Sunday, February 22, 2009
diabetes diets
There are a variety of methods for categorizing the conditions that cause hypoglycemia, but none of these schemes is completely satisfactory. One approach is to divide the causes into those involving increased insulin levels, those involving increased glucose consumption, or those involving decreased glucose production. In reality, however, most of the causes of hypoglycemia embrace a combination of these mechanisms. An alternative and more useful scheme is based on the history and physical examination findings. The key features of this approach are to assess whether the hypoglycemia occurs with fasting or postprandially, and whether the affected person appears healthy. In general, the hypoglycemia that occurs with fasting or that is found in people who appear generally ill is a more ominous form of the disorder
diabetes control diet
Table 3-5 Symptoms of Hypoglycemia
Adrenergic
Neuroglycopenic
Anxiety
Headache
Nervousness
Blurred vision
Tremulousness
Paresthesias
Sweating
Weakness
Hunger
Tiredness
Palpitations
Confusion
Irritability
Dizziness
Pallor
Amnesia
Nausea
Incoordination
Flushing
Abnormal mentation
Angina
Behavioral change
Feeling cold
Difficulty waking in the morning
Senile dementia
Organic personality syndrome
Transient hemiplegia
Transient aphasia
Seizures
Coma
Adrenergic
Neuroglycopenic
Anxiety
Headache
Nervousness
Blurred vision
Tremulousness
Paresthesias
Sweating
Weakness
Hunger
Tiredness
Palpitations
Confusion
Irritability
Dizziness
Pallor
Amnesia
Nausea
Incoordination
Flushing
Abnormal mentation
Angina
Behavioral change
Feeling cold
Difficulty waking in the morning
Senile dementia
Organic personality syndrome
Transient hemiplegia
Transient aphasia
Seizures
Coma
gestational diabetes diet
What are the common symptoms of hypoglycemia?
The symptoms of hypoglycemia can be divided into two categories: adrenergic and neuroglycopenic (Table 3-5). A substantial reduction in the blood glucose level stimulates the release of cortisol, GH, glucagon, and catecholamines. The attendant rise in sympathetic nervous system activity is experienced as nervousness, sweating, and palpitations. Because the brain is
P.119critically dependent on glucose for normal neuronal functioning, inadequate delivery of glucose to the brain rapidly results in alterations in mentation, which can take many forms. The signs and symptoms of neuroglycopenia can even mimic those associated with structural brain lesions or psychiatric conditions.
The symptoms of hypoglycemia can be divided into two categories: adrenergic and neuroglycopenic (Table 3-5). A substantial reduction in the blood glucose level stimulates the release of cortisol, GH, glucagon, and catecholamines. The attendant rise in sympathetic nervous system activity is experienced as nervousness, sweating, and palpitations. Because the brain is
P.119critically dependent on glucose for normal neuronal functioning, inadequate delivery of glucose to the brain rapidly results in alterations in mentation, which can take many forms. The signs and symptoms of neuroglycopenia can even mimic those associated with structural brain lesions or psychiatric conditions.
gestational diabetes diet
What constitutes medically significant hypoglycemia?
Medically significant hypoglycemia is diagnosed on the basis of only three findings (Whipple's triad): (a) blood glucose level of less than 50 mg/dL; (b) the
P.118presence of symptoms consistent with hypoglycemia; and (c) the resolution of symptoms after the ingestion of carbohydrates. The lower limit of normal for glucose is 70 mg/dL, but this is the lower limit for “healthy†people after a 12-hour fast. During a 72-hour fast, up to 40% of “healthy†women may have blood glucose values below 45 mg/dL and some as low as between 20 and 30 mg/dL. These low values may also be seen in apparently healthy women 3 to 4 hours after the administration of 75 g of glucose orally (the oral glucose tolerance test), but almost none have symptoms of hypoglycemia and, therefore, medically significant hypoglycemia. Conversely, many people who exhibit symptoms consistent with hypoglycemia 3 to 4 hours after eating, which respond to the ingestion of carbohydrate, also do not have true hypoglycemia. The blood glucose levels in these individuals are rarely less than 50 mg/dL at the time they experience symptoms. These people have a condition that has been called postprandial syndrome or functional hypoglycemia.
Medically significant hypoglycemia is diagnosed on the basis of only three findings (Whipple's triad): (a) blood glucose level of less than 50 mg/dL; (b) the
P.118presence of symptoms consistent with hypoglycemia; and (c) the resolution of symptoms after the ingestion of carbohydrates. The lower limit of normal for glucose is 70 mg/dL, but this is the lower limit for “healthy†people after a 12-hour fast. During a 72-hour fast, up to 40% of “healthy†women may have blood glucose values below 45 mg/dL and some as low as between 20 and 30 mg/dL. These low values may also be seen in apparently healthy women 3 to 4 hours after the administration of 75 g of glucose orally (the oral glucose tolerance test), but almost none have symptoms of hypoglycemia and, therefore, medically significant hypoglycemia. Conversely, many people who exhibit symptoms consistent with hypoglycemia 3 to 4 hours after eating, which respond to the ingestion of carbohydrate, also do not have true hypoglycemia. The blood glucose levels in these individuals are rarely less than 50 mg/dL at the time they experience symptoms. These people have a condition that has been called postprandial syndrome or functional hypoglycemia.
gestational diabetes diet
In the hypercalcemic patient, what are the laboratory findings seen in the setting of hyperparathyroidism?
For the sake of simplicity, the many causes of hypercalcemia can be separated into two categories according to the PTH level and laboratory findings result from the presence or absence of the action of PTH. (Tables 3-2 and 3-3).
For the sake of simplicity, the many causes of hypercalcemia can be separated into two categories according to the PTH level and laboratory findings result from the presence or absence of the action of PTH. (Tables 3-2 and 3-3).
type 2 diabetes diet
What two medical conditions account for most cases of hypercalcemia?
Of the many causes of hypercalcemia listed in Table 3-1, the most common are malignancy (45%) and hyperparathyroidism (45%). The lengthy differential diagnosis (see Table 3-1) includes the other 10% of the causes. Hence, from a practical standpoint, hypercalcemic disorders can be broken down into two categories: parathyroid hormone (PTH)-mediated hypercalcemia and non–PTH-mediated hypercalcemia.
Of the many causes of hypercalcemia listed in Table 3-1, the most common are malignancy (45%) and hyperparathyroidism (45%). The lengthy differential diagnosis (see Table 3-1) includes the other 10% of the causes. Hence, from a practical standpoint, hypercalcemic disorders can be broken down into two categories: parathyroid hormone (PTH)-mediated hypercalcemia and non–PTH-mediated hypercalcemia.
diabetes diet
What conditions can cause hypercalcemia?
The causes of hypercalcemia that need to be considered in any patient who exhibits a bona fide elevation in the serum calcium level as documented in at least three repeat determinations are listed in Table 3-1.
The causes of hypercalcemia that need to be considered in any patient who exhibits a bona fide elevation in the serum calcium level as documented in at least three repeat determinations are listed in Table 3-1.
Tuesday, February 3, 2009
symptoms of child diabetes
This study began in 1977 as a multicenter clinical trial designed to establish, in type 2 diabetic patients, whether the risk of macrovascular or microvascular complications could be reduced by intensive blood glucose control with oral hypoglycemic agents or insulin and whether any particular therapy was of advantage. Newly diagnosed type 2 diabetic patients aged 25-65 years were recruited between 1977 and 1991, and a total of 3867 were studied over 10 years. The median age at baseline was 54 years; 44% were overweight (> 120% over ideal weight); and baseline HbA1c was 9.1%. Therapies were randomized to include a control group on diet alone and separate groups intensively treated with either insulin, chlorpropamide, glyburide, or glipizide. Metformin was included as a randomization option in a subgroup of 342 overweight patients, and much later in the study an additional subgroup of both normal-weight and overweight patients who were responding unsatisfactorily to sulfonylurea therapy were randomized to either continue on their sulfonylurea therapy alone or to have metformin combined with it.
In 1987, an additional modification was made to evaluate whether tight control of blood pressure with stepwise antihypertensive therapy would prevent macrovascular and microvascular complications in 758 hypertensive patients among this UKPDS population compared with 390 of them whose blood pressure was treated less intensively. The tight control group was randomly assigned to treatment with either an angiotensin-converting enzyme (ACE) inhibitor (captopril) or a ß-blocker (atenolol). Both drugs were stepped up to maximum dosages of 100 mg/d and then, if blood pressure remained higher than the target level of < 150/85 mm Hg, more drugs were added in the following stepwise sequence: a diuretic, slow-release nifedipine, methyldopa, and prazosin — until the target level of tight control was achieved. In the control group, hypertension was conventionally treated to achieve target levels < 180/105 mm Hg, but these patients were not prescribed either ACE inhibitors or ß-blockers.
Intensive glycemic therapy in the entire group of 3897 newly diagnosed type 2 diabetic patients followed over 10 years showed the following: Intensive treatment with either sulfonylureas, metformin, combinations of those two, or insulin achieved mean HbA1c levels of 7%. This level of glycemic control decreases the risk of microvascular complications (retinopathy and nephropathy) in comparison with conventional therapy (mostly diet alone), which achieved mean levels of HbA1c of 7.9%. Weight gain occurred in intensively treated patients except when metformin was used as monotherapy. No cardiovascular benefit and no adverse cardiovascular outcomes were noted regardless of the therapeutic agent. Hypoglycemic reactions occurred in the intensive treatment groups, but only one death from hypoglycemia was documented during 27,000 patient-years of intensive therapy.
When therapeutic subgroups were analyzed, some unexpected and paradoxical results were noted. Among the obese patients, intensive treatment with insulin or sulfonylureas did not reduce microvascular complications compared with diet therapy alone. This was in contrast to the significant benefit of intensive therapy with these drugs in the total group. Furthermore, intensive therapy with metformin was more beneficial in obese persons than diet alone with regard to fewer myocardial infarctions, strokes, and diabetes-related deaths, but there was no significant reduction by metformin of diabetic microvascular complications as compared with the diet group. Moreover, in the subgroup of obese and nonobese patients in whom metformin was added to sulfonylurea failures, rather than showing a benefit, there was a 96% increase in diabetes-related deaths compared with the matched cohort of patients with unsatisfactory glycemic control on sulfonylureas who remained on their sulfonylurea therapy. Chlorpropamide also came out poorly on subgroup analysis in that those receiving it as intensive therapy did less well as regards progression to retinopathy than those conventionally treated with diet.
