During more recent years there has been a lot of interest in identifying even earlier signs of dysglycemia, predictive of future risk of diabetes. Complications of hyperglycemia High glucose concentrations can cause injury to a large number of organs and tissues.

In contrast, other cells, such as β cells, neuronal, and endothelial cells, are unable to activate this control of glucose afflux and they equilibrate their intracellular glucose level to the extracellular concentrations, and therefore are more susceptible to the effect of hyperglycemia.

In the context of diabetes, hyperglycemia can cause acute and chronic complications, which represent important determinants of morbidity and mortality, and have a negative impact on the prognosis of people affected by this disease.

Acute complications of hyperglycemia Hyperglycemia can cause serious acute complications, presenting as endocrine emergencies, such as diabetic ketoacidosis DKA and hyperosmolar hyperglycemic state HHS. Although both DKA and HHS can present across the whole age spectrum, DKA tends to be more common in young people with diabetes, whereas HHS is more common among older patients.

However, it is now clear that both conditions can occur in the context of both T1D or T2D. On the other hand, some patients with T1D can present some features of HHS, such as severe hyperglycemia. In addition, DKA is a common complication in patients with known diabetes, where it may be the consequence of poor compliance with insulin treatment, acute illness, or malfunction of diabetes care equipment.

Early identification and treatment of DKA are essential to minimize the associated morbidity and mortality. Treatment of DKA requires strict monitoring of the patient, correction of hyperglycemia, acidosis and ketosis, and replacement of fluid and electrolyte losses.

Another important action is the identification and treatment of precipitating events. Prevention of DKA at diagnosis is of paramount importance and should be based on intensive community interventions and education of healthcare providers to raise awareness.

In addition, preventive strategies should be applied to avoid episodes of DKA in patients with an already known diagnosis of diabetes. This requires patient education and access to specific diabetes programs and services. Hyperosmolar hyperglycemic state HHS is the most serious acute hyperglycemic emergency in patients with T2D.

Chronic complications of diabetes—vascular complications Hyperglycemia is a key determinant of vascular complications of diabetes, also known as chronic diabetes complications. As a result of microvascular complications, diabetes is an important determinant of blindness, end-stage renal disease, and a variety of debilitating neuropathies.

Diabetic nephropathy is a common microvascular complication of diabetes, which manifests with progressive increases in urinary albumin excretion, along with changes in glomerular filtration rate, ultimately leading to the development of end-stage renal disease.

Diabetic nephropathy represents the major cause of end-stage renal disease in both developed and developing countries and it is an independent risk factor for cardiovascular disease. Diabetic retinopathy is one of the leading causes of blindness in people of working age. This complication can be diagnosed already after five years from the onset of diabetes, and almost all patients will show variable degrees of retinopathy after 20 years of diabetes.

Abnormalities of the autonomic nervous system can also occur in patients with diabetes, with early subclinical manifestations, such as decreased heart rate variability, being detectable within a year of diagnosis in patients with T2D, and within two years in patients with T1D.

With regard to macrovascular complications, epidemiologic data indicate that people with diabetes have a two- to fourfold increased risk of developing cardiovascular disease, which in turn is a key contributor of mortality. Hyperglycemia and vascular damage Hyperglycemia contributes to the development of vascular complications through several mechanisms: activation of the polyol and hexosamine pathways, diacylglycerol-protein kinase C DAG-PKC , increased production of advanced glycation end products AGE , increased synthesis of growth factors, cytokines, and oxidative stress.

Aldose reductase reduces the aldehyde form of glucose to sorbitol, which is then oxidized to fructose by sorbitol dehydrogenase and then again enters into glycolysis. The hexosamine pathway converts fructosephosphate into N-acetyl glucosamine, which has been implicated in the activation of the transcriptional factor Sp1, leading to increased synthesis of factors, such as transforming growth factor beta-1 TGF-ß1 and plasminogen activator inhibitor-1 PAI-1 , which in turn are associated to the development of vascular complications.

In addition, the hexosamine pathway is also associated with increased oxidative stress and the effects of the activation of this pathway can be prevented by overexpression of antioxidants, such as superoxide dismutase.

AGEs have been implicated in several biologic activities, mostly by binding to the AGE-specific receptors RAGEs on many cells. In particular, they can induce oxidative stress and release of cytokines and growth factors, which in turn accelerate chronic inflammation and endothelial dysfunction.

Growing evidence suggests that increased oxidative stress, induced by the above hyperglycemia-activated pathways, is a key factor in the pathogenesis of endothelial dysfunction and vascular disease. Several mitochondrial and other intracellular pathways are implicated in the increased production of oxidant species concomitant with a reduction in antioxidants in the context of diabetes.

Intervention to improve glycemic control The Diabetes Control and Complications Trial DCCT and its follow-up study, the Epidemiology of Diabetes Interventions and Complications EDIC , have clearly shown the role of strict glycemic control in reducing the risk of vascular complications in subjects with T1D.

The DCCT studied a cohort of 1, subjects, aged 13—39 years, with T1D for 1—15 years 42 by comparing intensive insulin administered three or more times daily by injection or an external pump versus conventional one or two daily insulin injections insulin therapy. Therefore, the EDIC study highlighted the need of implementing intensive management as soon as diabetes is diagnosed.

However, recent data suggest that epigenetic modulations, such as histones and DNA methylation, may be involved in persistent changes of gene expression associated with vascular complications of diabetes and lead to metabolic memory.

Chronic versus acute hyperglycemia in the pathogenesis of vascular complications Hemoglobin A1C HbA1c is the main parameter which has been used for over 30 years to monitor long-term glycemic control. However, HbA1c measurement does not give any information about individual daily glucose fluctuations short-term fluctuations or acute hyperglycemia.

