- Insulin regulates GLUT4 in the Ventromedial Hypothalamus to Restore the Sympathoadrenal Response to Hypoglycemia in Diabetic Rats. [Journal Article]
- AJAm J Physiol Endocrinol Metab 2018 Sep 18
- It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin...
It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin-diabetic Sprague-Dawley rats were infused with either insulin (3mU/day) or artificial cerebrospinal fluid (aCSF) bilaterally into the ventromedial hypothalamus (VMH) for 2 weeks and compared to nondiabetic rats. Rats underwent hyperinsulinemic (50 mU.kg-1.min-1) hypoglycemic (~45 mg/dl) clamps. Diabetic rats demonstrated an impaired CRR to hypoglycemia noted by an high glucose infusion rate (GIR) and blunted epinephrine and glucagon responses. The defective sympathoadrenal response was restored with chronic infusion of insulin into the VMH. Diabetic rats had decreased VMH Akt phosphorylation and decreased VMH glucose transporter 4 (GLUT4) content, which was also restored with chronic infusion of insulin into the VMH. Separate experiments in non-diabetic rats in which VMH GLUT4 translocation was inhibited with an infusion of indinavir was notable for an impaired CRR to hypoglycemia indicated by increased GIR and diminished epinephrine and glucagon responses. Results suggest that in this model of diabetes, VMH insulin deficiency impairs the sympathoadrenal response to hypoglycemia and chronic VMH insulin infusion is sufficient to normalize the sympathoadrenal response to hypoglycemia, via restoration of VMH GLUT4 expression.
- Titration and optimization trial for the initiation of insulin glargine 100 U/mL in inadequately controlled type-2 diabetes patients on oral antidiabetic drugs. [Journal Article]
- DODiabetes Obes Metab 2018 Sep 18
- For patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, addition of basal-insulin is recommended, but titration and optimisation of basal insulin therapy in primary care i...
For patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, addition of basal-insulin is recommended, but titration and optimisation of basal insulin therapy in primary care is not well understood. Therefore, we conducted an observational trial in 2,470 T2DM patients upon initiation of insulin-glargine 100U/L (Gla-100) on top of OADs. Physicians were free to choose either a so-called "Davies", "Fritsche" or "individual" titration algorithm. We found that FBG and HbA1c levels were effectively reduced by Gla-100; 65.9% of patients achieved the primary endpoint (FBG level of ≤110 mg/dL or an individual HbA1c target). There were no significant differences in efficacy and safety between the employed algorithms. Mean FBG decreased by 59mg/dL over 12 months, while mean HbA1c decreased by 1.4%. From a starting dose of 11.7U/day, the Gla-100 dosage was 22.8U/day at 12 months, with similar values in each group. Rates of hypoglycaemia were low and did not differ by titration algorithm. We conclude that Gla-100 was effective at reducing FBG and HbA1c independent of the titration algorithm, but observed that algorithms were inconsistently applied in clinical practice. This article is protected by copyright. All rights reserved.
- Which are the significance of low level of glycated hemoglobin A1c? [Journal Article]
- ABAnn Biol Clin (Paris) 2018 Oct 01; 76(5):531-536
- Glycated hemoglobin A1c (HbA1c) reflects the mean blood glucose over the lifespan of red blood cells and has become a valuable tool both for diagnosis and monitoring of diabetes. Nevertheless, some f...
Glycated hemoglobin A1c (HbA1c) reflects the mean blood glucose over the lifespan of red blood cells and has become a valuable tool both for diagnosis and monitoring of diabetes. Nevertheless, some factors may under-estimate the HbA1c value, compromising its application. The aim of this retrospective study was to evaluate the incidence rate of HbA1c lower than 4% and to identify some clinical and biological factors that can potentially reduce the HbA1c level. Between January 1st 2015 and October 1st 2017, we selected 17 patients with a HbA1c level lower than 4% that were measured in our laboratory of biochemistry at the university medical center of Caen. From the medical records, we identified medical conditions, treatments and biological parameters that could potentially explain a decrease of HbA1c level. Meanwhile the measurement of HbA1c, 8/16 patients had hemoglobin level lower than 100 g/L and 5/6 presented with reticulocytosis (>100 G/L). Ten patients over 17 suffered from hepatopathy (cirrhosis from various etiologies) with abnormal liver blood tests for 12 patients. Two patients showed hemolytic anemia and another one was investigated for hypoglycemia due to congenital hyperinsulinism. Finally, 3 patients were treated with drugs known to lower HbA1c levels. True hypoglycemia periods but also other circumstances which are known to alter erythrocytes lifespan or the glycation process may decrease HbA1c level. Such biological result should be critically interpreted and alternative biological markers should be considered.
- Ertugliflozin as a monotherapy for the treatment of type II diabetes. [Journal Article]
- EOExpert Opin Pharmacother 2018 Sep 18
- Sodium-dependent glucose transporter 2 (SGLT2) inhibitors are novel, potent oral anti-diabetic agents, which act via inhibiting SGLT2-mediated renal glucose reabsorption and thus increasing urinary g...