Intensive antihypertensive therapy to a mean of 144/82 mm Hg had beneficial effects on microvascular disease as well as on all diabetes-related end points, including virtually all cardiovascular outcomes, in comparison with looser control at a mean of 154/87 mm Hg. In fact, the advantage of reducing hypertension by this amount was substantially more impressive than the benefit achieved by improving the degree of glycemic control from a mean HbA1c of 7.9% to 7%. More than half of the patients needed two or more drugs for adequate therapy of their hypertension, and there was no demonstrable advantage of ACE inhibitor therapy over therapy with ß-blockers with regard to diabetes end points. Use of a calcium channel blocker added to both treatment groups appeared to be safe over the long term in this diabetic population despite some controversy in the recent literature about its safety in diabetics. (current MD&T 2005)
In 1987, an additional modification was made to evaluate whether tight control of blood pressure with stepwise antihypertensive therapy would prevent macrovascular and microvascular complications in 758 hypertensive patients among this UKPDS population compared with 390 of them whose blood pressure was treated less intensively. The tight control group was randomly assigned to treatment with either an angiotensin-converting enzyme (ACE) inhibitor (captopril) or a ß-blocker (atenolol). Both drugs were stepped up to maximum dosages of 100 mg/d and then, if blood pressure remained higher than the target level of < 150/85 mm Hg, more drugs were added in the following stepwise sequence: a diuretic, slow-release nifedipine, methyldopa, and prazosin — until the target level of tight control was achieved. In the control group, hypertension was conventionally treated to achieve target levels < 180/105 mm Hg, but these patients were not prescribed either ACE inhibitors or ß-blockers.
Intensive glycemic therapy in the entire group of 3897 newly diagnosed type 2 diabetic patients followed over 10 years showed the following: Intensive treatment with either sulfonylureas, metformin, combinations of those two, or insulin achieved mean HbA1c levels of 7%. This level of glycemic control decreases the risk of microvascular complications (retinopathy and nephropathy) in comparison with conventional therapy (mostly diet alone), which achieved mean levels of HbA1c of 7.9%. Weight gain occurred in intensively treated patients except when metformin was used as monotherapy. No cardiovascular benefit and no adverse cardiovascular outcomes were noted regardless of the therapeutic agent. Hypoglycemic reactions occurred in the intensive treatment groups, but only one death from hypoglycemia was documented during 27,000 patient-years of intensive therapy.
When therapeutic subgroups were analyzed, some unexpected and paradoxical results were noted. Among the obese patients, intensive treatment with insulin or sulfonylureas did not reduce microvascular complications compared with diet therapy alone. This was in contrast to the significant benefit of intensive therapy with these drugs in the total group. Furthermore, intensive therapy with metformin was more beneficial in obese persons than diet alone with regard to fewer myocardial infarctions, strokes, and diabetes-related deaths, but there was no significant reduction by metformin of diabetic microvascular complications as compared with the diet group. Moreover, in the subgroup of obese and nonobese patients in whom metformin was added to sulfonylurea failures, rather than showing a benefit, there was a 96% increase in diabetes-related deaths compared with the matched cohort of patients with unsatisfactory glycemic control on sulfonylureas who remained on their sulfonylurea therapy. Chlorpropamide also came out poorly on subgroup analysis in that those receiving it as intensive therapy did less well as regards progression to retinopathy than those conventionally treated with diet.
Intensive antihypertensive therapy to a mean of 144/82 mm Hg had beneficial effects on microvascular disease as well as on all diabetes-related end points, including virtually all cardiovascular outcomes, in comparison with looser control at a mean of 154/87 mm Hg. In fact, the advantage of reducing hypertension by this amount was substantially more impressive than the benefit achieved by improving the degree of glycemic control from a mean HbA1c of 7.9% to 7%. More than half of the patients needed two or more drugs for adequate therapy of their hypertension, and there was no demonstrable advantage of ACE inhibitor therapy over therapy with ß-blockers with regard to diabetes end points. Use of a calcium channel blocker added to both treatment groups appeared to be safe over the long term in this diabetic population despite some controversy in the recent literature about its safety in diabetics. (current MD&T 2005)
symptoms and conditions of type 2 diabetes
This investigation involved 153 obese men who were moderately insulin-resistant and who were followed for only 27 months. Intensive insulin treatment resulted in mean HbA1c differences from conventional insulin treatment (7.2% versus 9.5%) that were comparable to those reported from the Kumamoto Study. However, a difference in cardiovascular outcome in this study has prompted some concern. While conventional insulin therapy resulted in 26 total cardiovascular events, there were 35 total cardiovascular events in the intensively treated group. This difference in the relatively small population was not statistically significant, but when the total events were broken down to major events (myocardial infarction, stroke, cardiovascular death, congestive heart failure, or amputation), the 18 major events in the group treated intensively with insulin were reported to be statistically greater (P =. 04) than the ten major events occurring with conventional treatment. While this difference may be a chance consequence of studying too few patients for too short a time, it raises the possibility that insulin-resistant patients with visceral obesity and long-standing type 2 diabetes may develop a greater risk of serious cardiovascular mishap when intensively treated with high doses of insulin. At the end of the study, 64% of the intensively treated group were either receiving (1) an average of 113 units of insulin per day when only two injections per day were used or (2) a mean dosage of 133 units per day when multiple injections were used. Unfortunately, the UKPDS (see below), which did not discern any effect of intensive therapy on cardiovascular outcomes, does not resolve the concern generated by the Veterans Administration Study since their patient population consisted of newly diagnosed diabetic patients in whom the obese subgroup seemed to be less insulin-resistant, requiring a median insulin dose for inte
physiological symptoms of diabetes
The Kumamoto study involved a relatively small number of patients with type 2 diabetes (n = 110) who were nonobese and only slightly insulin-resistant, requiring less than 30 units of insulin per day for intensive therapy. Over a 6-year period, it was shown that intensive insulin therapy, achieving a mean HbA1c of 7.1%, significantly reduced microvascular end points compared with conventional insulin therapy achieving a mean HbA1c of 9.4%. Cardiovascular events were neither worsened nor improved by intensive therapy, and weight changes were likewise not influenced by either form of treatment. (current MD&T 2005)
first signs of diabetes symptoms
This study was aimed at discovering whether treatment with either diet and exercise or metformin could prevent the onset of type 2 diabetes in people with impaired glucose tolerance; 3234 overweight men and women aged 25-85 years with impaired glucose tolerance participated in the study. Intervention with a low-fat diet and 150 minutes of moderate exercise (equivalent to a brisk walk) per week reduced the risk of progression to type 2 diabetes by 71% compared with a matched control group. Participants taking 80 mg of metformin twice a day reduced their risk of developing type 2 diabetes by 31%, but this intervention was relatively ineffective in those who were either less obese or in the older age group.
With the demonstration that intervention can be successful in preventing progression to diabetes in these subjects, a recommendation has been made to change the terminology from the less comprehensible "impaired glucose tolerance" to "prediabetes." The latter is a term which the public can better understand and thus respond to by implementing healthier diet and exercise habits.
With the demonstration that intervention can be successful in preventing progression to diabetes in these subjects, a recommendation has been made to change the terminology from the less comprehensible "impaired glucose tolerance" to "prediabetes." The latter is a term which the public can better understand and thus respond to by implementing healthier diet and exercise habits.
feet cracking open symptoms of diabetes
While patients with type 2 were not studied in the DCCT, the eye, kidney, and nerve abnormalities are quite similar in both types of diabetes, and it is likely that similar underlying mechanisms apply. Several important differences, however, must be considered. Since patients with type 2 diabetes are generally older with a high incidence of macrovascular disease, an episode of severe hypoglycemia entails much greater risk than it would in a younger patient with type 1 diabetes. Moreover, weight gain may be much greater in obese persons with type 2 diabetes in whom intensive insulin therapy is attempted. These risks take on a greater relevance in older patients with type 2 diabetes because the prevalence of microangiopathy is relatively lower than in those patients with type 1 diabetes; preventing microvascular disease in patients with type 2 diabetes is much less likely to influence morbidity and mortality because of the greater consequences of their macrovascular disease.
To address the issues raised by the DCCT findings as well as a previous concern that sulfonylureas may increase cardiovascular deaths, as reported in 1970 by the University Group Diabetes Program, randomized clinical trials of intensive therapy have been conducted in patients with type 2 diabetes.
( from current MD&T 2005)
To address the issues raised by the DCCT findings as well as a previous concern that sulfonylureas may increase cardiovascular deaths, as reported in 1970 by the University Group Diabetes Program, randomized clinical trials of intensive therapy have been conducted in patients with type 2 diabetes.
( from current MD&T 2005)
complications symptoms of diabetes
At the time of diagnosis of type 1 diabetes, patients still have significant B cell function. This explains why soon after diagnosis patients go into a partial clinical remission ("honeymoon") requiring little or no insulin. This clinical remission is short-lived, however, and eventually patients lose all B cell function and have more labile glucose control. Attempts have been made to prolong this partial clinical remission using drugs such as cyclosporine, azathioprine, prednisone, and antithymocyte globulin. These drugs have had limited efficacy, and there are concerns about toxicity and the need for continuous treatment.
Newer agents that may induce immune tolerance and appear to have few side effects have been used in new-onset type 1 patients. Two small studies, one with a heat shock protein peptide (DiaPep277) and another with an anti-CD3 antibody, have demonstrated that these agents can preserve endogenous insulin production. Larger phase 2 clinical trials are currently in progress.
Newer agents that may induce immune tolerance and appear to have few side effects have been used in new-onset type 1 patients. Two small studies, one with a heat shock protein peptide (DiaPep277) and another with an anti-CD3 antibody, have demonstrated that these agents can preserve endogenous insulin production. Larger phase 2 clinical trials are currently in progress.
causes and symptoms of diabetes
A long-term therapeutic study involving 1441 type 1 patients reported that "near" normalization of blood glucose resulted in a delay in the onset and a major slowing of the progression of established microvascular and neuropathic complications of diabetes during a follow-up period of up to 10 years. Multiple insulin injections (66%) or insulin pumps (34%) were used in the intensively treated group, who were trained to modify their therapy in response to frequent glucose monitoring. The conventionally treated groups used no more than two insulin injections, and clinical well-being was the goal with no attempt to modify management based on HbA1c determinations or the glucose results.
In one-half of the subjects, a mean hemoglobin A1c of 7.2% (normal: < 6%) and a mean blood glucose of 155 mg/dL were achieved using intensive therapy, while in the conventionally treated group HbA1c averaged 8.9% with an average blood glucose of 225 mg/dL. Over the study period, which averaged 7 years, there was an approximately 60% reduction in risk between the two groups in regard to diabetic retinopathy, nephropathy, and neuropathy. Intensively treated patients had a threefold greater risk of serious hypoglycemia as well as a greater tendency toward weight gain. However, there were no deaths definitely attributable to hypoglycemia in any subjects in the DCCT study, and no evidence of posthypoglycemic cognitive damage was detected.
The general consensus of the American Diabetes Association is that intensive insulin therapy associated with comprehensive self-management training should become standard therapy in type 1 patients after the age of puberty. Exceptions include those with advanced renal disease and the elderly, since in these groups the detrimental risks of hypoglycemia outweigh the benefits of tight glycemic control. (current MD&T 2005)
In one-half of the subjects, a mean hemoglobin A1c of 7.2% (normal: < 6%) and a mean blood glucose of 155 mg/dL were achieved using intensive therapy, while in the conventionally treated group HbA1c averaged 8.9% with an average blood glucose of 225 mg/dL. Over the study period, which averaged 7 years, there was an approximately 60% reduction in risk between the two groups in regard to diabetic retinopathy, nephropathy, and neuropathy. Intensively treated patients had a threefold greater risk of serious hypoglycemia as well as a greater tendency toward weight gain. However, there were no deaths definitely attributable to hypoglycemia in any subjects in the DCCT study, and no evidence of posthypoglycemic cognitive damage was detected.
