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.

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.

Diet is a critical component of treatment, and is in many cases effective on its own. For example, a recent mini-study showed that many diabetic cats stopped needing insulin after changing to a low carbohydrate diet.

The rationale is that a low-carbohydrate diet reduces the amount of insulin needed and keeps the variation in blood sugar low and easier to predict. Also, fats and proteins are metabolized slower than carbohydrates, reducing dangerous blood-sugar peaks right after meals.

Recent recommended diets are trending towards a low carbohydrate diet for cats rather than the formerly-recommended high-fiber diet. Carbohydrate levels are highest in dry cat foods made out of grains (even the expensive "prescription" types) so cats are better off with a canned diet that is protein and fat focused. Both prescription canned foods made for diabetic cats and regular brand foods are effective. Owners should aim to supply no more than 10% of the daily energy requirement of cats with carbohydrates.

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.

The method usually employed is a dose of slow-acting insulin, twice daily, to keep the blood sugar within a recommended range for the entire day. With this method, it is important for the cat to avoid large meals or high-carbohydrate food. Meals may also be timed to coincide with peak insulin activity. Once-daily doses are not recommended, since insulin usually metabolizes faster in cats than in humans or dogs. For example, an insulin brand that lasts 24 hours in people may only be effective for about 12 in a cat.

Cats may be treated with animal insulin (bovine-based insulin is most similar to cat insulin), or with human synthetic insulin. The best choice of insulin brand and type varies from animal-to-animal and may require some trial-and-error. The human synthetic insulin, Humulin N /Novolin N/ NPH, is usually a poor choice for cats, since cats metabolize insulin about twice as fast. The Lente and Ultralente versions were popular for feline use until summer 2005, when they were discontinued.

Until the early 1990s, the most recommended type for pets was bovine/porcine-derived PZI, but that type was phased out over the 1990s and is now difficult to find in many countries. There are sources in the US and UK, and many vets are now starting to recommend them again for pets, but they have been discontinued by most manufacturers as of 2007-2008. A new synthetic PZI analogue called ProZinc is now available.

Caninsulin (known in the USA as Vetsulin) is a brand of porcine-based insulin approved for cats which is available with a veterinarian's prescription. According to the manufacturer's website, the insulin's action profile in cats was similar to that of NPH insulin, and lowered blood sugar quickly, but for only about 6–8 hours. Vetsulin was recalled in the USA in November 2009 due to inconsistent strength; it was available again as of April 2013.

Two ultra-slow time-release synthetic human insulins became available in 2004 and 2005, generically known as insulin detemir (Levemir) and insulin glargine (Lantus). Studies have had good results with insulin glargine in cats. Follow-up research shows that Levemir can be used with a similar protocol and that either insulin, on this protocol, can lead uncomplicated feline cases to remission, with the most success being in cats who start on these protocols as soon as possible after diagnosis.

The progression to type 2 diabetes mellitus is not inevitable for those with prediabetes. The progression into diabetes mellitus from prediabetes is approximately 25% over three to five years.

The American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) have developed "lifestyle intervention" guidelines for preventing the onset of type 2 diabetes:

- Healthy meals (a diet with no saturated and trans fats, sugars, and refined carbohydrates, as well as limited the intake of sodium and total calories)

- Physical exercise (30–45 minutes of cardio vascular exercise per day, five days a week)

- Reducing weight by as little as 5–10 percent may have a significant impact on overall health

Most of the commercially available prescription diabetes foods are high in fiber, complex carbohydrates, and have proven therapeutic results. Of primary concern is getting or keeping the animal eating, as use of the prescribed amount of insulin is dependent on eating full meals. When no meal is eaten, there is still a need for a basal dosage of insulin, which supplies the body's needs without taking food into consideration. Eating a partial meal means a reduction in insulin dose. Basal and reduced insulin dose information should be part of initial doctor–client diabetes discussions in case of need.

