Obesity is associated with intrahepatic inflammation that promotes insulin resistance and type 2 diabetes. Tumor necrosis factor receptor-associated factor (TRAF)2 is a key adaptor molecule that is known to mediate proinflammatory cytokine signaling in immune cells; however, its metabolic function remains unclear. We examined the role of hepatic TRAF2 in ...

Pancreatic-derived factor (PANDER) is a cytokine-like protein that is highly expressed in pancreatic islets. In vitro, PANDER pretreatment or viral-mediated overexpression promotes apoptosis of islet β cells. Under conditions of insulin resistance, chronic hyperglycemia potently activates PANDER expression and stimulates the cosecretion of insulin and PANDER in β cells. PANDER ...

BACKGROUND & AIMS: Obesity-related insulin resistance contributes to cardiovascular disease. Cannabinoid receptor-1 (CB(1)) blockade improves insulin sensitivity in obese animals and people, suggesting endocannabinoid involvement. We explored the role of hepatic CB(1) in insulin-resistance and inhibition of insulin signaling pathways. METHODS: Wild-type mice and mice with disruption of CB(1) (CB(1)(-/-)mice), ...

Three new diterpenoids, 2-O-lactoylborapetoside B (1), 6'-O-lactoylborapetoside B (2), and tinocrispol A (3), and nine known diterpenoids (4-12) were isolated from an EtOH extract of Tinospora crispa vines. Their structures were elucidated by spectroscopic analyses. The C-6 glucosyloxy group in borapetoside C (6) was revised to be α-oriented. The in ...

BACKGROUND AND AIM: The role of insulin resistance in predicting virological response to therapy of chronic hepatitis C is debated. We assessed the association between basal (defined as homeostasis model assessment of insulin resistance (HOMA-IR)>2) and post-load insulin resistance (as oral glucose insulin sensitivity index<9.8mg/kg/min) with the rapid and sustained ...

Increased flux through the glycerolipid synthesis pathway impairs the ability of insulin to inhibit hepatic gluconeogenesis, but the exact mechanism remains unknown. To determine the mechanism by which glycerolipids impair insulin signaling, we overexpressed glycerol-3-phosphate acyltransferase-1 (GPAT1) in primary mouse hepatocytes. GPAT1 overexpression impaired insulin-stimulated phosphorylation of Akt-S473 and -T308, ...

The ability of pancreatic β-cells to adapt the rate of insulin release in accordance to changes in circulating glucose levels is essential for glucose homeostasis. Two spatial barriers, imposed by the plasma membrane and inner mitochondrial membrane, need to be overcome in order to achieve stringent coupling between the different ...

Since their introduction, insulin analogues are the preferred choice for short-acting insulin due to their superior pharmacologic profiles, leading to greater flexibility and convenience of dosing and, thus, greater patient satisfaction and improved quality of life. Over the past few years, clinical experience with insulin analogues in pregnancy has increased. ...

Objective: To compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs.Methods: In a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control ...

The aim of this study was to compare coefficient of variation of fasting capillary blood glucose (FBG) between insulin glargine and NPH in T2DM with poorly controlled by oral antidiabetic drugs. The results demonstrated that insulin glargine was more potent in improving glycemic control than NPH with stable FBG.

The risk of malignancy in patients using insulin glargine was evaluated. Patients with diabetes mellitus have increased rates of cancers including breast, colon, and pancreatic cancers. Since nondiabetic patients with increased levels of insulin have similar rates of the same cancers, hyperinsulinemia could be key. Normally, insulin produces metabolic effects ...

To compare two progressive approaches [once-daily insulin glargine plus ≤3 mealtime lispro (G+L) vs. insulin lispro mix 50/50 (LM50/50) progression once up to thrice daily (premix progression, PP)] of beginning and advancing insulin in patients with type 2 diabetes (T2D) and inadequate glycaemic control on oral therapy, with the aim ...

Results from a representative German database and from two German health services research studies revealed an unequal distribution between basal supported oral therapy (BOT) and basal-bolus therapy (ICT) regimens in Type 2 diabetics treated with either insulin glargine (GLA) or human insulin (Neutral Protamine Hagedorn; NPH). This study assesses whether ...

The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia ...

Insulin analogues provide clinically important benefits for people with diabetes, including more predictable action profiles and lower risk of hypoglycemia compared with human insulin. However, it has been suggested that certain insulin analogues may lead to greater activation of insulin-like growth factor-1 (IGF-1) signaling, with risk for adverse mitogenic effects. ...

In continuation to part I, a literature review is presented concerning biochemical problems of forensic post mortem cases of unclear hyperglycaemia or hypoglycaemia. Clinical parameters for this purpose were recently reviewed. Particular attention was paid to the detection of diabetic ketoacidosis, of hyperosmolar coma, insulinoma, insulin-induced or oral diabetic-induced hypoglycaemia. ...

Insulin is normally added to oral glucose-lowering drugs in people with type 2 diabetes when glycaemic control becomes suboptimal. We evaluated outcomes in people starting insulin therapy with neutral protamine Hagedorn (NPH), detemir, glargine or premixed insulins. Insulin-naïve people with type 2 diabetes (n = 8009), ≥ 35 years old, ...

The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen. This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] ...

The addition of basal insulin to existing oral therapy can help patients with type 2 diabetes (T2D) achieve glycaemic targets. This study compares the efficacy and safety of insulin lispro protamine suspension (ILPS) and insulin glargine in insulin-naive patients with T2D and inadequate control on oral antihyperglycaemic medication (OAM). An ...

The aim of this study was to examine the fear of hypoglycaemia and its association with demographic and disease-specific variables in a large and unselective population of adult patients with Type 1 diabetes. Questionnaires were sent by post to all patients with Type 1 diabetes who were identified in the ...

We compared blood glucose profile when glargine or detemir was injected once daily before dinner in combination with pre-meal insulin lispro by a crossover design. Glargine showed lower post-dinner and bedtime glucose levels in Type 1 diabetes, and lower pre-dinner and post-dinner glucose levels in Type 2 diabetes than detemir.

We conducted a systematic review of randomized controlled trials that evaluated the effectiveness of insulin regimens (basal, biphasic, prandial, and basal-bolus) with insulin analogues to reach the haemoglobin A1c target of <7% in patients with type 2 diabetes. We identified 48 trials, with 85 arms and 30,588 patients. There were ...

Diabetes mellitus has reached epidemic proportions worldwide, eliciting extensive research on both the disease process and its treatment. Regardless of diabetes type, the progressive nature of the disease makes insulin the long-term mainstay of diabetes management. Recently, the insulin analog glargine was reported in several epidemiologic studies to be associated ...

To estimate absolute and relative incidence rates of hypoglycaemia when using once-daily evening or morning regimens of insulin glargine (glargine) versus once-daily evening NPH insulin (NPH) using individual patient data (IPD). Randomized controlled trials with accessible IPD and including white European people with type 2 diabetes (T2DM) using glargine or ...

Glucokinase is a key enzyme involved in regulating insulin secretion from the pancreatic ß-cell. The unique role of glucokinase in human glucose physiology is illustrated by the fact that genetic mutations in glucokinase can either cause hyperglycaemia or hypoglycaemia. Heterozygous inactivating mutations in glucokinase cause maturity-onset diabetes of the young ...

To describe how in-depth analysis of adverse events can reveal underlying causes. Triggers for adverse events were developed using the hospital's computerised medical record (naloxone for opiate-related oversedation and administration of a glucose bolus while on insulin for insulin-related hypoglycaemia). Triggers were identified daily. Based on information from the medical ...

Postprandial hypoglycaemia is increasingly recognised as a complication of gastric bypass surgery. While post-bypass hypoglycaemia is often responsive to dietary modification, a subset of individuals develop life-threatening neuroglycopenia, with loss of consciousness, seizures and motor vehicle accidents. Such patients require complex nutritional and medical management strategies to reduce postprandial insulin ...

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines ...

IMPORTANCE OF THE FIELD: Most guidelines suggest that failure of oral antidiabetic drugs should be followed by the addition of a basal insulin with aggressive titration of the dose. In most countries, neutral protamine Hagedorn (NPH)-insulin, glargine and detemir are the only choices. Clinical trials show that the metabolism and ...

BACKGROUND: This study reports on the effectiveness of exenatide compared to insulin glargine or NPH insulin in patients with type 2 diabetes mellitus, unable to achieve glycemic control with oral glucose-lowering therapies in a clinical care setting. PATIENTS AND METHODS: Patients with type 2 diabetes mellitus (n = 47) whose ...

Insulin glargine was the first long-acting human insulin analogue to be authorised in the European Union, in the early 2000s, for the treatment of diabetes mellitus. It has about a 6-fold increase in affinity for the insulinlike growth factor 1 (EGF-1) receptor compared with natural human insulin, which may stimulate ...

HISTORY AND CLINICAL FINDINGS: A 42-year-old woman was found by her husband with unconsciousness and seizure at night three weeks after delivery of her fifth child. At a blood glucose level of 25 mg/dl, she received an intravenous infusion of glucose by the called emergency physician, leading to a rapid ...

Two long-acting insulin analogues, insulin glargine and insulin detemir, have been developed as alternatives to neutral protamine Hagedorn (NPH) insulin, which has been the preferred basal insulin preparation for decades. The aim was to directly compare the pharmacodynamic properties of the long-acting insulin analogues and NPH insulin after a single ...

