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DOI:10.4158/EP13441.OR
© 2014 AACE.
Original Article
EP13441.OR
PREVALENCE OF DIABETES, PREDIABETES AND STRESS HYPERGLYCEMIA, INSULIN
THERAPY AND METABOLIC CONTROL IN PATIENTS ON TOTAL PARENTERAL
NUTRITION (PROSPECTIVE MULTICENTER STUDY)
Running title: Diabetes in parenteral nutrition.
Study group of hyperglycemia in parenteral nutrition. Nutrition area of the Spanish Society of
Endocrinology and Nutrition (SEEN).
Gabriel Olveira PhD1,2; María J. Tapia MD1; Julia Ocón PhD3; Carmen Cabrejas-Gómez MD3; María D.
Ballesteros-Pomar PhD4; Alfonso Vidal-Casariego MD4; Carmen Arraiza-Irigoyen MD5; Josefina Olivares
MD6; María C. Conde-García PhD7; Álvaro García-Manzanares MD7; Francisco Botella-Romero PhD8; Rosa
P. Quílez-Toboso MD8; Lucio Cabrerizo PhD9; Pilar Matía MD9; Luisa Chicharro MD10; Rosa Burgos PhD10;
Pedro Pujante MD11; Mercedes Ferrer PhD11; Ana Zugasti PhD12; Estrella Petrina MD12; Laura Manjón
MD13; Marta Diéguez MD13; María J. Carrera MD14; Anna Vila-Bundo MD14; Juan R. Urgelés MD15;
Carmen Aragón-Valera MD16; Olga Sánchez-Vilar MD16; Irene Bretón MD17; Pilar García-Peris PhD17;
Araceli Muñoz-Garach MD18; Efren Márquez PhD18; Dolores del Olmo PhD19; José Luis Pereira MD20;
María C. Tous MD20
From: 1Unidad de Gestión Clínica de Endocrinología y Nutrición, IBIMA, Hospital Regional Universitario
de Málaga/ Universidad de Málaga. Malaga, Spain. 2CIBERDEM, CIBER of Diabetes and Associated
Metabolic Diseases (CB07/08/0019), Instituto de Salud Carlos III, Spain 3Endocrinology and Nutrition
4
Service. Hospital Clínico Universitario Lozano Blesa. Zaragoza. Spain Endocrinology and Nutrition
5
Service. Complejo Asistencial Universitario de León. Spain Endocrinology and Nutrition Service.
Complejo hospitalario de Jaén. Spain 6Endocrinology and Nutrition Service. Hospital Son Llàtzer (Palma
de Mallorca). Spain 7Endocrinology and Nutrition Service. Hospital General Mancha Centro. Alcázar de
San Juan. Ciudad-Real. Spain 8Endocrinology and Nutrition Service. Complejo Hospitalario Universitario
de Albacete. Spain 9Endocrinology and Nutrition Service. Hospital Clínico San Carlos. Madrid. Spain
10
Clinical Nutrition Unit. University hospital Vall d'Hebron. Barcelona. Spain 11Endocrinology and
Nutrition Service. Hospital Universitario Virgen de la Arrixaca. Murcia. Spain 12Clinical Nutrition Unit.
Complejo Hospitalario de Navarra. Spain 13Endocrinology and Nutrition Service. Hospital de Cabueñes.
Gijón. Asturias. Spain 14Endocrinology and Nutrition Service. Hospital del Mar. Barcelona. Spain
15
Endocrinology and Nutrition Service. Hospital Universitario Son Espases. Palma de Mallorca. Spain
16
Endocrinology and Nutrition Service. Fundación Jiménez Díaz. Madrid. Spain 17Endocrinology and
Nutrition Service. Hospital Universitario Gregorio Marañón. Madrid. Spain 18Endocrinology and Nutrition
Service. Hospital Clínico Universitario Virgen de la Victoria. Málaga. Spain 19Endocrinology and Nutrition
Service. Hospital Universitario Severo Ochoa. Leganés. Madrid. Spain 20Endocrinology and Nutrition
Service. Hospital Universitario Virgen del Rocio. Sevilla. Spain.