The general consensus of the American Diabetes Association is that intensive insulin therapy associated with comprehensive self-management training should become standard therapy in type 1 patients after the age of puberty. Exceptions include those with advanced renal disease and the elderly, since in these groups the detrimental risks of hypoglycemia outweigh the benefits of tight glycemic control. (current MD&T 2005)
what are the symptoms of gestational diabetes
This NIH-sponsored multicenter study was designed to determine whether the development of type 1 diabetes could be prevented or delayed by immune intervention therapy. Daily low-dose insulin injections were administered for up to 8 years in first-degree relatives of type 1 diabetics who were selected as being at high risk for development of type 1 diabetes because of detectable islet cell antibodies and reduced early-insulin release. Unfortunately, this immune intervention failed to affect the onset of type 1 diabetes as compared with a randomized untreated group. A related study using oral insulin in lower risk first-degree relatives who have islet cell antibodies but whose early insulin release remains intact also failed to show an effect on the onset of type 1 diabetes. After an average of 4.3 years of observation, type 1 diabetes developed in about 35% of persons in both the oral insulin and the placebo groups.
(current MD&T 2005)
(current MD&T 2005)
what are symptoms of diabetes
Diabetes mellitus requires ongoing medical care as well as patient and family education both to prevent acute illness and to reduce the risk of long-term complications. The Diabetes Control and Complications Trial of type 1 diabetes and the United Kingdom Prospective Diabetes Study of type 2 diabetes (see below) both indicate that the therapeutic objective is to restore known metabolic derangements toward normal in order to prevent and delay progression of diabetic complications.
symptoms of type i diabetes
Nondiabetic glycosuria (renal glycosuria) is a benign asymptomatic condition wherein glucose appears in the urine despite a normal amount of glucose in the blood, either basally or during a glucose tolerance test. Its cause may vary from an autosomally transmitted genetic disorder to one associated with dysfunction of the proximal renal tubule (Fanconi's syndrome, chronic renal failure), or it may merely be a consequence of the increased load of glucose presented to the tubules by the elevated glomerular filtration rate during pregnancy. As many as 50% of pregnant women normally have demonstrable sugar in the urine, especially during the third and fourth months. This sugar is practically always glucose except during the late weeks of pregnancy, when lactose may be present.
symptoms of diabetes type 1 2
Secondary hyperglycemia has been associated with various disorders of insulin target tissues (liver, muscle, and adipose tissue) (Table 27-6). Other secondary causes of carbohydrate intolerance include endocrine disorders — often specific endocrine tumors — associated with excess production of growth hormone, glucocorticoids, catecholamines, glucagon, or somatostatin. In the first four situations, peripheral responsiveness to insulin is impaired. With excess of glucocorticoids, catecholamines, or glucagon, increased hepatic output of glucose is a contributory factor; in the case of catecholamines, decreased insulin release is an additional factor in producing carbohydrate intolerance, and with excess somatostatin production it is the major factor.
A rare syndrome of extreme insulin resistance associated with acanthosis nigricans afflicts either young women with androgenic features as well as insulin receptor mutations or older people, mostly women, in whom a circulating immunoglobulin binds to insulin receptors and reduces their affinity to insulin.
Medications such as diuretics, phenytoin, niacin, and high-dose glucocorticoids can produce hyperglycemia that is reversible once the drugs are discontinued or when diuretic-induced hypokalemia is corrected. Chronic pancreatitis or subtotal pancreatectomy reduces the number of functioning B cells and can result in a metabolic derangement very similar to that of genetic type 1 diabetes except that a concomitant reduction in pancreatic A cells may reduce glucagon secretion so that relatively lower doses of insulin replacement are needed. Insulin-dependent diabetes is occasionally associated with Addison's disease and autoimmune thyroiditis (Schmidt's syndrome, or polyglandular failure syndrome). This occurs more commonly in women and represents an autoimmune disorder in which there are circulating antibodies to adrenocortical and thyroid tissue, thyroglobulin, and gastric parietal cells. (current MD&T)
A rare syndrome of extreme insulin resistance associated with acanthosis nigricans afflicts either young women with androgenic features as well as insulin receptor mutations or older people, mostly women, in whom a circulating immunoglobulin binds to insulin receptors and reduces their affinity to insulin.
Medications such as diuretics, phenytoin, niacin, and high-dose glucocorticoids can produce hyperglycemia that is reversible once the drugs are discontinued or when diuretic-induced hypokalemia is corrected. Chronic pancreatitis or subtotal pancreatectomy reduces the number of functioning B cells and can result in a metabolic derangement very similar to that of genetic type 1 diabetes except that a concomitant reduction in pancreatic A cells may reduce glucagon secretion so that relatively lower doses of insulin replacement are needed. Insulin-dependent diabetes is occasionally associated with Addison's disease and autoimmune thyroiditis (Schmidt's syndrome, or polyglandular failure syndrome). This occurs more commonly in women and represents an autoimmune disorder in which there are circulating antibodies to adrenocortical and thyroid tissue, thyroglobulin, and gastric parietal cells. (current MD&T)
symptoms of diabetes mellitus
Circulating lipoproteins are just as dependent on insulin as is the plasma glucose. In type 1 diabetes, moderately deficient control of hyperglycemia is associated with only a slight elevation of LDL cholesterol and serum triglycerides and little if any change in HDL cholesterol. Once the hyperglycemia is corrected, lipoprotein levels are generally normal. However, in obese patients with type 2 diabetes, a distinct "diabetic dyslipidemia" is characteristic of the insulin resistance syndrome. Its features are a high serum triglyceride level (300-400 mg/dL), a low HDL cholesterol (less than 30 mg/dL), and a qualitative change in LDL particles, producing a smaller dense particle whose membrane carries supranormal amounts of free cholesterol. These smaller dense LDL particles are more susceptible to oxidation, which renders them more atherogenic. Since a low HDL cholesterol is a major feature predisposing to macrovascular disease, the term "dyslipidemia" has preempted the term "hyperlipidemia," which mainly denoted the elevated triglycerides. Measures designed to correct the obesity and hyperglycemia, such as exercise, diet, and hypoglycemic therapy, are the treatment of choice for diabetic dyslipidemia, and in occasional patients in whom normal weight was achieved, all features of the lipoprotein abnormalities cleared. Since primary disorders of lipid metabolism may coexist with diabetes, persistence of lipid abnormalities after restoration of normal weight and blood glucose should prompt a diagnostic workup and possible pharmacotherapy of the lipid disorder. Chapter 28 discusses these matters in detail. (current MD&T 2005)
post meal 150 a1c 6.1 but no symptoms of diabetes in child
Two continuous glucose monitoring systems are currently available for clinical use. The system manufactured by MiniMed Medtronic involves inserting a subcutaneous sensor (rather like an insulin pump cannula) that measures glucose concentrations in the interstitial fluid for 72 hours. The glucose values are not available for evaluation at time of measurement — the data are downloaded to a computer in a physician's office after collection. The other system ("Glucowatch") measures glucose in interstitial fluid extracted through intact skin by applying a low electric current (reverse iontophoresis). This process can cause local skin irritation, and sweating distorts the glucose measurement. Both systems require calibration with finger blood glucose measurements. The main value of these systems appears to be in identifying episodes of asymptomatic hypoglycemia, especially at night.
symptoms of pre diabetes
Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful. In type 1 patients in whom "tight" metabolic control is attempted, they are indispensable. A portable battery-operated glucometer provides a digital readout of the intensity of color developed when glucose oxidase paper strips are exposed to a drop of capillary blood for up to 45 seconds. A large number of blood glucose meters are now available. All are accurate, but they vary with regard to speed, convenience, size of blood samples required, and cost. Popular models include those manufactured by LifeScan (One Touch), Bayer Corporation (Glucometer Elite, DEX), Roche Diagnostics (Accu-Chek), Abbott Laboratories (ExacTech, Precision, FreeStyle), and Home Diagnostics (Prestige). One Touch Ultra, for example, requires only 0.3 mL of blood and gives a result in 5 seconds — and illustrates how there has been continued progress in this technologic area. Various glucometers appeal to a particular consumer need and are relatively inexpensive, ranging from $50.00 to $100.00 each. The more expensive models compute blood glucose averages and can be attached to printers for data records and graph production. Test strips remain a major expense, costing 50-75 cents apiece. In self-monitoring of blood glucose, patients must prick a finger with a 28-gauge lancet (Monolet, Ames Co.), which can be facilitated by a small plastic trigger device such as an Autolet (Ames Co.), SoftClix (Boehringer-Mannheim), or Penlet (Lifescan, Inc.). When used for multiple patients, as in a clinic, physician's office, or hospital ward, disposable finger-rest platforms are required to avoid inadvertent transmission of blood-borne viral diseases. Some meters such as the FreeStyle (Abbott Laboratories) have been approved for measuring glucose in blood samples obtained at alternative sites such as the forearm and thigh. There is, however, a 5- to 20-minute lag in the glucose response on the arm with respect to the glucose response on the finger. Forearm blood glucose measurements could therefore result in a delay in detection of rapidly developing hypoglycemia.
The accuracy of data obtained by glucose monitoring requires education of the patient in sampling and measuring procedures as well as in proper calibration of the instruments. Bedside glucose monitoring in a hospital setting requires rigorous quality control programs and certification of personnel to avoid errors.
The accuracy of data obtained by glucose monitoring requires education of the patient in sampling and measuring procedures as well as in proper calibration of the instruments. Bedside glucose monitoring in a hospital setting requires rigorous quality control programs and certification of personnel to avoid errors.
symptoms of diabetes in children
Serum fructosamine is formed by nonenzymatic glycosylation of serum proteins (predominantly albumin). Since serum albumin has a much shorter half-life than hemoglobin, serum fructosamine generally reflects the state of glycemic control for only the preceding 2 weeks. Reductions in serum albumin (eg, nephrotic state or hepatic disease) will lower the serum fructosamine value. When abnormal hemoglobins or hemolytic states affect the interpretation of glycohemoglobin or when a narrower time frame is required, such as for ascertaining glycemic control at the time of conception in a diabetic woman who has recently become pregnant, serum fructosamine assays offer some advantage. Normal values vary in relation to the serum albumin concentration and are 1.5-2.4 mmol/L when the serum albumin level is 5 g/dL.
symptoms of canine diabetes
Glycated hemoglobin is abnormally high in diabetics with chronic hyperglycemia and reflects their metabolic control. It is produced by nonenzymatic condensation of glucose molecules with free amino groups on the globin component of hemoglobin. The higher the prevailing ambient levels of blood glucose, the higher will be the level of glycated hemoglobin.
