Creatinine is a chemical waste molecule that is generated from muscle metabolism. Creatinine is produced from creatine, a molecule of major importance for energy production in muscles. Creatinine has been found to be a fairly reliable indicator of kidney function. As the kidneys become impaired the creatinine level in the blood will rise. Normal levels of creatinine in the blood vary from gender and age of the individual.
Metformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet) belongs to a class of drugs called biguanides. Metformin is first-line therapy for most type 2 diabetics. It works to stop the liver from making excess glucose, and has a low risk of hypoglycemia. Hypoglycemia, or very low blood sugar can cause symptoms such as sweating, nervousness, heart palpitations, weakness, intense hunger, trembling, and problems speaking. Many patients lose some weight taking metformin, which is also helpful for blood sugar control.
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.
In type 1 diabetes, other symptoms to watch for include unexplained weight loss, lethargy, drowsiness, and hunger. Symptoms sometimes occur after a viral illness. In some cases, a person may reach the point of diabetic ketoacidosis (DKA) before a type 1 diagnosis is made. DKA occurs when blood glucose is dangerously high and the body can't get nutrients into the cells because of the absence of insulin. The body then breaks down muscle and fat for energy, causing an accumulation of ketones in the blood and urine. Symptoms of DKA include a fruity odor on the breath; heavy, taxed breathing; and vomiting. If left untreated, DKA can result in stupor, unconsciousness, and even death.
DM affects at least 16 million U.S. residents, ranks seventh as a cause of death in the United States, and costs the national economy over $100 billion yearly. The striking increase in the prevalence of DM in the U.S. during recent years has been linked to a rise in the prevalence of obesity. About 95% of those with DM have Type 2, in which the pancreatic beta cells retain some insulin-producing potential, and the rest have Type 1, in which exogenous insulin is required for long-term survival. In Type 1 DM, which typically causes symptoms before age 25, an autoimmune process is responsible for beta cell destruction. Type 2 DM is characterized by insulin resistance in peripheral tissues as well as a defect in insulin secretion by beta cells. Insulin regulates carbohydrate metabolism by mediating the rapid transport of glucose and amino acids from the circulation into muscle and other tissue cells, by promoting the storage of glucose in liver cells as glycogen, and by inhibiting gluconeogenesis. The normal stimulus for the release of insulin from the pancreas is a rise in the concentration of glucose in circulating blood, which typically occurs within a few minutes after a meal. When such a rise elicits an appropriate insulin response, so that the blood level of glucose falls again as it is taken into cells, glucose tolerance is said to be normal. The central fact in DM is an impairment of glucose tolerance of such a degree as to threaten or impair health. Long recognized as an independent risk factor for cardiovascular disease, DM is often associated with other risk factors, including disorders of lipid metabolism (elevation of very-low-density lipoprotein cholesterol and triglycerides and depression of high-density lipoprotein cholesterol), obesity, hypertension, and impairment of renal function. Sustained elevation of serum glucose and triglycerides aggravates the biochemical defect inherent in DM by impairing insulin secretion, insulin-mediated glucose uptake by cells, and hepatic regulation of glucose output. Long-term consequences of the diabetic state include macrovascular complications (premature or accelerated atherosclerosis with resulting coronary, cerebral, and peripheral vascular insufficiency) and microvascular complications (retinopathy, nephropathy, and neuropathy). It is estimated that half those with DM already have some complications when the diagnosis is made. The American Diabetes Association (ADA) recommends screening for DM for people with risk factors such as obesity, age 45 years or older, family history of DM, or history of gestational diabetes. If screening yields normal results, it should be repeated every 3 years. The diagnosis of DM depends on measurement of plasma glucose concentration. The diagnosis is confirmed when any two measurements of plasma glucose performed on different days yield levels at or above established thresholds: in the fasting state, 126 mg/dL (7 mmol/L); 2 hours postprandially (after a 75-g oral glucose load) or at random, 200 mg/dL (11.1 mmol/L). A fasting plasma glucose of 100-125 mg/dL (5.5-6.9 mmol/L) or a 2-hour postprandial glucose of 140-199 mg/dL (7.8-11 mmol/L) is defined as impaired glucose tolerance. People with impaired glucose tolerance are at higher risk of developing DM within 10 years. For such people, lifestyle modification such as weight reduction and exercise may prevent or postpone the onset of frank DM. Current recommendations for the management of DM emphasize education and individualization