BACKGROUND: Even though several oral anti-diabetic drugs (OAD) with various modes of action are replacing sulfonylurea (SU), some patients seem to be dependent on SU for adequate glycemic control. Therefore, we evaluated the clinical characteristics of such patients. METHODS: We selected the patients with type 2 diabetes who met following criteria from 2009 to 2014 at Seoul National University Hospital: glycated hemoglobin (HbA1c) was maintained below 7.5% for at least 6 months under small dose of SU (glimepiride < or =2 mg/day or equivalent dose); after discontinuation of SU, HbA1c increased > or =1.2% within 3 months or > or =1.5% within 6 months; and after resuming SU, HbA1c reduction was > or =0.8% or reduction of fasting plasma glucose was > or =40 mg/dL within 3 months. Patients with impaired hepatic or renal function, and steroid users were excluded. RESULTS: Nineteen subjects were enrolled: after averaged 4.8+/-1.5 months of SU-free period, HbA1c increased from 6.7%+/-0.4% to 8.8%+/-0.8% even though adding other OAD such as gliptins. However, HbA1c decreased to 7.4%+/-0.7% after resuming SU within 2.4+/-0.8 months. There was no sexual predominance. Despite their old age (67+/-11 years) and long duration of diabetes (18+/-10 years), fasting C-peptide was relatively well-reserved (3.9+/-2.6 ng/mL), and nephropathy was not observed (albumin-creatinine ratio 21.2+/-16.6 mg/g and estimated glomerular filtration rate 75.8+/-18.0 mL/min/1.73 m2). Strong family history was also noted (73.7%). CONCLUSION: Despite hypoglycemia risk of SU, it seemed indispensable for a subset of patients with regard to insulin secretion. Genetic influences would be evaluated.
Blood Glucose ; C-Peptide ; Diabetes Mellitus ; Dipeptidyl-Peptidase IV Inhibitors ; Fasting ; Glomerular Filtration Rate ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Insulin ; Seoul

BACKGROUND: The current perception threshold (CPT) could be quantified by stimulating Abeta and C fibers at 2,000 and 5 Hz, respectively. C fibers play a role in the autonomic nervous system and are involved in temperature and pain sensation. We evaluated the usefulness of CPT for diagnosing distal polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) in diabetic patients. METHODS: The CPT was measured in the index finger (C7 level) and in the third toe (L5 level) in diabetic patients aged 30 to 69 years. We assessed DPN according to the neuropathy total symptom score-6 (NTSS-6) and 10-g monofilament pressure sensation. Subjects with a NTSS-6 >6 or with abnormal 10-g monofilament sensation were defined to have DPN. CAN was evaluated by spectral analysis of heart rate variability and by Ewing's traditional tests. RESULTS: The subjects with DPN had significantly higher CPT at all of the frequencies than the subjects without DPN (P<0.05). Abnormal 10-g monofilament sensation and NTSS-6 >6 could be most precisely predicted by CPT at 2,000 and 5 Hz, respectively. However, only 6.5% and 19.6% of subjects with DPN had an abnormal CPT at 2,000 Hz at the C7 and L5 levels. Although CPT at 5 Hz showed a negative correlation with the power of low and high frequency in the spectral analysis (P<0.05), only 16.7% of subjects with CAN exhibited an abnormal CPT at the same frequency. CONCLUSION: Although the CPT is significantly associated with neuropathic symptoms or signs corresponding to the nerve fiber stimulated, it provides little additional information compared with conventional evaluations.
Autonomic Nervous System ; Diabetes Mellitus* ; Diabetic Neuropathies* ; Fingers ; Heart Rate ; Humans ; Nerve Fibers ; Nerve Fibers, Unmyelinated ; Polyneuropathies ; Sensation ; Toes

BACKGROUND: A decrease in core body temperature caused by heat distribution depends on the anesthetic agent used. The purpose of this study is to investigate the effects of sevoflurane and propofol on core temperature during laparoscopic major abdominal surgery requiring pneumoperitoneum of more than 90 min. METHODS: Fifty adult patients undergoing laparoscopic major abdominal surgery were randomly assigned to either a sevoflurane group (n = 25) or a propofol group (n = 25). In the sevoflurane group, anesthesia was induced with propofol 2 mg/kg, remifentanil 1.0 microg/kg, and maintained with 0.8-2.0 vol% sevoflurane and 0.1-0.2 microg/kg/min remifentanil. In the propofol group, anesthesia was induced with the effect-site concentration of propofol of 5.0 microg/ml and remifentanil 4 ng/ml, and maintained with the effect-site concentration of propofol of 2-3.5 microg/ml and remifentanil 3-5 ng/ml. Core body temperature was measured with an esophageal stethoscope with a temperature sensor after the start of the pneumoperitoneum (baseline) and at 15-min intervals until completion of surgery. RESULTS: During the study period, core temperature was comparable between the two groups. When compared with baseline values, core temperatures in both groups were significantly decreased 45 min after pneumoperitoneum. CONCLUSIONS: This study demonstrated that in patients undergoing prolonged laparoscopic surgery, a decrease in core body temperature during sevoflurane-remifentanil anesthesia was not different than propofol-remifentanil anesthesia, and the incidence of hypothermia of the two groups did not differ.
Adult ; Anesthesia ; Body Temperature ; Hot Temperature ; Humans ; Hypothermia ; Incidence ; Laparoscopy ; Methyl Ethers ; Piperidines ; Pneumoperitoneum ; Propofol ; Stethoscopes

