The administration of sodium bicarbonate solution to rapidly improve the acid levels in the blood is controversial. There is little evidence that it improves outcomes beyond standard therapy, and indeed some evidence that while it may improve the acidity of the blood, it may actually worsen acidity inside the body's cells and increase the risk of certain complications. Its use is therefore discouraged, although some guidelines recommend it for extreme acidosis (pH<6.9), and smaller amounts for severe acidosis (pH 6.9–7.0).

Potassium levels can fluctuate severely during the treatment of DKA, because insulin decreases potassium levels in the blood by redistributing it into cells via increased sodium-potassium pump activity. A large part of the shifted extracellular potassium would have been lost in urine because of osmotic diuresis. Hypokalemia (low blood potassium concentration) often follows treatment. This increases the risk of dangerous irregularities in the heart rate. Therefore, continuous observation of the heart rate is recommended, as well as repeated measurement of the potassium levels and addition of potassium to the intravenous fluids once levels fall below 5.3 mmol/l. If potassium levels fall below 3.3 mmol/l, insulin administration may need to be interrupted to allow correction of the hypokalemia.

Potassium replacement is often required as the metabolic problems are corrected. It is generally replaced at a rate 10 mEq per hour as long as there is adequate urinary output.

Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12 liters. Attempts to correct this usually take place over 24 hours with initial rates of normal saline often in the range of 1 L/h for the first few hours or until the condition stabilizes.

Treatment depends upon the underlying cause:

- Hypoglycaemic diabetic coma: administration of the hormone glucagon to reverse the effects of insulin, or glucose given intravenously.

- Ketoacidotic diabetic coma: intravenous fluids, insulin and administration of potassium and sodium.

- Hyperosmolar diabetic coma: plenty of intravenous fluids, insulin, potassium and sodium given as soon as possible.

Treatment of hyperglycemia requires elimination of the underlying cause, such as diabetes. Acute hyperglycemia can be treated by direct administration of insulin in most cases. Severe hyperglycemia can be treated with oral hypoglycemic therapy and lifestyle modification.

In diabetes mellitus (by far the most common cause of chronic hyperglycemia), treatment aims at maintaining blood glucose at a level as close to normal as possible, in order to avoid these serious long-term complications. This is done by a combination of proper diet, regular exercise, and insulin or other medication such as metformin, etc.

Those with hyperglycaemia can be treated using sulphonylureas or metformin or both. These drugs help by improving glycaemic control

Dipeptidyl peptidase 4 inhibitor alone or in combination with basal insulin can be used as a treatment for hyperglycemia with patients still in the hospital.

Ketosis is deliberately induced by use of a ketogenic diet as a medical intervention in cases of intractable epilepsy. Other uses of low-carbohydrate diets remain controversial. Carbohydrate deprivation to the point of ketosis has been argued to have both negative and positive effects on health.

Diabetes can be treated but is life-threatening if left alone. Early diagnosis and treatment by a qualified veterinarian can help in preventing nerve damage, and, in rare cases, lead to remission. Cats do best with long-lasting insulin and low carbohydrate diets. Because diabetes is a disease of carbohydrate metabolism, a move to a primarily protein and fat diet reduces the occurrence of hyperglycemia.

Oral medications like Glipizide that stimulate the pancreas, promoting insulin release (or in some cases, reduce glucose production), are less and less used in cats, and these drugs may be completely ineffective if the pancreas is not working. These drugs have also been shown in some studies to damage the pancreas further or to cause liver damage. Some owners are reluctant to switch from pills to insulin injections, but the fear is unjustified; the difference in cost and convenience is minor (most cats are easier to inject than to pill), and injections are more effective at treating the disease.

A pH under 7.1 is an emergency, due to the risk of cardiac arrhythmias, and may warrant treatment with intravenous bicarbonate. Bicarbonate is given at 50-100 mmol at a time under scrupulous monitoring of the arterial blood gas readings. This intervention, however, has some serious complications in lactic acidosis, and in those cases, should be used with great care.

If the acidosis is particularly severe and/or intoxication may be present, consultation with the nephrology team is considered useful, as dialysis may clear both the intoxication and the acidosis.

Food should be offered at the first signs of possible hypoglycemia. If the animal refuses it, a sugar solution (corn syrup, honey, pancake syrup, etc.) should be poured on the finger and rubbed on its gums or under the tongue (sublingually). The solution must be applied this way to prevent possible aspiration of it. Intervet suggests one tablespoon of a sugar solution rubbed onto the gums, regardless of the size of the dog. Another hypoglycemia formula is 1 gram of glucose for every kilogram (2.2 lb) of the animal's body weight. Since sugar acts quickly, a response should be seen within a minute or two.

