Children's blood sugar levels are often slightly lower than adults'. Overnight fasting glucose levels are below 70 mg/dL (3.9 mM) in 5% of healthy adults, but up to 5% of children can be below 60 mg/dL (3.3 mM) in the morning fasting state. As the duration of fasting is extended, a higher percentage of infants and children will have mildly low plasma glucose levels, usually without symptoms. The normal range of newborn blood sugars continues to be debated. It has been proposed that newborn brains are able to use alternate fuels when glucose levels are low more readily than adults. Experts continue to debate the significance and risk of such levels, though the trend has been to recommend maintenance of glucose levels above 60–70 mg/dL the first day after birth.

Diabetic hypoglycemia represents a special case with respect to the relationship of measured glucose and hypoglycemic symptoms for several reasons. First, although home glucose meter readings are often misleading, the probability that a low reading, whether accompanied by symptoms or not, represents real hypoglycemia is much higher in a person who takes insulin than in someone who does not.

The concentration of ketone bodies may vary depending on diet, exercise, degree of metabolic adaptation and genetic factors. Ketosis can be induced when a ketogenic diet is followed for more than 3 days. This induced ketosis is sometimes called nutritional ketosis. This table shows the concentrations typically seen under different conditions

Note that urine measurements may not reflect blood concentrations. Urine concentrations are lower with greater hydration, and after adaptation to a ketogenic diet the amount lost in the urine may drop while the metabolism remains ketotic. Most urine strips only measure acetoacetate, while when ketosis is more severe the predominant ketone body is β-hydroxybutyrate. Unlike glucose, ketones are excreted into urine at any blood level. Ketoacidosis is a metabolic derangement that cannot occur in a healthy individual who can produce insulin, and should not be confused with physiologic ketosis.

The following is a brief list of hormones and metabolites which may be measured in a critical sample. Not all tests are checked on every patient. A "basic version" would include insulin, cortisol, and electrolytes, with C-peptide and drug screen for adults and growth hormone in children. The value of additional specific tests depends on the most likely diagnoses for an individual patient, based on the circumstances described above. Many of these levels change within minutes, especially if glucose is given, and there is no value in measuring them after the hypoglycemia is reversed. Others, especially those lower in the list, remain abnormal even after hypoglycemia is reversed, and can be usefully measured even if a critical specimen is missed.

Part of the value of the critical sample may simply be the proof that the symptoms are indeed due to hypoglycemia. More often, measurement of certain hormones and metabolites at the time of hypoglycemia indicates which organs and body systems are responding appropriately and which are functioning abnormally. For example, when the blood glucose is low, hormones which raise the glucose should be rising and insulin secretion should be completely suppressed.

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.

The diagnosis is based on a combination of typical clinical features and exclusion by a pediatric endocrinologist of other causes of "hypoglycemia with ketosis," especially growth hormone deficiency, hypopituitarism, adrenal insufficiency, and identifiable inborn errors of metabolism such as organic acidoses.

The most useful diagnostic tests include measurement of insulin, growth hormone, cortisol, and lactic acid at the time of the hypoglycemia. Plasma acylcarnitine levels and urine organic acids exclude some of the important metabolic diseases. When the episodes are recurrent or severe, the definitive test is a hospitalization for a supervised diagnostic fast. This usually demonstrates "accelerated fasting"—a shorter time until the glucose begins to fall, but normal metabolic and counterregulatory responses as the glucose falls. As the glucose reaches hypoglycemic levels, the insulin is undetectable, counterregulatory hormones, fatty acids, and ketones are high, and glucagon injection elicits no rise of glucose.

Children "outgrow" ketotic hypoglycemia, presumably because fasting tolerance improves as body mass increases. In most the episodes become milder and more infrequent by 4 to 5 years of age and rarely occur after age 9. Onset of hypoglycemia with ketosis after age 5 or persistence after age 7 should elicit referral and an intensive search for a more specific disease.

Ketones in the urine or blood, as detected by urine strips or a blood ketone testing meter, may indicate the beginning of diabetic ketoacidosis (DKA), a dangerous and often quickly fatal condition caused by high glucose levels (hyperglycemia) and low insulin levels combined with certain other systemic stresses. DKA can be arrested if caught quickly.