Background: Prevailing insulin regimens for glycemic control in hospitalized patients have changed over time. We aimed to determine whether the current basal-bolus insulin (BBI) regimen is superior to the previous insulin regimen, mainly comprising split-mixed insulin therapy. Methods: This was a single tertiary center, retrospective observational study that included non-critically ill patients with type 2 diabetes mellitus who were treated with split-mixed insulin regimens from 2004 to 2007 (period 1) and with BBI from 2008 to 2018 (period 2). Patients from each period were analyzed after propensity score matching. The mean difference in glucose levels and the achievement of fasting and preprandial glycemic targets by day 6 of admission were assessed. The total daily insulin dose, incidence of hypoglycemia, and length of hospital stay were also evaluated. Results: Among 244 patients from each period, both fasting glucose (estimated mean±standard error, 147.4±3.1 mg/dL vs. 129.4±3.2 mg/dL, P<0.001, day 6) and preprandial glucose (177.7±2.8 mg/dL vs. 152.8±2.8 mg/dL, P<0.001, day 6) were lower in period 2 than in period 1. By day 6 of hospital admission, 42.6% and 67.2% of patients achieved a preprandial glycemic target of <140 mg/dL in periods 1 and 2, respectively (relative risk, 2.00; 95% confidence interval, 1.54 to 2.59), without an increased incidence of hypoglycemia. Length of stay was shorter in period 2 (10.23±0.26 days vs. 8.70±0.26 days, P<0.001). Conclusion BBI improved glycemic control in a more efficacious manner than a split-mixed insulin regimen without increasing the risk of hypoglycemia in a hospital setting.

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in highfat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphateactivated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFDtreated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

BACKGROUND: The identification of a marker for hypoglycemia could help patients achieve strict glucose control with a lower risk of hypoglycemia. 1,5-Anhydro-D-glucitol (1,5-AG) reflects postprandial hyperglycemia in patients with well-controlled diabetes, which contributes to glycemic variability. Because glycemic variability is related to hypoglycemia, we aimed to evaluate the value of 1,5-AG as a marker of hypoglycemia. METHODS: We enrolled 18 adults with type 2 diabetes mellitus (T2DM) receiving insulin therapy and assessed the occurrence of hypoglycemia within a 3-month period. We measured 1,5-AG level, performed a survey to score the severity of hypoglycemia, and applied a continuous glucose monitoring system (CGMS). RESULTS: 1,5-AG was significantly lower in the high hypoglycemia-score group compared to the low-score group. Additionally, the duration of insulin treatment was significantly longer in the high-score group. Subsequent analyses were adjusted by the duration of insulin treatment and mean blood glucose, which was closely associated with both 1,5-AG level and hypoglycemia risk. In adjusted correlation analyses, 1,5-AG was negatively correlated with hypoglycemia score, area under the curve at 80 mg/dL, and low blood glucose index during CGMS (P=0.068, P=0.033, and P=0.060, respectively). CONCLUSION: 1,5-AG level was negatively associated with hypoglycemia score determined by recall and with documented hypoglycemia after adjusting for mean glucose and duration of insulin treatment. As a result, this level could be a marker of the risk of hypoglycemia in patients with well-controlled T2DM receiving insulin therapy.
Adult ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Glucose ; Humans ; Hyperglycemia ; Hypoglycemia* ; Insulin*

