Apiradee Sriwijitkamol

Advances in the development of AMPK-activating compounds

Background: AMP-activated protein kinase (AMPK) is an energy sensing enzyme that controls glucose and lipid metabolism. Objective: This review summarizes the present data on AMPK as a pharmacologic target for the treatment of metabolic disorders. Methods: The mechanisms governing AMPK activity and how this enzyme controls different metabolic pathways are reviewed briefly, and details about the effect that AMPK activators have on glucose metabolism are provided. Conclusion: Evidence obtained using the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) suggests that AMPK promotes glucose transport into skeletal muscles and that this enzyme inhibits hepatic glucose production. AICAR also induces fatty acid oxidation in muscle and inhibits cholesterol synthesis in the liver. The metabolic effects of AICAR on glucose and lipid metabolism indicate that AMPK may be a good pharmacologic target for the treatment of type 2 diabetes and hypercholesterolemia. Novel AMPK-specific compounds are allowing researchers to examine whether this enzyme is a useful pharmacologic target for the treatment of human disease and whether chronic activation of AMPK will be safe.

Hyperglycemia and glycemic variability are associated with the severity of sepsis in nondiabetic subjects

Purpose: The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. Methods: Nondiabetic sepsis inpatients and healthy controls received a 72‐hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post–oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis‐related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and <9 were compared. Results: Thirty nondiabetic sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV24h were higher in patients with SOFA ≥9 than in patients with SOFA <9 (MGL24h 195 ± 17 vs 139 ± 27, P < .001; SD24h 32 [28, 36] vs 19 [5, 58], P = .02; and MAGE24h 94 [58, 153] vs 54 [16, 179], P = .01). Conclusion: Nondiabetic sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV24h were associated with sepsis severity. HighlightsTo evaluate glucose variability from continuous glucose monitoring in sepsis without diabetes mellitus.The nondiabetic sepsis patients had higher glucose variability than the control group.Glucose variability during first 24 hours was associated with severity of sepsis.

Withdrawal of sulfonylureas from patients with type 2 diabetes receiving long-term sulfonylurea and insulin combination therapy results in deterioration of glycemic control: a randomized controlled trial

Background The benefit of sulfonylureas (SUs) to patients with type 2 diabetes mellitus receiving long-term insulin treatment is unclear. This study evaluated glycemic control and beta-cell function after SU withdrawal in these patients. Methods In this 8-week randomized controlled study, patients with type 2 diabetes who had been treated with insulin for at least 3 years plus moderate to high doses of SUs were randomly assigned to withdrawal (n=16) or continuation (n=16) of SUs. Clinical characteristics, glycemic control, hypoglycemic events, and insulin secretion, including homeostasis model assessment of beta-cell function (HOMA-B) score, C-peptide concentration, and Matsuda index, were evaluated at baseline and after 2 and 8 weeks. Results Thirty patients (16 in the SU withdrawal group and 14 in the SU continuation group) completed the study. Median duration of diabetes was 17 (range 5–40) years. Baseline clinical characteristics, glycemic control, and HOMA-B were similar in the two groups, but the mean fasting C-peptide concentration was higher in the SU withdrawal group. After 8 weeks, the SU withdrawal group showed a significant increase in mean glycosylated hemoglobin levels from 7.8%±0.5% (62±5 mmol/mol) to 8.6%±1.2% (71±13 mmol/mol; P=0.002), whereas the SU continuation group showed a slight but not significant increase from 7.7%±0.5% (61±5 mmol/mol) to 7.9%±1.2% (63±13 mmol/mol; P=0.37). Insulin secretion, as measured by C-peptide and HOMA-B, decreased by 18% and 36%, respectively, in the SU withdrawal group. Hypoglycemic events were significantly more frequent in the SU continuation group whereas body weight did not change significantly in either group. Conclusion Withdrawal of SU from patients with type 2 diabetes receiving long-term combination treatment with SU and insulin resulted in deterioration of glycemic control and insulin secretion.

Decreased health-related quality of life in patients with diabetic foot problems

Purpose The aim of this study was to investigate health-related quality of life (HRQoL) in patients with diabetic foot problems and compare the HRQoL between diabetic patients with: 1) diabetic foot problems (DF), including diabetic foot ulcer (DFU) or amputation (AMPU); 2) other diabetic complications (COM), such as diabetic retinopathy (DR), end-stage renal disease (ESRD), or coronary artery disease (CAD); and 3) no diabetic complication (CON). Patients and methods A total of 254 diabetic patients were studied in a cross-sectional setting. HRQoL was evaluated using Thai version of the Euro Quality of Life Questionnaire (EuroQoL), with five dimensions and five-level scale (EQ-5D-5L). Utility scores were calculated using time trade-off methods. Results A total of 141 patients in the DF group (98 DFU and 43 AMPU groups), 82 in the COM group (27 DR, 28 ESRD, and 27 CAD groups), and 31 in the CON group were interviewed. The mean age was 63.2±12.1 years, body mass index was 24.9±4.7 kg/m2, mean hemoglobin A1c was 7.7±2.1%, duration of diabetes was 13.1±9.9 years, and the mean utility scores were 0.799±0.25. After having DF, 21% of patients had lost their jobs. The COM group had lower utility scores than the CON group. Among the diabetic complications, the DF group had the lowest mean utility scores as compared to the COM and CON groups (0.703±0.28 in the DF group, 0.903±0.15 in the COM group, and 0.961±0.06 in the CON group, P<0.01). There was no difference in the mean utility scores between DFU and AMPU groups. Patients in the DF group reported moderate-to-severe problem in all dimensions more than the other groups. Conclusion DF have the greatest negative impact on HRQoL. Therefore, diabetic foot care should be emphasized in clinical practice to prevent foot complications.

