The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubules; specifically, it acts on proteins called aquaporins and more specifically aquaporin 2 in the following cascade. When released, ADH binds to V2 G-protein coupled receptors within the distal convoluted tubules, increasing cyclic AMP, which couples with protein kinase A, stimulating translocation of the aquaporin 2 channel stored in the cytoplasm of the distal convoluted tubules and collecting ducts into the apical membrane. These transcribed channels allow water into the collecting duct cells. The increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.

If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin insensitivity or insulin resistance), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.[62]

Classic symptoms of DM are polyuria, polydipsia, and weight loss. In addition, patients with hyperglycemia often have blurred vision, increased food consumption (polyphagia), and generalized weakness. When a patient with type 1 DM loses metabolic control (such as during infections or periods of noncompliance with therapy), symptoms of diabetic ketoacidosis occur. These may include nausea, vomiting, dizziness on arising, intoxication, delirium, coma, or death. Chronic complications of hyperglycemia include retinopathy and blindness, peripheral and autonomic neuropathies, glomerulosclerosis of the kidneys (with proteinuria, nephrotic syndrome, or end-stage renal failure), coronary and peripheral vascular disease, and reduced resistance to infections. Patients with DM often also sustain infected ulcerations of the feet, which may result in osteomyelitis and the need for amputation.
The word diabetes (/ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɪs/) comes from Latin diabētēs, which in turn comes from Ancient Greek διαβήτης (diabētēs), which literally means "a passer through; a siphon".[114] Ancient Greek physician Aretaeus of Cappadocia (fl. 1st century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease.[115][116] Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through,"[114] which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go".[115] The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.

Pramlintide is only appropriate for certain people with diabetes who use insulin and are having problems maintaining their blood sugar levels. Because of the potential for severe hypoglycemia with the use of pramlintide is with insulin, adjustments to insulin dosage and more frequent glucose monitoring may be necessary. Insulin and pramlintide should not be mixed in the same syringe.
Some patients with type 2 DM can control their disease with a calorically restricted diet (for instance 1600 to 1800 cal/day), regular aerobic exercise, and weight loss. Most patients, however, require the addition of some form of oral hypoglycemic drug or insulin. Oral agents to control DM include sulfonylurea drugs (such as glipizide), which increase pancreatic secretion of insulin; biguanides or thiazolidinediones (such as metformin or pioglitazone), which increase cellular sensitivity to insulin; or a-glucosidase inhibitors (such as acarbose), which decrease the absorption of carbohydrates from the gastrointestinal tract. Both types of diabetics also may be prescribed pramlintide (Symlin), a synthetic analog of human amylin, a hormone manufactured in the pancreatic beta cells. It enhances postprandial glucose control by slowing gastric emptying, decreasing postprandial glucagon concentrations, and regulating appetite and food intake; thus pramlintide is helpful for patients who do not achieve optimal glucose control with insulin and/or oral antidiabetic agents. When combinations of these agents fail to normalize blood glucose levels, insulin injections are added. Tight glucose control can reduce the patient’s risk of many of the complications of the disease. See: illustration

The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of Memphis.[111] The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[111] This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).[113]

Dipsogenic diabetes insipidus. Researchers have not yet found an effective treatment for dipsogenic diabetes insipidus. People can try sucking on ice chips or sour candies to moisten their mouths and increase saliva flow, which may reduce the desire to drink. For a person who wakes multiple times at night to urinate because of dipsogenic diabetes insipidus, taking a small dose of desmopressin at bedtime may help. Initially, the health care provider will monitor the patient’s blood sodium levels to prevent hyponatremia, or low sodium levels in the blood.
Whilst diabetes insipidus usually occurs with polydipsia, it can also rarely occur not only in the absence of polydipsia but in the presence of its opposite, adipsia (or hypodipsia). "Adipsic diabetes insipidus" is recognised[11] as a marked absence of thirst even in response to hyperosmolality.[12] In some cases of adipsic DI, the person may also fail to respond to desmopressin.[13]

^ Emadian A, Andrews RC, England CY, Wallace V, Thompson JL (November 2015). "The effect of macronutrients on glycaemic control: a systematic review of dietary randomised controlled trials in overweight and obese adults with type 2 diabetes in which there was no difference in weight loss between treatment groups". The British Journal of Nutrition. 114 (10): 1656–66. doi:10.1017/S0007114515003475. PMC 4657029. PMID 26411958.
Purified human insulin is most commonly used, however, insulin from beef and pork sources also are available. Insulin may be given as an injection of a single dose of one type of insulin once a day. Different types of insulin can be mixed and given in one dose or split into two or more doses during a day. Patients who require multiple injections over the course of a day may be able to use an insulin pump that administers small doses of insulin on demand. The small battery-operated pump is worn outside the body and is connected to a needle that is inserted into the abdomen. Pumps can be programmed to inject small doses of insulin at various times during the day, or the patient may be able to adjust the insulin doses to coincide with meals and exercise.
Diet and moderate exercise are the first treatments implemented in diabetes. For many Type II diabetics, weight loss may be an important goal in helping them to control their diabetes. A well-balanced, nutritious diet provides approximately 50-60% of calories from carbohydrates, approximately 10-20% of calories from protein, and less than 30% of calories from fat. The number of calories required by an individual depends on age, weight, and activity level. The calorie intake also needs to be distributed over the course of the entire day so surges of glucose entering the blood system are kept to a minimum.
Your body uses a system of organs and hormone signals to regulate body fluids. The kidneys play an important role in this fluid regulation by removing extra fluid from your bloodstream. The bladder stores this fluid waste until you urinate it out. Your body regulates fluid levels by making less urine when you need to replace fluid lost to sweating, or by making more urine when there is too much fluid in your body.
Another non-insulin injection for people with diabetes is exenatide (Byetta). This medication, originally derived from a compound found in the saliva of the Gila monster, triggers insulin release from the pancreas when blood glucose levels rise. Exenatide is meant to be used along with oral diabetes drugs. It is dosed twice daily and should be injected within an hour of the morning and evening meals. Recently, the FDA warned that exenatide may increase the risk of severe even fatal pancreatitis (inflammation of the pancreas) and that the drug should be discontinued and not restarted if signs and symptoms of pancreatitis develop (severe abdominal pain, for example). It is not for use in people with type 1 diabetes.
This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.
Clinical Manifestations. Diabetes mellitus can present a wide variety of symptoms, from none at all to profound ketosis and coma. If the disease manifests itself late in life, patients may not know they have it until it is discovered during a routine examination, or when the symptoms of chronic vascular disease, insidious renal failure, or impaired vision cause them to seek medical help.
Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries,[104] where more than 80% of diabetic deaths occur.[108] The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030.[109] The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet).[104][109] The global number of diabetes cases might increase by 48% between 2017 and 2045.[9]
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