Acting Insulin Analogues Research Articles

Optimization of a mass spectrometric analytical method for the quality assessment of insulin and its analogs.

The principal aim of this study was to optimize analytical methodology based on mass spectrometry for the evaluation of the quality of recombinant human insulin and its analogs. In this study ESI-MS was used to assess the quality of human insulin, short acting insulin analogs, insulin lispro, insulin aspart and insulin glulisine and long acting analogs including insulin glargine, insulin degludec, and insulin detemir, in respective pharmaceutical formulations. In this study, with the aimed to optimize analytical conditions, different factors influencing the analytical performance such as pH, ionic strength, sample dilution, organic solvent addition were addressed. The study results demonstrated that MS is a suitable technique for the analysis of biotechnological compounds like insulin and its analogs. Although the obtained results provide an important information regarding this methodology, further studies are needed to validate this analytical approach and check for its suitability to be used in the regulatory environment.

Treatment of acute diabetic metabolic crises in adults (Update2023) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorder

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of aphysiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.

Role of New Insulin Analogs in the Management of Diabetes. A Clinical Review

This paper has reviewed different insulin analogs currently available in the market and pharma industry, their safety, efficacy and their roles in the diabetes management, comparing with human regular and NPH insulin. Traditional insulins (human regular and NPH insulins) do not have constant or smoother pharmacokinetic and pharmacodynamic profiles and are usually associated with erratic blood glucose profiles with hypoglycemia or hyperglycemia when compared with analog insulins. Similarly they do not match physiologic insulin profiles with basal bolus format. According to the medical literature, current insulin analogs are more efficacious and also it has been documented in research trials that recent insulin analogs are better and safer as compared to human regular and NPH insulin in terms of hypoglycemia and HbA1c reductions. Hence this paper has reviewed these insulins analogs (longer acting basal and rapid acting insulin analogs) for their safety and efficacy in terms of hypoglycemia and HbA1c control, for the management of both type-1 and type-2 diabetics in hospitals and clinics.

Insulin in Frail, Older People with Type 2 Diabetes—Low Threshold for Therapy

The global prevalence of comorbid diabetes and frailty is increasing due to increasing life expectancy. Frailty appears to be a metabolically heterogeneous condition that may affect the clinical decision making on the most appropriate glycaemic target and the choice of the most suitable hypoglycaemic agent for each individual. The metabolic profile of frailty appears to span across a spectrum that starts at an anorexic malnourished (AM) frail phenotype on one end and a sarcopenic obese (SO) phenotype on the other. The AM phenotype is characterised by significant weight loss and less insulin resistance compared with the SO phenotype, which is characterised by significant obesity and increased insulin resistance. Therefore, due to weight loss, insulin therapy may be considered as an early option in the AM frail phenotype. Insulin-related weight gain and the anabolic properties of insulin may be an advantage to this anorexic phenotype. There is emerging evidence to support the idea that insulin may improve the muscle function of older people with diabetes, although this evidence still needs further confirmation in future large-scale prospective studies. Long acting insulin analogues have a lower risk of hypoglycaemia, comapred to intermediate acting insulins. Additionally their simple once daily regimen makes it more appropriate in frail older patients. Future research on the availability of new once-weekly insulin analogues is appealing. The goals of therapy are to achieve relaxed targets, avoid hypoglycaemia and to focus on the maintenance of quality of life in these vulnerable patients.

One hundred years after the discovery of insulin: a new revolution for patients living with type 1 diabetes?

The year 2021 saw the 100-year celebration of the discovery of insulin as a treatment for type 1 diabetes, saving lives of people previously condemned by the disease. However, insulin replacement, so different from physiological secretion, remains a challenge. Until the 1990s, people living with type 1 diabetes were treated with two injections of intermediate insulin and prandial regular insulin injections. Their kinetics led to frequent hypoglycemia, justifying meals taken at fixed times, with fixed amount of carbohydrates avoiding fast sugars. The development of rapid and then long acting insulin analogues in the 1990s and 2000s and the principle of patient empowerment have reduced these constraints by introducing the notion of functional insulin therapy, dissociating meals managed by rapid insulins from basal insulin (= insulin for living). Meals can be taken at variable times, with variable carbohydrate content and without food restrictions. But the revolution started 5 years ago, with the development of continuous glucose monitoring systems, freeing the patient from blood glucose controls, coupled thereafter to an insulin pump driven by artificial intelligence in the very recent hybrid closed-loop systems. These systems showed significant glucose control improvement, together with reduction of both the time spent in hypoglycemia and the mental burden on the individual, pending a cure for the disease for the next century.