Effect of Moringa oleifera Leaf Capsules on Glycemic Control in Therapy-Naïve Type 2 Diabetes Patients: A Randomized Placebo Controlled Study

Background Studies showed effects of Moringa oleifera (MO) on lowering blood sugar levels in animal and diabetes patients. The aims of this study were to determine the effect of MO leaf capsules on glucose control in therapy-naïve type 2 diabetes mellitus (T2DM) and to evaluate its safety. Method This was a prospective randomized placebo controlled study. Therapy-naïve T2DM was randomly assigned to receive either 8 grams per day of MO leaf capsules (MO leaf group) or placebo for 4 weeks. Clinical and laboratory characteristics were recorded at screening and at the end of 4-week study. 9-point plasma glucose was obtained before and every week during the study. Results Thirty-two T2DM patients were enrolled. The mean age was 55 years and the mean HbA1C was 7.0%. There was no significant difference in FPG and HbA1C between groups. MO leaf group had SBP reduction by 5 mmHg as compared to baseline but this difference had no statistical significance. There were no adverse effects of MO leaf. Conclusions Moringa oleifera leaf had no effect on glycemic control and no adverse effects in T2DM. Interestingly, this study demonstrated that MO leaf had a tendency on blood pressure reduction in T2DM, and this result needs further investigation.

Langerhans Cell Histiocytosis: A Rare Cause of Central Diabetes Insipidus

Objective: To report adult patients with Langerhans cell histiocytosis who presented with a recent onset of polyuria, secondary amenorrhea and galactorrhea. Methods: We report the clinical presentations, laboratory test results, imaging findings, histological findings and clinical courses of two cases of adult Langerhans cell histiocytosis. Results: Our evaluation revealed the presence of central diabetes insipidus. Magnetic resonance imaging of the pituitary showed a thickening of the pituitary stalk. The skeleton survey, chest radiography and biochemistry revealed an osteolytic lesion at the frontal bone only in the first case; the other case was within normal limits. A biopsy was performed at the frontal bone in the first case and at the pituitary stalk in the other case. The pathologic examination confirmed the diagnosis of Langerhans cell histiocytosis. Replacement therapy with an intranasal administration of desmopressin can resolve symptoms. The stalk lesion decreased in size without specific treatment. Conclusions: We reported two cases of adult Langerhans cell histiocytosis. These patients presented with central diabetes insipidus and galactorrhea. Both MRI findings revealed a unifocal infiltration of the infundibulum. The pathologic examination confirmed the diagnosis of Langerhans cell histiocytosis. Replacement therapy with an intranasal administration of desmopressin helped resolve symptoms. The stalk lesion decreased in size without specific treatment. Long-term follow up with proper supplementation to correct hormonal deficiencies may be the proper management in patients with isolated sellar or bone involvement that frequently experience a slower progression of the disease.

Correlation Between Third Trimester Glycemic Variability in Non-Insulin-Dependent Gestational Diabetes Mellitus and Adverse Pregnancy and Fetal Outcomes:

Background: Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic complication. Despite optimal glycemic control from self-monitoring blood glucose (SMBG) in non-insulin-dependent GDM, variations in pregnancy outcomes persist. Glycemic variability is believed to be a factor that causes adverse pregnancy outcomes. Continuous glucose monitoring system (CGMS) detects interstitial glucose values every 5 minutes, and glycemic variability data from CGMS during the third trimester may be a predictor of fetal birth weight and pregnancy outcomes. The aim of this study was to investigate correlation between third trimester glycemic variability in non-insulin-dependent GDM and fetal birth weight. Method: This prospective study was conducted in 55 pregnant volunteers with non-insulin-dependent GDM that were recruited at 28 to 32 weeks’ gestation from the outpatient clinic of the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital during the study period of August 1 to December 31, 2016. Patients had CGMS installed for at least 72 hours and glycemic variability data were analyzed. Results: Of 55 enrolled volunteers, the data from 47 women were included in the analysis. Mean CGMS duration was 85.5 ± 12.83 hours. No statistically significant correlation was identified between glycemic variability in third trimester and birth weight percentiles, or between third trimester CGMS parameters and pregnancy outcomes in the study. Conclusion: Based on these findings, third trimester glycemic variability data from CGMS are not a predictor of fetal birth weight percentile, and no significant association was found between CGMS parameters and adverse pregnancy outcomes; thus, CGMS is not necessary in non-insulin-dependent GDM.

High prevalence of diabetes and abnormal glucose tolerance in Thai women with previous gestational diabetes mellitus

Highlights • Eighty-one percent of pGDM women developed AGT within 4 years after delivery.• First risk factors for AGT was PG ≥ 150 mg/dl at 1 h after a 50 g-GCT.• Second risk factors was ≥3 abnormal PG values in a 100 g-OGTT.

Rare Cause of Recurrent Hypoglycemia: Insulin Autoimmune Syndrome

We report a case of insulin autoimmune syndrome associated with several autoantibodies, presenting with recurrent hypoglycemia, predominantly in the postprandial period, which improved by dietary management and spontaneously resolved within two months. Differentiation from other causes of hyperinsulinemic hypoglycemia, such as insulinoma, is important to avoid unnecessary invasive procedures or surgical interventions. The 75-gram oral glucose tolerance test (OGTT) and mixed meal test showed a typical pattern, which may be useful indirect evidence of insulin autoimmune syndrome.