Insulin-like growth factor-1 deficiency caused by hepatocellular adenoma leads to growth arrest, primary amenorrhea and metabolic syndrome: a case report and 4 years follow up.

BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign neoplasm, seldom ascribed as the cause of endocrine and metabolic derangement. We herein report a case of primary amenorrhea, growth arrest and metabolic syndrome. En bloc resection of the tumor normalized all the disturbances. CASE PRESENTATION: A 16-year-old girl complained of primary amenorrhea and growth arrest for the past 2 years. Her height and weight were at the 3rd percentile, whereas waist circumference was at the 90th percentile for chronological age. She was hypertensive on admission. Plasma cholesterol, triglyceride and uric acid were elevated. Evaluation of GH/IGF-1 axis showed extremely low IGF-1 concentration, which was unresponsive to hGH stimulation. Computer tomography identified a huge liver mass (18.2 cm×13.7 cm×21 cm). The patient underwent an uneventful open right hepatic lobectomy. The tumor was en bloc resected. Immunohistochemistry indicated an unclassified HCA, which was confirmed by genetic screening. IGF-1 concentration, blood pressure, lipid profile and ovarian function were all normalized after surgery, and the girl had reduction in waist circumference and gain in height during the follow up. CONCLUSION: We provide evidence that liver-derived IGF-1 has a direct effect on skeletal and pubertal development, blood pressure, visceral adiposity and dyslipidemia independent of insulin resistance and obesity in the circumstance of undernutrition. Though rare, we propose the need to look into HCA cases for the existence of IGF-1 deficiency and its impact on metabolic derangement.

Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial.

OBJECTIVE: To evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia. DESIGN: Multicentre, open label, randomised trial. SETTING: 15 hospitals in China between December 2017 and December 2020. PARTICIPANTS: 412 patients with newly diagnosed type 2 diabetes and significant hyperglycaemia (HbA1c ≥8.5%). INTERVENTIONS: All randomised participants initially received SIIT for 2-3 weeks, followed by linagliptin 5 mg/day, metformin 1000 mg/day, combination linagliptin plus metformin, or lifestyle modification alone (control) for 48 weeks. MAIN OUTCOME MEASURES: The primary outcome was the percentage of participants achieving HbA1c <7.0% at week 48 after SIIT. Secondary outcomes included glycaemic control, ß cell function, and variations in insulin sensitivity. RESULTS: 412 participants were randomised. At baseline, the mean age was 46.8 (standard deviation 11.2) years, mean body mass index was 25.8 (2.9), and mean HbA1c was 11.0% (1.9%). At week 48, 80% (78/97), 72% (63/88), and 73% (69/95) of patients in the linagliptin plus metformin, linagliptin, and metformin groups, respectively, achieved HbA1c <7.0%, compared with 60% (56/93) in the control group (P=0.02 overall; P=0.003 for linagliptin plus metformin versus control; P=0.12 for linagliptin versus control; P=0.09 for metformin versus control). Additionally, 70% (68/97), 68% (60/88), and 68% (65/95) of patients in the linagliptin plus metformin, linagliptin, and metformin group, respectively, achieved HbA1c <6.5% compared with 48% (45/93) in the control group (P=0.005 overall; P=0.005 for linagliptin plus metformin versus control; P=0.01 for linagliptin versus control; P=0.008 for metformin versus control; all were significant after adjustment for multiple comparisons). Thus, compared with the control group, participants in the linagliptin plus metformin group were more likely to achieve HbA1c <7.0% at week 48 (odds ratio 2.78, 95% confidence interval 1.37 to 5.65; P=0.005). Moreover, the linagliptin plus metformin group showed the most significant improvement in fasting plasma glucose and ß cell function indices. All treatments were well tolerated. CONCLUSIONS: The intense simplified strategy using subsequent oral therapies post-SIIT, especially the linagliptin plus metformin combination, sustainably improved glycaemic control and ß cell function in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia. This approach offers a promising direction for decision making in the clinical management of type 2 diabetes mellitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT03194945.

