnosed and undertreated. The establishment of a FH registry could facilitate a deeper understanding of this disease. We described the clinical characteristics of subjects with FH from the Thai FH Registry, compared our data with the regional and global data, and identified gaps in the care of these subjects. METHODS: A multicenter, nationwide prospective FH registry was established in Thailand. Our data were compared with those of the European Atherosclerosis Society-FH Studies Collaboration. Multiple logistic regression analyses were performed for variables associated with lipid-lowering medication (LLM) use and the attainment of low-density lipoprotein-cholesterol (LDL-C) goal. RESULTS: The study includes 472 subjects with FH (mean age at FH diagnosis: 46±12 years, 61.4% women). A history of premature coronary artery disease was found in 12%. The percentage of LLM use in subjects with a Dutch Lipid Clinic Network score of ≥ 6 (probable or definite FH) in our registry (64%) was slightly lower than the regional data but higher than the global data. Among those who received statins, 25.2% and 6.4% achieved LDL-C levels of ＜100 mg/dL and ＜70 mg/dL, respectively. Women with FH were less likely to achieve LDL-C ＜70 mg/dL (adjusted odds ratio: 0.22, 95% confidence interval: 0.06-0.71, p=0.012). CONCLUSIONS: FH in Thailand was diagnosed late, and treatment was inadequate for the majority of subjects. Women with FH were less likely to achieve LDL-C goals. Our insights could potentially help raise awareness and narrow the gap in patient care.

The Accuracy of Continuous Glucose Monitoring in the Medical Intensive Care Unit.

OBJECTIVE: To assess the accuracy of continuous glucose monitoring (CGM) in medical intensive care unit (MICU) patients. METHODS: A Medtronic Enlite® sensor accuracy was assessed versus capillary blood glucose (CBG) and plasma glucose (PG) using the mean absolute relative difference (MARD), surveillance error grid (SEG) analysis and modified Bland-Altman plots. RESULTS: Using CBG as a reference, MARD was 6.6%. Overall, 99.7% of the CGM readings were within the "no risk" zone. No significant differences in accuracy were seen within vasopressor subgroups. Using PG as the reference, MARD was 8.8%. The surveillance error grid analysis showed 95.2% of glucose readings were within the "no risk" zone. There were no device-related adverse events. CONCLUSION: The CGM sensor showed acceptable accuracy in MICU patients, regardless of vasopressor use.

Effects of intermittent very-low calorie diet on glycemic control and cardiovascular risk factors in obese patients with type 2 diabetes mellitus: A randomized controlled trial.

AIMS/INTRODUCTION: Very few studies assess the effectiveness of different protocols of intermittent very-low calorie diet (VLCD) in patients with diabetes. This study was designed to compare the effects of 2 days/week and 4 days/week of intermittent VLCD on glycemic control, diabetes remission, metabolic parameters and quality of life in patients with type 2 diabetes and obesity. MATERIALS AND METHODS: Participants with obesity and type 2 diabetes were recruited and randomly assigned to three groups, consisting of control, 2 days/week and 4 days/week of intermittent VLCD. In the intermittent VLCD groups, participants received a 600-kcal diet per day on restricted days and ad libitum food consumption on non-restricted days. Glycemic control, rate of diabetes remission, metabolic parameters and quality of life were evaluated at baseline, weeks 2, 10 and 20. RESULTS: A total of 40 participants were enrolled. The mean body mass index was 30.1 ± 5.9 kg/m2 , and the mean glycated hemoglobin was 7.4 ± 1.2%. At week 20, there was an improvement in glycemic control in both intermittent VLCD groups with significant decreases in glycated hemoglobin levels and insulin resistance index throughout the study periods. Diabetes remission without the need for medications was equally found in 29% of participants in both intermittent VLCD groups. Serum triglyceride, bodyweight, body mass index and fat mass were also significantly decreased in both VLCD groups. No serious adverse events were encountered. CONCLUSION: Intermittent VLCD was highly effective in achieving optimal glycemic control. The effects of 2 days/week and 4 days/week of intermittent VLCD on diabetes remission were relatively similar.

ANGPTL3 and ANGPTL8 in Thai subjects with hyperalphalipoproteinemia and severe hypertriglyceridemia.

