An estimate of the need for continuous glucose monitoring in type 2 diabetes with intensive insulin treatment in secondary healthcare.

AIM: To estimate the proportion of persons with type 2 diabetes (T2DM) receiving intensive insulin treatment in the secondary healthcare who could be candidates for continuous glucose monitoring (CGM), based on different HbA1c criteria. For comparison, the results are also presented as proportion of persons with type 1 diabetes (T1DM) in the same region. PATIENTS AND METHODS: In the Central Denmark Region, we identified all persons with T1DM (n = 6179) and T2DM (n = 4315) who had a minimum of one contact to a diabetes outpatient clinic from September 2021 to September 2022. Insulin regimen and HbA1c measured after a minimum of 2 months with a stable insulin regimen were retrieved from the healthcare administrative electronic platform used in the region. RESULTS: The numbers of persons with T1DM and T2DM with HbA1c meeting the criteria were 5145 and 3090, respectively. The fraction of T2DM with basal-bolus insulin was 35.3%, and the fraction with basal-bolus insulin and HbA1c >53 (7%) mmol/mol or >58 (7.5%) mmol/mol was 20.5% and 16.6%, respectively. These proportions correspond to 19.4%, 14.4% and 11.7% of the persons with T1DM in the same geographical area. CONCLUSION: The proportion of persons with T2DM in secondary healthcare undergoing intensive insulin treatment who could be candidates for CGM corresponded to only a minor fraction of persons with T1DM in the same region, irrespective of any HbA1c criteria applied.

No insulin degludec dose adjustment required after aerobic exercise for people with type 1 diabetes: the ADREM study.

AIMS/HYPOTHESIS: It is generally recommended to reduce basal insulin doses after exercise to reduce the risk of post-exercise nocturnal hypoglycaemia. Based on its long t½, it is unknown whether such adjustments are required or beneficial for insulin degludec. METHODS: The ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise test in the afternoon. All participants wore blinded continuous glucose monitors for 6 days, measuring the incidence of (nocturnal) hypoglycaemia and subsequent glucose profiles. RESULTS: We recruited 18 participants (six women, age 38 ± 13 years, HbA1c 56 ± 8 mmol/mol [7.3 ± 0.8%], mean ± SD). Time below range (i.e. glucose <3.9 mmol/l) the night after the exercise test was generally low and occurrence did not differ between the treatment regimens. During the subsequent whole day, time below range was lower for D40 compared with CON (median [IQR], 0 [0-23] vs 18 [0-55] min, p=0.043), without differences in the number of hypoglycaemic events. Time above range (i.e. glucose >10 mmol/l) was greater for D20-P vs CON (mean ± SEM, 584 ± 81 vs 364 ± 66 min, p=0.001) and D40 (385 ± 72 min, p=0.003). CONCLUSIONS/INTERPRETATION: Post-exercise adjustment of degludec does not mitigate the risk of subsequent nocturnal hypoglycaemia in people with type 1 diabetes. Although reducing degludec reduced next-day time below range, this did not translate into fewer hypoglycaemic events, while postponing degludec should be avoided because of increased time above range. Altogether, these data do not support degludec dose adjustment after a single exercise bout. TRIAL REGISTRATION: EudraCT number 2019-004222-22 FUNDING: The study was funded by an unrestricted grant from Novo Nordisk, Denmark.

Intranasal insulin treatment partially corrects the altered gene expression profile in the hippocampus of developing rats with perinatal iron deficiency.

Perinatal iron deficiency (FeD) targets the hippocampus and leads to long-term cognitive deficits. Intranasal insulin administration improves cognitive deficits in adult humans with Alzheimer's disease and type 2 diabetes and could provide benefits in FeD-induced hippocampal dysfunction. To objective was to assess the effects of intranasal insulin administration intranasal insulin administration on the hippocampal transcriptome in a developing rat model of perinatal FeD. Perinatal FeD was induced using low-iron diet from gestational day 3 until postnatal day (P) 7, followed by an iron sufficient (FeS) diet through P21. Intranasal insulin was administered at a dose of 0.3 IU twice daily from P8 to P21. Hippocampi were removed on P21 from FeS control, FeD control, FeS insulin, and FeD insulin groups. Total RNA was isolated and profiled using next-generation sequencing. Gene expression profiles were characterized using custom workflows and expression patterns examined using ingenuity pathways analysis (n = 7-9 per group). Select RNAseq results were confirmed via qPCR. Transcriptomic profiling revealed that mitochondrial biogenesis and flux, oxidative phosphorylation, quantity of neurons, CREB signaling in neurons, and RICTOR-based mTOR signaling were disrupted with FeD and positively affected by intranasal insulin treatment with the most benefit observed in the FeD insulin group. Both perinatal FeD and intranasal insulin administration altered gene expression profile in the developing hippocampus. Intranasal insulin treatment reversed the adverse effects of FeD on many molecular pathways and could be explored as an adjunct therapy in perinatal FeD.