Retrospective trial of long acting analogues detemir and degludec usage in children and adolescents to overcome glucose variability caused by dawn phenomenon and reverse dawn phenomenon

Backgraund: Children with type 1 diabetes mellitus (T1DM) need more insulin late in the evening (reverse dawn phenomenon (RDP)), and adolescents need more insulin yearly in the morning (dawn phenomenon (DP)); these cause blood glucose variability. Modern long acting insulin analogues allow to achieve satisfactory glycemic control.Aims: To study the characteristics of insulin therapy in children and adolescents with T1DM using insulin analogues detemir and degludec to overcome blood glucose variability caused by DP and RDP in different age periods.Materials and methods: We analyzed medical documents of 200 patients using detemir, admitted to pediatric endocrinology department in 2013–2019, at mean age 9.0 years (5.4; 13.0), with T1DM for 1.3 years (0.5; 3.0); and medical documents of 50 patients switched to degludec in 2018–2019 at mean age 12.0 years (10.5; 14.5) with T1DM for 3.0 years (1.5; 6.0). Before degludec they were on intensive insulin therapy with glargine (22), detemir (26), or insulin pump (2); 16 patients (32%) presented with clinical characteristics of DP, and 5 (10%) — RDP.Results: 67 children of 108 (62%) aged 1–9 years had redistribution of detemir doses to daytime; 58 adolescents of 92 (63%) aged 10–17 лет — to nighttime. Patients switched to degludec demonstrated decrease in HbA1с from 8.7% (7.8; 9.9) to 8.0% (7.4; 9.0) (р<0.001); fasting blood glucose from 9.8 mmol/l (7.4; 11.7) to 7.7 mmol/l (6.4; 8.6) (р<0.001); within-day variability from 35.2% (31.6; 40.9) to 23.5% (19.7; 28.6) (р<0.001); daily insulin dose from 0.98 U/kg/day (0.82; 1.14) to 0.87 U/kg/day (0.75; 1.07) (р=0.002). Sub-groups of patients with DP and RDP demonstrated decrease in fasting blood glucose (from 11.5 mmol/l (9.8; 13.8) to 7.5 mmol/l (6.6; 9.1) (р<0.001)), and late evening blood glucose (from 11.0 mmol/l (10.2; 11.2) to 8.0 mmol/l (6.7; 9.5) (р= 0.03)) correspondently. Achieved levels of glycemic control did not differ between sub-groups of patients initially using glargine or detemir.Conclusions: Compensation of T1DM may be complicated due to DP and RDP. Switching to degludec allowed to achieve better glycemic control and lowering of blood glucose variability caused by DP and DRP.

Fully closed-loop insulin delivery—are we nearly there yet?

Fully closed-loop insulin delivery—are we nearly there yet?

Availability and Use of Long-Acting Insulin Analogues Including Their Biosimilars across Africa: Findings and Implications

Background: Prevalence rates of diabetes mellitus are growing across Africa with an appreciable number likely to be on insulin to manage their condition. This has significant implications on future morbidity and mortality exacerbated by high complication rates. Complication rates in patients requiring insulins are enhanced by hypoglycaemia. Long acting insulin analogues were developed to reduce hypoglycaemia and improve patient compliance. However, they are typically appreciably more expensive than human and other insulins in Africa, and continuing controversies surrounding their benefits limits their listing on national Essential Medicine Lists (EMLs). Biosimilars can reduce the prices long-acting insulin analogues. This needs assessing. Methods: Mixed methods approach including documentation of insulin utilisation patterns and prices among a range of African countries. In addition, input from senior level government, academic, and healthcare professionals from across Africa on the current situation with long-acting insulin analogues as well as potential changes needed to enhance future funding of long-acting analogue biosimilars. Results: There is variable listing of long-acting insulin analogues on national EMLs across Africa due to their high prices and issues of affordability. Even when listed, utilisation of long-acting insulin analogues is limited by similar issues including affordability. Appreciably lowering the prices of long-acting insulin analogues via biosimilars should enhance future listing on EMLs and use accompanied by educational and other initiatives. However, this will require increased competition to lower prices. Conclusion: There are concerns with value and funding of long-acting insulin analogues across Africa including biosimilars. A number of activities have been identified to improve future funding and listing on EMLs.

