Presentazione standard di PowerPoint · - Merk. Dichiara altresì il proprio impegno ad astenersi,...

Sistema Integrato Microinfusore-Monitoraggio Continuo della Glicemia ‘SAP’

Monteporzio Catone 18 maggio 2019

Angela [email protected]

DALLA MEDICINA DELLE PATOLOGIE ALLA SFIDA DELLE COMPLESSITA’: evoluzione e prospettive nella

gestione della malattia diabetica

Monte Porzio Catone, 18 maggio 2019

Il /la dr./ssa Angela Napoli dichiara di aver ricevuto negli ultimi due anni compensi o finanziamenti dalle seguenti Aziende Farmaceutiche e/o

Diagnostiche:

- Guidotti- Merk

Dichiara altresì il proprio impegno ad astenersi, nell’ambito dell’evento, dal nominare, in qualsivoglia modo o forma, aziende farmaceutiche e/o

denominazione commerciale e di non fare pubblicità di qualsiasi tipo relativamente a specifici prodotti di interesse sanitario (farmaci,

strumenti, dispositivi medico-chirurgici, ecc.).

CGM provides detailed data on the direction and rate of change of glucose levels.

Real-time systems display contemporaneous glucose readings, enabling users to respond to changes as they occur.

RCTs in motivated, non-pregnant women suggest that regular use of CGM, defined as atleast 6 days per week, improves glycaemic control

Results in pregnant women have been conflicting

Previous studies provided data only for intermittent retrospective use or for earlygeneration systems that were too inaccurate or uncomfortable for regular use.

The role of real-time CGM throughout pregnancy has not been established and no studieshave included women planning pregnancy

CONCEPTT Collaborative GroupCGM in pregnant women with type 1 diabetes (CONCEPTT): a Multicentre International RCT

Multicentre, Open-label, Randomised Controlled Trialwomen aged 18–40 years with type 1 diabetes• Pregnant (≤13 weeks and 6 days’ gestation) or • Planning Pregnancyfrom 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA.

Two trials in parallel for Pregnant Participants and for Participants Planning pregnancy.

In both trials, participants were randomly assigned to • CGM in addition to capillary glucose monitoring (INTERVENTION) • Capillary glucose monitoring alone. (CONTROL)Randomisation was stratified by• Insulin delivery (pump or injections) • Baseline Glycated Haemoglobin (HbA1c).

Feig DS,Donovan LE, CorcoyR, et al. Lancet 2017


After Enrolment,

A run-in phase with a masked CGM device before they were eligible for randomisation. (iPro2 Professional CGM, Medtronic, Northridge, CA, USA) during whichglucose values were recorded but were not visible to the user or clinical team.

Eligibility required thatparticipants wear the sensor for 6 days, provide at least 96 h of glucose values includinga minimum of 24 h overnight, and obtain at least four capillary glucose tests daily.



European 83-89%Primary OutcomeChange in HbA1c from Randomisation

to 34 weeks’ gestationin Pregnant women

to 24 weeks or Conceptionin Women planning pregnancy

in all randomised participants with baseline assessments.

Secondary OutcomesObstetric and Neonatal Health Outcomes



Clinical Characteristics Pregnancy CGM Pregnancy Control Planning CGM Planning Controln 108 107 53 57

Age 31.4±4.5 31.5±4.9 33.5±3.5 32.4±3.6

D. Duration 17 (6-28) 16 (6.6-26.4) 18 (6.2-30) 19 (9-28)

BMI 30 20 12 13 21HBA1C at randomization 6.8±0.67 6.95±0.66 7.57±0.77 7.57±0,58Smoking% 12% 21 6 11Folic A % 50 51 55 47

Insulin Pump % 46 45 74 74Hypertension 4 9 21 12

D. Complications 25 28 34 40

Severe Hypo in past year 12 7 6 12

CONCEPTT Collaborative Group at Baseline

Primary glycemic outcome: partecipants’ HbA1c levels according to pregnancy status

CGM Control Feig DS, Donovan LE, Corcoy R, et al. Lancet 2017

CONCEPTT Collaborative Group

Pregnant CGM users

More Time in Target (68% vs 61%; p=0·0034)

Less Time Hyperglycaemic(27% vs 32%; p=0·0279)

than did pregnant Controls

ComparableSevere Hypoglycaemia episodes18 CGM and 21 controlTime spent Hypoglycaemic(3% vs 4%; p=0·1)

CONCEPTT Collaborative Group. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a

multicentre international RCT.


Pregnant CGM users spent substantially higher time in target (68%) compared with previous studies, with approximately 10% or 2·4 h/day less hypoglycaemia

Of note, 19 (16%) of 119 Danish women had 59 severe hypoglycaemia episodesvs 23 (11%) of 207 Women in CONCEPPT study with 39 severe hypoglycaemia episodes.

This suggests that, over the past decade, the burden of severe hypoglycaemia has substantially reduced.

Only a minority of pregnant women(

Outcomes Pregnancy CGM Pregnancy Control pvalue

Hypertensive disorders 18% 74% ns

CS 63% 106 ns

Neonates (n) 105 36 43

Median Customized Centiles 92 96 0.0489

SGA 2% 2% ns

LGA >90° centile 53 69 0.02

Extremely Large>97° centile 36 44 ns

Macrosomia >4000g 23% 27 ns

Neonatal Hypoglycemia requiring i.v. dextrose

15 28 0.02

High Level Neonatal Care (NICU>24 hr) 27% 43 0.015

Infant Length of Hospital stay 3.1 4 0.0091Composite Neonatal Outcome 42,9 52,8 ns

