|Year : 2022 | Volume
| Issue : 2 | Page : 76-87
Minimizing hypoglycemia with insulin therapy: The “THINK” strategy
Gagan Priya1, Emmy Grewal2
1 Department of Endocrinology, Fortis Hospital, Mohali, Punjab, India
2 Department of Endocrinology, Max Hospital, Mohali, Punjab, India
|Date of Submission||04-May-2022|
|Date of Decision||13-May-2022|
|Date of Acceptance||14-May-2022|
|Date of Web Publication||16-Jul-2022|
Department of Endocrinology, Fortis Hospital, Phase 8, Mohali - 160 059, Punjab
Source of Support: None, Conflict of Interest: None
Iatrogenic hypoglycemia is the most feared and common complication of insulin therapy. Hypoglycemia can have serious consequences and can be potentially life-threatening. In addition to the neurological manifestations of severe hypoglycemia, hypoglycemia may be associated with cognitive dysfunction, cardiovascular events, arrhythmias, and increased mortality. Recurrent episodes of hypoglycemia may lead to hypoglycemia unawareness, which increases the risk of severe hypoglycemia. Therefore, prevention of hypoglycemia remains a priority in persons with diabetes on insulin therapy. The “THINK” strategy provides a comprehensive approach for diabetes care providers to minimize the risk of hypoglycemia related to insulin therapy by mitigating factors that increase the risk. This requires setting reasonable glycemic Targets keeping in mind a person's risk of hypoglycemia; choosing the right Tools such as insulin formulation and regimen with lower risk and adequate glucose monitoring; judicious Titration of insulin doses; use of modern Technology such as continuous glucose monitoring, continuous subcutaneous insulin infusion, and sensor augmented pumps in patients at high risk; maintaining Harmony between insulin dose, diet, physical activity, and changes in lifestyle; Individualization of diabetes therapy; ensuring there are No errors in insulin administration; and empowering patients with Knowledge about hypoglycemia. The THINK strategy offers a handy tool for tailoring insulin therapy to minimize hypoglycemia risk.
Keywords: Hypoglycemia prevention, hypoglycemia unawareness, hypoglycemia, insulin therapy, nocturnal hypoglycemia, severe hypoglycemia
|How to cite this article:|
Priya G, Grewal E. Minimizing hypoglycemia with insulin therapy: The “THINK” strategy. Chron Diabetes Res Pract 2022;1:76-87
|How to cite this URL:|
Priya G, Grewal E. Minimizing hypoglycemia with insulin therapy: The “THINK” strategy. Chron Diabetes Res Pract [serial online] 2022 [cited 2023 Mar 29];1:76-87. Available from: https://cdrpj.org//text.asp?2022/1/2/76/351261
| Introduction|| |
Iatrogenic hypoglycemia is the most feared complication of insulin therapy. It can significantly add to diabetes-related morbidity and can be potentially life-threatening. The fear of hypoglycemia with insulin among persons with diabetes as well as diabetes care providers poses a formidable barrier to its optimal utilization.
Hypoglycemia Assessment Tool study reported a high incidence of self-reported hypoglycemia in individuals with Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) with overall rates (events/patient-year) of 73.3 in T1DM and 19.3 in T2DM. Severe hypoglycemia was reported at an event rate of 4.9 in T1DM and 2.5 in T2DM. Even though hypoglycemia is less common in T2DM than T1DM, the risk remains significant in persons with T2DM on insulin, especially in elderly and those with long-standing disease or comorbidities. In a meta-analysis of population-based studies including 532,542 patients with T2DM, the incidence of hypoglycemia was 23/person-year for mild–moderate episodes and 1/person-year for severe episodes in patients on insulin. The occurrence of asymptomatic hypoglycemia with insulin therapy seems to be even higher. Continuous glucose monitoring (CGM) studies suggest that the incidence of asymptomatic episodes can be as high as 63% in T1DM and 47% in T2DM.
