Sodium-glucose cotransporter 2 inhibitors are antidiabetic drugs that increase urinary glucose excretion by inhibiting proximal tubular reabsorption of glucose in the kidney. Some sodium-glucose cotransporter 2 inhibitors have been shown to afford effective glycemic control and to decrease the risks of major adverse cardiovascular events. However, these drugs may increase the risk of diabetic ketoacidosis. This is a rare complication that occurs in less than 0.1% of treated patients with type 2 diabetes. The condition may be euglycemic, and is triggered by controllable precipitating factors such as surgery, infection, and insulin reduction or omission. It is important to understand individual patient profiles and to prevent diabetic ketoacidosis by appropriate prescribing, by withholding sodium-glucose cotransporter 2 inhibitors when indicated, and by counseling patients on sick day management.
Counseling ; Diabetic Ketoacidosis ; Glucose ; Humans ; Hypoglycemic Agents ; Insulin ; Ketone Bodies ; Ketosis* ; Kidney ; Precipitating Factors ; Sick Leave ; Sodium-Glucose Transporter 2

No abstract available.
Diabetes Mellitus, Type 2 ; Exercise ; Humans ; Insulin ; Insulin Resistance

BACKGROUND: Weight loss through low-calorie diets (LCDs) decreases visceral fat (VF). However, the effects on muscle mass, changes of dietary quality, and insulin sensitivity are unknown for Korean obese type 2 diabetic subjects. Therefore, this study examined such effects of LCDs. METHODS: A total of 30 obese type 2 diabetic subjects (body mass index, 27.0 +/- 2.2 kg/m2) were randomly assigned to an LCD or control group. Subjects on LCDs took 500~1,000 kcal fewer energy than their usual dietary intake (1,000~1,500 kcal/day) over the course of 12 weeks. The abdominal VF and femoral muscle mass were evaluated by computed tomography, and insulin sensitivity was assessed using an insulin tolerance test (Kitt; rate constant for plasma glucose disappearance, %/min). Dietary nutrient intake consumed by subjects was assessed by 3-day food records. RESULTS: The percent VF reduction was -23.4 +/- 17.2% in the LCD group and -9.8 +/- 11.8% in the control group after 12 weeks (P < 0.001, P = 0.002). However, significant decrease in femoral mass or proportional change of marcronutrient intake and mean adequacy ratio were not found in the LCD group, as compared to the control group. Insulin sensitivity improved in the LCD group, as compared to the control group (P = 0.040). CONCLUSION: LCD effectively improved insulin sensitivity and reduced abdominal VF without reduction of femoral muscle and dietary quality in obese type 2 diabetic subjects.
Caloric Restriction ; Diabetes Mellitus, Type 2 ; Glucose ; Insulin ; Insulin Resistance ; Intra-Abdominal Fat ; Muscles ; Plasma ; Weight Loss

BACKGROUND: Combination fitness regimens (including aerobic and resistance exercises) are effective for improving cardio-respiratory fitness, reducing visceral fat and increasing insulin sensitivity in diabetic patients. The combination exercise intensity that a patient is capable of is limited by his or her aerobic capacity and one repetition maximum (1RM). We investigated the relationships between 1RM, aerobic exercise capacity and body mass index in patients with type 2 diabetes. METHODS: A total of 177 (men: 85, women: 92) diabetic subjects with HbA1c < or = 10% were enrolled. Muscle strength and 1RM were assessed bychest press (upper body) and leg press (lower body). We assessed aerobic capacity by VO2max and muscle mass by bioimpedance analysis. RESULTS: There was no correlation between 1RM and VO2max in type 2 diabetic patients (upper: P = 0.122, lower: P = 0.138 for men, and upper: P = 0.952, lower: P = 0.570 for women). However, 1RM was significantly correlated with muscle mass both in men and women (upper: r = 0.493, P < 0.001, r = 0.315, P = 0.002 lower: r = 0.437 P < 0.001, r = 0.307, P =0.003, respectively). There was also a significant correlation between 1RM and BMI. In obese male subjects with BMI > or = 25 kg/m2, we observed a significant correlation between muscle mass and BMI (r = 0.374, P = 0.032), but this correlation was not observed in women. CONCLUSION: Clinicians treating Korean type 2 diabetic subjects should recommend resistance exercise to their patients. In particular, obese women with diabetes may receive greater benefits by increasing muscle mass through resistance exercises.
Body Mass Index ; Diabetes Mellitus ; Exercise ; Female ; Humans ; Insulin Resistance ; Intra-Abdominal Fat ; Leg ; Male ; Muscle Strength ; Muscles ; Resistance Training