Prediction of recurrent gestational diabetes mellitus: a retrospective cohort study.

BACKGROUND: Women after gestational diabetes mellitus (GDM) are at increased risk for development of GDM recurrence. It was the aim of our study to evaluate factors for prediction of risk of recurrence. METHODS: In this retrospective cohort study we included 159 women with GDM and a subsequent pregnancy. Putative risk factors for GDM recurrence were analyzed by logistic regression models. Results were compared to a cohort of age-matched women without GDM as controls (n = 318). RESULTS: The overall risk of GDM recurrence was 72.3% (115/159). Risk factors of recurrence were a body mass index (BMI) ≥ 30 kg/m2 before the index pregnancy (odds ratio (OR) 2.8 [95% CI 1.3-6.2], p = 0,008), a BMI ≥ 25 kg/m2 before the subsequent pregnancy (OR 2.7 [95% CI 1.3-5.8]. p = 0.008), a positive family history (OR 4.3 [95% CI 1.2-15.4], p = 0.016) and insulin treatment during the index pregnancy (OR 2.3 [95% CI 1.1-4.6], p = 0.023). Delivery by caesarean section (index pregnancy) was of borderline significance (OR 2.2 [95% CI 0.9-5.2], p = 0.069). Interpregnancy weight gain, excessive weight gain during the index pregnancy and fetal outcome where not predictive for GDM recurrence. Neonates after GDM revealed a higher frequency of transfer to intensive care unit compared to healthy controls (OR 2.3 [95% CI 1.1-4.6], p = 0.0225). The best combined risk model for prediction of GDM recurrence including positive family history and a BMI ≥ 25 kg/m2 before the subsequent pregnancy revealed moderate test characteristics (positive likelihood ratio 7.8 [95% CI 1.1-54.7] and negative likelihood ratio 0.7 [95% CI 0.6-0.9]) with a positive predictive value of 96.6% in our cohort. CONCLUSIONS: A positive family history of diabetes mellitus in combination with overweight or obesity were strongly associated with recurrence of a GDM in the subsequent pregnancy. Normalization of the pregravid BMI should be an effective approach for reducing the risk of GDM recurrence.

The effects of early short-term insulin treatment vs. glimepiride on beta cell function in newly diagnosed type 2 diabetes with HbA1c above 9.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a complex metabolic impairment. Beta cell (BC) failure is the most challenging among its pathogenetic mechanisms. Recognizing reversible contributors to BC failure could guide individualized approach to early T2D treatment. The aim of this study was to compare early short-term insulin treatment vs. glimepiride, both added to metformin, on BC function, glycemic and lipid control, during 12-month follow-up. METHODS: Eighty newly diagnosed T2D patients, 30-65 years of age, presenting with HbA1c ≥ 9% were enrolled in the study. They were randomly assigned to single-month initial insulin therapy (INS) added to metformin, or to glimepiride and metformin (OAD) as only treatment. Subjects assigned to initial insulin intervention were thereafter switched to OAD. C-peptide (C-Pep) was analyzed at baseline and 2 hours after standardized test meal (STM). All subjects were STM-retested after 3 and 12 months. HbA1c, serum lipids, BMI, HOMA IR, and HOMA B were assessed over follow-up. RESULTS: HbA1c was lower in INS vs OAD at 3-months: 6.26 ± 0.18% vs 6.78 ± 0.10% (p = 0.016), remaining so by 12 months (p =0.056). BMI-adjusted ΔC-Pep was greater in INS vs. OAD at 3 months (4.60 ± 0.59 vs. 3.21 ± 0.34 m2 /kg; p = 0.044), persisting by 12months (4.57 ± 0.56 vs. 3.04 ± 0.34 m2/kg; p = 0.023). Average ΔC-Pep improvement from recruitment to 3 months was 100.8% in INS,vs. 51.3% in OAD. Prevalence of STM-ΔC-Pep response greater than 2.4 ng/mL had risen 3.2-fold by 12 months in the INS, vs. 2.4-fold only in the OAD group (p = 0.018). DISCUSSION: Early short-term insulin intervention in newly diagnosed T2D improves beta cell function more than glimepiride, both added to metformin, resulting in a superior and longer lasting glycemic and lipid control.

Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in people with type 2 diabetes: The DELIVER-G study.

AIMS: To provide real-world data on the addition of basal insulin (BI) in people with type 2 diabetes mellitus (PWD2) suboptimally controlled with glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. However, real-world data on the addition of BI to GLP-1RA therapy are limited. MATERIALS AND METHODS: We used a US electronic medical record data source (IBM® Explorys®) that includes approximately 4 million PWD2 to assess the real-world impact of adding the second-generation BI analogue insulin glargine 300 U/mL (Gla-300) to GLP-1RA therapy. Insulin-naïve PWD2 receiving GLP-1RAs who also received Gla-300 between March 1, 2015 and September 30, 2019 were identified; participants were required to have data for ≥12 months before, and ≥6 months after, addition of Gla-300. RESULTS: The mean (standard deviation [SD]) age of participants (N = 271) was 57.9 (10.8) years. Baseline glycated haemoglobin (HbA1c) was 9.16% and was significantly reduced (-0.97 [SD 1.60]%; P < 0.0001) after addition of Gla-300; a significant increase in the proportion of PWD2 achieving HbA1c control was observed after addition of Gla-300 (HbA1c <7.0%: 4.80% vs. 22.14%, P < 0.0001; HbA1c <8.0%: 19.56% vs. 51.29%, P < 0.0001). The incidence of overall (8.49% vs. 9.59%; P = 0.513) and inpatient/emergency department (ED)-associated hypoglycaemia (0.37% vs. 0.74%; P = 1.000), as well as overall (0.33 vs. 0.46 per person per year [PPPY]; P = 0.170) and inpatient/ED-associated hypoglycaemia events (0.01 vs. 0.04 PPPY; P = 0.466) were similar before and after addition of Gla-300. CONCLUSIONS: In US real-world clinical practice, adding Gla-300 to GLP-1RA significantly improved glycaemic control without significantly increasing hypoglycaemia in PWD2. Further research into the effect of adding Gla-300 to GLP-1RA therapy is warranted.

Changing Patterns of Antihyperglycaemic Treatment among Patients with Type 2 Diabetes in Hungary between 2015 and 2020-Nationwide Data from a Register-Based Analysis.

Background and objectives: In the last couple of years, pharmacological management of patients with type 2 diabetes mellitus (T2DM) have been markedly renewed. The aim of this study was to analyse the changes in prescribing patterns of antidiabetic drugs for treating patients with T2DM in Hungary between 2015 and 2020. Material and Methods: In this retrospective, nationwide analysis, we used the central database of the National Health Insurance Fund. We present annual numbers and their proportion of T2DM patients with different treatment regimens. Results: In the period of 2015−2020, the number of incident cases decreased from 60,049 to 29,865, while prevalent cases increased from 682,274 to 752,367. Patients with metformin (MET) monotherapy had the highest prevalence (31% in 2020). Prevalence of insulin (INS) monotherapy continuously but slightly decreased from 29% to 27% while that of sulfonylurea (SU) monotherapy markedly decreased from 37% to 20%. Dipeptidyl peptidase (DPP-4) inhibitors remained popular in 2020 as monotherapy (5%), in dual combination with MET (12%) and in triple combination with MET and SU (5%). The prevalence of patients with sodium-glucose co-transporter-2 (SGLT-2) inhibitors increased from 1% to 4% in monotherapy, from <1% to 6% in dual combination with MET, and from <1% to 2% in triple oral combination with MET and SU or DPP-4-inhibitors. The prevalence of patients using glucagon-like peptide-1 receptor agonists (GLP-1-RAs) also increased but remained around 1−2% both in monotherapy and combinations. For initiating antihyperglycaemic treatment, MET monotherapy was the most frequently used regime in 2020 (50%), followed by monotherapy with SUs (16%) or INS (10%). After initial MET monotherapy, the incidence rates of patients with add-on GLP-1-RAs (2%, 3%, and 4%) and those of add-on SGLT-2 inhibitors (4%, 6%, and 8%) slowly increased in the subsequent 24, 48, and 72 months, respectively. Conclusions: In the period of 2015−2020, we documented important changes in trends of antihyperglycaemic therapeutic patterns in patients with T2DM which followed the new scientific recommendations but remained below our expectations regarding timing and magnitude. More efforts are warranted to implement new agents with cardiovascular/renal benefits into therapeutic management in time, in a much larger proportion of T2DM population, and without delay.