Honey, syrup, or sugar, as simple carbohydrates, act rapidly and will make the blood glucose rise, but the rise will not last very long, as they are broken down quickly by the body. Feeding something containing complex carbohydrates when the pet is able to eat will make sure another hypoglycemia event does not overtake the rapid rise in blood glucose levels from the sugar solution. Complex carbohydrates take longer to be broken down by the body, so they do not raise blood glucose levels until some time after being eaten. A small meal should be fed and the animal taken for medical evaluation to determine if further treatment is needed. Treatment of a serious hypoglycemia episode is similar to that of diabetic humans: using glucose or glucagon infusions, depending on severity.

The general form of this treatment is an intermediate-acting basal insulin with a regimen of food and insulin every 12 hours, with the insulin injection following the meal. The most commonly used intermediate-acting insulins are NPH, also referred to as isophane, or Caninsulin, also known as Vetsulin, a porcine Lente insulin. While the normal diabetes routine is timed feedings with insulin shots following the meals, dogs unwilling to adhere to this pattern can still attain satisfactory regulation. Most dogs do not require basal/bolus insulin injections; treatment protocol regarding consistency in the diet's calories and composition along with the established feeding and injection times is generally a suitable match for the chosen intermediate-acting insulin.

With Lantus and protamine zinc insulin (PZI) being unreliable in dogs, they are rarely used to treat canine diabetes. Bovine insulin has been used as treatment for some dogs, particularly in the UK. Pfizer Animal Health discontinued of all three types of its veterinary Insuvet bovine insulins in late 2010 and suggested patients be transitioned to Caninsulin. The original owner of the insulin brand, Schering-Plough Animal Health, contracted Wockhardt UK to produce them. Wockhardt UK has produced both bovine and porcine insulins for the human pharmaceutical market for some time.

Certain medications increase the risk of hyperglycemia, including corticosteroids, octreotide, beta blockers, epinephrine, thiazide diuretics, niacin, pentamidine, protease inhibitors, L-asparaginase, and some antipsychotic agents. The acute administration of stimulants such as amphetamine typically produces hyperglycemia; chronic use, however, produces hypoglycemia. Some of the newer psychotropic medications, such as Zyprexa (Olanzapine) and Cymbalta (Duloxetine), can also cause significant hyperglycemia.

Thiazides are used to treat type 2 diabetes but it also causes severe hyperglycemia.

In many cases, neonatal diabetes may be treated with oral sulfonylureas such as glyburide. Physicians may order genetic tests to determine whether or not transitioning from insulin to sulfonylurea drugs is appropriate for a patient.

The transfer from insulin injections to oral glibenclamide therapy seems highly effective for most patients and safe. This illuminates how the molecular understanding of some monogenic form of diabetes may lead to an unexpected change of the treatment in children. This is a spectacular example of how the pharmacogenomic approach improves in a tremendous way the quality of life of the young diabetic patients.

Insulin Therapy

- Long Acting Insulin: (Insulin glargine)-is a hormone that works by lowering levels of blood glucose. It starts to work several hours after an injection and keeps working for 24 hours. It is used to manage blood glucose of diabetics. It is used to treat Type 1 and 2 diabetes in adults and Type 1 diabetes in kids as young as 6 years old.

- Short Acting Insulin (e.g. Novolin or Velosulin)-It works similarly to natural insulin and takes up to 30 minutes and lasts for about 8 hours depending on the dosage used.

- Intermediate Insulin: (e.g. NPH insulin)- Usually taken in combination with a short acting insulin. Intermediate acting insulin starts to activate within the first hour of injecting and enters a period of peak activity lasting for 7 hours.

Sulfonylureas

- Sulfonylureas: This medication signals the pancreas to release insulin and help the body's cells use insulin better. This medicaiton can lower A1C levels ( AIC is defined as a measurement of the blood glucose after previous 2–3 months) by 1-2%.

Some clinicians regard eliminating carbohydrates as unhealthy and dangerous. However, it is not necessary to eliminate carbohydrates from the diet completely to achieve ketosis. Other clinicians regard ketosis as a safe biochemical process that occurs during the fat-burning state. Ketosis, which is accompanied by gluconeogenesis (the creation of glucose de novo from pyruvate), is the specific state that concerns some clinicians. However, it is unlikely for a normally functioning person to reach life-threatening levels of ketosis, defined as serum beta-hydroxybutyrate (B-OHB) levels above 15 millimolar (mM) compared to ketogenic diets among non diabetics, which "rarely run serum B-OHB levels above 3 mM." This is avoided with proper basal secretion of pancreatic insulin. People who are unable to secrete basal insulin, such as type 1 diabetics and long-term type II diabetics, are liable to enter an unsafe level of ketosis, eventually resulting in a coma that requires emergency medical treatment. The anti-ketosis conclusions have been challenged by a number of doctors and advocates of low-carbohydrate diets, who dispute assertions that the body has a preference for glucose and that there are dangers associated with ketosis.

