Eda Cengiz

A Tale of Two Compartments: Interstitial Versus Blood Glucose Monitoring

Self-monitoring of blood glucose was described as one of the most important advancements in diabetes management since the invention of insulin in 1920. Recent advances in glucose sensor technology for measuring interstitial glucose concentrations have challenged the dominance of glucose meters in diabetes management, while raising questions about the relationships between interstitial and blood glucose levels. This article will review the differences between interstitial and blood glucose and some of the challenges in measuring interstitial glucose levels accurately.

Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D Exchange clinic registry

Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) are common serious acute complications of type 1 diabetes (T1D). The aim of this study was to determine the frequency of SH and DKA and identify factors related to their occurrence in the T1D Exchange pediatric and young adult cohort.

Effect of Pramlintide on Prandial Glycemic Excursions During Closed-Loop Control in Adolescents and Young Adults With Type 1 Diabetes

OBJECTIVE Even under closed-loop (CL) conditions, meal-related blood glucose (BG) excursions frequently exceed target levels as a result of delays in absorption of insulin from the subcutaneous site of infusion. We hypothesized that delaying gastric emptying with preprandial injections of pramlintide would improve postprandial glycemia by allowing a better match between carbohydrate and insulin absorptions. RESEARCH DESIGN AND METHODS Eight subjects (4 female; age, 15–28 years; A1C, 7.5 ± 0.7%) were studied for 48 h on a CL insulin-delivery system with a proportional integral derivative algorithm with insulin feedback: 24 h on CL control alone (CL) and 24 h on CL control plus 30-μg premeal injections of pramlintide (CLP). Target glucose was set at 120 mg/dL; timing and contents of meals were identical on both study days. No premeal manual boluses were given. Differences in reference BG excursions, defined as the incremental glucose rise from premeal to peak, were compared between conditions for each meal. RESULTS CLP was associated with overall delayed time to peak BG (2.5 ± 0.9 vs. 1.5 ± 0.5 h; P < 0.0001) and reduced magnitude of glycemic excursion (88 ± 42 vs. 113 ± 32 mg/dL; P = 0.006) compared with CL alone. Pramlintide effects on glycemic excursions were particularly evident at lunch and dinner, in association with higher premeal insulin concentrations at those mealtimes. CONCLUSIONS Pramlintide delayed the time to peak postprandial BG and reduced the magnitude of prandial BG excursions. Beneficial effects of pramlintide on CL may in part be related to higher premeal insulin levels at lunch and dinner compared with breakfast.

Reduced Hypoglycemia and Increased Time in Target Using Closed-Loop Insulin Delivery During Nights With or Without Antecedent Afternoon Exercise in Type 1 Diabetes

OBJECTIVE Afternoon exercise increases the risk of nocturnal hypoglycemia (NH) in subjects with type 1 diabetes. We hypothesized that automated feedback-controlled closed-loop (CL) insulin delivery would be superior to open-loop (OL) control in preventing NH and maintaining a higher proportion of blood glucose levels within the target blood glucose range on nights with and without antecedent afternoon exercise. RESEARCH DESIGN AND METHODS Subjects completed two 48-h inpatient study periods in random order: usual OL control and CL control using a proportional-integrative-derivative plus insulin feedback algorithm. Each admission included a sedentary day and an exercise day, with a standardized protocol of 60 min of brisk treadmill walking to 65–70% maximum heart rate at 3:00 p.m. RESULTS Among 12 subjects (age 12–26 years, A1C 7.4 ± 0.6%), antecedent exercise increased the frequency of NH (reference blood glucose <60 mg/dL) during OL control from six to eight events. In contrast, there was only one NH event each on nights with and without antecedent exercise during CL control (P = 0.04 vs. OL nights). Overnight, the percentage of glucose values in target range was increased with CL control (P < 0.0001). Insulin delivery was lower between 10:00 p.m. and 2:00 a.m. on nights after exercise on CL versus OL, P = 0.008. CONCLUSIONS CL insulin delivery provides an effective means to reduce the risk of NH while increasing the percentage of time spent in target range, regardless of activity level in the mid-afternoon. These data suggest that CL control could be of benefit to patients with type 1 diabetes even if it is limited to the overnight period.

Is an automatic pump suspension feature safe for children with type 1 diabetes? An exploratory analysis with a closed-loop system.

OBJECTIVES It has been proposed that the first step towards a closed-loop artificial pancreas might be to use a continuous glucose sensor to automatically suspend the basal insulin delivery based on projected low sensor glucose values. METHODS We reviewed our recent experience with an artificial pancreas system, utilizing a proportional-integrative-derivative (PID) algorithm, in 17 adolescents with type 1 diabetes (T1D) to assess the safety and efficacy of this maneuver. RESULTS During 34 h of closed-loop automated insulin delivery, 18 pump suspensions > or =60 min (90 +/- 18 min) occurred in eight subjects. Sensor glucose levels fell from 159 +/- 42 mg/dL to a nadir of 72 +/- 13 mg/dL. Corresponding plasma glucose levels fell from 168 +/- 51 to 72 +/- 16 mg/dL, with values <60 mg/dL recorded in only four of the 18 events. CONCLUSIONS These data suggest that automatic pump suspension using the PID algorithm may be an effective means to prevent hypoglycemia in youth with T1D.

A contrast between children and adolescents with excellent and poor control: the T1D exchange clinic registry experience

Optimizing glycemic control in pediatric type 1 diabetes (T1D) is essential to minimizing long‐term risk of complications. We used the T1D Exchange database from 58 US diabetes clinics to identify differences in diabetes management characteristics among children categorized as having excellent vs. poor glycemic control.

Effect of insulin feedback on closed-loop glucose control: a crossover study.

Background: Closed-loop (CL) insulin delivery systems utilizing proportional-integral-derivative (PID) controllers have demonstrated susceptibility to late postprandial hypoglycemia because of delays between insulin delivery and blood glucose (BG) response. An insulin feedback (IFB) modification to the PID algorithm has been introduced to mitigate this risk. We examined the effect of IFB on CL BG control. Methods: Using the Medtronic ePID CL system, four subjects were studied for 24 h on PID control and 24 h during a separate admission with the IFB modification (PID + IFB). Target glucose was 120 mg/dl; meals were served at 8:00 AM, 1:00 PM, and 6:00 PM and were identical for both admissions. No premeal manual boluses were given. Reference BG excursions, defined as incremental glucose rise from premeal to peak, and postprandial BG area under the curve (AUC; 0–5 h) were compared. Results are reported as mean ± standard deviation. Results: The PID + IFB control resulted in higher mean BG levels compared with PID alone (153 ± 54 versus 133 ± 56 mg/dl; p < .0001). Postmeal BG excursions (114 ± 28 versus 114 ± 47 mg/dl) and AUCs (285 ± 102 versus 255 ± 129 mg/dl/h) were similar under both conditions. Total insulin delivery averaged 57 ± 20 U with PID versus 45 ± 13 U with PID + IFB (p = .18). Notably, eight hypoglycemic events (BG < 60 mg/dl) occurred during PID control versus none during PID + IFB. Conclusions: Addition of IFB to the PID controller markedly reduced the occurrence of hypoglycemia without increasing meal-related glucose excursions. Higher average BG levels may be attributable to differences in the determination of system gain (Kp) in this study. The prevention of postprandial hypoglycemia suggests that the PID + IFB algorithm may allow for lower target glucose selection and improved overall glycemic control.

Diabetic Ketoacidosis at Diabetes Onset: Still an All Too Common Threat in Youth

OBJECTIVE To define the demographic and clinical characteristics of children at the onset of type 1 diabetes (T1D), with particular attention to the frequency of diabetic ketoacidosis (DKA). STUDY DESIGN The Pediatric Diabetes Consortium enrolled children with new-onset T1D into a common database. For this report, eligible subjects were aged <19 years, had a pH or HCO(3) value recorded at diagnosis, and were positive for at least one diabetes-associated autoantibody. Of the 1054 children enrolled, 805 met the inclusion criteria. A pH of <7.3 and/or HCO(3) value of <15 mEq/L defined DKA. Data collected included height, weight, hemoglobin A1c, and demographic information (eg, race/ethnicity, health insurance status, parental education, family income). RESULTS The 805 children had a mean age of 9.2 years, 50% were female; 63% were non-Hispanic Caucasian. Overall, 34% of the children presented in DKA, half with moderate or severe DKA (pH <7.2). The risk for DKA was estimated as 54% in children aged <3 years and 33% in those aged ≥ 3 years (P = .006). In multivariate analysis, younger age (P = .002), lack of private health insurance (P < .001), African-American race (P = .01), and no family history of T1D (P = .001) were independently predictive of DKA. The mean initial hemoglobin A1c was higher in the children with DKA compared with those without DKA (12.5% ± 1.9% vs 11.1% ± 2.4%; P < .001). CONCLUSION The incidence of DKA in children at the onset of T1D remains high, with approximately one-third presenting with DKA and one-sixth with moderate or severe DKA. Increased awareness of T1D in the medical and lay communities is needed to decrease the incidence of this life-threatening complication.

New-generation diabetes management: glucose sensor-augmented insulin pump therapy

Diabetes is one of the most common chronic disorders with an increasing incidence worldwide. Technologic advances in the field of diabetes have provided new tools for clinicians to manage this challenging disease. For example, the development of continuous subcutaneous insulin infusion systems have allowed for refinement in the delivery of insulin, while continuous glucose monitors provide patients and clinicians with a better understanding of the minute to minute glucose variability, leading to the titration of insulin delivery based on this variability when applicable. Merging of these devices has resulted in sensor-augmented insulin pump therapy, which became a major building block upon which the artificial pancreas (closed-loop systems) can be developed. This article summarizes the evolution of sensor-augmented insulin pump therapy until present day and its future applications in new-generation diabetes management.

Acceleration of insulin pharmacodynamic profile by a novel insulin infusion site warming device.

Subcutaneously injected rapid‐acting insulin analogs do not replicate physiologic insulin action due to delays in their onset and peak action resulting in postprandial glucose excursions. The InsuPatch (IP) is a novel insulin infusion site warming device developed to accelerate insulin action by increasing blood flow to the area of insulin absorption. Thirteen adolescents with type 1 diabetes (T1D, mean age 14 ± 4 yr) were enrolled in this study to investigate the effect of the IP on the pharmacodynamics and pharmacokinetics of a 0.2 unit/kg bolus dose of aspart insulin using the euglycemic clamp technique.