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Basal insulin

Martin M Grajower
Hypoglycemia is the major side effect of insulin therapy. The elderly are especially vulnerable to episodes of hypoglycemia, and with greater risks of complications such as falls. Two new long-acting basal insulins, glargine-300 (Gla-300) and degludec, are associated with lower incidences of hypoglycemia than previously available basal insulins. One of them, Gla-300, was studied in the elderly and has a lower incidence of hypoglycemia in patients over 65 years old. These new data should be incorporated into decision making when treating the elderly patient with insulin, whether they have type 1 or 2 diabetes...
March 2018: Endocrine Practice
Nicholette D Palmer, Hayrettin Okut, Fang-Chi Hsu, Maggie C Y Ng, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Jill M Norris, Carlos Lorenzo, Jerome I Rotter, Richard N Bergman, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease. Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study. Setting: Community-based. Participants: 1111 Mexican Americans...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Robyn K Pollom, Timothy Costigan, Lyndon B Lacaya, Liza L Ilag, Priscilla A Hollander
INTRODUCTION: To compare efficacy and safety of Basaglar® [insulin glargine 100 units/mL; LY insulin glargine (LY IGlar)] to Lantus® [insulin glargine 100 units/mL; SA insulin glargine (SA IGlar)] in older (≥ 65 years) or younger (< 65 years) patients with type 2 diabetes (T2D). METHODS: This subgroup analysis of a phase 3, randomized, double-blind, multinational, 24-week study compared LY IGlar and SA IGlar on several clinical efficacy (change in glycated hemoglobin (A1c), basal insulin dose, weight) and safety outcomes (incidence of adverse events, insulin antibodies, hypoglycemia incidence and rates) in patients either ≥ 65 or < 65 years...
March 14, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Mary Courtney Moore, David E Kelley, Raul C Camacho, Peter Zafian, Tian Ye, Songnian Lin, Niels C Kaarsholm, Ravi Nargund, Terri M Kelly, Margaret Van Heek, Stephen F Previs, Christopher Moyes, Marta S Smith, Ben Farmer, Phil Williams, Alan D Cherrington
We evaluated the hepatic and nonhepatic responses to glucose-responsive insulin (GRI). Eight dogs received GRI or regular human insulin (HI) in random order. A primed, continuous intravenous infusion of [3-3 H]glucose began at -120 min. Basal sampling (-30 to 0 min) was followed by 2 study periods (150 min each), P1 and P2. At 0 min, somatostatin and GRI (36±3 pmol/kg/min) or HI (1.8 pmol/kg/min) were infused IV; basal glucagon was replaced intraportally. Glucose was infused intravenously to clamp plasma glucose at 80 mg/dL (P1) and 240 mg/dL (P2)...
March 14, 2018: Diabetes
Özlem Korkmaz, Günay Demir, Hafize Çetin, İlkin Mecidov, Yasemin Atik Altınok, Samim Özen, Şükran Darcan, Damla Gökşen
AIM: To compare continuous subcutaneous insulin infusion therapy (CSII) with multiple daily insulin therapy (MDI) on metabolic control in children and adolescents with type 1 diabetes mellitus (T1DM) over the long term. METHOD: 52 T1DM patients treated with CSII and monitored for at least 1 year prior to and at least five years following CSII were included. 38 age and sex-matched MDI controls with a 5-year follow up were recruited. RESULTS: Mean age of the subjects, duration of diabetes and CSII therapy were 17...
February 28, 2018: Journal of Clinical Research in Pediatric Endocrinology
Jean-Claude Henquin
In vitro studies of human pancreatic islets are critical for understanding normal insulin secretion and its perturbations in diabetic β-cells, but the influence of islet preparation characteristics and organ donor attributes in such experiments is poorly documented. Preparations from normal donors were tested with a standardized protocol evaluating dynamic insulin secretion induced by glucose, tolbutamide, and cAMP (forskolin). Secretion rates, normalized to insulin content (fractional insulin secretion), were analyzed as a function of preparation and donor characteristics...
