Basal-bolus Therapy Research Articles

Faster-Acting Insulin Aspart vs. Insulin Aspart in Basal-Bolus Therapy Improved Postprandial Glycemic Control in Uncontrolled T2D in the Onset® 2 Trial

A multicentre, double-blind, treat-to-target trial evaluated the efficacy of faster-acting insulin aspart (faster aspart) vs. insulin aspart (IAsp) in adults with uncontrolled type 2 diabetes (T2D) on basal insulin and oral antidiabetic drugs. After optimizing basal insulin glargine during an 8-week run-in (mean HbA1c at baseline 7.9%), subjects were randomized 1:1 to mealtime faster aspart (n=345) or IAsp (n=344), each with insulin glargine and metformin. Bolus insulin was titrated using a simple, daily, patient-driven titration algorithm.

The relationship between HbA1c values and the occurrence of hypoglycemia as assessed by continuous glucose monitoring in patients with type 1 diabetes

BackgroundWe aimed to examine the relationship between the occurrence of hypo-/hyperglycemia and HbA1c values, as assessed by continuous glucose monitoring (CGM) in patients with type 1 diabetes.MethodsThe study subjects comprised 101 type 1 diabetic patients on basal-bolus insulin therapy, who were put on masked CGM immediately after admission. The subjects were divided into four groups equally by HbA1c values and the 24-h CGM data were compared among the groups.ResultsGroups A to D comprised 24 patients with HbA1c ≤7.2 %, 26 patients with 7.2 % <HbA1c ≤8.2 %, 27 patients with 8.2 % <HbA1c ≤9.2 %, and 24 patients with HbA1c >9.2 %, respectively. The higher the HbA1c values, the significantly higher the 24-h mean glucose levels [median (25–75 percentiles)], with the HbA1c in groups A to D being 133 (114–155), 158 (132–188), 182 (152–206), and 186 (143–215) mg/dL, respectively (P < 0.001). Conversely, the higher the HbA1c values, the significantly shorter the time in hypoglycemia (<70 mg/dL), with the time in groups A to D being 170 (58–341), 78 (0–210), 45 (0–105), and 20 (0–105) min, respectively (P = 0.014); and the higher the HbA1c values, the significantly shorter the time in nocturnal hypoglycemia, with the time in groups A to D being 120 (5–269), 25 (0–120), 0 (0–60), and 0 (0–89) min, respectively (P = 0.019). No significant difference was seen between groups A to D in the standard deviations (SDs) of 24-h glucose values at 53 (40–65), 54 (45–70), 64 (55–76), and 58 (48–80), respectively.ConclusionIn type 1 diabetic patients, lower HbA1c was not associated with lower SD of 24-h glucose values, but may result in increased hypoglycemia.Trial Registration Current controlled trials UMIN000019190

Pregnancy snapshot: a retrospective, observational case–control study to evaluate the potential effects of maternal diabetes treatment during pregnancy on macrosomia

Objective: Pregnancy in women with diabetes is associated with increased incidence of macrosomia (high birth weight) versus women without diabetes. Macrosomia increases the risk of complications during delivery and neonatally. The potential effect on macrosomia incidence certain diabetes treatments may have is not fully established. This study aims to identify whether specific components of the prenatal care of mothers with diabetes are associated with increased macrosomia risk in a real-world U.S. setting. Research design and methods: Retrospective, observational case-controlled study of mothers either without diabetes, or with type 1 (T1D), type 2 (T2D), or gestational diabetes mellitus (G.D.M.), using data from a U.S. insurance claims database. Treatment selection was at physician discretion. Main outcome measure: Incidence of macrosomia. Results: For mothers with T2D, use of neutral protamine Hagedorn (N.P.H.) insulin and glyburide increased during pregnancy, from 3.4% to 33.3%, and 3.7% to 16.5%, respectively. The most common G.D.M. treatments during pregnancy were glyburide (15.5%), N.P.H. (12.9%), basal–bolus therapy (10.0%), and metformin (8.1%). Endocrinologist care during pregnancy was associated with insulin use – but not glyburide use – for mothers with G.D.M., and with insulin use for mothers with T1D and T2D (compared with mothers not visiting an endocrinologist). Glyburide was associated with higher odds for macrosomia: G.D.M. (odds ratio [O.R.] 1.53, 95% confidence interval [C.I.] 1.38–1.69, p < 0.0001); T2D (O.R. 1.93, 95% C.I. 1.51–2.47, p < 0.0001). Endocrinologist care was associated with lower odds for macrosomia overall (O.R. 0.86, 95% C.I. 0.81–0.92) and for mothers with G.D.M. (O.R. 0.85, 95% C.I. 0.75–0.97, p = 0.0156) when the sub-populations were examined in separate models. Conclusions: Healthcare utilization and endocrinologist care were related to positive birth outcomes, especially with G.D.M. Further research into the safety and efficacy of glyburide in pregnancy is warranted. This study cannot infer causality and may not be representative of current U.S. healthcare practice.

Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia: The HypoAna trial

AimInsulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night. MethodsThis 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal–bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996). ResultsAnalogue-based treatment resulted in a 6% (2–10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32–46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36–57%]; P<0.0001) and asymptomatic (28% [14–39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. ConclusionIn T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.

Study of Insulin Requirement Modeling in Hospitalized Elderly Patients with Type 2 Diabetes at a Late Stage of Stepwise Escalation Therapy.

This study explored the relationships between exogenous insulin requirements and endogenous variables in elderly patients with type 2 diabetes (T2D). Patients with T2D 65 years of age or older were enrolled for a short hospitalization period in order to start or change their basal-bolus therapy. The following data were collected: age, sex, diabetes duration, body mass index, glycosylated hemoglobin, estimated glomerular filtration rate (eGFR), and triglyceride (TG) levels. Data from 71 elderly T2D patients (31 men/40 women; 75.7 ± 6 years of age) were analyzed by data mining techniques. The total daily dose of insulin (TDI) ranged from 0.24 U/kg to 2.5 U/kg (ratio >1:10). Three clusters of patients were identified: Cluster 1 (n = 22) consisted of older patients (age, 82.05 ± 3.6 years) (P < 0.0001) with a TDI of 0.59 ± 0.21 U/kg/day and lower TG level (1.1 ± 0.4 mmol/L) (P < 0.0001). Cluster 2 (n = 22) consisted of patients with a TDI of 0.71 ± 0.24 U/kg/day with a higher eGFR (75.3 ± 18.8 mL/min) (P < 0.001) and a shorter duration of diabetes (13.6 ± 6.4 years) (P < 0.001). Cluster 3 (n = 27) consisted of patients with a larger proportion of macroangiopathic complications (P < 0.05), having a TDI of 1.31 ± 0.54 U/kg/day, higher TG level (2.2 ± 0.7 mmol/L) (P < 0.001), and lower eGFR (46.3 ± 16 mL/min). The average basal-bolus ratio was 43%/57% with a maximum bolus requirement due to carbohydrate intake at breakfast. Insulin requirements in elderly T2D patients vary widely. Age, TG level, and eGFR appeared to be the most predictive factors of TDI. Because of the small sample size, further studies would be required to extrapolate these results.

A 1-year, prospective, observational study of Japanese outpatients with type 1 and type 2 diabetes switching from insulin glargine or detemir to insulin degludec in basal-bolus insulin therapy (Kumamoto Insulin Degludec Observational study).