Evaluating the role of time in range as a glycemic target during short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Tight glycemic control during short-term intensive insulin therapy (SIIT) is critical for inducing diabetes remission in patients with newly diagnosed type 2 diabetes (T2D). This work aimed to investigate the role of time in range (TIR) during SIIT as a novel glycemic target by predicting clinical outcomes. METHODS: SIIT was given to 116 patients with newly diagnosed T2D, with daily eight-point capillary glucose monitored. Glycemic targets (fasting/premeal glucose, 3.9-6.0 mmol/L; 2 h postprandial blood glucose, 3.9-7.8 mmol/L) were achieved and maintained for 2 weeks. TIRPIR was calculated as the percentage of glucose points within these glycemic targets during the maintenance period and was compared to TIR3.9-7.8mmol/L and TIR3.9-10.0mmol/L . Acute insulin response (AIR), HOMA-IR, HOMA-B, and disposition index (DI) were measured. Patients were followed up for 1 year to observe clinical outcomes. RESULTS: TIRPIR , TIR3.9-7.8mmol/L , and TIR3.9-10.0mmol/L were 67.2 ± 11.2%, 80.8 ± 9.2%, and 90.1 ± 6.2%, respectively. After SIIT, ß-cell function and insulin sensitivity improved remarkably, and the 1-year remission rate was 55.2%. △AIR and △DI were positively correlated with all the TIR values, whereas only TIRPIR was correlated with △HOMA-IR (r = -0.22, p = 0.03). Higher TIRPIR but not TIR3.9-7.8mmol/L or TIR3.9-10.0mmol/L was robustly associated with diabetes remission; patients in the lower TIRPIR tertile had an elevated risk of hyperglycemia relapse (hazard ratio 3.4, 95% confidence interval 1.6-7.2， p = .001). Only those with TIRPIR ≥ 65% had a one-year remission rate of over 60%. CONCLUSIONS: These findings advocate TIRPIR ≥ 65% as a novel glycemic target during SIIT for clinical decision-making.

Application of glycemic qualification rate based on fingerstick glucose monitoring in women with gestational diabetes mellitus.

OBJECTIVE: To explore the appropriate application of glycemic qualification rate (GQR) calculated by fingerstick blood glucose (BG) monitoring for patients with gestational diabetes mellitus (GDM) by analyzing the relationship between BG control and adverse pregnancy outcomes. METHODS: Fingerstick Blood Glucose data during the second and third trimester of singleton pregnant women diagnosed with GDM were collected. GQR which is defined as the percentage of fingerstick BG values reaching the targets of BG control in a period of time was calculated. Patients were divided into three groups according to tertiles (tertile 1, GQR <56.25%; tertile 2, GQR 56.25-75%; and tertile 3, GQR ≥75%). Pregnant outcomes were compared among the three groups. Univariate analysis and logistic regression were performed to analyze the potential relationship between GQR and pregnancy outcomes. Receiver operating characteristic (ROC) curves were calculated to determine the cutoff values. We also explored that whether twice or three times monitoring per day would be adequate for GQR calculation, so we brought in two or three glucose measuring times per day to explore the relationship between new GQR and adverse outcomes. RESULTS: A total of 311 patients diagnosed with GDM were analyzed. In univariate analysis, the incidences of cesarean section of tertile 1-3 groups were 61.4%, 58.7%, and 44.9%, respectively (p < .05). The incidences of neonatal hypoglycemia of tertiles 1-3 groups were 19.8%, 18.6%, and 8.7% (p < .05). The difference of composite outcomes was statistically significant (p = .001). After adjustment, the patients with worse BG control (lower GQR) had higher risk of cesarean section (tertile 1 - aOR = 2.029, 1.128-3.648), neonatal hypoglycemia (tertile 1: aOR = 2.498, 1.082-5.766) as well as composite outcomes. The ROC curve of GQR indicated the predictive value for neonatal hypoglycemia (area under the ROC curve (AUC) 0.612 (0.532-0.692)) and neonatal composite outcomes (AUC 0.593 (0.528-0.657)) with optimal cutoff values of 81.1% and 73.5%, respectively. We also explored that whether twice or three times monitoring per day would be adequate for GQR calculation. The result showed that GQR only calculated by FBG + 2hPG after lunch (2h AL) per day also had well relationship with cesarean section (tertile 1: OR = 2.412, 1.322-4.398), neonatal hypoglycemia (tertile 1: aOR = 4.497, 1.607-12.586), and neonatal composite outcomes (tertile 1: aOR = 1.959, 95% confidence interval (CI): 1.114-3.444, p = .020). CONCLUSIONS: The GQR calculated by the easily applicable fingerstick BG is related to occurrence of cesarean section and neonatal hypoglycemia in GDM women. GQR ≥ 80% is recommended for better pregnancy outcomes. As for the number of points monitoring per day, GQR calculated by FBG + 2h AL was an optimal option for better pregnancy outcomes if mothers needed to simplify the process of monitoring.

