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Severe Insulin Resistance Treatment

Insulin Resistance Syndromes

Insulin Resistance Syndromes

Diagnosis Biochemical diagnostic thresholds for severe insulin resistance (IR) are arbitrary, and should ideally be defined relative to BMI-adjusted population normal ranges, however one set of approximate diagnostic criteria is as follows: A: Non-diabetic and B.M.I. <30 kg/m2 Fasting insulin above 150 pmol/l OR Peak insulin on oral glucose tolerance testing above 1,500 pmol/l B: Absolute insulin deficiency and B.M.I. <30 kg/m2 Exogenous insulin requirement > 3U/kg/day. C: Partial beta cell decompensation and/or B.M.I. >30 kg/m2 Insulin levels are more difficult to interpret in the context of obesity or pre-existing diabetes, where glucotoxicity, and mixtures of endogenous and exogenous insulin in the circulation confuse the biochemical picture. In these settings the clinical history and features such as acanthosis nigricans are particularly useful in making a diagnosis of likely monogenic severe IR. Subjective clinical judgement is also required. Generic clinical features of severe insulin resistance Severe insulin resistance (IR) usually presents in one of three ways: Persistent hyperglycaemia despite large doses of insulin in patients with diabetes - Note, however, that many cases are unrecognised in the prediabetic phase. Indeed, a very common early feature of severe IR is spontaneous and symptomatic postprandial hypoglycaemia which may require medical intervention. This may dominate the clinical picture for years before hyperglycemia supervenes, which only occurs in the face of beta cell decompensation. Acanthosis Nigricans - The commonest presentation of monogenic severe IR is with the skin condition acanthosis nigricans (Figure 1). Ovarian hyperandrogenism, or “Polycystic Ovary Syndrome” - This may be severe, and oligo- or amenorrhoea are frequently the first Continue reading >>

Payperview: A Clinical Approach To Severe Insulin Resistance - Karger Publishers

Payperview: A Clinical Approach To Severe Insulin Resistance - Karger Publishers

A Clinical Approach to Severe Insulin Resistance Savage D.a Semple R.a Chatterjee V.a Wales J.b Ross R.c O'Rahilly S.a I have read the Karger Terms and Conditions and agree. Extreme forms of insulin resistance are a rare cause of type 2 diabetes. However, individualswith severe insulin resistance pose unique diagnostic and therapeutic challenges,and have often acted as experiments of nature providing important novel informationregarding endocrine physiology and mechanistic insights relevant to the study of more commondisorders. Progress in understanding the molecular pathogenesis of such syndromes isalso beginning to yield novel therapeutic options. Severe insulin resistance typically presentsin 1 of 3 ways: (1) disordered glucose metabolism including both diabetes and/orparadoxical hypoglycaemia; (2) acanthosis nigricans, a velvety hyperpigmentation of axilliaryand flexural skin often associated with skin tags; or (3) hyperandrogenism in girls (hirsutism,oligo-/amenorrhoea and polycystic ovaries). Lipodystrophy is a major cause ofsevere insulin resistance and needs to be looked for very carefully, particularly in thepatients with significant dyslipidaemia and fatty liver. Specific treatments are now availablefor some forms of severe insulin resistance; for example, leptin replacement in patients withgeneralized lipodystrophy. In the absence of a specific diagnosis and therapy, metformin isa useful insulin sensitizer and should be used in conjunction with aggressive diet and exerciseinterventions. Continue reading >>

Syndromes Of Severe Insulin Resistance

Syndromes Of Severe Insulin Resistance

Division of Endocrinology, Beth Israel Deaconess Medical Center and Joslin Diabetes Center, Boston, Massachusetts 02215 Search for other works by this author on: Division of Endocrinology, Beth Israel Deaconess Medical Center and Joslin Diabetes Center, Boston, Massachusetts 02215 Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., D.Sc., Division of Endocrinology, RN 325, 99 Brookline Avenue, Boston, Massachusetts 02215. Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 9, 1 September 1998, Pages 30253030, Nicholas A. Tritos, Christos S. Mantzoros; Syndromes of Severe Insulin Resistance, The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 9, 1 September 1998, Pages 30253030, AN exceedingly large number of studies have convincingly demonstrated that insulin resistance occurs in association with a variety of physiological and pathophysiological states, including obesity, noninsulin-dependent diabetes mellitus (NIDDM), polycystic ovary syndrome (PCOS), and the constellation of central obesity, hypertension, glucose intolerance, and hyperlipidemia known as metabolic syndrome or syndrome X ( 1 , 2 ) ( Table 1 ). In addition, a number of rare, albeit very interesting, syndromes characterized by extreme insulin resistance have been described over the past 20 yr ( 3 , 4 ). These syndromes are not only clinically important, but have also significantly contributed to our knowledge of the mechanisms of insulin action and resistance. In this review, we focus on syndromes characterized by extreme insulin resistance. We present the tools and criteria for the diagnosis of severe insulin resistance and review the clinical phenotypes of type A and type B syndromes of insulin Continue reading >>