Neonatal Health Outcomes: Large for Gestational Age (LGA) rates LGA: 69% vs 53%, p: 0,02OR: 0·51, 95% CI 0·28 to 0·90; p=0·0210)

according to Country

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Control CGM

Outcome in Pregnant CGM users’ Offsprings

Fewer Neonatal Intensive Care Admissions lasting more than 24 h (OR 0·48; 0·26 to 0·86; p=0·0157)Fewer incidences of Neonatal Hypoglycaemia (OR 0·45; 0·22 to 0·89; p=0·0250)1-day shorter length of hospital stay

Fig S2 Neonatal Birthweight Percentiles According To Country. The number of neonates from Ireland and the USA were too small to be included in this post hoc country specific analyses

We found no apparent benefit of CGM in women planning pregnancyThe most common adverse events were skin reactionsThe most common serious adverse events were gastrointestinal

Adverse Events Pregnancy trial Planning pregnancy trial

CGM participants 51 (48%) 12 (27%)

Control participants 43 (40%) 21 (37%)

Skin reactions CGM 48% vs C 8% CGM 44% vs C 9%

Serious Adverse Events 13 (6%) 3 (3%)

CGM participants 8 (7%) 2 (4%)

Control participants 5 (5%) 1 (2%)

Gastrointestinal(nausea vomiting)

n= 4 n= 3

Adverse and Serious Adverse Events in the CONCEPTT Study

The CONCEPTT study showed that an antenatal CGM system as an adjunct to capillary monitoring, is associated with a lower incidence of LGA, fewer neonatal intensive care unit admissions (>24 h), and a decreased incidence of neonatal hypoglycemia in pregnancy of women with type1 diabetes

We need additional studies to see if new technologies such as insulin delivery systems with insulin suspend facility, provide better outcomes than MDI/Old technologies (CSII).the usefulness of CGMS among pregnant women with GDM and type 2 diabetes.

The ’AACE/ACE’ consensus statement declares that CGM in pregnancy can supplement BGM, in particular for monitoring nocturnal hypoglycemia or hyperglycemia and postprandial hyperglycemia’.

Feig D. (2017). Murphy H. ( 2018). P.Raman Cochrane Systematic Review ( 2017), Moy FM, Cochrane Database Syst Rev (2017) Mulla B( 2018)AACE/ACE ( 2016) SID-AMD2018

Insulin Pump during Delivery: CSII vs SAP

PROFILE A PROFILE B PROFILE CBasal Rate in Use 50% of Actual Basal Rate 0,1-0,2 U/h (CBG < 70mg/dl)

CBG70-120/140mg/dl

3.8-6,6/7.7mMol/L

Profile A: Last few days before delivery basal insulin infusion basal rate.Profile B: 50% Profile AProfile C: Minimal Insulin Infusion Basal Rate: 0.1-0,2IU/h. Profile C is not recommended in type1 diabetic women under SAP with ‘the preventive insulin suspension function’ activated

WITHIN THE END OF GESTATIONWomen were educated to set up the pump with 3 different insulin basal rates, activating the single most appropriate one, according to the current CBG values.

An Alternative standardized Intravenous Protocol (IVP) must be available in case relevant metabolic deterioration

Experiences of Continuous Subcutaneous Insulin Infusion in Pregnant Women with Type 1 Diabetes During Delivery from Four Italian Centers: A Retrospective Observational Study. Raffaella Fresa, … and Angela Napoli DIABETES TECHNOLOGY & THERAPEUTICS 15(4) 2013

Throughout THE FIRST PHASE OF THE PROCEDURE, when there are Minimal Changes in Maternal Metabolic Demand if CBG VALUES are at TARGET

⇒ PROFILE A

From the BEGINNING OF ACTIVE LABOR or

IMMEDIATELY BEFORE ANESTHESIA (for 60’)⇒ PROFILE B or C

I.Requirement quickly decreases because of Increased Energy Expenditure for Cervical Dilation + Rapid Changes in Maternal Hormone Concentrations that soon occur after the extraction of the fetus.

PROFILE A PROFILE B PROFILE CBasal Rate in Use 50% of Actual Basal Rate 0,1-0,2 U/h (CBG < 70mg/dl)

Experiences of Continuous Subcutaneous Insulin Infusion in Pregnant Women with Type 1 Diabetes During Delivery from Four Italian Centers: A Retrospective Observational Study. Raffaella Fresa, … and Angela Napoli DIABETES TECHNOLOGY & THERAPEUTICS 15(4) 2013

C.B.G. & Basal Rate in Peri-Partum period with CSII ± SAP

1.3 U/hT0’

0.6 U/hT60’

0.5 U/h24h

AdmissionPROFILE A Delivery

PROFILE B86% of women Delivery

PROFILe Cin 2/5 Spontaneous Labor & 4/4 Induction Labor

Food x OSPROFILE B

Prepartum Delivery 24hr afterSAP 90 85 122 mg/dlCSII 114 127 122 mg/dl

Average InsulinInfusion Rate (U/h)

C.B.Glucose (mg/dl)

Basale Rate: 54% HALF of previous one

Experiences of Continuous Subcutaneous Insulin Infusion in Pregnant Women with Type 1 Diabetes During Delivery from Four Italian Centers: A Retrospective Observational Study. R. Fresa, DIABETES TECHNOLOGY & THERAPEUTICS 15(4) 2013

Day beforethe

SpontaneousDelivery

Delivery Day

New approach to adjust insulin doses using trend arrows in adults with diabetesApproach to adjusting insulin dose using trend arrow data (Dexcom G5).

Pre-meal and Correction ≥4 Post.mealThe approach is based on anticipated glucose change

and typical insulin sensitivity ranges in adults.

A Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System for the Management of Adults With Diabetes. Grazia Aleppo et al

Grazie

Angela [email protected]

Danne T, Nimri R, Battelino T, et al. International consensus on use of continuous glucose monitoring. Diabetes Care 2017;40:1631–1640

Suggested CGM Metrics for Pregnancy according to Recent International Consensus StatementCGM accuracy (MARD)= mean absolute relative difference between CGM & SMBG values.