The major form of glycohemoglobin is termed hemoglobin A1c, which normally comprises only 4-6% of the total hemoglobin. The remaining glycohemoglobins (2-4% of the total) consist of phosphorylated glucose or fructose and are termed hemoglobin A1a and hemoglobin A1b. Some laboratories measure the sum of these three glycohemoglobins and report it as hemoglobin A1, but more laboratories are converting to the more intricate but highly specific HbA1c assay. There are now monoclonal immunoassays for measuring HbA1c. Machines based on this technology can be used in clinicians' offices. They use capillary blood and give a result in about 9 minutes, allowing immediate feedback to the patients regarding their glycemic control.
Since glycohemoglobins circulate within red blood cells whose life span lasts up to 120 days, they generally reflect the state of glycemia over the preceding 8-12 weeks, thereby providing an improved method of assessing diabetic control. Measurements should be made in patients with either type of diabetes mellitus at 3- to 4-month intervals so that adjustments in therapy can be made if glycohemoglobin is either subnormal or if it is more than 2% above the upper limits of normal for a particular laboratory. In patients monitoring their own blood glucose levels, glycohemoglobin values provide a valuable check on the accuracy of monitoring. In patients who do not monitor their own blood glucose levels, glycohemoglobin values are essential for adjusting therapy. Use of glycohemoglobin for screening is controversial. Sensitivity in detecting known diabetes cases by hemoglobin A1c measurements is only 85%, indicating that diabetes cannot be excluded by a normal value. On the other hand, elevated hemoglobin A1c assays are fairly specific (91%) in identifying the presence of diabetes.
Occasionally, fluctuations in hemoglobin A1 are due to an acutely generated, reversible, intermediary (aldimine-linked) product that can falsely elevate glycohemoglobins when measured with "short-cut" chromatographic methods. This can be eliminated by using specific HPLC methods that detect HbA1c or by dialysis of the hemolysate before chromatography. When hemoglobin variants are present, such as negatively charged hemoglobin F, acetylated hemoglobin from high-dose aspirin therapy, or carbamoylated hemoglobin produced by the complexing of urea with hemoglobin in uremia, falsely high "hemoglobin A1" values are obtained with commonly used chromatographic methods. In the presence of positively charged hemoglobin variants such as hemoglobin S or C, or when the life span of red blood cells is reduced by increased hemolysis or hemorrhage, falsely low values for "hemoglobin A1" result.
(current MD&T 2005)
The major form of glycohemoglobin is termed hemoglobin A1c, which normally comprises only 4-6% of the total hemoglobin. The remaining glycohemoglobins (2-4% of the total) consist of phosphorylated glucose or fructose and are termed hemoglobin A1a and hemoglobin A1b. Some laboratories measure the sum of these three glycohemoglobins and report it as hemoglobin A1, but more laboratories are converting to the more intricate but highly specific HbA1c assay. There are now monoclonal immunoassays for measuring HbA1c. Machines based on this technology can be used in clinicians' offices. They use capillary blood and give a result in about 9 minutes, allowing immediate feedback to the patients regarding their glycemic control.
Since glycohemoglobins circulate within red blood cells whose life span lasts up to 120 days, they generally reflect the state of glycemia over the preceding 8-12 weeks, thereby providing an improved method of assessing diabetic control. Measurements should be made in patients with either type of diabetes mellitus at 3- to 4-month intervals so that adjustments in therapy can be made if glycohemoglobin is either subnormal or if it is more than 2% above the upper limits of normal for a particular laboratory. In patients monitoring their own blood glucose levels, glycohemoglobin values provide a valuable check on the accuracy of monitoring. In patients who do not monitor their own blood glucose levels, glycohemoglobin values are essential for adjusting therapy. Use of glycohemoglobin for screening is controversial. Sensitivity in detecting known diabetes cases by hemoglobin A1c measurements is only 85%, indicating that diabetes cannot be excluded by a normal value. On the other hand, elevated hemoglobin A1c assays are fairly specific (91%) in identifying the presence of diabetes.
Occasionally, fluctuations in hemoglobin A1 are due to an acutely generated, reversible, intermediary (aldimine-linked) product that can falsely elevate glycohemoglobins when measured with "short-cut" chromatographic methods. This can be eliminated by using specific HPLC methods that detect HbA1c or by dialysis of the hemolysate before chromatography. When hemoglobin variants are present, such as negatively charged hemoglobin F, acetylated hemoglobin from high-dose aspirin therapy, or carbamoylated hemoglobin produced by the complexing of urea with hemoglobin in uremia, falsely high "hemoglobin A1" values are obtained with commonly used chromatographic methods. In the presence of positively charged hemoglobin variants such as hemoglobin S or C, or when the life span of red blood cells is reduced by increased hemolysis or hemorrhage, falsely low values for "hemoglobin A1" result.
(current MD&T 2005)
symptoms of borderline diabetes
Plasma or serum from venous blood samples has the advantage over whole blood of providing values for glucose that are independent of hematocrit and that reflect the glucose concentration to which body tissues are exposed. For these reasons, and because plasma and serum are more readily measured on automated equipment, they are used in most laboratories. If serum is used or if plasma is collected from tubes that lack an agent to block glucose metabolism (such as fluoride), samples should be refrigerated and separated within 1 hour after collection.
(2) Criteria for laboratory confirmation of diabetes mellitus —
If the fasting plasma glucose level is 126 mg/dL or higher on more than one occasion, further evaluation of the patient with a glucose challenge is unnecessary. However, when fasting plasma glucose is less than 126 mg/dL in suspected cases, a standardized oral glucose tolerance test may be done (Table 27-5).
For proper evaluation of the test, the subjects should be normally active and free from acute illness. Medications that may impair glucose tolerance include diuretics, contraceptive drugs, glucocorticoids, niacin, and phenytoin.
Because of difficulties in interpreting oral glucose tolerance tests and the lack of standards related to aging, these tests are being replaced by documentation of fasting hyperglycemia.
(current MD&T 2005)
(2) Criteria for laboratory confirmation of diabetes mellitus —
If the fasting plasma glucose level is 126 mg/dL or higher on more than one occasion, further evaluation of the patient with a glucose challenge is unnecessary. However, when fasting plasma glucose is less than 126 mg/dL in suspected cases, a standardized oral glucose tolerance test may be done (Table 27-5).
For proper evaluation of the test, the subjects should be normally active and free from acute illness. Medications that may impair glucose tolerance include diuretics, contraceptive drugs, glucocorticoids, niacin, and phenytoin.
Because of difficulties in interpreting oral glucose tolerance tests and the lack of standards related to aging, these tests are being replaced by documentation of fasting hyperglycemia.
(current MD&T 2005)
sign and symptoms of diabetes type 2
a. Glucosuria —
A specific and convenient method to detect glucosuria is the paper strip impregnated with glucose oxidase and a chromogen system (Clinistix, Diastix), which is sensitive to as little as 0.1% glucose in urine. Diastix can be directly applied to the urinary stream, and differing color responses of the indicator strip reflect glucose concentration.
A normal renal threshold for glucose as well as reliable bladder emptying is essential for interpretation.
b. Ketonuria —
Qualitative detection of ketone bodies can be accomplished by nitroprusside tests (Acetest or Ketostix). Although these tests do not detect ß-hydroxybutyric acid, which lacks a ketone group, the semiquantitative estimation of ketonuria thus obtained is nonetheless usually adequate for clinical purposes.
A specific and convenient method to detect glucosuria is the paper strip impregnated with glucose oxidase and a chromogen system (Clinistix, Diastix), which is sensitive to as little as 0.1% glucose in urine. Diastix can be directly applied to the urinary stream, and differing color responses of the indicator strip reflect glucose concentration.
A normal renal threshold for glucose as well as reliable bladder emptying is essential for interpretation.
b. Ketonuria —
Qualitative detection of ketone bodies can be accomplished by nitroprusside tests (Acetest or Ketostix). Although these tests do not detect ß-hydroxybutyric acid, which lacks a ketone group, the semiquantitative estimation of ketonuria thus obtained is nonetheless usually adequate for clinical purposes.
recognizing the symptoms of diabetes
While many patients with type 2 diabetes present with increased urination and thirst, many others have an insidious onset of hyperglycemia and are asymptomatic initially. This is particularly true in obese patients, whose diabetes may be detected only after glycosuria or hyperglycemia is noted during routine laboratory studies. Occasionally, type 2 patients may present with evidence of neuropathic or cardiovascular complications because of occult disease present for some time prior to diagnosis. Chronic skin infections are common. Generalized pruritus and symptoms of vaginitis are frequently the initial complaints of women. Diabetes should be suspected in women with chronic candidal vulvovaginitis as well as in those who have delivered large babies (> 9 lb, or 4.1 kg) or have had polyhydramnios, preeclampsia, or unexplained fetal losses.
Obese diabetics may have any variety of fat distribution; however, diabetes seems to be more often associated in both men and women with localization of fat deposits on the upper segment of the body (particularly the abdomen, chest, neck, and face) and relatively less fat on the appendages, which may be quite muscular. Standardized tables of waist-to-hip ratio indicate that ratios of "greater than 0.9" in men and "greater than 0.8" in women are associated with an increased risk of diabetes in obese subjects. Mild hypertension is often present in obese diabetics. Eruptive xanthomas on the flexor surface of the limbs and on the buttocks and lipemia retinalis due to hyperchylomicronemia can occur in patients with uncontrolled type 2 diabetes who also have a familial form of hypertriglyceridemia.
Obese diabetics may have any variety of fat distribution; however, diabetes seems to be more often associated in both men and women with localization of fat deposits on the upper segment of the body (particularly the abdomen, chest, neck, and face) and relatively less fat on the appendages, which may be quite muscular. Standardized tables of waist-to-hip ratio indicate that ratios of "greater than 0.9" in men and "greater than 0.8" in women are associated with an increased risk of diabetes in obese subjects. Mild hypertension is often present in obese diabetics. Eruptive xanthomas on the flexor surface of the limbs and on the buttocks and lipemia retinalis due to hyperchylomicronemia can occur in patients with uncontrolled type 2 diabetes who also have a familial form of hypertriglyceridemia.
symptoms of diabetes in women
Increased urination is a consequence of osmotic diuresis secondary to sustained hyperglycemia. This results in a loss of glucose as well as free water and electrolytes in the urine. Thirst is a consequence of the hyperosmolar state, as is blurred vision, which often develops as the lenses are exposed to hyperosmolar fluids.
Weight loss despite normal or increased appetite is a common feature of type 1 when it develops subacutely. The weight loss is initially due to depletion of water, glycogen, and triglycerides; thereafter, reduced muscle mass occurs as amino acids are diverted to form glucose and ketone bodies.
Lowered plasma volume produces symptoms of postural hypotension. Total body potassium loss and the general catabolism of muscle protein contribute to the weakness.
Paresthesias may be present at the time of diagnosis, particularly when the onset is subacute. They reflect a temporary dysfunction of peripheral sensory nerves, which clears as insulin replacement restores glycemic levels closer to normal, suggesting neurotoxicity from sustained hyperglycemia.
When absolute insulin deficiency is of acute onset, the above symptoms develop abruptly. Ketoacidosis exacerbates the dehydration and hyperosmolality by producing anorexia and nausea and vomiting, interfering with oral fluid replacement.