Screening for ketonuria is done frequently for acutely ill patients, presurgical patients, and pregnant women. Any diabetic patient who has elevated levels of blood and urine glucose should be tested for urinary ketones. In addition, when diabetic treatment is being switched from insulin to oral hypoglycemic agents, the patient's urine should be monitored for ketonuria. The development of ketonuria within 24 hours after insulin withdrawal usually indicates a poor response to the oral hypoglycemic agents. Diabetic patients should have their urine tested regularly for glucose and ketones, particularly when acute infection or other illness develops.

In conditions associated with acidosis, urinary ketones are tested to assess the severity of acidosis and to monitor treatment response. Urine ketones appear before there is any significant increase in blood ketones; therefore, urine ketone measurement is especially helpful in emergency situations.

Several medical treatments shift potassium ions from the bloodstream into the cellular compartment, thereby reducing the risk of complications. The effect of these measures tends to be short-lived, but may temporize the problem until potassium can be removed from the body.

- Insulin (e.g. intravenous injection of 10-15 units of regular insulin along with 50 ml of 50% dextrose to prevent the blood sugar from dropping too low) leads to a shift of potassium ions into cells, secondary to increased activity of the sodium-potassium ATPase. Its effects last a few hours, so it sometimes must be repeated while other measures are taken to suppress potassium levels more permanently. The insulin is usually given with an appropriate amount of glucose to prevent hypoglycemia following the insulin administration.

- Salbutamol (albuterol), a β-selective catecholamine, is administered by nebulizer (e.g. 10–20 mg). This medication also lowers blood levels of K by promoting its movement into cells.

- Sodium bicarbonate may be used with the above measures if it is believed the person has metabolic acidosis.

Severe cases require hemodialysis or hemofiltration, which are the most rapid methods of removing potassium from the body. These are typically used if the underlying cause cannot be corrected swiftly while temporizing measures are instituted or there is no response to these measures.

Potassium can bind to agents in the gastrointestinal tract. Sodium polystyrene sulfonate with sorbitol (Kayexalate) has been approved for this use and can be given by mouth or rectally. However, careful clinical trials to demonstrate the effectiveness of sodium polystyrene are lacking, and use of sodium polystyrene sulfonate, particularly if with high sorbitol content, is uncommonly but convincingly associated with colonic necrosis. There are no systematic studies (>6 months) looking at the long-term safety of this medication. Another medication by the name of patiromer was approved in 2015.

Loop diuretics (furosemide, bumetanide, torasemide) and thiazide diuretics (e.g., chlorthalidone, hydrochlorothiazide, or chlorothiazide) can increase kidney potassium excretion in people with intact kidney function.

Fludrocortisone, a synthetic mineralocorticoid, can also increase potassium excretion by the kidney in patients with functioning kidneys. Trials of fludrocortisone in patients on dialysis have shown it to be ineffective.

Patiromer is a selective sorbent that is taken by mouth and works by binding free potassium ions in the gastrointestinal tract and releasing calcium ions for exchange, thus lowering the amount of potassium available for absorption into the bloodstream and increasing the amount that is excreted via the feces. The net effect is a reduction of potassium levels in the blood serum.

Modulating and ameliorating diabetic complications may improve the overall quality of life for diabetic patients. For example; when elevated blood pressure was tightly controlled, diabetic related deaths were reduced by 32% compared to those with less controlled blood pressure.

Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate.

Ketoacidosis is a pathological metabolic state marked by extreme and uncontrolled ketosis. In ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acids that the pH of the blood is substantially decreased. In extreme cases ketoacidosis can be fatal.

Ketoacidosis is most common in untreated type 1 diabetes mellitus, when the liver breaks down fat and proteins in response to a perceived need for respiratory substrate. Prolonged alcoholism may lead to alcoholic ketoacidosis.

Ketoacidosis can be smelled on a person's breath. This is due to acetone, a direct by-product of the spontaneous decomposition of acetoacetic acid. It is often described as smelling like fruit or nail polish remover. Ketosis may also give off an odor, but the odor is usually more subtle due to lower concentrations of acetone.