% Time in range [TiR]

Cord C-Peptide>566 pmol/L based on >90percentile in the HAPO StudyCord C-Peptide>2725 pmol/L based on >90percentile in the CONCEPTT Study

Tab S17 CGM Problems and Skin Reactions CONCEPTT study

Problems encountered with CGM use were commonplace, with more than 80% of women reporting frustrationsof CGM use, such as connectivity issues, alarms, and calibration errors, and almost 50% experiencing skinreactions, such as bleeding, erythema, and discomfort.

The increased contacts for sensor-related diabetes management issues might also reflect the heightened anxiety of pregnant women seeing the 288 daily glucose values in real time, and the initial support required to incorporate CGM data into their diabetes routines.

The increased rate of change of glucose concentrations most likely reflects CGM users’ actions taken in responseto out-of-range glucose levels.

Post-hoc analysis showed that adjusting for additional contacts did not affect treatment effect and was unrelatedto changes in HbA1c.

Furthermore, contact for non-sensor related issues did not differ between groups.

However, exposure to hyperglycaemia— the so-called prandial problem—persists.

Post-prandial hyperglycaemia was also evident in our recent closedloop study in pregnant women with type 1 diabetes,32 which achieved comparable time in target to the CGM users in the present study. These results indicate that additional strategies might be required to minimise postprandial excursions, such as faster acting insulins or adjunctive therapies.

Automated insulin delivery options might also give women more confidence to administer larger pre-meal boluses, especially for the evening meal, with less fear of nocturnal hypoglycaemia.

Notably, although women in the CGM group showed a greater decrease in hypoglycaemia avoidancebehaviour than did women in the control group, they did not have less worry, suggesting that automatedinsulin delivery might be more effective for reduction in maternal fear of hypoglycaemia.

Insulin Pump during Delivery

Optimal Glycemic Targets during Delivery: 70 to 90-120 mg/dl, acceptable up to 140mg/dL3.8-6,6 acceptable up to 7.7mMol/L

Achieving such tight glycaemic control requires close monitoring and care as it can be challenging given the extremely rapid decrease in insulin requirement due to

• Dramatic hormonal changes in maternal hormone concentrations that occursoon after the extraction of the fetus and placenta expulsion

• Increased energy expenditure because of cervical dilatation in case of vaginaldeliveries, or of surgery procedure in case of cesarean section.

Consequently, from the beginning of Active labor or immediately beforeanesthesia, the insulin requirement halves at least or reaches almost zero, compared with the prepartum dosage.

Lepercq J et al: A standardized protocol to achieve normoglycaemia during labour and delivery in women with type 1 diabetes. Diabet Metab 2008. Stenninger Eet al : Continuous subcutaneous glucose monitoring system in diabetic mothers during labour and postnatal glucose adaptation of their infants. Diabet Med

2008 Rosenberg VA, et al : Intrapartum maternal glycemic control in women with insulin

requiring diabetes: a randomized clinical trial of rotating fluids versus insulin drip. Am J Obstet Gynecol 2006

Neonatal HypoGlycemia

Mothers BGL NeonatalHypo Yes

NeonatalHypo No

OR

TIME IN TARGET4-7mmoL/moL (70-140mg/dL)

55±37% 65±35% * 0.992 *

7–10 mmol/L (140-180mg/dL) 31 ± 34% 18 ± 27% * 1.013 *

Diabet. Med. 34, 725–731 (2017)

ConclusionsThese data support a BGL range of 4–7 mmol/l as an intrapartum target.

Glycaemic control in the 2 trimester is associated with Neonatal Hypoglycaemia.

Improvement in Ante- and Intrapartum glycaemic control may reduce neonatalhypoglycaemia in women with pre-existing diabetes.

122 in 261 births cases (47%) of neonatal hypoglycaemia (glucose≤ 2.6 mmol/l) (45mg/dL)

New technologies, are widely used by women with type1 diabetesduring preconception care and subsequent pregnanciesA safe and effective Peripartum Metabolic Management with CSII in Women with Type1 diabetes needs• Standardised protocol• Education program• Team with expertise

conclusioniPeripartum Metabolic Management with CSII in Women with Type1 diabetes

Profile A: usual basal (days before delivery)Profile B: 50% Profile AProfile C: Minimal Infusion Rate : 0.1-0,2IU/h. Profile C non recommended in SAP if the preventive suspension is active (CSII-Sensor)

Experiences of Continuous Subcutaneous Insulin Infusion in Pregnant Women with Type 1 Diabetes During Delivery from Four Italian Centers: A Retrospective Observational Study. R. Fresa, DIABETES TECHNOLOGY & THERAPEUTICS 15(4) 2013

⇒ PROFILE A At HOSPITAL ADMISSION if ‘CBG VALUES’ at TARGET (70-140mg/dl)

⇒ PROFILe B or C From the BEGINNING OF ACTIVE PHASE OF LABOR

SOON BEFORE ANESTHESIA in case of CS (60’)

PROFILO A PROFILO B PROFILO CBasal Rate in Uso 50% del Basal Rate in Uso 0,1-0,2 U/h (CBG < 70mg/dl)

CBG70-120/140mg/dl

3.8-6,6/7.7mMol/L

Cesarean Section Spontaneous Labor Induced Labor

Number of Patients 56 5 4At Admission

IBR (U/h) 1.4 ± 0.4 1.3 ± 0.4 1.1 ± 0.3

CBG (mg/dL) 96 ± 24 98 ± 12 92 ± 18Anesthesia or Second Stage of Labor

0 min

IBR (U/h) 1.4 ± 0.4 1.3 ± 0.4 1.1 ± 0.3

CBG (mg/dL) 106 ± 33 77 ± 8 89 ± 1930 min

IBR (U/h) 0.6 ± 0.4 0.6 ± 0.3 0.55 ± 0.1

CBG (mg/dL) 109 ± 42 94 ± 17 88 ± 460 min

IBR (U/h) 0.6 ± 0.4 0.4 ± 0.3 0.15 ± 0.1

CBG (mg/dL) 123 ± 49 101 ± 33 86 ± 9

Table 3. C.B.G. values & I.B.R. in Different Modalities & Stages of DeliveryNo Differences in Different Delivery Modalities