Validation of Controlled Attenuation Parameter Measured by FibroScan as a Novel Surrogate Marker for the Evaluation of Metabolic Derangement.

Background/Objectives: Renaming non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) suggests a shift of emphasis to the accompanying metabolic disturbance. Controlled attenuation parameter (CAP) measured by FibroScan has been shown to be correlated with hepatic steatosis. We aim to validate its usefulness as a novel surrogate marker for evaluating metabolic derangement. Subjects/Methods: Volunteers were recruited from medical staff at our hospital to undergo CAP measurements. Anthropometrics, CAP, and laboratory assessments for metabolic profiles and insulin resistance were collected. CAP < 238 dB/m denoted no hepatic steatosis, 238 ≤ CAP ≤ 259 dB/m denoted mild, 260 ≤ CAP ≤ 291 dB/m denoted moderate, and CAP > 291 dB/m denoted severe hepatic steatosis according to previous reports. Results: Data of 824 participants were included for analysis. The age was 53.2 ± 15.4 years, body mass index (BMI) was 23.6 ± 3.1 kg/m2, 24.4% were male subjects, and 22.0% met the criteria for metabolic syndrome (MetS). Taking the group with CAP < 238 dB/m as control, subjects with mild, moderate, and severe hepatic steatosis had increased odds of MetS by 3.51-, 3.32-, and 5.12-fold, respectively, after adjusting for multiple confounders (p = 0.020). Metabolic profiles, insulin resistance, and presence of MetS were similar between normal-weight subjects with CAP ≥ 238 dB/m and overweight subjects with CAP < 238 dB/m. Even in subjects with no MetS components, those with CAP ≥ 238 dB/m had higher BMI, waist circumferences, uric acid, triglyceride, white blood cell count, and insulin resistance, whereas lower adiponectin and estimated glomerular filtration rate. Waist circumference [OR 1.11 (1.04, 1.18), p = 0.001] and homeostatic model assessment of insulin resistance (HOMA-IR) [OR 2.39 (1.18, 4.83), p = 0.016] were predictive of hepatic steatosis according to CAP ≥ 238 dB/m. Conclusions: CAP is a convenient, sensitive, and non-invasive indicator for metabolic derangement. Prospective studies are needed to further validate its usefulness as a surrogate marker for the transition of metabolic status over time.

The Association between a 24-Hour Blood Pressure Pattern and Circadian Change in Plasma Aldosterone Concentration for Patients with Aldosterone-Producing Adenoma.

The absence of nocturnal blood pressure (BP) decline is associated with hypertensive complications. Data regarding circadian BP patterns in patients with aldosterone-producing adenoma (APA) are limited and equivocal. We evaluated the circadian BP profile in patients with APA and its relationship with the circadian aldosterone rhythm. BP in patients with APA and in those with essential hypertension (EH) were assessed through in-hospital 24-h ambulatory blood pressure monitoring. Over a 24-h in-hospital period, plasma aldosterone levels taken at midnight, 0400, 0800, 1200, 1600, and 2000 h were measured. To evaluate a correlation between BP and hormone rhythm, we included 27 patients with APA (APA group) and 27 patients with EH (EH group). Both groups had similar age, sex ratio, body mass index, duration of hypertension, family history of hypertension, and lipid profiles. The day-night BP differences in both patient groups were similar, whether expressed as absolute values or percentages. The proportions of patients with dipping BP profiles were also comparable (APA group, 5 of 27; EH group, 7 of 27; χ2 = 0.429; P = 0.513). At each time point, APA group plasma aldosterone concentrations (PACs) were higher than those of the EH group. A circadian change in relation to PAC was observed in both groups. A correlation between PAC and BP was statistically nonsignificant in most study patients in either group. Our data indicated that the circadian BP pattern was not associated with a change in PAC levels in patients with APA.