The patient's level of consciousness can vary depending on the degree of hyperosmolality. When insulin deficiency develops relatively slowly and sufficient water intake is maintained, patients remain relatively alert and physical findings may be minimal. When vomiting occurs in response to worsening ketoacidosis, dehydration progresses and compensatory mechanisms become inadequate to keep serum osmolality below 320-330 mosm/L. Under these circumstances, stupor or even coma may occur. The fruity breath odor of acetone further suggests the diagnosis of diabetic ketoacidosis.
Hypotension in the recumbent position is a serious prognostic sign. Loss of subcutaneous fat and muscle wasting are features of more slowly developing insulin deficiency. In occasional patients with slow, insidious onset of insulin deficiency, subcutaneous fat may be considerably depleted.
Weight loss despite normal or increased appetite is a common feature of type 1 when it develops subacutely. The weight loss is initially due to depletion of water, glycogen, and triglycerides; thereafter, reduced muscle mass occurs as amino acids are diverted to form glucose and ketone bodies.
Lowered plasma volume produces symptoms of postural hypotension. Total body potassium loss and the general catabolism of muscle protein contribute to the weakness.
Paresthesias may be present at the time of diagnosis, particularly when the onset is subacute. They reflect a temporary dysfunction of peripheral sensory nerves, which clears as insulin replacement restores glycemic levels closer to normal, suggesting neurotoxicity from sustained hyperglycemia.
When absolute insulin deficiency is of acute onset, the above symptoms develop abruptly. Ketoacidosis exacerbates the dehydration and hyperosmolality by producing anorexia and nausea and vomiting, interfering with oral fluid replacement.
The patient's level of consciousness can vary depending on the degree of hyperosmolality. When insulin deficiency develops relatively slowly and sufficient water intake is maintained, patients remain relatively alert and physical findings may be minimal. When vomiting occurs in response to worsening ketoacidosis, dehydration progresses and compensatory mechanisms become inadequate to keep serum osmolality below 320-330 mosm/L. Under these circumstances, stupor or even coma may occur. The fruity breath odor of acetone further suggests the diagnosis of diabetic ketoacidosis.
Hypotension in the recumbent position is a serious prognostic sign. Loss of subcutaneous fat and muscle wasting are features of more slowly developing insulin deficiency. In occasional patients with slow, insidious onset of insulin deficiency, subcutaneous fat may be considerably depleted.
symptoms of childhood diabetes
Patients with type 1 diabetes present with a characteristic symptom complex. An absolute deficiency of insulin results in accumulation of circulating glucose and fatty acids, with consequent hyperosmolality and hyperketonemia.
Patients with type 2 diabetes may or may not present with characteristic features. The presence of obesity or a strongly positive family history for mild diabetes suggests a high risk for the development of type 2 diabetes.
Patients with type 2 diabetes may or may not present with characteristic features. The presence of obesity or a strongly positive family history for mild diabetes suggests a high risk for the development of type 2 diabetes.
early symptoms of diabetes
An estimated 16 million people in the United States are known to have diabetes, of which 1.4 million have type 1 diabetes and approximately 14.5 million have type 2 diabetes. The remainder, numbered only in the thousands, comprise a third group that was designated as "other specific types" by the American Diabetes Association (Table 27-3). These other types include disorders for which causes are known. Among these are the rare monogenic defects of either B cell function or of insulin action, primary diseases of the exocrine pancreas, endocrinopathies, and drug-induced diabetes. (current MD&T 2005)
can you give me some symptoms signs of diabetes
Wolfram syndrome is an autosomal recessive neurodegenerative disorder first evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD. It is due to mutations in a gene named WFS1, which encodes a 100.3 KDa transmembrane protein localized in the endoplasmic reticulum. The function of the protein is not known. The diabetes mellitus, which is nonimmune and not linked to specific HLA antigens, usually presents in the first decade together with the optic atrophy. Cranial diabetes insipidus and sensorineural deafness develop during the second decade in 60-75% of patients. Ureterohydronephrosis, neurogenic bladder, cerebellar ataxia, peripheral neuropathy, and psychiatric illness develop later in many patients. (current MD&T 2005)
can you give me some symptoms signs of diabetes
Wolfram syndrome is an autosomal recessive neurodegenerative disorder first evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD. It is due to mutations in a gene named WFS1, which encodes a 100.3 KDa transmembrane protein localized in the endoplasmic reticulum. The function of the protein is not known. The diabetes mellitus, which is nonimmune and not linked to specific HLA antigens, usually presents in the first decade together with the optic atrophy. Cranial diabetes insipidus and sensorineural deafness develop during the second decade in 60-75% of patients. Ureterohydronephrosis, neurogenic bladder, cerebellar ataxia, peripheral neuropathy, and psychiatric illness develop later in many patients. (current MD&T 2005)
symptoms of juvenile diabetes
Since sperm do not contain mitochondria, only the mother transmits mitochondrial genes to her offspring. Diabetes due to a mutation of mitochondrial DNA that impairs the transfer of leucine or lysine into mitochondrial proteins has been described. Most patients have a mild form of diabetes that responds to oral hypoglycemic agents; some have a nonimmune form of type 1 diabetes. Two-thirds of patients with this subtype of diabetes have a hearing loss, and a smaller proportion (15%) had a syndrome of myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). (Current MD&T 2005)
symptoms of gestational diabetes
Defects in one of their insulin receptor genes have been found in more than 40 people with diabetes, and most have extreme insulin resistance associated with acanthosis nigricans. In very rare instances when both insulin receptor genes are abnormal, newborns present with a leprechaun-like phenotype and seldom live through infancy.
causes and symptoms of juvenile diabetes
Defects in one of their insulin receptor genes have been found in more than 40 people with diabetes, and most have extreme insulin resistance associated with acanthosis nigricans. In very rare instances when both insulin receptor genes are abnormal, newborns present with a leprechaun-like phenotype and seldom live through infancy.
symptoms of type ii diabetes
BR>This is a very rare subtype of nonobese type 2 diabetes, with no more than ten families having been described. Since affected individuals were heterozygous and possessed one normal insulin gene, diabetes was mild, did not appear until middle age, and showed autosomal dominant genetic transmission. There is generally no evidence of clinical insulin resistance, and these patients respond well to standard therapy.
signs and symptoms of diabetes
This subgroup is a relatively rare monogenic disorder characterized by non-insulin-dependent diabetes with autosomal dominant inheritance and an age at onset of 25 years or younger. Patients are nonobese, and their hyperglycemia is due to impaired glucose-induced secretion of insulin. Six types of MODY have been described. Except for MODY 2, in which a glucokinase gene is defective, all other types involve mutations of a nuclear transcription factor that regulates islet gene expression.
MODY 2 is quite mild, associated with only slight fasting hyperglycemia and few if any microvascular diabetic complications. It generally responds well to hygienic measures or low doses of oral hypoglycemic agents. MODY 3 — the most common form — accounts for two-thirds of all MODY cases. The clinical course is similar to that of idiopathic type 2 diabetes in terms of microangiopathy and failure to respond to oral agents with time.
MODY 2 is quite mild, associated with only slight fasting hyperglycemia and few if any microvascular diabetic complications. It generally responds well to hygienic measures or low doses of oral hypoglycemic agents. MODY 3 — the most common form — accounts for two-thirds of all MODY cases. The clinical course is similar to that of idiopathic type 2 diabetes in terms of microangiopathy and failure to respond to oral agents with time.
symptoms of feline diabetes
Patients with this most common form of diabetes have an insensitivity to endogenous insulin. When an associated defect of insulin production prevents adequate compensation for this insulin resistance, nonketotic mild diabetes occurs. Hyperplasia of pancreatic B cells is often present and probably accounts for the fasting hyperinsulinism and exaggerated insulin and proinsulin responses to glucose and other stimuli seen early in the disease. After several years' duration of diabetes, chronic deposition of amyloid in the islets may combine with inherited genetic defects to progressively impair B cell function.
The mechanisms underlying the insulin resistance of type 2 diabetes are poorly understood. Obesity is generally associated with abdominal distribution of fat, producing an abnormally high waist-to-hip ratio. This "visceral" obesity, due to accumulation of fat in the omental and mesenteric regions, correlates with insulin resistance; subcutaneous abdominal fat seems to have less of an association with insulin insensitivity. Exercise may affect the deposition of visceral fat as suggested by CT scans of Japanese wrestlers, whose extreme obesity is predominantly subcutaneous. Their daily vigorous exercise program prevents accumulation of visceral fat, and they have normal serum lipids and euglycemia despite daily intakes of 5000-7000 kcal and development of massive subcutaneous obesity. Several adipokines, secreted by fat cells, can affect insulin action in obesity. Two of these, leptin and adiponectin, seem to increase sensitivity to insulin, presumably by increasing hepatic responsiveness. Two others — tumor necrosis factor-a, which inactivates insulin receptors, and the newly discovered peptide resistin — interfere with insulin action on glucose metabolism and have been reported to be elevated in obese animal models. Mutations or abnormal levels of these adipokines may contribute to the development of insulin resistance in human obesity.
Hyperglycemia per se can impair insulin action by causing accumulation of hexosamines in muscle and fat tissue and inhibiting glucose transport (acquired glucose toxicity). Correction of hyperglycemia reverses this acquired insulin resistance.
The mechanisms underlying the insulin resistance of type 2 diabetes are poorly understood. Obesity is generally associated with abdominal distribution of fat, producing an abnormally high waist-to-hip ratio. This "visceral" obesity, due to accumulation of fat in the omental and mesenteric regions, correlates with insulin resistance; subcutaneous abdominal fat seems to have less of an association with insulin insensitivity. Exercise may affect the deposition of visceral fat as suggested by CT scans of Japanese wrestlers, whose extreme obesity is predominantly subcutaneous. Their daily vigorous exercise program prevents accumulation of visceral fat, and they have normal serum lipids and euglycemia despite daily intakes of 5000-7000 kcal and development of massive subcutaneous obesity. Several adipokines, secreted by fat cells, can affect insulin action in obesity. Two of these, leptin and adiponectin, seem to increase sensitivity to insulin, presumably by increasing hepatic responsiveness. Two others — tumor necrosis factor-a, which inactivates insulin receptors, and the newly discovered peptide resistin — interfere with insulin action on glucose metabolism and have been reported to be elevated in obese animal models. Mutations or abnormal levels of these adipokines may contribute to the development of insulin resistance in human obesity.
Hyperglycemia per se can impair insulin action by causing accumulation of hexosamines in muscle and fat tissue and inhibiting glucose transport (acquired glucose toxicity). Correction of hyperglycemia reverses this acquired insulin resistance.
symptoms of type 1 diabetes
1. Immune-mediated type 1 diabetes mellitus —
Immune-mediated type 1 diabetes is felt to result from an infectious or toxic insult to persons whose immune system is genetically predisposed to develop a vigorous autoimmune response either against altered pancreatic B cell antigens or against molecules of the B cell resembling the viral protein (molecular mimicry). Extrinsic factors that affect B cell function include damage caused by viruses such as mumps or coxsackie B4 virus, by toxic chemical agents, or by destructive cytotoxins and antibodies released from sensitized immunocytes. Specific HLA immune response genes are believed to predispose patients to a destructive autoimmune response against their own islet cells (autoaggression), which is mediated primarily by cytotoxic T cells. Amelioration of hyperglycemia in patients given an immunosuppressive agent (eg, cyclosporine) shortly after onset of type 1 diabetes lends further support to the pathogenetic role of autoimmunity.