BACKGROUND: The role of ANGPTL3 and ANGPTL8 in lipid regulation in patients with very high levels of HDL-cholesterol and triglyceride is unknown. OBJECTIVE: We examined plasma levels of ANGPTL3 and ANGPTL8 in subjects with hyperalphalipoproteinemia (HALP) and in those with severe hypertriglyceridemia (HTG). METHODS: Plasma ANGPTL3 and ANGPTL8 levels were measured by ELISA in 320 subjects, consisting of HALP subjects with HDL-cholesterol ≥100 mg/dl (n=90) and healthy controls (n=90) and subjects with triglyceride ≥886 mg/dl (n=89) and control subjects (n=51). RESULTS: The mean plasma ANGPTL3 level was significantly higher in the HALP group compared to that of the controls (297 ± 112 ng/mL vs. 230 ± 100 ng/mL, p<0.001). Similarly, the mean plasma ANGPTL8 level was also higher in the HALP group (30 ± 11 ng/mL vs. 20 ± 8 ng/mL, p<0.001). Both ANGPTL3 and ANGPTL8 levels positively correlated with HDL-cholesterol levels. In the severe HTG group, plasma ANGPTL3 level was significantly higher than those in the control group (223 ± 105 ng/mL vs. 151 ± 60 ng/mL, p<0.001), but not ANGPTL8 (23 ± 20 ng/mL vs. 31 ± 23 ng/mL in controls, p=0.028). Only ANGPTL3, but not ANGPTL8, levels positively correlated with triglyceride levels. CONCLUSION: Plasma level of ANGPTL3 was increased in both HALP and severe HTG whereas an increase in plasma level of ANGPTL8 was found only in HALP, and not in severe HTG, suggesting that both ANGPTL3 and ANGPTL8 might play distinct roles in lipid regulation on these two extremes of dyslipidemia.

Comparison of Point-of-Care Testing and Hospital-Based Methods in Screening for Potential Type 2 Diabetes Mellitus and Abnormal Glucose Regulation in a Dental Setting.

This study aimed to compare the screening methods between point-of-care (POC) testing and hospital-based methods for potential type 2 DM and abnormal glucose regulation (AGR) in a dental setting. A total of 274 consecutive subjects who attended the Faculty of Dentistry, Mahidol University, Bangkok, Thailand, were selected. Demographic data were collected. HbA1c was assessed using a finger prick blood sample and analyzed with a point-of-care (POC) testing machine (DCA Vantage®). Hyperglycemia was defined as POC HbA1c ≥ 5.7%. Random blood glucose (RBG) was also evaluated using a glucometer (OneTouch® SelectSimple™) and hyperglycemia was defined as RBG ≥ 110 mg/dl or ≥140 mg/dl. The subjects were then sent for laboratory measurements for fasting plasma glucose (FPG) and HbA1c. The prevalence of AGR (defined as FPG ≥ 100 mg/dl or laboratory HbA1c ≥ 5.7%) and potential type 2 DM (defined as FPG ≥ 126 mg/dl or laboratory HbA1c ≥ 6.5%) among subjects was calculated and receiver operating characteristic (ROC) analysis was performed using FPG and HbA1c for the diagnosis of AGR and potential type 2 DM. The prevalence of hyperglycemia defined as POC HbA1c ≥ 5.7%, RBG ≥ 110 mg/dl, and RBG ≥ 140 mg/dl was 49%, 63%, and 32%, respectively. After the evaluation using laboratory measurements, the prevalence of AGR was 25% and 17% using laboratory FPG and HbA1c criteria, respectively. Based on the ROC curves, the performances of POC HbA1c and RBG in predicting FPG-defined potential type 2 DM were high (AUC = 0.99; 95% CI 0.98-0.99 and AUC = 0.94; 95% CI 0.86-1.0, respectively) but lower in predicting AGR (AUC = 0.72; 95% CI 0.67-0.78 and AUC = 0.65; 95% CI 0.59-0.70, respectively). This study suggested that POC testing might be a potential tool for screening of subjects with potential type 2 DM in a dental setting.

Erratum: Suwattipong et al. Comparison of Point-of-Care Testing and Hospital-Based Methods in Screening for Potential Type 2 Diabetes Mellitus and Abnormal Glucose Regulation in a Dental Setting. Int. J. Environ. Res. Public Health 2021, 18, 6459.