12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury.

Radiation enteropathy is a common complication in cancer patients following radiation therapy. Thus, there is a need for agents that can protect the intestinal epithelium against radiation. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to induce differentiation and/or apoptosis in multiple cell lines and primary cells. In the current report, we studied the function of TPA in radiation induced enteropathy in cultured rat intestinal epithelial cell line IEC-6 after ionizing radiation (IR) and in mice after high dose total-body gamma-IR (TBI). In IEC-6 cells, there were reduced apoptosis and cell cycle arrest in TPA treated cells after IR. We detected a four-fold increase in crypt cell survival and a two-fold increase in animal survival post TBI in TPA treated mice. The beneficial effects of TPA were accompanied by upregulation of stem cells markers and higher level of proteins that are involved in PKC signaling pathway. In addition, TPA also decreased the TBI-augmented levels of the DNA damage indicators. The effects were only observed when TPA was given before irradiation. These results suggest that TPA has the ability to modulate intestinal crypt stem cells survival and this may represent a promising countermeasure against radiation induced enteropathy.

Effects of Liraglutide Combined with Short-Term Continuous Subcutaneous Insulin Infusion on Glycemic Control and Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Pilot Study.

The objective of this paper is to investigate the effects of liraglutide in combination with short-term continuous subcutaneous insulin infusion (CSII) therapy on glycemic control and beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Thirty-nine eligible newly diagnosed T2DM patients were recruited and randomized to receive either of two therapies: short-term CSII alone (CSII alone group) or CSII in combination with liraglutide (CSII + Lira group) for 12 weeks. Blood glucose control, homeostasis model assessment (HOMA) indices, and acute insulin response (AIR) were compared between the two groups. The patients in CSII + Lira group achieved euglycemia with equivalent insulin dosage in shorter time (1 (0) versus 2 (3) days, P = 0.039). HbA1c at the end of study was comparable between two groups (6.3 ± 0.7% versus 6.0 ± 0.5%, for CSII alone group and CSII + Lira group, resp., P = 0.325). The increment of AIR was higher in CSII + Lira group (177.58 (351.57) µU · min/mL versus 58.15 (51.30) µU · min/mL, P < 0.001). However, after stopping liraglutide, its effect on beta cell function disappeared completely. Liraglutide combined with short-term CSII was effective in further improving beta cell function, but the beneficial effects did not sustain after suspension of the therapy.

[The comparison of insulin aspart and human soluble insulin used in insulin pump therapy in newly diagnosed type 2 diabetic patients].

OBJECTIVE: To compare the efficacy of insulin aspart and human soluble insulin used in insulin pump therapy on the islets beta cell function in newly diagnosed type 2 diabetic patients. METHODS: Fifty-nine hospitalized newly diagnosed type 2 diabetic patients, 35 males and 24 females, aged 51 +/- 12, were and randomly divided into 2 groups to undergo insulin pump therapy with insulin aspart (aspart group, n = 30) or human soluble insulin (human insulin group, n = 29) for 2 weeks. The targets of glycemic control included fasting blood glucose (FBG) < 6.1 mmol/L and 2 h postprandial blood glucose (PBG) < 8.0 mmol/L. The changes of blood glucose, and the time and the doses of insulin needed for good glycemic control were compared between the two groups. The frequency of hypoglycemia and pump-related side effects were recorded. RESULTS: On the 2nd day of insulin pump therapy, FBG and 3 meals PBG levels were significantly reduced in both groups while the post-breakfast and post-dinner blood glucose levels were far more decreased in the aspart group than in the human insulin group (8.4 mmol/L +/- 2.8 mmol/L vs 11.3 mmol/L +/- 3.8 mmol/L, and 9.0 mmol/L +/- 2.4 mmol/L vs 10.7 mmol/L +/- 2.8 mmol/L, both P < 0.05). The FBG and 3 meals PBG were significantly lowered in the aspart group than in the human insulin group on the 7th day and after the stopping of insulin pump therapy. The time of good glycemic control of the aspart group was 2.0 d, significantly shorter than that of the human insulin group (6.0 d, P < 0.01). The mean dose of insulin used during insulin pump therapy in the aspart group was 0.6 U/kg, significantly less than that in the human insulin group (0.8 U/kg, P = 0.002). There was no significant difference in the AIR, mean area under the curve (AUC) of insulin and C peptide during IVGTT, HOMA-beta and proinsulin between the two groups before and after insulin pump therapy. No pump-related side effects were observed in both groups. CONCLUSION: In newly diagnosed type 2 diabetic patients with short term insulin pump therapy, the use of insulin aspart was more effective and faster with less doses of insulin in acquiring good glucose control compared with humulin R.

Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission.

AIMS: To investigate the insulin requirement profiles during short-term intensive continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes and its relationship with long-term glycemic remission. METHODS: CSII was applied in 104 patients with newly diagnosed type 2 diabetes. Daily insulin doses were titrated and recorded to achieve and maintain euglycemia for 2 weeks. Measurements of blood glucose, lipid profiles as well as intravenous glucose tolerance tests were performed before and after the therapy. Afterwards, patients were followed up for 1 year. RESULTS: Total daily insulin dose (TDD) was 56.6±16.1IU at the first day when euglycemia was achieved (TDD-1). Thereafter, TDD progressively decreased at a rate of 1.4±1.0IU/day to 36.2±16.5IU at the end of the therapy. TDD-1 could be estimated with body weight, FPG, triglyceride and waist circumference in a multiple linear regression model. Decrement of TDD after euglycemia was achieved (ΔTDD) was associated with reduction of HOMA-IR (r=0.27, P=0.008) but not with improvement in ß cell function. Patients in the lower tertile of ΔTDD had a significantly higher risk of hyperglycemia relapse than those in the upper tertile within 1 year (HR 3.4, 95%CI [1.4, 8.4], P=0.008). CONCLUSIONS: There is a steady decline of TDD after euglycemia is achieved in patients with newly diagnosed type 2 diabetes treated with CSII, and ΔTDD is associated with a better long-term glycemic outcome.

Daidzein and genistein fail to improve glycemic control and insulin sensitivity in Chinese women with impaired glucose regulation: A double-blind, randomized, placebo-controlled trial.

SCOPE: This randomized, double-blind, and placebo-controlled trial evaluated the effect of isolated daidzein and genistein on glycemic control and insulin sensitivity in 165 Chinese women aged 30-70 with impaired glucose regulation (IGR). METHODS AND RESULTS: Participants were randomly assigned to one of three groups with a daily dose of 10 g of soy protein plus (i) no addition, (ii) 50 mg of daidzein, or (iii) 50 mg of genistein for 24 wk. Fasting glucose (FG), insulin, and glycosylated hemoglobin (HbA1c ), and glucose concentrations at 30, 60, 120, and 180 min and insulin concentrations at 30, 60, and 120 min after an oral 75-g glucose tolerance test were assessed at baseline and at 12 and 24 wk postintervention. a total of 158 and 151 subjects completed the measures at wk 12 and 24, respectively. There were no significant differences in the changes (%) of FG and the 2-h glucose, HbA1c , fasting, and 2-h insulin or the area under the curve of glucose and insulin between the three treatment groups at wk 12 or 24 (all p > 0.05). CONCLUSION: Neither isolated daidzein nor genistein has a significant effect on glycemic control and insulin sensitivity in Chinese women with IGR over a 6-month supplementation period.