Ретроспективное исследование применения аналогов инсулина продленного действия детемир и деглудек у детей и подростков для преодоления вариабельности гликемии, обусловленной феноменами «утренней и вечерней зари»

Backgraund: Children with type 1 diabetes mellitus (T1DM) need more insulin late in the evening (reverse dawn phenomenon (RDP)), and adolescents need more insulin yearly in the morning (dawn phenomenon (DP)); these cause blood glucose variability. Modern long acting insulin analogues allow to achieve satisfactory glycemic control. Aims: To study the characteristics of insulin therapy in children and adolescents with T1DM using insulin analogues detemir and degludec to overcome blood glucose variability caused by DP and RDP in different age periods. Materials and methods: We analyzed medical documents of 200 patients using detemir, admitted to pediatric endocrinology department in 2013–2019, at mean age 9.0 years (5.4; 13.0), with T1DM for 1.3 years (0.5; 3.0); and medical documents of 50 patients switched to degludec in 2018–2019 at mean age 12.0 years (10.5; 14.5) with T1DM for 3.0 years (1.5; 6.0). Before degludec they were on intensive insulin therapy with glargine (22), detemir (26), or insulin pump (2); 16 patients (32%) presented with clinical characteristics of DP, and 5 (10%) — RDP. Results: 67 children of 108 (62%) aged 1–9 years had redistribution of detemir doses to daytime; 58 adolescents of 92 (63%) aged 10–17 лет — to nighttime. Patients switched to degludec demonstrated decrease in HbA1с from 8.7% (7.8; 9.9) to 8.0% (7.4; 9.0) (р<0.001); fasting blood glucose from 9.8 mmol/l (7.4; 11.7) to 7.7 mmol/l (6.4; 8.6) (р<0.001); within-day variability from 35.2% (31.6; 40.9) to 23.5% (19.7; 28.6) (р<0.001); daily insulin dose from 0.98 U/kg/day (0.82; 1.14) to 0.87 U/kg/day (0.75; 1.07) (р=0.002). Sub-groups of patients with DP and RDP demonstrated decrease in fasting blood glucose (from 11.5 mmol/l (9.8; 13.8) to 7.5 mmol/l (6.6; 9.1) (р<0.001)), and late evening blood glucose (from 11.0 mmol/l (10.2; 11.2) to 8.0 mmol/l (6.7; 9.5) (р= 0.03)) correspondently. Achieved levels of glycemic control did not differ between sub-groups of patients initially using glargine or detemir. Conclusions: Compensation of T1DM may be complicated due to DP and RDP. Switching to degludec allowed to achieve better glycemic control and lowering of blood glucose variability caused by DP and DRP.

Effect of basal insulin therapy with glargine U300 versus basal bolus insulin therapy in hospitalized patients with type 2 diabetes. Real-world study from India