With the advent of more physiological insulin preparations and modes of delivery, while a clear reduction in the incidence of severe hypoglycemia is reported in clinical trials, the occurrence of severe episodes in observational studies continues to remain high. The estimated rates of severe hypoglycemic events are 110–320/100 patient-years in T1DM and 10–70/100 patient-years for T2DM.
| Defining hypoglycemia|| |
Traditionally, hypoglycemia was defined by the fulfillment of 3 criteria (Whipple's triad): the occurrence of typical clinical symptoms, documented low plasma glucose, and relief of symptoms with the correction of glucose levels. From the perspective of diabetes therapy, the American Diabetes Association defines hypoglycemia as an episode of abnormally low plasma glucose that can lead to patient harm.,,,, The definition has been changing over time [Table 1], leading to variations in its reported incidence in various studies.
| Factors leading to increased risk of hypoglycemia|| |
In normal physiology, even a small decline in blood glucose triggers compensatory homeostatic responses to restore levels into normal range. These counter-regulatory mechanisms include suppression of endogenous insulin secretion and increase in glucagon secretion, followed by increased secretion of epinephrine and cortisol. The risk of hypoglycemia is inherent to exogenous insulin therapy because serum insulin levels remain elevated despite a fall in blood glucose. In addition, with critical reduction in islet cells, persons with T1DM and long-standing T2DM also have impaired glucagon secretion. Epinephrine secretion may also be impaired in patients with long-standing diabetes. Defective glucose counter-regulation significantly increases the risk of hypoglycemia. Seminal clinical trials have suggested that the risk of hypoglycemia, including severe hypoglycemia, invariably increased with intensive glycemic control.,,
The various factors that contribute to increased risk of hypoglycemia with insulin therapy are enlisted in [Table 2].
|Table 2: Factors increasing the risk of hypoglycemia with insulin therapy|
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| Risks Associated with Hypoglycemia|| |
Hypoglycemia can have a significant negative impact [Table 3] and can be potentially life-threatening.,,, Nocturnal hypoglycemia with insulin therapy is common and accounted for 43% of all hypoglycemic episodes and 55% of severe episodes in the Diabetes Control and Complications (DCCT) trial. Nocturnal hypoglycemia can be particularly dangerous as patients may not be able to recognize warning symptoms during sleep. Undetected nocturnal hypoglycemia can lead to significant anxiety, hypoglycemia unawareness, severe hypoglycemia, and neurocognitive deficits.
Patients who have recurrent episodes of hypoglycemia may develop impaired awareness of hypoglycemia, which ultimately predisposes them to severe hypoglycemia and altered sensorium. Hypoglycemia unawareness can occur due to several causes that may lead to a blunted plasma epinephrine and norepinephrine response to hypoglycemia. Patients with long-standing diabetes and autonomic neuropathy or those who have recurrent hypoglycemic episodes are at greater risk. Some patients may develop hypoglycemia-associated autonomic failure that is characterized by defective counter-regulation as well as impaired awareness. However, hypoglycemia awareness can be restored if episodes of hypoglycemia are strictly avoided for a few months.
Therefore, prevention of hypoglycemia remains a priority in persons with diabetes, especially in those who are on insulin therapy. However, in clinical practice, hypoglycemia prevention with antidiabetic medications, especially insulin, remains an unmet need. There is a need to increase awareness about hypoglycemia among diabetes care providers as well as persons with diabetes and their caregivers and to devise therapeutic plans that not only target optimal metabolic control but also minimize the risk of hypoglycemia.
| The “Think” Strategy|| |
A framework for minimizing the risk of hypoglycemia related to insulin treatment will be of use to diabetes care providers. For this review, we suggest an innovative “THINK” strategy (Targets, Tools, Titration, Technology, Harmony, Individualization, No errors, and Knowledge), and discuss its individual parameters. “THINK” [Table 4] and [Figure 1] is a ready reckoner for diabetes care providers when initiating and monitoring insulin therapy.
|Table 4: The “THINK” strategy to minimize the risk of hypoglycemia with insulin therapy|
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|Figure 1: The “THINK” strategy for prevention of hypoglycemia with insulin therapy|
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| Targets|| |
Seminal trials such as the United Kingdom Prospective Diabetes Study and DCCT have highlighted the need for intensive glycemic control to reduce the risk of long-term complications. Subsequent studies such as the Action to Control Cardiovascular Risk in Diabetes, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, and Veterans Affairs Diabetes Trial suggested that intensive glucose-lowering does not confer similar benefits in patients with long-standing diabetes. Further, the risk of hypoglycemia was substantially higher with intensive control.,
There is a need to determine glycemic targets for each patient keeping in mind the risk–benefit ratio of intensive glycemic control. The factors to be considered include the duration of diabetes, life expectancy, presence of macro- and microvascular complications and other comorbidities, and susceptibility to hypoglycemia [Table 5]. This has been highlighted in various guidelines. Targets should be relaxed for patients with long-standing diabetes, frail elderly individuals, those with limited life-expectancy, cardiovascular disease, and chronic kidney disease, or those at greater risk of hypoglycemia, recurrent hypoglycemia, or hypoglycemia unawareness.
| Tools|| |
Optimized insulin therapy that achieves desired targets without increasing the risk of hypoglycemia requires choosing the right tools, including the type of insulin, insulin regimen, delivery device, and glucose monitoring.