Short-term continuous subcutaneous insulin infusion combined with insulin sensitizers rosiglitazone, metformin, or antioxidant α-lipoic acid in patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND: Short-term continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes has been proved effective in improving metabolic control and ß-cell function, thus inducing long-term drug-free remission. A randomized controlled trial was conducted to investigate whether CSII in combination with rosiglitazone, metformin, or α-lipoic acid separately brings about extra benefits. PATIENTS AND METHODS: One hundred sixty patients with newly diagnosed type 2 diabetes were randomized to one of four treatment groups: CSII alone, CSII in combination with rosiglitazone or metformin for 3 months, or CSII with α-lipoic acid intravenous infusion for 2 weeks. Duration of CSII treatment was identical in the four groups. Glucose and lipid profiles, homeostasis model assessment (HOMA) indices, acute insulin response (AIR), intramyocellular lipid (IMCL) level, and malondialdehyde level were compared before and after intervention. RESULTS: The near-normoglycemia rate at the third month in CSII alone and that in combination with rosiglitazone, metformin, or α-lipoic acid was 72.5%, 87.5%, 90%, and 75%, respectively (metformin group vs. CSII alone, P=0.045). The metformin group achieved euglycemia in a shorter time (2.6 ± 1.3 vs. 3.7 ± 1.8 days, P=0.020) with less daily insulin dosage and was more powerful in lowering total cholesterol, increasing AIR and HOMA ß-cell function, whereas reduction of IMCL in the soleus was more obvious in the rosiglitazone group but not in the metformin group. The efficacy of combination with α-lipoic acid was similar to that of CSII alone. CONCLUSIONS: Short-term CSII in combination with rosiglitazone or metformin is superior to CSII alone, yet the efficacy of the two differs in some way, whereas that with α-lipoic acid might not have an additive effect.

Impact of vitamin D on chronic kidney diseases in non-dialysis patients: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Recent studies have supported a role for both newer and more established vitamin D compounds in improving proteinuria, although systematic evaluation is lacking. Furthermore, concerns remain regarding the influence of vitamin D on the progression of renal function. We analyzed the efficacy and safety of vitamin D in non-dialysis patients and compared the use of newer versus established vitamin D compounds by performing a meta-analysis of randomized controlled trials. DESIGN: A literature search of PubMed (1975 to September, 2012), EMBASE.com (1966 to September, 2012) and Ovid EBM Reviews (through September, 2012) was conducted. RESULTS: Eighteen studies were eligible for final inclusion; of these, six explored the effects of vitamin D on proteinuria, twelve studied the effects of supplementation on renal function, and fifteen discussed the incidence of hypercalcemia. Compared to the placebo or no interference, both the newer and established vitamin D sterols reduced proteinuria to a similar extent (RR, 2.00; 95% CI, 1.42 to 2.81). No decrease in the glomerular filter rate was observed (SMD, -0.10; 95%CI, -0.24 to 0.03), and the risk for dialysis initiation was 1.48 (95% CI, 0.54 to 4.03) with vitamin D treatment. Additionally, there was an increased risk of hypercalcemia for patients treated with either newer or established vitamin D compounds as compared with the controls (RR, 4.78; 95% CI, 2.20 to 10.37). The head-to-head studies showed no differences in the effects of either newer or established compounds on proteinuria or the risk of hypercalcemia. No serious adverse events were associated with the administration of vitamin D. CONCLUSIONS: Vitamin D therapy appears to decrease proteinuria and have no negative influence on renal function in non-dialysis patients. But the occurrence of hypercalcemia should be evaluated when vitamin D is provided. No superiority for newer versus established vitamin D analogue is found.

Fufang Xue Shuan Tong capsules inhibit renal oxidative stress markers and indices of nephropathy in diabetic rats.

Fufang Xue Shuan Tong (FXST) capsules, a traditional Chinese medicine, have been used to treat diabetic nephropathy for many years. FXST has been shown to attenuate elevated levels of oxidative stress in the retina of diabetic rats. However, whether FXST protects kidneys through the same mechanism(s) remains unclear. In this study, diabetes was induced in rats by administration of a high-fat diet and low-dose streptozotocin. Rats were administered low (450 mg/kg/day), middle (900 mg/kg/day) or high (1800 mg/kg/day) doses of FXST orally for 3 months. Another group was administered 50 mg/kg/day orally for the same period. The results indicated that all doses of FXST reduced urinary protein excretion and creatinine clearance and ameliorated the diabetic nephropathy-related mesangial matrix expansion. However, only middle and high doses of FXST prevented glomerular hypertrophy in diabetic rats, and the high dose showed the greatest inhibitory effect with regard to mesangial matrix expansion. Furthermore, superoxide dismutase activities were significantly elevated, whereas malondialdehyde levels were significantly reduced in the renal cortex following FXST treatment. The kidney-protective role of FXST is not inferior to that of captopril, one of the most commonly used drugs for the treatment of diabetic nephropathy. In conclusion, FXST retards the progression of diabetic nephropathy, while high-dose FXST shows the most prominent effect in counteracting the pathological changes of diabetic nephropathy. The renoprotective action of FXST is induced by the reduction of oxidative stress in diabetic nephropathy.