March 2018: Physiological Reports
Sheng Y Ang, Bronwyn A Evans, Daniel P Poole, Romke Bron, Jesse J DiCello, Ross A D Bathgate, Martina Kocan, Dana S Hutchinson, Roger J Summers
Insulin-like peptide 5 (INSL5) is a newly discovered gut hormone expressed in colonic enteroendocrine L-cells but little is known about its biological function. Here, we show using RT-qPCR and in situ hybridisation that Insl5 mRNA is highly expressed in the mouse colonic mucosa, colocalised with proglucagon immunoreactivity. In comparison, mRNA for RXFP4 (the cognate receptor for INSL5) is expressed in various mouse tissues, including the intestinal tract. We show that the human enteroendocrine L-cell model NCI-H716 cell line, and goblet-like colorectal cell lines SW1463 and LS513 endogenously express RXFP4...
April 2018: Journal of Molecular Endocrinology
Hussain N Alhamami, Md Main Uddin, A S M Hasan Mahmood, Karen P Briski
The hypothalamic energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK), an important regulator of counter-regulatory responses to hypoglycemia, responds to pharmacological manipulation of hindbrain AMPK activity. Dorsomedial hindbrain A2 noradrenergic neurons express hypoglycemia-sensitive metabolo-sensory biomarkers, including AMPK. Here, adult male rats were pretreated by intra-caudal fourth ventricular administration of the selective neurotoxin 6-hydroxydopamine (6-OHDA) to determine if catecholamine signaling from the aforesaid site governs hypothalamic AMPK activation during insulin-induced hypoglycemia (IIH)...
March 10, 2018: Neuroscience
Laurentiu M Pop, Andrea Mari, Tong-Jin Zhao, Lori Mitchell, Shawn Burgess, Xilong Li, Beverley Adams-Huet, Ildiko Lingvay
AIM: To investigate the physiological mechanisms leading to rapid improvement in diabetes after Roux-en-Y Gastric Bypass (RYGB). In particular, the roles of concurrent peri-operative dietary restrictions, which may also alter glucose metabolism, have not been completely elucidated. MATERIALS AND METHODS: To assess the differential contributions of diet and surgery to the mechanisms leading to the rapid improvement in diabetes after RYGB we enrolled ten patients with type 2 diabetes scheduled to undergo RYGB...
March 13, 2018: Diabetes, Obesity & Metabolism
Apichaya Niyomchan, Daranee Visitnonthachai, Sumitra Suntararuks, Pronrumpa Ngamsiri, Piyajit Watcharasit, Jutamaad Satayavivad
A strong correlation between chronic arsenic exposure and neuropsychological disorders leads to a growing concern about a potential risk of arsenic related neurodegeneration. Evidently, brain insulin signaling contributes to physiological effects, including energy homeostasis, and learning and memory. Arsenic has been shown to impair insulin signaling in adipocytes and myocytes, however, this impairment has not yet been explored in neurons. Here we showed that NaAsO2 caused significant reduction in basal levels of glucose, plasma membrane glucose transporter, GLUT 3 and Akt phosphorylation in differentiated human neuroblastoma SH-SY5Y cells...
March 8, 2018: Neurotoxicology
Meirong Bai, Jing He, Liangfa Kang, Jun Nie, Ruixue Yin
Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy. Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements. Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network. Core-shell microspheres were fabricated through a two-step high-speed shear-emulsification method...
March 7, 2018: International Journal of Biological Macromolecules
Tianwei Gu, Ting Hong, Pengzi Zhang, Sunyinyan Tang, Yan Bi, Hai Lu, Lichuang Men, Dongwei Ma, Dalong Zhu
INTRODUCTION: In Asia, patients with type 2 diabetes mellitus (T2DM) often have suboptimal glycemic control for many years prior to initiating basal insulin. Active titration of basal insulin is also required to improve glycemic outcomes. This pooled analysis was conducted to determine the impact of patient baseline covariates on the required dose of basal insulin and treatment response, for the improved management of Asian patients with T2DM. METHODS: Data on insulin-naïve Asian patients with T2DM who initiated and fully titrated insulin glargine 100 U/mL (Gla-100) for ≥ 20 weeks were pooled from seven randomized, controlled, treat-to-target trials...
March 9, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Subu Surendran Rajasekaran, Jaeyoon Kim, Gian-Carlo Gaboardi, Jesper Gromada, Stephen B Shears, Karen Tiago Dos Santos, Eduardo Lima Nolasco, Sabrina de Souza Ferreira, Christopher Illies, Martin Köhler, Chunfang Gu, Sung Ho Ryu, Joilson O Martins, Elisabetta Darè, Christopher J Barker, Per-Olof Berggren
Diphosphoinositol pentakisphosphate (IP7 ) is critical for the exocytotic capacity of the pancreatic β-cell, but its regulation by the primary instigator of β-cell exocytosis, glucose, is unknown. The high Km for ATP of the IP7 -generating enzymes, the inositol hexakisphosphate kinases (IP6K1 and 2) suggests that these enzymes might serve as metabolic sensors in insulin secreting β-cells and act as translators of disrupted metabolism in diabetes. To investigate this hypothesis, we now show that glucose stimulation, which increases the ATP/ADP ratio, leads to an early rise in IP7 concentration in β-cells...
March 6, 2018: Cellular Signalling
Ian Blumer, Jeremy H Pettus, Tricia Santos Cavaiola
Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone...
March 9, 2018: Postgraduate Medicine
A C Bennett, A Van Camp, V López, C Smith
The link between obesity-induced systemic inflammation and decreased insulin signalling is well-known. It is also known that peripherally produced inflammatory cytokines can cross the blood-brain barrier, resulting in the release of neurotoxins that can ultimately lead to the demise of central nervous system integrity. A high-mesembrine Sceletium tortuosum extract was recently shown to possess cytoprotective and mild anti-inflammatory properties in monocytes and to target specific p450 enzymes to reduce adrenal glucocorticoid synthesis...
March 9, 2018: Journal of Physiology and Biochemistry
Landon Wood, Karen Roelofs, Lauren G Koch, Steven L Britton, Darleen A Sandoval
OBJECTIVE: Bariatric surgery is currently our most effective strategy at weight loss, yet the mechanisms for its success remain unknown. Low exercise capacity, in humans and rodents, predicts poor metabolic outcome. The objective of this manuscript was to determine if bariatric surgery could restore metabolic perturbations in rats with low intrinsic exercise capacity. METHODS: We performed vertical sleeve gastrectomy (VSG) or sham surgery in high fat-fed rats selectively bred for low running capacity...
February 26, 2018: Molecular Metabolism
Johannes M Werzowa, Marcus D Säemann, Alexander Mohl, Michael Bergmann, Christopher C Kaltenecker, Wolfgang Brozek, Andreas Thomas, Michael Haidinger, Marlies Antlanger, Johannes J Kovarik, Chantal Kopecky, Peter X K Song, Klemens Budde, Julio Pascual, Manfred Hecking
Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment...
2018: PloS One
Lingyan Wu, Lina Zhang, Bohan Li, Haowen Jiang, Yanan Duan, Zhifu Xie, Lin Shuai, Jia Li, Jingya Li
Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic "brown-like" cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood...
2018: Frontiers in Physiology
D Canistro, F Vivarelli, S Cirillo, A Soleti, B Albertini, N Passerini, G Merizzi, M Paolini
PURPOSE: We previously showed the positive effects of the new antioxidant molecule bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in reducing basal hyperglycaemia and relieving glucose intolerance in a diabetes model. However, the chemical properties of IAC did not allow an efficient oral administration, thus representing the main failing of that study. Here, we tested the effect of a new oral delivery system based on solid lipid microparticles (SLMs) in a diabetes mouse model...
March 6, 2018: Journal of Endocrinological Investigation
Bahendeka Silver, Kaushik Ramaiya, Swai Babu Andrew, Otieno Fredrick, Sarita Bajaj, Sanjay Kalra, Bavuma M Charlotte, Karigire Claudine, Anthony Makhoba
A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A). Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A). Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin...
March 5, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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