Frequent Hypoglycemic Events Research Articles

Effects of Switching from Degludec to Glargine U300 in Patients with Insulin-Dependent Type 1 Diabetes: A Retrospective Study.

Background and Objectives: Degludec (Deg) and glargine U300 (Gla-300) are insulin analogs with longer and smoother pharmacodynamic action than glargine U100 (Gla-100), a long-acting insulin that has been widely used for many years in type 1 and type 2 diabetes. Both improve glycemic variability (GV) and the frequency of hypoglycemia, unlike Gla-100. However, it is unclear which insulin analog affects GV and hypoglycemia better in patients with insulin-dependent type 1 diabetes. We evaluated the effects of switching from Deg to Gla-300 on the day-to-day GV and the frequency of hypoglycemia in patients with insulin-dependent type 1 diabetes treated with Deg-containing basal-bolus insulin therapy (BBT). Materials and Methods: We conducted a retrospective study on 24 patients with insulin-dependent type 1 diabetes whose treatment was switched from Deg-containing BBT to Gla-300-containing BBT. We evaluated the day-to-day GV measured as the standard deviation of fasting blood glucose levels (SD-FBG) calculated by the self-monitoring of blood glucose records, the frequency of hypoglycemia (total, severe, and nocturnal), and blood glucose levels measured as fasting plasma glucose (FPG) levels and hemoglobin A1c (HbA1c). Results: The characteristics of the patients included in the analysis with high SD-FBG had frequent hypoglycemic events, despite the use of Deg-containing BBT. For this population, SD-FBG and the frequency of nocturnal hypoglycemia decreased after the switch from Deg to Gla-300. Despite the decrease in the frequency of nocturnal hypoglycemia, the FPG and HbA1c did not worsen by the switch. The change in the SD-FBG had a negative correlation with the SD-FBG at baseline and a positive correlation with serum albumin levels. Conclusions: Switching from Deg to Gla-300 improved the SD-FBG and decreased the frequency of nocturnal hypoglycemia in insulin-dependent type 1 diabetes treated with Deg-containing BBT, especially in cases with low serum albumin levels and a high GV.

Why Do So Many People with Type 2 Diabetes Who Take Insulin Have Lipohypertrophy? Fate or Educational Deficiencies?

Cutaneous lipohypertrophy (LH) is a thickened, "rubbery" lesion in the subcutaneous tissue following multiple injections performed at the same site, i.e., an incorrect injection technique. It is widespread, averaging 47% of insulin patients worldwide, and has severe direct and indirect consequences. Direct consequences consist mainly of poor metabolic control and frequent hypoglycemic events (HYPOs), and indirect ones of markedly increased healthcare costs related to hospital access due to acute events and long-term disease complications. This observation also holds for Italy, despite the National Health System organization expecting every patient with diabetes to undergo a series of visits by different care team members, each performing a specific treatment/education task. Indeed, the recent literature points to poor awareness of LH relevance and metabolic consequences among doctors from general and diabetic hospital wards, with educational deficiencies on correct injection practice in nurses too. The aim was to establish if, to what extent, and by whom they had received training on correct insulin injection techniques, and how many initially received notions had persisted over time. We investigated the possible causes of such a failure from the point of view of 1160 insulin-requiring subjects with type 2 diabetes (T2DM), reporting for the first time to specialized diabetic structures through a validated questionnaire and, in the same patients, we searched for LH by inspection/palpation according to international guidelines, further confirmed by ultrasound scans. We then analyzed differences in education and injecting behavior between subjects classified as LH+ or LH- depending on the presence or absence of LH lesions. We documented significant educational gaps, with 50% of patients failing to refer to healthcare professionals and relying on their peers with diabetes, thought to be more experienced in 15% of the cases. Seventy-five percent of LH- patients received education from healthcare providers, while 90% of LH+ learned from another patient or could not remember how they knew, and 68% of LH+ versus 52% of LH- (p < 0.01) patients had failed to receive training on injection techniques by healthcare providers. All of this enabled the most disabling features of diabetes from the very beginning of the disease history. This study documents, from the patients' point of view, that educational gaps are significant and that, even in initially trained subjects, education on correct injection techniques has a fleeting effect if not regularly recalled. Therefore, to rehabilitate LH+ patients as soon as possible and prevent LH- patients from inadvertently slipping into the other group, there is an urgent need to educate doctors and nurses repeatedly on the importance of correctly injecting insulin to improve patients' knowledge and skills.