Choice of insulin formulation
Choosing the right type of insulin formulation to fit the patient's profile is of utmost importance. Conventional insulin formulations (regular insulin, Neutral Protamine Hagedorn [NPH] insulin, and premixed human insulin) are associated with a greater risk of hypoglycemia. This is because of inherent limitations in their time–action profiles, which do not mimic physiological insulin secretion. Regular human insulin has a delayed onset and longer duration of action that does not match prandial insulin release. NPH has a distinct peak at 4–6 h with a duration of action of 12–18 h, which makes it less ideal as a basal insulin. In addition, the absorption of NPH-based insulins is highly variable. Therefore, these conventional insulins are associated with a greater risk of overall, nocturnal, and late postprandial hypoglycemia.
New-generation insulins have significantly less hypoglycemia risk than human insulins. Rapid-acting insulin analogs have faster onset and shorter duration of action and are associated with less risk of late postprandial hypoglycemia than regular insulin. In trials, they were associated with reduced risk of nocturnal hypoglycemia by 45% and severe hypoglycemia by 20%. When compared to NPH, insulin glargine (U-100) and detemir have a relatively flat time–action profile and significantly lower risk of overall and nocturnal hypoglycemia in both T1DM and T2DM.,,, Furthermore, ultra-long basal insulins such as U-300 glargine and degludec have flat and stable time–action profile and offer even lower risk of hypoglycemia compared to U-100 glargine. These newer ultra-long analogs further reduce the risk of nocturnal hypoglycemia over glargine by 25%.
While the risk of overall hypoglycemia was reported to be similar with analog premix insulin compared to human premix insulin, the risk of nocturnal and major hypoglycemia episodes was significantly lower., The risk of nocturnal and confirmed hypoglycemia is further reduced with insulin aspart-degludec coformulation compared to biphasic aspart.
Most insulin trials have a noninferiority and treat-to-target design and usually exclude patients at high risk of hypoglycemia. Hence, they are likely to underestimate the benefits of newer insulins in patients at greater risk of hypoglycemia. Therefore, most guidelines recommend that insulin analogs be preferred over conventional insulins due to their lower risk of hypoglycemia.,
Choice of insulin regimen and delivery device
Insulin regimen should be tailored to the current glycemic status and dominant glucose trends, dietary and exercise habits, and patient expectations.
Basal insulin added to other antidiabetic medications (oral or injectable) is the most common insulin regimen recommended for insulin initiation in persons with T2DM. This offers lower risk of hypoglycemia, especially with newer basal insulin analogs. Premix insulin analogs and basal bolus regimens are used for intensification of insulin therapy but require more frequent monitoring of blood glucose and appropriate dose titration. Premix insulin-based regimens offer less flexibility in meal timings than basal alone or basal-plus regimens with resultant increased hypoglycemia risk.
For patients with T1DM or patients with T2DM who have significant insulinopenia, a standard basal bolus or multiple daily injections (MDI) regimen and insulin pumps using insulin analogs offer the most physiological replacement strategy and lower risk of hypoglycemia. MDI also offers flexibility and ability to individually titrate basal and prandial insulin doses.
Concomitant use of sulfonylureas and glinides in persons with T2DM may increase the risk of hypoglycemia. While insulin secretatogues can be continued with basal insulin, their use is best avoided along with more intensive regimens of premix insulin or basal-bolus insulin. On the other hand, the risk of hypoglycemia is less with concomitant use of metformin, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, sodium glucose co-transporter 2 (SGLT2) inhibitors, and glucagon-like polypeptide-1 receptor agonists., However, appropriate reductions in insulin dose guided by self-monitoring of blood glucose (SMBG) profile should be considered when adding another antidiabetic agent.
Appropriate insulin delivery devices should also be chosen to minimize errors in insulin administration that can lead to hypoglycemia. Insulin pen devices allow for more accurate dose administration with less chances of dosing errors. A meta-analysis suggests that insulin pens are associated with a lower risk of hypoglycemia compared to vials and syringes. Newer insulin delivery devices such as insulin pumps have been consistently associated with lower risk of hypoglycemia (as discussed later).
SMBG is extremely vital in minimizing the risk of hypoglycemia. Patients on insulin therapy should be counseled to frequently monitor blood glucose and also maintain records of the same. The frequency of SMBG can be tailored to suit the individual needs of the patient, dietary and exercise patterns, hypoglycemia risk, and the insulin regimen. In patients with T1DM and in those with T2DM on MDI, 3–4 time point profile should be maintained every day, while the frequency of monitoring can be reduced in persons with T2DM taking once daily basal or premix regimens. Monitoring is also recommended before and after vigorous exercise. In addition, patients should also be instructed to check blood glucose in case of suspected symptoms of hypoglycemia. Monitoring should be intensified whenever insulin and other antidiabetic medications are adjusted and during any acute illness. Hypoglycemia episodes should be recorded as patients may not be able to recall mild episodes later. Patients with recurrent hypoglycemia, hypoglycemia unawareness, and severe hypoglycemia should be instructed to increase monitoring to 6–7 time points a day. Regular blood glucose monitoring at bedtime has been found to be helpful in predicting and preventing nocturnal hypoglycemia. CGM can be particularly useful in high-risk patients (as discussed later).
| Titration|| |
There is a need to carefully titrate insulin doses based on dietary patterns, exercise schedule, expected targets, trends of SMBG, and risk factors for hypoglycemia. It is advisable to start insulin at lower doses, especially in persons at greater risk of hypoglycemia, and then titrate upward based on SMBG or CGM records. Dose up-titration should be done once in 3–7 days as frequent up-titration may result in increased hypoglycemia risk. Basal insulin dose is titrated based on fasting plasma glucose values and prandial insulin can be titrated according to postprandial glucose values. Prandial doses can also be titrated on the basis of carbohydrate counting and SMBG using an estimate of total amount of carbohydrate consumed and the insulin-to-carbohydrate ratio. Studies suggest that patient-led self-titration of insulin doses can be very effective.,
| Technology|| |
Improvements in technology have focused on enabling early detection of hypoglycemia and its prediction with CGM, providing more physiological insulin delivery with insulin pump, and the use of closed-loop insulin systems. These technological innovations have significantly focused on the prevention of hypoglycemia when improving glycemic control.
Continuous glucose monitoring
CGM systems measure interstitial fluid glucose every 5 min to provide information about trends of blood glucose values. CGM has been shown to significantly reduce the number of hypoglycemic episodes and time spent in hypoglycemia. A meta-analysis reported that the use of CGM improved glycemic control without increase in hypoglycemia risk in patients with T1DM and T2DM. CGM devices that relay real-time information (rt-CGM) and also predict hypoglycemia using glucose trends are particularly useful in patients at risk of hypoglycemia. CGM when added to MDI or continuous subcutaneous insulin infusion (CSII) was shown to significantly reduce the occurrence of hypoglycemia in individuals with T1DM with a history of hypoglycemia unawareness or severe hypoglycemia.,
Continuous subcutaneous insulin infusion
CSII can closely mimic physiological insulin delivery. It allows for fine tuning of basal insulin delivery to match changes in insulin sensitivity and also administration of multiple small prandial bolus doses to match carbohydrate intake. In addition, bolus wizard calculators and insulin pump algorithms help calculate bolus insulin dose based on carbohydrate counting and current blood glucose. Therefore, it avoids inadvertent errors in bolus insulin dose calculation.
Insulin pumps have been found to be particularly useful in patients at high risk of hypoglycemia. Trials comparing CSII with NPH-based MDI regimens have consistently shown lower risk of hypoglycemia. While some studies comparing CSII with long-acting basal insulin-based MDI regimens have not shown lower risk of overall hypoglycemia, the rates of nocturnal hypoglycemia were significantly lower., Summers et al. reported 30% lower incidence of hypoglycemia over long-term follow-up period of 10 years with CSII compared to MDI in patients with T1DM. In another meta-analysis, Pickup and Sutton suggested significantly lower rates of severe hypoglycemia with CSII than MDI. Such technologies are particularly useful in subjects with hypoglycemia unawareness. However, CSII is useful in selected individuals who are highly motivated and capable of using the technology effectively.