Leptin To Treat Severe Insulin Resistance - Pilot Study

Leptin To Treat Severe Insulin Resistance - Pilot Study

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information This pilot study will evaluate the safety and effectiveness of leptin therapy in two children with severe insulin resistance syndrome. Patients with this condition often have high blood sugar levels and may have hormone imbalances, a constant feeling of warmth, fertility problems, large appetite, and enlarged liver due to fat accumulation. Leptin is a hormone produced by fat cells. It influences appetite, affects levels of reproductive hormones, and possibly manages how the body reacts to insufficient food. Certain people with severe insulin resistance syndromes have decreased amounts of fat tissue and make little or no leptin. A 13-year-old male and an 11-year-old female with severe insulin resistance will participate in this study. They will have the following tests and procedures before beginning 4 months of leptin therapy: Insulin tolerance test - measures blood sugar levels after intravenous (IV) administration of insulin. Blood samples are collected through the IV tube at various intervals during the 1-hour test. Ultrasound of the liver and, if abnormalities are found, possibly liver biopsies. Fasting blood tests - to measure blood count, blood lipids, and various hormones and assess liver function. Resting metabolic rate - to measure the amount of oxygen breathed at rest in order to calculate how many calories are required to maintain resting body functions. Magnetic resonance imaging of the liver and other organs, and of muscle and fat. Pelvic ultrasound in female patient - to detect ovarian cysts. Estimation of body fat - measurements of height, weight, waist, hip size, and skin folds over the arms and abdomen to estimate body fat Continue reading >>

Signs Of Insulin Resistance

Signs Of Insulin Resistance

What is insulin resistance? Insulin is a hormone made by your pancreas. It allows your cells to use glucose (sugar) for energy. People with insulin resistance have cells throughout their bodies that don’t use insulin effectively. This means the cells have trouble absorbing glucose, which causes a buildup of sugar in their blood. If your blood glucose levels are higher than normal, but not high enough to be considered type 2 diabetes, you have a condition called prediabetes caused by insulin resistance. It’s not entirely clear why some people develop insulin resistance and others don’t. A sedentary lifestyle and being overweight increases the chance of developing prediabetes and type 2 diabetes. The effects of insulin resistance Insulin resistance typically doesn’t trigger any noticeable symptoms. You could be insulin resistant for years without knowing, especially if your blood glucose levels aren’t checked. The American Diabetes Association (ADA) estimates that nearly 70 percent of individuals with insulin resistance and prediabetes will go on to develop type 2 diabetes if significant lifestyle changes aren’t made. Some people with insulin resistance may develop a skin condition known as acanthosis nigricans. This condition creates dark patches often on the back of the neck, groin, and armpits. Some experts believe it may be caused by a buildup of insulin within skin cells. There’s no cure for acanthosis nigricans, but if caused by a specific condition, treatment may allow for some of your natural skin color to return. Insulin resistance increases the risk of being overweight, having high triglycerides, and having elevated blood pressure. Since insulin resistance increases your risk for progressing to diabetes, you may not notice right away if you develop Continue reading >>

Treatment Approach To Patients With Severe Insulin Resistance

Treatment Approach To Patients With Severe Insulin Resistance

In Brief Patients with severe insulin resistance require >2 units/kg of body weight or 200 units/day of insulin. Yet, many patients do not achieve glycemic targets despite using very high doses of insulin. Insulin can cause weight gain, which further contributes to worsening insulin resistance. This article describes the pharmacological options for managing patients with severe insulin resistance, including the use of U-500 insulin and newer agents in combination with insulin. An increasing number of patients have severe insulin resistance and require large doses of insulin. Managing patients with severe insulin resistance is challenging because it is difficult to achieve good glycemic control using conventional treatment approaches (1). Moreover, weight gain, hypoglycemia, regimen complexity, and cost are frequent concerns as insulin doses escalate. Insulin resistance is characterized by an impaired response to either endogenous or exogenous insulin (2). Although insulin resistance is a common feature of type 2 diabetes, cases of severe insulin resistance remain relatively uncommon but are likely increasing as the prevalence of diabetes and obesity surges. The degree of insulin resistance can be measured using the euglyemic insulin clamp technique, but this is not a clinically useful method of determining whether a patient has severe insulin resistance in practice (3). The most widely reported and clinically useful definitions of severe insulin resistance are based on exogenous insulin requirements using either the number of units per kilogram of body weight per day or the total daily dose (1). Patients who require >1 unit/kg/day are considered to have insulin resistance, and those requiring >2 units/kg/day have severe resistance (3). Alternatively, a total daily insul Continue reading >>

What Is Severe Insulin Resistance?