Aims/IntroductionThe aim of the present prospective observational study was to assess long‐term efficacy and safety of insulin degludec as a part of a basal–bolus therapy for Japanese patients with type 1 or type 2 diabetes in routine clinical practice.Materials and MethodsIn the present study, 93 type 1 diabetes patients and 135 type 2 diabetes patients treated with insulin glargine or detemir were switched from their basal insulin to insulin degludec. The primary end‐points were the changes in glycated hemoglobin (HbA1c) from baseline at 3, 6 and 12 months. The secondary end‐points were changes in body mass index, insulin dose, frequency of hypoglycemia and adverse events.ResultsHbA1c levels from baseline were significantly reduced at 3, 6, and 12 months by 0.4, 0.4 and 0.3% in type 1 diabetes patients, respectively, and by 0.5, 0.5 and 0.3% in type 2 diabetes patients, respectively. Body mass index in type 1 diabetes patients increased significantly (P < 0.05), whereas that in type 2 diabetes patients did not change. Basal insulin dose decreased significantly at 3 months after switching (P < 0.05), and returned baseline dose at 12 months in type 1 diabetes and type 2 diabetes patients. The frequency of both total and nocturnal hypoglycemia decreased significantly in type 1 diabetes and type 2 diabetes patients (P < 0.05). The result of multiple regression analysis showed that baseline HbA1c was a significant independent variable of the percentage change in HbA1c with switching.ConclusionIn both type 1 diabetes and type 2 diabetes patients, switching from insulin glargine or insulin detemir to insulin degludec led to improvement of glycemic control with a significant reduction of hypoglycemia.

Hypoglycemia Event Rates: A Comparison Between Real-World Data and Randomized Controlled Trial Populations in Insulin-Treated Diabetes.

IntroductionHypoglycemia is the most common adverse effect of diabetes therapy, particularly insulin treatment. Hypoglycemia is associated with considerable clinical and economic burden, and may be under-reported. The aim of this study was to com pare the frequency of hypoglycemic events reported in real-world settings with those reported in clinical trials.MethodsWe conducted a structured literature review in PubMed to identify hypoglycemic event rates in patients with type 1 diabetes mellitus (T1DM) and insulin-treated type 2 diabetes mellitus (T2DM) from real-world data (RWD) and randomized controlled trials (RCTs). The search was restricted to English language, full-text publications from 2010 onwards, reporting on treatment of T1DM or T2DM with basal only, basal-bolus, or premix insulin.ResultsThe final dataset included 30 studies (11 RWD studies and 19 RCTs). Six studies (RWD, n = 2; RCT, n = 4) reported hypoglycemia event rates in people with T1DM. For all reported categories of hypoglycemia (severe, non-severe, and nocturnal), rates were consistently higher in RWD studies compared with RCTs. Twenty-five studies (RWD, n = 10; RCT, n = 15) reported hypoglycemia event rates in people with insulin-treated T2DM. For T2DM basal-oral therapy; the highest rates were observed in RWD studies, although there was an overlap with RCT rates. For basal-bolus therapy, there was considerable between-study variability but higher rates of severe and non-severe hypoglycemia were generally observed in RWD studies. For T2DM premix insulin, reported rates of hypoglycemia in RWD studies and RCTs were similar.ConclusionWe found that higher rates of hypoglycemia are observed in real-world settings compared with clinical trial settings, although there is a large degree of overlap. Due to the inherent constraints of RCTs, they are likely to underestimate the burden of hypoglycemia in clinical practice. Further, high-quality RWD are needed to determine a more accurate incidence of hypoglycemia in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0157-z) contains supplementary material, which is available to authorized users.

The Impact of Continuous Subcutaneous Insulin Infusion Therapy on Efficacy and Safety in a Cohort of Type 1 Diabetes Patients: A 3-Year Prospective Study.

Several studies have found improved glycemic control with continuous subcutaneous insulin infusion compared with multiple daily insulin injections for patients with type 1 diabetes, albeit for a relatively short-period of follow-up. This prospective study presents for the first time the optimization of glycemic control with insulin pumps in a cohort of Greek patients with type 1 diabetes for a 3-year follow-up period during the socioeconomic crisis in Greece. Ninety-four patients, previously on intensified basal-bolus insulin therapy with poor glycemic control, were initially recruited. Glycosylated hemoglobin (HbA1c), hypoglycemic and diabetic ketoacidosis episodes, pump-related side effects, lipidemic profile, 24-h urine albumin excretion, body mass index, blood pressure, and total daily insulin requirements (bolus and basal) were recorded during the 3-year follow-up. Statistical analysis was initially conducted for the entire study population and after body mass index and gender stratification. Seventy-nine patients completed the study. A statistically significant decrease of HbA1c level (P < 0.0001) was observed at the end of Year 1 and was retained for the following years for the whole population. Similarly, significantly fewer hypoglycemic episodes occurred during the follow-up period (P < 0.0001) compared with study entry. Insulin pump treatment was not accompanied with weight changes across all body mass index strata. Continuous subcutaneous insulin infusion achieved almost optimal glycemic control, reduced the number of hypoglycemic episodes without weight gain, and was well tolerated for the whole study period. Finally, this therapeutic approach was accompanied with lower daily insulin requirements.