In patients with marked fluctuations in glucose concentrations who are exposed to the risk of both hyperglycemia and hypoglycemia, HbA1c levels may still indicate adequate metabolic control.

Extensive evidence indicates that short-term fluctuations in glucose acute hyperglycemia can play a key role in the pathogenesis of diabetic vascular complications, independently from the effect on HbA1c. The contribution of FPG and PPG to long-term glycemic control varies across the range of HbA1c concentrations.

In particular, it has been shown that, whereas the relative contribution of PPG decreases from the lowest to the highest quintiles of HbA1c, the relative contribution of FPG increases with higher levels of HbA1c.

Acute hyperglycemia has been associated with increased renal perfusion, hyperfiltration, increased oxidative stress, decreased motor and sensory nerve conduction, increased collagen production in the kidney, and increased retinal perfusion. All these mechanisms can contribute to the development of microvascular complications.

Again, all these mechanisms can contribute to the development of macrovascular complications. Although there is some increasing evidence for a role of acute hyperglycemia, such as PPG, in the development of vascular complications, there is still a need of further data, mainly obtained from interventional studies exploring drugs specifically targeting PPG.

Short-term glucose variability, which represents the intraday glucose fluctuations from peaks to nadirs, is another parameter, reflecting short-glucose fluctuations and which has been investigated in relation to diabetic vascular complications.

In vitro studies have shown a significant effect of glucose fluctuations in the activation of oxidative stress pathways, induction of epigenetic changes in key genes, and endothelial dysfunction.

Several studies performed in patients with T2D have shown a direct association between glucose variability and the development or progression of retinopathy, cardiovascular disease and mortality.

Conclusions Hyperglycemia is a well-known metabolic derangement, which can contribute to the development of serious acute DKA, HHS and chronic complications micro- and macrovascular disease. Several studies have clearly shown a strong association between chronic hyperglycemia and the development of both micro- and macrovascular complications of diabetes.

In addition, there is growing evidence suggesting that acute hyperglycemia, particularly PPG, plays a role in the pathogenesis of complications.

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You may opt-out of email communications at any time by clicking on the unsubscribe link in the e-mail. Many factors can contribute to hyperglycemia, including: Not using enough insulin or other diabetes medication Not injecting insulin properly or using expired insulin Not following your diabetes eating plan Being inactive Having an illness or infection Using certain medications, such as steroids or immunosuppressants Being injured or having surgery Experiencing emotional stress, such as family problems or workplace issues Illness or stress can trigger hyperglycemia.

Long-term complications Keeping blood sugar in a healthy range can help prevent many diabetes-related complications. Long-term complications of hyperglycemia that isn't treated include: Cardiovascular disease Nerve damage neuropathy Kidney damage diabetic nephropathy or kidney failure Damage to the blood vessels of the retina diabetic retinopathy that could lead to blindness Feet problems caused by damaged nerves or poor blood flow that can lead to serious skin infections, ulcerations and, in some severe cases, amputation Bone and joint problems Teeth and gum infections.

Emergency complications If blood sugar rises very high or if high blood sugar levels are not treated, it can lead to two serious conditions. To help keep your blood sugar within a healthy range: Follow your diabetes meal plan. If you take insulin or oral diabetes medication, be consistent about the amount and timing of your meals and snacks.

The food you eat must be in balance with the insulin working in your body. Monitor your blood sugar. Depending on your treatment plan, you may check and record your blood sugar level several times a week or several times a day.

Careful monitoring is the only way to make sure that your blood sugar level stays within your target range. Note when your glucose readings are above or below your target range.

Carefully follow your health care provider's directions for how to take your medication. Adjust your medication if you change your physical activity. The adjustment depends on blood sugar test results and on the type and length of the activity.

If you have questions about this, talk to your health care provider. By Mayo Clinic Staff. Aug 20, Show References. Hyperglycemia high blood glucose. American Diabetes Association. Accessed July 6, What is diabetes?

National Institute of Diabetes and Digestive and Kidney Diseases. Wexler DJ. Management of persistent hyperglycemia in type 2 diabetes mellitus. Hirsch IB, et al. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis.

Managing diabetes. Inzucchi SE, et al. Glycemic control and vascular complications in type 2 diabetes mellitus. Comprehensive medical evaluation and assessment of comorbidities: Standards of Medical Care in Diabetes — Diabetes Care. The big picture: Checking your blood glucose. Castro MR expert opinion.

Mayo Clinic, Rochester, Minn. July 7, Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment. Take care of your diabetes during sick days and special times. Accessed July 7, Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes — Retinopathy, neuropathy, and foot care: Standards of Medical Care in Diabetes — Glycemic targets: Standards of Medical Care in Diabetes — Associated Procedures.

A1C test. Show the heart some love! If ketones are present, it is likely that you do not have enough insulin in your body. This means you may need to increase your dose or give yourself an extra dose.

Talk to your diabetes team about how to do this if you are unsure. You should also try to drink plenty of sugar-free fluids to prevent dehydration. Having high blood sugar levels regularly is not something you should live with.

This is because in the long-term it can increase your risk of developing diabetes complications , such as neuropathy and retinopathy. If you notice that your blood sugar levels are often high, above 10mmol you should contact your diabetes healthcare team.

They will review your treatment and provide you with advice on how to get your blood sugar levels back within your target range. This advice may include increasing your medication. In the video below, Lynsey talks to Khalida about feeling anxious after getting a high blood sugar level reading.

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