Bruising: A Neglected, Though Patient-Relevant Complication of Insulin Injections Coming to Light from a Real-Life Nationwide Survey.

IntroductionDespite the availability of sophisticated devices and suitable recommendations on how to best perform insulin injections, lipohypertrophy (LH) and bruising (BR) frequently occur as a consequence of improper injection technique.AimThe purpose of this nationwide survey was to check literature-reported LH risk factors or consequences for any association with BRMethodThis was a cross-sectional, observational, multicenter study based on the identification of skin lesions at all patient-reported insulin injection sites in 790 subjects with diabetes. General and injection habit-related elements were investigated as possible BR risk factors.ResultsWhile confirming the close relationship existing between LH and a full series of factors including missed injection site rotation, needle reuse, long-standing insulin treatment, frequent hypoglycemic events (hypos), and great glycemic variability (GV), the observed data could find no such association with BR, which anyhow came with high HbA1c levels, missed injection site rotation, and long-standing insulin treatment.ConclusionBR most likely depends on the patient’s habit of pressing the injection pen hard onto the skin. Despite being worrisome and affecting quality of life, BR seems to represent a preliminary stage of LH but does not affect the rate of hypos and GV.Trial Registration207/19.09.2017

Glucose Homeostasis, Fetal Growth and Gestational Diabetes Mellitus in Pregnancy after Bariatric Surgery: A Scoping Review.

Background: Pregnancies in women with a history of bariatric surgery are becoming increasingly prevalent. Surgically induced metabolic changes benefit mother and child, but can also lead to some adverse pregnancy outcomes. Knowledge about glucose homeostasis in these pregnancies could elucidate some of the mechanisms behind these outcomes. This review focusses on glucose homeostasis and birth weight. Methods: We considered papers dealing with glucose homeostasis, gestational diabetes mellitus (GDM) and/or small-for-gestational age infants (SGA) in pregnancies with a history of sleeve gastrectomy (SG) or Roux-en-y gastric bypass (RYGB). Results: Since an OGTT is unreliable to diagnose GDM in a pregnancy after bariatric surgery, the true incidence of GDM is unknown. Alternative screening strategies are needed. Furthermore, these pregnancies are marked by frequent hypoglycemic events as well as wide and rapid glycemic excursions, an issue that is very likely underreported. There is a lack of uniformity in reporting key outcomes and a large variation in study design and control population. Conclusion: Alteration of glucose homeostasis in a pregnancy after bariatric surgery should be further studied using unequivocal definition of key concepts. Glycemic control may prove to be a modifiable risk factor for adverse pregnancy outcomes such as the delivery of an SGA baby.

Vildagliptin vs. insulin treatment alone in diabetic acute coronary syndrome patients.