Ketones are produced by the liver as part of fat metabolism and are normally not found in sufficient quantity to be measured in the urine or blood of non-diabetics or well-controlled diabetics. The body normally uses glucose as its fuel and is able to do so with sufficient insulin levels. When glucose is not available as an energy source because of untreated or poorly treated diabetes and some other unrelated medical conditions, it begins to use fat for energy instead. The result of the body turning to using fat instead of glucose for energy means ketone production that is measurable when testing either urine or blood for them.

Ketone problems that are more serious than the "trace or slight" range need immediate medical attention; they cannot be treated at home. Veterinary care for ketosis/ketoacidosis can involve intravenous (IV) fluids to counter dehydration, when necessary, to replace depleted electrolytes, intravenous or intramuscular short-acting insulin to lower blood glucose levels, and measured amounts of glucose or force feeding, to bring the metabolism back to using glucose instead of fat as its source of energy.

When testing urine for ketones, the sample needs to be as fresh as possible. Ketones evaporate quickly, so there is a chance of getting a false negative test result if testing older urine. The urine testing strip bottle has instructions and color charts to illustrate how the color on the strip will change given the level of ketones or glucose in the urine over 15 (ketones–Ketostix) or 30 (glucose–Ketodiastix) seconds. Reading the colors at those time intervals is important because the colors will continue to darken and a later reading will be an incorrect result. Timing with a clock or watch second hand instead of counting is more accurate.

At present, there is only one glucometer available for home use that tests blood for ketones using special strips for that purpose–Abbott's Precision Xtra. This meter is known as Precision, Optium, or Xceed outside of the US. The blood ketone test strips are very expensive; prices start at about US$50 for ten strips. It is most likely urine test strips–either ones that test only for ketones or ones that test for both glucose and ketones in urine would be used. The table above is a guide to when ketones may be present.

The use of an inexpensive glucometer and blood glucose testing at home can help avoid dangerous insulin overdoses and can provide a better picture of how well the condition is managed.

A 2003 study of canine diabetes caregivers who were new to testing blood glucose at home found 85% of them were able to both succeed at testing and to continue it on a long-term basis. Using only one blood glucose reading as the reason for an insulin dose increase is to be avoided; while the results may be higher than desired, further information, such as the lowest blood glucose reading or nadir, should be available to prevent possible hypoglycemia.

Urine strips are not recommended to be used as the sole factor for insulin adjustments as they are not accurate enough. Urine glucose testing strips have a negative result until the renal threshold of 10 mmol/L or 180 mg/dL is reached or exceeded for a period of time. The range of negative reading values is quite wide-covering normal or close to normal blood glucose values with no danger of hypoglycemia (euglycemia) to low blood glucose values (hypoglycemia) where treatment would be necessary. Because urine is normally retained in the bladder for a number of hours, the results of urine testing are not an accurate measurement of the levels of glucose in the bloodstream at the time of testing.

Glucometers made for humans are generally accurate using canine and feline blood except when reading lower ranges of blood glucose (<80 mg/dL), (<4.44 mmol/L). It is at this point where the size difference in human vs animal red blood cells can create inaccurate readings. Glucometers for humans were successfully used with pets long before animal-oriented meters were produced. A 2009 study directly compared readings from both types of glucometers to those of a chemistry analyzer. Neither glucometer's readings exactly matched those of the analyzer, but the differences of both were not clinically significant when compared to analyzer results. All glucometer readings need to be compared to same sample laboratory values to determine accuracy.

Attacks of DKA can be prevented in those known to have diabetes to an extent by adherence to "sick day rules"; these are clear-cut instructions to person on how to treat themselves when unwell. Instructions include advice on how much extra insulin to take when sugar levels appear uncontrolled, an easily digestible diet rich in salt and carbohydrates, means to suppress fever and treat infection, and recommendations when to call for medical help.

People with diabetes can monitor their own ketone levels when unwell and seek help if they are elevated.

Cranial imaging is not used for diagnosis of this condition. However, if MRI is performed, it may show cortical restricted diffusion with unusual characteristics of reversible T2 hypointensity in the subcortical white matter.

Serum glucose levels are measured to document the degree of hypoglycemia. Serum electrolytes calculate the anion gap to determine presence of metabolic acidosis; typically, patients with glycogen-storage disease type 0 (GSD-0) have an anion gap in the reference range and no acidosis. See the Anion Gap calculator.

Serum lipids (including triglyceride and total cholesterol) may be measured. In patients with glycogen-storage disease type 0, hyperlipidemia is absent or mild and proportional to the degree of fasting.

