Total Daily Insulin Requirements Research Articles

Offlabel use of Medtronic MiniMed 780G in the management of cystic fibrosis related diabetes in people requiring insulin total daily doses below 8 units: encouraging data from our population.

Cystic fibrosis (CF)-related diabetes (CFRD), characterized by partial to complete impaired insulin secretion, is the most common extra-pulmonary complication of CF. Actually, insulin is the only approved therapy for its management. Advanced hybrid closed loop (AHCL) systems are the gold standard therapy for type 1 diabetes and have been proposed for other insulin-dependent forms of diabetes, including CFRD. With AHCL systems, people with CFRD can better manage several typical disease-related issues, such as minimal insulin requirements, its variability due to exacerbations or concomitant steroid therapies, nutritional behaviors, the co-existence of CF complications as intestinal malabsorption or liver disease. SmartGuard, the AHCL system for Medtronic Minimed 780G, requires a minimum of 8 units per day to operate. In this paper, we expose a case of two young women with CFRD with total daily insulin requirements < 8 UI, using off-label SmartGuard system over a 3 years of follow-up period, suggesting an evaluation of its use also in people with minimal insulin needs, considering its beneficial impact in glucose control and quality of life.

Associations between daily step count classifications and continuous glucose monitoring metrics in adults with type 1 diabetes: analysis of the Type 1 Diabetes Exercise Initiative (T1DEXI) cohort.

Adults with type 1 diabetes should perform daily physical activity to help maintain health and fitness, but the influence of daily step counts on continuous glucose monitoring (CGM) metrics are unclear. This analysis used the Type 1 Diabetes Exercise Initiative (T1DEXI) dataset to investigate the effect of daily step count on CGM-based metrics. In a 4 week free-living observational study of adults with type 1 diabetes, with available CGM and step count data, we categorised participants into three groups-below (<7000), meeting (7000-10,000) or exceeding (>10,000) the daily step count goal-to determine if step count category influenced CGM metrics, including per cent time in range (TIR: 3.9-10.0 mmol/l), time below range (TBR: <3.9 mmol/l) and time above range (TAR: >10.0 mmol/l). A total of 464 adults with type 1 diabetes (mean±SD age 37±14 years; HbA1c 48.8±8.1 mmol/mol [6.6±0.7%]; 73% female; 45% hybrid closed-loop system, 38% standard insulin pump, 17% multiple daily insulin injections) were included in the study. Between-participant analyses showed that individuals who exceeded the mean daily step count goal over the 4 week period had a similar TIR (75±14%) to those meeting (74±14%) or below (75±16%) the step count goal (p>0.05). In the within-participant comparisons, TIR was higher on days when the step count goal was exceeded or met (both 75±15%) than on days below the step count goal (73±16%; both p<0.001). The TBR was also higher when individuals exceeded the step count goals (3.1%±3.2%) than on days when they met or were below step count goals (difference in means -0.3% [p=0.006] and -0.4% [p=0.001], respectively). The total daily insulin dose was lower on days when step count goals were exceeded (0.52±0.18 U/kg; p<0.001) or were met (0.53±0.18 U/kg; p<0.001) than on days when step counts were below the current recommendation (0.55±0.18 U/kg). Step count had a larger effect on CGM-based metrics in participants with a baseline HbA1c ≥53 mmol/mol (≥7.0%). Our results suggest that, compared with days with low step counts, days with higher step counts are associated with slight increases in both TIR and TBR, along with small reductions in total daily insulin requirements, in adults living with type 1 diabetes. The data that support the findings reported here are available on the Vivli Platform (ID: T1-DEXI; https://doi.org/10.25934/PR00008428 ).

Managing type 1 diabetes mellitus with a ketogenic diet.

Traditional guidelines for type 1 diabetics do not restrict carbohydrates to improve clinical outcomes for patients. This paper highlights the favorable blood glucose control outcomes when a type 1 diabetic focuses on caloric intake from protein and healthy fats instead of the traditional carbohydrate-focused meals. We followed a male type 1 diabetic in his 20s adopting a ketogenic diet through a process of slowly lowering total daily carbohydrate intake. Diabetes-related biomarkers were measured throughout the process. Diabetes-related biomarkers saw massive improvements and ended up in the official non-diabetic range. Total daily insulin requirements dropped by 70%. The patient also experienced great improvements in his quality of life. This study demonstrates the possibility of improving diabetes-related biomarkers through dietary changes, which have positive effects on health outcomes in patients living with this disease. The adaptation of a ketogenic diet improved diabetes-related biomarkers in this patient. Diabetes-related biomarkers, such as HbA1c, are the main risk factors for developing complications in diabetics. The ketogenic diet is a feasible approach to minimizing the risk of developing complications in diabetics. Total daily insulin requirements dropped by 67% adapting a ketogenic diet. The patient experienced enormous changes in the quality of life after adapting to the new diet. The safe and physiological state of ketosis might be associated with additional benefits for the patient.

1136-P: Type A Insulin Resistance Masquerading as Type 1 Diabetes Mellitus

More than 150 mutations in the INSR gene encoding the insulin receptor have been identified causing a spectrum of insulin resistance syndromes from mild (type A insulin resistance) to more severe (Rabson-Mendenhall syndrome, Donahue syndrome). Type A insulin resistance typically presents in childhood or early adulthood. We describe a 19-year-old male with type A insulin resistance due to heterozygous INSR gene mutation, c.3470A&amp;gt;G (His1157Arg). This mutation has previously been identified in female patients with hyperglycemia, insulin resistance. The patient presented at age 14 with polyuria, polydipsia, hyperglycemia (glucose 200s) without acidosis, and normal BMI (50th%) and was presumed to have type 1 diabetes. He was treated with insulin though required escalating doses to 2-2.5 units/kg/day and was started on metformin to improve insulin sensitivity which had a minor effect on total daily insulin requirements. HbA1c was typically 7-9% for several years with this treatment plan and BMI remained near 50th%. The patient was subsequently lost to follow-up and after self-discontinuing insulin for approximately 1 year, re-presented with hyperglycemia, the absence of ketonuria or acidosis, elevated insulin level (92.2 μIU/ml), negative islet cell antibodies, HbA1c 10.9%. Notably, he did not have acanthosis nigricans. Subsequent genetic testing revealed a mutation in the INSR gene consistent with type A insulin resistance. This case highlights the importance of considering monogenic forms of diabetes and insulin resistance syndromes in lean patients who require higher-than-expected insulin doses with presumed type 1 diabetes. Disclosure E.A.Los: Other Relationship; Medtronic. K.Wirthwein: None.

PSUN223 The Three Different Clinical Phenotypes of Checkpoint Inhibitor-Induced Diabetes Mellitus

Abstract Checkpoint inhibitor-induced diabetes mellitus (CIADM) is a rare but morbid complication of cancer immunotherapies. The most common presentation is acute hyperglycemia and severe insulin deficiency. Our experience managing 25 patients in our new Immune-Related Adverse Events (IRAE) clinic indicates that there are three distinct CIADM phenotypes. Many of our patients required admission for diabetic ketoacidosis (15/25), amongst whom we can distinguish fulminant type 1 diabetes mellitus (9/15) from ketosis-prone type 2 diabetes mellitus (T2a-CIADM) (6/15) using serum c-peptide levels. The T1-CIADM patients have decreased serum c-peptide levels that did not improve on recheck obtained 12-28 weeks following insulin initiation (mean c-peptide = 0.2 ng/mL [NR = 1.1-4.4 ng/mL], range = 0-0.5 ng/mL). In contrast, serum c-peptide levels recovered into the reference range in T2a-CIADM patients within 12 weeks of hospital discharge (mean c-peptide = 2.9 ng/mL, range 2.1-9.3 ng/mL). It does not appear sufficient to identify T1-CIADM using traditional islet cell autoantibodies (GAD-65, IA-2A, IAA and ZnT8A) as 54% of our patients (6/11) were negative. This is consistent with other published reports. None of the T2a-CIADM patients were autoantibody-positive. Three of our GAD-65-positive T1-CIADM had preexisting islet cell autoantibodies in pretreatment serum obtained through involvement in clinical trials. None of the controls for these index cases had islet cell autoantibodies and only 2/156 developed GAD-65 autoantibodies during ICI treatment. These patients had no evidence of impaired glucose tolerance or a concerning family history. This suggests that latent autoimmune diabetes in adults (LADA) is accelerated with ICI-exposure resulting in the autoantibody-positive T1-CIADM subgroup. Interestingly (but perhaps expected), there was more reported family history of diabetes in our T2a-CIADM (6/9) than T1-CIADM patients (1/11). Our third observed phenotype (T2b-CIADM) consists of five additional patients referred for significant progression of known T2DM. These patients were prescribed oral medications and had reasonable blood glucose control (HbA1c &amp;lt; 8%) before starting immunotherapy. Three patients experienced rapid deterioration in blood glucose control (manifesting as polyuria/polydipsia) and were hospitalized for severe hyperglycemia. None had laboratory evidence of DKA/HHS. All three patients were discharged on multiple daily insulin injections (MDI). The differences in total daily insulin requirements (TDD) between clinical phenotypes highlight possible dissimilarities in underlying physiology. Those patients designated T2b-CIADM have a mean TDD of 1.2 units/kg/day (range = 0.8-2.3 units/kg/day) indicating the presence of insulin resistance. The patients who have new disease (T1-CIADM and T2a-CIADM) seem to need doses more reminiscent of B-cell dysfunction (mean = 0.5 units/kg/day, range 0.2-1.3 units/kg/day). We have not observed any return of insulin secretion in four patients who discontinued ICI treatment after three years of follow-up. It is important that we continue to investigate the mechanisms contributing to CIADM as uncontrolled hyperglycemia can impact the immune system and alter the antineoplastic effects of ICIs. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Intensification of Insulin Treatment With Insulin Degludec/Aspart in Type 2 Diabetic Patients: A 2-Year Real-World Experience.