OBJECTIVE: Although the choice of starting insulin for people with type 2 diabetes mellitus (T2DM) is often a basal or premix insulin analog, there is little evidence to base this decision on. This analysis aimed to determine if measurable clinical characteristics prior to starting insulin could predict differences in improved ...

BACKGROUND: Diabetes treatments are needed that are convenient, provide effective glycaemic control, and do not cause weight gain. We aimed to test the hypothesis that improvement in haemoglobin A(1c) (HbA(1c)) achieved with once weekly exenatide was superior to that achieved with insulin glargine titrated to glucose targets. METHODS: In this ...

OBJECTIVE: Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe hypoglycaemia in a cohort of patients with type 1 diabetes. DESIGN: ...

BACKGROUND: Insulin detemir and insulin glargine are synthetic long-acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time-action profile, while insulin detemir has significantly less within-subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events. OBJECTIVES: ...

BACKGROUND: Patients with type 2 diabetes appear to be at relatively low risk of severe hypoglycaemia and hypoglycaemia unawareness in the early stages of disease. However, declining endogenous insulin secretory capacity due to beta-cell dysfunction/failure eventually produces vulnerability similar to type 1 diabetes. Severe hypoglycaemia itself is associated with serious ...

The objective of this Phase 4, open-label, multicentre, observational study was to fulfil food and drug administration (FDA) postapproval requirement to evaluate in healthcare practices the risk of insulin-induced severe hypoglycaemia following initiation of pramlintide therapy in N = 1297 patients with type 1 diabetes mellitus (T1DM) and type 2 ...

Insulin analogues were designed to provide more physiologic pharmacokinetic and pharmacodynamic properties compared with human insulin. This article examines the literature over a 2-year period, focusing on studies directly comparing analogue and human insulin in controlled clinical trials and large observational studies documenting the introduction of, or change to, analogue ...

Impaired awareness of hypoglycaemia (IAH) is a major risk factor for severe hypoglycaemia in Type 1 diabetes. Although biochemical hypoglycaemia is asserted to be more frequent in IAH, this has not been estimated accurately. The aim of this study was to use Continuous Glucose Monitoring (CGM) to quantify hypoglycaemia in ...

OBJECTIVE: The objective of the study was to evaluate pharmacodynamic (PD) intrasubject variability of a single, s.c. dose of insulin lispro protamine suspension (ILPS) compared with insulin glargine in subjects with type 1 diabetes mellitus and additionally, to compare the intrasubject variability of pharmacokinetic parameters of both insulins. DESIGN: This ...

AIMS/HYPOTHESIS: Prolongation of the heart rate corrected QT interval (QTc) is seen during episodes of hypoglycaemia in type 1 diabetes. We studied the relationship between spontaneous hypoglycaemia and the QT interval and hypothesised that the choice of heart rate correction affects the observed change in QTc. METHODS: Twenty-one participants with ...

Background: Insulin glargine is a relatively new medication in the treatment of diabetes mellitus, and there have only been six case reports of overdoses in the literature with this specific insulin. Objectives: We present a unique case of insulin glargine overdose that presented with persistent hypoglycemia and required prolonged in-hospital ...

BACKGROUND: The clinical importance of glycaemic control in patients with diabetes has been well established. This study aimed to explore twice-daily biphasic insulin aspart 30 (BIAsp 30) for insulin initiation in patients with type 2 diabetes mellitus (T2DM) who had poor glycaemic control with human insulins (HIs). We use data ...

OBJECTIVE: To compare rapid-acting insulin analogues with regular human insulin in terms of hemoglobin A1c, hypoglycemia, and insulin dose when used in a basal-bolus regimen in patients with type 1 diabetes mellitus. METHODS: MEDLINE and congress proceedings were searched for randomized controlled trials comparing prandial insulins in a basal-bolus regimen ...

CONTEXT AND OBJECTIVE: Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect. METHODS: Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated. In cross-over fashion, ...

AIMS: The efficacy of two basal insulins, insulin lispro protamine suspension (ILPS) and insulin detemir, was compared in basal-bolus regimens in Type 1 diabetes. METHODS: In this 32-week, multinational, parallel-group, randomized, controlled trial, adult patients with Type 1 diabetes received ILPS or insulin detemir, injected twice daily (before breakfast and ...

Insulin glargine and lispro mix 75/25 (75% insulin lispro protamine suspension and 25% insulin lispro injection [LM75/25]) represent 2 common starter insulin regimen classes: basal and premixed. After initiation of starter insulin therapy, if patients with type 2 diabetes mellitus (DM) are unable to achieve a glycosylated hemoglobin (HbA1c) level ...

Current guidelines for the management of type 2 diabetes advocate the attainment of sustained near normal glycaemia levels. Metformin is widely accepted as the treatment of choice for the initiation of pharmacotherapy; however, secondary failure of oral monotherapy occurs in 60% of patients resulting in the need for multiple pharmacotherapies. ...