Vildagliptin, an oral antidiabetic of the dipeptidyl peptidase-4 (DPP-4) inhibitor drugs, exhibits an overall low risk of hypoglycemia with less frequent hypoglycemic events in type 2 diabetes mellitus (T2DM) patients than other antidiabetic drugs. We hypothesized that among hospitalized acute coronary syndrome (ACS) patients, the addition of vildagliptin to subcutaneous insulin therapy would reduce the risk of hypoglycemic events. One hundred ACS T2DM adult patients naive to DPP-4 inhibitors were enrolled during admission to the ICCU. Patients were divided into two randomized controlled groups: a subcutaneous rapid-acting insulin-only therapy group and an oral vildagliptin plus subcutaneous insulin group. The trial was open label with no placebo arm. Mean glucose values, insulin values given for correction per hospitalization, and the number of hypoglycemic events (glucose < 70 mg/dL) were documented. Eight hypoglycemia events occurred in the insulin-only group and none in the insulin plus DPP-4 inhibitor group (P < 0.001). Patients with acute myocardial infarction experienced a higher number of hypoglycemic events compared with unstable angina diagnosed patients. No significant differences were found regarding glucose level (P = 0.462) and administered insulin units (P = 0.639). In T2DM patients, the addition of DPP-4 inhibitors to routine subcutaneous insulin therapy may significantly reduce hypoglycemic events while maintaining acceptable recommended ranges of glucose. Further studies on a larger scale are required to verify these results and to support that DPP-4 inhibitors added to today's standard insulin-only treatment in hospitalized diabetic ACS patients may improve overall glycemic control and provide a potential treatment option in this challenging clinical setting.

Association of time in blood glucose range with outcomes following cardiac surgery

BackgroundThe importance of optimal postoperative glycemic control in cardiac patients remains unclear. Various glycemic targets have been prescribed to reduce wound infection and overall mortality rates.Aim of the work: To assess glucose control, as determined by time in range (TIR), in patients with glycemic targets of 6.0 to 8.1 mmol/L, and to determine factors related to poor control.MethodsThis prospective descriptive study evaluated 227 consecutive patients, 100 with and 127 without diabetes, after cardiac surgery. Patients received insulin to target glucose concentrations of 6.0 to 8.1 mmol/L. Data analyzed included patient age, gender, race, Euro score, cardiopulmonary bypass time (CPB), aortic cross clamp time (ACC), length of ventilation, stay in the intensive care unit (ICU) and stay in the hospital. Patients were divided into two groups, those who maintained > 80% and < 80% TIR. Outcome variables were compared in diabetics and non-diabetics.ResultsPatients with >80% and <80% TIR were matched in age, sex, gender, and Euro score. Failure to maintain target glycemia was significantly more frequent in diabetics (p = 0.001), in patients with glycated hemoglobin (HbA1c) > 8% (p = 0.0001), and in patients taking dopamine (p = 0.04) and adrenaline (p = 0.05). Times of CPB and ACC, length of stay in the ICU and ventilation were significantly higher in patients with TIR <80% than >80%. Rates of hypoglycemia, acute kidney injury, and in-hospital mortality were similar in the two groups, although the incidence of wound infection was higher in patients with TIR <80%. Both diabetics and non-diabetics with low TIR had poorer outcomes, as shown by length of stay and POAF. No significant differences were found between the two ethnic groups (Arabs and Asians).ConclusionPatients with >80% TIR, whether or not diabetics, had better outcomes than those with <80% TIR, as determined by wound infection, lengths of ventilation and ICU stay. Additionally, they were not subject to frequent hypoglycemic events. Preoperatively high HbA1C is likely a good predictor of poor glycemic control.

Biologic Agents in Islet Transplantation

Islet transplantation is today an accepted modality for treating selected patients with frequent hypoglycemic events or severe glycemic lability. Despite tremendous progress in islet isolation, culture, and preservation, clinical use is still restricted to a limited subset, and lifelong immunosuppression is required. Issues surrounding limited islet revascularization and immune destruction remain. One of the major challenges is to prevent alloreactivity and recurrence of autoimmunity against β-cells. These two hurdles can be effectively reduced by immunosuppressive therapy combining induction and maintenance treatments. The introduction of highly potent and selective biologic agents has significantly reduced the frequency of acute rejection and has prolonged graft survival, while minimizing the complications of this therapeutic scheme. This review will address the most important biological agents used in islet transplantation. We provide a historical perspective of their introduction into clinical practice and their role in current clinical protocols, aiming at improved engraftment efficiency, increased long-term survival, and better overall results of clinical islet transplantation.