Basale halved:-54%

1.3U/h⇒0.6 U/h

SAP

Profile BDelivery

CS9-10 a.m

CBG value IBR

24 h after delivery 99 ± 34 mg/dL 0.6 ± 0.4 U/h (-57%)(5.5 mmol/L)

36 h 107 ± 36 mg/dL 0.5 ± 0.3 U/h (-64%) (5.9 mmol/L)

Oral Feeding occurred after 51±18 h

Stable Postpartum BG Profiles in Women who underwent to CS

R.Fresa et al, DTT 2013

http://www.google.it/url?sa=i&rct=j&q=italy+pictures&source=images&cd=&cad=rja&docid=ZRJJQJStftnHJM&tbnid=_RBFB9rSN_1UOM:&ved=0CAUQjRw&url=http://knowledgetoday.wharton.upenn.edu/2011/11/italy-and-the-global-economy-an-end-to-la-dolce-vita/&ei=lswfUfuqFY3Bswa4jYDYDw&bvm=bv.42553238,d.Yms&psig=AFQjCNH-0creit3akLRGL7_rse3z3zNpSA&ust=1361124783634619http://www.google.it/url?sa=i&rct=j&q=italy+pictures&source=images&cd=&cad=rja&docid=ZRJJQJStftnHJM&tbnid=_RBFB9rSN_1UOM:&ved=0CAUQjRw&url=http://knowledgetoday.wharton.upenn.edu/2011/11/italy-and-the-global-economy-an-end-to-la-dolce-vita/&ei=lswfUfuqFY3Bswa4jYDYDw&bvm=bv.42553238,d.Yms&psig=AFQjCNH-0creit3akLRGL7_rse3z3zNpSA&ust=1361124783634619

V.M.Age 27 yrs oldtype 1D from the age of 24 yrs(2010)1° pregnancyLast period 06/09/2016

Vaginal Delivery05 /06/2017 Induction by Prostaglandinesat 10 a.m.

06/06/2017 Active phasearound 2 a.m.

Delivery at 7.26 a.m.Gestational week:

E.Drever et al. Insulin Pump use compared with intravenous insulin during labour and delivery. The INSPIRED observational cohort Diabetic medicine , 2016

R. Fresa .. and A. Napoli Experiences Of Continuous Subcutaneous Insulin Infusion In Pregnant Women With Type 1 Diabetes During Delivery From Four Italian Centers: A Retrospective Observational Study. Diabetes Technology & Therapeutics 15(4) 2013

Conclusion

Continuation of CSII or SAP therapy during Labour & Delivery is Safe & Efficacious.

Women who continue CSII have better glucose control during delivery than those who switch to IV Insulin

CSII should be standard practice to allow women the option of continuing CSII during Labour & Delivery

N Engl J Med 375;7 nejm.org August 18, 2016

• An open-label, randomized, crossover study comparing overnight closed-loop therapy with sensor-augmented pump therapy, followed by a continuation phase in which the closed-loop system was used day and night.

• 16 type 1 diabetic pregnant women. 14 using the closed-loop system until delivery• The primary outcome was the percentage of time that overnight glucose levels were

within the target range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]).

NEJM, 2016

CGM prima, durante e dopo il parto con Closed-loop

- 24h Before Delivery: Median Glucose values 110 mg/dl

86.8% in the target range

- 48h After Delivery: Median Glucose values 117 mg/dl

73.7% in the target range

- Cesarean Section (all) at 36.9 gestational week

Zoe A et al, Closed-loop insulin delivery during pregnancy in women with type1 diabetes. N Engl J Med 375;7 nejm.org 2016

Adapted from Zoe et al

E.Drever et al. Insulin Pump use compared with intravenous insulin during labour and delivery. The INSPIRED observational cohort Diabetic medicine , 2016

R. Fresa .. And A. Napoli Experiences Of Continuous Subcutaneous Insulin Infusion In Pregnant Women With Type 1 Diabetes During Delivery From Four ItalianCenters: A Retrospective Observational Study. Diabetes Technology & Therapeutics 15(4) 2013

Conclusion

Continuation of CSII or SAP therapy during Labour & Delivery is Safe & Efficacious.

Women who choose to continue CSII have better glucose control during delivery than those who switch to IV Insulin

CSII should be standard practice to allow women the option of continuing CSII during Labour & Delivery

65 type1D Pregnant Women: 51 MDI, 14 CSII, Excellent Pregestational Metabolic Control (HbA1C≤6%),

9 week

37 week

16 week

Glucose & Sustrates Loss forGluconeogenesis

⇑ Fetal Glucose NeedType1D Women with excellentpregestationl diabetes(HbA1C≤6%) IR Peak at 9 g.w. Nadir at 16 gwsecond peak at 37 gw

Two changes of direction facilitate hypoglycemia occurrence particularly in early pregnancy before g.w16

0,7 U/kg at the 1st, 0,8 U/kg at the 2° and 0,9 U/kg at the 3rd trimester(García-Patterson A, 2010).

Saturday 23 February, 2019h 02.09 SpontaneousDelivery

50% basal from the Active PhaseBG 84-106mg/dl

1 st pregnancyFridayh14.00 prostaglandines

A Colatrella and Napoli Continuous Glucose Monitoring System (CGMS) in normotolerant women with and without previous gestational diabetes mellitus (GDM) during breast-feeding.

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CGM in Two normotolerant breastfeeding women with and without previous gestational diabetes mellitus

Grafico Dall'Osso

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0.3263888889

0.3298611111

0.3333333333

0.3368055556

0.3402777778

0.34375

0.3472222222

0.3506944444

0.3541666667

0.3576388889

0.3611111111

0.3645833333

0.3680555556

0.3715277778

0.375

0.3784722222

0.3819444444

0.3854166667

0.3888888889

0.3923611111

0.3958333333

0.3993055556

0.4027777778

0.40625

0.4097222222

0.4131944444

0.4166666667

0.4201388889

0.4236111111

0.4270833333

0.4305555556

0.4340277778

0.4375

0.4409722222

0.4444444444

0.4479166667

0.4513888889

0.4548611111

0.4583333333

0.4618055556

0.4652777778

0.46875

0.4722222222

0.4756944444

0.4791666667

0.4826388889

0.4861111111

0.4895833333

0.4930555556

0.4965277778

0.5

0.5034722222

0.5069444444

0.5104166667

0.5138888889

0.5173611111

0.5208333333

0.5243055556

0.5277777778

0.53125

0.5347222222

0.5381944444

0.5416666667

0.5451388889

0.5486111111

0.5520833333

0.5555555556

0.5590277778

0.5625

0.5659722222

0.5694444444

0.5729166667

0.5763888889

0.5798611111

0.5833333333

0.5868055556

0.5902777778

0.59375

0.5972222222

0.6006944444

0.6041666667

0.6076388889

0.6111111111

0.6145833333

0.6180555556

0.6215277778

0.625

0.6284722222

0.6319444444

0.6354166667

0.6388888889

0.6423611111

0.6458333333

0.6493055556

0.6527777778

0.65625

0.6597222222

0.6631944444

0.6666666667

0.6701388889

0.6736111111

0.6770833333

0.6805555556

0.6840277778

0.6875

0.6909722222

0.6944444444

0.6979166667

0.7013888889

0.7048611111

0.7083333333

0.7118055556

0.7152777778

0.71875

0.7222222222

0.7256944444

0.7291666667

0.7326388889

0.7361111111

0.7395833333

0.7430555556

0.7465277778

0.75

0.7534722222

0.7569444444

0.7604166667

0.7638888889

0.7673611111

0.7708333333

0.7743055556

0.7777777778

0.78125

0.7847222222

0.7881944444

0.7916666667

0.7951388889

0.7986111111

0.8020833333

0.8055555556

0.8090277778

0.8125

0.8159722222

0.8194444444

0.8229166667

0.8263888889

0.8298611111

0.8333333333

0.8368055556

0.8402777778

0.84375

0.8472222222

0.8506944444

0.8541666667

0.8576388889

0.8611111111

0.8645833333

0.8680555556

0.8715277778

0.875

0.8784722222

0.8819444444

0.8854166667

0.8888888889

0.8923611111

0.8958333333

0.8993055556

0.9027777778

0.90625

0.9097222222

0.9131944444

0.9166666667

0.9201388889

0.9236111111

0.9270833333

0.9305555556

0.9340277778

0.9375

0.9409722222

0.9444444444

0.9479166667

0.9513888889

0.9548611111

0.9583333333

0.9618055556

0.9652777778

0.96875

0.9722222222

0.9756944444

0.9791666667

0.9826388889

0.9861111111

0.9895833333

0.9930555556

0.9965277778

0

0.0034722222

0.0069444444

0.0104166667

0.0138888889

0.0173611111

0.0208333333

0.0243055556

0.0277777778

0.03125

0.0347222222

0.0381944444

0.0416666667

0.0451388889

0.0486111111

0.0520833333

0.0555555556

0.0590277778

0.0625

0.0659722222

0.0694444444

0.0729166667

0.0763888889

0.0798611111

0.0833333333

0.0868055556

0.0902777778

0.09375

0.0972222222

0.1006944444

0.1041666667

0.1076388889

0.1111111111

0.1145833333

0.1180555556

0.1215277778

0.125

0.1284722222

0.1319444444

0.1354166667

0.1388888889

0.1423611111

0.1458333333

0.1493055556

0.1527777778

0.15625

0.1597222222

0.1631944444

0.1666666667

0.1701388889

0.1736111111

0.1770833333

0.1805555556

0.1840277778

0.1875

0.1909722222

0.1944444444

0.1979166667

0.2013888889

0.2048611111

0.2083333333

0.2118055556

0.2152777778

0.21875

0.2222222222

0.2256944444

0.2291666667

0.2326388889

0.2361111111

0.2395833333

0.2430555556

0.2465277778

0.25

0.2534722222

0.2569444444

0.2604166667

0.2638888889

0.2673611111

0.2708333333

0.2743055556

0.2777777778

0.28125

0.2847222222

0.2881944444

0.2916666667

0.2951388889

0.2986111111

0.3020833333

0.3055555556

0.3090277778

0.3125

0.3159722222

0.3194444444

0.3229166667

0.3263888889

0.3298611111

0.3333333333

0.3368055556

0.3402777778

0.34375

0.3472222222

0.3506944444

0.3541666667

0.3576388889

0.3611111111

0.3645833333

0.3680555556

0.3715277778

0.375

0.3784722222

0.3819444444

0.3854166667

0.3888888889

0.3923611111

0.3958333333

0.3993055556

0.4027777778

0.40625

0.4097222222

0.4131944444

0.4166666667

0.4201388889

0.4236111111

0.4270833333

0.4305555556

0.4340277778

0.4375

0.4409722222

0.4444444444

0.4479166667

0.4513888889

0.4548611111

0.4583333333

0.4618055556

0.4652777778

0.46875

0.4722222222

0.4756944444

0.4791666667

0.4826388889

0.4861111111

0.4895833333

0.4930555556

0.4965277778

0.5

0.5034722222

0.5069444444

0.5104166667

0.5138888889

0.5173611111

0.5208333333

0.5243055556

0.5277777778

0.53125

0.5347222222

0.5381944444

0.5416666667

0.5451388889

0.5486111111

0.5520833333

0.5555555556

0.5590277778

0.5625

0.5659722222

0.5694444444

0.5729166667

0.5763888889

0.5798611111

0.5833333333