In the original article [...].

Genetic and functional studies of the LMF1 gene in Thai patients with severe hypertriglyceridemia.

Severe hypertriglyceridemia (HTG) due to chylomicronemia is associated with acute pancreatitis and is related to genetic disturbances in several proteins involved in triglyceride (TG) metabolism. Lipase maturation factor 1 (LMF1) is a protein essential for the maturation of lipoprotein lipase (LPL). In this study, we examined the genetic spectrum of the LMF1 gene among subjects with severe HTG and investigated the functional significance of 6 genetic variants in vitro. All 11 exons of the LMF1 gene were sequenced in 101 Thai subjects with severe HTG. For an in vitro study, we performed site-directed mutagenesis, transient expression in cld cells, and measured LPL protein and LPL activity. We identified 2 common variants [p.(Gly36Asp) and p.(Pro562Arg)] and 12 rare variants [p.(Thr143Met), p.(Asn249Ser), p.(Ala287Val), p.(Met346Val), p.(Thr395Ile), p.(Gly410Arg), p.(Asp433Asn), p.(Asp491Asn), p.(Asn501Tyr), p.(Ala504Val), p.(Arg523His), and p.(Leu563Arg)] in 29 patients. In vitro study of the p.(Gly36Asp), p.(Asn249Ser), p.(Ala287Val), p.(Asn501Tyr), p.(Pro562Arg) and p.(Leu563Arg) variants, however, revealed that both LPL mass and LPL activity in each of the transfected cells were not significantly different from those in the wild type LMF1 transfected cells, suggesting that these variants might not play a significant role in severe HTG phenotype in our subjects.

Salivary and serum interleukin-17A and interleukin-18 levels in patients with type 2 diabetes mellitus with and without periodontitis.

OBJECTIVE: Interleukin (IL)-17A and IL-18 have been proposed to play important roles in periodontitis and type 2 diabetes mellitus (DM), but human data are conflicting. The present study aimed to investigate the roles of IL-17A and IL-18 in periodontitis and DM by measuring salivary and serum levels, respectively. MATERIALS AND METHODS: A total of 49 participants with type 2 DM and 25 control subjects without type 2 DM were recruited. A periodontal screening and recording (PSR) index (0, 1-2, 3, and 4) was used to classify whether these subjects had periodontitis. Salivary and serum IL-17A and IL-18 levels were measured by enzyme-linked immunosorbent assay. Multiple linear regression analyses were used to evaluate the associations between these cytokines and clinical parameters. RESULTS: Salivary IL-17A levels were not significantly different between patients with DM and controls, however, the levels were significantly higher in controls with periodontitis than those without periodontitis (p = 0.031). Salivary IL-17A levels were significantly associated with the PSR index (ß = 0.369, p = 0.011). Multiple linear regression analyses revealed the association of salivary IL-18 levels and fasting plasma glucose (ß = 0.270, p = 0.022) whereas serum IL-18 levels were associated with HbA1C (ß = 0.293, p = 0.017). No correlation between salivary and serum levels of IL-17A and IL-18 was found. CONCLUSION: Salivary IL-17A was strongly associated with periodontitis, whereas salivary IL-18 was associated with FPG and serum IL-18 was associated with HbA1C. These results suggest the role of these cytokines in periodontal inflammation and DM.

Whole exome sequencing for diagnosis of hereditary thrombocytopenia.

Hereditary thrombocytopenia comprises extremely diverse diseases that are difficult to diagnose by phenotypes alone. Definite diagnoses are helpful for patient (Pt) management.To evaluate the role of whole exome sequencing (WES) in these Pts.Cases with unexplained long-standing thrombocytopenia and/or suggestive features were enrolled to the observational study. Bleeding scores and blood smear were evaluated. The variant pathogenicity from WES was determined by bioinformatics combined with all other information including platelet aggregometry, flow cytometry, and electron microscopy (EM).Seven unrelated Pts were recruited. All were female with macrothrombocytopenia. Clinical bleeding was presented in four Pts; extra-hematological features were minimal and family history was negative in every Pt. WES successfully identified all the 11 responsible mutant alleles; of these, four have never been previously reported. Pt 1 with GNE-related thrombocytopenia showed reduced lectin binding by flow cytometry, increased glycogen granules by EM and a novel homozygous mutation in GNE. Pts 2 and 3 had phenotypic diagnoses of Bernard Soulier syndrome and novel homozygous mutations in GP1BB and GP1BA, respectively. Pt 4 had impaired microtubule structures, concomitant delta storage pool disease by EM and a novel heterozygous TUBB1 mutation. Pt 5 had sitosterolemia showing platelets with reduced ristocetin responses and a dilated membrane system on EM with compound heterozygous ABCG5 mutations. Pts 6 and 7 had MYH9 disorders with heterozygous mutations in MYH9.This study substantiates the benefits of WES in identifying underlying mutations of macrothrombocytopenia, expands mutational spectra of four genes, and provides detailed clinical features for further phenotype-genotype correlations.