Insulin therapy and body weight: benefits of biphasic human insulin analogue NovoMix 30

Body weight (BW) excess is a characteristic problem for type 2 diabetes mellitus (T2DM) both as its pathogenetic feature and as a side effect of blood glucose lowering therapy. In the latter case reduction of glycosuria and frequent hypoglycemic events are primarily blamed for BW gain, but additional factors like direct effect of insulin on lipogenesis and influence of its supraphysiologic levels on regulation of appetite via CNS structures are also under discussion.Advances of the last years have brought new hope due to introduction of drug classes that do not affect BW. However, fraction of patients dependent on exogenous insulin shows stable trend for growth. Deterioration of beta-cell secretory capacity makes insulin an ultimately indispensable tool in the foreseeable future. As so, insulin therapy modalities with minimal impact on BW are preferable. In this regard human insulin analogues of both rapid and prolonged action have certain advantages.Current article addresses influence of pre-mixed insulin preparation NovoMix 30 (Novo Nordisk, Denmark) on BW. A summary of several studies of substantial duration (up to 3 years) suggests a neutral effect on BW in various categories of T2DM patients (including obese and elder patients).Therapy with pre-mixed preparations is an adequately safe and effective T2DM treatment modality and is advantageous for patients in whom BW gain is particularly unfavorable.

Comparative efficacy assessment for various insulin regimens in patients with type 2 diabetes mellitus, ischaemic heart disease and frequent hypoglycemic events

Aims. To study influence of combined treatment with human insulin analogues (insulin aspart and insulin detemir) on glycemic control,insulin resistance and development of ischaemic heart disease (IHD) in patients with type 2 diabetes mellitus (T2DM) and frequenthypoglycemic events in comparison with that of human insulins (soluble and isophane). Materials and methods. 54 patients (mean age 61.2?0.7) with T2DM and IHD participated in this study. All included patients experiencedfrequent mild and moderate hypoglycemic events (3+ episodes per week). We analyzed frequency and severity of hypoglycemia,parameters of glycemic and lipid metabolism, number of ischaemic episodes per day, duration and depth of ST depression, circadianindex, incidence of different types of arrhythmia and conduction abnormalities as measured by Holter ECG monitoring.All patients were subdivided into two groups by random sampling: 21 patient (first group) carried on with human soluble insulin andisophane in an optimized basal-bolus regimen. In 33 patients, comprising second group, treatment was changed for combination ofinsulin aspart (NovoRapid?, Novo Nordisk, Denmark) and insulin detemir (Levemir?, Novo Nordisk, Denmark). Follow-up periodwas set to 6 months. Results. In patients with frequent hypoglycemic experience different types of arrhythmia and heart conduction abnormalities wereobserved in 75.9% of cases. Most patients had complex types of arrhythmic disorders (70.4%) with ventricular extrasystole being themost common one. Signs of myocardial ischaemia were registered in 48.1% of patients.After 6 months of follow-up patients from the second group demonstrated a statistically significant decrease in fasting and postprandiallevels of glycemia (p=0.000001). Both groups also had a significantly lower rate of hypoglycemic events. Moreover, in the second groupall episodes of hypoglycemia were mild and occurred only in 36.4% of cases. Additionally, after 6 months of treatment with humaninsulin analogues ventricular extrasystoles were registered only in 24.2% of patients, while rate and duration of ischaemic episodesdropped to 4.25?1.51 (p=0.012, comparing with first group). Conclusion. Treatment with human insulin analogues NovoRapid? and Levemir? is associated with 1.6% decrease in HbA1c levels.Mild hypoglycemia was 72.2% less frequent, as compared with rates in the group on human soluble and isophane insulin, while moderateand severe hypoglycemic events were not observed at all. In turn, decrease in frequency and severity of hypoglycemia was associatedwith substantial improvement in cardiovascular status due to lower number and duration of ischaemic episodes (including painlessvariant) and lower frequency of heart rhythm disorders.