BACKGROUND: Our goal was to investigate the effects of low intensity resistance training on body fat, muscle mass and strength, cardiovascular fitness, and insulin sensitivity in type 2 diabetes. METHODS: Twenty-eight overweight women with type 2 diabetes were randomly assigned to a resistance training group (RG, n = 13) or a control group (CG, n = 15). RG performed resistance training using elastic bands, of which strength was equal to 40 to 50% of one repetition maximum (1RM), for three days per week. Each exercise consisted of three sets for 60 minutes. We assessed abdominal fat using computed tomography, muscle mass using dual-energy X-ray absorptiometry, and muscle strength using Keiser's chest and leg press. Insulin sensitivity was measured using the insulin tolerance test, and aerobic capacity was expressed as oxygen uptake at the anaerobic threshold (AT-VO2) before and after the 12-week exercise program. RESULTS: The age of participants was 56.4 +/- 7.1 years, duration of diabetes was 5.9 +/- 5.5 years, and BMI was 27.4 +/- 2.5 kg/m2, without significant differences between two groups. During intervention, a greater increase in muscle mass and greater decreases in both total fat mass and abdominal fat were observed in RG compared to those of CG (P = 0.015, P = 0.011, P = 0.010, respectively). Increase in 1RM of upper and lower extremities was observed in the RG (P = 0.004, P = 0.040, respectively), without changes in AT-VO2 and insulin resistance in either group. CONCLUSION: In conclusion, the low intensity resistance training was effective in increasing muscle mass and strength and reducing total fat mass without change of insulin sensitivity in type 2 diabetic patients.
Abdominal Fat ; Absorptiometry, Photon ; Adipose Tissue ; Anaerobic Threshold ; Diabetes Mellitus, Type 2 ; Female ; Humans ; Insulin ; Insulin Resistance ; Leg ; Lower Extremity ; Muscle Strength ; Muscles ; Overweight ; Oxygen ; Resistance Training ; Thorax

BACKGROUND: It is difficult to improve muscle strength with only aerobic exercise training in type 2 diabetes patients. Resistance training is effective for improving muscle mass, muscle strength and insulin sensitivity. One repetition maxima (1RM), or the maximum amount of weight a subject can lift in a single repetition, may be a useful unit for evaluating the results of resistance training in type 2 diabetic patients. This study was aimed to assess baseline values for 1RM in a sample of Korean type 2 diabetes mellitus patients that are scaled for intensity and load of exercise, and to assess the relationship of 1RM to age. METHODS: A total of 266 (male: 95, female: 171) Korean patients with type 2 diabetes mellitus were included in the study sample. Maximal muscle strength was assessed by measuring 1RM for each subject (KEISER, Fresno, CA, USA). Two different exercises were used to measure 1RM: the chest press for the upper extremities, and the leg press for the lower extremities. RESULTS: Both upper and lower values of 1RM decreased with age in men and women; upper 1RM: r = -0.454, P<0.001 in men, r = -0.480, P< 0.001 in women, lower 1RM: r = -0.569, P<0.001 in men, and r = -0.452, P<0.001 in women. Values of 1RM significantly decreased in men only after the age of 70. In women, values of 1RM continuously decreased after the age of 60. CONCLUSION: The maximal muscle strength of individuals with type 2 diabetes decreases with age. We believe that resistance training is especially beneficial for type 2 diabetes mellitus patients after the sixth decade of life.
Diabetes Mellitus, Type 2 ; Exercise ; Female ; Humans ; Insulin Resistance ; Leg ; Male ; Muscle Strength ; Muscles ; Resistance Training ; Thorax ; Upper Extremity