Insulin degludec aspart: One-year real world experience.

Background:This retrospective analysis describes the use of insulin degludec aspart (IDegAsp) in India.Material and Methods:All subjects who had received IDegAsp for 52 weeks at two endocrine centers were included in this study.Results:Forty-eight subjects (40 men), with mean age of 54.33 ± 9.63 years and mean duration of diabetes of 6.33 ± 2.96 years, started IDegAsp as insulin of initiation (16), as an intensification regime (4), as de-escalation from basal-bolus therapy (16), or as switch from premixed insulin (12). The dose of IDegAsp fell from 43.17 ± 21.18 U/day or 0.56 ± 0.23 U/kg to 37.75 ± 17.13U/day (0.51 ± 0.12 U/kg) at 24 weeks and 41.41 ± 15.33 U/day (0.56 ± 0.17 U/kg) at 52 weeks. Hemoglobin A1c (HbA1c), which was 9.52 ± 1.27% at the start of therapy, fell to 7.51 ± 0.46% at 26 weeks and to 7.48 ± 0.40% at 52 weeks. Fasting plasma glucose fell from 154.08 ± 33.30 mg% to 108.58 ± 22.26 mg% at 26 weeks and 102.17 ± 12.79 mg% at 52 weeks. Of the 48 subjects, 39 (81.25%) achieved a target of HbA1c <7.0% at both 26 and 52 weeks. No episode of hypoglycemia was reported in the 4 weeks preceding the analysis.Conclusion:This communication highlights the efficacy, safety, and tolerability, while providing insight into the usage patterns of IDegAsp.

Neurological complications in patients with diabetes mellitus type 1 treated with different methods of insulinotherapy

Thirty-four patients, aged from 18 to 40 years, with diabetes mellitus type 1 receiving insulinotherapy, with a duration of the disease 14.25±9.25 years, have been examined. By the time of the study the patients of the first group have been treated with continuous subcutaneous insulin infusion therapy (CSII) for 4.5±1.5 years following 11.3±5.4years of standard basal-bolus therapy; the patients of the second group have been treated with basal-bolus insulin therapy for 12.7±7.7 years. Neurological status and the presence of vegetative symptoms of the patients were assessed, following tests were performed: MMSE, MoCA, HADS, TSS, NSS, NDS. The results demonstrated that the patients from the group of CSII therapy have had less signs and symptoms of neuropathy, cognitive disorders and better emotional condition than the patients from the group of basal-bolus therapy.

In-Silico Trials for Glucose Control in Hospitalized Patients with Type 2 Diabetes.

Although various basal-bolus insulin therapy (BBIT) protocols have been used in the clinical environment, safer and more effective BBIT protocols are required for glucose control in hospitalized patients with type 2 diabetes (T2D). Modeling approaches could provide an evaluation environment for developing the optimal BBIT protocol prior to clinical trials at low cost and without risk of danger. In this study, an in-silico model was proposed to evaluate subcutaneous BBIT protocols in hospitalized patients with T2D. The proposed model was validated by comparing the BBIT protocol and sliding-scale insulin therapy (SSIT) protocol. The model was utilized for in-silico trials to compare the protocols of adjusting basal-insulin dose (BBIT1) versus adjusting total-daily-insulin dose (BBIT2). The model was also used to evaluate two different initial total-daily-insulin doses for various levels of renal function. The BBIT outcomes were superior to those of SSIT, which is consistent with earlier studies. BBIT2 also outperformed BBIT1, producing a decreased daily mean glucose level and longer time-in-target-range. Moreover, with a standard dose, the overall daily mean glucose levels reached the target range faster than with a reduced-dose for all degrees of renal function. The in-silico studies demonstrated several significant findings, including that the adjustment of total-daily-insulin dose is more effective than changes to basal-insulin dose alone. This research represents a first step toward the eventual development of an advanced model for evaluating various BBIT protocols.

