Clinical Outcomes After 1 Year of Augmented Insulin Pump Therapy in Patients with Diabetes in a Specialized Diabetes Center in Medellín,Colombia

Abstract

Background:

Type 1 diabetes can be difficult to control. Augmented pump therapy (CSII-rtCGM) has become an important tool for controlling blood glucose and decreasing hypoglycemia.

Methods:

Describe the results 1 year after starting CSII-rtCGM in patients with diabetes in Medellín, Colombia. This is an observational, retrospective study. Patients with type 1 and type 2 diabetes started on CSII-rtCGM between January 2008 and June 2015 were included. Qualitative variables were analyzed as absolute or relative frequencies. Quantitative variables were obtained through central tendency and dispersion according to the normal distribution of the analyzed variable using Kolmogorov–Smirnov. SPSS 19 from IBM was used.

Results:

Two hundred forty-seven patients were identified, of those 183 were included. The starting HbA1C was 8.7% ± 1.7% and 7.4% ± 0.8% (P < 0.05) 1 year later. 16.5% of patients had been admitted to the hospital before starting CSII-rtCGM, after 1 year the admission rate was 6.0% (P < 0.05). The incidence of severe hypoglycemia at the beginning was 32%, 1 year later it was 7.1%.

Conclusion:

CSII-rtCGM therapy improves glucose control and decreases severe hypoglycemic events and hospital admission rate.

Introduction

The increase in prevalence of diabetes in the last decades is alarming. It is estimated that in patients 18 years or older it can be present in up to 8.8% of the population, this corresponds to 415 million people worldwide; the numbers based on projections can increase up to 642 million in the next 25 years.¹

Insulin therapy as seen in the Diabetes Control and Complications Trial (DCCT) in type 1 diabetes^2,3 and the U.K. Prospective Diabetes Study (UKPDS) in type 2 diabetes^4

–7 has shown to decrease complications. A better understanding of physiology and technological advances has given rise to new insulin preparations and better delivery methods. Multiple daily injections (MDI), the most common treatment modality, have some limitations: dose adjustments can only be done by units, it offers less flexibility, and stacking increases the risk of hypoglycemia. CSII can overcome some of these barriers. Another advantage of CSII therapy is that incorporating continuous glucose (CSII-rtCGM) provides additional information and it can stop insulin infusion during hypoglycemia. Multiples trials have shown that pump therapy can decrease the incidence of frequent, nocturnal, exercise-related and asymptomatic hypoglycemia. It can decrease glycemic variability, dawn phenomena, and improve glycemic control.^6,8,9

The objective of this present study is to describe the results after 1 year of CSII-rtCGM in diabetic patients, which was started in a specialized center in Medellín, Colombia.

Materials and Methods

This is a retrospective, observational, and analytical study done between January 2008 and June 2015 in two specialized diabetes centers in Medellín (Colombia). They are private practice centers affiliated to a teaching center. Type 1 and 2 diabetes patients who were trained and started on pump therapy were included. Patients who did not have complete follow-up information were excluded.

Data were obtained from the medical records. One of the authors assessed all the eligibility criteria and filled out a prespecified form. To minimize potential bias, another author audited the medical records and the data were collected.

A descriptive analysis of the variables was done and presented as absolute and relative frequency for the qualitative variables. For the quantitative variables, the mean and the median were obtained, as well as the standard deviation and interquartile range (25%–75%) depending on the normal distribution of the variable being analyzed with Kolmogorov–Smirnov.

HbA1c was obtained at baseline and 1 year after CSII-rtCGM HbA1c. A comparison was performed by repeated-measures models. The frequency of hypoglycemia and hospital admissions was compared between the year before pump start and 1 year after initiation. The chi-square test was used. Statistical significance was considered when P < 0.05. IBM SPSS 19 software was used to analyze data.

Adverse events related to CSII-rtCGM such as severe hypoglycemia and hyperglycemic crisis were described at 3, 6, and 12 months. Allergy, infection, and catheter or infusion set obstruction were described after 1 year of therapy.

The protocol was evaluated and approved by the Health Ethics Committee from Universidad Pontificia Bolivariana.

Results

Two hundred forty-seven patients were identified, 183 met the inclusion criteria (Fig. 1). Basal characteristics are presented in Table 1.

FIG. 1.

Subject disposition.

Table 1.