What Is Severe Insulin Resistance?

Severe insulin resistance and lipodystrophy are rare metabolic disorders. They occur when the body does not use the insulin it produces properly. Insulin is a hormone (a chemical signal that travels in the bloodstream) made by the pancreas.It controls how the body uses sugars and fats and is essential for life. Its absence is the underlying problem in type 1 diabetes. However, from person to person there are significant differences in how sensitive the tissues of the body are to insulin. In other words, in some people a very small amount of insulin produces a large change in the blood levels of glucose and fats (these people are said to be very insulin sensitive), while in others much larger amounts are required to produce the same change (these people are said to be insulin resistant). Those with severe insulin resistance are those whose bodies respond least well to insulin. Although many with severe insulin resistance do go onto develop diabetes, severe insulin resistance is NOT the same as diabetes: as long as the pancreas can produce enough insulin to overcome the insulin resistance diabetes does not develop. However even before diabetes appears, insulin levels in the body may be extremely high, and this can produce a range of different problems in its own right. Rarely, people are born with severe insulin resistance and remain severely insulin resistant throughout their lives. Far more frequently insulin resistance develops only at puberty or in later life, while in some people it is only a temporary condition caused by other situations or illnesses. Most commonly a tendency towards insulin resistance is inherited, but only in the presence of environmental or lifestyle factors does it become a problem. Consequences of severe insulin resistance include development Continue reading >>

Treatment Approach To Patients With Severe Insulin Resistance

Treatment Approach To Patients With Severe Insulin Resistance

Go to: Evaluating Patients There are several known causes of severe insulin resistance, including several rare disorders and genetic conditions (Table 1) (3). Several medications are known to contribute to insulin resistance, including glucocorticoids, protease inhibitors, atypical antipsychotics, and calcineurin inhibitors. In patients with severe insulin resistance, an effort should be made to discontinue such agents or switch to alternative medications if possible (5). Poor medication-taking behaviors or “pseudoresistance” should be ruled out before modifying or intensifying therapy. Pseudoresistance may be the result of nonadherence, poor injection technique, improper insulin storage, or malingering for secondary gain. Pseudoresistance can be ruled out by conducting a modified insulin tolerance test (3). During such a test, patients are administered a witnessed dose of short-acting insulin in the clinic, and their blood glucose is monitored every 30 minutes for a period of 4–8 hours. Patients should be fasting for the test and should have a blood glucose level >150 mg/dL. A witnessed insulin dose approximately equal to what an average person with diabetes might require (insulin dose [units] = blood glucose [mg/dL] – 100 / (1,500 / weight [kg] × 1.0)] should be given. If there is not an appropriate drop in blood glucose within 4 hours, a second dose should be given. If normoglycemia or hypoglycemia is not achieved after either dose, the test confirms that a patient likely has severe insulin resistance. Continue reading >>

Insulin Resistance

Insulin Resistance

What medical conditions are associated with insulin resistance? While the metabolic syndrome links insulin resistance with abdominal obesity, elevated cholesterol, and high blood pressure; several other medical other conditions are specifically associated with insulin resistance. Insulin resistance may contribute to the following conditions: Type 2 Diabetes: Overt diabetes may be the first sign insulin resistance is present. Insulin resistance can be noted long before type 2 diabetes develops. Individuals reluctant or unable to see a health-care professional often seek medical attention when they have already developed type 2 diabetes and insulin resistance. Fatty liver: Fatty liver is strongly associated with insulin resistance. Accumulation of fat in the liver is a manifestation of the disordered control of lipids that occurs with insulin resistance. Fatty liver associated with insulin resistance may be mild or severe. Newer evidence suggests fatty liver may even lead to cirrhosis of the liver and, possibly, liver cancer. Arteriosclerosis: Arteriosclerosis (also known as atherosclerosis) is a process of progressive thickening and hardening of the walls of medium-sized and large arteries. Arteriosclerosis is responsible for: Other risk factors for arteriosclerosis include: High levels of "bad" (LDL) cholesterol Diabetes mellitus from any cause Family history of arteriosclerosis Skin Lesions: Skin lesions include increased skin tags and a condition called acanthosis nigerians (AN). Acanthosis nigricans is a darkening and thickening of the skin, especially in folds such as the neck, under the arms, and in the groin. This condition is directly related to the insulin resistance, though the exact mechanism is not clear. Acanthosis nigricans is a cosmetic condition strongly Continue reading >>