Can Fasting Glucose Levels or Post-Breakfast Glucose Fluctuations Predict the Occurrence of Nocturnal Asymptomatic Hypoglycemia in Type 1 Diabetic Patients Receiving Basal-Bolus Insulin Therapy with Long-Acting Insulin?

ObjectiveTo investigate whether the occurrence of nocturnal asymptomatic hypoglycemia may be predicted based on fasting glucose levels and post-breakfast glucose fluctuations.Patients and MethodsThe study subjects comprised type 1 diabetic patients who underwent CGM assessments and received basal-bolus insulin therapy with long-acting insulin. The subjects were evaluated for I) fasting glucose levels and II) the range of post-breakfast glucose elevation (from fasting glucose levels to postprandial 1- and 2-hour glucose levels). The patients were divided into those with asymptomatic hypoglycemia during nighttime and those without for comparison. Optimal cut-off values were also determined for relevant parameters that could predict nighttime hypoglycemia by using ROC analysis.Results64 patients (mean HbA1c 8.7 ± 1.8%) were available for analysis. Nocturnal asymptomatic hypoglycemia occurred in 23 patients (35.9%). Fasting glucose levels (I) were significantly lower in those with hypoglycemia than those without (118 ± 35 mg/dL vs. 179 ± 65 mg/dL; P < 0.001). The range of post-breakfast glucose elevation (II) was significantly greater in those with hypoglycemia than in those without (postprandial 1-h, P = 0.003; postprandial 2-h, P = 0.005). The cut-off values determined for relevant factors were as follows: (I) fasting glucose level < 135 mg/dL (sensitivity 0.73/specificity 0.83/AUC 0.79, P < 0.001); and (II) 1-h postprandial elevation > 54 mg/dL (0.65/0.61/0.71, P = 0.006), 2-h postprandial elevation > 78 mg/dL (0.65/0.73/0.71, P = 0.005).ConclusionsNocturnal asymptomatic hypoglycemia was associated with increases in post-breakfast glucose levels in type 1 diabetes. Study findings also suggest that fasting glucose levels and the range of post-breakfast glucose elevation could help predict the occurrence of nocturnal asymptomatic hypoglycemia.

Insulin pumps: Beyond basal-bolus.

Insulin pumps are a major advance in diabetes management, making insulin dosing easier and more accurate and providing great flexibility, safety, and efficacy for people who need basal-bolus insulin therapy. They are the preferred treatment for people with type 1 diabetes and many with type 2 diabetes who require insulin. This article reviews the basics of how insulin pumps work, who benefits from a pump, and how to manage inpatients and outpatients on insulin pumps.

Systematic Literature Review of Basal Bolus Insulin Analogue Therapy during Pregnancy