Sodium-dependent glucose transporter 2 (SGLT2) inhibitors are novel, potent oral anti-diabetic agents, which act via inhibiting SGLT2-mediated renal glucose reabsorption and thus increasing urinary glucose excretion. SGLT2 inhibitors improve glycemic control in a β-cell function-independent manner, which is associated with low risk of hypoglycaemia. Ertugliflozin (SteglatroTM) is a new oral SGLT2 inhibitor for the treatment of patients with type 2 diabetes mellitus (T2DM) as a monotherapy or in combination with other anti-diabetic agents. Areas covered: This review summarizes the collected data concerning the pharmacokinetics, clinical efficacy, as well as safety and tolerability profiles of ertugliflozin given as a monotherapy for the management of T2DM. Expert opinion: Good glycemic control is crucial to the management of T2DM, and accordingly, anti-diabetic agents with various anti-hyperglycemic mechanisms are developed one after another. Based on the available clinical trials of ertugliflozin as a monotherapy for T2DM, it could be found that ertugliflozin effectively improves the glycemic control, body weight and blood pressure of patients with a low risk of hypoglycemia. It is also found that ertugliflozin moderately reduces their blood pressure, which is beneficial for decreasing the risk of cardiovascular disease. These attributes show the good potential of ertugliflozin as an adjunct treatment to diet and exercise for improving glycemic control in patients with T2DM.
- Indications for islet or pancreatic transplantation: Statement of the TREPID Working Group on behalf of the Société Francophone du Diabète (SFD), Société Francaise d'Endocrinologie (SFE), Société Francophone de Transplantation (SFT) and Société Française de Néphrologie-Dialyse-Transplantation (SFNDT). [Review]
- DMDiabetes Metab 2018 Sep 14
- While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. Fo...
While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macroangiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.
- Effects of Dapagliflozin on 24-Hour Glycemic Control in Patients with Type 2 Diabetes: A Randomized Controlled Trial. [Journal Article]
- DTDiabetes Technol Ther 2018 Sep 14
- CONCLUSIONS: Compared with placebo, dapagliflozin improved measures of glycemic control and variability as assessed by CGM. Glycemic improvements were more pronounced in the group on background metformin than those receiving basal insulin.
- The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study. [Journal Article]
- ADActa Diabetol 2018 Sep 17
- CONCLUSIONS: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity.
- [Effects of insulin caliper for blood glucose control on glucose control in emergent and critical patients]. [Journal Article]
- ZWZhonghua Wei Zhong Bing Ji Jiu Yi Xue 2018; 30(8):771-776
- CONCLUSIONS: For emergent and critical patients, insulin caliper for blood glucose control presents favorable application value for achieving glucose control target, reducing glycemic fluctuation, and lowering the incidence of hypoglycemia.
- Capillary glycaemia responses to strength exercises performed before or after high-intensity interval exercise in Type 1 diabetes under real-life settings. [Journal Article]
- CTComplement Ther Med 2018; 40:116-119
- This study investigated the influence of performing strength exercises before or after high-intensity interval exercise on glycaemia during and postexercise in T1DM patients. Nine physically active a...
This study investigated the influence of performing strength exercises before or after high-intensity interval exercise on glycaemia during and postexercise in T1DM patients. Nine physically active adults with T1DM executed 30 min of strength exercises (SE) (3 sets at 10 RM) before 30 min of high-intensity interval exercise (HIIE) (10 × 60-s bout at ∼90% HRmax interspersed with 60 s recovery) (SE + HIIE) or performed the reverse order (HIIE + SE) or rested in this period. Capillary glucose levels were measured each 15 min during and 60 min postexercise recovery. Significant lower glucose levels were observed in SE + HIIE at 60, 75 and 90 min, in comparison with REST. HIIE + SE lowered glycaemia at 30, 45 and 60 min compared with baseline concentrations, while SE + HIIE postponed this glucose decayment to 60 min, when compared with baseline levels. An increased glycaemia at 105 min compared with end-exercise levels were also observed in HIIE + SE. Carbohydrates ingested during exercise to correct hypoglycemia, insulin dosage at same day before and after protocols, and nocturnal hypoglycemia episodes were similar among the three conditions. It is concluded that the performance of HIIE before SE decreases glycaemia already at the end of first exercise modality, while the reverse order postpones it to the end of second exercise, although HIIE + SE improves glycemic stability throughout recovery. T1DM patients who tend to develop exercise-associated hypoglycemia may perform strength exercises before high-intensity interval exercise in a single session.
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- Recurrent Severe Hypoinsulinemic Hypoglycemia Responsive to Temozolomide and Bevacizumab in a Patient With Doege-Potter Syndrome. [Review]
- AJAm J Med Sci 2018; 356(2):181-184
- Nonislet cell tumor hypoglycemia is rare. We highlight the diagnosis and treatment of recurrent severe hypoglycemia in a 49-year-old woman with malignant solitary fibrous tumor of the pleura (Doege-P...
Nonislet cell tumor hypoglycemia is rare. We highlight the diagnosis and treatment of recurrent severe hypoglycemia in a 49-year-old woman with malignant solitary fibrous tumor of the pleura (Doege-Potter syndrome). The clinical, laboratory and radiologic findings of the case are presented and a brief literature review is provided. Of note, imaging studies showed a large mass in the right hemithorax and pathology and immunehistochemical stains confirmed a malignant solitary fibrous tumor of the pleura. She was a poor surgical candidate owing to a large tumor burden. She was treated with a combination of temozolomide and bevacizumab to which she responded with resolution of hypoglycemia. The treatment of choice for hypoglycemia in patients with the Doege-Potter syndrome is surgical excision. We here report that a combination of temozolomide and bevacizumab may be a viable option in patients with inoperable disease.