Basal Characteristics of Patients on CSII-rtCGM

	All patients (N = 183)	Patients younger than 18 years (N = 45)	Patients older than 60 years (N = 9)
Women% (n)	69.4% (127)	57.8% (26)	66.7% (6)
Average age ± SD, years	32 ± 15.4	14.2 ± 2.9	66.5 ± 3.6
Type 1 diabetes (T1DM)% (n)	94.5% (173)	97.8% (44)	78.8% (7)
Type 2 diabetes (T2DM)% (n)	4.9% (9)	2.2% (1)	22.2% (2)
Other types of diabetes% (n)—after pancreatectomy secondary to nesidioblastosis	0.55% (1)	0	0
Diabetes duration ± SD, years	14 ± 9.6	4.29 ± 3.2	27.9 ± 9.1
Rate of severe hypoglycemia (event/patient/year)	0.6	0.7	0.5
A1C ± SD	8.7 ± 1.7	8.8 ± 1.58	7.8 ± 0.58

The criteria for starting CSII-rtCGM were as follows: 57.4% glycemic control; 20.8% severe hypoglycemia; 13.7% frequent, asymptomatic, nocturnal, or exercise-related hypoglycemia; 7.1% dawn phenomena; and the remainder because of glycemic variability.

After variance analysis with repeated measures, the starting glycated hemoglobin (HbA1c) was 8.7% ± 1.7%; after the first year of therapy, it was 7.4% ± 0.8%. The difference was statistically significant (P < 0.05) despite the type of diabetes, time since diagnosis, or criteria for starting therapy.

The starting HbA1c at the beginning of CSII-rtCGM differed if the therapy was started because of poor glycemic control or because of hypoglycemia as can be seen in Figure 2.

FIG. 2.

Patient distribution in relation to HbA1c and reason for prescribing CSII-rtCGM, basal (left panel) and after 12 months (right panel).

16.5% of patients had been admitted to the hospital at least once because of diabetes-related complications before CSII-rtCGM, with a frequency of hospital admission of 0.22 hospital admission/patient/year. One year later, the incidence of hospital admission was 6.0% and the frequency observed was 0.04 hospital admission/patient/year (P < 0.05). Twenty-seven patients who were admitted before pump start did not have any admissions.

The rate and frequency of severe hypoglycemia decreased significantly (P < 0.05) (Table 2).

Table 2.

Follow-Up Clinical Results After 1 Year of CSII-rtCGM

		Follow up
	Basal	3 months	6 months	12 months
HbA1c% ± SD	8.7 ± 1.7	7.7 ± 0.9	7.6 ± 0.8	7.4 ± 0.8^a
Severe hypoglycemia
Prevalence%	32	8.2	7.1	7.1
Rate (events/patient/year)	0.6	0.4	0.3	0.3
Catheter obstruction%	NA	25.1	18	21.3
Hyperglycemic crisis, no. of patients	NA	1	1	1
Sensor allergy%	NA	13.1	13.7	12.6
Infusor allergy%	NA	2.2	2.7	1.6
Sensor and/or infusor allergy, no. of patients	NA	1	2	1

The difference was always statistically significant (P < 0.05) independent of type of diabetes, time since diagnosis, or reason for prescription.

In the group of patients with severe hypoglycemia, the initial frequency was 1.5 events/patient/year; 1 year later, the frequency was 1.0 event/patient/year (P = 0.023).

Hyperglycemic crisis (diabetic ketoacidosis [DKA]) was present in 3 of the 183 patients at the end of the first year of CSII-rtCGM; in the first trimester, it only occurred in one patient.

Adverse events related to CSII-rtCGM are reported in Table 2.

Discussion

Intensive glucose control has been shown to improve clinical outcomes,^3
–5 The main barrier is an increased frequency of hypoglycemia.⁶ CSII-rtCGM has improved glycemic control, with less hypoglycemia and better quality of life.^7,9,10 The present study supports these findings.

The patients' demographic characteristics have been previously described by Aristizábal et al. in a recent publication.¹¹

HbA1c before CSII-rtCGM was 8.7% ± 1.7%; 1 year later it was 7.4% ± 0.8%. These results are similar to what has been previously published by Gomez et al. with an initial HbA1c of 8.97% decreasing to 7.5%.¹² Other publications have reported less decrease in HbA1c. In a meta-analysis by Pickup et al. with a follow-up between 2 and 24 months, the impact of CSII-rtCGM was 0.5%.^13,14 It is likely that the lower efficacy of these results could be because of the heterogeneity of the studies and because they were done at different periods of time. The high adherence to real-time continuous glucose monitoring could also explain these different results; as technology and insulin preparations improve, it is likely that there can be better glucose control. Other meta-analyses show HbA1c reduction that ranges from 0.5% to 0.62%.^13

–18

The majority of randomized controlled trials and meta-analyses only include patients with type 1 diabetes (T1DM). When studies combine T1DM and type 2 diabetes (T2DM) or just analyze T2DM patients, the reduction in HbA1c is greater.^18

–21 The reductions in HbA1c in T2DM in this study are similar to what has been previously reported.

