In some cases, a pancreas transplant can restore proper glucose regulation. However, the surgery and accompanying immunosuppression required may be more dangerous than continued insulin replacement therapy, so is generally only used with or some time after a kidney transplant. One reason for this is that introducing a new kidney requires taking immunosuppressive drugs such as cyclosporine, which allows the introduction of a new pancreas to a person with diabetes without any additional immunosuppressive therapy. However, pancreas transplants alone may be beneficial in people with extremely labile type 1 diabetes mellitus.

A low-carbohydrate diet, exercise, and medications is useful in type 1 DM. There are camps for children to teach them how and when to use or monitor their insulin without parental help. As psychological stress may have a negative effect on diabetes, a number of measures have been recommended including: exercising, taking up a new hobby, or joining a charity among others.

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.

Medications used to treat diabetes do so by lowering blood sugar levels. There are a number of different classes of anti-diabetic medications. Some are available by mouth, such as metformin, while others are only available by injection such as GLP-1 agonists. Type 1 diabetes can only be treated with insulin, typically with a combination of regular and NPH insulin, or synthetic insulin analogs.

Metformin is generally recommended as a first line treatment for type 2 diabetes, as there is good evidence that it decreases mortality. It works by decreasing the liver's production of glucose. Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type II DM. These include agents that increase insulin release, agents that decrease absorption of sugar from the intestines, and agents that make the body more sensitive to insulin. When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications. Doses of insulin are then increased to effect.

Since cardiovascular disease is a serious complication associated with diabetes, some have recommended blood pressure levels below 130/80 mmHg. However, evidence supports less than or equal to somewhere between 140/90 mmHg to 160/100 mmHg; the only additional benefit found for blood pressure targets beneath this range was an isolated decrease in stroke risk, and this was accompanied by an increased risk of other serious adverse events. A 2016 review found potential harm to treating lower than 140 mmHg. Among medications that lower blood pressure, angiotensin converting enzyme inhibitors (ACEIs) improve outcomes in those with DM while the similar medications angiotensin receptor blockers (ARBs) do not. Aspirin is also recommended for people with cardiovascular problems, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.

Weight loss surgery in those who are obese is an effective measure to treat diabetes. Many are able to maintain normal blood sugar levels with little or no medication following surgery and long-term mortality is decreased. There however is some short-term mortality risk of less than 1% from the surgery. The body mass index cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.

People with diabetes can benefit from education about the disease and treatment, good nutrition to achieve a normal body weight, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.

There is no single dietary pattern that is best for all people with diabetes. For overweight people with type 2 diabetes, any diet that the person will adhere to and achieve weight loss on is effective.

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%.

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.

Chronic hyperglycemia due to any cause can eventually cause blood vessel damage and the microvascular complications of diabetes. The principal treatment goals for people with MODY — keeping the blood sugars as close to normal as possible ("good glycemic control"), while minimizing other vascular risk factors — are the same for all known forms of diabetes.

The tools for management are similar for all forms of diabetes: blood testing, changes in diet, physical exercise, oral hypoglycemic agents, and insulin injections. In many cases these goals can be achieved more easily with MODY than with ordinary types 1 and 2 diabetes. Some people with MODY may require insulin injections to achieve the same glycemic control that another person may attain with careful eating or an oral medication.

When oral hypoglycemic agents are used in MODY, the sulfonylureas remain the oral medication of first resort. When compared to patients with type 2 diabetes, MODY patients are often more sensitive to sulphonylureas, such that a lower dose should be used to initiate treatment to avoid hypoglycaemia. Patients with MODY less often suffer from obesity and insulin resistance than those with ordinary type 2 diabetes (for whom insulin sensitizers like metformin or the thiazolidinediones are often preferred over the sulfonylureas).