of therapy. Controlled studies have shown that rigorous maintenance of plasma glucose levels as near to normal as possible at all times substantially reduces the incidence and severity of long-term complications, particularly microvascular complications. Such control involves limitation of dietary carbohydrate and saturated fat; monitoring of blood glucose, including self-testing by the patient and periodic determination of glycosylated hemoglobin; and administration of insulin (particularly in Type 1 DM), drugs that stimulate endogenous insulin production (in Type 2 DM), or both. The ADA recommends inclusion of healthful carbohydrate-containing foods such as whole grains, fruits, vegetables, and low-fat milk in a diabetic diet. Restriction of dietary fat to less than 10% of total calories is recommended for people with diabetes, as for the general population. Further restriction may be appropriate for those with heart disease or elevated cholesterol or triglyceride levels. The ADA advises that high-protein, low-carbohydrate diets have no particular merit in long-term weight control or in maintenance of a normal plasma glucose level in DM. Pharmaceutical agents developed during the 1990s improve control of DM by enhancing responsiveness of cells to insulin, counteracting insulin resistance, and reducing postprandial carbohydrate absorption. Tailor-made insulin analogues produced by recombinant DNA technology (for example, lispro, aspart, and glargine insulins) have broadened the range of pharmacologic properties and treatment options available. Their use improves both short-term and long-term control of plasma glucose and is associated with fewer episodes of hypoglycemia. SEE ALSO insulin resistance
Accelerated atherosclerosis is the main underlying factor contributing to the high risk of atherothrombotic events in DM patients. CAD, peripheral vascular disease, stroke, and increased intima-media thickness are the main macrovascular complications. Diabetics are 2–4 times more likely to develop stroke than people without DM.2 CVD, particularly CAD, is the leading cause of morbidity and mortality in patients with DM.4 Patients with T2DM have a 2- to 4-fold increase in the risk of CAD, and patients with DM but without previous myocardial infarction (MI) carry the same level of risk for subsequent acute coronary events as nondiabetic patients with previous MI.5 Furthermore, people with diabetes have a poorer long-term prognosis after MI, including an increased risk for congestive heart failure and death.
Hypoglycemia means abnormally low blood sugar (glucose). In patients with diabetes, the most common cause of low blood sugar is excessive use of insulin or other glucose-lowering medications, to lower the blood sugar level in diabetic patients in the presence of a delayed or absent meal. When low blood sugar levels occur because of too much insulin, it is called an insulin reaction. Sometimes, low blood sugar can be the result of an insufficient caloric intake or sudden excessive physical exertion.
Although age of onset and length of the disease process are related to the frequency with which vascular, renal, and neurologic complications develop, there are some patients who remain relatively free of sequelae even into the later years of their lives. Because diabetes mellitus is not a single disease but rather a complex constellation of syndromes, each patient has a unique response to the disease process.
They may need to take medications in order to keep glucose levels within a healthy range. Medications for type 2 diabetes are usually taken by mouth in the form of tablets and should always be taken around meal times and as prescribed by the doctor. However, if blood glucose is not controlled by oral medications, a doctor may recommend insulin injections.
DM is a strong independent predictor of short- and long-term recurrent ischemic events, including mortality, in acute coronary syndrome (ACS),6,7 including unstable angina and non-ST-elevation MI (NSTEMI),8 ST-elevation MI (STEMI) treated medically,9 and ACS undergoing percutaneous coronary intervention (PCI).10,11 Furthermore, the concomitant presence of cardiovascular risk factors and comorbidities that negatively affect the outcomes of ACS is higher in DM patients.12
Patients with type 1 diabetes require life-long treatment with exogenous (artificial) insulin to regulate their blood sugar levels. This insulin may be given through the use of a hypodermic needle (seen right), or other methods such as the use of an insulin pump. Over time, many patients suffer chronic complications: vascular, neurological and organ-specific (such as kidney and eye disease). The frequency and severity of these complications is related to duration that the patient has suffered the disease for, and by how well their blood sugar levels have been controlled. If blood sugar levels, blood pressure and lipids are tightly controlled, many complications of diabetes may be prevented. Some patients may develop the major emergency complication of diabetes, known as ketoacidosis (extremely high blood glucose levels accompanied with extremely low insulin levels), which has a mortality rate of 5-10%.
