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Managing hyperglycemia

Managing hyperglycemia

See 'Established cardiovascular or kidney disease' above. Alogliptin Managjng acute coronary syndrome in Mwnaging with type 2 diabetes. Each component hypergycemia the composite contributed to the benefit, and the HR for cardiovascular death Hperglycemia 0. Moraes Sport-Specific Drills and Techniques, Vitamin and mineral deficiencies and blood pressure J, Cremonesi M, et al. Johnston PS, Feig PU, Coniff RF, et al. Of note, we avoid use of SGLT2 inhibitors in patients with frequent bacterial urinary tract infections or genitourinary yeast infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis eg, pancreatic insufficiency, drug or alcohol abuse disorder because of increased risk while using these agents. This activity was funded by the American Diabetes Association and the European Association for the Study of Diabetes. Managing hyperglycemia

Managing hyperglycemia -

Intravenous insulin infusion is the preferred route of insulin delivery in critical care as doses can be rapidly adjusted to altered requirements. For stable patients, insulin can be added directly to the parenteral nutrition bag. If parenteral nutrition is infused continuously over 24 hours, the subcutaneous injection of a long-acting insulin combined with correctional bolus insulin may be adequate.

The aim of this review is to give an overview of the management of parenteral nutrition-associated hyperglycemia in inpatients with diabetes.

Intravenous IV infusion of nutrients, i. parenteral nutrition PN , is a form of nutritional support indicated when the nutritional requirements cannot be met by oral intake or enteral nutrition EN. PN usually contains glucose, lipids, and amino acids.

Electrolytes, vitamins and trace elements are added to the PN bag or provided separately. PN can be administered either continuously or cyclically e. overnight 2. Consequently, diabetes is also on the rise in patients who require nutritional support.

Although overweight and obesity are highly prevalent among patients with type 2 diabetes mellitus T2DM , malnutrition and weight loss during hospitalization are harmful in these patients since they are accompanied by major muscle loss and associated with adverse outcome 7 — 9.

Therefore, nutritional therapy is indicated in all malnourished patients and in certain cases PN is indicated regardless of the initial body mass index. Risks of PN include complications associated with the central venous catheter septic and mechanical complications, thrombosis, catheter occlusion as well as acute- and long-term metabolic complications e.

Hyperglycemia is often induced by nutritional support, even in patients without a diagnosis of diabetes stress hyperglycemia. Overall, more than half of all inpatients receiving PN experience hyperglycemia 12 — Underlying diabetes and hyperglycemia before starting PN are predictors for PN-associated hyperglycemia 13 , Cheung et al.

showed that the complication risk in patients receiving PN increases by a factor of 1. In particular, hyperglycemia in patients receiving PN is associated with an increased risk of cardiac complications OR 1.

The renal threshold in patients with insulin resistance is at The indication for nutritional support in patients with diabetes is primarily due to concomitant diseases and follows the same principles of nutritional support as for patients without diabetes. However, patients with diabetes have a particularly high insulin need, due to the decreased insulin sensitivity during acute illness inflammation combined with the lack of insulin in patients with type 1 diabetes mellitus T1DM or insulin resistance in T2DM The same PN admixtures may be used for patients with and without diabetes with additional insulin administration.

Alternatively, the PN composition may be adapted to facilitate blood glucose control. The insulin administration is not only crucial to control blood glucose, but a lack of insulin may also increase muscle catabolism during acute illness.

As a beneficial side effect, adding insulin to PN results in more rapid correction of malnutrition anabolic effect while glucose should be administered as soon as blood glucose levels are in target range to prevent a catabolic metabolic state The aim of this review is to give an overview of the management of PN-associated hyperglycemia in inpatients with diabetes.

Consensus statements among organizations of health care professionals involved in inpatient diabetes care e. American Diabetes Association, The Endocrine Society as well as artificial nutrition e.

European Society of Clinical Nutrition and Metabolism [ESPEN], American Society for Parenteral and Enteral Nutrition [ASPEN] , recommend a blood glucose target of 7. During the first days of PN, frequent monitoring of glycemia is required and can be reduced when the patient has reached a stable metabolic state Both the nutritional and the insulin regimen need to be considered when controlling blood glucose in patients with diabetes receiving PN Figure 1.

