European Journal of Cardiovascular Medicine

Diabetes mellitus, a complex metabolic disorder characterized by blood sugar and insulin dysregulation, has an estimated global prevalence of more than 425 million people, and the number of people with the disease is set to rise to 629 million in 2045. ^[1] This will impose a substantial burden on patients, caregivers, health systems, and the economy. ^[2] Diabetes mellitus requires continuous medical care with multifactorial risk-reduction strategies beyond glycemic control. ^[3]

People with well-controlled diabetes can live long and healthy lives with interprofessional management emphasizing optimal, individualized care. ^[4] However, this reality can be a challenge for people with diabetes and their families. The ineffective management of glycemia may result in hyperglycemia or hypoglycemia, and the maintenance of these conditions can result in multiple health complications. In patients with diabetes, hyperglycemia is the sum of the fasting and postprandial elevation in blood glucose. ^[5] The preprandial versus postprandial patient self-monitoring of blood glucose targets is a complex issue. Currently, the glycemic recommendation of the American Diabetes Association (ADA) for premeal glucose target in nonpregnant adults with diabetes is 80 to 130 mg/dL (4.4 to 7.2 mmol/L), and postprandial plasma glucose target one to two hours after the start of a meal is 180 mg/dL (10.0 mmol/ L). Hypoglycemia is the sum of the fasting and postprandial decrease in blood glucose, and because many people with diabetes demonstrate impaired counter-regulatory responses to hypoglycemia and/ or experience hypoglycemia unawareness, a measured glucose level < 70 mg/dL (3.9 mmol/L) is considered clinically important, independent of the severity of acute hypoglycemic symptoms. ^[6]

Most observational studies have found that hyperglycemia and hypoglycemia result in severe complications: adverse outcomes in patients receiving critical care; risk of developing pancreatic ductal adenocarcinoma, one of the leading causes of organ failure; major risk factors for dementia ; increased risk of hospitalization and unplanned readmission; as well asincreased costs, hospital length of stay, and mortality and morbidity attributable to cardiovascular, cerebrovascular, and fall events. ^[7] Within nursing practice, it is critical to identify relevant causal factors, independently modified by a professional nurse, and associated conditions not independently modified by a professional nurse. The nursing diagnosis of risk for unstable blood glucose level contributes to the management of diabetes and minimizes the chances of complications for patients and families.

A risk factor refers to ‘‘any attribute, characteristic, or exposure of an individual, which increases the likelihood of developing a noncommunicable disease.’’ ^[8] (p.3) as a component of the nursing diagnosis, risk factors are ‘‘environmental factors and physiological, psychological, genetic, or chemical elements that increase the vulnerability of an individual, family group, or community to an unhealthy event.’’ ^[9] (p.39) In clinical judgment, risk factors are essential elements contributing to an accurate diagnosis. A nursing diagnosis of risk is a clinical judgment concerning the susceptibility for developing an undesirable response to health conditions or life processes. ^[10]

It is through the characterization of these factors that nurses can plan and intervene accurately in the control of serum glucose levels in people with or without diabetes. The nursing diagnosis ‘‘risk for unstable blood glucose level’’ reveals the susceptibility to variation in serum glucose levels in relation to the normal range that can compromise health. ^[11] Through this diagnosis, it is possible to predict the susceptibility for people with diabetes to experience hyperglycemia or hypoglycemia, which may reveal the inadequate control of the glycemia, the lack of adherence to the therapeutic regimen, or the difficulty in changing life habits. However, according to the NANDA International Nursing Diagnoses, the risk for unstable blood glucose level is a nursing diagnosis with a level of evidence of 2.1, demanding a concept analysis. ^[12] A systematic literature review is recommended to identify and synthesize risk factors for hyperglycemia or hypoglycemia in adults with type 2 diabetes mellitus (T2DM) in continuous drug therapy. The results could contribute to important information and evidence for clinicians and nurses, and the refinement of nursing knowledge.

Studies around the world have explored which factors are associated with episodes of alteration of blood glucose level. A nationwide, population-based cohort study developed in South Korea with patients with T2DM found that several indicators could independently predict an increased risk of severe hypoglycemia. ^[13] These patients were older, female, had been managing diabetes for a prolonged period, had a low body mass index used insulin or multiple classes of glucose-lowering medications, smoked, drank alcohol, did not exercise, exhibited hypertension or chronic kidney disease, and had a history of severe hypoglycemia, multiple comorbidities, and low or high glucose levels. A multicenter, crosssectional survey of Muslim patients with diabetes investigated Ramadan fasting and found that the hypoglycemia group were significantly younger; patients with hypoglycemia had been diabetic for a significantly longer period; and patients with type 1 diabetes mellitus had a higher risk of hypoglycemia. ^[14] A retrospective observational study conducted in an outpatient clinic in northern Taiwan investigated the changes in blood sugar in patients with T2DM when traveling abroad. The results showed that the hypoglycemic episodes were associated with the number of times the patients had crossed time zones. ^[15]

A preliminary search was conducted in PROSPERO, MEDLINE, Cochrane Database of Systematic Reviews, and the JBI Database of Systematic Reviews and Implementation Reports, and no current or in-progress systematic reviews on the topic were identified. The objective of this review is to identify and synthesize the exposures for hyperglycemia or hypoglycemia in adults with pharmacologically treated T2DM in any scenarios and environments for health care.

This study was a prospective cohort study conducted at Department of Medicine and Psychiatry, Malla Reddy Institute of Medical sciences. The clinic treats patients with various complications. Based on medical records, there were 4129 subjects with diabetes. A consecutive recruitment method was performed from October 2016 to January 2017. The inclusion criteria were T2DM patients, aged more than 18 years, who had regularly visited the clinic for at least one year. The exclusion criteria were pregnancy, psychiatric disorders, and insufcient clinical information recorded. This study was approved by Ethical Committee of Faculty of Medicine. Informed consent was obtained from all subjects. All methods were carried out according with relevant guidelines and regulations.

Te primary outcome of this study was any event(s) of severe hypoglycemia within the past year, which was asked to the subject during the subjects’ visit. We used the 2018 American Diabetes Association (ADA) defnition of severe hypoglycemia, which was an event of hypoglycemia, associated with severe cognitive impairment requiring external assistance for recovery, with or without plasma glucose concentration17. Te risk factors for severe hypoglycemia included in this study were age, level of education, subjects understanding of hypoglycemia symptoms, HbA1c levels, duration of T2DM, chronic kidney disease (CKD), decompensated chronic liver disease (CLD), history of previous severe hypoglycemia, self-monitoring of blood glucose (SMBG) application, sulfonylurea (SU) use, and insulin use. Data regarding those risk factors were taken from the subjects’ medical records one year before data collection, except for subjects’ understanding of hypoglycemia.

Subjects’ understanding of hypoglycemia was defned as subjects’ ability to mention at least three neuroglycopenic symptoms of hypoglycemia18. Chronic kidney disease (CKD) was defined as having impaired renal function for at least three months, assessed based on estimated glomerular fltration rate (e-GFR)18. Decompensated CLD was defned as having Child–Pugh Score of more than 10 (C)19. Self-monitoring of blood glucose (SMBG) application was defned as well-performed if the frequency of blood glucose monitoring in a week was by the recommendation from the Indonesian Society of Endocrinology (PERKENI), which vary according to subjects’ T2DM treatment regimen20.

Statistical analysis was conducted using SPSS Statistics for Windows, Version 20.0. Missing risk factors data were flled in using multiple imputation techniques. We presented continuous variables with mean and standard deviations (SD) or median and interquartile range (IQR), while nominal variables with counts and percentages. Te normality test was assessed using the Kolmogorov Smirnov. Bivariate analysis was performed using chisquare test. Using a multiple logistic regression test, all variables in bivariate analysis with a p value less than 0.25 were included in multivariate analysis. Te estimation of association was presented as odds ratio (OR). Te risk factor model was developed by calculating the coefcient formula divided by the standard error for the related variable.

A total of 100 patients with T2DM were interviewed. The median age was 56 years. Most of the patients were female (74%). The family type was nuclear in 54% and majority of them were either retired or homemakers (68%). Among them, 34.6% of the patients were illiterate, 30% of them had completed only primary school, 30.8% had middle school education, 3.6% had high school education, and only 0.8% was graduates/postgraduates. The mean (SD) per capita income of the patients was INR2849 (INR3668) (USD1 ≈ INR70). Among the patients, 32% had diabetes for more than 10 years. Mean duration of diabetes was 6.83 years. Body mass index (BMI) of >25 kg/m2 was found in 57.9% of the patients. The mean (SD) of the BMI was 26 (11.45) kg/m2 . The mean (SD) of HbA1c level was 7% (1.72%) and the maximum documented level was 13%. HbA1c levels were more than 6.5% in 56.4% of the study population. All patients were either on metformin or on combination of metformin with glibenclamide/glynase. Only 5 (5%) of them were on insulin along with oral drug combinations. Among the diabetic patients, 55% had some comorbidities like hypertension (41.8%), cardiovascular complications (4.4%), or renal problems (0.5%). The background variables are given in Table 1.

Table 1. Background characteristics.

Hypoglycemic episodes were reported in 50 of the 100 diabetic patients. The prevalence of hypoglycemia was estimated to be 57.44% (95% CI 52.48-62.25) Among the 50 patients with hypoglycemia, 77.7% were female. Severe hypoglycemia requiring help from other persons or medical assistance for plasma glucose correction was prevalent among 24 (10.7%) patients who had hypoglycemia. Of those patients with severe episodes, hospital admission and plasma glucose correction were required for 7 (29.17%). A total of 11.6% of the hypoglycemic patients had symptoms daily; 21.9% of them had 2 to 3 episodes in a week, and almost half (48.2%) had 2 to 3 episodes a month, while it was rare among 18.3%. The details of the symptoms of hypoglycemia are in Table 2. The other symptoms were epigastric pain, nausea, and sleep (0.4%) each. The first symptom of hypoglycemia was dizziness, which was reported in 72.3% of the individuals. This was followed by sweating in 44.2% of them (Table 2). The most common self-reported etiological factor for the hypoglycemic episode was missing food or delayed food intake, which was seen in 200 patients (90%; Figure 1). The majority of them (56.7%) ate the missed-out meal and were relieved of the symptoms (Figure 2).