Correspondence address: Gabriel Olveira // María J Tapia
Nutrition Unit, 4ª planta, Pabellón A, Hospital Regional Universitario de Málaga.
CIBERDEM, CIBER of Diabetes and Associated Metabolic Diseases (CB07/08/0019), Instituto de Salud
Carlos III, Spain; Avenida Carlos Haya, Malaga 29010, Spain
E-mail: [email protected]
[email protected]
DOI:10.4158/EP13441.OR
© 2014 AACE
ABSTRACT
Objective: The prevalence of carbohydrate metabolism disorders in patients who
receive total parenteral nutrition (TPN) is not well known. These disorders can affect
the treatment, metabolic control and prognosis of affected patients. The aims of this
study were to determine the prevalence in noncritically ill patients on TPN of diabetes,
prediabetes and stress hyperglycemia; the factors affecting hyperglycemia during TPN;
and the insulin therapy provided and the metabolic control achieved.
Methods: We undertook a prospective multicenter study involving 19 Spanish
hospitals. Noncritically ill patients who were prescribed TPN were included, and data
were collected on demographic, clinical and laboratory variables (glycated hemoglobin,
C-reactive protein (CRP), capillary blood glucose) as well as insulin treatment.
Results. The study included 605 patients. Before initiation of TPN, the prevalence of
known diabetes was 17.4%, unknown diabetes 4.3%, stress hyperglycemia 7.1% and
prediabetes 27.8%. During TPN therapy 50.9% of patients had at least one capillary
blood glucose >180 mg/dL. Predisposing factors were age, levels of CRP and glycated
hemoglobin, the presence of diabetes, infectious complications, the number of grams of
carbohydrates infused and the administration of glucose-elevating drugs. Most (71.6%)
patients were treated with insulin. The mean capillary blood glucose levels during TPN
were: known diabetes (178.6±46.5 mg/dL), unknown diabetes (173.9±51.9), prediabetes
(136.0±25.4), stress hyperglycemia (146.0±29.3) and normal (123.2±19.9) (p<0.001).
Conclusion: The prevalence of carbohydrate metabolism disorders is very high in
noncritically ill patients on TPN. These disorders affect insulin treatment and the degree
of metabolic control achieved.
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Keywords: Parenteral nutrition, diabetes mellitus, insulin, prediabetes, stress
hyperglycemia.
Abbreviations:
BMI = body mass index; CRP = C-reactive protein; HbA1c = glycated hemoglobin;
TPN = total parenteral nutrition.
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INTRODUCTION
Diabetes mellitus presents epidemic proportions in most parts of the world (1).
The estimated prevalence of diabetes in Spain is 14% of the adult population (2,3). The
prevalence of diabetes in the hospital setting is also very high (4,5), and in this case it is
associated with increases in mortality, hospital stay, and costs (6).
Stress hyperglycemia is a frequent complication among hospitalized patients
(with and without diabetes) and it is also associated with a poor clinical outcome and
increased mortality (7). However, there is a lack of reliable data about the prevalence of
this disorder as the literature gives different definitions, none of which is accepted
internationally (8-10).
Approximately 2-3% of patients admitted to hospital are estimated to receive
total parenteral nutrition (TPN) to either treat or prevent malnutrition (10). However, the
use of TPN is itself a risk factor for the onset or aggravation of hyperglycemia,
independently of a prior history of diabetes (11-12), and hyperglycemia is associated
with increases in morbidity and mortality (13-17).
Nonetheless, the prevalence of diabetes, stress hyperglycemia and prediabetes in
patients on TPN, particularly those on noncritical wards, has received less attention.
Data are available from retrospective studies involving just a few patients or applying
criteria for diabetes and hyperglycemia based solely on the clinical history or on venous
or capillary blood glucose levels, without considering the glycated hemoglobin values;
in addition to using different cut points for the definition of hyperglycemia (14,18-21).