To evaluate the effects of insulin degludec/insulin aspart (IDegAsp) coformulation as an intensification of insulin treatment for glycemic control in patients with type 2 diabetes (T2D) in a long term real-world clinical setting. This retrospective non-interventional study, included 210 patients with T2D who to IDegAsp coformulation from prior insulin treatment in a tertiary endocrinology center between September 2017 and December 2019. The baseline data was taken as the index date and defined as the first IDegAsp prescription claim. Previous insulin treatment modalities, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight were recorded, respectively at the 3rd, 6th, 12th, and 24th months of the IDegAsp treatment. Out of the total 210 patients, 166 patients under insulin treatment switched to twice-daily IDegAsp treatment, 35 patients switched to once daily IDegAsp and twice premeal short-acting insulin regimen as a modified basal-bolus (BB) treatment, and nine patients commenced with once-daily IDegAsp treatment. HbA1c decreased from 9.2% ± 1.9% to 8.2% ± 1.6% in 6 months, 8.2% ± 1.7% in the first year, and 8.1% ± 1.6% in the second year of the therapy (p< 0.001). FPG decreased from 209.0 ± 85.0 mg/dL to 147.0 ± 62.6 mg/dL in the second year (p< 0.001). The required total daily dose of insulin increased in the second year of IDegAsp treatment compared to baseline. However, there was a borderline significance increase in IDegAsp requirement for the whole group at the two-year follow-up (p = 0.05). Patients who were administered twice daily IDegAsp injections required more total insulin in the first and second years due to added premeal short-acting insulin injections (p < 0.05). The frequency of patients with HbA1c < 7% was 31.8% in first year and 35.8% in second year under IDegAsp treatment.Insulin dose was de-escalated in 28.5% of the patients under BB treatment, while 15% under twice-daily IDegAsp required increased BB treatment. Intensification of insulin treatment with IDegAsp coformulation improved glycemic control in patients with T2D. The total daily insulin requirement increased but the IDegAsp requirement lightly increased at the two-year follow-up. Patients under BB treatment required de-escalation of insulin treatment.

A Scoping Review Evaluating the Effect of SGLT-2 Inhibitors on Insulin Dose Requirements in Insulin-Dependent Patients With Type 2 Diabetes.

Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with type 2 diabetes. A scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols and Scoping Reviews (PRISMA-ScR) guidelines. The search was conducted in PubMed; citation mapping was completed in Web of Science. Filters for human studies, English language, and a publication date, from January 1, 2005 to April 12, 2021, were applied. Studies assessing insulin dose requirements with concurrent use of an SGLT2 inhibitor for patients with type 2 diabetes were included. Sixteen studies were included and demonstrated that addition of an SGLT2 inhibitor typically reduced TDI requirements. Insulin reductions were often statistically significant, occurring in studies evaluating (1) within subjects who received SGLT2 inhibitors, and (2) between subjects receiving SGLT2 inhibitors versus placebo. Compared with placebo, insulin dose reduction ranged from -0.72 to -19.2 units. However, studies were relatively small, not designed to assess TDI change, and some utilized fixed dose insulin protocols or empiric insulin dose reductions. Lowering insulin requirements may have benefits, such as decreased hypoglycemia risk, insulin resistance, and cost. Addition of an SGLT2 inhibitor may modestly reduce TDI requirements for patients with type 2 diabetes. Evidence indicating SGLT2 inhibitor use reduces TDI may lead to additional implementation in practice and inform future research. Further research is needed to clarify insulin type (i.e., basal or prandial) and degree of TDI reduction expected with addition of an SGLT2 inhibitor.

Comparison of Premixed Human Insulin 30/70 to Biphasic Aspart 30 in Well-Controlled Patients with Type 2 Diabetes Using Continuous Glucose Monitoring.

Aim: To compare in terms of glycemic variability two premixed insulins, Premixed Human Insulin 30/70 (PHI) and Biphasic Aspart 30 (BiAsp30), using Continuous Glucose Monitoring (CGM) and to estimate the correlation of Glycated Albumin (GA) and Fructosamine (FA) with CGM data. Patients-Data: A total of 36 well-controlled patients with type 2 Diabetes Mellitus (T2DM) underwent 7-day CGM with PHI and subsequently with BiAsp30. GA and FA were measured at the first and last day of each week of CGM. Results: BiAsp30 was associated with lower Average Blood Glucose (ABG) during the 23:00–03:00 period (PHI: 135.08 ± 28.94 mg/dL, BiAsp30: 117.75 ± 21.24 mg/dL, p < 0.001) and the 00:00–06:00 period (PHI: 120.42 ± 23.13 mg/dL, BiAsp30: 111.17 ± 14.74 mg/dL, p = 0.008), as well as with more time below range (<70 mg/dL) (TBR) during the 23:00–03:00 period in the week (PHI: 3.65 ± 5.93%, BiAsp30: 11.12 ± 16.07%, p = 0.005). PHI was associated with lower ABG before breakfast (PHI: 111.75 ± 23.9 mg/dL, BiAsp30: 128.25 ± 35.9 mg/dL, p = 0.013). There were no differences between the two groups in ABG, Time In Range and Time Below Range during the entire 24-h period for 7 days, p = 0.502, p = 0.534, and p = 0.258 respectively, and in TBR for the 00:00–06:00 period p = 0.253. Total daily insulin requirements were higher for BiAsp30 (PHI: 47.92 ± 12.18 IU, BiAsp30: 49.58 ± 14.12 IU, p = 0.001). GA and FA correlated significantly with ABG (GA: r = 0.512, p = 0.011, FA: r = 0.555, p = 0.005). Conclusions: In well-controlled patients with T2DM, BiAsp30 is an equally effective alternative to PHI.

Hybrid closed-loop glucose control with faster insulin aspart compared with standard insulin aspart in adults with type 1 diabetes: A double-blind, multicentre, multinational, randomized, crossover study.

To evaluate the use of hybrid closed-loop glucose control with faster-acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D). In a double-blind, multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% [57 ± 8 mmol/mol]) underwent two 8-week periods of unrestricted living comparing hybrid closed-loop with Fiasp and hybrid closed-loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed-loop system incorporating the Cambridge model predictive control algorithm was used. In an intention-to-treat analysis, the proportion of time sensor glucose was in the target range (3.9-10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed-loop with Fiasp vs. hybrid closed-loop with standard insulin aspart; mean-adjusted difference -0.6% [95% CI -1.8% to 0.7%]; p < .001 for non-inferiority [non-inferiority margin 5%]). The proportion of time with sensor glucose less than 3.9 mmol/L (median [IQR] 2.4% [1.2%-3.2%] vs. 2.9% [1.7%-4.0%]; p = .01) and less than 3.0 mmol/L (median [IQR] 0.4% [0.2%-0.7%] vs. 0.7% [0.2%-0.9%]; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred. The use of Fiasp in the CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.

Continuous glucose monitoring systems in well-controlled children with type 1 diabetes mellitus.

Numerous studies have demonstrated the clinical benefits of using continuous glucose monitoring (CGM) systems among patients with type 1 diabetes (T1D). Aim of the study was to assess the effectiveness of CGM on metabolic control in children with T1D and well-controlled disease prior to the study. This prospective analysis included 99 children (46 girls) at the median age of 11.23 years and diabetes duration of at least 1 year (median: 5.16 years), generally well controlled metabolically (median HbA1c: 7.0%), and treated with continuous subcutaneous insulin infusion (CSII). The patients had used CGM for at least 150 days. We analysed the participants in subgroups based on baseline HbA1c<7%, ≥ 7%, age, and sex. Children with baseline HbA1c<7% were characterized by significantly increased HbA1c after the median of 273 days (217; 320) of CGM usage (6.3% vs. 6.6%, respectively; p=0.002). No significant change in HbA1c was noted in children with baseline HbA1c ≥ 7% (7.5% vs. 7.4%, respectively; p=0.191), but 20% of the group reached the target of HbA1c<7.0%. The analysis of CGM data revealed that no group achieved the CGM targets of good metabolic control. Total daily insulin requirements remained stable in both groups (p=0.752; p=0.274), but the amount of basal insulin increased statistically in both groups (p=0.009; p ≤ 0.001). The application of CGM provides detailed information concerning glycaemic control and is beneficial in some, but not all, T1D children with good diabetes control.

Effects of GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Heart Transplant Patients with Type 2 Diabetes: a Case Series

Background Type 2 diabetes mellitus (T2D) is common in post-heart transplant patients. Commonly used T2D medications, especially insulin, can promote weight gain and are not associated with cardiovascular (CV) benefits. Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) are two drug classes that produce CV benefits in T2D and promote weight loss with minimal risk of hypoglycemia. Their use has not been previously evaluated in this particular group, and there have been theoretical concerns about safety in immunosuppressed patients. Methods Patients with T2D are sequentially referred by the Heart Transplant program to the Cardiometabolic Center of Excellence (CMCE) at our institution, allowing minimal selection bias. CMCE provides treatment algorithms that emphasize the use of cardioprotective T2D medications. We analyzed this initial series of transplant patients with T2D who have been on GLP-1 RA and/or SGLT-2i with at least two visits at CMCE. Results Among 15 patients, the mean age was 59.4 ± 2.6 years, 66.7% were males, 73.3% were Caucasians, 33.3% had history of ischemic cardiomyopathy and baseline eGFR was 53.5 ± 7.9 mL/min/1.73m2. The median time from transplant was 4.6 (1.6 - 10.5) years. The median follow-up time at CMCE was 5.4 (2.8 - 10.9) months. At baseline, 73% were on insulin, 40% on Metformin, 13% on Sulfonylurea, 13% on Dipeptidyl peptidase-4 inhibitors, and 7% on Thiazolidinediones. Following initiation of therapy at CMCE, 86.7% of patients were on a combination of GLP-1 RA and SGLT-2i, while the rest were taking only GLP-1 RA. Overall, the median total daily insulin requirements decreased substantially from 94 (40.5 - 124) to 34 (5 - 60) units at latest clinic visit; p = 0.003. Further, median hemoglobin A1c dropped from 7.7% (7.3 - 9.5) to 6.6% (6 - 8.5); p = 0.007. There was also a significant reduction in mean body weight (241.9 ± 35.8 at baseline vs. 217.1 ± 34.2 lbs at follow-up; p = 0.001), and mean body mass index (34.9 ± 4.5 vs. 31.1 ± 3.7; p = 0.001). Only one patient experienced side effects as one episode of severe nausea with Liraglutide that resolved when switched to Semaglutide. No infectious complications (including urinary tract or genital mycotic infections) were observed. Conclusions In this limited case series, combination therapy with GLP-1 RA and SGLT-2i was well tolerated in heart transplant patients and associated with favorable results in insulin requirement, hemoglobin A1c, and body weight. Type 2 diabetes mellitus (T2D) is common in post-heart transplant patients. Commonly used T2D medications, especially insulin, can promote weight gain and are not associated with cardiovascular (CV) benefits. Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) are two drug classes that produce CV benefits in T2D and promote weight loss with minimal risk of hypoglycemia. Their use has not been previously evaluated in this particular group, and there have been theoretical concerns about safety in immunosuppressed patients. Patients with T2D are sequentially referred by the Heart Transplant program to the Cardiometabolic Center of Excellence (CMCE) at our institution, allowing minimal selection bias. CMCE provides treatment algorithms that emphasize the use of cardioprotective T2D medications. We analyzed this initial series of transplant patients with T2D who have been on GLP-1 RA and/or SGLT-2i with at least two visits at CMCE. Among 15 patients, the mean age was 59.4 ± 2.6 years, 66.7% were males, 73.3% were Caucasians, 33.3% had history of ischemic cardiomyopathy and baseline eGFR was 53.5 ± 7.9 mL/min/1.73m2. The median time from transplant was 4.6 (1.6 - 10.5) years. The median follow-up time at CMCE was 5.4 (2.8 - 10.9) months. At baseline, 73% were on insulin, 40% on Metformin, 13% on Sulfonylurea, 13% on Dipeptidyl peptidase-4 inhibitors, and 7% on Thiazolidinediones. Following initiation of therapy at CMCE, 86.7% of patients were on a combination of GLP-1 RA and SGLT-2i, while the rest were taking only GLP-1 RA. Overall, the median total daily insulin requirements decreased substantially from 94 (40.5 - 124) to 34 (5 - 60) units at latest clinic visit; p = 0.003. Further, median hemoglobin A1c dropped from 7.7% (7.3 - 9.5) to 6.6% (6 - 8.5); p = 0.007. There was also a significant reduction in mean body weight (241.9 ± 35.8 at baseline vs. 217.1 ± 34.2 lbs at follow-up; p = 0.001), and mean body mass index (34.9 ± 4.5 vs. 31.1 ± 3.7; p = 0.001). Only one patient experienced side effects as one episode of severe nausea with Liraglutide that resolved when switched to Semaglutide. No infectious complications (including urinary tract or genital mycotic infections) were observed. In this limited case series, combination therapy with GLP-1 RA and SGLT-2i was well tolerated in heart transplant patients and associated with favorable results in insulin requirement, hemoglobin A1c, and body weight.

Reduction in Subcutaneous Insulin Requirements in Tetraplegic Type 1 Diabetic with Cervical Spinal Cord Injury Following Pramlintide Treatment

To report a massive increase in subcutaneous insulin requirements following spinal cord injury in a type 1 diabetic and how it was managed over a 22-month period with pramlintide. A case report and brief literature review is presented. The patient is a 43-year-old male who was diagnosed with type 1 diabetes mellitus at age 18. He remained relatively well-controlled without end-organ complications until age 37, when he developed a spinal epidural abscess following a methicillin-resistant Staphylococcus aureus cellulitis of the foot. The patient became ventilator-dependent and tetraplegic. He remained in rehabilitation for 18 months and returned home with a total daily dose of subcutaneous insulin of 600 U (4 U/kg); a 500 U increase over his prespinal cord injury requirements. Total daily intravenous insulin requirement was determined to be 259 U (1.96 U/kg). The patient was started on pramlintide. Twenty-two months after the onset of pramlintide treatment his total daily dose of subcutaneous insulin was decreased to 150 U (1.3 U/kg). Maintenance of glycemic control and obesity in type 1 diabetics with spinal cord injury may be complicated by autonomic dysregulation and the inability to induce activity-related lifestyle changes. Our patient exhibited clinical evidence of impaired subcutaneous insulin absorption that was not ameliorated by site changes, leading to massive insulin requirements which greatly reduced his quality of life. Following treatment with pramlintide, he decreased the volume of his insulin injections and lost 19 kg (41 pounds). Uncovering the precise mechanisms by which pramlintide benefited our patient requires further studies.

Improvement of metabolic control after 3-month use of real-time continuous glucose monitoring in patients with type 1 diabetes: a multicenter study in Greece.

To assess the efficacy of a real-time continuous glucose monitoring (RT-CGM) system added to insulin pump therapy for 3 months, in sub-optimally controlled adults with type 1 diabetes mellitus (T1D). This was a prospective, multicenter, non-randomized, post-market release study. A total of 43 adult patients with T1D on insulin pump therapy and inadequate glycemic control (HbA1c > 7.0%) participated in the study. The primary endpoint was the change from baseline HbA1c levels. Secondary objectives were to evaluate the impact of the RT-CGM system on glucose variability, daily insulin requirements, and the frequency of hypoglycemic and ketoacidosis events. At 3 months, the baseline HbA1c values decreased from 8.0 (7.6, 8.7) to 7.1 (6.7, 8.0) % (p < 0.001). Nineteen participants (44.2%) had a posttreatment HbA1c level ≤ 7%. Average total daily insulin requirements, as well as the average number of insulin boluses per day, increased significantly after the use of the RT-CGM system. The number of hypoglycemic events recorded did not differ between the first week and last week of RT-CGM usage, while no severe hypoglycemic episodes, ketoacidosis events, or hospitalizations related to diabetes occurred during the 3-month follow-up period. Addition of a RT-CGM system to insulin pump therapy for 3 months in inadequately controlled patients with T1D resulted in improved HbA1c levels, without increasing the risk of hypoglycemic events.

Glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus.

The role of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the treatment of type 1 diabetes mellitus (T1DM), including efficacy and safety evidence, is reviewed. Currently approved treatment options for glycemic control in T1DM include insulin, which combats insulin deficiency but does not effectively target disease progression or alpha cell dysfunction; and pramlintide, whose use requires multiple daily doses and involves a high likelihood of gastrointestinal side effects. GLP-1 RAs have a unique mechanism of action in T1DM, addressing alpha cell dysfunction and thereby suppressing inappropriate glucagon secretion. GLP-1 RA dosing varies from once weekly to twice daily, and the class is well tolerated in patients with type 2 diabetes. Among the GLP-1 RAs, exenatide and liraglutide have been studied in patients with T1DM, with published evidence consistently demonstrating weight loss, decreases in total daily insulin requirements, and modest improvements in glycemic control. GLP-1 RA therapy appears to be well tolerated in patients with T1DM and is associated with nonsignificant increases in hypoglycemia risk. GLP-1 RA therapy represents an important add-on therapy option for achieving decreased insulin doses, weight loss, and modest improvements in HbA1c levels without significantly increasing hypoglycemia risk in patients with T1DM. Patients who have detectable C-peptide and/or are overweight or cannot achieve glycemic goals without hypoglycemia have been found to benefit the most from GLP-1 RA therapy. Further studies are warranted to evaluate these agents' potential impact on clinical outcomes such as microvascular and macrovascular complications.

A statistical virtual patient population for the glucoregulatory system in type 1 diabetes with integrated exercise model.

PurposeWe introduce two validated single (SH) and dual hormone (DH) mathematical models that represent an in-silico virtual patient population (VPP) for type 1 diabetes (T1D). The VPP can be used to evaluate automated insulin and glucagon delivery algorithms, so-called artificial pancreas (AP) algorithms that are currently being used to help people with T1D better manage their glucose levels. We present validation results comparing these virtual patients with true clinical patients undergoing AP control and demonstrate that the virtual patients behave similarly to people with T1D.MethodsA single hormone virtual patient population (SH-VPP) was created that is comprised of eight differential equations that describe insulin kinetics, insulin dynamics and carbohydrate absorption. The parameters in this model that represent insulin sensitivity were statistically sampled from a normal distribution to create a population of virtual patients with different levels of insulin sensitivity. A dual hormone virtual patient population (DH-VPP) extended this SH-VPP by incorporating additional equations to represent glucagon kinetics and glucagon dynamics. The DH-VPP is comprised of thirteen differential equations and a parameter representing glucagon sensitivity, which was statistically sampled from a normal distribution to create virtual patients with different levels of glucagon sensitivity. We evaluated the SH-VPP and DH-VPP on a clinical data set of 20 people with T1D who participated in a 3.5-day outpatient AP study. Twenty virtual patients were matched with the 20 clinical patients by total daily insulin requirements and body weight. The identical meals given during the AP study were given to the virtual patients and the identical AP control algorithm that was used to control the glucose of the virtual patients was used on the clinical patients. We compared percent time in target range (70–180 mg/dL), time in hypoglycemia (<70 mg/dL) and time in hyperglycemia (>180 mg/dL) for both the virtual patients and the actual patients.ResultsThe subjects in the SH-VPP performed similarly vs. the actual patients (time in range: 78.1 ± 5.1% vs. 74.3 ± 8.1%, p = 0.11; time in hypoglycemia: 3.4 ± 1.3% vs. 2.8 ± 1.7%, p = 0.23). The subjects in the DH-VPP also performed similarly vs. the actual patients (time in range: 75.6 ± 5.5% vs. 71.9 ± 10.9%, p = 0.13; time in hypoglycemia: 0.9 ± 0.8% vs. 1.3 ± 1%, p = 0.19). While the VPPs tended to over-estimate the time in range relative to actual patients, the difference was not statistically significant.ConclusionsWe have verified that a SH-VPP and a DH-VPP performed comparably with actual patients undergoing AP control using an identical control algorithm. The SH-VPP and DH-VPP may be used as a simulator for pre-evaluation of T1D control algorithms.

Assessment of Newly Proposed Clinical Criteria to Identify HNF1A MODY in Patients with an Initial Diagnosis of Type 1 or Type 2 Diabetes Mellitus.

The most common form of maturity-onset diabetes of the young (MODY) is caused by mutations in the hepatocyte nuclear factor 1A (HNF1A) gene. However, most HNF1A mutation-carriers are initially misdiagnosed with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus; hence, they often receive nonoptimal treatment. The aim of our study was to test newly proposed clinical criteria for the identification of HNF1A MODY in patients with a diagnosis of T1DM or T2DM. To achieve this, the following criteria to preselect patients for screening were used: for T1DM: TDIR (total daily insulin requirement) > 0.3 IU of insulin/kg and the percentage of basal insulin > 30% of TDIR; for T2DM: sulphonylurea- (SU-) based oral treatment (monotherapy or combined with Metformin) > 15 years and BMI < 30 kg/m2. We reviewed the clinical data of 140 patients with T1DM and 524 clinically diagnosed with T2DM. On the basis of these criteria, we found a HNF1A mutation in 1 out of 2 individuals with a diagnosis of T1DM and 1 out of 11 selected individuals with a diagnosis of T2DM. We believe that the simplicity of the proposed criteria might prove useful in clinical practice, as an alternative to more time-consuming classical diagnostic techniques.

The Initial Assessment of Daily Insulin Dose in Chinese Newly Diagnosed Type 2 Diabetes.

Background. It has been well accepted that insulin therapy is the ideal treatment for newly diagnosed diabetic patients. However, there was no study about assessment of the initial insulin dosage in new onset Chinese patients with type 2 diabetes. Research Design and Methods. 65 newly diagnosed patients with type 2 diabetes (39 males/26 females; HbA1c ≥ 11.80 ± 0.22%) were investigated. All patients had random hyperglycaemia (at 21.8 ± 3.9 mmol/L) on the first day of admission and received insulin infusion intravenously (5 U/per hour). When the blood glucose level dropped to around 10 mmol/L, patients were then transferred to continuous subcutaneous insulin infusion (CSII). The reduction of blood glucose levels in response to per unit of insulin (RBG/RI) was recorded. The target glucose level was achieved in about 3 days. The total daily insulin dose (TDD) and basal insulin dose (TBD) were calculated. Results. TDD was 45.97 ± 1.28 units and TBD was 19.00 ± 0.54 units. TBD was about 40% of the total daily insulin requirement. There was a negative correlation between the ratio of RBG/RI and TDD. Conclusions. TDD was correlated with blood glucose reduction in response to intravenous insulin infusion in Chinese new onset patients with type 2 diabetes.

A Comparison of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Insulin Injection in Children with Type I Diabetes in Kuwait: Glycemic Control, Insulin Requirement, and BMI.

Continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) are two methods currently used to manage type I diabetes mellitus (T1DM). Here we compare our experiences with CSII and MDI in a large cohort of pediatric patients in Kuwait. Data on 326 patients with T1DM who were started on CSII between 2007 and 2012 were retrospectively compared with those of 326 patients on MDI. They were matched for sex, age at diagnosis, T1DM duration, glycemic control, insulin requirement, and body mass index (BMI). Data were collected at baseline and every three months and included glycated hemoglobin (HbA1c), insulin dose, and adverse events (severe hypoglycemia, diabetic ketoacidosis, and skin problems). The main reason for switching to CSII was to achieve better glycemic control (37%), followed by reducing hypoglycemia, and improving the quality of life (13.3% each). Although HbA1c decrease was most significant in the first year, it continued to be significantly lower in the CSII group compared to the MDI throughout the study period. Total daily insulin requirements were significantly lower in the CSII group. BMI increased in both groups, but the difference was significant only at the end of the fifth year. There was no significant change in the rate of diabetic ketoacidosis in either group. The CSII patients had more severe hypoglycemic episodes at baseline; however, it significantly decreased throughout the study period. Only five patients discontinued CSII therapy and two of these restarted within three months. CSII is a safe intensive insulin therapy in youngsters with T1DM and achieved markedly fewer severe hypoglycemic episodes and lower daily insulin requirements.

Clinical profile of patients using normal, high and very high insulin doses in type 2 diabetes

AimsInsulin requirement varies between patients with diabetes due to insulin resistance. The clinical profile of patients based on their insulin requirement has not been studied earlier. We stratified the patients based on total daily insulin requirement (TDIR) and studied their clinical profile and carbohydrate consumption. Materials & methodsSixty patients with type 2 diabetes (aged 30–75 years, using stable insulin dose for last 6 months, HbA1c between 6–7.5%, negative screening tests for Acromegaly and Cushing's disease) participated in this clinical observational study. All patients with major illness, surgery or diabetic ketoacidosis were excluded. The patients were divided into 3 groups: Group 1 (TDIR<1U/kg, n=30), Group 2 (TDIR 1–2U/kg, n=20) and Group 3 (TDIR>2U/kg, n=10). Data are presented as mean±S.D and comparison between three groups was done using one way ANOVA test. ResultsThe patients (27M: 33F) had mean age 54.3 ± 12.3 years, diabetes duration 10.1±4.7 years and an A1c of 7±0.38%. Patients in group 3 had lower body weight, BMI and highest carbohydrate consumption when compared with the other two groups (P<0.05). Hypoglycemic episodes and complications did not differ between the groups. ConclusionOur data showed that the low body weight and high carbohydrate intake are associated with increased insulin requirement. The clinical implications of our study are to check the carbohydrate intake in patients with high insulin requirement.

Converting Continuous Insulin Infusion to Subcutaneous Insulin Glargine After Cardiac Surgery Using Percentage-Based Versus Weight-Based Dosing: A Pilot Trial

Most studies report using percentage of total daily insulin (TDI) for converting therapy from continuous insulin infusion to subcutaneous insulin in cardiac surgery patients. Few studies have evaluated the efficacy of using body weight to calculate the basal insulin dose. To compare the efficacy and safety of dosing insulin glargine by weight versus percentage of TDI in cardiac surgery patients transitioning from continuous insulin infusion to subcutaneous insulin. We conducted a prospective, randomized, open-label, pilot study. Study patients who had a preoperative weight less than 100 kg and were receiving at least 6 hours of a continuous insulin infusion were randomized to receive either 50% of their TDI requirement or 0.5 units/kg of glargine as a one-time dose 2 hours before stopping the continuous insulin infusion. All patients were administered subcutaneous corrective insulin. Blood glucose monitoring occurred before each meal, at bedtime, and with morning laboratory tests for 24 hours after administration of the glargine dose. A total of 200 blood glucose measurements were performed in each group. The percentage of blood glucose measurements in target range (80-140 mg/dL) was similar between the weight-based group and the percentage-based group (66% vs 64%, p = 0.75). Median blood glucose after transition was 120 mg/dL (interquartile range [IQR] 99-147) in the weight-based group compared to 127 mg/dL (IQR 107-149; p = 0.03) in the percentage-based group. The median glargine dose was higher in the weight-based group (41 units; IQR 36-44) than in the weight-based group (24 units; IQR 14-30, p < 0.001). The rate of hypoglycemia (blood glucose <60 mg/dL) was 2.5% in each group. In this small cohort, dosing insulin glargine by weight proved to be safe, but larger scale studies are needed before adopting weight-based dosing in this patient population.