0.5868055556

0.5902777778

0.59375

0.5972222222

0.6006944444

0.6041666667

0.6076388889

0.6111111111

0.6145833333

0.6180555556

0.6215277778

0.625

0.6284722222

0.6319444444

0.6354166667

0.6388888889

0.6423611111

0.6458333333

0.6493055556

0.6527777778

0.65625

0.6597222222

0.6631944444

0.6666666667

0.6701388889

0.6736111111

0.6770833333

0.6805555556

0.6840277778

0.6875

0.6909722222

0.6944444444

0.6979166667

0.7013888889

0.7048611111

0.7083333333

0.7118055556

0.7152777778

0.71875

0.7222222222

0.7256944444

0.7291666667

0.7326388889

0.7361111111

0.7395833333

0.7430555556

0.7465277778

0.75

0.7534722222

0.7569444444

0.7604166667

0.7638888889

0.7673611111

0.7708333333

0.7743055556

0.7777777778

0.78125

0.7847222222

0.7881944444

0.7916666667

0.7951388889

0.7986111111

0.8020833333

0.8055555556

0.8090277778

0.8125

0.8159722222

0.8194444444

0.8229166667

0.8263888889

0.8298611111

0.8333333333

0.8368055556

0.8402777778

0.84375

0.8472222222

0.8506944444

0.8541666667

0.8576388889

0.8611111111

0.8645833333

0.8680555556

0.8715277778

0.875

0.8784722222

0.8819444444

0.8854166667

0.8888888889

0.8923611111

0.8958333333

0.8993055556

0.9027777778

0.90625

0.9097222222

0.9131944444

0.9166666667

0.9201388889

0.9236111111

0.9270833333

0.9305555556

0.9340277778

0.9375

0.9409722222

0.9444444444

0.9479166667

0.9513888889

0.9548611111

0.9583333333

0.9618055556

0.9652777778

0.96875

0.9722222222

0.9756944444

0.9791666667

0.9826388889

0.9861111111

0.9895833333

0.9930555556

0.9965277778

0

0.0034722222

0.0069444444

0.0104166667

0.0138888889

0.0173611111

0.0208333333

0.0243055556

0.0277777778

0.03125

0.0347222222

0.0381944444

0.0416666667

0.0451388889

0.0486111111

0.0520833333

0.0555555556

0.0590277778

0.0625

0.0659722222

0.0694444444

0.0729166667

0.0763888889

0.0798611111

0.0833333333

0.0868055556

0.0902777778

0.09375

0.0972222222

0.1006944444

0.1041666667

0.1076388889

0.1111111111

0.1145833333

0.1180555556

0.1215277778

0.125

0.1284722222

0.1319444444

0.1354166667

0.1388888889

0.1423611111

0.1458333333

0.1493055556

0.1527777778

0.15625

0.1597222222

0.1631944444

0.1666666667

0.1701388889

0.1736111111

0.1770833333

0.1805555556

0.1840277778

0.1875

0.1909722222

0.1944444444

0.1979166667

0.2013888889

0.2048611111

0.2083333333

0.2118055556

0.2152777778

0.21875

0.2222222222

0.2256944444

0.2291666667

0.2326388889

0.2361111111

0.2395833333

0.2430555556

0.2465277778

0.25

0.2534722222

0.2569444444

0.2604166667

0.2638888889

0.2673611111

0.2708333333

0.2743055556

0.2777777778

0.28125

0.2847222222

0.2881944444

0.2916666667

0.2951388889

0.2986111111

0.3020833333

0.3055555556

0.3090277778

0.3125

0.3159722222

0.3194444444

0.3229166667

0.3263888889

0.3298611111

0.3333333333

0.3368055556

0.3402777778

0.34375

0.3472222222

0.3506944444

0.3541666667

0.3576388889

0.3611111111

0.3645833333

0.3680555556

0.3715277778

0.375

0.3784722222

0.3819444444

0.3854166667

0.3888888889

0.3923611111

0.3958333333

0.3993055556

0.4027777778

0.40625

0.4097222222

0.4131944444

0.4166666667

0.4201388889

0.4236111111

0.4270833333

0.4305555556

0.4340277778

0.4375

0.4409722222

0.4444444444

0.4479166667

0.4513888889

0.4548611111

0.4583333333

0.4618055556

0.4652777778

0.46875

0.4722222222

0.4756944444

0.4791666667

0.4826388889

0.4861111111

0.4895833333

0.4930555556

0.4965277778

0.5

0.5034722222

0.5069444444

0.5104166667

0.5138888889

0.5173611111

0.5208333333

0.5243055556

0.5277777778

0.53125

0.5347222222

0.5381944444

0.5416666667

0.5451388889

0.5486111111

0.5520833333

0.5555555556

0.5590277778

0.5625

0.5659722222

0.5694444444

0.5729166667

0.5763888889

0.5798611111

0.5833333333

0.5868055556

0.5902777778

0.59375

0.5972222222

0.6006944444

0.6041666667

0.6076388889

0.6111111111

0.6145833333

0.6180555556

0.6215277778

0.625

0.6284722222

0.6319444444

0.6354166667

0.6388888889

0.6423611111

0.6458333333

0.6493055556

0.6527777778

0.65625

0.6597222222

0.6631944444

0.6666666667

0.6701388889

0.6736111111

0.6770833333

0.6805555556

0.6840277778

0.6875

0.6909722222

0.6944444444

0.6979166667

0.7013888889

0.7048611111

0.7083333333

0.7118055556

0.7152777778

0.71875

0.7222222222

0.7256944444

0.7291666667

0.7326388889

0.7361111111

0.7395833333

0.7430555556

0.7465277778

0.75

0.7534722222

0.7569444444

0.7604166667

0.7638888889

0.7673611111

0.7708333333

0.7743055556

0.7777777778

0.78125

0.7847222222

0.7881944444

0.7916666667

0.7951388889

0.7986111111

0.8020833333

0.8055555556

0.8090277778

0.8125

0.8159722222

0.8194444444

0.8229166667

0.8263888889

0.8298611111

0.8333333333

0.8368055556

0.8402777778

0.84375

0.8472222222

0.8506944444

0.8541666667

0.8576388889

0.8611111111

0.8645833333

0.8680555556

0.8715277778

0.875

0.8784722222

0.8819444444

0.8854166667

0.8888888889

0.8923611111

0.8958333333

0.8993055556

0.9027777778

0.90625

0.9097222222

0.9131944444

0.9166666667

0.9201388889

0.9236111111

0.9270833333

0.9305555556

0.9340277778

0.9375

0.9409722222

0.9444444444

0.9479166667

0.9513888889

0.9548611111

0.9583333333

0.9618055556

0.9652777778

0.96875

0.9722222222

0.9756944444

0.9791666667

0.9826388889

0.9861111111

0.9895833333

0.9930555556

0.9965277778

0

0.0034722222

0.0069444444

0.0104166667

0.0138888889

0.0173611111

0.0208333333

0.0243055556

0.0277777778

0.03125

0.0347222222

0.0381944444

0.0416666667

0.0451388889

0.0486111111

0.0520833333

0.0555555556

0.0590277778

0.0625

0.0659722222

0.0694444444

0.0729166667

0.0763888889

0.0798611111

0.0833333333

0.0868055556

0.0902777778

0.09375

0.0972222222

0.1006944444

0.1041666667

0.1076388889

0.1111111111

0.1145833333

0.1180555556

0.1215277778

0.125

0.1284722222

0.1319444444

0.1354166667

0.1388888889

0.1423611111

0.1458333333

0.1493055556

0.1527777778

0.15625

0.1597222222

0.1631944444

0.1666666667

0.1701388889

0.1736111111

0.1770833333

0.1805555556

0.1840277778

0.1875

0.1909722222

0.1944444444

0.1979166667

0.2013888889

0.2048611111

0.2083333333

0.2118055556

0.2152777778

0.21875

0.2222222222

0.2256944444

0.2291666667

0.2326388889

0.2361111111

0.2395833333

0.2430555556

0.2465277778

0.25

0.2534722222

0.2569444444

0.2604166667

0.2638888889

0.2673611111

0.2708333333

0.2743055556

0.2777777778

0.28125

0.2847222222

0.2881944444

0.2916666667

0.2951388889

0.2986111111

0.3020833333

0.3055555556

0.3090277778

0.3125

0.3159722222

0.3194444444

0.3229166667

0.3263888889

0.3298611111

0.3333333333

0.3368055556

0.3402777778

0.34375

0.3472222222

0.3506944444

0.3541666667

0.3576388889

0.3611111111

0.3645833333

0.3680555556

0.3715277778

0.375

0.3784722222

0.3819444444

0.3854166667

0.3888888889

0.3923611111

0.3958333333

0.3993055556

0.4027777778

0.40625

0.4097222222

0.4131944444

0.4166666667

Sensor Glucose

hh/mm

mg/dL

146

146

142

143

142

140

137

137

134

129

123

123

123

122

120

113

118

119

121

120

121

116

106

101

106

120

124

110

115

115

117

110

114

117

115

120

119

112

113

113

117

108

116

122

122

118

125

127

125

122

123

128

132

133

132

139

152

157

158

158

140

140

136

141

141

128

129

132

130

131

131

131

148

167

183

193

197

200

196

196

187

177

175

159

144

133

125

117

109

101

95

91

88

84

83

90

87

83

79

77

76

73

69

67

78

88

95

108

110

112

113

115

116

117

118

118

117

114

114

112

112

115

127

141

138

134

129

127

126

125

124

123

123

122

122

123

123

124

114

112

111

110

111

122

125

125

120

121

120

119

118

118

117

115

118

115

117

116

113

120

121

127

143

161

169

179

178

177

175

167

155

147

148

136

127

116

111

104

111

115

107

106

116

110

112

114

121

120

117

111

112

111

105

111

128

139

140

124

118

114

113

131

135

129

124

129

128

126

125

123

121

125

127

132

130

129

134

135

133

133

131

130

133

134

137

138

136

137

139

138

139

136

134

136

134

133

137

149

161

177

187

194

197

201

202

201

209

214

206

189

178

163

151

143

145

148

141

131

126

121

116

120

119

118

126

129

134

142

138

135

130

125

121

119

118

120

122

128

129

135

132

131

134

132

134

134

134

132

132

129

130

129

132

131

128

127

130

128

122

121

119

116

110

119

117

121

124

121

117

129

127

119

129

133

132

130

131

128

124

119

117

120

120

124

120

119

119

115

114

118

118

120

125

127

119

106

103

97

99

111

114

118

127

137

137

137

155

155

151

146

144

141

136

131

126

123

121

119

119

117

116

115

115

115

115

118

116

109

116

113

113

116

119

122

122

121

120

121

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145

137

129

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109

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107

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100

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115

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109

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84

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78

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76

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93

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98

91

88

84

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89

100

107

112

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93

84

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78

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122

146

170

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177

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160

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192

178

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145

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Dall'Osso Cl.

First NameLast NamePatient IDMonitor IDSample #DayDateTimeISIGVCTRMeter BGPaired Meter BGSlopeOffsetValid ISIGTimeSensor GlucoseGlucose UnitsPower UpMedie hDSLink EventDisconnectRange ErrorMemory FullCal ErrorNoise FlagInsulinMealExerciseOtherMonitor SW VersionMonitor DownloadPC Download SW

Dall OssoClara1711970550-00000gio9-Nov-0615:3540.6-0.4815:35mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A


Dall OssoClara1711970550-00002gio9-Nov-0615:45289.8-1.2415:45mg/dL126.615.6


Dall OssoClara1711970550-00004gio9-Nov-0615:5528-0.5415:55mg/dL115.21.4





Dall OssoClara1711970550-00009gio9-Nov-0616:2023.9-0.5816:20mg/dL86.217.7totale1°2°3°4°

Dall OssoClara1711970550-000010gio9-Nov-0616:2523-0.5916:25mg/dL95.330.4124.0133.8126.3113.9130.5

Dall OssoClara1711970550-000011gio9-Nov-0616:3023-0.616:30mg/dL120.314.824.523.122.220.928.0

Dall OssoClara1711970550-000012gio9-Nov-0616:3522.8-0.67.6932216:35146mg/dL125.17.8

Dall OssoClara1711970550-000013gio9-Nov-0616:4022.2-0.617.6932216:40146mg/dL117.92.8dienottedienottedienottedie

Dall OssoClara1711970550-000014gio9-Nov-0616:4522-0.611171177.69321.516:45142mg/dL117.31.4129.8122.8130.7119.7108.0133.3131.6

Dall OssoClara1711970550-000015gio9-Nov-0616:5022-0.627.71321.616:50143mg/dL160.514.818.329.220.47.219.824.431.7

Dall OssoClara1711970550-000016gio9-Nov-0616:5521.5-0.627.73321.416:55142mg/dL114.317.0

Dall OssoClara1711970550-000017gio9-Nov-0617:0021.6-0.627.74321.117:00140mg/dL119.118.4tot dietot notte

Dall OssoClara1711970550-000018gio9-Nov-0617:0521.4-0.627.76320.717:05137mg/dL124.70.7122.9125.3

Dall OssoClara1711970550-000019gio9-Nov-0617:1021.1-0.627.77320.617:10137mg/dL129.45.725.223.0


Dall OssoClara1711970550-000021gio9-Nov-0617:2020.6-0.637.79319.517:20129mg/dL167.346.7TOT

Dall OssoClara1711970550-000022gio9-Nov-0617:2520.2-0.637.8318.817:25123mg/dL174.042.4METER151.0135.5107.3112.0126.8

Dall OssoClara1711970550-000023gio9-Nov-0617:3019.5-0.637.81318.817:30123mg/dL126.74.9METER DS51.333.69.421.233.4



Dall OssoClara1711970550-000026gio9-Nov-0617:4518.8-0.637.84318.317:45120mg/dL122.39.9Medie orarie0-11.22.33.44.55.66.77.88.99.110.1111.12

Dall OssoClara1711970550-000027gio9-Nov-0617:5018.6-0.647.85317.417:50113mg/dL126.17.11 g

Dall OssoClara1711970550-000028gio9-Nov-0617:5518.3-0.647.8631817:55118mg/dL119.92 g86.295.3120.3125.1117.9117.3160.5114.3119.1124.7129.4135.9

Dall OssoClara1711970550-000029gio9-Nov-0618:0017.4-0.647.88318.118:00119mg/dL113.13 g

Dall OssoClara1711970550-000030gio9-Nov-0618:0518-0.647.89318.318:05121mg/dL140.34 g

Dall OssoClara1711970550-000031gio9-Nov-0618:1018.1-0.647.9318.218:10120mg/dL119.3


Dall OssoClara1711970550-000033gio9-Nov-0618:2018.2-0.647.92317.718:20116mg/dL130.912.1313.1414.1515.1616.1717.1818.1919.2020.2121.2222.2323.24

Dall OssoClara1711970550-000034gio9-Nov-0618:2518.3-0.657.94316.418:25106mg/dL125.31 g143.8126.6114.9115.2122.3143.9150.0159.8

Dall OssoClara1711970550-000035gio9-Nov-0618:3017.7-0.657.95315.718:30101mg/dL117.02 g167.3174.0126.7126.20.00.00.00.00.00.00.0

Dall OssoClara1711970550-000036gio9-Nov-0618:3516.4-0.647.96316.318:35106mg/dL112.33 g

Dall OssoClara1711970550-000037gio9-Nov-0618:4015.7-0.637.9731818:40120mg/dL116.34 g


Dall OssoClara1711970550-000039gio9-Nov-0618:5018-0.658316.818:50110mg/dL120.4

Dall OssoClara1711970550-000040gio9-Nov-0618:5518.5-0.668317.418:55115mg/dL118.5







Dall OssoClara1711970550-000047gio9-Nov-0619:3017.6-0.66831819:30120mg/dL115.8


Dall OssoClara1711970550-000049gio9-Nov-0619:4018-0.66831719:40112mg/dL106.1


Dall OssoClara1711970550-000051gio9-Nov-0619:5017-0.668317.119:50113mg/dL82.2

Dall OssoClara1711970550-000052gio9-Nov-0619:5517.1-0.668317.619:55117mg/dL93.91.0A/1.1A13-Nov-06MMT-7310 3.0A





Dall OssoClara1711970550-000057gio9-Nov-0620:2018.2-0.668317.820:20118mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A







Dall OssoClara1711970550-000064gio9-Nov-0620:5518.4-0.688.01319.520:55132mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A

Dall OssoClara1711970550-000065gio9-Nov-0621:0019-0.698.01319.621:00133mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A




































Dall OssoClara1711970550-0000101ven10-Nov-060:0017.6-0.78.04315.60:00101mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A






Dall OssoClara1711970550-0000107ven10-Nov-060:3013.4-0.77.973140:3090mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A


Dall OssoClara1711970550-0000109ven10-Nov-060:4014-0.77.93130:4083mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A


Dall OssoClara1711970550-0000111ven10-Nov-060:5013-0.77.83212.10:5077mg/dL1.0A/1.1A13-Nov-06MMT-7310 3.0A































































































































































































Dall OssoClara171197

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