If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might be necessary. This is most commonly fast-acting insulin given just before eating to blunt glucose rises after meals. Care needs to be taken to avoid low blood sugar levels due to excessive insulin. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits. A 2016 Cochrane review concluded that quality evidence is not yet available to determine the best blood sugar range for improving health for pregnant women with GDM and their babies.

There is some evidence that certain medications by mouth might be safe in pregnancy, or at least, are less dangerous to the developing fetus than poorly controlled diabetes. The medication metformin is better than glyburide. If blood glucose cannot be adequately controlled with a single agent, the combination of metformin and insulin may be better than insulin alone. Another review found good short term safety for both the mother and baby with metformin but unclear long term safety.

People may prefer metformin by mouth to insulin injections. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.

Almost half of the women did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight. With no long-term studies into children of women treated with the drug, there remains a possibility of long-term complications from metformin therapy. Babies born to women treated with metformin have been found to develop less visceral fat, making them less prone to insulin resistance in later life.

There is evidence that prediabetes is a curable disease state. Intensive weight loss and lifestyle intervention, if sustained, may improve glucose tolerance substantially and prevent progression from IGT to type 2 diabetes. The Diabetes Prevention Program (DPP) study found a 16% reduction in diabetes risk for every kilogram of weight loss. Reducing weight by 7% through a low-fat diet and performing 150 minutes of exercise a week is the goal. In observational studies, individuals following vegetarian diets are about half as likely to develop diabetes, compared with non-vegetarians. The ADA guidelines recommend modest weight loss (5–10% body weight), moderate-intensity exercise (30 minutes daily), and smoking cessation.

There are claims in the media that a high-fat, high-protein, low carbohydrates diet can reverse prediabetes, but scientific evidence is not conclusive as to whether this diet has any efficacy.

For patients with severe risk factors, prescription medication may be appropriate. This may be considered in patients for whom lifestyle therapy has failed, or is not sustainable, and who are at high-risk for developing type 2 diabetes. Metformin and acarbose help prevent the development of frank diabetes, and also have a good safety profile. Evidence also supports thiazolidinediones but there are safety concerns, and data on newer agents such as GLP-1 receptor agonists, DPP4 inhibitors or meglitinides are lacking.

Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes. Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy.

Any diet needs to provide sufficient calories for pregnancy, typically 2,000 – 2,500 kcal with the exclusion of simple carbohydrates. The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more. Ingesting more fiber in foods with whole grains, or fruit and vegetables can also reduce the risk of gestational diabetes.

Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM.

Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low. Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows:

- fasting capillary blood glucose levels <5.5 mmol/L

- 1 hour postprandial capillary blood glucose levels <8.0 mmol/L

- 2 hour postprandial blood glucose levels <6.7 mmol/L

Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.

Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child.

Typical opioid medications, such as oxycodone, appear to be no more effective than placebo. In contrast, low-quality evidence supports a moderate benefit from the use of atypical opioids (e.g., tramadol and tapentadol), which also have SNRI properties. Opioid medications are recommended as second or third-line treatment for DPN.

TCAs include imipramine, amitriptyline, desipramine, and nortriptyline. They are generally regarded as first or second-line treatment for DPN. Of the TCAs, imipramine has been the best studied. These medications are effective at decreasing painful symptoms but suffer from multiple side effects that are dose-dependent. One notable side effect is cardiac toxicity, which can lead to fatal abnormal heart rhythms. Additional common side effects include dry mouth, difficulty sleeping, and sedation. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects.

There is no known direct treatment. Current treatment efforts focus on managing the complications of Wolfram syndrome, such as diabetes mellitus and diabetes insipidus.

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.

There are no known ways of preventing LADA type 1 diabetes, though some researchers believe it could be stopped at a very early stage if a diagnosis is made prior to the body's destruction of its beta cells.

C-peptide had shown promising results in treatment of diabetic complications incidental to vascular degeneration. Creative Peptides, Eli Lilly, and Cebix all had drug development programs for a C-peptide product. Cebix had the only ongoing program until it completed a Phase IIb trial in December 2014 that showed no difference between C-peptide and placebo, and it terminated its program and went out of business.

Many observational and clinical studies have been conducted to investigate the role of vitamins on diabetic complications,

In the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study, vitamin supplementations were associated with 24% reduction on the risk of diabetes, observed during 20 years of follow-up.

Many observational studies and clinical trials have linked several vitamins with the pathological process of diabetes; these vitamins include folate, thiamine, β-carotene, and vitamin E, C, B12, and D.

- "Vitamin D:"

Vitamin D insufficiency is common in diabetics. Observational studies show that serum vitamin D is inversely associated with biomarkers of diabetes; impaired insulin secretion, insulin resistance, and glucose intolerance.

It has been suggested that vitamin D may induce beneficial effects on diabetic complications by modulating differentiation and growth of pancreatic β-cells and protecting these cells from apoptosis, thus improving β-cells functions and survival. Vitamin D has also been suggested to act on immune system and modulate inflammatory responses by influencing proliferation and differentiation of different immune cells., Moreover, deficiency of vitamin D may contribute to diabetic complications by inducing hyperparathyroidism, since elevated parathyroid hormone levels are associated with reduced β-cells function, impaired insulin sensitivity, and glucose intolerance. Finally, vitamin D may reduce the risk of vascular complications by modulating lipid profile.

- "Antioxidants" may have beneficial effects on diabetic complications by reducing blood pressure, attenuating oxidative stress and inflammatory biomarkers, improving lipid metabolism, insulin-mediated glucose disposal, and by enhancing endothelial function.

Vitamin C has been proposed to induce beneficial effects by two other mechanisms. It may replace glucose in many chemical reactions due to its similarity in structure, may prevent the non-enzymatic glycosylation of proteins, and might reduce glycated hemoglobin (HbA1c) levels. Secondly, vitamin C has also been suggested to play a role in lipid regulation as a controlling catabolism of cholesterol to bile acid.

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.

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.

In some forms of MODY, standard treatment is appropriate, though exceptions occur:

- In MODY2, oral agents are relatively ineffective and insulin is unnecessary.

- In MODY1 and MODY3, insulin may be more effective than drugs to increase insulin sensitivity.

- Sulfonylureas are effective in the K channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested that the reduced clearance of sulfonylureas stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently to the mouse model and that there was no consistent decrease in the clearance of sulfonylureas in randomly selected HNF1A-MODY and HNF4A-MODY patients.

Triamcinolone is a long acting steroid preparation. When injected in the vitreous cavity, it decreases the macular edema (thickening of the retina at the macula) caused due to diabetic maculopathy, and results in an increase in visual acuity. The effect of triamcinolone is transient, lasting up to three months, which necessitates repeated injections for maintaining the beneficial effect. Best results of intravitreal Triamcinolone have been found in eyes that have already undergone cataract surgery. Complications of intravitreal injection of triamcinolone include cataract, steroid-induced glaucoma and endophthalmitis. A systematic review found evidence that eyes treated with the intravitreal injection of triamcinolone had better visual acuity outcomes compared to eyes treated with macular laser grid photocoagulation, or sham injections.

If a diagnosis of GCA is suspected, treatment with steroids should begin immediately. A sample (biopsy) of the temporal artery should be obtained to confirm the diagnosis and guide future management, but should not delay initiation of treatment. Treatment does not recover lost vision, but prevents further progression and second eye involvement. High dose corticosteroids may be tapered down to low doses over approximately one year.

Treatment depends on the severity of the hyperglycemia and the estimated duration of the steroid treatment. Mild hyperglycemia in an immunocompetent patient may not require treatment if the steroids will be discontinued in a week or two. Moderate hyperglycemia carries an increased risk of infection, especially fungal, and especially in people with other risk factors such as immunocompromise or central intravenous lines. Insulin is the most common treatment.