No abstract available.
Blood Glucose* ; Glucose*

Adipsic hypernatremia is a rare disorder of hypothalamic osmoreceptor dysfunction for thirst. It is frequently associated with a deficiency in antidiuretic hormone (ADH) release. We report the first case in Korea of adipsic hypernatremia combined with subnormal ADH response to osmotic stimuli without any demonstrable structural lesion. A 69-year-old woman was admitted to the hospital with general weakness. In a hypernatremic hyperosmolar state, she denied thirst and did not drink spontaneously. Her plasma ADH level was markedly subnormal but she had no large volume of dilute urine. Investigation of osmoregulation by infusion of hypertonic saline revealed adipsia and an absolute deficiency in antidiuretic hormone release, despite a serum osmolarity in excess of 321 mOsmol/kg. There was no structural lesion of the hypothalamus and no abnormal finding in hypothalamic-pituitary function. After diagnosis, she was treated successfully with intentional water intake alone.
Aged ; Female ; Humans ; Hypernatremia ; Hypothalamus ; Korea ; Osmolar Concentration ; Plasma ; Thirst ; Water-Electrolyte Balance

BACKGROUND: Subjects with normal glucose tolerance (NGT) who have a high 1-hour postload plasma glucose level (> or =155 mg/dL; NGT 1 hour-high) have been shown to be at higher risk for type 2 diabetes than subjects with NGT 1 hour-low postload plasma glucose level (<155 mg/dL). We compared beta-cell function in subjects with NGT 1 hour-high, NGT 1 hour-low, and impaired glucose tolerance (IGT). METHODS: We classified subjects into NGT 1 hour-low (n=149), NGT 1 hour-high (n=43), and IGT (n=52). The beta-cell function was assessed based on insulinogenic index (IGI), oral disposition index (DI), and insulin secretion-sensitivity index-2 (ISSI-2). RESULTS: Insulin sensitivity was comparable between the subjects with NGT 1 hour-high and NGT 1 hour-low. The beta-cell function with/without adjusting insulin sensitivity was significantly different among the three groups. The IGI (pmol/mmol) was 116.8+/-107.3 vs. 64.8+/-47.8 vs. 65.8+/-80.6 (P=0.141), oral DI was 3.5+/-4.2 vs. 1.8+/-1.4 vs. 1.8+/-3.1 (P<0.001), and ISSI-2 was 301.2+/-113.7 vs. 213.2+/-67.3 vs. 172.5+/-87.5 (P<0.001) in NGT 1 hour-low, NGT 1 hour-high, and IGT, respectively. Post hoc analyses revealed that oral DI and ISSI-2 were significantly different between NGT 1 hour-low and NGT 1 hour-high but comparable between NGT 1 hour-high and IGT. CONCLUSION: Among Korean subjects with NGT, those who have a higher 1-hour postload glucose level have a compromised insulin-sensitivity adjusted beta-cell function to a similar degree as IGT subjects.
Blood Glucose* ; Glucose Tolerance Test ; Glucose* ; Insulin ; Insulin Resistance

BACKGROUND: Alstrom syndrome and Bardet-Biedl syndrome are autosomal recessively inherited ciliopathies with common characteristics of obesity, diabetes, and blindness. Alstrom syndrome is caused by a mutation in the ALMS1 gene, and Bardet-Biedl syndrome is caused by mutations in BBS1-16 genes. Herein we report genetically confirmed cases of Alstrom syndrome and Bardet-Biedl syndrome in Korea using whole exome sequencing. METHODS: Exome capture was done using SureSelect Human All Exon Kit V4+UTRs (Agilent Technologies). HiSeq2000 system (Illumina) was used for massive parallel sequencing. Sanger sequencing was used for genotype confirmation and familial cosegregation analysis. RESULTS: A 21-year old Korean woman was clinically diagnosed with Alstrom syndrome. She had diabetes, blindness, obesity, severe insulin resistance, and hearing loss. Whole exome sequencing revealed a nonsense mutation in exon 10 of ALMS1 (c.8776C>T, p.R2926X) and a seven base-pair deletion resulting in frameshift mutation in exon 8 (c.6410_6416del, p.2137_2139del). A 24-year-old Korean man had Bardet-Biedl syndrome with diabetes, blindness, obesity, and a history of polydactyly. Whole exome sequencing revealed a nonsynonymous mutation in exon 11 of the BBS1 gene (c.1061A>G, p.E354G) and mutation at the normal splicing recognition site of exon 7 of the BBS1 gene (c.519-1G>T). CONCLUSION: We found novel compound heterozygous mutations of Alstrom syndrome and Bardet-Biedl syndrome using whole exome sequencing. The whole exome sequencing successfully identified novel genetic variants of ciliopathy-associated diabetes.
Alstrom Syndrome ; Bardet-Biedl Syndrome ; Blindness ; Codon, Nonsense ; Diabetes Mellitus ; Exome* ; Exons ; Female ; Frameshift Mutation ; Genotype ; Hearing Loss ; Humans ; Insulin Resistance ; Korea ; Obesity ; Obesity, Morbid ; Polydactyly ; Young Adult