2. Idiopathic type 1 diabetes mellitus —
Fewer than 10% of subjects have no evidence of pancreatic B cell autoimmunity to explain their insulinopenia and ketoacidosis. This subgroup has been classified as "idiopathic type 1 diabetes" and designated as "type 1B." Although only a minority of patients with type 1 diabetes fall into this group, most of these are of Asian or African origin.
Immune-mediated type 1 diabetes is felt to result from an infectious or toxic insult to persons whose immune system is genetically predisposed to develop a vigorous autoimmune response either against altered pancreatic B cell antigens or against molecules of the B cell resembling the viral protein (molecular mimicry). Extrinsic factors that affect B cell function include damage caused by viruses such as mumps or coxsackie B4 virus, by toxic chemical agents, or by destructive cytotoxins and antibodies released from sensitized immunocytes. Specific HLA immune response genes are believed to predispose patients to a destructive autoimmune response against their own islet cells (autoaggression), which is mediated primarily by cytotoxic T cells. Amelioration of hyperglycemia in patients given an immunosuppressive agent (eg, cyclosporine) shortly after onset of type 1 diabetes lends further support to the pathogenetic role of autoimmunity.
2. Idiopathic type 1 diabetes mellitus —
Fewer than 10% of subjects have no evidence of pancreatic B cell autoimmunity to explain their insulinopenia and ketoacidosis. This subgroup has been classified as "idiopathic type 1 diabetes" and designated as "type 1B." Although only a minority of patients with type 1 diabetes fall into this group, most of these are of Asian or African origin.
early symptoms of adult onset diabetes
This form of diabetes is immune-mediated in over 90% of cases and idiopathic in less than 10%. The rate of pancreatic B cell destruction is quite variable, being rapid in some individuals and slow in others. Type 1 diabetes is usually associated with ketosis in its untreated state. It occurs at any age but most commonly arises in children and young adults with a peak incidence before school age and again at around puberty. It is a catabolic disorder in which circulating insulin is virtually absent, plasma glucagon is elevated, and the pancreatic B cells fail to respond to all insulinogenic stimuli. Exogenous insulin is therefore required to reverse the catabolic state, prevent ketosis, reduce the hyperglucagonemia, and reduce blood glucose.
The highest incidence of immune-mediated type 1 diabetes is in Scandinavia and northern Europe, where the yearly incidence per 100,000 youngsters 14 years of age or less is as high as 37 in Finland, 27 in Sweden, 22 in Norway, and 19 in the United Kingdom. The incidence of type 1 diabetes generally decreases across the rest of Europe to 10 in Greece and 8 in France. Surprisingly, the island of Sardinia has as high an incidence as Finland (37) even though in the rest of Italy, including the island of Sicily, it is only 10 per 100,000 per year. The United States averages 15 per 100,000, with higher incidences in states more densely populated with persons of Scandinavian descent such as Minnesota. The lowest incidence of type 1 diabetes worldwide was found to be less than 1 per 100,000 per year in China and parts of South America.
Certain human leukocyte antigens (HLA) are strongly associated with the development of type 1 diabetes. About 95% of type 1 patients possess either HLA-DR3 or HLA-DR4, compared with 45-50% of white controls. HLA-DQ genes are even more specific markers of type 1 susceptibility, since a particular variety (HLA-DQB1*0302) is found in the DR4 patients with type 1, while a "protective" gene (HLA-DQB1*0602) is often present in the DR4 controls. In addition, most patients with type 1 diabetes at diagnosis have circulating antibodies to islets (islet cell antibodies, ICA), insulin (IAA), glutamic acid decarboxylase (GAD 65), and to tyrosine phosphatases (IA-2 and IA2-ß). These antibodies facilitate screening of siblings of affected children as well as adults with atypical features of type 2 for an autoimmune cause of their diabetes (Table 27-2). The antibody levels decline with increasing duration of the disease. Also, once patients are treated with insulin, low levels of anti-insulin antibodies develop.
Certain unrecognized patients with a milder expression of type 1 diabetes initially retain enough B cell function to avoid ketosis but later in life develop increasing dependency on insulin therapy as their B cell mass diminishes. Islet cell antibody surveys among northern Europeans indicate that up to 15% of "type 2" patients may actually have this mild form of type 1 diabetes (latent autoimmune diabetes of adulthood; LADA).
The highest incidence of immune-mediated type 1 diabetes is in Scandinavia and northern Europe, where the yearly incidence per 100,000 youngsters 14 years of age or less is as high as 37 in Finland, 27 in Sweden, 22 in Norway, and 19 in the United Kingdom. The incidence of type 1 diabetes generally decreases across the rest of Europe to 10 in Greece and 8 in France. Surprisingly, the island of Sardinia has as high an incidence as Finland (37) even though in the rest of Italy, including the island of Sicily, it is only 10 per 100,000 per year. The United States averages 15 per 100,000, with higher incidences in states more densely populated with persons of Scandinavian descent such as Minnesota. The lowest incidence of type 1 diabetes worldwide was found to be less than 1 per 100,000 per year in China and parts of South America.
Certain human leukocyte antigens (HLA) are strongly associated with the development of type 1 diabetes. About 95% of type 1 patients possess either HLA-DR3 or HLA-DR4, compared with 45-50% of white controls. HLA-DQ genes are even more specific markers of type 1 susceptibility, since a particular variety (HLA-DQB1*0302) is found in the DR4 patients with type 1, while a "protective" gene (HLA-DQB1*0602) is often present in the DR4 controls. In addition, most patients with type 1 diabetes at diagnosis have circulating antibodies to islets (islet cell antibodies, ICA), insulin (IAA), glutamic acid decarboxylase (GAD 65), and to tyrosine phosphatases (IA-2 and IA2-ß). These antibodies facilitate screening of siblings of affected children as well as adults with atypical features of type 2 for an autoimmune cause of their diabetes (Table 27-2). The antibody levels decline with increasing duration of the disease. Also, once patients are treated with insulin, low levels of anti-insulin antibodies develop.
Certain unrecognized patients with a milder expression of type 1 diabetes initially retain enough B cell function to avoid ketosis but later in life develop increasing dependency on insulin therapy as their B cell mass diminishes. Islet cell antibody surveys among northern Europeans indicate that up to 15% of "type 2" patients may actually have this mild form of type 1 diabetes (latent autoimmune diabetes of adulthood; LADA).
symptoms of type 2 diabetes
B. Type 2 Diabetes
This represents a heterogeneous group comprising milder forms of diabetes that occur predominantly in adults but occasionally in juveniles. More than 90% of all diabetics in the United States are included under this classification. Circulating endogenous insulin is sufficient to prevent ketoacidosis but is inadequate to prevent hyperglycemia in the face of increased needs owing to tissue insensitivity. In most cases of this type of diabetes, the cause is unknown.
Tissue insensitivity to insulin has been noted in most type 2 patients irrespective of weight and has been attributed to several interrelated factors. These include a putative (and as yet undefined) genetic factor, which is aggravated in time by additional enhancers of insulin resistance such as aging, a sedentary lifestyle, and abdominal-visceral obesity. In addition, there is an accompanying deficiency in the response of pancreatic B cells to glucose. Both the tissue resistance to insulin and the impaired B cell response to glucose appear to be further aggravated by increased hyperglycemia (glucose toxicity), and both defects are ameliorated by treatment that reduces the hyperglycemia toward normal. Most epidemiologic data indicate strong genetic influences, since in monozygotic twins over 40 years of age, concordance develops in over 70% of cases within a year whenever one twin develops type 2 diabetes. Attempts to identify genetic markers for type 2 have as yet been unsuccessful, though linkage to a gene on chromosome 2 encoding a cysteine protease, calpain-10, has been reported in a Mexican-American population. However, its association with other ethnic populations and any role it plays in the pathogenesis of type 2 diabetes remain to be clarified.
Two subgroups of patients are currently distinguished by the absence or presence of obesity. The degree and prevalence of obesity varies among different racial groups. While obesity is apparent in no more than 30% of Chinese and Japanese patients with type 2, it is found in 60-70% of North Americans, Europeans, or Africans with type 2 and approaches 100% of patients with type 2 among Pima Indians or Pacific Islanders from Nauru or Samoa.
1. Obese type 2 patients —
Patients with this most common form of diabetes have an insensitivity to endogenous insulin. When an associated defect of insulin production prevents adequate compensation for this insulin resistance, nonketotic mild diabetes occurs. Hyperplasia of pancreatic B cells is often present and probably accounts for the fasting hyperinsulinism and exaggerated insulin and proinsulin responses to glucose and other stimuli seen early in the disease. After several years' duration of diabetes, chronic deposition of amyloid in the islets may combine with inherited genetic defects to progressively impair B cell function.
The mechanisms underlying the insulin resistance of type 2 diabetes are poorly understood. Obesity is generally associated with abdominal distribution of fat, producing an abnormally high waist-to-hip ratio. This "visceral" obesity, due to accumulation of fat in the omental and mesenteric regions, correlates with insulin resistance; subcutaneous abdominal fat seems to have less of an association with insulin insensitivity. Exercise may affect the deposition of visceral fat as suggested by CT scans of Japanese wrestlers, whose extreme obesity is predominantly subcutaneous. Their daily vigorous exercise program prevents accumulation of visceral fat, and they have normal serum lipids and euglycemia despite daily intakes of 5000-7000 kcal and development of massive subcutaneous obesity. Several adipokines, secreted by fat cells, can affect insulin action in obesity. Two of these, leptin and adiponectin, seem to increase sensitivity to insulin, presumably by increasing hepatic responsiveness. Two others — tumor necrosis factor-a, which inactivates insulin receptors, and the newly discovered peptide resistin — interfere with insulin action on glucose metabolism and have been reported to be elevated in obese animal models. Mutations or abnormal levels of these adipokines may contribute to the development of insulin resistance in human obesity.
Hyperglycemia per se can impair insulin action by causing accumulation of hexosamines in muscle and fat tissue and inhibiting glucose transport (acquired glucose toxicity). Correction of hyperglycemia reverses this acquired insulin resistance.
2. Nonobese type 2 patients —
These patients generally show an absent or blunted early phase of insulin release in response to glucose; however, it can be elicited in response to other insulinogenic stimuli such as acute intravenous administration of sulfonylureas, glucagon, or arginine.
Although insulin resistance may be detected with special tests, it does not seem to be clinically relevant to the treatment of most nonobese type 2 patients, who generally respond to appropriate therapeutic supplements of insulin in the absence of rare associated conditions such as lipoatrophy or acanthosis nigricans.