Common Drugs And Medications To Treat Diabetes Mellitus With Severe Insulin Resistance

Common Drugs And Medications To Treat Diabetes Mellitus With Severe Insulin Resistance

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Insulin Resistance Causes And Symptoms

Insulin Resistance Causes And Symptoms

One in three Americans—including half of those age 60 and older1— have a silent blood sugar problem known as insulin resistance. Insulin resistance increases the risk for prediabetes, type 2 diabetes and a host of other serious health problems, including heart attacks, strokes2 and cancer.3 What is Insulin Resistance? Insulin resistance is when cells in your muscles, body fat and liver start resisting or ignoring the signal that the hormone insulin is trying to send out—which is to grab glucose out of the bloodstream and put it into our cells. Glucose, also known as blood sugar, is the body’s main source of fuel. We get glucose from grains, fruit, vegetables, dairy products, and drinks that bring break down into carbohydrates. How Insulin Resistance Develops While genetics, aging and ethnicity play roles in developing insulin sensitivity, the driving forces behind insulin resistance include excess body weight, too much belly fat, a lack of exercise, smoking, and even skimping on sleep.4 As insulin resistance develops, your body fights back by producing more insulin. Over months and years, the beta cells in your pancreas that are working so hard to make insulin get worn out and can no longer keep pace with the demand for more and more insulin. Then – years after insulin resistance silently began – your blood sugar may begin to rise and you may develop prediabetes or type 2 diabetes. You may also develop non-alcoholic fatty liver disease (NAFLD), a growing problem associated with insulin resistance that boosts your risk for liver damage and heart disease. 5 Signs and Symptoms of Insulin Resistance Insulin resistance is usually triggered by a combination of factors linked to weight, age, genetics, being sedentary and smoking. - A large waist. Experts say the be Continue reading >>

Severe Insulin Resistance In A Patient With Type 2 Diabetes

Severe Insulin Resistance In A Patient With Type 2 Diabetes

Severe insulin resistance in a patient with type 2 diabetes Severe insulin resistance in a patient with type 2 diabetes Patients with severe insulin resistance may benefit from concentrated insulin. Mrs. D, aged 58 years, has a history of uncontrolled type 2 diabetes mellitus. She visited her primary care nurse practitioner's office, reporting that her diabetes specialist had recently moved away and there is a 1-month waiting period to be seen by a different diabetes specialist. The patient is concerned about her continued elevated blood glucose level, which ranges from 200 to 400 mg/dL. She reported worsening of vision, frequent urination, and increased thirst. She denied urinary hesitancy or discomfort during urination. The patient's medical history included class III obesity , hypertension, hyperlipidemia, recurrent urinary tract infections, diabetic neuropathy, and a myocardial infarction 3 years ago. She was diagnosed with type 2 diabetes mellitus 20 years ago. The patient had been on oral hypoglycemic agents for 4 years prior to transitioning to insulin therapy. With progressive weight gain secondary to a sedentary lifestyle and poor dietary habits, she had required a steady increase in insulin dosage during the past few years. She now takes more than 240 units of insulin daily via subcutaneous injections. For the last month, her former diabetes specialist had been titrating up her insulin regimen due to persistent hyperglycemia. The patient performs self-monitoring of her blood glucose level about 4 to 5 times daily, usually prior to administering her scheduled insulin doses: fasting, pre-lunch, pre-dinner, and at bedtime. The patient's medication profile includes: Insulin aspart 42 units before each meal (breakfast, lunch, and dinner) Insulin aspart as a supple Continue reading >>

Use Of A Controlled Fast For The Treatment Of Severe Insulin Resistance In Patients With Type 2 Diabetes

Use Of A Controlled Fast For The Treatment Of Severe Insulin Resistance In Patients With Type 2 Diabetes