BACKGROUND: Exercise offers protection against atherosclerosis and insulin resistance. We evaluated the benefits of exercise at different levels of intensity for ameliorating inflammation, endothelial dysfunction, and insulin resistance in a sample of type 2 diabetic subjects. METHODS: Fifty-nine overweight women with type 2 diabetes were randomly assigned to control (CG, N = 18), moderate-intensity exercise (MEG, N = 17), and vigorous-intensity exercise (VEG, N = 14) groups. Patients in the two experimental groups completed a 12-week exercise program, with their exercise activities monitored by accelerometers. We assessed the patients' body weights, total abdominal fat (TF), subcutaneous fat (SF) and visceral fat (VF) via computed tomography, measurements of plasma levels of hs-C-reactive protein (hs-CRP) and interleukin-6 (IL-6), assessment of endothelial function by brachial artery flow-mediated dilation (FMD), and evaluation of insulin sensitivity by insulin tolerance tests, at baseline, at the end of the 12-week interventions, and one year after initiation of the study. RESULTS: At baseline, the average age of all subjects was 54 +/- 7 years, and average body mass index (BMI) was 26.9 +/- 2.5 kg/m2. During the intervention, patients in the MEG and VEG groups expended comparable amounts of activity-related calories (488.6 +/- 111.9 kcal/day, 518.8 +/- 104.1 kcal/day, respectively). Although BMI, TF, and SF decreased similarly in the MEG and VEG groups (deltaBMI: -1.1 +/- 0.7, -0.8 +/- 0.5, deltaTF: -4,647 +/- 3,613 mm2, -2,577 +/- 2,872 mm2, deltaSF: -2,057 +/- 2,021 mm2, -1,141 +/- 1,825 mm2, respectively), compared to control (P<0.01), hs-CRP, IL-6, and FMD remained constant in both exercise groups even after completion of the 12-week exercise intervention. Insulin sensitivity improved only in patients subjected to vigorous exercise (VEG). Visceral fat loss was observed only in patients subjected to moderate exercise (MEG). At one-year follow up, these values had all returned to baseline. CONCLUSION: Exercise vigorous enough to result in significant weight and fat reduction did not ameliorate inflammation and endothelial dysfunction as measured at the end of a 12-week exercise intervention, nor did it result in sustained improvements in insulin sensitivity in type 2 diabetic subjects.
Abdominal Fat ; Atherosclerosis ; Body Mass Index ; Body Weight ; Brachial Artery ; Diabetes Mellitus, Type 2 ; Exercise ; Female ; Follow-Up Studies ; Humans ; Inflammation ; Insulin ; Insulin Resistance ; Interleukin-6 ; Intra-Abdominal Fat ; Overweight ; Plasma ; Subcutaneous Fat

BACKGROUND: Sulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic beta-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor gamma (PPARgamma), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARgamma transcriptional activity and on the glucose uptake via PPARgamma. METHODS: Transcription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARgamma transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 microM) were used as treatment, and rosiglitazone at 1 and 10 microM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARgamma were observed. In addition, 3T3-L1 adipocytes were treated with rosiglitazone (10 microM), glimepiride (100 microM) or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake. RESULTS: Sulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARgamma transcriptional activity, gliquidone being the most potent PPARgamma agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARgamma transcriptional activity and glucose uptake were reduced compared to those after treatment with rosiglitazone alone. This competitive effect of glimepiride was observed only at high concentrations that are not achieved with clinical doses. CONCLUSION: Sulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARgamma. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARgamma agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations.
Adipocytes ; Diabetes Mellitus, Type 2 ; Glipizide ; Glucose ; Insulin ; Insulin Resistance ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; PPAR gamma ; Receptors, Cytoplasmic and Nuclear ; Sulfonylurea Compounds ; Thiazolidinediones ; Transcriptional Activation

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene. To date, more than 1,000 germline and somatic mutations of the VHL gene have been reported. We present a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus. METHODS: A 30-year-old woman presented with gestational diabetes mellitus. She sequentially showed multiple pancreatic cysts, spinal cord hemangioblastoma, cerebellar hemangioblastoma, and clear cell type renal cell carcinomas. Also, her father and brother had brain hemangioblastomas. Each of the three exons of the VHL gene was individually amplified by polymerase chain reaction and direct sequencing was performed using an ABI 3730 DNA analyzer. RESULTS: DNA sequence analysis to determine the presence of VHL mutation in her family revealed del291C, a novel frameshift mutation. CONCLUSION: We found a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus.
Adult ; Brain ; Carcinoma, Renal Cell ; Diabetes, Gestational* ; DNA ; Exons ; Fathers ; Female ; Genes, Tumor Suppressor* ; Hemangioblastoma ; Humans ; Pancreatic Cyst ; Polymerase Chain Reaction ; Pregnancy ; Sequence Analysis, DNA ; Siblings ; Spinal Cord ; von Hippel-Lindau Disease

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene. To date, more than 1,000 germline and somatic mutations of the VHL gene have been reported. We present a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus. METHODS: A 30-year-old woman presented with gestational diabetes mellitus. She sequentially showed multiple pancreatic cysts, spinal cord hemangioblastoma, cerebellar hemangioblastoma, and clear cell type renal cell carcinomas. Also, her father and brother had brain hemangioblastomas. Each of the three exons of the VHL gene was individually amplified by polymerase chain reaction and direct sequencing was performed using an ABI 3730 DNA analyzer. RESULTS: DNA sequence analysis to determine the presence of VHL mutation in her family revealed del291C, a novel frameshift mutation. CONCLUSION: We found a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus.
Adult ; Brain ; Carcinoma, Renal Cell ; Diabetes, Gestational* ; DNA ; Exons ; Fathers ; Female ; Genes, Tumor Suppressor* ; Hemangioblastoma ; Humans ; Pancreatic Cyst ; Polymerase Chain Reaction ; Pregnancy ; Sequence Analysis, DNA ; Siblings ; Spinal Cord ; von Hippel-Lindau Disease