Diabetes mellitus
Thursday, May 27, 2010
Prevention - Delay of Type 2 Diabetes
Recommendations
* Individuals at high risk for developing diabetes need to become aware of the benefits of modest weight loss and participating in regular physical activity. (A)
* Patients with IGT should be given counseling on weight loss as well as instruction for increasing physical activity. (A)
* Patients with IFG should be given counseling on weight loss as well as instruction for increasing physical activity. (E)
* Follow-up counseling appears important for success. (B)
* Monitoring for the development of diabetes in those with pre-diabetes should be performed every 1–2 years. (E)
* Close attention should be given to, and appropriate treatment given for, other CVD risk factors (e.g., tobacco use, hypertension, dyslipidemia). (A)
* Drug therapy should not be routinely used to prevent diabetes until more information is known about its cost-effectiveness. (E)
DETECTION AND DIAGNOSIS OF GDM - Diagnosing And Managing Diabetes
Recommendations
* Screen for diabetes in pregnancy using risk factor analysis and, if appropriate, use of an OGTT. (C)
* Women with GDM should be screened for diabetes 6–12 weeks postpartum and should be followed up with subsequent screening for the development of diabetes or pre-diabetes. (E)
Risk assessment for GDM should be undertaken at the first prenatal visit. Women with clinical characteristics consistent with a high risk for GDM (those with marked obesity, personal history of GDM, glycosuria, or a strong family history of diabetes) should undergo glucose testing as soon as possible. An FPG 126 mg/dl or a casual plasma glucose 200 mg/dl meets the threshold for the diagnosis of diabetes and needs to be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present. High-risk women not found to have GDM at the initial screening and average-risk women should be tested between 24 and 28 weeks of gestation. Testing should follow one of two approaches:
Diagnosing And Managing Diabetes- Screening for Diabetes
Recommendations
* Screening to detect pre-diabetes (IFG or IGT) and diabetes should be considered in individuals 45 years of age, particularly in those with a BMI 25 kg/m2. Screening should also be considered for people who are <45 years of age and are overweight if they have another risk factor for diabetes (Table 3). Repeat testing should be carried out at 3-year intervals. (E)
* Screen for pre-diabetes and diabetes in high-risk, asymptomatic, undiagnosed adults and children within the health care setting. (E)
* To screen for diabetes/pre-diabetes, either an FPG test or 2-h OGTT (75-g glucose load) or both are appropriate. (B)
* An OGTT may be considered in patients with IFG to better define the risk of diabetes. (E)
Diagnosing And Managing Diabetes -Classification and Diagnosis
A. Classification
In 1997, the ADA issued new diagnostic and classification criteria; in 2003, modifications were made regarding the diagnosis of impaired fasting glucose (IFG). The classification of diabetes includes four clinical classes:
* Type 1 diabetes (results from ß-cell destruction, usually leading to absolute insulin deficiency).
* Type 2 diabetes (results from a progressive insulin secretory defect on the background of insulin resistance).
* Other specific types of diabetes due to other causes, e.g., genetic defects in ß-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug or chemical induced (such as in the treatment of AIDS or after organ transplantation).
* Gestational diabetes mellitus (GDM) (diagnosed during pregnancy).
B. Diagnosis
Recommendations
* The FPG is the preferred test to diagnose diabetes in children and nonpregnant adults. (E)
* The use of the A1C for the diagnosis of diabetes is not recommended at this time. (E)
Sunday, September 04, 2005
Diabetes
Up to 4 percent of Americans have diabetes. Vascular disease accounts for over 70 percent of deaths in adults with diabetes.
Classification and pathophysiology
Type 1 diabetes mellitus primarily occurs in children and adolescents. Patients with type 1 diabetes have an absolute deficiency of endogenous insulin and require exogenous insulin for survival.
Type 2 diabetes accounts for 90% of individuals with diabetes mellitus, and the incidence increases in frequency with age, obesity and physical inactivity. The initial problem in type 2 diabetes is resistance to the action of insulin at the cellular level.
Diabetes Mellitus and Thyroid Disorders
To begin with, the talk of diabetes, I want to give you a definition, a working definition the sort of phenotype of the child - or adult for that matter - with type I or insulin-dependent diabetes. Such patients are insulinopenic by definition. That is to say, they are absolutely dependent on exogenous insulin for survival. Without insulin they are prone to ketoacidosis. They typically, without insulin, would be lean and complain of recent weight loss. The development of the disease actually is rather insidious. It may occur over years, although the presentation phase can be fairly abrupt. You usually see this form of diabetes under age 40, but there are reports of individuals as old as 87-years-of-age developing type I diabetes … for whatever that’s worth.
Now a couple of words about the epidemiology of diabetes in the United States. Now the incidence of the disease - and I will remind you that that’s defined as the number of new cases in a defined population per unit time … we are talking now of under 19-years-of-age - is 16 new cases per 100,000 children per year, or 1.6 per 10,000. The prevalence, which is the number of existing cases in a defined population in a moment of time, is 140 cases per 100,000 or 1.4 cases per thousand children walking around. Of 1,000 children out there, 1.4 of them have diabetes. At a large high school of 3,000 students, 4.2 children with have diabetes, type I. That number actually may be on the rise. The mean age of onset is Junior High School age or so, 11 years in females, 12 ½ years in males. The incidence by gender varies slightly with age, but overall it’s equal.