Attitudes toward diabetes affect maintenance of drug-free remission in patients with newly diagnosed type 2 diabetes after short-term continuous subcutaneous insulin infusion treatment.

OBJECTIVE: Short-term intensive insulin treatment in patients with newly diagnosed type 2 diabetes can improve ß-cell function and insulin sensitivity, which results in long-term remission without need for further antidiabetes medication. Patient attitudes toward their disease were assessed using the Diabetes Care Profile (DCP) tool to evaluate the potential impact on maintaining long-term remission. RESEARCH DESIGN AND METHODS: Newly diagnosed patients with type 2 diabetes were recruited and treated with continuous subcutaneous insulin infusion (CSII) for 2-3 weeks. They were also invited to participate in diabetes self-management intervention during hospitalization and complete a DCP questionnaire on attitudes toward diabetes at baseline and 3, 6, and 12 months after suspension of CSII. RESULTS: Near normoglycemia was achieved by 118 patients after short-term CSII, with 65 remaining in drug-free remission for >1 year. They had significantly better glycemic control and greater restoration of acute insulin response after CSII as well as higher educational attainment compared with patients experiencing relapse. They also achieved higher scores in positive attitude, (belief in) importance of care, care ability, self-care adherence, and less negative attitude. Differences between the two groups became greater over time. Cox proportional hazards model analysis indicated that greater self-care adherence (hazard ratio 0.184, P < 0.001) and homeostasis model assessment of insulin resistance before treatment (0.854, P = 0.053) were independent predictors for long-term remission, whereas elevated 2-h postprandial plasma glucose after CSII (1.156, P = 0.015) was a risk factor for relapse. CONCLUSIONS: Attitudes toward diabetes affect long-term drug-free remission in newly diagnosed patients with type 2 diabetes after short-term CSII.

Fulminant type 1 diabetes mellitus with rhabdomyolysis: have we overlooked the situation?

Fulminant type 1 diabetes mellitus (FT1DM) is characterized as remarkably abrupt onset and severe metabolic disorder. Prominent derangement of serum electrolytes was frequently observed, which could be associated with rhabdomyolysis. But the issue was not touched upon in most of the articles concerning FT1DM. Herein, we reported 2 cases. Since the clinical features of rhabdomyolysis vary, and creatine kinase levels are not routinely tested in young patients, the situation of rhabdomyolysis associated with FT1DM may be overlooked.

Remission of hyperglycemia following intensive insulin therapy in newly diagnosed type 2 diabetic patients: a long-term follow-up study.

BACKGROUND: Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve beta-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship between the glycemic remission and beta-cell function and assess the variables predictive of long-term near-normoglycemic remission. METHODS: Eighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion (CSII) and followed up longitudinally. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, hemoglobin A1c (HbA1c) and insulin were measured at baseline, after CSII and at 2-year visit. The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group. RESULTS: The duration to be diagnosed of the patients (from the time that patients began to have diabetic symptoms until diagnosis) in the remission group was shorter than that in the non-remission group (1.00 month vs 4.38 months, P = 0.040). The increase of the acute insulin response (AIR) was maintained after 2 years in the remission group compared with AIR measured immediately after intervention (413.05 pmol*L(-1)*min(-1) vs 408.99 pmol*L(-1)*min(-1), P = 0.820). While AIR in the non-remission group significantly declined (74.71 pmol*L(-1)*min(-1) vs 335.64 pmol*L(-1)*min(-1), P = 0.030). Cox model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio (OR) 1.019, P = 0.038, while fasting plasma glucose (FPG) and post-breakfast plasma glucose (PPG) after CSII were the risk factors (OR 1.397, P = 0.024 and OR 1.187, P = 0.035, respectively). CONCLUSION: The near-normoglycemic remission is closely associated with long-term maintenance of beta-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII.