Mean Daily Glucose Levels Research Articles

1486-P: Effects of the COVID-19 Booster Vaccine on Glycemia and Insulin Resistance in People with Type 1 Diabetes—A Prospective Pilot Study

Background: Inflammation is well-known to worsen glycemia in people with type 1 diabetes (T1D). COVID-19 vaccines are vital for protection against SARS-CoV-2 infection, but by necessity trigger an acute immune response. Case reports have described hyperglycemic crises shortly after a booster dose. However, effects of COVID-19 vaccines on glycemic control in T1D is poorly understood. Methods: This was a prospective cohort study of adults with T1D receiving a COVID-19 booster dose. At the baseline visit a blinded Dexcom G6 Pro CGM was placed, subjects received COVID-19 booster vaccine 3-4 days later, and returned 6 days post-vaccination to have the CGM removed. Primary outcome was change in mean daily glucose level from baseline. Secondary outcomes included total daily insulin dose (TDI), total daily insulin resistance (TDIR = mean glucose * TDI), and time in range (TIR = %glucose readings between 70-180mg/dL). Data were transformed as necessary to maintain normality. Results: We enrolled 20 adults with T1D; one subject was excluded for nonadherence with study procedures. Baseline characteristics included (mean±SD) age: 48.9±19.4y, sex: 68.4%F, BMI: 29.6±6.2kg/m2, A1c: 7.0±1.0%. 42% received a Moderna and 58% Pfizer-BioNTech booster. Mean glucose on Day#2 post-vaccination was significantly greater than baseline (165.1±27.4 vs 154.5±30.2 mg/dL, p=0.04), as was TDIR (7970±4113 vs 7036±3999; p=0.02). No other days had significant differences in glycemic metrics as compared to baseline. There were no differences in any outcome metrics between booster vaccine manufacturers. Conclusions: These results suggest that adults with T1D may experience transient glycemic elevations after receiving a COVID-19 booster. Clinicians may need to warn people with T1D to be more vigilant with glucose testing and insulin dosing temporarily after vaccination. Larger studies are warranted to corroborate these findings. Disclosure M.Zilbermint: Consultant; EMD Serono, Other Relationship; American Association of Clinical Endocrinologists. M.Motevalli: None. K.Batty: None. J.Venner-walcott: None. A.Edwards: None. T.Burley: None. K.Jackson: None. M.Akhtar: None. A.Demidowich: Research Support; Dexcom, Inc. Funding Dexcom, Inc. (IIS-2021-136)

Surgical treatment for morbid obesity in patients with type 2 diabetes mellitus

Shortly after its implementation, laparoscopic sleeve gastrectomy (LSG) has become the most commonly performed bariatric surgery. It is widely believed that DM2 and the associated chronic hyperglycemia (expressed by glycated hemoglobin – HbA<sub>1c</sub>) increase the risk of postoperative complications and mortality, what has been confirmed in some branches of surgery. Hence research on its effect on postoperative outcomes after LSG is extremely valuable. There is a lack of studies analyzing the influence of LSG on prediabetes and DM2 at various time intervals after surgery, especially in the perioperative period, what is important from the perspective of patient care. A retrospective, multicenter observational study of LSG patients and a prospective observational study in DM2 patients and control group that were enrolled in either LSG or LRYGB with comparison of the 24-hours glucose fluctuations over a 10-day perioperative period using a continuous glucose monitoring system were conducted. Preoperative HbA<sub>1c</sub> levels did not significantly increase the chance of developing perioperative and postoperative complications, as well as prolonged hospital stay after LSG. HbA<sub>1c</sub> >7.3% increased the risk of hospital re-admission. The period of reactive hyperglycemia was recorded in response to the surgical trauma on the 1<sup>st</sup> and 2<sup>nd</sup> postoperative days after LSG and LRYGB. From the 3rd day, significantly lower mean daily glucose levels were observed in patients with DM2 after LRYGB compared to patients after LSG. Regardless of DM2, significantly lower mean daily glucose levels were present in all LRYGB patients at from 7<sup>th</sup> to 10</sup>th</sup> day as compared to the LSG.

Reference Ranges of Glycemic Variability in Infants after Surgery-A Prospective Cohort Study.

We aimed to define reference ranges of glycemic variability indices derived from continuous glucose monitoring data for non-diabetic infants during post-operative intensive care treatment after cardiac surgery procedures. We performed a prospective cohort intervention study in a pediatric intensive care unit (PICU). Non-diabetic infants aged 0–12 months after corrective cardiovascular surgery procedures were fitted upon arrival to the PICU with a continuous glucose monitoring system (iPro2, Medtronic, Minneapolis, MN, USA). Thirteen glycemic variability indices were calculated for each patient. Complete recordings of 65 patients were collected on the first postoperative day. During the first three postsurgical days 5%, 24% and 43% of patients experienced at least one hypoglycemia episode, and 40%, 10% and 15%—hyperglycemia episode, respectively, in each day. Due to significant differences between the first postoperative day (mean glycemia 130 ± 31 mg/dL) and the second and third day (105 ± 18 mg/dL, 101 ± 22.2 mg/dL; p < 0.0001), we proposed two separate reference ranges—for the acute and steady state patients. Thus, for individual glucose measurements, we proposed a reference range between 85 and 229 mg/dL and 69 and 149 mg/dL. For the mean daily glucose level, ranges between 122 and 137 mg/dL and 95 and 110 mg/dL were proposed. In conclusion, rt-CGM revealed a very high likelihood of hyperglycemia in the first postsurgical day. The widespread use of CGM systems in a pediatric ICU setting should be considered as a safeguard against dysglycemic episodes; however, reference ranges for those patients should be different to those used in diabetes care.

What is the role of glycemic control in the development of preeclampsia among women with type 1 diabetes?

To investigate the role of glycemic control in development of preeclampsia (PE) in women with type 1 diabetes mellitus (T1DM). An observational case-control study comparing 244 women with type 1 diabetes and 488 controls was conducted. Among women with T1DM HbA1c, average daily glucose values, fasting, preprandial, 1-hour and 2-hour postprandial glucose levels, and daily 3 meals postprandial glucose areas were evaluated. Uterine artery pulsatility indices (PI) at 16, 20, 24weeks' gestation were obtained. Data analysis included rates of PE in both groups, and association between glycemic control, uterine artery PI and development of PE among women with T1DM. PE developed in 13.1% of diabetic women and in 3.5% of women in the control group (odds ratio 4.2; 95% CI 2.2-8.1). In multivariate logistic regression analysis, HbA1c in the 1st trimester, mean daily glucose level in the 1st and 2nd trimester, daily 3 meal postprandial glucose area in the 1st and 2nd trimester, and the uterine arteries PI at 24weeks' gestation were found to be associated with development of PE. The uterine arteries PI showed a significant positive correlation with the 3 meal postprandial glucose area at 16, 20, 24weeks. In women with T1DM, poor glycemic control early in pregnancy is associated with an increased risk of subsequent PE. An association between poor placentation, as indicated by the increased PI of uterine arteries, and a maternal metabolic factor, that is the 3 meal post-prandial glucose area, has been shown, supporting the increased rate of PE among women with T1DM.

Peri-transplant glycaemic control as a predictor of pancreas transplant survival.

The relationship between peri-transplant glycaemic control and outcomes following pancreas transplantation is unknown. We aimed to relate peri-transplant glycaemic control to pancreas graft survival and to develop a framework for defining early graft dysfunction. Peri-transplant glycaemic control profiles over the first 5 days postoperatively were determined by an area under the curve [AUC; average daily glucose level (mmol/L) × time (days)] and the coefficient of variation of mean daily glucose levels. Peri-transplant hyperglycaemia was defined as an AUC ≥35 mmol/day/L (daily mean blood glucose ≥7 mmol/L). Risks of graft failure associated with glycaemic control and variability and peri-transplant hyperglycaemia were determined using covariate-adjusted Cox regression. We collected 7606 glucose readings over 5 days postoperatively from 123 pancreas transplant recipients. Glucose AUC was a significant predictor of graft failure during 3.6 years of follow-up (unadjusted HR [95% confidence interval] 1.17 [1.06-1.30], P = .002). Death censored non-technical graft failure occurred in eight (10%) recipients with peri-transplant normoglycaemia, and eight (25%) recipients with peri-transplant hyperglycaemia such that hyperglycaemia predicted a 3-fold higher risk of graft failure [HR (95% confidence interval): 3.0 (1.1-8.0); P = .028]. Peri-transplant hyperglycaemia is strongly associated with graft loss and could be a valuable tool guiding individualized graft monitoring and treatment. The 5-day peri-transplant glucose AUC provides a robust and responsive framework for comparing graft function.

Effect of Peripheral Electrical Stimulation (PES) on Nocturnal Blood Glucose in Type 2 Diabetes: A Randomized Crossover Pilot Study.

BackgroundRegulation of hepatic glucose production has been a target for antidiabetic drug development, due to its major contribution to glucose homeostasis. Previous pre-clinical study demonstrated that peripheral electrical stimulation (PES) may stimulate glucose utilization and improve hepatic insulin sensitivity. The aim of the present study was to evaluate safety, tolerability, and the glucose-lowering effect of this approach in patients with type 2 diabetes (T2DM).MethodsTwelve patients with T2DM were recruited for an open label, interventional, randomized trial. Eleven patients underwent, in a crossover design, an active, and a no-intervention control periods, separated with a two-week washout phase. During the active period, the patients received a daily lower extremity PES treatment (1.33Hz/16Hz burst mode), for 14 days. Study endpoints included changes in glucose levels, number of hypoglycemic episodes, and other potential side effects. Endpoints were analyzed based on continuous glucose meter readings, and laboratory evaluation.ResultsWe found that during the active period, the most significant effect was on nocturnal glucose control (P < 0.0004), as well as on pre-meal mean glucose levels (P < 0.02). The mean daily glucose levels were also decreased although it did not reach clinical significance (P = 0.07). A reduction in serum cortisol (P < 0.01) but not in insulin was also detected after 2 weeks of treatment. No adverse events were recorded.ConclusionsThese results indicate that repeated PES treatment, even for a very short duration, can improve blood glucose control, possibly by suppressing hepatic glucose production. This effect may be mediated via hypothalamic-pituitary-adrenal axis modulation.Trial registrationClinicalTrials.gov NCT02727790

CARDIOVASCULAR COMPLICATIONS AND CARBOHYDRATE METABOLISM IN CORONARY SHUNTING “OFF-PUMP” ACCORDING TO THE REGIMEN OF GLUCOSE LOWERING TREATMENT IN ISCHEMIC HEART DISEASE AND DIABETES

Aim. To study the shortest term results of coronary bypass (CBG) under “off-pump” circumstances and the condition of carbohydrate metabolism in ischemic disease patients (IHD) with comorbid diabetes 2 type (DM2) under various regimens of perioperation glucose lowering therapy. Material and methods. In the study, the IHD and DM2 patients included, receiving oral glucose lowering drugs (OGLD), with the mean age 57,5 (53-62) y.o., men 99 (78,6%). Before operation the patients were selected to the groups of OGLD (n=61) and insulin (IN) (n=65). In OGLD group the intake of the drugs was continued during perioperation period. In the IN group there was switch to short insulin. The dynamics of carbohydrate metabolism markers in different timeline intervals of postoperation period was studied, and its relation with the glucose lowering regimen. The early postoperation cardiovascular complications (CVC) rate was measured: myocardial infarction, stroke, atrial fibrillation. The carbohydrate metabolism parameters in subgroups of patients was measured, with CVC and without. Results. At baseline there were no differences in carbohydrate metabolism parameters in groups. Loading IN, mean daily glucose levels, its variability and glycemia below the recommended perioperation range (6,1-10,0 mM/L) were lower than in OGLD group. Total number of CVC also predominated in IN group (20,0% vs. 8,2%, p=0,049). Complication subgroups and non-complicated, significantly differed by the baseline glycosilated hemoglobin, mean level of glucose and its daily variability in all timeline intervals studied, as by the prevalence of glucose &lt;6,1 mM/L 0ne day before operation, just before and just after. Conclusion. Patients underwent CBG as off-pump, after switch on short IN, comparing to OGLD patients, have higher mean glycemia level, its variability and number of shifts from recommended range, as higher rate of post-operation CVC.

CARDIOVASCULAR COMPLICATIONS AND CARBOHYDRATE METABOLISM IN CORONARY SHUNTING “OFF-PUMP” ACCORDING TO THE REGIMEN OF GLUCOSE LOWERING TREATMENT IN ISCHEMIC HEART DISEASE AND DIABETES

Aim. To study the shortest term results of coronary bypass (CBG) under “off-pump” circumstances and the condition of carbohydrate metabolism in ischemic disease patients (IHD) with comorbid diabetes 2 type (DM2) under various regimens of perioperation glucose lowering therapy. Material and methods. In the study, the IHD and DM2 patients included, receiving oral glucose lowering drugs (OGLD), with the mean age 57,5 (53-62) y.o., men 99 (78,6%). Before operation the patients were selected to the groups of OGLD (n=61) and insulin (IN) (n=65). In OGLD group the intake of the drugs was continued during perioperation period. In the IN group there was switch to short insulin. The dynamics of carbohydrate metabolism markers in different timeline intervals of postoperation period was studied, and its relation with the glucose lowering regimen. The early postoperation cardiovascular complications (CVC) rate was measured: myocardial infarction, stroke, atrial fibrillation. The carbohydrate metabolism parameters in subgroups of patients was measured, with CVC and without. Results. At baseline there were no differences in carbohydrate metabolism parameters in groups. Loading IN, mean daily glucose levels, its variability and glycemia below the recommended perioperation range (6,1-10,0 mM/L) were lower than in OGLD group. Total number of CVC also predominated in IN group (20,0% vs. 8,2%, p=0,049). Complication subgroups and non-complicated, significantly differed by the baseline glycosilated hemoglobin, mean level of glucose and its daily variability in all timeline intervals studied, as by the prevalence of glucose <6,1 mM/L 0ne day before operation, just before and just after. Conclusion. Patients underwent CBG as off-pump, after switch on short IN, comparing to OGLD patients, have higher mean glycemia level, its variability and number of shifts from recommended range, as higher rate of post-operation CVC.

Liraglutide Improves Glycemic and Blood Pressure Control and Ameliorates Progression of Left Ventricular Hypertrophy in Patients with Type 2 Diabetes Mellitus on Peritoneal Dialysis.

Diabetes mellitus (DM) is a multifactorial disease associated with cardiovascular complications. Patients undergoing peritoneal dialysis also experience an increased incidence of cardiovascular disease. To prevent progression of cardiovascular complications in DM patients, glycemic control is important. In this study, we examined the efficacy and safety of the glucagon-like peptide analog liraglutide for treating type 2 diabetes patients undergoing peritoneal dialysis. Sixteen type 2 diabetes patients on peritoneal dialysis were enrolled. Before liraglutide initiation, 11 patients were on insulin therapy, three were on oral antidiabetic agents, and two were on diet therapy. Of the 16 patients, 12 had switched to liraglutide because of severe hypoglycemia and four because of hyperglycemia. Echocardiography was performed at baseline and 12 months after liraglutide initiation. Hemoglobin A1c, glycosylated albumin, and fasting/postprandial glucose levels gradually decreased after liraglutide initiation. After 6 and 12 months of treatment, postprandial glucose levels showed a significant difference from baseline. Moreover, the mean daily glucose level and glycemic fluctuations decreased. Systolic blood pressure upon waking also decreased. In addition, after 12 months, left ventricular mass index (LVMI) decreased and left ventricular ejection fraction increased. Changes in LVMI positively correlated with morning systolic blood pressure and fasting glucose levels. One patient restarted insulin because of anorexia but severe hypoglycemia was not observed. These findings suggest that liraglutide therapy in type 2 diabetes patients undergoing peritoneal dialysis is safe and effective for decreasing glucose levels, glycemic fluctuations, and blood pressure, apart from improving left ventricular function.

In-hospital daily insulin dose predicts long-term adverse outcome in patients with diabetes with ST-elevation myocardial infarction treated with successful primary percutaneous angioplasty.

IntroductionEarly initiation of reperfusion therapy including primary percutaneous coronary revascularization (PPCI) has been recognized as a crucial factor determining clinical outcomes in the acute phase of myocardial infarction. In unstable patients with type 2 diabetes mellitus (T2D) the clear benefit from PPCI was proven. We aim to evaluate the prognostic value of factors describing glycometabolic state on admission in patients with T2D undergoing PPCI in acute ST-elevation myocardial infarction (STEMI).Material and methodsProspective analysis of clinical and laboratory variables (mean daily short acting exogenous insulin dose (DID), admission blood glucose, glycated hemoglobin (HbA1c), microalbuminuria) was performed in 112 consecutive patients with T2D with STEMI who underwent PPCI. Women comprised 58% of the group.ResultsInsulin dosing was targeted to obtain a mean daily glucose level < 7.8 mmol/l. During 12-month follow-up 33 (29.5%) major adverse cardiac events (major adverse cardiac events (MACE) consisting of death, reinfarction, and repeated target vessel revascularization) were reported. Microalbuminuria was present in 68 (60.5%) patients. The mean HbA1c level was 7.9%. In the multivariate logistic regression model only DID > 44 IU remained an independent risk factor for MACE (p = 0.02, OR = 5.2).ConclusionsIn patients with diabetes with STEMI treated with PPCI, simple measurement of DID during hospitalization can add valuable prognostic information about the future risk of MACE.

Persistent perioperative hyperglycemia as an independent predictor of poor outcome after aneurysmal subarachnoid hemorrhage

The authors of previous studies have shown that admission hyperglycemia or perioperative hyperglycemic events may predispose a patient to poor outcome after aneurysmal subarachnoid hemorrhage (SAH). The results of experimental evidence have suggested that hyperglycemia may exacerbate ischemic central nervous system injury. It remains to be clarified whether a single hyperglycemic event or persistent hyperglycemia is predictive of poor outcome after aneurysmal SAH. Ninety-seven patients undergoing treatment for aneurysmal SAH were observed, and all perioperative variables were entered into a database of prospectively recorded data. Daily serum glucose values were retrospectively added. Patients were examined at hospital discharge (14-21 days after SAH onset), and Glasgow Outcome Scale (GOS) scores were prospectively documented. The GOS score at last follow-up was retrospectively determined. Serum glucose greater than 200 mg/dl for 2 or more consecutive days was defined as persistent hyperglycemia. Outcome was categorized as "poor" (dependent function [GOS Score 1-3]) or "good" (independent function [GOS Score 4 or 5]) at discharge. The independent association of 2-week and final follow-up outcome (GOS score) with the daily serum glucose levels was assessed using a multivariate analysis. In the univariate analysis, increasing age, increasing Hunt and Hess grade, hypertension, ventriculomegaly on admission computed tomography scan, Caucasian race, and higher mean daily glucose levels were associated with poor (dependent) 2-week outcome after aneurysmal SAH. In the multivariate analysis, older age, the occurrence of symptomatic cerebral vasospasm, increasing admission Hunt and Hess grade, and persistent hyperglycemia were independent predictors of poor (dependent) outcome 2 weeks after aneurysmal SAH. Admission Hunt and Hess grade and persistent hyperglycemia were independent predictors of poor outcome at last follow-up examination a mean 10 +/- 3 months after aneurysmal SAH. Isolated hyperglycemic events did not predict poor outcome. Patients with persistent hyperglycemia were 10-fold more likely to have a poor (dependent) 2-week outcome and sevenfold more likely to have a poor outcome a mean 10 months after aneurysmal SAH independent of admission Hunt and Hess grade, occurrence of cerebral vasospasm, or all comorbidities. Patients with persistent hyperglycemia were seven times more likely to have a poor outcome at a mean of 10 months after aneurysmal SAH. Isolated hyperglycemic events were not predictive of poor outcome. Serum glucose levels in the acute setting of aneurysmal SAH may help predict outcomes months after surgery.

The Impact of a Normoglycemic Management Protocol on Clinical Outcomes in the Trauma Intensive Care Unit

The purpose of this study was to determine if protocol-driven normoglycemic management in trauma patients affected glucose control, ventilator-associated pneumonia, surgical-site infection, and inpatient mortality. A prospective, consecutive-series, historically controlled study design evaluated protocol-driven normoglycemic management among trauma patients at Vanderbilt University Medical Center. Those mechanically ventilated > or =24 hours and > or =15 years of age were included. A glycemic-control protocol required insulin infusion therapy for glucose >110 mg/dL. Control patients included those who met criteria, were admitted the year preceding protocol implementation, and had hyperglycemia treated at the physician's discretion. Eight hundred eighteen patients met study criteria; 383 were managed without protocol; 435 underwent protocol. The protocol group had lower glucose levels 7 of 14 days measured. After admission, both groups had mean daily glucose levels <150 mg/dL. No difference in pneumonia (31.6% vs 34.5%; p = .413), surgical infection (5.0% vs 5.7%; p = .645) or mortality (12.3% vs 13.1%; p = .722) occurred between groups. If one episode of blood glucose level was > or =150 mg/dL (n = 638; 78.0%), outcomes were worse: higher daily glucose levels for 14 days after admission (p < .001), pneumonia rates (35.9% vs 23.3%; p = .002), and mortality (14.6% vs 6.1%; p = .002). One or more days of glucose > or =150 mg/dL had a 2- to 3-fold increase in the odds of death. Protocol use in these patients was not associated with outcome improvement. Protocol-driven management decreased glucose levels 7 of 14 days after admission without outcome change. One or more glucose levels > or =150 mg/dL were associated with worse outcome.

Reduction of Nosocomial Infections in the Surgical Intensive-Care Unit by Strict Glycemic Control

To investigate whether hyperglycemia in glucose-intolerant patients without diabetes could lead to increased nosocomial infections in the surgical intensive-care unit (ICU). A prospective, randomized, controlled clinical trial was conducted in the surgical ICU of a large teaching hospital in Hartford, Connecticut. Adult patients admitted to a 12-bed surgical ICU requiring treatment of hyperglycemia (glucose values > or = 140 mg/dL) were randomly assigned to receive standard insulin therapy (target glucose range, 180 to 220 mg/dL) or strict insulin therapy (target glucose range, 80 to 120 mg/dL) throughout their ICU stay. Demographic data, comorbidities, and confounding variables were analyzed. Outcome measures included mean daily serum glucose values, mean daily insulin doses, and number of nosocomial infections during the ICU stay. The study was completed by 61 critically ill surgical patients (27 in the standard glucose control group and 34 in the strict glucose control group). A significant reduction (P<0.001) in mean daily glucose level was achieved in the strict glycemic control group (125 +/- 36 mg/dL) in comparison with the standard glycemic control group (179 +/- 61 mg/dL). Furthermore, a significant reduction (P<0.05) in the incidence of total nosocomial infections, including intravascular device, bloodstream, intravascular device-related bloodstream, and surgical site infections, was observed in the strict glucose control group in comparison with the standard glucose control group. The incidence of hypoglycemia (glucose levels <60 mg/dL) was significantly increased (P<0.001) in the strict glycemic control group in comparison with the standard glycemic control group (32% versus 7.4% of patients or 0.8% versus 0.1% of total serum glucose values, respectively). Strict glycemic control is a safe and effective method for reducing the incidence of nosocomial infections in a predominantly nondiabetic, general surgical ICU patient population.