Insulin treatment improves liver histopathology and decreases expression of inflammatory and fibrogenic genes in a hyperglycemic, dyslipidemic hamster model of NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent comorbidities in patients with Type 2 diabetes. While many of these patients eventually will need treatment with insulin, little is known about the effects of insulin treatment on histopathological parameters and hepatic gene expression in diabetic patients with co-existing NAFLD and NASH. To investigate this further, we evaluated the effects of insulin treatment in NASH diet-fed hamsters with streptozotocin (STZ) -induced hyperglycemia. METHODS: Forty male Syrian hamsters were randomized into four groups (n = 10/group) receiving either a NASH-inducing (high fat, fructose and cholesterol) or control diet (CTRL) for four weeks, after which they were treated with STZ or sham-injected and from week five treated with either vehicle (CTRL, NASH, NASH-STZ) or human insulin (NASH-STZ-HI) for four weeks by continuous s.c. infusion via osmotic minipumps. RESULTS: NASH-STZ hamsters displayed pronounced hyperglycemia, dyslipidemia and more severe liver pathology compared to both CTRL and NASH groups. Insulin treatment attenuated dyslipidemia in NASH-STZ-HI hamsters and liver pathology was considerably improved compared to the NASH-STZ group, with prevention/reversal of hepatic steatosis, hepatic inflammation and stellate cell activation. In addition, expression of inflammatory and fibrotic genes was decreased compared to the NASH-STZ group. CONCLUSIONS: These results suggest that hyperglycemia is important for development of inflammation and profibrotic processes in the liver, and that insulin administration has beneficial effects on liver pathology and expression of genes related to inflammation and fibrosis in a hyperglycemic, dyslipidemic hamster model of NAFLD.

Associations of hypoglycemia, glycemic variability and risk of cardiac arrhythmias in insulin-treated patients with type 2 diabetes: a prospective, observational study.

BACKGROUND: Insulin-treated patients with type 2 diabetes (T2D) are at risk of hypoglycemia, which is associated with an increased risk of cardiovascular disease and mortality. Using a long-term monitoring approach, we investigated the association between episodes of hypoglycemia, glycemic variability and cardiac arrhythmias in a real-life setting. METHODS: Insulin-treated patients with T2D (N = 21, [mean ± SD] age 66.8 ± 9.6 years, BMI 30.1 ± 4.5 kg/m2, HbA1c 6.8 ± 0.4% [51.0 ± 4.8 mmol/mol]) were included for a one-year observational study. Patients were monitored with continuous glucose monitoring ([mean ± SD] 118 ± 6 days) and an implantable cardiac monitor (ICM) during the study period. RESULTS: Time spend in hypoglycemia was higher during nighttime than during daytime ([median and interquartile range] 0.7% [0.7-2.7] vs. 0.4% [0.2-0.8]). The ICMs detected 724 episodes of potentially clinically significant arrhythmias in 12 (57%) participants, with atrial fibrillation and pauses accounting for 99% of the episodes. No association between hypoglycemia and cardiac arrhythmia was found during daytime. During nighttime, subject-specific hourly incidence of cardiac arrhythmias tended to increase with the occurrence of hypoglycemia (incident rate ratio [IRR] 1.70 [95% CI 0.36-8.01]) but only slightly with increasing time in hypoglycemia (IRR 1.04 [95% CI 0.89-1.22] per 5 min). Subject-specific incidence of cardiac arrhythmias during nighttime increased with increasing glycemic variability as estimated by coefficient of variation whereas it decreased during daytime (IRR 1.33 [95% CI 1.05-1.67] and IRR 0.77 [95% CI 0.59-0.99] per 5% absolute increase, respectively). CONCLUSIONS: Cardiac arrhythmias were common in insulin-treated patients with T2D and were associated with glycemic variability, whereas arrhythmias were not strongly associated with hypoglycemia. TRIAL REGISTRATION: NCT03150030, ClinicalTrials.gov, registered May 11, 2017. https://clinicaltrials.gov/ct2/show/NCT03150030.

Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin-treated adults with type 2 diabetes and risk factors for hypoglycaemia.

AIMS: To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes. MATERIALS AND METHODS: We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.9─10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels. RESULTS: At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed. CONCLUSIONS: Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.

The effects of exercise training versus intensive insulin treatment on skeletal muscle fibre content in type 1 diabetes mellitus rodents.

BACKGROUND: Intensive-insulin treatment (IIT) strategy for patients with type 1 diabetes mellitus (T1DM) has been associated with sedentary behaviour and the development of insulin resistance. Exercising patients with T1DM often utilize a conventional insulin treatment (CIT) strategy leading to increased insulin sensitivity through improved intramyocellular lipid (IMCL) content. It is unclear how these exercise-related metabolic adaptations in response to exercise training relate to individual fibre-type transitions, and whether these alterations are evident between different insulin strategies (CIT vs. IIT). PURPOSE: This study examined glycogen and fat content in skeletal muscle fibres of diabetic rats following exercise-training. METHODS: Male Sprague-Dawley rats were divided into four groups: Control-Sedentary, CIT- and IIT-treated diabetic sedentary, and CIT-exercised trained (aerobic/resistance; DARE). After 12 weeks, muscle-fibre lipids and glycogen were compared through immunohistochemical analysis. RESULTS: The primary findings were that both IIT and DARE led to significant increases in type I fibres when compared to CIT, while DARE led to significantly increased lipid content in type I fibres compared to IIT. CONCLUSIONS: These findings indicate that alterations in lipid content with insulin treatment and DARE are primarily evident in type I fibres, suggesting that muscle lipotoxicity in type 1 diabetes is muscle fibre-type dependant.

Intranasal Insulin Treatment Attenuates Metabolic Distress and Early Brain Injury After Subarachnoid Hemorrhage in Mice.

BACKGROUND: Intranasal administration of insulin to the brain bypasses the blood brain barrier (BBB) and can increase cerebral glucose uptake and prevent energy failure. Intranasal insulin treatment has shown neuroprotective effects in multiple central nervous system (CNS) lesions, but the effects of intranasal insulin on the metabolic and pathological process of subarachnoid hemorrhage (SAH) are not clear. This study is designed to explore the effects of intranasal insulin treatment on metabolic distress and early brain injury (EBI) after experimental SAH. METHODS: SAH model was built by endovascular filament perforation method in adult male C57BL/6J mice, and then, insulin was administrated via intranasal route at 0, 24, and 48 h post-SAH. EBI was assessed according to the neurological performance, BBB damage, brain edema, neuroinflammatory reaction, and neuronal apoptosis at each time point. To evaluate metabolic conditions, microdialysis was used to continuously monitor the real-time levels of glucose, pyruvate, and lactate in interstitial fluid (ISF) in living animals. The mRNA and protein expression of glucose transporter-1 and 3 (GLUT-1 and -3) were also tested by RT-PCR and Western blot in brain after SAH. RESULTS: Compared to vehicle, intranasal insulin treatment promoted the relative mRNA and protein levels of GLUT-1 in SAH brain (0.98 ± 0.020 vs 0.33 ± 0.016 at 24 h, 0.91 ± 0.25 vs 0.21 ± 0.013 at 48 h and 0.94 ± 0.025 vs 0.28 ± 0.015 at 72 h in mRNA/0.96 ± 0.023 vs 0.36 ± 0.015 at 24 h, 0.91 ± 0.022 vs 0.22 ± 0.011 at 48 h and 0.95 ± 0.024 vs 0.27 ± 0.014 at 72 h in protein, n = 8/Group, p < 0.001). Similar results were also observed in GLUT-3. Intranasal insulin reduced the lactate/pyruvate ratio (LPR) and increased ISF glucose level. It also improved neurological dysfunction, BBB damage, and brain edema and attenuated the levels of pro-inflammatory cytokines as well as neuronal apoptosis after SAH. CONCLUSIONS: The intranasal insulin treatment protects brain from EBI possibly via improving metabolic distress after SAH.