Treatment consists most simply of correcting blood sugar and insulin levels, which will halt ketone production. If the severity of the case warrants more aggressive measures, intravenous sodium bicarbonate infusion can be given to raise blood pH back to an acceptable range. However, serious caution must be exercised with IV sodium bicarbonate to avoid the risk of equally life-threatening hypernatremia.

Diabetic coma was a more significant diagnostic problem before the late 1970s, when glucose meters and rapid blood chemistry analyzers were not universally available in hospitals. In modern medical practice, it rarely takes more than a few questions, a quick look, and a glucose meter to determine the cause of unconsciousness in a patient with diabetes. Laboratory confirmation can usually be obtained in half an hour or less. Other conditions that can cause unconsciousness in a person with diabetes are stroke, uremic encephalopathy, alcohol, drug overdose, head injury, or seizure.

Fortunately, most episodes of diabetic hypoglycemia, DKA, and extreme hyperosmolarity do not reach unconsciousness before a family member or caretaker seeks medical help.

Standard intravenous preparations of potassium phosphate are available and are routinely used in malnourished patients and alcoholics. Oral supplementation is also useful where no intravenous treatment are available. Historically one of the first demonstrations of this was in concentration camp victims who died soon after being re-fed: it was observed that those given milk (high in phosphate) had a higher survival rate than those who did not get milk.

Monitoring parameters during correction with IV phosphate

- Phosphorus levels should be monitored after 2 to 4 hours after each dose, also monitor serum potassium, calcium and magnesium. Cardiac monitoring is also advised.

Direct removal of lactate from the body (e.g. with hemofiltration) is difficult, with limited evidence for benefit. In type A lactic acidosis, treatment consists of effective management of the underlying cause, and limited evidence supports the use of sodium bicarbonate solutions to improve the pH (which is associated with increased carbon dioxide generation and may reduce the calcium levels).

In type B lactic acidosis produced by medication, withdrawal of the medication may be necessary to resolve the lactic acidosis.

Lactic acidosis in the context of mitochondrial disorders (type B3) may be treated with a ketogenic diet and possibly with dichloroacetate (DCA), although this may be complicated by peripheral neuropathy and has a weak evidence base.

Three common causes of ketoacidosis are alcohol, starvation, and diabetes, resulting in alcoholic ketoacidosis, starvation ketoacidosis, and diabetic ketoacidosis respectively.

In diabetic ketoacidosis, a high concentration of ketone bodies is usually accompanied by insulin deficiency, hyperglycemia, and dehydration. Particularly in type 1 diabetics the lack of insulin in the bloodstream prevents glucose absorption, thereby inhibiting the production of oxaloacetate through reduced levels of pyruvate, and can cause unchecked ketone body production (through fatty acid metabolism) potentially leading to dangerous glucose and ketone levels in the blood. Hyperglycemia results in glucose overloading the kidneys and spilling into the urine (transport maximum for glucose is exceeded). Dehydration results following the osmotic movement of water into urine (Osmotic diuresis), exacerbating the acidosis.

In alcoholic ketoacidosis, alcohol causes dehydration and blocks the first step of gluconeogenesis by depleting oxaloacetate. The body is unable to synthesize enough glucose to meet its needs, thus creating an energy crisis resulting in fatty acid metabolism, and ketone body formation.

There are several classes of anti-diabetic medications available. Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality; however, this conclusion is questioned. Metformin should not be used in those with severe kidney or liver problems.

A second oral agent of another class or insulin may be added if metformin is not sufficient after three months. Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and glucagon-like peptide-1 analogs. There is no significant difference between these agents. Rosiglitazone, a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels. Additionally it is associated with increased rates of heart disease and death. Angiotensin-converting enzyme inhibitors (ACEIs) prevent kidney disease and improve outcomes in those with diabetes. The similar medications angiotensin receptor blockers (ARBs) do not. A 2016 review recommended treating to a systolic blood pressure of 140 to 150 mmHg.

Injections of insulin may either be added to oral medication or used alone. Most people do not initially need insulin. When it is used, a long-acting formulation is typically added at night, with oral medications being continued. Doses are then increased to effect (blood sugar levels being well controlled). When nightly insulin is insufficient, twice daily insulin may achieve better control. The long acting insulins glargine and detemir are equally safe and effective, and do not appear much better than neutral protamine Hagedorn (NPH) insulin, but as they are significantly more expensive, they are not cost effective as of 2010. In those who are pregnant insulin is generally the treatment of choice.

Vitamin D supplementation to people with type 2 diabetes can improve markers of insulin resistance and HbA1c.