While patients in the early stage of T2DM can be managed with non-insulin glucose lowering drugs, oral antidiabetic drugs in hospitalized patients are not recommended in most patients with severe illness. Moreover, evidence supporting the efficacy of oral antidiabetic drugs to reduce hyperglycemia in response to PN is very weak and most patients with diabetes require supplemental insulin when glucose is infused Therefore, this review focuses on the nutritional and insulin regimen during PN.

Figure 1 Hyperglycemia management of patients with diabetes receiving parenteral nutrition. Nutritional strategies can improve blood glucose control in patients receiving PN. While these strategies have been studied in critically ill patients with insulin resistance, it is often unclear how these findings can be translated to non-critically ill patients with diabetes.

Oral glucose has a greater stimulatory effect on insulin secretion than IV glucose due to the incretin effect, mediated by the secretion of glucose-dependent insulinotropic peptide GIP and glucagon-like peptide 1 GLP-1 as well as other gastrointestinal peptides In post-operative patients with diabetes, the combination of PN with EN leads to reduced blood glucose concentrations, reduced insulin resistance, increased GIP and improved intestinal permeability compared to PN alone 26 , However, a combination of PN with oral intake or EN is not possible in certain clinical situations and the whole nutritional requirements need to be covered by PN total PN.

To determine the energy needs, the ESPEN recommends an indirect calorimetry measurement or an estimation with prediction equations, e. Harris-Benedict 28 , or a weight-based formula, e.

Reducing the energy supply can lead to a better blood glucose control and thus reduce the risk of hyperglycemia There is no evidence for whether these recommendations can be transferred to non-critically ill patients with diabetes while preventing malnutrition and its related negative clinical outcomes.

In clinical practice, it is thus necessary to evaluate if a short-term energy deficit is tolerable or if longer-term PN is required. Generally, moderate amounts of glucose should be administered initially in patients with diabetes.

As soon as the patient is in a stable metabolic condition, the PN administration should be increased to total requirements to prevent catabolism. In clinical practice, PN is often administered in a gradually increasing mode to improve metabolic tolerance and to reduce the risk of refeeding syndrome Besides reducing the absolute PN administration, adapting the macronutrient distribution may be a potential approach to avoid unfavorable consequences of excess glucose while covering the complete energy requirements.

This is especially useful if PN is required long-term and a calorie deficit is not acceptable. When compounding PN, the hospital pharmacy can increase the fat content and decrease the glucose part to obtain an isocaloric admixture with reduced glucose.

Despite a lack of evidence for the benefit and safety of isocaloric, glucose reduced PN in non-critically ill patients with hyperglycemia 27 , it may be considered as a strategy for optimal blood glucose control in patients with diabetes.

Replacing glucose in PN by fructose or sorbitol is not recommended in patients with diabetes because these substrates do not improve the metabolic situation and plasma levels of these substrates are not routinely measured.

Despite the fact that fructose, glycerol, sorbitol and xylitol are metabolized rapidly and in the beginning independent of insulin and have a lower effect on blood glucose concentration compared to glucose infusion 36 , there is no difference in glycemic control or in insulin demand between glucose and a glucose-fructose-xylitol mixture in patients with diabetes Furthermore, glucose is a widely available and affordable carbohydrate substrate in PN and should be the first choice for patients with diabetes Finally, in critically ill and surgical patients, glutamine-supplemented PN 0.

Glutamine also improves blood glucose profile through a positive effect on glucose oxidation and insulin resistance Although no studies were conducted specifically on the effect of glutamine-supplemented PN in patients with diabetes, critically ill patients receiving glutamine-supplemented PN have less hyperglycemia and need insulin less frequently than patients receiving PN without glutamine 42 — A post-hoc analysis of the Insulin in Parenteral Nutrition INSUPAR trial investigated the effect of PN with fish oil emulsions rich in ω-3 polyunsaturated fatty acids PUFA in T2DM While patients with fish oil enriched PN had significantly lower triglyceride levels compared with other lipid emulsions, there were no differences in mean capillary glucose, glycemic variability, and insulin dose.

However, there were significantly more hypoglycemic events in the fish oil group, which might have been caused by an overrepresentation of patients with end-organ damage and significantly longer PN duration in the fish oil group.

Therefore, further research to examine the effect of ω-3 PUFA in patients with diabetes receiving PN is needed The preferred method to manage blood glucose in patients with diabetes receiving PN is to administer a rapid-acting insulin IV.

Moreover, any combination of the above may be used and practice varies widely among patient populations, disciplines and individual clinicians. The advantages and particularities of these options are summarized below. Ideally, insulin is administered continuously with an IV infusion in patients receiving PN Figure 2 due to favorable pharmacokinetics in these patients.

This is especially important for unstable and critically ill patients where maximal flexibility of the management is needed in order to allow imminent adaptation to rapidly changing circumstances, yet without increasing the risk of hypoglycemia. In critically ill patients, higher levels of glucagon, cortisol and catecholamines further favor hyperglycemia and insulin resistance 47 , In order to achieve stable glycemia within the defined target range, frequent adaptations of the insulin infusion rate are recommended.

The application of IV insulin boluses may lead to serious glycemic fluctuations and provoke dyselectrolytemia, in particular hypokalemia As a starting point, the insulin dose in Table 1 can be used and blood glucose levels should be checked every two hours.

Woolfson et al. Figure 2 Parenteral nutrition and insulin infusion in unstable patients with diabetes [adapted from 46 ]. Table 2 Dynamic insulin administration according to the current blood glucose and the direction of change since the previous measurement [according to 49 ].

It is recommended to indicate on the PN bag that insulin is running on a separate IV infusion in order to check the insulin application when PN is paused or stopped.

In patients with T1DM, a minimal infusion rate of 0. Adding insulin to PN is a convenient and physiologically favorable method to treat hyperglycemia. However, manipulating a PN bag increases the risk of infectious complications.

Nevertheless, the hospital pharmacy may add insulin to PN bags or, if the hospital pharmacy allows, the insulin may be added to PN bags directly on the ward. This form of insulin delivery is particularly advantageous for cyclic administration of PN or when PN needs to be stopped frequently, e.

for examinations requiring a fasted state, since the insulin stops when the nutrition stops Furthermore, it is useful in general wards, when separate IV insulin administration is not feasible.

Nevertheless, it is inappropriate in unstable conditions since the frequency of dosage adjustment should not be more than every 24 hours and the insulin concentration cannot be adapted once it is in the PN bag.

Due to higher amounts of rapidly metabolized carbohydrate contents of PN in comparison to oral food, insulin needs are slightly higher than for oral nutrition Obese patients with T2DM and significant insulin resistance may require as much as 1 IU of insulin for every 5 g of glucose while thin patients with T1DM may require only 1 IU for every 20 g of glucose In patients switched from IV insulin to insulin added to the PN bag, insulin requirements can be estimated according to Figure 3.

The amount of insulin can be titrated every one to two days, based on blood glucose monitoring. Since more frequent adjustments are impractical and costly, the concurrent use of rapid- or short-acting insulin as correction every six hours will help to fine-tune glycemic management 20 , Figure 3 Insulin dose added to PN bag considering the glucose content of PN and the insulin resistance Glu, glucose; IV, intravenous; PN, parenteral nutrition 51 — No differences were observed in the effectiveness to achieve an adequate metabolic control venous blood glucose, capillary glucose, glycemic variability parameters, total insulin and capillary glucose decrements during PN infusion.

However, glycemic control after PN interruption was better in the group with glargine insulin. While no difference in the rate of hyperglycemia was observed, hypoglycemia was more frequent in the group with glargine insulin Post-acute, stable patients can be transitioned from IV to subcutaneous insulin administration.

It is important to overlap IV and subcutaneous insulin delivery, starting subcutaneous administration two to three hours prior to IV discontinuation. The scheme in Table 3 can serve as a rule of thumb and if in doubt, a diabetes specialist should be consulted.

In particular within the first 24 hours after transition, additional glucose corrections may be necessary in order to achieve adequate glycemic control. If glycemic targets cannot be achieved within the first 48 hours, switching back to IV insulin infusions should be considered.

Table 3 Scheme for injection of subcutaneous insulin during parenteral nutrition. In stable patients with diabetes receiving continuous PN, the subcutaneous injection of a long-acting insulin is useful The use of ultra-long-acting insulin should be restricted to very stable situations due to limited flexibility.

In case of oral intake in addition to PN, a long-acting insulin should be combined with short-acting insulin to cover prandial carbohydrate intake 51 , 55 and, even if patients are on total PN, basal insulin should always be combined. Dosage of the short-acting insulin is based on preprandial blood glucose and expected carbohydrate intake.

Table 4 shows a scheme for insulin dosage adjustment based on preprandial blood glucose measurements and normal insulin sensitivity.

Note that this scheme is a rule of thumb and the amount of insulin must be adapted according to glycemic control, dietary changes and insulin resistance. Table 4 Scheme for injection of rapid-acting insulin for patients receiving parenteral nutrition meal insulin, assuming oral or enteral intake of about 20 g carbohydrate and normal insulin sensitivity.

A combination of long-acting and short-acting insulin is also recommended in case of combined PN and EN, in particular in case of the application of EN by boluses. Of note, changes in the application of PN afford an instant adaptation of the insulin regimen in order to prevent hypoglycemia. Continuous glucose monitoring CGM devices have become the standard glucose monitoring tool for patients with diabetes CGM measures interstitial glucose levels and can transmit them to a smartphone with a control algorithm to administer insulin subcutaneously via an insulin pump Figure 4.

This forms a hybrid closed-loop, i. automatic insulin administration for basal requirements and depending of the type of insulin pump automated glycemic corrections, or a fully closed-loop, i.

with additional automated coverage of dietary carbohydrate intake or supply Figure 4 A continuous glucose monitor arm measures interstitial glucose levels and transmits them to a smartphone with a control algorithm. An insulin pump abdomen delivers a rapid-acting insulin.

Patients with T1DM may be admitted to the hospital with a hybrid closed-loop system. Current guidelines of the American Diabetes Association ADA state that diabetes self-management may be appropriate for patients with adequate oral intake, who successfully self-manage their diabetes at home and have a good understanding of sick-day management As people receiving PN do not have adequate oral intake, the use of a semi-closed loop system under PN needs to be closely supervised by a diabetologist.

A further limitation is the delayed pharmacokinetics of the subcutaneous insulin administered via the insulin pump compared to IV administration. Fully closed-loop systems are not yet available commercially, but can be used in research settings.

If properly done, such a closed-loop system allows better blood glucose control than standard insulin therapy in hospitalized patients receiving nutritional support. In a randomized-controlled trial of 43 inpatients, the blood glucose levels were within the target range during eight additional hours daily in the closed-loop group, without increasing the risk of hypoglycemia A study investigating continuous subcutaneous insulin infusion found significantly decreased glycemic variability and insulin requirements compared to a multiple daily injection regimen in patients with T2DM receiving PN after gastrointestinal surgery Although some evidence about the efficacy of hybrid closed-loop systems in patients receiving PN exists, official recommendations are not available yet.

Medication may be added to PN if i it is stable, ii it is compatible, iii evidence supports the clinical value, and iv the frequency of dosage adjustment is not more than 24 hours Insulin is a potential candidate for admixture to PN. Insulin administration within the PN bag or via a Y-site is recommended by both International Societies for Clinical Nutrition, the ESPEN and ASPEN, if stability of both the PN admixture and the insulin have been tested previously 62 , However, unless compatibility is stated by the manufacturer, hospital pharmacists must always be consulted when insulin should be admixed directly into the PN admixture bag, since there may be many physicochemical issues associated with frequent harmful events There are only few data on the insulin stability in a PN admixture and they mainly refer to administration via Y-site.

There is no data available regarding admixture of insulin analogues and it is impossible to extrapolate the results for different insulins and PN admixtures. Other formulations such as NPH, lispro, aspart or glargine are incompatible with PN admixtures.