Among this heterogeneous subgroup of patients with nonobese type 2 diabetes, the majority are idiopathic. However, with increasing frequency, a variety of etiologic genetic abnormalities have been documented in a subset of these patients who have recently been reclassified within a group designated "other specific types." (current MD&T 2005)
This represents a heterogeneous group comprising milder forms of diabetes that occur predominantly in adults but occasionally in juveniles. More than 90% of all diabetics in the United States are included under this classification. Circulating endogenous insulin is sufficient to prevent ketoacidosis but is inadequate to prevent hyperglycemia in the face of increased needs owing to tissue insensitivity. In most cases of this type of diabetes, the cause is unknown.
Tissue insensitivity to insulin has been noted in most type 2 patients irrespective of weight and has been attributed to several interrelated factors. These include a putative (and as yet undefined) genetic factor, which is aggravated in time by additional enhancers of insulin resistance such as aging, a sedentary lifestyle, and abdominal-visceral obesity. In addition, there is an accompanying deficiency in the response of pancreatic B cells to glucose. Both the tissue resistance to insulin and the impaired B cell response to glucose appear to be further aggravated by increased hyperglycemia (glucose toxicity), and both defects are ameliorated by treatment that reduces the hyperglycemia toward normal. Most epidemiologic data indicate strong genetic influences, since in monozygotic twins over 40 years of age, concordance develops in over 70% of cases within a year whenever one twin develops type 2 diabetes. Attempts to identify genetic markers for type 2 have as yet been unsuccessful, though linkage to a gene on chromosome 2 encoding a cysteine protease, calpain-10, has been reported in a Mexican-American population. However, its association with other ethnic populations and any role it plays in the pathogenesis of type 2 diabetes remain to be clarified.
Two subgroups of patients are currently distinguished by the absence or presence of obesity. The degree and prevalence of obesity varies among different racial groups. While obesity is apparent in no more than 30% of Chinese and Japanese patients with type 2, it is found in 60-70% of North Americans, Europeans, or Africans with type 2 and approaches 100% of patients with type 2 among Pima Indians or Pacific Islanders from Nauru or Samoa.
1. Obese type 2 patients —
Patients with this most common form of diabetes have an insensitivity to endogenous insulin. When an associated defect of insulin production prevents adequate compensation for this insulin resistance, nonketotic mild diabetes occurs. Hyperplasia of pancreatic B cells is often present and probably accounts for the fasting hyperinsulinism and exaggerated insulin and proinsulin responses to glucose and other stimuli seen early in the disease. After several years' duration of diabetes, chronic deposition of amyloid in the islets may combine with inherited genetic defects to progressively impair B cell function.
The mechanisms underlying the insulin resistance of type 2 diabetes are poorly understood. Obesity is generally associated with abdominal distribution of fat, producing an abnormally high waist-to-hip ratio. This "visceral" obesity, due to accumulation of fat in the omental and mesenteric regions, correlates with insulin resistance; subcutaneous abdominal fat seems to have less of an association with insulin insensitivity. Exercise may affect the deposition of visceral fat as suggested by CT scans of Japanese wrestlers, whose extreme obesity is predominantly subcutaneous. Their daily vigorous exercise program prevents accumulation of visceral fat, and they have normal serum lipids and euglycemia despite daily intakes of 5000-7000 kcal and development of massive subcutaneous obesity. Several adipokines, secreted by fat cells, can affect insulin action in obesity. Two of these, leptin and adiponectin, seem to increase sensitivity to insulin, presumably by increasing hepatic responsiveness. Two others — tumor necrosis factor-a, which inactivates insulin receptors, and the newly discovered peptide resistin — interfere with insulin action on glucose metabolism and have been reported to be elevated in obese animal models. Mutations or abnormal levels of these adipokines may contribute to the development of insulin resistance in human obesity.
Hyperglycemia per se can impair insulin action by causing accumulation of hexosamines in muscle and fat tissue and inhibiting glucose transport (acquired glucose toxicity). Correction of hyperglycemia reverses this acquired insulin resistance.
2. Nonobese type 2 patients —
These patients generally show an absent or blunted early phase of insulin release in response to glucose; however, it can be elicited in response to other insulinogenic stimuli such as acute intravenous administration of sulfonylureas, glucagon, or arginine.
Although insulin resistance may be detected with special tests, it does not seem to be clinically relevant to the treatment of most nonobese type 2 patients, who generally respond to appropriate therapeutic supplements of insulin in the absence of rare associated conditions such as lipoatrophy or acanthosis nigricans.
Among this heterogeneous subgroup of patients with nonobese type 2 diabetes, the majority are idiopathic. However, with increasing frequency, a variety of etiologic genetic abnormalities have been documented in a subset of these patients who have recently been reclassified within a group designated "other specific types." (current MD&T 2005)
symptoms of type 2 diabetes
B. Type 2 Diabetes
This represents a heterogeneous group comprising milder forms of diabetes that occur predominantly in adults but occasionally in juveniles. More than 90% of all diabetics in the United States are included under this classification. Circulating endogenous insulin is sufficient to prevent ketoacidosis but is inadequate to prevent hyperglycemia in the face of increased needs owing to tissue insensitivity. In most cases of this type of diabetes, the cause is unknown.
Tissue insensitivity to insulin has been noted in most type 2 patients irrespective of weight and has been attributed to several interrelated factors. These include a putative (and as yet undefined) genetic factor, which is aggravated in time by additional enhancers of insulin resistance such as aging, a sedentary lifestyle, and abdominal-visceral obesity. In addition, there is an accompanying deficiency in the response of pancreatic B cells to glucose. Both the tissue resistance to insulin and the impaired B cell response to glucose appear to be further aggravated by increased hyperglycemia (glucose toxicity), and both defects are ameliorated by treatment that reduces the hyperglycemia toward normal. Most epidemiologic data indicate strong genetic influences, since in monozygotic twins over 40 years of age, concordance develops in over 70% of cases within a year whenever one twin develops type 2 diabetes. Attempts to identify genetic markers for type 2 have as yet been unsuccessful, though linkage to a gene on chromosome 2 encoding a cysteine protease, calpain-10, has been reported in a Mexican-American population. However, its association with other ethnic populations and any role it plays in the pathogenesis of type 2 diabetes remain to be clarified.
Two subgroups of patients are currently distinguished by the absence or presence of obesity. The degree and prevalence of obesity varies among different racial groups. While obesity is apparent in no more than 30% of Chinese and Japanese patients with type 2, it is found in 60-70% of North Americans, Europeans, or Africans with type 2 and approaches 100% of patients with type 2 among Pima Indians or Pacific Islanders from Nauru or Samoa.
1. Obese type 2 patients —
Patients with this most common form of diabetes have an insensitivity to endogenous insulin. When an associated defect of insulin production prevents adequate compensation for this insulin resistance, nonketotic mild diabetes occurs. Hyperplasia of pancreatic B cells is often present and probably accounts for the fasting hyperinsulinism and exaggerated insulin and proinsulin responses to glucose and other stimuli seen early in the disease. After several years' duration of diabetes, chronic deposition of amyloid in the islets may combine with inherited genetic defects to progressively impair B cell function.
The mechanisms underlying the insulin resistance of type 2 diabetes are poorly understood. Obesity is generally associated with abdominal distribution of fat, producing an abnormally high waist-to-hip ratio. This "visceral" obesity, due to accumulation of fat in the omental and mesenteric regions, correlates with insulin resistance; subcutaneous abdominal fat seems to have less of an association with insulin insensitivity. Exercise may affect the deposition of visceral fat as suggested by CT scans of Japanese wrestlers, whose extreme obesity is predominantly subcutaneous. Their daily vigorous exercise program prevents accumulation of visceral fat, and they have normal serum lipids and euglycemia despite daily intakes of 5000-7000 kcal and development of massive subcutaneous obesity. Several adipokines, secreted by fat cells, can affect insulin action in obesity. Two of these, leptin and adiponectin, seem to increase sensitivity to insulin, presumably by increasing hepatic responsiveness. Two others — tumor necrosis factor-a, which inactivates insulin receptors, and the newly discovered peptide resistin — interfere with insulin action on glucose metabolism and have been reported to be elevated in obese animal models. Mutations or abnormal levels of these adipokines may contribute to the development of insulin resistance in human obesity.
Hyperglycemia per se can impair insulin action by causing accumulation of hexosamines in muscle and fat tissue and inhibiting glucose transport (acquired glucose toxicity). Correction of hyperglycemia reverses this acquired insulin resistance.
2. Nonobese type 2 patients —
These patients generally show an absent or blunted early phase of insulin release in response to glucose; however, it can be elicited in response to other insulinogenic stimuli such as acute intravenous administration of sulfonylureas, glucagon, or arginine.
Although insulin resistance may be detected with special tests, it does not seem to be clinically relevant to the treatment of most nonobese type 2 patients, who generally respond to appropriate therapeutic supplements of insulin in the absence of rare associated conditions such as lipoatrophy or acanthosis nigricans.
Among this heterogeneous subgroup of patients with nonobese type 2 diabetes, the majority are idiopathic. However, with increasing frequency, a variety of etiologic genetic abnormalities have been documented in a subset of these patients who have recently been reclassified within a group designated "other specific types." (current MD&T 2005)
This represents a heterogeneous group comprising milder forms of diabetes that occur predominantly in adults but occasionally in juveniles. More than 90% of all diabetics in the United States are included under this classification. Circulating endogenous insulin is sufficient to prevent ketoacidosis but is inadequate to prevent hyperglycemia in the face of increased needs owing to tissue insensitivity. In most cases of this type of diabetes, the cause is unknown.
Tissue insensitivity to insulin has been noted in most type 2 patients irrespective of weight and has been attributed to several interrelated factors. These include a putative (and as yet undefined) genetic factor, which is aggravated in time by additional enhancers of insulin resistance such as aging, a sedentary lifestyle, and abdominal-visceral obesity. In addition, there is an accompanying deficiency in the response of pancreatic B cells to glucose. Both the tissue resistance to insulin and the impaired B cell response to glucose appear to be further aggravated by increased hyperglycemia (glucose toxicity), and both defects are ameliorated by treatment that reduces the hyperglycemia toward normal. Most epidemiologic data indicate strong genetic influences, since in monozygotic twins over 40 years of age, concordance develops in over 70% of cases within a year whenever one twin develops type 2 diabetes. Attempts to identify genetic markers for type 2 have as yet been unsuccessful, though linkage to a gene on chromosome 2 encoding a cysteine protease, calpain-10, has been reported in a Mexican-American population. However, its association with other ethnic populations and any role it plays in the pathogenesis of type 2 diabetes remain to be clarified.
Two subgroups of patients are currently distinguished by the absence or presence of obesity. The degree and prevalence of obesity varies among different racial groups. While obesity is apparent in no more than 30% of Chinese and Japanese patients with type 2, it is found in 60-70% of North Americans, Europeans, or Africans with type 2 and approaches 100% of patients with type 2 among Pima Indians or Pacific Islanders from Nauru or Samoa.