Use of a Controlled Fast for the Treatment of Severe Insulin Resistance in Patients with Type 2 Diabetes Patients with type 2 diabetes Patients with type 2 diabetes and severe insulin resistance often require large doses of insulin therapy to achieve target glycemic control. As insulin dose increases over time, patients may have decreased benefits with treatment, as well as unfavorable metabolic side effects such as weight gain and increased hunger. The purpose of this IRB-approved study is to describe our experience on the effect of a controlled, prolonged fast on insulin requirements, hyperglycemic control, and weight loss in patients with type 2 diabetes and severe insulin resistance. A total of 15 patients completed a controlled, prolonged fast consisting of carb-free clear liquids for the treatment of severe insulin resistance. Insulin was reduced by 50% in the first 36 hours and then adjusted individually. Pre-fast and post-fast (up to 6 months) data was collected assessing the effects on HbA1C, total insulin requirements, weight, and BMI. A total of 18 fasts were completed by the 15 patients. The majority were 72 hours in length (13), 3 were 60 hours, 1 was 48 hours, and 1 was 96 hours. Two of the fasts were observed in the hospital, while the remainder occurred at home under the medical supervision of a physician. The mean HbA1C was 9.95% prior to the fast and reduced to 9.14% at 1 month post-fast and 9.20% at 2-6 months post-fast. The mean insulin requirements were 275 units prior to the fast, 132 units at 2 weeks post-fast, 144 units at 1 month post-fast, and 201 units at 2-6 months post-fast. The mean weight was 266 pounds prior to the fast, 258 pounds at 2 weeks post-fast, 251 pounds at 1 month post-fast, and 242 pounds at 2-6 months post-fast. The mean BMI Continue reading >>

Insulin Resistance

Insulin Resistance

What is insulin resistance? Insulin is a hormone that facilitates the transport of blood sugar (glucose) from the bloodstream into cells throughout the body for use as fuel. In response to the normal increase in blood sugar after a meal, the pancreas secretes insulin into the bloodstream. With insulin resistance, the normal amount of insulin secreted is not sufficient to move glucose into the cells – thus the cells are said to be “resistant” to the action of insulin. To compensate, the pancreas secretes insulin in ever-increasing amounts to maintain fairly adequate blood-sugar movement into cells and a normal blood-sugar level. What are some insulin resistance symptoms? There are usually no obvious, outward signs of insulin resistance. However, when you are severely insulin resistant, dark patches of skin called acanthosis nigricans can develop on the back of the neck. Sometimes a dark ring forms around the neck. These dark patches can also occur on the elbows, knees, knuckles and armpits. More importantly, insulin has less visible effects on metabolic reactions throughout the body, including converting calories into fat. Insulin resistance influences the liver enzymes that produce cholesterol and acts on the kidneys (which can contribute to high blood pressure). High insulin levels also have a role in the process that regulates inflammation. In time, insulin resistance can lead to type 2 diabetes, itself a risk factor for heart disease. Insulin resistance can be diagnosed with blood tests that show low levels of HDL cholesterol (the “good” cholesterol), a high triglyceride level, a high fasting insulin level or a high uric acid level. What are the causes of insulin resistance? There are genetic factors that can contribute to the development of insulin resista Continue reading >>

Use Of U-500 Insulin In The Treatment Of Severe Insulin Resistance

Use Of U-500 Insulin In The Treatment Of Severe Insulin Resistance

Volume 3, Issue 4 , October 2008, Pages 211-218 Use of U-500 insulin in the treatment of severe insulin resistance Author links open overlay panel ElaineCochranMSN, CRNP Get rights and content Background: Glycemic control is essential in the management of diabetes. However, many patients with diabetes are not achieving therapeutic targets, partly because they are receiving insufficient doses of insulin. This is particularly problematic in patients with severe insulin resistance, defined as insulin requirement >200 units/kg per day (>3 units/kg per day for pediatric patients). It is difficult to use U-100 forms of insulin at doses >200 units/kg per day because of the volume of insulin being administered subcutaneously. U-500, a concentrated form of insulin, may be useful in the treatment of these patients. Objective: Current practice regarding the use of U-500 insulin has been published elsewhere. This article presents an updated algorithm for the administration and dosing of U-500 insulin, based on clinical experience with severe forms of insulin resistance. Guidelines are provided for dose escalation of U-500 insulin. Methods: We reviewed the results of treatment with U-500 insulin in patients with severe insulin resistance. We analyzed the results, updated a pre-existing algorithm, provided additional practical information on the administration and dosing of U-500 insulin, and compared the cost of U-500 with that of U-100 insulin. Results: To date, we have treated 56 patients (age range, 954 years) with severe insulin resistance using U-500 insulin. Doses ranged from 1.5 to 566 units/kg per day. Based on the pharmacodynamic properties of U-500 insulin, this concentrated form must be administered and dosed differently than regular U-100 insulin. U-500 insulin cost mor Continue reading >>

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