Background. Basal-bolus insulin therapy is the most widely accepted method of glycemic control in non-critically ill patients with T2DM. In this regimen glargine U100 is the most commonly used basal insulin. American Diabetes Association recommends either basal or basal bolus therapy for patients with type 2 diabetes mellitus admitted in general medical and surgical ward with ideal glycemic target ranging between 140–180 mg/dL by estimating four or 6 hourly capillary blood glucose per day. Insulin glargine U300 is a second generation long acting insulin analogue, which has a prolonged pharmacokinetic /pharmacodynamic profile compared to insulin glargine U100 resulting in glucose lowering activity exceeding 24 hours. Aim. To assess the efficacy and safety of basal insulin regimen (glargine U300) compared to a basal-bolus insulin regimen in patients with type 2 diabetes. Methods. A prospective single centred parallel group study comparing the efficacy and safety of basal insulin regimen with basal-bolus insulin regimen. A total of 60 patients with type 2 diabetes mellitus admitted in general medical and surgical ward for elective surgery and medical emergency were randomized to either of the two regimens. The baseline glycaemic parameters were assessed by capillary blood glucose testing thrice before meal and at bedtime with a target capillary blood glucose (CBG) between 140–180 mg/dL. All pa-tients were followed up for seven days. Results. The number of CBG readings within the target range were higher in basal insulin monotherapy (glargine U300) compared to basal-bolus regimen using (glargine U100 and regular human insulin) which was statistically significant. The incidence of hypoglycaemia was lower in the basal insulin regimen. Fewer units of insulin were required in the basal insulin regimen with lower glycaemic variability as compared to basal-bolus regimen. Conclusion. Glargine U 300 monotherapy as a basal insulin is non-inferior to basal- bolus therapy in non-critically ill hospitalised patients in glycaemic control, with fewer incidences of hypoglycaemia, less amount of insulin requirement to achieve target capillary blood glucose level and lower glycaemic variability.

Predictors of the maximal oxygen consumption in adult patients with type1 diabetes treated with personal insulin pumps.

Aims/IntroductionRegular physical activity for adults with type 1 diabetes mellitus improves cardiorespiratory fitness (CF) and quality of life. The aim of our study was to evaluate clinical and biochemical features that might be associated with CF in a homogenous group of adults with type 1 diabetes mellitus who are all treated with a personal insulin pump (continuous subcutaneous insulin infusion).Materials and MethodsWe assessed CF in 62 patients (74.2% of whom were men) who fulfilled the eligibility criteria. To determine maximal oxygen consumption, the march‐running test on the treadmill was carried out. Two hours before the test, the patients consumed a defined meal covered by a dose of rapid acting insulin analog that was reduced by 25% from their regular dose. Basal insulin infusion was reduced by 50% for an hour. Additionally, the Perceived Stress Scale‐10 questionnaire was used to measure the perception of stress.ResultsThere was no episode of severe hypoglycemia during or after the test. In the final model, independent predictors of maximal oxygen consumption were sex, body fat percentage, lactate at 20 min after CF test and Perceived Stress Scale‐10 score. Of interest, neither short‐term (continuous glucose monitoring) nor long‐term (glycosylated hemoglobin) metabolic control parameters were predictors of CF.ConclusionsIn our selected homogenous group of patients with type 1 diabetes mellitus treated with personal insulin pumps, higher CF was associated with a lower percentage of body fat, male sex, higher lactate level after the CF test and the Perceived Stress Scale‐10 score. The proposed protocol in our cohort proved to be safe with regard to glycemic control.

Management of diabetic ketoacidosis: Role of Rapid Acting Insulin Analogs in comparison to regular intravenous insulin.

Background: Diabetic ketoacidosis (DKA) is an acute metabolic healthcare crisis in patients with diabetes mellitus. The current study aimed to compare the effectiveness of rapid-acting insulin analog administered subcutaneously with regular insulin infused intravenously among the DKA patients.&#x0D; Methodology: In this prospective open labelled study, 100 consecutive DKA patients were randomly assigned to two groups. Group 1 patients were admitted to the intensive care unit (ICU) and treated with intravenous regular insulin infusion. Group 2 patients were managed in the emergency medical ward with subcutaneous rapid-acting insulin. Response to the therapy was assessed by the follow-up investigations of the biochemical parameters, including blood glucose concentration, serum ketones, pH, serum electrolytes including bicarbonates, sodium and potassium concentration until the resolution of DKA. Furthermore, the overall duration of therapy (blood glucose level &lt; 250 mg/dl), time and amount of insulin administered until the resolution of DKA, were also assessed.&#x0D; Results: The baseline clinical and biochemical parameters were similar between the two treatment groups except for blood glucose and sodium concentration. The mean random blood sugar (RBS), acid-base parameters and concentration of ketone bodies were significantly improved from admission until the resolution of DKA. There was no significant difference in the duration of therapy (p=0.07). While the time and amount of insulin therapy required until resolution of DKA were significantly reduced among the patients treated subcutaneously with rapid-acting insulin, i.e. 16.36 ± 6.92 hrs and 59.28 ± 30.05 units (p&lt;0.05).&#x0D; Conclusion: The patients with less complicated DKA can be managed with rapid-acting insulin analog in the medical wards obviating the need for admission to the ICU. With relatively better outcomes, it is an effective alternative to regular intravenous insulin infusion for DKA resolution.