However, the zinc contained as stabilizer for polypeptides in pharmaceutical solutions is also present in the trace elements solutions added in PN admixture bags and may cause insulin hexamerisation Further chemical reactions may occur such as insulin glycation and interactions between insulin or its binding components and potential degradation products of the PN components e.

lipid peroxides. Another relevant factor, the adsorption to the infusion set and PN bag may occur depending on the material and the PN flow rate. The adsorption phenomenon is well documented but not well quantified. However, it reduces the expected and actual insulin delivery and is unaccounted for in therapy, contributing to high glycemic variability and poor control Adsorption is not constant, e.

Furthermore, adsorption increases as the flow rate decreases. A study of Knopp et al. This may have significant implications in some care settings, e.

Some recommendations to reduce these losses have been made insulin flushing, co-delivery of proteins but did not find their place in clinical practice wasting of insulin, time-consuming. Moreover, different analytical methods to measure insulin and different laboratory conditions e. light exposure, temperature may affect the results.

In a study of Henry et al. The reasons for these physicochemical effects are not fully understood to date Considering that chemical reactions can cause conformational modification, decreasing the recognition, it is impossible to predict metabolic or clinical consequences.

Thus, there is a need for clinical trials and other analytical tools Very few and heterogeneous studies, mostly excluding patients with diabetes, are available regarding the clinical effect of insulin added directly into PN bags.

A recent meta-analysis comparing subcutaneous insulin glargine with regular insulin added to the PN bag did not show any differences in mean blood glucose levels or frequency of hypoglycemia nor on the reduction patterns of hyperglycemia or rates of hypoglycemia The currently scarce evidence and the clinical practice support the direct admixture of insulin in PN bags in stable inpatients, demonstrating good glycemic control and safety profile However, insulin should only be added into PN bags once glycemia and PN regimen are stable, according to specific personalized protocols and under close blood glucose monitoring and surveillance of the clinical situation In general, PN can be discontinued without any reduction steps 62 , e.

in patients undergoing an intervention requiring be fasted. Rebound hypoglycemia when stopping PN with added insulin is very rare in adults Nevertheless, PN is usually tapered off, since oral nutrition is built up gradually.

Continuous insulin administration must be adapted when the PN is stopped. When PN is interrupted, patients with T2DM should be followed with careful glucose monitoring.

If hyperglycemia occurs, insulin should be administered. Patients with T1DM require overlapping insulin when PN is interrupted; otherwise hyperglycemia will develop if no insulin is administered and the shorter half-life of IV insulin increases the risk of ketosis The amount and type of insulin depends on the expected duration of the interruption.

Because of the possibility of accidental discontinuation of insulin administration when PN with insulin added to the bag is interrupted, some clinicians recommend that patients with T1DM receive a part of their basal insulin as an injection. This approach may also be useful for insulin dependent T2DM patients.

Hyperglycemia is frequent in patients receiving PN and inadequate blood glucose management as well as insulin administration increase the risk for adverse outcome. Blood glucose management of patients with diabetes receiving PN is complex and requires multiprofessional collaboration in a nutritional support team including physicians, diabetes specialists, pharmacists, dieticians, diabetes counseling and nurses.

Establishing the blood glucose targets and control strategies necessitates interdisciplinary involvement while the responsibility for blood glucose control should be clearly defined and monitored. It is important to provide a defined protocol for insulin administration, so that it is carried out in a consistent manner by all health care personnel KS, ER, and ZS contributed to the conception.

KS wrote the first draft of the manuscript. ER, CD, and AB wrote sections of the manuscript. ZS supervised the work. All authors contributed to manuscript revision, read, and approved the submitted version. This research was funded by the Division of Clinical Pharmacy and Epidemiology, University of Basel third-party grant FO and the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital research fund WFE The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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ESPEN Guidelines on Chronic Intestinal Failure in Adults. Clin Nutr 35 2 — PubMed Abstract CrossRef Full Text Google Scholar. National Diabetes Inpatient Audit NaDIA - United Kingdom Google Scholar.

Lau LH, Lew J, Borschmann K, Thijs V, Ekinci EI. Prevalence of Diabetes and Its Effects on Stroke Outcomes: A Meta-Analysis and Literature Review. J Diabetes Investig 10 3 — Bach LA, Ekinci EI, Engler D, Gilfillan C, Hamblin PS, MacIsaac RJ, et al.