Currently standard insulin therapy for pregnancies complicated by diabetes mellitus (DM) is a combination of intermediate Neutral Protamine Hagedorn (NPH) and regular human insulin. In contrast, for non-pregnant individuals with diabetes, standard insulin therapy is basal bolus therapy (BBT) using a combination of rapid- and long-acting insulin analogues designed to mimic physiologic biphasic insulin secretion by the pancreatic beta cells. Although there are published reports describing use of BBT during pregnancy, due to the lack of strong clinical evidence regarding safety and efficacy of BBT during pregnancy, its use has not been adopted as standard insulin administration during pregnancies complicated by diabetes mellitus. To evaluate the evidence for this discrepant clinical management, we conducted a systematic review. Search strategy and selection criteria: PubMed, Medline, Cochrane Database of Systematic Reviews for publications between 1996 and 2014. Search terms: lispro, apart, glargine, detemir, glulisine, Humalog, NovoLog, Lantus, Levemir, Apidra, pregnancy, and diabetes. Included: randomized clinical trials, prospective and retrospective cohort analyses, case-control studies and case series and reports. Search limited to human studies and English language. Excluded: review articles. Nineteen studies were identified that assessed safety/efficacy of rapid-acting insulin analogues, lispro and aspart, and 23 studies that assessed the long-acting insulin analogues, glargine and detemir, in pregnant patients complicated with pregestational (PGDM) and gestational diabetes mellitus (GDM). The principal efficacy endpoint examined in the selected studies was glycated hemoglobin levels. Other study outcome variables to assess maternal glycemic control included fasting and postprandial glucose levels, large for gestational age (LGA) infants, mean birth weight, congenital malformations, and incidence of hypoglycemic events. Compared to conventional insulin therapy, insulin analogue use provided similar overall glycemic control in pregnancy. In addition, they contributed to greater postprandial glucose control. There was no compelling evidence that insulin analogue use was associated with any significant differences in maternal and neonatal outcomes, particularly in terms of incidences in maternal and neonatal hypoglycemia, LGA, and congenital malformations. Given the documented benefits of physiological insulin replacement, we found no reason that BBT should not be standard prenatal care for pregnancies complicated by DM.

Effectiveness and tolerability of treatment intensification to basal-bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study.

BackgroundDue to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT) regimen in T2DM patients in daily clinical practice.MethodsThis noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT).ResultsA total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean −0.94% and −0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean −1.29% and −1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1).ConclusionIntensifying glargine-based BOT or glulisine-based SIT to a BBT regimen in poorly controlled T2DM patients in daily routine care led to marked improvements of glycemic control and was well tolerated.

PDB73 - Health Utilities Associated with Hypoglycemic Events in Type 2 Diabetes Mellitus (T2DM) Patients Receiving Basal-Bolus Insulin Therapy

PDB73 - Health Utilities Associated with Hypoglycemic Events in Type 2 Diabetes Mellitus (T2DM) Patients Receiving Basal-Bolus Insulin Therapy

The relationships between glucose variability and renal function in type 2 diabetes patients on basal-bolus insulin therapy

Aim. To assess the relationship of glucose variability (GV) and renal function in patients with type 2 diabetes on basal-bolus insulin therapy.Materials and methods. We observed 101 females with type 2 diabetes, aged 47–79 years, with a glomerular filtration rate (GFR) 30 mL/min/1.73 m2. Insulin was combined with metformin in 45 of these women. The mean glucose and standard deviation, continuous overlapping net glucose action, lability index, J-index, low blood glucose index (LBGI), high blood glucose index (HBGI), M-value and mean absolute glucose (MAG) were calculated based on the results of blinded continuous glucose monitoring. The prevalence of episodes of low interstitial glucose (3.9 and 2.8 mmol/L) of at least 20-min duration was estimated.Results. Patients with a GFR of 30–44 mL/min/1.73 m2 had significantly lower HBGI, J-index, MAG and M-value compared with those with better filtration (all p 0.05); LBGI was not dependent on GFR. The GFR values were weakly and positively correlated with HBGI, J-index, M-value and MAG. Multiple regression analysis showed that GFR is an independent predictor of MAG (p = 0.04). No significant differences were found in the prevalence of episodes of low interstitial glucose between patients with different GFR ranges.Conclusions. GV parameters are related to renal function in type 2 diabetic women on basal-bolus insulin therapy. Patients with stage 3b chronic kidney disease have reduced GV, predominantly in the hyperglycaemic band, compared with those with better filtration.

Lower limbs edema by insulin glargine treatment: two other cases in pediatrics.