The artificial pancreas.

Advances in diabetes technologies have enabled the development of artificial pancreas (closed-loop) systems for people with diabetes. We review the key studies which have led to the adoption of the artificial pancreas in clinical practice and consider ongoing challenges and areas for future enhancements. Studies have demonstrated safety and efficacy of closed-loop insulin delivery systems in free-living settings over periods of up to 6 months for children and adults with type 1 diabetes. Since 2017, four hybrid closed-loop systems have been approved by regulatory bodies worldwide, but these systems are not entirely automated, requiring user interaction to deliver mealtime insulin boluses. Improving usability of these devices in the real-world setting is an important challenge. The artificial pancreas has become the gold standard for the treatment of type 1 diabetes. First-generation systems are increasingly being adopted in clinical practice, however further work is required, developing advanced systems and faster acting insulin analogues to allow complete automation and further reduce the burden of type 1 diabetes.

MON-640 Endogenous Insulin and C-Peptide Suppression Test Using a Rapid-Acting Insulin Analog in the Diagnosis of Insulinoma

C-peptide suppression test (CPS) was shown to diagnose the cause of hyperinsulinemic hypoglycemia, i.e. insulinoma, as effectively as supervised 72-hour fast test with less time consuming and cost. In the conventional CPS, regular insulin (RI) is used to induce hypoglycemia that subsequently suppresses endogenous insulin secretion. As RI is measurable in plasma insulin (PI) assay, plasma C-peptide (PCP) but not PI response is therefore used for assessment of endogenous insulin secretion in CPS using RI. As rapid acting insulin analogs (RA) are not measurable in a selected PI assay, both PCP and PI levels can be used to assess endogenous insulin secretion if an RA is used instead of RI in CPS. There is no study on PI and PCP responses to RA in insulinoma. This study aimed to examine efficacy of modified CPS, so-called insulin and C-peptide suppression test (ICPS) by using an RA (insulin aspart) in the diagnosis of insulinoma. Ten patients, 7 with histopathological proven insulinoma (IN) and 3 with non-insulinoma (non-IN), underwent ICPS. Blood samples were collected for measurement of plasma glucose (PG), PCP, and PI using a Roche Cobas 8000 module e602 which does not measure insulin aspart at before and every 10-20 minutes during intravenous infusion of insulin aspart at the rate of 0.05-0.075 unit/kg/hr. The test was terminated if the patients had a PG level of <40 mg/dL. There was no difference in baseline biochemical data between two groups. At the end of the test, IN had significantly higher PCP level (range: 0.60-10.20 vs. 0.31-0.48 ng/mL and median: 4.67 vs. 0.47 ng/mL; p = 0.017), lower percentage of PCP suppression (range: 2.10-53.10% vs. 63.08-91.24% and mean: 24.78 ± 19.4% vs. 73.17 ± 15.7%; p = 0.005), higher PI level (range: 1.13-113.70 vs. 0.22-0.73 µIU/mL and median: 21.29 vs. 0.49 µIU/mL; p = 0.017) and lower percentage of PI suppression (range: -14.63-81.32% vs. 88.14-96.10% and mean: 28.45 ± 36.2% vs. 93.31 ± 4.5%; p = 0.003) than did the non-IN. No overlapping of these parameters was observed between IN and non-IN. Using the same cut-off levels as the supervised 72-hour fast test, the insulin criterion (≥3 µIU/mL) in ICPS had a sensitivity of 86% and a specificity of 100% and the C-peptide criterion (≥0.6 ng/mL) in ICPS had a sensitivity of 100% and a specificity of 100%. There was a high correlation of 89% between using PCP and PI responses. In conclusion, ICPS using an RA is effective in the diagnosis of insulinoma.