It is possible to regulate diabetes without any diet change. If the animal will not eat a prescribed diet, it is not in the dog's best interest to insist on it; the amount of additional insulin required because a non-prescription diet is being fed is generally between 2–4%. Semi moist foods should be avoided as they tend to contain a lot of sugars. Since dogs with diabetes are prone to pancreatitis and hyperlipidemia, feeding a low-fat food may help limit or avoid these complications. A non-prescription food with a "fixed formula" would be suitable because of the consistency of its preparation. Fixed formula foods contain precise amounts of their ingredients so batches or lots do not vary much if at all. "Open formula" foods contain the ingredients shown on the label but the amount of them can vary, however they must meet the guaranteed analysis on the package. These changes may have an effect on the control of diabetes. Prescription foods are fixed formulas, while most non-prescription ones are open formula unless the manufacturer states otherwise.

Some research has suggested breastfeeding decreases the risk in later life and early introduction of gluten-containing cereals in the diet increases the risk of developing islet cell autoantibodies; various other nutritional risk factors are being studied, but no firm evidence has been found.

Giving children 2000 IU of vitamin D daily during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure.

Children with antibodies to beta cell proteins (i.e. at early stages of an immune reaction to them) but no overt diabetes, and treated with niacinamide (vitamin B), had less than half the diabetes onset incidence in a seven-year time span than did the general population, and an even lower incidence relative to those with antibodies as above, but who received no niacinamide.

People with type 1 diabetes and undiagnosed celiac disease have worse glycaemic control and a higher prevalence of nephropathy and retinopathy. Gluten-free diet, when performed strictly, improves diabetes symptoms and appears to have a protective effect against developing long-term complications. Nevertheless, dietary management of both these diseases is challenging and these patients have poor compliance of the diet.

Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise. Intensive lifestyle measures may reduce the risk by over half. The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss. High levels of physical activity reduce the risk of diabetes by about 28%. Evidence for the benefit of dietary changes alone, however, is limited, with some evidence for a diet high in green leafy vegetables and some for limiting the intake of sugary drinks. In those with impaired glucose tolerance, diet and exercise either alone or in combination with metformin or acarbose may decrease the risk of developing diabetes. Lifestyle interventions are more effective than metformin. A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal. While low vitamin D levels are associated with an increased risk of diabetes, correcting the levels by supplementing vitamin D3 does not improve that risk.

Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of beta cells (on the basis of reduced insulin usage), but its kidney toxicity and other side effects make it highly inappropriate for long-term use.

Anti-CD3 antibodies, including teplizumab and otelixizumab, had suggested evidence of preserving insulin production (as evidenced by sustained C-peptide production) in newly diagnosed type 1 diabetes patients. A probable mechanism of this effect was believed to be preservation of regulatory T cells that suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. The duration of the effect is still unknown, however. In 2011, Phase III studies with otelixizumab and teplizumab both failed to show clinical efficacy, potentially due to an insufficient dosing schedule.

An anti-CD20 antibody, rituximab, inhibits B cells and has been shown to provoke C-peptide responses three months after diagnosis of type 1 diabetes, but long-term effects of this have not been reported.

Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range. Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes may be used in combination with education, however the benefit of self monitoring in those not using multi-dose insulin is questionable. In those who do not want to measure blood levels, measuring urine levels may be done. Managing other cardiovascular risk factors, such as hypertension, high cholesterol, and microalbuminuria, improves a person's life expectancy. Decreasing the systolic blood pressure to less than 140 mmHg is associated with a lower risk of death and better outcomes. Intensive blood pressure management (less than 130/80 mmHg) as opposed to standard blood pressure management (less than 140/85–100 mmHg) results in a slight decrease in stroke risk but no effect on overall risk of death.

Intensive blood sugar lowering (HbA<6%) as opposed to standard blood sugar lowering (HbA of 7–7.9%) does not appear to change mortality. The goal of treatment is typically an HbA of around 7% or a fasting glucose of less than 7.2 mmol/L (130 mg/dL); however these goals may be changed after professional clinical consultation, taking into account particular risks of hypoglycemia and life expectancy. Despite guidelines recommending that intensive blood sugar control be based on balancing immediate harms with long-term benefits, many people—for example people with a life expectancy of less than nine years who will not benefit, are over-treated.

It is recommended that all people with type 2 diabetes get regular eye examination. There is weak evidence suggesting that treating gum disease by scaling and root planing may result in a small short-term improvement in blood sugar levels for people with diabetes. There is no evidence to suggest that this improvement in blood sugar levels is maintained longer than 4 months. There is also not enough evidence to determine if medications to treat gum disease are effective at lowering blood sugar levels.