Pharmacokinetic and the effect of capsaicin in Capsicum frutescens on decreasing plasma glucose level.

BACKGROUND: The active substance found in Capsicum frutescens (capsicum) that gives hot and spicy flavor is capsaicin, and it seems to have many pharmacological effects. OBJECTIVE: The present research was conducted to study the effect of capsicum on plasma glucose level and to correlate its action with the pharmacokinetic properties of capsaicin in capsicum. MATERIAL AND METHOD: The crossover study was performed in 12 healthy volunteers by performing the OGTT while receiving placebo or 5 grams of capsicum. The insulin secretion and capsaicin level in plasma were measured using the HPLC method. RESULTS: The results of the OGTT showed that plasma glucose levels in volunteers who received capsicum were significantly lower than those in the placebo group at 30 and 45 minutes (p < 0.05). Furthermore, plasma insulin levels were significantly higher at 60, 75, 105, and 120 minutes (p < 0.05). When comparing before and after capsicum intake, the results showed the insulin levels were maintained The pharmacokinetic parameters of capsaicin shown as C(max), T(max), AUC(0-t), T1/2 are 2.47 +/- 0.13 ng/ml, 47.08 +/- 1.99 min, 103.6 +/- 11.3 ng x min/ml, and 24.87 +/- 4.97 min, respectively. CONCLUSION: In conclusion, the present study found that 5 grams of capsicum presented capsaicin levels that were associated with a decrease in plasma glucose levels and the maintenance of insulin levels. The present result might have clinical implications in the management of type 2 diabetes.

Xerostomia, hyposalivation, and oral microbiota in type 2 diabetic patients: a preliminary study.

BACKGROUND AND OBJECTIVE: Mouth dryness is one of the major problems that can lead to several oral diseases such as dental caries, periodontitis and oral infection. Mouth dryness has also been associated with type 2 diabetes mellitus (DM). The objective of the present study was to investigate the prevalence of xerostomia (feeling of mouth dryness), hyposalivation (the reduction of saliva), and oral microbiota in Thai patients with type 2 DM. MATERIAL AND METHOD: One hundred and fifty-four ambulatory patients with type 2 DM and 50 non-diabetic control subjects were interviewed for symptoms of xerostomia. The medical records of these subjects were reviewed for pertinent medical history and laboratory investigations regarding their diabetic control. Oral examination and measurement of hyposalivation using a modified Schirmer test (MST) were performed The presence of oral microbial flora was investigated using a modified dip-slide test. RESULTS: The prevalence of xerostomia was 62% in patients with type 2 DM compared with 36% in the nondiabetic control group (p = 0.001). The prevalence of hyposalivation (defined as MST values < or = 25 mm at 3 min) was 46% in the patient group, whereas only 28% of the control group had hyposalivation (p = 0.03). Patients with hyposalivation had significantly higher numbers of mutans streptococci, Lactobacillus spp., and Candida spp. in the saliva compared with those without hyposalivation. CONCLUSION: These results suggested that xerostomia and hyposalivation were prevalent in patients with type 2 DM and were associated with higher numbers of oral pathogens in the saliva.

Immediate and long-term effects of a very-low-calorie diet on diabetes remission and glycemic control in obese Thai patients with type 2 diabetes mellitus.