Biosynthetic Human Insulin and Insulin Analogs.

Biosynthetic human insulins and analogs have replaced animal insulins and permitted structural modifications to alter the rate of absorption, duration of action, improve reproducibility of effects, and modulate relative efficacy in various target tissues. Several forms of rapidly acting insulins nearly achieve rapid pharmacokinetics and pharmacodynamics similar to first-phase insulin release. There is need for even faster-acting analogs to mimic normal physiology and improve control of postprandial glycemic excursions. Two biosynthetic insulin analogs have sufficiently long duration of action for use as once-daily basal insulins; controversy persists regarding their respective risks of hypoglycemia and relative glycemic variability. Basal-bolus therapy and insulin pump therapy, including closed-loop automated insulin delivery, require rapid-acting insulin analogs. The longer acting insulins can provide stable, reproducible basal insulin with reduced rates of hypoglycemia, particularly nocturnal hypoglycemia, greater efficacy in reducing mean glucose and glucose variability while increasing time in glucose target range. Inhalable human insulin provides very rapid action. Premixture of rapid-acting analogs with protamine has been useful for some patients with type 2 diabetes. An insulin analog with preferential efficacy at the liver has been developed and tested clinically but not marketed. Current research is aimed at developing even faster-acting insulin analogs. Long-acting basal insulins coformulated with GLP-1 receptor agonists or with a rapidly acting insulin analog have valuable clinical applications. Excipients, chaperones, local heating of the infusion site, and hyaluronidase have also been used to accelerate the absorption of insulin analogs. Biosynthetic human insulins have radically revolutionized management of both type 1 and type 2 diabetes worldwide. The ability to manipulate the structure and formulation of insulin provides for more physiologic pharmacokinetics and pharmacodynamics, enabling improved glycemic control, reduced risk of hypoglycemia, and reduced rates of long-term complications.

An unusual use of personal insulin pump by a patient with type 1 diabetes on a ketogenic diet — a case report

In this case report we present a 28-year-old woman with type 1 diabetes mellitus on a ketogenic diet for 5 months, using a personal insulin pump in an unusual way. The patient was admitted to the Department of Internal Medicine and Diabetology due to vomiting and diarrhea that had lasted for several days. On a daily basis, she used personal insulin pump for only several hours a day (a 5-hour basal rate of 0.6 units/hour of fast-acting insulin) in order to avoid dawn phenom­enon, without any prandial insulin, and she used continuous glucose monitoring for 24 hours a day for glycemia control. Additionally she was taking 30 units of long acting insulin analog before sleep. The patient was unwilling to change her treatment method and she was discharged from the hospital against medical advice. Due to the increase in popularity of ketogenic diet, there is a need for large studies assessing its safety and efficacy. Moreover, our case draws attention to the fact that patients can use modern technologies, which are developed to improve the glycemic control, in un­conventional ways.

A View Beyond HbA1c: Role of Continuous Glucose Monitoring.

Hemoglobin A1C (HbA1c) is used as an index of average blood glucose measurement over a period of months and is a mainstay of blood glucose monitoring. This metric is easy to measure and relatively inexpensive to obtain, and it predicts diabetes-related microvascular complications. However, HbA1c provides only an approximate measure of glucose control; it does not address short-term glycemic variability (GV) or hypoglycemic events. Continuous glucose monitoring (CGM) is a tool which helps clinicians and people with diabetes to overcome the limitations of HbA1c in diabetes management. Time spent in the glycemic target range and time spent in hypoglycemia are the main CGM metrics that provide a more personalized approach to diabetes management. Moreover, the glucose management indicator (GMI), which calculates an approximate HbA1c level based on the average CGM-driven glucose level, facilitates individual decision-making when the laboratory-measured HbA1c and estimated HbA1c are discordant. GV, on the other hand, is a measure of swings in blood glucose levels over hours or days and may contribute to diabetes-related complications. In addition, addressing GV is a major challenge during the optimization of glycemia. The degree of GV is associated with the frequency, duration, and severity of the hypoglycemic events. Many factors affect GV in a patient, including lifestyle, diet, the presence of comorbidities, and diabetes therapy. Recent evidence supports the use of some glucose-lowering agents to improve GV, such as the new ultra-long acting insulin analogs, as these agents have a smoother pharmacodynamic profile and improve glycemic control with fewer fluctuations and fewer nocturnal hypoglycemic events. These newer glucose-lowering agents (such as incretin hormones or sodium–glucose cotransporter 2 inhibitors) can also reduce the degree of GV. However, randomized trials are needed to evaluate the effect of GV on important diabetes outcomes. In this review, we discuss the role of HbA1c as a measure of glycemic control and its limitations. We also explore additional glycemic metrics, with a focus on time (duration) in glucose target range, time (duration) in hypoglycemia, GV, GMI, and their correlation with clinical outcomes.