The guidelines for preventing impaired fasting glucose are the same as those given for preventing type 2 diabetes in general. If these are adhered to, the progression to clinical diabetes can be slowed or halted. In some cases, a complete reversal of IFG can be achieved. Certain risk factors, such as being of Afro-Caribbean or South Asian ethnicity, as well as increasing age, are unavoidable, and such individuals may be advised to follow these guidelines, as well as monitor their blood glucose levels, more closely.

Inhalable insulin has been developed. The original products were withdrawn due to side effects. Afrezza, under development by the pharmaceuticals company MannKind Corporation, was approved by the FDA for general sale in June 2014. An advantage to inhaled insulin is that it may be more convenient and easy to use.

Transdermal insulin in the form of a cream has been developed and trials are being conducted on people with type2 diabetes.

There is no known preventive measure for type 1 diabetes. Type 2 diabeteswhich accounts for 85–90% of all casescan often be prevented or delayed by maintaining a normal body weight, engaging in physical activity, and consuming a healthy diet. Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish. Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes. Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.

The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.

The risk of progression to diabetes and development of cardiovascular disease is greater than for impaired fasting glucose.

Although some drugs can delay the onset of diabetes, lifestyle modifications play a greater role in the prevention of diabetes. Patients identified as having an IGT may be able to prevent diabetes through a combination of increased exercise and reduction of body weight. "Drug therapy can be considered when aggressive lifestyle interventions are unsuccessful."

The blood glucose can usually be raised to normal within minutes with 15-20 grams of carbohydrate, although overtreatment should be avoided if at all possible. It can be taken as food or drink if the person is conscious and able to swallow. This amount of carbohydrate is contained in about 3-4 ounces (100-120 mL) of orange, apple, or grape juice, about 4-5 ounces (120-150 mL) of regular (non-diet) soda, about one slice of bread, about 4 crackers, or about 1 serving of most starchy foods. Starch is quickly digested to glucose, but adding fat or protein retards digestion. Composition of the treatment should be considered, as fruit juice is typically higher in fructose which takes the body longer to metabolize than simple dextrose alone. Following treatment, symptoms should begin to improve within 5 to 10 minutes, although full recovery may take 10–20 minutes. It should be noted that over treatment does not speed recovery, and will simply produce hyperglycemia afterwards, which ultimately will need to be corrected. On the other hand, since the excess of insulin over the amount required to normalize blood sugar may continue to reduce blood sugar levels after treatment has produced an initial normalization, continued monitoring is required to determine if further treatment is necessary.

Treatment is typically achieved via diet and exercise, although metformin may be used to reduce insulin levels in some patients (typically where obesity is present). A referral to a dietician is beneficial. Another method used to lower excessively high insulin levels is cinnamon as was demonstrated when supplemented in clinical human trials.

A low carbohydrate diet is particularly effective in reducing hyperinsulinism.

A healthy diet that is low in simple sugars and processed carbohydrates, and high in fiber, and vegetable protein is often recommended. This includes replacing white bread with whole-grain bread, reducing intake of foods composed primarily of starch such as potatoes, and increasing intake of legumes and green vegetables, particularly soy.

Regular monitoring of weight, blood sugar, and insulin are advised, as hyperinsulinemia may develop into diabetes mellitus type 2.

It has been shown in many studies that physical exercise improves insulin sensitivity. The mechanism of exercise on improving insulin sensitivity is not well understood however it is thought that exercise causes the glucose receptor GLUT4 to translocate to the membrane. As more GLUT4 receptors are present on the membrane more glucose is taken up into cells decreasing blood glucose levels which then causes decreased insulin secretion and some alleviation of hyperinsulinemia. Another proposed mechanism of improved insulin sensitivity by exercise is through AMPK activity. The beneficial effect of exercise on hyperinsulinemia was shown in a study by Solomon et al. (2009), where they found that improving fitness through exercise significantly decreases blood insulin concentrations.

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.

If a person cannot receive oral glucose gel or tablets, such as the case with unconsciousness, seizures, or altered mental status, then emergency personnel (EMTs/Paramedics and in-hospital personnel) can establish a peripheral or central IV line and administer a solution containing dextrose and saline. These are normally referred to as Dextrose (Concentration) Water, and come in 5%, 10%, 25% and 50%. Dextrose 5% and 10% come in IV bag and syringe form, and are mainly used in infants and to provide a fluid medium for medications. Dextrose 25% and 50% are heavily necrotic due to their hyperosmolarity, and should only be given through a patent IV line - Any infiltration can cause massive tissue necrosis. CAUTION: Dextrose 25% and 50% can easily cause necrosis in small veins. It is MUCH safer to use a Dextrose 10% solution when treating hypoglycemia via IV in children under the age of 14. When using Dextrose 25% in a child it is safer to administer it through a central line or an intra-oseous line.

Clinical Trials of NDM

- The research article is entitled, "A Successful Transition to sulfonamides treatment in male infant with novel neonatal diabetes mellitus (NDM) caused by the ABBC8 gene mutation and 3 years follow up". It is a case study on the transitioning of treatments from insulin therapy to sulfonamides therapy. NDM is not initiated by an autoimmune mechanism but mutations in K-sensitve channel, "KCNJ11, ABCC8" and "INS" genes are successful targets for changing treatments from insulin to sulfonamides therapy.

- Introduction: Within this study a two month old male was admitted into the intensive care unit, because the he was showing signs of diabetic ketoacidosis. Other symptoms include, respiratory tract infection, sporous, dehydration, reduced subcutaneous fat, Candida mucous infection. The infant's family history was negative for diseases of importance to hereditary and the eldest sibling was healthy.

- Experiment: The current treatment plan consist of therapy for ketoacidosis was started upon admissions into the hospital. Also, subcutaneous insulin was given (0.025-0.05 units/kg/h) and adjusted to the glycaemic profiles and the patient was converted to euglycaemic state. After 24 hours, oral intake of insulin started and treatment continued with subcutaneous short acting insulin then intermediate acting insulin plus 2 dosage of short acting insulin. A genetic analysis was conducted for NDM and mutation of KCNJ11, "ABCC8" and "INS" genes have been given. Sequence analysis showed a rare heterogeneous missense mutation, PF577L, in the patient's exon 12 of ABCC8 gene. This confirms diagnosis of NDM caused by heterozygous mutation in the SUR1 subunit of the pancreatic ATP-sensitive potassium channel, because his parents' white blood cells did not show signs of this mutation.

- Results: Switching from the insulin therapy to the sulfonamides was a successful treatment. It is the current regimen used to treat NDM.

- Discussion/Conclusion: ABCC8 gene produces SUR1 protein subunit that interacts with pancreatic ATP-sensitive potassium channel. When the channel opens a large amount of insulin is released. Mutations that occur in ABCC8 are associated with congential hyperinsulinism and PNDM or TNDM. Patients that have mutations in their potassium channel, improved their glucose levels with sulfonylurea regimen and glibenclamide showed successful results in managing glucose levels as well.

- A 2006 study showed that 90% of patients with a KCNJ11 mutation were able to successfully transition to sulfonylurea therapy.

About 80% of all LADA patients initially misdiagnosed with type 2 (and who have GAD antibodies) will become insulin-dependent within 3 to 15 years (according to differing LADA sources).

The treatment for Type 1 diabetes/LADA is exogenous insulin to control glucose levels, prevent further destruction of residual beta cells, reduce the possibility of diabetic complications, and prevent death from diabetic ketoacidosis (DKA). Although LADA may appear to initially respond to similar treatment (lifestyle and medications) as type 2 diabetes, it will not halt or slow the progression of beta cell destruction, and people with LADA will eventually become insulin-dependent. People with LADA have insulin resistance similar to long-term type 1 diabetes; some studies showed that people with LADA have less insulin resistance, compared with those with type 2 diabetes; however, others have not found a difference.

It is estimated that between 6-50% of all persons, depending on population, diagnosed with type 2 diabetes might actually have LADA. This number accounts for an estimated 5–10% of the total diabetes population in the U.S. or, as many as 3.5 million persons with LADA. People with LADA typically have a normal BMI or may be underweight due to weight loss prior to diagnosis. Some people with LADA, however, may be overweight to mildly obese.

Contrary to popular belief, some people having LADA do carry a family history of type 2 diabetes.

Gestational diabetes affects 3–10% of pregnancies, depending on the population studied.

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%.