Table 2. Most Common Symptoms of Hypoglycemia.

It was found that only 21.9% of the patients reported such symptoms to the medical practitioner. Moreover, only 23% of the diabetic patients carried glucose with them when they went out. Most of the patients (89.3%) who received treatment at the rural center checked their plasma glucose levels every 3 months. A total of 5.4% of them checked even more frequently and 5.4% of the patients did not check their levels regularly. None of them could afford a glucometer for self-monitoring their glucose levels. The present study showed that female patients were at a higher risk of developing hypoglycemia compared with the male patients (OR 1.3, 95% CI 1.05-1.5, P < .05). Patients with higher fasting blood sugar levels had an increased risk of hypoglycemic episodes; it was not statistically significant (Table 3).

Table 3. Factors Associated With Self-Reported Hypoglycemia.

The current study was a part of the project undertaken in a rural health center in Tamil Nadu with the objective to find the prevalence of self-reported hypoglycemia and its associated risk factors among all the patients with T2DM who were registered at the center. All patients with T2DM who were undergoing regular treatment at the center who consented were included in the study. The study results can be generalized to any primary health center or a diabetic clinic where patients are receiving treatment. This study was done in a primary health care setting, which is a common setting in the Indian population as it is where first contact of the patient happens with the physician. It was found that 224 patients (57.43%, 95% CI 52.48-62.25) had hypoglycemic episodes. The narrow confidence interval indicates that the study has good internal validity and sufficient sample size. Marrett reported that 63 % of patients with T2DM had symptoms of hypoglycemic episodes of which 46% were mild, 37% moderate, 13% severe, and 4% very severe. Study by Shriraam found the prevalence of any one symptom of hypoglycemia as 78.1% who fit in the operational definition of relief of symptom on intake of glucose. The study setting was in a tertiary care hospital where severe hypoglycemia was reported among 19% of the patients. However, in the present study, severe hypoglycemic episodes were less (10%). In another survey done by the American Association of Clinical Endocrinologists, 20% of the diabetic patients required assistance for hypoglycemic episodes and 6% required hospitalization for the same. The first symptom of hypoglycemia was dizziness followed by sweating in the present study. Similar first symptom of dizziness was reported in another study in a tertiary care hospital.

Miller conducted a retrospective interview among patients with T2DM and reported a prevalence of 16% hypoglycemia among patients on oral hypoglycemic agents compared with 30% prevalence among those on insulin therapy. In the rural setting, very few people (4.6%) were on insulin; hence the association of hypoglycemia with insulin therapy could not be established.

The most common situation where hypoglycemia developed was a missed meal, which was observed in 89.3% of the patients. Similar findings were observed in another study, where 87% of the patients reported a missed meal as the etiological factor. This indicates the importance of education to the patients about consuming meals at the right time that would prevent episodes of hypoglycemia.

Women were at a higher risk of developing hypoglycemia. The reason for this could be that in Indian culture, women in general consume meals only after their spouses complete their meal. It is important to educate patients as well as the family members regarding timely meals in diabetic elderly women, which would help in preventing hypoglycemia.

Limitations

As the patients belonged to a lower socioeconomic status in a rural, low-resource setting, there was no possibility of measuring plasma glucose concentration at the time of the hypoglycemic episode. Therefore, the exact prevalence of these episodes is a challenge to measure. The accuracy of the prevalence of self-reported hypoglycemia may have been affected by patient recall especially when the event has been mild.29 It could also be affected by the individual’s ability to identify the episode as a hypoglycemic event, as it is essential for the patient to differentiate hypoglycemic symptoms and other nonrelated symptoms. There is a possibility of underestimate of the exact prevalence.

As the most common cause of these episodes is a delayed or a missed meal, there is a possibility of this occurring in normal individuals also. These symptoms are more frequent and much exaggerated in diabetic patients, which require proper preventive measures.

Strengths

This is the first study done to estimate the prevalence of hypoglycemia in a rural health center where the resources are limited. This study throws light on the high prevalence of hypoglycemic episodes in the rural population. Even in the near future, it is impossible to document hypoglycemia by glucose measurement in India especially in a rural setting. This is the best way possible to document hypoglycemia.

Hypoglycemia is highly prevalent among the diabetic patients treated in the rural health center. It is to be noted that 10% of them had severe episodes of hypoglycemia. Only a fifth of the patients reported symptoms to the medical practitioner. This implies that it is essential for the primary care physicians to enquire about the symptoms of hypoglycemia to all the patients at every visit. It is highly essential to educate the diabetic patients about symptoms of hypoglycemia and the importance of reporting such episodes to the doctor. The patients should be emphasized about the importance of carrying glucose in hand to tackle hypoglycemic episodes.

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