Effect of adding vildagliptin to insulin in haemodialysed patients with type 2 diabetes: The VILDDIAL study, a randomized, multicentre, prospective study.

AIM: To evaluate the effect of adding the dipeptidyl-peptidase-4 inhibitor vildagliptin to insulin on the glycaemic control of patients with type 2 diabetes undergoing haemodialysis. METHODS: Overall, 65 insulin-treated patients with type 2 diabetes undergoing haemodialysis (HbA1c: 7.3% ± 1.1%; age: 70.5 ± 8.5 years) were randomized (1:1) either to receive vildagliptin 50 mg/day in addition to insulin (vildagliptin-insulin group) or to pursue their usual insulin regimen (insulin-only group). Continuous glucose monitoring (CGM) was performed for 48 ± 6 hours at baseline and at week 12. The primary study endpoint was change from baseline in mean interstitial glucose using CGM. The secondary endpoints included other CGM variables and glucose control markers. RESULTS: After 12 weeks, a greater reduction in mean CGM glucose from baseline was observed in the vildagliptin-insulin group compared with the insulin-only group, although the between-treatment difference was not statistically significant (mean difference [CI 95%]: -0.96 mmol/L [-2.09; 0.18] vs. -0.29 mmol/L [-1.29; 0.76], P = 0.32). However, a significant decrease from baseline in HbA1c, glycated albumin and insulin daily doses was observed in the vildagliptin-insulin group versus the insulin-only group (-0.6% [-1.19; -0.1], P < 0.01), in the vildagliptin-insulin group versus no change in the insulin-only group (-130.6 µmol/L [-271; 10.7] vs. +36.2 µmol/L [-164.4; 236.9], P = 0.04 and - 5.9 IU/day [-1.8; 7.1] vs. +1.1 IU/day [-14.5; 16.6], P = 0.01, respectively). There was no significant difference in the percentage of time spent in hypoglycaemia using CGM, occurrence of severe hypoglycaemia or number of adverse events. CONCLUSION: In this study, vildagliptin added to insulin improved glycaemic control with an associated insulin-sparing effect in patients with type 2 diabetes undergoing haemodialysis and was well tolerated.

Pharmacotherapy of Children and Adolescents with Type 1 Diabetes Mellitus.

Insulin treatment in children and adolescents with autoimmune type 1 diabetes has changed tremendously in the last 20 years with the knowledge of DCCT trial regarding near-normal glucose levels on the micro- and macrovascular outcome. Intensified insulin therapy is now standard of care. Carb counting however was introduced systematically only recently in several countries. In industrialized countries most patients in this age group are treated with continuous subcutaneous insulin injections. Nowadays this is combined with continuous subcutaneous glucose measurement commencing sensor-augmented pump therapy. Predictive low glucose suspend reduces the frequency of hypoglycemic events. Still not available for children is a commercially available closed loop system. However, treatment goals are still frequently not reached especially in the group of adolescents. Therefore several additive drugs are tested to improve treatment results. There are new insulins with faster and longer action profile in the pipeline to better mimic physiologic insulin profiles. Smart insulins may be able to mimic reaction on blood sugar levels. The broad facet of treatment modalities helps pediatric diabetes teams to individualize therapy and so improve patients' health-related quality of life.

Factors associated with quality of life in patients with diabetic hypoglycaemia.

AIMS AND OBJECTIVES: To identify determinants of quality of life among patients who had experienced hypoglycaemia and who were undergoing insulin treatment. BACKGROUND: Patients with diabetes receiving insulin treatment are at high risk for hypoglycaemia, which tends to affect their quality of life. DESIGN: With a cross-sectional and observational study design (see the STROBE checklist and Appendix S1). METHODS: One hundred and fifty patients with type 2 diabetes who had received insulin treatment and had experienced hypoglycaemia (<70 mg/dl) in the last 6 months were recruited. Data were collected from May 2016-February 2018 using the Knowledge of Hypoglycaemia Scale, Fear of Hypoglycaemia Scale, Social Support Scale and the simplified Taiwanese version of the Quality of Life Scale developed by the World Health Organization. RESULTS: Factors found to be associated with quality of life in patients with hypoglycaemia included having an educational level of senior high school or above, being on an insulin regimen only, engaging in regular exercise, diabetes complications, fear of hypoglycaemia and greater social support, which accounted for 28.5% of the total variance. CONCLUSIONS: During the process of glycaemic control, patients inevitably experience hypoglycaemic episodes. Therefore, healthcare providers should assist patients with disease management to improve their quality of life. Future studies should also recruit patients who claim to have experienced hypoglycaemic symptoms, rather than considering only those with blood glucose levels below 70 mg/dl, to expand the generalisability of the findings. Future studies may also focus on the management of hypoglycaemia in patients on an insulin regimen, and on examining the effect of health education programmes on prevention of hypoglycaemia. RELEVANCE TO CLINICAL PRACTICE: The present findings could provide a reference for healthcare providers to consolidate nursing care guidelines and to improve such patients' quality of life.

Association of diabetes treatment with long-term glycemic patterns in patients with type 2 diabetes mellitus: A prospective cohort study.

AIM: This study aimed to analyze diabetes treatment and treatment changes in association with long-term glycemic patterns in an Asian population with diabetes. MATERIALS AND METHODS: This was a prospective cohort study of 6218 patients with type 2 diabetes managed in public primary care clinics in Singapore. Clinical data from 2011 to 2016 were extracted from electronic medical records, including serial HbA1c measurements and dispensed antidiabetic medication records. Patterns of longitudinal HbA1c trajectories were identified using latent class growth analysis, and patients' annual treatment plans were compared between subgroups with different HbA1c patterns. RESULTS: We identified four distinct HbA1c patterns. Eighty-one percent of patients were classified in the low-stable group, where monotherapy and dual therapy with oral agents were the most common treatments. We also identified three groups with poorer control, with moderate-stable (14%), moderate-increase (3%), and high-decrease (2%) HbA1c patterns. Insulin treatment was most prevalent in these groups, with 61% to 72% of subjects receiving insulin treatment in 2016. More than 60% of subjects in poorer control groups had experienced treatment intensification during follow-up. Addition of multiple insulin injections was the most common intensification in moderate-increase and high-decrease groups. CONCLUSIONS: Treatment reflected and was appropriate to the extent of dysglycemia in this population. A small group of patients had deteriorating glycemic control, in spite of being treated with multiple insulin injections, suggesting non-response or non-adherence to treatment. Further investigation is needed to identify reasons for the deteriorating control observed and design effective interventions for these patients.

Inpatient Management of T2DM and Hyperglycemia in Older Adults.

PURPOSE OF REVIEW: This review aims to provide a summary of the evaluation and treatment of older adults (≥ 65 years) with type 2 diabetes and/or hyperglycemia in the hospital. RECENT FINDINGS: Caring for these older adults requires special considerations. Diabetes is a risk factor for hospitalization and hyperglycemia in the hospital is associated with increased complications and mortality. Treatment plans for hospitalized older adults with diabetes should include a comprehensive geriatric assessment. This team-based approach aims to develop an individualized care plan, with consideration of the patients' personal goals, comorbidities, functional status, life expectancy, and hypoglycemia risk. Studies from hospitalized middle age and older adults with hyperglycemia can help guide diabetes treatment goals and management in older adults. Further studies, examining both glucose targets and care management assessments and treatment plan specifically targeting older adults in the hospital setting, are needed.

Efficacy and safety of insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Chinese adults with type 2 diabetes: A phase III, open-label, 2:1 randomized, treat-to-target trial.

AIMS: To assess the efficacy and safety of twice-daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self-mixed or basal insulin ± metformin. MATERIALS AND METHODS: We conducted a 26-week, phase III, open-label, treat-to-target, 2:1 randomized trial. Hierarchical testing was used with non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01-5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes. RESULTS: Non-inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified. CONCLUSIONS: The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.