Marta, 13 years aged, suffered from type 1 diabetes from the age of 9 years. She was admitted in our clinic for a progressive appearance of edema in both legs (Fig. 1). The edema was located in the pretibial and ankle region, bilaterally, mainly on the left; the skin was normal, not hot and not erythematous. Femoral and popliteal pulses were normal. Left and right ankle diameters were, respectively, 29.5 and 28 cm. The family history was negative for diseases associated with edema. The metabolic control has always been good (yearly mean HbA1c 7.5 % 58 mmol/mol). She was on multi-daily injections (MDI) therapy, and the need of insulin was 0.7 U/kg/day. Up to 3 months before the occurrence of edema, she had been treated with human insulin (Humulin R and Humulin I ). During the adolescence, as the lifestyle was changing, we decided to start basal bolus therapy. Boluses of fast analogues were administered on the arms and in abdomen, while insulin glargine was administered exclusively on both thighs, alternating the right and the left thigh every day. All the most common causes of edema have been ruled out with specific investigations: Color Doppler ultrasound of the arteries and veins of the limbs excluded vascular diseases; ECG and transthoracic echocardiography excluded cardiac failure. Blood count, C-reactive protein (CRP) and VES, serum electrolytes, protein electrophoresis and the liver, thyroid and kidney function tests were within the normal range. Moreover, we rejected other causes of edema due to infection diseases. To exclude obstruction of the inferior vena cava or the thoracic duct, the patient underwent, respectively, abdominal ultrasound and chest X-rays, which did not show pathognomonic features. In addition, we also ruled out the Turner syndrome with the high-definition karyotype study. Medical history, clinical examination and laboratory findings excluded the involvement of systemic diseases. No other medicaments except for insulin had been assumed so, suspecting that the cause of the edema could have been the local mechanism of absorption of basal insulin, we replaced insulin glargine with rapid and intermediate human insulin. After 1-month edema was still present, but significantly reduced (diameter 25 cm in both legs). The complete resolution occurred after 3 months from the suspension of glargine even if a slight worsening of metabolic control (HbA1c 8.5 % 69 mmol/mol) was observed. Managed by Antonio Secchi.

Prevalence of dysglycaemic events among inpatients with diabetes mellitus: a Singaporean perspective.

As the effectiveness of intensive glycaemic control is unclear and recommended glycaemic targets are inconsistent, this study aimed to ascertain the prevalence of dysglycaemia among hospitalised patients with diabetes mellitus in an Asian population and evaluate the current standards of inpatient glycaemic control. A retrospective observational study was conducted at a secondary hospital. Point-of-care blood glucose (BG) values, demographic data, medical history, glycaemic therapy and clinical characteristics were recorded. Dysglycaemia prevalence was calculated as proportions of BG-monitored days with at least one reading exceeding the cut points of 8, 10 and 15 mmol/L for hyperglycaemia, and below the cut point of 4 mmol/L for hypoglycaemia. Among the 288 patients recruited, hyperglycaemia was highly prevalent (90.3%, 81.3% and 47.6% for the respective cut points), while hypoglycaemia was the least prevalent (18.8%). Dysglycaemic patients were more likely than normoglycaemic patients to have poorer glycated haemoglobin (HbA1c) levels (8.4% ± 2.6% vs. 7.3% ± 1.9%; p = 0.002 for BG > 10 mmol/L) and longer lengths of stay (10.1 ± 8.2 days vs. 6.8 ± 4.7 days; p = 0.007 for BG < 4 mmol/L). Hyperglycaemia was more prevalent in patients on more intensive treatment regimens, such as basal-bolus combination therapy and the use of both insulin and oral hypoglycaemic agents (100.0% and 96.0%, respectively; p < 0.001 for BG > 10 mmol/L). Inpatient glycaemic control is suboptimal. Factors (e.g. type of treatment regimen, discipline and baseline HbA1c) associated with greater prevalence of dysglycaemia should be given due consideration in patient management.

Efficacy and safety of insulin degludec in Japanese patients with type1 and type2 diabetes: 24-week results from the observational study in routine clinical practice.

This is first observational prospective study of insulin degludec in routine clinical practice that we evaluated the effect on glycemic control and risk of hypoglycemia in basal‐bolus insulin therapy. We found that insulin degludec can maintain glycemic control at a lower insulin dose and frequency of hypoglycemia in type 1 diabetes, while it can improve glycemic control at equally insulin dose in type 2 diabetes.These results mean that insulin degludec is of use in routine clinical practice.