Diabetes insipidus
Diabetes insipidus affects about three out of 100,000 persons. This disorder is caused by a deficiency or ineffectiveness of vasopressin (ADH). It can be transient or chronic. Diabetes insipidus is characterized by excretion of excessive quantities of dilute urine and excessive thirst due to a compromised ability to conserve free water. Diabetes insipidus is easily distinguished from other causes of polyuria by the absence of a solute load (particularly glucose) and an abnormally low urine concentration.
Two types of diabetes insipidus are recognized: neurogenic (central) and nephrogenic (peripheral) (Table 4). Many underlying conditions can produce diabetes insipidus (Table 5). The most common form is neurogenic diabetes insipidus and is classified as either idiopathic or secondary to an intracranial event. Causes of diabetes insipidus in adults include idiopathic (25 percent), benign brain tumors (20 percent), blunt head trauma (17 percent), neurosurgery (9 percent), metastatic cancer (8 percent), and ischemic or toxic brain injury (6 percent). In contrast, only 8 percent of diabetes insipidus in children is idiopathic. The most common causes of childhood cases are tumors, neurosurgery, trauma, and meningitis. Idiopathic diabetes insipidus is invariably permanent and more often affects males.
Diabetes
Screening for diabetes is absolutely the most important thing that people on the front lines can do, and then we will talk about treatment for the rest of the time, focusing on the oral agents in particular, and I am talking about type II diabetes, type I diabetes is something that I think, first of all it’s the minority of diabetes and most people will feel more comfortable sending those people to internists or endocrinologists. We will focus on the definition of diabetes because they actually have changed over the last couple of years, the recommendations for screening which are also relatively new. The risk factors that should alert you to screen somebody for diabetes to begin with and then what we use for goals of treatment and how you can actually achieve some of those goals.
First to tell you why screening is so important, I don’t have to tell you that diabetes is a terrible disease, it causes a lot of problems, but just to give you some numbers, it causes 30 times the rate of blindness and is the most preventable cause of blindness in this country, one of the most preventable causes, twice at least the rate of heart disease, these are people who are dying of heart disease and stroke at a huge rate over the general or nondiabetic population, 17 times the rate of renal failure and a huge increase in the rate of amputations and it’s the leading cause of nontraumatic amputations.
Friday, September 02, 2005
2005 DIETARY GUIDELINES FOR AMERICANS
ADEQUATE NUTRIENTS WITHIN CALORIE NEEDS
* Consume a variety of nutrient-dense foods and beverages within and among the basic food groups while choosing foods that limit the intake of saturated and trans fats, cholesterol, added sugars, salt, and alcohol.
* Meet recommended intakes within energy needs by adopting a balanced eating pattern, such as the U.S. Department of Agriculture (USDA) Food Guide or the Dietary Approaches to Stop Hypertension (DASH) Eating Plan.
WEIGHT MANAGEMENT
* To maintain body weight in a healthy range, balance calories from foods and beverages with calories expended.
* To prevent gradual weight gain over time, make small decreases in food and beverage calories and increase physical activity.
Thursday, September 01, 2005
The Story of Insulin
Insulin Synthesis
The insulin-making cells of the body are called beta cells, and they are found in the pancreas gland. These cells clump together to form the “islets of Langerhans”, named for the German medical student who described them.
The synthesis of insulin begins at the translation of the insulin gene, which resides on chromosome 11. During translation, two introns are spliced out of the mRNA product, which encodes a protein of 110 amino acids in length. This primary translation product is called preproinsulin and is inactive. It contains a signal peptide of 24 amino acids in length, which is required for the protein to cross the cell membrane.
Once the preproinsulin reaches the endoplasmic reticulum, a protease cleaves off the signal peptide to create proinsulin. Proinsulin consists of three domains: an amino-terminal B chain, a carboxyl-terminal A chain, and a connecting peptide in the middle known as the C-peptide.
Within the endoplasmic reticulum, proinsulin is exposed to several specific peptidases that remove the C-peptide and generate the mature and active form of insulin. In the Golgi apparatus, insulin and free C-peptide are packaged into secretory granules, which accumulate in the cytoplasm of the beta cells. Exocytosis of the granules is triggered by the entry of glucose into the beta cells. The secretion of insulin has a broad impact on metabolism.
Insulin Structure
In 1958, Frederick Sanger was awarded his first Nobel Prize for determining the sequence of the amino acids that make up insulin. This marked the first time that a protein had had the order of its amino acids (the primary sequence) determined.
Insulin is composed of two chains of amino acids named chain A (21 amino acids) and chain B (30 amino acids) that are linked together by two disulfide bridges. There is a 3rd disulfide bridge within the A chain that links the 6th and 11th residues of the A chain together.
In most species, the length and amino acid compositions of chains A and B are similar, and the positions of the three disulfide bonds are highly conserved. For this reason, pig insulin can be used to replace deficient human insulin levels in diabetes patients. Today, porcine insulin has largely been replaced by the mass production of human proinsulin by bacteria (recombinant insulin).
Insulin molecules have a tendency to form dimers in solution, and in the presence of zinc ions, insulin dimers associate into hexamers. Whereas monomers of insulin readily diffuse through the blood and have a rapid effect, hexamers diffuse slowly and have a delayed onset of action. In the design of recombinant insulin, the structure of insulin can be modified in a way that reduces the tendency of the insulin molecule to form dimers and hexamers but that does not interrupt binding to the insulin receptor. In this way, a range of preparations of insulin is made, varying from short acting to long acting.
Insulin secretion
Rising levels of glucose inside the pancreatic beta cells trigger the release of insulin: