Diabetes mellitus (DM) is a major health problem due to its prevalence, mortality and cost. The International Diabetes Federation estimated in 2014 its global prevalence at 8.3% [1
]. Moreover, it imposes a large and growing economic burden on the health-care system and society [2
] due to the increase in the number of people with diagnosed diabetes, the increased frequency of chronic complications and the wider application of new and expensive technologies and treatments [5
Disease-related malnutrition is common in diabetic patients [6
]. It is present in 21.2% of hospitalized older diabetics [7
]. Hospital related malnutrition is associated with treatment intolerance, poor prognosis, increased hospital-acquired infections, poor wound healing and longer hospitalizations [8
Diabetes-specific enteral nutritional formulas are postulated as effective alternatives for nutritional treatment in diabetic subjects, being associated with maintenance of glycemic control [9
], due to their content of slowly digested and absorbed carbohydrates and monounsaturated fats [9
]. Nevertheless, the long-term benefits on glycemic control or the economic impact of such formulas are unclear [6
]. For a product intervention to represent a good value, it should not only be efficacious but also be worth the scarce resources that were given up to purchase it [13
The objective of this study is to assess the effect of enteral supplementation with the hypercaloric diabetes-specific formula (HDSF) Glucerna® 1.5 Cal, from Abbott Nutrition, on the use of health-care resources, health-care costs, glucose control (short- and long-term) and nutritional status in type-2 diabetes mellitus (T2DM) older malnourished patients in a real life setting.
Data from 93 patients were included in the study. Mean (SD) age was 84.9 (10.8) years, 48.4% were males. Most of the subjects (75.3%) were living at home, and 22.6% lived in nursing homes. Mean (SD) BMI was 23.55 (3.16) kg/cm2
and mean (SD) time since the diagnosis of T2DM was 7.6 (4.8) years. Before starting oral supplementation, mean (SD) HbA1c was 6.62% (1.44%) and subjects were treated with metformin (26%), insulin glargine (19%), sulfonylureas (17%) or other oral drugs. One out of four (23%) received no drug treatment. Most subjects (91%) presented at least one comorbidity, hypertension (80%), dyslipidemia (63%) and heart diseases (51%) being the most common. Complications of diabetes were present in roughly one of five (neuropathy 22%, nephropathy 18%, and retinopathy 18%). Mean Charlson index was 4.8 (1.6), with 44% of the sample having values between four and five, defining high load of comorbidity (Table 1
3.1. Use of Health-Care Resources and Health-Care Costs
The sample health-care resources consumption was significantly reduced after the instauration of the HDSF. The mean (SD) number of hospital admissions decreased significantly from 1.0 (1.2) in the year before intervention to 0.4 (0.8) in the year of nutrition intervention (54.7% decrease, p
< 0.001). The same happened with the number of days in hospital, falling from 14.77 (22.73) to 5.30 (12.94) days (64.1% drop, p
< 0.001). The number of visits to the emergency department also decreased from 1.89 (1.68) to 0.80 (0.95) (57.7%, p
< 0.001) (Figure 1
In addition, gross hospitalization costs were also significantly reduced from a mean ± (SD) of €7,177 ± €11,700.57 ($10,016.10 ± $16,329.12) to €2,468 ± €6,270.84 ($3,444.30 ± $8,751.48) per patient (65.6% per patient, p
< 0.001). If the overrun of using an HDSF instead of a standard formula (€1,830.84) ($2,555.09) is added to the hospitalization cost after the enteral nutrition, this cost would still be reduced by 40%, from a mean (SD) of €7,177 ± €11,700.57 ($10,016.10 ± $16,329.12) to €4,298.87 ± €6,270.84 ($5,999.43 ± $8,751.48) (p
< 0.182) (Figure 2
3.2. Glucose Control Status
The supplementation with HDSF maintained glycemic control. Glucose decreased non-significantly from a mean of 129 mg/dL to 123 mg/dL, while HbA1c was 6.62% at baseline and 6.45% (p
= 0.143) after nutrition intervention (Table 2
). Moreover, the percentage of patients with HbA1c levels ≤ 7.5% increased after the nutritional treatment from 69.9% to 78.5%.
3.3. Nutritional Laboratory Parameters
After the supplementation with HDSF, there was an improvement in most of the sample nutritional parameters. Albumin and hemoglobin significantly increased by 10.6%, from 3.12 to 3.45 mg/dL and by 6.4%, from 11.35 g/dL to 12.08 g/dL, respectively. The lipid profile also improved, being that the HDL increased 2.4%, while the LDL and triglycerides decreased 2.4% and 8.9%, respectively. Finally, ferritin values diminished 35.7%, while vitamins B9
increased 12.9% and 27.1%, respectively (Table 2
3.4. Cost Per Controlled Patient
Of the 93 patients included in the study, 22 (23.7%) achieved the first composite endpoint (HbA1c < 8.0% and albumin > 3.6 g/dL) and 20 (21.5%) reached the second composite endpoint (HbA1c ≤ 7.5% and albumin ≥ 3.6 g/dL). The cost per controlled patient reaching the first and second composite endpoints was €31,207.39 ($43,552.50) and €34,328.13 ($47,907.76), respectively.
3.5. Correlation and Regression Analysis
To assess the relation between the use of resources and the HDSF administration, changes in use of health-care resources and health-care costs were correlated with changes in glycemic control variables and with changes in laboratory parameters.
A statistically significant (p < 0.05) direct correlation was found between the variation in HbA1c and the change in hospitalization length, hospitalization costs and hospitalization plus HDSF overrun costs and between variations in glucose and the change in the number of emergency visits. Increments in HbA1c were associated with longer hospitalizations and increased costs and greater glucose values were associated with higher number of emergency visits.
Variations on the hemoglobin and lymphocyte count were indirectly correlated with the variation in hospitalization length and cost, being that an increment in the hemoglobin value or in the lymphocyte count was associated with lesser hospitalizations length and cost. Statistically significant correlations (p
< 0.05) are presented in Table 3
A multivariate regression analysis to assess whether changes in nutritional and glycemic clinical parameters could explain changes in hospitalization costs associated with the treatment of diabetic malnourished patients was performed, considering the latter as the dependent variable. Results showed that an appropriate improvement in hemoglobin levels may predict a reduction in hospitalization expenses (regression coefficient −3167.2; p = 0.010).
Diabetes mellitus places a considerable burden on patients in terms of morbidity and mortality and on the society in terms of costs [19
]. Diabetic patients are at risk of both malnutrition [11
] and hospital readmissions [20
], often requiring nutritional support [10
]. Enteral HDSF have been specially developed for the treatment of malnourished diabetic patients, as well as for maintaining glycemic control [10
] which, if not managed, can have profound consequences on clinical outcomes [23
This study explored the effect of an HDSF on the use of health-care resources, health-care costs, glycemic control and nutritional status when prescribed to treat malnutrition in older diabetic patients. Results show that the administration of the HDSF was associated with less use of health care resources. There was a health-care costs reduction, even if the excess cost of the formula (compared with formulas used to treat malnourished non-diabetic patients) is taken into account. Excess hospitalization and longer hospital stays can be seen as quality indicators of diabetes care [24
]. Ordoñez et al
] reported that nutritional status influenced the length of stay and clinical outcomes in hospitalized patients. Hamdy et al
] analyzed clinical variables and real cost data from 125,000 hospital inpatient episodes over a 10-year period, further confirming that the use of “glycemia-targeted specialized nutrition” on malnourished diabetics significantly improved health-care efficiency reducing the length of hospitalizations and episodes costs compared to standard formulas, where the cost of the billable glycemia-targeted or standard product was included.
In line with these findings and despite HDSFs being more expensive than standard formulas, a net global saving in hospitalization costs was found in the present analysis. These savings in hospitalization costs can be considered paramount given the exponential increment on health-care costs observed after the age of 50 years [26
] and to the extra costs associated with malnutrition (up to €5,829 ($8,134.85) per patient) [27
]. Moreover, the indirect cost savings associated with the decrease in hospitalizations, the economic benefits related to avoiding insulinizations or the possible improvement in patients’ and carers’ Health-Related Quality of Life (HRQoL) have not been considered, which could translate into additional benefits.
Our results showed that patients’ glucose and HbA1c were unchanged with nutritional intervention, even with a large increase in caloric intake (up to 660 kcal/day with optimal compliance) needed in a malnutrition setting. In addition, the percentage of patients with HbA1c ≤ 7.5%, an indicator of good glycemic control in older patients [16
], increased with the nutritional support, avoiding new patient insulinization or a change in the glucose-lowering drug treatment. Other publications have shown similar findings. The systematic review of Elia et al.
] showed that DSFs improved glycemic control, compared to standard formulas. Lansink et al.
] published a study with T2DM patients receiving either specific or standard formula, finding that the HDSF did not affect fasting glucose levels and contributed to improving glycemic control. Finally, the systematic review published by Ojo et al.
] concluded that HDSF was more effective controlling glucose profiles, including postprandial glucose, HbA1c and insulinemic response. However, this is the first study that shows the effect of HDSF on patients’ glycemic control during one-year follow up.
Some laboratory parameters related to malnutrition were improved, with significant increases in albumin and hemoglobin after intervention. Although some have cautioned against using albumin as a measure of nutritional status due to its association with other clinical phenomena such as inflammation [28
]. In situations of clinical stability in older people living in the community, albumin could be a good marker of nutritional status [17
]. Moreover, anemia has been found to be associated with hypoalbuminemia and malnutrition in geriatric populations [29
Other nutritional variables such as creatinine, HDL, lymphocytes and vitamins B9
were also enhanced, although the differences were not significant. Nonetheless, the lack of statistical significance does not necessarily mean absence of clinical relevance [30
], indicating that the general improvement in nutritional status in the context of malnutrition should be taken under consideration.
Despite its higher acquisition charge, the costs per controlled patient (with two different definitions, HbA1c < 8.0%/albumin > 3.6 g/dL and HbA1c < 7.5%/albumin > 3.6 g/dL) with HDSF were €31,207.39 ($43,552.50) and €34,328.13 ($47,907.76), respectively. Although the values are not comparable, a reasonable threshold for the willingness to pay for each quality adjusted life years according to National Institute for Health and Care Excellence (NICE) guidelines would be within a range of £20,000 ($29,412) to £30,000 ($44,118) [31
], giving an idea of the value for money obtained from implementing the treatment with HDSF. This cost estimation offers the advantage of trading off the cost and effect of the HDSF and is suitable for a short time horizon such as the one used in this analysis, where standardized benefit outcomes as quality-adjusted life years are less appropriate. However, this approach does not provide any willingness to pay contexts and constitutes an outcome measure specific for malnourished diabetic patients [18
Significant relationships were found between the improvement in HbA1c, glucose parameters and hemoglobin, and the decrease in health-care resources use and health-care costs, indicating that the control of glycemic parameters and the improvement in general nutritional status is related to hospitalization cost and health-care resources spent reduction. Moreover, a multivariate regression demonstrated that hemoglobin improvement can predict lower health-care costs. Hemoglobin has been proposed as a valuable marker of nutritional status [32
]. Serum levels of hemoglobin are a biochemical indicator routinely used by clinicians to monitor nutritional status in chronically critically ill patients [33
]. In this sense, a negative and significant but weak correlation between hemoglobin (as a nutritional indicator) and the duration of patient hospital stays has been previously demonstrated [34
] in hospitalized adult and elderly patients.
This study has limitations common in observational retrospective database studies, such as the inability to control for data not captured. The use of each subject as its own control may allow for other not controlled confounding factors to partially explain the results, as changes in health condition and in utilization of health care resources after initation of HDSF may be related to the supplement or to other concomitant factors. To reduce this potential risk, acute diseases or surgical procedures before HDSF prescription were ruled out because of their potential confounding effect on malnutrition diagnostic criteria. Furthermore, no evident change in approach to care or in providers after initiation of HDSF happened in any subject that was performed in a single center and by a single team, the only nutrition team in the area.
Compliance with the intervention could not be properly assessed. However, the main nutritional parameters were available for the majority of patients (albumin accessible for 100% and HbA1c for 90.3% of the patients). More studies including safety variables related to glycemic control, such as hypoglycemias, should be performed to explore other outcomes associated to HDSF, although the fact that changes in the pharmacologic treatment were not necessary might suggest that hypoglycemias were not frequent in this population.
Finally, the presented information should be analyzed in its context since the data included represent a specific population; however, we feel that this is an interesting contribution to the literature on the health economic benefit of diabetes specific formulations for malnourished patients with T2DM.