The presence of undiagnosed prediabetes or diabetes, as well as prior metabolic control
measured by the HbA1c, can affect the prevalence of hyperglycemia in these patients,
and thus the need for insulin therapy and the degree of metabolic control (22), which
can all influence the prognosis.
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Clinical practice guidelines and consensus statements recommend a premeal
blood glucose level <140 mg/dL for most noncritically ill patients in conjunction with
random blood glucose values <180 mg/dL (5,10,12,23). Values above 180 mg/dL are
associated with a greater incidence of complications and death in hospitalized patients
that receive parenteral nutrition (13,14,16,17). However, the best insulin regimen to use
in these patients is unknown, and few studies have examined the efficacy and degree of
metabolic control achieved (10,19,24,25).
The aims, therefore, of this multicenter prospective study were to determine:
1. The prevalence of diabetes, stress hyperglycemia and prediabetes in noncritically ill
patients receiving TPN
2. The factors associated with having high blood glucose levels (>180 mg/dL) during
TPN infusion.
3. The insulin treatment given and the degree of metabolic control achieved in each
subgroup of patients under conditions of daily clinical practice.
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METHODS
This prospective multicenter study involved 19 hospitals in Spain (16 university
hospitals and 3 non-university hospitals). The study included all hospitalized
noncritically ill patients (i.e., patients in the non-intensive care unit setting) who started
TPN as a sole source of nutrition between September and December 2010.
Patients were excluded if they were in intensive care units, were receiving
parenteral nutrition together with enteral nutrition, pregnant, or <14 years of age. The
study was approved by the Research Ethics Committee of Carlos Haya Regional
University Hospital, and all the participants gave written informed consent.
Prior to starting the TPN infusion a blood sample was drawn to measure the
glycated hemoglobin, following the international recommendations for standardization
of the HbA1c measurement (26). Measurements were also made of fasting plasma blood
glucose and CRP (with an autoanalyzer) at the laboratories of each hospital.
We classified the patients according to their fasting venous blood glucose levels
before starting TPN and the HbA1c concentrations as follows:
• Patients were considered to have known diabetes if they had a documented
history of diabetes.
• Patients were considered to have unknown diabetes if there was no record of
having diabetes mellitus but the HbA1c was ≥6.5%
• Patients were considered to have prediabetes if the HbA1c was ≥5.7% but
<6.5%.
• Patients were considered to have stress hyperglycemia if their HbA1c was
<5.7% but their blood glucose was ≥126 mg/dL prior to TPN infusion.
Data were recorded on demographic variables; diagnosis on admission; prior
comorbidity (history of kidney or liver failure, respiratory or cardiac diseases,
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transplant); anthropometric data (weight, height, calculation of BMI); type of TPN;
concomitant prescription of glucose-elevating drugs (steroids, somatostatin, tacrolimus
or cyclosporine).
The TPN formula at all the hospitals was provided as a total nutrient admixture
(‘3 in 1’) solution containing carbohydrates, proteins and lipids. All the TPN patients
were seen daily by a member of the hospital Nutrition Unit, who made any adjustments
in accordance with the relevant guidelines (27). Prospective measurements were made
of capillary blood glucose each 6 hours, though if the blood glucose levels were <140
mg/dL the measurements were made every 8 hours. The blood glucose monitor used
was the usual model in each hospital. If a patient had hyperglycemia, insulin treatment
was started following the consensus recommendations (5). The insulin regimen was
recorded and the patients were classified into two groups: subcutaneous only vs.
intravenous insulin (in or outside TPN), independently of whether subcutaneous insulin
was also associated. The mean daily insulin dose was also recorded.
Data analysis. The comparisons between the qualitative variables were done with the
Chi-square test, with Fisher’s correction when necessary. The distribution of the
quantitative variables was examined with the Kolmogorov-Smirnov test. The
differences between the quantitative variables were analyzed with the ANOVA. We
designed multivariate logistic regression models in which the dependent variable was
having at least one capillary blood glucose measurement >180 mg/dL during the TPN
infusion. The potential predictors included age (in three age groups), grams of
carbohydrates infused, glycated hemoglobin (in three groups: <5.7, 5.7-6.4, ≥6.5),
baseline venous blood glucose, and CRP (divided into sample tertiles: <25, 25-116,
>116) prior to starting TPN, presence of prior known diabetes, infectious complications
during the TPN, and prescription concomitant to the TPN of glucose-elevating drugs,
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adjusting also for gender and BMI and previous comorbidity. For all the calculations
significance was set at p<0.05 for two tails. Statistical analyses were performed using
SPSS 15.0 (SPSS Inc., Chicago IL, 2006)
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RESULTS
The study included 605 patients. The characteristics of the patients and the TPN
infused are shown in Table 1. Of the 605 patients, 106 (17.5%) received corticosteroids,
57 (9.4%) octreotide or somatostatin, and 13 (2.1%) tacrolimus or cyclosporine.
Figure 1 represents the percentages of patients with carbohydrate metabolism
disorders and Table 2 shows the clinical and TPN characteristics in the patients
according to the particular carbohydrate metabolism disorder. Significant differences
were found between the groups in age, BMI, the prior presence of comorbidity, grams
of carbohydrates infused, and the values of venous blood glucose and HbA1c.
Table 3 shows the logistic regression data for the risk of having a capillary blood
glucose concentration >180 mg/dL during TPN infusion. After adjustment, an increased
risk was significantly associated with the CRP level (>116 mg/L - third tertile), grams
of carbohydrates in the TPN, age >65 years, HbA1c concentration >5.7%, the presence
of diabetes, infectious complications, or the concomitant use of glucose-elevating drugs.
Although the venous blood glucose level prior to starting TPN was not quite significant
(p=0.056), after taking the HbA1c out of the model, those persons with baseline venous
blood glucose levels >140 mg/dL had a relative risk that was 2.2 times greater (95% CI,
1.279 -3.811; p=0.004) than those whose levels were lower. All the other variables
mentioned above remained significant.
A total of 433 (71.6%) patients received insulin at some time during their TPN
infusion (55.4% only subcutaneously and 44.6% with IV insulin: 35.8% in the bag and
subcutaneous, and 8.8% with insulin perfusion independently of the TPN), with or
without subcutaneous correctional insulin dosing. Table 4 shows the type and dose of
the insulin therapy used and the degree of metabolic control achieved during the TPN
infusion in the various patient groups, according to their prior metabolic status.
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Significant differences were seen in all the variables related with the type of insulin
treatment used as well as with the metabolic control achieved.
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DISCUSSION
This study shows that the prevalence of carbohydrate metabolism disorders
(diabetes, prediabetes and hyperglycemic stress) is very high (56.6%) in noncritically ill
patients receiving TPN. Furthermore, there was a notable association between this high
prevalence and the need for insulin therapy, its form of administration (IV vs.
subcutaneous only) and the dose used, as well as with the degree of metabolic control
achieved in conditions of daily clinical practice.
Prevalence of carbohydrate metabolism disorders
Unlike other studies (14, 17-21), in our work we defined the presence of diabetes,
prediabetes and hyperglycemia before TPN infusion not only from the chart data but
also from the laboratory findings (including venous blood glucose concentrations and
measurement of the HbA1c in all the patients before starting treatment). This approach
gives more value to the data as the prevalence of diabetes may well be underestimated if
it is based solely on the clinical history or chart data (4). Indeed, in our study 4.3% of
the patients had unknown diabetes. The American Diabetes Association recommends
using HbA1c as a diagnostic test to improve diabetes screening (8). HbA1c is also
important for predicting which patients are at risk for hyperglycemia upon admission
and the value is not substantially affected by acute illness, so it may be feasible to use it
as a screening assay for diabetes in the acute care setting (28). Roehl et al, in a
retrospective study of 1388 patients, used the HbA1c to predict the insulin
requirements, but in this case the authors only documented whether the patients had a
value measured within 3 months of starting PN (30% of all the patients) and did not use
it to classify the patients (22). The prevalence of known diabetes reported in other
studies undertaken in patients on TPN (critical and noncritical) ranges from 15-27%;
thus the 17.4% in our series is within this range (15-18,22,29).
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The prevalence of prediabetes or stress hyperglycemia in patients on TPN
(21.8% and 7.1% respectively) has not as yet been reported. These figures might vary
depending on the cut point used for the HbA1c and venous blood glucose levels (810,13). In addition, other studies that did not measure the HbA1c may have classified
both entities as stress hyperglycemia or simply TPN-associated hyperglycemia.
Whatever the situation, even in patients with no carbohydrate metabolism
disorder prior to starting TPN (43.4% of the sample), 70% still had at least one capillary
blood glucose reading above 140 mg/dL and 31% above 180 mg/dL after starting TPN.
This just strengthens the importance of monitoring capillary blood glucose levels in all
patients on TPN, independently of the prior presence of carbohydrate metabolism
disorders (8, 10, 22-24).
Factors associated with hyperglycemia during TPN
Given the proposal that a blood glucose concentration of 180 mg/dL be used as the cut
point for poor metabolic control and that a higher level is associated with increased
morbidity and mortality in patients on TPN (5,10,12-14,16,17,23) as well as being a
good predictor of insulin requirements (22), we wished to determine the factors
predicting hyperglycemia above this level. The risk of having capillary blood glucose
levels above 180 mg/dL was greater in those patients who had high CRP levels (above
the 66th percentile in our sample -116 mg/L), were aged older than 65 years, had
HbA1c concentrations above 5.7% (and especially 6.5%), had received glucoseelevating drugs concomitantly with the TPN, experienced infectious complications, had
diabetes mellitus, or had received more intravenous infusion of glucose. The presence of
any of these factors should alert the physician and the nutritional support team to
anticipate the hyperglycemia and predict PN insulin requirements to maintain optimal
blood glucose control and prevent complications. A few of these factors have also been
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found to predict hyperglycemia or the need for insulin therapy in patients on TPN
(21,22,30). In our study, although the baseline blood glucose concentration before
starting TPN was not significant in the logistic regression model (p=0.056), this was due
to the inclusion of other factors, e.g., HbA1c, which are strongly associated with the risk
for hyperglycemia and that mask the contribution of the baseline blood glucose level.
Thus, practically speaking and given the absence of HbA1c levels (which are not always
available in patients who are to receive TPN, at least initially) venous blood glucose
concentrations above 140 mg/dL (before starting TPN) should also condition a more
aggressive attitude when prescribing insulin therapy for these patients (10).
Insulin treatment and degree of metabolic control achieved
The use of insulin added to the TPN bag, with adjustments made in
subcutaneous insulin, is a common practice that has been shown to be effective in
managing hyperglycemia in these patients (19, 23-25). Nevertheless, no randomized
studies have yet compared the efficacy and effectiveness of different insulin therapy
regimens in TPN.
In our study the prior carbohydrate metabolism status greatly affected the need
for insulin, its route of administration, the dose used, and the metabolic control
achieved. Although insulin was required by almost 60% of those patients with no prior
alteration, the IV route was only used in 17%. In these latter patients the mean blood
glucose concentrations were 123 mg/dL, and 99% of them reached mean blood glucose
concentrations below 180 mg/dL during TPN infusion.
Of the patients with stress hyperglycemia and prediabetes, 84% and 68%
received insulin, respectively. Only a small proportion of these (12% and 6%,
respectively) were poorly controlled (blood glucose concentrations above 180 mg/dL).
These groups experienced a very similar behavior, and it was relatively easy to achieve
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the desired metabolic control (5,10,12,23) with subcutaneous insulin in most cases; IV
insulin was only necessary in about one in four cases.
However, even though the patients with diabetes (both known and unknown)
received more doses of insulin (0.47 and 0.8 IU/kg, respectively), and that in most of
these (61% and 68%) it was given IV (generally in the TPN bag), the control was
worse, with the desired levels failing to be achieved in about one in every three persons.
This occurred despite the infusion of significantly fewer carbohydrates per kg of weight
(compensated with greater doses of insulin per gram of carbohydrates). The mean doses
used in patients with diabetes were similar to those described elsewhere (19, 25).
The relationship between insulin sensitivity and insulin secretion (or exogenous
insulin supplementation), the glucose disposal index, is thought to be approximately
hyperbolic; thus the product of these two variables is constant for individuals with the
same degree of glucose tolerance (31), given that the TPN (where high doses of glucose
infusions are given) is often used concomitantly with other glucose-raising drugs and/or
in clinical situations causing an increase in insulin resistance or suppression of insulin
secretion, and high insulin doses are sometimes required in order to achieve adequate
metabolic control.
Limitations and future research
In our study, the blood samples were not centralized nor was the same blood glucose
monitor used, which could contribute to small under- or over-estimates of the real blood
glucose values. Nor were the HbA1c values corrected according to the presence of
anemia or chronic renal failure or hemolysis. This therefore assumes the risk that some
patients who had these comorbidities were not in fact included in the correct group.
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The definition of stress hyperglycemia assumes it to be transient, disappearing on
resolution of the disease causing the admission. However, we did not undertake any
long-term follow-up of these patients to reassess their metabolic status after reaching
clinical stability (10). Additionally, as this was not a randomized study but rather based
on clinical practice, then generalizations cannot be drawn from this observational study.
Thus, we cannot know which type of insulin therapy is more effective to control persons
with carbohydrate metabolism disorders, particularly known diabetes.
In conclusion, the prevalence of carbohydrate metabolism disorders is very high
in noncritically ill patients who receive TPN. This affects both the insulin therapy given
and the degree of metabolic control achieved. The data reported herein may form the
basis to draw up protocols for the prevention and treatment of hyperglycemia in patients
on TPN, as well as for designing prospective studies to determine the best insulin
therapy regimen in patients with carbohydrate metabolism disorders, particularly
diabetes.
ACKNOWLEDGEMENTS
Sources of funding: The authors thank the Spanish Society of Endocrinology and
Nutrition for help with the publication expenses of this manuscript.
Statement of Authorship: G.O. and M.-J.T. contributed to the conception and design of
the study; acquisition, analysis, and interpretation of the data; and statistical analysis
and drafting of the manuscript. Both authors are the guarantors of the paper and, as
such, had full access to all the data in the study, taking responsibility for the integrity of
the work as a whole, from inception to published article.
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J.O., C.C.-G., M.-D.B-P., A.V.-C., C.A.-I., J.O., M.-C.C.-G., A.G.-M., F.B.-R., R.P.Q.-T., L.C., P.M., L.C., R.B., P.P., M.F., A.Z., L.M., M.D., M.-J.C., A.V.-B., J.-R.U.,
C. A.-V., O.S.-V., I.B., P.G.-P., A.M.-G., E.M., D.O., J.-L.P. and M.-C.T. contributed
to data acquisition and critical review of the manuscript.
Conflicts of interest Statement: None of the authors has any conflict of interest to
disclose.
The authors are very grateful to the patients for their participation in the study.
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DOI:10.4158/EP13441.OR
© 2014 AACE
Figure 1. Prevalence of diabetes and stress hyperglycemia in hospitalized patients
receiving TPN
Data are expressed as percentages.
•
Known diabetes: a documented history of diabetes.
•
Unknown diabetes: no record of having diabetes mellitus + HbA1c ≥6.5%
•
Prediabetes: HbA1c ≥5.7% but <6.5%.
•
Stress hyperglycemia: HbA1c <5.7% + blood glucose ≥126 mg/dL prior to TPN
infusion.
Table 1: Patient and TPN characteristics
Variables
Age (years)
63.2±15.7
Men /women (%)
56.7/43.3
No. days hospitalized
No. days on TPN
BMI (kg/m2)
33.6 ± 26.7
13 ± 11
25.2 ±5.5
Daily TPN characteristics
kcal administered
1.630 ± 323
kcal/kg body weight
25.1 ± 5.7
Carbohydrates g/kg
3.2 ± 0.7
Amino acids g/kg
1.26 ± 0.3
Lipids g/kg
0.9 ± 0.2
Total carbohydrates (TPN + dextrose-containing solutions) g/kg
3.8 ± 0.8
Venous blood glucose (fasting) *
119.4 ± 41.9
Capillary blood glucose (during TPN infusion), mean mg/dL
140 ±36.5
Treatment with insulin
433 (71.6)
Insulin units/kg body weight **
0.42 ± 0.6
Insulin units/g carbohydrates **
0.15 ± 0.2
HbA1c (%)
5.75 ± 0.8
CRP level (mg/L)
94.3 ± 96.3
Diagnosis n (%)
Surgery
360 (59.5)
Oncology (solid and hematologic)
114 (18.8)
Digestive
89 (14.7)
Infectious disorders
42 (6.9)
Previous comorbidity ***
149 (24.6)
Glucose-elevating treatment ****
158 (26.1)
Data are means ± SD or n (%) unless otherwise indicated. CRP, C-reactive protein. TPN, total
parenteral nutrition. BMI, body mass index.
* Prior to starting parenteral nutrition.
** Includes just those patients who received insulin therapy during TPN.
*** Includes a history of kidney or liver failure, respiratory or cardiac diseases, transplant.
**** Includes: steroids, somatostatin, tacrolimus or cyclosporine.
Table 2. Clinical characteristics of the patients and the TPN infused according to the
carbohydrate metabolism disorder diagnosed
Variables
Normal
Stress
Prediabetes
hyperglycemia
Unknown
Known
P
diabetes
diabetes
value
No. patients
263
43
168
26
105
Age (years)
60.5 ± 17.1
63.0 ± 14.6
64.5 ± 15.4
68.0 ± 13.8
67.0 ± 11.8
0.002
No. Days
32.9 ± 23.9
26.8 ± 16.1
36.0 ± 33.4
35.4 ± 22.9
34.2 ± 25.8
ns
No. Days on TPN
13.5 ± 12.0
10.9 ± 7.9
13.6 ± 10.8
10.5 ± 7.0
12.9 ± 11.9
ns
BMI (kg/m2) *
24.1 ± 5.6
24.8 ± 3.9
25.5 ± 4.9
26.8 ± 5.0
27.4 ± 6.4
< 0.001
53 (20.2)
10 (23.3)
37 (22)
7 (26.9)
42 (40.0)
< 0.001
25.4 ± 5.6
26.1 ± 4.4
25.3 ± 5.0
22.0 ± 4.8
23.9 ± 4.2
0.003
3.28 ± 0.8
3.26 ± 0.7
3.14 ± 0.6
2.76 ± 0.6
2.93 ± 0.6
< 0.001
97.8 ± 13.8
152.1 ± 22.7
115.8 ± 34.0
141.6 ± 27.5
162.2 ± 63.2
< 0.001
HbA1c (%) *
5.2 ± 0.4
5.3 ± 0.3
5.9 ± 0.2
7.2 ± 0.9
6.7 ± 1.1
< 0.001
CRP mg/L *
81.8 ± 92.9
100.2 ± 103.4
103.4 ± 95.8
117.8 ± 103.5
101.9 ± 98.9
ns
hospitalized
Presence of any
prior comorbidity
*
Kcal/kg body
weight
TPN
carbohydrates
g/kg
Baseline venous
blood glucose
mg/dL *
Data are means ± SD or n (%) unless otherwise indicated. CRP, C-reactive protein. TPN, total
parenteral nutrition. BMI, body mass index.
* Prior to starting parenteral nutrition.
Table 3. Logistic regression analysis: adjusted risk of presenting capillary blood glucose
higher than 180 mg/dL during TPN infusion
B
Odds ratio
95 % CI
Lower
P value
Upper
Age (years)
< 40
< 0.001
40-64
0.631
1.880
0.866
4.084
0.111
≥ 65
1.347
3.847
1.771
8.357
0.001
HbA1c (%)
< 5.7
< 0.001
5.7-6.4
0.833
2.301
1.427
3.709
0.001
≥ 6.5
2.309
10.061
3.118
32.465
< 0.001
CRP level (mg/L)
< 25
0.045
25-116
0.393
1.481
0.882
2.488
0.138
>116
0.671
1.957
1.150
3.330
0.013
Venous blood glucose (fasting) prior to TPN (mg/dL)
0.007
1.007
1.000
1.015
0.056
Total carbohydrates (g/day)
0.008
1.008
1.001
1.015
0.023
Prior known diabetes
1.928
6.876
2.678
17.653
< 0.001
Infectious complications during hospitalization
0.642
1.901
1.124
3.215
0.017
Glucose-elevating treatment
0.673
1.961
1.189
3.234
0.008
Footnote: Included also in the model but without statistical significance: gender, BMI.
CRP, C-reactive protein. TPN, total parenteral nutrition. BMI, body mass index.
Table 4. Type of insulin treatment used and degree of metabolic control achieved during
TPN infusion, according to prior metabolic status.
Variables
Normal
Stress
Prediabetes
hyperglycemia
No. patients
Unknown
Known
P
diabetes
diabetes
value
105
263
43
168
26
155 (58.5)
36 (83.7)
114 (67.9)
24 (92.3)
104 (99.0)
None
108 (41.1)
7 (16.3)
54 (32.1)
2 (7.7)
1 (1.0)
Just SC
110 (41.4)
25 (58.1)
65 (38.7)
8 (30.8)
32 (30.5)
IV, with/without SC
45 (17.1)
11 (25.6)
49 (29.2)
16 (61.5)
72 (68.5)
< 0.001
Insulin units per kg body
0.23 ± 0.3
0.23 ± 0.3
0.32 ± 0.3
0.47 ± 0.4
0.80 ± 0.9
< 0.001
0.07 ± 0.09
0.06 ± 0.05
0.11 ± 0.11
0.19 ± 0.13
0.27 ± 0.31
< 0.001
123.2 ± 19.9
146.0 ± 29.3
136.0 ± 25.4
173.9 ± 51.9
178.6 ± 46.5
< 0.001
<140 mg/dL (n 370)
217 (82.5)
21 (48.8)
108(64.3)
6 (23.1)
18 (17.1)
140-180 mg/dL (n 175)
44 (16.7)
17 (39.5)
50 (29.8)
13 (50.0)
51 (48.6)
>180 mg/dL (n 60)
2 (0.8)
5 (11.7)
10 (5.9)
7 (26.9)
36 (34.3)
< 0.001
Any blood glucose >140 *
182 (70.3)
37 (88.1)
140 (84.8)
25 (100)
98 (98)
< 0.001
Any blood glucose >180 *
81 (30.8)
24 (55.8)
84 (50.0)
22 (84.6)
97 (92.4)
< 0.001
% blood glucose >140
16.6 ± 21.6
36.0 ± 30.9
28.2 ± 27.7
53.7 ± 29.7
54.9 ± 29.8
< 0.001
2.7 ± 7.6
9.3 ± 16.4
7.9 ± 14.7
26.4 ± 28.1
32.4 ± 26.8
< 0.001
Insulin treatment *
< 0.001
Type of insulin treatment
3 groups *
weight **
Insulin units per gram of
carbohydrate in TPN **
Capillary blood glucose
mean mg/dL *
Mean capillary blood
glucose
3 groups *
mg/dL *
% blood glucose >180
mg/dL *
Data are means ± SD or n (%) unless otherwise indicated. TPN, total parenteral nutrition. BMI,
body mass index. SC, subcutaneous. IV, intravenous
* During TPN infusion
** Only includes patients who received insulin during TPN.