When the HbA1c is analyzed at 3, 6, and 12 months, the difference is always statistically significant (P < 0.05); this is similar to what has been presented in other publications.^{20

–30}

After 1 year of CSII-rtCGM, 50% of patients had an HbA1c less than 7.4%, and 75% less than 8%.

Hospital admission rate decreased 1 year after beginning CSII-rtCGM. 16.5% of patients had been admitted at least once because of diabetes-related complications before CSII-rtCGM, with a frequency of hospital admission of 0.22 hospital admission/patient/year. One year later, the incidence of hospital admission was 6.0% and the frequency observed was 0.04 hospital admission/patient/year (P < 0.05). Twenty-seven patients who were admitted before pump start did not have any admissions.

In this patient population, DKA was present in only 3 out of 183 patients by the end of the year.^31
–33 Scaramuzza et al. report a frequency of 0.3 events/100 patients/year for diabetic ketoacidosis³⁰ and Bergenstal et al. describe a frequency of 0.01 event/100 patients/year, but there are no data of events before starting CSII-rtCGM.³¹

DKA used to be a feared complication of pump therapy, but with current training and technology this is not a common complication.³⁴ More recent reports have demonstrated lower rates of hyperglycemic crisis in patients on pump therapy when compared to MDI.^9,35

Hypoglycemia is the main limiting factor for intensive glucose control. Avoiding severe hypoglycemia is crucial in the management of diabetes. Before CSII-rtCGM was started the prevalence was 32%, with a frequency of 0.6 events/patient/year; after the first year of therapy the prevalence decreased to 15.8%, with a frequency of 0.3 events/patient/year (P < 0.0005). Gomez et al. described a rate of 0.37 events/patient/year of hypoglycemia with CSII-rtCGM.¹² Other publications have also reported a decrease in hypoglycemia. Karagianni et al. report an initial hypoglycemic prevalence of 65% with 4 ± 1.2 events/month and by the end of the intervention it was 47% with a frequency of 2.8 ± 1.4 events/month.²² Scaramuzza et al. described an initial frequency of 11.9 events/100 patients/year and 4.1 events/100 patients/year after the intervention.³⁰ Severe hypoglycemia was reported by Bergenstal et al. with a frequency of 13.31 events/100 patients/year after 1 year of follow-up.³¹

In the group of patients who were started on CSII-rtCGM because of severe hypoglycemia, the initial frequency was 1.5 events/patient/year, 1 year after CSII-rtCGM the frequency decreased to 1.0 events/patient/year (P < 0.023). Not only was severe hypoglycemia decreased but HbA1c improved.

Between 1970 and 1980s, CSII had a great incidence of adverse events; there were reports of malfunctioning in up to 25% of patients and battery failures of 14%. The prevalence of infections could reach up to 30%.^36
–38 Given the diversity and wide variety of CSII-rtCGM available today around the world, it is difficult to estimate the real prevalence of related adverse events.³⁹ It is likely that as technology has evolved adverse events might have decreased.

The most frequent side effect in this study was catheter obstruction in 25.1%, 18%, and 21.3% at 3, 6, and 12 months, respectively; it is important to note that this obstruction led to hyperglycemia but not to DKA. Wheeler et al. report a similar prevalence of 20%,⁴² and Renard et al. in 2010 describe 30%.³⁷ Pickup et al. described catheter torsion and obstruction in 64.1% and 54.3%, respectively.³⁸ This complication has been decreasing as historical data published by Mecklenburg et al. described a prevalence of 81% in 1986.³⁹

Sensor allergy had a prevalence of 13.7% at 6 months and 12.6% at 1 year. Infusor allergy had an incidence between 1.6% and 2.7%. Allergic reactions were usually mild to moderate. The literature, as well as this study, demonstrates that cutaneous infections are common although rarely severe.^36,42 There is a greater predisposition when the catheter is left for more than 72 h and the sensor for more than 6 days.³⁶

Sensor-related infection was present in one patient during the first trimester, two in the second trimester, and only one after 1-year follow-up. No patient presented catheter-related infections. This is different from what has been described in the literature.^17,43,44 Mecklenburg et al. in 1986 described a prevalence of 29% at the catheter site.³⁹ Pickup et al. 28 years later reported infections as the second most frequent problem at the infusion site with a prevalence of 17.4%.³⁸ There are two other studies published in 2014, which did not report infections as an adverse event.^35,42 It is possible that some of the different results reported are linked to aseptic techniques or to the duration of the studies.^35,42 There can also be under reporting of this adverse event.