Urine (first voided specimen with dipstick test for ketones and reducing substances) may be analyzed. In patients with glycogen-storage disease type 0, urine ketones findings are positive, and urine-reducing substance findings are negative. However, urine-reducing substance findings are positive (fructosuria) in those with fructose 1-phosphate aldolase deficiency (fructose intolerance).

Serum lactate is in reference ranges in fasting patients with glycogen-storage disease type 0.

Liver function studies provide evidence of mild hepatocellular damage in patients with mild elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.Plasma amino-acid analysis shows plasma alanine levels as in reference ranges during a fast.

Evaluation of a patient with suspected glycogen-storage disease type 0 requires monitored assessment of fasting adaptation in an inpatient setting.

Patients typically have hypoglycemia and ketosis, with lactate and alanine levels in the low or normal part of the reference range approximately 5–7 hours after fasting.

A glucagon tolerance test may be needed if the fast fails to elicit the expected rise in plasma glucose. Lactate and alanine levels are in the reference range.

By contrast, a glucagon challenge test after a meal causes hyperglycemia, with increased levels of plasma lactate and alanine.

Oral loading of glucose, galactose, or fructose results in a marked rise in blood lactate levels.

Diabetic ketoacidosis may be diagnosed when the combination of hyperglycemia (high blood sugars), ketones in the blood or on urinalysis and acidosis are demonstrated. In about 10% of cases the blood sugar is not significantly elevated ("euglycemic diabetic ketoacidosis").

Arterial blood gas measurement is usually performed to demonstrate the acidosis; this requires taking a blood sample from an artery. Subsequent measurements (to ensure treatment is effective), may be taken from a normal blood test taken from a vein, as there is little difference between the arterial and the venous pH. Ketones can be measured in the urine (acetoacetate) and blood (β-hydroxybutyrate). When compared with urine acetoacetate testing, capillary blood β-hydroxybutyrate determination can reduce the need for admission, shorten the duration of hospital admission and potentially reduce the costs of hospital care. At very high levels, capillary blood ketone measurement becomes imprecise.

In addition to the above, blood samples are usually taken to measure urea and creatinine (measures of kidney function, which may be impaired in DKA as a result of dehydration) and electrolytes. Furthermore, markers of infection (complete blood count, C-reactive protein) and acute pancreatitis (amylase and lipase) may be measured. Given the need to exclude infection, chest radiography and urinalysis are usually performed.

If cerebral edema is suspected because of confusion, recurrent vomiting or other symptoms, computed tomography may be performed to assess its severity and to exclude other causes such as stroke.

Insulin is given to reduce blood glucose concentration; however, as it also causes the movement of potassium into cells, serum potassium levels must be sufficiently high or dangerously low blood potassium levels may result. Once potassium levels have been verified to be greater than 3.3 mEq/l, then an insulin infusion of 0.1 units/kg/hr is started. The goal for resolution is a blood glucose of less than 200 mg/dL.

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.

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.

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.

In the fetus, the normal range differs based on which umbilical vessel is sampled (umbilical vein pH is normally 7.25 to 7.45; umbilical artery pH is normally 7.20 to 7.38). In the fetus, the lungs are not used for ventilation. Instead, the placenta performs ventilatory functions (gas exchange). Fetal respiratory acidemia is defined as an umbilical vessel pH of less than 7.20 and an umbilical artery PCO of 66 or higher or umbilical vein PCO of 50 or higher.

A 1988 study over 41 months found that improved glucose control led to initial "worsening of complications" but was not followed by the expected improvement in complications. In 1993 it was discovered that the serum of diabetics with neuropathy is toxic to nerves, even if its blood sugar content is normal.

Research from 1995 also challenged the theory of hyperglycemia as the cause of diabetic complications. The fact that 40% of diabetics who carefully controlled their blood sugar nevertheless developed neuropathy made clear other factors were involved.

In a 2013 meta-analysis of 6 randomized controlled trials involving 27,654 patients, tight blood glucose control reduced the risk for some macrovascular and microvascular events but without effect on all-cause mortality and cardiovascular mortality.

Treatment of uncompensated metabolic acidosis is focused upon correcting the underlying problem. When metabolic acidosis is severe and can no longer be compensated for adequately by the lungs, neutralizing the acidosis with infusions of bicarbonate may be required.

