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The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.

Over the past decade there have been many advances in diabetes technologies, such as continuous glucose monitors (CGMCGM: A device that measures glucose values in the subcutaneous space via a sensor and is transmitted to a receiver/smartphone.s), insulin-delivery devices, and hybrid closed loop systemsHybrid Closed Loop (HCL) Systems:An insulin pump able to deliver variable insulin dosages based on CGM values using an algorithm.. Now most CGMs (Medtronic-Guardian, Dexcom-G6, and Abbott-Libre-2) have MARD values of < 10%, in contrast to two decades ago when the MARD used to be > 20%. In addition, the majority of the new CGMs do not require calibrations, and the latest CGMs last for 10–14 days. An implantable 6-months CGM by Eversense-3 is now approved in the USA and Europe. Recently, the FDA approved Libre 3 which provides real-time glucose values every minute. Even though it is approved as an iCGM it is not interoperable with automatic-insulin-delivery (AID) systems. The newer CGMs that are likely to be launched in the next few months in the USA include the 10–11 days Dexcom G7 (60% smaller than the existing G6), and the 7-days Medtronic Guardian 4. Most of the newer CGM have several features like automatic initialization, easy insertion, predictive alarms, and alerts. It has also been noticed that an arm insertion site might have better accuracy than abdomen or other sites, like the buttock for kids. Lag time between YSI and different sensors have been reported differently, sometimes it is down to 2–3 min; however, in many instances, it is still 15–20 min, especially when the rate of change of glucose is > 2 mg/min. We believe that in the next decade there will be a significant increase in the number of people who use CGM for their day-to-day diabetes care.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n= 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: −7.59 units (U) (95% confidence interval (CI) −11.79, −3.39; P= 0.040 versus placebo); 70 mg volagidemab: −6.64 U (95% CI −10.99, −2.29; P= 0.084 versus placebo); placebo: −1.27 U (95% CI −5.4, 2.9)) without meeting the prespecified significance level (P< 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was −0.53 (95% CI −0.89 to −0.17, nominal P= 0.004) in the 35 mg volagidemab group and −0.49 (95% CI −0.85 to −0.12, nominal P= 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.

The incidence of preeclampsia (PE) is increased in women with diabetes (∼20% vs ∼5% in the general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, the Hp 2-2 phenotype is associated with cardiorenal disease.

In SUSTAIN 1-3, semaglutide reduced BW and IR vs comparators. Post hocanalyses showed that IR improvement was positively associated with, and primarily mediated by, WL effects of semaglutide.

ABSTRACTThe prevalence of diabetes is increasing globally. Technology to improve care among individuals with diabetes is constantly being developed. Women living with Type 1 Diabetes Mellitus (T1DM) have unique challenges affecting their glucose control relating to menstrual cycles, pregnancy, and menopause. The purpose of this review is to examine the literature related to the use of technology to help women with T1DM manage their diabetes during the reproductive years, pregnancy, and beyond. Continuous subcutaneous insulin infusion (CSII) therapy can provider equivalent or better glucose control when compared with multiple daily injections (MDI), with less hypoglycemia, diabetic ketoacidosis, and weight gain. The CSII therapy has features that could help improve glucose control over the menstrual cycle, menopause, and pregnancy, although the most studied of these stages is pregnancy. Continuous glucose monitoring (CGM) can be combined with any insulin delivery system (MDI or CSII) to provide data on glucose values every few minutes and show glucose trends over time. CGM introduction can highlight glucose variability for women with T1DM, may be beneficial during pregnancy, and can reduce hypoglycemia. Sensor-augmented pump therapy and hybrid artificial pancreas (closed-loop) systems are promising tools that improve outcomes among individuals with diabetes. The use of modern technology to improve glucose and metabolic control among menopausal women with diabetes has not been well studied. Internet and phone-based technologies are emerging as important tools that may help with diabetes self-care for women living with diabetes.

Insulin glulisine (Apidra®, Sanofi-Aventis), a new and recently approved rapid-acting insulin analogue, mimics the pharmacokinetic and pharmacodynamic profiles of physiological human insulin, but has a rapid onset, peak effect at 1h, and a shorter duration of action (~ 4 h). Its rapid-action properties are maintained across subject types. Formal clinical evaluations show that insulin glulisine can be administered safely and effectively pre- and postmeal. When injected immediately premeal, insulin glulisine provides superior postprandial blood glucose control compared with regular human insulin (RHI) injected 30min premeal. These data highlight the flexibility in the dosing schedule with insulin glulisine. Clinical trials have demonstrated that insulin glulisine elicits a greater reduction in glycosylated haemoglobin at end point than RHI, in both type 1 and 2 diabetes mellitus. In addition, the safe administration of insulin glulisine by continuous subcutaneous insulin infusion has been demonstrated in patients with type 1 diabetes. In conclusion, insulin glulisine is an effective, safe and well-tolerated rapid-acting insulin analogue.

Objective: To compare the efficacy and safety of insulin glulisine (GLU), a new rapid-acting insulin analogue, injected 0 to 15 minutes before or immediately after meals, with regular human insulin (RHI), injected 30 to 45 minutes before meals. Methods: Patients with type 1 diabetes (N = 860) received once-daily insulin glargine and subcutaneous injections of either GLU (premeal or postmeal) or premeal RHI in this open-label, randomized, controlled, multicen-ter, parallel-group, 12-week study. Results: Baseline to endpoint changes in mean gly-cated hemoglobin (as A1c equivalents) (A1c) occurred in the premeal GLU, postmeal GLU, and premeal RHI groups (-0.26%, -0.11%, and -0.13%, respectively). The reduction in A1c was greater for the premeal GLU group in comparison with the RHI group (P = 0.02) and the post-meal GLU group (P = 0.006); no significant between-treatment difference was found for postmeal GLU versus RHI. Overall, blood glucose profiles were similar in all 3 treatment groups but were significantly lower for premeal GLU 2-hour postbreakfast measurements (premeal versus postmeal GLU, P = 0.0017; premeal GLU versus RHI, P = 0.0001) and 2-hour postdinner measurements (premeal GLU versus RHI, P = 0.0001; premeal versus postmeal GLU, P = 0.0137). Severe hypoglycemic episodes were comparable for premeal GLU, postmeal GLU, and pre-meal RHI groups (8.4%, 8.4%, and 10.1%, respectively). Body weight increased (+0.3 kg) in the RHI and premeal GLU groups; however, weight decreased in the postmeal GLU group (-0.3 kg; between-treatment difference, P = 0.03). Conclusion: Better A1c reductions were obtained with premeal GLU, but postmeal administration of GLU was as safe and effective as premeal GLU or RHI in combination with insulin glargine and was not associated with weight gain.

Background: The goal of new therapies introduced for type 1 diabetes should be to decrease hypoglycemic episodes while improving glycemic control.Methods: A database was used to computer match the baseline A1C values in 196 subjects with type 1 diabetes receiving multiple daily injections (MDI) consisting of four or more injections per day. There were 98 patients transferred from NPH to insulin glargine (Lantus®, Aventis Pharmaceuticals, Bridgewater, NJ), and 98 patients remained on NPH throughout the study. The gender distribution and mean age (∼32 years), duration of diabetes (∼16 years), and duration of treatment (∼13 months) were not significantly different between the groups. The majority of patients were well controlled (>50% in both groups had an A1c <7%).Results: The mean A1C values were not significantly different in the groups at baseline or at follow-up. Severe hypoglycemic episodes per patient per year were significantly lower in the glargine group compared with the NPH group (0.5 vs. 1.2, respectively; P = 0.04). The mean end-of-study total (P = 0.03) and long-acting (P = 0.0001) doses were significantly reduced from baseline in the group that switched to glargine, but not in the group that remained on NPH, with no change in the short-acting dose in either group. The weight gain was significantly higher in the NPH group at the end of the study (P = 0.004) with no significant change in the glargine group.Conclusions: Transfer to glargine treatment from NPH in MDI regimens significantly reduces severe hypoglycemic episodes despite a decline in long-acting basal insulin without significant weight gain.

Patient and health care provider evaluations are critical in establishing the accuracy and usability of new blood glucose meter systems. The objective of our study was to evaluate the clinical performance and ease of use of a blood glucose meter that uses a 10-test disk (Ascensia® Breeze® meter system, Bayer Healthcare LLC, Elkhart, IN). Meter capillary blood glucose results were compared with laboratory glucose results from 100 subjects with diabetes at two diabetes centers. Five health care professionals also tested subject blood samples. The subjects completed a questionnaire rating the ease of use of the meter, and their ability to learn to use the meter was also evaluated. Analytical accuracy of the meter system was assessed using ISO 15197:2003 performance criteria. Subject and health care professional meter glucose results were within 20% of laboratory glucose results [or 15 mg/dL (0.83 mmol/L) for specimens with less than 75 mg/dL (4.17 mmol/L) glucose levels] for 93.4% and 94.4% of results, respectively. Clinical accuracy of the system was evaluated using Parkes error grid analysis. The error grid analyses showed that 100% of subject and health care professional meter blood glucose results were in Zones A (92%) and B (8%). In the ease-of-use questionnaire, 91% of subject ratings of the meter were favorable. Subjects learned to operate the meter properly using the meter instructional material with little or no assistance from the health care professionals. The 10-test disk was rated as a prominent favorable feature. The new meter was accurate and precise in the hands of subjects with diabetes and health care professionals. Subjects found the meter easy and intuitive to learn to use. The study subjects were able to correctly use the meter after independently reviewing the user guide.

This study compared external insulin pump treatment using insulin lispro or insulin aspart with multiple daily injections (MDI; four or more injections per day) using insulin glargine and insulin lispro or insulin aspart. An electronic database was used to retrieve various parameters of glycemic control for 515 adult patients with type 1 diabetes. An insulin pump was used by 216 patients, and 299 patients were taking insulin glargine for at least 6 months. The mean age (~33 years), duration of diabetes (~16 years), and duration of treatment (~12 months) were similar for both the pump and insulin glargine groups. The mean (±SEM) A1C values were significantly reduced in both groups from the baseline to the end of the study (7.7 ± 0.1% to 7.5 ± 0.1% for the pump group and 8.0 ± 0.1% to 7.7 ± 0.1% for the insulin glargine group, P< 0.001) with similar weight gain (P> 0.05) in both groups. The insulin glargine group significantly reduced basal insulin intake at follow-up. The premeal boluses were similar throughout the study for both groups. The subjects reporting severe hypoglycemic episodes were similar in the two groups; however, there were 12 cases of diabetic ketoacidosis reported in the pump group and none in the insulin glargine group. Patients with type 1 diabetes can achieve similar glycemic control using insulin glargine with premeal insulin lispro or by using an external infusion pump with insulin lispro or insulin aspart. However, costs and episodes of diabetic ketoacidosis are significantly higher for insulin pump users.

Objective: To evaluate glycemic control and maternal and fetal outcomes of patients with type 1 diabetes treated with insulin lispro before and during pregnancy. Methods: We undertook a retrospective review of medical records of 62 women with type 1 diabetes who were treated with insulin lispro before and during pregnancy in an outpatient center specializing in the care of patients with diabetes. Outcome measures included maternal glycemic control, hypoglycemic episodes, microvascular complications, duration of gestation, fetal birth weight, and major congenital malformations. Results: The mean hemoglobin A1c level (&#45 standard error) was reduced from 7.2 &#45 0.2% at conception to 5.8 &#45 0.1% at the time of delivery. Of the 62 patients, 14 experienced at least one episode of severe hypoglycemia. No significant change was found in mean eye grade score for retinopathy or in albumin excretion rate during pregnancy. The mean duration of gestation was 37 weeks. The mean infant birth weight was 3.4 kg, with 24% of the pregnacies resulting in macrosomia. Major congenital malformations occurred in 2 of the 62 infants (3.2%). Conclusion: In our experience, insulin lispro therapy during pregnancy in patients with type 1 diabetes resulted in normalization of glycemic control and had no detectable adverse effects on maternal or fetal outcomes. A prospective, randomized study with adequate sample size needs to be performed in order to confirm these conclusions. (Endocr Pract. 2003;9:187-193)

The effect of sucrose consumption on glycemic control in children with insulin-dependent diabetes mellitus is unclear. Eight young subjects, 7–16 years of age, with a duration of diabetes of 2–8 years participated in this study. All subjects consumed four different breakfasts—oatmeal (OM) alone, oatmeal–sucrose (OMS), oatmeal–protein (OMP), and oatmeal with protein and sucrose (OMPS)—on four different days. Addition of sucrose resulted in a slightly greater area under the tolerance curve in 50% of the subjects; however, in 38% of subjects, the area decreased. The peak glucose level was lowest for OM, but there was no statistical difference in the peak levels of the four test meals. The most significant effect on glucose response was a delay in the peak time when protein was added to the meals. Peak times for OM and OMS (mean of 38 min) when fed alone were significantly (p< 0.05, ANOVA) shorter when compared to the peak time for OMP and OMPS (mean of 54 min). The average recovery time for OMP was longest. Other indices (tolerance index and change of rise in blood glucose) measured were not significantly different among the test meals. This study demonstrates that adding limited sucrose to OM cereal has little effect on the blood glucose response in children with diabetes. Addition of protein and fat clearly delays the glycemic response.

The effect of sucrose consumption on glycemic control in children with insulin-dependent diabetes mellitus is unclear. Eight young subjects, 7–16 years of age, with a duration of diabetes of 2–8 years participated in this study. All subjects consumed four different breakfasts—oatmeal (OM) alone, oatmeal–sucrose (OMS), oatmeal–protein (OMP), and oatmeal with protein and sucrose (OMPS)—on four different days. Addition of sucrose resulted in a slightly greater area under the tolerance curve in 50 of the subjects; however, in 38 of subjects, the area decreased. The peak glucose level was lowest for OM, but there was no statistical difference in the peak levels of the four test meals. The most significant effect on glucose response was a delay in the peak time when protein was added to the meals. Peak times for OM and OMS (mean of 38 min) when fed alone were significantly (p< 0.05, ANOVA) shorter when compared to the peak time for OMP and OMPS (mean of 54 min). The average recovery time for OMP was longest. Other indices (tolerance index and change of rise in blood glucose) measured were not significantly different among the test meals. This study demonstrates that adding limited sucrose to OM cereal has little effect on the blood glucose response in children with diabetes. Addition of protein and fat clearly delays the glycemic response.

• The relationship between high-normal blood pressure (BP) levels and early diabetic nephropathy is currently unknown. Blood pressure levels were checked longitudinally for a mean of 6.6 years in 230 subjects to determine their relationship to early diabetic nephropathy as monitored by microalbuminuria. High-normal BP level correlated with the presence of microalbuminuria. Microalbuminuria was 2.8 times as common in subjects with high-normal BP levels compared with those subjects with BP levels below the 90th percentile for their age. The elevated microalbumin excretion was primarily associated with high-normal diastolic BP levels. Our data suggest that either microalbuminuria or high-normal BP levels can precede the other. In a logistics model, diastolic BP and mean HbA1 (over 6.6 years) entered the model at similar levels, followed by duration of diabetes. When the influence of mean HbA1 was removed using logistic regression, the diastolic BP level remained a significant associated factor for the presence of microalbuminuria.(Arch Intern Med. 1990;150:639-641)

• Vitreous fluorophotometry was performed on 240 eyes of 120 young subjects who had insulin-dependent diabetes mellitus (type I) and various grades of retinopathy. The concentration of fluorescein was measured in the anterior chamber and posterior vitreous 1 hour after intravenous injection of fluorescein. There was a significant association (P&lt;.001) between the grade of retinopathy and the level of posterior vitreous leakage. The amount of posterior vitreous leakage in each eye also had a significant association with borderline elevation of diastolic blood pressure. Subjects with excessive posterior vitreous leakage had significantly higher levels of urinary microalbumin excretion. In a multiple linear regression analysis for posterior vitreous leakage, retinal grade consistently entered the model at a significant level (P≤.00001 to .003). Blood pressure also entered the model for posterior vitreous leakage at a significant level for retinal grades of the right and left eyes and of the worst eye. These results demonstrate an association between leakage of retinal and renal vessels, possibly linked at least in part to elevation in diastolic blood pressure.

• The natural course of early diabetic retinopathy in young subjects with insulin-dependent diabetes mellitus was evaluated during 693 patient visits for 259 subjects during a mean of 2.4 years. Diabetic retinopathy is considered a progressive disease among people with insulin-dependent diabetes mellitus (type I). Improvement of early retinopathy has not been recognized as a part of the natural course. In our experience, 25% of observations in subjects with early diabetic retinopathy (grades 2 and 3) showed improvement. Thus, 28 of 174 observations of diabetic retinopathy improved from grade 2 to grade 1, and 34 of 79 observations improved from grade 3 to grades 2 or 1. Markov chains indicate that 25% of observations of diabetic retinopathy will change from grade 1 to grade 5 or 6 in 17.0 years and 25% will change from grade 2 to grade 5 or 6 in 16.0 years. Future studies of diabetic retinopathy should consider a matrix of estimated transition probabilities, depending on the population, to judge probabilities of transition between states of retinopathy.

Recombinant human hyaluronidase (rHuPH20) is FDA-approved to increase dispersion and absorption of injected drugs. In CSII, a single pretreatment of the cannula site with rHuPH20 accelerates exposure and action of bolus doses of rapid analogs for up to 3 days of catheter use.

The three most commonly used basal insulins in patients with type 2 diabetes are neutral protamine Hagedorn (NPH) insulin and the long-acting insulin analogues glargine and detemir. Although randomised controlled trials have shown equivalent efficacy of these three insulins, inconsistencies in safety exist. We aimed to assess the safety and efficacy of these three basal insulins in real-world clinical setting in the ORBIT (Observational Registry for Basal Insulin Treatment) study.

The purpose of this study was to compare office and 24-h ambulatory blood pressure (ABP) values for adolescent and young adult males and females of Anglo, Hispanic, and African-American descent. One hundred and eighteen healthy subjects (62 females, 56 males) participated, with an ethnic distribution of 50 Anglo, 32 Hispanic, and 36 African-American subjects. All subjects came to the clinic for height, weight, sitting blood pressure (BP), and to begin 24-h ABP monitoring using the SpaceLabs model 90207 automatic noninvasive monitor. The monitor recorded readings every 0.5 h from 06:00 to 22:00 and every hour at night from 22:00 to 06:00. Office systolic and diastolic BP values were higher for all males compared to all females. Mean 24-h, nighttime, and daytime systolic ABP values were also significantly higher for males compared to females. The 24-h mean and daytime systolic ABP values were significantly different by ethnic groups. The African-American subjects always had the highest readings. Mean 24-h diastolic ABP was also significantly different by ethnic groups, with the African-American subjects being higher than the Anglos or the Hispanics. Diastolic ABP (24-h mean, daytime, and nighttime) values (for all subjects combined) increased gradually and varied significantly with age. This study provides preliminary normative data about ABP in an understudied population (ie, teenagers and young adults of different ethnic backgrounds). It also shows that higher blood pressures are present among males and among subjects of African-American descent in the teenage and young adult population. © 1997 American Journal of Hypertension, Ltd. Am J Hypertens 1997;10:18–23