1. Obese type 2 patients —
Patients with this most common form of diabetes have an insensitivity to endogenous insulin. When an associated defect of insulin production prevents adequate compensation for this insulin resistance, nonketotic mild diabetes occurs. Hyperplasia of pancreatic B cells is often present and probably accounts for the fasting hyperinsulinism and exaggerated insulin and proinsulin responses to glucose and other stimuli seen early in the disease. After several years' duration of diabetes, chronic deposition of amyloid in the islets may combine with inherited genetic defects to progressively impair B cell function.
The mechanisms underlying the insulin resistance of type 2 diabetes are poorly understood. Obesity is generally associated with abdominal distribution of fat, producing an abnormally high waist-to-hip ratio. This "visceral" obesity, due to accumulation of fat in the omental and mesenteric regions, correlates with insulin resistance; subcutaneous abdominal fat seems to have less of an association with insulin insensitivity. Exercise may affect the deposition of visceral fat as suggested by CT scans of Japanese wrestlers, whose extreme obesity is predominantly subcutaneous. Their daily vigorous exercise program prevents accumulation of visceral fat, and they have normal serum lipids and euglycemia despite daily intakes of 5000-7000 kcal and development of massive subcutaneous obesity. Several adipokines, secreted by fat cells, can affect insulin action in obesity. Two of these, leptin and adiponectin, seem to increase sensitivity to insulin, presumably by increasing hepatic responsiveness. Two others — tumor necrosis factor-a, which inactivates insulin receptors, and the newly discovered peptide resistin — interfere with insulin action on glucose metabolism and have been reported to be elevated in obese animal models. Mutations or abnormal levels of these adipokines may contribute to the development of insulin resistance in human obesity.
Hyperglycemia per se can impair insulin action by causing accumulation of hexosamines in muscle and fat tissue and inhibiting glucose transport (acquired glucose toxicity). Correction of hyperglycemia reverses this acquired insulin resistance.
2. Nonobese type 2 patients —
These patients generally show an absent or blunted early phase of insulin release in response to glucose; however, it can be elicited in response to other insulinogenic stimuli such as acute intravenous administration of sulfonylureas, glucagon, or arginine.
Although insulin resistance may be detected with special tests, it does not seem to be clinically relevant to the treatment of most nonobese type 2 patients, who generally respond to appropriate therapeutic supplements of insulin in the absence of rare associated conditions such as lipoatrophy or acanthosis nigricans.
Among this heterogeneous subgroup of patients with nonobese type 2 diabetes, the majority are idiopathic. However, with increasing frequency, a variety of etiologic genetic abnormalities have been documented in a subset of these patients who have recently been reclassified within a group designated "other specific types." (current MD&T 2005)
what are the symptoms of diabetes
Type 1 diabetes:
• Polyuria, polydipsia, and weight loss associated with random plasma glucose = 200 mg/dL. • Plasma glucose of 126 mg/dL or higher after an overnight fast, documented on more than one occasion. • Ketonemia, ketonuria, or both. • Islet autoantibodies are frequently present.
Type 2 diabetes:
• Most patients are over 40 years of age and obese. • Polyuria and polydipsia. Ketonuria and weight loss generally are uncommon at time of diagnosis. Candidal vaginitis in women may be an initial manifestation. Many patients have few or no symptoms. • Plasma glucose of 126 mg/dL or higher after an overnight fast on more than one occasion. After 75 g oral glucose, diagnostic values are 200 mg/dL or more 2 hours after the oral glucose. • Hypertension, dyslipidemia, and atherosclerosis are often associated.
• Polyuria, polydipsia, and weight loss associated with random plasma glucose = 200 mg/dL. • Plasma glucose of 126 mg/dL or higher after an overnight fast, documented on more than one occasion. • Ketonemia, ketonuria, or both. • Islet autoantibodies are frequently present.
Type 2 diabetes:
• Most patients are over 40 years of age and obese. • Polyuria and polydipsia. Ketonuria and weight loss generally are uncommon at time of diagnosis. Candidal vaginitis in women may be an initial manifestation. Many patients have few or no symptoms. • Plasma glucose of 126 mg/dL or higher after an overnight fast on more than one occasion. After 75 g oral glucose, diagnostic values are 200 mg/dL or more 2 hours after the oral glucose. • Hypertension, dyslipidemia, and atherosclerosis are often associated.
american association diabetes educators
Recommended Approach to Dx of DM in HK
Symptomatic pt:FPG or RPG on 2 occasions.Epidemiological survey:FPG or 2hrPG after OGTT.DM screening:No risk factors: FPG.Risk factor +ve: OGTT or (FPG + HbA1c).OGTT if:Hx of IGTKnown IFGFPG>5.6mmol/l and HbA1c>5.5%
Risk Factors for DM
Consider Screening for glucose intolerance and other CVS risk factors:
Age >45.Overweight (BMI >23kg/m2).HT.Dyslipidemia (esp high TG).Hx of gestational diabetes.FH (1st degree relatives) of DM.
Dx Criteria of DM
DM: FPG >7.0 or RPG >11.1 or 2hPG >11.1IGT: FPG <7.0 2hpg="7.8-<11.1IFG:" fpg =" 6.1-<7.0NFG:" l =" 100mg/dl6.1mmol/l" l =" 126mg/dl7.8mmol/l" l =" 200mg/dl">300mg/dOvernight urine:Normal: <20mcg/minmicro:>200mcg/minEMU or spot urine albumin:Normal: <20mg/lmicro:>200mg/lEMU or spot urine Alb:Cr ratio (ACR):Normal: M<2.5,>38mg/mmol
Notes:
If 1st test +ve, repeat 1-2 more times: 2/3 +ve results before diagnosing microalbuminuria. Spot urine ACR is simple and can be used as screening test.
Treatment Target Values
Ideal value shown here.US = unsatisfactoryAdjust Tx goals acc. to age, risk factors and co-existing complications.
FPG = 4-6mmol/l [US if >8]HbA1c <1.1x>1.3]BMI <23>27]Waist circumferenceM <75cm>90cm (>36")]F <70cm>80cm (>32")]SBP <135mmhg>160]DBP <85mmhg>95]Total CE <4.5mmol/l>6.2]HDL-CE >1.1mmol/l [US <0.9]ldl-ce>4.2]TG <1.5mmol/l>2.8]
Definition of Obesity
[Using BMI = BW (kg) / Height (m)2]
WHOOverweight: BMI = 25-<30obesity:>30National Diabetes Data GroupObesity: BMI >25 (F) or >27 (M)International Obesity Task Force (for Asians)Overweight: BMI >23At-risk: BMI = 23-<25obese bmi =" 25-<30Obese">30
Etiological Classification of Diabetes
Type 1 diabetes mellitus(absolute insulin deficiency)AutoimmuneIdiopathicType 2 diabetes mellitus(range from insulin resistant with relative insulin deficiency to predominately secretory type with or without insulin resistance).Other specific types:Genetic defects of B-cell functionMODY type 1-5Mitochondrial DNA mutationOthersGenetic defects in insulin actionType A insulin resistanceLeprechaunismRabson-Mendenhall synLipoatrophic diabetesOthersDiseases of exocrine pancreasPancreatitisHaemochromatosisOthersEndocrinopathiesAcromegalyCushing's synOthersDrug or chemical-induced (eg. thiazides, steroids).Infections (eg. congenital Rubella).Uncommon forms of immune- mediated diabetes (eg. 'stiff man' syn).Other genetic syndromes sometimes associated with diabetes:Down's synFriedreich's ataxiaHuntington's choreaKlinefelter's synLawrence-Moon-Biedel synMyotonic dystrophyPorphyriaPrader-Willi synTurner's synWolfram's synOthersGestation diabetes(Include fomer categories of gestational IGT and gestational DM).
Symptomatic pt:FPG or RPG on 2 occasions.Epidemiological survey:FPG or 2hrPG after OGTT.DM screening:No risk factors: FPG.Risk factor +ve: OGTT or (FPG + HbA1c).OGTT if:Hx of IGTKnown IFGFPG>5.6mmol/l and HbA1c>5.5%
Risk Factors for DM
Consider Screening for glucose intolerance and other CVS risk factors:
Age >45.Overweight (BMI >23kg/m2).HT.Dyslipidemia (esp high TG).Hx of gestational diabetes.FH (1st degree relatives) of DM.
Dx Criteria of DM
DM: FPG >7.0 or RPG >11.1 or 2hPG >11.1IGT: FPG <7.0 2hpg="7.8-<11.1IFG:" fpg =" 6.1-<7.0NFG:" l =" 100mg/dl6.1mmol/l" l =" 126mg/dl7.8mmol/l" l =" 200mg/dl">300mg/dOvernight urine:Normal: <20mcg/minmicro:>200mcg/minEMU or spot urine albumin:Normal: <20mg/lmicro:>200mg/lEMU or spot urine Alb:Cr ratio (ACR):Normal: M<2.5,>38mg/mmol
Notes:
If 1st test +ve, repeat 1-2 more times: 2/3 +ve results before diagnosing microalbuminuria. Spot urine ACR is simple and can be used as screening test.
Treatment Target Values
Ideal value shown here.US = unsatisfactoryAdjust Tx goals acc. to age, risk factors and co-existing complications.
FPG = 4-6mmol/l [US if >8]HbA1c <1.1x>1.3]BMI <23>27]Waist circumferenceM <75cm>90cm (>36")]F <70cm>80cm (>32")]SBP <135mmhg>160]DBP <85mmhg>95]Total CE <4.5mmol/l>6.2]HDL-CE >1.1mmol/l [US <0.9]ldl-ce>4.2]TG <1.5mmol/l>2.8]
Definition of Obesity
[Using BMI = BW (kg) / Height (m)2]
WHOOverweight: BMI = 25-<30obesity:>30National Diabetes Data GroupObesity: BMI >25 (F) or >27 (M)International Obesity Task Force (for Asians)Overweight: BMI >23At-risk: BMI = 23-<25obese bmi =" 25-<30Obese">30
Etiological Classification of Diabetes
Type 1 diabetes mellitus(absolute insulin deficiency)AutoimmuneIdiopathicType 2 diabetes mellitus(range from insulin resistant with relative insulin deficiency to predominately secretory type with or without insulin resistance).Other specific types:Genetic defects of B-cell functionMODY type 1-5Mitochondrial DNA mutationOthersGenetic defects in insulin actionType A insulin resistanceLeprechaunismRabson-Mendenhall synLipoatrophic diabetesOthersDiseases of exocrine pancreasPancreatitisHaemochromatosisOthersEndocrinopathiesAcromegalyCushing's synOthersDrug or chemical-induced (eg. thiazides, steroids).Infections (eg. congenital Rubella).Uncommon forms of immune- mediated diabetes (eg. 'stiff man' syn).Other genetic syndromes sometimes associated with diabetes:Down's synFriedreich's ataxiaHuntington's choreaKlinefelter's synLawrence-Moon-Biedel synMyotonic dystrophyPorphyriaPrader-Willi synTurner's synWolfram's synOthersGestation diabetes(Include fomer categories of gestational IGT and gestational DM).
Subscribe to:
Posts (Atom)
