Biphasic Insulin Research Articles

7363 Comparing the Effectiveness of Various Insulin in Insulin Naive Type 2 Diabetes Mellitus Patients: A Study from Central India

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. N. Kumari: None. A. Gwal: None. Introduction: Insulin is the cornerstone of treatment of type 2 diabetes mellitus (T2DM) and is the most efficacious treatment option. The evaluation of efficacy and safety of insulin therapy in real world setting is desirable as numerous options are currently available. This study aimed to compare the efficacy and safety of four different insulins in patients with T2DM. Methods: We conducted a retrospective observational study at our tertiary care hospital using medical records of patients with glycated hemoglobin (HbA1c) >8.5% who were not controlled on oral antidiabetic (OAD) medication and received add-on insulin treatment (Glargine U300, Lispro Biphasic 25/75, Glargine U100, IdegAsp). Glycemic control and incidence of hypoglycemia were analyzed from baseline to 6 months. Results: 101 patients were included. Mean age 56.4 years. 61.4% men. Mean duration of T2DM 13.3 years. 23 (22.8%), 27 (26.7%), 27 (26.7%), and 24 (23.8%) patients received Glargine U300, Lispro Biphasic 25/75, Glargine U-100, IdegAsp insulin respectively. At baseline, the mean (SD) HbA1c were 11.93% (1.85), 10.61% (1.55), 10.65% (1.59), and 10.58% (1.89) in patients receiving Glargine U300, Lispro Biphasic 25/75, Glargine U100, and IdegAsp, respectively. HbA1c, fasting plasma glucose (FPG) & post-prandial plasma glucose (PPG) improved significantly from baseline to 6 months across all four treatment groups (p<0.001). Glargine U300 showed a significantly greater mean reduction in HbA1c by 4.57% compared to Lispro Biphasic 25/75 (3.39%; p=0.032), Glargine U100 (2.88%; p=0.004), and IdegAsp (2.38%; p<0.001). The mean reduction in FPG, PPG, total cholesterol and triglycerides were comparable across all four treatment groups. The mean insulin doses (SD) were 15.48 (5.65) U, 23.83 (9.49) U, 20.44 (8.76) U, and 34.17 (14.57) U at baseline and 18.89 (5.39) U, 35.52 (10.37) U, 26.07 (8.92) U, and 43.58 (15.76) at 6 months, respectively. The doses of all insulins were titrated to fasting, post-meal, or pre-dinner SMBG readings as appropriate. There were no significant changes observed in the mean body weight and insulin dose in all four subgroups. The incidence of hypoglycemia (<70 mg/dL and <54 mg/dL) was numerically lower in Glargine U300 (3 and 1) group, than in Lispro Biphasic 25/75 (8 and 5), Glargine U100 (3 and 2), and IdegAsp (7 and 3) groups. As expected, biphasic insulin had a higher numerical incidence of hypoglycemia. Conclusion: All insulins demonstrated significant improvements in glycemic parameters over the study period. However, Glargine U300 demonstrated a significantly higher reduction in HbA1c with minimal hypoglycemia events compared to other insulins and can be considered in OAD uncontrolled patients. Our results should be interpreted with caution as the study was retrospective and had a small sample size. Presentation: 6/3/2024

Insulin-induced Lipohypertrophy in a Patient with Type 2 Diabetes

Abstract Lipohypertrophy (LH) is a common side effect of insulin treatment in patients with diabetes, characterized by soft, benign nodules in the subcutaneous tissue. This case report describes the management of insulin-induced LH in a 66-year-old male with type 2 diabetes. The patient had been on a combination of oral antidiabetic agents (ODAs) and biphasic human insulin for 5 years, experiencing the symptoms of numbness, leg swelling, fatigue, and frequent hypoglycemic episodes. Upon examination, LH with skin pigmentation was observed at the insulin injection sites on both calves. The patient’s laboratory investigations revealed poor glycemic control with high glycated hemoglobin percentage. To address the condition, the patient was advised to change the injection site, use proper site rotation, and change the insulin needle daily. The insulin therapy was modified by switching to biphasic premixed analog insulin injected 5 min before meals using the insulin pen. In addition, ODAs were adjusted for better glycemic control. Following these interventions, the patient reported improved glucose levels and stable kidney function. This case report emphasizes the importance of early detection and appropriate management of insulin-induced LH through patient education and insulin therapy adjustments. Health-care providers should remain vigilant for LH and educate patients on proper injection practices to optimize diabetes management and prevent complications.

Hypertonicity during a rapid rise in D-glucose mediates first-phase insulin secretion.

Biphasic insulin secretion is an intrinsic characteristic of the pancreatic islet and has clinical relevance due to the loss of first-phase in patients with Type 2 diabetes. As it has long been shown that first-phase insulin secretion only occurs in response to rapid changes in glucose, we tested the hypothesis that islet response to an increase in glucose is a combination of metabolism plus an osmotic effect where hypertonicity is driving first-phase insulin secretion. Experiments were performed using perifusion analysis of rat, mouse, and human islets. Insulin secretion rate (ISR) and other parameters associated with its regulation were measured in response to combinations of D-glucose and membrane-impermeable carbohydrates (L-glucose or mannitol) designed to dissect the effect of hypertonicity from that of glucose metabolism. Remarkably, the appearance of first-phase responses was wholly dependent on changes in tonicity: no first-phase in NAD(P)H, cytosolic calcium, cAMP secretion rate (cAMP SR), or ISR was observed when increased D-glucose concentration was counterbalanced by decreases in membrane-impermeable carbohydrates. When D-glucose was greater than 8 mM, rapid increases in L-glucose without any change in D-glucose resulted in first-phase responses in all measured parameters that were kinetically similar to D-glucose. First-phase ISR was completely abolished by H89 (a non-specific inhibitor of protein kinases) without affecting first-phase calcium response. Defining first-phase ISR as the difference between glucose-stimulated ISR with and without a change in hypertonicity, the peak of first-phase ISR occurred after second-phase ISR had reached steady state, consistent with the well-established glucose-dependency of mechanisms that potentiate glucose-stimulated ISR. The data collected in this study suggests a new model of glucose-stimulated biphasic ISR where first-phase ISR derives from (and after) a transitory amplification of second-phase ISR and driven by hypertonicity-induced rise in H89-inhibitable kinases likely driven by first-phase responses in cAMP, calcium, or a combination of both.

Insulin therapy for elderly patients with type 2 diabetes mellitus

The prevalence of type 2 diabetes among older people is increasing every year. The main pathogenetic mechanisms of type 2 diabetes in elderly patients include disruption of the intestinal microbiota, cellular aging, oxidative stress and mitochondrial dysfunction, immune and inflammatory processes. Short-chain fatty acids produced by the intestinal microbiota influence inflammatory processes in pancreatic β-cells. Cellular senescence causes the secretion of different cytokines, chemokines, growth factors and proteases, exacerbating the proinflammatory state and increasing insulin resistance of the tissues. Oxidative stress and mitochondrial dysfunction decrease the ATP synthesis process and increase the formation of reactive oxygen species. Changes in the immune system in elderly patients contribute to autoimmune processes and systemic inflammation. Clinical features of diabetes mellitus in old age include asymptomatic progression, impaired recognition of hypoglycemia, impaired cognitive function, and muscle atrophy. The progressive decline in β-cells function in type 2 diabetes requires insulin therapy in many patients. Biphasic insulins allow to control both basal and postprandial glycemia, are easy to use and are indicated for patients who have difficulty counting amount of carbohydrates. However, it is worth remembering a balanced approach to prescribing and deintensifying therapy.

Glycaemic outcomes in hospital with IDegAsp versus BIAsp30 premixed insulins.

IDegAsp (Ryzodeg70/30), a unique premixed formulation of long-acting insulin degludec and rapid-acting insulin aspart, is increasing in use. Management of IDegAsp during hospitalisation is challenging because of degludec's ultra-long duration of action. We investigated inpatient glycaemia in patients treated with IDegAsp compared to biphasic insulin aspart (BIAsp30; Novomix30). We performed a retrospective observational study at two hospitals assessing inpatients with type 2 diabetes treated with IDegAsp or BIAsp30 prior to and during hospital admission. Standard inpatient glycaemic outcomes were analysed based on capillary blood glucose (BG) measurements. We assessed 88 individuals treated with IDegAsp and 88 HbA1c-matched individuals treated with BIAsp30. Patient characteristics, including insulin dose at admission, were well matched, but the IDegAsp group had less frequent twice-daily insulin dosing than the BIAsp30 group (49% vs 87%, P < 0.001). Patient-days with BG <4 mmol/L were not different (10.6% vs 9.9%, P = 0.7); however, the IDegAsp group had a higher patient-day mean BG (10.4 (SD 3.4) vs 10.0 (3.4) mmol/L, P < 0.001), and more patient-days with mean BG >10 mmol/L (48% vs 38%, P < 0.001) compared to the BIAsp30 group. Glucose was higher in the IDegAsp group in the evening (4 PM to midnight) (11.6 (SD 4.0) vs 10.9 (4.6) mmol/L, P = 0.004), but not different at other times during the day. Inpatients treated with IDegAsp compared to BIAsp30 had similar hypoglycaemia incidence, but higher hyperglycaemia incidence, potentially related to less frequent twice-daily dosing. With the increasing use of IDegAsp in the community, development of hospital management guidelines for this insulin formulation is needed.

Anaesthetic Management for Rt Emphysematous Pyelonephritis with Grade I Hydroureteronephrosis with Perinephric Abscess with Left Lobar Pneumonia

ntroduction: A perinephric abscess is usually a complication of urologic infection which results from fat necrosis. Before the era of antibiotics, perinephric abscesses were due to prolonged bacteremia. More than 3/4 of perinephric abscesses are now due to complications of urinary tract infections. Case Report: We present a 71 year old female case with Right Emphysematous Pyelonephritis Grade I Hydroureteronephrosis with left perinephric abscess, left lobar pneumonia posted for bilateral DJ stenting with perinephric drain placement under continuous spinal anesthesia. Presented with H/o lower back pain, associated with fever since 3 days and H/o burning micturition, since 6 months. She is known case of Type 2 DM since 23 years and on Inj. Biphasic Insulin, Tablet vildagliptin, Tablet Dapaglifazone, known case of hypothyroidism and on tablet Thyroxin 50 mg OD in morning. H/o stroke 20 years back right side Upper &amp; lower limb affected. H/o previous appendectomy 20 years back, CT–KKUB suggestive of Emphysematous Pyelonephritis, right side with grade I HUN, left perinephric fat with ill diffused hypodense area in upper lobe of left kidney. Non obstructive left renal calculus 4.0mm. ECG shows RBBB, Saturation was 92% on Roomair, On ABG analysis severe metabolic acidosis found. We planned to administer continuous spinal anesthesia. Patient was explained about the continuous spinal anesthesia &amp; written informed consent was taken. Tablet Alprazolam 0.25 mg, and tablet Rantac, 15 was given previous night and in morning on the day of surgery. Nil per oral is maintained 8 hours before surgery. A 18 Gauge IV cannula was secured, a 5 lead Electrocardiogram, Pulse Oximeter, NIBP and ETCo2 monitoring was done. Under strict aseptic precautions, L3 L4 space was identified and using 18G tuhoy needle, Lumbar puncture is done. Injection Bupivacaine 0.8cc given, block is achieved till T8 level. Surgery was lasted for one and half hour. Vitals were stable. Patient shifted to recovery room and was under observation for an hour, patient was shifted to post operative ward. Conclusion: This is an Original case report, which provide a successful management of anesthesia, of bilateral DJ stenting with perinephric drain placement under continuous spinal anesthesia. Anesthesia Management for Right Emphysematous Pylonephritis with grade I HUN. With perinephric abscess with left lobar Pneumonia.

Efficacy and Safety of Insulin Degludec/Insulin Aspart versus Biphasic Insulin Aspart 30 in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D). We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis. We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups. Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

Readily releasable β cells with tight Ca2+-exocytosis coupling dictate biphasic glucose-stimulated insulin secretion.

Biphasic glucose-stimulated insulin secretion (GSIS) is essential for blood glucose regulation, but a mechanistic model incorporating the recently identified islet β cell heterogeneity remains elusive. Here, we show that insulin secretion is spatially and dynamically heterogeneous across the islet. Using a zinc-based fluorophore with spinning-disc confocal microscopy, we reveal that approximately 40% of islet cells, which we call readily releasable β cells (RRβs), are responsible for 80% of insulin exocytosis events. Although glucose up to 18.2 mM fully mobilized RRβs to release insulin synchronously (first phase), even higher glucose concentrations enhanced the sustained secretion from these cells (second phase). Release-incompetent β cells show similarities to RRβs in glucose-evoked Ca2+ transients but exhibit Ca2+-exocytosis coupling deficiency. A decreased number of RRβs and their altered secretory ability are associated with impaired GSIS progression in ob/ob mice. Our data reveal functional heterogeneity at the level of exocytosis among β cells and identify RRβs as a subpopulation of β cells that make a disproportionally large contribution to biphasic GSIS from mouse islets.

Functionally heterogeneous β cells regulate biphasic insulin secretion.

Functionally heterogeneous β cells regulate biphasic insulin secretion.

Real-world study of the concomitant use of biphasic insulin aspart 30/70 with GLP-1 receptor agonist versus first-generation basal insulin with GLP-1 receptor agonistin type 2 diabetes.

Combining insulin with a glucagon-like peptide-1 receptor agonist (GLP-1RA) to treat type 2 diabetes (T2D) is common. While many studies have investigated concomitant therapy with basal insulin+GLP-1RA, few have reported on premixed insulin+GLP-1RA. We aimed to address this gap using data from the Clinical Practice Research Datalink Aurum database in England. This retrospective cohort study with propensity score matching assessed glycaemic levels and other clinical outcomes in people with T2D, comparing biphasic insulin aspart 30/70 (BIAsp 30) + GLP-1RA with basal insulin (insulin detemir/glargine U100) + GLP-1RA (from 2006 to 2021). In total, 4770 eligible people were identified; 1511 had a BIAsp 30 + GLP-1RA regimen and were propensity score-matched to an equal number receiving basal+GLP-1RA. There was no significant difference in glycated haemoglobin (HbA1c) reduction between cohorts at 6 months (p = 0.15), with a decrease of -1.07 (95% CI: -1.16; -0.98) %-points (-11.7 mmol/mol [95% CI: -12.7; -10.7]) in the BIAsp 30 + GLP-1RA cohort, versus -0.97 (95% CI: -1.07; -0.88) %-points (-10.6 mmol/mol [95% CI: -11.7; -9.6]) in the basal+GLP-1RA cohort. Body mass index (BMI) decreased by -0.35 kg/m2 (95% CI: -0.52;-0.18) at 6 months with BIAsp 30 + GLP-1RA, versus -0.72 kg/m2 (95% CI: -0.90;-0.54) with basal+GLP-1RA (p = 0.003). BMI was influenced by the initiation sequence of GLP-1RA in relation to insulin (p < 0.0001). Hypoglycaemia rates were low and not significantly different between cohorts. Combining BIAsp 30 + GLP-1RA provides glycaemic control with no significant difference to that of propensity score-matched people receiving basal insulin+GLP-1RA, with no increase in hypoglycaemia risk or weight gain.

Effect of Fasting Ramadan on Different Laboratory Parameters on Type 2 Diabetic Mellitus Patients

Background Diabetes mellitus (DM) is one of the most common chronic diseases in nearly all countries, and continues to increase in numbers and significance, as changing lifestyles lead to reduced physical activity, and increased obesity. It has been estimated that by the year 2030, there will be 8.6 million adult with diabetes in Egypt, making it the country with the tenth largest population of diabetic in the world. Diabetes is associated with reduced life expectancy, significant morbidity due to micro and macro vascular complications and diminished quality of life. Objective To study the impact of Ramadan fasting on metabolic parameters and anthropometry in type 2 DM in Egypt. Patients and Methods This study was conducted on 80 type 2 diabetic patients who were intending to fast Ramadan. During Ramadan (2014) the average fasting hours were 15 h. Patients were recruited from the internal medicine outpatient clinic at Ain Shams University hospitals and from the nutrition institute. 6 Patients were under insulin treatment (Biphasic human insulin) &amp; 74 patients were under oral hypoglycemic treatment {52 on combination treatment sulfonylurea + metformin &amp; 9 on metformin only &amp;13 of them were on sulfonylurea only}. Results We found that there was a statistically significant increase as regard lipid profile (serum triglycerides, serum total cholesterol, LDL-cholesterol and HDL-cholesterol) in after Ramadan measurement. Also CVD risk parameters have untimely increased after Ramadan this parameters including (10 years risk (Framingham score) systolic and diastolic blood pressure). In addition (Creatinine, HOMA IR and fasting insulin) showed increased level in after Ramadan measurement which indicate deterioration of blood glucose parameters. There was no statistical significant changes seen as regard anthropometric measures (BMI, WHR) in pre Ramadan and after Ramadan measurement. Also there was no statistical significant changes regarding fasting, 2 hours plasma glucose, A1c levels between pre-Ramadan fasting &amp; after-Ramadan. In addition CRP and ACR showed no significant changes as regard measurement between before and after Ramadan. Conclusion Ramadan fasting appears to have significant effect on lipid profiles that could adversely impact cardiovascular outcome. These effects are mostly due to quality and quantity of food intake during Ramadan and the negative impact of sedentary life style. In addition the number of fasting days and period of daily fasting could affect glycemic control and renal function tests. Bad dietary habits, lack of exercise and irregular drug intake during Ramadan has a negative impact on glycemic control.

A pathway model of glucose-stimulated insulin secretion in the pancreatic β-cell.

The pancreas plays a critical role in maintaining glucose homeostasis through the secretion of hormones from the islets of Langerhans. Glucose-stimulated insulin secretion (GSIS) by the pancreatic β-cell is the main mechanism for reducing elevated plasma glucose. Here we present a systematic modeling workflow for the development of kinetic pathway models using the Systems Biology Markup Language (SBML). Steps include retrieval of information from databases, curation of experimental and clinical data for model calibration and validation, integration of heterogeneous data including absolute and relative measurements, unit normalization, data normalization, and model annotation. An important factor was the reproducibility and exchangeability of the model, which allowed the use of various existing tools. The workflow was applied to construct a novel data-driven kinetic model of GSIS in the pancreatic β-cell based on experimental and clinical data from 39 studies spanning 50 years of pancreatic, islet, and β-cell research in humans, rats, mice, and cell lines. The model consists of detailed glycolysis and phenomenological equations for insulin secretion coupled to cellular energy state, ATP dynamics and (ATP/ADP ratio). Key findings of our work are that in GSIS there is a glucose-dependent increase in almost all intermediates of glycolysis. This increase in glycolytic metabolites is accompanied by an increase in energy metabolites, especially ATP and NADH. One of the few decreasing metabolites is ADP, which, in combination with the increase in ATP, results in a large increase in ATP/ADP ratios in the β-cell with increasing glucose. Insulin secretion is dependent on ATP/ADP, resulting in glucose-stimulated insulin secretion. The observed glucose-dependent increase in glycolytic intermediates and the resulting change in ATP/ADP ratios and insulin secretion is a robust phenomenon observed across data sets, experimental systems and species. Model predictions of the glucose-dependent response of glycolytic intermediates and biphasic insulin secretion are in good agreement with experimental measurements. Our model predicts that factors affecting ATP consumption, ATP formation, hexokinase, phosphofructokinase, and ATP/ADP-dependent insulin secretion have a major effect on GSIS. In conclusion, we have developed and applied a systematic modeling workflow for pathway models that allowed us to gain insight into key mechanisms in GSIS in the pancreatic β-cell.

Genetic ablation of synaptotagmin-9 alters tomosyn-1 function to increase insulin secretion from pancreatic β-cells improving glucose clearance.

Stimulus-coupled insulin secretion from the pancreatic islet β-cells involves the fusion of insulin granules to the plasma membrane (PM) via SNARE complex formation-a cellular process key for maintaining whole-body glucose homeostasis. Less is known about the role of endogenous inhibitors of SNARE complexes in insulin secretion. We show that an insulin granule protein synaptotagmin-9 (Syt9) deletion in mice increased glucose clearance and plasma insulin levels without affecting insulin action compared to the control mice. Upon glucose stimulation, increased biphasic and static insulin secretion were observed from ex vivo islets due to Syt9 loss. Syt9 colocalizes and binds with tomosyn-1 and the PM syntaxin-1A (Stx1A); Stx1A is required for forming SNARE complexes. Syt9 knockdown reduced tomosyn-1 protein abundance via proteasomal degradation and binding of tomosyn-1 to Stx1A. Furthermore, Stx1A-SNARE complex formation was increased, implicating Syt9-tomosyn-1-Stx1A complex is inhibitory in insulin secretion. Rescuing tomosyn-1 blocked the Syt9-knockdown-mediated increases in insulin secretion. This shows that the inhibitory effects of Syt9 on insulin secretion are mediated by tomosyn-1. We report a molecular mechanism by which β-cells modulate their secretory capacity rendering insulin granules nonfusogenic by forming the Syt9-tomosyn-1-Stx1A complex. Altogether, Syt9 loss in β-cells decreases tomosyn-1 protein abundance, increasing the formation of Stx1A-SNARE complexes, insulin secretion, and glucose clearance. These outcomes differ from the previously published work that identified Syt9 has either a positive or no effect of Syt9 on insulin secretion. Future work using β-cell-specific deletion of Syt9 mice is key for establishing the role of Syt9 in insulin secretion.

Moderate-intensity endurance training improves late phase β-cell function in adults with type 2 diabetes

Physical activity is important for type 2 diabetes treatment, yet the underlying mechanisms for these beneficial effects of exercise are not fully understood. Here, we investigated the effects of exercise training on biphasic β-cell insulin secretory function, a key factor regulating blood glucose. Adults with type 2 diabetes (7F/3M, age 49± 5 years, BMI 30± 3kg/m2) completed a 10-week moderate-intensity exercise program and multiple components of glucose homeostasis were measured. Training improved glycemic control, insulin sensitivity, and processing of proinsulin-to-insulin. Training increased late phase β-cell function by 38% (p= 0.01), which was correlated with changes in VO2peak suggesting training response-dependent effects. Ras-Responsive Element Binding Protein 1 (RREB1) concentrations, a protein postulated to increase type 2 diabetes risk, were inversely correlated with increases in training-induced late-phase disposition index, consistent with an inhibitory role of RREB1 on insulin secretion. Moderate-intensity exercise training improves late-phase β-cell function and glycemic control in adults with type 2 diabetes.

Real-world study of ethnic differences in glycaemic control and clinical characteristics among insulin-naïve people with type 2 diabetes initiating biphasic insulin aspart 30/70: A retrospective, observational cohort study in England.

This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin-naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England. Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin-naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index. In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %-point changes [95% CI of -2.32 (-2.36; -2.28) (White); -1.91 (-2.02; -1.80) (South Asian); -2.55 (-2.69; -2.40) (Black); and -2.64 (-3.24; -2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m2 : White, 0.92 (0.86; 0.99); South Asian, 0.60 (0.41; 0.78); Black, 1.41 (1.16; 1.65); and Chinese, 0.32 (-0.67; 1.30)]. In the overall population, hypoglycaemic event rates increased from 0.92 events per 100 patient-years before the index to 3.37 events per 100 patient-years post index; event numbers were too low to be analysed by subgroup. Among insulin-naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.

Estimation of biphasic isophane insulin 30/70 by using validated RP-HPLC technique

Estimation of biphasic isophane insulin 30/70 by using validated RP-HPLC technique

Quality of life, patient satisfaction, and cardiovascular outcomes of the randomised 2 x 3 factorial Copenhagen insulin and Metformin therapy (CIMT) trial – A detailed statistical analysis plan

BackgroundThe evidence on the effects of metformin and insulin in type 2 diabetes patients on quality of life, patient satisfaction, and cardiovascular outcomes is unclear. MethodsThe Copenhagen Insulin and Metformin Therapy (CIMT) trial is an investigator-initiated multicentre, randomised, placebo-controlled trial with a 2 × 3 factorial design conducted at eight hospitals in Denmark. Participants with type 2 diabetes were randomised to metformin (n = 206) versus placebo (n = 206); in combination with open-label biphasic insulin aspart one to three times daily (n = 137) versus insulin aspart three times daily in combination with insulin detemir once daily (n = 138) versus insulin detemir once daily (n = 137).We present a detailed description of the methodology and statistical analysis of the clinical CIMT outcomes including a detailed description of tests of the assumptions behind the statistical analyses. The outcomes are quality of life (Short Form Health Survey (SF-36)), Diabetes Medication Satisfaction Questionnaire, and Insulin Treatment Satisfaction Questionnaire (assessed at entry and 18 months after randomisation) and cardiovascular outcomes including time to a composite of either myocardial infarction, stroke, peripheral amputation, coronary revascularisation, peripheral revascularisation, or death. DiscussionsThis statistical analysis plan ensure the highest possible quality of the subsequent post-hoc analyses. Trial registrationThe protocol was approved by the Regional Committee on Biomedical Research Ethics (H-D-2007-112), the Danish Medicines Agency (EudraCT: 2007-006665-33 CIMT), and registered within ClinicalTrials.gov (NCT00657943, 8th of April 2008).

Insulin Fact Sheet in Type 1 and 2 Diabetes Mellitus and Trends of Antidiabetic Medication Use in Insulin Users with Type 2 Diabetes Mellitus: 2002 to 2019.

This study investigated the trends of insulin use among Korean patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Changes in prescription of antidiabetic medications in T2DM patients taking insulin therapy were evaluated. We analyzed data from the National Health Insurance Service database in Korea to evaluate the prevalence of insulin users and trends of insulin use in T1DM and T2DM patients from January 2002 to December 2019. We also investigated numbers and types of antidiabetic medications in insulin users with T2DM. The overall total number of insulin users increased from 2002 to 2019, reaching 348,254 for T2DM and 20,287 for T1DM in 2019 compared with 109,974 for T2DM and 34,972 for T1DM in 2002. The proportion of patients using basal analogs and short acting analogs have increased and those using human insulin, premixed insulin, or biphasic human insulin have decreased (rapid acting analogs: 71.85% and 24.12% in T1DM and T2DM, respectively, in 2019; basal analogs: 76.75% and 75.09% in T1DM and T2DM, respectively, in 2019). The use of other antidiabetic medication in addition to insulin increased for T2DM, especially in dual therapy, reaching up to 52.35% in 2019 compared with 16.72% in 2002. The proportion of the patients using basal or rapid acting analogs increased among all insulin users in both T1DM and T2DM patients. Among patients with T2DM, the proportion of patients using antidiabetic medications in addition to insulin was significantly increased compared to those who used insulin alone.

The Impact of Medical Nutritional Therapy on the Efficacy of Premix Insulin in Glycemic Control in Patients with Type 2 Diabetes.

Medical nutritional therapy (MNT) is a key component in the treatment of Diabetes mellitus (DM). MNT is completely individual and should be present in the treatment of diabetes from the very beginning, continuously with pharmacological therapy, taking into account lifestyle, dietary habits and the type of antidiabetic therapy. Mistakes that are made when planning the diet are the absence of individual adjustment of the diet, which means that the number and time of meals, as well as the amount of UH per meal, is not adjusted to the patients' oral or insulin therapy according to their pharmacokinetics and pharmacodynamics. This study investigated the effect of MNT with reduced carbohydrate content (MNT M-ADA) on the efficacy of human and analogue premix insulin in patients with T2DM. Subjects were randomized into two groups (human and analog premix insulins), and then each group into two subgroups of 30 subjects each. One subgroup each on therapy with human and analog biphasic insulins was educated about MNT and learned to count UH, and then they applied MNT M-ADA for 24 weeks, unlike the other two subgroups. In this review, we present only the subgroup analysis on human and analog premix insulins that applied MNT M-ADA (200 g UH/day). Efficacy outcomes in the analysis of these subgroups were estimated changes in each subgroup from baseline to end point (week 24) and differences between subgroups at the end of the study in levels of glycated hemoglobin (HbA1c), self-measured glucose values (SMBG) and frequency of hypoglycemia. Both subgroups of subjects with MNT M-ADA improved glycemic control, which was assessed by improvements in HBA1C, SMBG levels, without an increase in the frequency of hypoglycemia, but at the end of the study there was no statistically significant difference in the mentioned parameters between the subgroups. The effectiveness of MNT M-ADA in people with T2DM did not depend on the type of insulin, both insulin regimens are effective if the amount of ingested UH is taken into account.

Exploring the relationship between pancreatic fat and insulin secretion in overweight or obese women without type 2 diabetes mellitus: A preliminary investigation of the TOFI_Asia cohort.

While there is an emerging role of pancreatic fat in the aetiology of type 2 diabetes mellitus (T2DM), its impact on the associated decrease in insulin secretion remains controversial. We aimed to determine whether pancreatic fat negatively affects β-cell function and insulin secretion in women with overweight or obesity but without T2DM. 20 women, with normo- or dysglycaemia based on fasting plasma glucose levels, and low (< 4.5%) vs high (≥ 4.5%) magnetic resonance (MR) quantified pancreatic fat, completed a 1-hr intravenous glucose tolerance test (ivGTT) which included two consecutive 30-min square-wave steps of hyperglycaemia generated by using 25% dextrose. Plasma glucose, insulin and C-peptide were measured, and insulin secretion rate (ISR) calculated using regularisation deconvolution method from C-peptide kinetics. Repeated measures linear mixed models, adjusted for ethnicity and baseline analyte concentrations, were used to compare changes during the ivGTT between high and low percentage pancreatic fat (PPF) groups. No ethnic differences in anthropomorphic variables, body composition, visceral adipose tissue (MR-VAT) or PPF were measured and hence data were combined. Nine women (47%) were identified as having high PPF values. PPF was significantly associated with baseline C-peptide (p = 0.04) and ISR (p = 0.04) in all. During the 1-hr ivGTT, plasma glucose (p<0.0001), insulin (p<0.0001) and ISR (p = 0.02) increased significantly from baseline in both high and low PPF groups but did not differ between the two groups at any given time during the test (PPF x time, p > 0.05). Notably, the incremental areas under the curves for both first and second phase ISR were 0.04 units lower in the high than low PPF groups, but this was not significant (p > 0.05). In women with overweight or obesity but without T2DM, PPF did not modify β-cell function as determined by ivGTT-assessed ISR. However, the salient feature in biphasic insulin secretion in those with ≥4.5% PPF may be of clinical importance, particularly in early stages of dysglycaemia may warrant further investigation.