AIM: A very-low-calorie diet (VLCD) can reverse the underlying defects of type 2 diabetes mellitus (DM) in obese subjects. We determined the efficacy, safety, and durability of VLCD in Thai patients with DM and obesity. METHODS: Twenty Thai patients with DM and obesity were enrolled. After a 2-week trial, VLCD (600 kcal/day) was continued for 8 weeks, followed by a 4-week transition period. Data on diabetes remission (fasting plasma glucose level <126 mg/dl and HbA1c <6.5% without the use of glucose-lowering medications), glycemic control, metabolic parameters, and quality of life (QOL) were collected along with indices of insulin resistance (IR) and beta cell function. Glycemic control 12 months after discontinuation of VLCD was also examined. RESULTS: Among 19 patients (age 48 ± 2 years, BMI 27.7 kg/m2) who completed the study, rapid improvement in glycemic control was observed in the first 2 weeks of VLCD. At both 8 and 12 weeks, diabetes remission was achieved in 79%. Significant weight loss was accompanied by a significant reduction in IR and an increase in beta cell function, starting at 4 weeks of VLCD. QOL also significantly increased. At 12 months after VLCD, however, DM remission was achieved in approximately 30%. CONCLUSION: Very-low-calorie diet was effective and safe in inducing short-term diabetes remission in Thai subjects by ameliorating beta cell function and IR. Optimal long-term glycemic control was potentially durable as one-third of subjects remained without diabetes medication 12 months after VLCD.

Salivary and serum cystatin SA levels in patients with type 2 diabetes mellitus or diabetic nephropathy.

OBJECTIVE: To investigate putative salivary biomarkers for screening and diagnosis of type 2 diabetes mellitus and diabetic nephropathy. DESIGN: Saliva and serum samples were collected from 29 patients with type 2 diabetes, 20 patients with diabetic nephropathy, eight patients with non-diabetic induced nephropathy, and 25 healthy subjects. Initially, pooled unstimulated saliva samples from six sex- and age-matched healthy subjects and six patients with type 2 diabetes were subjected to two-dimensional gel electrophoresis, followed by mass spectrometry. Protein expression of cystatin SA in the saliva of patients with type 2 diabetes was further examined in saliva and serum using enzyme-linked immunosorbent assay (ELISA). RESULTS: Two-dimensional gel electrophoresis revealed upregulation of salivary cystatin SA in patients with type 2 diabetes. ELISA showed a weak trend of increasing salivary cystatin SA levels in patients with type 2 diabetes, compared with those levels in healthy subjects. When patients were stratified according to periodontal status, linear regression analyses revealed that salivary cystatin SA levels were associated with Periodontal Screening and Recording (PSR) index (ß = 0.297, p < 0.05) when the analysis was adjusted for age, sex, HbA1C, estimated glomerular filtration rate (eGFR), and number of teeth. Serum cystatin SA levels were negatively associated with eGFR (ß = -0.534, p < 0.0001) when the analysis was adjusted for age, sex, HbA1C, number of teeth, and PSR index. CONCLUSIONS: Salivary cystatin SA was associated with periodontal disease severity; moreover, serum cystatin SA levels could reflect kidney function.

A novel germline mutation, IVS4+1G>A, of the POU1F1 gene underlying combined pituitary hormone deficiency.

BACKGROUND: POU1F1 is a pituitary transcription factor that plays a pivotal role in pituitary development and expression of the GH, PRL and TSH beta genes. Therefore, abnormalities of the POU1F1 gene are known to be responsible for a phenotype causing combined pituitary hormone deficiency (CPHD) involving growth hormone, prolactin and thyrotropin. METHODS: We described an 18-year-old Thai man, from a consanguineous family, who presented with short stature and cognitive deficit. He underwent endocrinological and molecular investigations. RESULTS: Hormonal studies showed that the patient had GH deficiency and secondary hypothyroidism, consistent with CPHD. Direct DNA sequencing revealed a novel homozygous mutation at the splice site of exon 4, IVS4+1G>A. It is the first splice site mutation in the POU1F1 gene described to date. Of the 7 other family members studied for this mutation by restriction enzyme digestions, 5 were heterozygous. They were all unaffected, suggesting a recessive pattern of inheritance. CONCLUSIONS: We described a novel POU1F1 splice site mutation, IVS4+1G>A, the first of its kind, in a Thai patient with CPHD. Recessive inheritance is suggested. We also noted preventable morbidities which resulted from delay in diagnosis of concomitant pituitary hormone defects in newborns suspected of CPHD.