It is likely that the results obtained in this study are due to technology use and the training and diabetes education delivered in these centers. This study supports the concept that team work leads to great results in diabetes care.

Some of the limitations of this article are its retrospective nature and the potential bias in data collection.

Conclusion

This study describes clinical outcomes in diabetic patients enrolled in a pump program in two specialized centers in Medellín (Colombia). The main reason for prescribing CSII-rtCGM was poor glucose control and frequent and severe hypoglycemia. HbA1c reduction was 1.3% after the first year of CSII-rtCGM. Severe hypoglycemia and the hospital admission rate were also decreased in a significant manner. Safety results are comparable with what has been described previously in the literature. It is important to note that training and management are done in a center with a high degree of expertise in diabetes care and pump use. The teams are composed of endocrinologists, pediatricians, general practitioners, educators, dieticians, psychologists/psychiatrists, and pharmacists.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

International Diabetes Federation: IDF Diabetes Atlas. 7. Brussels, Belgium: International Diabetes Federation, 2015.

Diabetes Control and Complications Trial (DCCT): results of feasibility study. The DCCT Research Group. Diabetes Care, 1987; 10:1–19.

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med, 1993; 329:977–986.

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet, 1998; 352:837–853.

Pickup

: Insulin-pump therapy for type 1 diabetes mellitus. N Engl J Med, 2012; 366:1616–1624.

Yeh

H-C

, Brown

, Maruthur

, et al.: Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med, 2012; 157:336–347.

Langendam

, Luijf

, Hooft

, et al.: Continuous glucose monitoring systems for type 1 diabetes mellitus. Cochrane Database Syst Rev, 2012; 1:CD008101.

Grunberger

, Abelseth

, Bailey

, et al.: Consensus statement by the american association of clinical endocrinologists/american college of endocrinology insulin pump management task force. Endocr Pract, 2014; 20:463–489.

Chantelau

, Spraul

, Mühlhauser

, et al.: Long-term safety, efficacy and side-effects of continuous subcutaneous insulin infusion treatment for type 1 (insulin-dependent) diabetes mellitus: a one centre experience. Diabetologia, 1989; 32:421–426.

10.

Hashimoto

, Kawamura

, Kashihara

, et al.: Factors associated with basal insulin dose in Japanese children and young adult type 1 diabetics. J Diabetes Investig, 2012; 3:276–282.

11.

Aristizábal

, Ramírez

, Hincapié-García

, et al. Epidemiological characterization of diabetic patients on therapy with continuous subcutaneous insulin infusion and continuous glucose monitoring in real time. Endocrinol Nutr, 2015; 62:451–457.

12.

Gómez

, Grizales

, Veloza

, et al.: Factores asociados con el control glucémico óptimo en pacientes tratados con bomba de insulina y monitorización continua de glucosa en tiempo real. Av En Diabetol, 2013; 29:74–80.

13.

Pickup

, Sutton

: Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med, 2008; 25:765–774.

14.

Pickup

, Mattock

, Kerry

: Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ, 2002; 324:705.

15.

Pańkowska

, Błazik

, Dziechciarz

, et al.: Continuous subcutaneous insulin infusion vs. multiple daily injections in children with type 1 diabetes: a systematic review and meta-analysis of randomized control trials. Pediatr Diabetes, 2009; 10:52–58.

16.

Jeitler

, Horvath

, Berghold

, et al.: Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis. Diabetologia, 2008; 51:941–951.

17.

Fatourechi

, Kudva

, Murad

, Elamin

, Tabini

, Montori

. Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections. J Clin Endocrinol Metab, 2009; 94:729–740.

18.

Reznik

: Continuous subcutaneous insulin infusion (CSII) using an external insulin pump for the treatment of type 2 diabetes. Diabetes Metab, 2010; 36:415–421.

19.

Herman

, Ilag

, Johnson

, et al.: A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes. Diabetes Care, 2005; 28:1568–1573.

20.

Sudhakaran

, Anjana

, Rao

, et al.: Role of continuous subcutaneous insulin infusion in patients with recalcitrant diabetes in South India. Diabetes Technol Ther, 2009; 11:733–737.

21.

Papargyri

, Ojeda

, Corrales

, et al.: An observational 7-year study of continuous subcutaneous insulin infusion for the treatment of type 1 diabetes mellitus. Endocrinol Nutr, 2014; 61:141–146.

22.

Karagianni

, Sampanis

, Katsoulis

, et al.: Continuous subcutaneous insulin infusion versus multiple daily injections. Hippokratia, 2009; 13:93–96.

23.

Cohen

, Hong

, Van Drie

, et al.: Long-term metabolic effects of continuous subcutaneous insulin infusion therapy in type 1 diabetes. Diabetes Technol Ther, 2013; 15:544–549.

24.

Balsa

, Neves

, Alves

, et al.: Continuous subcutaneous insulin infusion. Acta Médica Port, 2011; 24 Suppl 2:147–156.

25.

Wood

, Moreland

, Volkening

, et al.: Durability of insulin pump use in pediatric patients with type 1 diabetes. Diabetes Care, 2006; 29:2355–2360.

26.

Hanas

, Adolfsson

: Insulin pumps in pediatric routine care improve long-term metabolic control without increasing the risk of hypoglycemia. Pediatr Diabetes, 2006; 7:25–31.

27.

Skogsberg

, Fors

, Hanas

, et al.: Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus. Pediatr Diabetes, 2008; 9:472–479.

28.

Hermanides

, Nørgaard

, Bruttomesso

, et al.: Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial. Diabet Med J Br Diabet Assoc, 2011; 28:1158–1167.

29.

Hirsch

, Abelseth

, Bode

, et al.: Sensor-augmented insulin pump therapy: results of the first randomized treat-to-target study. Diabetes Technol Ther, 2008; 10:377–383.

30.

Scaramuzza

, Iafusco

, Rabbone

, et al.: Use of integrated real-time continuous glucose monitoring/insulin pump system in children and adolescents with type 1 diabetes: a 3-year follow-up study. Diabetes Technol Ther, 2011; 13:99–103.

31.

Bergenstal

, Tamborlane

, Ahmann

, et al.: Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med, 2010; 363:311–320.

32.

Janez

: Continuous subcutaneous insulin infusion in adult type 1 diabetes mellitus: data from a registry at the University Medical Centre Ljubljana, Slovenia. J Int Med Res, 2012; 40:1546–1551.

33.

Cobelli

, Renard

, Kovatchev

: Artificial pancreas: past, present, future. Diabetes, 2011; 60:2672–2682.

34.

Ross

, Milburn

, Reith

, et al.: Clinical review: insulin pump-associated adverse events in adults and children. Acta Diabetol, 2015; 52:1017–1024.

35.

Wheeler

, Heels

, Donaghue

, et al.: Insulin pump-associated adverse events in children and adolescents—a prospective study. Diabetes Technol Ther, 2014; 16:558–562.

36.

Heinemann

, Fleming

, Petrie

, et al.: Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting, and research needs: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group. Diabetes Care, 2015; 38:716–722.

37.

Renard

, Guerci

, Leguerrier

A-M

, et al.: Lower rate of initial failures and reduced occurrence of adverse events with a new catheter model for continuous subcutaneous insulin infusion: prospective, two-period, observational, multicenter study. Diabetes Technol Ther, 2010; 12:769–773.

38.

Pickup

, Yemane

, Brackenridge

, et al.: Nonmetabolic complications of continuous subcutaneous insulin infusion: a patient survey. Diabetes Technol Ther, 2014; 16:145–149.

39.

Mecklenburg

, Guinn

, Sannar

, et al.: Malfunction of continuous subcutaneous insulin infusion systems: a one-year prospective study of 127 patients. Diabetes Care, 1986; 9:351–355.

40.

Schober

, Rami

: Dermatological side effects and complications of continuous subcutaneous insulin infusion in preschool-age and school-age children. Pediatr Diabetes, 2009; 10:198–201.

41.

Van Bon

, Bode

, Sert-Langeron

, et al.: Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial. Diabetes Technol Ther, 2011; 13:607–614.

42.

Wheeler

, Donaghue

, Heels

, et al.: Family perceptions of insulin pump adverse events in children and adolescents. Diabetes Technol Ther, 2014; 16:204–207.

43.

Heinemann

, Krinelke

: Insulin infusion set: the Achilles heel of continuous subcutaneous insulin infusion. J Diabetes Sci Technol, 2012; 6:954–964.

44.

Hirsch

, Abelseth

, Bode

, Fischer

, Kaufman

, Mastrototaro

, et al. Sensor-augmented insulin pump therapy: results of the first randomized treat-to-target study. Diabetes Technol Ther, 2008; 10:377–383.