Sensor-augmented pump and closed-loop insulin delivery
Insulin pump has been combined with rt-CGM as a “closed-loop system” with features to suspend insulin delivery in the event of hypoglycemia or predicted hypoglycemia., Such sensor-augmented pumps (SAP) are useful in patients with recurrent hypoglycemia, hypoglycemia unawareness, and severe hypoglycemia. The incidence of severe and moderate hypoglycemia as well as nocturnal hypoglycemia was significantly reduced in patients with hypoglycemia unawareness using SAP with low glucose or predicted low glucose suspend feature.,, Recent studies using such closed-loop systems have reported significantly less time spent in hypoglycemia.,,
Newer systems that incorporate glucagon delivery along with insulin are under development. Glucose-responsive insulin and glucagon delivery is being evaluated to minimize hypoglycemia risk.,
Other technological advancements
Glucagon has been used in the management of hypoglycemia. However, the biggest challenge has been the availability of stable formulations. Newer more stable formulations are under development (intranasal glucagon, biochaperone glucagon, dasiglucagon, and nonaqueous glucagon). Mini doses of glucagon administered subcutaneously have been used to prevent hypoglycemia in children during periods of poor oral intake or exercise. Research is also focused on the development of once weekly insulins and glucose-responsive 'smart' insulins., The concomitant use of SGLT2 or dual SGLT1-SGLT2 inhibitors like ipragliflozin and sotagliflozin with insulin had limited success.,
Pancreas and islet cell transplantation results in recovery of the physiological islet cell hormonal responses to hypoglycemia with suppression of endogenous insulin secretion and increase in glucagon secretion when blood glucose falls below a threshold. Pancreatic islet cell transplantation significantly reduces the risk of hypoglycemia compared to MDI or CSII and can be considered for patients with intractable and severe hypoglycemia not improving with focused education and use of advanced technologies such as SAP. Pancreas transplantation is usually performed simultaneous with kidney transplantation and amelioration of troublesome hypoglycemia for over a decade has been documented. The need for lifelong immunosuppression, however, remains a major limiting factor.
| Harmony|| |
Insulin replacement should mimic the physiological insulin secretion as closely as possible. There needs to be synchronization between patient's dietary and meal patterns, physical activity, and insulin dose regimen. Patients on MDI or CSII, especially those with T1DM, benefit from carbohydrate counting and use of bolus dose calculators to avoid inadvertent high boluses. Insulin pumps also provide information on “active insulin” or “insulin-on-board” which helps avoid insulin stacking from repeated unnecessary boluses that can lead to hypoglycemia. Such bolus calculators were related with a trend toward fewer hypoglycemia episodes. Patients who are using bedtime NPH or predinner premix insulins often require bedtime snack to avoid nocturnal hypoglycemia due to the late peak of NPH insulin.
Moderate to vigorous exercise can result in a significant improvement in insulin sensitivity, leading to increased risk of hypoglycemia, which may last for several hours after exercise. Therefore, insulin doses need to be adjusted for any planned moderate to vigorous physical activity. This can be accomplished by reducing the dose of bolus insulin for a meal taken 1–2 h prior to exercise. Postexercise bolus can also be reduced in case of evening exercise to reduce the risk of nocturnal hypoglycemia. For insulin pump users, it has been suggested that basal insulin rate is reduced by 50% 1 h prior, during, and 1 h after exercise. In addition, hypoglycemia risk can be reduced by intake of a carbohydrate snack prior to exercise. Insulin injection into the limbs should be avoided prior to exercise as the insulin absorption may become faster following exercise.
Patients undergoing intensive lifestyle modification may have marked improvements in insulin sensitivity with rapid weight reduction. Antidiabetic therapy including insulin should be deintensified in such individuals to reduce the risk of hypoglycemia, as was witnessed in the Look-Action for Health in Diabetes trial.
Any change in routine such as long-distance travel, vacation, fasting, or festivities should be matched with appropriate change in insulin dose and timing. Fasting for religious or other reasons may also increase the risk of hypoglycemia. Insulin dose and other antidiabetic medications should be modified in accordance with the type and pattern of food intake. Basal and premix insulin doses usually need to be reduced and bolus insulin can be titrated based on carbohydrate intake., Patients planning long-distance travel across time zones as well as those planning vacations should also discuss the insulin dose plan with their diabetes care provider to avoid inadvertent hypoglycemia.
| Individualization|| |
There can be no one-size-fits-all strategy in insulin therapy. Person-centered care to improve glycemic control when minimizing hypoglycemia requires individualization of treatment in terms of glycemic targets, nutrition and physical activity plan, insulin formulation, regimen and doses, and use of more advanced technologies such as CGM and CSII. The treatment plan should take into consideration the patient's age, glycemic status, life expectancy, comorbidities, lifestyle, risk of hypoglycemia, and cultural and personal preferences. Patient's self-care capabilities, support system, resources, socioeconomic concerns, and expectations from treatment should be an important part of the shared decision-making process.