Circulating miR-146a, miR-34a and miR-375 in type 2 diabetes patients, pre-diabetic and normal-glycaemic individuals in relation to ß-cell function, insulin resistance and metabolic parameters.

The pathogenesis of type 2 diabetes (T2D) is associated with a progressive loss of pancreatic ß-cell mass. It is known that miR-146a, miR-34a, and miR-375 are involved in ß-cell functionality. In this work, we evaluated the levels of these miRNAs in normal-glycaemic individuals, pre-diabetic, and T2D patients in relation to ß-cell functionality, insulin resistance, and metabolic parameters. The relative expression of the miRNAs was evaluated in serum samples by real-time polymerase chain reaction. In a principal component analysis, we observed that T2D patients and pre-diabetic individuals were not associated with ß-cell functionality. However, in a correlation matrix analysis, we detected that miR-34a was related to miR-146a and insulin resistance. The relative expression of miR-375 was correlated with cholesterol and low-density lipoprotein levels. A decrease of ß-cell function in pre-diabetic individuals and T2D patients was observed. The insulin resistance was higher in pre-diabetic individuals and T2D patients. The relative expression of miR-146a in pre-diabetic individuals, T2D patients with insulin treatment, and T2D patients with nephropathy and diabetic foot was decreased. In addition, miR-34a was increased in T2D patients who were overweight and obese. The relative expression of miR-375 was increased in T2D patients with poor glycaemic control, while a decrease was seen in T2D patients with nephropathy and diabetic foot. Circulating miR-375, miR-34a, and miR-146a were not associated with ß-cell functionality, but their expression was differentially affected by glycaemia, obesity, insulin treatment, and the presence of nephropathy and diabetic foot.

Inercia clínica en el tratamiento con insulina en el primer nivel de atención.

INTRODUCTION: Refusal of physicians to prescribe insulin to their patients has been scarcely evaluated; the delay in treatment intensification hinders adequate and quality care. OBJECTIVE: To identify the perception of primary care physicians about barriers to initiate insulin treatment in patients with diabetes. METHOD: Using the Smith Index and multivariate analysis, the relevance and grouping of concepts related to barriers to insulin prescription were assessed in 81 family doctors. RESULTS: Only 35.8% of physicians showed confidence for prescribing insulin; almost half of them rated treatment intensification between moderately and little important (39.5% and 6.2%). Barriers were related to the physician (39.5%), the patient (37%), insulin treatment (11.1%) and the institution (6.2%); 6.2 % of physicians did not perceive any barrier. The barriers were grouped in 5 factors that explained 62.48% of the variance: patient cultural level, lack of medical skills, fear of adverse events, insecurity and lack of training. CONCLUSION: Clinical inertia was not the result of a complex medical condition or patient comorbidities, but of doctor's perception and confidence in his/her clinical and communication skills.

INTRODUCCIÓN: Poco se ha evaluado el rechazo de los médicos a prescribir insulina a sus pacientes; el retraso en intensificar el tratamiento impide una atención adecuada y de calidad. OBJETIVO: Identificar la percepción de los médicos acerca de las barreras para iniciar la insulina en los pacientes con diabetes. MÉTODO: Por Índice Smith y análisis multivariado, en 81 médicos familiares se evaluó la relevancia y agrupación de los conceptos relacionados con las barreras para la prescripción de insulina. RESULTADOS: 35.8 % de los médicos mostró confianza en prescribir insulina; casi la mitad calificó la intensificación del tratamiento entre moderadamente y poco importante (39.5 y 6.2 %). Las barreras se relacionaron con el médico (39.5 %), el paciente (37 %), el tratamiento con insulina (11.1 %) y la institución (6.2 %); 6.2 % de los médicos no percibió ninguna barrera. Las barreras se agruparon en cinco factores, que explicaron 62.48 % de la varianza: cultura de los pacientes, falta de habilidades, miedo a los eventos adversos, inseguridad y falta de capacitación. CONCLUSIÓN: La inercia clínica no resultó de una condición clínica compleja o comorbilidades del paciente, sino de la percepción del médico y de su confianza en sus habilidades clínicas y comunicativas.