Treatment of acute diabetic metabolic crises in adults (Update 2019) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorders

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of aphysiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.

Efficacy and safety of adding single dose insulin glargine in patients with type 2 diabetes uncontrolled by oral hypoglycemic drugs

Abstract:&#x0D; Unfortunately, a Significant number of type 2 diabetic patients on oral hypoglycemic agents are not achieving the desired and recommended target of glycemic control in terms of reduction of HbA1c and fasting plasma glucose, this is largely because most of them are reluctant to use insulin injections for many reasons, mainly the painful injection, fear of hypoglycemia or inability to adapt to a complex regimen of multiple insulin injections. it has been recommended by many diabetes associations ( the American diabetes association(ADA) and the European association for the study of diabetes(EASD) ), in their algorithm of management of hyperglycemia in patients with uncontrolled diabetes (HbA1c &lt; 7 %) to add a basal ( long acting) insulin to their oral drug regimen as a more simple initial step of adding insulin that is acceptable by most patients and capable of achieving target glycemic levels. insulin glargine is the preferred long acting insulin analogue for its pharmacodynamic properties (peakless action profile with low incidence of hypoglycemia and longer duration of action) , furthermore, its pen formulary makes it less painful than conventional human insulin syringe injections.

Long-Acting Insulin Analogues and Risk of Breast Cancer—Meta-analysis

Observational studies on the association between prescription of long acting insulin analogues (glargine and detemir) and the risk of breast cancer (BC) report conflicting results. We performed a meta-analysis of prospective studies on the risk of breast cancer among diabetic patients exposed to long acting insulin analogues following PRISMA guidelines. Summary relative risks (SRR) were computed using a random-effect model. Thirteen studies were identified which reported data on insulin glargine which included 438,214 subjects and 4,041 BC cases over a median follow-up of 2.8 years. In 11 studies, including 94.8 % of BC, the comparator groups included diabetic patients treated with non-glargine insulin. The SRR was 1.11 (95% CI: 0.98, 1.24), with little heterogeneity (I2=27%). Among prevalent users of insulin, based on 7 studies, the SRR of BC (1,425 cases) associated with prescription of glargine was 1.(95% CI: 0.90, 1.23), with moderate heterogeneity among studies (I2=40%). One influential study (Wu et al. 2017) accounted for most of the heterogeneity. When it was removed from the meta-analysis, the I2 dropped to 0% with a SRR of 0.99 (95% CI: 0.88, 1.12). Among new users of insulin, based on 10 studies, the SRR of BC (3,847 cases) associated with prescription of glargine was 1.12 (95% CI: 0.96, 1.29), with moderate heterogeneity among studies (I2=41%). One influential study (Ruiter et al. 2012) accounted for most of the heterogeneity. When it was removed from the meta-analysis, the I2 dropped to 0% with a SRR of 1.07 (95% CI: 0.96, 1.21). Only three studies reported on detemir, with a SRR for BC (1,947 cases) of 1.09 (95% CI: 0.77, 1.57). There seems to be consistent evidence showing no association between the prescription of long acting insulins and risk of BC. However, most of these studies had a short duration of follow-up. In addition, only three studies were identified reporting the risk of BC associated with use of detemir. Disclosure M. Bota: None. P. Autier: Other Relationship; Self; Sanofi. P. Boyle: Other Relationship; Self; Sanofi.