High-risk patients such as the elderly and those with multiple comorbidities benefit from simplified regimens, deintensification of treatment, and preferential use of insulins with lower risk of hypoglycemia. In patients with impaired awareness of hypoglycemia, hypoglycemia prevention is of utmost importance. Hypoglycemia unawareness can be reversed with a period of more lax glycemic control and strict avoidance of hypoglycemic episodes.
Hypoglycemia may result from errors in insulin administration including dose, type, and technique of insulin. Several different strengths of insulin preparations are available, the most common being 40 U/ml and 100 U/ml; these must be administered with appropriate insulin syringes. Using a 40 U/ml syringe for a 100 U/ml vial can result in delivery of significantly higher dose of insulin administered. Such errors in insulin administration should be strictly avoided.
Correct insulin technique is also important. A longer needle length or inability to raise a skinfold may result in inadvertent intramuscular injection, resulting in faster insulin absorption and hypoglycemia. Injection into sites of lipohypertrophy can also result in errors in insulin absorption. Lipohypertrophy is quite common, reported to be present in as many as 42.9% of patients. Common causes were lack of site rotation and spacing. The risk of severe hypoglycemia was 2.7 times higher in patients with lipohypertrophy. This is due to both erratic insulin absorption and increased insulin doses.
| Knowledge|| |
Human factors play a major role in many hypoglycemic episodes. Therefore, the importance of structured diabetes self-management education programs for patients and their caregivers to empower them regarding prevention, early detection, and management of hypoglycemia has been repeatedly emphasized. Education about hypoglycemia should be a part of structured education in addition to the principles of nutrition and lifestyle advise, SMBG, insulin administration, and dose self-titration. Patient empowerment should focus on the knowledge about factors that increase the risk of hypoglycemia, need for regular SMBG and insulin dose titration, reasonable targets, early recognition of hypoglycemia symptoms, and its timely management. [Figure 2] provides a flowchart for the management of hypoglycemia.
The Diabetes Teaching and Treatment Program was first developed in Germany with focus on intensive SMBG, individually targeting basal and premeal doses, carbohydrate counting, and structured education. Similar programs have been developed in many centers. Some of the educational programs that have been successful in reducing hypoglycemia risk include Dose Adjustment for Normal Eating, Blood Glucose Awareness Training, Hypoglycemia Anticipation, Awareness, and Treatment Training, and Hypoglycemia-specific Education Program.,, Almost 50% reduction in severe hypoglycemia over the long term has been reported with such programs.
| Conclusion|| |
While research to develop more physiological insulin delivery continues, it is important to focus on minimizing the risk of hypoglycemia following the general principles of person-centered care, shared decision-making, and patient empowerment.
Diabetes care providers, persons with diabetes, and their caregivers should have a good understanding of the factors which contribute to hypoglycemia, the limitations of current insulin regimens, the need to set reasonable targets, frequent SMBG, and insulin dose titration as well as early recognition and prompt management of hypoglycemia. Hypoglycemia prevention requires the formulation of a rationale plan of diet, physical activity, monitoring, insulin, and structured diabetes self-care education.
There is a need for regular active assessment of any history of recent hypoglycemic episodes and awareness of hypoglycemia symptoms of patients periodically. Previous episodes of hypoglycemia must be taken into consideration when making treatment plan. In patients at high risk of hypoglycemia, more relaxed glycemic targets, deintensification of treatment, patient empowerment, and simpler insulin regimens with new-generation analogs that have a lower risk of hypoglycemia should be considered. If a patient has recurrent hypoglycemia, hypoglycemia unawareness, or severe hypoglycemia, more focused diabetes education related to avoiding factors that lead to hypoglycemia is needed. These patients should also be considered for newer glucose monitoring and insulin delivery technologies such as CGM and CSII. SAP are especially useful in this setting. In patients with refractory hypoglycemia despite the use of advanced technologies and focused education, islet cell transplantation should be considered. Thus, the THINK strategy that we have discussed can be a useful framework for diabetes care providers in their efforts to plan and implement effective measures for preventing /minimizing hypoglycemia from insulin therapy.
Statement of human and animal rights
This review is based on previously conducted and published studies. No additional studies on human participants or animals were performed by any of the authors for the purpose of this article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]