Causes include:

The newest mnemonic was proposed in "The Lancet" reflecting current causes of anion gap metabolic acidosis:

- G — glycols (ethylene glycol & propylene glycol)

- O — oxoproline, a metabolite of paracetamol

- L — L-lactate, the chemical responsible for lactic acidosis

- D — D-lactate

- M — methanol

- A — aspirin

- R — renal failure

- K — ketoacidosis, ketones generated from starvation, alcohol, and diabetic ketoacidosis

The mnemonic MUDPILES is commonly used to remember the causes of increased anion gap metabolic acidosis.

- M — Methanol

- U — Uremia (chronic kidney failure)

- D — Diabetic ketoacidosis

- P — Paracetamol, Propylene glycol (used as an inactive stabilizer in many medications; historically, the "P" also stood for Paraldehyde, though this substance is not commonly used today)

- I — Infection, Iron, Isoniazid (which can cause lactic acidosis in overdose), Inborn errors of metabolism (an especially important consideration in pediatric patients)

- L — Lactic acidosis

- E — Ethylene glycol (Note: Ethanol is sometimes included in this mnemonic as well, although the acidosis caused by ethanol is actually primarily due to the increased production of lactic acid found in such intoxication.)

- S — Salicylates

Another frequently used mnemonic is KARMEL.

- K — Ketoacidosis

- A — aspirin

- R — Renal failure

- M — Methanol

- E — Ethylene glycol

- L — Lactic acidosis

Another frequently used mnemonic is KULT.

- K — Ketoacidosis (DKA, AKA)

- U — Uremia

- L — Lactic acidosis

- T — Toxins (Ethylene glycol, methanol, as well as drugs, such as aspirin, Metformin)

The preferred mnemonic of D. Robert Dufour, the chief of the Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center, is DUMPSALE, which omits the I of MUDPILES as the proposed values of *I* are exceedingly rare in clinical practice.

- D — Diabetic ketoacidosis

- U — Uremia

- M — Methanol

- P — Paraldehyde

- S — Salicylates

- A — Alcoholic ketoacidosis

- L — Lactic acidosis

- E — Ethylene Glycol

The mnemonic for the [rare, in comparison] toxins is ACE GIFTs: Aspirin, Cyanide, Ethanolic ketosis, Glycols [ ethylene and propylene ], Isoniazid, Ferrous iron, Toluene. Most of these cause a lactic acidosis.

Diabetes mellitus is characterized by recurrent or persistent high blood sugar, and is diagnosed by demonstrating any one of the following:

- Fasting plasma glucose level ≥ 7.0 mmol/l (126 mg/dl)

- Plasma glucose ≥ 11.1 mmol/l (200 mg/dl) two hours after a 75 g oral glucose load as in a glucose tolerance test

- Symptoms of high blood sugar and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)

- Glycated hemoglobin (HbA) ≥ 48 mmol/mol (≥ 6.5 DCCT %).

A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 126 mg/dl (7.0 mmol/l) is considered diagnostic for diabetes mellitus.

Per the World Health Organization people with fasting glucose levels from 6.1 to 6.9 mmol/l (110 to 125 mg/dl) are considered to have impaired fasting glucose. people with plasma glucose at or above 7.8 mmol/l (140 mg/dl), but not over 11.1 mmol/l (200 mg/dl), two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease. The American Diabetes Association since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9 mmol/l (100 to 125 mg/dl).

Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.

When acidosis is present on blood tests, the first step in determining the cause is determining the anion gap. If the anion gap is high (>12 mEq/L), there are several potential causes.

High anion gap metabolic acidosis is a form of metabolic acidosis characterized by a high anion gap (a medical value based on the concentrations of ions in a patient's serum). An anion gap is usually considered to be high if it is over 12 mEq/L.

High anion gap metabolic acidosis is caused generally by acid produced by the body. More rarely, high anion gap metabolic acidosis may be caused by ingesting methanol or overdosing on aspirin. The Delta Ratio is a formula that can be used to assess elevated anion gap metabolic acidosis and to evaluate whether mixed acid base disorder (metabolic acidosis) is present.

The list of agents that cause high anion gap metabolic acidosis is similar to but broader than the list of agents that cause a serum osmolal gap.

There are two types of this inherited condition, "glycogen storage disease IXa1" and "glycogen storage disease IXa2" that affect the liver of an individual. Mutations in PHKA2 have been seen in individuals with glycogen storage disease IXa2.

The diagnosis of glycogen storage disease IX consists of the following:

- Complete blood count

- Urinalysis

- Histological study of the liver (via biopsy)

- Genetic testing

- Physical exam