When you have Type 2 diabetes, you may start out with something called insulin resistance. This means your cells do not respond well to the insulin you are making. "Insulin levels may be quite high, especially in the early stages of the disease. Eventually, your pancreas may not be able to keep up, and insulin secretion goes down," Rettinger explains. Insulin resistance becomes more common as you put on more weight, especially weight around your belly.
Infections. Poorly controlled diabetes can lead to a variety of tissue infections. The most commonly encountered is a yeast infection (Candida) and the presence of dry mouth further increases one’s risk (see PATIENT INFORMATION SHEET – Oral Yeast Infections). Typically, affected areas appear redder than the surrounding tissue and commonly affected sites include the tongue, palate, cheeks, gums, or corners of the mouth (see Right). There is conflicting data regarding cavity risk in the diabetic patient, but those who have dry mouth are clearly at increased risk for developing cavities.
A healthy lifestyle can prevent almost all cases of type 2 diabetes. A large research study called the Diabetes Prevention Program, found that patients who made intensive changes including diet and exercise, reduced their risk of developing diabetes by 58%. Patients who were over 60 years old seemed to experience extra benefit; they reduced their risk by 71%. In comparison, patients who were given the drug metformin for prevention only reduced their risk by 31%.
Diabetes can occur temporarily during pregnancy, and reports suggest that it occurs in 2% to 10% of all pregnancies. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 35% to 60% of women with gestational diabetes will eventually develop type 2 diabetes over the next 10 to 20 years, especially in those who require insulin during pregnancy and those who remain overweight after their delivery. Women with gestational diabetes are usually asked to undergo an oral glucose tolerance test about six weeks after giving birth to determine if their diabetes has persisted beyond the pregnancy, or if any evidence (such as impaired glucose tolerance) is present that may be a clue to a risk for developing diabetes.
Excessive thirst typically goes hand-in-hand with increased urination. As your body pulls water out of the tissues to dilute your blood and to rid your body of sugar through the urine, the urge to drink increases. Many people describe this thirst as an unquenchable one. To stay hydrated, you drink excessive amounts of liquids. And if those liquids contain simple sugars (soda, sweet iced tea, lemonade, or juice, for example) your sugars will skyrocket even higher.
Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy. This is partly due to a number of complications with which it is associated, including: two to four times the risk of cardiovascular disease, including ischemic heart disease and stroke; a 20-fold increase in lower limb amputations, and increased rates of hospitalizations. In the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of nontraumatic blindness and kidney failure. It has also been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer's disease and vascular dementia. Other complications include acanthosis nigricans, sexual dysfunction, and frequent infections.
In Type II diabetes, the pancreas may produce enough insulin, however, cells have become resistant to the insulin produced and it may not work as effectively. Symptoms of Type II diabetes can begin so gradually that a person may not know that he or she has it. Early signs are lethargy, extreme thirst, and frequent urination. Other symptoms may include sudden weight loss, slow wound healing, urinary tract infections, gum disease, or blurred vision. It is not unusual for Type II diabetes to be detected while a patient is seeing a doctor about another health concern that is actually being caused by the yet undiagnosed diabetes.
Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).
Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.
Diabetes can be looked for by testing a urine sample for sugar but for a diagnosis, a blood sample is required. This may be a simple measurement of the sugar level, usually fasting. Alternatively, a test called an HbA1c can be used which estimates sugar levels over the past couple of months. If someone has typical symptoms of diabetes, only a single abnormal test is required. Where there are no symptoms, a second confirmatory test is required. Sometimes, particularly in pregnancy, a glucose tolerance test is performed which involves blood tests before and 2 hours after a sugary drink.
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.
The United Kingdom Prospective Diabetes Study (UKPDS) was a clinical study conducted by Z that was published in The Lancet in 1998. Around 3,800 people with type 2 diabetes were followed for an average of ten years, and were treated with tight glucose control or the standard of care, and again the treatment arm had far better outcomes. This confirmed the importance of tight glucose control, as well as blood pressure control, for people with this condition.
Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic. If one identical twin has diabetes, the chance of the other developing diabetes within his lifetime is greater than 90%, while the rate for nonidentical siblings is 25–50%. As of 2011, more than 36 genes had been found that contribute to the risk of type 2 diabetes. All of these genes together still only account for 10% of the total heritable component of the disease. The TCF7L2 allele, for example, increases the risk of developing diabetes by 1.5 times and is the greatest risk of the common genetic variants. Most of the genes linked to diabetes are involved in beta cell functions.