The High Burden of Inpatient Diabetes Mellitus: The Melbourne Public Hospitals Diabetes Inpatient Audit. Med J Aust 6 —8. Taylor JE, Campbell LV, Zhang L, Greenfield JR. High Diabetes Prevalence and Insulin Medication Errors in Hospital Patients. Intern Med J 48 12 — Leibovitz E, Giryes S, Makhline R, Zikri Ditch M, Berlovitz Y, Boaz M.

Malnutrition Risk in Newly Hospitalized Overweight and Obese Individuals: Mr NOI. Eur J Clin Nutr 67 6 —4. Sorensen J, Kondrup J, Prokopowicz J, Schiesser M, Krahenbuhl L, Meier R, et al. EuroOOPS: An International, Multicentre Study to Implement Nutritional Risk Screening and Evaluate Clinical Outcome.

Clin Nutr 27 3 —9. Felder S, Braun N, Stanga Z, Kulkarni P, Faessler L, Kutz A, et al. Unraveling the Link Between Malnutrition and Adverse Clinical Outcomes: Association of Acute and Chronic Malnutrition Measures With Blood Biomarkers From Different Pathophysiological States.

Ann Nutr Metab 68 3 — Sobocki J, Sitges-Serra A, Dudrick SJ. Complications Associated With Central Venous Catheter Insertion and Care. In: Sobotka L, Allison SP, Forbes A, Meier RF, Schneider SM, Soeters PB, et al. Basics in Clinical Nutrition , 5 ed, vol. Prague: Galén Sobotka L, Wanten G, Camilo ME, Van Gossum A.

Metabolic Complications of Parenteral Nutrition. Ask your doctor how often you should check and what your glucose sugar levels should be. Checking your blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia.

You can often lower your blood glucose level by exercising. If you have ketones, do not exercise. Exercising when ketones are present may make your blood glucose level go even higher. You'll need to work with your doctor to find the safest way for you to lower your blood glucose level.

Cutting down on the amount of food you eat might also help. Work with your dietitian to make changes in your meal plan.

If exercise and changes in your diet don't work, your doctor may change the amount of your medication or insulin or possibly the timing of when you take it.

Hyperglycemia can be a serious problem if you don't treat it, so it's important to treat as soon as you detect it. If you fail to treat hyperglycemia, a condition called ketoacidosis diabetic coma could occur. Ketoacidosis develops when your body doesn't have enough insulin. Without insulin, your body can't use glucose for fuel, so your body breaks down fats to use for energy.

When your body breaks down fats, waste products called ketones are produced. Your body cannot tolerate large amounts of ketones and will try to get rid of them through the urine. Unfortunately, the body cannot release all the ketones and they build up in your blood, which can lead to ketoacidosis.

Many people with diabetes, particularly those who use insulin, should have a medical ID with them at all times. In the event of a severe hypoglycemic episode, a car accident, or other emergency, the medical ID can provide critical information about the person's health status, such as the fact that they have diabetes, whether or not they use insulin, whether they have any allergies, etc.

Emergency medical personnel are trained to look for a medical ID when they are caring for someone who can't speak for themselves. Medical IDs are usually worn as a bracelet or a necklace.

Traditional IDs are etched with basic, key health information about the person, and some IDs now include compact USB drives that can carry a person's full medical record for use in an emergency.

Melanie J. Davies yyperglycemia, David A. KernanAllergy relief pills MathieuGeltrude MingronePeter Sport-Specific Drills and TechniquesYyperglycemia TsapasHypeerglycemia Sport-Specific Drills and Techniques. WexlerJohn B. Buse; Management of Hyperglycemia in Type 2 Diabetes, A Consensus Report by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD. Diabetes Care 1 December ; 41 12 : — Managin happens because the body either cannot Allergy symptom relief enough insulin to process the Hyperglyceemia in the blood hyperg,ycemia it cannot use the Manabing effectively enough. Sport-Specific Drills and Techniques are several reasons why your blood sugar levels may be too high. It may be that:. Overeating and not moving enough can also lead to high levels of blood sugar. Maintaining high levels of blood sugar makes it even more difficult for your body to produce the insulin needed to process it.

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